The tyrosine phosphatase HD-PTP: A novel player in endothelial migration.
Endothelial migration, pivotal step of angiogenesis, is tightly tuned by tyrosine phosphorylation of different substrates, which results from the coordinated action of tyrosine kinases and phosphatases. Here we report that the tyrosine phosphatase HD-PTP has a role in modulating endothelial motility. Indeed, we found that endothelial cells downregulating HD-PTP after transfection with siRNA acquire a scattered and spindle-shaped phenotype and migrate more than controls. We also show that HD-PTP binds Focal Adhesion Kinase (FAK), a crucial regulator of cell migration. This interaction is strongly inhibited by treatment with basic Fibroblast Growth Factor, an angiogenic factor which stimulates endothelial cell migration. In cells downregulating HD-PTP, FAK is hyperphosphorylated on tyrosine residues and localizes in the focal adhesions, at the leading edge of the cell. We suggest that HD-PTP contributes to the regulation of endothelial motility by modulating the tyrosine phosphorylation of FAK.


Heterologous expression of tyrosinase recapitulates the misprocessing and mistrafficking in oculocutaneous albinism type 2: effects of altering intracellular pH and pink-eyed dilution gene expression.
The processing and trafficking of tyrosinase, a melanosomal protein essential for pigmentation, was investigated in a human epithelial 293 cell line that stably expresses the protein. The effects of the pink-eyed dilution (p) gene product, in which mutations result in oculocutaneous albinism type 2 (OCA2), on the processing and trafficking of tyrosinase in this cell line were studied. The majority of tyrosinase was retained in the endoplasmic reticulum-Golgi intermediate compartment and the early Golgi compartment in the 293 cells expressing the protein. Coexpression of p could partially correct the mistrafficking of tyrosinase in 293 cells. Tyrosinase was targeted to the late endosomal and lysosomal compartments after treatment of the cells with compounds that correct the tyrosinase mistrafficking in albino melanocytes, most likely through altering intracellular pH, while the substrate tyrosine had no effect on the processing of tyrosinase. Remarkably, this heterologous expression system recapitulates the defective processing and mistrafficking of tyrosinase observed in OCA2 albino melanocytes and certain amelanotic melanoma cells. Coexpression of other melanosomal proteins in this heterologous system may further aid our understanding of the details of normal and pathologic processing of melanosomal proteins.


A screw position change at an early postoperative stage preceding the subsequent occurrence of screw loosening.
The authors recently proposed the novel radiologic assessment method to measure chronological screw position changes precisely. The aim of this study was to predict the late occurrence of screw loosening, which was diagnosed by the radiographic lucent zone, by evaluating screw position changes at an early postoperative stage using the novel method. Forty-three patients who underwent thoracolumbar screw fixation and follow-up computed tomography (CT) scans on the day, between 1 and 5 weeks, and at more than 6 months after surgery were retrospectively evaluated. Screw images were generated from CT data. Screw position changes were evaluated by superposing screw images on the day and between 1 and 5 weeks after surgery. Screw loosening was diagnosed by the radiographic lucent zone on CT images at 6 months or later post-surgery, and patients were classified into screw loosening and non-loosening groups. The early screw position changes were compared between the two groups. Significant differences in early screw position changes were found between the screw loosening and non-loosening groups in Mann-Whitney U test (p = 0.001). On the receiver operating characteristic (ROC) curve analysis, the area under the ROC curve was 0.791, and the best cutoff value of early screw position change for the prediction of screw loosening was 0.83 mm with a sensitivity of 64.0% and a specificity of 88.9%. We calculated a cutoff value of the screw position changes at an early postoperative stage for the prediction of subsequent development of screw loosening with the radiographic lucent zone.


Production of 3-acetyldeoxynivalenol in shake culture.
In order to produce deoxynivalenol (DON), conditions for the production of 3-acetyldeoxynivalenol (Ac-DON) in shake culture were studied. A selected isolate of DON-producer,F. graminearum strain R2118, produced about 70mg/mL of Ac-DON when cultured at 25°C for 4 days in a medium consisting of 3% sucrose, 0.1% peptone, and 0.1% yeast extract. From the mass culture (10 L) of the strain, 792 mg of Ac-DON were isolated and 384 mg of DON were obtained after hydrolysis of the acetate.


A hierarchy of needs for remote undergraduate medical education: lessons from the medical student experience.
The disruption of undergraduate medical education (UME) by the COVID-19 pandemic has sparked rapid, real-time adjustments by medical educators and students. While much is known about online teaching in general, little guidance is available to medical educators on how to adapt courses not originally designed for the online environment. To guide our faculty in this transition we conducted a needs assessment of students enrolled in virtual courses across all 4 years of UME training. Using a mixed-methods approach, we conducted a single-institution virtual learning needs assessment in May and June of 2020. We developed and disseminated a survey to assess student experiences with virtual learning. We conducted quantitative and qualitative analysis of responses (n = 255 or 39%) to identify emergent themes. We identified six interdependent themes that need to be met for medical students to fully reach their learning potential: access to stable internet and quiet study spaces, flexible course design with asynchronous, self-paced components, clear expectations for engagement with content and each other, a sense of connectedness with faculty and peers, synchronous classes that maximize interactivity, and assessments that foster a sense of learning over performance. Interpersonal relationships with faculty and peers affected students' sense of learning more than any other factor. Based on our findings we propose a hierarchy of needs for virtual learning that provides guidance on adapting existing medical school courses to the remote setting and overcoming common challenges. We highlight opportunities for how virtual elements may enrich in-person courses going forward, including in the clinical setting. Although the solutions required to meet the threshold of need at each level may differ based on the context, attending to these same fundamental needs can be extrapolated and applied to learners across a range of environments beyond the virtual.


Charges of a different kind. Providers say overzealous prosecutors are wrongly trying to transform poor medical judgment into criminal intent.
Patient-safety advocate Charles Denham, left, is among some in the industry alarmed by a trend toward prosecuting providers in criminal courts for bad care rather than deferring to the civil solutions in outlets such as medical boards. Some fear the criminal cloud could lead to fewer people entering or staying in the field. However, if the caregiver is guilty of gross negligence, Denham says: "Hang 'em".


Aggregation behaviour of black carbon in aquatic solution: Effect of ionic strength and coexisting metals.
Black Carbon (BC) is an important constituent of both aquatic and terrestrial environment, but also has several adverse effects on human health, aquatic life, and contributes to the global climate change. Thus, to understand the fate and transport of BC nanoparticles (NPs) in the environment, it's important to understand the colloidal stability or aggregation behaviour and factors affecting it, under various environmental conditions, including both aquatic and atmospheric. This study investigated the individual influence of ionic strengths, valence (Na+, Ca2+ and Mg2+), metals (Zn2+, Cu2+, Ni2+ and Cd2+), and organic substances (PO43- and Humic Acid: HA) on the effective diameter or hydrodynamic diameter and zeta potential of BC-NPs in aquatic systems. A dynamic light scattering (DLS) principle-based 90 Plus Particle Size Analyzer was used for measurements of BC particle size and zeta potential at varying ionic chemistry. The results showed that strong ionic strength promotes aggregation of BC-NPs till the repulsion forces become dominant due to more negative zeta potential. The Aggregation of BC-NPs was observed to be significantly dependent on the ionic valence, where divalent ions caused more aggregation than monovalent ions. Metal ions at higher concentration (around 1 mM) promoted the aggregation rate of BC-NPs, and Cu+2 dominated among all selected metals. Conversely, organic matter (PO43- and HA) tends to promote stabilisation of BC-NPs instead of aggregation. Though this study investigated individual effect of substances, influence of possible environmental combination of substances will help to get more clear idea.


Cyclophilin A-dependent restriction to capsid N121K mutant human immunodeficiency virus type 1 in a broad range of cell lines.
Human immunodeficiency virus type 1 (HIV-1) infection of most human cells is dependent on cyclophilin A (CypA); however, the opposite phenomenon, known as CypA-dependent inhibition, is also observed in the combination of some capsid (CA) mutations and cell lines. Here, we identified a CA N121K mutant whose infection of 293T, Jurkat, and HeLa cells was impaired by CypA. The N121K mutant could be a useful tool for analyzing the mechanisms underlying CypA-dependent restriction.


Usefulness of serum endothelin levels in predicting death and myocardial infarction but not coronary progression in postmenopausal women with coronary disease (from the Women's Angiographic Vitamin and Estrogen [WAVE] study).
We performed a cohort study of 392 postmenopausal women who had coronary disease to assess whether baseline serum endothelin-1 level predicts angiographic disease progression, nonfatal myocardial infarction, or death. Angiographic progression was defined as the annualized change in minimal lumen diameter of all qualifying lesions for each patient. Twenty-nine patients died or had a myocardial infarction during follow-up. Each picogram per milliliter increase in endothelin-1 was associated with a 1.8-fold increased risk of death or myocardial infarction. After adjustment for potential confounders, endothelin-1 remained a predictor of clinical events but was not correlated with angiographic progression.


Pili Annulati with Severe Trichorrhexis Nodosa: A Case Report and Review of the Literature.
Pili annulati is generally classified as a hair shaft disorder without fragility. However, increased susceptibility to weathering is common. Severe breakage due to trichorrhexis nodosa is uncommon. We report a case and review the literature on this topic.


Treatment of proptosis with fat removal orbital decompression in Graves' ophthalmopathy.
Retrospective evaluation of 41 proptosis reduction procedures using fat removal orbital decompression (FROD) according to a modified Olivari's technique. Trans-septal excision of extraconal and intraconal fat was done under the microscope through the upper and lower eyelid blepharoplasty approach. Proptosis was measured with a Hertel exophthalmometer. Mean excision of 7.31 + 1.9 ml (range 3.25-12 ml) of orbital fat reduced proptosis on average by 4.7 + 2.4 mm (range 1-11 mm). Side effects were few, limited only to ocular motility disturbances. There was no significant effect on visual fileds. A postoperative drop in IOP was noted in patients with preoperative IOP above 21 mmHg. Efficient palpebral lengthening can be achieved with combined section of the levator aponeurosis horns in the upper eyelid, and/or auricular cartilage graft in the lower eyelid. FROD reduces proptosis in Grave's ophthalmopathy.


