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pubmed_536_24334 | PROBLEM
Homing of lymphocytes and NK cells into the decidua and its regulation has been very controversially discussed. Therefore, we aimed to establish an in vivo simulation method for analysis of homing behavior, which might be also useful for other cells such as stem or tumor cells.
METHOD OF STUDY
A human term placenta has been perfused with medium to elute blood and then with maternal autologous carboxyfluorescein succinimidyl ester (CFSE)-labeled peripheral blood lymphocytes for 3 hr and rinsed for another 2 hr. Tissue was analysed histologically for detection of labeled cells. Labeled lymphocytes and beads in perfusate have been identified and counted by flow cytometry.
RESULTS
At the moment of tissue fixation for histology, the perfusate was free of labeled cells. Labeled perfused lymphocytes have been found adhered and integrated in vessel wall structures, in decidual stroma and as colonies in individual villi.
CONCLUSION
Placenta perfusion with a lymphocyte suspension is feasible without plugging the tube system. Time is sufficient for cells to adhere and to migrate into the stroma. Also some villi have been infiltrated which might be caused by inflammatory stimuli. The perfusion system might be useful to test substances for their capacity to influence homing of lymphocytes or other cells. | 10.1111/j.1600-0897.2008.00666.x |
pubmed_1050_2661 | DNA replication is an exceptional point of therapeutic intervention for many cancer types and several small molecules targeting DNA have been developed into clinically used antitumor agents. Many of these molecules are naturally occurring metabolites from plants and microorganisms, such as the widely used chemotherapeutic doxorubicin. While natural product sources contain a vast number of DNA binding small molecules, isolating and identifying these molecules is challenging. Typical screening campaigns utilize time-consuming bioactivity-guided fractionation approaches, which use sequential rounds of cell-based assays to guide the isolation of active compounds. In this study, we explore the use of biolayer interferometry (BLI) as a tool for rapidly screening natural product sources for DNA targeting small molecules. We first verified that BLI robustly detected DNA binding using designed GC- and AT-rich DNA oligonucleotides with known DNA intercalating, groove binding, and covalent binding agents including actinomycin D (1), doxorubicin (2), ethidium bromide (3), propidium iodide (4), Hoechst 33342 (5), and netropsin (6). Although binding varied with the properties of the oligonucleotides, measured binding affinities agreed with previously reported values. We next utilized BLI to screen over 100 bacterial extracts from our microbial library for DNA binding activity and found three highly active extracts. Binding-guided isolation was used to isolate the active principle component from each extract, which were identified as echinomycin (8), actinomycin V (9), and chartreusin (10). This biosensor-based DNA binding screen is a novel, low-cost, easy to use, and sensitive approach for medium-throughput screening of complex chemical libraries. Graphical abstract. | 10.1007/s00216-020-03079-5 |
pubmed_92_4543 | INTRODUCTION
The World Health Organization reviewed the classification for serrated colonic polyps in 2010. A new entity, sessile serrated adenoma, was included with two variants: with and without cytological dysplasia. This lesion's malignant potential has been recognized and according to the new classification, many polyps may be reclassified. The impact of this change is yet to be assessed.
OBJECTIVE
Analyze the proportion of lesions that were reclassified according to the new World Health Organization classification and the variables that influenced it.
MATERIAL AND METHODS
Every patient with at least one sessile serrated adenoma diagnosed in a 5 year period was included. All polyps (regardless of type) resected during the study period were reviewed. Data concerning polyp's characteristics and patient variables were collected. Forty consecutive patients were included [13 female, mean age at 1st sessile serrated adenoma -59 yrs (34-80)].
RESULTS
Were reviewed 247 polyps: hyperplastic--42%; conventional adenomas--29%; sessile serrated adenoma--24%; serrated adenomas--5%. Sixty-three polyps were reclassified: 43 hyperplastic, 12 serrated adenomas, 7 sessile serrated adenoma and 1 conventional adenoma with low grade dysplasia. Reclassification was significantly greater for hyperplastic polyps when compared with the other subtypes. Forty-three of one hundred and four (41%) hyperplastic polyps were reclassified all as sessile serrated adenoma. In these polyps the probability of reclassification was independent from polyp location but was greater if polyp size ≥ 5 mm.
DISCUSSION
This is a single center, rectrospective study. The fact that it was done in an Oncology Referral Institution with a Family Risk Clinic may have influenced the results. Nevertheless the impressive reclassification rate for Hyperplastic Polyps and the fact that they were reclassified mainly as Serrated Adenomas makes these results relevant to daily practice.
CONCLUSION
Our results suggest that, according to the new World Health Organization classification for serrated colonic polyps, a considerable proportion of hyperplastic polyps will be reclassified. The serrated pathway of colorectal carcinogenesis has probably been underestimated and at-risk patients may have been under inappropriate surveillance. | 10.20344/amp.4725 |
pubmed_623_12171 | Persistent pain after iliac vein stenting is rare. Surgical removal of two oversized (20-mm) iliac vein stents was performed in a 36-year-old woman because of severe back pain of 2½ years' duration. Clamping or venotomy were not required for stent removal, which was done by extraction of each wire of the stent through small puncture wounds in the vein wall. Duplex scanning confirmed residual pseudointima obstructing the orifice of the right common iliac vein. The pseudointima was surgically removed. The patient recovered without complications, and her pain completely resolved. | pubmed_623_12171 |
pubmed_651_12889 | Patterns of local cerebral glucose utilization were measured with positron emission tomography using the fluorine-18-labeled fluorodeoxyglucose (18FDG) method in 8 patients with Parkinson's disease, in 13 patients with Huntington's disease, in 15 subjects at risk for Huntington's disease, and in aged-matched normal control subjects. On the average, global cerebral metabolism in patients with Parkinson's disease was moderately reduced (20%), but the relative distribution of glucose utilization throughout the brain in these patients was normal. These results support the conclusion that alterations of the nigrostriatal pathway in Parkinson's disease have no major selective effect on the metabolism of particular cerebral regions. In Huntington's disease, however, there was a characteristic decrease in glucose utilization in the caudate nuclei and putamen, and this local hypometabolism appeared early and preceded bulk tissue loss. In patients with Huntington's disease, glucose utilization typically was normal throughout the rest of the brain, regardless of the severity of symptoms and despite the apparent shrinkage of brain tissue. The results also suggest the possibility that the caudate nuclei may be hypometabolic in some asymptomatic subjects who are potential carriers of the autosomal dominant gene for Huntington's disease. | 10.1002/ana.410150723 |
pubmed_908_15151 | To fertilize the egg, sperm cells must reside in the female reproductive tract for several hours during which they undergo chemical and motility changes collectively called capacitation. During capacitation, the sperm develop a unique type of motility known as hyperactivated motility (HAM). The semen contains Zn2+ in millimolar concentrations, whereas in the female reproductive tract, the concentration is around 1 µM. In this study, we characterize the role of Zn2+ in human sperm capacitation focusing on its effect on HAM. Western blot analysis revealed the presence of GPR39-type Zn-receptor localized mainly in the sperm tail. Zn2+ at micromolar concentration stimulates HAM, which is mediated by a cascade involving GPR39-adenylyl cyclase (AC)-cyclic AMP (cAMP)-protein kinase A-tyrosine kinase Src (Src)-epidermal growth factor receptor and phospholipase C. Both the transmembrane AC and the soluble-AC are involved in the stimulation of HAM by Zn2+ . The development of HAM is precisely regulated by cAMP, in which relatively low concentration (5-10 µM) stimulated HAM, whereas at 30 µM no stimulation occurred. A similar response was seen when different concentrations of Zn2+ were added to the cells; low Zn2+ stimulated HAM, whereas at relatively high Zn2+ , no effect was seen. We further demonstrate that the Ca2+ -channel CatSper involved in Zn2+ -stimulated HAM. These data support a role for extracellular Zn2+ acting via GPR39 to regulate signaling pathways in sperm capacitation, leading to HAM induction. | 10.1002/mrd.22996 |
pubmed_660_11592 | Acute knee pain is a common complaint among patients presenting to outpatient clinics. Although most injuries are minor and resolve without surgical intervention, some injuries, such as extensor mechanism injuries, tibial plateau fractures, and multi-ligament knee injuries, require prompt evaluation by an orthopedic surgeon. A thorough history and physical examination combined with radiographs are usually sufficient to diagnose these more urgent injuries. If the diagnosis remains uncertain, magnetic resonance imaging is the imaging modality of choice in diagnosing ligamentous, tendinous, meniscal, and chondral injuries. | pubmed_660_11592 |
pubmed_286_2441 | Background: Achieving and sustaining optimal glycemic control in type 2 diabetes (T2DM) is difficult because of socio-cultural and psychosocial factors including diabetes fatalism. Diabetes fatalism is 'a complex psychological cycle characterized by perceptions of despair, hopelessness, and powerlessness'. Purpose: The purpose of this paper is to explore whether diabetes fatalism and other psychosocial and socio-cultural variables are correlates of glycemic control in Lebanese population with T2DM. Methods: A convenience sample of 280 adult participants with T2DM were recruited from a major hospital in greater Beirut-Lebanon area and from the community. Diabetes fatalism was assessed using the Arabic version of 12-item Diabetes Fatalism Scale. Multiple linear regression models were used to assess the relationship between HbA1c and psychosocial and socio-cultural characteristics including diabetes fatalism. Four models were run to examine the independent association between HbA1c and diabetes fatalism and to identify which of the 3 subscales (emotional distress, spiritual coping and perceived self-efficacy) were associated with HbA1c. Results: The mean age of the participants was 58.24(SD = 13.48) and the majority were females (53.76%), while 32.73% of the sample had diabetes for more than 10 years. Fully adjusted multiple linear regression models showed that higher scores on diabetes fatalism and the emotional distress subscale (P = 0.018) were significantly associated with higher HbA1c values. In addition, having diabetes for more than 11 years (P = 0.05) and a higher number of diabetes complications (P < 0.001) were associated with higher HbA1c levels. However, advanced age (P = 0.055), female gender (P = 0.003), and diabetes education (P = 0.011) were significantly associated with lower HbA1c levels. Conclusion: This is the first study in the Arab region that identifies diabetes fatalism as an independent predictor of glycemic control among Lebanese. Future studies should further investigate this construct to guide interventions that can address it for better diabetes outcomes. | 10.1080/13557858.2017.1373075 |
pubmed_484_22031 | The results of this study confirm the importance of virus infection in nephropathy onset and progression. Virus-like inclusions were found at electron microscopy in 70 (46 children and 24 adults) of 136 total diagnostic biopsies. In another group of patients (68 adults--50 males and 18 females) with virus-like inclusions in the kidney biopsy studied electron microscopically detected 12 types of viruses observed by PCR in the tissue, present either separately or in various combinations, 2 or 3 simultaneously. The most widespread were Herpes simplex virus, adenovirus and hantovirus. Interrelationship between morphological forms of nephropathies and observed viruses is analyzed. Parvovirus B19 was observed only in FSGS/G and arteryohyalinosis. | pubmed_484_22031 |
pubmed_1065_8527 | We analyze the transport properties of a neutral tracer in a carrier fluid flowing through percolationlike porous media with spatial correlations. We model convection in the mass transport process using the velocity field obtained by the numerical solution of the Navier-Stokes and continuity equations in the pore space. We find that the resulting statistical properties of the tracer show a transition from a subdiffusion regime at low Peclet number to an enhanced diffusion regime at high Peclet number. | 10.1103/physreve.61.583 |
pubmed_383_23593 | Congenital anomalies (CAs) are structural or functional disorders that occur during intrauterine life. Longitudinal cohort studies provide unique opportunities to investigate potential causes and consequences of these disorders. In this data note, we describe how we identified cases of major CAs, with a specific focus on congenital heart diseases (CHDs), in the Avon Longitudinal Study of Parents and Children (ALSPAC). We demonstrate that combining multiple sources of data including data from antenatal, delivery, primary and secondary health records, and parent-reported information can improve case ascertainment. Our approach identified 590 participants with a CA according to the Euro Registers of Congenital Anomalies (EUROCAT) guidelines, 127 of whom had a CHD. We describe the methods that identified these cases and provide statistics on subtypes of anomalies. The data note contains details on the processes required for researchers to access these data. | 10.12688/wellcomeopenres.16339.1 |
pubmed_65_6483 | The transglutaminase (TGase) family of enzymes, of which seven different members are known in the human genome, participate in many biological processes involving cross-linking proteins into large macromolecular assemblies. The TGase 2 enzyme is known to be present in neuronal tissues and may play a role in neuronal degenerative diseases such as Alzheimer's disease (AD) by aberrantly cross-linking proteins. In this paper, we demonstrate by reverse transcriptase-polymerase chain reaction and immunological methods with specific antibodies that in fact three members, the TGase 1, TGase 2, and TGase 3 enzymes, and are differentially expressed in various regions of normal human brain tissues. Interestingly, the TGase 1 and 3 enzymes and their proteolytically processed forms are involved in terminal differentiation programs of epithelial cell development and barrier function. In addition, we found that the levels of expression and activity of the TGase 1 and 2 enzymes were both increased in the cortex and cerebellum of AD patients. Furthermore, whereas normal brain tissues contain approximately 1 residue of cross-link/10,000 residues, AD patient cortex and cerebellum tissues contain 30-50 residues of cross-link/10,000 residues. Together, these findings suggest that multiple TGase enzymes are involved in normal neuronal structure and function, but their elevated expression and cross-linking activity may also contribute to neuronal degenerative disease. | 10.1074/jbc.274.43.30715 |
pubmed_639_19449 | Corynebacterium bovis, the causative agent of hyperkeratotic dermatitis in immunodeficient mice, is a significant problem in preclinical oncology research. Infection results in lifelong skin colonization and a decrease in successful engraftment of patient-derived xenograft tumor models. The use of antimicrobial agents for C. bovis is controversial in light of reports of poor efficacy and the possibility of selection for resistant strains. The purpose of this study was to describe the antimicrobial susceptibilities of C. bovis isolates obtained exclusively from immunodeficient rodents in order to aid in antimicrobial dose determination. Between 1995 and 2018, 15 isolates were collected from 11 research institutions across the United States. Antimicrobial susceptibility testing was performed for 24 antimicrobials commonly used against gram-positive bacteria. Our results provide an updated understanding of the susceptibility profiles of rodent C. bovis isolates, indicating little variability between geographically and temporally distant isolates. These results will facilitate appropriate antimicrobial use to prevent and treat C. bovis infections in immunodeficient rodents. | 10.30802/AALAS-CM-20-000107 |
pubmed_132_23713 | BACKGROUND
Staphylococcus aureus infections are a major cause of morbidity and mortality worldwide. Clindamycin is widely used in the treatment of staphylococcal infections; however, it is our impression that in the last few years, inducible clindamycin resistance (ICR) has become more prevalent.
OBJECTIVE
To assess the prevalence of ICR in methicillin-sensitive Staphylococcus aureus (MSSA) infections among pediatric patients in Israel.
METHODS
We reviewed the files of children diagnosed with MSSA infections during the period January 2006 to June 2007 forfull antibiogram (includingthe D-test for ICR), phage typing and randomly amplified polymorphic DNA.
RESULTS
Altogether, 240 MSSA isolates were recovered, mainly from wounds and abscesses. ICR was detected in 62 of 68 erythromycin-resistant/clindamycin-sensitive strains (91%); the ICR rate for the total number of isolates was 26% (62/240). Phage type analysis demonstrated that 38 of 61 ICR isolates (62%) were sensitive to group 2, compared to 42 of 172 isolates (24%) that did not express ICR (P < 0.01). On randomly amplified polymorphic DNA, phage type 2 isolates expressing ICR belonged to the same clone, which was different from ICR isolates sensitive to other phages and from isolates not expressing ICR.
