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pubmed_167_11002 | PURPOSE
Treatment modalities for glottic cancer comprise surgery, (chemo-)radiation, and combined treatment options. Glottic cancer involving the anterior commissure (AC) requires special preoperative assessment and surgical skills, as it is commonly considered a risk factor for local recurrence. The aim of this study is to analyze the oncological effectiveness of transoral laser microsurgery (TLM) in the early glottic cancer involving the AC.
METHODS
We retrospectively analyzed the data of all patients with primary, early staged (T1-2) glottic squamous cell carcinoma who were treated between 2004 and 2014. Patients were preferably treated by TLM (rather than open surgical techniques) if appropriated transoral exposure of the endolarynx was ensured. Voice outcomes were not assessed.
RESULTS
186 patients with early glottic cancer were included, 143 were treated by TLM and 43 by other therapy modalities [OT open surgical techniques (n = 32) or primary (chemo-)radiation (n = 11)], respectively. In 84 patients (59%) of the TLM cohort, the AC was involved (OT cohort n = 29 (73%), p = 0.143). The 1-, 3-, and 5-year local control rates after TLM were 91%, 86%, and 81% in patients without AC infiltration and 84%, 74%, and 70% in patients with AC infiltration, respectively, showing no statistical difference (p = 0.180). The 5-year disease-free survival and laryngeal preservation rate (LPR) did not differ with regard to AC infiltration (p = 0.215 and p = 0.261). Comparing the treatment modalities, the 5-year LPR was 90% for TLM and 83% for OT regardless of infiltration of the AC (p = 0,653 and p = 0.267, respectively).
CONCLUSION
TLM is an effective surgical treatment for early glottic cancer with AC involvement in patients with adequate transoral laryngeal exposure. | 10.1007/s00405-018-5261-4 |
pubmed_995_1417 | In experiments performed on 190 white inbred rats of various age, effects of total deep hypothermia on mitotic activity of basal epidermocytes, quantity of non-pigmented granular dendrocytes and lymphocytes of epidermis, tissue dermal basophils has been studied. Age difference in changes of the parameters examined at cold effect have been stated. A suggestion is made on existence in the skin of a local regularity system "basal epidermocyte--non-pigmented granular dendrocyte--intraepidermal lymphocyte--tissue dermal basophils", participating in regulation of protective properties of the organ. | pubmed_995_1417 |
pubmed_549_66 | A mucocele is a collection of mucus, which is lined by the mucus-secreting epithelium of a paranasal sinus. Paranasal sinus mucoceles occur as a result of inflammation, tumor, trauma or surgical manipulation. The anterior clinoid process may be pneumatized by an extension of the sphenoid paranasal sinus air space during normal development. Mucocele of the anterior clinoid process is rare. We report a patient with mucopyocele of the anterior clinoid process that resulted in rapid monocular visual loss. The left optic canal was exposed extradurally via a supraorbital craniotomy and the mucopyocele was totally excised. The optic canal was decompressed by drilling the superior, lateral and medial rims, to achieve circumferential decompression of the optic nerve. The patient's vision improved postoperatively. | 10.1016/j.jocn.2009.09.019 |
pubmed_195_22786 | BACKGROUND AND PURPOSE
We assessed the first evaluation at a large ventilation clinic in the Netherlands to: (i) determine what proportion of patients with motor neuron disease would benefit from earlier referral; and (ii) examine the patient preferences regarding ventilatory support.
METHODS
Observational study at a single centre with a catchment area of 7.6 million inhabitants. Data on disease status, the referral process and patients' preferences regarding ventilatory support were collected during the first home ventilation services (HVS) assessment and analysed for correlation with the presence of daytime hypercapnia and suspected nocturnal hypoventilation. The latter conditions require immediate (within 48 h) or subacute (within 3 weeks) initiation of ventilatory support.
RESULTS
Vital capacity (in percentage of predicted value, VC%pred) was assessed by referring physicians in 84% of the 217 referred patients; the mean VC%pred was 69% (SD 16). One-hundred and ninety-one patients attended the first HVS assessment without ventilatory support, at a median of 21 days following referral: 18% had respiratory failure (daytime hypercapnia), 19% had normocapnia but were suspected of nocturnal hypoventilation, and 63% had normocapnia without symptoms. Following the HVS assessment, 25 patients (13%) declined home mechanical ventilation; this occurred more often in patients with (14/70) compared with patients without respiratory impairment (11/121; P < 0.05).
CONCLUSION
A meaningful proportion of patients who desire ventilatory support are referred to a ventilation clinic after already developing respiratory failure. Future studies could examine means, including more sensitive respiratory measures, to detect those patients who could benefit from earlier referral. | 10.1111/ene.12096 |
pubmed_689_3078 | Bruton's tyrosine kinase (BTK) inhibitors suppressing the aberrant activation of BTK have led to a paradigm shift in the therapy of B-cell malignancies. However, there is an urgent need to discover more selective covalent BTK inhibitors owing to the off-target adverse effects of the approved inhibitor, ibrutinib. Herein, we disclose the discovery and preliminary activity studies of novel BTK inhibitors carrying 1-amino-1H-imidazole-5-carboxamide as a hinge binder. The most potent BTK inhibitor 26 demonstrates impressive selectivity, favorable pharmacokinetic properties, and robust antitumor efficacy in vivo, which indicates its potential as a novel therapeutic option for B-cell lymphomas. Importantly, to the best of our knowledge, this is the first example of a 1-amino-1H-imidazole-5-carboxamide scaffold used as the hinge binder of kinase inhibitors, which will largely expand the chemical diversity of kinase inhibitors. | 10.1021/acs.jmedchem.1c01559 |
pubmed_546_9672 | The maxillary blood supply is essential for preserving the vitality of the affected maxillary region, integration of the grafting material, and wound healing such as following sinus floor elevation. Although it is well established that edentulous maxillae demonstrate a decreasing vascularity as bone resorption progresses, the vascular conditions relevant to sinus floor elevation procedures have not been investigated yet. This study deals with maxillary arteries relevant to sinus floor elevation surgery and examines the vascularization of the lateral maxilla after tooth loss. The vessels of the lateral maxilla of 18 maxillary specimens (10 male, 8 female, mean age 67 years) were prepared anatomically and the local main arteries, the number of macroscopically discernible branches and anastomoses, their calibers, and the distance between the caudal main branches and the alveolar ridge recorded. The lateral maxilla is supplied by branches of the posterior superior alveolar artery (PSAA) and the infraorbital artery (IOA) that form an anastomosis in the bony lateral antral wall, which also supplies the Schneiderian membrane. This intraosseous anastomosis was found in all of the specimens. Eight of 18 also showed an extraosseous anastomosis between PSAA and IOA, vestibular to the antral wall, giving off an average of 3 branches cranially and 5 branches caudally. The two anastomoses form a double arterial arcade to supply the lateral antral wall and, partly, the alveolar process. The PSAA had a mean caliber of 1.6 mm and exhibited an average of 2 endosseous and 1 extraosseous branches. The IOA had a mean diameter of 1.6 mm and showed an average of 1 endosseous and 3 extraosseous branches. The mean distance between the intraosseous anastomosis and the alveolar ridge was 19 mm in 2 defined measuring sites. Its mean length was 44.6 mm. The epiperiosteal vestibular anastomosis was situated further cranially at a mean distance of 23 to 26 mm from the alveolar ridge and had a mean length of 46 mm. The rather large caliber of the vessels supplying the lateral antral wall seems to be crucial to the fact that the periosteal blood supply is maintained even in severe maxillary atrophy and after complete disappearance of the centro-medullary vessels. | 10.1034/j.1600-0501.1999.100105.x |
pubmed_595_12029 | AIMS
To determine whether reductions in frequency of heroin use were associated with reductions in the use of other drugs over a 24-month period.
DESIGN
Longitudinal cohort, with follow-up at 3, 12 and 24 months.
PARTICIPANTS
Six hundred and fifteen heroin users recruited for the Australian Treatment Outcome Study.
SETTING
New South Wales, Australia.
FINDINGS
The proportion reporting weekly heroin use declined significantly at 3, 12 and 24 months. Reductions in heroin use were associated with longer periods in both residential rehabilitation (RR) and maintenance treatment (MT). Less frequent use of other opioids, cocaine, amphetamine, cannabis and benzodiazepines were noted over follow-up, with alcohol use remaining stable. Across follow-up, lower frequency heroin use was associated with reduced likelihood of frequent use of other opioids, cocaine, amphetamine and benzodiazepines. Alcohol and cannabis use were unrelated to heroin use. Longer periods spent in RR were associated with declines in the use of all other drug classes, with MT associated with declines in other opioid and alcohol use.
CONCLUSIONS
There was no evidence for drug substitution in the face of reduced heroin use in this cohort of treatment seekers. The fear that a successful reduction in heroin use amongst treatment seekers will precipitate an increase in the use of other drugs appears ill-founded. | 10.1016/j.drugalcdep.2006.03.004 |
pubmed_142_8116 | Detecting deposits of amyloid β fibrils in the brain is of paramount importance for an early diagnosis of Alzheimer's disease. A number of PET tracers have been developed for amyloid imaging, but many suffer from poor specificity and large signal to background ratio. Design of tracers with specificity and improved binding affinity requires knowledge about various potential binding sites in the amyloid β fibril available for the tracers and the nature of the local microenvironment of these sites. In this study we investigate the local structure of fibrils using two important probes, namely, thioflavin T (a fluorescent probe) and AZD2184 (a PET tracer). The target structures for amyloid-β(1-42) fibril are based on reported NMR solution models. By explicitly considering the effect of fibril flexibility on the available binding sites for all these models, the binding affinity of these probes has been investigated. The binding profiles of AZD2184 and thioflavin T were studied by molecular docking and molecular dynamics simulation methods. The two compounds were found to bind at the same sites of the fibril: three of which are within the fibril, and one is on the two sides of the Met35 residue on the surface. The binding affinity of AZD2184 and thioflavin T is found to be higher at the core sites than on the surface due to more contact residues. The binding affinity of AZD2184 is much higher than that of thioflavin T at every site due to electrostatic interaction and spatial restriction, which is in good agreement with experimental observation. However, the structural change of thioflavin T is much more significant than that of AZD2184, which is the chemical basis for its usage as a fluorescent probe. The ramifications of these results for the design and optimization of PET radioligands and fluorescent probes are briefly discussed. | 10.1021/acs.jpcb.5b05964 |
pubmed_922_594 | We experienced a case of a 36-year-old female with rapidly progressive glomerulonephritis (RPGN) due to anti-neutrophil cytoplasmic antibody (ANCA)-associated nephritis and systemic lupus erythematosus (SLE) nephritis. Chiral amino acid metabolomics revealed a prominent profile of D-serine in this patient. At the fulminant period of RPGN, the level of plasma D-serine, a potential biomarker in CKD that reflects actual glomerular filtration ratio (GFR), was extremely high. On the other hand, urinary fractional excretion (FE) of D-serine, which was usually much higher than that of L-isoform, was 0% in this patient. These abnormal D-serine profiles normalized in response to the intensive treatment. Normalizations of blood D-serine levels were in parallel with those of blood creatinine levels and potentially reflect the recovery of GFR. FE of D-serine increased transiently before the normalization of D-serine profile, suggesting that kidney promotes urinary excretion of D-serine for the normalization of plasma D-serine level. These unexplored clinical features of D-serine well reflected the clinical course of this patient. Blood D-serine level can also serve as a biomarker in acute kidney injury (AKI) or RPGN, and, in combination with FE of D-serine, may render the clinical practitioners to judge the efficacy of intensive treatments. | 10.1007/s13730-019-00411-6 |
pubmed_691_15140 | Four Cynomologous monkeys (Mecaca fascicularis) received 2000 Rad whole brain irradiation. One remained untreated and exhibited loss of hair, facial edema, brain edema and hydrocephalus. There was loss of alertness and motor activity. One was scheduled to be treated with phenobarbital, but died in 24 hours after irradiation. One animal received 2 mg/kg dexamethasone I.M. daily. It died two weeks after irradiation apparently due to treatment related infection. One animal received 20 mg/kg sodium meclofenamate (Meclomen) orally daily. This animal showed no brain edema and only minimal hydrocephalus, delayed and incomplete hair loss and no facial edema. Further studies of this treatment appear to be justified. | pubmed_691_15140 |
pubmed_18_13944 | BACKGROUND
Although Temozolomide is effective against glioblastoma, the prognosis remains dismal and new regimens with synergistic activity are sought for.
METHODS
In this phase-I/II trial, pegylated liposomal doxorubicin (Caelyx, PEG-Dox) and prolonged administration of Temozolomide in addition to radiotherapy was investigated in 63 patients with newly diagnosed glioblastoma. In phase-I, PEG-Dox was administered in a 3-by-3 dose-escalation regimen. In phase-II, 20 mg/m2 PEG-Dox was given once prior to radiotherapy and on days 1 and 15 of each 28-day cycle starting 4 weeks after radiotherapy. Temozolomide was given in a dose of 75 mg/m2 daily during radiotherapy (60 Gy) and 150-200 mg/m2 on days 1-5 of each 28-day cycle for 12 cycles or until disease progression.
RESULTS
The toxicity of the combination of PEG-Dox, prolonged administration of Temozolomide, and radiotherapy was tolerable. The progression free survival after 12 months (PFS-12) was 30.2%, the median overall survival was 17.6 months in all patients including the ones from Phase-I. None of the endpoints differed significantly from the EORTC26981/NCIC-CE.3 data in a post-hoc statistical comparison.
CONCLUSION
Together, the investigated combination is tolerable and feasible. Neither the addition of PEG-Dox nor the prolonged administration of Temozolomide resulted in a meaningful improvement of the patient's outcome as compared to the EORTC26981/NCIC-CE.3 data. | 10.1186/1471-2407-9-308 |
pubmed_979_12181 | In 1987-88, the first of two surveys conducted questioned the administrator's viewpoint on choice of reporting authority for plant operations and clinical engineering departments as well as the job satisfaction and prestige associated with these responsibilities. The second tested the response of clinical engineers on similar issues as well as the effect of certain organizational factors on their degree of functional involvement in the equipment-management process. In the first survey, two-thirds of the administrators chose a structure that, as shown in the second survey, leads to a higher degree of involvement and satisfaction for clinical engineers. Other organizational factors that have an effect are: the type of hospital (teaching and nonteaching), the presence of qualified university-degree engineers, and ensuring that the clinical engineering role within the health care institution is recognized and supported. Teaching hospitals are found to provide a better climate than nonteaching ones for the support of the research and education activities. Clinical engineering departments, whose role has been recognized and supported by their institution, are more substantially involved in all aspects of the equipment-management process than those who are still seeking this recognition. Finally, departments where university-degree engineers have been hired again show more involvement and commitment to the quality and efficiency of their operation. | pubmed_979_12181 |
pubmed_201_20996 | BACKGROUND
The fungicide benzovindiflupyr belongs to the class of succinate dehydrogenase inhibitors (SDHIs). Certain SDHIs have shown plant physiological effects, so-called secondary effects, that appeared to be related to the plant water status. Therefore, the effect of benzovindiflupyr on transpiration of leaves and whole wheat plants was studied under controlled conditions. Furthermore, wheat yield trials under controlled and natural drought stress in the field were conducted.
