Severe acute malnutrition's recovery rate still below the minimum standard: predictors of time to recovery among 6- to 59-month-old children in the healthcare setting of Southwest Ethiopia.
Despite currently available, scientifically proven treatments and national guideline, the SAM recovery rate is still considerably behind expectations, and it continues to have a devastating impact on under-five children. Identifying predictors of time to recovery might help to reach the minimal criterion established by the WHO and the national Sphere which decreases child mortality. Therefore, the current study assessed time to recovery and its predictors among children aged 6-59 months admitted with SAM in the Healthcare Setting of Southwest Ethiopia, 2021. An institutional-based multicenter retrospective follow-up study was conducted on 486 children aged 6 to 59 months admitted with SAM cases. Data were entered into Epi-Data version 4.6 and exported to Stata version 14 for further analysis. Cox-Snell residual plot was used to assess the final model's overall goodness of fit. Finally, a significant predictor of time to recovery was identified using Weibull survival regression model, at 0.05 significance level. Overall, 68.72 (95% CI 64.8, 73) of the children recovered and 4.32% died. The overall incidence density was 3.35/100-person day. Independent predictors of time to recovery were, starting complementary feeding at six months (AHR = 1.44; 95%, CI 1.073, 1.935), pneumonia at baseline (AHR = 1.33, 95%, CI 1.049, 1.696), amoxicillin (AHR = 1.31, 95%, CI 1.021, 1.685), and folic acid supplementation (AHR = 1.82, 95% CI 1,237, 2.665). The recovery from SAM at study area after a maximum of 60 days of treatment was below the accepted minimum standard. Complementary feeding, pneumonia, treated by amoxicillin, and folic acid supplementation were predictors of time to recovery. Therefore, providing folic acid and amoxicillin for those in need as well as the earliest possible treatment of concomitant conditions like pneumonia is highly recommended.


The urinary excretion of epigenetically modified DNA as a marker of pediatric ALL status and chemotherapy response.
The active DNA demethylation process may be linked to aberrant methylation and may be involved in leukemogenesis. We investigated the role of epigenetic DNA modifications in childhood acute lymphoblastic leukemia (ALL) diagnostics and therapy monitoring. We analyzed the levels of 5-methyl-2'-deoxycytidine (5-mdC) oxidation products in the cellular DNA and urine of children with ALL (at diagnosis and during chemotherapy, n = 55) using two-dimensional ultra-performance liquid chromatography with tandem mass spectrometry (2D UPLC-MS/MS). Moreover, the expression of Ten Eleven Translocation enzymes (TETs) at the mRNA and protein levels was determined. Additionally, the ascorbate level in the blood plasma was analyzed. Before treatment, the ALL patients had profoundly higher levels of the analyzed modified DNA in their urine than the controls. After chemotherapy, we observed a statistically significant decrease in active demethylation products in urine, with a final level similar to the level characteristic of healthy children. The level of 5-hmdC in the DNA of the leukocytes in blood of the patient group was significantly lower than that of the control group. Our data suggest that urinary excretion of epigenetic DNA modification may be a marker of pediatric ALL status and a reliable marker of chemotherapy response.


The role of ureteral stenting in the management of surgical injury of the ureter.
From 1965 through 1976, 35 patients with surgical injury of the ureter were treated by operations requiring ureteral anastomoses. Stenting devices were used in 31 patients with only 2 failures. Stents were omitted in 4 patients with 2 failures. We have been satisfied with and prefer stenting ureteral anastomoses in the management of surgical ureteral injury, particularly when there is delayed recognition of the injury or previous irradiation. Previous objections to stenting are unjustified.


Electron microscopic observation of scirrhous carcinoma of the stomach.
Electron microscopic findings obtained from seven scirrhous carcinomas of the stomach were analyzed dividing each carcinoma into superficial, deep, and peripheral parts. Proliferation of collagen fibrils, disappearance of plasma membranes, and extracellular release of cell organellae of cancer cells were considered to be peculiar findings to this type of cancer. These phenomena were observed frequently at the deep part of the cancer, but rarely at the peripheral and superficial parts. Replacement of damaged cells by the proliferated collagen fibrils at the central area of the cancer and disconnection of cancer cells from scirrhous lesion at the peripheral part were considered to contribute to the biological behaviour of this carcinoma.


Maternal depression and physical health problems in early pregnancy: findings of an Australian nulliparous pregnancy cohort study.
to investigate the relationship between physical health problems and depressive symptoms in early pregnancy. baseline questionnaire, prospective pregnancy cohort study. six metropolitan public maternity hospitals in Victoria, Australia. 1507 nulliparous women recruited in early pregnancy. nine per cent of women (131/1500) scored ≥ 13 on the EPDS indicating probable clinical depression in early pregnancy (mean gestation=15 weeks). The five most commonly reported physical health problems were as follows: exhaustion (86.9%), morning sickness (64.3%), back pain (45.6%), constipation (43.5%) and severe headaches or migraines (29.5%). Women scoring ≥ 13 on the EPDS reported a mean of six physical health problems compared with a mean of 3.5 among women scoring <13 on the EPDS. Women reporting five or more physical health problems had a three-fold increase in likelihood of reporting depressive symptoms (Adj OR=3.13, 95% CI 2.14-4.58) after adjusting for socio-demographic factors, including maternal age. the findings from this large multi-centre study show that women experiencing a greater number of physical health problems are at increased risk of reporting depressive symptoms in early pregnancy. early detection and support for women experiencing physical and psychological health problems in pregnancy is an important aspect of antenatal care. The extent of co-morbid physical and psychological health problems underlines the need for comprehensive primary health care as an integral component of antenatal care.


Physiologic risk stratification is important to long-term mortality, complications, and readmission in thoracic endovascular aortic repair.
Use of the American Society of Anesthesiologists (ASA) physical status classification is important for periprocedural risk stratification. However, the collective effect after adjustment for the Society for Vascular Surgery (SVS) medical comorbidity grading system on long-term all-cause mortality, complications, and discharge disposition is unknown. We examined these associations in patients after thoracic endograft placement. Data from three thoracic endovascular aortic repair (TEVAR) trials through 5 years of follow-up were included. Patients with acute complicated type B dissection (n = 50), traumatic transection (n = 101), or descending thoracic aneurysm (n = 66) were analyzed. The patients were stratified into three groups according to the ASA class: I-II, III, and IV. Multivariable proportional hazards regression models were used to examine the effect of ASA class on 5-year mortality, complications, and rehospitalizations after adjustment for SVS risk score and potential confounders. The largest proportion of patients treated by TEVAR across the ASA groups (n = 217) was ASA IV (n = 97; 44.7%; P < .001), followed by ASA III (n = 83; 38.2%) and ASA I-II (n = 37; 17.1%). Among the ASA groups, the ASA I-II patients were, on average, 6 years younger than those with ASA III and 3 years older than those with ASA IV (ASA I-II: age, 54.3 ± 22.0 years; ASA III: age, 60.0 ± 19.7 years; ASA IV: age, 51.0 ± 18.4 years; P = .009). Multivariable adjusted 5-year outcome models showed that ASA class IV, independent of the SVS score, conferred an increased risk of mortality (hazard ratio [HR], 3.83; 95% confidence interval [CI], 1.19-12.25; P = .0239) and complications (HR, 4.53; 95% CI, 1.69-12.13; P = .0027) but not rehospitalization (HR, 1.84; 95% CI, 0.93-3.68; P = .0817) compared with ASA class I-II. Procedural ASA class is associated with long-term outcomes among post-TEVAR patients, independent of the SVS score. The ASA class and SVS score remain important to patient counseling and postoperative outcomes beyond the index operation.


Increased IL-8 concentrations in the cerebrospinal fluid of patients with unipolar depression.
Unipolar depression is a common and debilitating disorder. Immunological explanatory approaches have become increasingly important in recent years and can be studied particularly well in the cerebrospinal fluid (CSF). Previous studies discerned alterations in interleukin (IL)-6 and IL-8 levels; however, findings regarding IL-8 were partly contradictory. The aim of the present study was to investigate the concentrations of different cytokines and chemokines, focusing on IL-8, in the CSF of patients with unipolar depression. Participants included 40 patients with unipolar depression and 39 mentally healthy controls with idiopathic intracranial hypertension. CSF cytokine levels were measured using a magnetic bead multiplexing immunoassay. IL-8 levels in the CSF of the patient group with depression were significantly higher than those in the control group (Mean ± SD: 38.44 ± 6.26 pg/ml versus 21.40 ± 7.96 pg/ml; p < .001). The significance of the results is limited by the retrospective design and methodological aspects. The main findings of this study were significantly higher concentrations of IL-8 in the CSF of patients with unipolar depression than in the control group. The detection of high CSF IL-8 levels in this study supports the idea that inflammatory processes might play a role in the pathophysiology of a subgroup of patients with depression.


Role of pulmonary vascular resistance measurements in preoperative evaluation of candidates for pulmonary resection.
Pulmonary function tests (PFT), arterial blood gases (ABG), lung scanning, and pulmonary artery balloon occlusion with measurement of pulmonary vascular resistance (PVR) have all been used for preoperative evaluation of pulmonary function. These tests, however, do not always accurately predict tolerance to lung resection. We have evaluated a new technique which promises to increase the accuracy of preoperative evaluation of pulmonary function. Utilizing a balloon flotation catheter, we measured PVR at varying cardiac outputs. Forty-five patients underwent this study without morbidity or mortality. Five of 30 patients who subsequently underwent pulmonary surgery died of respiratory failure. All of these deaths were from the high-risk group as determined by PVR. Only one of the five had been judged to be at high risk by PFT and ABG. This technique has the advantages of low morbidity and simplicity and should be especially helpful in the evaluation of those patients who have borderline pulmonary function as determined by the more standard tests.


