index
stringlengths
10
17
text
stringlengths
101
18k
doi
stringlengths
2
72
pubmed_621_3459
Female pattern hair loss (FPHL) was originally described as synonymous with androgenetic alopecia. However, the role of androgens in FPHL has not been proven, and the etiology is not yet defined. Several patterns of hair loss in women have been described, in addition to descriptions of scarring alopecias mimicking FPHL. In this paper, we discuss FPHL as an entity other than androgenetic alopecia and suggest that de-emphasizing the physicians reliance on pattern in the diagnosis of hair loss in women, and instead utilizing other tools including dermoscopy and histopathology, would benefit clinician's efforts in treating alopecias.
10.1111/j.1473-2165.2012.00607.x
pubmed_1054_7466
Skeletal muscle fibers of the frog Rana temporaria were held just taut and stimulated transversely by unidirectional electrical fields. We observed the reversible effects of stimulus duration (0.1-100 ms) and strength on action potentials, intracellular Ca2+ transients (monitored by aequorin), and contractile force during fixed-end contractions. Long duration stimuli (e.g., 10 ms) induced a maintained depolarization on the cathodal side of a cell and a maintained hyperpolarization on its anodal side. The hyperpolarization of the side facing the anode prevented the action potential from reaching mechanical threshold during strong stimuli. Variation of the duration or strength of a stimulus changed the luminescent response from a fiber injected with aequorin. Thus, the intracellular Ca2+ released during excitation-contraction coupling could be changed by the stimulus parameters. Prolongation of a stimulus at field strengths above 1.1 x rheobase decreased the amplitude of aequorin signals and the force of contractions. The decreases in aequorin and force signals from a given fiber paralleled one another and depended on the stimulus strength, but not on the stimulus polarity. These changes were completely reversible for stimulus strengths up to at least 4.2 x rheobase. The graded decreases in membrane depolarization, aequorin signals, and contractile force were correlated with the previously described folding of myofibrils in fibers allowed to shorten in response to the application of a long duration stimulus. The changes in aequorin signals and force suggest an absence of myofilament activation by Ca2+ in the section of the fiber closest to the anode. The results imply that injected aequorin distributes circumferentially in frog muscle with a coefficient of at least 10(-7) cm2/s, which is not remarkably different from the previously measured coefficient of 5 x 10(-8) cm2/s for its diffusion lengthwise.
10.1016/S0006-3495(81)84748-0
pubmed_403_6533
Naked oats (Avena nuda L.) is rich in protein, fat, vitamin, mineral elements and so on, and is one of the world's recognized cereal crops with the highest nutritional and healthcare value. In July 2019, leaf spot was detected on A. nuda in Zhangbei experimental station of Hebei Agricultural University. The incidence of disease is 10% to 20%. The symptoms were similar to anthracnose disease, the infected leaves had fusiform or nearly fusiform yellowish-brown spots, yellow halo around the spots. Numerous acervuli with black setae diagnostic of fungi in the genus Colletotrichum were present on necrotic lesions. To identify the pathogen, ten symptomatic leaves were collected, and only one disease spot was isolated from each leaf. Small square leaf pieces (3 to 5 mm) were excised from the junction of diseased and healthy tissues with a sterile scalpel and surface disinfested with 75% alcohol for 30s, 0.1% corrosive sublimate for 1 min, rinsed three times in sterile water. Plant tissues were then transferred on potato dextrose agar (PDA), and incubated at 25°C for 7 days. Two fungal isolates were obtained and purified by single-spore isolation method. All fungi have the same morphology and no other fungi were isolated. The aerial mycelium was gray black. The conidia were colorless and transparent, falcate, slightly curved, tapered toward the tips, and produced in acervuli with brown setae. The length and width of 100 conidia were measured and size ranged from 1.86 to 3.84 × 8.62 to 29.81 μm. These morphological characteristics were consistent with the description of Colletotrichum cereale (Crouch et al. 2006). To further assess the identity of the species, the genomic DNA of two fungal isolates (LYM19-4 and LYM19-10) was extracted by a CTAB protocol. The ribosomal DNA internal transcribed spacer (ITS) region as well as, the glyceraldehyde-3-phosphate dehydrogenase (GAPDH), actin (ACT), and the beta-tubulin 2 (Tub2) partial genes were amplified and sequenced with primers ITS4/5, GDF/GDR, ACT-512F/ACT-783R, and T1/Bt2b, respectively (Carbone et al. 1999; Templeton et al. 1992; O'Donnell et al. 1997; Glass et al. 1995). The sequences of the ITS-rDNA region (MW040121, MW040122), the GAPDH sequences (MW052554, MW052555), the ACT sequences (MW052556, MW052551) and the Tub2 sequences (MW052552, MW052553) of the two single-spore isolates were more than 99% identical to C. cereale isolate CGMCC3.15110 (JX625159, KC843517, KC843534 and JX625186). Maximum likelihood tree based on concatenated sequences of the four genes were constructed using MEGA7. The results showed the strains isolated from A. nuda were closely related to C. cereale, as supported by high bootstrap values. A pathogenicity test of the C. cereale isolates was performed on first unfolding leaves of A. nuda. Koch's postulates were carried out with isolates by spraying a conidial suspension of 106 conidia/mL on leaves of healthy A. nuda. Four replicated pots were inoculated at a time, 10 leaves each pot, while sterile distilled water was used as the control. All treated plants were placed in a moist chamber (25°C, 16-h light and 8-h dark period). Anthracnose symptoms developed on the inoculated plants 7 days post inoculation while all control plants remained healthy. Microscopic examination showed the surface of infected leaves had the same acervuli, setae, and conidia as the original isolate. The pathogenicity test was repeated three times. C. cereale was previously reported as the causal agent of anthracnose on feather reed grass in US (Crouch et al. 2009). To our knowledge, this is the first report of C. cereale as the causal agent of A. nuda anthracnose in China.
10.1094/PDIS-10-20-2109-PDN
pubmed_122_16104
The atopic march recognizes the increased occurrence of asthma, allergic rhinitis, or both after atopic dermatitis (AD) onset. Mechanisms for developing atopic comorbidities after AD onset are poorly understood but can involve the impaired cutaneous barrier, which facilitates cutaneous sensitization. The association can also be driven or amplified in susceptible subjects by a systemic TH2-dominant immune response to cutaneous inflammation. However, these associations might merely involve shared genetic loci and environmental triggers, including microbiome dysregulation, with the temporal sequence reflecting tissue-specific peak time of occurrence of each disease, suggesting more of a clustering of disorders than a march. Prospective longitudinal cohort studies provide an opportunity to explore the relationships between postdermatitis development of atopic disorders and potential predictive phenotypic, genotypic, and environmental factors. Recent investigations implicate disease severity and persistence, age of onset, parental atopic history, filaggrin (FLG) mutations, polysensitization, and the nonrural environment among risk factors for development of multiple atopic comorbidities in young children with AD. Early intervention studies to repair the epidermal barrier or alter exposure to the microbiome or allergens might elucidate the relative roles of barrier defects, genetic locus alterations, and environmental exposures in the risk and sequence of occurrence of TH2 activation disorders.
10.1016/j.jaci.2018.11.006
pubmed_435_6815
Neurons of the hypothalamic suprachiasmatic nucleus (SCN) express clock genes, which regulate their own transcription and generate daily output signals driving circadian rhythmic behavior and physiology. The neuropeptide VIP and its specific receptor, the VPAC2 receptor, are important for synchronization of clock neurons. In the present study, we characterized PER1 and PER2 expressing neurons in wild-type and VPAC2-deficient mice. We found evidence for distinct spatiotemporal circadian oscillation in the expression of the PER genes in two separate clusters of SCN neurons. In wild-type mice corresponding to the SCN shell and ventral core, high expression of PER was found at lights-off most likely representing an evening clock (E-clock). In another smaller cluster of neurons located in the central core of the SCN, PER expression peaks in antiphase at lights-on and could represent a morning clock (M-clock). BMAL1 immunoreactivity was found to be expressed in antiphase to PER in M and E neurons, respectively. PER was found in 98% of neurons expressing vasopressin (AVP) and in 92% of VIP neurons. The chemotype of M neurons was not identified. M but not E cells were responsive to long but not short photoperiods. The expression of the VPAC2 receptor was found in both M and E cells, and VPAC2-deficient mice displayed markedly blunted PER expression in both cell clusters of the SCN. Conclusion: These observations support the existence of M and E clocks involved in circadian and seasonal adaptation, which seem dependent on intact VIP/VPAC2 signaling in the SCN.
10.1111/ejn.14482
pubmed_1121_18721
Throughout 2020, the COVID-19 pandemic has had a major impact on the care of non-communicable diseases across the world and diabetes is no exception. Whereas many branches of medicine have adapted to telemedicine, this is difficult and challenging for the diabetic foot which often requires "hands on" treatment. This review covers the challenges that have faced clinicians across the world in the management of complex diabetic foot problems and also includes some illustrative case vignettes which show how it is possible to manage foot ulcers without the usual access to laboratory and radiological testing. There is no doubt that the COVID-19 experience when handling diabetic foot problems will likely transform our approach to the management of diabetic foot disease especially in the areas of digital health and smart technology.
10.3390/medicina57020097
pubmed_929_3734
INTRODUCTION MYH9-related disease (MYH9-RD) is a rare autosomal dominant disorder caused by mutations in MYH9, which is responsible for encoding nonmuscle myosin heavy chains IIA (NMMHCIIA). MYH9-RD is clinically characterized by congenital macrothrombocytopenia, granulocyte inclusions variably associated with the risk of developing progressive sensorineural deafness, cataracts and nephropathy. PATIENT CONCERNS A 5-year-old boy had a history of a mild bleeding tendency and chronic thrombocytopenia, first identified at four months of age. No other family members were noted to have similar clinical features or hematologic disorders. DIAGNOSES The boy was diagnosed with MYH9-RD. Light microscopic examination of peripheral blood films (Wright-Giemsa stain) showed marked platelet macrocytosis with giant platelets and basophilic Döhle-like inclusions in 83% of the neutrophils. Immunofluorescence analysis disclosed a type II pattern, manifested by neutrophils which contained several circle-to-oval shaped cytoplasmic NMMMHCA-positive granules. Sequencing analysis of MYH9-RD genes was carried out and revealed a novel missense mutation of c.97T>G (p.W33G) in the patient but not in his parents. INTERVENTION No treatment is necessary. Recognition of MYH9-RD is important to Avoiding unnecessary and potentially harmful treatments. OUTCOMES The patient's condition remained stable during the follow-up. CONCLUSIONS As a result of identifying this missense mutation in this particular case, we have added c.97T>G (p.W33G) to the broad spectrum of potential MYH9 mutations.
10.1097/MD.0000000000018887
pubmed_795_18347
PURPOSE The technique of double-echo chemical shift gradient echo magnetic resonance imaging (MRI) with the fast low-angle shot (double-echo FLASH) sequence provides in-phase and opposed-phase images in a single breath hold. The purpose of this study was to evaluate the efficacy of dynamic MRI with double-echo FLASH imaging for the detection of hypervascular hepatocellular carcinoma by comparing it with dynamic helical computed tomography (CT) imaging with double arterial phase. MATERIALS AND METHODS Twenty-nine patients with 67 hypervascular hepatocellular carcinoma nodules who underwent both dynamic MRI with double-echo FLASH imaging (repetition time/echo time/flip angle: 160/3.6, 7.0/80 degrees ) and dynamic helical CT imaging with double arterial phase were enrolled in the study. For dynamic MRI, precontrast, arterial, portal venous, and equilibrium phase images were obtained before and approximately 19, 60, and 120 seconds, respectively, after intravenous injection of 0.1 mmol/kg of gadopentetate dimeglumine at a rate of 2 ml/s. For dynamic CT imaging, quadraphase images, including early arterial, late arterial, portal venous, and equilibrium phases, were obtained serially approximately 20, 30, 70, and 180 seconds, respectively, after intravenous administration of 2 ml/kg of 300 mgI/ml of nonionic contrast medium at a rate of 5 ml/s. Three masked observers independently interpreted images obtained with each technique in random order, separately and without patient identifiers. Sensitivity and positive predictive values as well as the area below the alternative-free response receiver operating characteristic curve (Az) for each imaging technique were calculated and compared statistically. RESULTS Mean sensitivity and positive predictive values of MRI for hypervascular hepatocellular carcinoma were 48% and 94%, respectively, and those of CT imaging were 47% and 91%, respectively. In 11 (38%) of the 29 patients, at least one observer judged dynamic MRI to be superior, whereas in 5 patients (17%), dynamic CT was judged to be superior. There was no significant difference in the sensitivity and positive predictive values between these techniques (p > 0.05). There was no significant difference either in mean Az values between CT (0.55) and MRI (0.57) (p = 0.61). CONCLUSION Dynamic MRI with double-echo FLASH imaging can detect hypervascular hepatocellular carcinoma as well as dynamic helical CT imaging with double arterial phase.
10.1097/00004728-200211000-00022
pubmed_716_12153
This study predicts analytically effective elastic moduli of substructures within an equine hoof wall. The hoof wall is represented as a composite material with a hierarchical structure comprised of a sequence of length scales. A bottom-up approach is employed. Thus, the outputs from a lower spatial scale serve as the inputs for the following scale. The models include the Halpin-Tsai model, composite cylinders model, a sutured interface model, and classical laminate theory. The length scales span macroscale, mesoscale, sub-mesoscale, microscale, sub-microscale, and nanoscale. The macroscale represents the hoof wall, consisting of tubules within a matrix at the mesoscale. At the sub-mesoscale, a single hollow tubule is reinforced by a tubule wall made of lamellae; the surrounding intertubular material also has a lamellar structure. The lamellae contain sutured and layered cells at the microscale. A single cell is made of crystalline macrofibrils arranged in an amorphous matrix at the sub-microscale. A macrofibril contains aligned crystalline rod-like intermediate filaments at the nanoscale. Experimentally obtained parameters are used in the modeling as inputs for geometry and nanoscale properties. The predicted properties of the hoof wall material agree with experimental measurements at the mesoscale and macroscale. We observe that the hierarchical structure of the hoof wall leads to a decrease in the elastic modulus with increasing scale, from the nanoscale to the macroscale. Such behavior is an intrinsic characteristic of hierarchical biological materials. This study can serve as a framework for designing impact-resistant hoof-inspired materials and structures.
10.1016/j.jmbbm.2022.105529
pubmed_216_688
A buccal patch for systemic administration of carvedilol in the oral cavity has been developed using two different mucoadhesive polymers. The formulations were tested for in vitro drug permeation studies, buccal absorption test, in vitro release studies, moisture absorption studies and in vitro bioadhesion studies. The physicochemical interactions between carvedilol and polymers were investigated by Fourier transform infrared (FTIR) Spectroscopy. According to FTIR the drug did not show any evidence of an interaction with the polymers used and was present in an unchanged state. XRD studies reveal that the drug is in crystalline state in the polymer matrix. The results indicate that suitable bioadhesive buccal patches with desired permeability could be prepared. Bioavailability studies in healthy pigs reveal that carvedilol has got good buccal absorption. The bioavailability of carvedilol from buccal patches has increased 2.29 folds when compared to that of oral solution. The formulation AC5 (HPMC E 15) shows 84.85 + 0.089% release and 38.69 + 6.61% permeated through porcine buccal membrane in 4 hr. The basic pharmacokinetic parameters like the C(max), T(max) and AUC(total) were calculated and showed statistically significant difference (P<0.05) when given by buccal route compared to that of oral solution.
10.2174/156720107779314785
pubmed_794_18803
BACKGROUND Non-alcoholic fatty liver disease (NAFLD) is a common chronic disease that can cause liver deterioration if insufficiently diagnosed and untreated. The verification of whether exercise interventions improve liver enzymes and lipid and glucose parameters is scant. AIM We conducted this systematic review and meta-analysis to examine the efficacy of aerobic and resistance exercise interventions in patients with NAFLD. METHODS We searched the related studies in the PubMed, Embase, Cochrane Library, and Web of Science databases. We screened 1129 articles published before September 1, 2021, based on the inclusion and exclusion standards, after which 17 articles with a total of 1168 participants were finally included. The indices of liver enzymes and lipid and glucose metabolism were gathered and examined by Stata SE. RESULTS The outcomes suggested that aerobic and resistance exercise can markedly improve the parameters of liver enzymes, blood lipids, and glucose, and especially visceral adipose tissue (weighted mean different [WMD] = -8.3 at 95% CI [-11.59 to -5.00], p < 0.0001), in patients with NAFLD. CONCLUSION This study demonstrated that aerobic and resistance exercises positively affect NAFLD treatment. To further quantify the effects on patients with NAFLD, a more specific and uniform exercise program should be proposed.