CONCLUSIONS
Inducible clindamycin resistance is common among methicillin-sensitive Staphylococcus aureus in Israeli children. The D-test should be performed routinely in all MSSA isolates. | pubmed_132_23713 |
pubmed_938_17290 | The complete nucleotide sequence of the xynA gene coding for a xylanase (XYLA) expressed by Pseudomonas fluorescens subspecies cellulosa, has been determined. The structural gene consists of an open reading frame of 1833 bp followed by a TAA stop codon. Confirmation of the nucleotide sequence was obtained by comparing the predicted amino acid sequence with that derived by N-terminal analysis of purified forms of the xylanase. The signal peptide present at the N terminus of mature XYLA closely resembles signal peptides of other secreted proteins. Truncated forms of the xylanase gene, in which the sequence encoding the N-terminal signal peptide had been deleted, still expressed coli. XYLA contains domains which are homologous to an endoglucanase expressed by the same organism. These structures include serine-rich sequences. Bal31 deletions of xynA revealed the extent to which these conserved sequences, in XYLA, were essential for xylanase activity. Downstream of the TAA stop codon is a G + C-rich region of dyad symmetry (delta G = 24 kcal) characteristic of E. coli Rho-independent transcription terminators. | 10.1111/j.1365-2958.1989.tb00271.x |
pubmed_529_19455 | INTRODUCTION
Extremely atrophic maxillae can be considered the most important indication for three-dimensional maxillary reconstruction. Different bone-augmentation techniques have been suggested to accomplish this. This article illustrates a minimally invasive approach to rehabilitation of the extremely atrophic maxilla.
MATERIAL AND METHODS
A 63-year-old male patient was referred for restoration of his totally edentulous maxilla with a fixed full-arch implant-prosthetic rehabilitation. Four short implants in the premaxillary region and 2 longer implants in the pterygomaxillary regions were inserted with piezoelectric implant site preparation.
DISCUSSION
At the 1-year follow-up appointment, no clinical or radiographic changes in the soft-tissue contours or crestal bone levels were observed.
CONCLUSION
This surgical approach, based on the combination of short implants in the premaxillary regions and pterygoid implants in the pterygomaxillary regions, represents a way to shorten treatment timing, minimize the risk of surgical complications, and reduce patient discomfort and costs. | 10.1097/ID.0000000000000603 |
pubmed_550_20535 | BACKGROUND
The aim of the present study was to investigate the clinical implication of metabolic syndrome and carotid artery morphologies on coronary plaque vulnerability in Japanese men with acute coronary syndrome (ACS).
METHODS AND RESULTS
Consecutive ACS Japanese men (n=225) underwent emergent coronary angiography and B-mode ultrasonography within 1 week of the acute coronary event. With a 11.3-MHz linear array transducer, the morphologies of common carotid artery were examined. Common carotid arteries with an intima-media thickness>1.1 mm and interadventitial diameter>8.0 mm were considered to be undergoing carotid artery remodeling. Patients were divided into 2 groups based on the number of complex plaques identified by coronary angiography. Abdominal obesity, low level of high-density lipoprotein and carotid artery remodeling were more often observed in patients with multiple, complex coronary plaques than in patients with a single, complex plaque (p<0.03, p<0.03 and p=0.0001, respectively). Metabolic syndrome and carotid artery remodeling were independent predictors of multiple, complex coronary plaques (odds ratio 1.86, p<0.05; odds ratio 5.96, p<0.0001).
CONCLUSION
Metabolic syndrome and carotid artery remodeling might be useful indicators to assess the efficacy of aggressive treatments for secondary prevention of cardiovascular events in ACS Japanese men. | 10.1253/circj.71.1229 |
pubmed_191_2851 | OBJECTIVE
To review systematically the psychosocial risk factors for poststroke depression.
METHODS
Medline was searched using the key words "poststroke depression" (PSD) for the period January 1, 1966, to June 30, 2000; using the key words "cerebrovascular disease" and "depression" it was searched from June 1, 1996, to June 30, 2000. Corollary articles were obtained from the bibliographies. Inclusion criteria were as follows: original research in French or English; prospective, case-control or cross-sectional study design; assessment of PSD in the first 6 months following the stroke; an acceptable definition of depression; an acceptable definition of stroke; and at least one psychosocial risk factor. Interrater reliability was tested for the selection and quality of the articles. A qualitative risk factor analysis was conducted.
RESULTS
The risk factors most consistently associated with PSD are a past history of depression, past personal psychiatric history, dysphasia, functional impairments, living alone, and poststroke social isolation. Risk factors not associated with PSD are dementia and cognitive impairment. Controversial risk factors are age, socioeconomic status (SES), prior social distress, dependency in regard to activities of daily living (ADL), and sex.
CONCLUSIONS
Over approximately 30 years, some 25 qualitative studies have addressed psychosocial risk factors for PSD. Further studies should aim for quantitative analysis. The results suggest that identifying psychiatric history and preventing social deterioration and impairment should be part of multidisciplinary efforts to care for poststroke patients. | 10.1177/070674370104600905 |
pubmed_989_13859 | Individual growth rates are intrinsically related to survival and lifetime reproductive success and hence, are key determinants of population growth. Efforts to quantify age-size relationships are hampered by difficulties in aging individuals in wild populations. In addition, species with complex life-histories often show distinct shifts in growth that cannot be readily accommodated by traditional modelling techniques. Amphibians are often characterized by rapid larval growth, cessation of growth prior to metamorphosis, and resumption of growth in the adult stage. Compounding issues of non-linear growth, amphibian monitoring programs typically sample larval and adult populations using dissimilar methods. Here we present the first multistage growth model that combines disparate data collected across life-history stages. We model the growth of the endangered Reticulated Flatwoods Salamander, Ambystoma bishopi, in a Bayesian framework, that accounts for unknown ages, individual heterogeneity, and reconciles dip-net and drift fence sampling designs. Flatwoods salamanders achieve 60% of growth in the first 3 months of life but can survive for up to 13 years as a terrestrial adult. We find evidence for marked variability in growth rate, the timing and age at metamorphosis, and maximum size, within populations. Average size of metamorphs in a given year appeared strongly dependent on hydroperiod, and differed by >10mm across years with successful recruitment. In contrast, variation in the sizes of emerging metamorphs appeared relatively constant across years. An understanding of growth will contribute to the development of population viability analyses for flatwoods salamanders, will guide management actions, and will ultimately aid the recovery of the species. Our model formulation has broad applicability to amphibians, and likely any stage-structured organism in which homogenous data cannot be collected across life-stages. The tendency to ignore stage-structure or omit non-conforming data in growth analyses can no longer be afforded given the high stakes of management decisions, particularly for endangered or at-risk populations. | 10.1371/journal.pone.0237737 |
pubmed_1089_21005 | Benthic marine dioflagellate microalgae belonging to the genus Prorocentrum are a major source of okadaic acid (OA), OA analogues and polyketides. However, dinoflagellates produce these valuable toxins and bioactives in tiny quantities, and they grow slowly compared to other commercially used microalgae. This hinders evaluation in possible large-scale applications. The careful selection of producer species is therefore crucial for success in a hypothetical scale-up of culture, as are appropriate environmental conditions for optimal growth. A clone of the marine toxic dinoflagellate P. belizeanum was studied in vitro to evaluate its capacities to grow and produce OA as an indicator of general polyketide toxin production under the simultaneous influence of temperature (T) and irradiance (I0). Three temperatures and four irradiance levels were tested (18, 25 and 28 °C; 20, 40, 80 and 120 µE·(m-2)·s(-1)), and the response variables measured were concentration of cells, maximum photochemical yield of photosystem II (PSII), pigments and OA. Experiments were conducted in T-flasks, since their parallelepipedal geometry proved ideal to ensure optically thin cultures, which are essential for reliable modeling of growth-irradiance curves. The net maximum specific growth rate (µ(m)) was 0.204 day(-1) at 25 °C and 40 µE·(m-2)·s(-1). Photo-inhibition was observed at I0 > 40 μEm(-2)s(-1), leading to culture death at 120 µE·m(-2)·s(-1) and 28 °C. Cells at I0 ≥ 80 µE·m(-2)·s(-1) were photoinhibited irrespective of the temperature assayed. A mechanistic model for µ(m)-I0 curves and another empirical model for relating µ(m)-T satisfactorily interpreted the growth kinetics obtained. ANOVA for responses of PSII maximum photochemical yield and pigment profile has demonstrated that P. belizeanum is extremely light sensitive. The pool of photoprotective pigments (diadinoxanthin and dinoxanthin) and peridinin was not able to regulate the excessive light-absorption at high I0-T. OA synthesis in cells was decoupled from optimal growth conditions, as OA overproduction was observed at high temperatures and when both temperature and irradiance were low. T-flask culture observations were consistent with preliminary assays outdoors. | 10.3390/toxins6010229 |
pubmed_103_14416 | The secretion of antimicrobial compounds is an ancient mechanism with clear survival benefits for microbes competing with other microorganisms. Consequently, mechanisms that confer resistance are also ancient and may represent an underestimated reservoir in environmental bacteria. In this context, β-lactamases (BLs) are of great interest due to their long-term presence and diversification in the hospital environment, leading to the emergence of Gram-negative pathogens that are resistant to cephalosporins (extended spectrum BLs = ESBLs) and carbapenems (carbapenemases). In the current study, protein sequence databases were used to analyze BLs, and the results revealed a substantial number of unknown and functionally uncharacterized BLs in a multitude of environmental and pathogenic species. Together, these BLs represent an uncharacterized reservoir of potentially transferable resistance genes. Considering all available data, in silico approaches appear to more adequately reflect a given resistome than analyses of limited datasets. This approach leads to a more precise definition of BL clades and conserved motifs. Moreover, it may support the prediction of new resistance determinants and improve the tailored development of robust molecular diagnostics. | 10.1038/srep43232 |
pubmed_321_703 | Prolonged severe lymphopenia has been shown to persist beyond a year in glioma patients after radiation therapy (RT) with concurrent and adjuvant chemotherapy. This study examines the differential impact of concurrent versus adjuvant chemotherapy on lymphopenia after RT. WHO grade II-III glioma patients who received RT with concurrent and/or adjuvant chemotherapy from 2007 to 2016 were retrospectively analyzed. Concurrent chemotherapy was temozolomide (TMZ), and adjuvant chemotherapy was either TMZ or procarbazine/lomustine/vincristine (PCV). Absolute lymphocyte count (ALC) was analyzed at baseline, 1.5, 3, 6, and 12 months after the start of RT. Univariable and multivariable logistic regression were used to identify the clinical variables in predicting acute or late lymphopenia. There were 151 patients with evaluable ALC: 91 received concurrent and adjuvant TMZ (CRT + ADJ), 32 received only concurrent TMZ (CRT), and 28 received only adjuvant TMZ or PCV (ADJ). There were 9 (10%) versus 6 (19%) versus 0 (0%) cases of grade 3 lymphopenia (ALC < 500/mm3) at 6 weeks and 4 (6%) versus 0 (0%) versus 3 (17%) cases at 12 months in CRT + ADJ, CRT and ADJ groups, respectively. On multivariable analyses, concurrent chemotherapy (odds ratio [OR] 72.3, p < 0.001), female sex (OR 10.8, p < 0.001), and older age (OR 1.06, p = 0.002) were the most significant predictors for any grade ≥ 1 lymphopenia (ALC < 1000/mm3) at 1.5 months. Older age (OR 1.08, p = 0.02) and duration of adjuvant chemotherapy (OR 1.19, p = 0.003) were significantly associated with grade ≥ 1 lymphopenia at 12 months. Thus, concurrent chemotherapy appears as the dominant contributor to the severity of acute lymphopenia after RT in WHO grade II-III glioma patients, and duration of adjuvant chemotherapy appears as the key factor to prolonged lymphopenia. | 10.1007/s11060-017-2668-5 |
pubmed_960_7535 | This is the second of two articles exploring the meaning of 'evidence-based practice'. The first, in last month's issue, considered what is meant by 'evidence'. This month, Jan Draper examines how literature reviews can help nurses make sense of the variety of evidence available to them. | 10.7748/nop2004.10.16.7.28.c2334 |
pubmed_202_15118 | BACKGROUND
Sutureless cataract surgery has recently increased in popularity because of the rapid visual rehabilitation and the inherent reduction of surgically induced astigmatism.
METHODS
This procedure is dependent on a lamellar, multiplaned incision. As with new surgical techniques, associated complications become evident with time. Recently, there have been several cases of infectious endophthalmitis after this procedure. The authors report on nine cases of sterile endophthalmitis. In all nine cases, surgery was performed with refrigerated balanced salt solution (BSS) and 100 mg of cefazolin and/or 20 mg of methylprednisolone sodium succinate, given subconjunctivally, at its completion.
RESULTS
All nine cases occurred in a period of time during which 68 cases were performed using refrigerated BSS for irrigation. These nine cases came from two different surgeons using basically the same surgical technique. After the investigation of these complications, the refrigerated BSS was discontinued, and there have been no episodes of sterile endophthalmitis in the last 650 cases.
CONCLUSION
It appears that refrigerated BSS should be avoided if periocular injections are going to be used. It may be that the cold BSS fails to allow sufficient tissue swelling to seal the surgical incision, allowing for subconjunctival injections to seep into the wound, and leading to a sterile endophthalmitis. | 10.1016/s0161-6420(92)31748-8 |
pubmed_591_14240 | PURPOSE
Several single nucleotide polymorphisms (SNPs) have been reported to be associated with clinicopathological profiles in sporadic breast cancer based on studies conducted on major population groups. The knowledge of the effects of these common genetic variants in South Asian populations remains limited. The present study aimed to investigate the association between a selected set of SNPs and the clinicopathological profiles in sporadic breast cancer in Sri Lankan women.
METHODS
A total of 350 postmenopausal women with histologically confirmed invasive breast cancer were genotyped for 58 SNPs located in 36 breast cancer related genes. The clinicopathological factors that were investigated included age of onset, tumor histologic grade, and lymph node involvement, as well as estrogen receptor (ER), progesterone receptor, and human epidermal growth factor receptor 2 (HER2) status. Association testing was performed using logistic regression models adjusted for confounding factors.
RESULTS
Seven SNPs showed significant associations with clinicopathological profiles in breast cancer. The G allele of BRCA1:rs799917 (p=0.047; β [standard error; SE]=-1.069 [0.537]) and the G allele of NQO2:rs17136117 (p=0.040, β [SE]=1.901 [0.923]) were found to be associated with age of onset between 50 and 59 years. The C allele of CDH1:rs13689 (odds ratio [OR], 2.121; p=0.033) was found to be associated with ER-positive breast cancer. The A allele of AKT1:rs1130214 (OR, 2.095; p=0.011) and the C allele of NQO2:rs2071002 (OR, 1.632; p=0.045) were associated with HER2-positive breast cancer. The C allele of BRCA2:rs15869 (OR, 1.600; p=0.041) and the C allele of CCND1:rs7177 (OR, 1.555; p=0.041) were associated with high tumor histologic grade.
CONCLUSION
The common genetic variants identified in the AKT1, BRCA1, BRCA2, CCND1, CDH1, and NQO2 genes could serve as potential clinical and prognostic biomarkers in sporadic breast cancer patients. Further studies are required to validate our current findings in other populations. | 10.4048/jbc.2018.21.2.165 |
pubmed_1034_4435 | Initial staging is a key part of the initial evaluation of non-small cell lung cancer. It relies on the 7th edition of the TNM classification. Proposals have been recently developed for the 8th edition of the classification, which is due to be enacted in early 2017. Among these proposals, the weight of tumor size has been increased and new N descriptors have been introduced to further describe N category depending on the number station involved. Regarding M descriptors, oligometastatic disease is distinguished from multiple distant extrathoracic metastases. | 10.1016/j.pneumo.2016.12.006 |
pubmed_1070_13730 | OBJECTIVE
To establish a rabbit model bearing endometrial carcinoma and observe the magnetic resonance imaging (MRI) features of the metastatic lymph nodes.
