A 16q deletion involving FOXF1 enhancer is associated to pulmonary capillary hemangiomatosis.
Pulmonary capillary hemangiomatosis (PCH) is an uncommon pulmonary disorder, with variable clinical features depending on which lung structure is affected, and it is usually linked to pulmonary arterial hypertension. Congenital PCH has been very rarely described and, so far, the only causative gene identified is EIF2AK4, which encodes for a translation initiation factor. However, not all PCH cases might carry a mutation in this gene. We report the clinical and cytogenetic characterization of a patient (male, newborn, first child of healthy non-consanguineous parents) died after three days of life with severe neonatal pulmonary hypertension, due to diffuse capillary hemangiomatosis diagnosed post mortem. Conventional karyotyping, Microarray-Based Comparative Genomic Hydridization (CGHa) and quantitative PCR were performed. CGHa revealed a heterozygous chromosome 16q23.3q24.1 interstitial deletion, spanning about 2.6 Mb and involving a FOXF1 gene enhancer. Quantitative PCR showed that the proband's deletion was de novo. Microsatellite analysis demonstrate that the deletion occurred in the maternal chromosome 16. FOXF1 loss of function mutation have been so far identified in alveolar capillary dysplasia with misalignment of pulmonary veins (ACD/MPV), a lung disease different from PCH. Our data suggest the hypothesis that disruption of the FOXF1 gene enhancer could be a genetic determinant of PCH. Moreover, our findings support the idea that FOXF1 is a paternally imprinted gene.


PEG-catalytic water splitting in the interface of a bipolar membrane.
This paper investigates the effect of polyethylene glycol (PEG) on the water dissociation of bipolar membranes. To do this, bipolar membranes were prepared by immersing anion exchange membranes in different-concentration solutions of different-molecular-weight PEGs and then casting the solutions of sulfonated polyphenylene oxide (SPPO) on the anion exchange membranes. All the bipolar membranes with PEG in the interface are evaluated by current-voltage curves. The experimental results prove that PEG has excellent catalytic function for water dissociation. Furthermore, this function is enhanced by both PEG amount (PEG concentration) and PEG molecular weight in the interface of a bipolar membrane.


Variation in practice patterns and resource utilization surrounding management of intussusception at freestanding Children's Hospitals.
To characterize variation in practice patterns and resource utilization associated with the management of intussusception at Children's Hospitals. A retrospective cohort study (1/1/09-6/30/11) of 27 Children's Hospitals participating in the Pediatric Health Information System database was performed. Hospitals were compared with regard to their rates of operative management following attempted enema reduction, prophylactic antibiotic utilization, same-day discharge for those successfully managed non-operatively, 48-h readmission rates, and case-related cost and charges. 2544 patients were identified (median: 93 cases/center) with a median age of 17 months. The rate of operation following attempted enema reduction varied significantly across hospitals (overall rate: 21.1%: range: 11%-62.8%; p<0.0001). For patients managed non-operatively, significant variability was found for prophylactic antibiotic utilization (overall rate: 23.3%; range: 1.4%-93.2%; p<0.0001), same-day discharge (overall rate: 15.2%; range: 0%-83.8%; p<0.0001), readmission rates (overall rate: 17.5%; range: 5.3%-32.1%; p<0.0001), treatment-related costs (overall median: $2490; range: $829-$5905; p<0.0001), and charges (overall median: $6350; range: $2497-$10,306; p<0.0001). Variability in costs and charges was even greater when analyzing all patients (operative and non-operative) with intussusception (overall cost median: $2865; range: $1574-$6763; p<0.0001; overall charge median: $7110; range: $3544-$22,097; p<0.0001). Significant variation in practice patterns and resource utilization exists between Children's Hospitals in the management of intussusception. Prospective analysis of practice variation and appropriately risk-adjusted outcomes through a collaborative quality-improvement platform could accelerate the dissemination of best-practice guidelines for optimizing cost-effective care.


Naturally occurring human IgG antibodies to intracellular and cytoskeletal components of human platelets.
Immunoblotting of platelets that have been subjected to SDS-PAGE has revealed that sera from normal individuals contain IgG which binds to many platelet components. This binding was seen with autologous and heterologous platelets using serum of males and of nulliparous females who had not received blood transfusions. Although binding patterns of different sera were not identical, almost all sera caused IgG binding to platelet components of 87-90 kD, 140 kD (identified as vinculin) and 220-240 kD (tentatively identified as talin and actin-binding protein). Purified IgG showed the same binding pattern as whole serum and F(ab')2 fragments retained their ability to bind to many components. The titre of IgG binding in serum was 1:50-1600 while that of alloantibodies to the PlA1 antigen was 1:3200. IgG binding components were not secreted when platelets were stimulated and were rarely associated with isolated membranes, but were located either in platelet cytoplasm or cytoskeletons. IgG binding was decreased by absorbing sera with lysed platelets or isolated cytoskeletons, but only slightly with intact platelets. Microaffinity purification of IgG which formed a major band on immunoblots showed that it was antibody with specificity for vinculin or its degradation products. These findings suggest that normal sera contain naturally occurring IgG antibodies with specificity for intracellular platelet antigens and that in some cases their titre approaches that of antibodies of pathological significance.


Epidermal growth factor promotes the chemotactic migration of cultured rat intestinal epithelial cells.
The RIE-1 cell line is an untransformed, epithelial cell line derived from the rat small intestine. We report that epidermal growth factor (EGF), which regulates the proliferation of RIE-1 cells, also directs their movement. We measured cell migration through gelatin-coated filters in blind-well Boyden chambers. The migration of RIE-1 cells was stimulated up to approximately 100-fold by EGF, with a half-maximal response at 1-2 ng/ml and a maximal effect at 10 ng/ml. Further analysis showed that the RIE-1 cells responded directionally to a gradient of EGF in solution. Other growth factors tested did not stimulate RIE-1 cell migration, and EGF did not stimulate the migration of fibroblasts in this assay. We conclude that EGF is a potent and specific chemo-attractant for RIE-1 intestinal epithelial cells and suggest that EGF might influence epithelial cell migration in vivo.


Differential impact of COVID-19 on urological surgeries in public and private institutions between 2019 and 2021 in France.
The COVID-19 pandemic disrupted all routine health care services in 2020. To date, data regarding adjustment and coverage of surgical backlog in the post-COVID era actually remains scarce. The aim of this study was to compare the number of urological procedures coded between 2019 and 2021 in public and private institutions to (i) quantify the variation in surgical activity linked to the shutdown in 2020 and (ii) study the adjustment of procedures over the year 2021. This is a comprehensive retrospective analysis of all urological surgeries coded between January 1, 2019 and December 31, 2021 in France. Data were extracted from the open access dataset of the national Technical Agency for Information on Hospital Care (ATIH) website. In total, 453 urological procedures were retained and allocated in 8 categories. Primary outcome was the impact of COVID-19 analyzed by the 2020/2019 variation. The secondary outcome was the post-COVID catch-up analyzed by the 2021/2019 variation. Surgical activity in public hospitals dropped by 13.2% in 2020 compared to 7.6% in the private sector. The most impacted areas were functional urology, stones and BPH. Incontinence surgery did not recover at all in 2021. BPH and stone surgeries were far less impacted in the private sector, with even explosive activity in 2021, post-COVID period. Onco-urology procedures were roughly maintained with a compensation in 2021 in both sectors. The recovery of surgical backlog was much more efficient in the private sector in 2021. The pressure on the health system associated to the multiple COVID-19 waves may generate a gap between public and private surgical activity in the future.


Is Exercise Helpful or Harmful in Dealing With Specific Arrhythmia.
Exercise is universally known to benefit health by lowering risk for cardiovascular disease and mortality. However, in patients with pre-existing cardiac conditions, including channelopathies, cardiomyopathies and coronary artery disease, exercise can cause sudden cardiac death (SCD). In this review, we explore exercise related risks and current recommendations for specific conditions. The risk of myocardial infarction (MI) during strenuous exercise in asymptomatic individuals with coronary artery disease is decreased with habitual exercise, especially if they have a normal ejection fraction and no ischemia. Furthermore, cardiac rehabilitation has been shown to be beneficial in heart failure. On the other hand, surgery is recommended for certain anomalous coronaries prior to engaging in vigorous activity. In addition, both exercise-induced disease progression and SCD in arrhythmogenic cardiomyopathy restrict ability to engage in competitive sports, as is the case in hypertrophic cardiomyopathy. Other diseases, like myocarditis only cause temporary risk for SCD. Previously considered benign, common conditions like early repolarization do increase SCD risk. Finally, certain gear including thicker chest protectors for athletes engaging in sports with hard, small spherical objects decrease risk of commotio cordis. While significant advances have been achieved in diagnosing and treating previously unrecognized conditions that predispose to sudden cardiac death, more research is needed to further tailor recommendations to allow beneficial exercise in those with rarer conditions that are under-represented in large systemic studies.


Oncogene-mediated metabolic gene signature predicts breast cancer outcome.
Breast cancer remains the second most lethal cancer among women in the United States and triple-negative breast cancer is the most aggressive subtype with limited treatment options. Trop2, a cell membrane glycoprotein, is overexpressed in almost all epithelial cancers. In this study, we demonstrate that Trop2 is overexpressed in triple-negative breast cancer (TNBC), and downregulation of Trop2 delays TNBC cell and tumor growth supporting the oncogenic role of Trop2 in breast cancer. Through proteomic profiling, we discovered a metabolic signature comprised of TALDO1, GPI, LDHA, SHMT2, and ADK proteins that were downregulated in Trop2-depleted breast cancer tumors. The identified oncogene-mediated metabolic gene signature is significantly upregulated in TNBC patients across multiple RNA-expression clinical datasets. Our study further reveals that the metabolic gene signature reliably predicts poor survival of breast cancer patients with early stages of the disease. Taken together, our study identified a new five-gene metabolic signature as an accurate predictor of breast cancer outcome.


Prevalence of torus palatinus in Turkish schoolchildren.
Torus palatinus (TP) is the most common exostosis of the maxillofacial skeleton. It usually does not cause symptoms, but removal may be required if it interferes with the function, denture placement, or suffers from recurring traumatic surface ulceration. Large variations in the prevalence of TP have been reported in different populations and were associated with age and sex. The aim of this study is to investigate the prevalence, size, and location of TP in a population of young Turkish. A total of 1,943 schoolchildren, 1,056 males and 887 females, ranging in age from 5 to 15 years were assessed for the prevalence, size and location of TP. Inspection and palpation were examined for the presence or absence of TP. The prevalence of the TP in study population was 30.9%. TP was found significantly more in females than in males (34.3, 28.1%, P<0.005). The more of TP were smaller than 2 cm (91.5%), and in molar location (62.9%). This study indicated that the prevalence of TP in Turkish population was high. There was a strong correlation between the prevalence of TP and age or sex.