Delayed estrogen actions diminish food consumption without changing food approach, motor activity, or hypothalamic activation elicited by corticostriatal µ-opioid signaling.
Mu-opioid receptor (μ-OR) signaling in forebrain sites including nucleus accumbens (Acb) and ventromedial prefrontal cortex (vmPFC) modulates reward-driven feeding and may play a role in the pathophysiology of disordered eating. In preclinical models, intra-Acb or intra-vmPFC μ-OR stimulation causes overeating and vigorous responding for food rewards. These effects have been studied mainly in male animals, despite demonstrated sex differences and estrogen modulation of central reward systems. Hence, the present study investigated sex differences and estrogen modulation of intra-Acb and intra-vmPFC μ-OR-driven feeding behaviors. First, the dose-related effects of intra-Acb and intra-vmPFC infusions of the μ-OR-selective agonist, DAMGO, were compared among intact female, ovariectomized (OVX) female, and intact male rats. The DAMGO feeding dose-effect function was flattened in intact females relative to the robust, dose-dependent effects observed in OVX females and intact males. Thus, in intact females, intra-Acb DAMGO failed to elevate food intake relative to vehicle, while intra-vmPFC DAMGO elevated food intake, but to a smaller degree compared to males and OVX females. Next, to explore the possible role of estrogen in mediating the diminished DAMGO response observed in intact females, OVX rats were given intra-Acb or intra-vmPFC infusions of DAMGO either immediately after a subcutaneous injection of 17-beta-estradiol 3-benzoate (EB; 5 μg/0.1 mL) or 24 h after EB injection. Intra-Acb DAMGO effects were not changed at the immediate post-EB time point. At the delayed post-EB timepoint, significant lordosis was noted and the duration of intra-Acb DAMGO-driven feeding bouts was significantly reduced, with no change in the number of bouts initiated, locomotor hyperactivity, or Fos immunoreactivity in hypothalamic feeding and arousal systems. Similarly, EB failed to alter the motor-activational effects of intra-vmPFC DAMGO while reducing feeding. These findings indicate that delayed, presumably genomically mediated estrogen actions modulate the μ-OR-generated motivational state by reducing consummatory activity while sparing goal-approach and general arousal/activity. The results additionally suggest that EB regulation of consummatory activity occurs outside of forebrain-μ-OR control of hypothalamic systems.


Estimation of conduction velocity in bulbospinal excitatory pathways to sympathetic outflows in cat spinal cord.
Experiments were performed on cats to measure the conduction velocity of the bulbospinal sympatho-excitatory axons. The lateral white matter of the cervical spinal cord and regions of the medulla were systematically explored for sympatho-excitatory points whilst recording from two sympathetic preganglionic outflows simultaneously. These were chosen a suitable distance apart to give a clear difference in latency to enable precise calculation of axonal conduction velocity between the two outflows. In addition, in a few cases conduction velocity was also measured by determining the latency shift of evoked responses, resulting from moving the stimulating electrode a known distance closer to the recording site. Conduction velocities of sympatho-excitatory axons in the spinal cord determined by these two procedures lay in the range 1.6-7.9 m/s.


Identification of the MAT1 locus in Stagonosporopsis tanaceti, and exploring its potential for sexual reproduction in Australian pyrethrum fields.
Stagonosporopsis chrysanthemi, S. inoxydabilis, and S. tanaceti are closely related Ascomycetes associated with ray blight of the Asteraceae. To date, only S. tanaceti has been identified in Australia, incurring substantial losses to the pyrethrum industry. In contrast to the homothallic S. chrysanthemi and S. inoxydabilis, a sexual state has not been observed for S. tanaceti. The MAT1 locus in S. tanaceti was identified through de novo assembly of shotgun reads, and was further used to develop primers for amplification of the full-length MAT1/2 locus in S. chrysanthemi and S. inoxydabilis. As expected, S. chrysanthemi and S. inoxydabilis possessed a MAT1/2 locus typical of homothallic Dothideomycetes with two adjacent MAT1-1 and MAT1-2 idiomorphs. However, only MAT1-1 could be detected in the assembled genome of S. tanaceti. Although a sexual mode of reproduction cannot be ruled out for S. tanaceti, evidence so far suggests this is absent or occurring at very low frequency in Australian pyrethrum fields.


Insulin inhibition of endothelial prostacyclin production.
Graft thrombosis is a common cause of early graft failure in pancreatic transplantation, even in the absence of rejection. Altered endothelial cell (EC) production of thromboactive substances may play a primary role in this and other settings of thrombosis where intraluminal insulin concentrations are high. We therefore investigated the effect of insulin on EC production of prostacyclin (PGI2), a potent endogenous antagonist of platelet aggregation and vasodilator. Confluent monolayers of human umbilical vein endothelial cells (HUVEC) were incubated for 15 min in Hanks'/Hepes buffer containing 0, 50, 250, or 500 microU/ml of human insulin or 0, 500, 1000, or 2000 microU/ml of porcine insulin. PGI2 production was assessed by exposing the monolayers to either 20 microM arachidonic acid (stimulated) or arachidonic acid vehicle (basal) for an additional 15 min. Test buffers were then assayed by RIA for 6-keto-PGF1 alpha, the stable metabolite of PGI2. The results of these experiments indicate that human insulin inhibits both basal and arachidonic acid-stimulated production of PGI2 from HUVEC in a dose-dependent manner. Inhibition of stimulated production was significant at concentrations of 250-500 microU/ml. Porcine insulin also inhibited arachidonic acid-stimulated production of PGI2 from HUVEC in a dose-dependent manner. However, HUVEC were less sensitive to porcine insulin than to human insulin and a concentration of 2000 microU/ml was required for significant inhibition. We therefore conclude that insulin, in locally high concentrations, inhibits endothelial PGI2 production in vitro. The ability of insulin to alter the production of thromboresistant substances from endothelium may facilitate thrombosis in circumstances where counterregulatory mechanisms are disturbed by injury or transplantation.


A quinary layer transition metal oxide of NaNi1/4Co1/4Fe1/4Mn1/8Ti1/8O2 as a high-rate-capability and long-cycle-life cathode material for rechargeable sodium ion batteries.
A well-crystallized single-phase quinary layer transition metal oxide of NaNi1/4Co1/4Fe1/4Mn1/8Ti1/8O2 was successfully synthesized. It exhibited excellent cycle performance and high rate capability as a cathode material for sodium-ion batteries.


Bladder tissue regeneration using acellular bi-layer silk scaffolds in a large animal model of augmentation cystoplasty.
Acellular scaffolds derived from Bombyx mori silk fibroin were investigated for their ability to support functional tissue regeneration in a porcine model of augmentation cystoplasty. Two bi-layer matrix configurations were fabricated by solvent-casting/salt leaching either alone (Group 1) or in combination with silk film casting (Group 2) to yield porous foams buttressed by heterogeneous surface pore occlusions or homogenous silk films, respectively. Bladder augmentation was performed with each scaffold group (6 × 6 cm(2)) in juvenile Yorkshire swine for 3 m of implantation. Augmented animals exhibited high rates of survival (Group 1: 5/6, 83%; Group 2: 4/4, 100%) and voluntary voiding over the course of the study period. Urodynamic evaluations demonstrated mean increases in bladder capacity over pre-operative levels (Group 1: 277%; Group 2: 153%) which exceeded nonsurgical control gains (144%) encountered due to animal growth.In addition, animals augmented with both matrix configurations displayed increases in bladder compliance over pre-operative levels(Group 1: 357%; Group 2: 338%) similar to growth-related elevations observed in non-surgical controls (354%) [corrected]. Gross tissue evaluations revealed that both matrix configurations supported extensive de novo tissue formation throughout the entire original implantation site which exhibited ultimate tensile strength similar to nonsurgical counterparts. Histological and immunohistochemical analyses showed that both implant groups promoted comparable extents of smooth muscle regeneration and contractile protein (α-smooth muscle actin and SM22α) expression within defect sites similar to controls. Parallel evaluations demonstrated the formation of a transitional, multi-layered urothelium with prominent cytokeratin, uroplakin, and p63 protein expression in both matrix groups. De novo innervation and vascularization processes were evident in all regenerated tissues indicated by synaptophysin-positive neuronal cells and vessels lined with CD31 expressing endothelial cells. Ex vivo organ bath studies demonstrated that regenerated tissues supported by both silk matrices displayed contractile responses to carbachol, α,β-methylene-ATP, KCl, and electrical field stimulation similar to controls. Our data detail the ability of acellular silk scaffolds to support regeneration of innervated, vascularized smooth muscle and urothelial tissues within 3 m with structural, mechanical, and functional properties comparable to native tissue in a porcine model of bladder repair.


New valid spectrofluorimetric method for determination of selected cephalosporins in different pharmaceutical formulations using safranin as fluorophore.
A new validated spectrofluorimetric method has been developed for the determination of some cephalosporins namely; cefepime, cefaclor, cefadroxil, cefpodoxime and cefexime. The method was based on the reaction of these drugs with safranin in slightly alkaline medium (pH 8.0), to form ion-association complexes. The fluorescent products were extracted into chloroform and their fluorescence intensities were measured at 544-565 nm after excitation at 518-524 nm. The reaction conditions influencing the product formation and stability were investigated and optimized. The relative fluorescence intensity was proportional to the drug concentration in the linear ranges of 0.15-1.35, 0.35-1.25, 0.35-1.25, 0.20-1.44 and 0.20-1.25 μg/mL for cefepime, cefaclor, cefadroxil, cefpodoxime proxetil and cefexime, respectively. The detection limits were 40, 100, 100, 60 and 70 ng/mL, respectively. The performance of the developed method was evaluated in terms of Student's t-test and variance ratio F-test to find out the significance of proposed methods over the reference spectrophotometric method. Various pharmaceutical formulations were successfully analyzed using the proposed method and the results were in good agreement with those of the previously reported methods.


Human Drug Discrimination: Elucidating the Neuropharmacology of Commonly Abused Illicit Drugs.
Drug-discrimination procedures empirically evaluate the control that internal drug states have over behavior. They provide a highly selective method to investigate the neuropharmacological underpinnings of the interoceptive effects of drugs in vivo. As a result, drug discrimination has been one of the most widely used assays in the field of behavioral pharmacology. Drug-discrimination procedures have been adapted for use with humans and are conceptually similar to preclinical drug-discrimination techniques in that a behavior is differentially reinforced contingent on the presence or absence of a specific interoceptive drug stimulus. This chapter provides a basic overview of human drug-discrimination procedures and reviews the extant literature concerning the use of these procedures to elucidate the underlying neuropharmacological mechanisms of commonly abused illicit drugs (i.e., stimulants, opioids, and cannabis) in humans. This chapter is not intended to review every available study that used drug-discrimination procedures in humans. Instead, when possible, exemplary studies that used a stimulant, opioid, or Δ9-tetrahydrocannabinol (the primary psychoactive constituent of cannabis) to assess the discriminative-stimulus effects of drugs in humans are reviewed for illustrative purposes. We conclude by commenting on the current state and future of human drug-discrimination research.