10.1055/a-1742-4257
pubmed_60_9101
BACKGROUND Governments in several countries attempt to strengthen user participation through instructing health care organisations to plan and implement activities such as user representation in administrational boards, improved information to users, and more individual user participation in clinical work. The professionals are central in implementing initiatives to enhance user participation in organisations, but no controlled studies have been conducted on the effect on professionals from implementing institutional development plans. The objective was to investigate whether implementing a development plan intending to enhance user participation in a mental health hospital had any effect on the professionals' knowledge, practice, or attitudes towards user participation. METHODS This was a non-randomized controlled study including professionals from three mental health hospitals in Central Norway. A development plan intended to enhance user participation was implemented in one of the hospitals as a part of a larger re-organizational process. The plan included i.e. establishing a patient education centre and a user office, purchasing of user expertise, appointing contact professionals for next of kin, and improving of the centre's information and the professional culture. The professionals at the intervention hospital thus constituted the intervention group, while the professionals at two other hospitals participated as control group. All professionals were invited to answer the Consumer Participation Questionnaire (CPQ) and additional questions, focusing on knowledge, practice, and attitudes towards user participation, two times with a 16 months interval. RESULTS A total of 438 professionals participated (55% response rate). Comparing the changes in the intervention group with the changes in the control group revealed no statistically significant differences at a 0.05 level. The implementation of the development plan thus had no measurable effect on the professionals' knowledge, practice, or attitudes at the intervention hospital, compared to the control hospitals. CONCLUSION This is the first controlled study on the effect on professionals from implementing a development plan to enhance user participation in a mental health hospital. The plan had no effect on professionals' knowledge, practice, or attitudes. This can be due to the quality of the development plan, the implementation process, and/or the suitability of the outcome measures.
10.1186/1472-6963-11-296
pubmed_386_5822
BACKGROUND/AIMS Chemoresistance of breast cancer is a growing problem and still a major clinical obstacle to successful treatment in clinical patients. miR-760 was significantly downregulated in chemoresistance breast cancer tissues compared to chemo-sensitive tissues in our previous study. However, the role of miR-760 in modulating drug resistance remains largely unexplored. In this study, we sought to determine the expression pattern of miR-760 targeted mRNAs, and explore their potential functions and participated-pathways in breast cancer drug resistance cells. RESULTS Compared to parental cell line MCF-7, miR-760 was downregulated by 6.15 folds in MCF-7/Adr cells. The qRT-PCR result showed that compared to miR-760 negative control cells group, miR-760 was up-regulated 15.817 folds after miR-760 lentiviral transfection in miR-760 mimics group. The microarray data showed that 270 genes were dysregulated over 2-fold change in MCF-7/Adr cells after miR-760 overexpressed, including 241 up-regulated and 29 downregulated genes. GO analysis result appeared that the predicted target genes of miR-760 mainly regulated DNA binding, protein binding, molecular function, nucleic acid binding, and so on; the pathway analysis data demonstrated that these target genes mainly involved in cell cycle, TGF-beta signaling pathway, mRNA processing reactome, G protein signaling, apoptosis, Wnt signaling pathway, and other signaling pathways. There were 3 predicted target genes (RHOB, ANGOTL4, ABCA1) of miR-760 were selected at a P value<0.05 and the fold enrichment was>40. CONCLUSION Our study explored the genes expression pattern after miR-760 overexpresssed, and confirmed 3 dominantly dysregulated genes, which could expand the insights into the miR-760 function and molecular mechanisms in drug resistance of breast cancer. This study might afford a comprehensive understanding of miR-760 as prognostic biomarkers during clinical treatment, and we supposed that the miR-760 expression levels in drug resistance carcinoma tissues could be pursued to develop new strategies for targeted therapies in chemoresistant breast cancer patients.
pubmed_386_5822
pubmed_540_5485
BACKGROUND Focal segmental glomerulosclerosis (FSGS) is characterized by podocyte damage and severe proteinuria. The exact mechanism of podocyte damage and loss remains unclear. Necroptosis, a lytic form of programmed cell death mediated by RIP3 and MLKL, has emerged as an important cell death pattern in multiple tissues and cell types. Necroptosis in FSGS has not been investigated. METHODS Public GEO data regarding podocyte treated with vehicle or adriamycin (ADR) was identified and analyzed. Cultured human podocytes were used to explore the activation of necroptosis upon ADR stimulation. The expression of necroptosis pathway molecules, p-RIP3 and p-MLKL, was examined in the glomeruli and defoliated urinary podocytes of patients with FSGS. The effect of necroptosis inhibition was assessed in ADR-induced glomerulopathy mice using GSK872. RESULTS Publicly available RNA-sequencing data analysis showed that both necroptosis and NLRP3 inflammasome pathway were up-regulated in ADR-injured podocyte. Immunofluorescent staining showed increased expression of p-RIP3 and p-MLKL, the active forms of RIP3 and MLKL, in podocytes of FSGS patients and ADR-induced glomerulopathy mice but not in the normal control. GSK872, an RIP3 kinase inhibitor, significantly inhibited the expression of p-RIP3, p-MLKL and activation of NLRP3 in cultured podocytes treated with ADR. GSK872 treatment of mice with ADR-induced nephropathy resulted in the reduced expression of p-RIP3, p-MLKL, NLRP3 and caspase-1 p20. GSK872 also significantly inhibited the expression of p-MLKL in the podocytes of ADR-induced nephropathy, resulting in the attenuation of proteinuria and renal histological lesions. CONCLUSION Necroptosis pathway might be a valuable target for the treatment of FSGS.
10.1007/s10157-022-02258-1
pubmed_898_12586
Carotid artery stenosis accounts for up to 20% of ischemic strokes. Since the 1950 s, one of the primary surgical treatment for this condition is carotid endarterectomy (CEA). Because of improvement of medical therapy for carotid artery atherosclerosis and the increased use of carotid artery stents, CEA is indicated if the risk of stroke and death are low. The goal of this study is to characterize the impact of pre-operative stroke and stroke risk factors on post-operative CEA patient outcomes, using the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) Targeted Vascular Module on CEA. Using the Targeted Vascular Module of the ACS-NSQIP, 22,116 patients who underwent CEA were identified from 2011 to 2016. Univariate analysis and multivariable logistic regression analyses were conducted to identify significant risk factors that predispose patients to stroke. Patients with pre-operative stroke comprise 42.1% of the group, with post-operative stroke being the second most common complication (2.1%). Pre-operative stroke patients were also at a higher risk for transient ischemic attacks, post-operative restenosis, post-operative distal embolization, and other complications. Patients with pre-operative risk factors, including stroke or stroke-like symptoms, high risk physiologic factors, high risk anatomic factors, and contralateral internal carotid artery stenosis were at a higher risk of developing post-operative stroke and other complications. Patients with these pre-operative risk factors should be closely monitored for post-operative complications in an effort to improve patient outcomes.
10.1016/j.jocn.2020.01.077
pubmed_1032_16411
AIM To assess the efficacy and tolerance of certolizumab pegol (CP) in patients with Crohn's disease (CD) treated in the Department of inflammatory bowel diseases of the A.S. Loginov Moscow Clinical Research Center and to determine the predictors of response to therapy. MATERIALS AND METHODS All patients with CD who had received the treatment of CP were observed prospectively for at least 6 months or until the date of discontinuation of the drug. The effectiveness of the study was assessed response to therapy by the 6th week, maintaining the clinical response (6th and 26th weeks), the dynamics of endoscopic parameters by the 10th and 54th week of therapy, long-term maintenance of remission, healing fistula. Used univariant and multivariate analyses of predictors of response to treatment. RESULTS The study included 39 patients: 12 (30.7%) men and 27 (69.3%) female, the average duration of observation was 104 weeks. The interdepartmental range was in the range from 28 to 158 weeks. Clinical improvement occurred in 38 out of 39 (97.4 %) patients with CD. Comparative analysis of response to treatment with CP have bionaive patients previously treated with another inhibitor of TNF-α. In the group of bionaive response to therapy in a month, 6 months and at the end of the observation period occurred at 100.0%, 95.0% and 95.0%, respectively. In the group of patients previously treated with GSI, the response rate was about 94.4 %, 88.9 % and 77.7% week 54 endoscopic response and endoscopic remission was maintained in 46,2% and 30,1% patients, complete healing of the mucosa on the background of maintenance therapy, CP, was preserved in 20.5% of patients with Crohn's disease. In the group of patients with perianal lesions (n=13) complete closure of all fistulas was observed in 5 (38.6 %) patients, partial response was observed in 4 patients (30,7%) patients, in 4 (30.7 %) closure of fistulas occurred. The frequency of adverse events was 0 cases (0.0%). The dose escalation was required in 3 patients (7,7%) patients with CD. Dose escalation in our study required patients with high initial CDAI and previous inefficiencies of the other two inhibitors of TNF-α. Reliable predictors of secondary loss of response and need for dose escalation of the drug has been the continued level of CRP &gt;5 mg/l after 2 weeks initiation of therapy CP and smoking. CONCLUSION The obtained results demonstrate the efficacy and tolerability profile of CP appropriate for long-term CD therapy in real clinical practice.
10.26442/terarkh201890674-80
pubmed_920_9451
BACKGROUND Quality improvement and patient safety (QIPS) have been assigned a higher profile in CanMEDS 2015, CanMEDS-Family Medicine 2017 and new accreditation standards, prompting an initiative at Dalhousie University to create a vision for integrating QIPS into postgraduate medical education. OBJECTIVE The purpose of this study is to describe the implementation of a QIPS strategy across residency education at Dalhousie University. METHODS A QIPS task force was formed, and a literature review and needs assessment survey were completed. A needs assessment survey was distributed to all Dalhousie residency programme directors. 12 programme directors were interviewed individually to collect additional feedback. The results were used to develop a 'road map' of recommendations with a graduated timeline. RESULTS A task force report was released in February 2018. 46 recommendations were developed with a timeframe and responsible party identified for each. Implementation of the QIPS strategy is underway, and evaluation and challenges faced will be described. CONCLUSIONS We have developed a multiyear strategy that is available to provide guidance and support to all programmes in QIPS. The development and implementation of this QIPS framework may serve as a template for other institutions who seek to integrate these competencies into residency training.
10.1136/postgradmedj-2021-140261
pubmed_407_16992
RNA turnover plays an important role in both virulence and adaptation to stress in the Gram-positive human pathogen Staphylococcus aureus. However, the molecular players and mechanisms involved in these processes are poorly understood. Here, we explored the functions of S. aureus endoribonuclease III (RNase III), a member of the ubiquitous family of double-strand-specific endoribonucleases. To define genomic transcripts that are bound and processed by RNase III, we performed deep sequencing on cDNA libraries generated from RNAs that were co-immunoprecipitated with wild-type RNase III or two different cleavage-defective mutant variants in vivo. Several newly identified RNase III targets were validated by independent experimental methods. We identified various classes of structured RNAs as RNase III substrates and demonstrated that this enzyme is involved in the maturation of rRNAs and tRNAs, regulates the turnover of mRNAs and non-coding RNAs, and autoregulates its synthesis by cleaving within the coding region of its own mRNA. Moreover, we identified a positive effect of RNase III on protein synthesis based on novel mechanisms. RNase III-mediated cleavage in the 5' untranslated region (5'UTR) enhanced the stability and translation of cspA mRNA, which encodes the major cold-shock protein. Furthermore, RNase III cleaved overlapping 5'UTRs of divergently transcribed genes to generate leaderless mRNAs, which constitutes a novel way to co-regulate neighboring genes. In agreement with recent findings, low abundance antisense RNAs covering 44% of the annotated genes were captured by co-immunoprecipitation with RNase III mutant proteins. Thus, in addition to gene regulation, RNase III is associated with RNA quality control of pervasive transcription. Overall, this study illustrates the complexity of post-transcriptional regulation mediated by RNase III.
10.1371/journal.pgen.1002782
pubmed_665_17548
Mutualist symbiotic Wolbachia endobacteria are found in most filarial nematodes. Wolbachia are essential for embryogenesis and for larval development into adults, and thus represent a new target for anti-filarial drug development. Tetracycline antibiotics deplete Wolbachia in animal model filaria Litomosoides sigmodontis and Brugia pahangi, as well as in the human parasites Brugia malayi, Onchocerca volvulus and Wuchereria bancrofti. Very little is known about the molecular details of the symbiotic interaction between Wolbachia and filarial nematodes. Nematode genes that respond to anti-Wolbachia antibiotic treatment may play important roles in the symbiosis. Differential display PCR was used to detect several candidate genes that are up-regulated after 3, 6, 15, 30 and 36 days of tetracycline treatment. One of these genes, Ls-ppe-1, was similar to a family of phosphate permeases, and had putative orthologues in O. volvulus and B. malayi. Ls-ppe-1 steady-state mRNA levels were elevated by day 3-6 of treatment, and remained elevated through to 70 days post-treatment. In Caenorhabditis elegans, the knockdown of a homologous phosphate permease results in embryonic lethality, with the production of degenerating embryos, a phenotype also seen in filarial nematodes after depletion of Wolbachia with tetracycline. The potential role of Ls-ppe-1 in the nematode-bacterial symbiosis is discussed.
10.1016/j.ijmm.2005.12.019
pubmed_340_15840
The aim of this study was to improve the gene delivery efficacy of chitosan oligomer polyplexes by introducing a trisaccharide branch that targets cell-surface lectins. For this purpose, chitosan oligomers were substituted by a trisaccharide with the N-acetylglucosamine residue at the free end, and the ability of the trisaccharide-substituted chitosan oligomers (TCO) polyplexes to transfect various cell lines in vitro and lung tissue after in vivo administration to mice was investigated. Live-cell confocal microscopy showed improved cellular uptake in HEK 293 cells (11-fold, p<0.001) for the TCO polyplexes compared with the linear chitosan oligomers. Colloidal stability was also enhanced with the substituted form, which suggests that the trisaccharide branch stabilised the polyplexes by means of a steric stabilisation mechanism. Interestingly, gene expression levels in the human liver hepatocyte (HepG2) cells were 10-fold higher with the TCO polyplexes than those mediated by polyethyleneimine. A similar improvement was obtained in a human bronchial epithelial cell line (16HBE14o-). Transfection with the TCO was significantly inhibited (by 30-80%), for all the cell lines tested, in the presence of the free trisaccharide branch, confirming lectin-mediated uptake. Finally, in vivo studies showed that, 24 h after lung administration to mice, luciferase gene expression was 4-fold higher with the TCO than with the corresponding linear chitosan oligomers.
10.1016/j.jconrel.2006.06.029
pubmed_839_16167
BACKGROUND Approximately one-quarter of high school students currently use cigarettes. Previous research has suggested some youth use smoking as a method for losing weight. The purpose of this study was to describe the association of current cigarette use with specific healthy and unhealthy weight control practices among 9th-12th grade students in the United States. METHODS Youth Risk Behavior Survey data (2005) were analyzed. Behaviors included current cigarette use, trying to lose weight, and current use of 2 healthy and 3 unhealthy behaviors to lose weight or to keep from gaining weight. Separate logistic regression models calculated adjusted odds ratios (AORs) for associations of current cigarette use with trying to lose weight (Model 1) and the 5 weight control behaviors, controlling for trying to lose weight (Model 2). RESULTS In Model 1, compared with students who were not trying to lose weight, students who were trying to lose weight had higher odds of current cigarette use (AOR = 1.30, 95% CI: 1.15-1.49). In Model 2, the association of current cigarette use with the 2 healthy weight control behaviors was not statistically significant. Each of the 3 unhealthy weight control practices was significantly associated with current cigarette use, with AORs for each behavior approximately 2 times as high among those who engaged in the behavior, compared with those who did not. CONCLUSION Some students may smoke cigarettes as a method of weight control. Inclusion of smoking prevention messages into existing weight management interventions may be beneficial.