Immunogenicity and protective efficacy of Burkholderia pseudomallei BLF1-N and BLF1-C terminal domains against BLF1 toxin.
Burkholderia lethal factor 1 (BLF1), a glutamine deamidase, is a key virulence factor that plays significant role in B. pseudomallei pathogenesis. To elucidate the BLF1 immunological responses, two truncated BLF1 structural units, BLF1-C (90-211 amino acids) with structural similarity to T. maritima Chemoreceptor glutamine deamidase (CheD) protein, and BLF1-N (1-89 amino acids) disparate to CheD were identified from the 23 kDa BLF1 protein. Both the components were devoid of toxicity in mice and elicited an antibody titer of 1:16,000 that reacted with the respective truncated proteins and BLF1. A549 cell lines supplemented with anti BLF1-N and BLF1-C antibodies exhibited 73.47% and 83.24% survival when treated with BLF1 toxin. Passive i.p. transfer with antibodies elicited by BLF1-C that contained LSGC active site resulted in 80% protection while anti BLF1-N (devoid of LSGC) antibodies provided 51.4% protection, establishing the role of BLF1-N terminal also in deamidase action. The truncated proteins also elicited cell mediated immune responses through proliferation of CD4+ T cells, IFN-γ and IL-4 cytokines but with bias towards Th2 subsets. BLF1-C and BLF1-N immunization resulted in 80% and 60% active protection when challenged with BLF1 toxin while the sham immunized mice exhibited severe histopathological changes like necrosis in liver, lung, spleen and kidney similar to that observed in melioidosis and were killed within 7 days post challenge. The higher level of active and passive protection by BLF1-C protein could be attributed to the comparatively higher level of immune responses and inclusion of LSGC residues.


Beyond Pattern Recognition: Radiology-Pathology-Clinical Correlation.
Radiology-pathology correlation is essential for multidisciplinary collaboration in diagnosis and understanding the mechanism of CNS damage in infectious processes. The microscopic acute inflammatory processes are well established and are supplemented by a variety of less-invasive microbial and immunohistochemical investigations. Understanding the pathogenesis of pathogen spread and neuroinvasion, vascular and immune-mediated brain, and spinal cord damage are essential for interpreting radiological images.


In vitro synthesis of a putative precursor to the mitochondrial enzyme, carbamyl phosphate synthetase.
A simple and rapid procedure is described for purification of carbamyl phosphate synthetase from the matrix fraction of rat liver mitochondria. Antibodies to the enzyme were raised in sheep and purified from antiserum by affinity chromatography on enzyme-bound Sepharose columns. When membrane-free polyribosomes, isolated from a cytosolic fraction of rat liver, were incubated in a messenger-dependent rabbit reticulocyte protein-synthesizing system in the presence of [35S]methionine, the purified antibody precipitated a product of translation representing 0.2% of total trichloroacetic acid-insoluble radioactivity. It demonstrated mobility characteristics in sodium dodecyl sulfate-polyacrylamide gels expected for a polypeptide of molecular mass approximately 5500 daltons larger than the mature mitochondrial form of the enzyme (160,000 daltons). Proteolysis of both the mature and presumptive in vitro precursor forms of the enzyme yielded respective sets of peptide fragments which gave similar patterns upon gel electrophoresis. Excess mitochondrial enzyme effectively competed with the in vitro product for interaction with anti-carbamyl phosphate synthetase antibody.


Quantification of African cassava mosaic virus (ACMV) and East African cassava mosaic virus (EACMV-UG) in single and mixed infected Cassava (Manihot esculenta Crantz) using quantitative PCR.
The quantity of genomic DNA-A and DNA-B of African cassava mosaic virus (ACMV) and East African cassava mosaic virus Uganda (Uganda variant, EACMV-UG) was analysed using quantitative PCR to assess virus concentrations in plants from susceptible and tolerant cultivars. The concentrations of genome components in absolute and relative quantification experiments in single and mixed viral infections were determined. Virus concentration was much higher in symptomatic leaf tissues compared to non-symptomatic leaves and corresponded with the severity of disease symptoms. In general, higher titres were recorded for EACMV-UG Ca055 compared to ACMV DRC6. The quantitative assessment also showed that the distribution of both viruses in the moderately resistant cassava cv. TMS 30572 was not different from the highly susceptible cv. TME 117. Natural mixed infections with both viruses gave severe disease symptoms. Relative quantification of virus genomes in mixed infections showed higher concentrations of EACMV-UG DNA-A compared to ACMV DNA-A, but a marked reduction of EACMV-UG DNA-B. The higher concentrations of EACMV-UG DNA-B compared to EACMV DNA-A accumulation in single infections were consistent. Since DNA-B is implicated in virus cell-to-cell spread and systemic movement, the abundance of the EACMV-UG DNA-B may be an important factor driving cassava mosaic disease epidemic.


Inhibitory effects by oral administration of ginsenoside Rh2 on the growth of human ovarian cancer cells in nude mice.
Recently two new compounds, ginsenosides Rh1 and Rh2, have been isolated from an ethanol extract of the processed root of Panax ginseng CA Meyer, and Rh2 (but not Rh1) has been found to cause growth inhibition of cultured B16 melanoma cells. We have also demonstrated that Rh2 caused inhibition of cultured human ovarian cancer cell (HRA) proliferation. The effect of oral administration of Rh2 on tumor growth and survival of nude mice bearing HRA cells was examined. Nude mice were inoculated subcutaneously in the right flank with 10(6) HRA cells. After 7 days of tumor inoculation 2 mg/kg cis-diamminedichloroplatinum(II) (cisplatin) was administered intraperitoneally once a week for 5 weeks. In Rh2-treated groups. Rh2 was dissolved in absolute ethanol, adjusted with distilled water to 1, 15, and 120 microM, and 0.4 ml of each concentration was administered orally by canula every day for 90 days, from the next day of tumor inoculation. The tumor volume, hematocrit and body weight were measured every week. On days 56 and 63 after tumor inoculation, the tumor volumes in all groups treated with Rh2 were significantly less than those in an ethanol-treated control group and also in cisplatin treated group. After 70 days, the tumor growth in nude mice treated with 15 microM and 120 microM Rh2 was significantly inhibited compared to that in a cisplatin treated group as well as a control group. Consequently, the survival of nude mice treated with 15 microM and 120 microM Rh2 was also significantly prolonged, compared to that of cisplatin treated mice. No toxic effects were observed in any of the mice.


A prospective comparative study of radiotherapy effect upon scar quality.
The effect of radiation on uncomplicated postoperative scars is unclear. This study aimed to analyze irradiated and non-irradiated scars in patients with unilateral breast cancer, who underwent oncoplastic breast reduction surgery and radiation therapy (RT), to identify how postoperative scar changes with radiation. Twenty breast scars in 10 patients were analyzed after unilateral breast-conserving surgery, oncoplastic breast reduction, and RT. Scars were assessed using the Vancouver scar scale (VSS) by two independent blinded observers and three-dimensional scar analysis camera. Paired t-test between irradiated and non-irradiated scars in each patient and correlation of scar score differences with potential contributing factors were analyzed. The VSS was significantly lower for the irradiated scar than that for the non-irradiated contralateral scar (1.40 vs. 4.05, p = 0.001), although time interval from the last radiation to scar assessment had a negative correlation with paired differences of VSS (Spearman's correlation coefficient: -0.637, p = 0.048). Compared with the non-irradiated scar, the irradiated scar showed a significantly high level of hemoglobin (1.04 vs. 1.26, p = 0.017) and melanin (0.55 vs. 0.63, p = 0.03). Postoperative scars with radiation showed better results in objective and subjective assessments than scars without radiation. These findings suggest that radiation has a positive effect on general scar maturation.


L2,1-Extreme Learning Machine: An Efficient Robust Classifier for Tumor Classification.
With the development of cancer research, various gene expression datasets containing cancer information show an explosive growth trend. In addition, due to the continuous maturity of single-cell RNA sequencing (scRNA-seq) technology, the protein information and pedigree information of a single cell are also continuously mined. It is a technical problem of how to classify these high-dimensional data correctly. In recent years, Extreme Learning Machine (ELM) has been widely used in the field of supervised learning and unsupervised learning. However, the traditional ELM does not consider the robustness of the method. To improve the robustness of ELM, in this paper, a novel ELM method based on L2,1-norm named L2,1-Extreme Learning Machine (L2,1 -ELM) has been proposed. The method introduces L2,1-norm on loss function to improve the robustness, and minimizes the influence of noise and outliers. Firstly, we evaluate the new method on five UCI datasets. The experiment results prove that our method can achieve competitive results. Next, the novel method is applied to the problem of classification of cancer samples and single-cell RNA sequencing datasets. The experimental results on The Cancer Genome Atlas (TCGA) datasets and scRNA-seq datasets prove that ELM and its variants has great potential in the classification of cancer samples.


Coagulation mechanisms of humic acid in metal ions solution under different pH conditions: A molecular dynamics simulation.
Humic acid (HA) exerts a variety of significant environmental and geochemical influences on the soils, sediments and aqueous environments. The interaction with metal ions induces strong HA-metal complexation, thus effecting the transport of the toxic metals as well as the colloidal aggregation of HA. In the present work, we systematically report and analyze the aggregation mechanisms of HAs in solutions filled with different heavy cations (Ag+, Cd2+ and Cr3+) or common metal ions (Na+, Ca2+ and Al3+) under neutral and low pH conditions by using molecular dynamic simulations. We aim to explore the effects of pH, metal ions type and other possible weak interactions on the aggregation capabilities of HA. Scrutiny of the simulation results showed that the aggregation of HAs under neutral condition was driven by the HA-metal complexation which combined the effects of electrostatic attraction and inter-molecular bridging between cations and COO- groups. Larger extent of aggregation was found in heavy metal ions compared with the common ones. On the other hand, under low pH condition, due to the protonation states of carboxyl and phenolic group, the aggregation of HAs was stabilized mainly by weak forces, such as hydrogen bonds between different functional groups. In addition, other weak interactions such as the hydrophilic and hydrophobic effects, the cation-π interactions have also been proposed to be progressive effects on the coagulation behavior. Our computational studies give supplement to the experimental observation and provide insights into the intrinsic mechanisms of the aggregation behavior of HAs and their complexation with metal ions. Such computational modelling supplied a highly effective tool for qualitatively evaluating their roles in environmental remediation.