Persistent negative symptoms in first-episode schizophrenia: a prospective three-year follow-up study.
Negative symptoms are a core feature of schizophrenia. The evolution and trajectory of primary negative symptoms were under-studied. We aimed at evaluating the prevalence and stability of primary negative symptoms, and factors associated with persistent primary negative symptoms in a first-episode sample. Ninety-three Hong Kong Chinese aged 18 to 55 years presenting with first-episode schizophrenia-spectrum disorder were studied. Data on premorbid adjustment, socio-demographics, and baseline clinical and cognitive profiles were obtained. Psychopathological and vocational reassessments were conducted at 12, 24 and 36 months. Primary negative symptoms were defined as the presence of clinically significant negative symptoms excluding depression and extra-pyramidal signs. At baseline, 25.8% of subjects exhibited primary negative symptoms. A quarter of patients had their initial primary negative symptoms status retained 12 months after treatment initiation. In both Year 2 and Year 3 of study period, around 70% of subjects had their primary negative symptoms status maintained for 12 months. At the end of three-year follow-up, 23.7% were categorized as having persistent primary negative symptoms. Male sex, unemployment at intake, prolonged duration of untreated psychosis, poorer premorbid academic and social functioning, poorer insight and worse vocational outcome were found to be associated with persistent primary negative symptoms. Clinical status of primary negative symptoms in first-episode schizophrenia-spectrum disorder was unstable in the initial year of treatment. Baseline symptom assessment may not reliably predict development of persistent primary negative symptoms. Studying negative symptoms should take into account the longitudinal perspective, especially in the early course of psychotic disorders.


A proteomic biosensor for enteropathogenic E. coli.
The study of proteins and the molecules with which they interact on an organismwide scale is critical to understanding basic biology, and understanding and improving human health. New platform technologies allowing label-free, quantitative array-based analysis of proteins are particularly desirable. We have developed an analytical technology, reflective interferometry (RI), which provides specific, rapid, and label-free optical detection of biomolecules in complex mixtures. In order to evaluate the suitability of RI for proteomics, we have prepared a series of arrays bearing the extracellular domain of the secreted enteropathogenic Escherichia coli (EPEC) protein Translocated Intimin Receptor (Tir). These arrays are able to selectively detect the extracellular domain of the protein Intimin, Tir's natural binding partner. Furthermore, we demonstrate the use of RI and Tir-functionalized arrays for the selective detection of EPEC directly from culture.


Mega-dose intravenous octreotide for the treatment of carcinoid crisis: a systematic review.
Carcinoid crises are rare life-threatening events involving cardiac instability when carcinoid tumours release vasoactive peptides. Such events can occur in the perioperative setting. Octreotide, a somatostatin analogue, is administered as a bolus dose of 100-500 μg iv or by infusion to treat carcinoid crises. Due to the apparent low risk-to-benefit profile, a much higher dose is sometimes used in urgent situations. The purpose of this study was to assess the evidence for administering doses or hourly infusions of octreotide that exceeded 1,500 μg iv to treat carcinoid crises. We also sought to identify which patients may require large doses and to describe the adverse effects of such doses. We systematically searched Medline, EMBASE, and Cochrane databases and hand-searched reference lists of relevant articles in 2006 and again in 2010 and 2011. All study designs were included in our search. Resolution of crisis symptoms was the primary outcome. Eighteen articles were included. No patient died during a carcinoid crisis. A retrospective chart review of 89 patients with carcinoid heart disease reported octreotide doses of 25-54,000 μg to treat carcinoid crises, although neither crisis symptoms nor outcomes were described. In the included case reports, carcinoid crises were managed effectively using octreotide 25-500 μg iv. Previous exposure to octreotide and carcinoid heart disease may warrant the need for higher doses. In addition to the low quality of the articles and the small sample size, inconsistent use of the term "carcinoid crisis" and paucity of reported outcomes were also limitations of this systematic review. These findings highlight the need for further investigation into dose-response relationships of octreotide for the treatment of carcinoid crisis.


T2 mapping of cartilage in the equine distal interphalangeal joint with corresponding histology using 0.27 T and 3.0 T magnetic resonance imaging.
Low-field magnetic resonance imaging (MRI) is widely available to equine veterinarians yet is insensitive at detecting cartilage damage in the distal interphalangeal joint (DIPJ). T2 mapping is a quantitative imaging technique that can detect cartilage damage before morphological change is apparent. Validation of a T2 mapping sequence on a low-field MR system. Correlation of the mean T2 relaxation time in sections of cartilage with varying levels of pathology using low- and high-field MRI. Cross-sectional study. Eight phantoms with known (nominal) T2 values underwent low-field (0.27 T) MRI and 38 ex vivo DIPJs were imaged. A further 9 ex vivo DIPJs were imaged on both the low- and high-field MR systems. Immediately after imaging, the DIPJs were disarticulated and samples collected for histology. Histological sections were graded using the Osteoarthritis Research Society International (OARSI) scoring system. Fiji ImageJ software with the MRIAnalysisPak plugin was used to calculate T2 maps and draw the regions of interest (ROIs). There was close agreement between the nominal and the measured T2 values in the phantom study. Spearman's rank correlation demonstrated significant positive correlation between low- and high-field T2 measurements, rho 0.644 (p < 0.001). The intrarater agreement for T2 measurements was excellent, intraclass correlation coefficient (ICC) = 0.99 (95% confidence interval [CI] = 0.99-1.00), the inter-rater agreement was excellent, ICC = 0.88 (95% CI = 0.82-0.92) and there was good intrarater agreement for OARSI scores (к = 0.76). Only a small number of histological samples were analysed. Both articular cartilage surfaces were measured within the ROI. There were no OARSI grade 0 control samples. A T2 mapping sequence on a low-field 0.27 T MR system was validated. There was a positive correlation between low- and high-field T2 measurements. The findings suggest a higher mean T2 relaxation time in pathological cartilage tissue examined in this study compared to normal equine cartilage tissue.


Production in Pichia pastoris of complementary protein-based polymers with heterodimer-forming WW and PPxY domains.
Specific coupling of de novo designed recombinant protein polymers for the construction of precisely structured nanomaterials is of interest for applications in biomedicine, pharmaceutics and diagnostics. An attractive coupling strategy is to incorporate specifically interacting peptides into the genetic design of the protein polymers. An example of such interaction is the binding of particular proline-rich ligands by so-called WW-domains. In this study, we investigated whether these domains can be produced in the yeast Pichia pastoris as part of otherwise non-interacting protein polymers, and whether they bring about polymer coupling upon mixing. We constructed two variants of a highly hydrophilic protein-based polymer that differ only in their C-terminal extensions. One carries a C-terminal WW domain, and the other a C-terminal proline-rich ligand (PPxY). Both polymers were produced in P. pastoris with a purified protein yield of more than 2 g L(-1) of cell-free broth. The proline-rich module was found to be O-glycosylated, and uncommonly a large portion of the attached oligosaccharides was phosphorylated. Glycosylation was overcome by introducing a Ser → Ala mutation in the PPxY peptide. Tryptophan fluorescence monitored during titration of the polymer containing the WW domain with either the glycosylated or nonglycosylated PPxY-containing polymer revealed binding. The complementary polymers associated with a Kd of ~3 µM, regardless of glycosylation state of the PPxY domain. Binding was confirmed by isothermal titration calorimetry, with a Kd of ~9 µM. This article presents a blueprint for the production in P. pastoris of protein polymers that can be coupled using the noncovalent interaction between WW domains and proline-rich ligands. The availability of this highly specific coupling tool will hereafter allow us to construct various supramolecular structures and biomaterials.


Mutation screening in a cohort of patients with lissencephaly and subcortical band heterotopia.
The authors describe clinical, neuroimaging and molecular findings in a group of 15 patients with classic lissencephaly (LIS) and subcortical band heterotopia (SBH). A 1385A-->C mutation was found in the LIS1 gene in one patient with LIS more severe than expected for individuals with missense mutations in LIS1. The authors believe that the site of the mutation, present in a functionally critical region of the protein, could explain the unusual severe phenotype found in this patient.


Self-starvation in context: towards a culturally sensitive understanding of anorexia nervosa.
Extreme forms of self-starvation can be traced across time and place, and may be construed using a variety of explanatory models. Curiously, the prevailing biomedical definition of anorexia nervosa has assigned primacy to the exclusive use of 'fat phobia' by the affected subjects to justify their diminished food intake. This paper assembles evidence to show that this culturally constructed version of fat phobic anorexia nervosa has neglected the full metaphorical significance of self-starvation and, when applied in a cross-cultural context, may constitute a category fallacy. By delegitimizing other rationales for non-eating and thereby barring subjective expressions, this regnant interpretive strategy may obscure clinicians' understanding of patients' lived experience, and even jeopardize their treatment. Nonetheless, it is a relatively simple task to attune the extant diagnostic criteria to a polythetic approach which will avert cultural parochialism in psychiatric theory and practice. As a corollary of the archival and ethnocultural study of extreme self-starvation, there is, contrary to epistemological assumptions embedded in the biomedical culture of contemporary psychiatry, no 'core psychopathology' of anorexia nervosa.


Cord Blood Metabolites Associated with Newborn Adiposity and Hyperinsulinemia.
To evaluate the association between cord blood amino acid and acylcarnitine profiles and measures of adiposity and hyperinsulinemia in healthy newborns. A cross-sectional study of 118 full-term infants born to mothers without gestational diabetes was performed. Cord blood leptin, C-peptide, acylcarnitine, and amino acid levels were measured. Body composition was measured by air displacement plethysmography. Multivariate linear regression and principal component analysis were used to analyze associations of cord blood metabolites with newborn anthropometrics, leptin, and C-peptide. Acylcarnitines AC C2, AC C4-DC/Ci4-DC, and AC C8:1-OH/C6:1-DC were positively associated with leptin, and AC C14, AC C14:2, AC C16, AC C18, and AC C18:2 were negatively associated with C-peptide (P ≤ .0016). Principal component analysis revealed a positive association between factor 1(AC C2, AC C3, AC C5, AC C4/Ci4, AC C4-OH, AC C4-DC/Ci4-DC, glutamate/glutamine, and glycine) and adiposity measures. The positive association of AC C2 and AC C4-DC/Ci4-DC levels with leptin may reflect excess fat stores, higher fatty acid oxidation rate, and mitochondrial dysfunction leading to accumulation of acylcarnitine intermediates. Principal component analysis revealed a positive association between branched chain amino acid and ketone body metabolites and adiposity, confirming prior findings in adults. Cord blood acylcarnitine profiles may identify at-risk children before obesity or insulin resistance develops.


