Blood Eosinophils Are Associated with Efficacy of Targeted Therapy in Patients with Advanced Melanoma.
Eosinophils appear to contribute to the efficacy of immunotherapy and their frequency was suggested as a predictive biomarker. Whether this observation could be transferred to patients treated with targeted therapy remains unknown. Blood and serum samples of healthy controls and 216 patients with advanced melanoma were prospectively and retrospectively collected. Freshly isolated eosinophils were phenotypically characterized by flow cytometry and co-cultured in vitro with melanoma cells to assess cytotoxicity. Soluble serum markers and peripheral blood counts were used for correlative studies. Eosinophil-mediated cytotoxicity towards melanoma cells, as well as phenotypic characteristics, were similar when comparing healthy donors and patients. However, high relative pre-treatment eosinophil counts were significantly associated with response to MAPKi (p = 0.013). Eosinophil-mediated cytotoxicity towards melanoma cells is dose-dependent and requires proximity of eosinophils and their target in vitro. Treatment with targeted therapy in the presence of eosinophils results in an additive tumoricidal effect. Additionally, melanoma cells affected eosinophil phenotype upon co-culture. High pre-treatment eosinophil counts in advanced melanoma patients were associated with a significantly improved response to MAPKi. Functionally, eosinophils show potent cytotoxicity towards melanoma cells, which can be reinforced by MAPKi. Further studies are needed to unravel the molecular mechanisms of our observations.


Metagenome Analysis of Speleothem Microbiome from Subterranean Cave Reveals Insight into Community Structure, Metabolic Potential, and BGCs Diversity.
The Borra caves, the second largest subterranean karst cave ecosystem in the Indian sub-continent, are located at the Ananthagiri hills of Araku Valley in the Alluri district of Andhra Pradesh, India. The present investigation applied a shotgun metagenomic approach to gain insights into the microbial community structure, metabolic potential, and biosynthetic gene cluster (BGC) diversity of the microbes colonizing the surface of the speleothems from the aphotic zone of Borra caves. The taxonomic analysis of the metagenome data illustrated that the speleothem-colonizing core microbial community was dominated mainly by Alpha-, Beta-, and Gamma-Proteobacteria, Actinobacteria, Firmicutes, and Bacteroidetes. The key energy metabolic pathways analysis provides strong evidence of chemolithoautotrophic and chemoheterotrophic modes of nutrition in the speleothem-colonizing microbial community. Metagenome data suggests that sulfur reducers and sulfur-disproportionating microbes might play a vital role in energy generation in this ecosystem. Our metagenome data also suggest that the dissimilatory nitrifiers and nitrifying denitrifiers might play an essential role in conserving nitrogen pools in the ecosystem. Furthermore, metagenome-wide BGCs mining retrieved 451 putative BGCs; NRPS was the most abundant (24%). Phylogenetic analysis of the C domain of NRPS showed that sequences were distributed across all six function categories of the known C domain, including several novel subclades. For example, a novel subclade had been recovered within the LCL domain clade as a sister subclade of immunosuppressant cyclosporin encoding C domain sequences. Our result suggested that subterranean cave microbiomes might be a potential reservoir of novel microbial metabolites.


Calmodulin-binding proteins: A journey of 40 years.
The proteins which bind to calmodulin in a Ca2+-dependent and reversible manner are known as calmodulin-binding proteins. These proteins are involved in a multitude of processes in which Ca2+ and calmodulin play crucial roles. Our group elucidated the mechanism and importance of these proteins in normal and diseased conditions. Various calmodulin-binding proteins were discovered and purified from bovine tissue including a heat stable calmodulin-binding protein 70, calmodulin-dependent protein kinase VI and a high molecular weight calmodulin-binding protein (HMWCaMBP). We observed a complex interplay occurs between these and other Ca2+ and calmodulin-binding proteins during cardiac ischemia and reperfusion. Purified cardiac HMWCaMBP is a homolog form of calpastatin and an inhibitor of the Ca2+-activated cysteine proteases, calpains and therefore can have cardioprotective role in ischemic conditions. Calcineurin is a Ca2+ and calmodulin-dependent serine/threonine protein phosphatase showed increased phosphatase activity in ischemic heart through its direct interaction with Hsp70 and expression of calcineurin following ischemia suggests self-repair and favorable survival outcomes. Calcineurin was also found to be present in other tissues including the eye; where its expression and calcineurin phosphatase activity varied. In neurons, calcineurin may play a key role in initiating apoptosis-related pathways especially in epilepsy. In colorectal cancer we demonstrated high calcineurin phosphatase activity and simultaneous overexpression of calcineurin. The impact of calcineurin signaling on neuronal apoptosis in epilepsy and its use as a diagnostic marker for colorectal cancer requires in-depth study.


Human biomarkers in breath by photoacoustic spectroscopy.
Photoacoustic spectrometry provides a novel approach to the analysis of human breath biomarkers. This unique methodology has specific applications for determination of ethylene oxide, nitrous oxide, ammonia as well as other compounds of interest including sevoflurane, halothane, isoflurane, methane, ethane and propofol. The advantages and disadvantages of photoacoustic spectrometry for this purpose are evaluated.


Diastolic relaxation abnormalities during ischaemia and their association with high energy phosphate depletion, intracellular pH and myocardial blood flow.
Diastolic relaxation of cardiac muscle is an energy requiring process dependent upon restoration of a very low cytosolic calcium concentration. During demand ischaemia, induced by an increase in myocardial oxygen demand in the setting of restricted coronary blood flow, myocardial relaxation is impaired with a resultant decrease in left ventricular chamber distensibility. Metabolic studies suggest that high energy phosphate depletion alone cannot account for these relaxation abnormalities. Changes in myocardial pH and coronary blood flow modulate the impaired relaxation. The most likely hypothesis to explain impaired relaxation during demand ischaemia is that slow calcium uptake and incomplete calcium sequestration are characteristic of the physiology of angina pectoris and demand ischaemia, underlying the increased diastolic stiffness seen in these conditions.


Health Care Maintenance in Pediatric Inflammatory Bowel Disease.
Patients with pediatric inflammatory bowel disease (pIBD) are at an increased risk for complications and comorbidities including infection, nutritional deficiencies, growth delay, bone disease, eye disease, malignancy, and psychologic disorders. Preventative health maintenance and monitoring is an important part to caring for patients with pIBD. Although practice is variable and published study within pIBD is limited, this article summarizes the important field of health-care maintenance in pIBD. A multidisciplinary approach, including the gastroenterologist provider, primary care provider, social worker, psychologist, as well as other subspecialists is necessary.


Evidence for functional redundancy between C. elegans ADAM proteins SUP-17/Kuzbanian and ADM-4/TACE.
The ectodomain of LIN-12/Notch proteins is cleaved and shed upon ligand binding. In Caenorhabditis elegans, genetic evidence has implicated SUP-17, the ortholog of Drosophila Kuzbanian and mammalian ADAM10, as the protease that mediates this event. In mammals, however, biochemical evidence has implicated TACE, a different ADAM protein. We have investigated potential functional redundancy of sup-17 and the C. elegans ortholog of TACE, adm-4, by exploring their roles in cell fate decisions mediated by lin-12/Notch genes. We found that reduced adm-4 activity, like reduced sup-17 activity, suppresses an allele of glp-1 that encodes a constitutively active receptor. Furthermore, concomitant reduction of adm-4 and sup-17 activity causes the production of two anchor cells in the hermaphrodite gonad, instead of one--a phenotype associated with loss of lin-12 activity. Concomitant reduction of both sup-17 and adm-4 activity in hermaphrodites results in highly penetrant synthetic sterility, which appears to reflect a defect in the spermatheca. Expression of a truncated form of LIN-12 that mimics the product of ectodomain shedding rescues this fertility defect, suggesting that sup-17 and adm-4 may mediate ectodomain shedding of LIN-12 and/or GLP-1. Our results are consistent with the possibility that sup-17 and adm-4 are functionally redundant for at least a subset of LIN-12/Notch-mediated decisions in C. elegans.


Endoscopic axillo-breast approach for benign neck mass excision.
Benign neck masses are usually found in younger patients, who are more likely to be concerned about postoperative scars. Until recently, a direct approach through a transcervical incision along the mass has been accepted as a standard surgical procedure for the benign neck mass. However, this conventional transcervical approach leaves a visible scar on the neck, regardless of the size of the incision. We assumed that an endoscopic gasless axillo-breast (A-B) approach might be a good alternative method for excision of benign neck masses. The aim of this study was to determine the safety and feasibility of a gasless A-B approach for the excision of benign neck masses by comparing it to the conventional open approach. Case series. We prospectively compared the outcomes of endoscopic removal of benign neck lesions with the outcomes of conventional open surgery. Most patients in the endoscopy group were women, and the mean age was younger than in the open group. Although operative time was longer and amount of drainage was larger in the endoscopy group, there was no statistically significant difference in duration of drainage, hospitalization period, complication rate, and pain score. Endoscopically treated patients were more satisfied with the cosmetic outcome of the surgery than patients in the conventional open group. Endoscopic excision via an A-B approach without gas insufflation could be a good substitute for conventional transcervical excision in selected cases of benign neck lesion.


Striated muscle cells in the leptomeninges in cerebral dysplasia.
Non-neoplastic foci of skeletal muscle cells are rarely noted within human central nervous system. This report describes two children with developmental anomalies and striated muscle in the leptomeninges. Embryological displacement of notochordal or prechordal mesoderm in certain types of cranio-vertebral-cerebral dysplasia may account for the origin, the restricted sites and the infrequent observation of leptomeningeal striated muscle cells.


Asynchrony of ovule primordia initiation in Arabidopsis.
Plant ovule initiation determines the maximum of ovule number and has a great impact on the seed number per fruit. The detailed processes of ovule initiation have not been accurately described, although two connected processes, gynoecium and ovule development, have been investigated. Here, we report that ovules initiate asynchronously. The first group of ovule primordia grows out, the placenta elongates, the boundaries of existing ovules enlarge and a new group of primordia initiates from the boundaries. The expression pattern of different marker genes during ovule development illustrates that this asynchronicity continues throughout whole ovule development. PIN-FORMED1 polar distribution and auxin response maxima correlate with ovule primordia asynchronous initiation. We have established computational modeling to show how auxin dynamics influence ovule primordia initiation. Brassinosteroid signaling positively regulates ovule number by promoting placentae size and ovule primordia initiation through strengthening auxin response. Transcriptomic analysis demonstrates numerous known regulators of ovule development and hormone signaling, and many new genes are identified that are involved in ovule development. Taken together, our results illustrate that the ovule primordia initiate asynchronously and the hormone signals are involved in the asynchrony.


