Protective Effect of Commercial Grade Vitamin C against Alcohol-induced Testicular Damage in Male Wistar Rats.
Alcohol consumption has a negative effect on male fertility, but Vitamin C may be able to alleviate this effect. In this study, the protective effect of Vitamin C against alcohol-induced testicular damage in adult male Wistar rats was evaluated. This study was conducted in a University setting. Following a 14-day acclimatisation period, forty adult male Wistar rats were randomly divided into eight groups of five rats. The control group received only food and water, test group B received alcohol only, test group C to E received different doses of Vitamin C, test group F to G received different doses of Vitamin C and alcohol. After a 21-day treatment period, the testis were harvested and analysed for sperm parameters, antioxidant enzyme activity, level of lipid peroxidation and histopathological changes. All analyses was performed using SPSS (version 16) and Microsoft Excel (2019) using Student's t-test. The results showed that in groups administered with alcohol only, there was a decrease in sperm count. Sperm motility, morphology, viability and antioxidant enzyme activity, but increase in the level of lipid peroxidation. In groups treated with Vitamin C and alcohol, there was improvement in the sperm parameters, antioxidant enzymes activity and a decrease and decrease in lipid peroxidation. Furthermore, in the histology of the testis, regenerative changes were seen. The chronic consumption of alcohol can have a deleterious effect on the testis, but commercial-grade Vitamin C can reverse these effects.


Interaction between platelets and endothelial progenitor cells via LPA-Edg-2 axis is augmented by PPAR-δ activation.
Peroxisome proliferator-activated receptor (PPAR)-δ is a nuclear receptor regulating cell metabolism. The role of PPAR-δ in late endothelial progenitor cells (EPCs) has not been fully elucidated. We aim to understand the effects of PPAR-δ activation on late EPC and to reveal the underlying mechanism. Treatment with a highly selective PPAR-δ agonist (GW501516) induced proliferation of late EPCs and enhanced their vasculogenic potential. Search for the target molecule of PPAR-δ activation revealed endothelial differentiation gene (Edg)-2. Chromatin immunoprecipitation and promoter assays demonstrated that Edg-2 gene was specifically induced by PPAR-δ through direct transcriptional activation. Lysophosphatidic acid (LPA), an Edg ligand, mimicked the pro-vasculogenic effects of GW501516 in late EPCs whereas Edg antagonist (Ki16425) blocked these effects. Edg-2 is a membrane receptor for LPA which is a major growth factor from activated platelets. Thus, the interaction between platelets and late EPCs via the LPA-Edg-2 axis was assessed. Platelet supernatant boosted the pro-vasculogenic effects of GW501516, which was reversed by antagonist to PPAR-δ (GSK0660) or Edg (Ki16425). Both of in vivo Matrigel plug model and mouse skin punch-wound model demonstrated that the combination of platelets and PPAR-δ-activated late EPCs synergistically enhanced vascular regeneration. There exists a synergistic interaction between human platelets and late EPCs leading to vascular regeneration. This interaction consists of LPA from platelets and its receptor Edg-2 on the surface of EPCs and can be potentiated by PPAR-δ activation in EPCs. A PPAR-δ agonist is a good candidate to achieve vasculogenesis for ischemic vascular disease.


Serostatus of echovirus 11, coxsackievirus B3 and enterovirus D68 in cord blood: The implication of severe newborn enterovirus infection.
Maternal transplacental antibody is an important origins of passive immunity against neonatal enterovirus infection. Echovirus 11 (E11) and coxsackievirus B3 (CVB3) are important types causing neonatal infections. There were few investigations of enterovirus D68 (EVD68) infection in neonates. We aimed to investigate the serostatus of cord blood for these three enteroviruses and evaluate the factors associated with seropositivity. We enrolled 222 parturient (gestational age 34-42 weeks) women aged 20-46 years old between January and October 2021. All participants underwent questionnaire investigation and we collected the cord blood to measure the neutralization antibodies against E11, CVB3 and EVD68. The cord blood seropositive rates were 18% (41/222), 60% (134/232) and 95% (211/222) for E11, CVB3 and EVD68, respectively (p < 0.001). Geometric mean titers were 3.3 (95% CI 2.9-3.8) for E11, 15.9 (95% CI 12.5-20.3) for CVB3 and 109.9 (95% CI 92.4-131.6) for EVD68. Younger parturient age (33.8 ± 3.6 versus 35.2 ± 4.4, p = 0.04) was related to E11 seropositivity. Neonatal sex, gestational age and birth body weight were not significantly different between the seropositive group and the seronegative group. Cord blood seropositive rate and geometric mean titer of E11 were very low, so a large proportion of newborns are susceptible to E11. The circulation of E11 was low after 2019 in Taiwan. A large cohort of immune naïve newborns existed currently due to lack of protective maternal antibodies. It is imminent to monitor the epidemiology of neonates with enterovirus infections and strengthen the relevant preventive policies.


The effects of acrylamide on mouse germ-line and somatic cell chromosomes.
The industrial chemical acrylamide is suspected to induce potentially heritable genetic damage. While several studies in rodents have indicated that this substance can damage spermiogenic cells, resulting in dominant lethals and heritable translocations, cytogenetic assessments of premeiotic and meiotic cells after exposure have produced equivocal results. In the present study, various cytogenetic endpoints in both somatic and germ-line cells from acrylamide-treated mice were evaluated. Sister chromatid exchanges and micronuclei, but not chromosome aberrations, were induced in spleen cells; synaptonemal complex irregularities (asynapsis), but not chromosome aberrations, were induced in germ cells.


The effect of insulin and guanosine nucleotides on protein phosphorylations by sarcolemma membranes from skeletal muscle.
In a previous report we have shown that insulin increases the phosphorylation of an endogenous protein of mol. wt. 16 000 daltons in sarcolemma membranes. In the present work we have demonstrated that phosphorylations of exogenous histones by the sarcolemma membranes are also increased by insulin. These results indicate that insulin activates a cyclic-AMP-independent protein kinase in sarcolemma membranes. The stimulatory effect of insulin on protein phosphorylations is increased by GTP and its analogue GMP-P(NH)P. The insulin effect was increased 3--4-fold by micromolar concentrations of GTP. The effect by the analogue GMP-P(NH)P was somewhat less. In the absence of insulin guanosine nucleotides had no effect on phosphorylation of the proteins. The results suggest that GTP is a modulator in the activation of a sarcolemma membrane protein kinase by insulin.


Influence of scene statistics on colour constancy.
The light reflected from an object depends not only on the surface properties of this object but also on the illuminant. The same is true for the excitations of the photoreceptors, which serve as the basis for the perceived colour. However, our visual system has the ability to perceive constant surface colours despite changes in illumination. The average chromaticity of the retinal image of a scene depends on the illumination, and thus might be used by the visual system to estimate the illumination and to modulate the correction that subserves colour constancy. But this measure is not sufficient: a reddish scene under white light can produce the same mean stimulation as a neutral scene in red light. Higher order scene statistics-for example, the correlation between redness and luminance within the image-allow these cases to be distinguished. Here we report that the human visual system does exploit such a statistic when estimating the illuminant, and gives it a weight that is statistically appropriate for the natural environment.


An immunohistopathologic study of trilateral retinoblastoma.
We examined retinal and midline pineal tumors from four patients with trilateral retinoblastoma who had antibodies against neural-associated antigens including neuron-specific enolase, photoreceptor cell proteins (S-antigen and rhodopsin), and glial fibrillary acidic protein. Expression of neuron-specific enolase was observed in all four patients. S-antigen immunoreactivity was present in three of four ocular tumors and two of four pineal tumors examined, whereas results of labeling with rhodopsin and glial fibrillary acidic protein were negative in each of the ocular and pineal tumors.