CoIV plasmids pCoIV-B188 and pCoIV-K30: genetic maps according to restriction enzyme sites and landmark phenotypic characteristics.
The CoIV plasmids are large virulence plasmids of the incompatibility group IncFI. We have obtained the genetic maps of two of the most studied CoIV plasmids, pCoIV-B188 and pCoIV-K30, according to restriction enzyme sites and landmark phenotypic characteristics such as colicin V, the aerobactin iron uptake system, the transfer region, replication regions, and repeated sequences. Although the two plasmids differ in size (pCoIV-B188 is 80 kb and pCoIV-K30 is 144 kb), the maps reveal many regions which are apparently identical or very similar.


Geriatric update 2022: Preventing Alzheimer disease and more.
Articles published in 2020 and 2021 contain important research related to preventing Alzheimer dementia; the relationships between frailty, social isolation, and mortality; COVID-19 risks in patients with dementia; hospital-at-home programs; deprescribing antihypertensive drugs; bisphosphonate-related atypical femoral fractures; and cannabis use in older adults.


Comparison of synthetic mesh erosion and chronic pain rates after surgery for pelvic organ prolapse and stress urinary incontinence: a systematic review.
The aim of this study is to systematically compare rates of erosion and chronic pain after mesh insertion for pelvic organ prolapse (POP) and stress urinary incontinence (SUI) surgery. A systematic electronic search was performed on studies that evaluated the incidence of erosion and chronic pain after mesh insertion for POP or SUI. The primary outcome measurement was to compare mesh erosion rates for POP and SUI surgery. Secondary outcome measurements were incidence of de novo pain and a comparison of patient demographics for both surgeries. Twenty-six studies on 292,606 patients (n = 9077 for POP surgery and n = 283,529 for SUI surgery) met the inclusion criteria. Median follow-up was 26.38 ± 22.17 months for POP surgery and 39.33 ± 27.68 months for SUI surgery. Overall, the POP group were older (p < 0.0001) and had a lower BMI (p < 0.0001). Mesh erosion rates were significantly greater in the POP group compared to the SUI group (4% versus 1.9%) (OR 2.13; 95% CI 1.91-2.37; p < 0.0001). The duration from surgery to onset of mesh erosion was 306.84 ± 183.98 days. There was no difference in erosion rates between abdominal and transvaginal mesh for POP. There was no difference in erosion rates between the transobturator and retropubic approach for SUI. The incidence of chronic pain was significantly greater in the POP group compared to the SUI group (6.7% versus 0.6%) (OR 11.02; 95% CI 8.15-14.9; p < 0.0001). The duration from surgery to onset of chronic pain was 325.88 ± 226.31 days. The risk of mesh erosion and chronic pain is significantly higher after surgery for POP compared to SUI. These significant complications occur within the first year after surgery.


Magnetic resonance support vector machine discriminates essential tremor with rest tremor from tremor-dominant Parkinson disease.
The aim of the current study was to distinguish patients who had tremor-dominant Parkinson's disease (tPD) from those who had essential tremor with rest tremor (rET). We combined voxel-based morphometry-derived gray matter and white matter volumes and diffusion tensor imaging-derived mean diffusivity and fractional anisotropy in a support vector machine (SVM) to evaluate 15 patients with rET and 15 patients with tPD. Dopamine transporter single-photon emission computed tomography imaging was used as ground truth. SVM classification of individual patients showed that no single predictor was able to fully discriminate patients with tPD from those with rET. By contrast, when all predictors were combined in a multi-modal algorithm, SVM distinguished patients with rET from those with tPD with an accuracy of 100%. SVM is an operator-independent and automatic technique that may help distinguish patients with tPD from those with rET at the individual level.


Routine coronary arteriography before abdominal aortic aneurysm repair.
As cardiac complications constitute the principal cause of early and late morbidity and mortality after the surgical treatment of abdominal aortic aneurysm (AAA), a prospective study was planned to evaluate the effects of revascularization of coronary arteries on survival after AAA repair during early and long-term follow-up periods. A total of 125 patients underwent elective repair of AAA between 1986 and 1994. Coronary arteriography was performed in all cases. All cases with critical left anterior descending artery (LAD) lesions underwent a coronary artery bypass operation either simultaneously or shortly before AAA repair. In addition, percutaneous transluminal coronary angioplasty (PTCA) was performed for symptomatic and critical stenosis of arteries other than the LADs, or if noncritical but symptomatic stenosis of the LADs existed. Early and late follow-up data were obtained for all cases, and late-term cumulative survival rates were calculated. Coronary artery lesions were found in 66 (53%) cases. In 24 cases, AAA repairs were performed 2.3 (mean) months after coronary artery bypass grafting (CABG), whereas in 4 cases both procedures were performed simultaneously. PTCA was performed in 4 cases 3 to 4 days prior to the abdominal surgery. Even though the coronary artery lesions were found inoperable in 7 cases, these patients underwent repair of AAA because of rapidly expanding and painful aneurysms. Early mortality rate was 4% (5 cases), in which 3 of these were from the group inoperable for CABG. A mean follow-up of 3.17 years (3 to 87 months) was achieved for all discharged patients. Cumulative survival rates for 6 months and 1, 2, 3, and 6 years were 99%, 99%, 95%, 93%, and 89%, respectively. The results of this study emphasize the importance of coronary artery revascularization for early, and especially for late, survival after AAA repair.


Quality of multiple-choice questions in medical internship qualification examination determined by item response theory at Debre Tabor University, Ethiopia.
Assessment of cognitive competence is a major element of the internship qualification exam in undergraduate medical education in Ethiopia. Assessing the quality of exam items can help to improve the validity of assessments and assure stakeholders about the accuracy of the go/no decision to the internship. However, we know little about the quality of exam items utilized to ascertain fitness to join the medical internship. Therefore, this study aimed to analyze the quality of multiple-choice questions (MCQs) of the qualification exam administered to final-year medical students at Debre Tabor University (DTU), Ethiopia. A psychometric study was conducted to assess the qualities of 120 randomly selected MCQs and 407 distractors. Item characteristics were estimated using the item response theory (IRT) model. T-test, one-way ANOVA, and chi-square tests were run to analyze the univariate association between factors. Pearson's correlation test was done to determine the predictive validity of the qualification examination. Overall, 16, 51, and 33% of the items had high, moderate, and low distractor efficiency, respectively. About two-thirds (65.8%) of the items had two or more functioning distractors and 42.5% exhibited a desirable difficulty index. However, 77.8% of items administered in the qualification examination had a negative or poor discrimination index. Four and five option items didn't show significant differences in psychometric qualities. The qualification exam showed a positive predictive value of success in the national licensing examination (Pearson's correlation coefficient = 0.5). The psychometric properties of the medical qualification exam were inadequate for making valid decisions. Five option MCQs were not better than four options in terms of psychometric qualities. The qualification examination had a positive predictive validity of future performance. High-stakes examination items must be properly created and reviewed before being administered.


Atopic disorders and risk of childhood-onset type 1 diabetes in individuals.
Data on the relationship between Th2-biased atopic disorders and Th1-biased autoimmune diseases such as type 1 diabetes are conflicting. Many studies have not defined the time sequence of disease appearance, and few have investigated the role of candidate risk factors. The objective was to investigate whether the presence of parents' report of physician-diagnosed atopic disorders is lower among cases of type 1 diabetes before diagnosis, as compared with population-based control subjects, and whether this may be explained by candidate risk factors such as day-care attendance, breastfeeding habits, and perinatal factors. We designed a population-based case-control study in Norway with 545 cases of childhood-onset type 1 diabetes and 1668 control subjects. Families were contacted by mail, and they completed a questionnaire on physician-diagnosed atopic eczema, allergic rhino-conjunctivitis and asthma, and other relevant factors. Data on birth order, maternal age at delivery, birth weight, gestational age, pre-eclampsia, and caesarean section were obtained from the Medical Birth Registry of Norway by record linkage. Atopic eczema was inversely associated with risk of type 1 diabetes, odds ratio=0.55 (95% confidence interval 0.35-0.87) after adjustment for age, sex, maternal education, day-care attendance, duration of exclusive breastfeeding, and perinatal factors. Allergic rhino-conjunctivitis and asthma were not significantly associated with type 1 diabetes. Atopic eczema was associated with a lower risk of type 1 diabetes, independent of a number of candidate risk factors, suggesting that it may confer partial protection against type 1 diabetes.


Ethyl pyruvate significantly inhibits tumour necrosis factor-α, interleukin-1β and high mobility group box 1 releasing and attenuates sodium taurocholate-induced severe acute pancreatitis associated with acute lung injury.
In this study, we examined the effect of ethyl pyruvate (EP) on pulmonary inflammation in rats with severe pancreatitis-associated acute lung injury (ALI). Severe acute pancreatitis (SAP) was induced in rats by the retrograde injection of 5% sodium taurocholate into the pancreatic duct. Rats were randomly divided into the following experimental groups: control group, SAP group and EP-treated group. The tissue specimens were harvested for morphological studies, Streptavidin-peroxidase immunohistochemistry examination. Pancreatic or lung tissue oedema was evaluated by tissue water content. Serum amylase and lung tissue malondialdehyde (MDA) and myeloperoxidase (MPO) were measured. Meanwhile, the nuclear factor-κB (NF-κB) activation, tumour necrosis factor-α (TNF-α), interleukin-1β (IL-1β) levels and HMGB1 protein expression levels in the lung were studied. In the present study, we demonstrated that treatment with EP after SAP was associated with a reduction in the severity of SAP and lung injury. Treatment with EP significantly decreased the expression of TNF-α, IL-1β, HMGB1 and ameliorated MDA concentration, MPO activity in the lung in SAP rats. Compared to SAP group, administration of EP prevented pancreatitis-induced increases in nuclear translocation of NF-κB in the lung. Similarly, treatment with EP significantly decreased the accumulation of neutrophils and markedly reduced the enhanced lung permeability. In conclusion, these results demonstrate that EP might play a therapeutic role in pulmonary inflammation in this SAP model.


Clinical and Serological Characteristics of Ocular Toxoplasmosis in the Democratic Republic of Congo.
To describe demographic data, clinical features, and serological profiles in a cohort of Congolese patients with ocular toxoplasmosis (OT). Cross-sectional study, carried out between March 2020 and July 2021 in two ophthalmic clinics in Kinshasa. The study comprised 95 participants with OT. Fifty-three patients were male (55.8%). The mean age at presentation was 35.6 ± 14.1 years (range 8-69 years); 71 had active OT (74.7%), among them, 33 had primary OT (46.5%), and 38 had recurrences (53.5%). At presentation, 51 patients (53.7%) had visual impairment (VA < 6/18). Retinochoroidal lesions were located in the central retina in 60 patients (63.1%). Patients with primary OT tend to have higher IgG levels than those with recurrent OT (P = .01). We report the largest cohort of patients with OT in sub-Saharan Africa. In our setting, most patients had recurrent OT with multiple, extensive, and central retinochoroidal lesions.