Caiman's fat enriched with n-3 fatty acids: potential food supplement.
Broad-snouted caiman (Caiman latirostris) products (meat, fat and oil) are currently beginning to be valued as a food of special interest due to its high content of n-3 fatty acids. Thus, the objective of this study was to characterize the fats of caiman fed with diets enriched with flaxseeds (Linus usitatissimun) rich in n-3 fatty acids, lignans and antioxidants. Caimans were fed six days a week with: a control diet (C), and a diet enriched with ground flaxseed = 90% C + 10% flaxseed ground (FS), during 30 (FS30) and 60 (FS60) days. Animals fed the flaxseed-enriched diets increased linolenic acid content and reduced the n-6/n-3 ratio of fats relative to controls, and this improvement increased over time. The proportion of eicosapentaenoic acid also increased, but there was no difference at the time the enriched diets were offered. Caiman fat of the FS30 and FS60, showed a decrease in lipoperoxidation (24% and 40%) and reactive oxygen species (44% and 76%) accompanied by an increase in antioxidant systems. Consumption of a flax-enriched diet by caimans increases the content of essential fatty acids and improves the lipoperoxidative status of fat. This provides an enriched fat with potential for the development products for human consumption.


ACE inhibitors. Drug interactions of clinical significance.
ACE inhibitors are used widely in the treatment of hypertension and congestive heart failure, but there is only limited information on adverse interactions between ACE inhibitors and other cardiovascular or noncardiovascular drugs. The present article provides an overview of this issue, with emphasis on those interactions having the greatest clinical implications. In patients who have been sodium and/or volume depleted by thiazide or loop diuretics, the additional use of ACE inhibitors can lead to an excessive reduction in blood pressure and symptomatic hypotension. An increase in serum potassium levels may occur after coadministration of potassium-sparing diuretics and ACE inhibitors, resulting in hyperkalaemia especially in patients with renal insufficiency. The incidence of acute renal failure may be associated with ACE inhibitor therapy when these drugs are combined with nonsteroidal anti-inflammatory agents and given to patients whose renal function becomes increasingly dependent on angiotensin II and prostaglandins. There is some evidence, albeit scant, linking ACE inhibitors with the induction of lithium toxicity in patients maintained on lithium, and with the occurrence of severe hypersensitivity reactions in patients undergoing haemodialysis, venom immunisation or concomitant allopurinol therapy.


Anatomical evidence for segregated focal groupings of efferent cells and their terminal ramifications in the cerebellothalamic pathway of the monkey.
Patterns of termination of the cerebellothalamic pathway were investigated using anterograde tracing techniques. The thalamic projections from each of the deep cerebellar nuclei are topographically organized in two and possibly in three dimensions. First, the caudo-rostral cerebellar nuclear dimension is mapped onto the mediolateral dimension within the cell-sparse ventral lateral thalamic region (VPLo, VLc, VLps, and nucleus X). By correlating this topographic ordering with the previously established lamellar organization of the cell-sparse thalamic region a somatotopy is inferred within the deep cerebellar nuclei, with caudal body parts represented anteriorly and rostral body parts represented posteriorly in each nucleus. A second topography consists of the mapping of the mediolateral dimension of the dentate and interpositus nuclei onto the ventrodorsal dimension of the lamellae in the thalamus. Since the thalamic connections with motor cortex predict a somatotopic organization with distal body parts ventral and axial parts dorsal in thalamus, each cerebellar nucleus should, therefore, represent axial body parts laterally and distal parts medially. A third mapping dimension is shown for the dentatothalamic projection: dorsal parts of the dentate nucleus project posteriorly within the cell-sparse thalamic region, and ventral parts project anteriorly. The significance of this as regards representation of the body is not known. Subsidiary foci of terminations within the cell-sparse thalamic region are visible following tritiated amino acid injections into each of the deep cerebellar nuclei. Following dentate injections these foci appear as anteroposteriorly elongated, rod-like aggregations of terminations which are similar to the rod-like aggregations of thalamocortical relay cells which have been demonstrated following focal injections of horseradish peroxidase into the motor cortex. The interpositothalamic and the fastigiothalamic terminations are elongated and appear as focal clusters in all planes of section. The interpositothalamic clusters are distributed within posterodorsally curving planar sheets. An anterograde double labeling technique, using a combination of the autoradiographic technique with the axonal degeneration technique, was used to investigate the interrelations of the terminations from different nuclei and from different parts of the same nucleus. Rods from different parts of the dentate nucleus terminate independently of one another. Dentatothalamic rods and interpositothalamic clusters, though interdigitating within the same thalamic region, do not overlap. This topographic and modular organization of the cerebellothalamic pathway suggests that the cerebellar input may reflect both the somatotopic and the columnar organization of the motor cortex.


Phenotypic Bacterial Isolates, Antimicrobial Susceptibility pattern and Associated factors among Septicemia Suspected Patients at a hospital, in Northwest Ethiopia: Prospective cross-sectional study.
Septicemia is potentially fatal infection caused by pathogenic bacteria infiltrating the bloodstream, resulting in morbidity and mortality among Ethiopian hospital patients. Multidrug resistance is a therapeutic challenge in this patient population. There is an insufficiency data among hospitals in Ethiopia. Hence, this study aimed to assess the phenotypic bacterial isolates, antimicrobial susceptibility pattern, and associated factors among septicemia suspected patients. Prospective cross-sectional study was conducted among 214 septicemia suspected patients from February to June 2021 at Debre Markos Comprehensive Specialized hospital in northwest, Ethiopia. Blood samples were collected aseptically and processed to identify bacterial isolates by using different standard microbiological procedures. Antimicrobial susceptibility pattern was performed using the modified Kirby Bauer disc diffusion on Mueller Hinton agar. Epi-data V4.2 was used to enter data and SPSS V25 for analysis. The variables were assessed using a bivariate logistic regression model with a 95% confidence interval, and declared statistically significant; P-value was < 0.05. The overall bacterial isolates was found 45/214 (21%) in this study. Gram-negative and positive bacteria were 25/45(55.6%), 20/45(44.4%) respectively. The most common bacterial isolates were Staphylococcus aureus12/45 (26.7%), Klebsiella pneumoniae 8/45(17.8%), Escherichia coli 6/45 (13.3%). Gram-negative bacteria showed susceptibility to amikacin (88%), meropenem, imipenem (76%) but, (92%) resistance to ampicillin, (85.7%) amoxicillin-clavulanic acid. S.aureus (91.7%) was resistance to Penicillin, (58.3%) cefoxitin and (75%) susceptible to ciprofloxacillin. S.pyogenes and S.agalactia were (100%) susceptible to Vancomacin. Multidrug resistance was found in 27/45(60%) of the bacterial isolates. The main predictors related to patients suspected of septicemia were prolonged hospitalization (AOR = 2.29, 95% CI: 1.18, 7.22), fever (AOR = 0.39, 95%CI: 0.18, 0.85) and length of hospital stay (AOR = 0.13, 95%CI: 0.02, 0.82). Incidence of bacterial isolates among septicemia suspected patients were high. The majority of the bacterial isolates were multidrug-resistant. To prevent antimicrobial resistance, specific antibiotic utilization strategy should be applied.


The production of anorexigenic substances by intestinal flora.
The role of intestinal flora in the production of anorexigenic substance was investigated. Proteus mirabilis (P. mirabilis) and Escherichia coli (E. coli) were found to produce an anorexigenic substance, while Enterococcus faecalis (E. faecalis, type 1 and 2) and Staphylococcus intermedius (S. intermedius) did not. The anorexigenic substance was purified and was detected as, a single though broad band by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). The specific activity of the final form of the purified substance was 120 units/mg carbohydrate. The substance contained no protein residue and appeared to be a lipopolysaccharide. The evidence that intestinal flora produces an anorexigenic substance leads to an interesting assumption that the intestinal flora may be responsible for regulating food intake.


Enhancement of hemolytic and cytotoxic activity of staphylococcal alpha-toxin in vitro by incubation with cultured fibroblasts. Brief communication.
Staphylococcal alpha-toxin (alpha-toxin) was incubated with 3T3 or SV40-virus transformed mouse 3T3 fibroblasts during 2 hrs at room temperature. This resulted in about a two-fold increase in the hemolytic activity of alpha-toxin toward rabbit RBC. The concentration of alpha-toxin causing 50% hemolysis of rabbit RBC was lowered from about 120 ng/ml to about 65 ng/ml. Release of 86Rb from labeled RBC and isolated rabbit vagus nerves also occured at lower concentrations of alpha-toxin after preincubation with fibroblasts. The enhancement of hemolytic activity of alpha-toxin was still exerted by cultured fibroblasts preheated to 56 degrees C, but fibroblasts exposed to 100 degrees C were ineffective. The hemolytic activity of alpha-toxin toward rabbit RBC was also slightly enhanced by leucine aminopeptidase (5--20 microgram/ml) and aminopeptidase M (30--300 IU/ml).


Multiple concomitant oral cavity cancers: Incidence, management, and outcomes.
Little is known about the appropriate treatment and long-term survival of patients with multiple concomitant oral cavity cancers (MOC). The aim of this study was to clarify the clinicopathological features of MOC, to compare the prognosis of MOC patients with that of patients with single oral cavity cancers (SOC), and to describe reconstructive options based on the concept of economy in autologous tissue transfer. Data from 603 patients diagnosed with at least one squamous cell carcinoma of the oral cavity who underwent surgery for primary oral cavity cancers between 2006 and 2014 were reviewed retrospectively to identify MOC patients. Among 603 cases of surgically resected primary oral cancers, 20 cases (3.3%) with MOC were identified. Patients with MOC did not differ from patients with SOC in age, and their index lesions did not differ in pT value, pN value, pathological stage, extracapsule spread, or perineural or bone invasion. The 5-year overall and disease-free survival rates for MOC and SOC cases were 72.6% versus 68.7%, and 65.3% versus 64.8%, respectively (P = 0.785 and 0.770, respectively). The anterolateral thigh flap was widely applied. According to its origin of blood supply, the reconstructive options of MOC patients with separated defects were classified and proposed. MOC and SOC were similar in clinicopathological characteristics. The prognosis of patients with MOC was similar to that of patients with SOC. Resections were performed with curative intent. A multidisciplinary team management approach is essential for customized treatment in MOC patients.