Evaluation of alveolitis by studies of lung biopsies.
Immunocytochemical studies of lung biopsies from patients with cryptogenic fibrosing alveolitis and those having fibrosing alveolitis associated with scleroderma show that numerous T-cells occur in the alveolar walls and septa of all patients with these diseases, implying that cell-mediated hypersensitivity reactions are involved in the pathogenesis. However, B-lymphocytes, mainly within lymphoid follicles, are also present and, in the CFA group, such patients, and those with less than 50% T-suppressor/cytotoxic cells in the diffuse T-cell infiltrates, may have a poorer prognosis. Interleukin-2 receptor expression indicates that T-cell activation is occurring within the lungs, and there is evidence that interstitial monocytes/macrophages and alveolar epithelial cells may play a more important role in antigen presentation than alveolar macrophages. These observations on the features of the inflammatory response in the interstitial tissues of patients with fibrosing alveolitis need to be incorporated into the existing hypothesis on pathogenetic mechanisms based mainly on lavage findings of alveolar macrophages and granulocytes.


X-aptamers targeting Thy-1 membrane glycoprotein in pancreatic ductal adenocarcinoma.
Modified DNA aptamers incorporated with amino-acid like side chains or drug-like ligands can offer unique advantages and enhance specificity as affinity ligands. Thy-1 membrane glycoprotein (THY1 or CD90) was previously identified as a biomarker candidate of neovasculature in pancreatic ductal adenocarcinoma (PDAC). The current study developed and evaluated modified DNA X-aptamers targeting THY1 in PDAC. The expression and glycosylation of THY1 in PDAC tumor tissues were assessed using immunohistochemistry and quantitative proteomics. Bead-based X-aptamer library that contains 108 different sequences was used to screen for high affinity THY1 X-aptamers. The sequences of the X-aptamers were analyzed with the next-generation sequencing. The affinities of the selected X-aptamers to THY1 were quantitatively evaluated with flow cytometry. Three high affinity THY1 X-aptamers, including XA-B217, XA-B216 and XA-A9, were selected after library screening and affinity binding evaluation. These three X-aptamers demonstrated a high binding affinity and specificity to THY1 protein and the THY1 expressing cell lines, using THY1 antibody as a comparison. The development of these X-aptamers provides highly specific and non-immunogenic affinity ligands for THY1 binding in the context of biomarker development and clinical applications. They could be further exploited to assist molecular imaging of PDAC targeting THY1.


Suppression of metastatic hemangiosarcoma by a parvovirus MVMp vector transducing the IP-10 chemokine into immunocompetent mice.
We have previously shown that the growth of human tumor xenografts in immunodeficient mice can be efficiently suppressed upon infection with the autonomous parvovirus H-1 or with cytokine-transducing derivatives thereof. To further evaluate the benefits of implementing parvoviruses in cancer gene therapy, we have created a new recombinant vector, MVMp/IP-10, transducing the immunoactive, antiangiogenic chemokine IP-10, and used this virus to treat syngeneic tumors grown in immunocompetent mice. Intratumoral/intraperitoneal administration of only 3 x 10(7) replication units of MVMp/IP-10 per animal strongly inhibited the progression of established H5V cell-induced vascular tumors, a highly malignant mouse model for human cavernous hemangioma and Kaposi's sarcoma. Retardation of recurrent tumor growth and suppression of life-threatening metastatic dissemination to internal organs were accompanied by a striking delay in hemangioma-associated mortality. Parental MVMp did not have a significant effect under these conditions up to the dose of 10(10) infectious units/animal, but had strong antihemangiosarcoma activity when used to infect H5V cells ex vivo prior to implantation. In all cases, virus therapy was very well tolerated. Virus-induced suppression of hemangiosarcoma was dependent on host T cells and associated with intratumoral persistence of IFN gamma-expressing cytotoxic lymphocytes, and led to the reduced expression of hepatic plasminogen activator inhibitor-1 (PAI-1), a metastasis-linked marker. This proof of principle study demonstrates that MVMp/IP-10 can aid the treatment of vascular tumors and that autonomous parvovirus-based vectors can be considered potent tools for cancer gene therapy purposes.


GRK2 protein-mediated transphosphorylation contributes to loss of function of μ-opioid receptors induced by neuropeptide FF (NPFF2) receptors.
Neuropeptide FF (NPFF) interacts with specific receptors to modulate opioid functions in the central nervous system. On dissociated neurons and neuroblastoma cells (SH-SY5Y) transfected with NPFF receptors, NPFF acts as a functional antagonist of μ-opioid (MOP) receptors by attenuating the opioid-induced inhibition of calcium conductance. In the SH-SY5Y model, MOP and NPFF(2) receptors have been shown to heteromerize. To understand the molecular mechanism involved in the anti-opioid activity of NPFF, we have investigated the phosphorylation status of the MOP receptor using phospho-specific antibody and mass spectrometry. Similarly to direct opioid receptor stimulation, activation of the NPFF(2) receptor by [D-Tyr-1-(NMe)Phe-3]NPFF (1DMe), an analog of NPFF, induced the phosphorylation of Ser-377 of the human MOP receptor. This heterologous phosphorylation was unaffected by inhibition of second messenger-dependent kinases and, contrarily to homologous phosphorylation, was prevented by inactivation of G(i/o) proteins by pertussis toxin. Using siRNA knockdown we could demonstrate that 1DMe-induced Ser-377 cross-phosphorylation and MOP receptor loss of function were mediated by the G protein receptor kinase GRK2. In addition, mass spectrometric analysis revealed that the phosphorylation pattern of MOP receptors was qualitatively similar after treatment with the MOP agonist Tyr-D-Ala-Gly (NMe)-Phe-Gly-ol (DAMGO) or after treatment with the NPFF agonist 1DMe, but the level of multiple phosphorylation was more intense after DAMGO. Finally, NPFF(2) receptor activation was sufficient to recruit β-arrestin2 to the MOP receptor but not to induce its internalization. These data show that NPFF-induced heterologous desensitization of MOP receptor signaling is mediated by GRK2 and could involve transphosphorylation within the heteromeric receptor complex.


[Lectin-induced chemiluminescence of peripheral blood neutrophils in patients with ischemic heart disease before and after blood irradiation with helium-neon laser].
The blood taken from 35 patients with coronary heart disease and 30 healthy donors was irradiated with He-Ne laser, which resulted in a decrease in its count of segmented neutrophilic granulocytes. Lectins bound to various carbohydrate determinants onto the neutrophil surface were shown to affect changes occurring after luminol-depended chemiluminescence irradiation in patients and healthy persons in different ways. The patients' neutrophils contained lower levels of radiommunologically detectable leukotriene B4. Thromboxane B2 levels also dropped following the irradiation. The laser irradiation induced elimination of some less resistant cells from blood flow, i.e. "rejuvenation" of a cell population of neutrophilic granulocytes. The remaining cells differed in the composition and reactivity of surface lectin receptors and in the content of biologically active substances, which is likely to play the key role in the mechanism responsible for the therapeutical effect of He-Ne laser.


Spleen Stiffness Probability Index (SSPI): A simple and accurate method to detect esophageal varices in patients with compensated liver cirrhosis.
Recent findings pointed out that even low-risk esophageal varices (EVs) are markers of severe prognosis. Accordingly, we analyzed spleen stiffness (SS) as a non-invasive method to predict EVs of any grade in a cohort of patients with compensated liver cirrhosis. We measured SS and liver stiffness (LS) using point-Shear-Wave Elastography (pSWE) with Philips Affiniti 70 system in 210 cirrhotic patients who had undergone endoscopic screening for EVs. We compared SS and LS predictive capability for EVs of any grade. SS was higher in cirrhotic patients with EVs if compared to patients without EVs (p<0.001). The cut-off analysis detected 31kPa (100% sensitivity and negative predictive value) as the value to rule-out EVs and 69kPa (100% specificity and positive predictive value) to rule-in EVs. Besides, we developed the Spleen Stiffness Probability Index (SSPI), that can provide a probability of presence/absence of EVs. SSPI was the best model according to all discriminative and calibration metrics (AIC=120, BIC=127, AUROC=0.95, Pseudo-R2=0.74). SS demonstrated higher correlation with spleen bipolar diameter and spleen surface (r=0.52/0.55) if compared to LS (r=0.30/0.25) - and with platelet count as well (r=0.67 vs r=0.4). SS showed significantly higher performance than other parameters, proving to be the best non-invasive test in the screening of EVs: by directly applying SS cut-off of 31kPa, our department could have safely avoided endoscopy in 36% of patients. Despite cut-off analyses, it was possible to create a probability model that could further stratify low-risk from high-risk patients (for any grade of EVs).