Mitral valve replacement with preservation of chordae tendineae and papillary muscles.
An operative technique for mitral valve replacement (MVR) with preservation of the chordae tendineae to the anterior leaflet as well as the posterior leaflet is reported. This technique consists of the division of the anterior leaflet into anterior and posterior segments, the shifting and reattachment of the divided segments to the mitral ring of the respective commissural areas, and the use of a low-profile bileaflet prosthetic valve. A comparison of left ventricular function data between patients having operation with this technique and those having operation with the conventional method of MVR revealed significantly better improvement in cardiac index (p less than 0.06), left ventricular end-systolic volume index (p less than 0.05), and left ventricular ejection fraction (p less than 0.10) in the former group. Left ventricular wall motion improved in the anterolateral (p less than 0.01) and apical areas (p less than 0.02) in patients operated on with our technique. Maintenance of continuity between the mitral annulus and papillary muscles is expected to have a beneficial effect on postoperative left ventricular performance in spite of increased afterload.


Analysis of Outcomes of Pharyngo-laryngo-esophagectomy and Reconstruction with Longitudinal Comparison in a Single Institution.
Advanced hypopharyngeal tumours present complex clinical challenges, and where resection is attempted, there is a requirement for major reconstruction. Despite advances in surgical technique, outcomes remain poor for this patient group, and optimum treatment has yet to be established. We aimed to assess the treatment and outcomes of patients in our institution in the context of previous studies. All patients from 2008 to 2018 who underwent surgical management for hypopharyngeal tumours with pharyngo-laryngo-esophagectomy and flap-based reconstruction were included in the study. Demographic and outcome data were collected, and patient-reported outcomes were solicited from surviving patients using the EORTC QLQ H&N 43 questionnaire. Thirty patients were assessed, in which 12 had gastric pull-ups, 16 had free jejunum flaps, and 2 had free anterolateral thigh flaps. There was a 38% five-year survival rate. Overall, the rates of stricture (10.7%) and fistula (7.1%) were low. The majority of patients (53.6%) returned to a normal diet within three months with a soft or puree diet in 35.7% of patients. Some form of speech was possible in 92.9% of patients. The average questionnaire score for surviving patients was 87.3, with good outcomes related to eating and swallowing, but poorer outcomes for speech and communication. This study showed that outcomes for patients receiving complex reconstruction following hypopharyngeal tumour resection are improving over time. There is still scope for improvement of patient outcomes and refinement of optimum surgical management strategies.


Reduction of increased calcineurin activity rescues impaired homeostatic synaptic plasticity in presenilin 1 M146V mutant.
Alzheimer's disease (AD) is one of the most common neurodegenerative diseases characterized by memory loss and cognitive impairment. Whereas most AD cases are sporadic, some are caused by mutations in early-onset familial AD (FAD) genes. One FAD gene encodes presenilin 1 (PS1), and a PS1 mutation in methionine 146 impairs homeostatic synaptic plasticity (HSP). We have previously shown that Ca(2+) and calcineurin activity are critical regulators of HSP. Here, we confirm that endoplasmic reticulum-mediated Ca(2+) signals are increased in mutant PS1 neurons. We further show that calcineurin activity is abnormally elevated in the mutant and that inhibition of increased calcineurin activity stabilizes GluA1 phosphorylation, promoting synaptic trafficking of Ca(2+)-permeable α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, contributing to the recovery of impaired HSP found in the mutant. Because HSP is suggested to have roles during learning and memory formation, increased calcineurin activity-induced impairment of HSP can cause cognitive decline in FAD. Thus, reducing abnormally increased calcineurin activity in AD brain may be beneficial for improving AD-related cognitive decline.


Brn-3a is required for the generation of proprioceptors in the mesencephalic trigeminal tract nucleus.
The distribution of motor and proprioceptive neurons was investigated in the trigeminal nervous system of wild-type and Brn-3a knockout mice at embryonic day 18.5 and postnatal day 0. We found that the trigeminal motor nucleus (Mo5) contained abundant motoneurons in wild-type (mean number +/- SD per section = 128 +/- 22, range = 93-167) and knockout (mean number +/- SD per section = 121 +/- 23, range = 75-158) mice and that the cell size of Mo5 neurons was similar between these mice (wild-type, mean +/- SD = 165 +/- 59 microm2, range = 65-326 microm2; knockout, mean +/- SD = 167 +/- 59 microm2, range = 71-327 microm2). Mo5 neurons were immunoreactive for calcitonin gene-related peptide and such immunoreactive neurons were abundant in both wild-type and mutant mice. In the mesencephalic tract nucleus (Mes5) of wild-type mice, many proprioceptors (mean number +/- SD per section = 56 +/- 19, range = 27-85) that contained parvalbumin immunoreactivity were also observed. In knockout mice, however, Mes5 neurons could not be detected. The area of brainstems which normally contained the Mes5 was devoid of parvalbumin-immunoreactive proprioceptors. The present study suggests that Brn-3a is required for the development of proprioceptors but not motoneurons in the trigeminal nervous system.


Determining the prevalence of tuberculosis in emergency departments in the Eastern Cape region of South Africa and the utility of the World Health Organization tuberculosis screening tool.
South Africa (SA) faces a significant tuberculosis (TB) burden complicated by high rates of HIV-TB co-infection. In SA, emergency departments (EDs) play an important role in screening for TB. To determine the prevalence of TB in the ED and the effectiveness of the World Health Organization (WHO) TB screening tool. This was a cross-sectional observational study, conducted in the ED at Livingstone Hospital, Port Elizabeth, from 4 June to 15 July 2018. All patients aged >18 years and able to consent were administered the WHO TB screening questions and underwent a point-of-care HIV test and demographic data collection. Patients were followed up for 1 year and tracked in the National Health Laboratory Service database to determine TB status using laboratory testing. Over the study period, 790 patients were enrolled. Overall, 121 patients (15.3%) were TB-positive, with 46 (38.0%) diagnosed after presenting to the ED and 75 (62.0%) with a previous TB history determined by self-report or confirmed laboratory testing. A greater proportion of the TB-positive patients were HIV-positive (49.6%) compared with the TB-negative population (24.8%). TB-positive individuals were more likely to present to the ED with a chief complaint of shortness of breath (SoB) (18.2%) compared with the TB-negative population (10.5%). Overall, the WHO TB screening tool had poor sensitivity (46.5%) and specificity (62.5%) for identifying TB-positive patients in the ED. A multiple logistic regression analysis, controlled for age and sex, showed HIV status (odds ratio (OR) 2.81; p<0.001) and SoB (OR 2.19; p<0.05) to be significant predictors of TB positivity. Adding positive HIV status and a presenting complaint of SoB increased sensitivity to 78.3%. EDs in SA face a high burden of TB. While WHO screening guidelines identify some of these patients, including routine HIV testing in the ED could significantly affect the number of TB diagnoses made.


Motion-compensated reconstruction of magnetic resonance images from undersampled data.
Magnetic resonance imaging of patients who find difficulty lying still or holding their breath can be challenging. Unresolved intra-frame motion yields blurring artifacts and limits spatial resolution. To correct for intra-frame non-rigid motion, such as in pediatric body imaging, this paper describes a multi-scale technique for joint estimation of the motion occurring during the acquisition and of the desired uncorrupted image. This technique regularizes the motion coefficients to enforce invertibility and minimize numerical instability. This multi-scale approach takes advantage of variable-density sampling patterns used in accelerated imaging to resolve large motion from a coarse scale. The resulting method improves image quality for a set of two-dimensional reconstructions from data simulated with independently generated deformations, with statistically significant increases in both peak signal to error ratio and structural similarity index. These improvements are consistent across varying undersampling factors and severities of motion and take advantage of the variable density sampling pattern.


Survival following coronary artery bypass grafting in patients with severe angina pectoris (CASS). An observational study.
This observational study evaluates the effects of the severity of angina pectoris and the treatment method upon the survival of 4,209 patients in the Coronary Artery Surgery Study registry. In this nonrandomized study, these patients met the criteria used in the Coronary Artery Surgery Study randomized trial, except for the degree of angina pectoris and the method of selection of treatment. The 5 year survival rate was greater than or equal to 93% in patients with Class I and II angina pectoris and normal left ventricular function, regardless of the number of involved vessels or treatment received. Late survival of surgically treated patients with Class III and IV angina pectoris and normal left ventricular function was similar, regardless of the number of vessels involved (greater than or equal to 92% at 5 years). Nonoperatively treated patients with Class III and IV angina pectoris and normal left ventricular function had poorer 5 year survival rates, lowest (74%) in patients with three vessel disease (p less than 0.0001). This difference was also observed in patients with abnormal left ventricular function, three vessel disease, and Class III and IV angina pectoris; the 5 year survival rates were 82% for the operative group and 52% for the nonoperative group (p less than 0.0001). These data confirm the importance of clinical as well as anatomic factors in determining the prognosis of patients with ischemic heart disease and indicate that coronary artery bypass grafting can improve late survival in patients with triple vessel disease and severe angina pectoris.


Exploration of acid gastroesophageal reflux by 24-h pH metry in infants at risk of sudden infant death syndrome: a study of 50 cases.
This study focused on the frequency of pathological acid gastroesophageal reflux (AGER) on 50 children considered to be at risk for sudden infant death syndrome: that is to say, 30 near misses and 20 subsequent siblings. Four parameters were studied in a 24-h pH metry: (1) The percentage of time spent at pH less than 4. (2) The length of the longest reflux. (3) The number of refluxes greater than 5 min/h. (4) Esophageal clearance. In comparison to a control group of 46 normal children, we noted a rate of 20% of AGER on the near misses and 31% on children whose siblings had died from sudden infant death syndrome. The pH level of these two groups was significantly more often less than 4, compared to the normal children. The role of AGER in sudden infant death syndrome will, therefore, be discussed.


Assessment of causal associations between handgrip strength and cardiovascular diseases: A two sample mendelian randomization study.
Several observational studies have identified that handgrip strength was inversely associated with cardiovascular diseases (CVDs). Nevertheless, causality remains controversial. We conducted Mendelian randomization (MR) analysis to examine whether handgrip strength and risk of CVDs are causally associated. We identified 160 independent single nucleotide polymorphisms (SNPs) for right-hand grip strength and 136 independent SNPs for left-hand grip strength at the genome-wide significant threshold (P < 5 × 10-8) from UK Biobank participants and evaluated these in relation to risk of CVDs. MR estimates was calculated using the inverse-variance weighted (IVW) method and multiple sensitivity analysis was further conducted. Genetical liability to handgrip strength was significantly associated with coronary artery disease (CAD) and myocardial infarction (MI), but not stroke, hypertension, or heart failure. Additionally, there was significant association between right-hand grip strength and atrial fibrillation (OR, 0.967; 95% CI, 0.950-0.984; p = 0.000222), however, suggestive significance was found between left-hand grip strength and atrial fibrillation (OR, 0.977; 95% CI, 0.957-0.998; p = 0.033). Results were similar in several sensitivity analysis. Our study provides support at the genetic level that handgrip strength is negatively associated with the risk of CAD, MI, and atrial fibrillation. Specific handgrip strength interventions on CVDs warrant exploration as potential CVDs prevention measures.