10.1111/j.1746-1561.2009.00421.x
pubmed_724_10285
OBJECTIVE We sought to describe the operative technique in ulnar nerve compression caused by the epitrochleoanconeus muscle and a prominent medial head of the triceps. These anatomic features make the approach to the ulnar nerve at the elbow peculiar and may create technical difficulties during surgical treatment of this area. METHODS We reviewed patients who underwent surgery for cubital tunnel syndrome between November 1997 and December 2004. The presence of the epitrochleoanconeus muscle with prominent medial head of the triceps occurred in 3.2% of patients. A detailed and illustrated description of the surgical anatomy and the peculiarities of the surgical approach are provided. RESULTS Epitrochleoanconeus muscle and the prominent portion of the medial head of the triceps were sectioned and removed, and simple decompression of the ulnar nerve was performed. This treatment achieved complete recovery in all of the patients affected by moderate-grade syndrome (Dellon Grade 2 syndrome) who had not shown severe-grade syndrome preoperatively. CONCLUSION The simple decompression of the ulnar nerve with myotomy or removal of epitrochleoanconeus muscle and the prominent portion of the medial head of the triceps achieved good postoperative results. Experiences from the literature and alternative surgical options are reported.
10.1227/01.neu.0000317392.29551.aa
pubmed_171_374
Maize samples collected from storage bins and feed mills in Northern Italy between 1995 and 1999 were surveyed for the occurrence of aflatoxin B1 (AFB1), zearalenone (ZEA), deoxynivalenol (DON) and fumonisin (FB1); further, ergosterol was analysed as a fungal growth marker. The incidence and mean content of AFB1 were generally low; nevertheless, a remarkable contamination was found in two samples (109 and 158 microg kg(-1)), while five others exceeded 20 microg kg(-1). DON and ZEA mean levels were significantly higher in 1996 (2716 and 453 microg kg(-1)) with respect to the other years, when mean contents ranged from 7 to 30% and from 3 to 17%, respectively, expressed in per cent of 1996 contents. FB1 was present in all samples and was by far the most remarkable mycotoxin in Northern Italian maize, with the exception of samples from 1996. The average level was 3064 microg kg(-1), 69.6% of samples resulted over 1000 microg kg(-1) and 16.9% over 5000 microg kg(-1). Significant correlations were found between ergosterol and the major mycotoxin(s) in each year (FB1 in 1995 and 1997-99; ZEA + DON in 1996). Consequently, ergosterol seems to be a good index of the toxicological quality of maize. Climatic conditions influenced the growth of different fungal species. In 1996, the first 20 days of October were extremely rainy; these weather conditions delayed the harvest until the first week of November and favoured the growth of DON and ZEA producing fungi and the synthesis of mycotoxins. On the contrary, the temperate and dry climate of the other years supported the growth of FB1-producing fungi.
10.1080/02652030410001662020
pubmed_995_9326
A 57-year-old woman presented with palpitations, muscle weakness, bilateral proptosis, goiter, and tremor. The thyroxine (T4) level and the free T4 index were increased while the total triiodothyronine (T3) level was normal. Iodine 123 uptake was increased, and a scan revealed an enlarged gland with homogeneous uptake. Repeated studies again revealed an increased T4 level and free T4 index and normal total and free T3 levels. A protirelin test showed a blunted thyrotropin response. Treatment with propylthiouracil was associated with disappearance of symptoms and normal T4 levels, but after 20 months of therapy, hyperthyroidism recurred and the patient was treated with iodine 131. This was an unusual case of T4 toxicosis because the patient was not elderly and was not exposed to iodine-containing compounds or drugs that impair T4-to-T3 conversion. There was no evidence of abnormal thyroid hormone transport or antibodies.
pubmed_995_9326
pubmed_125_23041
The recent outbreak of the SARS-CoV-2 virus leading to the disease COVID 19, a global pandemic has resulted in an unprecedented loss of life and economy worldwide. Hence, there is an urgent need to discover effective drugs to control this pandemic. NSP16 is a methyltransferase that methylates the ribose 2'-O position of the viral nucleotide. Taking advantage of the recently solved structure of NSP16 with its inhibitor, S-Adenosylmethionine, we have virtually screened FDA approved drugs, drug candidates and natural compounds. The compounds with the best docking scores were subjected to molecular dynamics simulations followed by binding free energy calculations using the MM-PBSA method. The known drugs which were identified as potential inhibitors of NSP16 from SARS-CoV-2 included DB02498, DB03909, DB03186, Galuteolin, ZINC000029416466, ZINC000026985532, and ZINC000085537017. DB02498 (Carba-nicotinamide-adenine-dinucleotide) is an approved drug which has been used since the late 1960s in intravenous form to significantly lessen withdrawal symptoms from a variety of drugs and alcohol addicts and it has the best MM-PBSA binding free energy of-12.83 ± 0.52 kcal/mol. The second best inhibitor, Galuteolin is a natural compound that inhibits tyrosinase enzyme with MM-PBSA binding free energy value of -11.21 ± 0.47 kcal/mol. Detailed ligand and protein interactions were analyzed and common residues across SARS-CoV, SARS-CoV-2, and MERS-CoV were identified. We propose Carba-nicotinamide-adenine-dinucleotide and Galuteolin as the potential inhibitors of NSP16. The results in this study can be used for the treatment of COVID-19 and can also form the basis of rational drug design against NSP16 of SARS-CoV-2.
10.1080/07391102.2020.1802349
pubmed_191_13351
This study analysed the lived experiences of work stress of 21 community palliative care clinical nurse specialists from four centres in urban Essex, UK. Data were collected using an open-ended questionnaire and semi-structured interviews. Three major themes emerged: pressure of workload; relationships with health professionals; and the impact of the sadness of the client group. The pressure of workload was associated with nine sub-themes including staff shortages, client's or professionals' misperceptions of role, changing role, and erosion of normal support systems at work or at home. Relationships with some general practitioners seemed to cause most difficulty and social services seemed to have different priorities and to respond slowly. The impact of the sadness of the client group was only seen in four distinct situations. An overwork stress spiral is described that provides a salutary warning for managers, but also offers interesting solutions.
10.12968/ijpn.2001.7.11.9293
pubmed_1104_16973
In the last decade, a significant amount of research has been devoted to the pathogenesis and treatment of hepatic encephalopathy (HE). Non-invasive neuroimaging techniques such as magnetic resonance imaging and spectroscopy have become important research tools. The search for a suitable animal model of HE associated with cirrhosis is still ongoing. Moreover, consensus terminology and diagnostic criteria for HE in humans are badly needed.
10.1097/00042737-200104000-00005
pubmed_505_20646
Water and sediment samples collected from 18 wetland ponds within and outside industrial areas were examined for cadmium concentration and water quality parameters during the period of January to July 1996. The Cd contents in gill, liver, mantle and shell of freshwater mussel (Lamellidens marginalis) as well as leaves and roots of water hyacinth Eichhornia those occurred in these ponds were also estimated. Cd concentration ranged from 0.006 to 0.7025 mg/l in water and from 7 to 77 microg/gdw in sediments of all the ponds investigated. The amount of Cd occurring in water and sediment was much higher in concentrations in the ponds located in Captain Bheri and Mudiali farm close to industrial areas, compared to remaining ponds located outside the industrial belt. Lamellidens marginalis procured from Mudiali and Captain Bheri ponds showed regardless of size, tissue and season of collection significantly higher Cd concentration than did those from other ponds. Likewise, tissue Cd in Eichhornia collected from Mudiali pond was as high as 125-152 microg/gdw in root and 21-63 microg/gdw in leaves compared to 40-108 microg/gdw in root and 9-43 microg/gdw in leaves in the remaining ponds. Seasonal variability of Cd was clear-cut; the concentration was relatively higher in water and sediment in all ponds during summer than during monsoon season or winter. Size-wise, smaller groups showed the highest concentrations of Cd in all tissues of Lamellidens compared with medium and large size groups. Concentration factor for all tissues of Lamellidens regardless of size and season, was inversely proportional with the ambient Cd concentrations. Concentration factor estimated for all tissues in all ponds and all seasons was in the order: liver>gill>shell>mantle. As all ponds located outside the industrial belt showed Cd concentrations ranging from 0.006 to 0.049 mg/l, it is suggested that these wetlands do not pose serious risk to the environment.
10.1016/j.chemosphere.2003.10.016
pubmed_581_19230
OBJECTIVES: Noise pollution in pediatric intensive care units (PICU) contributes to poor sleep and may increase risk of developing delirium. The Environmental Protection Agency (EPA) recommends <45 decibels (dB) in hospital environments. The objectives are to assess the degree of PICU noise pollution, to develop a delirium bundle targeted at reducing noise, and to assess the effect of the bundle on nocturnal noise pollution. METHODS: This is a QI initiative at an academic PICU. Thirty-five sound sensors were installed in patient bed spaces, hallways, and common areas. The pediatric delirium bundle was implemented in 8 pilot patients (40 patient ICU days) while 108 non-pilot patients received usual care over a 28-day period. RESULTS: A total of 20,609 hourly dB readings were collected. Hourly minimum, average, and maximum dB of all occupied bed spaces demonstrated medians [interquartile range] of 48.0 [39.0-53.0], 52.8 [48.1-56.2] and 67.0 [63.5-70.5] dB, respectively. Bed spaces were louder during the day (10AM to 4PM) than at night (11PM to 5AM) (53.5 [49.0-56.8] vs. 51.3 [46.0-55.3] dB, P < 0.01). Pilot patient rooms were significantly quieter than non-pilot patient rooms at night (n=210, 45.3 [39.7-55.9]) vs. n=1841, 51.2 [46.9-54.8] dB, P < 0.01). The pilot rooms compliant with the bundle had the lowest hourly nighttime average dB (44.1 [38.5-55.5]). CONCLUSIONS: Substantial noise pollution exists in our PICU, and utilizing the pediatric delirium bundle led to a significant noise reduction that can be perceived as half the loudness with hourly nighttime average dB meeting the EPA standards when compliant with the bundle.
10.1177/0885066617728030
pubmed_655_16836
The roles of GABA during development, as either a putative neurotransmitter or a nonsynaptic trophic factor, are being discussed intensely in recent literature. We offer an anatomical framework to better understand these possible roles in the developing cerebral cortex. During the early development of the cerebral cortex, GABA-containing cells constitute an outstanding cell population in the primordial plexiform layer, but they later distribute into at least four compartments. These include (1) Cajal-Retzius cells in layer I and (2) the subplate cells. Certain of these GABA-containing cell groups may disappear either by ceasing their expression of GABA, dilution in a growing brain volume, or cell death, possibilities that are reviewed here. The chemical tags that characterize Cajal-Retzius cells, both in the forming isocortex and Ammon's horn, are discussed. Another cell population that also belongs to the primordial plexiform layer is formed by (3) the tangentially migrating cells of the deep intermediate layer. These migrate away from the isocortical primordium to invade, and contribute cells to, the forming stratum oriens of the Ammon's horn. Since these cells cross cortical area boundaries, their tangential migration is relevant to the issue of cortical area specification during development. Finally, GABA-immunoreactive cells in the developing cortical plate are considered to be (4) the future GABAergic interneurons. A hypothetical mechanism is presented here to explain their acquisition of laminar positions, which is known to take place simultaneously, and with an identical "inside-out gradient," to the pyramidal cells generated contemporarily.
pubmed_655_16836
pubmed_695_3798
This study investigated the risk of insomnia and hypnotics use among emergency physicians. This cross-sectional study recruited physicians working in Taiwanese hospitals in 2015 and the general population as the participants. Data from 1,097 emergency physicians obtained from the National Health Insurance Research Database were grouped into the case group, whereas 14,112 nonemergency physicians and 4,388 people from the general population were categorized into the control groups. This study used logistic regression and conditional logistic regression to compare the risks of insomnia between emergency and nonemergency physicians and between emergency physicians and the general population, respectively. The prevalence of insomnia among emergency physicians, nonemergency physicians and general population was 5.56%, 4.08%, and 1.73%, respectively. Compared with nonemergency physicians and the general population, emergency physicians had a significantly higher risk of insomnia. The proportions of emergency physicians, nonemergency physicians, and general population using hypnotics were 19.96%, 18.24%, and 13.26%, respectively. Among emergency physicians who used hypnotics, 49.77%, 25.57%, and 24.66% used only benzodiazepines, only nonbenzodiazepines, and both benzodiazepines and nonbenzodiazepines, respectively. Nonpharmacological interventions to improve insomnia and reminder of safe use of hypnotics to emergency physicians can serve as references for hospitals in developing health-promoting activities.
10.2486/indhealth.2020-0217
pubmed_402_18770
Hospital and laboratory data were analysed in three hospitals to estimate rotavirus disease burden in 1994-96. Community acquired gastroenteritis was diagnosed in 757 children of whom 41% tested positive for rotavirus. A total of 196 children had rotavirus nosocomial infections (39% of all rotavirus community-acquired and nosocomial cases). Infants less than 24 months old and children less than 3 months old comprised 74% and 11.9% of admissions for rotavirus, respectively. Almost 94% of children with rotavirus infection had severe gastroenteritis (score > or =11). The annual rate of rotavirus associated hospitalization in Poland in 1996 was 3.1/1000 children under the age of 60 months and 5.2/1000 infants under 24 months of age. The mean hospital stay was 9.5 d (+/-9.8 d). We estimated that 8918 children under 60 months of age were hospitalized for rotavirus gastroenteritis in 1996; they accounted for 84899 inpatient days. We conclude that rotavirus is a leading aetiological agent of severe gastroenteritis in young children in Poland and that the burden of this infection is significant. Rotavirus vaccine could significantly decrease the hospitalization rate and the financial impact of rotavirus gastroenteritis in Poland.
10.1111/j.1651-2227.1999.tb14327.x
pubmed_1051_16291
A table-top near-edge X-ray absorption fine structure (NEXAFS) spectroscopy system consisting of a soft X-ray source and an integrated spectrometer with a significantly improved resolution is presented. The soft X-ray source is based on a long-term stable and nearly debris-free picosecond laser-induced plasma generated in a pulsed krypton gas jet target. Photon energies ranging from 250 to 1000 eV can be used for the absorption spectroscopy of thin samples. The newly designed spectrometer accomplishes a spectral resolution of E/ΔE = 1535 at 430 eV, being close to typical synchrotron setups. Moreover, a simultaneous multi-edge analysis is possible. The performance of the new system is demonstrated by investigating the fine structure of the K- and L-absorption edges of various elements (carbon, calcium, oxygen, iron, nickel, and copper) for different types of samples. An excellent agreement with synchrotron spectra is achieved.