RESULTS
Transpiration of detached wheat leaves was reduced by benzovindiflupyr in a dose-dependent manner. Similarly, whole-plant transpiration decreased for several days following application of this fungicide. In 16 field trials under drought stress conditions that were classified as disease-free, treatment of wheat plants at the flag leaf stage or at heading with benzovindiflupyr showed a grain yield increase (+5.2%; P ≤ 0.01) that was partially attributed to an increased thousand-grain weight.
CONCLUSIONS
Water saving during pre-anthesis as a result of benzovindiflupyr application may be associated with better seed setting and filling under dry field conditions in wheat. The results of this research provide new insights into secondary effects of SDHIs that lead directly to yield improvements. © 2017 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry. | 10.1002/ps.4754 |
pubmed_449_3022 | The conventional upper 95 percentile references limit of serum calcium does not necessarily constitute an optimal decision limit in screening for patients with hyperparathyroidism. The design of optimal screening procedures has to consider (a) the prevalence of disease; (b) the relative importance of making correct classifications of patients; and (c) the influence of analytical imprecision and inaccuracy. Based on serum calcium determinations from three reference sample groups (healthy individuals, patients with hyperparathyroidism, and patients with hypercalcaemia due to malignant disease) optimal decision limits were calculated for different screening situations. Optimum was defined in terms of estimated 'costs' due to misclassification. Different values for disease prevalence were used, as well as different weighting factors reflecting the importance related to correct classification of healthy and pathological patients. For a disease prevalence of 5% the optimal decision limit varies between 2.59 and 2.65 mmol/l for a weighting ratio false positives to false negatives of between 1:5 to 5:1. For a prevalence of 0.1% the corresponding range was 2.67-2.72 mmol/l. Compared to classification on the basis of the conventional upper reference limit, the application of optimal decision limits means significantly lower costs due to misclassification. Analytical bias then has to be kept stable within +/- 0.01 mmol/l. Inter-laboratory analytical variation also has to be reduced to the same level in order to make it possible to transfer reference values, decision limits and single patient values to other laboratories. | pubmed_449_3022 |
pubmed_636_7581 | PURPOSE
This pilot study sought to examine the relationship between functional health patterns and accident proneness.
METHODS
A quantitative-descriptive design was employed assessing accident proneness by collecting data on the occurrence of accidents among a sample of university graduates, and examining this in relation to biographical data and information collated using the Functional Health Pattern Assessment Screening Tool (FHPAST). Data were analyzed using descriptive and inferential statistics.
FINDINGS
One FHPAST factor predicted more frequent sports accidents. Age was also shown to be a significant predictor but in a counterintuitive way, with greater age predicting less accident proneness.
CONCLUSION
The FHPAST may have a role to play in accident prediction.
IMPLICATIONS FOR NURSING PRACTICE
Functional health pattern assessment may be useful for predicting accidents. | 10.1111/j.2047-3095.2012.01207.x |
pubmed_426_15458 | The management of severely burned and exposed supportive osseous tissues is not fully standardized. We present two patients in whom extensive debridement and decortication of the involved bone may have contributed to subsequent stress fractures. We propose an alternative therapeutic approach for this problem, including: minimal debridement of the bone, early coverage of the exposed bone with vascularized muscle, and adequate prophylactic protection. | 10.1097/00005373-198703000-00019 |
pubmed_286_16885 | Hepatitis B is one of most etiologies of Liver cirrhosis in China, and clinically lacks the effective strategy for Hepatitis B caused cirrhosis (HBC) therapy. As a complementary and alternative medicine, Chinese Traditional Medicine (TCM) has special therapeutic effects for HBC. Here, we focus on the evolution process of HBC TCM syndromes, which was from Excessive (Liver-Gallbladder Dampness-Heat Syndrome, LGDHS) to Deficient (Liver-Kidney Deficiency Syndrome, LKYDS) via Excessive-Deficient syndrome (Liver-Depression and Spleen-Deficiency Syndrome, LDSDS). Using R package, 16 miRNAs in LGDHS/Normal, 48 miRNAs in LDSDS/LGDHS, and 16 miRNAs in LKYDS/LDSDS were identified, respectively. The miRNA-target networks show that the LDSDS was most stability and complicated. Subsequently, 4 kernel miRNAs with LGDHS-LDSDS process, and 5 kernel miRNAs with LDSDS-LKYDS process were screened. Using RT-qPCR data, p1 (hsa-miR-17-3p, -377-3p, -410-3p and -495) and p2 miRNA panel (hsa-miR-377-3p, -410-3p, -27a-3p, 149-5p and 940) were identified by Logistic Regression Model, which clearly improve the accuracy of TCM syndrome classification. The rebuilt miRNA-target network shows that the LDSDS is a critical point and might determine the evolution directions of HBC TCM syndrome. This study suggests that the identified kernel miRNAs act as potential biomarkers and benefit to evaluate the evolution tendency of HBC TCM syndromes. | 10.1038/s41598-017-11351-5 |
pubmed_547_6446 | Substrates destined for degradation by the 26 S proteasome are labelled with polyubiquitin chains. Rpn11/Mpr1, situated in the lid subcomplex, partakes in the processing of these chains or in their removal from substrates bound to the proteasome. Rpn11 also plays a role in maintaining mitochondrial integrity, tubular structure and proper function. The recent finding that Rpn11 participates in proteasome-associated deubiquitination focuses interest on the MPN+ (Mpr1, Pad1, N-terminal)/JAMM (JAB1/MPN/Mov34) metalloprotease site in its N-terminal domain. However, Rpn11 damaged at its C-terminus (the mpr1-1 mutant) causes pleiotropic effects, including proteasome instability and mitochondrial morphology defects, resulting in both proteolysis and respiratory malfunctions. We find that overexpression of WT (wild-type) RPN8, encoding a paralogous subunit that does not contain the catalytic MPN+ motif, corrects proteasome conformations and rescues cell cycle phenotypes, but is unable to correct defects in the mitochondrial tubular system or respiratory malfunctions associated with the mpr1-1 mutation. Transforming mpr1-1 with various RPN8-RPN11 chimaeras or with other rpn11 mutants reveals that a WT C-terminal region of Rpn11 is necessary, and more surprisingly sufficient, to rescue the mpr1-1 mitochondrial phenotype. Interestingly, single-site mutants in the catalytic MPN+ motif at the N-terminus of Rpn11 lead to reduced proteasome-dependent deubiquitination connected with proteolysis defects. Nevertheless, these rpn11 mutants suppress the mitochondrial phenotypes associated with mpr1-1 by intragene complementation. Together, these results point to a unique role for the C-terminal region of Rpn11 in mitochondrial maintenance that may be independent of its role in proteasome-associated deubiquitination. | 10.1042/BJ20040008 |
pubmed_980_23190 | METHODS
A retrospective study on SJS patients was conducted at a tertiary medical center. All patients diagnosed as SJS, with available serum amylase index, were included. Clinical data of all subjects were retrospectively collected and analyzed. Colonic mucosal biopsies were obtained to measure tight junction protein expression.
RESULTS
A total of nine patients were included in the present study for study analysis. The average serum amylase of the study cohort was 228.78 ± 204.18 U/L. Among which, five patients had a positive fecal occult blood test (FOBT). Colonic mucosal biopsies were obtained and stained with occludin and zonula occludens-1 (ZO-1). The expression of occludin and ZO-1 was significantly downregulated in SJS patients (p < 0.01), which was indicative of intestinal barrier dysfunction.
CONCLUSION
Hyperamylasemia often extends beyond pancreatic diseases. Clinical awareness of asymptomatic hyperamylasemia secondary to other systemic diseases can help avoid unnecessary overexamination and overtreatment. | 10.1155/2020/3531907 |
pubmed_26_13101 | OBJECTIVE
The aims are to briefly review treatment outcomes for impaired practitioners, and to explore how preventive and early intervention, and the accessing of and retention within treatment systems for impaired medical practitioners, and particularly psychiatrists, could be improved to maximize the doctors' chances of full recovery and to minimize danger to self and others.
METHODS
The literature on the treatment and care of medical practitioner impairment due to mental illness, and substance use, with special reference to impaired psychiatrists is briefly reviewed. The implications of deficiencies of usual clinical management of doctors impaired by mental illness and opportunities for improvement in services for them are explored, including the impact of the experience of being an impaired medical practitioner under psychiatric treatment. The roles of medical boards and advisory services are examined.
RESULTS
Medical practitioner impairment due to mental illness has a severe impact on doctors' lives and the lives of their families due to both the effects of the disorder and the experience of communal, professional and self stigma and discrimination. Deficiencies in usual practice in the treatment and rehabilitation of such individuals are identified, and alternatives explored.
CONCLUSIONS
Prevention, early detection, intervention, and treatment programs that are more continuous more sensitive to the needs of impaired practitioners, that are more continuous, better structured, and rehabilitation and recovery focused, may be more likely to produce a positive outcome. | 10.1080/10398560802579526 |
pubmed_1006_5296 | The submitted paper deals with one of the possible aspects of the investigation of nosocomial infections, i.e. investigations of the properties of hospital strains, their importance and possible use. The incidence of bacterial hospital strains was investigated in a surgical department of a district hospital of the North Bohemian region in October 1990; at the time of the survey 29 nosocomial infections (36.1%) were revealed by the prevalence method. Bacterial hospital strains were isolated from patients with a nosocomial infection, from the attending staff and the hospital environment. The following markers were investigated: biotyping, phagotyping, serotyping, toxin production, sensitivity to antimicrobial substances and sensitivity to disinfectants. Based on results of marking of hospital strains 7 incidences with a possible epidemiological association were detected where the hospital strain of equal or very similar properties dominated. The results of the investigation confirmed the important participation of the attending staff in the spread of nosocomial infections, in particular via contaminated hands, and drew attention to shortcomings as regards adherence to the hygienic and epidemiological regime in the investigated department. | pubmed_1006_5296 |
pubmed_257_3488 | Celiac disease is strongly associated with the HLA class II D-region serologic markers DR3 (DRw17) and DQw2. Moreover, by restriction fragment length polymorphism analysis, greater than 90% of DR3 (DRw17), DQw2 celiac disease patients have a polymorphic 4.0-kilobase Rsa I DP B gene DNA fragment. The present study sought to determine if there is a unique HLA class II D-region A or B gene structural variant on the DR3 (DRw17) haplotype found in celiac disease. The polymorphic second exons of the coding DRB, DQA and DQB, and DPA and DPB genes in celiac disease patients with the DR3 (DRw17) haplotype were sequenced after amplification by the polymerase chain reaction. To define the DP B genes associated with celiac disease, the second exons of the coding DP B genes from 27 celiac disease patients were amplified similarly and probed by using a panel of sequence specific oligonucleotides. The HLA-DR, -DQ, and -DP A and B gene second exon sequences of celiac disease patients were noted to be identical to sequences that can be found also, although at a significantly lower frequency, in unaffected individuals. This is compatible with a disease model wherein the HLA class II genes on the DR3 (DRw17) haplotype are necessary, but not sufficient, for the phenotypic expression of celiac disease. Analysis of the DP B genes revealed a significant increase in the frequency of the alleles DPB1 and DPB3 in celiac disease. Furthermore, the increased frequency of the 4.0-kilobase Rsa I DP B gene restriction fragment length polymorphism in celiac disease can be accounted for by the overrepresentation in disease of the alleles DPB1 and DPB3. The HLA-associated susceptibility to celiac disease appears to be multigenic, with specific, but structurally normal, allelic variants in the DP and DQ/DR subregions contributing to disease susceptibility. | 10.1073/pnas.86.16.6274 |
pubmed_604_2976 | This paper describes an analytical method involving a simple solvent extraction for the simultaneous liquid chromatography coupled to quadrupole tandem mass spectrometry (LC-MS/MS) determination of carbosulfan, its most toxic metabolite--carbofuran--, and its other main metabolites--3-hydroxycarbofuran, 3-ketocarbofuran, 3-hydroxy-7-phenolcarbofuran, 3-keto-7-phenolcarbofuran, 7-phenolcarbofuran and dibutylamine--in oranges. Chromatography was performed on a Zorbax Bonus-RP (150 mm x 2.1 mm, 5 microm). The mobile phase was a ternary gradient water-methanol-acetonitrile with 1.0 mM ammonium acetate at flow rate of 0.2 ml min(-1). The LC separation and MS/MS optimization were studied to select the most appropriate operating conditions. The method developed has also been validated. The limits of quantification (LOQs) were from 1 microg kg(-1) for carbofuran to 10 microg kg(-1) for 3-keto-7-phenolcarbofuran. Extracts spiked with carbosulfan and its metabolites, at LOQ level, yielded average recoveries in the range 60-94%, with relative standard deviations (R.S.D.s) less than 15%. Calibration curves for carbosulfan and its metabolites (range LOQ-1000LOQ) were linear, with coefficients of correlations better than 0.990. The method was successfully applied to establish the primary degradation products in oranges treated with carbosulfan. The LC-MS/MS method developed is simple, rapid, and suitable for the quantification and confirmation of carbosulfan and seven of its main metabolites in orange at levels lower than 10 microg kg(-1). | 10.1016/j.aca.2006.04.033 |
pubmed_546_5226 | Human antibody responses to latent membrane protein 1 (LMP1) in patients with Epstein-Barr virus (EBV)-related disease syndromes were analyzed in detail. Only by immunoblot analysis with purified recombinant LMP1 and by IFA on recombinant LMP1-expressing insect cells could human antibodies directed against LMP1 be detected. Low serum levels of LMP1-directed antibodies could be detected in 3 of 8 EBV-positive Hodgkin's disease patients, 3 of 40 nasopharyngeal carcinoma patients, 2 of 23 Burkitt's lymphoma patients, and 1 of 27 non-Burkitt's lymphoma patients. No LMP1-directed antibodies could be detected in healthy EBV carriers, infectious mononucleosis patients, or patients with chronic EBV disease. All sera contained significant levels of EBV antibodies directed against the immunodominant EBV proteins and peptides. From this study, it can be concluded that LMP1 is a protein with a very low immunogenicity for the humoral immune response in humans. | 10.1086/314704 |
pubmed_260_8936 | OBJECTIVE
To construct a novel in vitro endothelial cell system to explore the changes of nuclear factor-kappaB (NF-kappaB) and intercellular adhesion molecule-1 (ICAM-1) levels after exposure to various intermittent hypoxia (IH) and re-oxygenation, an IH/reoxygenation (ROX) model.