[HTA goes Europe: European collaboration on joint assessment and methodological issues becomes reality].
The standardisation of European HTA and thus the reduction of redundancies require clearly defined processes and methods. The HTA Core Model®, a tool developed by the European Network EUnetHTA, is intended to ensure the transparent production of standardised and high-quality assessments in international collaboration. The present paper describes the experience with already published EUnetHTA assessments as well as possibilities for national/local adaptations of these assessments. The integration of jointly developed methods in routine processes of individual HTA agencies will be explained on the basis of a selected example. Further methodological initiatives in Europe will be presented. So far, EUnetHTA has published four rapid assessments conducted through European cooperation between 6-9 HTA institutes during Joint Action 2 (2012-2015). Two assessments dealt with pharmaceuticals and two with non-pharmaceutical interventions. The overall duration of these assessments ranged from 7 to 9 months. There is initial information about the frequency and manner in which these assessments have been used for national/local HTA reports. According to a survey, a total of 28 HTA institutes have indicated that they want to make use of these assessments in their own context. In Austria, the Ludwig Boltzmann Institute for Health Technology Assessment (LBI-HTA) has produced two reports based on EUnetHTA assessments. A further step towards cross-border collaboration and harmonisation is the implementation of these tools in a national and regional context. Beginning in 2015 the LBI-HTA will adjust two programme lines to the format of the HTA Core Model® in order to increase the transferability of HTAs and to reduce redundancies. Barriers to European collaboration include the relevance of topics for individual HTA institutes and the timing of joint assessments. Implementing commonly developed methods as standard practice in local/national HTA institutes is mainly impeded by legislative requirements. Despite the initial positive experiences with international collaboration on specific topics and methods, the coming years will have to prove whether existing barriers can be overcome effectively.


Peptide-Tag Specific Nanobodies for Studying Proteins in Live Cells.
Single-domain antibodies such as nanobodies (Nbs) have substantially expanded the possibilities of advanced cellular imaging. In comparison to conventional antibodies, Nbs are characterized by small size, high stability, and solubility in many environments, including the cytoplasm. Nbs can be efficiently functionalized or modified according to the needs of the imaging approach. Target-specific Nbs can be easily converted into genetically encoded fluorescently labeled intrabodies, also known as chromobodies (CBs), which represent powerful tools to study the dynamics of different proteins of interest within living cells. In this context, CBs specific for a short peptide epitope provide a versatile alternative to bypass the limitations observed with larger fluorescent protein fusions and can be readily used to visualize and monitor peptide-tagged proteins for which specific Nbs are not available. Here, we present our novel detection system comprising a 15 amino acid peptide-tag (PepTag) in combination with a peptide-tag specific CB (PepCB). We provide protocols for adding the PepTag to different proteins of interest, reformatting the peptide-specific Nb (PepNb) into a CB for expression in mammalian cells, and establishment of stable cell lines expressing the PepCB for protein interaction assays and compound screenings.


Dopamine Inputs from the Ventral Tegmental Area into the Medial Prefrontal Cortex Modulate Neuropathic Pain-Associated Behaviors in Mice.
The medial prefrontal cortex (mPFC) is a brain region involved in the affective components of pain and undergoes plasticity during the development of chronic pain. Dopamine (DA) is a key neuromodulator in the mesocortical circuit and modulates working memory and aversion. Although DA inputs into the mPFC are known to modulate plasticity, whether and how these inputs affect pain remains incompletely understood. By using optogenetics, we find that phasic activation of DA inputs from the ventral tegmental area (VTA) into the mPFC reduce mechanical hypersensitivity during neuropathic pain states. Mice with neuropathic pain exhibit a preference for contexts paired with photostimulation of DA terminals in the mPFC. Fiber photometry-based calcium imaging reveals that DA increases the activity of mPFC neurons projecting to the ventrolateral periaqueductal gray (vlPAG). Together, our findings indicate an important role of mPFC DA signaling in pain modulation.


Vital functions for lethal caspases.
Caspases are a family of cysteine proteases expressed as inactive zymogens in virtually all animal cells. These enzymes play a central role in most cell death pathways leading to apoptosis but growing evidences implicate caspases also in nonapoptotic functions. Several of these enzymes, activated in molecular platforms referred to as inflammasomes, play a role in innate immune response by processing some of the cytokines involved in inflammatory response. Caspases are requested for terminal differentiation of specific cell types, whether this differentiation process leads to enucleation or not. These enzymes play also a role in T and B lymphocyte proliferation and, in some circumstances, appear to be cytoprotective rather than cytotoxic. These pleiotropic functions implicate caspases in the control of life and death but the fine regulation of their dual effect remains poorly understood. The nonapoptotic functions of caspases implicate that cells can restrict the proteolytic activity of these enzymes to selected substrates. Deregulation of the pathways in which caspases exert these nonapoptotic functions is suspected to play a role in the pathophysiology of several human diseases.


Orientation to the sun by animals and its interaction with crypsis.
Orientation with respect to the sun has been observed in a wide range of species and has generally been interpreted in terms of thermoregulation and/or ultraviolet (UV) protection. For countershaded animals, orientation with respect to the sun may also result from the pressure to exploit the gradient of coloration optimally to enhance crypsis.Here, we use computational modelling to predict the optimal countershading pattern for an oriented body. We assess how camouflage performance declines as orientation varies using a computational model that incorporates realistic lighting environments.Once an optimal countershading pattern for crypsis has been chosen, we determine separately how UV protection/irradiation and solar thermal inflow fluctuate with orientation.We show that body orientations that could optimally use countershading to enhance crypsis are very similar to those that allow optimal solar heat inflow and UV protection.Our findings suggest that crypsis has been overlooked as a selective pressure on orientation and that new experiments should be designed to tease apart the respective roles of these different selective pressures. We propose potential experiments that could achieve this.


Lipid Accumulation Product Predicts Diabetes Remission After Bariatric Surgery in Chinese Patients with BMI < 35 kg/m2: a Multicenter Cohort Study.
To evaluate whether preoperative visceral fat-related indexes, such as visceral adiposity index (VAI), lipid accumulation product (LAP), Chinese visceral adiposity index (CVAI), and metabolic score for visceral fat (METS-VF), are useful for predicting diabetes remission in Chinese patients with a BMI < 35 kg/m2 after bariatric surgery. A retrospective, multicenter cohort study enrolled 177 patients. Binary logistic regression and receiver operating characteristic (ROC) curves were used to identify predictors and clinically useful cutoff values, respectively. The correlation between the visceral fat-related index and body fat percentage was assessed. Complete remission of type 2 diabetes (T2DM) was observed in 66 patients (37.29%) 1 year after surgery. The VAI, LAP, CVAI, and METS-VF showed downward trends postsurgery. Patients with complete remission had a significantly shorter duration of diabetes and higher CVAI, VAI, LAP, and BMI values than those without complete remission. Binary logistic regression and ROC analysis confirmed that diabetes duration and LAP can predict diabetes remission after bariatric surgery, and a LAP of 67.725 is a useful threshold for predicting surgical efficacy. LAP was significantly positively correlated with VAT/total (%) (p < 0.05). Preoperative LAP is a feasible tool for predicting T2DM remission in patients with a BMI < 35 kg/m2 after bariatric surgery, and a LAP of 67.725 is a useful threshold for predicting surgical outcomes. LAP was significantly positively correlated with VAT content.


STAT1 participates in the induction of substance P expression in airway epithelial cells by respiratory syncytial virus.
The regulation effect and mechanism of respiratory syncytial virus (RSV) infection on the expression of tachykinin substance P (SP) in airway epithelial cells was investigated. The regulation of SP expression by RSV was investigated in the BEAS-2B airway epithelial cell line. RT-qPCR, immunofluorescence, and ELISA assay were used to examine the expression of the SP encoding gene TAC1, the intracellular SP protein expression, and the extracellular SP secretion. The mRNA expression of TAC1 and the intracellular SP protein level in BEAS-2B cells were significantly enhanced by RSV infection with multiplicity of infection (MOI) values of both 1 and 0.1 at 48 hours post infection. Heat-inactivated and UV-inactivated RSV, but not live RSV, significantly induced SP secretion in both control BEAS-2B cells and CX3CR1 receptor knockout cells without affecting the TAC1 gene expression or cell viability. RSV G protein (2-10 μg/ml) and fractalkine (10-50 ng/ml), both CX3CR1 receptor ligands, did not affect SP secretion in BEAS-2B cells. Inhibition of STAT1 phosphorylation by fludarabine (1 μM) markedly reduced the RSV-induced TAC1 gene expression and antagonized the inhibition of RSV replication by interferon-α in BEAS-2B cells. STAT1 participates in RSV infection-induced SP expression in airway epithelial cells.


Quantifying skin sensitivity caused by mechanical insults: A review.
Skin sensitivity (SS) is a commonly occurring response to a range of stimuli, including environmental conditions (e.g., sun exposure), chemical irritants (e.g., soaps and cosmetics), and mechanical forces (e.g., while shaving). From both industry and academia, many efforts have been taken to quantify the characteristics of SS in a standardised manner, but the study is hindered by the lack of an objective definition. A review of the scientific literature regarding different parameters attributed to the loss of skin integrity and linked with exhibition of SS was conducted. Articles included were screened for mechanical stimulation of the skin, with objective quantification of tissue responses using biophysical or imaging techniques. Additionally, studies where cohorts of SS and non-SS individuals were reported have been critiqued. The findings identified that the structure and function of the stratum corneum and its effective barrier properties are closely associated with SS. Thus, an array of skin tissue responses has been selected for characterization of SS due to mechanical stimuli, including: transepidermal water loss, hydration, redness, temperature, and sebum index. Additionally, certain imaging tools allow quantification of the superficial skin layers, providing structural characteristics underlying SS. This review proposes a multimodal approach for identification of SS, providing a means to characterise skin tissue responses objectively. Optical coherence tomography (OCT) has been suggested as a suitable tool for dermatological research with clinical applications. Such an approach would enhance the knowledge underlying the multifactorial nature of SS and aid the development of personalised solutions in medical and consumer devices.


Sleep-Related Disorders in Children with Attention-Deficit Hyperactivity Disorder: Preliminary Results of a Full Sleep Assessment Study.
We present the preliminary results of a prospective case-control sleep study in children with a diagnosis of attention-deficit hyperactivity disorder (ADHD). A deep sleep assessment including sleep questionnaires, sleep habits, a video-polysomnographic recording with full high-density electroencephalography (EEG) and cardiorespiratory polygraphy, multiple sleep latency test, and 1-week actigraphic recording were performed to verify whether children with ADHD may be classified into one of the following five phenotypes: (1) hypoarousal state, resembling narcolepsy, which may be considered a "primary" form of ADHD; (2) delayed sleep onset insomnia; (3) sleep-disordered breathing; (4) restless legs syndrome and/or periodic limb movements; and (5) sleep epilepsy and/or EEG interictal epileptiform discharges. Fifteen consecutive outpatients with ADHD were recruited (two female, mean age 10.6 ± 2.2, age range 8-13.7 years) over 6 months. The narcolepsy-like sleep phenotype was observed in three children, the sleep onset insomnia phenotype was observed in one child, mild obstructive sleep apnea was observed in three children, sleep hyperkinesia and/or PLMs were observed in five children, while IEDs and or nocturnal epilepsy were observed in three children. Depending on the sleep phenotype, children received melatonin, iron supplementation, antiepileptic drugs, or stimulants. Our study further highlights the need to design an efficient sleep diagnostic algorithm for children with ADHD, thereby more accurately identifying cases in which a full sleep assessment is indicated.