The importance of association between angiotensin-converting enzyme (ACE) Gene I/D polymorphism and diabetic peripheral neuropathy.
Diabetic peripheral neuropathy (DPN) is a microvascular complication of diabetes mellitus (DM) due to decreasing quality of life. In the present study, it is aimed to evaluate angiotensin-converting enzyme (ACE) Gene I/D polymorphism in Turkish population. Two hundred and thirty-five DPN patients and two hundred and eighty-one controls were enrolled in this study. Genomic DNA was isolated and genotyped using polymerase chain reaction (PCR) analyses for the ACE gene I/D polymorphism. Baseline characteristics of the DPN patients according to ACE genotypes were similar, except for history of hypertension. The frequency of II genotype was significantly higher in patients with positive history of hypertension than the patients with negative history of hypertension (p=0.013). DD genotype of I/D polymorphism was found to be a susceptibility factor for DPN in homozygous form (p=0.032). According to allele frequencies, D allele of I/D polymorphism was found to be a susceptibility factor for DPN (p=0.031). ACE gene I/D polymorphism may research in DM patients to determine genetic predisposition for DPN. It can be useful for taking early measures and avoiding DPN in a Turkish population.


MIgGGly (mouse IgG glycosylation analysis) - a high-throughput method for studying Fc-linked IgG N-glycosylation in mice with nanoUPLC-ESI-MS.
Immunoglobulin G (IgG) N-glycosylation is crucial for its effector functions. It is a complex trait, and large sample sets are needed to discover multiple genetic factors that underlie it. While in humans such high-throughput studies of IgG N-glycans became usual, only one has been carried out in mice. Here we describe and validate a method for the relative quantification of IgG Fc-linked N-glycans in a subclass-specific manner using nano-reverse phase liquid chromatography coupled with mass-spectrometry (nanoRP-LC-MS) applied to murine IgG. High-throughput data processing is ensured by the LaCyTools software. We have shown that IgG isolation procedure is the main source of technical variation in the current protocol. The major glycoforms were quantified reliably with coefficients of variation below 6% for all the analytes with relative abundances above 5%. We have applied our method to a sample set of 3 inbred strains: BALB/c, C57BL/6 and C3H and observed differences in subclass-specific and strain-specific N-glycosylation of IgG, suggesting a significant genetic component in the regulation of Fc-linked IgG N-glycosylation.


Early stages of status marmoratus.
Basal ganglionic lesions in three young infants were found in a prospective search for early stages of status marmoratus. The lesions had formed and had passed into glial scars well before myelination of the basal ganglia commenced. The myelinating fibers crossing the scarred tissue were disoriented; however, fiber structure was normal, and the numbers of myelin lamellae did not differ significantly between scars and non-scarred tissue. There was no indication of a derangement of the process of myelin formation or of the formation of anomalous myelin sheaths around non-neuronal processes.


Multicenter trial of everolimus in pediatric renal transplant recipients: results at three year.
There are few prospective clinical trials of mTOR inhibitors (or proliferation signal inhibitors) combined with CNI inhibitors in de novo pediatric renal transplantation. Results reported here are from a multicenter, open-label study in de novo pediatric renal transplant patients (<or=16 yr), in which patients received everolimus with cyclosporine and corticosteroids for one yr, then entered an extension study for a further two yr. Nineteen patients completed the one-yr study, of whom three discontinued study medication. Fifteen of the remaining 16 patients entered the extension study, eight of whom were aged <10 yr (Group 1) and seven were aged 10-16 yr (Group 2). Mean daily dose of everolimus during the first 36 months was 1.53 mg/m(2) BSA. Biopsy-proven acute rejection occurred in three patients in Group 2 and in one patient in Group 1. Biopsy-proven chronic allograft rejection was reported in four patients (two in each age group). Graft survival at one yr was 100%; one patient in Group 2 lost their graft subsequently during the extension. For patients entering the extension, patient survival at three yr was 100%. There were three cases of viral infection, including one case of cytomegalovirus infection. At three yr, mean total cholesterol was 5.5 +/- 0.8 mm/L (213 +/- 31 mg/dL) and four patients received statin therapy. Mean serum creatinine at 36 months was 96 +/- 36 microm/L (1.1 +/- 0.4 mg/dL). This is the first long-term prospective study to demonstrate that a regimen of everolimus, cyclosporine, and corticosteroids provides good efficacy, tolerability, and safety in de novo pediatric renal transplant patients.


Validation of the paediatric logistic organ dysfunction (PELOD) score: prospective, observational, multicentre study.
Multiple organ dysfunction syndrome is more frequent than death in paediatric intensive care units. Estimation of the severity of this syndrome could be a useful additional outcome measure in clinical trials in such units. We aimed to validate the paediatric logistic organ dysfunction (PELOD) score and estimate its validity when recorded daily (dPELOD). We did a prospective, observational, multicentre cohort study in seven multidisciplinary, tertiary-care paediatric intensive care units of university-affiliated hospitals (two French, three Canadian, and two Swiss). We included 1806 consecutive patients (median age 24 months; IQR 5-90). PELOD score includes six organ dysfunctions and 12 variables and was recorded daily. For each variable, the most abnormal value each day and during the whole stay were used in calculating the dPELOD and PELOD scores, respectively. Outcome was vital status at discharge. We used Hosmer-Lemeshow goodness-of-fit tests to evaluate calibration and areas under receiver operating characteristic curve (AUC) to estimate discrimination. 370 (21%) patients had no organ dysfunction, 471 (26%) had one, 457 (25%) had two, and 508 (28%) had three or more. Case fatality rate was 6.4% (115 deaths). PELOD score was significantly higher in non-survivors (mean 31.0 [SE 1.2]) than survivors (9.4 [0.2]; p<0.0001). Calibration (p=0.54) and discrimination (AUC=0.91, SE=0.01) of PELOD and dPELOD (p> or =0.39; AUC> or =0.79) scores were good. PELOD and dPELOD scores are valid outcome measures of the severity of multiple organ dysfunction syndrome in paediatric intensive care units; their use should significantly reduce the sample size required to complete clinical trials in critically ill children.


Alpha7 nicotinic acetylcholine receptor agonists: prediction of their binding affinity through a molecular mechanics Poisson-Boltzmann surface area approach.
A group of agonists for the alpha7 neuronal nicotinic acetylcholine receptors (nAChRs) was investigated, and their free energies of binding DeltaG(bind) were calculated by applying the molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) approach. This method, based on molecular dynamics simulations of fully solvated protein-ligand complexes, allowed us to estimate the contribution of both polar and nonpolar terms as well as the entropy to the overall free energy of binding. The calculated results were in a good agreement with the experimentally determined DeltaG(bind) values, thereby pointing to the MM-PBSA protocol as a valuable computational tool for the rational design of specific agents targeting the neuronal alpha7 nAChR subtypes.


The effects of oestrogens and progestogens on the postmenopausal endometrium.
Cyclical regimens of unopposed oestrogens are associated with the development of endometrial hyperplasia and the incidence of hyperplasia is dose-related. As no pattern of vaginal bleeding serves as a reliable indicator of underlying endometrial pathology and as hyperplasia can develop subsequent to the finding of a normal endometrium and at any time from 2 to 35 mth after the start of treatment, serial biopsies are required on every patient. Oral oestrone and oestradiol complexes both give rise in the plasma principally to oestrone and therefore the term "Hormone replacement therapy" is inappropriate. The incidence of hyperplasia during sequential oestrogen/progestogen therapy is greatly reduced and therefore progestogens are capable of protecting against the development of this condition. Sequential regimens can also reverse oestrogen-related hyperplasia to normal endometrium.


Subjective and objective cognitive function in adolescent with chronic fatigue following Epstein-Barr virus infection.
Cognitive difficulties are among the most disruptive and disabling problems reported by chronic fatigue syndrome (CFS) sufferers. Acute Epstein-Barr virus (EBV) infection is a trigger of chronic fatigue (CF) and CFS. The aim of this study was to investigate subjectively reported and objectively measured cognitive functioning in fatigued and non-fatigued adolescents six months after EBV infection. A total of 195 adolescents (12-19 years) with acute EBV infection were followed prospectively for six months, after which they were grouped as chronically fatigued (CF+) and non-fatigued (CF-) cases based on questionnaire score; the CF+-group was further subgrouped according to CFS diagnosis. A group of 70 healthy controls was also included. Groups were cross-sectionally compared on objective measures of processing speed, executive functions and memory, and subjective cognitive functioning. There were no group differences regarding objective cognitive measures, but the CF+-group reported significantly (p < 0.001) more cognitive problems (cognitive symptoms sum score = 9.5) compared to the CF--group (cognitive symptoms sum score = 5.3) and the healthy control group (cognitive symptoms sum score = 6.4). The CFS subgroup rated symptoms scores even higher but did not differ on cognitive performance tests. Subjective experiences of cognitive difficulties characterize adolescents with CF and CFS six months after acute EBV infection, whereas objective measures of cognitive impairment are inconspicuous.


Aqueous Ni-rich-cathode dispersions processed with phosphoric acid for lithium-ion batteries with ultra-thick electrodes.
Lithium-ion battery (LIB) production can benefit both economically and environmentally from aqueous processing. Although these electrodes have the potential to surpass electrodes conventionally processed with N-methyl-2-pyrrolidone (NMP) in terms of performance, significant issues still exist with respect to ultra-thick cathodes (≫4 mAh/cm2 areal capacities). A major concern for these types of electrodes with high-nickel active material stems from lithium leaching from active material, which drives the pH of the dispersion in excess of 12 and subsequently corrodes the current collector interface. As this corrosion reaction proceeds, hydrogen generation at the interface creates bubbles which cause severe cracking in the dried electrode surface. When areal loadings are increased, this effect becomes more pronounced and is detrimental to both mechanical and electrochemical properties of these electrodes. Herein, a technique for mitigating corrosion at the current collector by adjusting the pH of the dispersion with the addition of phosphoric acid is investigated. Phosphoric acid was added in 0.5 wt% increments between 0.0 and 1.5 wt%, and effects on rheology, adhesion, corrosion, and electrochemical performance were investigated. A technique is reported for producing aqueous processed cathodes with areal loadings of 6-8 mAh/cm2 with reduced surface cracking and superior high-rate discharge capacity (i.e. high-power performance) for this class of cathode loadings.


Red blood cell transfusion-induced non-transferrin-bound iron promotes Pseudomonas aeruginosa biofilms in human sera and mortality in catheterized mice.
Transfusion of storage-damaged red blood cells (RBCs) increases non-transferrin-bound iron (NTBI) levels in humans. This can potentially enhance virulence of microorganisms. In this study, Pseudomonas aeruginosa replication and biofilm production in vitro correlated with NTBI levels of transfused subjects (R2 = 0·80; P < 0·0001). Transfusion of stored RBCs into catheterized mice enhanced P. aeruginosa virulence and mortality in vivo, while pre-administration of apotransferrin reduced NTBI levels improving survival (69% vs 27% mortality; P < 0·05). These results suggest that longer RBC storage, by modulating the bioavailability of iron, may increase the risk of P. aeruginosa biofilm-related infections in transfused patients.