METHODS
We developed a gas control delivery system that permitted the exposure of ECV304 cell cultures, immortalized endothelial cell strain cultures of human umbilical vein endothelial cells (HUVEC), to IH/ROX cycles, simulating the pattern of hypoxic episodes seen in recurrent apnea. Cell samples were divided into the following groups according to IH duration/ROX duration. Group A (Intermittent Normoxia Group): 21% O(2) 15 s/21% O(2) 3 min 45 s; Group B (Standard Culture Group): no exposure; Group C: 1.5% O(2) 15 s/21% O(2) 3 min 45 s; Group D: 10% O(2) 15 s/21% O(2) 3 min 45 s; Fixed IH protocol as 1.5% O(2) 15s and ROX extent to 21% O(2), IH/ROX frequencies varied as 12 (Group C), 9.23 (Group E), 6.32 (Group F), 20 (Group G) and 40 (Group H) episodes per hour; Group I: 1.5% O(2) 30 s/21% O(2) 3 min 45 s; and after the exposure of Group C, the cell cultures were exposed to standard incubation device for 60 min (Group J) and 120 min (Group K). Prepared cell lysates and cell monolayers were analyzed for NF-kappaB levels and ICAM-1 levels in this IH model with enzyme-linked immunosorbent assay (ELISA) and cellular surface ELISA, and the cell total protein levels were measured with the method of bicinchoninic acid for standardization. SPSS 11.5 software package was used for statistical analysis.
RESULTS
NF-kappaB and ICAM-1 levels in Group C were (0.82 +/- 0.28) and (1562 +/- 56) pg/ml, and those in Group A were (0.37 +/- 0.07) and (768 +/- 80) pg/ml, which showed statistical significance as compared with Group C (D = 225.00, 176.04, P < 0.01, < 0.05, respectively). Their levels in Group D were (0.66 +/- 0.22) and (1113 +/- 76) pg/ml, which were also significantly lower than Group C (U = 25.00, 0.00, all P < 0.01). NF-kappaB and ICAM-1 levels in Group I were (0.45 +/- 0.16) and (1155 +/- 19) pg/ml, which were statistically significant compared with Group C (U = 27.00, 0.00, all P < 0.01). In the same time, IH group had the relatively highest NF-kappaB and ICAM-1 levels amongst groups C, E, F, G and H. Which had different IH frequencies (chi(2) = 35.63, 56.89, all P < 0.01). NF-kappaB levels in Group J [(0.6233 +/- 0.0534)] did not differ significantly from Group C (D = 36.00, P > 0.05) and NF-kappaB levels in Group K [(0.3050 +/- 0.0013)] were lower than Group C (D = 234.00, P < 0.01).
CONCLUSIONS
Our data indicated a selective and dose-dependent activation of inflammatory pathways on ECV304 cells by IH/ROX cycles with moderate frequencies, and a long time was needed for the cell rehabilitation from IH/ROX exposure. | pubmed_260_8936 |
pubmed_282_2765 | BACKGROUND
Carpal tunnel syndrome (CTS) and trigger digits are among the most common nontraumatic hand disorders treated by plastic surgeons. The onset of trigger digits after carpal tunnel release (CTR) has been inconsistently reported. This systematic review assessed the prevalence of trigger digits development in patients after CTR surgery.
METHODS
We searched the MEDLINE, EMBASE and SCOPUS databases for papers published between January 1966 and August 2016. Eligible studies contained quantitative data on the incidence of trigger digits after CTR. The primary outcome measure was the onset of trigger digits after CTR. The secondary outcome measure was the prevalence of digital involvement in patients who developed trigger digits after CTR.
RESULTS
A total of 5654 CTR surgeries were performed in the included nine studies, and 483 patients (8.5%) developed trigger digits after CTR. The reported incidence of trigger digits after CTR ranged from 5.2% to 31.7%. The time to development of trigger digits was approximately 6 months postoperatively. In the eight observational studies and in the randomized controlled trial, the thumb and ring finger were reported as the most commonly involved trigger digits, respectively.
CONCLUSIONS
The incidence of trigger digits after CTR surgery is not negligible. Thumbs and ring fingers are the most commonly involved digits. This topic should therefore be suitably addressed during preoperative consultations. | 10.1080/2000656X.2017.1345751 |
pubmed_660_25484 | BACKGROUND
Ornithine transcarbamylase deficiency, an inborn error of metabolism, is the most common urea cycle disorder and is caused by mutations in the OTC gene located on Xp21. In this study, the clinical and genetic characteristics of seven Korean patients with ornithine transcarbamylase deficiency were analyzed.
METHODS
During 2009-2012, a total of seven patients (three male and four female patients) from six unrelated families were diagnosed with ornithine transcarbamylase deficiency by biochemical or molecular analysis. OTC gene sequencing analysis was performed in six of these patients. Clinical manifestations, clinical courses, and the results of genetic studies were reviewed retrospectively.
RESULTS
The median follow-up period for the seven patients with ornithine transcarbamylase deficiency was 44 months (11.9-150 months). Clinical manifestations of ornithine transcarbamylase deficiency included vomiting and seizure, which were the most frequent signs at admission. Two of the four heterozygous female patients (50%) experienced severe neurological sequelae. The early onset male patient characterized severe neurological deficits. The late-onset male patient recovered completely from acute encephalopathy and coma without any neurological deficits. Direct sequencing and multiplex ligation-dependent probe amplification analysis of OTC gene revealed five different mutations. Of these mutations, two were novel (c.867-3T>C and c.664_667delinsAC).
CONCLUSION
Ornithine transcarbamylase deficiency was genetically heterogeneous in the seven Korean patients with confirmed ornithine transcarbamylase deficiency diagnosis by biochemical findings and/or genetic analysis, together with two novel mutations in the OTC gene. We hope that these data will contribute to a better understanding of the clinical course and distinct molecular genetic characteristics of Korean patients with ornithine transcarbamylase deficiency. | pubmed_660_25484 |
pubmed_516_7308 | OBJECTIVE
To examine how parental responses following pediatric injury may influence their child's posttraumatic stress symptoms (PTSS).
METHODS
Heart rate (HR) from 82 pediatric injury patients was measured during emergency medical services (EMSs) transport and following hospital admission. Twelve-hour urinary cortisol levels were assessed upon admission. Child PTSS and parental PTSS and general distress were assessed 6 weeks and 6 months after trauma.
RESULTS
Six-week parental PTSS predicted 6-month child PTSS even after controlling for demographics and general parent distress (DeltaR(2) = .08, p = .03). Parental PTSS moderated the relationship between (a) child cortisol levels and 6-month child PTSS (DeltaR2 = .08, p = .03) and between (b) hospital HR and 6-month child PTSS (DeltaR2 = .09, p = .03).
CONCLUSION
The present findings suggest that parental response to trauma may interact with child acute physiological responses to predict persistent child PTSS. | 10.1093/jpepsy/jsl005 |
pubmed_1030_24496 | A woman in her 30s presented to the emergency department with new-onset sore throat and fever. She had recently been diagnosed with Graves' disease 3 months prior. As a result, she was initiated on atenolol and methimazole for management. Her methimazole dosing had been stable at 15 mg daily for the month prior to presentation. Investigation revealed severe neutropenia and jaundice. She was found to have concomitant agranulocytosis and cholestatic jaundice secondary to methimazole.Methimazole was discontinued on admission and the patient received granulocyte colony-stimulating factor for an absolute neutrophil count (ANC) of zero. She was placed on broad-spectrum antibiotics and intravenous steroids for epiglottic and supraglottic oedema noted on bedside laryngoscopy. ANC and bilirubin improved over a 2-week hospital course. She was discharged on a temporary regimen of propranolol, dexamethasone and potassium iodide until she was able to undergo successful thyroidectomy for definitive management of Graves' disease outpatient. | 10.1136/bcr-2022-250113 |
pubmed_186_6228 | BACKGROUND
Even without treatment, most acute hepatitis E virus (HEV) infected patients resolve HEV but sometimes the disease leads to acute liver failure, chronic infection, or extrahepatic symptoms. The mechanisms of HEV pathogenesis appear to be substantially immune mediated. However, the immune responses to HEV are not precisely identified.
OBJECTIVES
This study aimed to evaluate the Th1/Th2 ratio by investigating serum soluble markers from Th1 and Th2 cells in acute HEV infected patients.
PATIENTS AND METHODS
This case-control study included 35 acute HEV infected patients and 35 age and gender matched anti-HEV negative healthy controls. The serum levels of Interferon (IFN)-γ, IL-4, soluble CD26 (sCD26) and sCD30 were determined by the enzyme-linked immunosorbent assay.
RESULTS
The results showed a significant difference in IFN-γ and sCD26 (P < 0.0001 and P = 0.001) yet not IL-4 and sCD30 (P = 0.354 and P = 0.159) between acute HEV patients and controls, respectively. There was a positive direct correlation between serum levels of sCD26 and IFN-γ in acute HEV patients (r = 0.64, P = 0.001). In addition, the ratio of sCD26/sCD30 in the acute HEV group was more than two folds higher than in the HEV negative controls.
CONCLUSIONS
Acute HEV infection shows a pattern of Th1-type immune response, and the direct significant positive correlation between the serum level of sCD26 and IFN-γ in acute HEV infected patients, suggests that the trend of sCD26 levels is a valuable marker for predicting hepatic inflammation in hepatitis E. | 10.5812/jjm.31110 |
pubmed_539_2981 | Isolated atrial tissue preparations provide convenient models for studying drug effects on the myocardium. However, there are several points we must be aware of. Interventions which change the beating rate also affect contractile force (Starling's Law). The membrane currents involved in the action potential as well as the excitation-contraction mechanisms differ between the atria and ventricle. Some membrane currents present only in the sino-atrial node and atrial myocardium may provide targets for novel bradycardiac agents and anti-atrial fibrillatory agents, respectively. The atrial tissue contains non-myocardial cells such as autonomic neurons and endocardial endothelial cells, which may be involved in the responses to various pharmacological stimuli. | 10.1254/fpj.117.203 |
pubmed_487_17006 | In the typical memory conjunction experiment, participants are presented with two "parent" stimulus items (e.g., blackmail and jailbird) that are later recombined to form a "conjunction lure" (e.g., blackbird). This paradigm is an efficient way to test false memories because participants frequently show false recognition for the recombined features of the previously studied stimuli. Two experiments are reported in which normative data for 96 memory conjunction triplets are presented. The first experiment provides descriptive statistics for how often the conjunction triplets show true and false recognition. Due to the variance in the rates of false recognition for the conjunction lure, the second experiment was conducted to help build an understanding of the factors that affect the rate of false recognition of the conjunction lures. Conceptual overlap of the first parent word and the conjunction item predicted false recognition. Digital files containing norms for 96 memory conjunction triplets may be downloaded from www.psychonomic.org/archive. | 10.3758/bf03192987 |
pubmed_299_9726 | OBJECTIVE
To evaluate the feature and difference between treadmill exercise test (TET) and myocardial perfusion imaging (MPI) in myocardial bridge patients with symptoms.
METHODS
The data from 97 patients, who underwent 256-slice CT coronary angiography (CTCA) on TET and MPI, were collected and analyzed retrospectively. The patients were divided into an incomplete MB group (n=41) and a complete MB group (n=56). They were also divided into three groups according to the narrow degree of mural coronary artery (MCA) during the cardiac systolic period (Nobel grade): a Nobel 1 grade group (n=44), a Nobel 2 grade group (n=42), and a Nobel 3 grade group (n=11). Besides, the abnormal TET and MPI patients were divided into a TET abnormal group (n=21) and a MPI abnormal group (n=31). The results of TET and MPI were compared among the total, the different MB type groups and the different Noble grade groups, while the complete MB thickness and length were also compared between the abnormal TET group and the MPI abnormal group.
RESULTS
The positive rate of MPI (39/97) was higher than that of TET (26/97) in total (χ2=8.048, P<0.01). But there was no significant difference in the positive rate of TET (5/41) and MPI (8/41) in the incomplete group (χ2=1.000, P>0.05). There was a significant difference in the positive rate of TET (21/56) and MPI (31/56) in the complete MB group (χ2=8.333, P<0.01). There were significant difference in the positive rate of TET (6/44) and MPI (12/44) in the Noble 1 grade group (χ2=4.500, P<0.05), or TET (11/42) and MPI (18/42) in the Nobel 2 grade group (χ2=5.444, P<0.05). But there was no difference in Nobel 3 grade group (P>0.05). The complete MB thickness was (3.4±0.6) and (2.9±0.8) mm between the TET abnormal group and the MPI abnormal group, with statistically difference (t=2.229, P<0.05). But the MB length was (16.6±5.5) and (15.7±7.1) mm, with no statistical difference (t=0.489, P>0.05).
CONCLUSION
MPI is more sensitive than TET in myocardial ischemia in patients with MB, especially to complete MB and mild-to-moderate systolic narrowing of MCA. The positive rate is low to incomplete MB, and it is highly sensitive to severe systolic narrowing of MCA. There is difference in the MB thickness between the two methods, but there is no difference in the MB length between the two methods. | 10.11817/j.issn.1672-7347.2016.06.007 |
pubmed_278_836 | Overexpressed gastrin is reported to promote oncogenesis and development of gastric cancer by inhibiting apoptosis of cancer cells; however, the underlying mechanism remains unclear. Our study is aimed at revealing the mechanism underlying the effect of gastrin on apoptosis of gastric cancer cells. Gastrin-interfering cell line was constructed by stably transfecting gastrin-specific pshRNA plasmid to gastric cancer cell line BGC-823. Then, differentially expressed proteins between untreated BGC-823 and gastrin-interfering BGC-823 cell lines were detected by the iTRAQ technique. GO and KEGG analysis was used to analyze the differentially expressed genes that code these differentially expressed proteins. The Annexin V-FITC staining assay was used to detect gastric cancer cell apoptosis. The DCFH-DA fluorescent probe staining assay was used to measure intracellular ROS. Mitochondrial membrane potential was detected by flow cytometry. Western blot was used to analyze the mitochondria respiratory chain proteins and apoptosis-related proteins. A total of 107 differentially expressed proteins were identified by iTRAQ. GO and KEGG analysis showed that proteins coded by the corresponding differentially expressed genes were mainly enriched in the mitochondrial oxidative respiratory chain, and the expression of three proteins (COX17, COX5B, ATP5J) was upregulated. The three proteins with higher scores were verified by Western blot. The apoptosis rate of the gastrin knockdown cancer cell was significantly increased; meanwhile, gastrin knockdown leads to increase of membrane potential and decrease of intracellular ROS production. Additionally, Bax was significantly increased, whereas NF-κB-p65 and Bcl-2 were downregulated after knockdown of gastrin. Concomitantly, pretreatment with NAC reversed the effect of gastrin on the Bax and Bcl-2 expression. Gastrin promotes the production of ROS from mitochondria, activates NF-κB, and inhibits apoptosis via modulating the expression level of Bcl-2 and Bax. | 10.1155/2021/5590037 |
pubmed_664_10146 | OBJECTIVE
Fomepizole is the antidote of choice in toxic alcohol poisonings. Potential side effects from frequent use of fomepizole were studied in a patient admitted 154 times with ethylene glycol (EG) poisoning. The intra-individual correlation between the serum-ethylene glycol (serum-EG) and the osmolal gap (OG) EG-kinetics, and other laboratory parameters were also studied.