Talked Over As If I Weren't There: Reflections From a Nurse and Educator.
Most nurses were taught in nursing school to avoid talking over a patient as if the patient were not there. This manuscript describes the author's experience of being talked over as a patient-what it meant to her as a nurse relating to the ethics of the situation and as an educator of future nurses. The American Nurses Association's Code of Ethics for Nurses with Interpretive Statements (2015) addresses the responsibility of nurses at all levels within an organization to sustain a work environment that ensures quality, safe patient care. Nurses who embody this responsibility are knowledgeable, skilled, and mindful of what they say and how they act and interact around, with, and over patients and toward each other.


Evaluating cervical neoplasia. LEEP as an alternative to cold knife conization.
To determine how the loop electrosurgical excision procedure (LEEP) compares to cold knife conization in providing an adequate diagnostic specimen. Between 1991 and 1995, 95 patients underwent either diagnostic LEEP or cold knife conization at Allegheny University Hospitals. The indications for the procedure were a cytologic/histologic discrepancy, unsatisfactory colposcopic evaluation, positive endocervical curettage or exclusion of invasion. Severe thermal artifact rendered the LEEP specimens uninterpretable in 4.4% of cases. A median number of two passes were required for LEEP excision of the transformation zone. The number of passes correlated with the amount of thermal artifact detected (P = .034). Regarding recurrence patterns, normal follow-up cervical cytology was similar for both groups: 96.7% in the LEEP group vs. 100% in the cold knife conization group. We conclude that LEEP is an acceptable diagnostic alternative to traditional cold knife conization. Thermal artifact remains a disadvantage that can be minimized by limiting the number of passes required to obtain a complete specimen.


Retinal ganglion cell layer and visual function in a patient with optic disc drusen.
To correlate the retinal ganglion cell pattern to visual acuity and visual field data in a patient with bilateral optic disc drusen, a quantitative clinicopathological study was carried out. Both retinae of a patient with optic drusen were whole-mounted. Retinal ganglion cell counts were made using a sampling scheme covering the whole retina and compared to the findings in 10 normal retinae. Relative ganglion cell reduction in the drusen retinae was correlated to clinical data. The total retinal ganglion cell count was reduced from 1244858+/-98736 in normal retinae to 305319 on the right and 527571 on the left eye with optic disc drusen. Large ganglion cells had a better chance of survival. Parafoveal ganglion cell loss was 57% for the right and 36% for the left eye, while visual acuity was 0.8 and 1.0 respectively. The mean light sensitivity loss increased from the centre (6.2 dB) to paracentral (9.9 dB), mid-peripheral (13.7 dB) and outer peripheral (15.0 dB) retina, while ganglion cell losses were smallest in outer peripheral retina (21.9%), followed by central (53.0%), mid-peripheral (70.9%) and paracentral retina (87.7%). These data validate Frisén's theory on central retinal resolution and provide the structural basis for the clinical rule that low visual acuity should not be attributed to disc drusen. Automated light sense perimetry gives an inadequate picture of retinal damage caused by optic disc drusen.


Insight into the mechanism of phosphate and cadmium co-transport in natural soils.
Phosphate is ubiquitous in the environment and can affect the transport of heavy metals in the subsurface systems. In this study, column experiments were conducted to systematically evaluate the effects of phosphate on the transport of Cd in natural soils (RS, BS) under different ionic strength (IS) conditions. The presence of phosphate significantly retarded the transport of Cd in the soils. The extent of retardation was closely associated with phosphate concentrations, IS and soil properties. Increasing phosphate adsorption induced more negative surface charges on soils, thereby contributing to greater retention of Cd through electrostatic attraction. In contrast, higher IS not only promoted mobility of Cd, but also reduced the retardation effect of phosphate on Cd transport in soils. Moreover, higher Fe/Al oxides contents in RS exhibited a more pronounced effect of phosphate on Cd retardation. Our results indicated that electrostatic interaction was the predominant mechanism controlling co-transport of Cd with phosphate, but no ternary surface complexes was observed in the Cd LIII-edge XANES spectra. Our findings highlight the critical role of phosphate in retarding Cd transport in natural soils, which should be considered in assessing environmental risks of heavy metals in the subsurface.


Our Experience in 576 Cases of Cochlear Implant Surgery by Veria Technique.
To study and analyse the result obtained in cochlear implantation by Veria technique and evaluate the incidence of surgical complications and their management. Between Jan 1, 2014 to Jan 1, 2019, 602 cochlear implantations by Veria technique were done out of which 576 patients were analysed retrospectively for the study. The age range was between 18 months and 60 years. All 576 patients were operated by Veria technique. Out of 576 patients, 57 (9.9%) had abnormal cochlear malformation. Cytomegalovirus (CMV) being the most common non genetic cause of congenital hearing loss accounting to 60%. The overall complication rate of 5.5% was observed in 576 implanted patients. The analysis of the results shows that this method has certain advantages, which are: it is simple and therefore the learning curve is fast; it is safe for the facial nerve, as the drilling is precisely controlled by the special perforator; it produces minimal bone trauma and due fast healing, it permits early fitting a few days after operation; it can be used for very small children where the mastoid may have not been yet sufficiently developed.


Do symplasmic networks in cambial zones correspond with secondary growth patterns?
The plasmodesmal (PD) network in the cambial zone of Arabidopsis thaliana hypocotyls was analysed using electron microscopy and dye-coupling studies and compared to those of internodes of Populus nigra and Solanum lycopersicum. In all species, PD densities and frequencies undergo alterations in topologically successive cambial walls reflecting species-specific patterns of PD degradation and PD insertion during cell development. Longitudinal PD fission is responsible for an abrupt increment of PD numbers in specific walls of the youngest derivatives at the xylem and/or phloem side. Here, PDs seem to mediate positional signalling to control tissue fate and early cell determination. PD numbers at all cambial interfaces of A. thaliana correspond to those of the herbaceous tomato, but are higher with the woody poplar. This suggests a positive correlation between PD frequencies and the rapidity of cell division activity. Photoactivated green fluorescent protein (26 kDa) did not diffuse through cambial PDs of A. thaliana. This is in keeping with the common size exclusion limit (SEL) of 8-10 kDa observed for PDs at the youngest interfaces of tomato and poplar which may mediate diffusive exchange of developmental signals of equal molecular size. The regular growth patterns in internodal cambial zones of poplar and tomato result from synchronized cell division activity of neighbouring initials. A. thaliana hypocotyls have an irregular mode of secondary growth. Here, signalling through PDs in misaligned radial walls between non-homologous derivatives may control tissue development. The observed organizational differences between the cambia cast doubts on the suitability of A. thaliana as a model plant for cambial research.


Membrane relationships in murine Meissner corpuscles: cytology of freeze-substituted tissue.
Mechanoreceptive sensory corpuscles (murine Meissner corpuscles) in the toe pad skin of mice, consisting of axon terminals and lamellar cells, were studied following freeze-substitution in order to clarify the plasma membrane relationships between axon terminals and lamellar cells. Tissue preservation of corpuscles was excellent when the corpuscle was located within 10 microns from the contact surface with the precooled metal block. The axolemmata appeared more electron-opaque than did plasma membranes of lamellar cells. The inner leaflet of the unit membranes was thicker than the outer leaflet in the axolemma, and the contour of cell plasma membranes was relatively smooth and straight. Characteristic focal or regional approximations of plasma membranes were noted between the axon and abutting lamellae. Such membrane appositions resembled gap junctions, although no gap junctions were found between the axon and lamellae in chemically fixed materials. Similar gap junction-like close appositions of plasma membranes also were found between neighboring lamellae. These approximations occurred more frequently than typical gap junctions seen in chemically fixed materials. These findings indicate that there may be a relationship of the plasma membranes in the axon terminals and in abutting lamellae as well as between neighboring lamellae that have not been identified as yet in conventional chemically fixed material. Another striking finding was that basal laminae on lamellar cells exhibited the same electron opacity as the surrounding connective tissue matrix and thus the two are indistinguishable from one another. Furthermore, the lamina lucida was not evident, and basal lamina material was directly contiguous with the plasma membrane.(ABSTRACT TRUNCATED AT 250 WORDS)


Advances in pathogenic mechanisms and management of radiation-induced fibrosis.
Radiation-induced fibrosis (RIF) is a severe long-term complication of the normal tissue following radiotherapy. Its prototypical characteristic is the persistent activation of myofibroblasts, resulting in proportion disorder and hyperplasia remodeling of the extracellular matrix comprising collagen. The continuous progress of RIF may contribute to multiple clinical manifestations such as hollow organ stenosis, impaired gaseous diffusion, and loss of tissue compliance significantly affecting the overall quality of daily life in patients with irradiated cancer. Traditionally, the potential mechanism of myofibroblast activation and differentiation has not been elucidated, and the process has been considered as static and irreversible. Recent studies have shown that RIF is a dynamic, multi-step process mediated by many regulated chemokines and cytokines. The RIF process includes release of reactive oxygen species (ROS), microvascular injury, recruitment of inflammatory cells, and activation of myofibroblasts. Numerous signaling pathways are involved in the initiation and progression of RIF, of which SMAD-regulated CTGF expression mediated by TGF-β1 is referred as the main axis. Current management strategies applied in clinical practice for patients with RIF are only supportive treatments, such as anti-inflammatory therapy using steroids; however, the efficacies achieved by these interventions are limited and unsatisfactory. Therefore, this review explores advances in RIF pathogenesis and anti-fibrosis therapy. We hope to provide clinicians with improved awareness and enormous promise in the management of RIF.


Impaired pregnenolone biosynthesis in adrenal cortex mitochondria by adriamycin.
Adrenal cortex mitochondria isolated from mongrel dogs were incubated with cholesterol in the presence and absence of adriamycin (ADM). The capacity for cholesterol side chain cleavage was assessed by determining the pregnenolone yield. ADM behaves as an inhibitor of pregnenolone biosynthesis with a calculated IC50 of 110 microM. The inhibitory effect follows a dose-response relationship depending upon ADM concentration.