10.1021/acs.analchem.1c04374
pubmed_849_1213
The aim of this study was the compare the donor patients who received intravenous (IV) morphine with patient-controlled analgesia (PCA) or epidural morphine during the early postoperative period who underwent liver transplantation. Forty patients were included in the study and randomly divided into 2 groups in a double-blinded manner. They were given IV morphine 5 mg (Group C), or epidural anesthesia adding morphine (2 mg; Group E) by epidural anesthesia technique starting 15 minutes before the estimated time of completion of surgery. All of the patients received PCA with IV morphine (Group C; PCA device was set to deliver 1 mg morphine with a lockout of 15 minutes and a 4-hour limit of 20 mg, and no continuous infusion) or epidural morphine (Group E; patient-controlled epidural analgesia [PCEA] device was set to deliver 0.5 mg morphine with a lockout of 30 minutes and a 4-hour limit of 10 mg, and no continuous infusion) and were followed up for 24 hours, and pain scores were evaluated by study nurses who were blinded to the study protocol. The visual analogue scale (VAS) scores at rest and at movement and morphine consumption at 12 and 24 hours after operation evaluation time points were significantly higher in Group E than those in Group C (P < .05). Furthermore, total morphine consumption in Group C was significantly higher than that in Group E (P < .05). Epidural morphine via PCEA was associated with decreased postoperative VAS scores and morphine consumption. These findings may be beneficial for managing postoperative analgesia protocols in liver transplant donor patients.
pubmed_849_1213
pubmed_245_2480
BACKGROUND Comprehensive geriatric assessment (CGA) in routine practice is not logistically feasible. Short geriatric screening tools are available for selecting patients for CGA. However none of them is validated in India. In this analysis we aim to compare the level of agreement between three commonly used short screening tools (Flemish version of TRST (fTRST), G8 and VES-13. METHODS Patients ≥65 years with a solid tumor malignancy undergoing cancer directed treatment were interviewed between March 2013 to July 2014. Geriatric screening with G8, fTRST and VES-13 tools was performed in these patients. G8 score ≤14, fTRST score ≥1 and VES-13 score ≥3 were taken as indicators for the presence of a high risk geriatric profile respectively. R version 3.1.2 was used for analysis. Cohen kappa agreement statistics was used to compare the agreement between the 3 tools. p value of 0.05 was taken as significant. RESULTS The kappa statistics value for agreement between G8 score and fTRST, between VES-13 and fTRST and between VES-13 and G8 were 0.12 (P = 0.04), 0.16 (P = 0.07) and 0.05 (P = 0.45) respectively. It was found that maximum agreement was observed for VES-13 and fTRST. The agreement value of VES-13 and fTRST observed was 59.44 %(39.63% for high risk profile and 19.81% for low risk profile). The agreement value of G-8 and fTRST was 39.62% (2.83% only for high risk profile and 36.79% for low risk profile). The lowest agreement was between G8 and VES-13, 35.84% (7.54% for high risk detection and 28.30% for low risk detection). CONCLUSION There was poor agreement (in view of kappa value been below 0.2) between the 3 short geriatric screening tools. Research needs to be directed to compare the agreement level between these 3 scales and CGA, so that the appropriate short screening tool can be selected for routine use.
10.4103/0973-1482.179062
pubmed_353_17875
Power, a concept at the heart of the health policy process, is surprisingly rarely explicitly considered in the health policy implementation literature for low and middle income countries. In an attempt to support empirical research on power, this paper outlines some of the key insights on power from implementation theory. It then describes examples of power that might be seen in health policy implementation settings, such as hospitals, clinics and the local bureaucracies in which these are embedded, and concludes with suggestions for ways of investigating power and ensuring sound judgments are made about its existence and its influence over policy implementation.
10.1093/heapol/czn021
pubmed_713_16445
BACKGROUND AND PURPOSE The purpose of this study was to evaluate the psychometric properties of the Brief Symptom Inventory (BSI) hostility and anxiety subscales in prison inmates. METHODS Reliability and construct validity of the BSI hostility and anxiety subscales were examined using Cronbach's alphas, factor analysis, and hypothesis testing. RESULTS Of the 373 male inmates, 63% were White with a mean age of 36 years. Cronbach's alphas for hostility and anxiety were 0.83 and 0.81, supporting internal consistency. Factor analysis demonstrated two dimensions, hostility and anxiety. Supporting construct validity, inmates with higher hostility as well as those with higher anxiety had a greater number of mentally unhealthy days and lower perceived control. CONCLUSION The BSI hostility and anxiety subscales are reliable and valid for use in prison inmates.
10.1891/JNM-D-19-00094
pubmed_10_1901
Variations in mitochondrial DNA (mtDNA) cytochrome b (mt-cyb) are frequently found within the healthy population, but also occur within a spectrum of mitochondrial and common diseases. mt-cyb encodes the core subunit (MT-CYB) of complex III, a central component of the oxidative phosphorylation system that drives cellular energy production and homeostasis. Despite significant efforts, most mt-cyb variations identified are not matched with corresponding biochemical data, so their functional and pathogenic consequences in humans remain elusive. While human mtDNA is recalcitrant to genetic manipulation, it is possible to introduce human-associated point mutations into yeast mtDNA. Using this system, we reveal direct links between human mt-cyb variations in key catalytic domains of MT-CYB and significant changes to complex III activity or drug sensitivity. Strikingly, m.15257G>A (p.Asp171Asn) increased the sensitivity of yeast to the antimalarial drug atovaquone, and m.14798T>C (p.Phe18Leu) enhanced the sensitivity of yeast to the antidepressant drug clomipramine. We demonstrate that while a small number of mt-cyb variations had no functional effect, others have the capacity to alter complex III properties, suggesting they could play a wider role in human health and disease than previously thought. This compendium of new mt-cyb-biochemical relationships in yeast provides a resource for future investigations in humans.
10.1002/humu.23024
pubmed_147_17468
Wnt/β-catenin signaling (WNT) has widespread roles during stem cell differentiation. Whether WNT suppresses or promotes insulin-producing cell (IPC) differentiation and function is still not known. In this study, we investigated the role of WNT signaling during human adipose-derived stem cell (hADSC) differentiation into IPCs. Western blot analysis revealed that several key components of WNT were dynamically regulated in a 12-day IPC differentiation assay. Specifically, protein levels of Wnt1, β-catenin, and GSK3β steadily increased from day 0 to day 9 and rapidly decreased by day 12 of differentiation. Similarly, endonuclear β-catenin levels peaked at day 9 and then, fell to pre-differentiation levels. The expression of two WNT pathway targets, TCF-1 and cyclin D1, closely followed the same pattern of regulation, confirming that WNT signaling was transiently activated during IPC differentiation. Interestingly, the inhibition of WNT signaling did not block IPC differentiation; instead, it resulted in the upregulation of IPC-specific markers, including PDX-1, insulin, IRS-1, and IRS-2. Notably, another IPC marker, glucokinase, remained downregulated since it is a direct target of WNT signaling. Next, we examined the effect of maintaining active WNT signaling from day 9 to day 12 of IPC differentiation. Differentiating cells were treated with Wnt1 on day 9, when WNT signaling is typically turned off, and subjected to gene expression analysis on day 12. Remarkably, Wnt1 treatment resulted in reduced expression of IPC-specific markers. Taken together, these data indicate that WNT may not be necessary for IPC differentiation but may be involved in IPC maturation.
pubmed_147_17468
pubmed_653_5454
Synthetic oligodeoxyribonucleotides (ODN) may prove useful immune modulators in equine medicine. It is however important to assess the effects of each specific ODN in the species it is intended to be used in. The present study therefore aimed to evaluate some ODN for induction of cytokine production; i.e. type I interferons (IFN), IFN-γ, tumor necrosis factor-α (TNF-α) and transforming growth factor-β (TGF-β), and proliferation of equine peripheral blood mononuclear cells (PBMC). A panel of four ODN containing unmethylated cytosine-guanosine sequences (CpG) was used: ODN 1 and ODN 8 representing A-class; ODN 2006 representing B-class and ODN 2395 representing C-class-ODN. In addition, two ODN where CpG-motifs were reversed to GpC were included; ODN 2137 otherwise identical to ODN 2006 and ODN 5328 otherwise identical to ODN 2395. Cytokine concentrations were measured in cell culture supernatants after 24h of induction and proliferation was determined after 72 h of induction. Each ODN was tested with PBMC from at least 5 individual horses with and without the addition of lipofectin to cell cultures. Type I IFN, IFN-γ and TNF-α production was readily induced by ODN 1, ODN 2006 and ODN 2395 both in the presence and absence of lipofectin and all three types of ODN induced similar levels of cytokines. Proliferation of PBMC was clearly induced by ODN 2006 and ODN 2395 while ODN 1 only induced low-level proliferation. The levels of proliferation induced were not influenced by the presence of lipofectin. TGF-β production was not induced by any of the tested ODN. ODN 8, ODN 2137 and ODN 5328 were largely inactive in all assays. Thus, responses seemed dependent on or increased by CpG-motifs but presence of CpG-motifs did not necessarily confer activity since ODN 8 was inactive despite its CpG-motifs. Taken together, with equine PBMC distinctions in induction of different leukocyte functions between A-, B-, and C-class ODN were less obvious than what has been observed for human cells. These observations further stress the presence of species differences in ODN-induced responses.
10.1016/j.vetimm.2012.02.004
pubmed_1082_3375
Recurrent chromosome translocations involving 11p13 and 14q11 are found in 5-10% of cases of T-ALL. The gene involved in the translocation on chromosome 14 is the T cell antigen receptor alpha or delta. The putative oncogene on chromosome 11 is rhombotin 2 (RBTN2)/translocated in T cell gene 2 (ttg-2), a member of the LIM family of proteins. In this paper we characterize a cell line KOPT-K1 that has a t(11;14)(p13;q11). The breakpoint on chromosome 11 involves an Alu-rich region with the break occurring between two Alu sequences on chromosome 11. In addition, approximately 70 bases from the break on chromosome 11 is a tetranucleotide repeat. Whether either of these structures played a role in the translocation is not known. No heptamer or nonamer sequences, implicated in other rearrangements were found near the breakpoint. The breakpoint on chromosome 11 maps more centromeric than previous translocations of this region. Despite this the RBTN2 gene is highly expressed in KOPT-K1. This cell line will be useful for investigating the role of RBTN2 in leukemogenesis and the mechanism by which the translocation alters the expression of RBTN2.
pubmed_1082_3375
pubmed_244_21546
To find out the role of hsa-miR-570-3p targeting CD274 in triple negative breast cancer (TNBC) via PI3K/AKT/mTOR signaling pathway. Hsa-miR-570-3p and CD274 expressions in 175 TNBC patients were detected by qRT-PCR and immunohistochemistry respectively. The human TNBC cell lines (MDA-MB-468 and MDA-MB-231) were used to verify the targeting relationship between hsa-miR-570-3p and CD274 via dual-luciferase reporter gene assay. Then, MDA-MB-468 and MDA-MB-231 cells were divided into Blank, miR-NC, miR-570-3p mimics, NC siRNA, CD274 siRNA, and miR-570-3p inhibitors + CD274 siRNA groups. Next, the biological activities of cells were detected by MTT, Cell-Light EdU, Annexin-V-FITC/PI, wound healing and Transwell invasion assays. Western blotting was conducted to detect protein expressions.MiR-570-3p expression was lower in tumor tissues than that in adjacent normal tissues, which was more obvious in CD274-positive TNBC patients, which targeted CD274 in TNBC cell lines. MiR-570-3p inhibited cell proliferation, invasion and migration, but induced cell apoptosis accompanying the upregulation of apoptotic proteins and downregulation of anti-apoptotic protein. CD274 siRNA had the similar results of miR-570-3p mimics, which could be reversed by miR-570-3p inhibitors. Besides, both miR-570-3p mimics and CD274 siRNA blocked PI3K/AKT/mTOR signaling pathway in TNBC cell lines. Hsa-miR-570-3p was downregulated and CD274 was upregulated in TNBC patients. Besides, hsa-miR-570-3p targeted CD274 to inhibit cell proliferation, invasion, migration, and induce cell apoptosis, which may be related to the suppression of PI3K/AKT/mTOR pathway.
10.1002/kjm2.12212
pubmed_509_8074
Asthma affects approximately 23 million American children and adults, resulting in almost 15 million physician office and hospital visits, and nearly 2 million emergency department visits each year. Despite the publication of National Asthma Education and Prevention Program guidelines, asthma remains poorly controlled, with annual costs estimated at up to $56 billion. Current guidelines recommend long-term treatment with inhaled corticosteroids (ICS) because of their superior effectiveness in managing the chronic airway inflammation that characterizes persistent asthma. ICS monotherapy should be explored before alternatives such as leukotriene modifiers and long-acting beta agonists (LABAs) are attempted, especially after the US Food and Drug Administration's 2010 warning that LABAs should never be used alone to treat asthma due to the increased risk of severe exacerbations leading to hospitalization in both children and adults, with a possibility of death. In the past, asthma treatment focused solely on the central airways, rather than the small, more distant airways, and most traditional ICS therapies are aerosols which deliver large particles to the central airways. Today, the importance of the role of small airway disease in asthma, particularly inflammation, is known. Targeting the small airways may help improve clinical outcomes and reduce healthcare utilization and costs. The ICS beclomethasone dipropionate HFA does not require a spacer and is characterized by small particle sizes that result in more of the drug being deposited in both the large and small airways. Studies have demonstrated that beclomethasone dipropionate HFA is clinically effective and cost efficient compared with other asthma monotherapies or combination therapies.
pubmed_509_8074
pubmed_625_15057
The present study was to analyze the water dynamics of Tricholoma matsutake Singer during hot air drying by low-field nuclear magnetic resonance (LF-NMR) and magnetic resonance imaging (MRI), and to investigate the volatile compounds in the pileus, upper stipe and lower stipe of fresh and dried Tricholoma matsutake Singer by headspace-gas chromatography-ion mobility spectrometry (HS-GC-IMS) and headspace solid-phase microextraction-gas chromatography-mass spectrometry (HS-SPME-GC-MS). Fresh samples were dried at 60 °C for 12 h. With the T2i relaxation times decreasing, the water migrated from the inner toward the periphery and then expelled during drying. The characteristic volatiles fingerprints of different parts of fresh and dried samples were established by HS-GC-IMS. The significant differences in volatile compounds were observed among different parts of the fresh sample and C8 compounds (70%-97%) were the principal components. After drying, the concentration of C8 compounds dramatically decreased and some volatile compounds (hexanal, heptanal, 2(5H)-furanone, acetophenone, nonanal, benzeneacetaldehyde) were formed. Thus, hot air treatment affected the volatile compounds in Tricholoma matsutake Singer.
10.1016/j.jchromb.2018.09.011
pubmed_801_20054
The critical role of thyroid hormone (TH) in brain development is well-established. Evidence shows that severe deficiencies lead to significant neurological dysfunction. Much less information is available on more modest perturbations of TH on brain function. The present study induced varying degrees of developmental hypothyroidism by administration of low doses of the TH synthesis inhibitor, propylthiouracil (PTU 0, 1, 2, and 3 ppm) to the drinking water of pregnant rats. This regimen produced dose-dependent reductions in circulating levels of T4 in dams and offspring on postnatal days (PN) 15 and 22, with return to control levels in adulthood upon termination of treatment at weaning. Modest reductions in T3 were observed in the high-dose group on PN15. Synaptic function in the dentate gyrus was examined in adult euthyroid offspring using in vivo field potentials. Excitatory synaptic transmission (excitatory postsynaptic potential [EPSP] slope amplitude) was significantly reduced at 2 and 3 ppm PTU, with no statistically reliable effect detected in the population spike. Paired-pulse functions estimating the integrity of inhibitory synaptic processing were modestly reduced by 3 ppm PTU. Long-term potentiation (LTP) of the EPSP slope was impaired at all dose levels. Trace fear conditioning to context and to cue was impaired at the highest dose level when a distractor stimulus was present, whereas conditioning in a standard trace fear paradigm paradoxically revealed "enhanced" performance at the intermediate dose and a return to control values in the high-dose group. Biphasic dose-response profiles were evident in some measures (trace fear conditioning and LTP) but not others and serve to exemplify the complexity of the role of TH in brain development and its consequences for brain function.