METHODS
VX(2) tumor grafts were orthotopically embedded into the endometrium of the rabbits. Three weeks after the implantation, the tumor and the metastatic retroperitoneal lymph nodes were examined with MRI, and the signal intensities and the size of the lymph nodes were compared with those in normal rabbits.
RESULTS
Orthotopic tumor growth was observed in all the rabbits. Tumor infiltration of the serosa and retroperitoneal lymph node metastasis occurred 3 weeks after tumor implantation. MRI demonstrated obviously lymph node enlargement in the tumor-bearing rabbits as compared with those of normal rabbits, while the signal intensity of the lymph nodes were comparable between them.
CONCLUSION
The endometrial carcinoma in this rabbit model well simulate the metastatic behavior of human endometrial carcinoma, and may serve as a good model for testing the efficacy of the contrast agents for MRI of the lymph nodes. | pubmed_1070_13730 |
pubmed_695_8560 | The development of antibiotic resistant in K. pneumoniae is an emerging thread worldwide due to the poor antimicrobial drugs. To overcome this issue, researchers are focused on plant material and their essential oils to fight against multi drug resistant bacteria. In this context, the current study was concentrated in medicinal plant of guva leaves and their essential oils to combat multi drug resistant bacterial infections. The essential oils were successfully screened and confirmed by HRLC-MS analysis. The anti-bacterial ability of the compounds were loaded into the chitosan nanoparticles and proved by FT-IR analysis. In addition, the chitosan loaded essential oils morphology was compared with chitosan alone in SEM analysis and suggested that the material was loaded successfully. Further, the anti-bacterial ability of the chitosan loaded essential oils were primarily confirmed by agar well diffusion method. At the 100 µg/mL of lowest concentration of chitosan loaded essential oils, the multi-drug resistant K. pneumoniae was inhibited with 96% and confirmed by minimum inhibition concentration experiment. Hence, all the experiments were proved that the essential oils were successfully loaded into the chitosan nanoparticles, and it has more anti-bacterial activity against multi-drug resistant K. pneumoniae. | 10.1016/j.sjbs.2020.09.025 |
pubmed_1044_17733 | PURPOSE OF REVIEW
The occurrence of cases of scrub typhus is on the rise in South Asian and Southeast Asian countries. The present review discusses neurological complications following scrub typhus to appraise clinicians practicing in endemic regions about considering this treatable disease in the differential diagnosis of acute febrile illnesses, especially when accompanied with clinical neurological features.
RECENT FINDINGS
While the association of aseptic meningitis, encephalitis, and meningoencephalitis with scrub typhus is well known, more recently described neurological syndromes associated with scrub typhus include acute disseminated encephalomyelitis, various cranial nerve palsies, cerebellitis, cerebrovascular diseases including cerebral venous sinus thrombosis, transverse myelitis, longitudinally extensive transverse myelitis, Guillain-Barré syndrome, opsoclonus-myoclonus syndrome, parkinsonism, and many more. Early diagnosis is key to successful treatment. While diagnostic confirmation is generally made by the detection of IgM antibody by either ELISA or indirect fluorescent antibody tests, conventional PCR using 56 kDa gene (cPCR) and loop-mediated isothermal amplification assay (LAMP assay), as well as a newly introduced metagenomic next-generation sequencing (mNGS), are currently available for detection of Orientia tsutsugamushi infection in clinically suspected cases. Scrub typhus is an acute febrile illness caused by Orientia tsutsugamushi. The cutaneous hallmark of the disease is the "eschar." Scrub typhus results in multisystem involvement. Neurological compromise is present in about 20% of scrub typhus patients and affects both the central nervous system and the peripheral nervous system. The postulated underlying mechanisms include direct invasion of the organism, a vasculitis-like process, or an immune-mediated injury. Diagnosis of scrub typhus is confirmed by detection of O. tsutsugamushi IgM antibody in serum. Awareness among clinicians regarding the varied presentations of this disease is very important in order to reduce morbidity and mortality. Co-infection with dengue and/or chickungunya viruses may occur in endemic regions. The history of an acute febrile illness preceding the neurological illness is crucial. A very careful search for the eschar is essential; however, the absence of the skin lesion cannot exclude the diagnosis of scrub typhus. Neurological manifestations mostly respond to doxycycline therapy. | 10.1007/s11910-022-01215-5 |
pubmed_756_24598 | BACKGROUND
Current models theorize that affective temperaments underlie the development and expression of mood psychopathology. Recent studies support the construct validity of affective temperaments in clinical and non-clinical samples. However, one concern is that affective temperaments may be describing characteristics that are better captured by models of normal personality. We conducted two studies examining: (a) the association of affective temperaments with domains and facets of normal personality, and (b) whether affective temperaments accounted for variance in mood symptoms and disorders, impairment, and daily-life experiences over-and-above variance accounted for by normal personality.
METHODS
Study 1 included 522 young adults who completed the TEMPS-A and the NEO-PI-3. Study 2 included 145 participants who were administered the TEMPS-A, NEO-FFI, interviews assessing psychopathology and impairment, and an assessment of daily life experiences.
RESULTS
Study 1 revealed that personality domains and facets accounted for one-third to one-half of the variance in affective temperaments. However, study 2 demonstrated that affective temperaments accounted for unique variance in measures of psychopathology, impairment, and daily-life experiences after partialling variance associated with personality domains. Specifically, cyclothymic/irritable temperament predicted bipolar disorders, impairment, borderline personality traits, urgency, and anger in daily life. Hyperthymic temperament predicted hypomanic episodes, grandiosity, sensation seeking, and increased activity in daily life.
LIMITATIONS
The study was limited by the fact that only domain, not facet-level, measures of FFM were available in study 2.
CONCLUSIONS
The findings support the validity of hyperthymic and cyclothymic/irritable temperaments as indicators of clinical psychopathology and indicate that they provide information beyond normal personality. | pubmed_756_24598 |
pubmed_822_4045 | Approximately 40-60% of people with multiple sclerosis (MS) have memory problems, which adversely impact on their everyday functioning. Evidence supports the use of external memory aids in people with stroke and brain injury, and suggests they may reduce everyday memory problems in people with MS. Previous reviews of people with MS have only evaluated randomised trials; therefore this review included other methodologies. The aim was to assess the efficacy of external memory aids for people with MS for improving memory functioning, mood, quality of life, and coping strategies. Seven databases were systematically searched. Intervention studies that involved training in the use of external memory aids, e.g., personal digital assistants, with at least 75% of people with MS, were included. Based on study design, quality was rated with the SCED or PEDro scale. Nine studies involving 540 participants were included. One single case experimental design (mean of 8 on SCED scale) and eight group studies (mean of 5 on PEDro scale) were included. One study reported a significant treatment effect on subjective memory functioning, two on mood, and two on coping strategies. There is insufficient evidence to support or refute the effectiveness of external memory aids for improving memory function in people with MS. | 10.1080/09602011.2015.1113997 |
pubmed_240_17731 | BACKGROUND
After the impressive response of rectal cancers to neoadjuvant therapy, it seems reasonable to ask: can we can excise the small ulcer locally or avoid a radical resection if there is no gross residual tumor? Does gross response reflect what happens to tumor cells microscopically after radiation?
OBJECTIVE
The aim of this study was to identify microscopic tumor cell response to radiation.
DESIGN
This study is a retrospective review of a prospectively collected database.
SETTING
This investigation was conducted at a single tertiary medical center.
PATIENTS
Patients were selected who had elective radical resection for rectal cancer after preoperative chemotherapy and radiation performed by 2 colorectal surgeons between 2006 and 2011.
MAIN OUTCOME MEASURES
The primary outcome measured was tumor presence after radiation therapy
RESULTS
Of the 75 patients, 20 patients were complete responders and 55 had residual cancer. Of these patients, 28 had no tumor cells seen outside the gross ulcer, and 27 (49.1%) had tumor outside the visible ulcer or microscopic tumor present with no overlying ulcer. Of these tumors, 81.5% were skewed away from the ulcer center. The mean distance of distal scatter was 1.0 cm from the visible ulcer edge to a maximum of 3 cm; 3 patients had tumor cells more than 2 cm distal to the visible ulcer edge. Tumor scatter outside the ulcer was not associated with poor prognostic factors, such as nodal and distant disease, perineural invasion, or mucin; however, it was associated with lymphovascular invasion (χ2 = 4.12, p = 0.038)
LIMITATIONS
There was limited access to clinical information gathered outside our institution.
CONCLUSIONS
Our study suggests that 1) after radiation, the gross ulcer cannot be used to determine the sole area of potential residual tumor, 2) cancer cells may be found up to 3 cm distally from the gross ulcer, so the traditional 2-cm margin may not be adequate, and 3) local excision of the ulcer or no excision after apparent complete response appears to be insufficient treatment for rectal cancer. | 10.1097/DCR.0b013e318269fdb3 |
pubmed_540_2501 | Objective.Brain-machine interfaces (BMIs) translate neural activity into motor commands to restore motor functions for people with paralysis. Local field potentials (LFPs) are promising for long-term BMIs, since the quality of the recording lasts longer than single neuronal spikes. Inferring neuronal spike activity from population activities such as LFPs is challenging, because LFPs stem from synaptic currents flowing in the neural tissue produced by various neuronal ensembles and reflect neural synchronization. Existing studies that combine LFPs with spikes leverage the spectrogram of the former, which can neither detect the transient characteristics of LFP features (here, neuromodulation in a specific frequency band) with high accuracy, nor correlate them with relevant neuronal activity with a sufficient time resolution.Approach.We propose a feature extraction and validation framework to directly extract LFP neuromodulations related to synchronized spike activity using recordings from the primary motor cortex of six Sprague Dawley rats during a lever-press task. We first select important LFP frequency bands relevant to behavior, and then implement a marked point process (MPP) methodology to extract transient LFP neuromodulations. We validate the LFP feature extraction by examining the correlation with the pairwise synchronized firing probability of important neurons, which are selected according to their contribution to behavioral decoding. The highly correlated synchronized firings identified by the LFP neuromodulations are fed into a decoder to check whether they can serve as a reliable neural data source for movement decoding.Main results.We find that the gamma band (30-80 Hz) LFP neuromodulations demonstrate significant correlation with synchronized firings. Compared with traditional spectrogram-based method, the higher-temporal resolution MPP method captures the synchronized firing patterns with fewer false alarms, and demonstrates significantly higher correlation than single neuron spikes. The decoding performance using the synchronized neuronal firings identified by the LFP neuromodulations can reach 90% compared to the full recorded neuronal ensembles.Significance.Our proposed framework successfully extracts the sparse LFP neuromodulations that can identify temporal synchronized neuronal spikes with high correlation. The identified neuronal spike pattern demonstrates high decoding performance, which suggest LFP can be used as an effective modality for long-term BMI decoding. | 10.1088/1741-2552/ac86a3 |
pubmed_906_17458 | In animal models of asthma, interleukin-13 (IL-13) induces goblet cell metaplasia, eosinophil infiltration of the bronchial mucosa, and bronchial hyperreactivity, but the basis of its effects on airway epithelia remain unknown. Lesions of the epithelial barrier, frequently observed in asthma and other chronic lung inflammatory diseases, are repaired through proliferation, migration, and differentiation of epithelial cells. An inflammatory process may then, therefore, influence epithelial regeneration. We have thus investigated the effect of IL-13 on mucociliary differentiation of human nasal epithelial cells in primary culture. We show that IL-13 alters ciliated cell differentiation and increases the proportion of secretory cells. IL-13 downregulates the actin-binding protein ezrin and other cytoskeletal components. IL-13 also impairs lateral cell contacts and interferes with the apical localization of ezrin seen in differentiated ciliated cells. In addition, an IL-4 antagonistic mutant protein (Y124D), which binds to the IL-4 receptor alpha subunit, a common chain of IL-4 and IL-13 receptors, inhibits IL-13's effects. IL-13 also decreases ciliary beat frequency in a time- and dose-dependent manner. These results suggest that, in human allergic asthmatic responses, IL-13 affects both ciliated and secretory cell differentiation, leading to airway damage and obstruction. | 10.1172/JCI13557 |
pubmed_1032_9167 | The great challenge in preparing a biomimetic enzyme sensor is to have sensitivity and selectivity equal to or better than its corresponding biological sensor. Porous electrodes possess a large surface area and are often used to greatly improve the sensor sensitivity. However, how to tailor the pore structure, especially the pore size distribution to further improve the sensitivity and selectivity of a biomimetic sensor, has not been investigated yet. The superoxide anion (O2˙-) plays essential roles in various biological processes and is of importance in clinical diagnosis and life science research. It is generally detected by the superoxide dismutase enzyme. Herein, we delicately tailor the pore structure of carbon nanofibers (CNFs) by pyrolysis to obtain an optimal mesopore structure for strong adsorption of DNA, followed by guiding the growth of Mn3(PO4)2 as a biomimetic enzyme toward highly sensitive detection of O2˙-. The Mn3(PO4)2-DNA/CNF sensor achieves the best sensitivity among the reported O2˙- sensors while possessing good selectivity. The enhancement mechanism is also investigated, indicating that the mesopore ratio of CNFs plays an essential role in the high sensitivity and selectivity due to their strong adsorption of DNA for guiding the growth of a large amount of uniform sensing components, Mn3(PO4)2, toward high sensitivity and selectivity. The biomimetic sensor was further used to in situ monitor O2˙- released from human keratinocyte cells and human malignant melanoma cells under drug stimulation, showing high sensitivity to real-time quantitative detection of O2˙-. This work provides a highly sensitive in situ real-time biomimetic O2˙- sensor for applications in biological research and diagnosis, while shedding light on the enhancement mechanism of the pore structure, especially the pore size distribution of a porous electrode for high performance sensing processes. | 10.1039/c8nr08829b |
pubmed_348_4952 | BACKGROUND
Incipient Alzheimer's disease (AD) is frequently suspected by neurologists and psychiatrists, but diagnosis is difficult to establish. The aim of this report was to analyse to what extent suspicion is confirmed by a comprehensive neuropsychological examination intended to distinguish different types of dementia.
METHODS
Descriptive data analysis was used for investigating the differential diagnoses of 47 outpatients with suspected AD referred to a department of neuropsychology by physicians in private practice. Data analysis was based upon the NINCDS-ADRDA diagnostic criteria of AD.
RESULTS
Only 38% of the outpatients examined with suspected AD met the NINCDS-ADRDA diagnostic criteria for AD or mixed dementia from a neuropsychological point of view, whereas 22% met criteria for other types of dementia. The remaining patients met criteria for distinct differential diagnoses (23%) or lacked pathological findings in neuropsychological functions (17%).
CONCLUSIONS
Neuropsychology is an essential part in the differential diagnosis of mild to moderate dementias. It can aid in differential therapeutic considerations concerning the treatment of dementia, for example in selecting appropriate treatments or avoiding expensive but inappropriate ones. | 10.1007/s00115-007-2384-z |
pubmed_419_21516 | PURPOSE
Urothelial carcinoma has a higher incidence in renal transplanted patients according to several registries (relative risk × 3), and the global prognosis is inferior to the general population. The potential impact of immunosuppressive therapy on the feasibility, efficacy, and complications of endovesical treatment, especially Bacillus Calmette-Guerin, has a low level of evidence. We performed a systematic review that aimed to assess the morbidity and oncological outcomes of adjuvant endovesical treatment in solid organ transplanted patients.
METHODS
Medline was searched up to December 2021 for all relevant publications reporting oncologic outcomes of endovesical treatment in solid organ transplanted patients with NMIBC. Data were synthesized in light of methodological and clinical heterogeneity.