Detection of antibodies to E2-protein of GB virus-C/hepatitis G virus in patients with acute posttransfusion hepatitis.
GB virus-C/hepatitis G virus (GBV-C/HGV) is an RNA virus that can be transmitted by transfusion with the diagnosis based on the detection of serum GBV-C/HGV RNA by reverse transcription-polymerase chain reaction. In order to evaluate the role of antibodies to the E2 protein (anti-E2) of GBV-C/HGV in patients with acute posttransfusion hepatitis, anti-E2 was measured in one patient with acute GBV-C/HGV infection, five patients with acute GBV-C/HGV and hepatitis C virus (HCV) coinfection, and four patients with positive pretransfusion GBV-C/HGV RNA who were superinfected with HCV after transfusion. One patient with acute GBV-C/HGV infection remained GBV-C/HGV RNA-positive 18 months after transfusion and did not develop anti-E2. Among five patients with acute GBV-C/HGV and HCV coinfection, one lost GBV-C/HGV RNA 28 months after transfusion and developed anti-E2 independent of serum alanine aminotransferase levels. The other four patients remained GBV-C/HGV RNA-positive and anti-E2-negative at the end of follow-up. Among four patients with positive pretransfusion GBV-C/HGV RNA and super-infected with HCV, one lost GBV-C/HGV RNA 2 months and one 10 months after superinfection and subsequently developed anti-E2. The other two patients remained GBV-C/HGV RNA-positive without anti-E2 at the end of follow-up. Sixty-five samples tested were mutually and exclusively positive for either GBV-C/HGV RNA or anti-E2; only one sample was positive for both GBV-C/HGV RNA and anti-E2. In conclusion, the development of anti-E2 of GBV-C/HGV usually indicates the clearance of serum GBV-C/HGV RNA in patients with acute posttransfusion hepatitis.


Usefulness of serum p53 antibody measurement in colorectal cancer: an examination of 1384 primary colorectal cancer patients.
Recently, the serum p53 antibody (S-p53Ab) has been used widely in clinical practice as a tumor marker for colorectal cancer (CRC). However, no large-scale studies have examined the usefulness of serial measurements of S-p53Ab or have established the relationship of this parameter with the clinicopathological factors of CRC. An ELISA for S-p53Ab was performed for 1384 primary CRC patients, and the results were categorized by the clinicopathological factors. The S-p53Ab positivity rate was 24.1 %, and was significantly higher in Stage III-IV than in Stage 0-II cases. However, no relationship was seen with the serum carcinoembryonic antigen (CEA) or carbohydrate antigen 19-9 (CA19-9) levels. The addition of the S-p53Ab assay to the CEA and CA19-9 measurements increased the overall diagnostic sensitivity to 50.9 % (CEA and/or CA19-9: 37.3 %). In patients who had undergone complete resection, S-p53Ab positivity was associated with a decrease in the relapse-free survival (p = 0.012), but it was not independent prognostic indicator. S-p53Ab positivity had no influence on the cancer-specific survival. The S-p53Ab positivity rate was higher than the positivity rates for CEA and/or CA19-9 in Stage 0-I CRC patients. Combining the use of the three tumor marker tests is a potentially effective method for detecting even early-stage CRC.


Flourishing and the Prioritization of Workplace Elements in General Surgery Residents.
To explore and begin to operationalize workplace elements that influence general surgery (GS) resident wellbeing. Tailoring workplace wellbeing interventions is critical to their success. Occupational science has revealed that a person-centered approach to identifying positive and negative workplace influences can inform tailoring while accounting for individual differences. To our knowledge, this approach has not been applied to the surgical training environment. A national sample of GS residents from 16 Accreditation Council for Graduate Medical Education training programs ranked the importance of workplace elements via an anonymous survey. Latent profile analysis was performed to identify shared patterns of workplace element prioritization and their relation to levels of flourishing, a measure of global wellbeing. GS trainee respondents (n = 300, 34% response rate - average for studies with this sample population) expressed a hierarchy of workplace element importance which differed by gender and race. "Skills to manage stress" and "a team you feel a part of" were prioritized higher by non-males than males. Residents of color and residents underrepresented in medicine, respectively, prioritized "recognition of work/effort" and "skills to manage stress" more than White and overrepresented in medicine residents. Flourishing prevalence varied by 40% with small differences in the specific profile of workplace element prioritization. Differences in prioritization of workplace elements reveal subtle but important differences that may guide the design of wellbeing interventions for different populations within surgery.


Hypnotherapy for the child with chronic eczema. A case report.
Chronic eczema in a child usually produces much discomfort and distress. Associated behaviour problems further complicate the issue. A comprehensive approach to treatment is therefore essential. Hypnotherapy may be a useful adjunct in the overall management. An illustrative case history is presented. Combining hypnotherapy with child guidance and medical treatment led to the relief of symptoms and improved behavioural pattern in a boy aged 10 years.


The totally occluded internal carotid artery: indications for surgery.
Surgery for treatment of the totally occluded internal carotid artery has been controversial since the first case was reported in 1958. Two cases and a review of the literature are presented to show that complete cerebral angiography should be the determining factor for operating in those patients with symptoms referable to the totally occluded internal carotid artery.


[Refixation of osteochondral fragments using absorbable implants. First results of a retrospective study].
An osteochondral lesion in a weight bearing joint causes therapeutic problems. Surgical therapy focuses on the restoration of the articular surface, unlimited motion of the joint and prevention of cartilaginous degeneration. A causal therapy to prevent posttraumatic osteoarthritis is the fixation of osteochondral fragments. Various absorbable implants for the purpose of refixation are available, but only a few have proved to be biocompatible. This retrospective study presents the preliminary results after refixation of osteochondral fragments of the ankle and knee joints. We used self-reinforced absorbable pins, nails and screws made of polylactide acid. The results for 15 patients with 17 fractures of 16 joints were evaluated. All patients were scored by the Tegner-activity-level, the McDermott-score and the DGKKT-score, and 13 of them were monitored by postoperative magnetic resonance imaging (MRI). The follow-up extended for an average of 14.3 months (range: 4-43 months). The clinical results for all patients were good (McDermott-score: Ø 89 points, DGKKT-score: Ø 78.8 points, Tegner: pre-op vs post-op=Ø 4.6 vs Ø 5.1) and the surgical therapy proved to be successful. The MRI showed the complete incorporation and vitality of the fragment as well as a congruence of the joint surface. The clinical course and the MRI gave little reference to an inflammatory reaction due to the implants that complicated the course of two patients. These results indicate that absorbable implants made of polylactide acid are biocompatible and effective in the fixation of osteochondral fragments.


Low-level phototherapy to improve exercise capacity and muscle performance: a systematic review and meta-analysis.
The aim of this study was to evaluate the effectiveness of pre-exercise low-level phototherapy (Light-Emitting Diode therapy [LEDtherapy] or Light Amplification by Stimulate Emission of Radiation therapy [LASERtherapy]) in increasing exercise capacity and muscle performance of people undergoing exercise when compared to placebo treatment. Randomized controlled trials and crossover studies were sought on CENTRAL, MEDLINE, EMBASE, SciELO, PEDro and LILACS from its inception up to February 2015. References lists of included studies were sought for additional relevant research. Two authors independently extracted data on study design, treatment parameters, exercise capacity (number of repetitions, time to exhaustion, blood lactate concentration and lactate dehydrogenase activity) and muscle performance (torque, power and strength) using an structured table. Agreement should be reached by consensus or by a third reviewer. Sixteen studies involving 297 participants were included. Improvement of number of repetitions (mean difference [MD] [95 % confidence interval] = 3.51 repetitions [0.65-6.37]; P = 0.02), delay in time to exhaustion (MD = 4.01 s [2.10-5.91]; P < 0.0001), reduction in lactate levels (MD = 0.34 mmol/L [0.19-0.48]; P < 0.00001) and increased peak torque (MD = 21.51 Nm [10.01-33.01]; P < 0.00001) were observed when LASERtherapy was applied. LEDtherapy meta-analyses were performed with two studies and retrieved no between-group statistically significant difference in power, lactate levels or time to exhaustion. Although our results suggest that LASERtherapy is effective in improving skeletal muscle exercise capacity, the quality of the current evidence is limited.


Genome-wide association study of temperament in bipolar disorder reveals significant associations with three novel Loci.
The many attempts to identify genes for bipolar disorder (BD) have met with limited success, which has generally been attributed to genetic heterogeneity and small gene effects. However, it is also possible that the categorical phenotypes used in genetic studies of BD are not the most informative or biologically relevant. Although quantitative phenotypes provide an alternative to categorical phenotypes based on diagnosis, they have not been fully exploited in BD genetics due to the lack of accessible biological measures. We have explored aspects of temperament as quantitative phenotypes that might define subtypes of BD with different clinical features and courses of illness. Temperament is a heritable personality factor that establishes the baseline level of reactivity, mood, and energy of a person. We have performed a genome-wide association study with genotype data from the Bipolar Genome Study and 1263 bipolar subjects that had completed the Temperament Evaluation of Memphis, Pisa, Paris, and San Diego Autoquestionnaire (TEMPS-A). The TEMPS-A is designed to assess lifelong, milder aspects of bipolar symptomatology and defines five temperaments: hyperthymic, dysthymic, cyclothymic, irritable, and anxious. The irritable temperament produced the most significant result with a genome-wide significant p value of 1.7 × 10(-8) on chromosome 1. The hyperthymic temperament produced additional genome-wide significant p values of 4.1 × 10(-8) and 2.1 × 10(-8) on chromosomes 12 and 22, respectively. These results suggest that aspects of temperament might define subtypes of BD that are more clinically and genetically homogenous, which might aid in the identification of predisposing genetic variants.