10.1093/toxsci/kfr244
pubmed_846_11340
A survey of 2,858 persons in three institutions indicates an overall prevalence of 14.1% for SIB. Topography of SIB, number of forms in each subject, and intensity and frequency are related to the circumstances surrounding SIB, personnel reactions, age, sex, diagnosis and degree of retardation. Analyses of these relationships provide an SIB profile for the aggressive/severely-profoundly retarded. Direct observation of SIB in the wards indicates a low rate of antecedent and subsequent events. These findings are interpreted in relation to alternative explanatory hypotheses of SIB.
pubmed_846_11340
pubmed_347_11882
OBJECTIVE Despite the frequency with which ventriculoperitoneal shunts are placed, ventricular catheter revision rates remains as high as 30%-40% at 1 year. Many neurosurgeons place ventricular catheters "blindly" depending on anatomical landmarks and personal experience. To determine whether intraoperative ultrasonography is beneficial for ventricular catheter placement, we performed a historical cohort study comparing shunts placed with intraoperative ultrasound (US) guidance to those placed blindly. METHODS We reviewed all shunts placed by the Department of Neurosurgery at the University of Virginia from January 2005 to January 2007. During that time 211 patients underwent 242 shunts, with US use determined by surgeon's preference. Ninety-two shunts were placed by the use of US guidance, and 150 were placed without US. Adults received 176 shunts, 56 with US. Children received 66 shunts, 36 with US. Mean follow-up was 21.6 months. The primary end points examined were shunt revision, ventricular catheter revision (VCR), and acute VCR (revision within 1 week for an improperly-placed catheter). RESULTS The use of US was associated with a statistically significant decrease in shunt revisions (odds ratio 0.492; 95% confidence interval 0.253-0.958). Of the shunts placed with US guidance, 21.7% required revision, compared with 29.3% without US. VCRs and acute VCRs occurred in 9.8% and 2.2%, respectively, for US shunts, compared with 14% and 5.3% without US. Pediatric revision rates were 30.6% with US versus 53.3% without, whereas adult rates were 16.1% and 23.3%, respectively. The benefit of US was more profound for occipital shunts. CONCLUSIONS The use of US for the placement of permanent cerebrospinal fluid shunt catheters is associated with a decreased risk of shunt revision.
pubmed_347_11882
pubmed_819_15167
Thirty children (mean age 6:11, range 4:3 to 11:0, SD = 2:3) with profound hearing impairments were followed longitudinally over a 3-year period and evaluated every 6 months with a battery of speech perception tests. The battery spanned several levels of perception, from pattern perception to open-set word recognition. The children were all enrolled in a single full-day educational program that used multichannel tactile aids in addition to hearing aids. Testing was conducted in Auditory alone (A), Tactile plus Auditory (TA), Tactile alone (T), and in one instance, Tactile plus Auditory plus Vision (TAV) conditions because the primary interest of the work was the relationship between auditory and tactile training on perception. Results indicated that children's performance improved with age, with the oldest children achieving open-set speech recognition in the TA condition. Performance in the TA condition generally exceeded that in both A and T conditions. Outcomes were compared to those from two studies in the literature for children of similar age with cochlear implants and tactile aids on the same tests. Results suggest that performance of children who had cochlear implants for an average of 21 months was similar to TA and TAV performance of children in the present study who had tactile experience over a similar period.
10.1044/jshr.3903.518
pubmed_787_15102
OBJECTIVE The aetiology of kidney stones is multifactorial, with environmental and genetic factors contributing to the pathogenesis. The aim of this study was to assess the role of genetic factors in kidney stone disease by examining the heritability of the trait in Icelandic patients. MATERIAL AND METHODS Medical records at all major hospitals and imaging centres in Iceland were searched for diagnostic codes indicative of kidney stones, yielding a cohort of 5954 incident patients with kidney stone disease. The list of patients was cross-matched with a genealogy database that covers the entire Icelandic nation. The risk ratio (RR) and kinship coefficient (KC) were calculated to determine the risk of kidney stones in relatives of stone formers and the relatedness among kidney stone patients. RESULTS The risk of kidney stones among family members of stone formers was significantly higher than in the general population. In 2959 patients with radiopaque stones, the RR ranged from 2.25 (p<0.001) for first degree relatives of probands (such as parents or siblings) to 1.07 (p<0.01) in fifth degree relatives. Moreover, for confirmed recurrent stone formers the RR of kidney stones in parents and offspring was in excess of 10 (p<0.001). The KC analysis shows that Icelandic patients with kidney stone disease are significantly more related to each other than is the average Icelander, even when considering only relatives separated by four meioses or more (p<0.05). CONCLUSIONS The results suggest that genetic factors may substantially influence the risk of kidney stone disease in Iceland.
10.3109/00365590903151479
pubmed_319_22828
PURPOSE To evaluate the use of perfluoropropane gas (C3F8) versus silicone oil (SO) for retinal detachment secondary to macular hole in patients with high myopia and posterior staphyloma. METHODS In a retrospective study, 30 eyes of 30 patients underwent pars plana vitrectomy, and C3F8 (17 patients) or SO (13 patients) tamponade; internal limiting membrane peeling was performed successfully at the first surgery in 23 patients. High-density silicone oil tamponade was used for reoperations. RESULTS The mean values of patients' characteristics were as follows: age, 57.7 years; axial length, 29.02 mm; spherical equivalent refraction, -15.40 diopters; initial best-corrected visual acuity, 2.35 logarithm of the minimum angle of resolution; final best-corrected visual acuity, 1.59 logarithm of the minimum angle of resolution. In C3F8 group, best-corrected visual acuity significantly improved (P < 0.001), passing from 2.34 to 1.36 logarithm of the minimum angle of resolution. Vision improvement from blindness to low vision was significantly greater (P = 0.009) in C3F8 group (16 of 17; 94%) than in SO group (6 of 13; 46%). A significant higher initial success (P = 0.025) was found in the C3F8 group (16 of 17; 94%) than in the SO group (7 of 13; 54%). Proliferative vitreoretinopathy was the cause of initial failure; all these subjects achieved anatomical success after being reoperated with high-density silicone oil tamponade. CONCLUSION C3F8 and internal limiting membrane peeling could represent the most effective strategy in highly myopic patients with macular hole retinal detachment. Other tamponade agents must be investigated.
10.1097/IAE.0b013e3182670fd7
pubmed_434_22240
The great diversity in the architecture of hardware devices allied to many communication protocols, has been hindering the implementation of systems that need to access these devices. Given these differences, it appears the need of providing the access of these devices in a transparent way. In this sense, the present work proposes a middleware, mult input and output for access the devices, as a way of abstracting the writing and reading data mechanisms in hardware devices, contributing this way, for increasing systems productivity, as the developers are just focused in their functional requirements.
10.1109/IEMBS.2010.5627674
pubmed_60_7713
Magnesium (Mg) alloys have been demonstrated to be potential orthopedic implants due to their biodegradability in vivo. To enhance its corrosion resistance and improve its osteogenesis, β-tricalcium phosphate (β-TCP) was coated on a Mg alloy (Mg-3AI-1Zn) by phosphating process. In vitro, the human osteosarcoma cell line (SaOS-2) showed significantly good adherence and proliferation on the surface of the β-TCP coated Mg alloy after 24-h incubation. The growth factor bone morphogenetic protein 2 (BMP-2) was highly expressed in SaOS-2 cultured with the β-TCP coated Mg alloy by Western blot analysis (p < 0.05). In vivo, the newborn bone at the implant/bone interface was formed at week 1 and matured at week 4 postimplantation. Villous tissue was found at the implant/bone interface at week 12 postimplantation. The contents of phosphorus and calcium on the surface of the β-TCP coated Mg alloy were decreased at week 4 and week 12 postimplantation, respectively. Immunohistochemical analysis of the experiment results demonstrated that the β-TCP coated Mg alloy implants provided a high BMP-2 expression during the first 4 weeks postimplantation. Compared with the naked Mg alloy which was degraded for 33% in vivo, only 17% of the β-TCP coated Mg alloy was degraded at week 12 postimplantation (p < 0.05). The in vitro cell tests showed that the β-TCP coating provided the Mg alloy with a significantly better surface cytocompatibility, and in vivo results also confirmed that the β-TCP coating exhibited greatly improved osteoconductivity and osteogenesis in the early 12 weeks postoperation period. Moreover, in vivo experiment demonstrated that the β-TCP coating layer could slow down the degradation of the naked Mg alloy at the early stage of implantation.
10.1002/jbm.a.33267
pubmed_311_9379
Attention maps have been fused in the VggNet structure (EAC-Net) [1] and have shown significant improvement compared to that of the VggNet structure. However, in [1], E-Net was designed based on the facial action unit (AU) center and for facial AU detection only. Thus, for the use of attention maps in every image type, this paper proposed a new convolutional neural network (CNN) structure, P_VggNet, comprising the following parts: P_Net and VggNet with 16 layers (VggNet-16). The generation approach of P_Net was designed, and the P_VggNet structure was proposed. To prove the efficiency of P_VggNet, we designed two experiments, which indicated that P_VggNet could more efficiently extract image features than VggNet-16.
10.1371/journal.pone.0208497
pubmed_110_10605
We evaluated whether or not increased sodium (Na) concentrations of cerebrospinal fluid (CSF) and stimulated activities of brain renin-angiotensin system (RAS) contribute to an enhanced hypertension by salt overload in spontaneously hypertensive rats (SHR). Long-term salt loading (1% NaCl solution as drinking fluid) accelerated the development of hypertension in SHR, but did not alter the blood pressure (BP) in normotensive Wistar-Kyoto rats (WKY). CSF Na concentration was elevated in uninephrectomized (Nx) group as compared to that in control SHR, while in WKY CSF Na was not influenced by the treatment. A fall in BP by intravenous AVP antagonist or hexamethonium was greater in salt-loaded SHR than in controls. This hypotensive response to the combined blockade of AVP and SNS correlated with CSF Na in SHR but not in WKY. Plasma concentration of AVP and epinephrine tended to increase in relation to the degree of salt loading in SHR but not in WKY. Pressor responses to intracerebroventricular (ICV) angiotensin II (AII) and NaCl were greater in SHR than in WKY, although these responses were not influenced by chronic salt load in either SHR or WKY. The enhanced hypertensive action of ICV NaCl in SHR was abolished by pretreatment with ICV AII antagonist. Chronic saline drinking enhanced the depressor effect of ICV captopril in SHR but not in WKY. These observations suggest that salt overload in SHR may cause an elevated CSF Na concentration and an enhanced activity of brain RAS, which may increase activity of SNS and release of AVP, resulting in an enhanced development of hypertension.
10.1253/jcj.52.1317
pubmed_312_18249
A population of gastric membrane vesicles of high K+ permeability and of lower density than endoplasmic tubulovesicles containing (H+-K+)-ATPase was detected in gastric mucosal microsomes from the rat fasted overnight. The K+-transport activity as measured with 86RbCl uptake had a Km for Rb+ of 0.58 +/- 0.11 mM and a Vmax of 13.7 +/- 1.9 nmol/min X mg of protein. The 86Rb uptake was reduced by 40% upon substituting Cl- with SO2-4 and inhibited noncompetitively by ATP and vanadate with a Ki of 3 and 30 microM, respectively; vanadate also inhibited rat gastric (H+-K+)-ATPase but with a Ki of 0.03 microM. Carbachol or histamine stimulation decreased the population of the K+-permeable light membrane vesicles, at the same time increased K+-transport activity in the heavy, presumably apical membranes of gastric parietal cells, and enabled the heavy microsomes to accumulate H+ ions in the presence of ATP and KCl without valinomycin. The secretagogue-induced shift of K+ permeability was blocked by cimetidine, a H2-receptor antagonist. Four characteristics of the K+ permeability as measured with 86RbCl were common in the resting light and the carbachol-stimulated heavy microsomes; (a) Km for +Rb, (b) anion sensitivity (Cl- greater than SO2-4), (c) potency of various divalent cations (Hg2+, Cu2+, Cd2+, and Zn2+) to inhibit Rb+ uptake, and (d) inhibitory effect of ATP, although the nucleotide sensitivity was latent in the stimulated heavy microsomes. The Vmax for 86RbCl uptake was about 10 times greater in the resting light than the stimulated heavy microsomes. These observations led us to propose that secretagogue stimulation induces the insertion of not only the tubulovesicles containing (H+-K+)-ATPase, but also the light membrane vesicles containing KCl transporter into the heavy apical membranes of gastric parietal cells.
pubmed_312_18249
pubmed_959_12760
There is increasing evidence that subjective caregiver burden is an important determinant of clinically significant anxiety in family carers. This meta-analysis aims to synthesise this evidence and investigate the relationship between subjective caregiver burden and anxiety symptoms in informal caregivers. We searched PubMed, CINAHL and PsycINFO up to January 2020. Combined estimates were obtained using a random-effects model. After screening of 4,312 articles, 74 studies (with 75 independent samples) were included. There was a large, positive association between subjective caregiver burden and anxiety symptoms (r = 0.51; 95% CI = 0.47, 0.54; I2 = 0.0%). No differences were found in subgroup analyses by type of study design (cross-sectional vs. longitudinal), sampling, control of confounders or care-recipient characteristics. Subjective caregiver burden is an important risk factor for anxiety in informal caregivers. Targeting subjective caregiver burden could be beneficial in preventing clinically significant anxiety for the increasing number of family carers worldwide.
10.1371/journal.pone.0247143
pubmed_667_2774
Encouraged by an experience with endoscopic transsphenoidal pituitary surgery, an endoscopic transsphenoidal technique was applied in a patient with a large chordoma in the posterior fossa. The patient was a 40-year-old man with a two-year history of progressive ataxia, a memory disorder and emotional instability. A magnetic resonance (MR) scan of the brain revealed a midline posterior fossa mass measuring 4 cm in diameter located between the clivus and the brainstem. The basilar artery and its bifurcation were encased by the tumor and the brainstem was also distorted by the tumor. Obstructive hydrocephalus was treated previously with a ventriculoperitoneal shunt and fractionated external beam radiation treatment was given without histological diagnosis at another hospital. Subtotal resection of the tumor was achieved utilizing an endoscopic transphenoidal technique through the patient's nostril. The portion of the tumor located behind the basilar artery was not resected in order to protect the brainstem perforating arteries. The patient showed dramatic improvement of his symptoms postoperatively. Residual tumor located behind the basilar artery was treated by stereotactic gamma-knife surgery. This is the first reported case of a large posterior fossa chordoma being treated by an endoscopic transsphenoidal technique.
pubmed_667_2774
pubmed_216_5370
OBJECTIVES Evaluate the effectiveness of CaHA injection for patients with glottal incompetence. METHODS Multi-center, open-label, prospective clinical study with each patient serving as his/her own control. Voice-related outcome measures were collected for pre-injection and 1, 3, and 6 months. RESULTS Sixty-eight patients were available for evaluation. Fifty percent of the injection procedures were done in office. Fifty-seven percent were diagnosed with unilateral paralysis and 42% with glottal incompetence with mobile vocal folds. Patient satisfaction 6 months post showed 56% had significantly improved voice and 38% reported moderately improved voice. Paired t tests from baseline to 6 months showed significant improvements on the VHI and VAS (vocal effort), CAPE-V judgments of voice severity and videoendostroboscopy ratings of glottal closure, and objective voice measures of glottal closure (MPT and S:Z ratio). CONCLUSIONS Preliminary results in this large cohort of patients demonstrate excellent clinical results.
10.1016/j.otohns.2006.07.014
pubmed_997_5947
The EFSA Panel on Plant Health performed a pest categorisation of Penthimiola bella (Hemiptera: Cicadellidae), the citrus leafhopper, for the European Union (EU). P. bella is native to the Afrotropical region; it has spread to Israel (first reported in 1974), Lebanon, and was reported from Morocco in 2018. Within the EU, P. bella is established in Portugal (Algarve) where it was first found on sweet oranges in 2012, and then in Spain in 2020, also on sweet oranges. P. bella is not listed in Annex II of Commission Implementing Regulation (EU) 2019/2072. It is a polyphagous species reported, among cultivated hosts, on sweet orange, grapefruit and avocado. It is also described as being found on unspecified trees and bushes in savannahs, mountain forests and rain forests in Africa. Climatic conditions in some parts of southern EU countries are favourable and host plants are available in those areas to support establishment and spread. Despite being present in Portugal for over 10 years, there is a lack of evidence of impacts; hence, the magnitude of impact following introduction is uncertain. Nevertheless, in South Africa, P. bella was reported as being an economically important pest of citrus and to cause damage to avocado fruit during the early stages of development. Phytosanitary measures are available to reduce the likelihood of entry and further spread. Except for having uncertain economic or environmental impacts as a result of its introduction, P. bella satisfies all the other criteria that are within the remit of EFSA to assess for it to be regarded as a potential Union quarantine pest.