A Prospective Study of Radiation Therapy After Immediate Lymphatic Reconstruction: Analysis of the Dosimetric Implications.
Axillary lymph node dissection (ALND) and regional nodal irradiation (RNI) are the primary causes of breast cancer-related lymphedema (BCRL). Immediate lymphatic reconstruction (ILR) is a novel surgical procedure that reduces the incidence of BCRL after ALND. The ILR anastomosis is placed in a location thought to be outside the standard radiation therapy fields to prevent radiation-induced fibrosis of the reconstructed vessels; however, there is excess risk of BCRL from RNI even after ILR. The purpose of this study was to understand the radiation dose distribution in relation to the ILR anastomosis. This prospective study included 13 patients treated with ALND/ILR from October 2020 to June 2022. A twirl clip deployed during surgery was used to identify the ILR anastomosis site during radiation treatment planning. All cases were planned using a 3D-conformal technique with opposed tangents and an obliqued supraclavicular (SCV) field. RNI deliberately targeted axillary Levels 1 to 3 and the SCV nodal region in 4 patients and was limited to Level 3 and SCV nodes in 9 patients. The ILR clip was located in Level 1 in 12 patients and Level 2 in 1 patient. In patients with radiation directed at only Level 3 and SCV, the ILR clip was still within the radiation field in 5 of these patients and received a median dose of 3939 cGy (range, 2025-4961 cGy). The median dose to the ILR clip was 3939 cGy (range, 139-4961 cGy) for the entire cohort. The median dose was 4275 cGy (range, 2025-4961 cGy) when the ILR clip was within any radiation field and 233 cGy (range, 139-280 cGy) when the clip was outside all fields. The ILR anastomosis was often directly irradiated with 3D-conformal techniques and received substantial radiation dose, even when the site was not deliberately targeted. Long-term analysis will help determine whether minimizing radiation dose to the anastomosis will decrease BCRL rates.


Exercise and Cardiovascular Risk among Masters Athletes with Type 2 Diabetes.
This review was designed to provide a scientific and clinical framework for the care of physically active men and women with an emphasis on the management of T2DM. The preventative and therapeutic benefits of physical activity (PA) on adult onset or Type 2 Diabetes Mellitus (T2DM) are well established. Individuals diagnosed with or are at risk for T2DM should be counseled and maximally supported to pursue an active or athletic lifestyle. Optimally, this translates into the adoption of an athletic lifestyle. "Masters athletes", men and women above the age of 35 who regularly train for and/or participate in competitive sport, represent a rapidly growing segment of the population. Although the high level of exercise characteristic of this population has numerous health benefits, it does not confer immunity from T2DM or cardiovascular (CV) disease. Providing effective care for men and women above the age of 35 who regularly train for and/or participate in competitive sport requires an understanding of the interplay between basic exercise physiology and the pathogenesis of insulin resistance.


The capacity of murine alveolar macrophages to stimulate antigen-dependent T-lymphocyte activation and proliferation.
To define the antigen-presenting capacity of alveolar macrophages (AM phi), their ability to activate antigen-specific T cells was determined. It was found that AM phi s are at least as potent as spleen cells at presenting alloantigen or soluble protein antigen plus I-region determinant to cloned T-cell hybridomas. Activation of those hybridomas, shown by interleukin 2 (IL-2) secretion, further indicated the presence on AM phi s of functional products of the I-A and I-E subregions. In addition, it was found that AM phi s are at least as potent as spleen cells and peritoneal macrophages at inducing, in a restricted fashion, specific proliferation of primed, propagated lymph node T cells. AM phi s are thus potent accessory cells in vitro, whose in vivo significance in this capacity remains to be defined.


Low and moderate grade retroperitoneal liposarcoma: Is adjuvant radiotherapy associated with improved survival in patients undergoing R1 resection?
Few studies evaluate the efficacy of adjuvant radiotherapy (aXRT) in patients with retroperitoneal liposarcoma undergoing resection to histologically positive (R1) margins. We queried the National Cancer Database to identify patients undergoing R1 resection for localized, large (>5 cm) low and moderate grade retroperitoneal liposarcoma between 2004 and 2016. Kaplan Meier method was used to compare overall survival (OS) for patients receiving aXRT to a 1:2 propensity-matched cohort of patients undergoing resection alone. A total of 322 (76.5%) patients underwent R1 resection alone, while 99 (23.5%) underwent resection followed by aXRT. The 99 receiving aXRT were successfully 1:2 propensity-score matched to 198 undergoing resection alone. There was no difference in 5-year OS between matched cohorts (69.7% vs 76.2%, p = 0.40). In patients undergoing R1 resection of moderate- and well-differentiated retroperitoneal liposarcoma, use of aXRT is not associated with an improvement in OS.


The relevance of NMDA receptor antibody-specific index for diagnosis and prognosis in patients with anti-NMDA receptor encephalitis.
The clinical implications of the presence of anti-N-methyl-D-aspartate receptor (NMDAR)-specific intrathecal immunoglobulin G synthesis and whether it determines the diagnosis of anti-NMDAR encephalitis have not been thoroughly investigated yet. Thus, the aim of this study was to investigate whether the detection of intrathecal anti-NMDAR-specific IgG synthesis contributes to the diagnostic confirmation of anti-NMDAR encephalitis, to disease severity, and to prognosis in patients with positive serum anti-NMDAR-IgG. In this study, patients with detectable anti-NMDAR IgG in serum and/or cerebrospinal fluid (CSF) were included and separated into two groups that either met the 2016 criteria by Graus et al. of definite anti-NMDAR encephalitis (n = 27) or did not (n = 15). In a total, of 80 paired CSF/serum samples, antibody titers were titrated manually and end-point titer levels were carefully determined in a blinded manner to the subgroup attribution. The disease course was assessed via the modified Rankin Scale (mRS) and prognosis was estimated by the anti-NMDAR Encephalitis One-Year Functional Status (NEOS) score. With respect to whether the diagnostic Graus criteria for definite anti-NMDAR encephalitis were fulfilled, a significantly unequal distribution of intrathecal anti-NMDAR antibody-specific synthesis could be shown with a high negative predictive value in case of a negative anti-NMDAR antibody-specific index (NMDAR AI, p = .008. OR = 23.9, sensitivity = 1.0, specificity = 0.4, negative predictive value = 1). A weak correlation was found between the CSF antibody titer and mRS value at the time of sample collection (rs = .37, p = .008, 95% CI [.09, .59]). During the disease course a higher delta-mRS value formed of the mRS at initial presentation minus that at the last recorded presentation correlated with a higher NMDAR AI at first lumbar puncture (rs = - .56, p = .017, 95% CI [- .83, - .11]). No association with the prognostic NEOS score was found. In conclusion, a negative antibody-specific index for anti-NMDAR IgG antibodies has a highly negative predictive value for the diagnosis of anti-NMDAR encephalitis. Yet, a positive NMDAR AI alone does not allow the diagnosis of anti-NMDAR encephalitis.


Inhibition of mTOR pathway by everolimus cooperates with EGFR inhibitors in human tumours sensitive and resistant to anti-EGFR drugs.
Inhibition of a single transduction pathway is often inefficient due to activation of alternative signalling. The mammalian target of rapamycin (mTOR) is a key intracellular kinase integrating proliferation, survival and angiogenic pathways and has been implicated in the resistance to EGFR inhibitors. Thus, mTOR blockade is pursued to interfere at multiple levels with tumour growth. We used everolimus (RAD001) to inhibit mTOR, alone or in combination with anti-EGFR drugs gefitinib or cetuximab, on human cancer cell lines sensitive and resistant to EGFR inhibitors, both in vitro and in vivo. We demonstrated that everolimus is active against EGFR-resistant cancer cell lines and partially restores the ability of EGFR inhibitors to inhibit growth and survival. Everolimus reduces the expression of EGFR-related signalling effectors and VEGF production, inhibiting proliferation and capillary tube formation of endothelial cells, both alone and in combination with gefitinib. Finally, combination of everolimus and gefitinib inhibits growth of GEO and GEO-GR (gefitinib resistant) colon cancer xenografts, activation of signalling proteins and VEGF secretion. Targeting mTOR pathway with everolimus overcomes resistance to EGFR inhibitors and produces a cooperative effect with EGFR inhibitors, providing a valid therapeutic strategy to be tested in a clinical setting.


Academic nursing leadership: Lessons learned during a pandemic: A qualitative research study.
In the wake of the pandemic and faculty shortage, strong academic nurse leaders (ANL) are needed to ensure quality education and professional standards are upheld while preparing future nurses. This team explored experiences and perspectives of ANLs during the pandemic in order to better understand the difficulties they faced, their triumphs and failures, and lessons learned. This descriptive-exploratory qualitative study captured leadership experiences of 11 academic leaders from a large, urban, Midwestern college of nursing. Three focus group sessions were conducted virtually using a structured question guide and content analysis of transcripts. Three themes emerged from analysis: Technology, Time and Change, and Well-being. Content analysis also revealed leadership strategies and "pearls of wisdom" offered by participants. ANLs faced many challenges during the pandemic that required them to remain steady and present, while practicing regular and effective communication to foster strong relationships. As higher education and healthcare environments develop more complexity and remain constantly changing, leaders must be strategic, emotionally intelligent, and innovative in their roles.


The epidemiology, pathophysiology, and natural history of chronic venous disease.
Chronic venous disease includes a spectrum of clinical presentations ranging from varicose veins through chronic lower extremity pain and edema to venous skin changes and ulceration. Such manifestations may result from primary venous insufficiency or be secondary to other disorders, primarily acute deep venous thrombosis. Regardless of etiology, chronic venous disease has significant socioeconomic consequences and is among the most common problems encountered in surgical practice. Ambulatory venous hypertension underlies most of the sequelae of chronic venous disease, although such hemodynamic derangements may result from either valvular incompetence or venous obstruction. Unfortunately, the factors responsible for the progression of disease from mild to severe manifestations are only beginning to be understood. However, a thorough understanding of the pathophysiology and natural history of chronic venous disease is essential in its management.