Preoperative knee deformity and kinematics impact postoperative knee kinematics in total knee arthroplasty.
The purpose of this study was to evaluate the relationship between the preoperative knee deformity/kinematic pattern and the postoperative knee kinematic pattern in posterior cruciate ligament substituting (PS)-total knee arthroplasty (TKA). This study involved 39 patients with medial osteoarthritis who underwent a primary PS-TKA using a computed-tomography-based navigation system. All the operations were performed by a single surgeon using a subvastus approach, modified gap technique and the same PS type of prosthesis (Genesis II™ total knee system, Smith & Nephew, Memphis, TN, USA). Knee deformity, kinematic pattern after capsule incision (preoperative knee kinematics), and kinematic pattern after implantation (postoperative knee kinematics) in PS-TKA were measured. Kinematic patterns were divided into two groups: a medial pivot group and a non-medial pivot group. Preoperative varus knee deformity was significantly larger in the non-medial pivot group than in the medial pivot group (femorotibial angle: 184.7±6.4° vs. 180.8±3.9°, P<0.05). In addition, preoperative knee kinematics were conserved postoperatively, at a rate of 82% (P<0.01). The severity of varus knee deformity and the preoperative knee kinematic pattern might have affected the postoperative knee kinematics in PS-TKA. This must be confirmed with a randomized controlled trial on a large population study. case control study, Level III.


Three-dimensional stereophotogrammetrical analysis of peristomal fixation of adhesive base plates during hands-free speech among laryngectomised patients related to tracheostoma volumes.
This study evaluates the relation between stoma volumes by means of objective three-dimensional measurements of laryngectomised individuals and peristomal fixation of adhesive baseplates during hands-free speech. A three-dimensional stereophotogrammetrical image was captured of the tracheostoma and its surrounding tissue for each participant. The placement of a baseplate adhesive was virtually simulated. Individual stoma volumes were calculated and related to the duration of lifetime of adhesive baseplates. Prospective trial in a university hospital setting. Twenty-four laryngectomised patients. Stoma volume in cm(3) and adhesive baseplate adherence in minutes. For the 24 three-dimensional images captured, the mean volume of the area under the adhesive (stoma volume) was 9.5 cm(3) (range 3.5-22.5). After relating the different volumes of all patients to their individual fixation score, a significant decrease in duration of adhesive lifetime was found with increasing volumes of the stoma (P = 0.001). An increase of 1 cm(3) in tracheostoma volume resulted in a decrease of 21% in median adhesive lifetime (95% confidence interval 10-31%). Longer lifetime of the adhesive baseplate in patients with smaller volume outcomes suggests that a more accurate fit between baseplate and stoma leads to better fixation. This should be taken into account when shaping a stoma during laryngectomy. On the other hand, a more custom-made patch that has a more accurate fit could increase the lifetime of fixation. We believe that our three-dimensional volumetric data can contribute to the development of such an adhesive.


[Studies on the relationship between D6S1581, a high frequency allele imbalance locus, and genetic susceptibility to nasopharyngeal carcinoma].
To investigate the relationship of nasopharyngeal carcinoma (NPC) with the high frequency allele imbalance locus D6S1581, and the NPC associated gene FBXO30 which is located near D6S1581. Genescan was used to genotype D6S1581 of 12 NPC pedigrees, 85 sporadic NPC patients and 181 normal volunteers. Then parametric/nonparametric linkage analysis and association analysis were performed. D6S1581 was linked with NPC, a Lod score of 2.611436 (P=0.00245) was obtained, and a significant difference in allele frequency was observed between familial NPC and control (P<0.005). These results suggest that D6S1581 is highly associated with NPC, and there may be one or more NPC associated genes near D6S1581, including FBXO30.


Application of aluminium ammonium-sulphate solution in treating massive haemorrhage of bladder origin.
The effect of the 1% aluminium ammonium-sulphate solution has been studied. As revealed by animal experiments and clinical examination, the new method can effectively be used without side-effects in the symptomatic treatment of the massive vesical haemorrhages of different origin.


[A new case of partial monosomy of chromosome 12,del(12)(p11.01 to p12.109) confirming the location of the gene for lactate dehydrogenase B].
A new case of partial monosomy of the short arm of chromosome 12 is described in a 17-year-old girl and compared with other observations reported in the literature. The breakpoints were localized to region 12p11----12p.12.1. Qualitative and quantitative activity of LDHB allowed a precise assignment of the structural gene to sub-band 12p12.2.


Conformational stabilities, infrared, and vibrational dichroism spectroscopy studies of tris(ethylenediamine) zinc(II) chloride.
The conformational stabilities of the transition metal complex of Zn (en)3Cl2 were studied using density functional theory (DFT). Deformational potential energy profiles (PEPs), and pathways between the different isomeric conformational energies were calculated using DFT/B3LYP/6-31G. The relative conformational energies of Delta(lambdalambdalambda), Delta(lambdalambdadelta), Delta(lambdadeltadelta) and Delta(deltadeltadelta) are 10.48, 7.08, 3.56, and 0.0 kcal/mol, respectively, which are small compared to the barrier heights for reversible phase transitions (49.56, 49.55, 49.52 kcal/mol, respectively). Frequency assignment was carried out by decomposing Fourier transform infrared (FTIR) spectra using Gaussian and Gaussview. The theoretical IR and vibrational dichroism spectroscopy (VCD) absorption spectra are presented for all conformations within the range of 400-3,500 cm(-1).


Nested and robust modeling techniques for fNIRS data with demographics and experiment related factors in n-back task.
Functional near-infrared spectroscopy (fNIRS) signals are used to measure relative changes in oxyhemoglobin (HbO) and deoxyhemoglobin (HbR) concentrations. Brain response studies constitute multilevel or nested datasets formed by different parts of the brain of individuals and multidimensional datasets. The changes in brain activities under specific stimuli are investigated with the help of statistical analysis. However, these studies ignore the dependence structure between the repeated measures of the same subject, which may cause inaccurate or incomplete findings. In this study, we adopt an advanced statistical method into HbO data controlling for variability within repeated measures of each subject while testing and measuring the degrees of the statistical significance between-subject factors and explanatory variables. The changes in HbO are investigated through a linear mixed model, taking experimental and demographic variables into account with open access neuroscience data. The channels nested within subjects are considered random to capture the differences among individuals. Our findings reveal that n-back conditions and mean response times of the subjects have statistically significant associations with mean HbO.


Requirement of the activation-induced deaminase (AID) gene for immunoglobulin gene conversion.
Three phenotypically distinct processes-somatic hypermutation, gene conversion, and switch recombination-remodel the functionally rearranged immunoglobulin (Ig) loci in B cells. Somatic hypermutation and switch recombination have recently been shown to depend on the activation-induced deaminase (AID) gene product. Here, we show that the disruption of the AID gene in the chicken B cell line DT40 completely blocks Ig gene conversion and that this block can be complemented by reintroduction of the AID complementary DNA. This demonstrates that the AID master gene controls all B cell-specific modifications of vertebrate Ig genes.


Evaluation of Normal Adrenal Gland Volume and Morphometry and Relationship with Waist Circumference in an Adult Population Using Multidetector Computed Tomography.
This study aims to determine the normal range of values of the right, left, and total volume and shape of the adrenal gland (AG) and to evaluate its relationship with gender, age, height, weight, body mass index (BMI), and waist circumference (WC) in multidetector computed tomography (MDCT) images. The study included 115 MDCT scans, of which 56 were men and 59 were women. For volume measurement, the outlines of the AG were drawn semi-automatically for all patients. Then, collecting the area in each slice, the volumes were automatically measured. The intraclass correlation coefficient (ICC) test was used to analyze intraobserver reliability for repeated measurements with a 95% confidence interval. Participant's age, gender, weight, height, BMI, and WC were obtained. p<0.05 was considered statistically significant. The mean age of participants was 49.5±17.7 (19-81). The average right AGV (RAGV), left AGV (LAGV), and total AGV were 3.47±1.33, 4.77±1.33, and 8.25±2.74, respectively. The ICC values for all measurements were >0.80-0.90, indicating good and excellent agreement. LAGV was measured as higher than the RAGV. A positive moderate correlation of the AGVs with BMI and WC was observed. The increase in BMI and WC, which are indicators of obesity, correlates with the increase in AGV, we think that the findings will be valuable in evaluating the pathophysiology of the hypothalamic-pituitary-adrenal axis.


A monoclonal antibody ameliorates local inflammation and osteoporosis by targeting TNF-α and RANKL.
This study aimed to generate a monoclonal antibody (mAb) targeting both tumor necrosis factor-α (TNF-α) and receptor activator of NF-κB ligand (RANKL) and to evaluate the therapeutic effects of this antibody on acute inflammation and osteoporosis. We used hybridoma techniques to generate potential mAbs and enzyme-linked immunosorbent assay (ELISA) to determine their specificity. Crystal violet staining was performed to measure the effective dose of the candidate mAbs. The neutralizing effect of the mAbs was evaluated by TNF-α-mediated cytotoxicity and RANKL-induced osteoclastogenesis assays. We further assessed the therapeutic effect of the mAbs in BALB/c mice with carrageenan-induced acute inflammation and ovariectomy-induced osteoporosis. We successfully generated an IgG1 isotype mAb that recognizes human TNF-α and RANKL, which we named 8G12. The 50% effective dose of 8G12 was approximately 1μg/mL. L929 cells treated with 8G12 exhibited decreased levels of apoptosis (20.04% compared to 63.28% in the positive controls). In addition, treatment with 8G12 inhibited osteoclastogenesis in a dose-dependent manner in vitro. Carrageenan-induced paw edema was significantly reduced in the 8G12-treated mice compared to the positive controls. Treatment with 8G12 also reduced the number of infiltrating leukocytes by more than 50%. The 8G12 treatment not only prevented bone loss but also increased the number, thickness and volume of trabeculae and reduced trabecular separation in ovariectomized mice. Our data suggest that the 8G12 effectively neutralizes the bioactivity of TNF-α and RANKL, ameliorating osteoporosis and inflammation. We therefore propose that 8G12 could be a candidate for generating therapeutic antibodies for treating inflammatory bone diseases.