10.2903/j.efsa.2022.7623
pubmed_588_10544
Many Italian scholars in the sixteenth century studied minerals. This was not only for the sake of increasing geological knowledge. Minerals, like all other natural phenomena, reflected divine order. Minerals were thought of as a broader category than the lifeless substances found beneath the crust of the earth. Stones, generated in animal and human bodies, were included among minerals, as well. The appearance of kidney stones, gall stones and bladder stones in early modern mineral collections point to the religious motives of the scholars that studied them. In this article, I will examine the mineralogical collection brought together and described by Michele Mercati (1541-1593), the so-called Metallotheca. I will map the circles of physicians, scholars and ecclesiastics in which Mercati lived and functioned. I will then investigate Mercati's descriptions of stones, grown inside animals and men. The specific connections between Mercati and the members of the Oratory of Rome, an influential religious organisation of the Sixteenth century, direct us towards a proper understanding of the significance of Mercati's minerals. Certain minerals, including stones originating in animate bodies, were thought of as approaching the supernatural. The proper attitude for the scholar of nature would then be to turn from curiosity into awe and even veneration.
pubmed_588_10544
pubmed_304_23158
BACKGROUND The effect of GH replacement on thyroid function in hypopituitary patients has hitherto been studied in small groups of children and adults with conflicting results. OBJECTIVE We aimed to define the effect and clinical significance of adult GH replacement on thyroid status in a large cohort of GH-deficient patients. PATIENTS AND METHOD We studied 243 patients with severe GH deficiency due to various hypothalamo-pituitary disorders. Before GH treatment, 159 patients had treated central hypothyroidism (treated group) while 84 patients were considered euthyroid (untreated group). GH dose was titrated over 3 months to achieve serum IGF-1 concentration in the upper half of the age-adjusted normal range. Serial measurements of serum T4, T3, TSH and quality of life were made at baseline and at 3 and 6 months after commencing GH replacement. RESULTS In the untreated group, we observed a significant reduction in serum T4 concentration without a significant increase in serum T3 or TSH concentration; 30/84 patients (36%) became hypothyroid and needed initiation of T4 therapy. Similar but lesser changes were seen in the treated group, 25 of whom (16%) required an increase in T4 dose. Patients who became hypothyroid after GH replacement had lower baseline serum T4 concentration, were more likely to have multiple pituitary hormone deficiencies and showed less improvement in quality of life compared with patients who remained euthyroid. CONCLUSION GH deficiency masks central hypothyroidism in a significant proportion of hypopituitary patients and this is exposed after GH replacement. We recommend that hypopituitary patients with GH deficiency and low normal serum T4 concentration should be considered for T4 replacement prior to commencement of GH in order to provide a robust baseline from which to judge the clinical effects of GH replacement.
10.1111/j.1365-2265.2006.02688.x
pubmed_401_7383
Vascular and lymphatic vessels drive breast cancer (BC) growth and metastasis. We assessed the cell growth (proliferation, migration, and capillary formation), gene-, and protein-expression profiles of Vascular Endothelial Cells (VECs) and Lymphatic Endothelial Cells (LECs) exposed to a conditioned medium (CM) from estrogen receptor-positive BC cells (MCF-7) in the presence or absence of Estradiol. We demonstrated that MCF-7-CM stimulated growth and capillary formation in VECs but inhibited LEC growth. Consistently, MCF-7-CM induced ERK1/2 and Akt phosphorylation in VECs and inhibited them in LECs. Gene expression analysis revealed that the LECs were overall (≈10-fold) more sensitive to MCF-7-CM exposure than VECs. Growth/angiogenesis and cell cycle pathways were upregulated in VECs but downregulated in LECs. An angiogenesis proteome array confirmed the upregulation of 23 pro-angiogenesis proteins in VECs. In LECs, the expression of genes related to ATP synthesis and the ATP content were reduced by MCF-7-CM, whereas MTHFD2 gene, involved in folate metabolism and immune evasion, was upregulated. The contrasting effect of MCF-7-CM on the growth of VECs and LECs was reversed by inhibiting the TGF-β signaling pathway. The effect of MCF-7-CM on VEC growth was also reversed by inhibiting the VEGF signaling pathway. In conclusion, BC secretome may facilitate cancer cell survival and tumor growth by simultaneously promoting vascular angiogenesis and inhibiting lymphatic growth. The differential effects of BC secretome on LECs and VECs may be of pathophysiological relevance in BC.
10.3390/ijms23137192
pubmed_369_24074
Label-free fluorescent assays were developed based on the competition of intramolecular DNA hybridization and aptamer-target binding. Using small molecule adenosine triphosphate (ATP) and biomacro-molecule thrombin as model targets, our design was proved to be a general method with good sensitivity and high selectivity.
10.1039/c2an16092g
pubmed_1044_25443
The rapid preparation of safe and efficient wound dressings that meet the needs of the entire repair process remains a major challenge for effective therapeutic wound healing. Natural, sprayable Ion2+-COS/SA multifunctional dual-network gel films created by the in situ coordination of chitooligosaccharide (COS), metal ions and sodium alginate (SA) using casting and an in-situ spray method were synthesized. The gel films exhibited excellent physicochemical properties such as swelling, porosity and plasticity at a COS mass fraction of 3%. Furthermore, at this mass fraction, the addition of bimetallic ions led to the display of multifunctional properties, including significant antioxidant, antibacterial and cytocompatibility properties. In addition, experiments in a total skin defect model showed that this multifunctional gel film accelerates wound healing and promotes skin regeneration. These results suggest that the sprayable Ion2+-COS/SA multifunctional pro-healing gel film may be a promising candidate for the clinical treatment of allodermic wounds.
10.3390/md20060401
pubmed_887_12056
In this report we describe the use of an IgA-depleted preparation of intravenous gamma-globulin in a patient with hypogammaglobulinemia and an anti-IgA antibody. An IgA containing intravenous gamma-globulin had previously produced anaphylactoid reactions, immune complex formation, and complement activation. The patient has had no reactions to the IgA-depleted preparation after 18 months of treatment; immune complex formation and complement activation have not been demonstrated, and the titer of antibody to IgA has diminished.
10.1016/0090-1229(86)90133-9
pubmed_842_13127
Many people diagnosed with mental illnesses struggle with illicit drug addiction. These individuals are often treated with psychiatric medications, yet little is known about how they experience this treatment. Research on the subjective experience of psychiatric medication use highlights the complex, contradictory, and ambiguous feelings often associated with this treatment. However, for those with mental illness and addiction, this experience is complicated by the need to manage both psychiatric medication and illicit drug use. Using ethnographic data from a study of heroin use in Northeast Ohio, we explore this experience by expanding the pharmaceutical self/imaginary (Jenkins, Pharmaceutical Self: The Global Shaping of Experience in an Age of Psychopharmacology, School for Advanced Research Press, Santa Fe, NM, 2010b) to include psychopharmaceuticals and illicit drugs, what we call the psychotropic self/imaginary. Through this lens we explore the ways participants interpret and manage their psychotropic drug use in relation to sociocultural, institutional, and political-economic contexts. This analysis reveals how participants seek desired effects of legally prescribed and illicit drugs to treat mental illness, manage heroin addiction, and maintain a perceived "normal" self. Participants manage their drug use using active strategies, such as selective use of psychiatric medications, in the context of structural constraints, such as restricted access to mental health care, and cultural contexts that blur distinctions between "good" medicines and "bad" drugs.
10.1007/s11013-011-9244-9
pubmed_994_17704
Introduction Elderly individuals with bilateral hearing loss often do not use hearing aids in both ears. Because of this, dichotic tests to assess hearing in this group may help identify peculiar degenerative processes of aging and hearing aid selection. Objective To evaluate dichotic hearing for a group of elderly hearing aid users who did not adapt to using binaural devices and to verify the correlation between ear dominance and the side chosen to use the device. Methods A cross-sectional descriptive study involving 30 subjects from 60 to 81 years old, of both genders, with an indication for bilateral hearing aids for over 6 months, but using only a single device. Medical history, pure tone audiometry, and dichotic listening tests were all completed. Results All subjects (100%) of the sample failed the dichotic digit test; 94% of the sample preferred to use the device in one ear because bilateral use bothered them and affected speech understanding. In 6%, the concern was aesthetics. In the dichotic digit test, there was significant predominance of the right ear over the left, and there was a significant correlation between the dominant side with the ear chosen by the participant for use of the hearing aid. Conclusion In elderly subjects with bilateral hearing loss who have chosen to use only one hearing aid, there is dominance of the right ear over the left in dichotic listening tasks. There is a correlation between the dominant ear and the ear chosen for hearing aid fitting.
10.1055/s-0034-1372508
pubmed_97_11381
A total of 98 adults previously treated for moderate to advanced periodontitis and on a trimonthly recall schedule were screened for the presence of critical levels of Actinobacillus actinomycetemcomitans, Prevotella (Bacteroides) intermedia, and Porphyromonas (Bacteroides) gingivalis. Patients with at least 2 positive sites were placed in a positive group and patients without or with low levels of these bacteria in a negative group. During the 30-month study the incidence of disease recurrence was greater in the positive group, but did not reach statistical significance. Positive patients with deeper pockets tended to be at greater risk of developing recurrent disease than those with shallower pockets. In the positive group only, both A. actinomycetemcomitans recovery and antibody levels to A. actinomycetemcomitans strain NCTC 9710 (serotype c) were inversely correlated with disease recurrence. The presence of A. actinomycetemcomitans and P. intermedia above critical levels did not reliably predict future episodes of disease recurrence in this population. The sparse recovery of P. gingivalis did not permit us to assess its diagnostic value. With the exception of P. gingivalis, for which insufficient data were available, the results indicate that the presence or absence of the above bacterial species cannot of itself serve as a reliable predictor of future episodes of recurrent disease in a population of treated patients on a regular trimonthly recall schedule.
10.1902/jop.1991.62.6.377
pubmed_49_5780
The differentiation and maturation of hematopoietic progenitor cells are regulated by certain growth factors. Several of these glycoproteins have been characterized, and their amino acid sequences have been delineated. Modern DNA technology provides sufficient quantities of these hormones for testing in clinical trials. Erythropoietin (EPO) has been shown to increase the hemoglobin level and hematocrit in patients with end-stage renal disease. Granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage CSF (GM-CSF) can increase the numbers of neutrophils and monocytes, in a dose-dependent fashion. The function of granulocytes and monocytes is also enhanced. Clinical studies of the toxicity and activity of G-CSF and GM-CSF have been conducted in patients with acquired immune deficiency syndrome, aplastic anemia, myelodysplastic syndromes, and neutropenia due to cancer and chemotherapy. In almost all patients the neutrophil count increased within 24 hours after the start of treatment. Side effects of G-CSF and GM-CSF are infrequent and usually mild. Combinations of CSFs may be even more effective.
pubmed_49_5780
pubmed_1003_11810
This work focuses on the mechanism of acute antibody-mediated rejection leading to graft loss and the mechanisms of accommodation permitting graft survival in ABO-incompatible kidney transplantation. As previously noted, accommodation occurs only with (i) post-transplant suppression of glycosyltransferase, a product of ABO histo-blood group genes in the graft and (ii) prevention of antigen-antibody reactions and delayed hyperacute rejection due to reduced antigenicity of enzyme-regulated histo-blood group antigens. This article discusses the mechanism of ABO histo-blood group glycosyltransferase suppression. Accommodation is always established in successful ABO-incompatible organ grafts and ABO-minor mismatch bone marrow transplantation. In the former, accommodation develops even though ABO histo-blood types of the recipient and the donor are incompatible. In the latter, infusion of donor-derived bone marrow causes the recipient's blood to be eventually replaced by blood of the donor's type. However, the recipient's organs retain their original tissue type. In successful bone marrow engraftment, accommodation is established regardless of ABO-incompatibility. In organ transplantation the recipient's ABO histo-blood type regulates the graft's ABO histo-blood type, while in bone marrow transplantation the new ABO histo-blood type from the donor suppresses and regulates the ABO histo-blood type in recipient organs. In other words, bone marrow-derived histo-blood type regulates the histo-blood type of the organs.
10.1111/j.1399-0012.2005.00392.x
pubmed_392_5323
BACKGROUND AND OBJECTIVES There are limited population-based data on small fiber neuropathy (SFN). We wished to determine SFN incidence, prevalence, comorbid conditions, longitudinal impairments, and disabilities. METHODS Test-confirmed patients with SFN in Olmsted, Minnesota, and adjacent counties were compared 3:1 to matched controls (January 1, 1998-December 31, 2017). RESULTS Ninety-four patients with SFN were identified, with an incidence of 1.3/100,000/y that increased over the study period and a prevalence of 13.3 per 100,000. Average follow-up was 6.1 years (0.7-43 years), and mean onset age was 54 years (range 14-83 years). Female sex (67%), obesity (body mass index mean 30.4 vs 28.5 kg/m2), insomnia (86% vs 54%), analgesic-opioid prescriptions (72% vs 46%), hypertriglyceridemia (180 mg/dL mean vs 147 mg/dL), and diabetes (51% vs 22%, p < 0.001) were more common (odds ratio 3.8-9.0, all p < 0.03). Patients with SFN did not self-identify as disabled with a median modified Rankin Scale score of 1.0 (range 0-6) vs 0.0 (0-6) for controls (p = 0.04). Higher Charlson comorbid conditions (median 6, range 3-9) occurred vs controls (median 3, range 1-9, p < 0.001). Myocardial infarctions occurred in 46% vs 27% of controls (p < 0.0001). Classifications included idiopathic (70%); diabetes (15%); Sjögren disease (2%); AL-amyloid (1%); transthyretin-amyloid (1%); Fabry disease (1%); lupus (1%); postviral (1%); Lewy body (1%), and multifactorial (5%). Foot ulcers occurred in 17, with 71% having diabetes. Large fiber neuropathy developed in 36%, on average 5.3 years (range 0.2-14.3 years) from SFN onset. Median onset Composite Autonomic Severity Score (CASS) was 3 (change per year 0.08, range 0-2.0). Median Neuropathy Impairment Scale (NIS) score was 2 at onset (range 0-8, change per year 1.0, range -7.9 to +23.3). NIS score and CASS change >1 point per year occurred in only AL-amyloid, hereditary transthyretin-amyloid, Fabry, uncontrolled diabetes, and Lewy body. Death after symptom onset was higher in patients with SFN (19%) vs controls (12%, p < 0.001), 50% secondary to diabetes complications. DISCUSSION Isolated SFN is uncommon but increasing in incidence. Most patients do not develop major neurologic impairments and disability but have multiple comorbid conditions, including cardiovascular ischemic events, and increased mortality from SFN onsets. Development of large fiber involvements and diabetes are common over time. Targeted testing facilitates interventional therapies for diabetes but also rheumatologic and rare genetic forms.
10.1212/WNL.0000000000012894
pubmed_312_14425
The efficacy of bronchoalveolar lavage and transbronchial biopsy in diagnosing lung infection was determined in 276 fiberoptic bronchoscopic examinations done on 171 patients with known or suspected acquired immunodeficiency syndrome. Of 173 pathogens (Pneumocystis carinii, cytomegalovirus, Mycobacterium avium-intracellulare, Cryptococcus neoformans, M. tuberculosis, Coccidioides immitis, and Histoplasma capsulatum) identified during the initial evaluation or in the subsequent month, the initial bronchoscopic examination detected 166 (96%). Bronchoalveolar lavage and transbronchial biopsy had sensitivities of 86% and 87%, respectively. When bronchoscopy included both bronchoalveolar lavage and transbronchial biopsy, the yield for all pathogens was 98% and the sensitivity for P. carinii infections was 100%. Follow-up for at least 3 weeks after examination failed to detect any additional false-negative results. Fiberoptic bronchoscopy is extremely accurate for the detection of pathogens in patients with the acquired immunodeficiency syndrome, especially when bronchoalveolar lavage and transbronchial biopsy are combined. In patients at high risk of complications from transbronchial biopsy, bronchoalveolar lavage is sufficiently accurate to be used alone.
10.7326/0003-4819-102-6-747
pubmed_669_16533
The exploration of functional materials relies greatly on the understanding of material structures and nanotechnologies. In the present work, chiral nematic cellulose nanocrystal (CNC) films were prepared by incorporation with four types of amino acids (AAs, glycine, histidine, phenylalanine, and serine) via evaporation-induced self-assembly. The films present ideal iridescence and birefringence that can be tuned by the amount of AAs added. The intercalation of AAs enlarged the pitch values, contributing to the red-shift trend of the reflective wavelength. Among the AAs, serine presented the most compatible intercalation into cellulose crystals. Interestingly, histidine and phenylalanine composite films showed high shielding capabilities of UV light in diverse wavelength regions, exhibiting multi-optical functions. The sustainable preparation of chiral nematic CNC films may provide new strategies for materials production from biocompatible lignocellulose.