RESULTS
Twenty-three retrospective studies enrolling 238 patients were included: 206 (96%) kidney transplants, 5 (2%) liver transplants, and 2 (1%) heart transplants. Concerning staging: 25% were pTa, 62% were pT1, and 22% were CIS. 140/238 (59%) patients did not receive adjuvant treatment, 50/238 (21%) received mitomycin C, 4/238 (2%) received epirubicin, and 46/238 (19%) received BCG. Disease-free survival reached 35% with TURBT only vs. 47% with endovesical treatment (Chi-square test p = 0.08 OR 1.2 [0.98-1.53]). The complication rate of endovesical treatment was 12% and was all minor (Clavien-Dindo I).
CONCLUSION
In solid organ transplanted patients under immunosuppressive treatment, both endovesical chemotherapy and BCG are safe, but the level of evidence concerning efficacy in comparison with the general population is low. According to these results, adjuvant treatment should be proposed for NMIC in transplanted patients as in the general population. | 10.1007/s00345-022-04188-9 |
pubmed_1111_10078 | The influence of host and parasite-related factors on the strongyle infection in 50 horses coming from 6 European countries and slaughtered in Italy for meat production was investigated using a multivariable modelling approach. The study was carried out by examining adult helminths, faecal eggs (identified by culture to the third larval stage) and mucosal larval stages of Cyathostominae. A modified Transmural Illumination technique (TMI) has been performed and Cyathostominae empty mucosal cysts were also evaluated in order to obtain further indications about small strongyles dynamic. All species found in this study were previously reported in European horses. Major differences were detected comparing Hungarian (#24) and Italian (#13) horses. Sex was confirmed as uninfluential, while relations with host age were only partially consistent with the development of acquired resistance. The analysis of both mucosal Cyathostominae larvae (more in Italy) and of the percentage of empty cysts (higher in Hungary) along with lower large strongyle abundance in Hungary allowed to hypothesise a wider use of anthelmintic treatments in Hungarian horses compared to Italian ones. The results regarding adult Cyathostominae (no significant differences nor regarding age or origin) suggested the important role of ecological interactions between larval and adult stages in regulating small strongyle populations. | 10.1016/j.vetpar.2011.02.024 |
pubmed_335_1428 | The World Health Organization has rated multidrug-resistant (MDR) Gram-negative bacteria including Pseudomonas aeruginosa (Psae) as serious threat to human health. We here addressed whether chronic murine gut inflammation facilitates intestinal MDR Psae colonization and whether bacterial infection subsequently worsens colonic immunopathology. Converse to wildtype counterparts, Psae colonized the intestines of IL-10-/- mice with chronic colitis following peroral challenge, but did not lead to changes in intestinal microbiota composition. Psae infection accelerated both macroscopic (i.e. clinical) and microscopic disease (i.e. colonic epithelial apoptosis), that were accompanied by increased intestinal pro-inflammatory immune responses as indicated by elevated colonic numbers of innate and adaptive immune cell subsets and enhanced secretion of pro-inflammatory cytokines such as TNF and IFN-γ in mesenteric lymph nodes of Psae-infected as compared to unchallenged IL-10-/- mice. Remarkably, Psae-induced pro-inflammatory immune responses were not restricted to the gut, but could also be observed systemically as indicated by increased TNF and IFN-γ concentrations in sera upon Psae-infection. Furthermore, viable commensals originating from the intestinal microbiota translocated to extra-intestinal compartments such as liver, kidney and spleen of Psae-infected IL-10-/- mice with chronic colitis only. Hence, peroral MDR Psae-infection results in exacerbated colonic as well as systemic pro-inflammatory immune responses during chronic murine colitis. | 10.1038/s41598-018-25034-2 |
pubmed_93_21456 | INTRODUCTION
All approved antipsychotic drugs share an affinity for the dopamine 2 (D(2)) receptor; however, these drugs only partially ameliorate the symptoms of schizophrenia. It is, therefore, of paramount importance to identify new treatment strategies for schizophrenia.
AREAS COVERED
Preclinical, clinical and post-mortem studies of the serotonin 5-HT(2A) system in schizophrenia are reviewed. The implications of a combined D(2) and 5-HT(2A) receptor blockade, which is obtained by several current antipsychotic drugs, are discussed, and the rationale for the development of more selective 5-HT(2A) receptor antagonists is evaluated. Moreover, the investigational pipeline of major pharmaceutical companies is examined and an Internet search conducted to identify other pharmaceutical companies investigating 5-HT(2A) receptor antagonists for the treatment of schizophrenia.
EXPERT OPINION
5-HT(2A) receptor antagonists appear to assume an intermediate position by being marginally superior to placebo but inferior to conventional antipsychotic drugs. Three previous 5-HT(2A) receptor antagonists have been discontinued after Phase II or III trials, and available Phase IIa data on the remaining 5-HT(2A) receptor antagonist will need substantial additional validation to be approved as a new treatment strategy against schizophrenia. | 10.1517/13543784.2011.601738 |
pubmed_219_20293 | The goal of this teaching case study is to demonstrate the novel use of (99m)Tc-HMPAO-labeled white blood cells (WBCs) in diagnosing chronic recurrent multifocal osteomyelitis (CRMO). (99m)Tc-HMPAO-labeled white blood cells were utilized to diagnose CRMO. Classically, CRMO is evaluated scintigraphically using (99m)Tc-methylene diphosphonate/hydroxymethylene diphosphonate. (99m)Tc-HMPAO-labeled WBCs were chosen over (111)In-labeled WBCs because of the former's improved imaging characteristics and decreased radiation dose. (99m)Tc-HMPAO-labeled WBCs were successful in diagnosing CRMO. (99m)Tc-HMPAO-labeled WBC scanning is specific for the diagnosis of CRMO. | 10.2967/jnmt.114.138073 |
pubmed_857_20033 | CHA1 of Saccharomyces cerevisiae is the gene for the catabolic L-serine (L-threonine) dehydratase, which is responsible for biodegradation of serine and threonine. We have previously shown that expression of the CHA1 gene is transcriptionally induced by serine and threonine. Northern (RNA) analysis showed that the additional presence of good nitrogen sources affects induction. This may well be due to inducer exclusion. To identify interactions of cis-acting elements with trans activators of the CHA1 promoter, we performed band shift assays of nuclear protein extracts with CHA1 promoter fragments. By this approach, we identified a protein-binding site of the CHA1 promoter. The footprint of this protein contains the ABF1-binding site consensus sequence. This in vitro binding activity is present irrespectively of CHA1 induction. By deletion analysis, two other elements of the CHA1 promoter, UAS1CHA and UAS2CHA, which are needed for induction of the CHA1 gene were identified. Each of the two sequence elements is sufficient to confer serine and threonine induction upon the CYC1 promoter when substituting its upstream activating sequence. Further, in a cha4 mutant strain which is unable to grow with serine or threonine as the sole nitrogen source, the function of UAS1CHA, as well as that of UAS2CHA, is obstructed. | 10.1128/mcb.13.12.7604-7611.1993 |
pubmed_476_5805 | OBJECTIVES
To explore communication and engagement in everyday situations between persons with young-onset dementia (YOD) living in a nursing home (NH) and the caregivers.
METHODS
The study draws on ethnographic methods aligned with participatory design. Three residents with YOD living in a NH and eight staff members were recruited. A narrative approach was used for data collection and analysis.
FINDINGS
Three narrative vignettes were developed representing everyday situations in which communication and engagement was enacted among residents and caregiver staff: (a) waiting for something to happen, (b) tensions about everyday communication, and (c) negotiating a combined living + working environment. The findings stress a paradoxical tension rooted in the NH as residence and workplace as well as place of calm and place of boredom. The everyday situations are interpreted differently from the perspective of the residents and staff.
CONCLUSION
The identified paradox of planned and spontaneous situations influences communication and engagement in everyday life, and the potentiality for active engagement embedded in contexts of units for residents with YOD. The degree to which everyday activities and encounters are redefined and renegotiated is an important part of caregiving practices in NH settings for residents with YOD. | 10.1080/17482631.2022.2035305 |
pubmed_68_18968 | Because of their chronic nature treatment of oral vesiculoerosive diseases remains a challenge to the oral medicine specialist. Even though oral vesiculoerosive diseases respond well to systemic steroids, adverse side effects sometimes limit their use. Potent topical steroids are becoming increasingly useful to treat these chronic conditions with good control. The purpose of this double-blind clinical trial was to compare clobetasol propionate and fluocinonide ointment in orabase as treatments for controlling oral vesiculoerosive diseases. Sixty patients were asked to participate (43 women and 17 men). Data are reported for 55 patients. Each patient was seen at baseline and at days 7, 14, 21, and 28. Variables evaluated were pain, erythema, atrophy, and size of lesion. Overall, both medications had a beneficial effect in the control of symptoms and signs of oral vesiculoerosive diseases with minimal side effects. Clobetasol propionate was better than fluocinonide as measured by more rapid control of pain (within 7 days). Candidiasis was observed in 13 patients at the end of treatment (most of them carriers of Candida). Therefore normal carriers should be identified and treatment with antifungal therapy instituted before the patient begins using topical steroids. | 10.1016/0030-4220(94)90318-2 |
pubmed_1015_10568 | A protocol for antepartum supervision which included "non stress fetal monitoring" (NSFM) and the "oxytocin Challenge Test" (OCT) was followed in a series of 640 high-risk pregnancies. The perinatal mortality in this group was compared with that obtained in a group of 3,049 non-selected deliveries which occurred during the same period of time and which were not monitored in the same way. The perinatal mortality which could be attributed to placental insufficiency in the first group (the supervised group) was at 4.68 per 1000, about half that of the non-supervised group (8.72 per 1000) in spite of the low number of high risk cases in the second group. When NSFM was normal in the week before delivery there was no single perinatal death due to placental insufficiency. When the NSFM was normal and the OCT was pathological the OCT Test was probably wrong. When the NSFM test was non-reactive placental insufficiency could be predicted in only 28 per cent of the cases although a combination of NSFM with a positive OCT Test predicted correctly 91.3 per cent of the cases of placental insufficiency. We consider that there is fetal distress due to placental insufficiency when having found signs indicative of fetal distress in delivery (a pH of less than 7.25, recent passage of meconium, the Apgar score less than 7 in the first minute, and pathological fetal heart rhythm (RFC) we can find no other cause to explain the signs such as a short cord, prematurity, obstetrical trauma, prolonged pregnancy and malformations, etc. | pubmed_1015_10568 |
pubmed_100_20634 | Activated macrophages at wound sites release many cytokines which positively affect skin wound healing. However, the molecular mechanisms controlling cytokine secretion from macrophages have not been elucidated. In the present study, we performed an RT-PCR analysis and found that 19 small GTPase Rab isoforms were expressed at skin wound sites, with six of them (i.e. Rab3B, Rab27B, Rab30, Rab33A, Rab37, and Rab40C) being upregulated during the inflammation and proliferation/migration phase of skin repair. We also found that gene expression of Rab37 in murine primary and RAW264.7 macrophages was significantly induced after stimulation with LPS. Overexpression of wild type and constitutively active Rab37 in RAW264.7 cells significantly increased TNF-α secretion, whereas knockdown of Rab37 by siRNA significantly decreased it. We also identified 29 putative Rab37-interacting proteins, including the membrane fusion regulating Munc13-1, using liquid chromatography/linear ion trap mass spectrometry (LC-MS/MS). Immunocytochemical analysis further revealed that TNF-α-containing vesicles were colocalized with both Rab37 and Munc13-1 in activated macrophages. Knockdown of Munc13-1 by siRNA significantly decreased TNF-α secretion. Taken together, these findings demonstrate that Rab37 interacts with Munc13-1 to control TNF-α secretion from activated macrophages. | 10.1002/eji.201141640 |
pubmed_785_8062 | Cholesterol is important for the formation of microdomains in supported lipid bilayers and is enriched in the liquid-ordered phase. To understand the interactions leading to this enrichment, we developed an AFM-based single-lipid-extraction (SLX) approach that enables us to determine the anchoring strength of cholesterol in the two phases of a phase-separated lipid membrane. As expected, the forces necessary for extracting a single cholesterol molecule from liquid-ordered phases are significantly higher than for extracting it from the liquid-disordered phases. Interestingly, application of the Bell model shows two energy barriers that correlate with the head and full length of the cholesterol molecule. The resulting lifetimes for complete extraction are 90 s and 11 s in the liquid-ordered and liquid-disordered phases, respectively. Molecular dynamics simulations of the very same experiment show similar force profiles and indicate that the stabilization of cholesterol in the liquid-ordered phase is mainly due to nonpolar contacts. | 10.1016/j.bpj.2014.07.018 |
pubmed_378_20930 | The stimulation by KCl of stomatal opening in isolated epidermal strips of Vicia faba was examined. In dark + normal air the opening response was maximal at 100 mm KCl while in light + CO(2)-free air it was maximal at about 10 mm KCl. CO(2)-free air was more influential than light in reducing the KCl concentration required for maximal opening. K(+) was essential while Cl(-) seemed to be of secondary importance in these processes.The use of (86)Rb(+) as a tracer for K(+) showed that the increase in stomatal aperture under various conditions was well correlated with K(+) uptake. The estimated amount of K(+) taken up by guard cells, along with a counter ion, was sufficient to account for the changes in solute potential associated with opening. It is suggested that the absorption of extracellular solutes, such as K(+), may be the primary mechanism of stomatal opening. Both opening and K(+) absorption are stimulated by light + CO(2)-free air.The increase in stomatal aperture was also well correlated with the decrease in stainable starch in guard cells under all conditions. It is suggested that this is a secondary change, although perhaps closely linked to K(+) absorption. | 10.1104/pp.43.12.1953 |
pubmed_304_23625 | Central roles in reproductive biology (i.e., growth and development of the oocyte, steroidogenesis, and ovulation) are played by the ovarian dominant follicle (DF). The DF is different from other follicles because it can escape atresia (the fate of all other follicles), and if exposed to the LH surge, its cells will differentiate into the corpus luteum. The DF was originally studied by looking at the surface of ovary through a surgical approach. Current studies employ a less-invasive ultrasound technique to track the growth and development of the DF. Recruitment and selection, the processes that give rise to the DF, and dominance, the physiological state of the mature DF, are important areas of basic research. Results of these basic studies are easily translated into real-world problems in farm animal reproduction. Superovulation, for example, overrides the selection mechanism and increases the number of ovulations. Understanding the factors that affect the size of the recruited pool should increase success rates (i.e., number of collected embryos) for superovulation. In most animals, the DF is short-lived, existing for long enough to allow for the final maturation of the oocyte. Some DF become atretic because they mature during the luteal phase and are never exposed to the LH surge. For other DF, the LH surge redirects the DF toward its ultimate demise (i.e., luteinization, ovulation, and differentiation into the corpus luteum). The DF is managed pharmacologically within protocols for timed AI. When timed AI fails, there may be abnormal corpus luteum development and early embryonic loss; outcomes that are secondary to inadequate follicular cell maturation and incomplete oocyte capacitation in the DF. Future work on the DF will clarify its underlying biological functions so that a variety of needs in farm animal reproduction can be efficiently managed. | 10.2527/jas.2006-663 |
pubmed_1129_18879 | OBJECTIVE
Patients with eosinophilic granulomatosis with polyangiitis (EGPA) frequently experience relapses, which lead to cumulative organ damage. In this retrospective observational study, we aimed to reveal the risk factors for relapse in EGPA.
METHODS
A total of 188 Japanese patients with EGPA diagnosed between 1996 and 2015 were identified from medical records in 10 hospitals. The diagnosis was based on the American College of Rheumatology 1990 criteria or Lanham's criteria. Baseline characteristics, treatments, asthma exacerbation, and relapses were evaluated by retrospective chart review.
RESULTS
The median followup period was 56 months. The median age at disease onset was 59.7 years. At the disease onset, 95.2% of the patients had a history of bronchial asthma and 44.7% were positive for antineutrophil cytoplasmic antibodies. The cumulative survival and relapse-free survival rates at 5 years were 89.6% and 64.0%, respectively. Multivariate analysis with 2 models, proportional hazards, and competing risk models, was performed to identify the factors associated with relapse. The proportional hazards model identified azathioprine (AZA) maintenance therapy and high eosinophil counts at onset as independent factors with lower relapse risks, and high immunoglobulin E (IgE) levels at onset as a risk factor for relapse. The competing risk model identified no statistically significant factors.