When Things Get Stuck: Gear Entrapment and Other Complications of Chronic Total Occlusion Percutaneous Coronary Intervention.
Complex coronary artery intervention stresses the limits of both the operator's skills as well as the equipment being used for the procedure. This article is focused on avoiding, recognizing and dealing with device failure and gear entrapment during complex coronary intervention. The operator must understand how to avoid these complications by understanding the limits of devices and the need for adequate vessel preparation. This article focuses on giving the reader an algorithmic approach to recognizing when device failure/entrapment occurs and what specific maneuvers can be done to retrieve different devices and equipment safely.


SMES survival and knowledge in emerging economies: evidence from Vietnam.
This paper evaluates how knowledge affecting the survival of new private small and medium sized enterprises (SMEs) in an emerging economy like Vietnam. The panel data extracted from the national surveys allow for comprehensive analysis during the period 2005-2011 with the semi-parametric Cox proportional hazard model. The study examines knowledge factors under controlling firm-specific and industrial factors. The findings express strong evidence that Vietnamese SMEs benefit strongly from knowledge development. The findings suggest firms to foster labor productivity, value added, and computerization. There is evidence of market selection, based on efficiency of investment. Besides, firms should improve return on sales, especially in growing market. Start-up SMEs should prepare sufficient total assets, not basing on leverage to enter the market. Start-up in industries with high growth, especially at the early stages of the life cycle will require more government support. These findings provide the evidence for policy improvement to help SMEs in the development of knowledge economy.


Mitochondrial malate dehydrogenase from watermelon: sequence of cDNA clones and primary structure of the higher-plant precursor protein.
The isolation and sequence of a cDNA clone encoding the complete mitochondrial malate dehydrogenase (mMDH) of watermelon cotyledons is presented. Taking advantage of the polymerase chain reaction technology partial cDNA clones from the central part, the 3' part and the 5' part of the mRNA were obtained with oligonucleotides based on directly determined amino acid sequences. Subsequently, two complete cDNA clones for mMDH were synthesized with a sense primer corresponding to the nucleotide sequence of the amino terminal end of pre-mMDH and two antisense primers corresponding to the major alternative adenylation sites found in the mRNA. The amino acid residues for substrate and cofactor binding identified by X-ray crystallography for pig heart cytoplasmic MDH are conserved in the 320 amino acid long mature higher-plant mMDH. A presequence of 27 amino acids is present at the amino terminal end of the precursor protein.


Ischemic etiology of heart failure identifies patients with more severely impaired exercise capacity.
Peak oxygen uptake (peak VO2) and the regression slope of ventilation against CO2 production during exercise (VE/VCO2 slope) are powerful prognostic indicators in patients with chronic heart failure (CHF). Our purpose was to evaluate the influence of CHF etiology on peak VO2 and VE/VCO2 slope, independently of demographic, clinical, Doppler-echocardiographic and neurohormonal factors. Data were collected from 239 CHF patients referred for a cardiopulmonary exercise test as part of their clinical evaluation. Patients were stratified according to their CHF etiology (ischemic versus non-ischemic). The etiology of heart failure was ischemic in 143 patients (60%) and non-ischemic in 96 (40%). Patients with ischemic etiology, compared with those with non-ischemic etiology, showed a lower peak VO2 (15.4+/-4.2 versus 17.8+/-4.8 ml/kg/min, p<0.0001) and a steeper VE/VCO2 slope (38.1+/-6.8 versus 34+/-5.3, p<0.0001). In the univariate model, age (r=-0.36, p<0.0001), female sex (r=-0.21, p=0.001), ischemic CHF etiology (r=-0.26, p<0.0001) and NYHA class (r=-0.52, p<0.0001) correlated with peak VO2. At multivariate analysis, ischemic CHF etiology (beta=-0.23, p=0.001) was a predictor of peak VO2 (R(2)=0.49) independently of age (beta=-0.23, p=0.001), female sex (beta=-0.25, p=0.0006) and NYHA class (beta=-0.31, p<0.0001). Similarly, ischemic etiology (beta=0.29, p=0.001) predicted the VE/VCO2 slope (R(2)=0.38) independently of E/A ratio (beta=0.27, p=0.01) and resting heart rate (beta=0.22, p=0.01). Etiology of heart failure may influence the functional capacity and the ventilatory response to exercise.


Mechanism of the lack of induction of UDP-glucuronosyltransferase activity in Gunn rats by 3-methylcholanthrene. Identification of a truncated enzyme.
Gunn rats lack UDP-glucuronosyltransferase (UDPGT) activity toward bilirubin. 4-Nitrophenol glucuronidation is mediated by several UDPGT isoforms that are distinct from bilirubin-UDPGT, one of which is induced after 3-methylcholanthrene (3-MC) administration in normal, but not in Gunn rats. In normal rats, 3-MC-inducible UDPGT mRNA concentration increased 15-fold in the liver and 3-fold in kidney after 3-MC (140 mg/kg) administration. Concentration of this mRNA is much lower in Gunn rat liver and kidney compared to normal. However, this mRNA was normally induced after 3-MC administration. By RNA blot hybridization, the mRNA in Gunn rat liver and kidney appeared to be of normal size. Nuclear run-on studies showed that the transcription rate for 3-MC-inducible UDPGT was 3-fold higher in Gunn rat liver and kidney than in normal and increased 3- to 5-fold after 3-MC administration. Immunotransblot studies revealed an Mr = 56,000 3-MC-inducible UDPGT in liver and kidney of normal, but not in Gunn rats. However, a new immunoreactive UDPGT band (Mr = 43,000) was present in Gunn, but not in normal rats. Cell-free translation of kidney mRNA from 3-MC-treated Gunn rats showed that the Mr = 43,000 UDPGT is synthesized as an Mr = 45,000 protein. Prior hybridization of the mRNA with an isoform-specific oligonucleotide spanning the initiation codon abolishes synthesis of this protein. These results suggest that a sequence abnormality in the 3-MC-inducible UDPGT mRNA in Gunn rats results in reduced mRNA concentration and synthesis of a truncated, enzymically inactive UDPGT.


Knowledge, attitude, and practice patterns and the purported reasons for delayed presentation of patients with sight-threatening diabetic retinopathy at a tertiary eyecare facility in Central India: A questionnaire-based study.
To identify the reasons for delayed presentation among patients with sight-threatening diabetic retinopathy (STDR) and to assess their knowledge, attitude, and practice (KAP) patterns in context to diabetes mellitus (DM) and diabetic retinopathy (DR). Single-center, cross-sectional, questionnaire-based KAP survey. All consecutive cases of STDR who presented to our tertiary eye care facility from June 2020 to November 2020 were recruited. The KAP scoring survey tool was incorporated into the questionnaire to help evaluate and represent the patient's disease. 170 patients with STDR were enrolled in the study. The mean age of patients was 54 ± 9.34 years (Range: 21-70 years); 110 patients (64.7%) were between 41 and 60 years; 131 patients (76%) had DM for more than 5 years. The STDR changes were more prevalent in patients with an educational qualification of high school or less (n = 142; 83.5%). Fifty-two patients (30.6%) had been informed regarding the detrimental effect of diabetes on the eyes and were recommended to consult an ophthalmologist by the treating physician. Of these, 24 (46.15%) patients were educated about retinal changes due to diabetes. Eighty-five (50%) patients in our study had good knowledge about DM; 13 (7.6%) patients had good knowledge about DR. For patients not compliant for follow-ups with the treating physician, the use of "home glucometers for self-monitoring (n = 60, 35.3%) was the most prevalent reason. The main reason for poor compliance for undergoing a dilated fundus examination by the ophthalmologist was "Had good vision, so didn't feel the need" in 143 (90.5%) patients. The absence of visual complaints, lack of knowledge, and failure to undergo a dilated fundus examination in the past were the prevalent risk factors in patients presenting with STDR. Knowledge/practice about DR was poor among the patients with STDR. The treating physicians and ophthalmologists were the most common sources for patient education.