Expression of aquaporin 1 in primary renal tumors: a prognostic indicator for clear-cell renal cell carcinoma.
Aquaporin 1 (AQP1) is a water channel expressed in many epithelial tissues and endothelium, including the proximal nephron of the kidney. We measured AQP1 expression in primary renal cell carcinomas (RCCs) and evaluated its significance and prognostic utility. We examined AQP1 expression in 559 sporadic renal tumors as well as in 43 normal kidney tissue samples and collected clinicopathologic and prognostic data. AQP1 expression was measured by using real-time quantitative polymerase chain reaction (PCR). All normal kidney samples presented substantial AQP1 expression. Among tumor subtypes, AQP1 expression was significantly higher in clear-cell and papillary RCCs, whereas it was lower in chromophobe RCCs, oncocytomas, and collecting-duct carcinomas. In clear-cell RCC, AQP1 was significantly higher in patients without symptomatic presentation or whose tumors were smaller, lower grade, or either lower stage or lacking in microvascular invasion. Von Hippel-Lindau (VHL) tumor suppressor gene mutational status did not affect expression level. Cox univariate and multivariate analyses strongly associated high AQP1 expression with better prognosis in cancer-specific and cancer-free survival tests in all patient cohorts, as well as in cancer-specific survival in a cohort of patients with advanced metastatic RCC. The time-dependent receiver operation characteristic (ROC) analyses, combined with logistic regression models, revealed that the addition of the AQP1 parameter to the University of California Los Angeles Integrated Staging System (UISS) prognostic score can improve the accuracy of predictions of both cancer death and recurrence for all patient cohorts as well as of cancer death for advanced cases within a 5-yr follow-up period in clear-cell RCC. High AQP1 expression was also associated with better outcome in a univariate cancer-specific survival test in papillary RCCs. AQP1 shows RCC subtype-specific expression, and its expression level provides useful prognostic information for patients with clear-cell RCC.


Impact of COVID-19 on Public Interest in Breast Cancer Screening and Related Symptoms: Google Trends Analysis.
The COVID-19 pandemic has led to a decrease in cancer screening due to the redeployment of health care resources and public avoidance of health care facilities. Breast cancer is the most common cancer diagnosed in female individuals, with improved survival rates from early detection. An avoidance of screening, resulting in late detection, greatly affects survival and increases health care resource burden and costs. This study aimed to evaluate if a sustained decrease in public interest in screening occurred and to evaluate other search terms, and hence interest, associated with that. This study used Google Trends to analyze public interest in breast cancer screening and symptoms. We queried search data for 4 keyword terms ("mammogram," "breast pain," "breast lump," and "nipple discharge") from January 1, 2019, to January 1, 2022. The relative search frequency metric was used to assess interest in these terms, and related queries were retrieved for each keyword to evaluate trends in search patterns. Despite an initial drastic drop in interest in mammography from March to April 2020, this quickly recovered by July 2020. After this period, alongside the recovery of interest in screening, there was a rapid increase in interest for arranging for mammography. Relative search frequencies of perceived breast cancer-related symptoms such as breast lump, nipple discharge, and breast pain remained stable. There was increase public interest in natural and alternative therapy of breast lumps despite the recovery of interest in mammography and breast biopsy. There was a significant correlation between search activity and Breast Cancer Awareness Month in October. Online search interest in breast cancer screening experienced a sharp decline at the beginning of the COVID-19 pandemic, with a subsequent return to baseline interest in arranging for mammography followed this short period of decreased interest.


Nucleotide-evoked relaxation of rat vas deferens: possible mechanisms.
ATP causes relaxation of the K(+)-contracted rat vas deferens. Possible sites of action were investigated. ATP and adenosine relaxed the vas deferens precontracted with 80 mM K(+); EC(50) values and maximal relaxations averaged, respectively, 760 microM and 56% for ATP and 74 microM and 30% for adenosine. The adenosine P1 receptor antagonist 8-(para-sulfophenyl)theophylline (8-SPT) reduced relaxations caused by adenosine and low concentrations of ATP, as did the Rp-diastereomer of adenosine 3',5'-cyclic phosphorothioate (Rp-cAMPS), an inhibitor of protein kinase A. The phosphodiesterase inhibitor 4-(3-butoxy-4-methoxybenzyl)-2-imidazolidinone (Ro 20-1724) augmented responses to adenosine and low concentrations of ATP. alpha,beta-Methylene ADP, an inhibitor of 5'-nucleotidase, reduced relaxations caused by ATP to a similar extent as did 8-SPT. In the presence of an almost saturating concentration of adenosine, ATP caused further relaxation. Conversely, in the presence of ATP, adenosine had little effect. Like ATP, UTP and other nucleoside triphosphates relaxed the vas deferens. The P2 receptor antagonists reactive blue 2, acid blue 25 and 4,4'-diisothiocyanotostilbene-2,2'-disulphonate (DIDS) attenuated the relaxation caused by ATP; suramin, pyridoxalphosphate-6-azophenyl-2',4'-disulphonate (PPADS), Evans blue, trypan blue, reactive red 2 and brilliant blue G had no effect. Three non-selective inhibitors of protein kinases, 1-(5-isoquinolinesulfonyl)-2-methylpiperazine (H-7), staurosporine and (8R*,9S*,11S*)-(-)-9-hydroxy-9-carboxy-8-methyl-2,3,9,10-tetrahydro-8,11-epoxy-1H,8H,11H-2,7b,11a-triazadibenzo[a,g]cycloocta[cde]trinden-1-one (K-252b), markedly reduced the relaxation caused by ATP. The results indicate that adenosine, derived from enzymatic dephosphorylation, contributes to the relaxant effect of ATP, presumably by activation of a smooth muscle adenosine receptor linked to the accumulation of cAMP and activation of protein kinase A. Yet, the main part of the response to ATP is mediated by a site distinct from the adenosine receptor. The pharmacological properties of this site differ from known P2 receptor subtypes. Possibly, the nucleotide-evoked relaxation is due to a phosphoryl transfer catalyzed by an ecto-protein kinase.


Perceived ideal body weight exacerbates bulimia and dieting in Bodybuilding Athletes.
The passion of bodybuilding athletes for a symmetric, lean, heavily muscled body leads them to carry out exhausting exercise programs and restrictive eating regimens, sometimes resulting in disordered eating behaviors. This study investigates potential exacerbators on the development of disordered eating in bodybuilding (professional and recreational) and strength athletes. This cross-sectional single time point study involved 103 Cypriot bodybuilding athletes of both sexes, performing at three levels: professional, recreational and strength athletes. The Eating Attitude Test 26 (EAT-26) and The Three Factor Eating Questionnaire (TFEQ-R21) were used to evaluate disordered eating and eating behaviors respectively. Scores on the items of the questionnaires according to sex were compared using the Mann-Whitney U test and differences according to bodybuilding performance status or/and body weight deviation category using the Kruskal-Wallis test. The current study was performed under the auspices of the Hellenic Center of Education & Treatment of Eating Disorders (KEADD). The degree of deviation between the perceived ideal body weight and the actual body weight was associated with increased risk of eating disorder. Athletes who desired a lower body weight recorded higher scores on EAT-26 overall (p=0.001), and the subscales of dieting (p=0.01) and bulimia (p=0.001). Cognitive restraint and emotional eating scales of TFEQ-R21 were more pronounced in the non-professional athletes (p=0.01). The emotional eating score was higher in women. There is a need for appropriate sport-specific, gender-specific preventive intervention to deescalate the risk of eating disorder, in both professional and non-professional bodybuilding athletes.


Two-dimensional electrophoresis image interpretation.
A novel method to interpret two-dimensional electrophoresis gels is presented. Genetic background and electrophoretic processes are summarized. Present methods to analyze gel images and to exploit series of gels are described, then their drawbacks are outlined. Artificial Intelligence techniques are introduced to build an image interpretation system which can compensate for certain failures of present methods and augment their efficiency. By reproducing methods of biological experts, this system automatically identifies proteins--whether isolated or inside constellations--on an electrophoretic gel. This system is based on a modular architecture, featuring image processing procedures, which allows extraction of parameters on the image and a top-down and bottom-up reasoning process. The reasoning process first matches extracted parameters to possible geometric models of proteins; it then returns to the image to determine possible missing elements on the gel. A prototype of this system was implemented and tested on plasma gels to identify apolipoproteins.


Effects of eicosatetraynoic acid (ETYA) on cultured pig thyroid cells. Relationships between the inhibition of the phosphatidate-phosphatidyl inositol cycle, the iodination and the cyclic AMP responsiveness to thyrotropin.
The arachidonate inhibition of the adenylate-cyclase system of cultured pig thyroid cells was not mediated by cyclooxygenase, lipoxygenase or peroxidase metabolites. Indeed ETYA, an inhibitor of cyclooxygenase and lipoxygenase, and methimazole, an inhibitor of peroxidase and iodination were without effect on the arachidonate inhibition. Moreover the effect of arachidonate was amplified by a combination with ETYA. In 32P incorporation experiments we observed a modification of the labelling of individual phospholipids of cultured pig thyroid cells resulting in a decrease into phosphatidylinositol (PI) and an increase into phosphatidate (PA) of arachidonate and ETYA-treated cells. These results may be explained by an inhibition of CDP-diacylglycerol: inositol transferase and conversely a stimulation of PI specific phospholipase C yielding a decrease in PI and an increase in PA, which inhibits in turn adenylate cyclase activity possibly by Ca2+ translocation.


Distance measurements in cardiac troponin C.
Intramolecular distance measurements were made in cardiac troponin C (cTnC) by fluorescence energy transfer using Eu3+ or Tb3+ as energy donors and Nd3+ or an organic chromophore as acceptors. The laser-induced luminescence of bound Eu3+ is quenched in Eu1Nd1cTnC with a lifetime of 0.328 ms, compared with 0.43 ms for Eu2cTnC. The enhanced decay corresponds to an energy transfer efficiency of 0.25, or a distance of 1.1 nm between the two high affinity sites. We have also labeled cTnC with 4-dimethylaminophenylazophenyl-4'-maleimide (DAB-Mal) at the two cysteine residues (Cys-35 and Cys-84). Energy transfer measurements were carried out between Tb3+ bound to the high affinity sites and the labels attached to the domain containing the low affinity site. Upon uv irradiation at pH 6.7, Tb1cTnCDAB emits tyrosine-sensitized Tb3+ luminescence that decays bioexponentially with lifetimes of 1.29 and 0.76 ms. The shorter lifetime is ascribed to energy transfer from Tb3+ to the DAB labels, yielding an average distance of 3.4 nm between the donor and the acceptors. At pH 5.0, however, the luminescence decays exclusively with a single lifetime of 1.31 ms, suggesting that under these conditions all Tb3+ ions are more than 5.2 nm away from the label. Thus cTnC, like skeletal TnC, undergoes a pH-dependent conformational transition which converts an elongated structure at lower pH's to a rather compact conformation in a more physiological medium.