Differential influence of local anesthetic upon two models of experimentally induced peripheral mononeuropathy in the rat.
Neuropathic pain remains a major complication of various forms of injury to peripheral nerves in humans. Recently, 2 models of peripheral mononeuropathy in the rat have been described which closely resemble the human condition. Bennett and Xie3 described one model induced by the placement of 4 loose ligatures around the entire sciatic nerve; Seltzer et al. have described a second model produced by the placement of a tight ligature around one-third to one-half of the sciatic nerve. It is the purpose of this work to compare the effect of these injuries on the time course and magnitude of hyperalgesia as measured by paw withdrawal latency to a radiant heat stimulus. In addition, to evaluate the hypothesis that neuropathic pain develops as a result of injury-associated discharges, some injuries were induced following anesthesia of the sciatic nerve. Our results show that the partial constriction neuropathy (PCN) described by Bennett and Xie3 develops in a faster time frame than that produced by the tight ligature, or partial transection neuropathy (PTN), described by Seltzer and co-workers. In addition, the PCN shows a reduction in both the duration and magnitude of behavioral hyperalgesia obtained for those animals in which local anesthetic (lidocaine) was applied to the sciatic nerve, while the PTN does not show this sensitivity. The data suggest that injury-related discharge is one important factor contributing to the generation of hyperalgesia in the PCN model. The mechanism(s) responsible for the generation of hyperalgesia in the early stages of the PTN model are not lidocaine-sensitive.(ABSTRACT TRUNCATED AT 250 WORDS)


The accuracy of virtual-surgical-planning-assisted treatment of hemifacial microsomia in adult patients: distraction osteogenesis vs. orthognathic surgery.
Hemifacial microsomia (HFM) is a common congenital craniofacial deformity with a high prevalence. Orthognathic surgery and distraction osteogenesis are two conventionally used treatments of HFM. The main objective of this retrospective study was to evaluate the accuracy of two treatments with the help of virtual surgical planning in adult HFM patients. Sixty-eight adult patients with unilateral HFM were enrolled in this study. Preoperative surgical planning and simulation were performed on three-dimensional computed tomography models. Orthognathic surgery or distraction osteogenesis was performed under the guidance of three-dimensional surgical templates. Postoperative evaluation of the intervention was performed by comparison of the affected ramus height, chin deviation and the occlusal cant in surgical planning and actual result. Outcome and feedback information (an average of 14 months) showed that virtual surgical planning was accurately transferred to actual surgery in both surgical approaches. There were no statistical differences between the accuracy of affected ramus height and the occlusal cant in two surgical approaches. The orthognathic group showed significantly higher accuracy in chin deviation. In conclusion, virtual surgical planning and three-dimensional surgical templates were proved to facilitate treatment planning and offer an accurate surgical result in the treatment of adult HFM patients.


Long-term follow-up study of 142 patients with vitiligo vulgaris treated by autologous, non-cultured melanocyte-keratinocyte cell transplantation.
Vitiligo vulgaris patients are difficult to treat surgically owing to large area involvement. Larger areas can be treated with the help of in vitro cultured melanocytes. These techniques are complex. In most of the studies published to date the number of patients reported is low and follow-up period short. To evaluate long-term efficacy and safety of melanocyte-keratinocyte cell transplantation in large number of vitiligo vulgaris patients. A simpler and modified method based on that of Olsson and Juhlin has been used. It uses shave biopsy skin sample up to 1/10th the size of recipient area. Skin sample is incubated, cells mechanically separated using trypsin-EDTA solution, and then centrifuged to prepare a suspension. Cell suspension is then applied to a dermabraded de-pigmented skin area and collagen dressing given to keep it in place. One hundred and forty-two patients with vitiligo vulgaris were treated and observed for a period up to 6 years. Eighty (56%) patients showed excellent, 15 (11%) showed good, 13 (9%) showed fair and 34 (24%) showed poor repigmentation, which was retained till the end of the respective follow-up period.


Thoracoscopic approach for oesophageal atresia: A real game changer?
Almost 23 years have passed since the first thoracoscopic procedure was done. However, according to the recent study in USA, only 16% of newborns with oesophageal atresia and distal tracheooesophageal fistula are managed by thoracoscopic approach with a very high 53% conversion rate. The aim of presentation based on experience of one paediatric surgery centre is to prove that thoracoscopic approach for this malformation is a powerful tool with a potential to change the current results. It requires considerable experience that comes only from the high number of operated cases. The technique is one amongst the many others means which taken together may really help to improve the results. Thus, the question of centralisation for special rare congenital malformations comes back to mind. Is it rational to operate on only 2 or 3 cases a year in a single centre, or is it the time for centralisation and close co-operation, as has been done with biliary atresia treatment in the UK? LEVEL OF EVIDENCE: III.


Adaptive chromatin remodeling and transcriptional changes of the functional kinome in tumor cells in response to targeted kinase inhibition.
Pharmacological inhibition of protein kinases induces adaptive reprogramming of tumor cell regulatory networks by altering expression of genes that regulate signaling, including protein kinases. Adaptive responses are dependent on transcriptional changes resulting from remodeling of enhancer and promoter landscapes. Enhancer and promoter remodeling in response to targeted kinase inhibition is controlled by changes in open chromatin state and by activity of specific transcription factors, such as c-MYC. This review focuses on the dynamic plasticity of protein kinase expression of the tumor cell kinome and the resulting adaptive resistance to targeted kinase inhibition. Plasticity of the functional kinome has been shown in patient window trials where triple-negative and human epidermal growth factor receptor 2-positive breast cancer patient tumors were characterized by RNAseq after biopsies before and after 1 week of therapy. The expressed kinome changed dramatically during drug treatment, and these changes in kinase expression were shown in cell lines and xenografts in mice to be correlated with adaptive tumor cell drug resistance. The dynamic transcriptional nature of the kinome also differs for inhibitors targeting different kinase signaling pathways (e.g., BRAF-MEK-ERK versus PI3K-AKT) that are commonly activated in cancers. Heterogeneity arising from differences in gene regulation and mutations represents a challenge to therapeutic durability and prevention of clinical drug resistance with drug-tolerant tumor cell populations developing and persisting through treatment. We conclude that understanding the heterogeneity of kinase expression at baseline and in response to therapy is imperative for development of combinations and timing intervals of therapies making interventions durable.


[Development of mammalian somatic cell genetics].
The history of somatic cell genetics from the late 1950s to the present day is considered. Studies in this field provided for the elucidation of numerous fundamental and applied problems, including spontaneous mutagenesis, gene mapping with somatic cell hybrids, and genetic mechanisms of carcinogenesis (e.g., cell protooncogenes, oncogenes, and tumor suppressor genes were revealed). The knocking-out technique allowed the effects of various genes to be analyzed.


An outbreak of skin rash by echovirus 25 in an infant home.
In September 1980 an outbreak of a skin eruption occurring in an infant home in Milan involved 15 children (aged five to 22 months) out of a total of 25. All of them showed a pink maculopapular rash, three had slight fever and eight mild gastroenteric symptoms (diarrhoea). The exanthem lasted three to four days and was distributed over the trunk and the face and only affected the limbs partially. Mild gastroenteric symptoms (abdominal pain or diarrhoea) were reported also by five subjects out of 13 of the staff. Specimens of stools from the 15 affected children and from the five nurses were submitted for virological examination. A strain of echovirus 25 was isolated on primary monkey kidney cells from the stools of eight children and from one adult.


Abdominal aortic aneurysm presenting to the orthopedic clinic as posterior hip and low back pain.
Abdominal aortic aneurysms (AAAs) are typically asymptomatic. When symptomatic, AAA may present as a chief concern of musculoskeletal hip and low back pain. Assessment in the orthopedic clinic should focus on a holistic examination of the patient.


Biocatalytic synthesis of hydroxylated natural products using aldolases and related enzymes.
Synthetic building blocks bearing hydroxylated chiral centers are important targets for biocatalysis. Many C-C bond forming enzymes have recently been investigated for new applications and new strategies towards the synthesis of natural products and related oxygenated compounds. Several old catalysts have been studied to increase our functional knowledge of natural aldolase-type enzymes, and new mutated catalysts or catalytic antibodies have been tested for their synthetic utility.


The use of small intestine in bladder reconstruction.
Reconstruction of the bladder is a treatment available to patients who have a diseased or damaged bladder, and small bowel is the most commonly used tissue. Augmentation cystoplasty increases the total bladder capacity, whereas substitution cystoplasty replaces the whole organ. This is either drained through a continent cutaneous stoma or is reanastomosed to the urethra as an orthotopic reconstruction. Although the treatment for invasive bladder cancer has not changed greatly in the last few decades, the use of orthotopic bladder reconstruction allows for a great improvement in the quality of life for patients who undergo cystectomy. These reconstructive techniques can also be offered to patients with other forms of pelvic malignancy that involve the bladder.


[Cystic and mucinous lesion in an antral ectopic pancreas].
We report a case of heterotopic pancreas located in the gastric antrum. The cystic formation contained mucus. Tumoral markers in the cyst fluid were within the range pancreatic cystic mucinous tumors. Pathology examination of the resected specimen did not evidence any proliferative lesions but showed papillary hyperplasia probably due to duct occlusion.


Effects of hCG on serum levels of testosterone, dihydrotestosterone and androstenedione in male mice.
The concentrations of testosterone (T), 5alpha-dihydrotestosterone (5alpha-DHT) and delta4-androstenedione (delta4 A) in the circulating blood were increased by a single subcutaneous injection of 10 IU of hCG in the mouse. The response of androgen synthesis to hCG stimulation was rapid and persisted over a period of 96 h. The increased supply of T to the peripheral organ(s) under the stimulation of hCG might contribute to an increase in circulating 5alpha-DHT. However, the changes in T/5alpha-DHT ratio implies that the stimulation of T and 5alpha-DHT production by hCG were not of the same degree.


[A decade of biologics in dermatology].
Basic research on psoriasis has identified a number of molecular targets which can be of therapeutic interest. While the first two biologics--alefacept and efalizumab--were developed primarily for dermatologists, other agents like cytokine antagonists (TNFα antagonists) were introduced primarily by other medical fields. Knowledge has provided new impulses for research, so that today many therapeutic strategies are being developed, not exclusively limited to biologics. Others branches of dermatology also have benefitted greatly from biologics like ipilimumab or omalizumab.


