Biotransformation enzymes in development of renal injury and urothelial cancer caused by aristolochic acid.
Ingestion of aristolochic acid (AA) is associated with the development of AA-nephropathy and Balkan endemic nephropathy, which are characterized by chronic renal failure, tubulointerstitial fibrosis, and urothelial cancer. Understanding which enzymes are involved in AA activation and/or detoxification is important in assessing susceptibility to AA. Xiao et al. demonstrate that hepatic cytochrome P450s in mice detoxicate AA and thereby protect kidney from injury. The relative contribution of enzymes activating AA to induce urothelial cancer in humans remains to be resolved.


A simple program in BASIC for the one-way analysis of variance of experimental data.
A BASIC program is presented to compute one-way analysis of variance of life data. The program is simple, powerful, direct and relatively short. It allows for judgement of significance at the chosen confidence limit. Applications of the program to some experimental therapeutic data are shown.


A new turtle confirms the presence of Bothremydidae (Pleurodira) in the Cenozoic of Europe and expands the biostratigraphic range of Foxemydina.
Pleurodira is a clade of Gondwanan turtles that reached Europe at the beginning of the Late Cretaceous. It is recognized as the most abundant and diverse group of freshwater turtles in the uppermost Cretaceous record of this continent, being represented by several members of Bothremydidae. Two well-preserved and relatively complete skulls are studied in this paper. They come from lower Eocene levels of the French locality of Saint-Papoul (Aude). These specimens are recognized as attributable to a new taxon, Tartaruscola teodorii gen. et sp. nov., identified as a bothremydid. This new form constitutes the only known unambiguous and valid representative of Bothremydidae in the Cenozoic of Europe. The new taxon is diagnosed by several autapomorphies and also by an exclusive combination of characters. It is one of the few members of Bothremydini identified in the Cenozoic record and the only one described for the Eocene outside of the Ouled Abdoun Basin of Morocco. Tartaruscola teodorii is identified as a member of Foxemydina, a clade recognized here as exclusive of the European record, and whose presence in post-Mesozoic levels is demonstrated in this paper. The European Foxemydina T. teodorii and the African Bothremydina Bothremys kellyi, both from the Ypresian, are the youngest members of Bothremydini hitherto known.


Effect of membrane potential on the kinetic parameters of the Na+ or H+ melibiose symport in Escherichia coli membrane vesicles.
Comparison of the transport properties of the melibiose permease of E. coli acting as a H+-symport or a Na+-symport has been performed by measuring initial rates of [3H]-melibiose transport or its accumulation in isolated membrane vesicles. The results show strikingly that although the membrane potential primarily drives melibiose accumulation by both types of symport, it selectively affects the apparent affinity constant Kt of the H+-melibiose symport while it specifically changes the maximal rate of transport (Vmax) of the Na+-melibiose symport. It is suggested that modification(s) of some partial reaction constants of a given transport cycle might lead to important changes in the kinetic properties of this transport system.


Prognostic value of fluorine-18 fluorodeoxyglucose positron emission tomography in patients with advanced non-small cell lung cancer: single center experience.
The purpose of this retrospective single-center study was to evaluate the prognostic implication on overall survival (OS) of the F-18 FDG PET scan in locally advanced or metastatic non small cell lung cancer (NSCLC) patients. We retrospectively reviewed 120 locally advanced or metastatic NSCLC patients (December 2004-November 2011) treated/followed at the Dicle University, School of Medicine, Department of Medical Oncology. SUVmax and other potential prognostic variables (n=18) were chosen for analysis. Univariate and multivariate analyses were conducted to identify prognostic factors for OS. Among 18 variables of univariate analysis, 6 were identified to bear prognostic significance: sex (p=0.01), performance status (PS) (p =0.03), stage (p=0.04), bone metastases (p=0.002), serum albumin (p=0.01) and blood glucose level (p=0.03). Multivariate analysis showed that PS, bone metastases and serum albumin level were independent prognostic factors for OS (p=0.01, p=0.004, p=0.003, respectively). PS, serum albumin levels and bone metastases were independent prognostic factors, while FDG uptake of the primary lesion was not associated with prognosis of OS in locally advanced or metastatic NSCLC patients.


Fine structure of the drum muscles of the piranha (serrasalminae, characidae).
The anterior and the posterior drum muscles of the piranha resemble each other in all essential fine structural aspects: myofibrils are slender; sarcomeres are short compared with those of other drum muscles; mitochondria, located in the periphery of the fibers, are numerous and show an irregular internal structure; and the sarcoplasmic reticulum is abundant. Triads appear at the level of the Z lines. The drum muscles have many motor endplates, which, however, lack the characteristic junctional-fold apparatus. No lipid substances could be demonstrated in these muscles. In the posterior drum muscle the fibers depart from their orderly longitudinal arrangement at irregular intervals.


A methodological framework for detecting ulcers' risk in diabetic foot subjects by combining gait analysis, a new musculoskeletal foot model and a foot finite element model.
Diabetic foot is one of the most debilitating complications of diabetes and may lead to plantar ulcers. In the last decade, gait analysis, musculoskeletal modelling (MSM) and finite element modelling (FEM) have shown their ability to contribute to diabetic foot prevention and suggested that the origin of the plantar ulcers is in deeper tissue layers rather than on the plantar surface. Hence the aim of the current work is to develop a methodology that improves FEM-derived foot internal stresses prediction, for diabetic foot prevention applications. A 3D foot FEM was combined with MSM derived force to predict the sites of excessive internal stresses on the foot. In vivo gait analysis data, and an MRI scan of a foot from a healthy subject were acquired and used to develop a six degrees of freedom (6 DOF) foot MSM and a 3D subject-specific foot FEM. Ankle kinematics were applied as boundary conditions to the FEM together with: 1. only Ground Reaction Forces (GRFs); 2. OpenSim derived extrinsic muscles forces estimated with a standard OpenSim MSM; 3. extrinsic muscle forces derived through the (6 DOF) foot MSM; 4. intrinsic and extrinsic muscles forces derived through the 6 DOF foot MSM. For model validation purposes, simulated peak pressures were extracted and compared with those measured experimentally. The importance of foot muscles in controlling plantar pressure distribution and internal stresses is confirmed by the improved accuracy in the estimation of the peak pressures obtained with the inclusion of intrinsic and extrinsic muscle forces.


Effects of antisense oligodeoxynucleotide to the alpha2A-adrenoceptors on the plasma corticosterone level and on elevated plus-maze behavior in rats.
Antisense strategy was used to investigate the role of alpha2A-adrenoceptor (alpha2A-AR) subtype in anxiety-related behavior. A 18-mer phosphorothioate oligodeoxynucleotide (AS-ODN) complementary to the alpha2A-AR mRNA was administered to the adult male rats for 3 days (1 nmol/5 microl/day) into the region of locus coeruleus (LC). Control groups received infusions of either oligodeoxynucleotide of a random sequence (RS-ODN) or saline. Treatment with AS-ODN significantly reduced the levels of alpha2A-AR mRNA in the brain stem. At the same time, AS-ODN treatment caused only a small reduction in [(3)H]clonidine binding (by 26-32%) in the brain stem which was not significant. Compared to both RS-ODN and saline controls, treatment with AS-ODN significantly increased the percentage of open arm entries in the elevated plus-maze while the total number of arm entries was unaltered. Also, AS-ODN treatment elevated basal levels of plasma corticosterone by 217% and 96% compared to both RS-ODN and saline controls. These changes in the hormone concentrations were at a level of marginal significance (p<0.1 versus random group). Taken together, the data indicate that administration of AS-ODN against alpha2A-ARs in the LC significantly reduced expression of alpha2A-AR mRNA in brain stem, moderately increased plasma corticosterone and had anxiolytic-like effect in the elevated plus-maze.


Management of Alcohol Use Disorder in Patients With Alcoholic Liver Disease.
Alcohol use disorder (AUD) is a common condition that develops on the background of heavy alcohol use and is characterised by the loss of control over alcohol use and a compulsion to use alcohol, often despite negative consequences. AUD is a leading cause for the resumption of alcohol use in patients with alcoholic liver disease (ALD) after treatment. Hence it is essential to screen all patients with ALD for the presence of AUD. Screening tools such as alcohol use disorders identification test (AUDIT) and AUDIT-C are used, following which the diagnosis and severity of AUD are determined using DSM-5 criteria. The management of AUD in patients with ALD is best carried out using an integrated approach involving psychiatrists and gastroenterologists/hepatologists. The treatment most often involves a combination of pharmacotherapy and psychosocial interventions which try to achieve and maintain abstinence. Although, there is limited evidence, Baclofen is the first line pharmacological agent for long-term management of AUD in patients with ALD. Intensive psychological interventions such as motivation enhancement therapy and cognitive behavioural therapy are also seen to be beneficial. Treatment retention and follow-up are vital and can positively influence outcomes.


Nuclear receptor coactivator 6 (NCoA6) promotes cell proliferation, migration, and invasion in pancreatic cancer.
Nuclear receptor coactivator 6 (NCoA6) is overexpressed in various cancers and considered a multifunctional coactivator of various transcription factors and nuclear receptors. However, the role of NCoA6 in pancreatic ductal adenocarcinoma (PDAC) remains unclear. NCoA6 expression data in PDAC were extracted from TCGA and GTEx databases, and their correlation with survival outcomes were analyzed using the Kaplan-Meier plotter database. NCoA6 protein expression in PDAC tissues was evaluated using immunohistochemistry. RNA-sequencing technology was used to sequence the transcriptome of NCoA6-silenced PANC-1 cells, followed by differential expression, GO/KEGG and GSEA analyses. The effects of NCoA6 on cell proliferation, migration, invasion, cell cycle, and apoptosis were determined in two representative cell lines (PANC-1 and SW1990). Western blotting, qPCR, and co-immunoprecipitation were performed to explore the mechanism of action of NCoA6 in PDAC cells. NCoA6 expression was markedly increased in PDAC tissues, and high NCoA6 expression was associated with poor survival prognosis. However, there was no significant relationship between NCoA6 expression and metastasis in PDAC patients. Our RNA-sequencing data analysis found 1194 significant differentially expressed genes between the control and NCoA6-silenced PANC-1 cells. GO/KEGG analysis results mainly focused on cytokine production, cytokine activity, and cytokine-cytokine receptor interactions. GSEA results showed that the knockdown of NCoA6 affected the expression of histone deacetylase 1 (HDAC1) targeted genes. NCoA6 knockdown suppressed proliferation, migration, and invasion of PDAC cells. Finally, western blotting, qPCR, and co-immunoprecipitation results showed that NCoA6 interacted with HDAC1 and that NCoA6 expression was negatively correlated with F-box and WD repeat domain-containing 7 (FBW7) and caudal-related homeobox transcription factor 2 (CDX2) expression in pancreatic cancer. NCoA6 has a profound effect on cell proliferation, migration, invasion, and prognosis of PDAC and is potentially related to the expression of HDAC1, FBW7, and CDX2. Our results may provide novel therapeutic strategies for PDAC patients.