Cell death by apoptosis in acute leukaemia.
We have previously demonstrated that when freshly isolated childhood T-cell acute lymphoblastic leukaemia cells are incubated in growth medium after isolation from blood, chromatin is rapidly cleaved into nucleosomal sized fragments that are multiples of 200 bp. The fragmentation is similar to that observed in other types of cells undergoing apoptosis or programmed cell death. In this study we describe a more comprehensive approach to the study of DNA fragmentation in leukaemia. Fragmentation was observed in freshly isolated cells from patients with T-cell acute lymphoblastic leukaemia and in one with common acute lymphoblastic leukaemia. Frozen samples of T-cell acute lymphoblastic leukaemia, common acute lymphoblastic leukaemia, and acute myeloid leukaemia cells also showed fragmentation of DNA. However, no fragmentation was evident in normal leukocytes treated under the same conditions. Ultrastructural studies on the isolated leukaemia cells demonstrate that the chromatin cleavage observed biochemically is associated with morphological changes characteristic of apoptosis.


Genomic Profile in a Non-Seminoma Testicular Germ-Cell Tumor Cohort Reveals a Potential Biomarker of Sensitivity to Platinum-Based Therapy.
Despite having a favorable response to platinum-based chemotherapies, ~15% of Testicular Germ-Cell Tumor (TGCT) patients are platinum-resistant. Mortality rates among Latin American countries have remained constant over time, which makes the study of this population of particular interest. To gain insight into this phenomenon, we conducted whole-exome sequencing, microarray-based comparative genomic hybridization, and copy number analysis of 32 tumors from a Mexican cohort, of which 18 were platinum-sensitive and 14 were platinum-resistant. We incorporated analyses of mutational burden, driver mutations, and SNV and CNV signatures. DNA breakpoints in genes were also investigated and might represent an interesting research opportunity. We observed that sensitivity to chemotherapy does not seem to be explained by any of the mutations detected. Instead, we uncovered CNVs, particularly amplifications on segment 2q11.1 as a novel variant with chemosensitivity biomarker potential. Our data shed light into understanding platinum resistance in a Latin-origin population.


Radiation dose, schedule, and novel systemic targets for radio-immunotherapy combinations.
Immunotherapy combinations are being investigated to expand the benefit of immune checkpoint blockade across many cancer types. Radiation combinations, in particular using stereotactic body radiotherapy, are of keen interest because of underlying mechanistic rationale, safety, and availability as a standard of care in certain cancers. In addition to direct tumor cytotoxicity, radiation therapy has immunomodulatory effects such as induction of immunogenic cell death, enhancement of antigen presentation, and expansion of the T-cell receptor repertoire as well as recruitment and increased activity of tumor-specific effector CD8+ cells. Combinations of radiation with cytokines and/or chemokines and anti-programmed death 1 and anticytotoxic T-lymphocyte antigen 4 therapies have demonstrated safety and feasibility, as well as the potential to improve long-term outcomes and possibly induce out of irradiated field or abscopal responses. Novel immunoradiotherapy combinations represent a promising therapeutic approach to overcome radioresistance and further enhance systemic immunotherapy. Potential benefits include reversing CD8+ T-cell exhaustion, inhibiting myeloid-derived suppressor cells, and reversing M2 macrophage polarization as well as decreasing levels of colony-stimulating factor-1 and transforming growth factor-β. Here, we discuss current data and mechanistic rationale for combining novel immunotherapy agents with radiation therapy.


Fetal choledochal cyst diagnosed at 22 weeks of gestation by three-dimensional ultrasonography: a case report.
Choledochal cyst is a cystic or fusiform dilatation of the extra- or intrahepatic bile duct that has rarely been reported in prenatal cases. Here we report a fetus with choledochal cyst diagnosed prenatally by three-dimensional (3-D) ultrasonography at 22 weeks of gestation. We demonstrated an image of choledochal cyst by using a new ultrasound technique, a 3-D multislice view. After close intrauterine followup, surgery was successfully performed and postoperative course was uneventful.


Small fiber function in drug naïve patients with idiopathic restless legs syndrome.
To assess whether idiopathic restless legs syndrome (RLS) is associated with small fiber abnormalities, we evaluated somatic and autonomic small fiber function in 56 patients with idiopathic RLS and 36 age-matched and sex-matched healthy controls using quantitative sensory testing and quantitative sudomotor axon reflex tests. The warm detection thresholds (WDT) of the hands (p=0.017) and feet (p=0.008) were higher in patients with RLS than in controls. Cooling detection thresholds (CDT) were higher in the feet of patients with RLS than controls (p<0.001), but CDT in the hands did not differ between groups (p=0.161). There were no significant between-group differences in total sweat volume and sweat production in the forearms, proximal legs, distal legs, and feet (p>0.1 each). These findings suggest that abnormal sensory perception in patients with idiopathic RLS may result from impairment of central somatosensory processing rather than small fiber neuropathy.


Herpes simplex virus evades natural killer T cell recognition by suppressing CD1d recycling.
Natural killer T cells, which are stimulated by lipids presented by CD1d molecules, are crucial in antiviral host defense. How viruses evade natural killer T cell recognition remains unclear. Here we show that infection with herpes simplex virus type 1 (HSV-1) reduced CD1d surface expression on antigen-presenting cells. HSV-1 did not inhibit CD1d protein synthesis or enhance constitutive CD1d endocytosis. Instead, HSV-1 prevented the reappearance of endocytosed CD1d on the cell surface by redistributing endocytosed CD1d to the lysosome limiting membrane. HSV-1 might also inhibit the transport of newly synthesized CD1d to the cell surface. Such inhibition of CD1d surface expression impaired antigen-presenting cell-mediated stimulation of natural killer T cells, supporting the idea that this mechanism may be an important HSV-1 immune evasion strategy.


2020 BioImage Analysis Survey: Community experiences and needs for the future.
In this paper, we summarize a global survey of 484 participants of the imaging community, conducted in 2020 through the NIH Center for Open BioImage Analysis (COBA). This 23-question survey covered experience with image analysis, scientific background and demographics, and views and requests from different members of the imaging community. Through open-ended questions we asked the community to provide feedback for the open-source tool developers and tool user groups. The community's requests for tool developers include general improvement of tool documentation and easy-to-follow tutorials. Respondents encourage tool users to follow the best practices guidelines for imaging and ask their image analysis questions on the Scientific Community Image forum (forum.image.sc). We analyzed the community's preferred method of learning, based on level of computational proficiency and work description. In general, written step-by-step and video tutorials are preferred methods of learning by the community, followed by interactive webinars and office hours with an expert. There is also enthusiasm for a centralized location online for existing educational resources. The survey results will help the community, especially developers, trainers, and organizations like COBA, decide how to structure and prioritize their efforts.


