Renal Disease in Primary Sjögren's Syndrome.
Primary Sjögren's syndrome (pSS) is a chronic autoimmune disorder characterised by lymphocytic infiltration of the exocrine glands, predominantly the salivary and lacrimal glands, leading to sicca symptoms. Patients may have extraglandular disease involving multiple organs, including the kidneys. 5% of patients with pSS can have renal involvement. Kidney disease in pSS presents a diagnostic challenge, as clinical symptoms are often insidious and can precede sicca symptoms. pSS affects the kidney through lymphocytic infiltration of renal tubules or immune complex deposition, leading to an array of clinical features. Tubulointerstitial nephritis is the most common histological pattern of kidney disease. Other tubular injuries include renal tubular acidosis with hypokalaemia, Fanconi's syndrome and diabetes insipidus. Glomerular disease is less common and typically involves an immune complex-mediated process. Optimal treatment for kidney diseases in pSS is not established, and treatment is guided by the pattern of disease. For tubulointerstitial nephritis, management involves electrolyte imbalance correction and the use of immunosuppression, including steroids. Treatment of glomerular disease is targeted to the histological pattern, and often requires a combination of immunosuppressive agents. The risk of end-stage kidney disease is low. Nevertheless, patients with pSS and kidney disease have significantly reduced quality of life.


Ventricular fibrillation during general anaesthesia in a seven-year-old patient with mitral valve prolapse.
A case report is presented of a seven-year-old boy who developed ventricular fibrillation during general anaesthesia with atracurium, O2, N2O and halothane, following tracheal intubation for hypospadias revision. He spontaneously defibrillated and the surgery was cancelled. Echocardiography done two days later was normal. The patient returned two weeks later for the same procedure. He developed nodal tachycardia, and premature ventricular contractions, which responded to lidocaine. A second echocardiographic examination done postoperatively while the child was crying showed mitral valve prolapse.


Results of the national registry of patients diagnosed with inflammatory bowel disease candidates for bariatric surgery (ReNacEIBar).
Our aim is to carry out a national registry of patients with inflammatory bowel disease (IBD) who underwent bariatric surgery, as well as evaluate the results and management of this type of patients in the usual clinical practice. National multicentric observational retrospective study, including patients, previously diagnosed with IBD who underwent bariatric surgery from January 2000 to December 2022. Forty-one patients have been included: 43,9% previously diagnosed with ulcerative colitis, 57,3% Crohn's disease, and an indeterminate colitis (2,4%). The preoperative BMI was 45.8 ± 6,1 kg/m2. Among the bariatric surgeries, 31 (75,6%) sleeve gastrectomy, 1 (2,4%) gastric bypass and 9 (22%) one anastomosis gastric have been carried out. During the postoperative period, 9.8% complications have been recorded. BMI was 29,5 ± 4,7 kg/m2 and percent total weight lost was 33,9 ± 9,1 % at 12 months. Bariatric surgery in patients with inflammatory bowel disease can be considered safe and effective. [[es]]Resumen INTRODUCCIóN: El objetivo principal es realizar un Registro Nacional de pacientes diagnosticados de enfermedad inflamatoria intestinal (EII) que son sometidos a cirugía bariátrica, así como evaluar los resultados y aspectos fundamentales del manejo de este tipo de pacientes en la práctica clínica habitual. METODOLOGíA: Estudio retrospectivo observacional multicéntrico nacional, en el que se incluyen pacientes diagnosticados previamente de EII, que hayan sido intervenidos de cirugía bariátrica desde enero de 2000 hasta diciembre de 2022. Se han incluido un total de 41 pacientes: 43,9% diagnosticados previamente de colitis ulcerosa, 53,7% de enfermedad de Crohn, y una colitis indeterminada (2,4%). El IMC preoperatorio ha sido de 45,8 ± 6,1 kg/m2. Se han realizado 31 (75,6%) gastrectomías verticales, 1 (2,4%) Bypass gástrico y 9 (22%) Bypass gástrico de una anastomosis. Se han registrado un 9,8% de complicaciones. A los 12 meses, el IMC medio fue de 29,5 ± 4,7 kg/m2, presentando un %PTP de 33,9 ± 9,1%. La cirugía bariátrica en pacientes previamente diagnosticados de EII se puede considerar eficaz en cuanto a pérdida de peso, y segura en relación con un porcentaje bajo de complicaciones.


Early screening of cervical cancer based on tissue Raman spectroscopy combined with deep learning algorithms.
Cervical cancer is the most common reproductive malignancy in the female reproductive system. The incidence rate and mortality rate of cervical cancer among women in China are high. In this study, Raman spectroscopy was used to collect tissue sample data from patients with cervicitis, cervical precancerous low-grade lesions, cervical precancerous high-grade lesions, well differentiated squamous cell carcinoma, moderately differentiated squamous cell carcinoma, poorly differentiated squamous cell carcinoma and cervical adenocarcinoma. The collected data were preprocessed using an adaptive iterative reweighted penalized least squares (airPLS) algorithm and derivatives. Convolutional neural network (CNN) and residual neural network (ResNet) classification models were constructed to classify and identify seven types of tissue samples. The attention mechanism efficient channel attention network (ECANet) module and squeeze-and-excitation network (SENet) module were combined with the established CNN and ResNet network models, respectively, to make the models have better diagnostic performance. The results showed that efficient channel attention convolutional neural network (ECACNN) had the best discrimination, and the average accuracy, recall, F1 and AUC values after five cross-validations could reach 94.04%, 94.87%, 94.43% and 96.86%, respectively.


Performance evaluation of the UV/H2O2 process on selected nitrogenous organic compounds: reductions of organic contents vs. corresponding C-, N-DBPs formations.
The presence of various organic contaminants in water sources is of concern due to their direct threats to human health and potential to react with disinfectants to form carcinogenic byproducts including trihalomethanes, haloacetic acids and nitrosamines in finished water. This study applied both medium-pressure and low-pressure ultraviolet light coupled with hydrogen peroxide (UV/H2O2) to evaluate its efficacy for degradation of selected nitrogenous organic compounds and corresponding disinfection byproduct (DBP) formation. Six organic compounds were chosen as target precursors based on their nitrogen contents and molecular structures. The results showed that higher oxidation capacity resulted in better reduction of organic matters and DBP formation potentials (DBPFPs). However, insufficient contact time and oxidant doses could lead to a rise of DBPFPs in the early stages of UV/H2O2 reactions. A greater percentage removal was achieved for organic carbon than organic nitrogen after UV/H2O2 treatment, especially for compounds with complicated structure such as diltiazem. During the UV/H2O2 treatment, the intermediate products include tertiary amine, dimethyl amine (DMA) or DMA-like structures, which are N-nitrosodimethylamine (NDMA) precursors after chlorination or chloramination. Furthermore, it was observed that using dissolved organic nitrogen and DMA to predict NDMAFP could lead to biased conclusions because of the complex nature of nitrogenous matters in aqueous environments.


Mechanisms underlying enhanced IgA production in Peyer's patch cells by membrane vesicles derived from Lactobacillus sakei.
We analyzed the mechanisms underlying enhanced IgA production in the cells of Peyer's patch cells via membrane vesicles derived from Lactobacillus sakei subsp. sakei NBRC 15893. Depletion of CD11c+ cells from Peyer's patch cells suppressed the enhanced IgA production mediated by membrane vesicles. Meanwhile, the stimulation of bone-marrow-derived dendritic cells with membrane vesicles increased gene expression of inducible nitric oxide synthase, retinaldehyde dehydrogenase 2, and several inflammatory cytokines. The production of nitric oxide and interleukin (IL)-6 by membrane vesicle stimulation was induced via Toll-like receptor 2 on bone marrow-derived dendritic cells. Inhibition of inducible nitric oxide synthase and retinaldehyde dehydrogenase 2, as well as the neutralization of IL-6 in Peyer's patch cells, suppressed the enhanced IgA production by membrane vesicle stimulation. Hence, nitric oxide, retinoic acid, and IL-6 induced by membrane vesicles play crucial roles in the enhanced IgA production elicited by membrane vesicles in Peyer's patch cells.


Double-edge Role of B Cells in Tumor Immunity: Potential Molecular Mechanism.
B cells are a heterogeneous population, which have distinct functions of antigen presentation, activating T cells, and secreting antibodies, cytokines as well as protease. It is supposed that the balance among these B cells subpopulation (resting B cells, activated B cells, Bregs, and other differentiated B cells) will determine the ultimate role of B cells in tumor immunity. There has been increasing evidence supporting opposite roles of B cells in tumor immunity, though there are no general acceptable phenotypes for them. Recent years, a new designated subset of B cells identified as Bregs has emerged from immunosuppressive and/or regulatory functions in tumor immune responses. Therefore, transferring activated B cells would be possible to become a promising strategy against tumor via conquering the immunosuppressive status of B cells in future. Understanding the potential mechanism of double-edge role of B cells will help researchers utilize activated B cells to improve their anti-tumor response. Moreover, the molecular pathways related to B cell differentiation are involved in its tumor-promoting effect, such as NF-κB, STAT3, BTK. So, we review the molecular and signaling pathway mechanisms of B cells involved in both tumor-promoting and tumor-suppressive immunity, in order to help researchers optimize B cells to fight cancer better.


Molecular characterization, expression and functional analysis of yak IFITM3 gene.
IFITM3 is interferon-induced transmembrane 3, which plays an extremely key role in anti-proliferation, anti-virus and anti-tumor diseases. In this study, the yak (Bos grunniens) IFITM3 (BgIFITM3) gene contained a 5'-untranslated region (UTR) (25 bp), a coding region (441 bp), and a 3'-UTR (115 bp). The expression of BgIFITM3 gene in liver was significantly higher than that in heart, spleen, lung and kidney (P < 0.01). BgIFITM3 protein was localized on the yak hepatocyte plasma membrane, and its expression was significantly different between 1 day and 15 months of age (P < 0.05). Moreover, the prokaryotic expression vector of BgIFITM3 protein was constructed and expressed successfully, with a molecular weight of 19.5 kDa. The activities of yak hepatocyte were significantly inhibited after treating with BgIFITM3 protein (10 and 20 μg/mL) (P < 0.01). The expression levels of ERBB-2, IRS-1, PI3KR-1, AKT-1 and MAPK-3 were significantly lower after treating with 20 μg/mL BgIFITM3 protein (P < 0.05). Besides, the activities of HepG2 cells were significantly inhibited after treating with BgIFITM3 protein (1, 10 and 20 μg/mL) (P < 0.05). While, the cloning ability and migration ability of HepG2 cells were significantly inhibited after treating with 10 μg/mL BgIFITM3 protein (P < 0.05). Finally, the mitochondria of HepG2 cells was concentrated, cristae widened, and the double film density of mitochondria was increased after treating with 10 μg/mL BgIFITM3 protein. After 10 μg/mL BgIFITM3 protein treating, the expression levels of VDAC-2, VDAC-3 and p53 genes were significantly increased, but the expression level of GPX-4 gene was significantly decreased (P < 0.01). Taken together, the BgIFITM3 protein could inhibit the proliferations of yak hepatocyte and HepG2 cells by regulating the PI3K/Akt pathway or ferroptosis-related genes, respectively. These results benefit for further study of the function of BgIFITM3 protein.