Valproate inhibits the conversion of testosterone to estradiol and acts as an apoptotic agent in growing porcine ovarian follicular cells.
Long-term valproate (VPA) treatment has been associated with hyperandrogenism and polycystic ovaries in women with epilepsy. The exact mechanisms of action of the drug on sex steroid hormone function are still unsettled. The aim of the present study was to investigate the action of VPA on basal and gonadotropin-stimulated steroid secretion in porcine ovarian follicular cells and to measure the conversion of testosterone to estradiol. Second, the action of VPA on proliferation and apoptosis of follicular cells was investigated. Small and medium follicles were obtained from pig ovaries on days 8-10 and 14-16 of the estrus cycle. Both follicular compartments, theca and granulosa cells, were cultured as a coculture resembling follicles in vivo. VPA in concentrations of 100 and 250 micrg/ml was added to the control or gonadotropin-stimulated cultures. VPA caused a significant increase in basal and luteinizing hormone (LH)-stimulated testosterone secretion from small follicles, whereas in medium follicles, an increased basal but decreased LH-stimulated testosterone secretion was found. VPA caused decreased basal and follicle-stimulating hormone (FSH)-stimulated estradiol secretion by small follicles, whereas only the higher concentration decreased estradiol secretion in medium follicles. The conversion of testosterone to estradiol by small follicles was decreased under the influence of VPA in testosterone-alone and in testosterone-plus-FSH-stimulated cultures, whereas this was seen at only the higher VPA concentration in medium follicles. VPA had no effect on cell proliferation and viability, whereas in a dose-dependent manner, VPA increased caspase-3 activity. VPA affected steroidogenesis in both unstimulated and gonadotropin-stimulated porcine ovarian follicular cells and inhibited the conversion of testosterone to estradiol. In addition, VPA may act as an apoptotic agent in both small and medium-sized follicles.


Influence of elbow flexion angle on mobilization of the proximal radio-ulnar joint: a motion analysis using cadaver specimens.
The purpose of this study was to determine the most effective elbow joint flexion angle for mobilization of the proximal radio-ulnar joint. Five fresh-frozen cadaveric elbows were used to measure displacement of the radial head in the antero-medial and postero-lateral directions by traction force of 2kgf and 4kgf, respectively. Simulation of the gliding of the proximal radio-ulnar joint was performed at four elbow flexion angles (0 degrees , 30 degrees , 60 degrees , 90 degrees). Data obtained from those flexion angles were compared using one-way repeated measures analysis of variance. Radial head displacement at 60 degrees and 90 degrees during antero-medial gliding were significantly greater than those at 0 degrees and 30 degrees (p<0.05) There were no significant differences in radial head displacement among four elbow flexion angles during postero-lateral gliding at 2kgf and 4kgf. Our findings suggest that proximal radio-ulnar joint mobilization in the antero-medial direction can be performed effectively at 60 degrees and 90 degrees elbow flexion.


Revision endoscopic ethmoidectomy for chronic rhinosinusitis.
In summary, revision endoscopic surgery for chronic rhinosinusitis can be performed safely by using the middle turbinate (or portion thereof) or the anterior wall of the sphenoid as a landmark. These cases are more difficult and may be more prone to bleeding and scarring. The surgeon should be thoroughly familiar with and not hesitate to switch to conventional techniques in the event of excessive bleeding, proptosis, or a loss of landmarks. Aggressive postoperative care and follow-up, including office endoscopic "touch-up" procedures, may be necessary to maintain control of aggressive disease, along with continued medical management and any indicated immunotherapy.


Developing and implementing a public health co-research program for Special Olympics athletes.
Individuals with intellectual and developmental disabilities are often the subject of research while rarely being included in formulating research questions, planning studies, and making decisions related to protocols and analyses. In turn, most research regarding people with intellectual and developmental disabilities is not carried out by researchers with disabilities themselves. We developed a co-research training program where individuals with intellectual and developmental disabilities were taught about research. The program was designed using best practices and existing materials resources. We recruited four participants from Special Olympics Massachusetts and conducted the training in the Fall of 2021. We evaluated the program with surveys, qualitative interviews, and tracking continued involvement of co-researchers in research projects. Participants were partners in the evaluation process. The training program was six sessions and included lessons about why research is important, how to conduct research, and an experiential learning project where co-researchers conducted a study of their coaches. The program was well received by participants, and one year later they were still involved with research projects. A co-researcher training focused on public health for Special Olympics athletes is feasible and beneficial for athletes, researchers, and Special Olympics programs. However, there are still barriers like a lack of funding and time, that need to be addressed to ensure wide program success.


Identification of mutations from phenotype-driven ENU mutagenesis in mouse chromosome 7.
We have used the new high-throughput mutation-scanning technique temperature-gradient capillary electrophoresis (TGCE) for the identification of point mutations induced by N-ethyl-N-nitrosourea (ENU) in the mouse genome. TGCE detects the presence of heteroduplex molecules formed between a wild-type gene segment and the corresponding homologous segment containing an induced mutation or a naturally occurring single nucleotide polymorphism (SNP). Partially denatured heteroduplex molecules are resolved from homoduplexes by virtue of their differential mobilities during capillary electrophoresis conducted in a finely controlled temperature gradient. Simultaneous heteroduplex analysis of 96 amplicons ranging from 150 to 600 bp in size is achieved in approximately 45 min without the need for predetermining the melting profile of each fragment. Initially, we exploited known mouse mutations to develop TGCE protocols for analyzing unpurified PCR samples amplified from crude tail-DNA preparations. TGCE was then applied to the rapid identification of three new ENU-induced mutations recovered from regional mutagenesis screens of a segment of mouse Chromosome 7. Enzyme assays and quantitative reverse transcription-PCR (qRT-PCR) methods validated these new mutations. Our data demonstrate that rapid mutation scanning with TGCE, followed by sequence verification only of detected positives, is an efficient approach to the identification of point mutations in the mouse genome.


High-efficiency dye-sensitized solar cell with three-dimensional photoanode.
Herein, we present a straightforward bottom-up synthesis of a high electron mobility and highly light scattering macroporous photoanode for dye-sensitized solar cells. The dense three-dimensional Al/ZnO, SnO(2), or TiO(2) host integrates a conformal passivation thin film to reduce recombination and a large surface-area mesoporous anatase guest for high dye loading. This novel photoanode is designed to improve the charge extraction resulting in higher fill factor and photovoltage for DSCs. An increase in photovoltage of up to 110 mV over state-of-the-art DSC is demonstrated.


[Leptospiroses].
Leptospirosis is a worldwide zoonosis, that is most frequently encountered in tropical and subtropical areas. In France, during the last years, its incidence has increased. Epidemiology is conditioned by a wide animal reservoir. Important clinical polymorphism makes diagnosis difficult. Laboratory abnormalities such as increased serum C-reactive protein and triglycerides and suggestive. Early diagnosis is now possible by using polymerase chain reaction methods. Early treatment with an aminopenicillin can improve prognosis which remains poor, especially in case of renal or pulmonary involvement. Pathophysiology of the disease still needs to be thoroughly studied.


Evans blue blocks P2X-purinoceptors in rat vas deferens.
In rat vas deferens, Evans blue 100 microM increased contractions elicited by high K+ and by noradrenaline but markedly reduced contractions elicited by the P2X-purinoceptor-selective agonist alpha,beta-methylene ATP (3 microM). The concentration-response curve of alpha,beta-methylene ATP was shifted to the right by Evans blue 30 microM and the maximal contraction was increased. In tissues incubated with nifedipine 10 microM, Evans blue 100 microM tended to increase the residual contraction elicited by noradrenaline and abolished the residual response to alpha, beta-methylene ATP (3 microM). The concentration-response curve of alpha,beta-methylene ATP was progressively shifted to the right by increasing concentrations of Evans blue in the presence of nifedipine; maximal contractions were increased by Evans blue 10 and 30 but not 100 microM. From the shifts to the right caused by Evans blue 30 microM, apparent pKB values of 5.9 (no nifedipine) and 6.0 (nifedipine present) were calculated. It is concluded that Evans blue blocks P2X-purinoceptors in rat vas deferens and in addition causes a non-receptor-specific enhancement of contractions.


Immune cascade of Spodoptera litura: cloning, expression, and characterization of inducible prophenol oxidase.
Haemolymph associated phenol oxidase is a critical component of invertebrate immune reaction and cuticle sclerotization. Phenol oxidase catalyses the conversion of mono-phenols to diphenols and quinones which finally leads to melanin formation. We have cloned the c-DNA encoding phenol oxidase from the haemocytes of Spodoptera litura and expressed it in Escherichia coli. The encoding gene is 2452bp with an open reading frame of 2091 bp translating into a 697 amino acid protein. Multiple alignment analysis of the predicted protein sequence shows close homology to other lepidopeteran PPOII type genes. The transcription of the gene is induced upon microbial challenge of 6th instar larvae with E. coli and is unresponsive to injury. Cloning of the ORF of SLPPO in-frame in the E. coli expression vector pQE30 resulted in its expression. Enzymatic analysis of the recombinant protein reveals that the recombinant protein is catalytically active on 4-methyl pyrocatechol upon activation by cetyl pyridinium chloride.


Axons will not be silenced! A balancing act of attractive receptors.
Axons crossing the CNS midline regulate their responsiveness to both attractive and repulsive cues. In this issue, Dailey-Krempel et al. find different modes of action for DCC isoforms and uncover evidence against the silencing model of axon guidance.


Kinetic analysis of RNA cleavage by coronavirus Nsp15 endonuclease: Evidence for acid-base catalysis and substrate-dependent metal ion activation.
Understanding the functional properties of severe acute respiratory syndrome coronavirus 2 nonstructural proteins is essential for defining their roles in the viral life cycle, developing improved therapeutics and diagnostics, and countering future variants. Coronavirus nonstructural protein Nsp15 is a hexameric U-specific endonuclease whose functions, substrate specificity, mechanism, and dynamics are not fully defined. Previous studies report that Nsp15 requires Mn2+ ions for optimal activity; however, the effects of divalent ions on Nsp15 reaction kinetics have not been investigated in detail. Here, we analyzed the single- and multiple-turnover kinetics for model ssRNA substrates. Our data confirm that divalent ions are dispensable for catalysis and show that Mn2+ activates Nsp15 cleavage of two different ssRNA oligonucleotide substrates but not a dinucleotide. Biphasic kinetics of ssRNA substrates demonstrates that Mn2+ stabilizes alternative enzyme states that have faster substrate cleavage on the enzyme. However, we did not detect Mn2+-induced conformational changes using CD and fluorescence spectroscopy. The pH-rate profiles in the presence and absence of Mn2+ reveal active-site ionizable groups with similar pKas of ca. 4.8 to 5.2. An Rp stereoisomer phosphorothioate modification at the scissile phosphate had minimal effect on catalysis supporting a mechanism involving an anionic transition state. However, the Sp stereoisomer is inactive because of weak binding, consistent with models that position the nonbridging phosphoryl oxygen deep in the active site. Together, these data demonstrate that Nsp15 employs a conventional acid-base catalytic mechanism passing through an anionic transition state, and that divalent ion activation is substrate dependent.