High-performing managers: leadership attributes for the 1990s.
Entrepreneurial, innovative, energetic, community-oriented leaders are needed for health care enterprises. Successful leaders work on a variety of challenging projects and are able to play multiple roles.


TEM-80, a novel inhibitor-resistant beta-lactamase in a clinical isolate of Enterobacter cloacae.
Enterobacter cloacae Ecl261 was isolated with Escherichia coli Ec257 from the urine of a patient living in a nursing home. Both isolates were resistant to ticarcillin (MICs, 1,024 microg/ml), without significant potentiation of its activity by 2 microg of clavulanate per ml (MICs, 512 microg/ml), and susceptible to naturally active cephalosporins. This inhibitor-resistant phenotype was conferred in both strains by similar conjugative plasmids of 40 kb (Ecl261) and 30 kb (Ec257), which also conveyed resistance to sulfonamides and trimethoprim. Clinical and transconjugant strains produced a beta-lactamase with a pI of 5.2 which belonged to the TEM family, as indicated by specific PCR amplification. Compared with TEM-1, this enzyme exhibited lower catalytic efficiencies (14- and 120-fold less for amoxicillin and ticarcillin, respectively), and higher concentrations of beta-lactamase inhibitors were required to yield a 50% reduction in benzylpenicillin hydrolysis (750-, 82-, and 50-fold higher concentrations for clavulanate, sulbactam, and tazobactam, respectively). Gene sequencing revealed four nucleotide differences with the nucleotide sequence of bla(TEM-1A). The first replacement (T32C), located in the promoter region, was described as being responsible for the increase in the level of beta-lactamase production. The three other changes led to amino acid substitutions that define a new inhibitor-resistant TEM (IRT) beta-lactamase, TEM-80 (alternate name, IRT-24). Two of them, Met69Leu and Asn276Asp, have previously been related to inhibitor resistance. The additional mutation, Ile127Val, was demonstrated by site-directed mutagenesis to have a very weak effect, at least alone, on the IRT phenotype. This is the first description of an IRT beta-lactamase in E. cloacae. The horizontal transfer of bla(TEM-80) may have occurred either from Ec257 to Ecl261 or in the reverse order.


Combined buccal mucosa graft and dorsal penile skin flap for repair of severe hypospadias.
Urethral reconstruction in severe hypospadias presents a great challenge. We have designed a method of combining a longitudinal dorsal island skin flap and buccal mucosa graft to create a neourethra in most severe hypospadias. Between January 2003 and March 2007, 17 patients (aged from 9 to 23 months) underwent severe hypospadias repair (13 penoscrotal and 4 scrotal hypospadias). Short urethral plate was divided in all cases and remaining curvature repaired by dorsal plication. We harvested and fixed a buccal mucosa graft to the ventral side of corpora cavernosa to be the first half of a neourethra. A longitudinal dorsal island skin flap was created and buttonholed ventrally. We sutured it together with the buccal mucosa graft to form the neourethra. We fixed the abundant flap pedicle laterally to cover all suture lines of the neourethra. We performed penile skin reconstruction using available penile skin. The mean (range) follow-up was 25 (7 to 58) months. We achieved satisfactory, functional, and aesthetic results in 14 patients. In 3 cases urethral fistula (2) and distal stricture (1) required secondary treatment. Combined longitudinal island skin flap and buccal mucosa graft could be a good choice for urethral reconstruction in most severe hypospadias repairs.


Increased risk of psoriasis: An immune sequela of herpes zoster? Evidence from a nationwide population-based cohort study.
Several cases of herpes zoster-induced psoriasis have been reported in the literature. Our nationwide retrospective cohort study is designed to examine the risk association between herpes zoster and psoriasis. From the Taiwan National Health Insurance Research Database, 26,623 patients from 1999 to 2013 with a diagnosis of herpes zoster and no prior history of psoriasis were selected as the study subjects. The control group was established during the study period from those without a herpes zoster diagnosis and was propensity score matched to minimize confounding factors. Both cohorts were followed for cases of psoriasis development. Data analysis was done via Kaplan-Meier analysis and Cox Proportional-Hazards Models. Comparing the study group to control, the adjusted hazard ratio was 1.66 (95% CI, 1.31-2.13: p < 0.05) after adjusting for covariates (age, gender, urbanization, selected comorbidities and selected medications use). Statistical analysis found no interaction effect among herpes zoster and other covariates for risk modification of psoriasis development. This study demonstrated an increased risk of psoriasis in patients diagnosed with herpes zoster.


The t(15;17) translocation alters a nuclear body in a retinoic acid-reversible fashion.
Nuclear bodies (NBs) are ultrastructurally defined granules predominantly found in dividing cells. Here we show that PML, a protein involved in the t(15;17) translocation of acute promyelocytic leukaemia (APL), is specifically bound to a NB. PML and several NB-associated proteins, found as auto-antigens in primary biliary cirrhosis (PBC), are co-localized and co-regulated. The APL-derived PML-RAR alpha fusion protein is shown to be predominantly localized in the cytoplasm, whereas a fraction is nuclear and delocalizes the NB antigens to multiple smaller nuclear clusters devoid of ultrastructural organization. RA administration (which in APL patients induces blast differentiation and consequently complete remissions) causes the re-aggregation of PML and PBC auto-antigens onto the NB, while PML-RAR alpha remains mainly cytoplasmic. Thus, PML-RAR alpha expression leads to a RA-reversible alteration of a nuclear domain. These results shed a new light on the pathogenesis of APL and provide a molecular link between NBs and oncogenesis.


Clinical evaluation of two "packable" posterior composite resins: two-year results.
The purpose of this study was to evaluate the clinical performance of two "packable" posterior composites: Prodigy Condensable/Optibond Solo-Kerr (PC-OS) and Definite/Etch & Prime-Degussa (D-EP). Thirty-six patients participated in this study. A total of 78 restorations (40 with D-EP and 38 with PC-OS) were made. Each patient received at least two restorations (one of each studied material). The materials were handled according to the manufacturer's instructions. The occlusal adjustments were made at the placement visit. The restorations were finished and polished after 1 week. They were evaluated at baseline, and after 1 year and 2 years by two independent evaluators using the USPHS criteria. Colored slides were made of all the restorations. After 2 years, 34 patients and 74 restorations (38 with D-EP and 36 with PC-OS) were available for evaluation. A total of 50% of PC-OS restorations received A criterion and 50% received B criterion (2.8% color, 11.1% marginal staining, 27.8% superficial staining, 2.8% anatomic form and 5.6% marginal adaptation). For D-EP, 60.5% of restorations received A criterion and 39.5% received B criterion (2.6% color, 5.3% marginal staining, 10.5% superficial staining, 7.9% anatomic form and 13.2% marginal adaptation). The C criterion was observed only for marginal adaptation with D-EP (2 restorations-5.3%). The obtained data were tabulated and statistically analyzed using the Fisher, Chi-square and McNemar tests. After 2 years, PC-OS showed a significant increase in superficial and marginal staining. For D-EP the marginal adaptation and superficial staining became significantly worse than baseline.


Myelin-associated glycoprotein in human retina.
The human retina is unmyelinated, but structural similarities have been noted between Müller cells, the main glial cell type of retina, and oligodendrocytes, the myelin-forming cells of the central nervous system. We now show that antibodies against myelin-associated glycoprotein, a minor component of central and peripheral myelin so far found only in myelin and myelin-forming cells, also stain Müller cells. Immunoblot analysis of retinal proteins indicates that the antigen detected is myelin associated glycoprotein. These results suggest a closer relationship between Müller cells and oligodendrocytes than previously suspected and raise questions about the functional role of myelin-associated glycoprotein.


Influence of electrical stimulation of the substantia nigra on spontaneous activity of raphe neurons in the anesthetized rat.
Recent studies of afferent connections of the anterior raphe using the horseradish peroxidase technique have demonstrated a major projection originating in the substantia nigra (SN). The present acute electrophysiological study examined the influence of stimulation of the afferent on the activity of individual neurons in the raphe of the posterior midbrain and anterior pons (n = 51), and of a control group of cells (n = 15) located 2 mm lateral to the raphe. The predominant effect of SN stimulation at 0.1-1.0 mA, 1 Hz or 10 Hz, was suppression of raphe activity, with 63% of the cells showing cessation of firing following SN pulses and only 8% showing excitation. The average duration of suppression was 200 msec at 1 Hz and 38 msec at 10 Hz. In contrast, 40% of the lateral cells were excited, with 27% of the cells showing suppression. The mean duration of total suppression of lateral cell firing was 61 and 17 msec at 1 and 10 Hz, respectively. The results from the raphe cells are consistent with recent reports of stimulation of other forebrain and brainstem afferents to the raphe in which suppression of raphe activity was the main effect.


Digital imaging of the human cornea in vivo with ultraviolet light.
We have a developed a novel and practical method of imaging the cornea under ultraviolet (UV) light using a digital medium. Wavelengths of 336-371 nm were used to illuminate the cornea. Images were recorded using a UV Nikkor lens and a digital charged coupled device (CCD). Images obtained showed ferritin lines not visible under white light. This study concluded that 336-371 nm is comparable to shorter wavelengths for the imaging of ferritin in the cornea and that a digital image capture system was comparable to that of film.


Systematic changes in the perceived posture of the wrist and elbow during formation of a phantom hand and arm.
Our previous study showed that a fully flexed or extended hand became perceived as an extended or flexed 'phantom' hand as ischemic anesthesia progressed (Inui et al. in J Physiol 589:5775-5784, 2011). Here, we examined what happened if the hand was held in the midposition before and during the anesthesia. Twenty healthy participants reported the perceived postures of their right wrist and elbow during an ischemic block of the right upper arm using the left hand and arm. If the actual arm and hand were fully extended, then the perceived position of the elbow and wrist moved toward flexion. Conversely, if they were fully flexed, then the perceived position of the joints moved toward extension. However, when the hand was held in the midposition before and during the anesthesia, the position of the wrist was perceived to be in the same position. Hence, the fully flexed or extended position of a limb was essential for systematic changes in the perceived posture of the limb during the anesthesia. Because the start of these changes occurred as somatosensory inputs were declining, the changes depended on the fading inputs from strongly stretched muscle and skin during the anesthesia.