Investigation of the binding of Salvianolic acid B to human serum albumin and the effect of metal ions on the binding.
The studies on the interaction between HSA and drugs have been an interesting research field in life science, chemistry and clinical medicine. There are also many metal ions present in blood plasma, thus the research about the effect of metal ions on the interaction between drugs and plasma proteins is crucial. In this study, the interaction of Salvianolic acid B (Sal B) with human serum albumin (HSA) was investigated by the steady-state, synchronous fluorescence and circular dichroism (CD) spectroscopies. The results showed that Sal B had a strong ability to quench the intrinsic fluorescence of HSA through a static quenching mechanism. Binding parameters calculated showed that Sal B was bound to HSA with the binding affinities of 10(5) L mol(-1). The thermodynamic parameters studies revealed that the binding was characterized by positive enthalpy and positive entropy changes, and hydrophobic interactions were the predominant intermolecular forces to stabilize the complex. The specific binding distance r (2.93 nm) between donor (HSA) and acceptor (Sal B) was obtained according to Förster non-radiative resonance energy transfer theory. The synchronous fluorescence experiment revealed that Sal B cannot lead to the microenvironmental changes around the Tyr and Trp residues of HSA, and the binding site of Sal B on HSA is located in hydrophobic cavity of subdomain IIA. The CD spectroscopy indicated the secondary structure of HSA is not changed in the presence of Sal B. Furthermore, The effect of metal ions (e.g. Zn(2+), Cu(2+), Co(2+), Ni(2+), Fe(3+)) on the binding constant of Sal B-HSA complex was also discussed.


Anatomic single-bundle anterior cruciate ligament reconstruction using a calcium phosphate-hybridized tendon graft: a randomized controlled trial with 2 years of follow-up.
To improve tendon-to-bone healing in anterior cruciate ligament (ACL) reconstruction, a novel technique via calcium phosphate (CaP)-hybridized tendon graft using an alternate soaking process was developed. The purpose of this study was to evaluate the clinical results of anatomic single-bundle ACL reconstruction using the CaP-hybridized tendon graft with up to 2 years follow-up, and compare the outcome with conventional ACL reconstruction and preoperative data. Ninety patients who required anatomic single-bundle ACL reconstruction were randomized to undergo either the CaP-hybridized tendon graft method (CaP group, n = 45) or the conventional method (conventional group, n = 45). At 1 and 2 years postoperatively, all patients were evaluated using KT-1000 arthrometry, pivot-shift test, International Knee Documentation Committee (IKDC) grade, Lysholm scale, and Tegner scale; at the same timepoints, bone tunnel enlargement was evaluated using computed tomography, and the tendon graft intensity was evaluated on magnetic resonance imaging. Tendon graft appearance was evaluated arthroscopically once after a period of up to 2 years postoperatively. Cases of re-rupture and adverse events were recorded in both groups. In both groups, the KT-1000 arthrometry, pivot-shift test, IKDC grade, and Lysholm scale results at 1 and 2 years postoperatively were superior to preoperative data; these results did not significantly differ between groups at either timepoint. The rate of increase of the cross-sectional area of the femoral bone tunnel in the CaP group was smaller than that in the conventional group at 1 year postoperatively. The other results did not significantly differ between the two groups at any timepoint. There were two cases of re-rupture in the CaP group, and six cases of re-rupture in the conventional group. There were no adverse events during follow-up in either group. Anatomic single-bundle ACL reconstruction using a CaP-hybridized tendon graft was safe, and resulted in improved clinical outcomes at 2 years postoperatively compared with preoperative data; the outcomes were comparable with the conventional method. A longer follow-up is needed to clarify the clinical effects of the CaP-hybridized tendon graft in anatomic single-bundle ACL reconstruction. UMIN, UMIN000019788 Registered 14 November 2015-Retrospectively registered.


Edge area metric complexity scoring of volumetric modulated arc therapy plans.
Aperture-based complexity metrics have been suggested as a method to score complexity of volumetric modulated arc therapy (VMAT) plans. The purpose of this study was to evaluate the edge area metric (EAM) for clinical VMAT plans on a control point and treatment plan level. EAM on a control point level was evaluated based on film measurements of 18 static beam openings originating from VMAT plans. EAM on a treatment plan level (arithmetic mean value of EAM scores for control points) was evaluated based on measurements with the Delta4® for 200 VMAT plans for four different treatment sites: pelvic, thorax, head and neck, and prostate. Measurements were compared to calculations and dose difference and gamma pass rates were evaluated. EAM scores on a control point level correlated with Pearson's r-values of -0.96 and -0.77 to dose difference and gamma pass rates, respectively. The prostate plans had the highest average EAM score. A connection between smaller PTVs and higher EAM scores was found. No correlation between the evaluation result and EAM on a plan level was found. EAM on a control point level was shown to correlate to the difference between measured and calculated 2D dose distributions of clinical VMAT beam openings. No correlation was found for EAM on a plan level for clinical treatment plans.


Effects of psychiatric comorbidities in persons with epilepsy on recurrent emergency department visits.
Coexisting mental health disorders in persons with epilepsy present as substantial burdens to patients and healthcare systems. In this retrospective study, we reviewed 160 patients presenting to a safety net hospital Emergency Department (ED) with seizures to investigate whether differences in clinical workup, follow-ups, and ED visit recurrence existed between epilepsy patients with epilepsy with and without a coexisting psychiatric disorder. Patients with epilepsy with a psychiatric comorbidity had more subsequent ED visits (45 % vs 26 %, p = 0.01) and fewer outpatient follow-up opportunities (74 % vs 87 %, p = 0.042) compared to patients with epilepsy without psychiatric comorbidities, highlighting a healthcare gap that needs to be addressed. Our findings suggest a need for ED providers to shift their clinical practice in favor of offering more outpatient follow-up opportunities, to ensure long-term management of seizures in patients with epilepsy with comorbid psychiatric disorders.


Non-erotic cognitive distractions during sexual activity in sexual minority and heterosexual young adults.
The present study examined 100 lesbian and gay college students and 100 heterosexual students to determine whether group differences exist in frequency of a range of non-erotic cognitive distractions during sexual activity. Non-erotic cognitive distraction is a descriptive term for both self-evaluative cognitions related to physical performance and body image concerns, as well as additional cognitive distractions (e.g., contracting an STI or emotional concerns) during sexual activity. Participants were matched on gender (96 males and 104 females), age, and ethnicity, and completed questionnaires assessing frequency of non-erotic cognitive distractions during sexual activity, as well as measures of additional variables (trait and body image anxiety, attitudes toward sexual minorities, self-esteem, and religiosity). Results indicated that sexual minorities experienced significantly more cognitive distractions related to body image, physical performance, and STIs during sexual activity than heterosexuals. Regarding gender, men reported more distractions related to STIs than women. Interaction effects were observed between sexual orientation and gender for body image-, disease-, and external/emotional-based distractions. Implications of these findings are discussed.


TrkA immunoreactive astrocytes in dendritic fields of the hippocampal formation across estrous.
Neurotrophins are important modulators of structural synaptic plasticity. (Through trophic action (Jordan. J Neurobiol 40:434-445, 1999), astrocytes serve as permissive substrates to support axonal regrowth (Ridet et al. Trends Neurosci 20:570-571, 1997), and are involved in estrogen-induced synaptic structural plasticity (Garcia-Segura et al. Cell Mol Neurobiol 16:225-237, 1996). Previously, we reported that tyrosine kinase A receptor (TrkA) immunoreactivity was present both in presynaptic neuronal processes (axons and terminals) and in select astrocytes of the male rat hippocampal formation (Barker-Gibb et al. J Comp Neurol 430:182-199, 2001). We show that the number of TrkA-immunoreactive astrocytes in female rats fluctuates 16-fold across the estrous cycle in dendritic fields of the hippocampal formation, with the greatest number at estrus after the peak plasma estradiol concentration of proestrus. Few TrkA-labeled astrocytes were found in ovariectomized animals; after estrogen replacement, this number increased by 12-fold in the hippocampal formation, indicating estrogen-mediated induction. Dual-labeling studies showed that TrkA-labeled astrocytes were also immunoreactive for vimentin, a protein expressed by reactive astrocytes. Ultrastructural analysis of the dentate gyrus molecular layer demonstrated that TrkA immunoreactive astrocytes are positioned primarily next to dendrites and unmyelinated axons. Because nerve growth factor (NGF) has been reported to stimulate astrocytes to function as substrates for axon growth (Kawaja and Gage. Neuron 7:1019-1030, 1991), these findings are consistent with the theory that TrkA immunoreactive astrocytes serve a role in structural plasticity, axon guidance, and synaptic regeneration across the estrous cycle in the hippocampal formation.


DHEA provides a microenvironment for endometrial stem cells neurogenesis.
Recently, transplantation of adult stem cells over embryonic stem cells increased in regenerative medicine. Among the adult stem cells, human endometrium stromal (hEnS) cells are under the strict control of the steroid hormones and have the potential to differentiate into other cell lineages including neural cells. Unfortunately these cells may lose their neurogenic differentiation ability upon extended expansion in cultures. To avoid the back-differentiation, it is important to establish growth conditions that support the rapid proliferation and stable differentiation of hEnS cells over extended periods of time without compromising their neuronal phenotype. Differentiation of transplanted cells is strongly influenced by environmental signals. The steroidal microenvironment of the stem cells plays a major role in controlling neurogenesis in the cultures. Dehydroepiandrosterone (DHEA) administration to the cultures could support this propose. DHEA enhance survival rates of dissociated neurons in cultures. It can activate AKT protein kinase pathway as well as nerve growth factor (NGF) that enhances neurogenesis efficiently. On the other hand it seems that DHEA increase survival rate of neural cells via production of brain derived neurotrophic factor (BDNF), indirectly. BDNF is a mediator product of the DHEA that promotes the differentiation and survival of neurons. Here, we offer that DHEA is a suitable candidate that could provide a microenvironment to stimulate neurogenesis and enhanced survival of newly formed neurons derived from hEnS cells. From the point that DHEA is the most abundant steroid in the body, marketed as a supplement and is increasingly self-prescription we hypothesized that it could be the safe and high available choice. This provides a better insight into the maintenance of neural cells for treatment of a wide variety of neurological diseases such as Alzheimer's and Parkinson's by non-invasively autologous cell therapy by hEnS cells especially in women.