Obstructive jaundice in a child with pancreatic hemangioma.
We report the case of a 2-year-old boy who presented with obstructive jaundice by pancreatic hemangioma. In this case, a minimal operation for obstructive jaundice without resection of the tumor was performed. Three years after the operation, the pancreatic hemangioma almost disappeared. We discuss treatment of the pancreatic hemangioma in children.


Does awareness of terminal status influence survival and quality of life in terminally ill cancer patients?
Clinical studies, with a proper scientific design, on the impact of disclosing a prognosis on a patient's psychological or physical conditions are rare. We investigated the effect of patient awareness of terminal status on survival and quality of life (QoL) in a palliative care setting. This is a prospective cohort study of patients with terminal cancer. Patients with cancer at a palliative care unit were enrolled consecutively. The patients' awareness of their terminal status was determined using a semistructured interview. Sociodemographic and clinical characteristics, including Eastern Cooperative Oncology Group performance status, depressed mood, and QoL, were investigated. To determine the independent effects of awareness of illness on survival and QoL, multivariate Cox proportional-hazards regression and multivariate linear regression were used, respectively. For the 262 cases analyzed, the median survival time (interquartile range) was 28.5 (15.8-55.3) days, and 76 (29.0%) patients were unaware of their prognosis. Patients who were aware survived for a shorter period than did those who were unaware (HR, 1.44; 95% CI, 1.07-1.93, p = 0.015) after adjusting for clinical variables including physical status and depression. Also, patients who were aware reported lower subjective QoL compared with patients who were unaware in a multivariate linear regression analysis (B, -0.10; 95% CI, -0.17 to -0.03, p = 0.008). Awareness of prognosis may negatively impact survival and QoL in terminally ill cancer patients. Therefore, the patient's preference for and individual susceptibility to receiving such information should be assessed carefully before disclosure.


The effects of white matter disease on the accuracy of automated segmentation.
Automated segmentation of the brain is challenging in the presence of brain pathologies such as white matter hyperintensities (WMH). A late-life depression population was used to demonstrate the effect of WMH on brain segmentation and normalization. We used an automated algorithm to detect WMH, and either filled them with normal-appearing white-matter (NAWM) intensities or performed a multi-spectral segmentation, and finally compared the standard approach to the WMH filling or multi-spectral segmentation approach using intra-class correlation coefficients (ICC). The presence of WMH affected segmentations for both approaches suggesting that studies investigating structural differences in populations with high WMH should account for WMH. We also investigated how functional data contrasts are affected using normalization between the standard compared to fill and multi-spectral approach. We found that the functional data was not affected. While replication with a larger sample is needed, this study shows that WMH can significantly affect the results of segmentation and these areas are not limited to those affected by WMH. It is clear that to study gray matter differences that some correction should be made to account for WMH. Future studies should investigate which methods for accounting for WMH are most effective.


Unique Morphometric Features of the Cerebellum and Cerebellocerebral Structural Correlation Between Autism Spectrum Disorder and Schizophrenia.
Although cerebellar morphological involvement has been increasingly recognized in autism spectrum disorder (ASD) and schizophrenia (SZ), the extent to which there are morphological differences between them has not been definitively quantified. Furthermore, although previous studies have demonstrated increased anatomical cerebellocerebral correlations in both conditions, differences between their associations have not been well characterized. We compared cerebellar volume between males with ASD (n = 31), males with SZ (n = 28), and typically developing males (n = 49). A total of 31 cerebellar subregions were investigated with the cerebellum segmented into their constituent lobules, in gray matter (GM) and white matter (WM) separately. Additionally, structural correlations with the contralateral cerebrum were analyzed for each cerebellar lobule. We found significantly larger WM volume in the bilateral lobules VI and Crus I in the ASD group than in other groups. While WM or GM volumes of these right lobules had positive associations with ASD symptoms, there was a negative association between GM volume of the right Crus I and SZ symptoms. We further observed, in the ASD group specifically, significant correlations between WM of the right lobule VI and WM of the left frontal pole (r = 0.67) and between GM of the right lobule VI and the left caudate (r = 0.60). Our findings support evidence that cerebellar morphology is involved in ASD and SZ with different mechanisms. Furthermore, this study showed that these biological differences require consideration when determining diagnostic criteria and treatment for these disorders.


Low titer, competitive insulin autoantibodies are spontaneously produced in autoimmune diseases of the thyroid.
The occurrence of multiple endocrine autoimmunity with organ-specific autoantibodies is well known. In this study we evaluated the presence of competitive insulin autoantibodies (IAA) in immune and non-immune diseases of the thyroid, utilizing a sensitive and specific radiobinding assay. We studied 37 patients with Graves' disease, 44 patients with Hashimoto's thyroiditis, 11 patients with non-immune thyroid diseases and 30 normal controls. In 5/37 (13.5%), 7/44 (15.9%) patients with Graves' and Hashimoto's diseases, respectively, but in none of those with non-immune thyroid disease or of the controls, IAA levels exceeded our upper limit of normal range (50 nunits/ml) (P < 0.01). Positive IAA levels ranged between 50 and 123 nunits/ml with fluctuation of these levels over time. Islet cell antibodies were not detected in any of the patients and the controls in the study. No association was found between propylthiouracile treatment and level of IAA. In none of 10 IAA-positive patients was the early phase insulin secretion of the intravenous glucose tolerance test below 46 mu units/ml, and in 2 subjects repeated tests after 3 years showed conserved insulin secretion. In conclusion, our findings show that 15% of patients with autoimmune thyroid diseases, produce specific IAA which do not seem to reflect aggressive beta cell destruction.


recA-dependent recombination between rRNA operons generates type II F' plasmids.
The formation of type II F' ilv cya metE plasmids from the Salmonella typhimurium Hfr strain SA722 occurs by general recombination between repeated rrn.


Loss of genetic variation in the two-locus multiallelic haploid model.
In the evolutionary biology literature, it is generally assumed that for deterministic frequency-independent haploid selection models, no polymorphic equilibrium can be stable in the absence of variation-generating mechanisms such as mutation. However, mathematical analyses that corroborate this claim are scarce and almost always depend upon additional assumptions. Using ideas from game theory, we show that a monomorphism is a global attractor if one of its alleles dominates all other alleles at its locus. Further, we show that no isolated equilibrium exists, at which an unequal number of alleles from two loci is present. Under the assumption of convergence of trajectories to equilibrium points, we resolve the two-locus three-allele case for a fitness scheme formally equivalent to the classical symmetric viability model. We also provide an alternative proof for the two-locus two-allele case.


Gallic acid alleviates gastric precancerous lesions through inhibition of epithelial mesenchymal transition via Wnt/β-catenin signaling pathway.
Gallic acid (GA) is a natural polyphenolic compound derived from Rhus chinensis Mill. with a variety of biological activities such as astringent sweat, cough, dysentery, hemostasis, and detoxification, and is widely used in China as a treatment for cough, bleeding, and gastrointestinal disorders. In recent years, the anticancer activity of GA has been demonstrated in a variety of cancers, affecting multiple cellular pathways associated with cancer onset, development and progression. To investigate the role and potential mechanism of GA on gastric precancerous lesions (GPL), the key turning point of gastritis to gastric cancer, with the aim of delaying, blocking or reversing the dynamic overall process of "inflammation-cancer transformation" and thus blocking GPL to prevent the development of gastric cancer. In this study, we established N-Nitroso-N-methylurea (MNU)-induced GPL mice model and induced precancerous lesions of gastric cancer cells (MC), i.e. epithelial mesenchymal transition (EMT), in human gastric mucosal epithelial cells (GES-1) with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). We used conventional pathology, immunohistochemistry, RNA sequencing, Western blot and other techniques to study the therapeutic effect of GA on GPL and its possiblemechanism in vitro and in vivo. The results showed that compared with normal GES-1 cells, MC cells had the characteristics of malignant cells such as abnormal proliferation, invasion and metastasis, accompanied by decreased expression of EMT-related protein E-cadherin and increased expression of N-cadherin and Vimentin. GA can inhibit the malignant behavior of MC cell proliferation and induce its G0/G1 phase arrest, which is achieved by downregulating the Wnt/β-catenin signaling pathway and thereby inhibiting the EMT process. However, when we incubated with the Wnt pathway activator (Wnt agonist 1), the effect of GA was reversed. Furthermore, analysis of human gastric specimens showed that activation of the Wnt/β-catenin pathway was significantly associated with GPL pathological changes. Meanwhile, GA reversed MNU-induced intestinal metaplasia and partial dysplasia in GPL mice. Taken together, these results indicate that GA prevents the occurrence and development of GPL by inhibiting the Wnt/β-catenin signaling pathway and then inhibiting the EMT process, which may become potential candidates for the treatment of GPL.


Ultrastructural and cytochemical studies on nucleolus-like bodies in early postimplantation rat embryos.
Fibrillar cytoplasmic bodies, generally referred to as nucleolus-like bodies (NLBs), have been observed in the embryonic ectodermal cells of early postimplantation rat embryos. The NLBs are not delineated by a membrane, and consist of 5-7 nm filaments. The diameter of the NLBs varies widely, but 0.7-1.2 micrometer is common. Small NLBs are frequently present in the vicinity of the nucleus, suggesting that the filamentous elements of the NLBs may originate from there, and also that these filaments may gradually gather and grow into the NLBs in the cytoplasm. Enzymatic treatment of ultrathin sections obtained from glycol methacrylate-embedded material reveal that a large part of NLBs is removed by digestion with pepsin or pronase, but that various fibrous materials remaining are sensitive to RNase digestion and stained with Bernhard's uranyl-EDTA method. These findings indicate that the NLBs consist of ribonucleoprotein.