10.3390/polym13244389
pubmed_840_19161
Physical inactivity is one of the major risk factors for cardiovascular diseases. Regular physical activity, conversely, is effective in reducing all-cause mortality, cardiovascular morbidity and mortality. Older and recent meta-analyses confirm the reduction of all-cause mortality and cardiovascular mortality by regular physical activity. So far, there is a dose-effect relationship especially from low to moderate training intensity; the steepness of this curve is more curvilinear with a decrease at higher categories of activity intensity. Regular physical activity even at low level of intensity should be a part of daily life and of lifestyle. The risks and side effects of physical activity can be neglected, preparticipation examination before training is strongly recommended. Counseling healthy persons and patients at any age for physical activity, and training prescription should be an essential part of physicians' work in general practice.
10.1007/s00059-006-2859-x
pubmed_246_1267
This investigation was undertaken to examine the extent to which tooth size and jaw size each contribute to dental crowding. Two groups of dental casts were selected on the basis of dental crowding. One group, consisting of 50 pairs of dental casts (18 males and 32 females), exhibited gross dental crowding. A second group, consisting of 54 pairs of dental casts (24 males and 30 females), exhibited little or no crowding. Means and standard deviations of the following parameters were used to compare the two groups: individual and collective mesiodistal tooth diameters, dental arch perimeters, and buccal and lingual dental arch widths. Statistically, the crowded and noncrowded groups could not be distinguished from each other on the basis of mesiodistal tooth diameters. However, significant differences were observed between the dental arch dimensions of the two groups. The crowded group was found to have smaller dental arch dimensions than the noncrowded group. The results of this study suggest that consideration be given to those treatment techniques which increase dental arch length rather than reduce tooth mass.
10.1016/0002-9416(83)90320-2
pubmed_623_18905
Lack of bone formation-related health problems are a major problem for the aging population in the modern world. As a part of the ongoing trend of developing natural substances that attenuate osteoporotic bone loss conditions, dioxinodehydroeckol (DHE) from edible brown alga Ecklonia cava was tested for its effects on osteoblastogenic differentiation in MC3T3-E1 pre-osteoblasts. DHE was observed to successfully enhance osteoblast differentiation, as indicated by elevated cell proliferation, alkaline phosphatase activity, intracellular cell mineralization, along with raised levels of osteoblastogenesis indicators at the concentration of 20 μM. Results suggested a possible intervening of DHE on the bone morphogenetic protein (BMP) signaling pathway, according to elevated protein levels of BMP-2, collagen-I, and Smads. In addition, the presence of DHE was also able to raise the phosphorylated extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) levels which are also activated by the BMP signaling pathway. In conclusion, DHE is suggested to be a potential bioactive compound against bone loss that could enhance osteoblastogenesis with a suggested BMP pathway interaction.
pubmed_623_18905
pubmed_555_719
1. The variation of the specific stoicheiometric catalatic activity of proto- and deuteroferrihaem with total ferrihaem concentration has been studied at 25 degrees C over a wide range of pH. For deuteroferrihaem the results imply that only monomeric ferrihaem species contribute significantly to the catalatic activity. Protoferrihaem is more highly dimerized in solution and, in this system, contributions to the catalatic activity from both monomeric and dimeric ferrihaem species were observed. The ratio of the specific activity of protoferrihaem monomer to that of dimer varied from approximately 20 at pH7 to 5x10(4) at pH12.2. 2. The specific activity of protoferrihaem monomer closely resembles that of deuteroferrihaem monomer, both in magnitude and pH-dependence. In both cases the activity is inversely proportional to [H(+)]. In contrast, the activity of catalase is independent of pH in the range 5-10. At pH13 the activity of ferrihaem monomer becomes equal to the maximal activity of catalase. The results are in good agreement with those reported by Brown et al. (1970b) and provide support for the assumptions upon which this previous analysis relied. 3. Information from the literature concerning the catalatic activity and dimerization of the iron(III) complex of 4,4',4'',4'''-tetrasulphophthalocyanine (Waldmeier & Sigel, 1971; Sigel et al., 1971) have been re-analysed. The results imply that both the monomeric and dimeric complexes contribute to catalatic activity and these activities closely resemble those of the corresponding protoferrihaem species.
10.1042/bj1350353
pubmed_750_18293
Purpose: Certified Public Health Dental Hygienists (CPHDH) perform traditional dental hygiene scope of practice duties, along with caries stabilization (interim therapeutic restorations) through collaborative agreements with a dentist, in the state of New Hampshire. The purpose of this pilot study was to assess the oral health status, dental needs, including referral and utilization, and satisfaction of care received by homebound individuals in their place of residence when provided by a CPHDH.Methods: A purposive sample of homebound individuals participated in a mixed methods study that included quantitative data from an intake survey, a retrospective chart review, and qualitative in-depth interviews.Results: Study participants (n=15) had an average of 22.4 natural teeth; 44% of participants had not seen a dentist for two or more years. Forty-three percent of participants required a referral to a dentist due to dental needs beyond the scope of the CPHDH. Themes from the interviews included: difficulty in accessing a traditional dental care delivery model despite a high value placed on oral health and a high need for dental care. In general, participants expressed satisfaction with care received by the CPHDH.Conclusion: Participants reported a positive experience and satisfaction with care received from a CPHDH suggesting that this is a viable approach to provide preventive oral health services and caries stabilization to populations with complex access to care challenges.
pubmed_750_18293
pubmed_675_17920
Bilateral cervical facet dislocation (BFD) with facet fracture (Fx) often causes tetraplegia but is rarely recreated experimentally, possibly due to a lack of muscle replication. Intervertebral axial compression (due to muscle activation) or distraction (due to inertial loading), when combined with excessive anterior translation, may influence interfacet contact or separation and the subsequent production of BFD with or without Fx. This paper presents a methodology to produce C6/C7 BFD+Fx using anterior shear motion superimposed with 300 N compression or 2.5 mm distraction. The effect of these superimposed axial conditions on six-axis loads, and C6 inferior facet deflections and surface strains, was assessed. Twelve motion segments (70 ± 13 yr) achieved 2.19 mm of supraphysiologic anterior shear without embedding failure (supraphysiologic shear analysis point; SSP), and BFD+Fx was produced in all five specimens that reached 20 mm of shear. Linear mixed-effects models (α = 0.05) assessed the effect of axial condition. At the SSP, the compressed specimens experienced higher axial forces, facet shear strains, and sagittal facet deflections, compared to the distracted group. Facet fractures had similar radiographic appearance to those that are observed clinically, suggesting that intervertebral anterior shear motion contributes to BFD+Fx.
10.1115/1.4050172
pubmed_796_9393
The capacity to synthesize both prostaglandins E1 (PGE1) and E2 (PGE2) has been determined in human lung mucoepidermoid carcinoma homogenates when [14C]-fatty acid precursors were added to the incubation medium. Only 10% of the total radioactivity recovered in PGs was found in PGF1 alpha and PGF2 alpha. The experiments were principally focused to inhibit the PGE2 synthesis either with pure eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids or with mixtures of both n-3 fatty acids obtained from fish oil. The results demonstrated that significant inhibitions were found when using 25 microM or a higher concentration of pure EPA or DHA in the incubation medium; however, 5 microM of mixtures of different EPA/DHA ratio caused the same inhibition. The results suggest that EPA and DHA, when added together, may enforce their inhibitory effect on PGE2 synthesis.
pubmed_796_9393
pubmed_179_10279
Cardiac abnormalities such as left ventricular hypertrophy, left ventricular dilation, and pulmonary hypertension in sickle cell anemia have been previously described. Hydroxyurea, a disease-modifying therapy for sickle cell anemia, has been used for several decades. Longitudinal assessment of echocardiographic abnormalities in children and young adults with sickle cell anemia receiving hydroxyurea therapy is lacking. The goal of this retrospective study was to determine the prevalence of echocardiographic abnormalities in children and young adults with sickle cell anemia and to examine the effects of hydroxyurea on reverse cardiac remodeling. We reviewed the records of patients with sickle cell anemia who underwent routine cardiac screening at Cohen Children's Medical Center between 2010 and 2017, followed by retrospective longitudinal analysis of echocardiograms performed on patients receiving treatment with hydroxyurea. Data on a total of 100 patients with sickle cell anemia were analyzed; 60 (60%) were being treated with hydroxyurea. Twenty-five (41.6%) of the patients on hydroxyurea had been treated for <1 year; these patients had a significantly greater prevalence of left ventricular dilation compared with those who had been on treatment for >1 year. Serial echocardiograms of patients receiving hydroxyurea were then analyzed. Left ventricular dilation and hypertrophy improved significantly with hydroxyurea treatment. In addition, the left ventricular volume and mass correlated negatively with duration of treatment with hydroxyurea. Our study provides evidence that prolonged hydroxyurea therapy may lead to reverse cardiac remodeling. Future studies should attempt to follow up this patient cohort for a longer duration.
10.1182/bloodadvances.2021005076
pubmed_909_22594
OBJECTIVE Previous study showed that the signaling pathway of dual-specificity tyrosine-phosphorylated and regulated kinase 1A (Dyrk1A)-alternative splicing factor (ASF)- alternative splicing of Ca(2+)/calmodulin-dependent protein kinase IIδ (CaMKIIδ) is related to myocardial hypertrophy. The aim of present study was to determine the effect and related mechamism of metoprolol on pressure overload induced myocardial hypertrophy. METHODS Pressure overload-induced hypertension was induced by coarctation of suprarenal abdominal aorta in rats. Rats were randomly divided into sham-operated control, hypertension and hypertension plus metoprolol (30 mg×kg(-1)×d(-1)) groups (n = 10 each). Blood pressure, the left ventricular weight to body weight ratio and cardiomyocytes area were measured, the protein expression of Dyrk1A and ASF were determined by Western blot and mRNA expression of alternative splicing of CaMKIIδ was detected by RT-PCR. RESULTS Four weeks after coarctation, cardiac hypertrophy was evidenced in rats of hypertensive group, and the protein expression of Dyrk1A was significantly upregulated, while the expression of ASF was significantly downregulated, the mRNA expression of CaMKIIδ A and B were significantly upregulated and mRNA expression of CaMKIIδ C was significantly downregulated compared to those in sham-operated control rats (all P < 0.05). Treatment with metoprolol effectively attenuated cardiac hypertrophy and reversed pressure overload induced changes on Dyrk1A and ASF, and alternative splicing of CaMKIIδ (all P < 0.05). CONCLUSION Metoprolol attenuates pressure overload-induced cardiac hypertrophy possibly through modulating Dryk1A-ASF-CaMKIIδ signaling pathways.
pubmed_909_22594
pubmed_699_1533
Vomiting is a major gastrointestinal (GI) sign of chronic enteropathy (CE) in dogs. Previous studies have reported clinical characteristics of dogs with CE, who developed diarrhea with or without vomiting as GI signs. However, to characterize clinical features of dogs with CE appropriately, dogs presenting with vomiting without diarrhea should be included in the analysis. Thus, this study aimed to characterize clinical features and outcomes of dogs that presented with vomiting without diarrhea. Based on their presenting GI signs, we retrospectively classified 66 dogs with CE into "Vomiting", "Diarrhea", or "Vomiting and diarrhea" groups and compared clinical and histological characteristics of each group. We found that 18 of the 66 dogs with CE (27%) presented with vomiting without diarrhea as a GI sign. Compared to the other 2 groups, the Vomiting group was significantly associated with food-responsive enteropathy (FRE), Beagle, lower clinical severity scores, higher plasma albumin levels, and higher histological scores for eosinophils in the duodenal lamina propria according to the univariate analysis. The multivariate analysis revealed that FRE and higher histological scores for eosinophils in the duodenal lamina propria were significant variables in the Vomiting group. Moreover, the survival time was the longest in the Vomiting group among dogs with CE. These findings are of clinical significance as they indicate that presenting with vomiting without diarrhea may not only be helpful in differentiating FRE from the other types of CE, but also in predicting the prognosis.
10.1016/j.vas.2022.100255
pubmed_372_3804
The purpose is to compare full-field digital mammography (FFDM), digital breast tomosynthesis (DBT) and contrast-enhanced spectral mammography (CESM) technologies on three mammography systems in terms of image quality and patient dose. Two Senographe Essential with DBT and CESM (denoted S1 and S2) and one Selenia Dimensions (S3) with FFDM and DBT were considered. Dosimetry methods recommended in the European protocol were used. Image quality was tested with CDMAM in FFDM and DBT and with ideal observer method in FFDM. Mean values of mean glandular dose (MGD) from whole patient samples on S1, S2 and S3 were as follows: FFDM 1.65, 1.84 and 2.23 mGy; DBT 2.03, 1.96 and 2.87 mGy; CESM 2.65 and 3.16 mGy, respectively. S3 exhibited better low-contrast detectability for the smallest sized discs of CDMAM and ideal observer in FFDM, and for the largest sized discs in DBT, at similar dose levels.
10.1093/rpd/ncab172
pubmed_937_19346
Shigella flexneri causes a self-limiting gastroenteritis in humans, characterized by severe localized inflammation and ulceration of the colonic mucosa. Shigellosis most often targets young children in underdeveloped countries. Invasion plasmid antigen C (IpaC) has been identified as the primary effector protein for Shigella invasion of epithelial cells. Although an initial model of IpaC function has been developed, no detailed structural information is available that could assist in a better understanding of the molecular basis for its interactions with the host cytoskeleton and phospholipid membrane. We have therefore initiated structural studies of IpaC, IpaC I', (residues 101-363 deleted), and IpaC Delta H (residues 63-170 deleted). The secondary and tertiary structure of the protein was examined as a function of temperature, employing circular dichroism and high resolution derivative absorbance techniques. ANS (8-anilino-1-napthalene sulfonic acid) was used to probe the exposure of the hydrophobic surfaces under different conditions. The interaction of IpaC and these mutants with a liposome model (liposomes with entrapped fluorescein) was also examined. Domain III (residues 261-363) was studied using linker-scanning mutagenesis. It was shown that domain III contains periodic, sequence-dependent activity, suggesting helical structure in this section of the protein. In addition to these structural studies, investigation into the actin nucleation properties of IpaC was conducted, and actin nucleation by IpaC and some of the mutants was exhibited. Structure-function relationships of IpaC are discussed.
10.1074/jbc.M208383200
pubmed_216_22188
PURPOSE Recent discoveries highlight the importance of the hedgehog signaling pathway in prostate growth regulation. We reviewed the role of hedgehog signaling in prostate development, adult prostate homeostasis and prostate cancer. MATERIALS AND METHODS A comprehensive review of all relevant literature was done. RESULTS Epithelial expression of hedgehog ligand during prostate development exerts autocrine and paracrine signaling activities that regulate growth and differentiation. Hedgehog signaling also occurs in the adult human prostate but to our knowledge the influence on epithelial proliferation and/or differentiation is unknown. Robust hedgehog signaling occurs frequently in prostate cancer, and autocrine and paracrine signaling have been shown to accelerate the growth of xenograft tumors. Autocrine signaling has been implicated in stimulating stem/progenitor cells and increased hedgehog pathway activity may be a characteristic of advanced, androgen independent cancer. The plant alkaloid cyclopamine is a specific chemical inhibitor of hedgehog signaling that produced sustained regression of established xenograft tumors. CONCLUSIONS Hedgehog signaling has an important role in prostate development and it appears to be a characteristic feature of prostate cancer. It stimulates tumor growth and may exert a specific role in the proliferation of tumor stem cells. The development of hedgehog inhibitors based on the action of cyclopamine holds promise for novel treatments to slow or arrest tumor growth.
10.1016/j.juro.2006.10.061
pubmed_944_24299
Describing new brain structures may open research avenues and improve our knowledge of brain functions and of brain disorders. It may also provide new neuroanatomical targets for treatments. A detailed understanding of neuroanatomy is a prerequisite of understanding the pathomechanisms underlying psychiatric disorders on a molecular and cellular level. The tail of the ventral tegmental area (tVTA), also known as rostromedial tegmental nucleus (RMTg), is a recently described region which may be a major inhibitory control centre for the dopaminergic systems. These systems participates to behavioural functions and are implicated in the aetiology, symptoms or treatment of neurological or psychiatric diseases, such as Parkinson's, schizophrenia, mood disorders, attention-deficit hyperactivity-disorder (ADHD) and drug abuse. Belonging to the reticular formation, the tVTA may constitute a major inhibitory GABAergic input to these dopaminergic systems. Moreover, it is sensitive to drugs of abuse, to stimulant or arousing drugs, to aversive stimuli and it could also be the main relay between lateral habenula and VTA. First described in rats, and proposed as a component of the emotional motor system implicated in basic survival behaviours, tVTA appears as a relevant structure for molecular psychiatry, which should foster research to define and study this brain region in the human brain.