Incidence of prostate cancer in Lithuania after introduction of the Early Prostate Cancer Detection Programme.
In Lithuania, prostate-specific antigen (PSA) testing is offered to healthy asymptomatic men as a screening test in the population-based Early Prostate Cancer Detection Programme (EPCDP). The aim of this study was to analyse the incidence of prostate cancer before and after introduction of the EPCDP in Lithuania. Prostate cancer incidence and mortality data from the Lithuanian Cancer Registry were analysed for the period 1990-2008. Age-specific incidence and mortality data were adjusted to the European Standard Population. There have been extraordinary changes in the incidence of prostate cancer in Lithuania following introduction of the EPCDP, and there is strong evidence that these changes are the result of increased detection rates, especially in men of screening age. Further observation of changes in prostate cancer incidence and mortality in Lithuania may help to determine the extent to which PSA testing at the population level influences incidence and mortality in the general population.


Life cycle assessment and society willingness to pay indexes of food waste-to-energy strategies.
Food waste (FW) has received increasing attention because of its immense production quantities and significance to resource and environmental impacts related to disposal approaches. We combined life cycle assessment (LCA) with society's willingness to pay (WTP) index to evaluate energy, water, and environmental impacts on three food waste-to-energy (FWTE) options in China. For anaerobic digestion (AD) mode, the results showed that 1140 MJ of energy consumption could be saved by power generation from methane, power transmission, and biodiesel production from per ton of FW; the cost of climate change for treating FW was 137.8 kg CO2e t-1 FW, failing to be climate-sound due to the end life of digestate in practice. The total impact to AD mode in the form of monetized value for WTP was 13.3 CNY t-1 FW, of which the collection and transportation, pretreatment, AD reaction, wastewater treatment, biodiesel production, and residue landfilling stages contributed by 10.5%, 6.5%, 19.3%, 27.6%, 4.7%, and 75.7%, respectively, while biogas utilization offset it by 43.9%. Notably, a considerable amount of water used in AD prevented it from showing an advantage compared to incineration (-5.1 CNY t-1 FW), which performed best overall attributing to the generated electricity compensated for primary energy demand, water, and terrestrial acidification to a great extent. Landfilling turned out to be an unappealing FW disposal method due to the low landfill gas capture ratio. Given that AD is touted for its environmental benefits, potential approaches-such as developing a reliable and supportive technology to facilitate digestate recycling into agriculture-were discussed to improve its competitiveness and attractiveness. Our study employed a way to accumulate and compare impact indicators to better interpret FW management impacts and advantages, considering energy recovery, resource recycling, and the environment.


Core Stability Exercises in Addition to Usual Care Physiotherapy Improve Stability and Balance After Stroke: A Systematic Review and Meta-analysis.
To systematically review the effect of core stability exercises in addition to usual care physiotherapy on patient outcomes after stroke. Cumulative Index to Nursing and Allied Health, MEDLINE, Physiotherapy Evidence Database (PEDro), PubMed, and EMBASE were searched to November 2018. Eleven randomized controlled trials that compared usual care physiotherapy with usual care physiotherapy with additional core stability exercises in people with stroke were included. The initial search yielded 1876 studies. Two independent reviewers applied inclusion and exclusion criteria and extracted data on methodological quality using the PEDro scale, participant characteristics, intervention details, outcome measures, and results. Postintervention means and SDs were pooled to calculate either the standardized mean difference (SMD) or the mean difference (MD) and 95% CIs using a random-effects model and inverse variance methods. There was moderate quality evidence to suggest the addition of core stability exercises to usual care physiotherapy improved trunk control (SMD, 0.94; 95% CI, 0.44-1.44; I2=69%), functional dynamic balance (SMD, 1.23; 95% CI, 0.5-1.97; I2=71%), and walking speed (MD, 0.27m/s; 95% CI, 0.01-0.52; I2=40%) in people with acute and chronic stroke. No significant effect was found when assessing functional ambulation categories or the timed Up and Go test, and mixed results were found for global functioning. The addition of core stability exercises to usual care physiotherapy after stroke may lead to improved trunk control and dynamic balance. Therefore, core stability exercises should be included in rehabilitation if improvements in these domains will help clients achieve their goals. Future trials should consider incorporating outcomes of body kinematics during functional tasks to assess movement quality and assess participation outcomes.


Effects of ankle instability on running gait ankle angles and its variability in young adults.
Considering that proprioceptive deficits seem to be responsible for chronic ankle instability, the precise control of ankle angles during running may be impaired. Thus, the aim of the study was to evaluate the influence of chronic ankle instability on intra-individual variability of ankle kinematics during running. Lower extremity running gait kinematics of 12 recreational athletes with chronic ankle instability (mean age: 24 years, SD: 3 years; strides analyzed: 40.0, SD=1.7) and 12 matched healthy controls (mean age: 27 years, SD: 6 years; strides analyzed: 40.2, SD=2.5) were registered on a treadmill. Mean ankle angles (inversion/eversion, plantarflexion/dorsiflexion) and intra-individual standard deviations (variability) were calculated at each percent of the running gait cycle. Group differences were examined using statistical parameter mapping. To estimate effect sizes, Hedges' g was calculated. No group differences in the inversion/eversion or plantar-/dorsiflexion ankle angle were found. The inversion/eversion variability was significantly higher (P<.050) in individuals with chronic ankle instability during the stance and swing phase. The highest Hedges' g values were registered at 15% (g=0.575, P<.000) and 95% (g=0.551, P=.002) of the running gait cycle. The plantar-/dorsiflexion ankle angle variability showed no significant differences. Patients with chronic ankle instability exhibit a higher variability of ankle kinematics during running. This indicates altered sensorimotor control which is probably an underlying mechanism of chronic ankle instability. Thus, variability measures may help to better quantify treatment effects in future.


Lessons and Recommendations from a Pentobarbital Shortage: US and Canada 2021.
In 2021, a shortage in the supply of the euthanasia drug pentobarbital sodium affected animal care professionals around the world, including in the United States and Canada. Pentobarbital sodium is the drug of choice for companion animal euthanasia in both countries. The decreased availability of pentobarbital sodium affected a number of animal care industries, forcing conservation of the drug and the use of alternative methods and other agents to facilitate humane death for all manner of animal species. Veterinary medical groups, laboratory research institutions, and the animal sheltering industry worked together to identify the best path forward to maintain routine euthanasia practices and to protect the welfare of animals. This article aims to explore the reasons behind the shortage and to highlight the necessary responses and adjustments made in order to continue providing euthanasia services in North America. Recommendations for handling future pentobarbital shortages are included.


Varus/valgus alignment of the femoral component in total knee arthroplasty.
The position of the femoral component in 362 total knee replacements was assessed radiologically. A subgroup of 32 knees, 18 of which had perfect alignment and 14 with imperfect alignment underwent CT scout scans of the femur from which the mechanical axis of the femur could be measured. Radiologically 92% of all components were implanted within 3 degrees of the target value. There was close correlation between the CT and X-ray measurements in the subgroup. Deviation from the mechanical axis was 1.16 degrees (range -2.5 to +2) in the perfectly aligned knees, validating both surgical technique and radiological assessment. Causes for inaccuracy in femoral placement and future likely developments are discussed.


Patterns of drug therapy in newly diagnosed Spanish patients with systemic lupus erythematosus.
This is the first Spanish multicentric inception lupus cohort, formed by SLE patients attending Spanish Internal Medicine Services since January 2009. We aimed to analyse drug therapy during the first year of follow-up according to disease severity. 223 patients who had at least one year of follow-up were enrolled upon diagnosis of SLE. Therapy with prednisone, pulse methyl-prednisolone, hydroxychloroquine, immunosuppressives and calcium/vitamin D was analysed. Prednisone was given to 65% patients, at a mean (SD) daily dose of 11 (10) mg/d. 38% patients received average doses >7.5 mg/d during the first year. Patients with nephritis and with a SLEDAI ≥6 were treated with higher doses of prednisone. 81% of patients were treated with hydroxychloroquine, with higher frequency among those with a SLEDAI ≥6 (88% vs. 68%, p<0.001). The use of immunosuppressive drugs and methyl-prednisolone pulses was higher in patients with a baseline SLEDAI ≥6, however, differences were no longer significant when patients with lupus nephritis were excluded. The use of calcium/vitamin D increased with the dose of prednisone, however, 43% of patients on medium-high doses of prednisone did not take any calcium or vitamin D. This study gives a real-world view of the current therapeutic approach to early lupus in Spain. The generalised use of hydroxychloroquine is well consolidated. There is still a tendency to use prednisone at medium to high doses. Pulse methyl-prednisolone and immunosuppressive drugs were used in more severe cases, but not as steroid sparing agents. Vitamin D use was suboptimal.


Differentiation of Bacteroides fragilis species by gas chromatographic detection of phenylacetic acid.
Of 382 strains tested, 261 strains of the species Bacteroides fragilis, B. thetaiotaomicron, B. ovatus, and B. distasonis produced phenylacetic acid; the remaining strains, belonging exclusively to the species B. vulgatus, failed to do so. This differentiation characteristic may be useful in routine clinical bacteriology.


Diabetes mellitus as a risk factor for cryptococcal meningitis in immunocompetent.
Cryptococcal meningoencephalitis (CM) is one of the major causes of mortality and morbidity in immunocompromised patients estimating 650,000 deaths each year. Across the globe, CM has been occasionally seen in apparently immunocompetent patients who otherwise don't have established risk factors. The clinical presentation of CM in immunocompetent hosts is subtle and often results in complications including persistent neurological deficits and death. We present a case of Cryptococcal neoformans meningitis in a diabetic female with no other identified risk factors. Although her clinical presentation was atypical, her clinical course was uncomplicated. The pathophysiology in immunocompetent hosts appears somewhat different, so is the clinical presentation. Since there are no separate evidence-based treatment recommendations, it is challenging to treat this group of patients. There seems to be a need for further studies for management in CM for HIV negative, non-transplant immunocompetent patients.