Dissocial behavior, the 5HTTLPR polymorphism, and maltreatment in women with bulimic syndromes.
We recently reported that, among bulimic women, previously abused carriers of the 5HTTLPR S allele showed special propensities towards novelty seeking (implying recklessness or impulsivity) and interpersonal insecurity. We subsequently re-analyzed our data, to examine the bearing of the 5HTTLPR polymorphism and prior sexual or physical maltreatment upon validated, higher-order personality-traits. Ninety women with bulimic syndromes were genotyped for 5HTTLPR "short" (S) and "long" (L(G) and L(A)) alleles, and then assessed for eating symptoms, history of sexual or physical abuse, and the higher-order personality traits Emotional Dysregulation, Dissocial Behavior, Inhibition, and Compulsivity. With a classification based on a biallelic model of 5HTTLPR (i.e., presence or absence of at least one S-allele copy), multiple regression indicated a significant proportion of variance in Dissocial Behavior to be explained by an abuse x genotype interaction-greater psychopathology occurring in abused S-allele carriers. A parallel analysis applying a triallelic model of 5HTTLPR (i.e., presence or absence of at least one copy of presumably low-function S or L(G) alleles) produced a similar pattern, but no statistically significant effect. The finding that bulimic 5HTTLPR S-allele carriers who are previously abused display elevations on Dissocial Behavior corroborates previous observations concerning phenomenological correlates of traumatic stress in 5HTTLPR S allele carriers. (c) 2007 Wiley-Liss, Inc.


Interaction of cortisol with the neural retina of the chick embryo in culture.
The uptake of cortisol and the kinetics of hormone-receptor interaction in the cytosol and cell nucleus were investigated in the intact tissue in organ culture. Cortisol is concentrated by the neural retina. The accumulation of the free steroid is temperature dependent but the effect of temperature decreases with the increase of cortisol in medium. Cortisol binding to specific receptors in the cytosol shows a sigmoidal type of kinetics which correlates well with the kinetics of glutamine-synthetase induction by cortisol. The temperature dependent translocation of the receptor-hormone complexes to the nuclei and the effect of detergents on the binding to nuclei are presented.


Kniest and Stickler dysplasia phenotypes caused by collagen type II gene (COL2A1) defect.
Kniest and Stickler dysplasia are two chondrodysplasias characterized by specific phenotypes. No basic defect has been found in patients with Kniest dysplasia, whereas Stickler dysplasia is one of four chondrodysplasias for which mutations of type II procollagen gene (COL2A1) have been identified. We studied a 2-year-old girl presenting with manifestations of Kniest dysplasia and her mother showing a Stickler phenotype. Analysing COL2A1 in both patients, we detected the same 28 basepair deletion spanning the 3'-exon/intron boundary of exon 12 in mother and daughter. We were able to prove a somatic mosaic status for this mutation in the mother which accounts for her milder Stickler-like phenotype.


Neuronal damage in the rat hippocampus in a new model of repeated reversible transient cerebral ischemia.
The influence of the interval of the repeated reversible transient cerebral ischemia on the neuronal damage in the hippocampal CA1 sector was investigated in the rats using a 4-vessel occlusion (4-VO) model. A single 3-min 4-VO did not produce any significant neuronal damage in the hippocampal CA1 sector, whereas the rats subjected to three 3-min 4-VO at 1-h intervals revealed a very severe neuronal damage which was much more severe than that in the rats subjected to a single 9-min 4-VO. In contrast, the rats subjected to three 3-min 4-VO at 6-h intervals revealed only a mild neuronal damage. The degree of the neuronal damage in the rats subjected to three 3-min 4-VO at 5-min intervals was similar to that in the rats subjected to a single 9-min 4-VO. The present study indicates that even such a brief, non-lethal ischemia as 3-min 4-VO can produce a severe neuronal damage if it occurs repeatedly at 1-h intervals.


Extreme anti-reflection enhanced magneto-optic Kerr effect microscopy.
Magnetic and spintronic media have offered fundamental scientific subjects and technological applications. Magneto-optic Kerr effect (MOKE) microscopy provides the most accessible platform to study the dynamics of spins, magnetic quasi-particles, and domain walls. However, in the research of nanoscale spin textures and state-of-the-art spintronic devices, optical techniques are generally restricted by the extremely weak magneto-optical activity and diffraction limit. Highly sophisticated, expensive electron microscopy and scanning probe methods thus have come to the forefront. Here, we show that extreme anti-reflection (EAR) dramatically improves the performance and functionality of MOKE microscopy. For 1-nm-thin Co film, we demonstrate a Kerr amplitude as large as 20° and magnetic domain imaging visibility of 0.47. Especially, EAR-enhanced MOKE microscopy enables real-time detection and statistical analysis of sub-wavelength magnetic domain reversals. Furthermore, we exploit enhanced magneto-optic birefringence and demonstrate analyser-free MOKE microscopy. The EAR technique is promising for optical investigations and applications of nanomagnetic systems.


Laparoscopic Heller Myotomy and Dor Fundoplication for the Treatment of Esophageal Achalasia After Sleeve Gastrectomy-a Video Vignette.
Esophageal dysmotility and disorders of the lower esophageal sphincter are well documented in morbidly obese patients. Esophageal achalasia has been reported in up to 1% of obese patients but the development of such esophageal motility disorder after laparoscopic sleeve gastrectomy (LSG) is extremely rare. The purpose of this video was to demonstrate the management of a type II esophageal achalasia diagnosed in a 46-year-old female patient 4-year after LSG. An intraoperative video has been anonymized and edited to demonstrate the feasibility of laparoscopic Heller myotomy and anterior Dor fundoplication on the mentioned patient. The operation started with the section of the perigastric adhesions. Proceeding in a clockwise direction, the esophagogastric junction, the anterior esophageal wall, and the His angle were freed. A residual slightly dilated fundus was found and isolated. After mobilization of the distal esophagus and identification of the anterior vagus nerve, a "hockey stick" myotomy was carried out for 6 cm on the esophagus and for 2 cm on the gastric side. An anterior Dor fundoplication was fashioned using the residual gastric fundus. Esophageal achalasia in patients that previously underwent LSG is exceptional but should always be suspected in case of pathognomonic symptoms onset. In tertiary referral centers, laparoscopic Heller myotomy and, if technically feasible, an anterior Dor fundoplication seem safe and effective to relieve gastroesophageal outflow obstruction and prevent gastroesophageal reflux.


Cytogenetic study of a testicular tumor in a translocation (13;14) carrier.
We performed chromosomal analysis of a primary testicular tumor from an individual who, on subsequent analysis of peripheral blood, was found to have a balanced (13q14q) translocation. Histologically, the tumor was a mixed germ cell neoplasm, predominantly embryonal carcinoma, with some teratomatous elements. The modal chromosome count of the tumor cells was 62, with most counts ranging from 54 to 66. In addition to a t(13q14q) chromosome (of constitutional origin), nine nonrandomly acquired chromosomal abnormalities were identified, including an abnormal chromosome #1 and a probable i(12p). These findings are further discussed and compared with cytogenetic data on human testicular neoplasms from the literature. This case is also discussed with regard to the possible association of a constitutional t(13q14q) and various malignancies and related disorders.


Induction of stress granules by interferon and down-regulation by the cellular RNA adenosine deaminase ADAR1.
Measles virus (MV) deficient in C protein (C(ko)) expression efficiently induces both stress granules (SG) and interferon (IFNβ), whereas isogenic wild-type (WT) and V mutant (V(ko)) viruses do not. We therefore examined the effect of IFNβ pretreatment on SG formation, and the roles played by the IFN-inducible double-stranded (ds) RNA-dependent protein kinase (PKR) and dsRNA adenosine deaminase (ADAR1). SG formation in ADAR1-sufficient cells infected with WT or V(ko) mutant virus was enhanced by IFN treatment and was PKR-dependent. SG formation in C(ko) virus-infected cells was already high without IFN treatment and was not further enhanced by IFN. IFN treatment alone, in the absence of infection, induced SG formation in ADAR1-deficient but not ADAR1-sufficient cells. Type I IFN-induced enhancement in SG formation occurred by a canonical IFN signaling response dependent upon STAT1 and STAT2. These results further establish ADAR1 as a suppressor of the interferon and SG innate immune responses.


Weight loss in obese men by caloric restriction and high-dose diazoxide-mediated insulin suppression.
To examine the concept whether high-dose diazoxide (DZX)-mediated insulin suppression, in combination with moderate caloric restriction and increased physical activity, can establish a weight loss of at least 15% in obese hyperinsulinaemic men. Open, uncontrolled, 6-month pilot study. Energy intake was reduced by 30%, and walking for at least 30 min a day was strongly recommended. DZX treatment was started at 50 mg t.i.d. and increased by 50 mg per dose every 4 weeks to a maximum of 300 mg t.i.d., unless hyperglycaemia or other side-effects occurred. Eighteen obese hyperinsulinaemic men with a body mass index of 30-35 kg/m(2). Measurements included body weight, body composition, blood pressure, glycaemic control, insulin response, adiponectin and serum lipids. Body weight decreased by 9.4 kg (95% CI: 5.6-13.2 kg, p < 0.001), waist circumference reduced by 9.2 cm (95% CI: 5.3-12.9 cm, p < 0.001) and total body fat mass decreased by 23.3% (95% CI: 13.7-32.9%, p < 0.001), without a concomitant change in soft tissue lean body mass or bone mass. Fat loss was inversely related to fasting insulin levels achieved at 6 months (r = -0.76, p < 0.002). Diastolic blood pressure decreased by 10.9 mmHg (95% CI: 6.5-15.4 mmHg, p < 0.002). Fasting and postmeal peak insulin levels were reduced by about 65% (p < 0.001) and decreased to the normal range for non-obese men. Fasting and postmeal peak glucose levels increased by 0.8 +/- 0.3 mmol/l (p = 0.01) and 1.4 +/- 0.7 mmol/l (p = 0.06) respectively. Haemoglobin A1c rose by 0.5% to 5.9 +/- 0.2%. High-dose DZX-mediated insulin suppression, in combination with moderate caloric restriction and lifestyle advice, is associated with a clinically relevant degree of weight reduction. A more extensive exploration is warranted to optimize this mode of treatment and to further clarify its risks and benefits.