[Changes in the cellularity and lipid concentration of the bone marrow in rats after a single gamma-ray irradiation].
A study was made of the influence of gamma-irradiation of rats (14.4, 9.6, 7.2 and 4.8 Gy) on the number of nucleate cells, and the concentration of triacylglycerides (TG) and phospholipids (PL). Cellularity and concentration of PL decreased while that of TG increased under the effect of radiation. The degree of the changes in the above parameters was a function of dose and time after irradiation.


Aerobic glycolysis: a study of human articular cartilage.
Cartilage generally is one of those tissues that exhibit aerobic glycolysis. In a previous study on rat epiphyseal cartilage it had been suggested that this phenomenon is related to potentially excessive production of pyruvate and acetyl coenzyme A, the latter derived from fatty acid oxidation and inhibiting pyruvate dehydrogenase activity. The present study has shown that, in human articular cartilage, the contribution from fatty acid oxidation is too small to account for this phenomenon although the total potential production of pyruvate could still be in excess of the requirements for acetyl coenzyme A for the Krebs' cycle. Of greater relevance may be the apparent correlations that have been found between the activities of lactate and glyceraldehyde 3-phosphate dehydrogenases (r = 0 X 82: 0.01 greater than p greater than 0.001) and between those of lactate and glucose 6-phosphate dehydrogenases (r = 0.92; p less than 0.001).


Transcriptional analysis of the leading region in F plasmid DNA transfer.
Transcriptional activity associated with the leading region (53.8-66.7F) in F DNA transfer has been shown by RNA-DNA hybridization studies to occur on the anterior segment extending from 59.4 to 66.7F. Promoter-probe analysis of cloned leading region segments detected two promoters within the transcribed portion of the leading region. The promoter active across the 64.7F EcoRI site on the transferred F strand was associated with the expression of two polypeptides, 6d and 13.5p, located between 64.7-66.6F. However, no definite role could be ascribed to the second promoter operative through the 66.6F Bg/II site located in close proximity to oriT, the origin of transfer.


Clinical trial designs for evaluating and exploiting cancer evolution.
The evolution of drug-resistant cell subpopulations causes cancer treatment failure. Current preclinical evidence shows that it is possible to model herding of clonal evolution and collateral sensitivity where an initial treatment could favourably influence the response to a subsequent one. Novel therapy strategies exploiting this understanding are being considered, and clinical trial designs for steering cancer evolution are needed. Furthermore, preclinical evidence suggests that different subsets of drug-sensitive and resistant clones could compete between themselves for nutrients/blood supply, and clones that populate a tumour do so at the expense of other clones. Treatment paradigms based on this clinical application of exploiting cell-cell competition include intermittent dosing regimens or cycling different treatments before progression. This will require clinical trial designs different from the conventional practice of evaluating responses to individual therapy regimens. Next-generation sequencing to assess clonal dynamics longitudinally will improve current radiological assessment of clinical response/resistance and be incorporated into trials exploiting evolution. Furthermore, if understood, clonal evolution can be used to therapeutic advantage, improving patient outcomes based on a new generation of clinical trials.


The impact of digital finance on SMEs financialization: Evidence from thirty million Chinese enterprise registrations.
Based on the registration information of 30 million Chinese enterprises, this study innovatively constructs a financialization index based on the text information of enterprise business scope. Then, the impact of digital finance on small and medium-sized enterprise (SME) financialization is examined. Specifically, this study screens out SMEs involved in financial transactions by counting the keyword information in their business scope. The level of SME financialization is measured at the provincial level, based on a large number of registration samples. Empirical results based on panel fixed effects show that digital finance significantly inhibits SME financialization. On average, for each standard deviation increase in digital finance, SME financialization decreases by 0.087 standard deviations. This conclusion remains valid after a series of robustness analyses. A mechanism analysis shows that digital finance inhibits SME financialization by alleviating financing constraints, especially by providing liquidity to SMEs with relatively high financing constraints. In addition, the risk consequences of SME financialization are further examined, and SME financialization is found to significantly increase bankruptcy risk, while digital finance alleviates financing constraints and thus reduces bankruptcy risk. This study provides a new perspective for the governance of SME financialization and the optimization of the survival environment for SMEs in the context of the digital economy.


N-acetylcysteine attenuates cardiopulmonary bypass-induced lung injury in dogs.
Cardiopulmonary bypass (CPB) is usually associated with inflammatory response that leads to various degrees of organ dysfunction in multiple systems, including lung injury. Our previous study showed that transforming growth factor beta1 (TGFβ1) was involved in CPB-induced lung injury. N-acetylcysteine (NAC) is an antioxidant and is able to prevent CPB-induced pneumocyte apoptosis through scavenging radical. Therefore, we investigated whether NAC may attenuate CPB-induced lung injury by inhibiting TGFβ1 expression. Fifty-four 18 to 24-month-old mongrel dogs (15-16 kg) were randomly divided into control group, CPB group and NAC group (n = 18). Six dogs in each group were killed prior to, as well as 30 and 60 minutes after the operation (T0, T1 and T2). Lung injury was evaluated by hematoxylin and eosin (H&E) staining. Respiratory index (RI), oxygenation index (OI), malondialdehyde (MDA) content and superoxide dismutase (SOD) activity in the lung were determined at each time point. TGFβ1 expression was determined using real time RT-PCR and immunohistochemistry. A serious lung injury was observed after CPB in dogs. RI and MDA content were increased significantly after CPB, whereas OI and SOD activity were decreased. H&E staining showed that NAC treatment obviously attenuated CPB-induced lung injury. NAC treatment upregulated OI and SOD activity and downregulated RI and MDA content in the lung tissues of dogs after CPB. Treatment with NAC significantly suppressed the TGFβ1 expression in the lung tissues at both mRNA and protein levels. Our results suggest that NAC is a potent agent against CPB-induced acute lung injury through inhibiting TGFβ1 expression.


Emerging metallo-beta-lactamase-mediated resistances: a summary report from the worldwide SENTRY antimicrobial surveillance program.
The rates of occurrence of metallo-beta-lactamase-mediated resistances in Pseudomonas aeruginosa, Acinetobacter species, and Serratia marcescens, among other gram-negative bacilli, have escalated since 2000, severely limiting treatment options in Asia, Europe, and Latin America to non-beta-lactam antimicrobial classes. Clinical isolates harboring metallo-beta-lactamases have also recently been reported in western Canada and in Texas, signaling the need for development of accurate diagnostic tests by clinical laboratories to detect their presence and for new, and more potent, antimicrobial agents.


A non-archimedean theory of interaction of chemical compounds with membranes.
The permeability of procaine across axon membranes and the effect of formaldehyde (FA), crotonic aldehyde (CA) and glutaraldehyde (GA) on the compound action potential of frog sciatic nerve was studied by utilizing a non-archimedean (NA) model of the relaxation process. Such models allow a characterization of biosystems exhibiting more than one time scale. Expansions using Laguerre polynomials have been obtained for relaxation functions. The new approach is tested by fitting the model to the experimental data of other authors, and then applying to extract molecular level information from macroscopic data.


Long-term use of an injectable contraceptive: effect of depot-norethisterone oenanthate on carbohydrate metabolism.
In order to determine the metabolic effects of long-term use of the injectable contraceptive norethisterone oenanthate, plasma glucose and serum insulin concentrations were studied in two groups of women who had used the method continuously for at least five years. Group 1 comprised 24 subjects, from whom only fasting blood samples were taken. Despite similar plasma glucose concentrations to those of the controls, the subjects had significantly increased serum insulin concentrations (164.5 (39.9) v 120.3 (34.3) pmol/l, p less than 0.01). In addition the insulin:glucose ratios were also significantly increased (34.3 (8.5) v 24.6 (6.7), p less than 0.01), consistent with decreased insulin sensitivity. Group 2 comprised 13 of the original 24 subjects who also had an oral glucose tolerance test. Basal plasma glucose concentrations were similar in the subjects and their controls, whilst the significantly increased insulin:glucose ratios (35.0 (7.7) v 28.7 (5.6), p less than 0.05) were consistent with the results of the larger group. Following oral glucose challenge, plasma glucose concentrations, serum insulin concentrations and insulin:glucose ratios were similar in the subjects and their controls throughout the test. Thus, long-term use of norethisterone oenanthate injections is associated with a decrease in peripheral insulin sensitivity. However, these changes are not associated with any evidence of oral glucose intolerance.


Monocular visual loss in a disseminated colorectal malignancy-A case report of a rare skull base metastasis.
Neoplasms of the orbit may be primary, secondary (infiltration from the adjacent structures), or metastatic (from distant structures). It can be divided into 3 histologic categories: benign, benign but locally aggressive, and malignant. Primary and secondary orbital tumors, including intra-orbital and optic nerve tumors are uncommon observations in daily medical practice. Orbital tumors represent approximately 0.1% of all tumors and approximately 18% of all orbital diseases. We report a case of a 42 year old male patient with colorectal malignancy with basal skull metastasis involving the orbital apex and involving the optic nerve causing visual loss.


Anaerobic and aerobic transformations affecting stability of dewatered sludge during long-term storage in a lagoon.
The goal of this work was to study long-term behavior of anaerobically digested and dewatered sludge (biosolids) in a lagoon under anaerobic and aerobic conditions to determine the stability of the final product as an indicator of its odor potential. Field lagoons were sampled to estimate spatial and temporal variations in the physical-chemical properties and biological stability characteristics such as volatile solids content, accumulated oxygen uptake, and soluble protein content and odorous compound assessment. The analyses of collected data suggest that the surface layer of the lagoon (depth of above 0.15 m) undergoes long-term aerobic oxidation resulting in a higher degree of stabilization in the final product. The subsurface layers (depth 0.15 m below the surface and deeper) are subjected to an anaerobic environment where the conditions favor the initial rapid organic matter degradation within approximately the first year, followed by slow degradation.


Surgical treatment of invasion of the upper aerodigestive tract by well-differentiated thyroid carcinoma.
Forty-eight patients with well-differentiated thyroid carcinoma invading upper aerodigestive tract structures have been described. Age at diagnosis was found to be a negative prognostic factor, and duration of disease before invasion was found to be a positive prognostic factor. Treatment with radical surgery and adjuvant therapy provided no improvement in survival over treatment with near-total (skeletonizing) excisions combined with adjuvant therapy. All patients treated with partial debulking procedures, with or without tracheotomy, died from disease. We believe that partial resection of upper aerodigestive tract structures without sacrifice of voice, normal breathing, or swallowing should be considered in patients with well-differentiated thyroid carcinoma.