A speech expression disorder in patients with severe diffuse brain injury who emerged from a vegetative or minimally conscious state.
The purpose of this study was to highlight a speech expression disorder considered as a mixed speech apraxia (SA) and dysarthria syndrome in patients with chronic severe diffuse brain injury (DBI) and to determine its correlation with anatomical localizations of brain lesions using neuroimaging. Among 140 patients with chronic severe DBI, eight showed this type of speech disorder. MRI (five patients) and FDG-PET (six patients) procedures were performed. Affected patients could comprehend verbally, read words silently and express words using a word board. Compared with SA, the disorder is characterized by similarities in regards to reduced phonation and marked facio-oral apraxia, but by distinct differences in terms of an accompanying dysphagia and pyramidal/extra-pyramidal symptoms that are similar to symptoms associated with dysarthria due to pseudobulbar palsy. Diffuse regions of the white matter including the left arcuate fasciculus (AF) were significantly decreased in fractional anisotropy value. However, there was no significant cortical metabolic damage in FDG-PET. The observed speech disorder in these patients is a characteristic entity related to dysfunction of speech expression and may be attributable to damage of not only the AF but also a number of fibres that are related to dysarthria, cognitive and emotional impairments and pyramidal/extra-pyramidal symptoms.


Principles and strategies of inclusive physical activity: a European Delphi study.
The article seeks to articulate a consensus of the opinions of a group of subject experts about the principles and strategies of inclusive physical activity. A 3-stage Delphi study involving a group of 34 Europe-based subject specialists was used to articulate shared expert opinions on the main research question: What are the key principles (general theories, values, or framework) that should guide practice of inclusive approaches to physical activity? What are the key strategies (practical approaches that can promote inclusive physical activity) of inclusive approaches to physical activity? Four core principles and four core strategies (and six less-supported principles/strategies for each) were identified through this process. The core principles were: focus on participants' needs; include disabled people in planning; focus on ability, not disability; and promote equal opportunities. The four core strategies were: adapt the rules and aims of the programme to the abilities of participants; apply adaptability of teaching/coaching methods; be accessible and available to participants; and establish models to make sure participants' voices are heard. The article concludes by offering ten concepts - drawn from the empirical findings - that might act as a starting-point for the development of the concept for an inclusive physical activity programme.


Clinical efficacy of different doses of lipo-prostaglandin E1 in the treatment of painful diabetic peripheral neuropathy.
To observe the clinical efficacy of different doses of alprostadil (lipo-prostaglandin E1, lipo-PGE1) in the treatment of painful diabetic peripheral neuropathy (DPN). Sixty patients with painful DPN were equally and randomly assigned into three groups. Two groups received different doses of lipo-PGE1 by intravenous drip injection (A group: low-dose lipo-PGE1; B group: high-dose lipo-PGE1) following intravenous bolus injection of mecobalamin (MeCbl, 0.5mg once daily (QD)); the third group received MeCbl alone (C group). All patients received optimized treatment to lower blood glucose, blood pressure, and blood lipids to target levels. The efficacy of lipo-PGE1 in the three groups of patients was observed after 3weeks of treatment. The overall response rate was 90% in the B group, significantly higher than that in the A and C groups (80% and 55%, respectively; P<0.05). During the observation period, there was no incidence of serious adverse reactions (e.g., acute heart failure, sudden drop in blood pressure, or malignant arrhythmias) in any of the three groups. High-dose lipo-PGE1 has better efficacy than low-dose lipo-PGE1 or MeCbl alone in the treatment of painful DPN.


Type III Sturge-Weber syndrome with migraine-like attacks associated with prolonged visual aura.
Sturge-Weber syndrome is known to be associated with migraine attacks and prolong aura even without cerebral infarction. We report the case of a 36-year-old woman with type III Sturge-Weber syndrome developing with prolonged left homonymous hemianopsia after an intractable migraine-like headache and becoming a permanent visual field defect at 18-month follow up. By adopting a multimodality imaging study, we suggested that the underlying mechanism of prolonged visual field defect was due to blood flow disturbance and vasogenic leakage under the leptomeningeal angioma combining with atrophy and the damaged integrity of white matter in right occipital lobe.


Comparison of PSA density and lesion volume strategies for selecting men with equivocal PI-RADS 3 lesions on bpMRI for biopsies.
To compare two strategies: Prostate-specific antigen density (PSAd) and lesion volume measurement in ruling out significant prostate cancer (sPCa) in men with equivocal Prostate Imaging Reporting and Data System (PI-RADS) category 3 index lesions on biparametric magnetic resonance imaging. In total, 130 men from our database had index lesions with PI-RADS scores of 3. Prostate volume was measured using the ellipsoid method, in accordance with PI-RADS version 2.1 criteria. Index lesion volumes were also measured using the ellipsoidal formula on the diffusion-weighted imaging sequence with the highest b-value and sagittal T2 sequences. Among 130 men with PI-RADS category 3 index lesions, 23 (18%) had sPCa. In total, 6 of the 89 men with PSAd < 0.15 ng/mL2 (7%) had sPCa, whereas 8 of the 49 men with index lesion volumes < 0.5 mL (16%) had sPCa. The difference was statistically significant (McNemar, p < 0.0001). The PSAd strategy performed better than the lesion volume strategy in ruling out sPCa in men with equivocal PI-RADS category 3 index lesions.


Multiple agminated Spitz nevi: report of two cases and review of the literature.
Spitz nevus is most commonly a benign solitary lesion. Multiple lesions arranged in clusters (agminated) are very rare. Malignant degeneration has not been reported. Although spontaneous involution may occur, the nevi are frequently treated by surgical excision. We describe two preschool girls with multiple agminated Spitz nevi, and review the current world literature on multiple Spitz nevi.


Status epilepticus alters neurogenesis and decreases the number of GABAergic neurons in the septal dentate gyrus of 9-day-old rats at the early phase of epileptogenesis.
The effects of a prolonged seizure, i.e. status epilepticus (SE), on neurogenesis of dentate granule cells (DGCs) in the immature dentate gyrus (DG) and possible changes in the phenotypes of the newborn neurons have remained incompletely characterized. We have now studied neurogenesis of DGCs in 9-day-old (postnatal, P9) rats 1 week after kainate (KA)-induced SE using 5-bromo-2-deoxyuridine (BrdU) immunostaining. The phenotype characterization of the newborn cells was carried out by immunofluorescence double labeling using doublecortin (DCX) and nestin as markers for immature cells, and glial fibrillary acid protein (GFAP) as a marker for glial cells. Newborn GABAergic neurons were further identified with antibodies for parvalbumin, glutamate decarboxylase 67 (GAD67), and the GABAA receptor α1 subunit, and mRNA expression of GABAergic and immature neurons was measured with quantitative real-time PCR (qPCR) in the DG. Our results show that the number of newborn as well as GABAergic neurons was significantly decreased after SE in the superior blade of the septal DG. The majority of the newborn BrdU-stained neurons co-expressed DCX, but neither nestin nor GFAP. In both experimental groups, newborn neurons were frequently localized in close contact, but not co-localized, with the cells positively stained for the GABAergic cell markers. Nestin and calretinin mRNA expression were significantly increased after SE. Our results suggest that SE-induced disruption of DGC neurogenesis and decreased number of GABAergic neurons could modify the connectivity between these cells and disturb the maturation of the GABAergic neurotransmission in the immature DG at the early epileptogenic phase.


Familial generalized resistance to thyroid hormones: report of three kindreds and correlation of patterns of affected tissues with the binding of [125I] triiodothyronine to fibroblast nuclei.
We here report three kindreds with a total of 19 persons affected with central and peripheral resistance to thyroid hormones: one kindred with 10 affected persons is the largest reported to date. Male to male transmission of the syndrome was evident in two kindreds, consistent with an autosomal dominant mode of inheritance. During several years of follow up, the degree of resistance to thyroid hormones did not ameliorate. Within a given kindred, a given tissue or tissues was consistently more resistant to thyroid hormone than other tissues. The pattern of tissues most affected in one kindred differed from that of another kindred, perhaps reflecting the inherited underlying molecular defects. Members of kindred A frequently had bone involvement, and several had learning disabilities and recurring infections, while most members of kindreds B and C had little bone involvement, but marked hepatic and cardiac resistance to thyroid hormones. Kinetic studies of the binding of [125I] triiodo-L-thyronine to nuclei from skin fibroblasts from affected patients from each of the kindreds demonstrated decreased maximum binding as compared to normal fibroblasts, but there was no correlation between this parameter and other features of the disease. Four of the 19 patients had previously been treated inappropriately with antithyroid therapies, demonstrating how the syndrome may be readily confused with Graves' disease by some clinicians. Behavior or school performance improved in all children treated with thyroid hormones, and a growth spurt was documented in six children, but objective improvement in IQ scores was not demonstrated, suggesting that initiation of hormone therapy at an early age may be important for maximum benefit.


Peritoneal cytokines and adhesion formation in endometriosis: an inverse association with vascular endothelial growth factor concentration.
To evaluate inflammatory/angiogenic cytokines-interleukin-1β (IL-1β), IL-6, IL-8, IL-12, interferon-γ (IFN-γ), tumor necrosis factor (TNF), and vascular endothelial growth factor A (VEGF-A)-in the peritoneal fluid of patients with endometriosis in relation to the occurrence and severity of pelvic adhesions and in control women without pelvic pathology. Case-control study. University research institution and hospital. Sixty-five women with laparoscopically and histopathologically confirmed endometriosis, including 40 women with pelvic adhesions, and 37 control women without pelvic pathology. Peritoneal fluid aspirated during routine diagnostic laparoscopic examination. Cytokines evaluated in the peritoneal fluid via specific enzyme-linked immunosorbent assays. Endometriosis and the revised American Fertility Society score of this disease were associated with statistically significantly increased levels of peritoneal IL-6 and IL-8 whereas the incidence and score of endometriosis-related pelvic adhesions were negatively associated with increased levels of VEGF-A. Notably, the concentration of VEGF-A predicted adhesion development and severity after adjustment for endometriosis severity. The adhesion score also correlated with increased levels of IL-6; however, after adjustment for endometriosis severity, the effect of this cytokine was no longer statistically significant. Increased levels of VEGF-A may be associated with a decreased rate of pelvic adhesion formation in the course of endometriosis.


Metabolomic Profiling of Phloem Sap from Different Pine Species and Implications on Black Capuchin.
In most commercial pine farms in southern Brazil, black capuchin causes damage to wood and financial losses when it removes bark from some pine species to feed upon underlying vascular tissues. Therefore, this study aimed to evaluate the variability of the primary metabolites of phloem saps from 10 different species of pine by NMR spectroscopy, as well as the aroma compounds using SPME-GC-MS. Each technique provided a different set of metabolites that we can correlate to monkey predilection. The PCA showed monosaccharide (detected by NMR) and α-pinene (pine-like and resinous flavor descriptors) as attractive compounds for monkeys. On the other hand, the low content of monosaccharide and the high content of β-phellandrene (citrus odor descriptor) was observed in less attacked pine species (P. patula). The data fusion on primary metabolites and aroma compounds corroborated the individual analyses, complementing the comprehension of the monkey predilection. Thus, P. elliottii was an avoided tree even with high content of sugars possibly due to its high content of β-phellandrene (citrus odor). The results are useful for further behavioral studies to determine the role that each highlighted metabolite plays in chemically mediated animal-plant interactions.