METHODS
Combined pro- and retrospective collection of material from three different hospitals, and results from autopsy.
RESULTS
A 26-year-old female with a dissociative disorder was admitted with EG poisoning a total of 154 times. Her admission data revealed a median pH of 7.31 (range 6.87-7.49), pCO(2): 4.2 kPa (1.2-6.7) (32 mmHg [9-50]), HCO-3: 15 mmol/L (4-26) (15 mEq/L [4-26]), base deficit (BD): 10 mmol/L (- 4 to 27) (10 mEq/L [-4 to 27]), serum-creatinine 65 μmol/L (40-133) (0.74 mg/dL [0.45-1.51]), OG 81 mOsm/kgH(2)O (25-132), and serum-EG 44 mmol/L (4-112) (250 mg/dL [25-700]). She was treated with fomepizole 99 times, ethanol 60 times (with a combination of both six times), and dialysis 73 times. The correlation between serum-EG and OG was good (r(2) = 0.76). She was finally found dead outside hospital with an EG blood concentration of 81 mmol/L (506 mg/dL). An autopsy revealed calcium oxalate crystals in the kidneys, slight liver steatosis, and slight edema of the lungs.
DISCUSSION
The frequent use of fomepizole in this young patient was not associated with any detectable side effects; neither on clinical examination and lab screening, nor on the later autopsy. Regarding the sequelae from the repetitive EG-poisoning episodes, her kidney function seemed to normalize after each overdose. She was treated with buffer and antidote without hemodialysis 81 times without complications, supporting the safety of this approach in selected cases. | 10.3109/15563650.2011.590140 |
pubmed_486_14390 | A man in his 60s with severe trismus was referred to our hospital. Based on computed tomography (CT), positron emission tomography/computed tomography (PET/CT), and biopsy, his initial diagnosis at another hospital was oropharyngeal cancer with cervical lymph node and distant metastases. After the review of the contrast-enhanced CT and reevaluated PET/CT images, we updated his diagnosis to left primary lung cancer that had metastasized to the cervical lymph nodes, bones, and skeletal muscles including the right medial pterygoid muscle. Since metastasis from primary lung cancer to the contralateral cervical lymph node is relatively rare, cervical lymph node metastases were thought to have originated from the metastatic lesion in the right medial pterygoid muscle. As metastases in the masticator muscles from lung cancer are rare, it is sometimes necessary to differentiate from primary head and neck lesions. Here, we report a rare case of lung cancer with the onset of trismus due to metastasis to the masticator muscle and perineural spread along the mandibular nerve. | 10.1007/s13691-019-00374-6 |
pubmed_495_585 | Integrin expression is normally confined to the basal layer of the epidermis, but when epidermal homeostasis is perturbed, the receptors are also expressed by suprabasal, differentiating keratinocytes. We have used the involucrin promoter to express functional human integrin subunits alpha 2, alpha 5, and beta 1 in the suprabasal epidermal layers of transgenic mice. In mice expressing alpha 5 or beta 1 alone or alpha 2 beta 1 or alpha 5 beta 1 heterodimers, there were hair and whisker abnormalities and a failure of eyelid fusion. In addition, mice expressing beta 1 alone or in combination with alpha 2 or alpha 5 exhibited epidermal hyper-proliferation, perturbed keratinocyte differentiation, and skin inflammation, all of which are features of a common human skin disease, psoriasis. | 10.1016/0092-8674(95)90211-2 |
pubmed_964_17513 | The clinical and pathological features of an apparently unique case of an endometrial cyst of the uterus are reported. The cyst was located within the myometrium of a 16-year-old woman suffering from dysmenorrhea. After excision of the cyst, patient's symptoms improved. On histological examination, the cyst most closely resembled an adenomyotic cyst. | 10.1620/tjem.178.339 |
pubmed_355_12546 | The method of sedimentation equilibrium has been used to determine the stoichiometry and binding constant for the interaction between hen egg white lysozyme and monoclonal antibody D1.3. The procedures described allow the relative binding affinities of 125I-labelled lysozyme and unlabelled lysozyme to be compared. The data indicate that labelled and unlabelled lysozyme bind to monoclonal D1.3 with similar affinity (binding constant, K = 1.6 x 10(9)/M). Using solid-phase methods estimates obtained for the binding constant were lower and dependent both on the amount of antigen coated on the plate and the dilution of primary antibody (D1.3). These data were not consistent with a simple equilibrium binding model, suggesting kinetic or orientation effects. In contrast sedimentation equilibrium experiments provide a rapid and accurate method for determining both the stoichiometry and binding constants for the interaction between antigens and antibodies. | 10.1016/0161-5890(93)90425-b |
pubmed_279_6926 | Familial hemiplegic migraine (FHM) is an autosomal dominant type of migraine and probably represents the most extreme end of migraine with aura. Reduced magnesium facilitates the development of spreading depression and possibly aura. Cellular magnesium levels are under genetic control. We hypothesized that FHM patients would have significantly reduced intracellular magnesium levels. We determined intracellular and plasma magnesium levels in blood of 38 afflicted and 11 non-afflicted members of three families with FHM and in 32 migraine patients (9 with and 23 without aura) and 32 age and sex matched healthy controls. We found no significant differences between the magnesium levels in the five study groups. We conclude that reduced blood magnesium is unlikely to be related to migraine pathophysiology. | 10.1046/j.1468-2982.1994.1401029.x |
pubmed_452_18089 | The ability to move towards or away from a light source, namely phototaxis, is essential for a number of species to find the right environmental niche and may have driven the appearance of simple visual systems. In this study we ask if the later evolution of more complex visual systems was accompanied by a sophistication of phototactic behaviour. The honey bee is an ideal model organism to tackle this question, as it has an elaborate visual system, demonstrates exquisite abilities for visual learning and performs phototaxis. Our data suggest that in this insect, phototaxis has wavelength specific properties and is a highly dynamical response including multiple decision steps. In addition, we show that previous experience with a light (through exposure or classical aversive conditioning) modulates the phototactic response. This plasticity is dependent on the wavelength used, with blue being more labile than green or ultraviolet. Wavelength, intensity and past experience are integrated into an overall valence for each light that determines phototactic behaviour in honey bees. Thus, our results support the idea that complex visual systems allow sophisticated phototaxis. Future studies could take advantage of these findings to better understand the neuronal circuits underlying this processing of the visual information. | 10.1038/s41598-020-64782-y |
pubmed_20_9761 | In nature, H2 production in Chlamydomonas reinhardtii serves as a safety valve during the induction of photosynthesis in anoxia, and it prevents the over-reduction of the photosynthetic electron transport chain. Sulphur deprivation of C. reinhardtii also triggers a complex metabolic response resulting in the induction of various stress-related genes, down-regulation of photosynthesis, the establishment of anaerobiosis and expression of active hydrogenase. Photosystem II (PSII) plays dual role in H2 production because it supplies electrons but the evolved O2 inhibits the hydrogenase. Here, we show that upon sulphur deprivation, the ascorbate content in C. reinhardtii increases about 50-fold, reaching the mM range; at this concentration, ascorbate inactivates the Mn-cluster of PSII, and afterwards, it can donate electrons to tyrozin Z(+) at a slow rate. This stage is followed by donor-side-induced photoinhibition, leading to the loss of charge separation activity in PSII and reaction centre degradation. The time point at which maximum ascorbate concentration is reached in the cell is critical for the establishment of anaerobiosis and initiation of H2 production. We also show that ascorbate influenced H2 evolution via altering the photosynthetic electron transport rather than hydrogenase activity and starch degradation. | 10.1111/pce.12701 |
pubmed_248_1002 | As the field of surgical robotics continues to evolve, it is important to keep patient safety in mind. This paper describes a safety control architecture aimed at moving an experimental system in the direction of intrinsically safe operation. The system includes safety features such as: a small number of states, Programmable Logic Controller (PLC) state transition control, active enable, brakes, E-STOP, and a surgeon foot pedal. | pubmed_248_1002 |
pubmed_983_20197 | OBJECTIVES
Sepsis caused by the bacterial contamination of blood products is a major infection risk associated with blood transfusion. Diversion of the initial 25 mL of blood and prestorage leukoreduction were implemented in Japan in 2007 for all donated blood products. We assessed the efficacy of these new collection procedures in preventing bacterial contamination of red blood cell (RBC) concentrates.
METHODS
Broad-range 16S ribosomal RNA polymerase chain reaction was used to determine bacterial contamination in segment samples of RBCs before and after implementation of the new collection procedures. To evaluate whether these new procedures reduced bacterial contamination, we compared bacterial contamination rates of blood samples from diversion pouches with those of segment samples from the same donor's RBCs.
RESULTS
The rate of bacterial contamination of RBCs before implementation of the new collection procedures was 1.27%. Most of the isolated bacteria were Staphylococcus epidermidis or Propionibacterium acnes. After implementation, this rate was significantly reduced to 0.10%. Of the 233 whole blood samples obtained from the Mie Red Cross Blood Center, 1.72% of blood samples from diversion pouches were contaminated, but no bacterial contamination was detected in segment samples from the same donor's RBCs after prestorage leukoreduction.
CONCLUSIONS
The new collection procedure significantly reduced bacterial contamination of RBC concentrates. | 10.1111/j.1365-3148.2011.01093.x |
pubmed_452_24171 | Cervical cancer is the fourth most common cancer worldwide in women. Apoptosis reactivation has become the main strategy for decreasing cancer proliferation. There is a need to extend the search for new drugs to implement more effective and less toxic strategies for cervical cancer treatment. Research has been carried out to find new drugs that have minimal side effects and that focus on the tumor microenvironment, particularly in the induction of cellular apoptosis and cell migration and the inhibition of angiogenesis. Potent toxins from snake venoms have shown potential as sources for the synthesis of new drugs with such characteristics. The present work aimed to describe cervical cancer characteristics, associated risk factors, current treatments and to highlight the effects of toxins isolated from the venom of snakes of the Viperidae family on cervical cancer cell lines. | 10.1007/s11033-020-05503-6 |
pubmed_1141_5902 | Acquired (non-Wilsonian) hepatocerebral degeneration (AHCD) is an irreversible neurological condition characterized by dementia, dysarthria, and motor disturbances. It has been described in patients with severe liver disease of many causes, and notably in patients with surgically or spontaneously created porto-systemic shunts. We report a case of AHCD in a patient with end-stage liver disease due to alcohol abuse and hepatitis C. In addition, this patient showed pathologic evidence of the less commonly reported "shunt myelopathy" in the absence of a surgically created porto-systemic shunt. The myelopathy was associated with a dramatic vacuolation involving especially the deep motor cortex. Electron microscopy suggested that the vacuolation was due mainly to disruption of abnormal astrocytes. | 10.1111/j.1750-3639.2000.tb00205.x |
pubmed_1041_19001 | OBJECTIVES
To determine if there is a beneficial effect of bariatric surgery in the management of Diabetes Mellitus in obese patients in a Caribbean setting.
METHODS
A retrospective review of charts of all obese patients with Type-2 Diabetes Mellitus (DM) who had undergone Laparoscopic Roux en Y gastric bypass (LRYGBP) over a 4 year period was undertaken and clinical data recorded. A questionnaire was prospectively administered via telephone to determine the quality of life.
RESULTS
Of 146 patients who underwent LRYGBP, 40 were found to have clinically significant DM. Patients of age < 50 years and females had a higher preponderance of DM. Patient body weight decreased significantly from a pre-operative131.2 ± 21.6 [Mean ± Standard Deviation (SD)] to 99.4 ± 16.6 after surgery (p < 0.0001). There was also a significant reduction of BMI from 47.0 ± 7.9 to 34.7 ± 5.8 (p < 0.0001). There was complete resolution of clinically significant DM in 85% of patients, while in 15% there was a significant reduction in the dosage of anti-diabetic medications. Perioperative complications were minimal and there was no mortality. 96% of the patients reported a drastic improvement in their quality of life.