Country-wide genotyping of Mycobacterium tuberculosis complex in Singapore, 2011-2017.
To describe the molecular epidemiology of Mycobacterium tuberculosis complex (MTBC) and factors associated with its transmission in Singapore. Spoligotyping, 24-loci mycobacterial interspersed repetitive units - variable number of tandem repeats (MIRU-VNTR) typing and demographic data from the national TB notification registry of MTBC culture-positive cases notified from January 2011 to December 2017 were analysed. Of the 12,046 culture-positive cases notified, complete spoligotyping and MIRU-VNTR typing results were available for 8690 (72.1%) belonging to 4950 (57.0%) local-born and 3740 (43.0%) foreign-born persons. From these, 4810 (55.3%) were identified in 883 clusters. The proportion of recent transmission was 45.2%. The East-Asian Lineage 2 accounted for 4045 (47.1%) of isolates, and disproportionately accounted for large clusters. Clustered cases were more likely to be older than 50 years, male, Malay, local-born, Singapore citizens or Permanent Residents, of lower socioeconomic status, imprisoned; to harbour East-Asian Lineage 2 strain; to have cavitary pulmonary TB, positive sputum smear or be recalcitrant treatment defaulters. They were less likely to have multidrug-resistant, or isoniazid or rifampicin mono-resistant TB. We demonstrated the diversity of MTBC strains and, notwithstanding the likely over-estimation of clustering using these genotyping methods, elucidated factors associated with TB transmission in Singapore.


Ileal conduit in era of systemic chemotherapy.
The records of 62 patients with invasive transitional cell carcinoma of the bladder whose planned treatment was radical cystectomy with ileal conduit urinary diversion and postoperative systemic chemotherapy were reviewed. Seven of the patients received radical cystectomy but not postoperative chemotherapy as planned, 3 of them (5%) for reasons directly related to complications from the urinary diversion. Fifty-five patients received the planned postoperative chemotherapy. Complications during chemotherapy that were related to the ileal conduit were urinary tract infection in 37 percent and stenosis at the ureteroileal anastomosis requiring percutaneous nephrostomy in 3.6 percent. Chemotherapy was not discontinued in any patient, however, because of complications specifically related to the urinary diversion. We conclude that the ileal conduit is well tolerated by patients who require systemic chemotherapy and is, today, the simplest, safest, and best diversion method when systemic chemotherapy is to follow radical cystoprostatectomy.


Alpha-glucosidase inhibition and timing of preprandial insulin in patients with insulin-dependent diabetes mellitus (IDDM).
Bay-m-1099, a new alpha-glucosidase inhibitor, was given along with insulin immediately before standard breakfasts, lunches and dinners to nine insulin-dependent diabetic patients to determine whether this combination therapy would produce postprandial glycemic control comparable to that achieved when insulin alone was administered 30 min prior to eating. To avoid potential hypoglycemia, 20% less insulin (0.12 vs. 0.15 U/kg) was given with Bay-m-1099. Despite plasma free insulin concentrations which were less than those observed when insulin alone was given (9.4 +/- 1.0 vs. 12.8 +/- 1.6 microU/ml/min, area under curves for all meals), postprandial hyperglycemia (area under curve) was not significantly different (P greater than 0.1) when insulin plus Bay-m-1099 was administered immediately before each meal (124 +/- 26 mg/ml/min) than when insulin was administered 30 min before each meal (113 +/- 17 mg/ml/min). Thus, the combination of immediate preprandial administration of an alpha-glucosidase inhibitor along with insulin resulted in glycemic control comparable to that achieved when more insulin was taken 30 min prior to eating. We conclude that use of alpha-glucosidase inhibitors could lessen the inconvenience of intensive insulin regimens by permitting patients to take their insulin immediately before eating and thus result in greater patient compliance.


Discovery of a novel small molecule with efficacy in protecting against inflammation in vitro and in vivo by enhancing macrophages activation.
Immune response and inflammation highly contribute to many metabolic syndromes such as inflammatory bowel disease (IBD), ageing and cancer with disruption of host metabolic homeostasis and the gut microbiome. Icariin-1 (GH01), a small-molecule flavonoid derived from Epimedium, has been shown to protect against systemic inflammation. However, the molecular mechanisms by which GH01 ameliorates ulcerative colitis via regulation of microbiota-mediated macrophages polarization remain elusive. In this study, we found that GH01 effectively ameliorated dextran sulfate sodium (DSS)-induced colitis symptoms in mice. Disruption of intestinal barrier function, commensal microbiota and its metabolites were also significantly restored by GH01 in a dose-dependent manner. Of note, we also found that GH01 enhanced phagocytic ability of macrophages and switched macrophage phenotype from M1 to M2 both in vitro and in vivo. Such macrophage polarization was highly associated with intestinal barrier integrity and the gut microbial community. Consequently, GH01 exhibited strong anti-inflammatory capacity by inhibiting TLR4 and NF-κB pathways and proinflammatory factors (IL-6). These findings suggested that GH01 might be a potential nutritional intervention strategy for IBD treatment with the gut microbial community-meditated macrophage as the therapeutic targets.


Axonal sprouting of GABAergic interneurons in temporal lobe epilepsy.
Temporal lobe epilepsy is one of the most common forms of epilepsy. Numerous contributing factors and compensatory mechanisms have been associated with temporal lobe epilepsy. One feature found in both humans and animal models is sprouting of hippocampal principal cell axons, which suggests that axonal sprouting may be a general phenomenon associated with temporal lobe epilepsy. This article highlights the evidence showing that hippocampal GABAergic interneurons also undergo axonal sprouting in temporal lobe epilepsy. The caveats and unanswered questions associated with the current data and the potential physiological consequences of reorganizations in GABAergic circuits are discussed.


Diets enriched in unsaturated fatty acids enhance apolipoprotein A-I catabolism but do not affect either its production or hepatic mRNA abundance in cynomolgus monkeys.
To determine the mechanisms whereby dietary fatty acids influence high density lipoprotein (HDL) cholesterol and apolipoprotein (apo) A-I concentrations, ten cynomolgus monkeys were fed each of three experimental diets enriched in saturated (SAT), monounsaturated (MONO), or polyunsaturated (POLY) fatty acids in a crossover design consisting of three 13-week periods, with each animal serving as its own control. Each diet contained 30% of energy as fat with 0.22 mg cholesterol/kcal and differed solely by the isocaloric substitution of fatty acids as 18% of total energy calories. The replacement of dietary saturated fatty acids with either monounsaturated or polyunsaturated fatty acids, respectively, resulted in significant reductions of plasma total cholesterol (-17%; -30%), HDL cholesterol (-32%; -41%), and apo A-I (-37%; -44%) concentrations, while no significant differences were noted in plasma lipid or apo A-I concentrations when the MONO and POLY phases were compared. Although the MONO and POLY diets were similar in their effects on plasma lipids and apolipoproteins, the HDL of monkeys fed the POLY diet, as compared with either the SAT or the MONO diets, contained more cholesteryl ester and phospholipid but less total protein, resulting in a significantly lower total lipid to protein constituent ratio. Metabolic experiments revealed that the significantly lower plasma apo A-I concentrations observed during both the MONO and POLY phases relative to SAT were directly attributable to enhanced HDL apo A-I catabolism. Conversely, neither HDL apo A-I production rates nor hepatic apo A-I mRNA concentrations were significantly affected by dietary fatty acid perturbation in this study. Taken together, these data indicate that fractional catabolic rate is the predominant mechanism by which dietary fatty acids differentially modulate circulating concentrations of HDL apo A-I in this species when all other dietary variables are held constant.


A learning curve for living donor liver transplantation.
The number of living donor liver transplantations performed has increased rapidly in many Eastern transplant centres. However, the impact of the transplant centres' experience and learning on the transplant outcomes are not well established. Aim of the study was to evaluate the learning curve for living donor liver transplantation in our centre. Data from 156 recipients and 156 donors who underwent surgery were reviewed. Intraoperative data and postoperative outcomes of both donors and recipients were retrospectively analysed. Recipients and donors were divided into three groups that consisted of 52 consecutive cases each. Surgical duration and intraoperative blood loss during donor surgery were decreased significantly between the earlier and the more recent cases (423±39 vs. 400±44 min and 959±523 vs. 731±278 mL, respectively; P<0.01). Rates of postoperative complications and functional changes were not statistically different amongst the three donor groups. Immediate complication rate of the first 52 recipients was higher than those of the second and third cohorts. Long-term survival rates of the three recipient groups were similar. The learning curve greatly influenced immediate outcomes of recipients during the early transplant period. However, it had little influence on donor outcome; long-term outcome improvement of recipients did not depend on the accumulation of experience alone.


Interpretable deep learning architectures for improving drug response prediction performance: myth or reality?
Interpretable deep learning (DL) models that can provide biological insights, in addition to accurate predictions, are of great interest to the biomedical community. Recently, interpretable DL models that incorporate signaling pathways have been proposed for drug response prediction (DRP). While these models improve interpretability, it is unclear whether this comes at the cost of less accurate DRPs, or a prediction improvement can also be obtained. We comprehensively and systematically assessed four state-of-the-art interpretable DL models using three pathway collections to assess their ability in making accurate predictions on unseen samples from the same dataset, as well as their generalizability to an independent dataset. Our results showed that models that explicitly incorporate pathway information in the form of a latent layer perform worse compared to models that incorporate this information implicitly. However, in most evaluation setups, the best performance was achieved using a black-box multilayer perceptron, and the performance of a random forests baseline was comparable to those of the interpretable models. Replacing the signaling pathways with randomly generated pathways showed a comparable performance for the majority of the models. Finally, the performance of all models deteriorated when applied to an independent dataset. These results highlight the importance of systematic evaluation of newly proposed models using carefully selected baselines. We provide different evaluation setups and baseline models that can be used to achieve this goal. Implemented models and datasets are provided at https://doi.org/10.5281/zenodo.7787178 and https://doi.org/10.5281/zenodo.7101665, respectively.


A Comprehensive Self-Management Irritable Bowel Syndrome Program Produces Sustainable Changes in Behavior After 1 Year.
We developed a comprehensive self-management (CSM) program that combines cognitive behavioral therapy with relaxation and dietary strategies; 9 sessions (1 hour each) over 13 weeks were shown to reduce gastrointestinal symptoms and increase quality of life in a randomized trial of patients with irritable bowel syndrome (IBS), compared with usual care. The aims of this study were to describe strategies patients with IBS selected and continued to use, 12 months after the CSM program began. We performed a cohort study to continue to follow 81 adults with IBS (87% female; mean age, 45 ± 15 years old) who received the CSM program in the previous clinical trial. During the last CSM session, participants selected strategies they intended to continue using to manage their IBS. CSM strategies were categorized into subthemes of diet (composition, trigger foods, meal size or timing, and eating behaviors), relaxation (specific relaxation strategies and lifestyle behaviors), and alternative thoughts (identifying thought distortions, challenging underlying beliefs, and other strategies). Twelve months later, participants were asked how often they used each strategy (not at all or rarely, occasionally, often, very often, or almost always). At the last CSM session, 95% of the patients selected the subthemes of specific relaxation strategies, 90% selected diet composition, and 90% identified thought distortions for continued use. At 12 months, 94% of the participants (76 of 81) were still using at least 6 strategies, and adherence was greater than 79% for all subthemes. We developed a CSM program to reduce symptoms and increase quality of life in patients with IBS that produced sustainable behavioral changes in almost all patients (94%) after 1 year of follow-up.