Tooth automatic segmentation from CBCT images: a systematic review.
To describe the current state of the art regarding technological advances in full-automatic tooth segmentation approaches from 3D cone-beam computed tomography (CBCT) images. In March 2023, a search strategy without a timeline setting was carried out through a combination of MeSH terms and free text words pooled through Boolean operators ('AND', 'OR') on the following databases: PubMed, Scopus, Web of Science and IEEE Explore. Randomized and non-randomized controlled trials, cohort, case-control, cross-sectional and retrospective studies in the English language only were included. The search strategy identified 541 articles, of which 23 have been selected. The most employed segmentation methods were based on deep learning approaches. One article exposed an automatic approach for tooth segmentation based on a watershed algorithm and another article used an improved level set method. Four studies presented classical machine learning and thresholding approaches. The most employed metric for evaluating segmentation performance was the Dice similarity index which ranged from 90 ± 3% to 97.9 ± 1.5%. Thresholding appeared not reliable for tooth segmentation from CBCT images, whereas convolutional neural networks (CNNs) have been demonstrated as the most promising approach. CNNs could help overcome tooth segmentation's main limitations from CBCT images related to root anatomy, heavy scattering, immature teeth, metal artifacts and time consumption. New studies with uniform protocols and evaluation metrics with random sampling and blinding for data analysis are encouraged to objectively compare the different deep learning architectures' reliability. Automatic tooth segmentation's best performance has been obtained through CNNs for the different ambits of digital dentistry.


Direct calculation of the ionic mobility in superionic conductors.
We describe an approach based on non-equilibrium molecular dynamics (NEMD) simulations to calculate the ionic mobility of solid ion conductors such as solid electrolytes from first-principles. The calculations are carried out in finite slabs of the material, where an electric field is applied and the dynamic response of the mobile ions is measured. We compare our results with those obtained from diffusion calculations, under the non-interacting ion approximation, and with experiment. This method is shown to provide good quantitative estimates for the ionic mobilities of two silver conductors, [Formula: see text]-AgI and [Formula: see text]-RbAg[Formula: see text]I[Formula: see text]. In addition to being convenient and numerically robust, this method accounts for ion-ion correlations at a much lower computational cost than exact approaches.


End-plate growth exceeds nerve terminal growth in juvenile mice.
An electron microscopic investigation of neuromuscular synapses of the tensor fasciae latae muscle in juvenile mice was carried out to determine the relationship between the presynaptic (nerve terminal) and postsynaptic (end-plate plaque) elements during the major phase of postnatal growth. In the first month of life growth of the synapse was accompanied by a decrease in the size of pre- and postsynaptic elements in cross section. A decrease in the fraction of the width of end-plate plaque opposed by nerve terminal was also observed to age 2 months, and in older animal some end-plate plaques were completely unopposed by nerve terminal. This implies that end plates grow at a faster rate than nerve terminals and suggests that the availability of uninnervated, differentiated end plate permits or promotes nerve terminal growth.


Beyond COVID-19: DO MS/NMO-SD patients treated with anti-CD20 therapies develop SARS-CoV2 antibodies?
Since 2019, a new coronavirus infection (COVID-19) due to an agent called SARS-CoV-2 spread rapidly worldwide. Patients with multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMO-SD) are often treated with immunosuppressants. Beyond their effect on the risk of COVID-19 infection, the consequences on the long-term immune response against the coronavirus remain unknown. Among 13 MS or NMOSD patients with confirmed COVID-19 included, all 5 patients treated with anti-CD20 therapies had a negative SARS-CoV-2 serology. To date, maximal precautions to prevent coronavirus infection should be maintained in MS/NMOSD patients already exposed to COVID-19 during anti-CD20 therapy.


Primal-scene experiences: quantitative assessment of an interview study.
Data are reported from detailed semistructured interviews with 25 males and 25 females, 18-30 years of age. Special attention is given to age and reactions at time of initial awareness of parents' sexual relationship and at time of any possible primal-scene witnessing, beliefs about parents' present sex lives, and interviewees' own ideas of how their parents' sexual attitudes and relationship may have influenced them. Particularly interesting are data indicating that primal-scene experiences, including actual witnessing, do not necessarily result in pathological consequences for psychosexual functioning or satisfaction. The importance of family-relationship patterns as determinants of reactions to primal-scene experience is emphasized.


Screening the hub genes and analyzing the mechanisms in discharged COVID-19 patients retesting positive through bioinformatics analysis.
After encountering COVID-19 patients who test positive again after discharge, our study analyzed the pathogenesis to further assess the risk and possibility of virus reactivation. A separate microarray was acquired from the Gene Expression Omnibus (GEO), and its samples were divided into two groups: a "convalescent-RTP" group consisting of convalescent and "retesting positive" (RTP) patients (group CR) and a "healthy-RTP" group consisting of healthy control and RTP patients (group HR). The enrichment analysis was performed with R software, obtaining the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Subsequently, the protein-protein interaction (PPI) networks of each group were established, and the hub genes were discovered using the cytoHubba plugin. In this study, 6622 differentially expressed genes were identified in the group CR, among which RAB11B-AS1, DISP1, MICAL3, PSMG1, and DOCK4 were up-regulated genes, and ANAPC1, IGLV1-40, SORT1, PLPPR2, and ATP1A1-AS1 were down-regulated. 7335 genes were screened in the group HR, including the top 5 up-regulated genes ALKBH6, AMBRA1, MIR1249, TRAV18, and LRRC69, and the top 5 down-regulated genes FAM241B, AC018529.3, AL031963.3, AC006946.1, and FAM149B1. The GO and KEGG analysis of the two groups revealed a significant enrichment in immune response and apoptosis. In the PPI network constructed, group CR and group HR identified 10 genes, respectively, and TP53BP1, SNRPD1, and SNRPD2 were selected as hub genes. Using the messenger ribonucleic acid (mRNA) expression data from GSE166253, we found TP53BP1, SNRPD1, and SNRPD2 as hub genes in RTP patients, which is vital to the management and prognostic prediction of RTP patients.


Neurologic complications of erythema-migrans-disease in childhood--clinical aspects.
Erythema-migrans-disease represents a tick-borne borreliosis with a high and widespread incidence according to first epidemiological surveys. The early symptom is a distinctive erythema migrans eventually followed by arthritis and cardiac involvement as well as neurologic complications in the form of lymphocytic meningoradiculitis Garin-Bujadoux-Bannwarth. In a one-year-period we observed 9 children who developed neurologic complications as the predominant feature of erythema-migrans-disease. Eight children suffered from a lymphocytic meningitis and/or a peripheral facial palsy and one child presented with a severe polyradiculoneuritis with complete transverse myelitis. In contrast to adults the clinical course of neurologic manifestations in children seems to be milder and shorter and not associated with the typical painful radiculitis. Acute Bell's palsy seems to be a rather common symptom, whereas other peripheral pareses of the mononeuritis multiplex type were not observed. With respect to the assumed frequency and because of the possibility of antibiotic therapy, erythema-migrans-disease should be ruled out in any case of so-called idiopathic facial palsy or aseptic meningitis, which are frequently encountered in children.


FOAM ROLLING AND INDICES OF AUTONOMIC RECOVERY FOLLOWING EXERCISE-INDUCED MUSCLE DAMAGE.
With the increased popularity of foam rolling as a recovery tool, it is important to explore possible mechanisms of action toward mitigating soreness and restoring athletic performance. The purpose of the present experiment was to assess the influence of foam rolling on gross measures of physical performance and indices of autonomic function following exercise-induced muscle damage (EIMD). In a between-group design, 40 participants performed a session of 40x15 meter sprints, inducing muscle damage. Immediately following sprinting and in the four days following, heart rate variability and pulse wave velocity were recorded, in addition to perceived muscle soreness, vertical jump, and agility. Nineteen subjects (mean±sd; age 23.1±5.0 yrs; BMI 25.6±3.3 kg.m-2) foam rolled their quadricep, gluteal, and gastrocnemius areas prior to testing each day, while 21 (mean±sd; age 24.2±3.4 yrs; BMI 26.3±4.0 kg.m-2) served as a control. Mean values from three days of baseline testing were compared to the area under the curve during five days of recovery after the performance of the repeated sprint protocol. The area under the curve was calculated by summing all five values recorded the recovery days, then these data were compared by condition using a two-tailed Mann-Whitney U test (alpha level = 0.05). Following EIMD, neither heart rate variability, pulse wave velocity, agility, nor vertical jumping performance versus previously measured baseline differed significantly between groups (p>0.05). Perceived muscle soreness was significantly diminished in the foam rolling condition (p<0.05). Mean Day 1 to Day 5 values for perceived muscle soreness in controls were 16.52, 30.24, 24.48, 17.19, and 11.10. Mean Day 1 to Day 5 values in foam rolling subjects were 12.63, 24.63, 21.79, 15.05, and 10.16. Foam rolling may be useful for reducing soreness following damaging exercise, but according to the outcomes measured in the present experiment, the effect does not appear to be mediated by the autonomic nervous system. 2c.


In Situ and ex Situ Study of Cubic La0.5Ba0.5CoO3-δ to Double Perovskite LaBaCo2O6-δ Transition and Formation of Domain Textured Phases with Fast Oxygen Exchange Capability.
The disordered La0.5Ba0.5CoO3-δ ↔ ordered LaBaCo2O6-δ transition was studied in detail using several complementary in situ (X-ray diffraction, thermogravimetry, and coulometric titration) and ex situ (transmission electron microscopy) techniques. This transition was found to proceed through the formation of complex domain textured intermediate products. They were shown to have strong affinity to oxygen and exhibit its fast absorption from ambient atmosphere (oxygen partial pressure ( pO2) 0.21 atm) at a temperature as low as 70 °C. The thermodynamic stability limits of the cubic and double perovskites were determined by coulometric titration. The stability diagram of the LaBaCo2O6-δ - La0.5Ba0.5CoO3-δ system was plotted as a result. Oxygen nonstoichiometry of the thermodynamically stable cubic perovskite La0.5Ba0.5CoO3-δ was measured as a function of pO2 in the temperature range between 1000 and 1100 °C using a coulometric titration technique.