CONCLUSIONS
Bariatric surgery for obese diabetic patients resulted in complete resolution, improved diabetes control and overall improvement in the quality of life. Due to better outcomes, the surgery can safely be recommended in the Caribbean multiethnic setting where there is a high prevalence of obesity and Diabetes Mellitus. | 10.1016/j.ijsu.2011.03.024 |
pubmed_522_5218 | Previous work demonstrated a sexually dimorphic ontogenic expression of gamma-aminobutyric acid receptors (GABA(B)R) in rat pituitary. As sex steroids determine sex-specific expression patterns, we now studied the effect of sex hormones on pituitary GABA(B)R expression. GABA(B)R subunits, measured by Western blot and by semi-quantitative RT-PCR and luteinizing hormone (LH), follicle-stimulating hormone (FSH) and testosterone measured by RIA were determined in two experimental designs: First experimental design: 8- and 15-day-old females (8F, 15F); 8F and 15F treated with 100 mug testosterone propionate (TP) on day 1 of life (8F100TP, 15F100TP), 8- and 15-day-old males (8M, 15M) and 8M and 15M castrated on day 1 (8MC, 15MC). Second experimental design: 8-day-old female and male animals: 8F, 8F100TP, 8F treated with 1 mug/day TP on days 1-4 (8F1TP), 8F treated with the androgen antagonist Flutamide (Flut: 2.5 mg/100 g BW of pregnant mother on days E17-E23) (8F-Flut), 8M, 8MC, 8M treated with Flut as above (8M-Flut) and 8MC-Flut. In these animals, in addition, GABA, glutamate, aspartate and taurine were measured by HPLC in hypothalami and cortex. In the first set of experiments, GABA(B1)R mRNA/protein expression was higher in 8F than in 15F, 8M or 15M. In 8F100TP, GABA(B1)R mRNA/protein decreased to male levels. TP treatment did not alter GABA(B1)R expression in 15F. There was no difference in GABA(B1)R expression between 8M and 15M and neonatal castration did not modify its expression. In the second set of experiments, TP (1 mug) or Flut did not modify GABA(B1)R in 8F, while 100 microg TP continued to decrease GABA(B1)R expression. In 8M, Flut, alone or with castration, increased GABA(B1)R mRNA/protein expression to 8F. Hypothalamic GABA content followed the same pattern as pituitary GABA(B)R expression in 8-day-old animals, suggesting a cross-regulation. With regard to hormonal levels, 100 microg, but not 1 microg TP altered gonadotropins at 8 days, although both treatments effectively androgenized females as evidenced by lack of cycling. We conclude that androgens, acting pre- and postnatally, decrease pituitary GABA(B)R subunit expression. | 10.1159/000082527 |
pubmed_563_6639 | Treatment and management of plant toxicosis is made more difficult when an alien plant species is ingested, as identification of the toxin may pose a challenge. High-resolution mass spectrometers are required for the toxicological analysis of samples in these cases owing to their ability to scan large mass ranges and accurately identify mass features. We present this case to highlight the value of this technology in clinical toxicology. A middle-aged woman reported visual impairment, dizziness and numbness of her mouth and tongue following the ingestion of a berry. Over time her condition deteriorated, warranting toxicological analysis. The tree the berry came from was identified as Cornynocarpus laevigatus, which is known to produce the karakin neurotoxin. The patient's samples and the husk and pulp of the berries were analysed using a high-resolution mass spectrometer. This resulted in the identification of the toxin in the berry kernel and husk and patient's hair, suggesting that karakin could have contributed to the patient's condition. | 10.7196/SAMJ.2022.v112i12.16667 |
pubmed_565_434 | The requirement for a safe diagnostic strategy should be based on an overall posttest incidence of venous thromboembolism of less than 1% during 3 month follow-up. Compression ultrasonography (CUS) has a negative predictive value (NPV) of 97% to 98% indicating the need of repeated CUS testing. Serial CUS testing is safe but you have to repeat 100 CUS to find 1 or 2 CUS positive for deep vein thrombosis (DVT), which is not cost-effective indicating the need to improve the diagnostic work-up of DVT by the use of clinical score assessment and D-dimer testing. The combination of a less sensitive D-dimer test (SimpliRed) and low clinical score does not, whereas the combination of a sensitive D-dimer test (ELISA VIDAS or Tinaquant) and low clinical score does safely exclude DVT without the need of CUS. The combination of a first negative CUS and a negative less sensitive D-dimer test (SimpliRed) or a sensitive ELISA D-dimer at a higher cut off level of 1,000 ng/ml safely excludes DVT with a NPV of > 99% without the need to repeated CUS in about 60%. The sequential use of a sensitive D-dimer and clinical score assessment will safely reduce the need for CUS testing by 40% to 60%. Large prospective outcome studies demonstrate that one negative examination with complete duplex color ultrasonography (CCUS) of the proximal and distal veins of the affected leg with suspected DVT is safe to withhold anticoagulant treatment with a NPV of 99.5%. This indicates that CCUS is equal or superior to serial CUS or the combined use of clinical score, D-dimer testing and CUS. Pulmonary angiography is the gold standard for segmental pulmonary embolism (PE) but not for subsegmental PE. A normal perfusion lung scan and a normal rapid ELISA VIDAS D-dimer test safely exclude PE. Helical spiral CT detects all clinically relevant PE and a large number of alternative diagnoses in symptomatic patients with a non-diagnostic ventilation perfusion scan (VP-scan) or a high probability VP-scan. Single-slice helical CT as the primary diagnostic test in patients with suspected PE in 5 retrospective studies and in 3 prospective management studies indicate that the NPV of a normal helical spiral CT, a negative CUS of the legs together with a low or intermediate pretest clinical probability is 99%. Helical spiral CT can replace both the VP-scan and pulmonary angiography to safely rule in and out PE. The combination of clinical assessment, a rapid ELISA VIDAS D-dimer followed by CUS will reduce the need for helical spiral CT by 40% to 50%. | pubmed_565_434 |
pubmed_695_14875 | Trogidae (Coleoptera) is a cosmopolitan family with about 350 described species within five extant genera (Zídek 2013, 2017; Strümpher et al. 2014, 2016; Nikolajev 2016). For South American, three genera are recorded: Trox Fabricius, 1775 (Troginae), Omorgus Erichson, 1847 (Omorginae), and Polynoncus Burmeister, 1876 (Omorginae) (Scholtz 1990; Strumpher et al. 2016; Huchet Costa-Silva 2018). | 10.11646/zootaxa.4868.2.6 |
pubmed_98_14863 | BACKGROUND
To assess the association of HSD17B13 rs72613567:TA allelic variant with liver disease, we performed the current review and meta-analysis.
METHODS
Seven studies were identified by a search of CNKI,CBM,MEDLINE, PubMed, EMBASE, and CENTRAL databases from inception to November 2021. Odds ratios (ORs) with 95% confidence interval (CI) were calculated using random effects model or fixed effects model based on the between-study heterogeneity. The Stata 14.0 software was employed for data analysis.
RESULTS
Statistical analysis showed that the HSD17B13 rs72613567:TA allelic variant can decrease the risk of hepatocellular carcinoma(HCC) in nonalcoholic fatty liver disease (NAFLD) patients, alcoholic fatty liver disease (ALD) patients and viral hepatitis patients (TA vs T OR = 0.766, 95% CI = 0.682-0.860, P = 0.000; TATA + TAT vs TT OR = 0.755, 95% CI = 0.645-0.885, P = 0.001) or healthy controls(TA vs T OR = 0.649, 95% CI = 0.431-0.977, P = 0.038). Besides, the HSD17B13 rs72613567:TA allelic variant can also provide protection from nonalcoholic fatty liver disease (NAFLD) not only in entire population (TA vs T OR = 0.669, 95% CI = 0.524-0.856, P = 0.001) but also in healthy people (TA vs T OR = 0.600, 95% CI = 0.464-0.777, P = 0.000). No significant publication bias found in this airticle.
CONCLUSION
The present findings suggest HSD17B13 rs72613567:TA allelic variant can reduce the risk of HCC and NAFLD in the entire population studied. | 10.1186/s12876-021-02067-y |
pubmed_37_81 | We have studied the properties of volatile secretions induced in laboratory mice, separately or combined influence of ionizing radiation and cyclophosphamide. The reaction of preference-avoidance response in the T-maze revealed that the urine samples of mice in the early period after exposure to ionizing radiation in doses of 2 and 4 Gy contain attractive for intact animals volatile components. While the introduction of cyclophosphamide in doses of 20 or 35 mg/g provokes the secretion of volatile components of aversive, repealing properties towards of intact individuals. Combined exposure to these factors leads to a reciprocal compensation of the impact of volatile secretions in the preference-avoidance response of intact mice. The examined effects depend to some extent on the dose of radiation and cyclophosphamide. Induced both by separate and associated exposure to radiation and cyclophosphamide volatile allocation have depressing effect of the humoral immune response, regardless of whether they are attractive or aversive properties. We are discussing their role in the mechanisms of chemosignaling. | pubmed_37_81 |
pubmed_443_552 | An increased degree of oxidative stress (OS) in chronic renal failure (CRF) and a possible role of free radicals in CRF have already been described. However, data on OS after renal transplantation are scarce. The aim of the present study was to estimate the degree of OS in renal transplant patients. The study included four groups: 1) 15 haemodialysis patients (HD group), 2) 11 renal transplant patients with stable function (SF group), 3) 12 renal transplant patients with chronic biopsy-proven rejection (CR group), and 4) 10 healthy controls (C group). Markers of OS (malondialdehyde and thiol group levels) and antioxidant activity (glutathione peroxidase and Cu,Zn-superoxide dismutase) were determined in plasma and in red blood cells of all examined individuals. After successful renal transplantation a significant improvement, but not normalization, of antioxidant enzyme activities accompanied by significantly reduced lipid peroxidation were found. In the CR group the degree of OS was increased, and our results suggest that OS may be a relevant pathophysiological factor for CR development. | 10.1007/s001470050443 |
pubmed_76_6503 | The binding of urokinase-type plasminogen activator (uPA) to its specific cell-surface receptor (uPAR) localises the proteolytic cascade initiated by uPA to the pericellular environment. Inhibition of uPA activity or prevention of uPA binding to uPAR might have a beneficial effect on disease states wherein this activity is deregulated, e.g. cancer and some inflammatory diseases. To this end, a bifunctional hybrid molecule consisting of the uPAR-binding growth-factor domain of uPA (amino acids 1-47; GFuPA) at the N-terminus of plasminogen-activator inhibitor type 2 (PAI-2) was produced in Saccharomyces cerevisiae. The purified protein inhibited uPA with kinetics similar to placental or recombinant PAI-2 and was also found to bind to U937 cells and to FL amnion cells. GFuPA-PAI-2 competed with uPA, the N-terminal fragment of uPA and a proteolytic fragment of uPA (amino acids 4-43) in cell binding experiments, indicating that the molecule bound to the cells via uPAR. Hence, both the uPA-inhibitory and uPAR-binding domains of the hybrid molecule were functional, demonstrating the feasibility of the novel concept of introducing an unrelated, functional domain onto a member of the serine-protease-inhibitor superfamily. | 10.1111/j.1432-1033.1992.tb17035.x |
pubmed_475_7688 | Snakebite envenoming is a serious public health problem in Central America, where approximately 5,500 cases occur every year. Panama has the highest incidence and El Salvador the lowest. The majority, and most severe, cases are inflicted by the pit viper Bothrops asper (family Viperidae), locally known as 'terciopelo', 'barba amarilla' or 'equis'. About 1% of the bites are caused by coral snakes of the genus Micrurus (family Elapidae). Despite significant and successful efforts in Central America regarding snakebite envenomings in the areas of research, antivenom manufacture and quality control, training of health professionals in the diagnosis and clinical management of bites, and prevention of snakebites, much remains to be done in order to further reduce the impact of this medical condition. This essay presents seven challenges for improving the confrontation of snakebite envenoming in Central America. Overcoming these challenges demands a coordinated partnership of highly diverse stakeholders though inter-sectorial and inter-programmatic interventions. | 10.1186/1678-9199-20-7 |
pubmed_914_19334 | This article examines and interprets the trends of epidemiological production in Brazil in the Public Health context. CAPES indicators from 2001 to 2006 were used as database. We analyzed 26 programs and select the 10 major ones to analyze their bibliographic production in indexed journals. It was observed that the total production of epidemiological articles accounted for 40% of production in Public Health and 55% of the production was published in international journals, especially Cadernos de Saúde Pública, Revista de Saúde Pública and Ciência & Saúde Coletiva. The most prevalent themes were public health nutrition, maternal and infant health and, infectious diseases, particularly AIDS. Environmental e worker's heath, oral health, violence and health of the elderly have been ratified as objects of study for the discipline, while meta-analysis and geoprocessing appear as a useful tool for health services. We conclude that the epidemiological production tends to increase in indexed publications, covering various topics and a wide spectrum of relevant issues to Brazilian health policy. | pubmed_914_19334 |
pubmed_220_12921 | Although the cure of acute leukaemia has improved significantly, many patients will still relapse and die. The unraveling of the molecular pathogenesis of acute leukaemia has lead to the identification of new prognostic factors and improved the detection of minimal residual disease. The treatment of relapsed acute leukaemia with chemotherapy remains unsatisfactory. Allogeneic or autologous blood and marrow transplant (BMT) can cure a subset of patients with relapsed acute leukaemia. The identification of the graft-vs-leukaemia (GVL) effect has lead to the development of donor lymphocyte infusions to re-induce remission in patients with relapsed leukaemia after allogeneic BMT and also stimulated the development of the less toxic nonmyeloablative allogeneic transplant approach. The identification of molecular targets of therapy and the development of monoclonal antibody-directed therapy has generated optimism. It is possible that combinations of chemotherapy, molecularly directed therapy, and immunotherapy may be combined to cure an increasing proportion of patients with acute leukaemia. | 10.1016/s0268-960x(03)00036-5 |
pubmed_1023_10712 | The effect of the association of gossypol and Lonidamine on the electron transport in Ehrlich ascites tumor mitochondria has been investigated by addition of drugs to isolated mitochondria. The results may be summarized as follows. (1) Low concentrations of gossypol increase the rate of oxygen consumption at the level of three energy-conserving sites of the respiratory chain. Higher concentrations result in an inhibition of oxygen consumption at (or near) both energy-conserving sites 1 and 2, while energy-conserving site 3 is unaffected. (2) Gossypol, at concentrations at which it exerts its uncoupling effect, stimulates ATPase activity. Higher concentrations inhibit the enzyme activity. (3) The addition of gossypol to mitochondria respiring on pyruvate plus malate or succinate induces a more oxidized state of NAD+ and cytochrome b, respectively. (4) Gossypol enhances the effect of Lonidamine on oxygen consumption. Lonidamine does not affect state 4 respiration, but in the presence of gossypol, it determines a marked decrease in the rate of oxygen consumption. The inhibition of oxidation of NAD-linked substrates is greater than that of FAD-linked substrates. (5) It may be concluded that gossypol is very effective in potentiating the effect of Lonidamine. Moreover, it may be suggested that the antitumor activity of Lonidamine is enhanced if it is used in combination with other drugs and/or treatments, such as hyperthermia, which modify the energy status of mitochondria. | 10.1016/0014-4800(84)90081-9 |
pubmed_704_2587 | Efficacious HIV-1 vaccination requires elicitation of long-lived antibody responses. However, our understanding of how different vaccine types elicit durable antibody responses is lacking. To assess the impact of vaccine type on antibody responses, we measured IgG isotypes against four consensus HIV antigens from 2 weeks to 10 years post HIV-1 vaccination and used mixed effects models to estimate half-life of responses in four human clinical trials. Compared to protein-boosted regimens, half-lives of gp120-specific antibodies were longer but peak magnitudes were lower in Modified Vaccinia Ankara (MVA)-boosted regimens. Furthermore, gp120-specific B cell transcriptomics from MVA-boosted and protein-boosted vaccines revealed a distinct signature at a peak (2 weeks after last vaccination) including CD19, CD40, and FCRL2-5 activation along with increased B cell receptor signaling. Additional analysis revealed contributions of RIG-I-like receptor pathway and genes such as SMAD5 and IL-32 to antibody durability. Thus, this study provides novel insights into vaccine induced antibody durability and B-cell receptor signaling. | 10.1038/s41598-020-69007-w |