CONCLUSION
Although potential benefit of AZA maintenance therapy in preventing relapse of EGPA was suggested by the proportional hazards model, there was a discrepancy in the results between the models. Eosinophil counts and IgE levels at onset were also identified as candidates of factors associated with relapse in EGPA. | 10.3899/jrheum.171352 |
pubmed_603_9726 | Myosin- and Rab-interacting protein (MyRIP), which belongs to the protein kinase A (PKA)-anchoring family, is implicated in hormone secretion. However, its mechanism of action is not fully elucidated. Here we investigate the role of MyRIP in myosin Va (MyoVa)-dependent secretory granule (SG) transport and secretion in pancreatic beta cells. These cells solely express the brain isoform of MyoVa (BR-MyoVa), which is a key motor protein in SG transport. In vitro pull-down, coimmunoprecipitation, and colocalization studies revealed that MyRIP does not interact with BR-MyoVa in glucose-stimulated pancreatic beta cells, suggesting that, contrary to previous notions, MyRIP does not link this motor protein to SGs. Glucose-stimulated insulin secretion is augmented by incretin hormones, which increase cAMP levels and leads to MyRIP phosphorylation, its interaction with BR-MyoVa, and phosphorylation of the BR-MyoVa receptor rabphilin-3A (Rph-3A). Rph-3A phosphorylation on Ser-234 was inhibited by small interfering RNA knockdown of MyRIP, which also reduced cAMP-mediated hormone secretion. Demonstrating the importance of this phosphorylation, nonphosphorylatable and phosphomimic Rph-3A mutants significantly altered hormone release when PKA was activated. These data suggest that MyRIP only forms a functional protein complex with BR-MyoVa on SGs when cAMP is elevated and under this condition facilitates phosphorylation of SG-associated proteins, which in turn can enhance secretion. | 10.1091/mbc.E12-05-0369 |
pubmed_964_4360 | PURPOSE
This study was designed to obtain representative estimates of the quality of life and probabilities of possible adverse effects among Medicare-age patients treated with external-beam radiation therapy for prostate cancer.
METHODS
Patients treated for local or regional prostate cancer with high-energy external-beam radiation between 1989 and 1991 were sampled from a claims data base of the Surveillance, Epidemiology, and End Results (SEER) program from three regions. Patients were surveyed primarily by mail, with telephone follow-up evaluation of non-respondents. There were 621 respondents (83% response rate). The results were compared with data from a previously published national survey of Medicare-age men who had undergone radical prostatectomy.
RESULTS
Although they were older at the time of treatment, radiation patients were less likely than surgical patients to wear pads for wetness (7% v 32%) and had a lower rate of impotence (23% v 56% for men < 70 years), while they were more likely to report problems with bowel dysfunction (10% v 4%). Both groups reported generally positive feelings about their treatments. Radiation and surgical patients reported similar rates of additional subsequent treatment (24% v 26% at 3 years after primary treatment). However, radiation patients were less likely to say they were cancer-free, and they reported more worry about cancer than did surgical patients.
CONCLUSION
The health-related quality of life of radiation and surgical patients, on average, is similar, but the pattern of experience with adverse consequences of treatment differs by treatment. | 10.1200/JCO.1996.14.8.2258 |
pubmed_898_854 | INTRODUCTION
This study aimed to determine the volumetric effects on the upper airways of growing patients with Class II malocclusion treated with the Herbst appliance (HA).
METHODS
Volumetric measurements of the upper airways of 42 skeletal Class II malocclusion patients (mean age: 13.8 ± 1.2 years; ranging from 12.0 to 16.9 years) were assessed using cone-beam computed tomography scans acquired before treatment (T0) and approximately 1 year later (T1). The sample comprised a Herbst appliance group (HA group [HAG]; n = 24), and a comparison group (comparison group [CG]; n = 18) of orthodontic patients who had received dental treatments other than mandibular advancement with dentofacial orthopedics.
RESULTS
In CG, nasopharynx and oropharynx volumes decreased slightly during the observation period (9% and 3%, respectively), whereas the nasal cavity volume increased significantly (12%; P = 0.046). In HAG, there was an increase in the volume of all regions (nasal cavity, 5.5%; nasopharynx, 11.7%; and oropharynx, 29.7%). However, only the oropharynx showed a statistically significant increase (P = 0.003), presenting significant volumetric changes along the time (T1-T0) in HAG.
CONCLUSION
Mandibular advancement with the HA significantly increased the volume of the oropharynx, but no significant volumetric modifications were observed in the nasal cavity and nasopharynx. | 10.1016/j.ajodo.2019.03.021 |
pubmed_254_6187 | The decline of milk production in crossbred cattle during the onset of summer was evaluated using lactation records of the cows (n = 48) maintained at the Livestock Research Station, Thiruvazhamkunnu, for the period between January 2019 and March 2019. Climate data were obtained from an automatic weather station maintained on the campus. The temperature-humidity index (THI) was used to assess the thermal stress on animals. Values varied between 70.78 and 83.93 during the study period, indicating that the cows were exposed to mild and moderate stress. Highly significant negative correlations (p < 0.01) were observed between the average temperature, THI, and milk production. Linear, logarithmic, power, and polynomial models linking milk production and THI were used to fit the data. The coefficient of determination (R2) in general exceeded 0.85 and these equations could be used to model the drop in milk production or predict production loss due to thermal stress. The rate of decline in daily milk production observed in the study was 2.13% per unit increase in THI. A general linear model that included THI, parity, and the stage of lactation as independent variables, and milk production as a response variable, was also tested. Parity and stages of lactation were observed to influence forenoon and afternoon milk production significantly (p < 0.01). The temperature-humidity index also had a significant effect on forenoon milk production (p < 0.05) and afternoon milk production (p < 0.01). | 10.1007/s11250-020-02525-x |
pubmed_921_8925 | OBJECTIVE
To compare the economic costs and benefits associated with using either diphtheria and tetanus toxoids and acellular pertussis vaccine (DTaP) or diphtheria and tetanus toxoids and whole-cell pertussis vaccine (DTwP) in the United States in 1997.
DESIGN
Standard cost-benefit analysis, from both the societal and health care system perspectives, was performed for each combination vaccine as well as for the pertussis components singly.
SETTING
A simulated cohort of 4.1 million children from birth to age 15 years.
MAIN OUTCOME MEASURES
Net costs (savings) and benefit-cost ratios (BCRs)
RESULTS
Without a vaccination program, diphtheria, tetanus, and pertussis disease caused more than 3 million cases and more than 28,000 deaths, at a cost of $23.6 billion. From the societal perspective, net savings because of the use of DTaP and DTwP were $22.510 million and $22.623 million, respectively. The net savings from the acellular pertussis component and the whole-cell pertussis component only were $4.362 million and $4.474 million, respectively. Benefit-cost ratios for DTaP from a societal and health care system perspective were 27:1 and 9:1, respectively. Sensitivity analyses of key variables did not result in appreciable changes in results.
CONCLUSIONS
Compared with no program, vaccination with DTaP or DTwP resulted in substantial savings, regardless of the perspective taken and for all sensitivity analyses conducted. Compared with DTwP, use of DTaP generated a small cost increase that might be offset by the value of other factors, such as increased confidence in pertussis vaccination resulting from reduced adverse events. Arch Pediatr Adolesc Med. 2000;154:797-803 | 10.1001/archpedi.154.8.797 |
pubmed_926_8337 | In 2 experiments in Pekin ducks the inevitable endogenous ileal flow (IEIF) of AA was estimated at changing intake and source of crude fiber (CF) or soybean oil (SO) level. Also the roles of dry matter intake (DMI) and BW or age as well as the proportion of IEIF in the dietary requirement for AA were studied. In experiment 1 three basal CP (20, 60, or 100 g/kg) diets were formulated containing a low CF (LCF, 30 g/kg) or high (HCF, 80 g/kg) level; achieved with cellulose supplementation. All diets were similar in every other respect including having SO content of 40 g/kg. Four floor pens of eight 85-day-old ducks were randomly allocated to each diet. Similar diets were mixed in experiment 2 but corn cob meal replaced cellulose as the fiber source. A high SO (HSO) series was also formed by increasing the SO level from 40 g/kg in the basal series to 100 g/kg. Thus the LCF series was concurrently classified as low SO (LSO) series to control SO effect. Each of the eventual 9 diets were fed to 5 floor pens of ten 65-day-old ducks. Ileal AA flow was measured after a 5 day feeding period in both experiments. Linear regression was calculated between ileal flow and dietary intake of individual AA. The IEIF interpreted as the y-intercept of each linear function responded neither to elevated ingestion of each CF type nor to SO level. Age and DMI had no effect on IEIF computed in relation to BW, but wide discrepancies resulted when related to DMI. Overall IEIF of AA varied between 14.3 to 129.8 mg/kg BW d-1. These flows were established in model computations to account for 10 to 64% of the recommended intake of limiting AA. In conclusion the ileal inevitable flow is constant within the dietary/age conditions investigated. However it is modulated by feed intake and accounts for a significant portion of total amino acid requirement. | 10.3382/ps/pex119 |
pubmed_216_24542 | Inflammatory responses to cell-associated or tissue-associated immune complexes are key elements in the pathogenesis of several autoimmune diseases, including rheumatoid arthritis, systemic lupus erythematosus and immune thrombocytopenic purpura. Effector cells, such as monocytes, macrophages and neutrophils, bind immune complexes in a process mediated by Fcgamma receptors, and these cells then initiate inflammatory reactions that lead to tissue destruction. Rituximab is an anti-CD20 monoclonal antibody that suppresses inflammation effectively in autoimmune diseases. It was initially approved by the FDA for the treatment of B-cell lymphomas and later for rheumatoid arthritis refractory to anti-tumor necrosis factor therapies. Rituximab is hypothesized to suppress disease injury in autoimmune diseases by promoting rapid and long-term elimination of circulating and possibly lymphoid-tissue-associated B cells. We suggest, however, that a different mechanism may underlie much of the therapeutic action of rituximab in autoimmune diseases: binding of tens of thousands of rituximab-IgG molecules to B cells generates decoy sacrificial cellular immune complexes that efficiently attract and bind Fcgamma receptor-expressing effector cells, which diminishes recruitment of these effector cells at sites of immune complex deposition and, therefore, reduces inflammation and tissue damage. | 10.1038/ncprheum0424 |
pubmed_142_3348 | BACKGROUND
Simulation-based interprofessional team training is thought to improve patient care. Participating teams often consist of both experienced providers and trainees, which likely impacts team dynamics, particularly when a resident leads the team. Although similar team composition is found in real-life, debriefing after simulations puts a spotlight on team interactions and in particular on residents in the role of team leader. The goal of the current study was to explore residents' perceptions of simulation-based interprofessional team training.
METHODS
This was a secondary analysis of a study of residents in the pediatric residency training program at the University of California, San Francisco (United States) leading interprofessional teams in simulated resuscitations, followed by facilitated debriefing. Residents participated in individual, semi-structured, audio-recorded interviews within one month of the simulation. The original study aimed to examine residents' self-assessment of leadership skills, and during analysis we encountered numerous comments regarding the interprofessional nature of the simulation training. We therefore performed a secondary analysis of the interview transcripts. We followed an iterative process to create a coding scheme, and used interprofessional learning and practice as sensitizing concepts to extract relevant themes.
RESULTS
16 residents participated in the study. Residents felt that simulated resuscitations were helpful but anxiety provoking, largely due to interprofessional dynamics. They embraced the interprofessional training opportunity and appreciated hearing other healthcare providers' perspectives, but questioned the value of interprofessional debriefing. They identified the need to maintain positive relationships with colleagues in light of the teams' complex hierarchy as a barrier to candid feedback.
DISCUSSION
Pediatric residents in our study appreciated the opportunity to participate in interprofessional team training but were conflicted about the value of feedback and debriefing in this setting. These data indicate that the optimal approach to such interprofessional education activities deserves further study. | 10.4103/1357-6283.161883 |
pubmed_368_22516 | BACKGROUND AND AIM
Technological advances in the field of biological imaging now allow multi-modal studies of human embryo anatomy. The aim of this study was to assess the high magnetic field μMRI feasibility in the study of small human embryos (less than 21mm crown-rump) as a new tool for the study of human descriptive embryology and to determine better sequence characteristics to obtain higher spatial resolution and higher signal/noise ratio.
METHODS
Morphological study of four human embryos belonging to the historical collection of the Department of Anatomy in the Faculty of Medicine of Reims was undertaken by μMRI. These embryos had, successively, crown-rump lengths of 3mm (Carnegie Stage, CS 10), 12mm (CS 16), 17mm (CS 18) and 21mm (CS 20). Acquisition of images was performed using a vertical nuclear magnetic resonance spectrometer, a Bruker Avance III, 500MHz, 11.7T equipped for imaging.
RESULTS
All images were acquired using 2D (transverse, sagittal and coronal) and 3D sequences, either T1-weighted or T2-weighted. Spatial resolution between 24 and 70μm/pixel allowed clear visualization of all anatomical structures of the embryos.
CONCLUSION
The study of human embryos μMRI has already been reported in the literature and a few atlases exist for educational purposes. However, to our knowledge, descriptive or morphological studies of human developmental anatomy based on data collected these few μMRI studies of human embryos are rare. This morphological noninvasive imaging method coupled with other techniques already reported seems to offer new perspectives to descriptive studies of human embryology. | pubmed_368_22516 |
pubmed_862_5379 | UNLABELLED
BACKGROUND, PURPOSE AND METHODS: This observational study assessed the effect of continuous intraventricular infusion of pentosan polysulphate (PPS) in seven patients at different clinical centres in the UK.
RESULTS
Complications of intraventricular catheterization were frequent. PPS was well-tolerated over a wide dose range (11-110 microg/kg/day) during the 6-month study. Four patients were assessed for the entire study period: one remained stable, two showed minimal deterioration and one progressed significantly.