Implementation of xSPECT, xSPECT bone and Broadquant from literature, clinical survey and innovative phantom study with task-based image quality assessment.
From patient and phantom studies, we aimed to highlight an original implementation process and share a two-years experience clinical feedback on xSPECT (xS), xSPECT Bone (xB) and Broadquant quantification (Siemens) for 99mTc-bone and 177Lu-NET (neuroendocrine tumors) imaging. Firstly, we checked the relevance of implemented protocols and Broadquant module on the basis of literature and with a homogeneous phantom study respectively. Then, we described xS and xB behaviours with reconstruction parameters (10i-0mm to 40i-20mm) and optimized the protocols through a blinded survey (7 physicians). Finally, the preferred 99mTc-bone reconstruction was assessed through an IEC NEMA phantom including liquid bone spheres. Conventional SNR, CNR, spatial resolution, Q.%error, and recovery curves; and innovative NPS, TTF and detectability score d' were performed (ImQuest software). We also sought to review the adoption of these tools in clinical routine and showed the potential of quantitative xB in the context of theranostics (Xofigo®). We showed the need of optimization of implemented reconstruction algorithms and pointed out a decay correction particularity with Broadquant. Preferred parameters were 1s-25i-8mm and 1s-25i-5mm for xS/xB-bone and xS-NET imaging respectively. The phantom study highlighted the different image quality especially for the enhanced spatial resolution xB algorithm (1/TTF10%=2.1 mm) and showed F3D and xB shared the best performances in terms of image quality and quantification. xS was generally less efficient. Qualitative F3D still remains the clinical standard, xB and Broadquant offer challenging perspectives in theranostics. We introduced the potential of innovative metrics for image quality analysis and showed how CT tools should be adapted to fit nuclear medicine imaging.


Pancreatic polypeptide-related tumors.
PP-producing tumors are mostly located in the pancreas and may present as three pathologic lesions: pure PP-omas, mixed tumors with minor PP cell population, and PP-cell hyperplasia. These tumors are among the most common multiple adenomas frequently found in patients with multiple endocrine neoplasia type 1. Hypersecretion and high circulating levels of PP are frequently found. They are symptomless but may be useful for the identification of the pancreatic tumors. Numerous types of extrapancreatic endocrine tumors are able to synthesize and secrete PP. They occur mostly but not exclusively in the gastrointestinal tract, particularly in the rectum. The inactivation of the MEN 1 gene at 11q13 appears to be involved in the development of pancreatic but not of rectal PP-producing tumors.


Obstetric Results after Fertility-Sparing Management of Non-Epithelial Ovarian Cancer.
To assess the recurrence and birth rates among patients with non-epithelial ovarian cancer. The study included 146 patients with germ cell (GCT, n = 84) and sex cord-stromal tumors (SCST, n = 62), who underwent fertility-sparing surgery. Adjuvant chemotherapy was administered to 86 (58.9%) patients. Most cases (133 out of 146) were staged FIGO I. The 5- and 10-year disease-free survival rates were 91% and 83%, respectively. The recurrence risk was not associated with tumor histology, stage or age. Twenty-four months after the treatment, the rate of recurrence was higher than the rate of childbearing. The childbearing rates kept rising after the treatment and exceeded the rate of recurrence after 2 years. The cumulative incidence rates of birth 36, 60 and 120 months after treatment were 13.24%, 20.75%, and 42.37%, respectively. Chemotherapy was not related to childbearing. The patients' age was related to the chance of childbearing. The prognoses of GCT and SCST are similar. Close follow-ups along with contraception should be offered to women during the first two years after treatment due to the increased risk of recurrence. After this period, relapses are rare and women can safely become pregnant.


Analysis of SCA8, SCA10, SCA12, SCA17 and SCA19 in patients with unknown spinocerebellar ataxia: a Thai multicentre study.
About 50 % of Thai patients with adult-onset spinocerebellar ataxia (SCA) was Machado-Joseph disease (MJD), SCA1, SCA2 and SCA6. The author investigated further on less common SCAs in the patients without any known mutations. DNA samples of 82 index patients who were genetically excluded MJD, SCA1, SCA2, SCA6, SCA7 and dentatorubro-pallidoluysian atrophy (DRPLA) were examined. Analysis of SCA8, SCA10, SCA12, SCA17 and SCA19 genes were comprehensively performed. Normal range of trinucleotide repeat expansion sizes of TATA-box-binding protein gene (TBP) were also determined in 374 control subjects. Eight patients carried ≥42 CAG/CAA repeat allele in the TBP consistent with SCA17. The pathological repeat alleles ranged from 42 to 57 repeats. All patients had significant degree of cognitive dysfunction. Other non-ataxic phenotypes comprised of parkinsonism, chorea, dystonia and myoclonus. A sporadic patient carried a heterozygous 41-repeat allele developed chronic progressive cerebellar degeneration commenced at the age of 28 years. Whilst, 2 % of the control subjects (8/374) carried the 41-repeat allele. Five of the carriers were re-examined, and revealed that four of them had parkinsonism and/or cognitive impairment without cerebellar signs. Analysis of other types of SCAs was all negative. This is the first study of SCA8, SCA10, SCA12, SCA17 and SCA19 in Thais. SCA17 appears to be an important cause of ataxia in Thailand. Although, the pathological cut-off point of the TBP repeat allele remains unclear, the finding suggests that the 41-repeat may be a pathological allele resulting late-onset or mild phenotype. Apart from ataxia, cognitive impairment and parkinsonism may be clinical presentations in these carriers.


Subversion of Toll-like receptor signaling by a unique family of bacterial Toll/interleukin-1 receptor domain-containing proteins.
Pathogenic microbes have evolved sophisticated molecular strategies to subvert host defenses. Here we show that virulent bacteria interfere directly with Toll-like receptor (TLR) function by secreting inhibitory homologs of the Toll/interleukin-1 receptor (TIR) domain. Genes encoding TIR domain containing-proteins (Tcps) were identified in Escherichia coli CFT073 (TcpC) and Brucella melitensis (TcpB). We found that TcpC is common in the most virulent uropathogenic E. coli strains and promotes bacterial survival and kidney pathology in vivo. In silico analysis predicted significant tertiary structure homology to the TIR domain of human TLR1, and we show that the Tcps impede TLR signaling through the myeloid differentiation factor 88 (MyD88) adaptor protein, owing to direct binding of Tcps to MyD88. Tcps represent a new class of virulence factors that act by inhibiting TLR- and MyD88-specific signaling, thus suppressing innate immunity and increasing virulence.


[Analysis of donor scoring systems in a single Hungarian transplant centre].
To ease organ shortage many transplant centres developed different donor scoring systems, however, a general consensus among clinicians on the use of these systems does not still exist. The aim of the authors was to analyse the effect of expanded criteria donor, deceased donor score and kidney donor risk index on postoperative kidney function and graft survival. Analysis of the characteristics of 138 kidney transplantations and 205 donors in a retrospective study of a five-year period. There was a trend towards rejecting donors in higher risk groups; 22.7% of standard criteria donors belonged to the high risk group of deceased donor score. Graft function was worse in high risk patients. High risk donors can be divided due to the use of deceased donor score. Patients with the highest risk had worse graft function and survival. With the use of these scoring systems grafts with favourable outcome can be selected more precisely.


Physical properties of surimi sausages subjected to high hydrostatic pressure treatment.
We aimed to investigate the effect of high pressure treatment (HPT) on the physical properties of surimi sausages. For protein gelation, high hydrostatic pressure of 400, 500, and 600 MPa was applied for 5, 15, and 30 min, respectively. Elasticity of samples containing 50% surimi was 36.68%, but that of samples containing 70% surimi was 36.87-42.88%. Shear and puncture forces for 50% surimi samples subjected to heat treatment were 1543.25 N and 3337.92 N/mm, respectively, while the shear and puncture forces for 70% surimi samples under all treatment conditions were 226.41-429.61 N and 911.72-1486.98 N/mm, respectively. After HPT, the number of pores increased from 27 to 73 with increasing pressure and time while the pores were elliptically shaped for samples subjected to heat treatment after HHPT. These results suggest that HPT improves the physical properties of surimi sausages with lower starch content.


Influence of noradrenaline and temperature on the isolated perfused rat heart.
Myocardial protection during open heart surgery is achieved by general cooling and cold cardioplegia. However sympathetic activation during the operation causes raised circulating catecholamine levels that might negatively influence the myocardial metabolism. Moreover, local liberation of catecholamines, in "poorly perfused' regions of the myocardium in patients with ischemic heart disease, might occur. In respect of these problems, we studied the influence of noradrenaline at different temperatures on the isolated perfused rat heart. The temperatures chosen were: 10, 20, 32, 37 and 39 degrees C. The results show clearcut adverse effect of noradrenaline at 32 degrees and higher, on metabolism and hemodynamic performance. At lower temperatures there still seem to be an adverse effect of noradrenaline although not statistically significant. The results of this study indicates the importance of presurgical myocardial protection especially of badly perfused myocardial areas. Such protection could be accomplished by beta-blockade and/or loading of the myocardium with glycogen by glucose-insulin-potassium infusion.


The efficacy of a serum screening service for neural-tube defects: the South Wales experience.
Serum-alpha-fetoprotein (AFP) levels were measured in more than 15 000 pregnant women in an investigation designed to examine the operational issues entailed in a large-scale population screening programme for antenatal detection of neural-tube defects. The proportion of open neural-tube defects (ONTD) terminated as a result of serum screening was 56.1% (66.6% for anencephaly and 40.7% for open spina bifida). The principle causes of poor efficacy were: failure of pregnant women to undergo screening (18.2% of ONTD were not screened); failure of the screening test to detect ONTD (20.4% of those screened were below the 90th centile); decisions against termination of detected ONTD (14% of ONTD detected by serum AFP were not terminated). Given present practices and knowledge it is doubtful whether overall efficacy levels above 65% for open spina bifida can be achieved under normal service conditions. The establishment of a regional or national screening programme on grounds of clinical efficacy alone may be premature. The decision would seem to hinge principally around a careful consideration of the economic issues.


Spinal-cord compression related to pseudohypoparathyroidism.
We report a 24-year-old male with pseudohypoparathyroidism and a 6-month history of sensory disturbance in both legs which was associated with difficulty in walking. His physical signs included a short stature, a thick neck, short fourth metacarpals and metatarsals, a spastic paraparesis and sphincteric disturbance. His serum electrolytes included low serum calcium and high serum phosphorus levels. CT reconstruction showed compression of the spinal cord in association with ossified ligamentum flavum at the C2-7 and T9-10 levels. These findings were confirmed by MRI scans.


Hydrogen and Methane-Based Breath Testing in Gastrointestinal Disorders: The North American Consensus.
Breath tests (BTs) are important for the diagnosis of carbohydrate maldigestion syndromes and small intestinal bacterial overgrowth (SIBO). However, standardization is lacking regarding indications for testing, test methodology and interpretation of results. A consensus meeting of experts was convened to develop guidelines for clinicians and research. Pre-meeting survey questions encompassing five domains; indications, preparation, performance, interpretation of results, and knowledge gaps, were sent to 17 clinician-scientists, and 10 attended a live meeting. Using an evidence-based approach, 28 statements were finalized and voted on anonymously by a working group of specialists. Consensus was reached on 26 statements encompassing all five domains. Consensus doses for lactulose, glucose, fructose and lactose BT were 10, 75, 25 and 25 g, respectively. Glucose and lactulose BTs remain the least invasive alternatives to diagnose SIBO. BT is useful in the diagnosis of carbohydrate maldigestion, methane-associated constipation, and evaluation of bloating/gas but not in the assessment of oro-cecal transit. A rise in hydrogen of ≥20 p.p.m. by 90 min during glucose or lactulose BT for SIBO was considered positive. Methane levels ≥10 p.p.m. was considered methane-positive. SIBO should be excluded prior to BT for carbohydrate malabsorption to avoid false positives. A rise in hydrogen of ≥20 p.p.m. from baseline during BT was considered positive for maldigestion. BT is a useful, inexpensive, simple and safe diagnostic test in the evaluation of common gastroenterology problems. These consensus statements should help to standardize the indications, preparation, performance and interpretation of BT in clinical practice and research.