pubmed_496_22877 | Lipoma is the most frequently encountered benign soft tissue tumor. However, intra-articular lipomas are rarely seen. Anterior knee pain is a frequent complaint of adults and is of diverse etiology. This 42-year-old female patient had severe anterior knee pain, unresponsive to medical treatment. Magnetic resonance imaging revealed an intra-articular tumor of the knee joint. Arthroscopic intervention and subsequent histological examination resulted in the diagnosis of strangulated lipoma originating from infrapatellar fat pad. We present clinical, radiological and operative features of this rare case of intra-articular lipoma. | 10.1007/s00167-004-0595-4 |
pubmed_93_5888 | Neopterin concentration in blood serum and tear fluid was estimated in 94 patients with endogenous uveitis and 28 healthy subjects. Neopterin concentration was found to be elevated in blood serum of patients with herpetic (12,31+1,1 micromol/L), tubercular uveitis (17,77+4,18 18 micromol/L) and uveitis associated with systemic conditions (12,31+1,1 micromol/L). Neopterin concentration in blood serum of healthy subjects was 8,45+0,61 micromol/L. Dynamics of neopterin concentration in blood serum of patients with uveitis varies depending on etiology. Neopterin concentration in tear fluid of healthy subjects appeared to be higher as compared with blood serum and was as high as 14,52+1,61 micromol/L (p < 0.05). Due to wide range of neopterin concentration in tear fluid, absence of significant correlation with blood serum concentration, apparently because of additional "local" production, authors propose to use only blood serum neopterin concentration for etiologocal diagnosis and control of treatment efficacy. | pubmed_93_5888 |
pubmed_142_2683 | Immune escape mutants with mutations in the hepatitis B surface antigen (HBsAg) major hydrophilic region (MHR) often emerge in association with diagnostic failure or breakthrough of HBV infection in patients with anti-HBs antibodies. Some mutants harboring substitutions to Asn in HBsAg MHR may have an additional potential N-glycosylation site. We have previously showed that sT123N substitution could generate additional N-glycosylated forms of HBsAg. In the present study, 1.3-fold-overlength HBV genomes containing the sT123N substitution were digested from the pHBV1.3-sT123N construct and subcloned into the pAAV vector to generate pAAV1.3-sT123N for hydrodynamic injection (HI) in mice. Viral expression and replication were phenotypically characterized by transient transfection. The results demonstrated that sT123N substitution impaired virion secretion, resulting in intracellular retention of HBcAg. Using the HBV HI mouse model, we found that mice mounted significantly stronger antibody responses to HBsAg and HBcAg, which accelerated HBsAg clearance. Thus, additional N-glycosylation generated by amino acid substitutions in HBsAg MHR may significantly modulate specific host immune responses and influence HBV infection in vivo. Our results help further the understanding of the role of immune escape mutants with N-linked glycosylation in the biology of HBV infection. | pubmed_142_2683 |
pubmed_660_2425 | Research on the consequences of perceiving disorder is largely sociological and concerns broken windows theory, which states that signs of social disorder cause further social disorder. The predominant psychological explanations for this phenomenon are primarily social. In contrast, I propose a parsimonious cognitive model ("world-is-random" model; WIR) that may partly account for these effects. Basically, WIR proposes that perceiving disorder primes randomness-related concepts, which results in a reduction to one's sense of personal control, which has diverse affective, judgmental, and behavioral consequences. I review recent developments on the psychological consequences of perceiving disorder and argue that WIR can explain all of these findings. I also cover select correlational findings from the sociological literature and explain how WIR can at least partly explain them. In a general discussion, I consider possible alternative psychological models and argue that they do not adequately explain the most recent psychological research on disorder. I then propose future directions which include determining whether perceiving disorder causes a "unique psychology" and delimiting boundary conditions. | 10.3389/fpsyg.2014.00606 |
pubmed_1013_2801 | Pyroptosis, as a novel identified programmed cell death, is closely correlated with tumor immunity and shows potential roles in cancer treatment. Discerning a pyroptosis-related gene signature and its correlations with tumor immune microenvironment is critical in head and neck squamous cell carcinoma (HNSCC). Transcriptome data and corresponding clinical data were downloaded from TCGA and GEO databases. Tumor mutation burden (TMB) data were obtained from TCGA database. Firstly, univariate and least absolute shrinkage and selection operator (LASSO) regression analyses were used to construct a six pyroptosis-related gene signature. Kaplan-Meier analysis, receiver operating characteristic (ROC) curves, and principal component analysis (PCA) results verified that the risk model has good performance in predicting the survival. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses revealed that the pyroptosis-related gene signature was immune related. Finally, the immune landscape and immunotherapy sensitivity prediction capabilities of the risk model were further explored. There were close correlations between the overall survival (OS) and various immune cells and immune functions. Single-sample gene set enrichment analysis (ssGSEA) showed that high risk group had decreased expression of various immune cells and lower activities of immune functions. Meanwhile, tumor mutation burden (TMB) data combining risk score could well predict the OS of HNSCC patients. However, tumor immune dysfunction and exclusion (TIDE) analysis revealed that there was no significant difference in the sensitivity to immunotherapies between high and low risk groups. Finally, a nomogram based on risk score and clinicopathological parameters was constructed. And, the risk model demonstrated better sensitivity and specificity than TIDE scores and T-cell-inflamed signature (TIS). In conclusion, although the risk model could not well predict the immune escape and response to immunotherapies, the signature established by pyroptosis-related genes, with better sensitivity and specificity than TIDE scores and TIS signature, could be used for predicting prognosis and immune status of HNSCC patients. | 10.1155/2022/1539659 |
pubmed_710_10555 | Re-irradiation can offer a potentially curative solution in case of progression after initial therapy; however, a second course of radiotherapy can be associated with an increased risk of severe side-effects. Particle therapy with protons and especially carbon ions spares surrounding tissue better than most photon techniques, thus it is of high potential for re-irradiation. Irradiation of tumors of the brain, head and neck and skull base involves several delicate risk organs, e.g. optic system, brainstem, salivary gland or swallowing muscles. Adequate local control rates with tolerable side-effects have been described for several tumors of these locations as meningioma, adenoid cystic carcinoma, chordoma or chondrosarcoma and head and neck tumors. High life time doses nonetheless lead to a different scope of side-effects, e.g. an enhanced rate of carotid blow outs has been reported. This review summarizes the current data on particle irradiation of the aforementioned locations and malignancies. | 10.1259/bjr.20190516 |
pubmed_477_887 | The first case of osteosarcoma in a 13 year old boy with Rothmund-Thomson syndrome is reported. The association between these two conditions is uncertain. | 10.1007/BF01644342 |
pubmed_526_9741 | BACKGROUND
Recurrence after liver resection for hepatocellular carcinoma (HCC) is common. Resection of extrahepatic recurrences such as lung metastasectomy (LM) has been well documented. Conversely, reports on the long-term outcomes of peritoneal metastasectomy (PM) are lacking. In this study, we compared the outcome of lung and peritoneal metastasectomy after hepatectomies for HCC in a tertiary institution.
METHODS
We reviewed retrospectively the data of 1,222 patients who underwent hepatectomies for HCC in Samsung Medical Center in Korea from January 2006 to August 2010. We studied the clinicopathologic factors between resected lung metastasis (LM) and peritoneal metastases (PM) and the long-term outcome of patient survival. Kaplan-Meier analysis was used to study the survival outcome.
RESULTS
The recurrence rate of resected HCC in this cohort was 41.6% (n = 508). Thirty-two patients with lung metastasis (23% of all lung metastasis) underwent LM whereas 13 patients (36% of all peritoneal metastasis) with peritoneal metastasis underwent PM. Two patients underwent PM and LM sequentially. Demographic and clinical data between the LM and PM groups were comparable. The mean prehepatectomy PIVKA-II level was greater in the LM group compared with the PM group (P = .029). On univariate analysis of pathologic factors, the median tumor size (P = .005), proportion of patients with tumor >75 mm (P = .005) and rate of microvascular invasion (P = .047) were greater in the LM group. The median time-to-recurrence in the LM group was 12 (4-45) months compared with 18 (1-102) months in the PM group (P = .896). The 1-year, 3-year, and 5-year overall survival of patients in the LM group was 92%, 55%, 55% (4-year) whereas that in the PM group was 90%, 75%, and 75%, respectively. The mean overall survival in the LM was comparable with that in the PM group (P = .578).
CONCLUSION
Twenty-three percent of patients with lung metastasis and 36.1% of patients with peritoneal metastasis could be considered for metastasectomy. The long-term survival of patients with PM and LM was comparable in this study. Although resection of LM improves survival in patients with resected HCC, we demonstrated favorable outcomes for PM as well, which in the past would have been considered palliative. | pubmed_526_9741 |
pubmed_100_23778 | A consortium of yeast geneticists have created -6000 individual ORF deletions, representing > 96% of the currently verified or predicted ORFs in S. cerevisiae. Importantly, molecular barcodes (each a unique 20 bp sequence termed either Uptag or Downtag) were used as identifiers for every ORF deletion. Microarray analyses of pooled yeast deletions has been used to identify thousands of genes involved in general fitness, haploinsufficiency, drug resistance and DNA damage repair. However, application of this powerful technology requires considerable expense, expertise and specialized equipment. While standard PCR techniques and specifically designed PCR primers can be used to confirm that a given ORF is in fact deleted, this procedure cannot be used to identify unknown deletions. In theory, every ORF deletion could be determined by barcode sequencing. However, neither a consolidated barcode database nor a reliable search engine is currently available for this purpose. To address this need, we have adapted a FASTA sequence program that utilizes the unique barcode database to allow users to identify individual ORF deletions, based upon simple sequencing reactions of PCR amplifications of either Uptag or Downtag barcodes. In silico and practical testing of this application reveals that it is an inexpensive, reliable and reproducible method for rapidly identifying unknown deletions. This approach allows laboratories to conduct small- or large-scale genetic screens with pooled yeast deletion strains and identify or verify any ORF deletion without the need for microarray technology. | 10.1002/yea.1894 |
pubmed_228_7700 | The clinical crown length of rabbit teeth has not been well documented. The aim of this study was to determine the clinical crown length of incisor and cheek teeth, and the periodontal probing depth in young healthy rabbits without clinical signs of dental disease. Two groups of 20 male rabbits were measured, the first in 2007 and the second in 2008/2009. The measurements were taken with rabbits under general anesthesia using a periodontal probe. The average crown length (mm) of the mandibular third and fourth premolar, and maxillary second premolar teeth was 3.1 +/- 0.4, 2.6 +/- 0.4, and 1.5 +/- 0.4, respectively. The periodontal probing depth for the cheek teeth in the maxilla and the mandible was very similar (0.5 - 1.0-mm). There was a minor difference in the average crown length (mm) of the mandibular (6.4 +/- 0.6) and maxillary (6.1 +/- 0.9) incisor teeth. The periodontal probing depth (mm) was different when comparing maxillary (2.2 +/- 0.4) and mandibular (5.1 +/- 0.8) incisor teeth. The divergence in tooth length in individual rabbits and between the two groups was minimal. Measuring the crown length of the rostral cheek and incisor teeth with a periodontalprobe is easy to do in the rabbit and should be integrated into the clinical examination. The measurement results of this study can be used as a reference when trimming teeth. | 10.1177/089875641102800205 |
pubmed_107_14569 | Phase I and II activities were examined in six rodent hepatoma cell lines and compared with those of cultured rat hepatocytes both in basal conditions and after exposure to 5 microM methylcholanthrene, 2 mM phenobarbital, and 15 microM beta-naphtoflavone. The metabolic profile of testosterone was also studied. The highest aryl hydrocarbon hydroxylase and 7-ethoxycoumarin O-deethylase activities were found in MH1C1 cells. Comparable values for 7-ethoxyresorufin O-deethylase activity, ranging from 21.6 to 42.9 pmol/mg x min, were observed in the hepatocytes and hepatoma cells, except the HTC cells. In contrast, only Fao cells showed 7-pentoxyresorufin O-depentylase activity at levels similar to those of hepatocytes (6.2 +/- 1.0 and 7.4 +/- 1.2 pmol/mg x min, respectively). Rat hepatocytes actively hydroxylated p-nitrophenol, but this activity was not measurable in hepatoma cells. Glutathione transferase activity was maintained in all the hepatoma cell lines at similar levels to those found in hepatocytes (684 +/- 56 nmol/mg x min). The seven hydroxylated metabolites of testosterone produced by cultured hepatocytes were negligible in hepatoma cells. Exposure of cells to inducers revealed that aryl hydrocarbon hydroxylase activity was mainly increased after treatment with 3-methylcholanthrene and beta-naphtoflavone, and the highest values were found in rat hepatocytes followed by MH1C1 and Fao cells. 3-Methylcholanthrene and naphtoflavone treatment also resulted in a marked increase in 7-ethoxyresorufin O-deethylase activity in hepatocytes as well as in H4IIC3, McA-Rh7777, MH1C1, and Fao cells.(ABSTRACT TRUNCATED AT 250 WORDS) | 10.1007/BF02631255 |
pubmed_140_23756 | Strategies for the formation of amide bonds, that is, one of the most basic and important transformations in organic synthesis, have so far focused predominantly on dehydration reactions. Herein, we report and demonstrate the practical utility of a novel decarboxylative amidation of α-ketoacids by using inexpensive tert-butyl hydroperoxide (TBHP), which is characterized by high yields, a broad substrate scope, mild reaction conditions, and a unique chemoselectivity. These features enable the synthesis of peptides from amino acid derived α-ketoacids under preservation of the stereochemical information. | 10.1002/chem.201904717 |
pubmed_556_7860 | Industrial hemp (Cannabis sativa L., Cannabaceae) is an ancient cultivated plant originating from Central Asia and historically has been a multi-use crop valued for its fiber, food, and medicinal uses. Various oriental and Asian cultures kept records of its production and numerous uses. Due to the similarities between industrial hemp (fiber and grain) and the narcotic/medical type of Cannabis, the production of industrial hemp was prohibited in most countries, wiping out centuries of learning and genetic resources. In the past two decades, most countries have legalized industrial hemp production, prompting a significant amount of research on the health benefits of hemp and hemp products. Current research is yet to verify the various health claims of the numerous commercially available hemp products. Hence, this review aims to compile recent advances in the science of industrial hemp, with respect to its use as value-added functional food ingredients/nutraceuticals and health benefits, while also highlighting gaps in our current knowledge and avenues of future research on this high-value multi-use plant for the global food chain. | 10.3390/molecules25184078 |
pubmed_389_20747 | PURPOSE
To evaluate the safety, efficacy, and appropriate perioperative timing of the use of topical bromfenac ophthalmic solution 0.07% after femtosecond laser-assisted laser in situ keratomileusis (LASIK).
SETTING
Keil LASIK Vision Center, Grand Rapids, Michigan, USA.
DESIGN
Prospective case series.
METHODS
Ocular discomfort was assessed 1, 2, and 5 hours postoperatively and the following morning using the Ocular Comfort Grading Assessment in patients treated with topical bromfenac 0.07% or artificial tears just before, just after, or before and after femtosecond laser-assisted LASIK. Visual outcomes and complications were noted up to 24 hours.
RESULTS
The study enrolled 64 patients (120 eyes). Patients who were treated with bromfenac 0.07% just before or before and after femtosecond laser-assisted LASIK showed the greatest statistically significant decrease in several discomfort scores within the first few hours in comparison with the control group. Two hours after surgery, the majority of patients who were treated before and after LASIK were sleeping comfortably. There were no significant differences in visual acuity; 1 day postoperatively, the uncorrected distance visual acuity was 20/20 in 106 eyes (89%) and 20/25 or better in 116 eyes (97%). At 3 months, all patients had binocular distance visual acuity of 20/20 or better and 86% of patients had 20/15 or better.