CONCLUSION
Mean survival of all patients was longer than reported values for natural history of specific prion disorders. Possible reasons for these findings are explored. | 10.1111/j.1468-1331.2008.02108.x |
pubmed_263_23471 | The relationship between external exposure and internal doses of polycyclic aromatic hydrocarbons (PAHs) has not been established for people living in industrial areas. This study was carried out to estimate the relationship between particle-phase PAH exposure and urinary 1-hydroxypyrene (1-OHP) levels among the adults living near a large petrochemical complex in Mailiao, Taiwan. We measured urinary 1-OHP in 781 residents above 35 years old and PM2.5 PAHs within a 20-km radius downwind from the petrochemical complex. Urinary 1-OHP was analyzed by high performance liquid chromatography, while 16 ambient particle-phase PAHs were measured by gas chromatography mass spectrometry. External exposures to individual PAHs at each study subject's address were estimated by kriging interpolation from air sampling results and regressed against the subjects' urinary 1-OHP levels, adjusting for confounding factors. The study population's urinary 1-OHP levels ranged from 0.001 to 3.005 μmol/mol-creatinine with significantly higher levels for females, grilled food consumers, and residents living close to roads. All 16 particle-phase PAHs were present in the study area with total PAH concentrations ranging from 0.111 to 1.982 ng/m(3). The spatial distribution of 4- and 5-ring PAHs identified high-concentration hotspots close to the complex in Mailiao. The multiple regression models showed that the adults' urinary 1-OHP levels were significantly correlated with 5 out of the 16 PAHs, including benzo[a]anthracene, benzo[k]fluoranthene, fluoranthene, pyrene, and dibenzo[a,h]anthracene; a 0.01 ng/m(3) increase in the concentration of these 5 PAHs at the study subjects' addresses was associated with a 20% elevation in urinary 1-OHP levels (μg/g-creatinine). Emissions from a petrochemical complex can elevate particle-phase PAH concentrations in surrounding areas and increase the urinary 1-OHP levels of adults living nearby. | pubmed_263_23471 |
pubmed_1023_2305 | When cultured Drosophila line S3 cells are incubated in the presence of the steroid hormone, ecdysterone, they flatten, elongate, and become motile. We show here that accompanying this morphological transformation there is a 5-fold increase in the rate of actin synthesis and a 2-fold increase in actin content. These increases, in turn, are primarily based on a 9-fold increase in the level of mRNA transcribed from the cytoplasmic actin A3 gene. We also find that during hormone treatment the cells go into proliferative arrest, accumulating in the G2 phase of the cell cycle. During this period the level of histone mRNA in the cells decreases significantly. | pubmed_1023_2305 |
pubmed_888_20668 | Oxidative stress and subsequent damage to cellular proteins, lipids, and nucleic acids, as well as changes to the glutathione system, are well documented in response to aerobic exercise. However, far less information is available on anaerobic exercise-induced oxidative modifications. Recent evidence indicates that high intensity anaerobic work does result in oxidative modification to the above-mentioned macromolecules in both skeletal muscle and blood. Also, it appears that chronic anaerobic exercise training can induce adaptations that act to attenuate the exercise-induced oxidative stress. These may be specific to increased antioxidant defenses and/or may act to reduce the generation of pro-oxidants during and after exercise. However, a wide variety of exercise protocols and assay procedures have been used to study oxidative stress pertaining to anaerobic work. Therefore, precise conclusions about the exact extent and location of oxidative macromolecule damage, in addition to the adaptations resulting from chronic anaerobic exercise training, are difficult to indicate. This manuscript provides a review of anaerobic exercise and oxidative stress, presenting both the acute effects of a single exercise bout and the potential for adaptations resulting from chronic anaerobic training. | 10.1139/h04-017 |
pubmed_304_9719 | This article describes the development and evolution of governing boards and summarizes critical findings from a research study on hospital governing boards. The purpose of the research was to examine factors that measure performance of governing boards and the relationship of governing board effectiveness to the organizational performance of hospitals. Board leaders from 64 nonprofit hospitals across the country were surveyed using the BSAQ tool, which measures board effectiveness in six areas of competency. Board competency scores of this group were compared with those of a previous group, which consisted of more than 300 nonprofit boards, and demonstrated significantly higher scores. A factor analysis conducted to compare the six competency factors between study groups revealed a strong single factor in this study. The factors that measure governing board performance were found to be consolidated into one single factor of collaborative board functioning consistent with emerging governance theory. This may support the concept of the importance of governing boards as collaborative, socially dynamic networks of leaders. The hospital performance was assessed using data from the nationally recognized program, Solucient's 100 Top Hospitals. The results demonstrate that higher performing boards did have better hospital performance in several dimensions, most notably in profitability and lower expenses. Lower expenses were related to higher scores for the BSAQ total score. Hospital profitability was positively correlated with all seven BSAQ scores. A more favorable Solucient ranking was related to hospitals that had a lower BSAQ political score. This was also found in a multiple regression model that predicted a favorable ranking when the BSAQ political score was lower. This may mean that these boards do what needs to be done to maintain excellent performance and do not let politics get in the way of their work. Although governance and its effect on hospital performance is a complex concept to study, this investigation yields findings of interest to leaders in the healthcare field. | pubmed_304_9719 |
pubmed_604_8156 | The Voyager 2 encounter has enhanced our understanding of earlier results and provided measurements beyond 160 Jupiter radii (R(J)) in the magnetotail. Significant fluxes of energetic sulfur and oxygen nuclei (4 to 15 million electron volts per nucleon) of Jovian origin were observed inside 25 R(J), and the gradient in phase space density at 12 R(J) indicates that the ions are diffusing inward. A substantially longer time delay versus distance was found for proton flux maxima in the active hemisphere in the magnetotail at Jovicentric longitudes lambda(III), = 260 degrees to 320 degrees than in the inactive hemisphere at lambda(III), = 85 degrees to l10 degrees . These delays can be related to the radial motion of plasma expanding into the magnetotail, and differences in the expansion speeds between the active and inactive hemispheres can produce rarefaction regions in trapped particles. It is suggested that the 10-hour modulation of interplanetary Jovian electrons may be associated with the arrival at the dawn magnetopause of a rarefaction region each planetary rotation. | 10.1126/science.206.4421.984 |
pubmed_944_10995 | Assessing nutrition knowledge of populations assists in drawing strategies for education programs. Nutrition-related problems are common in Kuwait, thus data on nutrition knowledge are needed. This study involved administration of a questionnaire to 1,037 first-year Kuwait University students. The overall nutrition knowledge score was rated as fair, with deficiency in specific areas of knowledge. Students' dietary habits, attitudes, and interest in nutrition information were assessed as fair. Our findings will aid in building a nutrition knowledge database in Kuwait. A simplified course on aspects of healthy nutrition and lifestyle to all Kuwait University students is highly recommended. | 10.1080/03670244.2011.552376 |
pubmed_617_3364 | BACKGROUND
Rectal carcinoid tumors 10 mm in diameter or smaller located within the submucosal layer can be cured by local excision including endoscopic treatment. But complete resection of these tumors with endoscopic polypectomy is difficult. This study aimed to evaluate the usefulness of endoscopic submucosal dissection (ESD) and endoscopic ultrasonography (EUS) for the treatment of rectal carcinoid tumors.
METHODS
In this study, 22 rectal carcinoid tumors in 21 patients were evaluated with EUS and treated using ESD from January 2004 to December 2008.
RESULTS
The mean size of the resected tumors was 6.1 mm (range, 2.0-10 mm) on histopathologic evaluations. When the sizes of the tumors shown by EUS and histopathologic evaluation were compared, the mean values were not significantly different. All the tumors were located within the submucosal layer, and the accuracy of the preoperative depth determination with EUS was 100% (22/22). The mean duration of the ESD procedure was 37 min (range, 20-71 min). The overall rate of en bloc resection with ESD was 100% (22/22). Although postoperative bleeding occurred in two cases (9%), both cases were successfully managed by endoscopic hemostasis. No perforation or recurrence was observed during the mean follow-up period of 30 months (range, 7-66 months).
CONCLUSIONS
Endoscopic submucosal dissection and preoperative assessment with EUS are effective for treating rectal carcinoid tumors and enabling en bloc resection. | 10.1007/s00464-009-0791-x |
pubmed_304_19288 | BACKGROUND
TNF-alpha is a pivotal proinflammatory cytokine increased in asthmatic airways. The TNF-alpha gene family might be linked to asthma or bronchial hyperresponsiveness (BHR), and TNF-alpha production might be modulated by CD14(+) cells.
OBJECTIVE
We investigated the association between asthma susceptibility or asthma-related phenotypes and TNF-alpha (-308G/A) polymorphism and examined the combined effect with CD14 (-159T/C) polymorphism in Korean children.
METHODS
Asthmatic (n = 788) and control (n = 153) children were evaluated for asthma phenotypes. Genotypes were determined by using the single-base extension method and PCR-restriction fragment length polymorphism.
RESULTS
There was no difference between asthmatic children and control subjects in terms of the allele frequencies of TNF-alpha (-308G/A) and CD14 (-159T/C). Significantly lower PC(20) values were seen in asthmatic (P = .016) children with the TNF-alpha risk allele (-308A). Higher frequencies of 1 or 2 copies of the risk allele were found in asthmatic children with moderate-to-severe BHR to methacholine and exercise compared with control children (adjusted odds ratio of 2.57 [95% CI, 1.30-5.08] and adjusted odds ratio of 2.04 [95% CI 0.99-4.20], respectively). In addition, asthmatic children with risk alleles at both loci had significantly greater BHR than those homozygous for the common alleles (P = .018).
CONCLUSION
The TNF-alpha promoter polymorphism (-308G/A) might be associated with severe BHR in Korean children with asthma. In addition, these children show a synergistic effect between the TNF-alpha promoter (-308A) and CD14 promoter (-159C) polymorphisms in terms of BHR.
CLINICAL IMPLICATIONS
The TNF-alpha polymorphism might be a disease-modifying gene in asthma and modulated by the CD14 gene. | 10.1016/j.jaci.2006.10.031 |
pubmed_304_2065 | Thioarsenicals are newly found arsenic metabolites in man and animals, and also in marine organisms. Dimethylmonothioarsinic acid (DMMTA(V)) and dimethyldithioarsinic acid (DMDTA(V)) are the only two thioarsenic metabolites detected in man and/or animals. However, their toxicological and biological significance is not known yet. The present study was performed to gain an insight into the significance of DMMTA(V) and DMDTA(V) in the metabolism of arsenic. The two thioarsenicals were synthesized chemically and injected intravenously into rats at the dose of 0.5 mg As/kg body weight. The distributions of arsenic in organs/tissues and body fluids were determined at 10 min and 12 h after the injection, and arsenic in liver and kidney supernatants, urine, plasma and red blood cell (RBC) lysates was subjected to speciation analysis by HPLC-ICP MS on a gel filtration GS 220 HQ column. Although both thioarsenicals are pentavalent arsenicals, they were distributed in organs/tissues and body fluids differently from the corresponding non-thiolated pentavalent arsenicals, and also from each other. Namely, DMMTA(V) was first found in organs/tissues at 10 min, and then redistributed and retained mostly in RBCs at 12 h, as in the case of trivalent dimethylarsinous acid (DMA(III)). On the other hand, although DMDTA(V) was also found in organs/tissues at 10 min, it had been efficiently excreted in urine in its intact form at 12 h. Thus, DMMTA(V) was unexpectedly distributed in and taken up by organs/tissues in a manner similar to DMA(III) rather than DMA(V), whereas DMDTA(V) was distributed similarly to DMA(V) as expected, but was much more efficiently excreted in urine. | 10.1016/j.taap.2006.10.027 |
pubmed_940_8051 | A set of 723 diagnostic sera from human patients, submitted for the microscopic agglutination test (MAT) for antibodies to a group of 6 leptospiral serovars, was also tested by MAT for antibodies to the recently-discovered Leptospira fainei serovar hurstbridge. MAT titres of > or = 128 to serovar hurstbridge were detected in 13.4% of these sera, and titres of > or = 512 in 7.2%. In contrast, none of 62 sera obtained from a control population of laboratory staff gave titres of > or = 128. The difference between the number of titres of > or = 128 given by the two groups of sera was highly significant (P < 0.01). The titres observed may have been due to cross-reactions with other leptospiral serovars, but this could not be demonstrated. An alternative explanation is that serovar hurstbridge is present in the human population. | 10.1017/s095026889800137x |
pubmed_942_22089 | BACKGROUND
Podocalyxin (podxl) is a heavily glycosylated transmembrane protein mainly found on the apical membrane of rat podocytes and also in endothelial, hematopoietic, and tumor cells. Despite of its interest no much is known about the transcriptional regulation of podxl in different cells. Thus, we aimed at studying the functional features of the 5'-regulatory region of the human Podxl gene.
RESULTS
The promoter region of the human Podxl gene has been cloned and its structure and function were analyzed. The primary DNA sequence is rich in G+C and is devoid of TATA or CAAT boxes. The sequence contains recognition sites for several putative transcription factors; however, the basic promoter activity seems to rely entirely on Sp1 transcription factor since supershift analysis was positive only for this factor. The region encompassed by 66 to -111 nts conferred the minimal transcriptional activity that increases as the number of Sp1 sites augmented with the length of the promoter fragment. In Sp1-lacking insect cells the Podxl promoter constructs showed activity only if cotransfected with an Sp1 expression plasmid. Finally, mutation of the Sp1 sites reduced the promoter activity. We analyzed whether methylation of the CpG dinucleotides present in the first approximately 600 nts of the promoter region of Podxl could explain the variable rates of expression in different types of cells. Inactivation of methyltransferases by 5'-aza-2'deoxicitidine showed a dose-dependent increase in the podxl content. Moreover, in vitro methylation of the promoter constructs -111,-181 and -210 led to an almost complete reduction of the promoter activity. A correlation was found between the degree of methylation of the CpG promoter dinucleotides and the rate of podxl expression in different cell lines.
CONCLUSION
Our results indicate that transcriptional regulation of Podxl is supported primarily by Sp1 site(s) and that DNA-methylation of the CpG promoter islands contributes to control the tissue specific expression of podxl. | 10.1186/1471-2199-7-17 |
pubmed_740_892 | This paper described the extraction procedure and determination method for the total flavonoids in ethanol extract from the leaves of Abutilon theophrasti Medic., and evaluated antibacterial and antioxidant activity. Maximum extraction yield was achieved using 60% ethanol, 1 : 30 (g/mL) of a ratio of material to solvent, 20 min of extraction time, 40 kHz of ultrasonic frequency, 100 W of ultrasonic power, 600C of extraction temperature and two extraction cycles. Total flavonoids content was 16.79 RE mg/g medicinal materials. The extracts had effective antibacterial activity against 24 test strains from S. aureus and E. coli, MICs ranged from 2.18 to 8.7 mg/mL; it was also revealed that the extracts demonstrated high flavonids content and potent antioxidant activity, achieved by hydroxyl radical, DPPH radical and ABTS radical scavenging. These results indicated thathe extract may be a promising plant demonstrating antibacterial and antioxidant activities. | pubmed_740_892 |
pubmed_117_15448 | Introduction: The prediction of antidepressant treatment response may improve outcome. Functional magnetic resonance imaging (fMRI) of emotion processing in major depressive disorder (MDD) may reveal regional brain function serving as predictors of response to treatment with selective serotonin reuptake inhibitor (SSRI). Methods: We examined the association between pre-treatment neural activity by means of fMRI during the perception of emotional stimuli in 22 patients with MDD and the treatment outcome after 6 weeks' medication with an SSRI. A whole brain correlation analysis with Beck Depression Inventory (BDI) change between pre- to post-treatment was conducted to identify neural regions associated with treatment response. Results: During the perception of positive stimuli, responders were characterized by more activation in posterior cingulate cortex (PCC), medial prefrontal cortex, and thalamus as well as middle temporal gyrus. During perception of negative stimuli, PCC, and pregenual anterior cingulate cortex showed the highest correlation with treatment response. Furthermore, responders exhibited higher activation to emotional stimuli than to neutral stimuli in all the above-mentioned regions, while non-responders demonstrated an attenuated neural response to emotional compared to neutral stimuli. Conclusion: Our data suggest that the activity of distinct brain regions is correlated with SSRI treatment outcome and may serve as treatment response predictor. While some regions, in which activity was correlated with treatment response, can be assigned to networks that have been implied in the pathophysiology of depression, most of our regions of interest could also be matched to the default mode network (DMN). Higher DMN activity has been associated with increased rumination as well as negative self-referential processing in previous studies. This may suggest our responders to SSRI to be characterized by such dysregulations and that SSRIs might modify the function associated with this network. | 10.3389/fpsyt.2020.538393 |
pubmed_918_23466 | Background: Because of the poor health conditions of elderly patients (age >65) with very-early-stage and early-stage hepatocellular carcinoma (HCC), primary treatment via hepatic resection (HR), or radiofrequency ablation (RFA) must be considered. However, few studies have examined this issue. Methods: A retrospective cohort was obtained from the Surveillance, Epidemiology, and End Results (SEER) database from 2004 to 2015. Patients were grouped by tumor size (0-20, 21-30, 31-35, and 31-50 mm) and age (>65 and ≤65). Overall survival (OS) and disease-specific survival (DSS) were assessed. Results: In total, 1912 patients aged >65 and 2,784 patients aged ≤65 were analyzed after propensity score matching (PSM). For patients >65 with tumors ≤20 mm, OS and DSS did not differ significantly between the RFA and HR groups (p = 0.47 and p = 0.76, respectively). For patients with tumors measuring 21-30 mm, the HR group had better OS and a trend toward better DSS compared with the RFA group (p = 0.03 and p = 0.09, respectively). For patients with tumors measuring 31-50 mm, the HR group had better OS and DSS compared with the RFA group (p < 0.001 for both). For patients <65, the HR group had better OS and DSS compared with the RFA group for all tumor sizes. Conclusions: For elderly patients (age >65), RFA is recommended for tumors ≤20 mm. For patients older than 65 with tumors measuring 21-50 mm and for those younger than 65 with tumors of any size, HR is the better choice. | 10.3389/fonc.2019.00113 |
pubmed_881_14905 | AIM
To ascertain the views of dental consultants on the relative importance of a range of topics relevant to specialist referral.