Psychological outcomes in midadulthood associated with mother's child-rearing attitudes in early childhood--evidence from the 1970 British birth cohort.
This study used longitudinal data from the 1970 British Cohort Study (BCS70) to examine the role of mother's child-rearing attitudes assessed when cohort members were aged 5 in children's psychological well-being (psychological functioning, psychological distress, life satisfaction and self-efficacy) at age 30. Although at the multivariate level mother's childrearing attitudes were not related to sons' psychological well-being in adult life, in daughters self-efficacy and life satisfaction at age 30 were related to mother's anti-child autonomy attitudes and mother's non-authoritarian child-rearing attitudes, respectively. In addition, mother's non-authoritarian childrearing attitudes had a protective effect against later psychological distress and low self-efficacy in daughters who had experienced significant material disadvantage in early childhood.


Surface orientation of hydrophilic groups in sulfonated poly(ether ether ketone) membranes.
Sulfonated poly(ether ether ketone) copolymers (SPEEK) with a range of sulfonate contents (SC 77-51%) were synthesized via nucleophilic substitution polycondensation from hydroquinone and sulfonated hydroquinone. Membranes obtained by solvent casting from dimethylacetamide onto glass surfaces were analyzed for surface behavior. The surfaces of a membrane were hydrophobic in air, but hydrophilic in water. This surface behavior was corroborated by water contact angle vs. time, using sessile drop measurements. Hydrophilic sulfonic group aggregates on SPEEK chain and various media contacting with the top or bottom surfaces of the membrane during the fabrication process caused differences in surface behavior. Angle-dependent XPS showed that there was a higher atomic S/C ratio of the bottom surface than on the corresponding top surface. The hydrophilic sulfonic groups were in higher concentration within the membrane, with the concentration gradually decreasing towards the surface for SPEEK-HQ-80 and SPEEK-HQ-70 membranes. Acidification with strong acid and higher temperature induced a more hydrophilic surface on a membrane than a milder acidification process. The depth profile at the membrane surface was examined by a combination of contact angle, XPS and ATR-FTIR.


Molecular chaperones in cellular protein folding: the birth of a field.
The early decades of Cell witnessed key discoveries that coalesced into the field of chaperones, protein folding, and protein quality control.


Cholecystokinin antagonists. Synthesis and biological evaluation of 3-substituted benzolactams.
A series of 1,3-substituted benzolactams are reported that are potent nonpeptidal antagonists of the peptide hormone cholecystokinin (CCK). Design considerations were based upon the natural product CCK antagonist asperlicin and the potent benzodiazepine antagonist series exemplified by L-364,718 (1). Compound 19, the most potent compound in the benzolactam series, had an IC50 = 3 nM for inhibition of binding of 125I-CCK-8 to CCK receptors in rat pancreatic tissue, and its racemic analogue 8 was found to be orally active in inhibiting CCK-induced gastric emptying in mice, with an ED50 = 2.6 mg/kg po. The effects of ring size, substitution at positions 1 and 3, and stereochemistry at position 3 are discussed. Conformational studies of compound 19 and L-364,718 have delineated similarities that these molecules share in their core conformations and substituent orientations.


Arguments for adjuncts.
It is commonly assumed across the language sciences that some semantic participant information is lexically encoded in the representation of verbs and some is not. In this paper, we propose that semantic obligatoriness and verb class specificity are criteria which influence whether semantic information is lexically encoded. We present a comprehensive survey of the English verbal lexicon, a sentence continuation study, and an on-line sentence processing study which confirm that both factors play a role in the lexical encoding of participant information.


Endophytic Cryphonectriaceae on native Myrtales: Possible origin of Chrysoporthe canker on plantation-grown Eucalyptus.
Chrysoporthe austroafricana (Cryphonectriaceae) is a damaging canker pathogen on Eucalyptus species in Southern Africa. Recent studies have shown that the fungus occurs on native Syzygium species and that it has apparently undergone a host range expansion from these native trees to infect non-native Eucalyptus. The aim of this study was to consider whether Chr. austroafricana and other Cryphonectriaceae might exist as endophytes in native Myrtaceae, providing a source of inoculum to infect non-native Myrtales. Healthy branches were collected from Myrtaceae in Mozambique, incubated in florist foam, allowed to dry gradually and monitored for the appearance of fruiting bodies resembling species in the Cryphonectriaceae. Isolates were identified based on DNA sequence data. Two species in the Cryphonectriaceae were obtained, representing the first evidence that species in the Cryphonectriaceae occur as endophytes on native Myrtales, thus providing a source of inoculum to infect non-native and susceptible trees. This has important implications regarding the movement of planting stock used by ornamental tree and forestry enterprises.


Comparison of two radiographic techniques for evaluation of hip joint laxity in 10 breeds of dogs.
To evaluate hip joint laxity in 10 breeds of dogs via 2 radiographic techniques. 500 clinically normal dogs. Prospective study. Radiographs obtained via routine hip joint evaluations performed in sedated dogs of 10 popular breeds were randomly selected from a database. Measurements of distraction index (DI) and hip-extended index (HEI) on 1 hip joint radiograph randomly chosen from each dog were made. Mean age of dogs was 20.7 months. Mean HEI was 0.17 (range, 0.0 to 0.72) and mean DI was 0.44 (range, 0.07 to 0.96). Borzois had uniformly tight hip joints as judged by use of both methods and were considered the gold standard by which hip joint laxity was judged (all Borzois had DI < or = 0.32). Overall, DI was significantly greater than HEI. Within each breed, mean DI was always greater than mean HEI. Significant differences were detected among breeds for HEI; however, compared with DI, the magnitude of differences among breeds was less. Distraction radiography detected the greatest range and magnitude of passive hip laxity in the 10 breeds of dogs. The difference in values between breeds known to have high prevalence of canine hip dysplasia and those in Borzois was greater for DI than for HEI. Breeds must be evaluated individually because of inherent differences in hip joint laxity.


Relationship of syringe-tip diameter to voids in elastomer impressions.
An in vitro study was done to determine the relationship between syringe-tip diameters and the number of bubbles in extruded strips of two vinyl silicone impression materials. Results disclosed the following. There were highly significantly fewer bubbles in impression material extrusions from the second half of the syringeful than from the first half (p less than .001). The smaller-tip orifices, 0.6 and 0.67 mm in diameter, caused highly significantly fewer bubbles in the extruded impression materials than did the larger tips (p less than .001). The reasons and clinical implications for these effects are unknown and are being explored. From subjective observations, it was concluded that the pneumatically powered syringe provided an easier means of extruding the impression material through small syringe-tip orifices than did the conventional hand-powered syringe.


Kinetics of the hydrogen abstraction *CH3 + alkane --> CH4 + alkyl reaction class: an application of the reaction class transition state theory.
Kinetics of the hydrogen abstraction reaction (*)CH(3) + CH(4) --> CH(4) + (*)CH(3) is studied by a direct dynamics method. Thermal rate constants in the temperature range of 300-2500 K are evaluated by the canonical variational transition state theory (CVT) incorporating corrections from tunneling using the multidimensional semiclassical small-curvature tunneling (SCT) method and from the hindered rotations. These results are used in conjunction with the Reaction Class Transition State Theory/Linear Energy Relationship (RC-TST/LER) to predict thermal rate constants of any reaction in the hydrogen abstraction class of (*)CH(3) + alkanes. Our analyses indicate that less than 40% systematic errors on the average exist in the predicted rate constants using the RC-TST/LER method while comparing to explicit rate calculations the differences are less than 100% or a factor of 2 on the average.


Orai, RyR, and IP3R channels cooperatively regulate calcium signaling in brain mid-capillary pericytes.
Pericytes are multifunctional cells of the vasculature that are vital to brain homeostasis, yet many of their fundamental physiological properties, such as Ca2+ signaling pathways, remain unexplored. We performed pharmacological and ion substitution experiments to investigate the mechanisms underlying pericyte Ca2+ signaling in acute cortical brain slices of PDGFRβ-Cre::GCaMP6f mice. We report that mid-capillary pericyte Ca2+ signalling differs from ensheathing type pericytes in that it is largely independent of L- and T-type voltage-gated calcium channels. Instead, Ca2+ signals in mid-capillary pericytes were inhibited by multiple Orai channel blockers, which also inhibited Ca2+ entry triggered by endoplasmic reticulum (ER) store depletion. An investigation into store release pathways indicated that Ca2+ transients in mid-capillary pericytes occur through a combination of IP3R and RyR activation, and that Orai store-operated calcium entry (SOCE) is required to sustain and amplify intracellular Ca2+ increases evoked by the GqGPCR agonist endothelin-1. These results suggest that Ca2+ influx via Orai channels reciprocally regulates IP3R and RyR release pathways in the ER, which together generate spontaneous Ca2+ transients and amplify Gq-coupled Ca2+ elevations in mid-capillary pericytes. Thus, SOCE is a major regulator of pericyte Ca2+ and a target for manipulating their function in health and disease.


Increased mesquite gum formation in nodal explants cultures after treatment with a microbial biomass preparation.
Prosopis laevigata nodal explants cultures were established in Murashige and Skoog medium. Simultaneously these cultures were subjected to stress with biotic elicitors and an environmental factor (temperature increase to promote heat stress) in order to promote and increase exuded mesquite gum production. The biotic elicitors were: Aspergillus nidulans and Pseudomonas pseudoalcaligenes both used in concentrations of 10, 20 and 30 mg, whereas the environmental condition was different incubation temperatures (25, 35 and 40 degrees C). The greatest gum production (approximately 13 mg of pooled gum from 100 explants after 14 days incubation) took place when the culture medium was added 10, 20 and 30 mg of autoclaved fungal mycelium of A. nidulans or 30 mg of autoclaved bacterial biomass of P. pseudoalcaligenes in combination with an incubation temperature of 35 degrees C. These treatments were non-significantly different among themselves (P < 0.05), but were significantly different to the rest of the treatments (P > 0.05).


Clozapine dosing patterns and clinical outcomes in patients with treatment resistant schizophrenia.
Clozapine is the only medication found to be effective for patients with treatment resistant schizophrenia-spectrum disorders (TRS) and its prescription patterns may impact on their outcomes. The study aims to explore the impact of clozapine dosing frequency, dose level and presence of pharmacological augmentation on the clinical, social and cognitive outcomes in patients with TRS. Patients with TRS and on clozapine were interviewed. Daily defined dose (DDD) and anticholinergic burden were calculated. Patients were categorized in three ways: the single daily dose (SDD) and multiple daily dose (MDD), ≤300 mg/day (LD) and >300 mg/day (HD) of clozapine, and clozapine monotherapy (MT) and augmentation therapy (AT). The impact of these clozapine prescription patterns and their interaction on patient outcomes were examined with ANOVA. Of 124 patients on clozapine, 98 patients (79%) had SDD, 59 patients (47.6%) received LD, and 58 patients (46.8%) had MT. Patients in the LD group had significantly better cognitive functions. Though no significant effect of clozapine dosing frequency on outcomes, among patients on LD, those on MDD had better processing speed, short-term and visual memory. Patients with MT had better motivation. Among patients on HD, those with MT had better motivation and vocational functioning. These results provide guidance to the clozapine prescription in a naturalistic setting to achieve optimizing outcomes for patients with TRS in social and cognitive functions. Further longitudinal studies are needed to verify the results.