A New Concept for the Treatment and Rehabilitation of Patients with Pathologic Comorbidities Using Cutting-Edge Digital Technologies in Dental Orthopaedics.
This article investigates the specific aspects of overactive or exaggerated vomiting reflexes affecting the procedure of dental examination and impression in patients with complete secondary adentia, who need orthopaedic dental treatment. The prevailing manifestation degree of exaggerated vomiting reflex was diagnosed among patients with complete secondary adentia and exaggerated vomiting reflex. Exaggerated vomiting reflexes occur when a patient suffers from dentophobia, the term, which is otherwise known as the fear of dentists. The study was performed using methods of mathematical statistics, including the Pearson χ2 criterion and the statistical probability criterion (p). The role of an exaggerated vomiting reflex was revealed in the development of patients' dentophobic experiences, and the nature of such experiences was established. Variations in dentophobic reactions were distinguished and management strategies were studied for patients with complete secondary adentia and exaggerated vomiting reflex. These studies were aimed at preventing the development of vomiting reflex during dental procedures and at identifying an optimal strategy for stopping exaggerated vomiting reflex. The role of the vomiting reflex in the orthopaedic treatment of dental patients was determined.


The Impact of Genetic Variants for Different Physiological Characterization of Type 2 Diabetes Loci on Gestational Insulin Signaling in Nondiabetic Pregnant Chinese Women.
We investigate the impact of genetic variants on transiently upregulated gestational insulin signaling. We recruited 1152 unrelated nondiabetic pregnant Han Chinese women (age 28.5 ± 4.1 years; body mass index [BMI] 21.4 ± 2.6 kg/m(2)) and gave them oral glucose tolerance tests. Matsuda index of insulin sensitivity, homeostatic model assessment of insulin resistance, indices of insulin disposition, early-phase insulin release, fasting state, and 0 to 120 minute's proinsulin to insulin conversion were used to dissect insulin physiological characterization. Several variants related to β-cell function were genotyped. The genetic impacts were analyzed using logistic regression under an additive model. By adjusting for maternal age, BMI, and the related interactions, the genetic variants in ABCC8, CDKAL1, CDKN2A, HNF1B, KCNJ11, and MTNR1B were detected to impact gestational insulin signaling through heterogeneous mechanisms; however, compared with that in nonpregnant metabolism, the genetic effects seem to be eminently and heavily influenced by maternal age and BMI, indicating possible particular mechanisms underlying gestational metabolism and diabetic pathogenesis.


Effects of dietary bile acids on formation of azoxymethane-induced aberrant crypt foci in F344 rats.
The present study has demonstrated the influence of bile acids (BAs) on the development and growth of azoxymethane (AOM)-induced aberrant crypt foci (ACF). Male F344 rats were treated with two doses of AOM (15 mg/kg) at 7 days apart and fed either basal MF or MF plus 0.4% of cholic (CA), deoxycholic (DCA), chenodeoxycholic (CDCA), lithocholic (LCA) and ursodeoxycholic (UDCA) acid mixed diets for 8 weeks after the first AOM dose. The mean number of ACF/colon of the rats fed CA, DCA, CDCA and LCA were higher than that of MF-fed group and the differences were statistically significant (P < 0.005). But the mean number of ACFs/colon was significantly (P < 0.005) lower in UDCA diet-fed rats compared to MF. UDCA-fed rats also showed a significant decrease in average crypt multiplicity (number of crypts/focus) of ACF compared to MF alone. The mean number of ACF with > or =5 crypts was about 2.5-3.7 times higher in case of CA, DCA, CDCA and LCA and about 8.2 times lower in UDCA compared to the control MF diet group. In a parallel study, feeding for 18 weeks of the same BAs mixed diets without AOM administration did not significantly induce ACF. Therefore, these data suggest that dietary BAs by themselves do not induce ACF in F344 rats but enhance or, in the case of UDCA, suppress the development and growth of AOM-induced ACF.


Differences in microtubule binding and self-association abilities of bovine brain tau isoforms.
We have fractionated tau isoforms by elution at increasing pH values using iron-chelated affinity chromatography, which discriminates between isoforms phosphorylated to different extents. Microtubule-associated tau elutes from the column at a pH gradient narrower than that of total brain tau. Neither under-phosphorylated nor highly phosphorylated isoforms are found in the microtubule-associated tau protein preparation. This indicates that phosphorylation at certain sites is needed for tau binding to microtubules, whereas phosphorylation at some other sites may prevent the association. The self-association ability of the different tau isoforms has also been analyzed. Tau isoforms containing three tubulin binding motifs form covalently bound dimers more efficiently than tau isoforms containing four motifs. This dimer-forming ability is notably diminished in the presence of a reducing agent, as determined by SDS-polyacrylamide gel electrophoresis, thus suggesting the involvement of cysteine residues. Additionally, tau forms larger aggregates, as detected by gel permeation chromatography, which are solubilized by SDS and cannot, therefore, be observed by SDS-polyacrylamide gel electrophoresis. These tau aggregates are observed even in the presence of reducing agents. These results support the idea that other regions in the tau molecule, besides the Cys-containing tubulin binding region, also contribute to tau self-association. Tau dimerization and aggregation may be prior steps to the formation of paired helical filaments.


The iliac crest and the radial forearm flap in vascularized oromandibular reconstruction.
Sixty cases (59 patients) of oromandibular reconstruction using vascularized iliac crests were compared with 13 in which radial osteocutaneous flaps were used. These patients were reviewed from the standpoint of cosmetic results and function as well as their operative and postoperative courses. In both groups, the results were generally good. However, revisionary surgery was more frequent in those receiving the iliac crest. This group also had a higher incidence of intraoral wound breakdown and bone exposure. Nevertheless, the sheer size of the iliac crest made it ideal for massive oromandibular defects, just as its natural curvature lent itself to precise replication of the mandible in bone-only reconstructions. Its bulk proved a major obstacle in small composite defects. The radial forearm flap carried thin, pliable, well-vascularized skin that was superior to groin skin for oral lining. Bone gaps of up to 9 cm could be handled with ease, thus making it complementary to the iliac crest over the wide spectrum of mandibular reconstruction.


Functional outcomes of structural peculiarities of striated muscle tropomyosin.
Tropomyosin is a dimer coiled-coil actin-binding protein. Adjacent tropomyosin molecules connect each other 'head-to-tail' via an overlap junction and form a continuous strand that winds around an actin filament and controls the actin-myosin interaction. High cooperativity of muscle contraction largely depends on tropomyosin characteristics. Here we summarise experimental evidence that local peculiarities of tropomyosin structure have long-range effects and determine functional properties of the strand, including changes in its bending stiffness and interaction with actin and myosin. Point mutations and posttranslational modifications help to probe the roles of the conserved 'non-canonical' residues, clusters of stabilising and destabilising core residues, and core gap in tropomyosin function. The data suggest that tropomyosin structural lability including a diversity of homo- and heterodimers of different isoforms provide a balance of stiffness, flexibility, and strength of interaction with partner sarcomere proteins necessary for fine-tuning of Ca2+ regulation in various types of striated muscles.


Evaluation of Heart Rate Variability in Children With Breath-Holding Episodes.
We evaluated heart rate variability in children with breath-holding episodes (BHEs). Sixty children with BHEs were included in the study; these individuals were further subdivided into children with cyanotic BHEs (n = 42) and children with pallid BHE (n = 18). Sixty healthy children of matched age and sex served as a control group. Twenty-four hour Holter monitoring was applied to all included children. Minimum, mean, maximum heart rate, rhythms, and corrected QT were evaluated. Time domain parameters of heart rate variability such as standard deviation of all R-R intervals, standard deviation of the average of R-R intervals in all five-minute segments of the entire recording, mean of the standard deviations of all N-N (normal-normal RR) intervals for all five-minute segments, root mean squares differences between adjacent R-R intervals, percentage of differences between adjacent R-R intervals that are greater than 50 milliseconds were also assessed. All time domain parameters of heart rate variability were significantly higher in children with pallid BHEs than those with cyanotic BHEs and control group. Minimum, mean, and maximum heart rate were significantly lower in children with pallid BHEs than those with cyanotic BHEs and control group. Asystole was observed in three children with pallid BHEs. Long corrected QT was observed in another two children with pallid BHEs. Heart rate variability increased significantly in children with pallid BHEs. Evaluation of heart rate variability is crucial for children with BHEs especially those with pallid episodes.


Re-expansion pulmonary edema after thoracentesis for iatrogenic pneumothorax and severe subcutaneous emphysema.
Subclavian central venous catheterization can cause severe complications, including tension pneumothorax, subcutaneous emphysema, and pneumomediastinum. Re-expansion pulmonary edema after thoracentesis is a life-threatening complication.


Natural killer activity of peripheral-blood mononuclear cells in breast cancer patients.
Natural killer (NK) activity of immune cells plays a central role in host defense against cancer and virus-infected cells. Natural cytotoxic activity of peripheral-blood mononuclear cells was assessed by a Calcein-AM release assay in 89 subjects. In the present study, we here demonstrated that NK activities of peripheral-blood mononuclear cells (PBMCs) from breast cancer patients were significantly lower as compared with that of healthy individuals. There were significant differences in the NK activities of PBMCs from HER2-negative breast cancer patients as compared with HER2-positive patients. Our results suggest that NK activity of PBMCs is lower in breast cancer indicating a role for immunological natural host defense mechanisms against cancer.


Risk of oral food challenges.
Oral food challenges are essential to the diagnosis of food allergy; however, little has been reported regarding the risks of performing food challenges in children with suspected food allergy. To examine the risk and reaction severity of failed oral food challenges. A retrospective chart review was performed on children who underwent food challenges to milk, egg, peanut, soy, and/or wheat in a university-based pediatric allergy clinic over a 7-year period. Of the 584 challenges completed, 253 (43%) resulted in an allergic reaction. There were 90 milk, 56 egg, 71 peanut, 21 soy, and 15 wheat failed challenges. Of patients who failed, there were 197 (78%) cutaneous, 108 (43%) gastrointestinal, 66 (26%) oral, 67 (26%) lower respiratory, and 62 (25%) upper respiratory reactions. No patients had cardiovascular symptoms. There was no difference between foods in the severity of failed challenges or the type of treatment required to reverse symptoms. All reactions were reversible with short-acting antihistamines +/- epinephrine, beta-agonists, and/or corticosteroids. No children required hospitalization, and there were no deaths. There are risks associated with food challenges, and the risks are similar for each of the foods studied. Given the benefits that result from a negative challenge, these risks are reasonable when challenges are performed under the guidance of an experienced practitioner in a properly equipped setting.