SUBJECTS
200 randomly selected dental consultants working in the UK in 1995.
MAIN OUTCOME MEASURES
Data items which referral letters should contain; standard of referral letters; appropriate reasons for referral; how referrals could be improved; should restrictions be placed on specialist referrals.
RESULTS
161 replies were received. Overall there was only slight variation between specialities with regard to data items, appropriateness of referral and standard of referral letter. The perceived standard of referral letters was adequate or better on 76% of occasions; 21% were deemed to be of a poor standard; 2% were described as appalling.
CONCLUSIONS
A Section 63 course on how to refer competently could be of benefit. Consultants were generally not in favour of restricting referrals to them. | 10.1038/sj.bdj.4809288 |
pubmed_151_19858 | The concept of Cell-Mediated Immunity (CMI) monitoring in transplantation has gained popularity over time and is now a reality. Significant technological advances have enabled us to test for multiple molecules and cells implicated in inflammatory or suppressive reactions to the graft. The main challenge nowadays is whether clinicians can use the information provided by the measurement of such markers to predict post-transplant outcome. To date a wide range of markers have been identified as promising biomarkers in the monitoring of individual responses to immunosuppression or in the determination of patient alloreactivity to the graft, which could prove helpful in the assessment of the occurrence of an adverse/side effect. Before these biomarkers are deemed suitable, standardisation of the methodology and validation of its feasibility in clinical outcome remains an ongoing challenge. The research community is currently facing a large effort towards the implementation of a standard methodology that is both highly reproducible and can reduce inter-laboratory variability, therefore generating consistency with data. The aim of this manuscript is to review the current literature regarding CMI monitoring in the field of solid organ transplantation (SOT), undertaking a comprehensive study of the latest findings. In addition, based upon current literature, we aim to propose a comprehensive classification of biomarkers to further aid our current understanding, taking in to account the type of transplantation, when its measurement should be applied and which would be the most suitable biomarker to assess. | 10.2174/1389203719666180730164542 |
pubmed_418_25700 | We need to understand the physics of how the skin of the finger pad deforms, and their tie to perception, to accurately reproduce a sense of compliance, or 'softness,' in tactile displays. Contact interactions with compliant materials are distinct from those with rigid surfaces where the skin flattens completely. To capture unique patterns in skin deformation over a range of compliances, we developed a stereo imaging technique to visualize the skin through optically clear stimuli. Accompanying algorithms serve to locate and track points marked with ink on the skin, correct for light refraction through stimuli, and estimate aspects of contact between skin and stimulus surfaces. The method achieves a 3-D spatial resolution of 60-120 microns and temporal resolution of 30 frames per second. With human subjects, we measured the skin's deformation over a range of compliances (61-266 kPa), displacements (0-4 mm), and velocities (1- 15 mm/s). The results indicate that the method can differentiate patterns of skin deformation between compliances, as defined by metrics including surface penetration depth, retention of geometric shape, and force per gross contact area. Observations of biomechanical cues of this sort are key to understanding the perceptual encoding of compliance. | 10.1109/HAPTICS.2018.8357145 |
pubmed_86_2468 | Is alcohol use a help or a hindrance for creativity? And, conversely, what effect does creative activity have on alcohol use? In order to answer these questions, relevant information was obtained from the biographies of 34 well known, heavy drinking, 20th century writers, artists or composers/performers. Analysis of this information yielded a number of interesting findings. Alcohol use proved detrimental to productivity in over 75% of the sample, especially in the latter phases of their drinking careers. However, it appeared to provide direct benefit for about 9% of the sample, indirect benefit for 50% and no appreciable effect for 40% at different times in their lives. Creative activity, conversely, can also affect drinking behavior, leading, for instance, to increased alcohol consumption in over 30% of the sample. Because of the complexities of this relationship, no simplistic conclusions are possible. | 10.1111/j.1360-0443.1990.tb03726.x |
pubmed_434_1746 | OBJECTIVE
To educate pharmacists regarding the hypothesis that the measles-mumps-rubella (MMR) vaccine is linked to the development of autism.
DATA SOURCES
Articles published from 1998 to 2009 were identified through electronic searches of Medline.
STUDY SELECTION
Articles were included if they evaluated or reviewed a possible link between the MMR vaccine and autism or discussed MMR epidemiology, legal proceedings involving the MMR vaccine and autism, or health professionals' impact on immunization decisions.
DATA SYNTHESIS
A total of 27 articles were identified. Of the articles, 74% (20 of 27) were included in the review because of their relevance to the study topic.
CONCLUSION
The evidence presented does not show a causal relationship between the MMR vaccine and autism. Myths presented to potentially support any relationship between the MMR vaccine and autism have not been proven. Expert testimony refuting initial scientific theories has led to Supreme Court decisions that do not support a link between the MMR vaccine and autism. Pharmacists and all health care providers are responsible for informing and educating parents and families regarding this information so that they can make informed decisions about immunizations. | 10.1331/JAPhA.2010.10004 |
pubmed_329_21862 | INTRODUCTION
The Kropp and Salle procedures have shown good short-term outcomes for managing neuropathic urinary incontinence. However, few studies have assessed their long-term results.
OBJECTIVE
This study aimed to evaluate the long-term outcomes of Kropp and Salle procedures, including: dryness, secondary interventions for incontinence or complications, upper urinary tract changes, and use of urethral catheterizations.
STUDY DESIGN
Consecutive patients undergoing Kropp and Salle procedures at the present institution (1983-2012) were retrospectively reviewed. Patients with <1-year follow-up or prior bladder neck (BN) continence procedures were excluded. Data were collected on postoperative dryness per urethra at 4-hourly and 3-hourly intervals, secondary interventions, lab tests, and imaging. Non-parametric tests were used for statistical analysis.
RESULTS
Thirty-eight patients had Kropp (K: 30 boys) and 12 had Salle procedures (S: 8 boys). Patients underwent surgery at similar median ages (K: 7.4 vs S: 8.7 years old, P = 0.51) and had similar median follow-up (6.9 vs 10.3 years, P = 0.10). Most patients had myelomeningocele, a prior/concomitant bladder augmentation (K: 73.7%, S: 58.3%) and catheterizable channel (K: 81.6%, S: 50.0%). Differences in all outcomes between Kropp and Salle procedures were statistically non-significant. The majority of patients did not have additional BN procedures for dryness (K: 84.2%, S: 66.7%). Of this group, K: 81.3% and S: 75.0% were dry for ≥4 h, K: 93.8% and S: 87.5% were dry for ≥3 h between catheterizations (Table). Of the minority of patients who underwent additional BN procedures for dryness (K: 15.8%, S: 33.3%), most achieved dryness for ≥4 h (K: 66.7%, S: 100%) and ≥3 h (100% for both). Among patients without an initial catheterizable channel, 57.1% had one subsequently created after a Kropp procedure, and 33.3% after a Salle. Among patients without bladder augmentation, approximately half underwent delayed augmentation (K: 50.0%, S: 40.0%). Ultimately, most patients required a secondary intervention under anesthesia for incontinence or complications (K: 79.0%, S: 66.7%). Few patients developed worsening hydronephrosis, vesicoureteral reflux or renal function (K: 2.6%, S: 0.0%). At the end of follow-up, few patients catheterized per urethra (K: 10.5%, S: 33.3%).
DISCUSSION
This was a retrospective study without urodynamic data. Originating from a tertiary center, the results may not apply to other clinical settings.
CONCLUSIONS
At the present institution the Kropp and Salle procedures attained similar dryness in 75-81% at 4-hourly intervals and 88-94% at 3-hourly intervals without additional BN procedures. Few patients required subsequent BN procedures to achieve dryness. However, the overall need for secondary procedures during long-term follow-up was high for both procedures. | 10.1016/j.jpurol.2016.06.011 |
pubmed_292_24506 | BACKGROUND
Bariatric procedures provide an effective means of short term weight loss and sustained weight control for the morbidly obese. The effect of bariatric procedures on smoking habit in obese subjects is not well known. Therefore, we examined the short term effect of bariatric surgery on smoking habit of severe obese patients up to 12 months from the intervention.
PATIENTS AND METHODS
Smoking habit was assessed in a cohort of 78 morbid smoking obese patients followed at our clinic for bariatric procedures. They underwent non surgical intra-gastric balloon (IB) or surgical procedures such as lap-band laparoscopic surgery (LAGB) or sleeve gastrectomy/gastric by-pass (SPG). Subjects were administered a written questionnaire about their smoking habit before and 3, 6 and 12 months after the procedures.
RESULTS
No differences were found among the three groups at 6 and 12 months after the procedures (IB 21 %, LAGB 6 %, SPG 5 %; and IB 14 %, LAGB 3 %, SPG 5 %). Only after 3 months, the rate of quitting of the IB group was higher than LAGB and SPG groups (36 %, 6 % and 5 %, respectively; p = 0.02).
CONCLUSIONS
Bariatric procedures have no effects on smoking habit of moderate-to-heavy smoker severe obese patients. The use of other traditional smoking cessation methods in patients undergone to bariatric procedures should be implemented. | 10.1186/s12971-015-0045-8 |
pubmed_454_13001 | IL-6 and IL-10 have previously been implicated in the pathogenesis of post-transplant lymphoproliferative disorders (PTLD) and, like peripheral lymphocyte populations, are markers of immune status that are amenable to study in vivo. Thus, we analyzed cytokine plasma levels as well as lymphocyte subsets in a longitudinal analysis of 38 adult transplant recipients undergoing treatment for PTLD. Pretherapeutically, we found significantly elevated IL-6 (13.8 pg/ml) and IL-10 plasma levels (54.7 pg/ml) - in the case of IL-10, even higher in treatment nonresponders than in responders (116 vs. 14 pg/ml). Over time, however, IL-10 levels did not correlate with the course of disease, whereas those of IL-6 did, falling in responders and rising in nonresponders. These findings were independent of histological EBV-status, treatment type, and total peripheral T-cell counts, which were significantly reduced in patients with PTLD. Our observations support the idea that although IL-10 is important for creating a permissive environment for post-transplant lymphoma development, IL-6 is associated with PTLD proliferation. The analysis of lymphocyte subsets further identified HLA-DR+ CD8+ lymphocyte numbers as significantly different in non-PTLD controls (33%), treatment responders (44%) and nonresponders (70%). Although the specificity of these cells is unclear, their increase might correlate with the impaired tumor-specific cytotoxic-T-lymphocyte (CTL)-response in PTLD. | 10.1111/j.1432-2277.2011.01282.x |
pubmed_934_6438 | The pathology of spinal cord injury (SCI) makes it appropriate for cell-based therapies. Treatments using neural stem cells (NSCs) in animal models of SCI have shown positive outcomes, although uncertainty remains regarding the optimal cell source. Pluripotent cell sources such as embryonic stem cells (ESCs) provide a limitless supply of therapeutic cells. NSCs derived using embryoid bodies (EB) from ESCs have shown tumorigenic potential. Clonal neurosphere generation is an alternative method to generate safer and more clinically relevant NSCs without the use of an EB stage for use in cell-based therapies. We generated clonally derived definitive NSCs (dNSCs) from ESC. These cells were transplanted into a mouse thoracic SCI model. Embryonic stem cell-derived definitive neural stem cell (ES-dNSC)-transplanted mice were compared with controls using behavioral measures and histopathological analysis of tissue. In addition, the role of remyelination in injury recovery was investigated using transmission electron microscopy. The SCI group that received ES-dNSC transplantation showed significant improvements in locomotor function compared with controls in open field and gait analysis. The cell treatment group had a significant enhancement of spared neural tissue. Immunohistological assessments showed that dNSCs differentiated primarily to oligodendrocytes. These cells were shown to express myelin basic protein, associate with axons, and support nodal architecture as well as display proper compact, multilayer myelination in electron microscopic analysis. This study provides strong evidence that dNSCs clonally derived from pluripotent cells using the default pathway of neuralization improve motor function after SCI and enhance sparing of neural tissue, while remaining safe and clinically relevant. | 10.1089/scd.2014.0096 |
pubmed_658_15598 | In human diseases related to tumor-suppressor genes, it is suggested that only the complete loss of the protein results in specific symptoms such as tumor formation, whereas simple reduction of protein quantity to 50%, called haploinsufficiency, essentially does not affect cellular behavior. Using a model of gene expression, it was presumed that haploinsufficiency is related to an increased noise in gene expression also in vivo [Cook, D. L., Gerber, A. N. & Tapscott, S. J. (1998) Proc. Natl. Acad. Sci. USA 95, 15641-15646]. Here, we demonstrate that haploinsufficiency of the tumor-suppressor gene neurofibromatosis type 1 (NF1) results in an increased variation of dendrite formation in cultured NF1 melanocytes. These morphological differences between NF1 and control melanocytes can be described by a mathematical model in which the cell is considered to be a self-organized automaton. The model describes the adjustment of the cells to a set point and includes a noise term that allows for stochastic processes. It describes the experimental data of control and NF1 melanocytes. In the cells haploinsufficient for NF1 we found an altered signal-to-noise ratio detectable as increased variation in dendrite formation in two of three investigated morphological parameters. We also suggest that in vivo NF1 haploinsufficiency results in an increased noise in cellular regulation and that this effect of haploinsufficiency may be found also in other tumor suppressors. | 10.1073/pnas.212386999 |
pubmed_730_19805 | This study investigated the question: is core temperature measurement influenced by whether exercise involves predominantly upper- or lower-body musculature? Healthy men were allocated to three groups: treadmill ergometry (T) n = 4, cycle ergometry (C) n = 6 and arm crank ergometry (AC) n = 5. Subjects underwent an incremental exercise test to exhaustion on an exercise-specific ergometer to determine maximum/peak oxygen consumption (VO2max). One week later subjects exercised for 36 min on the same ergometer at approximately 65% VO2max while temperatures at the rectum (T(re)) and esophagus (T(es)) were simultaneously measured. The VO2max (1 x min(-1)) for groups T [4.76 (0.50)] and C [4.35 (0.30)] was significantly higher than that for the AC group [2.61 (0.24)]. At rest, T(re) was significantly higher than T(es) in all groups (P < 0.05). At the end of submaximal exercise in the C group, T(re) [38.32 (0.11) degrees C] was significantly higher than T(es) [38.02 (0.12) degrees C, P < 0.05]. No significant differences between T(re) and T(es) at the end of exercise were noted for AC and T groups. The temperature difference (T(diff)) between T(re) and T(es) was dissimilar at rest in the three groups; however, by the end of exercise T(diff) was approximately 0.2 degrees C for each of the groups, suggesting that at the end of steady-state exercise T(re) can validly be used to estimate core temperature. | 10.1007/s004210050384 |
pubmed_819_19340 | Syphilis is an old disease with modern health challenges for clinicians. This article discusses the various clinical manifestations and stages of syphilis, reviews interpretation of the reactive syphilis serology, and summarizes syphilis treatment recommendations from the Centers for Disease Control 1993 sexually transmitted diseases treatment guidelines. | pubmed_819_19340 |
pubmed_686_14026 | Meiosis resembles mitosis but employs a unique "reductional" nuclear division to allow the production of haploid gametes from diploid cells. The crucial ploidy reduction step requires that sister kinetochores attach to microtubules emanating from the same spindle pole, achieving "monopolar attachment," which ensures that maternal and paternal chromosomes are segregated. Here we screened for factors required to establish monopolar attachment in fission yeast and identified a novel protein, Moa1. Moa1 is meiosis specific and localizes exclusively to the central core of the centromere, a region that binds meiotic Rec8-containing cohesin complexes but not mitotic Rad21/Scc1-containing complexes. Enforced cleavage of Rec8 in the central core region led to the disruption of monopolar attachment, as in moa1Delta cells, without diminishing Moa1 localization. Moa1 physically interacts with Rec8, implying that Moa1 functions only through Rec8, presumably to facilitate central core cohesion. These results prove that monoorientation of kinetochores is established in a cohesion-mediated manner. | 10.1016/j.cell.2005.09.013 |
pubmed_355_6944 | During the repigmentation of vitiliginous skin, melanocytes migrate from the outer root sheath of the hair follicle into the depigmented skin. We hypothesize that this requires changes in the local microenvironment that are conductive to melanocyte migration. One important change in the microenvironment could be the localized production of matrix proteins. We have previously employed time-lapse photography to evaluate the effect of inflammatory mediators and cytokines on melanocyte movement. We have adapted this system to study the effect of matrix proteins on melanocyte movement in vitro. Type IV collagen significantly increases melanocyte migration, whereas laminin and fibronectin have no effect. Cell/matrix interactions are in part controlled by cell-surface integrins. Integrins have been demonstrated to be important in controlling the migration of many cell types. We demonstrate that melanocytes express cell-membrane alpha 2, alpha 3, and alpha 5 integrins and that the enhanced melanocyte migration on type IV collagen is inhibited by specific function-blocking antibodies to integrins alpha 2 and alpha 3, but not to alpha 5 integrins. | 10.1111/1523-1747.ep12366064 |
pubmed_732_16756 | Rheumatoid arthritis (RA) is an autoimmune disease with unknown etiology though both genetic and environmental factors have been suggested to be involved in its pathogenesis. While infections and other environmental factors (e.g. smoking) have been studied extensively and show some association, a direct link between all the factors has been difficult to prove. With the recent advances in technology, it has become possible to sequence the commensals that are residing in our gut. The gut microbiome may provide the missing link to this puzzle and help solve the mystery of many leaky gut syndromes. The gut commensals are involved in maintaining host immune homeostasis and function suggesting that they might be critical in altering the immune system, which leads to autoimmune diseases like RA. Mouse models support the role of the gut microbiota in predisposition to RA. If that is true, the power of gut-derived commensal can be harnessed to our benefit by generating a biomarker profile along with genetic factors to define individuals at risk and by altering the gut microbial composition using various means. | pubmed_732_16756 |
pubmed_1097_25320 | Chemotherapy-induced activation of ADAM-17 results in increased growth factor shedding and activation of growth factor receptor-mediated pro-survival response. Enhanced ADAM-17 activity and HER ligand shedding results in resistance to chemotherapy in CRC. Therapies that decrease ADAM-17 activity in conjunction with current treatments may enhance response rates in advanced CRC patients. | 10.1158/1078-0432.CCR-10-1059 |
pubmed_596_8821 | BACKGROUND
Candidates for bariatric surgery frequently have co-morbid psychiatric problems.