Evaluation of peritoneal Carcinoembryonic Antigen as a survival prognostic factor in gastric cancer patients: a single western center experience.
The aim of this study is to define the importance of peritoneal CEA (pCEA) as a prognostic factor of overall survival (OS) and disease-free survival (DFS) in gastric cancer (GC) patients surgically treated with a curative intent In our department. A total of 64 patients affected by gastric cancer with intraoperatively measurement of CEA on peritoneal lavage were enrolled in the study. Patients were divided into two groups: (A) the peritoneal lavage CEA ( -) with CEA < 0.5 ng/ml and (B) the peritoneal lavage CEA ( +) with CEA ≥ 0.5 ng/ml. Then we analyzed OS and DFS of the two groups correlating them to others clinico-pathological features. Furthermore, we investigated the correlation between pCEA and peritoneal cytology. We demonstrated a strong significant difference in OS and in DFS in CEA ( +) patients. We emphasized that pCEA had a strong survival impact, in both OS and DFS, in selected patients affected by diffuse histotype GC (p = 0.0048 and p = 0.0030 respectively), stage III (p = 0.015 and p = 0.021, respectively) and distal gastric cancer (p = 0.0036 and p = 0.0017, respectively). There is a strong need to recognize prognostic factors that can help clinicians to stratify patients at high risk to develop post-surgical recurrences and moreover to recognize who could benefit from an aggressive surgical treatment of cytoreductive surgery and intra-peritoneal chemotherapy.pCEA is a good predictor of survival in advanced gastric cancer and could discriminate which patients need a more accurate follow-up program and an intensive therapeutic strategy.


Distal radius fracture management in elderly patients: a literature review.
Distal radius fracture management in elderly patients remains without consensus regarding the appropriate treatment or anticipated outcome. Forty-one studies that included at least 10 patients with a minimum mean age of 65 years and that were indexed in Medline or Embase were reviewed. Treatment methods included pins and plaster, external fixation, K-wires, bone cement, and open reduction and internal fixation with plates. The methodological quality of each study was evaluated through use of a grading scale. Despite study heterogeneity, higher rates of infection were noted with external fixation and K-wire stabilization. Stratifying patients into low-demand and high-demand groups may improve the management of distal radius fractures in elderly patients. In sedentary patients with low demands, functional outcomes are good despite the presence of deformity. Patients with higher demands may benefit from fracture stabilization with locking volar plates. Volar plating with fixed-angle screws may be particularly suitable for elderly patients who may take longer to heal a fracture, be more susceptible to pin-track infection, and demonstrate earlier tendon irritation leading to rupture.


Successful multimodal therapy for the metastasis of ascending colon after curative resection of esophageal cancer: a case report with long-term survival.
Solitary colonic metastasis from esophageal cancer is rare. The prognosis of patients with distant metastases from esophageal cancer is extremely poor. A case of long-term survival with colonic metastasis from esophageal cancer treated by multimodal therapy is reported. A 67-year-old man was diagnosed with middle thoracic esophageal squamous cell carcinoma. The patient received neoadjuvant chemotherapy and then underwent subtotal esophagectomy. Approximately 1 year after esophagectomy, an asymptomatic, solitary colonic mass was detected on the follow-up computed tomography for esophageal cancer. Preoperative colonoscopy showed a 5-cm type 3 tumor at the ascending colon, and histological findings of the biopsy specimen indicated possible metastasis from primary esophageal squamous cell carcinoma. The patient underwent laparoscopic ileocolic resection with D3 lymph noddle dissection. Histologically, the colonic tumor was confirmed to be a metastasis from the esophageal squamous cell carcinoma. To the best of our knowledge, only eight cases with resected solitary colonic metastasis, including the present case, have been reported, and the present patient achieved greater than 3-year survival after esophagectomy. Resection of an asymptomatic solitary organ metastasis from primary esophageal cancer appears to be a good therapeutic option, even following esophagectomy.


[X-Ray, false friend of the interventional cardiologist - Risks, evaluation, quality improvement - Status report from France-PCI registry].
Although indispensable, radiation exposure during cardiac catheterization procedures can cause specific radiation-induced diseases. These affect the patient but also the interventional cardiologist. Exposure to high or repeated radiation doses causes deterministic effects. Moreover, even low-dose exposure, especially when repeated, produces a risk of stochastic effets. In that respect, it is crucial to improve the radiation safety of cardiac angiography and interventions, to promote radiation protection and to maintain this exposure « As Low As Reasonably Achievable ». Thus, there is a necessity to spread knowledge about safety standards and recommandations to reduces the dose among interventionalists. Data collection and comparaison of practices are precious to this quality improvement process. For the year 2020, France-PCI registry had collected dosimetric datas related to 55 783 coronary angiographic and interventional procedures from 30 centers in France. Mean fluoroscopy time was 4,4 minutes for diagnostic procedures. Mean PDS was 1 767cGy.Cm2 and mean Air Kerma de 257Gy. Coronary percutaneous angioplasty procedures were related to approximately two to three times higher mean exposures. Mean exposure related to chronic coronary total occlusion treatment procedures was also two times higher than exposure related to non-CTO interventions. These data also highlighted wide disparities between centers.


Electron microscopic immunocytochemical localization of substance P in the area postrema of rat.
Electron microscopic immunocytochemistry was employed to examine the ultrastructure of processes containing substance P-like immunoreactivity (SP-LI) in the area postrema of rat. SP-LI was present within axons and axon terminals which formed synapses with dendrites of intrinsic neurons in the rat area postrema. Specialized contacts between labeled processes and perivascular or ependymal glia cells were not observed. These data suggested that substance P may act as a neurotransmitter involved primarily with neuronal (axodendritic) interactions within the area postrema.


Neurotoxic Methamphetamine Doses Increase LINE-1 Expression in the Neurogenic Zones of the Adult Rat Brain.
Methamphetamine (METH) is a widely abused psychostimulant with the potential to cause neurotoxicity in the striatum and hippocampus. Several epigenetic changes have been described after administration of METH; however, there are no data regarding the effects of METH on the activity of transposable elements in the adult brain. The present study demonstrates that systemic administration of neurotoxic METH doses increases the activity of Long INterspersed Element (LINE-1) in two neurogenic niches in the adult rat brain in a promoter hypomethylation-independent manner. Our study also demonstrates that neurotoxic METH triggers persistent decreases in LINE-1 expression and increases the LINE-1 levels within genomic DNA in the striatum and dentate gyrus of the hippocampus, and that METH triggers LINE-1 retrotransposition in vitro. We also present indirect evidence for the involvement of glutamate (GLU) in LINE-1 activation. The results suggest that LINE-1 activation might occur in neurogenic areas in human METH users and might contribute to METH abuse-induced hippocampus-dependent memory deficits and impaired performance on several cognitive tasks mediated by the striatum.


Quantitative phosphoproteomics reveals new roles for the protein phosphatase PP6 in mitotic cells.
Protein phosphorylation is an important regulatory mechanism controlling mitotic progression. Protein phosphatase 6 (PP6) is an essential enzyme with conserved roles in chromosome segregation and spindle assembly from yeast to humans. We applied a baculovirus-mediated gene silencing approach to deplete HeLa cells of the catalytic subunit of PP6 (PP6c) and analyzed changes in the phosphoproteome and proteome in mitotic cells by quantitative mass spectrometry-based proteomics. We identified 408 phosphopeptides on 272 proteins that increased and 298 phosphopeptides on 220 proteins that decreased in phosphorylation upon PP6c depletion in mitotic cells. Motif analysis of the phosphorylated sites combined with bioinformatics pathway analysis revealed previously unknown PP6c-dependent regulatory pathways. Biochemical assays demonstrated that PP6c opposed casein kinase 2-dependent phosphorylation of the condensin I subunit NCAP-G, and cellular analysis showed that depletion of PP6c resulted in defects in chromosome condensation and segregation in anaphase, consistent with dysregulation of condensin I function in the absence of PP6 activity.


Reduction performance of microplastics and their behavior in a vermi-wetland during the recycling of excess sludge: A quantitative assessment for fluorescent polymethyl methacrylate.
Large amounts of microplastics (MPs) that have accumulated in excess sludge may increase the environmental risk for its subsequent treatment. This study aimed to investigate the performance and mechanism of the reduction of MPs in excess sludge in a vermi-wetland. For this, 1 μm, 100 μm, and 500 μm of fluorescent MPs stained with Nile red were added to raw sludge, and their decreased numbers were quantified during the treatment of sludge. The results showed that the removal rates of chemical oxygen demand and total solids from the excess sludge were 63.44%-90.98% and 37.61%-51.56% in the vermi-wetland, respectively. The numbers of 1 μm, 100 μm, and 500 μm MPs could be reduced by 86.62%-95.69%, 95.44%-99.52%, and 100% in the vermi-wetland, respectively. These results indicate that the vermi-wetland is more effective at eliminating MPs. Further insight into the vermi-wetland stratification was obtained, and more than 74.87% of the MPs were intercepted in the vermicompost layer. Moreover, all the particle sizes of MPs were found in the excrement of earthworms. However, only 1 μm MPs were detected in their digestive organs. This study suggests that the interception effect is primarily responsible for elimination of MPs in excess sludge, and the bioturbation of earthworms plays an important role in the mobilization of MPs in vermi-wetlands.


Evaluation of fertigation management impacts of surface drip irrigation on reducing nitrate leaching using numerical modeling.
The objective of this study was to investigate the impacts of fertigation strategies on nitrate leaching and its uptake into maize plants. Field experimental data were employed to calibrate a numerical model (HYDRUS 2D/3D) for a surface drip irrigation system in a sandy clay loam soil. The calibrated model was used to simulate nitrate plant uptake and its leaching in different fertigation scenarios based on various fertigation durations and different start times of fertigation. Finally, nitrogen plant uptake was compared with maize N requirement during growth stages in two fertigation frequency scenarios. These simulations were also performed in sandy loam soil. The results show that, if fertigation is done at the end of irrigation, nitrate leaching in shorter fertigation duration will be less than the leaching in longer fertigation duration. However, in the case of fertigation at the beginning of irrigation, the nitrate leaching is higher if the fertigation duration is short, and vice versa. Furthermore, reducing the number of fertigation events in the sandy clay loam soil increases the nitrate plant uptake. However, in the sandy loam soil, a lesser number of fertigation events reduce nitrate uptake.