Drug resistance related genes in lung adenocarcinoma predict patient prognosis and influence the tumor microenvironment.
Lung adenocarcinoma (LUAD) is the predominant type of non-small lung cancer (NSCLC) with strong invasive ability and poor prognosis. The drug resistance related genes are potentially associated with prognosis of LUAD. Our research aimed to identify the drug resistance related genes and explore their potential prognostic value in LUAD patients. The data used in this study were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Firstly, we screened drug resistance related genes in LUAD by differential gene analysis, univariate Cox regression and drug sensitivity analyses. Subsequently, we constructed a risk score model using LASSO Cox regression analysis, and verified whether the risk score can predict the survival of LUAD patients independent of other factors. Moreover, we explored the immune infiltration of 22 immune cells between high-risk and low-risk patients. Totally 10 drug-resistance positively related genes (PLEK2, TFAP2A, KIF20A, S100P, GDF15, HSPB8, SASH1, WASF3, LAMA3 and TCN1) were identified in LUAD. The risk score model of LUAD constructed with these 10 genes could reliably predict the prognosis of LUAD patients. 18 pathways were significantly activated in high-risk group compared with low-risk group. In addition, the infiltration proportion of multiple immune cells was significantly different between high-risk and low-risk groups, and the proportion of M1 phagocytes was significantly higher in the high-risk group compared with the low-risk group. The drug resistance related genes (PLEK2, TFAP2A, KIF20A, S100P, GDF15, HSPB8, SASH1, WASF3, LAMA3 and TCN1) could predict the prognosis of LUAD patients. Clarifying the roles and mechanisms of these 10 genes in regulating drug resistance in LUAD will help to improve individualized clinical treatment protocols and predict patient sensitivity to treatment.


Fine structural changes in electrostimulated human skeletal muscle. Evidence for predominant effects on fast muscle fibres.
Physical education students were subjected to electrical stimulation of relatively high frequency and current amplitude for 19 days. A quantitative study of several morphological parameters was performed on biopsy samples from gastrocnemius, using stereological methods at both light and electron microscopic levels. The main results were: muscle fibre size was increased; nuclear volume was also increased, suggesting that a proliferation of nuclei had occurred; this was paralleled by an increased content of nuclear DNA. The size of single myonuclei was increased, and their heterochromatin fraction was decreased, these changes being most pronounced in type II fibres. The increase in the mitochondrial fraction was also greatest in type II fibres. It is concluded that this type of electrical stimulation has predominant effects on type II fibres.


Wegener's granulomatosis.
WG is an uncommon disease process with considerable risk of mortality if diagnosis and treatment are delayed. Skin, sinus, or oral mucosal lesions may be part of the initial presentation. This article provided the clinician with information concerning recognition, diagnosis, and treatment of WG. Early recognition and treatment are essential in limiting the potentially life-threatening aspects of the disease.


The suppression effects of thalidomide on human lung fibroblasts: cell proliferation, vascular endothelial growth factor release, and collagen production.
Expression of transforming growth factor (TGF)-β1 and increases in angiogenesis and deposition of extracellular matrix are the key features of tracheal granulation formation. The aim of this study was to investigate the potential role of thalidomide in preventing granulation tissue formation from the aspect of cellular effects in vitro, including fibroblast proliferation, vascular endothelial growth factor (VEGF) release, and collagen production. Human lung fibroblasts were obtained from bronchus and cultured. The effects of thalidomide on cell proliferation, migration, TGF-β1-induced VEGF, and signal pathway were investigated. Thalidomide (20 μM) not only inhibited cell proliferation after 24 h [fold increase of cell number, 0.85 ± 0.09 vs. 1.47 ± 0.14 (treatment vs. control group); P < 0.01] and 48 h of incubation (0.85 ± 0.10 vs. 1.97 ± 0.12; P < 0.001), it also inhibited cell migration and slowed wound closure at 24 h (P < 0.001). Thalidomide significantly attenuated TGF-β1-induced VEGF expression at both the mRNA and protein levels. Incubation of thalidomide with cells stimulated with TGF-β1 significantly inhibited their production of collagen. Thalidomide inhibited Smad3, STAT3, and subsequent p44/42 kinase phosphorylation. Thalidomide may inhibit human fibroblast proliferation and it is worthy of further in vivo investigation.


Determining nucleolar multiplicity and cell number from sectional data.
The occurrence of more than one nucleolus within the cellular nucleus (polynucleolarity) is a well-known phenomenon during the proliferative cell cycle, both under normal and pathological conditions (e.g. neoplasia). It can also be observed in neuronal nuclei at early stages of their maturation. Polynucleolarity merits investigation for cytological reasons. In an histological section, the observed number of nucleoli in a nucleus may be smaller than the actual number. In order to estimate the true distribution of the number of nucleoli per nucleus from the observed distribution, the mathematical relation between these distributions is derived on the basis of rather restrictive stereological assumptions. It is indicated how these distributions can be estimated from the data available and how the statistical uncertainties involved can be expressed. This paper arose from making cell counts. Two methods may be applied: all visible nuclear profiles are counted, nuclear profiles are only included if at least one nucleolus is visible in the section. We recommended a combination of these two methods. An advantage of our theory for determining cell number is that one can often manage without the rather restrictive stereological assumptions needed hitherto. The advantage of expressing statistical uncertainties in estimated nucleolar multiplicity probabilities and cell numbers is indicated.


Comparable outcome of alternative donor and matched sibling donor hematopoietic stem cell transplant for children with acute lymphoblastic leukemia in first or second remission using alemtuzumab in a myeloablative conditioning regimen.
HLA-matched sibling donor (MSD) stem cell transplantation can cure>60% of pediatric patients with acute lymphoblastic leukemia (ALL), but <30% of patients will have a sibling donor. Alternative donor (AD) transplantation can be curative but has a higher risk of graft-versus-host disease (GVHD). The addition of alemtuzumab (Campath 1-H) to AD transplants produces in vivo T cell depletion, which may reduce the risk for GVHD. We now report the outcome for 83 children with ALL (41 MSD, 42 AD) undergoing stem cell transplantation in first or second complete remission. All patients received myeloablative conditioning, including cyclophosphamide, cytarabine arabinoside, and total-body irradiation, with alemtuzumab administered to AD recipients. GVHD prophylaxis consisted of a calcineurin inhibitor with either short-course methotrexate or prednisone. Disease-free survival (DFS) for MSD recipients was 72.3% (95% confidence interval [CI], 55.4%-83.6%) versus 62.4% (95% CI, 45.2%-75.4%) for AD recipients. The 100-day mortality was 7.1% in the AD group and 2.4% in the MSD group. Relapse rates were identical (24%). Treatment-related mortality, principally viral infection, explained the difference in survival. For children undergoing stem cell transplantation (SCT) from alternative donors, alemtuzumab with a myeloablative conditioning regimen resulted in DFS comparable to MSD.


Roles of acid-extruding ion transporters in regulation of breast cancer cell growth in a 3-dimensional microenvironment.
The 3-dimensional (3D) microenvironment of breast carcinomas is characterized by profoundly altered pH homeostasis, reflecting increased metabolic acid production and a confined extracellular space characterized by poor diffusion, yet the relative contributions of specific pH-regulatory transporters to 3D growth are poorly understood. The aim of this work was to determine how 3D spheroid growth of breast cancer cells impacts the expression and spatial organization of major acid extruding proteins, and how these proteins in turn are required for spheroid growth. MCF-7 (Luminal-A) and MDA-MB-231 (Triple-negative) human breast cancer cells were grown as ~700-950 μm diameter spheroids, which were subjected to Western blotting for relevant transporters (2- and 3D growth), quantitative immunohistochemical analysis, and spheroid growth assays. Individual transporter contributions were assessed (i) pharmacologically, (ii) by stable shRNA- and transient siRNA-mediated knockdown, and (iii) by CRISPR/Cas9 knockout. In MCF-7 spheroids, expression of the lactate-H(+) cotransporter MCT1 (SLC16A1) increased from the spheroid periphery to its core, the Na(+),HCO3 (-) cotransporter NBCn1 (SLC4A7) was most highly expressed at the periphery, and the Na(+)/H(+) exchanger NHE1 (SLC9A1) and MCT4 (SLC16A3) were evenly distributed. A similar pattern was seen in MDA-MB-231 spheroids, except that these cells do not express MCT1. The relative total expression of NBCn1 and NHE1 was decreased in 3D compared to 2D, while that of MCT1 and MCT4 was unaltered. Inhibition of MCT1 (AR-C155858) attenuated MCF-7 spheroid growth and this was exacerbated by addition of S0859, an inhibitor of Na(+),HCO3 (-) cotransporters and MCTs. The pharmacological data was recapitulated by stable knockdown of MCT1 or NBCn1, whereas knockdown of MCT4 had no effect. CRISPR/Cas9 knockout of NHE1, but neither partial NHE1 knockdown nor the NHE1 inhibitor cariporide, inhibited MCF-7 spheroid growth. In contrast, growth of MDA-MB-231 spheroids was inhibited by stable or transient NHE1 knockdown and by NHE1 knockout, but not by knockdown of NBCn1 or MCT4. This work demonstrates the distinct expression and localization patterns of four major acid-extruding transporters in 3D spheroids of human breast cancer cells and reveals that 3D growth is dependent on these transporters in a cell type-dependent manner, with potentially important implications for breast cancer therapy.


Cannibalism in whitefish (Coregonus lavaretus).
Cannibalism in whitefish (Coregonus lavaretus) is studied on the basis of an evolutionary model. The model predicts that individuals may be cannibalistic if they gain sufficiently in terms of fitness relative to the reduction in survival caused by this behaviour. If cannibalistic forms mainly increase survival it is predicted that cannibalism is particularly likely to be an evolutionarily optimal strategy if only a few age classes are being cannibalized and if, simultaneously, many age classes are cannibalistic. The same pattern, although less apparent, emerges on the basis of a model assuming that cannibalistic forms mainly increase fecundity.The whitefish in River Sokna spawn during late October to late November. Males dominate the spawning run numerically. Growth rate in mature stages is low, 1.0 cm·y-1 for males and 1.3 cm·y-1 for females. Yearly survival rate in mature stages is 0.574, and survival from egg to mature is 0.000078%. Larger whitefish on the average lay more and larger eggs than do smaller. Females were more cannibalistic than males; in total cannibalism contributed to an egg mortality of at least 8.8%. This is consistent with the derived theoretical predictions.Our theoretical and empirical analyses on whitefish are supported by the observed lack of sexual differences in the cannibalistic behaviour of brown trout (Salmo trutta) and Arctic char (Salvelinus alpinus).