Molecular structure, IR and Raman spectra as well as DFT chemical calculations for alkylaminoacetylureas: vibrational characteristics of dicarbonylimide bridge.
The present work reports room temperature IR and Raman study of R-NH-CH2-CO-NH-CO-NH2 alkylaminoacetylureas (R=C3H7, C4H9, C5H11, C6H13, C7H15, C8H17, C9H19, C10H21, C12H25, C14H29, C16H33 and C18H37). The experimental energy levels have been compared to those obtained from DFT chemical quantum calculations performed with the use of B3LYP/6-31G (d,p) basis for the R=C3H7 derivative. Energies of 66 vibrational states have been calculated for this molecule. Its molecular symmetry was taken as C1 and was optimized in the both quantum models applied. The role of the hydrogen bond in the stabilization of the structure has been analyzed.


Restorative effect of adipose tissue-derived stem cells on impaired hepatocytes through Notch signaling in non-alcoholic steatohepatitis mice.
Adipose tissue-derived stem cells (ADSCs) have been suggested as a novel treatment for non-alcoholic steatohepatitis (NASH); however, the mechanisms underlying their therapeutic effect remain poorly understood. In this study, we aimed to investigate the association of Notch signaling, which is crucial for cellular proliferation and differentiation in ADSC-mediated treatment of NASH. Flow cytometry analysis of ADSCs showed that they expressed the Notch ligands JAG1, DLL1, and DLL4. The expression of genes associated with the Notch signaling pathway was attenuated in hepatocytes of NASH model mice. We further observed ADSC-mediated activation of Notch signaling in these hepatocytes in addition to an increase in proliferating cell nuclear antigen+ cells and a decrease in TdT-mediated dUTP-biotin nick end labeling+ apoptotic cells. Co-culture of palmitic acid-induced steatotic hepatocytes and ADSCs resulted in the activation of Notch signaling and reduction of apoptosis of steatotic hepatocytes. Moreover, inhibition of Notch signaling by a γ-secretase inhibitor and knockdown of Notch ligands using siRNA attenuated the anti-apoptotic effect of co-cultured ADSCs in vitro. Our findings show that the Notch signaling pathway is involved in the inhibition of apoptosis and restoration of cellular proliferation of hepatocytes from NASH mice following ADSC treatment.


[Time used for outpatient tumor pain therapy].
The insufficiency of pain therapy for cancer patients is a frequent complained. One reason for this deficit may be the great amount of time required for the management of patients with far advanced diseases. The objective of this paper is the calculation of time for this therapy. All relevant data on pain treatment of 126 patients were followed up in an anaesthesiology outpatient facility and their therapy was recorded retrospectively over a period of 52 months. During a period of 18,798 observation days 1,634 pain therapy consultations were performed, on average 13 per patient (1 to 95). The mean duration of therapy was 149 days. The percentage of consultations at home was 46%, most of them (80%) were scheduled, the remaining 20% were emergency consultations that were immediately necessary, at night or on Sundays. Altogether, the mean time for therapy including travel time was about 7 h until the end of the therapy. Only 13.5% of patients died in a hospital. Because of the great amount of time necessary for cancer pain therapy close collaboration of all physicians involved in analgesic/palliative care is essential. This requires a good basic knowledge of all colleagues about the specialties of cancer pain therapy as well as good commitment by the pain specialists.


Long-term outcomes of cardiac resynchronization therapy by left ventricular ejection fraction.
Despite our prior report suggesting heart failure (HF) risk reduction from cardiac resynchronization therapy with defibrillator (CRT-D) in mild HF patients with higher left ventricular ejection fraction (LVEF > 30%), data on mortality benefit in this cohort are lacking. We aimed to assess long-term mortality benefit from CRT-D in mild HF patients by LVEF > 30%. Among 1274 patients with mild HF and left bundle branch block enrolled in MADIT-CRT, we analysed long-term effects of CRT-D vs. implantable cardioverter defibrillator (ICD) therapy only, and reverse remodelling to CRT-D (left ventricular end-systolic volume percent change ≥ median at 1 year), on all-cause mortality and HF for the LVEF ≤ 30% and LVEF > 30 subgroups using Kaplan-Meier and Cox analyses. During long-term follow-up, CRT-D vs. ICD was associated with reduction in all-cause mortality in both patients with LVEF > 30% and LVEF ≤ 30% [hazard ratio (HR) 0.47, 95% confidence interval (CI) 0.25-0.85, P = 0.036 vs. HR 0.69, 95% CI 0.49-0.98, P = 0.013, interaction P = 0.261]. The efficacy of CRT-D vs. ICD only to reduce HF was similar in those with LVEF above and below 30% (HR 0.36, 95% CI 0.35-0.61, P < 0.001 vs. HR 0.46, 95% CI 0.35-0.61, P < 0.001; interaction P = 0.342). Patients with CRT-D-induced reverse remodelling had significant mortality reduction when compared to ICD, with either LVEF > 30% or LVEF ≤ 30% (HR 0.17 and 0.39), but no mortality benefit was seen in patients with less reverse remodelling. HF events, however, were reduced in both CRT-D-induced high and low reverse remodelling vs. ICD only, in both LVEF subgroups. In MADIT-CRT, left bundle branch block patients with higher LVEF (> 30%) derive long-term mortality benefit from CRT-D when exhibiting significant reverse remodelling. ClinicalTrials.gov ID NCT00180271, NCT01294449, and NCT02060110.


Mutant mouse models in evaluating novel approaches to antipsychotic treatment.
In this review we consider the application of mutant mouse phenotypes to the study of psychotic illness in general and schizophrenia in particular, as they relate to behavioral, psychopharmacological, and cellular phenotypes of putative import for antipsychotic drug development. Mutant models appear to be heuristic at two main levels; firstly, by indicating the functional roles of neuronal components thought to be of relevance to the putative pathobiology of psychotic illness, they help resolve overt behavioral and underlying cellular processes regulated by those neuronal components; secondly, by indicating the functional roles of genes associated with risk for psychotic illness, they help resolve overt behavioral and underlying cellular processes regulated by those risk genes. We focus initially on models of dopaminergic and glutamatergic dysfunction. Then, we consider advances in the genetics of schizophrenia and mutant models relating to replicable risk genes. Lastly, we extend this discussion by exemplifying two new variant approaches in mutant mice that may serve as prototypes for advancing antipsychotic drug development. There is continuing need not only to address numerous technical challenges but also to develop more "real-world" paradigms that reflect the milieu of gene × environment and gene × gene interactions that characterize psychotic illness and its response to antipsychotic drugs.


Hennekam syndrome presenting as nonimmune hydrops fetalis, congenital chylothorax, and congenital pulmonary lymphangiectasia.
We report a female infant with congenital lymphedema, facial anomalies, intestinal lymphangiectasia consistent with a diagnosis of Hennekam syndrome. At birth the patient presented with severe respiratory distress due to nonimmune hydrops fetalis, a congenital chylothorax (CC), and pulmonary lymphangiectasia. Hydrops fetalis may be present in newborns with the Hennekam syndrome. Lymphoscintigraphy can be useful in explaining pleural-pulmonary involvement of this generalized lymph vessel malformation syndrome.


Acidic surface functional groups control chemisorption of ammonium onto carbon materials in aqueous media.
Elucidation of mechanistic insight into the interaction of carbon materials' physicochemical surface properties and ammonium (NH4+) adsorption in aqueous media was made by conducting a systematic study using a wide range of carbon materials. Three types of biochars (rice husk, poultry litter, and enhanced poultry litter) and activated carbons (fresh and aged coconut shell-based and charcoal-based) were used for investigating the NH4+ adsorption mechanism. Poultry litter biochar, with lowest surface area (3 m2 g-1) and largest pore diameter (29 nm), showed the highest NH4+ adsorption capacity (0.34 mg NH4+g-1), while charcoal-based activated carbon, with the highest surface area (1133 m2 g-1) and small pore diameter (6 nm), had the least NH4+ adsorption capacity (0.09 mg NH4+g-1). The value of Freundlich isotherm constant 'n' was >1 for all tested carbon materials indicating chemisorption as the dominant sorption mechanism. Aging of the carbon surface resulted in 30% increase in NH4+ retention. Surface chemical properties that most influenced NH4+ chemisorption on to carbon materials were found to be acidic surface functional groups (ASFGs), elemental composition, ash content, and pH. The optimal conditions for NH4+ adsorption, regardless of type and source of carbon materials, were solution pH of 8, a high amount of ash content, and carboxyl, carbonyl, and phenolic functional groups. Evaluation of CEC and ASFGs indicated that CEC and ASFGs are not equivalent terms. Through this study, conducted on carbon adsorbents derived from different sources, with different surface physical and chemical properties, we established that ASFGs, and not CEC, play a critical role in ammonium chemisorption on carbon materials. The study showed that low cost and eco-friendly biochars, with optimal surface chemistry, can replace expensive activated carbons for NH4+ remediation in aqueous media.


Results of a phase II trial of S-1 as first-line treatment of metastatic pancreatic cancer (CESAR-study group).
S-1, an oral fluoropyrimidine derivative, has previously demonstrated anticancer efficacy in pancreatic cancer (PC), predominantly in Asian populations. This study evaluated the antitumor effect and safety of S-1 in Caucasian patients with metastatic PC. Chemotherapy-naïve patients received S-1 orally at 30 mg/m(2) twice daily (BID) for 2 weeks, repeated every 3 weeks. Primary endpoint was ORR. Secondary endpoints included PFS, OS and safety assessment. The trial had a Simon's two-stage design with 22 patients evaluable for efficacy in stage 1 and an additional 18 patients in stage 2, if ≥3/22 patients had a confirmed response at the first stage. Three out of 27 patients showed PR, however, detection of asymptomatic brain metastases in one of them prevented this study from proceeding to stage 2. The median PFS and OS for all patients was 3.5 and 9.1 months, respectively. The median duration of disease control for patients with SD or PR (n = 17) was 4.3 months. S-1 was well tolerated; fatigue was the most frequent grade 3/4 adverse event. Efficacy data of PFS and OS are at least comparable to gemcitabine, the current standard of care. S-1 is active in Caucasian patients with metastatic PC.


Functional anatomy of the cerebral cortex by computed tomography.
The authors describe the morphological characteristics that allow recognition of the individual computed tomography slice and determine its sequence in the series. In addition, each slices is "assembled" by defining the different cortical gyri, sulci, and cortical functional areas (based on Brodmann's maps). This work lays the foundation for correlative studies of location of lesions and the clinical picture.


Ambulatory blood pressure monitoring is a useful clinical tool in nephrology.
Hypertension is a key factor in the genesis and deterioration of many renal diseases and is also a risk factor for death in patients with end-stage renal disease. However, the standard methods of measurement are prone to variability, especially in patients undergoing dialysis. The technique of ambulatory blood pressure monitoring allows a better assessment of overall blood pressure levels and promises to assume a bigger role in the care of renal patients. Ambulatory blood pressure monitoring is widely used in hypertension trials, and the reports of several consensus meetings on the clinical uses of ambulatory blood pressure monitoring have been published. Two similar validation protocols now exist for ambulatory blood pressure monitors, and tables of population-based normal blood pressures for age and gender are available. The available evidence suggests that ambulatory blood pressure compared with blood pressure measured in the physician's office is better correlated to left ventricular mass in subjects with chronic renal disease. Furthermore, studies in subjects with chronic renal disease and those undergoing renal replacement therapy show that blood pressure control is suboptimal in many patients and that nocturnal blood pressure is generally higher than in control subjects. Further insights into overall blood pressure behavior in this population will certainly emerge in the future.