Impact of Supervisory Support on Turnover Intention: The Mediating Role of Burnout and Job Satisfaction in a Longitudinal Study.
High rates of provider turnover are problematic for our mental health system. Research indicates that supervisory support could alleviate some turnover intention by decreasing emotional exhaustion (a key component of burnout) as well as by increasing job satisfaction. However, the potential mediation mechanisms have not been rigorously tested. Longitudinal data collected from 195 direct clinical care providers at two community mental health centers identified positive effects of supervisory support on reduced turnover intention through reduced emotional exhaustion. Job satisfaction was not a significant mediator. Supervisory support may help mitigate turnover intention through work-related stress reduction.


Development of complex patterns of anthropogenic uplift and subsidence in the Delaware Basin of West Texas and southeast New Mexico, USA.
The Delaware Basin in west Texas and southeast New Mexico is now the largest global oil producing basin, averaging ∼400,000 m3 (∼2,500,000 barrels) per day in 2022. The shale-dominated strata targeted for production can co-produce 4-5 times more water than oil, necessitating disposal by injection of ∼1,400,000 m3 (∼8,700,000 barrels) of water per day in 2022. Through a comprehensive assimilation of regional Sentinel-1 satellite radar data and analysis of production and injection, we show how petroleum operations have caused the development of complex and accelerating patterns of surface deformation from 2015 through 2021. We observe uplift from reservoir swelling, subsidence from reservoir contraction, and the development of linear features that are indicative of faulting. Subsidence is predominantly caused by production, and an important finding of this study is that the magnitude of subsidence is linearly proportional to total production. Uplift is caused by pressurization from wastewater injection of shallow permeable strata. The patterns of uplift are complex and extend laterally well-beyond areas where injection was performed. Linear surface deformation features are observed throughout the Delaware Basin, and they are lengthening and densifying as uplift and subsidence accelerate. Many of the lineations can be linked to known strata-bounded faults and shallow seismicity in the southern Delaware Basin where they serve as permeable and anisotropic conduits for pore pressure migration. In the Northern Delaware Basin, co-seismic rupture is hosted along basement-rooted faults that may link to the linear surface features. Understanding these dynamic changes in Delaware Basin is a pressing concern for management of subsurface reservoirs and safeguarding the surface environment. Concerns include ongoing induced seismicity, hazard of drilling through over-pressured strata, maintenance of integrity for newer wellbores, mitigation of flows of brine and petroleum fluids at the surface of old wellbores, and management of the pore space resource for wastewater injection.


[Safety and reliability verification for manned spacecraft crew support facilities].
To verify reliability and safety of the crew support facilities on board manned spacecraft. Several comprehensive qualitative and quantitative projection verification technique, such as analysis, check, demonstration, tests and reliability assessment, were used. Work-items that were specified in the reliability and safety program were realized. Assurance measures for safety and reliability critical items were available. FMEA and SHA and FTA were brought in all around. Safety and reliability on equipment levels and system levels was fully carried out. The facility safety and reliability achieved design specification and met the requirements of spaceflight tests for manned spacecraft.


Abundance, size and polymer composition of marine microplastics ≥10μm in the Atlantic Ocean and their modelled vertical distribution.
We studied abundance, size and polymer type of microplastic down to 10μm along a transect from the European Coast to the North Atlantic Subtropical Gyre (NASG) using an underway intake filtration technique and Raman micro-spectrometry. Concentrations ranged from 13 to 501itemsm(-3). Highest concentrations were observed at the European coast, decreasing towards mid-Atlantic waters but elevated in the western NASG. We observed highest numbers among particles in the 10-20μm size fraction, whereas the total volume was highest in the 50-80μm range. Based on a numerical model size-dependent depth profiles of polyethylene microspheres in a range from 10-1000μm were calculated and show a strong dispersal throughout the surface mixed layer for sizes smaller than 200μm. From model and field study results we conclude that small microplastic is ubiquitously distributed over the ocean surface layer and has a lower residence time than larger plastic debris in this compartment.


Alcohol-induced breast cancer: a proposed mechanism.
Alcohol consumption increases the risk for breast cancer in women by still undefined means. Alcohol metabolism is known to produce reactive oxygen species (ROS), and breast cancer is associated with high levels of hydroxyl radical (*OH) modified DNA, point mutations, single strand nicks, and chromosome rearrangement. Furthermore, ROS modification of DNA can produce the mutations and DNA damage found in breast cancer. Alcohol dehydrogenase (ADH) and xanthine oxidoreductase (XOR) are expressed and regulated in breast tissues and aldehyde oxidase (AOX) may be present as well. Mammary gland XOR is an efficient source of ROS. Recently, hepatic XOR and AOX were found to generate ROS in two ways from alcohol metabolism: by acetaldehyde consumption and by the intrinsic NADH oxidase activity of both XOR and AOX. The data obtained suggests that: (1) expression of ADH and XOR or AOX in breast tissue provides the enzymes that generate ROS; (2) metabolism of alcohol produces acetaldehyde and NADH that can both be substrates for XOR or AOX and thereby result in ROS formation; and (3) ROS generated by XOR or AOX can induce the carcinogenic mutations and DNA damage found in breast cancer. Accumulation of iron coupled with diminished antioxidant defenses in breast tissue with advancing age provide additional support for this hypothesis because both result in elevated ROS damage that may exacerbate the risk for ROS-induced breast cancer.


The function of the co-chaperone ERdj4 in diverse (patho-)physiological conditions.
Accumulation of misfolded proteins in the endoplasmic reticulum (ER) induces a well-orchestrated cellular response to reduce the protein burden within the ER. This unfolded protein response (UPR) is controlled primarily by three transmembrane proteins, IRE1α, ATF6, and PERK, the activity of which is controlled by BiP, the ER-resident Hsp70 protein. Binding of BiP to co-chaperones via their highly conserved J-domains stimulates the intrinsic ATPase activity of BiP, thereby providing the energy necessary for (re-)folding of proteins, or for targeting of misfolded proteins to the degradation pathway, processes specified and controlled by the respective co-chaperone. In this review, our aim is to elucidate the function of the co-chaperone ERDJ4, also known as MDG1, MDJ7, or DNAJB9. Knockout and knockin experiments clearly point to the central role of ERDJ4 in controlling lipogenesis and protein synthesis by promoting degradation of SREBP1c and the assembly of the protein complex mTORC2. Accumulating data reveal that ERDJ4 controls epithelial-to-mesenchymal transition, a central process during embryogenesis, in wound healing, and tumor development. Overexpression of ERdj4 has been shown to improve engraftment of transplanted human stem cells, possibly due to its ability to promote cellular survival in stressed cells. High ERDJ4-plasma levels are specific for fibrillary glomerulonephritis and serve as a diagnostic marker. As outlined in this review, the functions of ERDJ4 are manifold, depending on the cellular (patho-) physiological state, the cellular protein repertoire, and the subcellular localization of ERDJ4.


Potassium Channel Block and Novel Autoimmune-Associated Long QT Syndrome.
This article reviews advances in the pathogenesis of anti-SSA/Ro antibody-induced corrected QT (QTc) prolongation in patients with autoimmune diseases; particularly connective tissue disease (CTD). Evidence shows that anti-SSA/Ro antibody-positive patients with CTD show QTc prolongation and complex ventricular arrhythmias. Molecular and functional data provide evidence that the human ether-a-go-go-related gene potassium channel conducting the rapidly activating delayed rectifier potassium current is directly inhibited by anti-SSA/Ro antibodies, resulting in action potential duration prolongation leading to QT interval lengthening. Routine electrocardiogram screening in anti-SSA/Ro antibody-positive patients and counseling for patients with other QTc prolonging risk factors is recommended.