A quantitative assessment of the carcinogenicity of hexavalent chromium by the oral route and its relevance to human exposure.
Hexavalent chromium (Cr(6+)) has long been recognized as an inhalation carcinogen. Useful data on its carcinogenicity by ingestion have been slower to develop. The 2008 NTP chronic bioassay of sodium dichromate dihydrate in drinking water found clear evidence of carcinogenicity in rodents and allows a generalizable estimate of the human ingestion cancer potency of Cr(6+). To estimate the human ingestion cancer potency of Cr(6+) and evaluate its relevance for human exposure. Tumors of the small intestine in male mice were selected as the critical endpoint, for the derivation of cancer potency. Following the 2005 USEPA Cancer Risk Assessment Guidelines, the point of departure in the dose-response data was defined using benchmark-dose modeling. Linear extrapolation was carried out from the point of departure and interspecies dose conversion was based on allometric scaling of body weight. Small intestine tumor incidence in male mice provided a robust and nearly identical fit with most available dose-response models using benchmark-dose modeling. A human equivalent cancer slope factor of 0.5 (mg/kg/day)(-1) was derived based on linear extrapolation from the point of departure. Statistical and kinetic analysis carried out on the NTP data as well as data reported in other studies support that the carcinogenicity of Cr(6+) did not result from an exceedance of the reduction capacity of the mouse gastrointestinal tract at the doses in the NTP study. Mouse gastric emptying time and human Cr(6+) dosing studies strongly suggest that even at doses considerably lower than those in the NTP study, Cr(6+) escapes reduction in both the mouse and human stomachs due to kinetic competition from Cr(6+) absorption and gastric emptying. The cancer potency derived from the NTP data is, therefore, deemed to be relevant and applicable to human exposure. Cr(6+) is, therefore, identified as "likely to be carcinogenic to humans" in accordance with the USEPA's cancer characterization rubric.


Effects of chilled-then-frozen storage (up to 52weeks) on an indicator of protein oxidation and indices of protein degradation in lamb M. longissimus lumborum.
This study investigated the protein oxidation properties of lamb following chilled-then-frozen storage. Experimental (n=360) M. longissimus lumborum (LL) were randomly sampled from the boning room of a commercial Australian abattoir, at 24h post mortem, and assigned to five chilled storage periods (0, 2, 4, 6 and 8weeks) and six subsequent frozen storage periods (0, 4, 8, 12, 24 and 52weeks). Upon completion of each storage treatment combination, corresponding LL were sub-sectioned and analysed for carbonyl content, protein solubility, nitrate/nitrite content, particle size analysis and estimated myoglobin fractions. The association between these protein measures and shear force was also explored. During chilled storage, particle size and sarcoplasmic protein solubility decreased which indicated protein degradation, while frozen storage only affected myoglobin oxidation. Tenderness was best explained by decreased particle size, decreased deoxymyoglobin and increased oxymyoglobin. No carbonyl effects were observed. It can be concluded that, according to these analyses, that in chilled-then-frozen lamb carbonyl formation was negligible.


Relationships among pain, fatigue, insomnia, and gender in persons with lung cancer.
To examine the relationships among pain, fatigue, insomnia, and gender while controlling for age, comorbidities, and stage of cancer in patients newly diagnosed with lung cancer within 56 days of receiving chemotherapy. Secondary data analysis. Accrual from four sites: two clinical community oncology programs and two comprehensive cancer centers. 80 patients newly diagnosed with lung cancer. Analysis from baseline observation of a randomized clinical intervention trial. Multinomial log-linear modeling was performed to explain the relationships among pain, fatigue, insomnia, and gender. Pain, fatigue, insomnia, and gender. For all people with lung cancer, fatigue (97%) and pain (69%) were the most frequently occurring symptoms; insomnia occurred 51% of the time. A model containing all main effects (two-way interactions of pain and fatigue, pain and insomnia, and insomnia and gender; and the three-way interaction of pain, fatigue, and insomnia, along with three covariates [age, comorbidities, and stage of cancer]) was a good fit to the data. Parameter estimates indicated that a statistically significant effect from the model was the three-way interaction of pain, fatigue, and insomnia. Gender did not make a difference. Age, comorbidities, and stage of cancer were not significant covariates. For people newly diagnosed with lung cancer undergoing chemotherapy, multiple symptoms occur simultaneously rather than in isolation; a symptom cluster exists, consisting of pain, fatigue, and insomnia; and no relationship was found among gender, pain, fatigue, and insomnia. By understanding this symptom cluster, healthcare providers can target specific troublesome symptoms to optimize symptom management and achieve the delivery of high-quality cancer care.


Concentrations of passively acquired IgG1 antibodies in the intestinal lumen of the neonatal calf.
Passively acquired specific antibodies in the intestinal lumen are thought to provide protective immunity against infections with rotaviruses and other enteropathogens. In this study, concentrations of functional antibody in the intestinal lumen derived from diet and circulation were measured using 2,4-dinitrophenol (DNP) specific antibody of the IgG1 isotype, radiolabelled with 125I. The labelled IgG1 antibody was administered to neonatal calves either orally in the daily milk diet for three consecutive days (Group 1), or by a single intravenous injection (Group 2). After equilibration, the concentrations of protein-bound 125I and the specific DNP binding activities of the labelled protein in the intestinal lumen were measured, and intestinal concentrations of functional IgG1 were estimated. In Group 1 calves, protein bound 125I concentrations in the pooled small intestinal contents at 2 and 12 h after a milk meal were 50.8 +/- 20.5% and 7.9 +/- 3.4%, respectively, of the milk concentration. Protein bound 125I concentrations in the small intestinal contents were 0.7 +/- 0.4% (mean +/- SD) of serum concentrations of Group 2 calves, and were similar at 2 and 12 h after a milk meal. For a calf with average serum passive IgG1 concentrations drinking milk with normal IgG1 content, these results predict IgG1 concentrations in the small intestinal contents of milk fed calves at 2 h after a milk meal to be 0.6 mg ml-1, half of which originates from the milk and half from the circulation. At 12 h after a milk meal, intestinal IgG1 concentrations fall to approximately 0.3 mg ml-1, most of which originates from the circulation. Antibody in the intestinal lumen originating from serum retained more antigen (DNP) binding affinity than that ingested in the milk diet. Therefore, both dietary and circulating IgG1 contribute significantly to passive IgG1 antibody concentrations in the small intestinal lumen of neonatal calves, but milk derived IgG1 antibody concentrations in the small intestinal lumen were not maintained between twice daily feedings.


Cysteine conjugates of acetaminophen and p-aminophenol are potent inducers of cellular impairment in human proximal tubular kidney HK-2 cells.
Acetaminophen (APAP) belong among the most used analgesics and antipyretics. It is structurally derived from p-aminophenol (PAP), a potent inducer of kidney toxicity. Both compounds can be metabolized to oxidation products and conjugated with glutathione. The glutathione-conjugates can be cleaved to provide cysteine conjugates considered as generally nontoxic. The aim of the present report was to synthesize and to purify both APAP- and PAP-cysteine conjugates and, as the first study at all, to evaluate their biological effects in human kidney HK-2 cells in comparison to parent compounds. HK-2 cells were treated with tested compounds (0-1000 µM) for up to 24 h. Cell viability, glutathione levels, ROS production and mitochondrial function were determined. After 24 h, we found that both APAP- and PAP-cysteine conjugates (1 mM) were capable to induce harmful cellular damage observed as a decrease of glutathione levels to 10% and 0%, respectively, compared to control cells. In addition, we detected the disappearance of mitochondrial membrane potential in these cells. In the case of PAP-cysteine, the extent of cellular impairment was comparable to that induced by PAP at similar doses. On the other hand, 1 mM APAP-cysteine induced even larger damage of HK-2 cells compared to 1 mM APAP after 6 or 24 h. We conclude that cysteine conjugates with aminophenol are potent inducers of oxidative stress causing significant injury in kidney cells. Thus, the harmful effects cysteine-aminophenolic conjugates ought to be considered in the description of APAP or PAP toxicity.


Halogen-substituted trimetoquinol analogs as thromboxane A2 receptor antagonists in platelets and aorta.
Trimetoquinol (TMQ) is a non-prostanoid compound that blocks prostaglandin H2/thromboxane A2 (TXA2) receptor-mediated responses initiated by a prostaglandin (PG) H2 analog, U46619, in human platelets and rat aorta. Ring fluorine-substituted TMQ analogs selectively antagonized PG-dependent human platelet activation induced by U46619, arachidonic acid, collagen, ADP or epinephrine; and were about 300-fold less potent as inhibitors of PG-independent responses mediated by thrombin or bacterial phospholipase C. For each inducer of the PG-dependent pathway, the rank order of inhibitory potency was identical (TMQ > 8-fluoro-TMQ > 5-fluoro- TMQ). Iodine substitution yielded a similar rank order of antagonism against U46619-induced platelet activation (TMQ > 8-iodo-TMQ > 5-iodo-TMQ), and all TMQ analogs inhibited platelet aggregation in whole blood as well as in platelet-rich plasma. Inhibition of specific [3H]SQ 29,548 binding by TMQ analogs was highly correlated with inhibition of functional responses to U46619. Radioligand binding experiments using TMQ analogs with rat platelets showed no interspecies difference in comparison with human platelets. The rank order of inhibitory potencies for the fluorinated (but not iodinated) TMQ analogs changed in rat thoracic aorta with 8-fluoro-TMQ > TMQ > or = 5-fluoro-TMQ as antagonists of U46619-induced vascular contraction. These findings demonstrate that the primary mechanism of antiplatelet action of TMQ analogs is related to a blockade of TXA2 receptor sites, and ring-halogenated TMQ analogs distinguish between TXA2-mediated functional responses in vascular smooth muscle and platelets.


Sympathetic thyroidal vasoconstriction is not blocked by a neuropeptide Y antagonist or antiserum.
Sympathetic nerve fibers to thyroid blood vessels contain both norepinephrine (NE) and neuropeptide Y (NPY). To assess the involvement of endogenous NPY in the sympathetic neural control of thyroid blood flow, appropriate doses of a selective NPY antagonist, alpha-trinositol, and an NPY antiserum (NPY-AS) were used during cervical sympathetic trunk stimulation in anesthetized rats. During all experiments, thyroid blood flow was continuously monitored by laser Doppler blood flowmetry. Neither alpha-trinositol nor NPY-AS blocked the thyroidal vasoconstriction evoked by either the first or second stimulation of the cervical sympathetic trunks. Our results suggest that NPY is not involved either directly or indirectly during acute sympathetic vasoconstriction in the rat thyroid gland.