Characterization of rotavirus strains from day care centers: pre- and post-rotavirus vaccine era.
In 2006 the rotavirus vaccine was included in the Brazilian Immunization Program. The aim of this study was to report the results of a 5-year surveillance study of rotavirus strains in children < 5 years with acute gastroenteritis from day care centers in the state of São Paulo, Brazil. This retrospective study was conducted with 30 day care centers from 2004 to 2008 with convenient surveillance fecal specimens, investigated by ELISA, SDS-PAGE, RT-PCR and gene sequencing to genotype characterization. Rotavirus infection was detected in 28.3% of samples (38/134). The most frequent genotypes detected were G9P[8] and G1P[8] in 2004; G1P[8] in 2005; GNTP[NT] in 2006; G2P[4] in 2007; and there were no cases in 2008. Mixed infections were not observed. Detection rate declined from 65.7% (23/35) in 2004 to 50% (9/18) in 2007. Genotype distribution varied according to collection year, accompanied by a reduction in detection rate. Use of rotavirus vaccine requires implementation of post-marketing surveillance to monitor rotavirus strain diversity and its efficacy against possible new emerging genotypes.


Efficacy and security of continent catheterizable channels at short and middle term for adult neurogenic bladder dysfunction.
The objective of this study was to assess the effectiveness and the complications rate following continent cutaneous channels (CCC) procedures, at short and medium term follow-up (FU). A continuous retrospective case series (2008-2018): all patients who have undergone a CCC for neurogenic bladder were included in our department. The primary outcome was the effectiveness of CCC defined by the status of catheterizability (by the patient or a care-giver), continence of the tube, and absence of reintervention at 3 and 12 months FU. The secondary outcome was the prevalence of postoperative complications at 3 and 12 months FU. Fifty-three patients were included during the study period in our department. Median follow up was 3,3 years (1.5-6.1). The overall effectiveness of CCC was 67.9% (n=36/53) at 3 months FU and 45,3% (n=24) at 12 months FU. The global rate of complications was 60.4% (n=32/53) at 3 months, and 73.6% (n=39/73) at 12 months FU. The statistical analysis showed no statistical differences on efficacy and complications in the different subgroups of CCC. In the current series, the effectiveness and the complications rates following CCC were comparable across the procedure types. 4.


Conformation and persistence length of chitosan in aqueous solutions of different ionic strengths via asymmetric flow field-flow fractionation.
Conformation of chitosan in acidic aqueous solutions is strongly influenced by ionic strength, but the conventional employed size exclusion chromatography is limited to high ionic strength. Here we show that conformation of chitosan in acetate buffer down to millimolar ionic strength can be studied via asymmetric flow field-flow fractionation (AF4), where the separation is governed by the diffusion properties of the chitosan molecules and assisted by the electrostatic repulsion of the polyelectrolyte from the channel membrane. The size of chitosan decreases with ionic strength due to increasing screening of the polyelectrolyte effect. The persistence length of chitosan in the solutions, obtained by fitting the conformation plot by the wormlike chain model, decreases linearly with the Debye screening length from 44.5 nm at a salt concentration of 1.25 mM dominated by the electrostatic contribution to 8.6 nm in 800 mM acetate buffer close to its intrinsic persistence length of 7.7 nm.


'Top cover neuropathy'--transient brachial plexopathy due to body armour.
Two cases of partial lesions of the brachial plexus (brachial plexopathy) occurring in soldiers wearing body armour are described. This is an occupational hazard which has not been reported before.


Hippocampal synaptic loss in early Alzheimer's disease and mild cognitive impairment.
One of the major neuropathological findings in the brains of individuals with Alzheimer's disease (AD) is a loss of synaptic contacts in both the neocortex and hippocampus. Here we report, for the first time, an estimate of the total number of synapses in the outer molecular layer (OML) of the human dentate gyrus, in individuals with early Alzheimer's disease (eAD), mild cognitive impairment (MCI), or no cognitive impairment (NCI). An unbiased stereologic sampling scheme coupled with transmission electron microscopy to directly visualize synaptic contacts, was used to estimate the total number of synapses in short postmortem autopsy tissue. Individuals with eAD had significantly fewer synapses than the other two diagnostic groups. Seventy-five percent of the individuals with MCI had synaptic values that were lower than the NCI group mean. The number of synapses showed a significant correlation with the subject's Mini-Mental State score and with cognitive tests involving delayed recall. Synaptic loss showed no relationship to Braak stage or to apoE genotype. The volume of the OML was significantly reduced in eAD compared to the other two diagnositic groups that were not different from each other. These data suggest that a loss of afferents from the entorhinal cortex underlie the synapse loss seen in eAD. This study supports the concept that synapse loss is an early event in the disease process and suggests that MCI may be a transition stage between eAD and NCI with synaptic loss a structural correlate involved in cognitive decline.


A 23-year study of mortality and development of co-morbidities in patients with obesity undergoing bariatric surgery (laparoscopic gastric banding) in comparison with medical treatment of obesity.
Several studies have shown that bariatric surgery reduces long term mortality compared to medical weight loss therapy. In a previous study we have demonstrated that gastric banding (LAGB) is associated with reduced mortality in patients with and without diabetes, and with reduced incidence of obesity co-morbidities (cardiovascular disease, diabetes, and cancer) at a 17 year follow-up. The aim of this study was to verify at a longer time interval (23 years) mortality and incidence of co-morbidities in patients undergoing LAGB or medical weight loss therapy. As reported in the previous shorter-time study, medical records of obese patients [body mass index (BMI) > 35 kg/m2 undergoing LAGB (n = 385; 52 with diabetes) or medical treatment (controls, n = 681; 127 with diabetes), during the period 1995-2001 (visit 1)] were collected. Patients were matched for age, sex, BMI, and blood pressure. Identification codes of patients were entered in the Italian National Health System Lumbardy database, that contains life status, causes of death, as well as exemptions, prescriptions, and hospital admissions (proxies of diseases) from visit 1 to June 2018. Survival was compared across LAGB patients and matched controls using Kaplan-Meier plots adjusted Cox regression analyses. Final observation period was 19.5 ± 1.87 years (13.4-23.5). Compared to controls, LAGB was associated with reduced mortality [HR = 0.52, 95% CI 0.33-0.80, p = 0.003], significant in patients with diabetes [HR = 0.46, 95% CI 0.22-0.94, p = 0.034], borderline significant in patients without diabetes [HR = 0.61, 95% CI = 0.35-1.05, p = 0.076]. LAGB was associated with lower incidence of diabetes (15 vs 75 cases, p = 0.001), of CV diseases (61 vs 226 cases, p = 0.009), of cancer (10 vs 35, p = 0.01), and of renal diseases (0 vs 35, p = 0.001), and of hospital admissions (92 vs 377, p = 0.001). The preventive effect of LAGB on mortality is maintained up to 23 years, even with a decreased efficacy compared with the shorter-time study, while the preventive effect of LAGB on co-morbidities and on hospital admissions increases with time.


Towards screening of inhalation formulations: measuring interactions with atomic force microscopy.
This review charts the progress of atomic force microscopy (AFM) to investigate particle interactions relevant to the performance of inhalers. AFM provides a unique opportunity to examine and quantify single particle behaviour of powdered drugs and excipients in a variety of environmental conditions. An introduction to AFM and particle interactions is given. Comparative experiments that rank adhesion between materials, and quantitative experiments that lead to the measurement of properties such as the work of adhesion and surface energy, are reviewed. The AFM has been widely used to investigate the effects of relative humidity and surface roughness on particle adhesion; these experiments are also reviewed. In the final section, the potential of this approach to screen formulations is discussed.


Immunological adjuvant effect of Glycyrrhiza uralensis saponins on the immune responses to ovalbumin in mice.
In this study, the haemolytic activities of Glycyrrhiza uralensis saponins (GLS) and its adjuvant potentials on the cellular and humoral immune responses of ICR mice against ovalbumin (OVA) were evaluated. We determined the haemolytic activity of GLS using 0.5% rabbit red blood cell. Haemolytic percents of GLS-treated red blood cell were 11.20 and 5.54% at the concentrations of 500 and 250 microg/ml, respectively. ICR mice were immunized subcutaneously with OVA 100 microg alone or with OVA 100 microg dissolved in saline containing Alum (200 microg), QuilA (10 and 20 microg), or GLS (50, 100, or 200 microg) on Days 1 and 15. Two weeks later (Day 28), concanavalin A (Con A)-, lipopolysaccharide (LPS)-, and OVA-stimulated splenocyte proliferation and OVA-specific serum antibodies were measured. GLS significantly enhanced the Con A-, LPS-, and OVA-induced splenocyte proliferation in the OVA-immunized mice at a dose of 100 microg (P<0.025). OVA-specific IgG, IgG1, and IgG2b antibody titers in serum were also significantly enhanced by GLS compared with OVA control group (P<0.025). Moreover, no significant differences (P>0.05) were observed between enhancing effect of GLS and QuilA on the OVA-specific IgG, IgG1, and IgG2b antibody responses to OVA in mice. The results suggest that GLS showed a slight haemolytic effect and enhanced significantly a specific antibody and cellular response against OVA in mice, and deserved further researches to be developed as immunological adjuvant.


Association between ambulatory blood pressure monitoring patterns with cognitive function and risk of dementia: a systematic review and meta-analysis.
The objective of this systematic review and meta-analysis is to investigate whether nocturnal blood pressure fall, expressed by dipping patterns according to 24 h ambulatory blood pressure monitoring (ABPM), is associated with abnormal cognitive function (cognitive impairment or dementia). We systematically searched PubMed, Embase, and Cochrane databases to identify original articles through December 2022. We included any study with at least ten participants reporting on all-cause dementia or cognitive impairment incidence (primary outcome) or validated cognitive tests (secondary outcome) among ABPM patterns. We assessed risk of bias using Newcastle-Ottawa Quality Assessment Scale. We pooled odds ratios (OR) and standardized mean differences (SMD) using random-effect models for primary and secondary outcome, respectively. In the qualitative synthesis, 28 studies examining 7595 patients were included. The pooled analysis of 18 studies showed that dippers had a 51% [OR 0.49(0.35-0.69)] lower risk of abnormal cognitive function and a 63% [OR 0.37(0.23-0.61)] lower risk of dementia alone, compared to non-dippers. Reverse dippers presented an up to sixfold higher risk [OR 6.06(3.15-11.64)] of abnormal cognitive function compared to dippers and an almost twofold higher risk [OR 1.81(1.26-2.6)] compared to non-dippers. Reverse dippers performed worse in global function neuropsychological tests compared with both dippers [SMD - 0.66(- 0.93 to - 0.39)] and non-dippers [SMD - 0.35(- 0.53 to - 0.16)]. Dysregulation of the normal circadian BP rhythm, specifically non-dipping and reverse dipping is associated with abnormal cognitive function. Further studies are required to determine potential underlying mechanisms and possible prognostic or therapeutic implications. PROSPERO database (ID: CRD42022310384).