METHODS
This study investigated the course and the prognostic significance of preoperative and postoperative anxiety and depressive disorders in 107 extremely obese bariatric surgery patients in a prospective design with face-to-face interviews (SCID) conducted prior to the surgery and postoperatively after 6-12 months and 24-36 months.
RESULTS
The point prevalence of depressive disorders but not of anxiety disorders decreased significantly after surgery. Preoperative depressive disorders predicted depressive disorders 24-36 months but not 6-12 months after surgery, whereas preoperative anxiety significantly predicted postoperative anxiety disorders at both follow-up time points. Preoperative lifetime and current depressive disorders were unrelated to postoperative weight loss whereas preoperative lifetime, but not current anxiety disorders were of negative prognostic value for postoperative weight loss. Patients with both depressive and anxiety disorders at baseline (current and lifetime) lost significantly less weight after surgery. Postoperative anxiety disorder was not associated with the degree of weight loss at any follow-up time-point; however postoperative depressive disorder was negatively associated with weight loss at the 24-36 month follow-up assessment point.
LIMITATIONS
Missing data, limited statistical power, self-reported height and weight are the limitations of this study.
CONCLUSIONS
As opposed to anxiety disorders, the point prevalence of depressive disorders decreased significantly after bariatric surgery. However, the presence of depressive disorders after bariatric surgery significantly predicted attenuated post-surgical improvements and may signal a need for clinical attention. | 10.1016/j.jad.2011.03.025 |
pubmed_1022_23841 | Pygmy hunter-gatherers from Central Africa have shared a network of socioeconomic interactions with non-Pygmy Bantu speakers since agropastoral lifestyle spread across sub-Saharan Africa. Ethnographic studies have reported that their diets differ in consumption of both animal proteins and starch grains. Hunted meat and gathered plant foods, especially underground storage organs (USOs), are dietary staples for pygmies. However, scarce information exists about forager-farmer interaction and the agricultural products used by pygmies. Since the effects of dietary preferences on teeth in modern and past pygmies remain unknown, we explored dietary history through quantitative analysis of buccal microwear on cheek teeth in well-documented Baka pygmies. We then determined if microwear patterns differ among other Pygmy groups (Aka, Mbuti, and Babongo) and between Bantu-speaking farmer and pastoralist populations from past centuries. The buccal dental microwear patterns of Pygmy hunter-gatherers and non-Pygmy Bantu pastoralists show lower scratch densities, indicative of diets more intensively based on nonabrasive foodstuffs, compared with Bantu farmers, who consume larger amounts of grit from stoneground foods. The Baka pygmies showed microwear patterns similar to those of ancient Aka and Mbuti, suggesting that the mechanical properties of their preferred diets have not significantly changed through time. In contrast, Babongo pygmies showed scratch densities and lengths similar to those of the farmers, consistent with sociocultural contacts and genetic factors. Our findings support that buccal microwear patterns predict dietary habits independent of ecological conditions and reflect the abrasive properties of preferred or fallback foods such as USOs, which may have contributed to the dietary specializations of ancient human populations. | 10.1371/journal.pone.0084804 |
pubmed_26_9194 | Protein C is an important inhibitor of blood coagulation. We investigated the effect of two polymorphisms within the promoter region of the protein C gene (C/T at position 2405 and A/G at position 2418) on risk of venous thrombosis and on plasma protein C levels. In addition the combined effect of the two polymorphisms with factor V Leiden and oral contraceptive use was investigated. Previous studies on these polymorphisms were small and were not able to investigate synergistic effects. In the Multiple Environmental and Genetic Assessment of risk factors for venous thrombosis (MEGA study), protein C levels were determined in 2,043 patients with venous thrombosis and 2,857 control subjects, and the two polymorphisms in 4,285 patients and 4,863 control subjects. The CC/GG genotype was associated with the lowest protein C levels. Compared to carriers of the TT/AA genotype - a genotype associated with higher protein C levels - the risk of venous thrombosis in CC/GG carriers was 1.3-fold increased (95% confidence interval 1.09-1.48). The combination of factor V Leiden with the CC/GG genotype led to a 4.7-fold increased risk, compared to non-carriers with the TT/AA genotype. Oral contraceptive use together with the CC/GG genotype resulted in a 5.2-fold increased risk. In conclusion, the CC/GG genotype is associated with lower levels of protein C and an elevated risk of venous thrombosis compared to the TT/AA genotype. There is no clear synergistic effect of the CC/GG genotype with factor V Leiden or oral contraceptive use on thrombotic risk. | pubmed_26_9194 |
pubmed_398_22881 | Caudal agenesis is a rare congenital anomaly resulting from an insult to the structures of the caudal eminence. It may be associated with anomalies of other structures derived from the caudal eminence: the hindgut and the urogenital system. Patients are more likely to present first to the pediatric surgeon (for evaluation of gastrointestinal anomalies), the urologist (for urogenital malformation or dysfunction), or the orthopedic surgeon (for lower extremity abnormalities), than to the neurosurgeon. Characteristic external features of the buttocks, hips, and lower extremities may suggest the diagnosis. MR imaging is the diagnostic modality of choice and should be used in all patients with suggestive external features or other caudal anomalies. The level of bone anomaly corresponds well to the level of weakness but not sensory loss. Sensation is usually relatively preserved. The caudal spinal cord is often truncated in cases of high bone lesions and tethered, with occasional association with a dysraphic lesion, in cases of low bone lesions. Early neurosurgical intervention is preferred in all cases of recognized occult spinal dysraphism. Progressive neurologic deficits may develop later in life in patients with unrecognized tethered cord or dural stenosis and require neurosurgical repair on diagnosis. A better understanding of the embryology of the caudal region and investigation of the teratogens that may interfere with this stage of development should lead to more effective treatment and prevention of caudal agenesis and the associated caudal anomalies. | pubmed_398_22881 |
pubmed_365_7029 | Tailored femtosecond laser pulses from a computer-controlled pulse shaper were used to optimize the branching ratios of different organometallic photodissociation reaction channels. The optimization procedure is based on the feedback from reaction product quantities in a learning evolutionary algorithm that iteratively improves the phase of the applied femtosecond laser pulse. In the case of CpFe(CO)2Cl, it is shown that two different bond-cleaving reactions can be selected, resulting in chemically different products. At least in this case, the method works automatically and finds optimal solutions without previous knowledge of the molecular system and the experimental environment. | 10.1126/science.282.5390.919 |
pubmed_1051_10761 | BACKGROUND
Machine learning (ML) is increasingly used to predict suicide deaths but their value for suicide prevention has not been established. Our first objective was to identify risk and protective factors in a general population. Our second objective was to identify factors indicating imminent suicide risk.
METHODS
We used survival and ML models to identify lifetime predictors using the Cohort of Norway (n=173,275) and hospital diagnoses in a Saskatoon clinical sample (n=12,614). The mean follow-up times were 17 years and 3 years for the Cohort of Norway and Saskatoon respectively. People in the clinical sample had a longitudinal record of hospital visits grouped in six-month intervals. We developed models in a training set and these models predicted survival probabilities in held-out test data.
RESULTS
In the general population, we found that a higher proportion of low-income residents in a county, mood symptoms, and daily smoking increased the risk of dying from suicide in both genders. In the clinical sample, the only predictors identified were male gender and older age.
CONCLUSION
Suicide prevention probably requires individual actions with governmental incentives. The prediction of imminent suicide remains highly challenging, but machine learning can identify early prevention targets. | 10.1186/s12888-022-03702-y |
pubmed_147_16186 | Superoxide (O(2)(-)) is a primary agent of intracellular oxidative stress. Genetic studies in many organisms have confirmed that excess O(2)(-) disrupts metabolism, but to date only a small family of [4Fe-4S] dehydratases have been identified as direct targets. This investigation reveals that in Escherichia coli O(2)(-) also poisons a broader cohort of non-redox enzymes that employ ferrous iron atoms as catalytic cofactors. These enzymes were inactivated by O(2)(-) both in vitro and in vivo. Although the enzymes are known targets of hydrogen peroxide, the outcome with O(2)(-) differs substantially. When purified enzymes were damaged by O(2)(-) in vitro, activity could be completely restored by iron addition, indicating that the O(2)(-) treatment generated an apoprotein without damaging the protein polypeptide. Superoxide stress inside cells caused the progressive mismetallation of these enzymes with zinc, which confers little activity. When O(2)(-) stress was terminated, cells gradually restored activity by extracting zinc from the proteins. The overloading of cells with zinc caused mismetallation even without O(2)(-) stress. These results support a model in which O(2)(-) repeatedly excises iron from these enzymes, allowing zinc to compete with iron for remetallation of their apoprotein forms. This action substantially expands the physiological imprint of O(2)(-) stress. | 10.1111/mmi.12263 |
pubmed_705_1834 | We conducted a double-blind, placebo-controlled study of 40 patients (aged 19 to 60 years) with clinical definite relapsing remitting (RR) MS and brain MRI confirmed. Patients were randomly assigned to receive a loading dose of immunoglobulin IgG (0.4 g/kg/body weight per day for 5 consecutive days), followed by single booster doses (0.4 g/kg/body weight) or placebo once every 2 months for 2 years. The primary outcome measures were change in the yearly exacerbation rate (YER), proportion of exacerbation-free patients, and time until first exacerbation. Neurologic disability, exacerbation severity, and changes in brain MRI lesion score were the secondary outcome measures, all determined at baseline, 1 year, and on completion. Treated patients showed a reduction in YER from 1.85 to 0.75 after 1 year and 0.42 after 2 years versus 1.55 to 1.8 after 1 year and to 1.4 after 2 years in the placebo group (p = 0.0006, overall), reflecting a 38.6% reduction in relapse rate. Six patients in the IVIg group were exacerbation free throughout the 2-year period of the study, whereas none were exacerbation free in the placebo group. The median time to first exacerbation was 233 days in the IVIg group versus 82 days in the placebo group (p = 0.003). Neurologic disability as measured by the Expanded Disability Status Scale (EDSS score) decreased by 0.3 in the IVIg group and increased by 0.15 in the placebo group. Total lesion score evaluated by brain MRI did not show a significant difference between groups. Side effects were minor and occurred in only 19 of 630 (3.0%) infusions administered in both groups. Our results suggest that IVIg may be safe and effective in reducing the frequency of exacerbations in RR-MS. | 10.1212/wnl.50.2.398 |
pubmed_977_9433 | Decline in winter sea-ice concentration (SIC) in the Barents-Kara Sea significantly impacts climate through increased heat release to the atmosphere. However, the past Barents-Kara SIC decrease rate is underestimated in the majority of Coupled Model Intercomparison Project Phase 6 (CMIP6) climate models. Here we show that climate model simulations can reproduce the Barents-Kara SIC trend for 1970-2017 when sea surface temperature (SST) variability in the Gulf Stream region is constrained by observations. The constrained warming of the Gulf Stream strengthens ocean heat transport to the Barents-Kara Sea that enhances the SIC decline. The linear trends between the SIC and SST are highly correlated in the CMIP6 ensemble, suggesting that the externally forced component of the Gulf Stream SST increase explains up to 56% of the forced Barents-Kara SIC trend. Therefore, future warming of the Gulf Stream can be an essential pacemaker of the SIC decline. | 10.1038/s41467-022-31117-6 |
pubmed_890_77 | Systemic lupus erythematosus (SLE) is an autoimmune syndrome associated with severe organ damage resulting from the activation of immune cells. Recently, a role for caspase-1 in murine lupus was described, indicating an involvement of inflammasomes in the development of SLE. Among multiple inflammasomes identified, the NLRP3 inflammasome was connected to diverse diseases, including autoimmune encephalomyelitis. However, the function of NLRP3 in SLE development remains elusive. In this study, we explored the role of NLRP3 in the development of SLE using the pristane-induced experimental lupus model. It was discovered that more severe lupus-like syndrome developed in Nlrp3-R258W mice carrying the gain-of-function mutation. Nlrp3-R258W mutant mice exhibited significantly higher mortality upon pristane challenge. Moreover, prominent hypercellularity and interstitial nephritis were evident in the glomeruli of Nlrp3-R258W mice. In addition, hyperactivation of the NLRP3 inflammasome in this mouse line resulted in proteinuria and mesangial destruction. Importantly, all of these phenotypes were largely attributed to the Nlrp3-R258W mutation expressed in myeloid cells, because Cre recombinase-mediated depletion of this mutant from such cells rescued mice from experimental lupus. Taken together, our study demonstrates a critical role for NLRP3 in the development of SLE and suggests that modulating the inflammasome signal may help to control the inflammatory damage in autoimmune diseases, including lupus. | 10.4049/jimmunol.1600659 |
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