CONCLUSION
Ocular discomfort after femtosecond laser-assisted LASIK was reduced with a single dose of topical bromfenac 0.07% given immediately before surgery or given just before and after surgery and was typically minimal in all groups the morning after surgery. | 10.1016/j.jcrs.2016.11.042 |
pubmed_240_11187 | An x-ray grating spectrometer was built in order to measure opacities in the 50 eV to 250 eV spectral range with an average spectral resolution <E∕δE> ∼ 50. It has been used at the LULI-2000 laser facility at École Polytechnique (France) to measure the Δn = 0, n = 3 transitions of several elements with neighboring atomic number: Cr, Fe, Ni, and Cu in the same experimental conditions. Hence a spectrometer with a wide spectral range is required. This spectrometer features one line of sight looking through a heated sample at backlighter emission. It is outfitted with one toroidal condensing mirror and several flat mirrors cutting off higher energy photons. The spectral dispersion is obtained with a flatfield grating. Detection consists of a streak camera sensitive to soft x-ray radiation. Some experimental results showing the performance of this spectrometer are presented. | 10.1063/1.4740266 |
pubmed_494_2740 | Whole body vibration (WBV) is theorized to enhance neural potentiation of the stretch reflex. The purpose of this study was to determine if WBV affects the quadriceps reflex from a patellar tendon tap. Subjects were 22 volunteers (age 23 +/- 2 yrs, ht 172.8 +/- 10.8 cm, body mass 68.6 +/- 12.3 kg). The stretch reflex was elicited from the dominant leg pre, post, and 30-min post WBV treatment. A matched control group repeated the procedure without WBV. WBV treatment consisted of 5, 1-min bouts at 26 Hz with a 1-min rest period between bouts while maintaining a standardized squatting position. Two-way ANOVAs were used to detect differences between groups over time for vastus medialis (VM) and vastus lateralis (VL) latency, EMG amplitude, electromechanical delay (EMD), and force output. No group x time interactions were detected for latency (VM; F ((2,40)) = 1.20, p = .313: VL; F ((2,40)) = 0.617, p = .544), EMG mean amplitude (VM; F ((2,40)) = 0.169, p = .845: VL; F ((2,40)) = 0.944, p = .398), EMD (VM; F ((2,40)) = 0.715, p = .495: VL; F ((2,40)) = 1.24, p = .301), or quadriceps force (F ((2,40)) = 1.11, p = .341) A single session WBV treatment does not affect the quadriceps stretch reflex in terms of timing or amplitude. | 10.1055/s-2008-1038885 |
pubmed_234_21708 | This paper reports the identification of two structural variations in the NC1 domain of rat and mouse type XII collagen. The long NC1 domain encoding 74 amino acids showed homology to chicken type XII and XIV collagens. The short NC1 domain was composed of 19 amino acids. Through genomic DNA analyses, two alternative exons were identified, each of which contained the variable NC1 sequence. With the amino-terminal NC3 splicing alternatives, we propose here a new descriptive nomenclature: types XIIA-1 and XIIB-1 which include a long NC1 sequence encoded by exon 1 (from the 3'-end), and types XIIA-2 and XIIB-2 which include a short NC1 sequence encoded by exon 2. Types XIIA-1 and XIIB-1, the predominant transcripts in 15-day old mouse embryos, showed decreased expression in 17-day old embryos when type XIIB-2 expression was sustained at constant levels. In adult mice, type XIIB-1 associates with ligament and tendon, whereas type XIIB-2 is expressed in various other tissues. The long NC1 domain contains an extended acidic region (pI = 3.4) followed by a terminal basic region (pI = 13.8). Because the short NC1 domain lacks these features, structural variations in the type XII collagen NC1 domain suggests different functional roles in a tissue-specific fashion. | 10.1074/jbc.274.31.22053 |
pubmed_83_25571 | Myocardial Infarction (MI) is a fatal heart disease that is a leading cause of death. The silent and recurrent nature of MI requires real-time monitoring on a daily basis through wearable devices. Real-time MI detection on wearable devices requires a fast and energy-efficient solution to enable long term monitoring. In this paper, we propose an MI detection methodology using Binary Convolutional Neural Network (BCNN) that is fast, energy-efficient and outperforms the state-of-the- art work on wearable devices. We validate the performance of our methodology on the well known PTB diagnostic ECG database from PhysioNet. Evaluation on real hardware shows that our BCNN is faster and achieves up to 12x energy efficiency compared to the state-of-the-art work. | 10.1109/EMBC44109.2020.9175232 |
pubmed_480_4545 | BACKGROUND
In a previous study we found that in chickweed the expression level of the pro-SmAMP2 gene was comparable or even higher to that of the β-actin gene. This high level of the gene expression has attracted our attention as an opportunity for the identification of novel strong promoters of plant origin, which could find its application in plant biotechnology. Therefore, in the present study we focused on the nucleotide sequence identification and the functional characteristics of the pro-SmAMP2 promoter in transgenic plants.
RESULTS
In chickweed (Stellaria media), a 2120 bp promoter region of the pro-SmAMP2 gene encoding antifungal peptides was sequenced. Six 5'-deletion variants -2120, -1504, -1149, -822, -455, and -290 bp of pro-SmAMP2 gene promoter were fused with the coding region of the reporter gene gusA in the plant expression vector pCambia1381Z. Independent transgenic plants of tobacco Nicotiana tabacum were obtained with each genetic structure. GUS protein activity assay in extracts from transgenic plants showed that all deletion variants of the promoter, except -290 bp, expressed the gusA gene. In most transgenic plants, the GUS activity level was comparable or higher than in plants with the viral promoter CaMV 35S. GUS activity remains high in progenies and its level correlates positively with the amount of gusA gene mRNA in T3 homozygous plants. The activity of the рro-SmAMP2 promoter was detected in all organs of the transgenic plants studied, during meiosis and in pollen as well.
CONCLUSION
Our results show that the рro-SmAMP2 promoter can be used for target genes expression control in transgenic plants. | 10.1186/s12896-016-0273-x |
pubmed_132_23267 | Amoeboid cells crawl using pseudopods, which are convex extensions of the cell surface. In many laboratory experiments, cells move on a smooth substrate, but in the wild cells may experience obstacles of other cells or dead material, or may even move in liquid. To understand how cells cope with heterogeneous environments we have investigated the pseudopod life cycle of wild type and mutant cells moving on a substrate and when suspended in liquid. We show that the same pseudopod cycle can provide three types of movement that we address as walking, gliding and swimming. In walking, the extending pseudopod will adhere firmly to the substrate, which allows cells to generate forces to bypass obstacles. Mutant cells with compromised adhesion can move much faster than wild type cells on a smooth substrate (gliding), but cannot move effectively against obstacles that provide resistance. In a liquid, when swimming, the extending pseudopods convert to side-bumps that move rapidly to the rear of the cells. Calculations suggest that these bumps provide sufficient drag force to mediate the observed forward swimming of the cell. | 10.1371/journal.pone.0027532 |
pubmed_113_2145 | This study aims to assess the treatment outcomes (functional and subjective) of full-arch fixed hybrid rehabilitations made of PEEK (poly-ether-ether-ketone) with milled crowns of nano-filled composite (NFC) supported on four to six implants. In this randomized clinical trial, 34 edentate patients in the upper and/or the lower jaws were treated with the fixed hybrid dentures. In 16 patients (47.1% of the sample), the implants were loaded immediately (IL) by means of a provisional fixed rehabilitation made of PMMA (polymethylmethacrylate) screwed on Multi-Unit (MU) abutments connected after emplacement of the implant; however, in the counterparts (n = 18) these MU abutments were covered by healing caps and were left unloaded during two months (conventional loading protocol-CL), when all patients received a fixed hybrid PEEK-NFC rehabilitation on the upper and/or the lower jaw. Treatment outcomes were assessed 12 months after prostheses delivery. Functional outcomes were calculated according to masticatory performance, estimated by mixing ability tests of two colored chewing gums after ten chewing strokes, by the occlusal force/area recorded by pressure-sensitive sheets, and by electromyography of masseters and temporal muscles at maximum biteforce. The subjective outcomes of the treatment were assessed using both the oral satisfaction scale (visual analog scale) and the Spanish version of the Oral Health Impact Profile (OHIP-20). The findings of the present study showed that treatment with fixed PEEK-NFC hybrid prostheses significantly improved the masticatory performance, bite force, occlusal pattern, quality of life, and satisfaction, with the IL group being those with significantly higher occlusal bite forces and greater satisfaction in comparison with CL group. It should be concluded that PEEK-NFC hybrid prostheses can improve several patient-centered outcomes and that loading protocol significantly affects the patient's self-rated satisfaction. | 10.3390/jcm10194589 |
pubmed_73_20760 | Recently published guidelines for the management of hospital-acquired pneumonia and ventilator-associated pneumonia are reviewed for recommendations regarding diagnosis and antimicrobial therapy to assess the implications for development of future clinical trials. Despite some differences (mostly related to likely pathogens), there is a general agreement about the recommended approach to management. All of the reviewed guidelines invariably recommend early, appropriate antimicrobial therapy and avoidance of excessive antimicrobials by deescalation of therapy on the basis of microbiological culture results and the clinical response of the patient. Developers of future clinical trials will need to be mindful of these recommendations to maintain best practice care for each investigator. | 10.1086/653048 |
pubmed_31_19047 | Microcystin-LR (MC-LR) is regarded as one of the most toxic microcystins (MCs) isoforms. Microcystins could cause multiple organs dysfunction, and more attention has been drawn to the toxic effects on the gastrointestinal disorder. By using ex vivo everted gut sac model in 6 fish (Carassius auratus, Megalobrama amblycephala, Hypophthalmichthys molitrix, Aristichthys nobilis, Ctenopharyngodon idellus and Cyprinus carpio) and determining the accumulation of MC-LR in zebrafish intestine, we found a dose-dependent manner in the absorption and accumulation of MC-LR. Until now, little studies have been reported concerning the gut microbiota composition caused by different MC-LR exposure. The present study is the first time characterized the phylogenetic composition and taxonomic of the bacterial communities growth in the intestines of zebrafish treated with MC-LR using 16S rRNA pyrosequencing. After 30 days of treatment with 0, 1, 5 or 20 μg/L MC-LR, the alpha and beta diversity did not generate significant differences, indicating the existence of a core microbiota. However, db-RDA analysis showed that treatment with 20 μg/L MC-LR changed the characteristics of high abundances microbiota. The expression of Oatp2b1, stress related enzyme activities in gut and their associations with gut microbiota were also determined. The identified phylotypes including Actinobacteria, Lactobacillus and some opportunistic pathogens highlight the increasing risks of pathogen invasion and recovery tendency via potential probiotics resistance in zebrafish exposed to MC-LR. | 10.1016/j.aquatox.2018.11.014 |
pubmed_701_3137 | We prospectively studied all patients hospitalized for connective tissue disease (CTD) in our French rheumatology clinic from January 1979 to December 1989. Our aims were 1) to determine if CTDs associated with occupational exposure to silica (Si) are currently observed in a rheumatology clinic, and, if so, 2) to describe the major features of Si-associated CTD, and 3) to specify which individuals are affected by Si-associated CTD. Patients were divided into 2 groups based on their responses to a questionnaire: those who had been exposed to Si, and those who had no occupational exposure to Si. Among the 764 patients with CTD studied, 24 (3%) were patients with Si-associated CTD and 740 (97%) were patients with non-Si-associated CTD. The sex ratio between the 2 groups was significantly different with a high frequency of men and of immigrants in the Si-associated CTD group. Two thirds of the patients exposed to Si were male miners or sandblasters, but the other third had more unusual exposures to Si, which may involve members of all socio-economics sectors and both sexes, such as sculpture or exposure to abrasive powders. Progressive systemic sclerosis (PSS) was significantly more prevalent in the Si-associated CTD group. This group also consisted of patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), dermatomyositis (DM), and other autoimmune diseases. Si-associated CTD was characterized by the frequency of radiologic lung fibrosis, impaired pulmonary function tests, secondary Sjögren syndrome, and antinuclear antibodies. The number of mineral particles and crystalline Si content were raised in all the bronchoalveolar lavage specimens of Si-exposed patients but in none of those of nonexposed patients. In some cases of Si-associated CTD, the disease was reversible after early cessation of Si exposure. Epidemiologic studies are required to confirm our hypothesis that not only PSS and RA but also SLE and DM are associated with occupational exposure to Si. Pending such results, exposure to Si should be sought in the history of any patient with CTD, especially in a male patient with pulmonary signs, and if present, exposure should be stopped. In the meantime, steps should be taken to ensure that workers exposed to Si in all environments have adequate protection. | 10.1097/00005792-199509000-00001 |
pubmed_674_18966 | MicroRNAs are small noncoding RNAs that work posttranscriptionally to negatively regulate protein levels. They influence neuronal and glial structure and function, neuroinflammatory signaling, cell death, neurogenesis, and other processes relevant to epileptogenesis. Functional studies using oligonucleotide inhibitors (antagomirs) and mimics (agomirs) to modulate microRNAs in rat and mouse models of epilepsy show effects on evoked and spontaneous seizures and attendant neuropathology. The present review summarizes recent findings and points to gaps in our knowledge of the underlying mechanisms and directions for the future. | 10.5698/1535-7511-17.1.43 |
pubmed_742_12378 | BACKGROUND
Nasal mucus is the first-line defense barrier against (aero-) allergens. However, its proteome and function have not been clearly investigated.
OBJECTIVE
The role of nasal mucus in the pathophysiology of allergic rhinitis was investigated by analyzing its proteome in patients with allergic rhinitis (n = 29) and healthy control subjects (n = 29).
METHODS
Nasal mucus was collected with a suction device, tryptically digested, and analyzed by using liquid chromatography-tandem mass spectrometry. Proteins were identified by searching the SwissProt database and annotated by collecting gene ontology data from databases and existing literature. Gene enrichment analysis was performed by using Cytoscape/BINGO software tools. Proteins were quantified with spectral counting, and selected proteins were confirmed by means of Western blotting.
RESULTS
In total, 267 proteins were identified, with 20 (7.5%) found exclusively in patients with allergic rhinitis and 25 (9.5%) found exclusively in healthy control subjects. Five proteins were found to be significantly upregulated in patients with allergic rhinitis (apolipoprotein A-2 [APOA2], 9.7-fold; α2-macroglobulin [A2M], 4.5-fold; apolipoprotein A-1 [APOA1], 3.2-fold; α1-antitrypsin [SERPINA1], 2.5-fold; and complement C3 [C3], 2.3-fold) and 5 were found to be downregulated (antileukoproteinase [SLPI], 0.6-fold; WAP 4-disulfide core domain protein [WFDC2], 0.5-fold; haptoglobin [HP], 0.7-fold; IgJ chain [IGJ], 0.7-fold; and Ig hc V-III region BRO, 0.8-fold) compared with levels seen in healthy control subjects.