Mechanistic approach towards diabetic neuropathy screening techniques and future challenges: A review.
Diabetic neuropathy, also called peripheral diabetic neuropathy (PDN), is among the most significant diabetes health consequences, alongside diabetic nephropathy, diabetic cardiomyopathy and diabetic retinopathy. Diabetic neuropathy is the existence of signs and indications of peripheral nerve damage in patients with diabetes after other causes have been governed out. Diabetic neuropathy is a painful and severe complication of diabetes that affects roughly 20% of people. The development of diabetic neuropathy is regulated by blood arteries that nourish the peripheral nerves and metabolic problems such as increased stimulation of polyol pathway, loss of myo-inositol and enhanced non-enzymatic glycation. It's divided into four types based on where neurons are most affected: autonomic, peripheral, proximal, and focal, with each kind presenting different symptoms like numbing, gastrointestinal disorders, and heart concerns. Pharmacotherapy for neuropathic pain is complex and for many patients, effective treatment is lacking; as a result, scientific proof recommendations are crucial. As a result, the current demand is to give the most vital medications or combinations of drugs that work directly on the nerves to help diabetic neuropathy patients feel less pain without causing any adverse effects. In diabetic neuropathy research, animal models are ubiquitous, with rats and mice being the most typically chosen for various reasons. This review covers the epidemiology, clinical features, pathology, clinical symptom, mechanism of diabetic neuropathy development, diagnosis, screening models of animals, diabetic neuropathy pharmacotherapy.


Long-term followup of 207 patients with bladder exstrophy: an evolution in treatment.
Between 1945 and 1985 a total of 207 patients (male-to-female ratio 2:1) was treated at our institution for exstrophy of the bladder. Primary anatomical bladder closure was performed in 137 patients, of whom 42 (31 per cent) eventually required urinary diversion. Primary urinary diversion was the initial treatment in 70 patients, including ureterosigmoidostomy in 40, ileal conduit in 17, colon conduit in 11 and cutaneous ureterostomy in 2. Secondary urinary diversion was necessary in 35 patients and included continent diversion in 7. Primary anatomical bladder closure, done within 72 hours of birth and followed by staged reconstruction of the bladder neck, was the most successful surgical regimen for the treatment of bladder exstrophy. Acceptable urinary continence was achieved in 82 per cent of our patients with this approach. However, multiple procedures often were required to achieve continence.


Release of oligosaccharides possessing reducing-end N-acetylgalactosamine from mucus glycoprotein in Streptomyces sp. OH-11242 culture medium through action of endo-type glycosidase.
A crude enzyme preparation from a culture medium of Streptomyces sp. OH-11242 contained endo-alpha-N-acetylgalactosaminidase activity. The activity could be induced by the addition of purified porcine gastric mucin to the culture medium. Oligosaccharides corresponding to approximately 2-14 glucose units were detected in the culture medium and also in an incubated reaction mixture of crude enzyme preparation and mucus glycoprotein. The resulting product with N-acetylgalactosamine at the reducing terminal implied the presence of a new type of endo-glycosidase liberating not only Gal beta 1-3GalNAc but also other larger oligosaccharides by hydrolysis of the O-glycosidic linkage between GalNAc and Ser (Thr).


Clindamycin-induced alteration of ganglionic function. I. Direct effects on ganglion cell properties.
The influence of the lincosamide antibiotic, clindamycin, on the properties of bullfrog sympathetic ganglion B cells has been determined in vitro using conventional voltage recording methods or single microelectrode voltage-clamp recording techniques. Individual neurons were depolarized with both bath application or local perfusion of clindamycin. The amplitude of the depolarization was not altered by pretreatment with 50 microM (+)-tubocurarine, 10-microM atropine, or 1.5 microM tetrodotoxin (TTX), indicating that the clindamycin-induced depolarization does not result from either the activation of (1) nicotinic receptors, (2) muscarinic receptors, or (3) voltage-gated sodium channels. Clindamycin partially inhibited IM, an action which accounts for part of the clindamycin-induced depolarization. The duration of the hyperpolarizing afterpotential (HAP) following the action potential was decreased in the presence of clindamycin. Clindamycin decreased the amplitude and maximum rate of rise (MRR) of TTX-insensitive action potentials. As calcium influx is thought to contribute to the depolarizing phase of the TTX-insensitive spikes, we suggest that the decrease in HAP duration by clindamycin results from a decrease in the somal calcium current. Further, it is suggested that a decrease in IM and HAP duration may be responsible for the increased excitability exhibited during exposure to clindamycin.


Compensation for unknown acquisition delay caused by digital receiver without external synchronization in NMR and MRI.
The unknown acquisition delay problem caused by a digital receiver without external synchronization in NMR and MRI applications is discussed in detail. An effective procedure is suggested for overcoming the problem. The main features of the proposed method include minimal hardware modifications and highly efficient algorithms. It is important to note that this method does not rely on any special architecture for the digital receiver. To test the method, a digital receiver was implemented using a commercially available single-chip IC. Finally, the method was verified on a 0.3-T home-built MRI system. The experimental results show that the proposed method may be a useful tool for correcting the unknown acquisition delay arising from commercially available digital receivers without external synchronization in NMR and MRI.


Comparison of the sealing ability of bioceramic sealer against epoxy resin based sealer: A systematic review & meta-analysis.
This systematic review and meta-analysis aimed to evaluate if bioceramic sealers had superior sealing properties to epoxy resin-based sealers. A systematic search was performed in the following databases: MEDLINE Ovid (from 1946 onwards), Scopus, Google Scholar, EBSCO, and a hand search of references of included articles was also done. In vitro and ex vivo studies were included. Risk of bias was assessed, and quantitative synthesis was performed for microleakage measured using vertical dye penetration, horizontal dye penetration, and dentin-sealer gap. Summary effect was reported as Standardized Mean Difference with 95% CI. Subgroup analysis was performed based on the imaging modalities, the obturation techniques, and the file systems employed. A total of 24 studies were included. Meta-analysis demonstrated no significant difference between the sealing ability of bioceramic sealer and epoxy resin-based sealer when measured using the microleakage tests [SMD -0.59(95%CI: 1.74,0.55)]. Subgroup analysis revealed no significant differences except when manual K-files were used. Heterogeneity was low when sub-group analysis was done. Bioceramic sealers and epoxy resin-based sealers both exhibited comparable sealing ability.


A new heterobifunctional reagent for immobilization of biomolecules on glass surface.
Synthesis of a new heterobifunctional reagent, [N-(2-trifluoroethanesulfonatoethyl)-N-(methyl)-triethoxysilylpropyl-3-amine] (NTMTA) is described for the immobilization of a variety of biomolecules on glass surface. Its triethoxysilyl group reacts with glass surface and trifluoroethanesulfonate ester structure reacts selectively with aminoalkyl/mercaptoalkyl function in biomolecules. The immobilization can be achieved by two ways involving two steps. The first route involves the reaction of NTMTA with glass beads followed by attachment of aminoalkyl- or mercaptoalkylated biomolecules. The second one involves the reaction of biomolecules, viz., oligonucleotides, proteins, etc., with NTMTA via their aminoalkyl or mercaptoalkyl functions to form a biomolecule conjugate, which is then reacted with glass beads (unmodified) to complete immobilization process. This has been demonstrated by successful immobilization of 5'-mercaptoalkyl- or aminoalkylated oligonucleotides and some commonly used enzymes on glass beads using NTMTA reagent.


[New agents in chemotherapy and new methods of their administration in the treatment of metastatic cancer of the breast].
Chemotherapy of metastatic breast cancer induces temporary tumor responses, without any incidence on vital prognosis. New drugs are sometimes less toxic than previous but are not more efficient. Such findings are observed with other schedules of chemotherapy. It is necessary to adapt treatment to expected goal: optimal efficacy or minimal toxicity.


Tibial nerve excursion during lumbar spine and hip flexion measured with diagnostic ultrasound.
Ultrasound imaging provides a method for non-invasive in vivo measurement of nerve motion resulting from joint movement. This study measured the proximal excursion of the tibial branch of the sciatic nerve at the popliteal fossa during forward bending in healthy subjects. Long-axis image sequences of the nerve were analysed using frame-by-frame cross-correlation software that calculated the longitudinal and axial movement of the nerve. Proximal excursion was calculated from the hypotenuse of these values. The mean proximal excursion recorded was 12.2 mm (SD 2.2 mm, n = 24). The reliability of three repeat measurements was found to be excellent (ICC 0.97, 95% CI 0.93-0.99; SEM 0.7 mm, n = 21). The protocol described provides a reliable method for analysing tibial nerve movement that could prove useful in future clinical studies.


Program directors' perceptions of importance of pediatric procedural skills and resident preparedness.
The Royal College of Physicians and Surgeons of Canada (RCPSC) objectives for training in pediatrics include 26 procedural skills, 11 of which are included in the final in-training evaluation report (FITER). The importance of each procedure for practice and the preparedness of pediatric residency graduates to perform these procedures are not known. A questionnaire was distributed to all pediatric residency program directors and members of the RCPSC Specialty Committee in Pediatrics (N = 21) in October 2010, requesting them to rate the perceived importance and preparedness of graduating pediatric residents in all procedural skills on a 5 point Likert scale, as well as the presence of a curriculum and documentation for each procedure. Mean importance and preparedness were calculated for each procedure. Response rate was 16/21 (76 %). Perceived preparedness was significantly lower than importance for the majority of procedures (p < 0.05). Ten procedures had a high mean importance rating (>3) but a low mean preparedness rating (<3). Presence of a curriculum and documentation for procedures varied across centers, and their presence was correlated with both perceived importance and preparedness (p < 0.0001). Many procedures in which pediatric residents are required to be competent by the RCPSC are felt to be important. Residents are not felt to be adequately prepared in several of the required procedures by the time of graduation. Procedures with high ratings of importance but low preparedness ratings should be targeted for curricular interventions.


Intermediate versus hard end points in clinical trials on hypertension.
The main features of randomized clinical trials performed in the field of hypertension treatment are reviewed, based either on the evaluation of clinical events or on the assessment of surrogate outcome measures. The advantages, limitations, and clinical relevance of each approach are highlighted.