Biochemical studies on bilharzial and nonbilharzial hyperoxaluria: effect of pyridoxine and allopurinol treatment.
The urinary excretion levels of oxalic acid, calcium, kynurenic, and xanthurenic acids and serum pyridoxal and pyridoxal phosphate concentrations were determined for nonbilharzial and bilharzial hyperoxaluric patients with or without urinary stones. The effects of pyridoxine and allopurinol treatment were also studied. The different groups studied showed elevated levels of urinary oxalic acid, calcium, kynurenic, and xanthurenic acids as well as decreases in serum pyridoxal and pyridoxal phosphate concentrations. These data indicate that nonbilharzial hyperoxaluric patients suffer from dietary B6 deficiency, whereas bilharzial hyperoxaluric patients may suffer from impaired pyridoxine phosphokinase activity. Pyridoxine supplementation is recommended for the treatment of nonbilharzial hyperoxaluric patients. Allopurinol may be the proper drug in the treatment of oxaluria and stone formation or of bilharzial patients.


Diagnosis of a difficult to differentiate case of early-onset hyperviscosity syndrome caused by IgM type multiple myeloma: a case report.
Hyperviscosity syndrome (HVS) can cause multiple organ damage if not treated immediately. IgM multiple myeloma (IgM MM) is a very rare form of myeloma with clinical features such as elevated serum IgM, and anemia, that resemble Waldenström macroglobulinemia (WM). Distinguishing between these two diseases is important, but can be a challenging problem. It is well known that MyD88 mutations and t(11;14) translocations are useful for differential diagnosis. We diagnosed HVS in a 29-year-old male with IgM MM. He was treated with triplet therapy, autologous hematopoietic stem cell transplantation, and carfilzomib consolidation therapy. His clinical course was monitored by serum IgM levels, and bone marrow myeloma cell counts by multiparameter flow cytometry analysis. After this series of treatments, his HSV disappeared and he reached stringent complete response. In cases of early onset of HVS, IgM MM should be considered in addition to WM.


Unreferenced spatial localization under monocular and dichoptic viewing conditions.
Knowledge of eye position in the brain is critical for localization of objects in space. To investigate the accuracy and precision of eye position feedback in an unreferenced environment, subjects with normal ocular alignment attempted to localize briefly presented targets during monocular and dichoptic viewing. In the task, subjects' used a computer mouse to position a response disk at the remembered location of the target. Under dichoptic viewing (with red (right eye)-green (left eye) glasses), target and response disks were presented to the same or alternate eyes, leading to four conditions [green target-green response cue (LL), green-red (LR), red-green (RL), and red-red (RR)]. Time interval between target and response disks was varied and localization errors were the difference between the estimated and real positions of the target disk. Overall, the precision of spatial localization (variance across trials) became progressively worse with time. Under dichoptic viewing, localization errors were significantly greater for alternate-eye trials as compared to same-eye trials and were correlated to the average phoria of each subject. Our data suggests that during binocular dissociation, spatial localization may be achieved by combining a reliable versional efference copy signal with a proprioceptive signal that is unreliable perhaps because it is from the wrong eye or is too noisy.


Polymorphous low grade adenocarcinoma: literature review and report of lower lip lesion with suspected lung metastasis.
Polymorphous low grade adenocarcinoma (PLGA) is an uncommon tumour that affects minor salivary glands mainly. It was known to be clinically benign and histologically polymorphic; sometimes misdiagnosed as pleomorphic adenomas, monomorphic adenomas, malignant pleomorphic adenomas, adenoid cystic carcinomas and adenocarcinoma not otherwise specified. More information about PLGA is cumulating in the current literature with new evidences suggesting that the tumour may not be as indolent as it was previously thought. A thorough understanding of the clinical and histological behaviour of the lesion has serious implications in management. Here, a case of lower lip lesion with suspected lung metastasis is reported to exemplify how the clinical behaviour of the lesion may affect management.


Geographic Heterogeneity in Behavioral and Social Drivers of COVID-19 Vaccination.
Little is known about how the drivers of COVID-19 vaccination vary across the U.S. To inform vaccination outreach efforts, this study explores geographic variation in correlates of COVID-19 nonvaccination among adults. Participants were a nationally representative sample of U.S. adults identified through random-digit dialing for the National Immunization Survey-Adult COVID Module. Analyses examined the geographic and temporal landscape of constructs in the Behavioral and Social Drivers of Vaccination Framework among unvaccinated respondents from May 2021 to December 2021 (n=531,798) and sociodemographic and geographic disparities and Behavioral and Social Drivers of Vaccination predictors of COVID-19 nonvaccination from October 2021 to December 2021 (n=187,756). National coverage with at least 1 dose of COVID-19 vaccine was 79.3% by December 2021, with substantial geographic heterogeneity. Regions with the largest proportion of unvaccinated persons who would probably get a COVID-19 vaccine or were unsure resided in the Southeast and Midwest (Health and Human Services Regions 4 and 5). Both regions had similar temporal trends regarding concerns about COVID-19 and confidence in vaccine importance, although the Southeast had especially low confidence in vaccine safety in December 2021, lowest in Florida (5.5%) and highest in North Carolina (18.0%). The strongest Behavioral and Social Drivers of Vaccination correlate of not receiving a COVID-19 vaccination was lower confidence in COVID-19 vaccine importance (adjusted prevalence ratio=5.19, 95% CI=4.93, 5.47; strongest in the Northeast, Southwest, and Mountain West and weakest in the Southeast and Midwest). Other Behavioral and Social Drivers of Vaccination correlates also varied by region. Contributors to nonvaccination showed substantial geographic heterogeneity. Strategies to improve COVID-19 vaccination uptake may need to be tailored regionally.


Identification of new synthetic PDE-5 inhibitors analogues found as minor components in a dietary supplement.
A dietary supplement sold in erotic shops was analysed. It contains dithiodesmethylcarbodenafil as the major component, which was already reported as an adulterant in dietary supplements. Additionally three more compounds were found and their structures were elucidated after isolation using NMR and mass spectroscopy. They were designated as isonitrosoprodenafil, dithiodesethylcarbodenafil and norcarbodenafil.


[The surface expression of CD25 at different stages of proliferative response in human lymphocytes. I. The role of JAK and Src tyrosine kinases as revealed by inhibitory analysis].
The long-lasting expression of an alpha-subunit of interleukin-3 receptor (IL-2Ralpha) was found to accompany the PHA-induced proliferation of human blood lymphocytes (HBL), so that to the end of the second day of mitogenic stimulation only, the large blasts may express the high affinity alphabetagamma(c) receptor for IL-2. With the selective pharmacological drugs to JAK (WHI-P131) and Src (PP2) it is shown that the non-receptor tyrosine kinases are involved in the surface CD25 expression. It is revealed that the PP-2-inhibitable expression of CD25 is timely associated with the initial stage of T cell activation, whereas WHI-P131-inhibitable expression was present during the whole G0/G1/S transition. These data indicate that at the early, antigen-dependent stage the expression of IL-2Ralpha is induced via Src-dependent signaling pathway, and prolonged increase in IL-2Ralpha expression is regulated by IL-2/IL-2 receptor interaction via JAK-dependent signaling pathway.


The mitochondrial phosphate carrier reconstituted in liposomes is inhibited by doxorubicin.
The phosphate carrier has been isolated from beef heart mitochondria in the presence of cardiolipin and reconstituted in asolectin vesicles. It has been found that 100 microM doxorubicin and 100 microM Br-daunomycin inhibit the unidirectional phosphate uptake in the reconstituted liposomes to the same extent as N-ethylmaleimide. The inhibition by Br-daunomycin is not due to covalent interaction with the carrier. The specific interaction between doxorubicin and cardiolipin is responsible for the inhibition of the phosphate carrier. Br-daunomycin interacts with 3 mitochondrial proteins of apparent Mr approximately 45 000, approximately 35 000 and approximately 30 000.


Prediction of feed comonomer and solvent composition for monomer-free polymer production.
A method has been developed to establish the desirable polymerization conditions for the production of monomer-free polymer at 100% conversion. The limits of desirable comonomer composition and solvent content in the feed are determined for both bulk and solution homo- and copolymerizations. An example of the result of the polymerization of 2-hydroxyethyl methacrylate and methyl methacrylate is used to illustrate the application of this method.