A membrane filtering method for the purification of giant unilamellar vesicles.
The use of giant unilamellar vesicles (GUVs) for investigating the properties of biomembranes is advantageous compared to the use of small-sized vesicles such as large unilamellar vesicles (LUVs). Experimental methods using GUVs, such as the single GUV method, would benefit if there was a methodology for obtaining a large population of similar-sized GUVs composed of oil-free membranes. We here describe a new membrane filtering method for purifying GUVs prepared by the natural swelling method and demonstrate that, following purification of GUVs composed of dioleoylphosphatidylglycerol (DOPG)/dioleoylphosphatidylcholine (DOPC) membranes suspended in a buffer, similar-sized GUVs with diameters of 10-30 μm are obtained. Moreover, this method enabled GUVs to be separated from water-soluble fluorescent probes and LUVs. These results suggest that the membrane filtering method can be applied to GUVs prepared by other methods to purify larger-sized GUVs from smaller GUVs, LUVs, and various water-soluble substances such as proteins and fluorescent probes. This method can also be used for concentration of dilute GUV suspensions.


Purification and assembly of human Argonaute, Dicer, and TRBP complexes.
The RNA-induced silencing complex (RISC) is a programmable gene-silencing machine involved in many aspects of eukaryotic biology. In humans, RISC is programmed or "loaded" with a small-guide RNA by the action of a tri-molecular assembly termed the RISC-loading complex (RLC). The human RLC is composed of the proteins Dicer, TRBP, and Argonaute2 (Ago2). To facilitate structural and biochemical dissection of the RISC-loading process, we have developed a system for the in vitro reconstitution of the human RLC. Here, we describe in detail methods for the expression and purification of recombinant Dicer, TRBP, and Ago2 and protocols for the assembly of RLCs and RLC subcomplexes. We also describe several simple assays to observe the biochemical activities of the assembled protein complexes.


Ythdf m6A Readers Function Redundantly during Zebrafish Development.
During the maternal-to-zygotic transition (MZT), multiple mechanisms precisely control massive decay of maternal mRNAs. N6-methyladenosine (m6A) is known to regulate mRNA decay, yet how this modification promotes maternal transcript degradation remains unclear. Here, we find that m6A promotes maternal mRNA deadenylation. Yet, genetic loss of m6A readers Ythdf2 and Ythdf3 did not impact global maternal mRNA clearance, zygotic genome activation, or the onset of gastrulation, challenging the view that Ythdf2 alone is critical to developmental timing. We reveal that Ythdf proteins function redundantly during zebrafish oogenesis and development, as double Ythdf2 and Ythdf3 deletion prevented female gonad formation and triple Ythdf mutants were lethal. Finally, we show that the microRNA miR-430 functions additively with methylation to promote degradation of common transcript targets. Together these findings reveal that m6A facilitates maternal mRNA deadenylation and that multiple pathways and readers act in concert to mediate these effects of methylation on RNA stability.


scyllo-inositol and myo-inositol levels in tissues of the skate Raja erinacea.
1. Many organs of the skate Raja erinacea have been found to contain scyllo-inositol levels that are much higher than myo-inositol, the opposite to that found in mammals. 2. Both inositols were found in all skate organs studied. 3. myo-Inosose-2 was found to accompany the inositols in many of these organs.


Thin Thermally Evaporated Organic Hole Transport Layers for Reduced Optical Losses in Substrate-Configuration Perovskite Solar Cells.
Parasitic optical absorption is one of the root causes of the moderate efficiency of metal halide perovskite solar cells (PSCs) with an opaque substrate configuration. Here, we investigate the reduction of these optical losses by using thin (7-10 nm), undoped, thermally evaporated 2,2',7,7'-tetrakis[N,N-di(4-methoxyphenyl)amino]-9,9'-spirobifluorene (spiro-OMeTAD), N,N'-di(1-naphthyl)-N,N'-diphenyl-(1,1'-biphenyl)-4,4'-diamine) (NPB), and tris(4-carbazoyl-9-ylphenyl)amine) (TCTA) hole transport layers (HTLs). Of these, NPB is found to offer the best compromise between efficiency and stability. In semitransparent n-i-p configuration PSCs with an indium tin oxide bottom and a MoO3/thin-Au/ZnS dielectric-metal-dielectric top electrode, NPB gives 14.9% and 10.7% efficiency for bottom and top illumination, respectively. The corresponding substrate-configuration PSC fabricated on an Au bottom electrode has 13.1% efficiency. Compared to a 14.0% efficient PSC with a thick spin-coated doped spiro-OMeTAD layer, the cell with NPB provides an improved short-circuit current density but has slightly lower open-circuit voltage and fill factor. Detailed analysis of the optical losses in the opaque devices demonstrates that evaporated NPB offers negligible parasitic absorption compared to solution-processed spiro-OMeTAD. The optical losses that remain are due to absorption and reflection of the transparent top electrode.


Genetic aspects of human obesity.
Obesity and its related metabolic consequences represent a major public health problem. Huge changes within the environment have undoubtedly contributed to the increased prevalence of obesity but genetic factors are also critical in determining an individual's predisposition to gain weight. The last two decades have seen a huge increase in the understanding of the mechanisms controlling appetitive behavior, body composition, and energy expenditure. Many regions throughout the central nervous system play critical roles in these processes but the hypothalamus, in particular, receives and orchestrates a variety of signals to bring about coordinated changes in energy balance. Reviewing data from human genetic and model organism studies, we consider how disruptions of hypothalamic pathways evolved to maintain energy homeostasis and go on to cause obesity. We highlight ongoing technological developments which continue to lead to novel insights and discuss how this increased knowledge may lead to effective therapeutic interventions in the future.


Does the use of antibiotic spacer disrupt induced membrane function?
Treatment of large segmental bone defects has been a challenging and long process for both physicians and patients. At present, the induced membrane technique is one of the reconstruction techniques commonly utilized in treating large segmental bone defects. It consists of a two-step procedure. In the first one, after bone debridement, the defect is filled with bone cement. The aim at this stage is to support and protect the defective area with cement. A membrane is formed around the area where cement was inserted 4-6 weeks after the first surgical stage. This membrane secretes vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), platelet-derived growth factor (PDGF), as shown in the earliest studies. In the second step, the bone cement is removed, and the defect is filled with cancellous bone autograft. In the first stage, antibiotics can be added to the applied bone cement, depending on the infection. Still, the histological and micromolecular effects of the added antibiotic on the membrane are unknown.This study investigates the molecular and histological effects of antibiotics addition into bone cement on the induced membrane.In this study, conducted on 27 male New Zealand rabbits, the 2 cm long defects of a bone were created in the rabbit femurs. Three groups were formed by placing antibiotic-free, gentamicin, and vancomycin-containing cement in the defect area.These groups were followed for six weeks, and the membrane formed at the end of 6 weeks was examined histologically. As a result of this study, it found that the membrane quality markers (Von Willebrand factor (vwf), Interleukin 6-8 (IL), Transforming growth factor beta (TGF-β), Vascular endothelial growth factor (VEGF) were significantly higher in the antibiotic-free bone cement group. Our study has shown that antibiotics added to the cement have negative effects on the membrane. Based on the results we obtained, it would be a better choice to use antibiotic-free cement in aseptic nonunions. However, more data is needed to understand the effects of these changes on the cement on the membrane.


Integrated PET/CT for the evaluation of para-aortic nodal metastasis in locally advanced cervical cancer patients with negative conventional CT findings.
The aim of this study was to evaluate the usefulness of integrated 2-[18F] fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (PET/CT) for the detection of para-aortic nodal status and to test whether PET/CT change management strategy in locally advanced cervical cancer (LACC) patients with negative conventional CT findings. Sixteen locally advanced (FIGO stage IIB-IVA) cervical squamous cancer patients with negative conventional CT findings were eligible to enter this prospective study. All patients underwent firstly PET/CT scans then extraperitoneal surgical exploration for para-aortic lymphadenectomy. Based on histopathologic confirmation, the accuracy, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of the PET/CT for para-aortic lymph node metastasis were estimated. The median age was 48.7 (range 42-67). The accuracy, sensitivity, specificity, PPV and NPV of the PET/CT were 75%, 50%, 83.3%, 50% and 83.3%, respectively. The treatment was modified in four of sixteen (25%) patients; four patients received EFRT in combination with cisplatin chemotherapy instead of standard pelvic field radiotherapy in combination with cisplatin chemotherapy. Our results, despite our study group is small, suggest that PET/CT is an effective imaging technique in the evaluation of LACC with negative CT findings. It may help planning the management especially selecting radiation field. However, larger controlled studies are needed to recommend PET/CT as an alternative to pre-treatment surgical staging.


Comparison of endogenous and radiolabeled bile acid excretion in patients with idiopathic chronic diarrhea.
Fecal recovery of radioactivity after ingestion of a bolus of radiolabeled bile acid is abnormally high in most patients with idiopathic chronic diarrhea. To evaluate the significance of this malabsorption, concurrent fecal excretion of both exogenous radiolabeled bile acid and endogenous (unlabeled) bile acid were measured in patients with idiopathic chronic diarrhea. Subjects received a 2.5-microCi oral dose of taurocholic acid labeled with 14C in the 24th position of the steroid moiety. Endogenous bile acid excretion was measured by a hydroxysteroid dehydrogenase assay on a concurrent 72-h stool collection. Both radiolabeled and endogenous bile acid excretion were abnormally high in most patients with chronic diarrhea compared with normal subjects, even when equivoluminous diarrhea was induced in normal subjects by ingestion of osmotically active solutions. The correlation between radiolabeled and endogenous bile acid excretion was good. However, neither radiolabeled nor endogenous bile acid excretion was as abnormal as is typically seen in patients with ileal resection, and none of these diarrhea patients responded to treatment with cholestyramine with stool weights less than 200 g. These results suggest (a) that this radiolabeled bile acid excretion test accurately reflects excess endogenous bile acid excretion; (b) that excess endogenous bile acid excretion is not caused by diarrhea per se; (c) that spontaneously occurring idiopathic chronic diarrhea is often associated with increased endogenous bile acid excretion; and (d) that bile acid malabsorption is not likely to be the primary cause of diarrhea in most of these patients.