Organic acid-induced triple fluorescent emission carbon quantum dots identification of distilled liquor.
An acid-sensitive carbon dot fluorescence sensing array was investigated for the differentiated recognition of distilled spirits. Due to the electrostatic interactions between CDs and organic acids, organic acids affect the protonation and fluorescence properties of CDs, which in turn modify the CDs triple fluorescence emission. The regular linear variation of the fluorescence sensor was found under acidic conditions (3.0 < pH < 6.2). A comprehensive study of acids with selectivity, different concentrations (0.1 mM, 1 mM, 10 mM, 40 mM), different types (8 species) and mixed acids (formic acid and acetic acid), and good quantification capability for acetic acid (0.01-1 mM). Demonstrating good recognition ability of the sensor array for complex analyte. On this basis, the fluorescence sensor array was applied to the classification and recognition of liquors. LDA has realized the identification of 16 kinds of Baijiu and 21 kinds of distilled liquors with an accuracy of 100%.


Effects of cultural background and education on handedness.
A 5-item handedness questionnaire was given to 317 subjects in four different groups: (1) 51 Tucano (Amazonian jungle) adolescents (36 male, 15 female); (2) 66 Spanish-speaking adolescents (43 male, 23 female) with similar age and educational background to the Tucano group; (3) 100 urban subjects (50 male, 50 female) with a low educational level; and (4) 100 urban subjects (50 male, 50 female) with a high level of education. Hand preference scores were not affected by sex or educational level. The incidence of left-handedness was lower in the Tucano group than in the other groups, despite the fact that the Tucano culture is a highly permissive one. The two rural groups showed less extreme hand preferences than the urban groups, and the Tucano in particular were less likely to indicate extreme hand preferences on any of the items. These results indicate significant effects of culture and environment on declared hand preference, and may be pertinent to recent discussions of cerebral organization in illiterates.


An unusual presentation of catastrophic failure of hip arthroplasty with a thigh mass.
In the advent of increasing demand for total hip arthroplasty, surveillance of these patients is imperative to identify potential complications requiring revision surgery. This is especially important in the young population, as revision is usually necessary during their lifetime. We present a case of a young female patient with a history of total hip arthroplasty 17 years prior, who presented with left hip pain and anterior thigh mass. The prosthetic hip had progressed to catastrophic failure with the cobalt-chrome femoral head having eroded through the polyethylene and acetabular socket. This was associated with significant metal debris and large fluid collection in the thigh. The patient required complex revision surgery but could have had a much lesser procedure with earlier intervention.


Temporal Trends in the Characteristics, Management and Outcomes of Patients With Acute Coronary Syndrome According to Their Killip Class.
Based on the historical Killip Classification, higher Killip class is associated with increased mortality in patients with acute coronary syndrome (ACS), yet data on current prognosis are lacking. We sought to examine temporal trends in the management and outcomes of patients admitted with an ACS by Killip class and to assess its contemporary prognostic value. Time-dependent analysis (early-period 2000 to 2008 vs late-period 2010 to 2016) in patients with lower (=1) and higher (≥2) Killip classes in a national ACS survey. Clinical outcomes included 30d MACE (death, myocardial infarction, stroke, unstable angina, stent thrombosis, urgent revascularization) and 1-year mortality. Included were 9,736 and 5,288 patients in the early and late time-periods of which 18.5% and 11.5% were categorized as higher Killip class, respectively (p <0.001). Baseline co-morbidities (diabetes, hypertension, dyslipidemia) were more prevalent in the late versus early time periods in both study groups (p <0.001). Rates of 30d MACE decreased in both Killip classes (p <0.001), yet 1-year mortality decreased only in patients with lower Killip class (p = 0.02), and remained extremely high (30%) in patients with higher Killip class (p = 0.75). Killip class was a significant independent predictor for 1-year mortality, both in the early (adjusted hazard ratio 3.23, confidence interval 2.8, 3.7) and late (adjusted hazard ratio 4.13, confidence interval 3.21, 5.32) time periods. In conclusion, even in the current era, patients presenting with ACS and higher Killip class have poor 1-year survival. Efforts should focus on improving the adherence to guideline-recommended therapies. The Killip classification system is still a reliable prognostic tool.


Nucleotide Binding, Evolutionary Insights, and Interaction Partners of the Pseudokinase Unc-51-like Kinase 4.
Unc-51-like kinase 4 (ULK4) is a pseudokinase that has been linked to the development of several diseases. Even though sequence motifs required for ATP binding in kinases are lacking, ULK4 still tightly binds ATP and the presence of the co-factor is required for structural stability of ULK4. Here, we present a high-resolution structure of a ULK4-ATPγS complex revealing a highly unusual ATP binding mode in which the lack of the canonical VAIK motif lysine is compensated by K39, located N-terminal to αC. Evolutionary analysis suggests that degradation of active site motifs in metazoan ULK4 has co-occurred with an ULK4-specific activation loop, which stabilizes the C helix. In addition, cellular interaction studies using BioID and biochemical validation data revealed high confidence interactors of the pseudokinase and armadillo repeat domains. Many of the identified ULK4 interaction partners were centrosomal and tubulin-associated proteins and several active kinases suggesting interesting regulatory roles for ULK4.


Salt stress in the renal tubules is linked to TAL-specific expression of uromodulin and an upregulation of heat shock genes.
Previously, our comprehensive cardiovascular characterization study validated Uromodulin as a blood pressure gene. Uromodulin is a glycoprotein exclusively synthesized at the thick ascending limb of the loop of Henle and is encoded by the Umod gene. Umod-/- mice have significantly lower blood pressure than Umod+/+ mice, are resistant to salt-induced changes in blood pressure, and show a leftward shift in pressure-natriuresis curves reflecting changes of sodium reabsorption. Salt stress triggers transcription factors and genes that alter renal sodium reabsorption. To date there are no studies on renal transcriptome responses to salt stress. Here we aimed use RNA-Seq to delineate salt stress pathways in tubules isolated from Umod+/+ mice (a model of sodium retention) and Umod-/- mice (a model of sodium depletion) ± 300 mosmol sodium chloride ( n = 3 per group). In response to salt stress, the tubules of Umod+/+ mice displayed an upregulation of heat shock transcripts. The greatest changes occurred in the expression of: Hspa1a (Log2 fold change 4.35, P = 2.48 e-12) and Hspa1b (Log2 fold change 4.05, P = 2.48 e-12). This response was absent in tubules of Umod-/- mice. Interestingly, seven of the genes discordantly expressed in the Umod-/- tubules were electrolyte transporters. Our results are the first to show that salt stress in renal tubules alters the transcriptome, increasing the expression of heat shock genes. This direction of effect in Umod+/+ tubules suggest the difference is due to the presence of Umod facilitating greater sodium entry into the tubule cell reflecting a specific response to salt stress.


Genitourinary Symptoms-Patient Help-Seeking and General Practitioner Management: An Outpatient Based Survey at a Tertiary Hospital in Southern Italy.
General knowledge of most common genitourinary diseases is often lacking. In this survey we evaluated the attention given by patients and general practitioners to genitourinary symptoms, and particularly to hematuria and potential early signs of genitourinary cancer. A structured self-administered questionnaire was administered to outpatients before the urological consultation. The questionnaire consisted of 4 multiple choice questions to record the level of patient awareness of urological symptoms, the importance given to gross hematuria, the interval between the onset and the visit, the regularity of physical examination and the first-level investigations indicated by the general practitioner before the urological consultation. A total of 327 self-administered questionnaires were obtained from 358 consecutive patients for a compliance rate of 91.3%. Asymptomatic gross hematuria was present in 91 cases (27.8%). The first episode of hematuria was not reported by 20% of the patients, with a median delay of 11 months. Only 77 patients (23.6%) in the last 5 years had received a physical examination including the external genitalia. Laboratory and/or imaging investigations were indicated before urological counseling in 172 (52.6%) patients. The majority of patients underestimated urological symptoms. Less than 25% and 50% of patients had a physical examination and first-level investigations performed before urological counseling, respectively. Our survey reveals an important lack of awareness of genitourinary symptoms that could be responsible for delayed diagnosis and inappropriate treatment.


Impact of SARS-COV-2 pandemic on elective and emergency surgery in a university hospital.
SARS-CoV-2 pandemic has caused an important impact in our country and elective surgery has been postponed in most cases. There's not known information about the decreasing and impact on surgery. Mortality of surgical patients with SARS-CoV-2 infection is estimated to be around 20%. We conducted prospective data recruitment of people inpatient in our Digestive and General Surgery section of Girona's University Hospital Dr. Josep Trueta from 03/14 to 05/11. Our objective is to analyze the impact that SARS-CoV-2 pandemic over elective and urgent surgery. During the peak occupation of our center Intensive Care Unit (303.8%) there was a reduction on elective (93.8%) and urgent (72.7%) surgery. Mortality of patients with SARS-CoV-2 infection who underwent surgery (n=10) is estimated to be a 10%. An 80% of these patients suffer complications (sever complications in 30%). The actual study shows a global reduction of the surgical activity (elective and urgent) during de SARS-CoV-2 pandemic. Global mortality of patients with SARS-CoV-2 infection are low, but the severe complications have been over the usual.


Nucleotide sequences of the Escherichia coli nagE and nagB genes: the structural genes for the N-acetylglucosamine transport protein of the bacterial phosphoenolpyruvate: sugar phosphotransferase system and for glucosamine-6-phosphate deaminase.
The genes coding for the enzymes of N-acetylglucosamine (GlcNAc) uptake and metabolism (nagA, nagB, and nagE) are located next to glutaminyl-tRNA synthetase gene (glnS) in the Escherichia coli genome. We determined the nucleotide sequence of the nagE (ptsN) gene, encoding the GlcNAc-specific enzyme II (NagE) of the phosphoenolpyruvate: sugar phosphotransferase system, and the sequence of the putative nagB gene, for glucosamine-6-phosphate deaminase. S1 mapping identified the mRNA transcript for nagE, indicating that nagE might be a sole constituent of the nagE operon, and divergent transcripts which are probably of the nagB, nagA genes. An evaluation of the hydrophobic and hydrophilic properties of NagE shows characteristics of a membrane protein. Also, NagE shows homologies to lactose permease and to the glucose-specific transport protein (enzyme IIGlc), and the glucose-specific phosphoryl carrier protein (enzyme IIIGlc). The latter two homologies are particularly interesting since no enzyme III-like protein for GlcNAc transport has been reported and enzyme IINag is of similar size as the combined enzymes IIGlc plus IIIGlc. This supports the idea that these two transport and phosphorylation systems may have evolved from a common ancestral gene.