Socio-economic factors and mortality in Switzerland.
This review paper is concerned with the topic of mortality differences by socio-economic group in Switzerland. After a short introduction to the topic and the pitfalls associated with it, the paper reviews work done in the course of a ten year programme investigating socio-economic mortality differentials in Switzerland. This programme was carried out by a working group at the Department of Social and Preventive Medicine of the University of Berne. The paper reviews methodological difficulties and pitfalls and relates the Swiss results to findings from other countries including England and Wales and Sweden. The disadvantages of socially isolated groups such as children of single women are shown. The relatively high mortality of groups under economic pressure, such as skilled manual workers in Switzerland, is demonstrated. The Swiss situation is interesting in that skilled manual workers have a higher mortality than the unskilled and semi-skilled groups. It is concluded that this is not an artifact but may be due to the fact that only Swiss workers were investigated and that Switzerland has a large proportion of foreign workers, especially in the less skilled groups. In addition, some results of an investigation of cancer mortality by occupation are reported too. Apart from some occupation-specific findings, there are some interesting cross-references to socio-economic differential mortality.


Niacin inhibits the synthesis of milk fat in BMECs through the GPR109A-mediated downstream signalling pathway.
Previous studies have shown the effect of niacin on dairy cow production, but no study on the role of niacin in milk fat synthesis has been performed. Therefore, the purpose of this study was to examine the effect of niacin on milk fat synthesis and its specific mechanism in BMECs. In this study, 0.5 mM niacin, a GPR109A-inhibiting plasmid, and an AMPK inhibitor were added to BMECs. Milk fat was measured by a triglyceride kit and BODIPY staining. The protein expression of GPR109A, FASN, SREBP1, AMPK, ACC, mTOR and S6K was measured by Western blotting. The gene expression of GPR109A, FASN, and SREBP1 was analysed by RT-PCR. Our results showed that 0.5 mM niacin could significantly reduce milk fat synthesis in BMECs and activate the AMPK/ACC signalling pathway by stimulating GPR109A, reducing the protein expression of p-mTOR and p-S6K, and reducing the expression of SREBP1 and FASN in BMECs. The present study clarified the effect of niacin on milk fat synthesis. The results show that niacin inhibits the synthesis of milk fat in BMECs through the downstream signalling pathway mediated by GPR109A. The function of niacin has been expanded, and knowledge of the new mechanism and signalling pathway will help improve the biosynthesis of milk fat.


[Erectile function of 522 patients with premature ejaculation].
To evaluate the erectile function of the patient with premature ejaculation. Questionnaires of Chinese Indes of Erectile Function (CIEF-5) were issued to 522 patients with premature ejaculation. Of the subjects invertigated, 341 (65.33%) claimed to have the problem of ED with premature ejaculation, and 433 (82.95%) scored below standard in CIEF-5. There was significant difference between the two groups. Premature ejaculation could significantly influence patients' self-esteem about their erectile function and hence their proper scores in CIEF-5. In most of the patients of premature ejaculation with different degres of erectile dysfunction, only a few with significantly low scores in CIEF-5 had premature ejaculation complicated with ED.


Phase II study of axitinib with doublet chemotherapy in patients with advanced squamous non-small-cell lung cancer.
Axitinib is an orally active and potent tyrosine kinase inhibitor of vascular endothelial growth factor receptors 1, 2 and 3. This phase II study assessed the efficacy and safety of axitinib combined with cisplatin/gemcitabine in chemotherapy-naïve patients with advanced/metastatic (stage IIIB/IV) squamous non-small-cell lung cancer (NSCLC). Axitinib (starting dose 5 mg twice daily [bid]; titrated up or down to 2-10 mg bid) was administered orally on a continuous schedule with cisplatin (80 mg/m(2) intravenously [i.v.] every 3 weeks) and gemcitabine (1,250 mg/m(2) i.v. on days 1 and 8 of each 3-week cycle), and was continued as monotherapy after completion of six cycles (maximum) of chemotherapy. The primary study endpoint was objective response rate, as defined by Response Evaluation Criteria in Solid Tumours. Of the 38 patients treated, one (2.6%) patient achieved a complete response and 14 (36.8%) patients had a partial response; nine (23.7%) patients showed stable disease and three (7.9%) patients had disease progression. Median progression-free survival was 6.2 months, and median overall survival was 14.2 months. The estimated probability of survival at 12 months and 24 months was 63.2% and 30.8%, respectively. The most frequent grade ≥3 toxicities were neutropaenia and hypertension (13.2% each). Three (7.9%) patients experienced haemoptysis, of which one case (2.6%) was fatal. Treatment with the combination of axitinib and cisplatin/gemcitabine demonstrated anti-tumour activity in patients with advanced/metastatic squamous NSCLC and the fatal haemoptysis rate was low. However, without a reference arm (cisplatin/gemcitabine alone), it is not conclusive whether the combination is better than chemotherapy alone. This study was registered at ClinicalTrials.gov, registration # NCT00735904, on August 13, 2008.


Reasons for variation in coverage in the NHS cervical screening programme.
In order to investigate reasons for variation in coverage of cervical screening, data from standard Department of Health returns were obtained for all Health Authorities for 1998/1999. Approximately 80% of the variation between health authorities is explained by differences in age distribution and area classification. Considerable differences between Health Authority and Office of National Statistics (ONS) population figures in City and Urban (London) areas for the age group 25-29 years and for City (London) for age group 30-34 years, suggest an effect of list inflation in these groups. Coverage as a performance indicator may be more accurately represented using the age range 35-64 years. Using this narrower age range, the percentage of health authorities meeting the 80% 5-year coverage target increases from 87% to 90%.


Phosphatidylserine increases in vivo the synaptosomal uptake of exogenous GABA in rats.
A sonicated liposome suspension of gamma-aminobutyric acid (GABA) and phosphatidylserine (liposome-entrapped GABA), intraperitoneally administered in rats, inhibited EEG epileptic activity induced by penicillin, whereas GABA did not. A significant increase (20.4%) in brain radioactivity accumulation occurred at 5 min after i.p. administration of [14C]GABA associated with phosphatidylserine in comparison with the administration of [14C]GABA; such an increase persisted after 20 min. However, the accumulation of radioactivity into brain synaptosomes demonstrated a 24.1% increase at 5 min and subsequently showed a 43.3% increase at 20 min after injection of liposome-entrapped GABA. The above findings suggest that phosphatidylserine stimulates exogenous GABA uptake into brain GABAergic nerve terminals.


Linguistic anomalies in the language of patients with schizophrenia.
In terms of thought disorder, the language of patients with schizophrenia itself could be a valuable resource. Some valuable studies on the language of patients with schizophrenia have been performed. However, most such studies have been confined to English-speaking countries, or at least those where Indo-European languages are spoken. Therefore, we investigated linguistic anomalies in the language of Korean patients with schizophrenia. Short texts written by 69 patients with schizophrenia from a single mental hospital and matched normal control participants were analyzed. We evaluated these texts in terms of semantic and syntactic errors. Then, we compared the error rates adjusted for text length between patients and normal control participants. We also divided the patients with schizophrenia into two groups by their duration of illness and compared these two groups to investigate the relationship between the duration of illness and linguistic anomalies. The patients with schizophrenia committed a total of 1.86 (2.52) semantic errors and 1.37 (1.79) syntactic errors per 100 characters, which were significantly more frequent than errors committed by normal control participants. Furthermore, there was a notably high number of semantic errors relative to syntactic errors in the language of patients with schizophrenia. Our study results are consistent with previous studies from English-speaking countries, implying that the linguistic anomalies of patients with schizophrenia are not confined to a single language. Because language is essential in mental function, further research on linguistic anomalies in patients with schizophrenia is recommended.


Spectrum of endocrine abnormalities associated with acanthosis nigricans.
Acanthosis nigricans is a marker for disorders of insulin action, endocrine abnormalities, and cancer of internal organs. To evaluate the clinical significance of this marker the systemic alterations and clinical features of 26 patients with acanthosis nigricans seen at two institutions were reviewed. Most subjects affected by acanthosis nigricans were female (20 patients), Caucasian (22 patients), in the third decade of life (13 patients), and overweight (24 patients greater than 120 percent ideal body weight). Gonadal disease, present in 17 patients, was expressed as polycystic ovary syndrome (11 cases), disorders of prolactin secretion (two cases, one with polycystic ovary syndrome), streak gonads (one case), and hypogonadism of the male (four cases). Thyroid disease and tinea versicolor were present in four patients each. Three patients were receiving insulin therapy for diabetes mellitus, and in two additional patients diabetes mellitus was detected during the diagnostic workup. All patients had elevated fasting insulin levels; most of them also had an exaggerated insulin response to a glucose load. Two of 18 patients tested had antibodies against the insulin receptor in the circulation. Skin biopsy of acanthosis nigricans lesions from all 26 patients showed a typical pattern of hyperkeratosis, acanthosis, and epidermal papillomatosis. Colloidal iron staining showed glycosaminoglycan infiltration of the papillary dermis (21 of 21 cases), consisting mainly of hyaluronic acid. It is concluded that: (1) hyperinsulinenemia and local dermal glycosaminoglycan deposition are regular features in acanthosis nigricans and (2) patients with acanthosis nigricans should be screened for diabetes mellitus, gonadal disease, and hypothyroidism.


Imperforate hymen with bilateral hydronephrosis: an unusual emergency department diagnosis.
Imperforate hymen is a rare diagnosis to make in the emergency department and important to treat immediately. Hydronephrosis is a known but rare complication of an imperforate hymen. We present the case of a premenstrual adolescent with an undiagnosed imperforate hymen complaining of increasing abdominal pain. The article discusses the history, physical examination, evaluation, differential diagnosis, ultrasound findings, complications, and prompt surgical treatment necessary.


Comparison of semiautomated and manual methods for the determination of thiamine in baby cereals and infant and dietary formulas.
Using a semiautomated method, the mean thiamine content of specific products ranged from 88 to 101% and 83 to 93% for baby cereals and infant and dietary formulas, respectively, of those obtained with the AOAC manual method. The best results were obtained when data for the semiautomated method were calculated from a standard curve obtained by using thiamine solutions which had been digested and hydrolyzed along with the samples.