Comparison of insulin resistance indices in predicting albuminuria among patients with type 2 diabetes.
Diabetes is the leading cause of kidney disease. Up to 40% of the population with diabetes experience diabetic kidney disease (DKD). The correlation of DKD with insulin resistance (IR) indices has been shown in previous studies. In this study, the objective was to evaluate surrogate IR indices, including the Triglyceride-Glucose (TyG) index, Visceral Adiposity Index (VAI), Lipid Accumulation Product (LAP), and Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) to find the most valuable index for the correlation between albuminuria and IR in the type 2 diabetes (T2D) population. Albuminuria is defined as urine albumin excretion of > 30 mg/day. In this cross-sectional study, 2934 participants were enrolled and evaluated for urinary albumin excretion, and albuminuria was detected in 526 of the entries. The logistic regression models and Receiver Operating Characteristic (ROC) curve analysis were performed to assess the relationship of TyG index, VAI, LAP, and HOMA-IR's with albuminuria in patients with T2D. The TyG index had the highest association (OR 1.67) with the presence of albuminuria in patients with T2D, followed by HOMA-IR (OR 1.127), VAI (OR 1.028), and LAP (OR 1.004). These four indices remained independent after adjustment for multiple confounders. Based on the ROC curve, TyG revealed the best area under the curve (AUC) for revealing albuminuria with sufficient accuracy (AUC: 0.62) in comparison with other measured indices. The calculated TyG index cut-off point for the presence of albuminuria was 9.39. Among the indices, TyG index had the most significant correlation with albuminuria in patients with T2D.


An integrated mini-computer system for the automatic control of pharmacological experiments and calculation of results.
A mini-computer system for the automation of pharmacological experiments and for the calculation, printing and storing of results is described. A link between the 1) control unit which powers the pumps, valves, etc., and 2) the computer which processes the digital data allows the synchronization of data collection with the time course of the experiment. Thus results may be immediately expressed in absolute (i.e. stimulus-induced change in tension, etc.) or relative (i.e. % change in response due to drug administration) terms.


LPS-induced PTGS2 manipulates the inflammatory response through trophoblast invasion in preeclampsia via NF-κB pathway.
Preeclampsia (PE) is a serious obstetric complication, in which trophoblast cell invasion and migration contribute to placental inflammation. In line with the discovery that mRNA prostaglandin endoperoxide synthase 2 (PTGS2) participates in the inflammatory responses in various disorders, our study aims to explore the role of PTGS2 in trophoblast invasion and further in inflammatory response in PE, ultimately providing new therapeutic targets. Bioinformatics analysis was exploited to examine PTGS2 expression in GSE40182 and find inflammatory response-relevant genes in downstream targets of PTGS2. HTR-8/SVneo cells were treated with lipopolysaccharide (LPS) and transfected with short hairpin RNA against PTGS2 (shPTGS2). Quantitative real-time polymerase chain reaction (qRT-PCR), Western blotting, and immunofluorence assays were performed to quantify the expressions of PTGS2 and involved genes (matrix metallopeptidase 2 (MMP-2), tissue inhibitors of metalloproteinase-2 (TIMP-2), p65, p-p65, IκB-α, p-IκB-α, PTGIS, CAV1, AGTR1). The migration and invasion of trophoblasts were detected through wound healing and Transwell assays. We screened out PTGS2 from GSE40182 dataset. LPS promoted cell migration and invasion, the expressions of PTGS2 and MMP-2, and reduced the expression of TIMP-2, while PTGS2 knockdown reversed all above effects of LPS. Activation of nuclear factor kappa-B (NF-κB) pathway was reinforced by LPS which also upregulated CAV1 and AGTR1 levels, and downregulated PTGIS level. Also, the effects of LPS were offset by PTGS2 knockdown. Altogether, PTGS2 silencing reverses the promoting effect of LPS on trophoblast invasion and inflammation in PE, making a breakthrough in the research regarding molecular mechanism of PE.


Renal handling of cadmium and cadmium-metallothionein: studies on the isolated perfused rat kidney.
The isolated kidney perfusion model was used to study the uptake of Cd and metallothionein (MT)-complexed Cd. Cd2+ at concentrations above 40 nM strongly depressed the glomerular filtration rate (GFR), whereas MT-complexed Cd (Cd-MT) at concentrations of 0.8-920 nM had no effect on the GFR. In contrast to Cd2+, Cd-MT was readily reabsorbed by the kidney and uptake saturation for Cd-MT occurred at 240 nM. The maximal transport rate for Cd-MT calculated in this study was 18 pmoles Cd-MT . g-1 . min-1. The accumulation of Cd in the kidney was more efficient in the experiment using Cd-MT, in which case the Cd kidney contents were about 2-4 times higher than compared to CdCl2.


The alpaca (Vicugna pacos) as a natural intermediate host of Taenia omissa (Cestoda: Taeniidae).
Three metacestodes were collected from the mesentery and the surface of the liver of three adult alpacas (Vicugna pacos) in a slaughterhouse located in Puno, Peru. Various features of the metacestodes were observed for morphological identification. A molecular diagnosis was performed by PCR-based sequencing of mitochondrial genes of cytochrome c oxidase subunit 1 (cox1) and the NADH dehydrogenase subunit 1 (nad1). All metacestodes were identified as Taenia omissa by morphology and molecular methods The isolates from alpacas showed significant sequence similarity with previously reported isolates of T. omissa (95.7-98.1% in cox1 and 94.6-95.1% in nad1). Our report is the first to detect T. omissa metacestodes in alpacas and to reveal that alpacas are natural intermediate hosts for this parasite.


Effect of weaning and feed provision times on the performance and several behavioural traits of post-weaning lambs.
The aim of the present study was to assess if weaning time (morning or evening) and feed provision (immediate or 4 h delayed) can influence growth performance and expression of juvenile lamb behaviour immediately after and at the age of 50-125 days old. Forty lambs were randomly assigned to 4 groups: E1 (evening + immediate), E2 (evening + delayed), M1 (morning + immediate) and M2 (morning + delayed). All lambs were especially active during the first hour after weaning. However, their activity within the first 24 h after weaning was mainly affected by their circadian rhythms, since lambs were more active during the day compared to night. On the other hand, no effect of alfalfa hay provision on lamb activity during these first 24 h was observed. At the age of 50-125 days old, body weight was measured, and an isolation and flight distance test was implemented. There were no significant differences among lambs in body weight, number of jumps and heart rates assessed during isolation test and flight distance. However, the number of vocalizations was lower (65-110th day, P < 0.05) for the E2 compared to E1 lambs. Breed also slightly affected (95th day, P < 0.05) the average heart rate of lambs, with greater values for Karagouniko compared to Chios lambs. It is concluded that no discernible effects of weaning or feeding time were observed on growth performance and the display of stress-induced behavioural components of juvenile lambs till the age of 125 days old.


Clinical Significance and Prognostic Value of the Maximum Standardized Uptake Value of 18F-Flurodeoxyglucose Positron Emission Tomography-Computed Tomography in Colorectal Cancer.
The role of 18F-flurodeoxyglucose (18F-FDG) positron emission tomography-computed tomography (PET/CT) in colorectal cancer (CRC) remains unclear. This study aimed to explore the association of the maximum standardized uptake value (SUVmax), a parameter of 18F-FDG PET/CT, with KRAS mutation, the Ki-67 index, and survival in patients with CRC. Data of 66 patients with CRC who underwent 18F-FDG PET/CT was retrospectively collected in our center. The clinical significance of the SUVmax in CRC and the association of the SUVmax with KRAS mutation and the Ki-67 index were determined. A meta-analysis was conducted by a systematic search of PubMed, Web of Science, and CNKI databases, and the data from published articles were combined with that of our study. The association of the SUVmax with KRAS mutation and the Ki-67 index was determined using the odds ratio to estimate the pooled results. The hazard ratio was used to quantitatively evaluate the prognosis of the SUVmax in CRC. By analyzing the data of 66 patients with CRC, the SUVmax was found not to be related to the tumor-node-metastasis stage, clinical stage, sex, and KRAS mutation but was related to the tumor location and nerve invasion. The SUVmax had no significant correlation with the tumor biomarkers and the Ki-67 index. Data of 17 studies indicated that the SUVmax was significantly increased in the mutated type compared with the wild type of KRAS in CRC; four studies showed that there was no remarkable difference between patients with a high and low Ki-67 index score regarding the SUVmax. Twelve studies revealed that the SUVmax had no significant association with overall survival and disease-free survival in CRC patients. Based on the combined data, this study demonstrated that the SUVmax of 18F-FDG PET/CT was different between colon and rectal cancers and associated with KRAS mutation but not the Ki-67 index; there was no significant association between the SUVmax and survival of patients with CRC.


Rapid determination of the approximate content of bastnäsite in ores using cathodoluminescence imaging.
A rapid determination of the rough content of the major rare earth element (REE)-bearing minerals (bastnäsite, monazite, and xenotime) can lead to a drastic reduction of the time required to analyze mineral ores for the extraction of REE metals, thus enabling the efficient exploration of mines with REE reserves. This study presents a method of using cathodoluminescence (CL) imaging to identify bastnäsite in mineral ores and determine the rough bastnäsite content rapidly. By investigating the luminescence colors in CL images and the peaks in CL spectra emitted by minerals in ores that include bastnäsite, the author found that bastnäsite can be identified by detecting dark red or red-orange luminescence in CL images of the ores in the wavelength range 420-680 nm or by detecting areas that emitted no luminescence in the 420-680 nm CL images but that do emit pale red luminescence in CL images in the broader wavelength range 350-1000 nm. The bastnäsite content in the ores can be estimated roughly from the fractional areas identified as bastnäsite in the CL images. The CL images can be obtained within 30 s. Therefore, CL imaging can prescreen mineral ores for subsequent more precise quantitative analyses (e.g., using inductively coupled plasma mass spectrometry or electron-probe microanalysis) by identifying mineral ores having a probable high bastnäsite content. This approach can drastically reduce the time required to explore mines with potential REE reserves.