4,4'-Bipyridine-dimethyl-glyoxime (1/1).
In the title compound, C(10)H(8)N(2)·C(4)H(8)N(2)O(2), both the dimethyl-glyoxime and the 4,4'-bipyridine mol-ecules have crystallographic C(i) symmetry. The mol-ecules stack along the a-axis direction with a dihedral angle of 20.4 (8)° between their planes. In the crystal, the components are linked by O-H⋯N hydrogen bonds into alternating chains along [120] and [1[Formula: see text]0].


Data-driven machine-learning analysis of potential embolic sources in embolic stroke of undetermined source.
Hierarchical clustering, a common 'unsupervised' machine-learning algorithm, is advantageous for exploring potential underlying aetiology in particularly heterogeneous diseases. We investigated potential embolic sources in embolic stroke of undetermined source (ESUS) using a data-driven machine-learning method, and explored variation in stroke recurrence between clusters. We used a hierarchical k-means clustering algorithm on patients' baseline data, which assigned each individual into a unique clustering group, using a minimum-variance method to calculate the similarity between ESUS patients based on all baseline features. Potential embolic sources were categorised into atrial cardiopathy, atrial fibrillation, arterial disease, left ventricular disease, cardiac valvulopathy, patent foramen ovale (PFO) and cancer. Among 800 consecutive ESUS patients (43.3% women, median age 67 years), the optimal number of clusters was four. Left ventricular disease was most prevalent in cluster 1 (present in all patients) and perfectly associated with cluster 1. PFO was most prevalent in cluster 2 (38.9% of patients) and associated significantly with increased likelihood of cluster 2 [adjusted odds ratio: 2.69, 95% confidence interval (CI): 1.64-4.41]. Arterial disease was most prevalent in cluster 3 (57.7%) and associated with increased likelihood of cluster 3 (adjusted odds ratio: 2.21, 95% CI: 1.43-3.13). Atrial cardiopathy was most prevalent in cluster 4 (100%) and perfectly associated with cluster 4. Cluster 3 was the largest cluster involving 53.7% of patients. Atrial fibrillation was not significantly associated with any cluster. This data-driven machine-learning analysis identified four clusters of ESUS that were strongly associated with arterial disease, atrial cardiopathy, PFO and left ventricular disease, respectively. More than half of the patients were assigned to the cluster associated with arterial disease.


Composite electrolyte used for low temperature SOFCs to work at 390°C.
A combination of yttria stabilized zirconia (YSZ) and Ba(NO3)2 commercial powders was used as electrolytes in the construction of symmetrical SOFC. As X-ray diffraction pattern and Raman spectra revealed, the YSZ-Ba(NO3)2 electrolyte in situ converted into YSZ and yttrium-doped barium zirconate (BZY) composite at 450°C in hydrogen atmosphere. The power maximum (Pmax) of YSZ-BZY based fuel cell can reach 634.06 mW cm-2 at 450°C. Notly, the Pmax can evenly maintain at 300 mW cm-2 as the operational temperature reduced to 390°C. The outstanding cell performance at low temperature indicate the excellent ion conductivity of the composite electrolyte. The promising ion conductivity is originated from the proton conduction of BZY, the oxygen conductivity of YSZ, and the enhanced ion conduction through interface transport. Our work demonstrates that the developed YSZ-BZY electrolyte holds enormous potential for LT-SOFCs.


Natural source of Cr(VI) in soil: The anoxic oxidation of Cr(III) by Mn oxides.
Cr(VI) from oxidation of geogenic Cr(III) minerals is gradually becoming the primary source of Cr(VI) in soils and groundwater instead of direct emissions. Thermodynamically, natural oxidants of Cr(III) are limited to O2 and Mn oxides. The oxidation of Cr(III) occurs commonly in oxic soils but the difference in the oxidative dissolution of Cr(III) by Mn oxides in different redox soils (especially under anoxic conditions) is not fully understood and field evidence is lacking. Here, the relationship between Cr(VI) and Mn oxides in basalt-origin soil profiles under three different redox conditions (anoxic, suboxic and oxic) was studied. The oxidative dissolution of chromite was validated by synthesising δ-MnO2 that was close to biogenic Mn oxides under anoxic and oxic conditions. In anoxic soils, high levels of Cr(VI) were detected in the same horizons as those where Cr(III)-minerals co-existed with Mn(III/IV) oxides, suggesting an exclusive pathway for Cr(VI) generation through oxidation by Mn oxides where there was a deficiency of other oxidants, such as O2. In oxic soils, the highly abundant Fe oxides combined with Cr(III) to form Cr(III)-Fe(III) oxyhydroxides and Cr(VI) was generated mainly via slow oxidation by O2. The chromite oxidation experiment results also indicated that a high abundance of Mn oxides could promote chromite oxidative dissolution to generate Cr(VI), even under anoxic conditions. Additionally, the form of Cr and the reactivity and abundance of Mn oxides and reducing agents controlled the net content of Cr(VI) in the soil. This study showed that, even under reducing conditions, Cr(III) is readily oxidised by Mn oxides to generate Cr(VI) in reductant-deficient and Mn-rich soils, which may lead to the continuous introduction of Cr(VI) into groundwater and agricultural soils.


Postischemic administration of CGX-1051, a peptide from cone snail venom, reduces infarct size in both rat and dog models of myocardial ischemia and reperfusion.
CGX-1051 is a synthetic version of a peptide originally isolated from the venom of cone snails. In the present studies, we tested the potential cardioprotective effect of CGX-1051 in a rat and dog model of myocardial ischemia/reperfusion. CGX-1051 was administered 5 minutes before reperfusion as intravenous bolus doses of 30, 100, and 300 microg/kg. Infarct size (IS) is reported as IS/area at risk (AAR). In the rat, the vehicle control group had an IS/AAR of 59.8+/-2.1%. Postischemic administration of CGX-1051 at doses of 30, 100, and 300 microg/kg resulted in an IS/AAR of 52.6+/-4.2%, 34.6+/-5.6% (P<0.05), and 40.8+/-5.2% (P<0.05), respectively. In the dog, the vehicle control group had an IS/AAR of 18.8+/-1.7%. Postischemic administration of CGX-1051 at doses of 30, 100, and 300 microg/kg resulted in an IS/AAR of 16.9+/-2.5%, 8.4+/-2.9% (P<0.05) and 9.9+/-2.4% (P<0.05), respectively. These results demonstrate that administration of CGX-1051 at a clinically relevant time point results in a dose-dependent reduction in IS in both rats and dogs.


Diagnostic and therapeutic technology assessment. Transrectal ultrasonography in prostatic cancer.
The DATTA panelists believe that transrectal ultrasound is established as safe for the screening and staging of prostatic cancer. The majority did not believe, however, that the effectiveness of the procedure has been established yet for either screening or staging. The panelists and the literature indicate, however, that transrectal ultrasound may well have a significant role to play in the future treatment of prostatic cancers.


Characteristics of cadmium immobilization in the cell wall of root in a cadmium-safe rice line (Oryza sativa L.).
Cultivating cadmium (Cd)-safe rice lines, which show low Cd accumulation in brown rice, is generally beneficial to ensure food safety. The Cd retention in root of Cd-safe rice line D62B plays an important role in its low Cd translocation from root to shoot. To understand the mechanism of Cd retention in root, a hydroponic experiment was conducted to investigate the subcellular distribution of Cd and the contribution of polysaccharides to Cd binding to the root cell wall of a Cd-safe rice line D62B with a common rice line Luhui17 as a control material. D62B retained more Cd in the root by sequestrated a higher proportion of Cd in the cell wall, further it transferred less Cd to shoot. Close to half of the Cd in the root cell wall of D62B was accumulated in the hemicellulose 1 (HC1), and the proportions of HC1 in it were 1.2-1.7 times higher than these of Luhui17. The proportion of Cd in the pectin showed a dose-dependent increase in two rice lines. D62B contained significantly higher uronic acid concentrations of the pectin and greater pectin methyl esterase (PME) activities than Luhui17 in the root cell wall. These results indicated that a superior Cd binding capacity of the cell wall polysaccharides in D62B played an important role in its Cd retention in root.