CONCLUSION
The allergic rhinitis mucus proteome shows an enhanced immune response in which apolipoproteins might play an important role. Furthermore, an imbalance between cysteine proteases and antiproteases could be seen, which negatively affects epithelial integrity on exposure to pollen protease activity. This reflects the important role of mucus as the first-line defense barrier against allergens. | pubmed_742_12378 |
pubmed_115_2681 | Two enzymes are involved in the polyol pathway: an aldose reductase that reduces glucose in sorbitol followed by its oxidation in fructose by sorbitol dehydrogenase. It has been previously shown that both enzymes are presented in the bovine epididymis, where they are associated with membranous vesicles called epididymosomes. Based on the distribution of these enzymes, it has been hypothesized that the polyol pathway can modulate sperm motility during the epididymal transit. In the present study, polyol pathway was investigated in semen and along the epididymis in humans in order to determine if sperm maturation can be associated with this sugar pathway. Western blot analysis shows that both aldose reductase and sorbitol dehydrogenase are associated with ejaculated spermatozoa and prostasomes in humans. These enzymes are also associated with epididymosomes collected during surgical vasectomy reversal. Western blot, Northern blot, and reverse transcription-polymerase chain reaction analysis show that aldose reductase and sorbitol dehydrogenase are expressed at the transcriptional and translational levels along the human epididymis. Unlike what occurs in the bovine model, distribution of these enzymes is rather uniform along the human excurrent duct. Immunohistological studies together with Western blot analysis performed on epididymosomes preparations indicate that the polyol pathway enzymes are secreted by the epididymal epithelium. These results indicate that the polyol pathway plays a role in human sperm physiology. | 10.2164/jandrol.05108 |
pubmed_840_2993 | Previous experimental findings demonstrating that the local administration of opioids produces dose-dependent and naloxone-reversible analgesic effects, which are restricted to the periphery, have now been confirmed in clinical studies. Accordingly, opioid receptors have been identified on peripheral sensory neurons of animals and humans. In addition to their efficacy in somatic pain, peripheral opioids potently inhibit visceral pain. These effects are enhanced under inflammatory conditions. Initial clinical trials have now examined local opioid effects in chronic inflammatory states such as arthritis. They demonstrated surprisingly long-lasting analgesic effects, probably caused by additional anti-inflammatory effects. The introduction of a new generation of opioids that act selectively in the periphery may open a novel approach to treating pain effectively without undesirable central side-effects such as respiratory depression and addiction. | 10.1097/00001503-199910000-00019 |
pubmed_453_16757 | The kinetics of colony formation by granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral blood progenitor cells (PBPCs) were monitored using clone-mapping experiments. Compared with normal resting bone marrow (BM), where the ratio of Day 7:Day 14 granulocyte-macrophage colony-forming cells (GM-CFCs) was 1:0.76-1.9, PB was found to be relatively deficient in progenitor cells with the capacity to form colonies by Day 7 (median ratio Day 7:Day 14 1:21). The most mature Day 7 GM-CFCs, those dispersing or extinguishing before Day 14, were almost absent in PB (< 1% of all GM-CFCs) but comprised 77% of Day 7 GM-CFCs and 32% of all GM-CFCs in BM. The expression patterns of high affinity receptors for G-CSF, GM-CSF, stem cell factor (SCF), and the ligand for flk-2 on CD38hi and CD38-/dim PB CD34+ cells were determined by binding of 125I-labeled ligand and autoradiography. G-CSF receptor (G-CSFR) expression was detected on approximately 25% of CD38-/dim cells (estimated mean 105 receptors per positive cell) and was higher in CD38hi cells (approximately 50% positive, with a mean of 227 receptors per cell). GM-CSFR expression was low (approximately 25% of cells positive, mean of 120 receptor per cell) and did not vary with CD38 expression. c-kit (SCFR) and flk-2 were expressed by > or = 90% and > or = 80% of CD34+ cells, respectively. SCF binding per cell was greater in the CD38hi population, while flk-2 expression did not vary with CD38 expression. These results confirm the heterogeneity of receptor expression by progenitor cells and imply differential regulation of receptor expression during maturation. | pubmed_453_16757 |
pubmed_365_22056 | New technique of extravesical antireflux surgery was presented and the treatment results were estimated in 16 children. No vesicoureteral reflux was noted in any children after operation during control cystographies. In chosen cases the presented technique corrects ureterovesical reflux, is mildly invasive and shortens child's hospitalization. | pubmed_365_22056 |
pubmed_303_5737 | Either an overabundance or a deficiency of trace metals in the food chain can ultimately affect adversely the health of livestock and man. Increasing interest in the United States in the distribution of metals in the environment and in metal pollutants has led to widespread interdisciplinary research sponsored by governmental, private and academic groups concerning the availability of trace elements for absorption by plants and animals, and the effects of trace elements throughout the food chain. The state of the art and the needs for research are reviewed by interdisciplinary committees in the National Academy of Sciences and in many government agencies. Research is encouraged through contracts and grants awarded by federal and state agencies and the National Science Foundation to universities for studies of specific metals, specific diseases and correlations between metals and health in specific geographic areas. Effects on the environment of coal-fired power plants, the mining and processing of metals, asbestos, and phosphate, and the disposal of industrial and nuclear wastes have also received much attention in the past few years. | 10.1098/rstb.1979.0096 |
pubmed_1140_9901 | OBJECTIVES
To assess the views of consultants in restorative dentistry on sedation services in secondary care for restorative dentistry and their involvement in the provision of this.
DESIGN
Postal questionnaire survey in the UK.
SETTING
Consultants in restorative dentistry.
RESULTS
There was an 80% response rate from 179 consultants. Among consultants in restorative dentistry there was a perceived need for sedation services in restorative dentistry within NHS hospitals other than for teaching purposes. Anxiety and level of trauma of dental treatment affected whether consultants felt it appropriate for patients to have such treatment under sedation. One third (48) of consultants treated patients under conscious sedation, a significant number of these held NHS posts and had graduated more recently. Of those (41) who provided treatment under conscious sedation in an NHS setting, most (38, 93%) provided treatment under intravenous sedation of whom only eight (21%) acted as operator/sedationist. Nearly all consultants (135, 94%) felt that specialist registrars in restorative dentistry should undergo some form of training in sedation.
CONCLUSIONS
Although consultants in restorative dentistry recognise the need for training in and the provision of sedation in secondary care for restorative dentistry, only one third of respondents currently provide this service. | 10.1038/sj.bdj.4812352 |
pubmed_1127_24830 | OBJECTIVE
The objectives of this study were to determine the reasons for returning medications unused and the types of unused medications returned based on therapeutic class.
SETTING
This study was conducted in a region of New Zealand covered by the Hutt Valley District Health Board. This region has approximately 51,000 households.
METHODS
A 'Disposal of Unwanted Medication Properly (DUMP)' campaign was conducted for a four week period in November 2007 in the Hutt Valley DHB region. A collection bag was delivered to every household for the collection and disposal of any unused medications. Participants were instructed to return the bags to a community pharmacy. Those returning medications were also asked to complete a questionnaire to determine why the medications were not used. A sample of the returned medications was identified and quantified and every completed questionnaire was analysed.
MAIN OUTCOME MEASURES
The main outcome measures included: types and quantities of medications returned, calculated costs of these medications and reasons for returns.
RESULTS
Over the four week period, 1,605 bags were returned for disposal. A total of 329 bags (20%) containing a total of 1,253 items were fully analysed. Only 653 questionnaires were completed (41%) all of which were analysed. The most commonly reported reason for not using the medication was that it had passed the expiry date (26%), the second was treatment change (24%), followed by condition resolved (15%). 'Alimentary tract & metabolism' and 'respiratory systems & allergies' accounted for 21 and 20% of cost respectively.
CONCLUSIONS
This study found that main reasons identified for patients having unwanted medications were 'treatment changes' and 'expired'. Additionally respiratory medications contributed 20% of the costs associated with unused medications. | 10.1007/s11096-009-9325-9 |
pubmed_749_4581 | AIM
This study aimed to determine clinical utility of genotype-guided dosing for warfarin in Han-Chinese.
METHODS
A total of 320 patients were randomly assigned International Warfarin Pharmacogenetic Consortium algorithm, Taiwan algorithm and optimal clinical care arms. The primary outcome of the study was the percentage of time in the therapeutic range during the first 90 days of treatment.
RESULTS
The percentage of time in the therapeutic range of the clinical care group in the first 2 weeks was significantly higher than the algorithm groups. This difference was no longer observed after 4 weeks. No difference in excessive anticoagulation (international normalized ratio ≥4.0) and adverse events was observed.
CONCLUSION
Genotype-guided dosing did not provide significant benefit. Loading dose with frequent international normalized ratio monitoring could provide sufficient control of anticoagulation. | 10.2217/pgs-2016-0154 |
pubmed_1097_5771 | Hypertensive emergencies must be distinguished from severe blood pressure elevations without acute target organ damage. Clinical examination (chest pain, dyspnoea, neurological disorders, ECG, retinal examination) and laboratory tests (blood and urine tests, cerebral imaging in case of neurological disorders) have to be immediately performed. Immediate referral to an intensive care unit is indicated, and an intravenous antihypertensive therapy has to be implemented. Blood pressure objectives depend on the associated acute pathology (myocardial infarction, pulmonary oedema, aortic dissection, severe pre-eclampsia and eclampsia of pregnancy, hypertensive encephalopathy, retinopathy, subarachnoid hemorrhage, cerebral hemorrhage, ischemic stroke treated or not with thrombolysis). | 10.1016/j.lpm.2010.03.015 |
pubmed_459_5485 | In vitro concanavalin A (Con A)-activated spleen cells suppressed the primary in vitro immune response of syngeneic spleen cells to sheep erythrocytes (SRBC) but enhanced the in vivo anti-SRBC responses when transferred to syngeneic untreated mice. Con-A-activated spleen cells injected into nude mice enabled these mice to respond to SRBC. | 10.1111/j.1365-3083.1985.tb01399.x |
pubmed_348_2792 | Patient M, a 45-year old female, was admitted for extractions with local anaesthetic, sedation and monitoring. This was to be carried out on an in patient basis due to the patient's extensive medical history which included rheumatic heart disease, previous deep vein thrombosis and severe ulcerative colitis. Patient M also gave a history of allergy to penicillin and lignocaine. The procedure was completed without incident, local anaesthesia having been achieved using Citanest with Octapressin (prilocaine 30 mg/ml and felypressin 0.03 unit/ml 2 ml cartridge). However, on recovery Patient M's oxygen saturations dropped to 90% on air and although she had no symptoms, the levels could not be improved with supplemental oxygen. A diagnosis of methaemoglobinaemia (MetHb) was established, a rare complication associated with the administration of prilocaine. Patient M was transferred to the high dependency unit and was given methylthioninium chloride (methylene blue) intravenously. Her oxygen saturations quickly returned to normal and she was discharged the following day. This case highlights issues relating to the risk of developing MetHb, what is considered the maximum safe dose of prilocaine and some incongruities the authors feel exist in the literature. | 10.1038/bdj.2007.1045 |
pubmed_43_13803 | Two-dimensional transition metal carbonitrides (MXene) have demonstrated great potential in many fields. However, the serious aggregation and poor thermodynamic stability of MXene greatly hinder their applications. Here, an interface-induced self-assembly strategy to synthesize ordered mesoporous carbon/Ti3 C2 Tx heterostructures (OMCTs) was developed. In this method, the composite monomicelles formed by Pluronic F127 and low-molecular-weight phenolic resol self-assembled on the surface of Ti3 C2 Tx to prevent the restacking of Ti3 C2 Tx and maintain its thermostability. The obtained OMCTs possessed high specific surface areas (259-544 m2 g-1 ), large pore volumes (0.296-0.481 cm3 g-1 ), and excellent thermodynamic stability (up to 600 °C). Benefiting from these advantages, OMCTs serving as the electrode materials for supercapacitor exhibited superior supercapacitor performances, including high capacitance of 247 F g-1 at 0.2 A g-1 , satisfactory rate performance of 190 F g-1 at 5 A g-1 , and cyclability. | 10.1002/cssc.202101374 |
pubmed_980_17852 | Chimeric antigen receptor (CAR)-T cell therapy has transformed the treatment of B cell malignancies, improving patient survival and long-term remission. Nonetheless, over 50% of patients experience severe treatment-related toxicities including cytokine release syndrome (CRS) and neurotoxicity. Differences in severity of toxic side-effects among anti-CD19 CARs suggest that the choice of costimulatory domain makes a significant contribution to toxicity, but comparisons are complicated by additional differences in the hinge and transmembrane (TM) domains of the most commonly used CARs in the clinic, segments that have long been considered to perform purely structural roles. In this perspective, we examine clinical and preclinical data for anti-CD19 CARs with identical antigen-binding (FMC63) and signalling (CD3ζ) domains to unravel the contributions of different hinge-TM and costimulatory domains. Analysis of clinical trials highlights an association of the CD28 hinge-TM with higher incidence of CRS and neurotoxicity than the corresponding sequences from CD8, regardless of whether the CD28 or the 4-1BB costimulatory domain is used. The few preclinical studies that have systematically varied these domains similarly support a strong and independent role for the CD28 hinge-TM sequence in high cytokine production. These observations highlight the value that a comprehensive and systematic interrogation of each of these structural domains could provide toward developing fundamental principles for rational design of safer CAR-T cell therapies. | 10.3390/cancers13010038 |
pubmed_46_19083 | The rabbit CD11c molecule has been characterized by use of new monoclonal antibody, mAb 3/22. Expression of the p150,95 integrin (CD11c/CD18) has been shown by flow cytometry and immunohistochemistry to be restricted to monocytes, macrophages, dendritic cells and a small population of lymphocytes in peripheral blood. No expression on neutrophils could be demonstrated. Incubation of the newly derived CD8+ T cell line, BJ/873, with mAb 3/22 causes homotypic aggregation, which has been shown to be cell surface event that is not dependent on intracellular signaling or on receptor cross-linking. Inhibition studies show that the ligands responsible for this aggregation are CD11c/CD18 and ICAM-1, both of which are expressed on BJ/873. One other rabbit T cell line, K34, that also expresses p150,95 and ICAM-1, shows a similar aggregation response when stimulated with 3/22. Cell lines that express p150,95 but not ICAM-1 do not aggregate. These observations suggest that ICAM-1 is a ligand for activated p150,95. | 10.1002/eji.1830260304 |
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