Use of NT-proBNP in routine testing and comparison to BNP.
B-type natriuretic peptide (BNP) is a strong diagnostic predictor of left-ventricular (LV)-dysfunction. Recently, the aminoterminal portion of pro-BNP (NT-proBNP) has been introduced, which could be even more sensitive because of its longer half-life. The aim of this study was to evaluate the new marker NT-proBNP within a large, heterogeneous population of patients with suspected cardiovascular disease at risk of cardiovascular dysfunction and to compare it with the established diagnostic parameter BNP. NT-proBNP and BNP were measured in 339 hospitalised patients undergoing diagnostic angiography (median age 66 years, 244 male vs. 95 female). Median values of NT-proBNP increased with worsening LV-dysfunction and higher NYHA class. The area under the receiver operator characteristics curve (AUC) of NT-proBNP for detecting severe systolic dysfunction or for detecting any systolic LV-dysfunction was 0.83 and 0.77, respectively. The latter improved (AUC=0.81) when patients with clinically relevant heart disease like valvular dysfunction were included, independent of the haemodynamic values. Compared to BNP, NT-proBNP tended to be more accurate in identifying lesser degrees of LV-dysfunction. Even after optimisation of target criteria, there was still a substantial overlap of NT-proBNP values between patients with and without relevant heart disease. Therefore, NT-proBNP is not suitable as a screening test for LV-dysfunction in the community. Nevertheless, because of its good negative predictive value, NT-proBNP could be an easy and effective tool to rule out severe systolic LV-dysfunction in high risk patients. No clinically significant advantage of BNP testing could be found.


Monocyte chemotactic protein-1 gene expression and translation in formed granulomatous calcified tissue in vivo.
Monocyte chemotactic protein-1 (MCP-1) and related molecules constitute the C-C class of the beta chemokine supergene family with inflammatory properties. However, the exact role, function, and implication in inflammatory diseases remain to be determined. Here we report that subcutaneous injections (0.2 ml) of a saturated water solution (1:40) of potassium permanganate crystals induces the generation of granuloma tissue at the site of injection in the rat, and reaches its peak of formation after 1 week. The size and weight of the granulomas were increased by i.p. lipopolysaccharide (LPS) (6 microgram/200 microliter) and inhibited by intraperitoneal (i.p.) dexamethasone (Dxs) 300 microgram/200 microliter) treatments in rats, injected 18 hours before sacrifice. Moreover, steady-state levels of MCP-1 mRNA in the granuloma tissue (control), were strongly generated. Rats treated i.p. with LPS produced an increase of MCP-1 mRNA in the granuloma tissue compared with controls (i.p. PBS-treated) whereas in animals treated with Dxs, there was a decrease in (P < 0.05) in formation of mRNA protein. When the granuloma tissues were homogenized the generation of MCP-1 was found in the supernatants. The level of MCP-1 was higher (P < 0.05) in the LPS-treated animals and lower (P < 0.05) in the Dxs group compared with the controls (treated with PBS). Similar results were obtained in the serum and in minced granuloma tissue where samples were further incubated in vitro with LPS (100 ng/ml) overnight. A Strong increase (P < 0.01) in MCP-1 in all samples was detected, but not in the minced granuloma tissue from Dxs-treated animals. Our data demonstrate that calcified tissue from chronic inflammation induced by KMnO4 generates MCP-1 gene expression and translation, an effect increased by LPS and decreased by Dxs.


Genetic and non-genetic risk factors associated with atrial fibrillation.
Atrial fibrillation (AF) is the most common arrhythmic disorder and its prevalence in the United States is projected to increase to more than twelve million cases in 2030. AF increases the risk of other forms of cardiovascular disease, including stroke. As the incidence of atrial fibrillation increases dramatically with age, it is paramount to elucidate risk factors underlying AF pathogenesis. Here, we review tissue and cellular pathways underlying AF, as well as critical components that impact AF susceptibility including genetic and environmental risk factors. Finally, we provide the latest information on potential links between SARS-CoV-2 and human AF. Improved understanding of mechanistic pathways holds promise in preventative care and early diagnostics, and also introduces novel targeted forms of therapy that might attenuate AF progression and maintenance.


Comparison of VMAT complexity-reduction strategies for single-target cranial radiosurgery with the Eclipse treatment planning system.
Complexity in MLC-based radiosurgery treatment delivery can be characterized by the efficiency of monitor unit (MU) utilization and the average MLC leaf separation distance for a treatment plan. A reduction in plan complexity may be desirable if plan quality is not impacted. In this study, a number of strategies are explored to determine how plan quality is affected by efforts to reduce plan complexity. Ten radiosurgery cases of varying complexity are retrospectively planned using six optimization strategies: an unconstrained volumetric modulated arc therapy (VMAT) technique, a MU-constrained VMAT technique, three techniques using various strengths of the aperture shape controller (ASC), and a hybrid technique consisting of a final-stage VMAT optimization applied to a dynamic conformal arc leaf sequence (ODCA). The plans are compared in terms of MU efficiency, MLC leaf-separation, conformity index (CI), gradient index (GI), and QA measurement results. The five VMAT techniques exhibited only minor differences in CI and GI values, though the ASC and MU-constrained techniques did require 6-20% fewer MU and had mean field apertures 5-19% larger. On average, the ODCA technique had CI values 3.5% lower and GI values 1.0-2.5% higher than the VMAT techniques, but also had a mean field aperture 24-47% larger and required 16-32% fewer MU. The QA measurement results showed a 0.61% variation in mean per-field 2%/1 mm gamma passing rates across all techniques (range 96.81%-97.42%), with no observed correlation between passing rate and technique. For simple targets, the ODCA technique achieved CI results that were equivalent to the unconstrained VMAT technique with an average 30% reduction in required MU, an average 50% increase in mean leaf separation distance, and brain V12Gy values within 0.38 cc of the VMAT technique for targets up to approximately 2 cm diameter. For MLC-based single-target radiosurgery, plan complexity can often be significantly reduced without an equivalent reduction in plan quality.


Genetic characterization of VP1 gene of seven Sacbrood virus isolated from three provinces in northern China during the years 2008-2012.
The genetic diversity of seven northern China isolated Sacbrood virus strains (SBV) has been analyzed, and hypervariable regions of the VP1 gene of 7 SBV were sequenced and characterized, in order to obtain epidemiological and immunological information, and to suggest typing criteria for SBV. Sequence analysis of hypervariable regions of the VP1 gene in the genome of these isolates revealed a sequence homology of 91.0-99.3% among all seven local SBV isolates from Apis cerana from China, with a similarity of 93.3-100.0% in deduced amino acid sequences. These local isolates shared 87.4-92.8% sequence homology with six SBV reference strains in GenBank (including two SBV reference strains from Apis cerana from China), which represents a 91.8-97.6% similarity in deduced amino acid sequences. Genetic analysis also showed that five SBV strains from Apis cerana from China had a 13-amino-acid deletion at amino acid positions 287-299, and two SBV strains infecting the Korean honeybee had a 17-amino-acid deletion at amino acid positions 284-300 in comparison with other SBV. Phylogenetic analysis revealed two major groups (AC genotype SBV infecting Apis cerana and AM genotype SBV infecting Apis mellifera). The AC genotype could be further divided into subgroups. Based on the results of phylogenetic analysis, a similarity scan of SBV nucleotide sequences was carried out by using Simplot software and results in similar results. Our results suggest possible typing criteria for SBV based on the phylogenetic tree and sequence homology, and also that the virus has host specificity and regional variations.


Preparation of novel ion exchange polyurethane foam and its application for separation and determination of palladium in environmental samples.
The new strong anion exchanger (PUFIX) from polyurethane foam was prepared by coupling of the primary amine of the foam matrix with ethyl iodide. PUFIX was characterized using different tools (IR spectra, elemental analysis, density and thermal analysis). The sorption properties of the new anion exchanger (PUFIX) and chromatographic behaviour for separation and determination of palladium(II) ions at low concentrations from aqueous iodide or thiocyanate media were investigated by a batch and dynamic processes. The maximum sorption of Pd(II) was in the pH range of 0.3-2. The kinetics of sorption of the Pd(II) by the PUFIX was found to be fast with average values of half-life of sorption (t(1/2)) of 3.32 min. The variation of the sorption of Pd(II) with temperature gives average values of DeltaH, DeltaS, DeltaG and DeltaE to be -38.3 kJ mol(-1), -100.7J K(-1) mol(-1), -8.3 and 11.8 kJ mol(-1), respectively. The sorption capacity of PUFIX was 1.69 mmol g(-1) for Pd(II), preconcentration factors of values approximately 250 and the recovery 99-100% were achieved (R.S.D. approximately 1.24%). The lower detection limit, 1.28 ng mL(-1) was evaluated using spectrophotometric method (R.S.D. approximately 2.46%).


Choanal polyp originating from the nasal septum: a case report.
Almost all nasal polyps originate from the mucosa of the lateral walls of the nasal cavity or from the paranasal sinuses. A choanal polyp is the intranasal portion of a cyst that has arisen from the wall of the maxillary sinus near the ostium. Medially based polyps, such as those that arise from the nasal septum, are rare. The literature cites a wide range of incidence rates for polyps originating from this structure, but choanal extension of this type of polyp is extremely unusual. This report describes a polyp that arose from the superior aspect of the posterior nasal septum and extended through the choana into the nasopharynx. The histology of this choanal lesion was typical of nasal polyps, but the site of origin is rare. The ethiopathogenesis of nasal polyps with its common location remains controversial so it is difficult to speculate what mechanism triggered the development of this lesion on the nasal septum. Some form of local inflammation may have induced choanal polyp formation at this atypical site.


Combined rigid and flexible ureteropyeloscopy.
The development of rigid and flexible ureteropyeloscopes has provided the means for direct visualization of the upper urinary collecting system. Each instrument has its own advantages and disadvantages. The combined use of these instruments extends the range of endoscopy throughout the intrarenal collecting system, permits irrigation and provides a working channel.