Heat-stable enterotoxigenic Escherichia coli and necrotizing enterocolitis: lack of an association.
During an outbreak of diarrhea in a special care nursery caused by heat-stable enterotoxigenic Escherichia coli (serotype 078:H11:K80), nine (4.3%) of the 205 infants in the nursery developed necrotizing enterocolitis. Cases of necrotizing enterocolitis were not significantly more common in infants colonized or infected with these organisms; heat-stable enterotoxigenic E. coli was isolated from 5(56%) of nine cases of necrotizing ecterocolitis and from 27(38%) of the 71 infants without necrotizing enterocolitis who were also cultured. Our findings suggest that caution should be taken in implicating enterotoxigenic E. coli as a cause of necrotizing enterocolitis.


Early oncologic outcomes of robotic vs. open radical cystectomy for urothelial cancer.
Oncologic outcomes of robotic cystectomy have focused on pathology and not on survival endpoints. We compared pathology, recurrence, and survival in a single surgeon series of open and robotic cystectomy since the introduction of robotic cystectomy. We identified all patients treated by a single surgeon with radical cystectomy for urothelial cancer from June 2007 to June 2010. Clinical, demographic, and pathologic data was abstracted from chart review. Mortality was obtained from institutional cancer registry and chart review. Patients were excluded from analysis for a relative contraindication to robotic surgery. The remaining cohort of patients undergoing robotic (n = 36) vs. open (n = 29) cystectomy with median follow-up 12.2 months were evaluated. The robotic cohort was more likely to be older and male (P < 0.05). Obesity, comorbidity, preoperative pathology, and receipt of neoadjuvant chemotherapy were not different between groups. Three patients had conversion from robotic to open cystectomy because of difficult dissection. Mean surgical time was longer in robotic cystectomy (410 vs. 345 minutes, P < 0.01). Cystectomy pathology was not different for robotic vs. open surgery for stage, margin status, or mean node count (robotic: 17.0, open: 15.5). On survival analysis robotic and open cystectomy outcomes were similar with respect to recurrence-free, disease-specific, and overall survival (all log-rank P values > 0.05). The Kaplan-Meier estimate for 2-year outcome for recurrence-free, disease-specific, and overall survival was 67% (95% CI: 41-83), 75% (95% CI: 53-88), 68% (95% CI: 47-82) for robotic cystectomy and 58% (95% CI: 29-79), 63% (95% CI: 34-82), 63% (95% CI: 34-82) for open cystectomy. Short-term oncologic outcomes were similar for open and robotic cystectomy. Increased sample size and further follow-up are necessary before claiming equivalent long-term survival.


Conference Report on TEDD & 3R Workshop at ZHAW Waedenswil.
On April 7, 2017, TEDD (Tissue Engineering for Drug Development and Substance Testing) and the Animal Research Foundation joined forces at ZHAW Waedenswil to present their latest scientific results in the domain of the 3Rs of biomedical research: how to Refine, Reduce and Replace animal testing with alternative approaches.


Crop response to El Niño-Southern Oscillation related weather variation to help farmers manage their crops.
Although weather is a major driver of crop yield, many farmers don't know in advance how the weather will vary nor how their crops will respond. We hypothesized that where El Niño-Southern Oscillation (ENSO) drives weather patterns, and data on crop response to distinct management practices exists, it should be possible to map ENSO Oceanic Index (ENSO OI) patterns to crop management responses without precise weather data. Time series data on cacao farm yields in Sulawesi, Indonesia, with and without fertilizer, were used to provide proof-of-concept. A machine learning approach associated 75% of cacao yield variation with the ENSO patterns up to 8 and 24 months before harvest and predicted when fertilizer applications would be worthwhile. Thus, it's possible to relate average cacao crop performance and management response directly to ENSO patterns without weather data provided: (1) site specific data exist on crop performance over time with distinct management practices; and (2) the weather patterns are driven by ENSO OI. We believe that the principles established here can readily be applied to other crops, particularly when there's little data available on crop responses to management and weather. However, specific models will be required for each crop and every recommendation domain.


Erratum: Hyperventilation-Triggered Vertigo and Nystagmus in Vestibular Paroxysmia.
This corrects the article on p. 507 in vol. 16, PMID: 32657077.


What is the impact of snakebite envenoming on domestic animals? A nation-wide community-based study in Nepal and Cameroon.
Snakebite envenoming is a life-threatening disease in humans and animals and a major public health issue in rural communities of South-East Asia and sub-Saharan Africa. Yet the impact of snakebite on domestic animals has been poorly studied. This study aimed to describe the context, clinical features, treatment, and outcomes of snakebite envenoming in domestic animals in Nepal and Cameroon. Primary data on snakebite in animals were recorded from a community-based nation-wide survey on human and animal snakebite in Nepal and Cameroon (Snake-byte project). Mobile teams collected data on snakebite in humans and animals in 13,879 and 10,798 households in Nepal and Cameroon respectively from December 2018 to June 2019. This study included 405 snakebite cases (73 in Nepal and 332 in Cameroon) in multiple types of animals. An interview with a structured questionnaire collected specific information about the animal victims. Snake bites in animals took place predominantly inside and around the house or farm in Nepal (92%) and Cameroon (71%). Other frequent locations in Cameroon were field or pasture (12%). A large diversity of clinical features was reported in all types of envenomed animals. They showed either a few clinical signs (e.g., local swelling, bleeding) or a combination of multiple clinical signs. Only 9% of animal victims, mainly cattle and buffaloes and less frequently goats, sheep, and dogs, received treatment, predominantly with traditional medicine. The overall mortality of snakebite was 85% in Nepal and 87% in Cameroon. Results from this nationwide study show an important impact of snakebite on animal health in Nepal and Cameroon. There is a need for cost-effective prevention control strategies and affordable snakebite therapies in the veterinary field to save animal lives and farmer livelihood in the poorest countries of the world. The WHO global strategy to prevent and control snakebite envenoming supports a One Health approach, which may help develop integrated solutions to the snakebite problem taking into account human and animal health.


Electrophoretic analysis of the estrogen receptor. Relationship of multiple receptor forms to the molybdate-stabilized form.
The origin of and relationships among multiple forms of the estrogen receptor from rat uteri were investigated using electrophoretic and conventional hydrodynamic methods of analysis. Evidence is presented that the molybdate-stabilized, multimeric receptor (Stokes radius approximately 70A; S20,w approximately 9.5 S; Mr approximately 290,000) corresponds to an acidic form of the receptor that has relatively high electrophoretic mobility. This discrete form, which appears to represent the untransformed state that does not bind to DNA, was converted to a number of derived forms by exposure to conditions that result in receptor transformation and/or subunit dissociation. In crude cytosol, transformation always generated receptor forms that were excluded from polyacrylamide gels, and it was shown that these are large heterogeneous aggregates. This explains previous failed attempts to analyze the receptor by polyacrylamide gel electrophoresis. Transformation of partially purified, molybdate-stabilized receptor never led to aggregate formation, but resulted instead in the generation of two relatively basic estrogen-binding species of low electrophoretic mobility. These components may represent the free or dissociated estrogen-binding subunits. Together, the results suggest a model for the molybdate-stabilized receptor wherein at least one of its components is an acidic, nonestrogen-binding subunit.


Salvianolic acid A attenuates steroid resistant nephrotic syndrome through suPAR/uPAR-αvβ3 signaling Inhibition.
Salvianolic acid A (SAA) is extracted from traditional Chinese medicine Salvia miltiorrhiza and is the main water-soluble and the biologically active ingredient. SAA possesses a variety of pharmacological activities and has an excellent protective effect on kidney disease, especially steroid resistant nephrotic syndrome (SRNS), and has advantages in improving the efficacy of glucocorticoids, but its mechanism needs to be further explored. The study was designed to explore the effect of suPAR and uPAR in SRNS patients and evaluate the potential effect of SAA in improving podocyte steroid resistance and explore its mechanism. The ELISA kits were used to detect the levels of suPAR in the blood and urine of subjects. The levels of uPAR, GRα, and GRβ expression in renal tissues of SRNS patients was detected by immunohistochemistry and analyzed using the Pearson method. In vitro studies, steroid resistance model was induced by the TNF-α and IFN-γ. The protein and mRNA expression of Nephrin, GR, GRα and GRβ were analyzed using western blot and qRT-PCR. The activity of GR-DNA binding was detected by using TransAM™ GR kits. Adriamycin further induced steroid resistance podocyte. Flow cytometry was used to detect the effect of SAA on podocyte apoptosis. ELISA assay was used to detect the suPAR expression in the podocyte supernatant. Western blot and qRT-PCR were used to detect the protein and mRNA expression of uPAR and Nephrin in podocytes. The serum and urine levels of suPAR were conspicuously higher in SRNS patients than healthy volunteers and SSNS patients, and the expression of uPAR in renal tissue of SRNS patients is negatively correlated with GRα, but positively correlated with GRβ. The combination of TNF-α and IFN-γ could conspicuously increase the GRβ expression and reduce GRα/GRβ, and induce steroid resistance in podocytes. Moreover, we found that SAA could reduce the apoptosis of podocytes and suppress the expression of suPAR/uPAR, and increase the expression of Nephrin. The level of suPAR and uPAR expression may have important value in predicting glucocorticoids resistance in patients with idiopathic nephrotic syndrome (INS). The combination of TNF-α and IFN-γ induce podocytes can establish steroid resistance model in vitro. SAA could improve glucocorticoids resistance of podocyte which can be attributed in part to regulate the suPAR/uPAR-αvβ3 signaling pathway.


HLA class I and II in black children with hepatitis B virus-associated membranous nephropathy.
The pathogenetic mechanisms by which individuals with chronic hepatitis B virus (HBV) infection develop membranous nephropathy (MN) are probably dependent on interactions between viral, host and environmental factors; some evidence suggests a genetic predisposition. HBVMN constitutes a major etiological group in black children with nephrotic syndrome. We therefore explored the HLA associations in black children with HBVMN. Thirty black children, age range 2 to 16 years, with biopsy-proven HBVMN, were the subjects of the study. HBV status was determined using third generation ELISA. HLA A, B and C antigens were determined using a two-stage lymphocytotoxic test. HLA DRB1* and DQB1* typing was done using sequence-specific primers. HLA class 1 and II antigen frequencies of the study subjects were compared to controls that were randomly chosen healthy blood donors from the same population. HLA DQB1*0603 was increased in patients with HBVMN compared to controls (chi2 = 13.65, RR = 4.3). DRB1*07 and DQB1*02 were increased in frequency in the study subjects but failed to reach statistical significance. There was no significant difference in the frequencies of class 1 antigens in the study group compared to controls. To our knowledge, this is the first report of HLA associations in black patients with HBVMN in whom Class 1 and 11 antigens were determined using molecular methodology. There was a high frequency of DQB1*0603 in subjects compared to controls, suggesting a possible genetic predisposition to the development of HBVMN.