10.3109/15622975.2011.598386
pubmed_954_2830
What is love and what part does it play in psychoanalysis? Where are the analyst and the analysand situated in relation to the roles defined as those of the "lover" and the "beloved"? Jacques Lacan explores these and other questions in his soon-to-be-published Seminar VIII: Transference by providing an extensive commentary on Plato's most famous dialogue on love, the Symposium. This paper outlines some of the major points about love that grow out of Lacan's reading of the dialogue and examines their relevance to the analytic setting. Can the analyst be characterized as a sort of modern-day Socrates?
10.1521/prev.2015.102.1.59
pubmed_1052_14853
BACKGROUND Bisphosphonates reduce the overall risk of fractures among patients with osteoporosis, and this beneficial effect is long-lasting. However, since bisphosphonates inhibit bone remodeling, they may enhance the formation and propagation of micro-cracks over time and patients may therefore be prone to atypical fatigue fractures, mainly in the subtrochanteric region and femoral shaft. OBJECTIVES To present two cases of subtrochanteric fractures related to bisphosphonate treatment, and review the current literature. CONCLUSIONS Despite the overall beneficial effect of bisphosphonates, further research is required to prevent this significant complication.
pubmed_1052_14853
pubmed_76_17120
Hormonal Replacement Therapy (HRT) is known to be accompanied by changes in blood lipid profile. The present prospective cohort study compared the blood lipid profile of healthy postmenopausal women treated with either (a) a preparation containing a fixed regimen of estradiol, estriol and norethisterone acetate (EENA, marketed under the trade name Trisequens); (b) a fixed protocol of conjugated equine estrogen and medroxyprogesterone acetate (CEEMPA, marketed under the trade name Premaril Plus); or with (c) a concurrent group which underwent no treatment. Blood lipid profiles (total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C), and triglycerides (TG)) were performed at the beginning of the study and at 3-month intervals, for 9 months. The EENA-treated women showed a significant and profound decrease in TC and LDL-C when compared with their initial values, with the control group, and with the CEEMPA group. The CEEMPA group showed an increase in HDL-C values and a decrease in LDL-C values when compared with their initial values and with the control group, but no increase was shown when compared with an EENA group. There was a favorable decrease in the TC/HDL-C and LDL-C/HDL-C ratios in both treatment protocols. As the primary goal of prevention of coronary artery disease is total cholesterol reduction, the EENA protocol seems to be preferred.
10.1016/0028-2243(92)90254-v
pubmed_987_25512
Macrophages are important in inflammation, and are involved in many physiological and pathological processes. Additionally, macrophages are important producers of eicosanoids, lipids that influence the inflammatory response. Our study aimed to explore the role of eicosanoids in the inflammatory response by studying the production of eicosanoids by macrophages on different stages of inflammation. Murine peritoneal macrophages (MPMs) were obtained at different stages of inflammation, which were then cultured in vitro with polyunsaturated fatty acids. Eicosanoids in MPMs were then detected by liquid chromatography-mass spectrometry. The metabolites derived from the cyclooxygenase (COX) pathway were increased, whereas those from the lipoxygenase (LOX) pathway were reduced. Additionally, the ratio of arachidonic acid (AA)-derived and eicosapentaenoic acid (EPA)-derived eicosanoids was dependent on the stage of inflammation. Moreover, the composition of macrophages with different phenotypes changed. To clarify the relationship between the phenotypes of macrophages and eicosanoids metabolism, we detected the eicosanoids in M1 and M2 differentiated THP-1 cells. Overall, M1 preferred AA, whereas M2 preferred EPA as substrate, which was related to the expression of COX and LOX. In conclusion, this study demonstrates that the difference in macrophage eicosanoids metabolism during the inflammatory response is related to the macrophage polarisation.
10.1016/j.prostaglandins.2022.106635
pubmed_249_10483
The present paper summarizes 13-years our center's experience in the treatment of essential thrombocythemia (ET). We analyzed a group of 36 patients treated with busulphan (Bu), 16 with hydroxyurea (HU) and 4 with interferon alpha (INF alpha). The results of therapy were assessed using proposed self-defined criteria of ET remission. The remission of ET was achieved in 75% of the patients treated with Bu and 57% treated with HU followed for at least 2 years. In the INF alpha treated group cytoreduction was achieved only in patients in whom initial dose of INF alpha was 6 mln I.U. per day. HU seems to be the drug of choice in younger patients because of possible mutagenic effect of Bu as well as in those, in whom Bu was administered in high total dose. During the cytoreductive or maintenance therapy with HU the blood morphology should be often controlled because of relatively high frequency (40%) of leukopenia. In each case of ET cytogenetic examination is necessary. Ph-positive ET determine the choice of the treatment.
pubmed_249_10483
pubmed_311_1112
BACKGROUND Sodium-glucose cotransporter 2 inhibitors (SGLT2is, gliflozins) are associated with lower all-cause mortality than other anti-diabetic agents in patients with type 2 diabetes. In patients who may benefit from SGLT2is, but cannot add them to a dipeptidyl peptidase-4 inhibitor (DPP4i, gliptin) treatment for various reasons, replacement of the DPP4i with a SGLT2i may be considered. OBJECTIVES Evaluate changes in metabolic parameters in patients with diabetes after replacing a DPP4i with the SGLT2i empagliflozin. DESIGN Panel study (cross-sectional and cohort hybrid). SETTING The diabetes outpatient clinics of Chang Gung Memorial Hospital at Linkou, a university hospital in Taiwan. PATIENTS AND METHODS We reviewed the medical records of patients who had been treated with anti-diabetic agents including a DPP4i between May 2016 and May 2017. Patients who switched from DPP4is to empagliflozin (switched-to-empagliflozin group) without changes to other anti-diabetic agents for at least 6 months were compared patients who continued taking an original antidiabetic agent. The body weight (BW), body mass index (BMI), and glycated hemoglobin (HbA1c) level at baseline and after 3 and 6 months were collected for analysis. MAIN OUTCOME MEASURES BW, BMI, HbA1c at baseline, 3 and 6 months. SAMPLE SIZE 236 patients. RESULTS The HbA1c level and BMI of 110 patients (71%) in the switched-to-empagliflozin group were significantly reduced at 6 months after the switch, and there was a significant negative correlation between baseline HbA1c and change in HbA1c (rho=-0.537, P less than .001). In another 45 patients (29%) who switched to empagliflozin, HbA1c did not have improve, but BW decreased after the switch. No significant change in HbA1c occurred in the group that remained on DPP4is. In addition, BW and BMI decreased regardless of the degree of glucose reduction in the switched-to-empagliflozin group (P less than .001 for both variables at 6 months vs baseline), but not in the patients who remained on DPP4is. CONCLUSIONS The study demonstrated the metabolic impact of switching from a DPP4i to a well-known SGLT2i, but further large-scale trials are needed to study the long-term effects of replacing a DPP4i with a SGLT2i. LIMITATIONS Retrospective design, a short observation period, a small number of patients, no evaluations of the quality of life, side effects, or the cost, and data limited to only empagliflozin. CONFLICT OF INTEREST No any relationship or support from the manufacturer of empagliflozin or other agents.
10.5144/0256-4947.2018.420
pubmed_1095_18036
Arabidopsis thaliana Protein Interactome Database (AtPID) is an object database that integrates data from several bioinformatics prediction methods and manually collected information from the literature. It contains data relevant to protein-protein interaction, protein subcellular location, ortholog maps, domain attributes and gene regulation. The predicted protein interaction data were obtained from ortholog interactome, microarray profiles, GO annotation, and conserved domain and genome contexts. This database holds 28,062 protein-protein interaction pairs with 23,396 pairs generated from prediction methods. Among the rest 4666 pairs, 3866 pairs of them involving 1875 proteins were manually curated from the literature and 800 pairs were from enzyme complexes in KEGG. In addition, subcellular location information of 5562 proteins is available. AtPID was built via an intuitive query interface that provides easy access to the important features of proteins. Through the incorporation of both experimental and computational methods, AtPID is a rich source of information for system-level understanding of gene function and biological processes in A. thaliana. Public access to the AtPID database is available at http://atpid.biosino.org/.
10.1093/nar/gkm844
pubmed_1070_14284
African Americans (AAs) tend to have lower total adiponectin levels compared to European Americans (EA); however, it is not known whether race affects adiponectin multimer distribution and their relationships to metabolic traits. We measured total adiponectin, high molecular weight (HMW), low molecular weight (LMW) (i.e., hexamer), and trimer adiponectin in 132 normoglycemic premenopausal women (75 AAs, 57 EAs), together with measures of total and abdominal fat, plasma lipids, insulin sensitivity (S(i)), and genetic admixture estimates. We found that lower total adiponectin in AAs was explained by reduced LMW, and trimer forms because levels of HMW did not differ between races. In EAs, HMW was highly correlated with multiple metabolic syndrome traits. In contrast, the LMW and trimer forms were most highly correlated with metabolic traits in AAs, including abdominal adiposity, lipids, and S(i). At similar levels of visceral adiposity, AAs exhibited significantly lower LMW adiponectin than EAs. Similarly, at comparable levels of HMW and LMW adiponectin, AAs were more insulin resistant than their EA counterparts. In conclusion, (i) serum adiponectin is lower in AAs predominantly as a result of reduced concentrations of LMW and trimers multimeric forms; (ii) LMW and trimer, not HMW, are most broadly correlated with metabolic traits in AAs. Thus, HMW adiponectin may exert less bioactivity in explaining the metabolic syndrome trait cluster in populations of predominant African genetic background.
10.1038/oby.2008.411
pubmed_1043_5281
Samples of ventricular cerebrospinal fluid, tumor cyst fluid, and subdural fluid were obtained from 30 patients at operation. The protein concentration and the specific gravity of each sample were measured and the corresponding mean absorption numbers were calculated from the numerical printout of the preoperative computerized tomogram. For fluids with a specific gravity greater than 1.005, a linear relationship was demonstrated between protein concentration and specific gravity. For protein concentrations greater than 300 mg/dl, there was a linear relationship between protein concentration and the mean absorption number. As the precision of present instrumentation improves, it is expected that a noninvasive technique for estimating intracranial protein concentration will have a number of clinical application.
10.1227/00006123-197907010-00003
pubmed_942_21381
BACKGROUND Osteoblastic metastases are commonly induced by prostate cancer. A canine prostate carcinoma xenograft (Ace-1) was developed and used to evaluate neoplastic prostate cell growth, metastasis, and effects on bone formation in nude mice. METHODS Characteristics of the Ace-1 cells were evaluated with histopathology, radiography, and bioluminescent imaging (BLI). Immunohistochemistry and quantitative RT-PCR were used to evaluate the expression of factors important in the development of osteoblastic metastases. RESULTS The Ace-1 cells were invasive and induced bone formation and destruction. Radiographs demonstrated a mixed osteoblastic/osteolytic reaction. Lung and lymph node metastases occurred in 30% of mice. The tumor cells expressed parathyroid hormone-related protein (PTHrP-141 isoform), cathepsin K, keratins 8/18, and vimentin, but not keratins 5/14, and were androgen receptor negative. Intracardiac (IC) injections resulted in metastases in vertebrae and long bones. CONCLUSIONS The Ace-1 xenograft is a useful model for investigating the pathogenesis of prostate cancer invasion and mixed osteoblastic/osteolytic bone metastases.
10.1002/pros.20408
pubmed_856_16493
Cancer recurrence remains a great fear for many cancer survivors following their initial, apparently successful, therapy. Despite significant improvement in the overall survival of many types of cancer, metastasis accounts for ~90% of all cancer mortality. There is a growing understanding that future therapeutic practices must accommodate this unmet medical need in preventing metastatic recurrence. Accumulating evidence supports dormant disseminated tumor cells (DTCs) as a source of cancer recurrence and recognizes the need for novel strategies to target these tumor cells. This review presents strategies to target dormant quiescent DTCs that reside at secondary sites. These strategies aim to prevent recurrence by maintaining dormant DTCs at bay, or eradicating them. Various approaches are presented, including: reinforcing the niche where dormant DTCs reside in order to keep dormant DTCs at bay; promoting cell intrinsic mechanisms to induce dormancy; preventing the engagement of dormant DTCs with their supportive niche in order to prevent their reactivation; targeting cell-intrinsic mechanisms mediating long-term survival of dormant DTCs; sensitizing dormant DTCs to chemotherapy treatments; and, inhibiting the immune evasion of dormant DTCs, leading to their demise. Various therapeutic approaches, some of which utilize drugs that are already approved, or have been tested in clinical trials and may be considered for repurposing, will be discussed. In addition, clinical evidence for the presence of dormant DTCs will be reviewed, along with potential prognostic biomarkers to enable the identification and stratification of patients who are at high risk of recurrence, and who could benefit from novel dormant DTCs targeting therapies. Finally, we will address the shortcomings of current trial designs for determining activity against dormant DTCs and provide novel approaches.
10.3389/fonc.2021.659963
pubmed_653_5448
PURPOSE Dietitians of Canada has collaborated with experts in knowledge translation and transfer, technology, and dietetic practice to develop and implement an innovative online decision-support system called Practice-based Evidence in Nutrition (PEN). A study was conducted to evaluate the perceived facilitators and barriers that enable dietitians to use or prevent them from using PEN. METHODS As part of the overall evaluation framework of PEN, a qualitative descriptive research design was used to address the research purpose. Individual, semi-structured telephone interviews with 17 key informants were completed, and the interview transcripts underwent qualitative content analysis. RESULTS Respondents identified several facilitators of and barriers to PEN use. Facilitators included specificity to dietetics, rigorous/expert review, easy accessibility, current content, credible/secure material, well-organized/easy-to-use material, material that is valuable to practice, and good value for money. Barriers included perceived high cost, fee structuring/cost to students, certain organizational aspects, and a perceived lack of training for pathway contributors. CONCLUSIONS This formative evaluation has indicated areas in which PEN could be improved and strategies to make PEN the standard for dietetic education and practice. Ensuring that PEN is meeting users' knowledge needs is of the utmost importance if dietitians are to remain on the cutting edge of scientific inquiry.
10.3148/73.1.2012.e233
pubmed_1055_3203
C. elegans inhabit environments that require detection of diverse stimuli to modulate locomotion in order to avoid unfavourable conditions. In a mammalian context, a failure to appropriately integrate environmental signals can lead to Parkinson's, Alzheimer's, and epilepsy. Provided that the circuitry underlying mammalian sensory integration can be prohibitively complex, we analyzed nematode behavioral responses in differing environmental contexts to evaluate the regulation of context dependent circuit reconfiguration and sensorimotor control. Our work has added to the complexity of a known parallel circuit, mediated by interneurons AVA and AIB, that integrates sensory cues and is responsible for the initiation of backwards locomotion. Our analysis of the galanin-like G-protein coupled receptor NPR-9 in C. elegans revealed that upregulation of galanin signaling impedes the integration of sensory evoked neuronal signals. Although the expression pattern of npr-9 is limited to AIB, upregulation of the receptor appears to impede AIB and AVA circuits to broadly prevent backwards locomotion, i.e. reversals, suggesting that these two pathways functionally interact. Galanin signaling similarly plays a broadly inhibitory role in mammalian models. Moreover, our identification of a mutant, which rarely initiates backwards movement, allowed us to interrogate locomotory mechanisms underlying chemotaxis. In support of the pirouette model of chemotaxis, organisms that did not exhibit reversal behavior were unable to navigate towards an attractant peak. We also assessed ionotropic glutamate receptor GLR-1 cell-specifically within AIB and determined that GLR-1 fine-tunes AIB activity to modify locomotion following reversal events. Our research highlights that signal integration underlying the initiation and fine-tuning of backwards locomotion is AIB and NPR-9 dependent, and has demonstrated the suitability of C. elegans for analysis of multisensory integration and sensorimotor control.
10.1371/journal.pgen.1006050