The One Minute Learner: Evaluation of a New Tool to Promote Discussion of Medical Student Goals and Expectations in Clinical Learning Environments.
The transition from pre-clerkship to clerkship curriculum in medical school presents many challenges to students. Student roles and supervising physicians' expectations vary widely. Efforts to ease this transition have included third-year orientations, skills sessions, field- specific training, and peer-to-peer communication/support. We developed a new tool, called The One Minute Learner (OML), to promote and structure discussion of student goals and expectations and empower student ownership of learning. The OML can be used quickly and easily by students and faculty to facilitate integration of medical students into the clinical setting. This paper describes the OML and reports evaluation of its effectiveness through student evaluations. We compared student responses to two end-of-clerkship questions for the academic year before the OML was implemented to the first year of implementation. Students rated their orientation to their roles and responsibility and rated the communication of what was expected of them. The percentage of students rating these highly increased dramatically: for "I was oriented to my responsibilities and role," the percentage rating it highly (4--5 on a 5-point Likert scale) increased from 47% to 82%. For "Expectations of my role were communicated to me clearly" the percentage rating it highly increased from 66% to 89%. The OML is a new tool that can promote and structure a proactive discussion between student and teacher about goals and expectations, leading to better integration of students into the variety of clinical setting in which they rotate.


Ectopic neural activity from myelinated afferent fibres in the lingual nerve of the ferret following three types of injury.
Sensory disturbances following nerve injury may result from abnormal neural activity initiated at the injury site. We have studied the activity generated in the lingual nerve after three types of injury which may have variable potentials for the initiation of sensory disturbances. We have also compared the results with those found after damage to the inferior alveolar nerve, another branch of the trigeminal nerve, to determine whether differences in nerve fibre type or location affect the level of abnormal activity. In anaesthetised adult male ferrets the left lingual nerve was either ligated and cut distally, chronically constricted, or sectioned and allowed to regenerate. Following recovery periods of 3 days-6 months, single unit electrophysiological recordings were made from central to the injury site. After all three types of injury, some of the damaged axons at the injury site developed spontaneous activity (up to 36% of units) and mechanical sensitivity (up to 35% of units). There were significantly fewer spontaneously active units after ligation than after the other two types of injury but the level of mechanical sensitivity was not significantly different between the three types of injury. There was a significant increase in the spontaneous activity between 3 weeks and later recovery periods following both ligation and section injuries, and this late increase was not seen in our previous studies on the inferior alveolar nerve. Differences in the time-course of ectopic activity in adjacent branches of the trigeminal nerve suggest that the fibre types or anatomical relationships affect the outcome of injury.


Previous caesarean or vaginal delivery: which mode is a greater risk of perinatal death at the second delivery?
To compare the risk of perinatal death after previous caesarean versus previous vaginal delivery, and pre-labour repeat caesarean versus trial of labour after previous caesarean. Using the data of the Berlin Perinatal Registry from 1993 to 1999, 7556 second parous women with a previous caesarean delivery were compared with 55142 second parous women with a previous vaginal delivery, and those 1435 women with pre-labour repeat caesarean were compared with 6121 women with a trial of labour after previous caesarean delivery. The rates of perinatal death, stillbirth and intrapartum/neonatal death were analysed using multivariable logistic regression to adjust for confounding variables and obstetric history. A previous caesarean delivery was associated with a 40% excess risk of perinatal death and a 52% excess risk of stillbirth (p<0.05); the risk of intrapartum/neonatal death was not significantly increased. There were no significantly higher rates of intrapartum/neonatal death and of stillbirth in women trying a vaginal birth versus pre-labour repeat caesarean. But in most cases of antepartum death, labour was induced for that reason. Consulting women about caesarean delivery for maternal request, the increased risk of perinatal death in further pregnancies should be discussed. After a previous caesarean delivery, a careful screening for several risk factors is necessary before recommending a trial of labour.


Don't Forget the Brain: Lifestyle Medicine in the Century of Neurodegeneration.
Neurology is often not discussed in lifestyle medicine circles, but it might be an area that will propel the cause of lifestyle medicine in the future. This is especially relevant in increasingly common neurodegenerative conditions such as Alzheimer's disease, which have no known disease modifying therapy but lifestyle factors are implicated in causation.


Applied physiology of water polo.
Water polo has been played for over a century. While the rules of the game have evolved considerably over this time, the sport has consistently remained, physiologically, a highly demanding activity. Much attention has been paid to the technical and strategic elements of the game; however, despite the potential for improvements in athletic performance and the maintenance of athletes' health, there are few published studies (particularly in English) on the physical and physiological demands and adaptations to water polo training and competition. Game analyses have demonstrated that water polo is an 'intermittent' sport comprised of intense bursts of activity of <15 seconds duration with intervening, lower intensity intervals averaging <20 seconds duration. Physiological measurements obtained during game play indicate a cumulative effect of the repeated sequences of activities and suggest there is a high metabolic demand on the athletes. The multiple individual skills and movements required for playing water polo also place considerable demands on the neuromuscular system. Observations of the frequency and duration of the different activities, and of the physiological responses to participating in a water polo match, are initial sources of information for designing training programmes specific to the game and to the different playing positions. The physical and physiological attributes of elite water polo players offer some insight into the minimum requirements for participation and the adaptations that result from training and competition. Further systematic documentation and experimentation are required to facilitate the design and specification of individual training programmes and to better understand the long term effects of water polo on athletes' health.


Universal versus selective screening for gestational diabetes mellitus among antenatal clinic attendees in Abakaliki: using the one-step 75 gram oral glucose tolerance test.
To compare universal screening with selective risk factor based screening for GDM, using the one-step 75 g oral glucose tolerance test (OGTT). A cross-sectional, comparison between universal and selective risk factor based screening for GDM, among 400 antenatal care clients at Alex-Ekwueme Federal University Teaching Hospital Abakaliki (AE-FUTHA). All the participants had 75 g OGTT at 24-28 weeks of gestation and risk factor screening for GDM. All 400 participants formed the universal group while participants with one or more of the considered risk factors formed the selective risk factor group. Data were analyzed using IBM SPSS version 20. Statistical comparison was done using t- test for continuous variables. Logistics regression was used to determine the level of associations of the independent predictors for hyperglycemia. Level of significance was set at P < 0.05. The point prevalence of GDM using universal and selective screening were 11.51 and 7.93% respectively, giving a selective screening miss rate of 31.11%. The sensitivity, specificity, positive predictive value and negative predictive value were 73.58, 48.82, 19.12 and 92.51% respectively for the selective risk factor based screening compared to universal screening. On multivariate analysis; age ≥ 35 years, weight ≥ 90 kg, history of previous GDM and hypertension were significantly related to the development of hyperglycemia. Selective risk factor based screening missed 31.11% of patients with GDM when compare to Universal screening with one step 75 g OGTT. Universal screening for GDM using the one step 75 g OGTT is recommended for pregnant women and more studies are needed to compare pregnancy outcomes for pregnant women diagnosed with GDM with and without risk factors.


Who benefits from disclosure? Exploration of attachment style differences in the effects of expressing emotions.
Pennebaker's disclosure paradigm is a powerful manipulation: writing or talking about emotional experiences has positive effects on health. Nevertheless, the effect does not work for all people and some studies, including those of the highly emotional event of bereavement, have failed to demonstrate any effect at all. This paper reviews empirical evidence and proposes an integrative model to help explain discrepant findings and assess individual differences in the manipulation's effectiveness. Taking bereavement as exemplary of an attachment-related loss experience, it examines the relationship between styles of attachment, internal representations of the self and other, and patterns of disclosure in the coping process. Research has shown disturbances in disclosure among insecurely attached persons. We argue that secure persons are less likely to benefit from the disclosure paradigm, since they are better able to disclose in ways that further the adjustment process in their everyday lives. Targeting persons with insecure attachment styles and providing attachment-style-specific disclosure instructions are likely to increase the power of the manipulation. Our examination of these individual difference patterns is compatible with recent cognitive and linguistic analyses underlying the disclosure paradigm's impact on health.


Polycyclic aromatic hydrocarbons in sediments and mussels of Corral Bay, south central Chile.
PAHs were measured in sediments and mussels (Mytilus chilensis) from Carboneros and Puerto Claro, located in Corral Bay, Valdivia. According to the ratio of phenanthrene/anthracene and fluoranthene/pyrene concentrations, these sites are medium polluted with PAHs originating mainly from pyrolytic sources. Fluoranthene was the major component measured in mussels (3.1-390 ng g(-1) dry weight) and sediments (6.9-74.1 ng g(-1) dry weight). In general, mussels were mainly exposed to the dissolved fraction of the lower molecular weight PAHs (tri- and tetra-aromatics) while the higher molecular ring systems (penta- and hexa-aromatics) were more bioavailable to sediments. Mussel PAHs content was relatively constant, with the exception of the 1999 summer season (March), when higher concentration values were found in both sites; however, PAHs residues in sediments showed a temporal variation.


Late recurrence of upper urinary tract urothelial tumours.
Two case reports of late recurrence of upper urinary tract urothelial tumours 13 years after ipsilateral local resection and 19 years after contralateral nephroureterectomy are used in the discussion on when to perform local resection. In accordance with existing literature we propose local resection in case of low-grade upper urinary tract urothelial tumours.


Relationship between dopamine agonist stimulation of inositol phosphate formation and cytidine diphosphate-diacylglycerol accumulation in brain slices.
Dopamine receptor-coupled stimulation of inositol phosphate formation has been characterized extensively, but little is known about the diacylglycerol arm of this dual-signaling pathway. This study examined several parameters of cytidine diphosphate-diacylglycerol (CDP-DG) accumulation as an index of agonist-stimulated DG formation. Rat brain slices pre-labeled with 5-[3H]cytidine were incubated with various test agents in the presence of LiCl and accumulated CDP-DG analyzed. Dopamine and SKF38393 significantly and dose-dependently stimulated CDP-DG accumulation. SKF38393 responses were inhibited by neomycin and reversed by myo-inositol or by exclusion of LiCl. Compared to inositol phosphate formation in 2-[3H]inositol-prelabeled slices, the CDP-DG responses were proportionately greater, while the agonist EC50 values were similar between the two assays. The D1-receptor antagonist SCH23390 inhibited SKF38393-mediated responses at 0.1-10 microM concentrations, whereas greater concentrations reversed the inhibition. SKF38393 effects were completely blocked by the DG kinase inhibitor R59022, thus precluding any role for phospholipase-D or de novo phosphatidate synthesis in the dopaminergic response. D609 which inhibits phosphatidylcholine-specific phospholipase-C (PLC), potently inhibited both CDP-DG accumulation and inositol phosphate formation. These findings demonstrate that the selective D1-receptor antagonist SCH23390 is a partial agonist at the D1-like dopamine receptor that couples to phosphoinositide signaling, that dopaminergic facilitation of phosphoinositide signaling is independent of de novo phosphatidate synthesis, and that the widely used enzyme inhibitor, D-609, is probably not selective for phosphatidylcholine-specific PLC in brain slice preparations. The greater sensitivity of the CDP-DG measurement presents this assay as a reliable and possibly superior index of dopamine receptor-coupled PLC activation in intact tissues.