Effectiveness of team-based learning methodology in teaching transfusion medicine to medical undergraduates in third semester: A comparative study.
Team-based learning (TBL) combines small and large group learning by incorporating multiple small groups in a large group setting. It is a teacher-directed method that encourages student-student interaction. This study compares student learning and teaching satisfaction between conventional lecture and TBL in the subject of pathology. The present study is aimed to assess the effectiveness of TBL method of teaching over the conventional lecture. The present study was conducted in the Department of Pathology, GMERS Medical College and General Hospital, Gotri, Vadodara, Gujarat. The study population comprised 126 students of second-year MBBS, in their third semester of the academic year 2015-2016. "Hemodynamic disorders" were taught by conventional method and "transfusion medicine" by TBL method. Effectiveness of both the methods was assessed. A posttest multiple choice question was conducted at the end of "hemodynamic disorders." Assessment of TBL was based on individual score, team score, and each member's contribution to the success of the team. The individual score and overall score were compared with the posttest score on "hemodynamic disorders." A feedback was taken from the students regarding their experience with TBL. Tukey's multiple comparisons test and ANOVA summary were used to find the significance of scores between didactic and TBL methods. Student feedback was taken using "Student Satisfaction Scale" based on Likert scoring method. The mean of student scores by didactic, Individual Readiness Assurance Test (score "A"), and overall (score "D") was 49.8% (standard deviation [SD]-14.8), 65.6% (SD-10.9), and 65.6% (SD-13.8), respectively. The study showed positive educational outcome in terms of knowledge acquisition, participation and engagement, and team performance with TBL.


Neuroendocrine differentiation in breast lesions.
A review of neuroendocrine features in breast carcinomas is presented and markers for neuroendocrine cells are discussed. Immunostaining for neuron specific enolase is the best screening marker for neuroendocrine cells in breast carcinomas, but immunoreactivity for hormones is not present in all neuron specific enolase (NSE) positive cases. Normal myoepithelial cells are also NSE positive. Thirty per cent of breast carcinomas are NSE positive. Biochemical demonstration of ACTH, PTH and calcitonin, and immunohistochemical demonstration of ACTH, bombesin, serotonin, prolactin, gastrin, VIP, leu-enkephalin, pancreatic polypeptide, beta-endorphin and sub P has been reported in breast carcinomas. Neuroendocrine cells have not been convincingly demonstrated in the normal breast or in benign breast lesions.


Differences in the melanosome distribution within the epidermal melanin units and its association with the impairing background of leukoderma in vitiligo and halo nevi: a retrospective study.
Skin color is determined by the number of melanin granules produced by melanocytes that are transferred to keratinocytes. Melanin synthesis and the distribution of melanosomes to keratinocytes within the epidermal melanin unit (EMU) within the skin of vitiligo patients have been poorly studied. The ultrastructure and distribution of melanosomes in melanocytes and surrounding keratinocytes in perilesional vitiligo and normal skin were investigated using transmission electron microscopy (TEM). Furthermore, we performed a quantitative analysis of melanosome distribution within the EMUs with scatter plot. Melanosome count within keratinocytes increased significantly compared with melanocytes in perilesional stable vitiligo (P < 0.001), perilesional halo nevi (P < 0.01) and the controls (P < 0.01), but not in perilesional active vitiligo. Furthermore, melanosome counts within melanocytes and their surrounding keratinocytes in perilesional active vitiligo skin decreased significantly compared with the other groups. In addition, taking the means-standard error of melanosome count within melanocytes and keratinocytes in healthy controls as a normal lower limit, EMUs were graded into 3 stages (I-III). Perilesional active vitiligo presented a significantly different constitution in stages compared to other groups (P < 0.001). The distribution and constitution of melanosomes were normal in halo nevi. Impaired melanin synthesis and melanosome transfer are involved in the pathogenesis of vitiligo. Active vitiligo varies in stages and in stage II, EMUs are slightly impaired, but can be resuscitated, providing a golden opportunity with the potential to achieve desired repigmentation with an appropriate therapeutic choice. Adverse milieu may also contribute to the low melanosome count in keratinocytes.


Coroners' investigations of suicide in Australia: The hidden toll of borderline personality disorder.
Borderline Personality Disorder (BPD) is associated with a high risk of death by suicide. Our study describes a population-based analysis of Coroners' investigations of suicides where there was evidence of a BPD diagnosis. We utilised the Victorian Suicide Register to identify suicides occurring between 2009 and 2013 where evidence of a BPD diagnosis was recorded. Of the 2870 suicides during this period, 181 (6.3%) had a BPD diagnosis recorded. Evidence of other diagnosed personality disorders was recorded in an additional 14 (0.5%) suicides and BPD was suspected in another 72 (2.5%) suicides. Information coded in the 181 diagnosed BPD suicides was compared with the 2689 suicides without a BPD diagnosis. Compared to the 'no BPD suicide group', the 'BPD suicide group' was younger, comprised a smaller proportion of women, had greater diagnostic complexity, a higher proportion of death by drug overdose, and a higher proportion of social and contextual stressors. 99% of people with a BPD diagnosis who died from suicide had contact with emergency and mental health services within 12 months of death; 88% sought help from these services within 6 weeks of death. These findings demonstrate the magnitude of this most severe outcome of mental illness, confirming that BPD belongs in the same category as schizophrenia, bipolar disorder and depressive disorder with respect to suicide representation. The help-seeking behaviours evident in almost all cases highlight a critical window of opportunity for providing timely support and treatment to help avert future deaths.


Antimicrobial therapy of Broviac catheter infections in pediatric hematology oncology patients.
Long-term therapy of pediatric oncology patients has been facilitated by permanent indwelling venous catheters. Over a 3-year period, 54 Broviac catheters were placed in 43 oncology patients and two hemophiliacs. There were 20 episodes of sepsis in 14 patients and the most common bacteria were S epidermidis (4), S aureus (4), and K pneumoniae (3). Catheter exit site infections occurred ten times in six patients; S aureus eight of ten. Antibiotic therapy without catheter removal was successful in 18 of 20 children with catheter sepsis and 8 of 10 patients with exit site infections. These data strongly suggest that although catheter-related infections are common, removal of Broviac catheters is not required for successful treatment of the infection.


Amamiichthys, a new genus for the sparid fish Cheimerius matsubarai Akazaki 1962, and redescription of the species, with designation of a neotype.
A new genus, Amamiichthys, is proposed for the sparid fish Cheimerius matsubarai Akazaki 1962. This genus differs from all other genera in the family Sparidae by the following combination of characters: both jaws with an outer row of small molariform teeth and an inner row of similar, even smaller teeth; frontal bone flat, coarse and porous; strongly bifurcate protuberance of upper ethmoid just beneath mid-region of anteriormost portion of frontal bone; head and body pinkish, gradually becoming silvery toward abdomen, with many small blue spots, some pairs overlapping. The type species, Amamiichthys matsubarai, is redescribed and a neotype designated.


The role of eye movements in motion detection.
The roles of small eye movements of fixation, and of different kinds of background in motion detection were studied. Minimum detectable displacement for a luminous line oscillating either in a blank field or in the presence of three types of background was measured under two viewing conditions: normal, when eye movements generate normal movements of the image on the retina, and stabilized when these retinal image movements were nearly eliminated. It was demonstrated that eye movements enhance motion detection for a sinusoidally moving target when the target is superimposed on a patterned background; they are detrimental when there is no background. In addition, it was found that the function relating threshold amplitude to frequency of movement is band-pass when the image is stabilized or when the bar moves on a blank field, and is more low-pass when both the background and the test target are subject to the effects of eye movements.


β-Secretase 1 and its Naturally Occurring Anti-Sense RNA are Down-Regulated in Gastric Cancer.
β-secretase (BACE1) and its naturally occurring anti-sense RNA (BACE1-AS) have established role in the pathologic process leading to Alzheimer's disease. Their possible implication in the neoangiogenesis suggests that they might be involved in the tumorigenesis events as well. In the present study, we compared transcript levels of these genes in 30 gastric cancer samples and their adjacent non-cancerous tissues (ANCTs) to find whether their altered expression might facilitate discrimination of these two sets of samples. Expressions of both genes were associated with site of primary tumor. Both genes were significantly down-regulated in tumoral tissues compared with ANCTs. Significant correlations were detected between transcript levels of these genes in both sets of samples. Transcript levels of BACE1 and BACE1-AS had the diagnostic power of 75% based on Receiver operating characteristic curve analysis. The current study provides evidences for contribution of BACE1 and BACE1-AS in gastric cancer evolution and suggests their potential as diagnostic markers.


Stiffness distribution in natural insect cuticle reveals an impact resistance strategy.
In nature, many insects have evolved hard cuticles to shelter their soft body, which is thought to be the "body-armour" for insects to protect against predators' sharp teeth or dynamic load damage caused by harsh environments. In recent years, researchers have found that the "body-armour" is composed of multi-layer materials with different elastic modulus from inside to outside. The gradient change rule of the formed material modulus reflects the evolutionary history of insect cuticle's adaptation to external changes. In this article, the mechanical properties of spatial hierarchical architecture of insect cuticle, especially for the shield-like beetle elytra under impact loading, was investigated to reveal the impact resistance strategy and in-depth mechanisms of crashworthy protection. The results show that both discontinuity at the cuticle layers interface and the distributions of stiffness gradients through layers' thickness have a great influence on preventing stress wave propagation and improving impact-tolerance. Insect cuticle such as beetle elytra with discontinuous exponential stiffness gradient (DC-EXP) along the thickness has been identified to result in the minimum values of stress and interaction force under impact loading, which leads to the best impact resistance property and defensive effect. Furthermore, we compared and discussed the protective properties of insect elytra with different sclerotized endocuticle under quasi-static compression and impact loading, respectively. The knowledge gained from this work reveals the advantages of nature's choice of the stiffness distribution and may serve to inspire further research of developing advanced multifunctional structures with improved impact resistance capability by programming reasonable stiffness distribution.


Urachal Abscess: A Rare Etiology of Acute Abdominal Pain in Adults.
Abdominal pain is a common cause of emergency department visits. It often poses a diagnostic challenge for physicians given the broad spectrum of its possible medical and surgical etiologies. We report the case of a 32-year-old man who presented to the emergency department with a complaint of lower abdominal pain for one week. Abdominal examination revealed suprapubic mass and tenderness. Laboratory investigation revealed elevated leukocyte count and inflammatory markers. An abdominal ultrasound examination showed a collection with poorly defined borders. Additionally, CT demonstrated a soft tissue mass adjacent to the anterior abdominal wall with an upward track to the umbilicus, conferring the diagnosis of a urachal abscess. The patient underwent successful management of the abscess with surgical excision. This case highlights the importance for clinicians to be aware of congenital urachal anomalies since early recognition of the urachal cyst is essential to determine the proper surgical management.