Mid-term Results of Revision Total Hip Arthroplasty Using Delta Ceramic-on-Ceramic Bearing.
Delta ceramic-on-ceramic (CoC) articulation affords excellent outcomes in primary total hip arthroplasty (THA). However, the safety and reliability of this bearing in revision THA need more evidence. This study aimed to report complications, radiological changes, clinical results, and survivorship of revision THA using Delta CoC articulation at minimum 5-year follow-up. We reviewed 118 revision THAs (113 patients: 68 men and 45 women) performed with use of Delta CoC bearing. Their mean age was 58.7 years (range, 30-90 years) and their mean body mass index was 24.6 kg/m2 (range, 15.2-32.5 kg/m2). These patients were followed up for 5-12 years (mean, 7.2 years). We evaluated squeak, grinding sensation, ceramic fracture, dislocation, periprosthetic joint infection (PJI), periprosthetic fracture, prosthetic loosening, ceramic wear, osteolysis, modified Harris hip score (mHHS), and survivorship with any reoperation after the revision as the endpoint. Two patients (1.7%) had grinding sensation, but no patient had ceramic fracture. Reoperations were necessary in 9 hips (7.6%) due to PJIs in 2, stem loosening in 2, cup loosening in 2, recurrent dislocation in 2, and periprosthetic fracture in 1. No hip had measurable wear or osteolysis. The average mHHS improved from 53.3 points before the revision to 82.3 points at the final follow-up. Survivorship was 91.6% (95% confidence interval, 86.3%-96.9%) at 12 years. The Delta ceramic bearing appeared a reliable option for revision THA, showing encouraging mid-term results with acceptable survivorship and a low complication rate.


Monitoring of functional changes after transient ischemia in gerbil cochlea.
Ischemia and reperfusion are involved in numerous sensorineural pathologies. A model of reversible cochlear ischemia has been designed in Mongolian gerbil. Selective labyrinthine ischemia of variable duration (4-10 min) was achieved through a posterior transcranial approach. Ischemia and reperfusion were controlled with the help of laser Doppler velocimetry. Functional changes were monitored every 1-10 s throughout experiments, using cochlear potentials and otoacoustic emissions. After interruption of blood flow, all signals rapidly began to decay. In contrast to cochlear potentials, otoacoustic emissions always exhibited a plateau before reaching noise floor only after approximately 4-5 min. Upon ischemia release, cochlear blood flow recovered instantly and completely and cochlear potentials rapidly improved in most cases, in contrast to otoacoustic emissions that underwent a delayed decay after immediate partial recovery. The phase and group latency of otoacoustic emissions exhibited only small changes throughout ischemia and reperfusion, suggesting adaptive rather than damaging mechanisms. Cochlear function returned to normal after 5 min 30 s ischemia but longer complete ischemia sometimes led to irreversible damage despite the systematic presence of some recovery just after ischemia release. This behavior suggests that reperfusion in itself can be deleterious to a sensorineural organ and this model can be useful for identifying the noxious mechanisms of ischemia and reperfusion.


Statistical considerations for confirmatory clinical trials for similar biotherapeutic products.
For the purpose of comparing the efficacy and safety of a Similar Biotherapeutic Product (SBP) to a Reference Biotherapeutic Product (RBP), the "Guidelines on Evaluation of Similar Biotherapeutic Products (SBPs)" issued by the World Health Organisation (WHO), states that equivalence or non-inferiority studies may be acceptable. While in principle, equivalence trials are preferred, non-inferiority trials may be considered if appropriately justified, such as for a medicinal product with a wide safety margin. However, the statistical issues involved in the design, conduct, analysis and interpretation of equivalence and non-inferiority trials are complex and subtle, and require that all aspects of these trials be given careful consideration. These issues are important in order to ensure that equivalence and non-inferiority trials provide valid data that are necessary to draw reliable conclusions regarding the clinical similarity of an SBP to an RBP.


Health-care utilization among dementia patients with or without comorbid depression in Taiwan: A nationwide population-based longitudinal study.
Few studies have examined the association of comorbid depression with health-care utilization among dementia patients. This study compared health-care utilization between dementia patients with and without comorbid depression. Using Taiwan's National Health Insurance Research Database, we identified 10,710 patients with newly diagnosed dementia between 2005 and 2014: 1785 had comorbid depression (group 1) and 8925 did not (group 2). Patients were tracked for 1 year to evaluate outpatient, emergency, and inpatient service utilization and length of hospital stay (LOS). Multivariable regression was applied to examine the association between comorbid depression and health-care utilization and analyze factors associated with inpatient visits and LOS. Group 1 had significantly fewer outpatient visits (β = -0.115; p < 0.001), more inpatient visits (β = 0.157; p = 0.005), and a longer LOS (β = 0.191; p < 0.001) than did group 2. The groups did not differ significantly in emergency visits (β = 0.030; p = 0.537). In group 1, age, gender, and specific comorbidities were predictors of inpatient visits; those factors and salary-based insurance premiums were predictors of LOS. Group 1 utilized less outpatient care but more inpatient care, suggesting health-care service for these patients may be needed to improvement.


A portable in vitro brain slice chamber.
A portable chamber is described which is suitable for maintaining live slices of brain tissue while they are being transported by automobile. The chamber supplies nutrient medium, oxygen, temperature control, and shock isolation.


Liability for unfounded "fear firing" under ADA: a real threat of violence, or just the postal worker metaphor?
Employers are sometimes confused with employee conduct that is truly a menace to the welfare of co-workers. Often, unusual behavior is perceived by others as being threatening but is not truly so. Managers must differentiate and act appropriately under the circumstances. This article outlines somes of the situations that may arise and provides guidance for managers' response within the rules set forth by the Americans with Disabilities Act (ADA). A policy of zero tolerance for disruptive acts may serve most practices well. The appropriate use of professional evaluations and employee assistance programs (EAPs) is also discussed.


Antioxidant response and quality of sunburn Beurré D'Anjou pears (Pyrus communis L.).
Sunburn is a physiological fruit disorder induced by exposure to excessive solar radiation. This disorder leads to significant losses in the yield of marketable fruits by negatively affecting quality parameters such as maturity and external color of the fruits. The purpose of this work was to characterize the physiological and biochemical aspects related to oxidative metabolism in Beurré D'Anjou pear fruit with different sunburn levels. Fruits were collected and classified into three sunburn levels at harvest: no sunburn (S0), mild sunburn (S1), and moderate sunburn (S2). On sunburned area, the maturity indices were measured on the fruit flesh, while external color, photosynthetic and photoprotective pigments, total phenols, electrolyte leakage, lipid peroxidation, antioxidant capacity and antioxidant enzymatic activities were determined on fruit peel. The hue angle and saturation of peel color of pears with different sunburn levels showed significant reduction with increasing damage. These changes in peel color were associated with a reduction in chlorophyll content and variations in carotenoid and anthocyanin levels. Due to metabolic changes resulting from defense and adaptive responses to high solar radiation, sunburned tissues showed significantly increased firmness, soluble solids content, and starch degradation, and lower acidity compared to undamaged fruits. We observed also increased antioxidant capacity in the peel of S1 and S2 fruit, related to higher phenolic contents and increased SOD and APX activities. Consistent with previous reports in apple, our study demonstrates that sunburn affects pear fruit quality traits and maturity state by enhancing oxidative metabolism.


Hemiarthroplasty augmented with bone graft for the failed hallux metatarsophalangeal Silastic® implant.
Symptomatic failure of Silastic® implants at the hallux metatarsophalangeal joint can result in the challenging problem of instability which may be painful. There is often marked bone loss making reconstruction difficult. Arthrodesis sacrifices joint movement while excision arthroplasty shortens the ray and is less acceptable to active patients. We describe a case in which reconstruction was achieved by using a porous coated metatarsophalangeal hemiarthroplasty augmented with bone graft with good early results. This previously unreported technique may offer an additional surgical option for reconstruction, maintaining joint movement without compromising future arthrodesis or excision arthroplasty as salvage measures. Long term follow up is required to confirm the success of this technique.


Biology of Dermacentor silvarum (Acari: Ixodidae) under laboratory conditions.
The minimum life cycle of Dermacentor silvarum Olenev had a mean duration of 87.5 days (range 74-102 days) under laboratory conditions [(27 +/- 1 degrees C), 70% RH, 6 L: 18 D]. The mean time in (days) for the different stages of its cycle was as follows: incubation period of eggs was 15.3 days; prefeeding, feeding and premoulting periods of larvae and nymphs averaged 5.5, 4.0 and 7.3 days, and 5.2, 5.0 and 14.6 days, respectively; prefeeding, feeding, preoviposition and oviposition periods of female adults lasted for 7.8, 4.5, 4.3 and 14.0 days, respectively. There existed a highly significant correlation between engorged body weight of females and egg masses laid (r = 0.9877, p<0.001). The reproductive efficiency index (REI) and reproductive fitness index (RFI) in females were 11.09 and 9.58, respectively. No relationship between nymphal engorged body weight and resultant sexes was observed. Delayed feeding and non-oviposition (in June and July) existed in females, and low temperature (-10 degrees C) treatment for 45 days could terminate oviposition diapause. However, the egg masses laid by post-diapause females were significantly smaller than those laid by females engorged in March, April and May.


Prevalence and clinical impact of Upper Gastrointestinal Symptoms in subjects treated with low dose aspirin: the UGLA survey.
Upper Gastrointestinal Symtoms (UGS) is a reason for discontinuation in patients treated by Low Dose Aspirin (LDA). The nationwide UGLA survey was designed to evaluate the prevalence and the pattern of UGS in patients on LDA, to assess the independent correlates of UGS and finally to determine their impact on treatment compliance. The UGLA survey was carried out on a representative sample of 10,000 subjects aged 50 or over. Prevalence and clinical impact of UGS related to LDA was appraised by standardised multi-choice questions. A total of 8106 propositus (8106/10,000) accepted to participate in the survey. Among them, 986 (12.2%) were treated with LDA. The prevalence of UGS was 15.4% in subjects on chronic LDA (152/986), 70% being gastroesophageal reflux (GER) (heartburn and/or regurgitation). UGS was reported to occur at least once a week in 60% of propositus (91/152) and daily life was reported to be moderately and severely impaired in 53% (81/152) and 20% (30/152) of them, respectively. UGS impacted compliance to treatment in 12% of propositus with UGS. A prior history of dyspeptic symptoms was predictive of LDA-related UGS (OR: 17.60; CI 95%: 11.52-26.88) whereas neither, gender nor aspirin dosage (ranging from 75 and 325 mg) predicted the occurrence of UGS. Fifteen percent of patients treated with LDA suffered UGS, mostly GER symptoms which had a negative impact on daily life in 3 out of 4 patients and on treatment compliance in 1 out of 8 patients.