Amyloid beta, tau, synaptic, neurodegeneration, and glial biomarkers in the preclinical stage of the Alzheimer's continuum.
The biological pathways involved in the preclinical stage of the Alzheimer's continuum are not well understood. We used NeuroToolKit and Elecsys® immunoassays to measure cerebrospinal fluid (CSF) amyloid-β (Aβ)42, Aβ40, phosphorylated tau (p-tau), total tau (t-tau), neurofilament light (NfL), neurogranin, sTREM2, YKL40, GFAP, IL6, S100, and α-synuclein in cognitively unimpaired participants of the ALFA+ study, many within the Alzheimer's continuum. CSF t-tau, p-tau, and neurogranin increase throughout aging only in Aβ-positive individuals, whereas NfL and glial biomarkers increase with aging regardless of Aβ status. We modelled biomarker changes as a function of CSF Aβ42/40, p-tau and p-tau/Aβ42 as proxies of disease progression. The first change observed in the Alzheimer's continuum was a decrease in the CSF Aβ42/40 ratio. This is followed by a steep increase in CSF p-tau; t-tau; neurogranin; and, to a lesser extent, in NfL and glial biomarkers. Multiple biological pathways are altered and could be targeted very early in the Alzheimer's continuum.


Effects of memantine on the twitch tension of mouse diaphragm.
The effects of memantine (50-175 microM) on the post-tetanic potentiation of the twitch tension were studied on the isolated mouse nerve diaphragm preparation. Memantine completely abolished the twitch tension elicited indirectly while it had no effect on the directly elicited twitch tension. Memantine also decreased the post-tetanic potentiation of amplitude of endplate potential and twitch tension. The duration of tetanic stimulation that induced a maximal decrease of twitch tension was 10-20 s. It is suggested that the effect of memantine on post-tetanic potentiation may be due to its voltage- and time-dependent effect on the ion channel-acetylcholine receptor complex.


COVID-19 detection using deep learning models to exploit Social Mimic Optimization and structured chest X-ray images using fuzzy color and stacking approaches.
Coronavirus causes a wide variety of respiratory infections and it is an RNA-type virus that can infect both humans and animal species. It often causes pneumonia in humans. Artificial intelligence models have been helpful for successful analyses in the biomedical field. In this study, Coronavirus was detected using a deep learning model, which is a sub-branch of artificial intelligence. Our dataset consists of three classes namely: coronavirus, pneumonia, and normal X-ray imagery. In this study, the data classes were restructured using the Fuzzy Color technique as a preprocessing step and the images that were structured with the original images were stacked. In the next step, the stacked dataset was trained with deep learning models (MobileNetV2, SqueezeNet) and the feature sets obtained by the models were processed using the Social Mimic optimization method. Thereafter, efficient features were combined and classified using Support Vector Machines (SVM). The overall classification rate obtained with the proposed approach was 99.27%. With the proposed approach in this study, it is evident that the model can efficiently contribute to the detection of COVID-19 disease.


False-positive hCG by enzyme immunoassay resulting in repeated chemotherapy.
In abnormal pregnancies, it is necessary to follow hCG levels to ensure resolution of the pregnancy, either spontaneously or after therapy. Lack of a normal resolution can be treated with methotrexate. A 32-year-old woman had a persistently elevated serum hCG level analyzed by enzyme immunoassay technique before and after being treated with three courses of methotrexate. Analysis of the serum samples by radioimmunoassay technique gave negative results. If the expected laboratory response is not forthcoming in the treatment of an abnormal pregnancy with methotrexate, hCG analysis by another assay method is recommended. False-positive hCG levels can result from the presence of heteroantibodies in the serum of the patient.


Pro/con debate: Is intensive insulin therapy targeting tight blood glucose control of benefit in critically ill patients?
You have decided to develop a protocol for insulin therapy in your intensive care unit (ICU). You wonder about the merit of using intensive insulin therapy (IIT) to maintain tight blood glucose control in your patients.


Functional observability and target state estimation in large-scale networks.
The quantitative understanding and precise control of complex dynamical systems can only be achieved by observing their internal states via measurement and/or estimation. In large-scale dynamical networks, it is often difficult or physically impossible to have enough sensor nodes to make the system fully observable. Even if the system is in principle observable, high dimensionality poses fundamental limits on the computational tractability and performance of a full-state observer. To overcome the curse of dimensionality, we instead require the system to be functionally observable, meaning that a targeted subset of state variables can be reconstructed from the available measurements. Here, we develop a graph-based theory of functional observability, which leads to highly scalable algorithms to 1) determine the minimal set of required sensors and 2) design the corresponding state observer of minimum order. Compared with the full-state observer, the proposed functional observer achieves the same estimation quality with substantially less sensing and fewer computational resources, making it suitable for large-scale networks. We apply the proposed methods to the detection of cyberattacks in power grids from limited phase measurement data and the inference of the prevalence rate of infection during an epidemic under limited testing conditions. The applications demonstrate that the functional observer can significantly scale up our ability to explore otherwise inaccessible dynamical processes on complex networks.


Inhalation toxicity studies on cigarette smoke (VIII). 6-week comparative experiments using modified flue-cured cigarettes: general toxicology.
Details are given of studies carried out to compare the inhalation toxicity to rats of smoke from cigarettes modified to give a range of deliveries of particulate matter. Dosimetry work showed that under conditions similar to those used for subsequent toxicity experiments, smoke particulates deposited in the lower respiratory system within the approximate dose range of 500--700 microgram TPM/g lung tissue. Respiratory monitoring showed that the response of animals to a range of smoke exposure conditions was similar and did not change during the course of the experiments. This observation was confirmed by monitoring of blood carboxyhaemoglobin levels after exposure to smoke. During exposure to smoke the rate of respiration decreased to approximately 40% of the pre-exposure rate. Tidal volume, after an initial slight decrease, showed a progressive increase throughout the smoke exposure period. Bodyweight gain was reduced in those animals subjected to smoke exposures. True sham-smoked animals showed a body weight gain intermediate between that of smoke and cage control rats. The clear indications of such between-group differences in response to treatment, coupled with the indicators of consistent dosing of animals under the defined exposure conditions, form a sound basis for the interpretation of terminal pathology.


Cardiac Rehabilitation in Patients With Lymphoma Undergoing Autologous Hematopoietic Stem Cell Transplantation: A Cardio-oncology Pilot Project.
Worldwide > 50,000 hematopoietic stem cell transplants (HSCTs) are performed annually. HSCT patients receive multiple cardiotoxic therapies (chemotherapy and radiation therapy) in addition to severe physical deconditioning during hospital admission. We hypothesized that guided exercise in a cardiac rehabilitation (CR) program following autologous HSCT is a safe and feasible intervention. Pilot project to assess for safety, feasibility and impact of 8 weeks of CR in HSCT patients following transplant. Consecutive patients with lymphoma underwent standard activity protocol testing before HSCT, at 6 weeks following HSCT (prior to CR), and at 14 weeks following HSCT (at completion of CR), consisting of grip strength (GS), gait speed (GtS), timed up-and-go (TUG), and 6-minute walk test (6MWT). CR consisted of 8 weekly visits for guided exercise. Activity tolerance protocol data of 30 patients (24 male, 6 female) from December 2014 to December 2016 were analyzed using repeated measures (analysis of variance [ANOVA]) to observe for changes in GS, GtS, TUG, and 6MWT. Statistically significant improvements were found in GS (P < 0.005), GtS (P = 0.02), and 6MWT (P = 0.001). These improvements show that guided CR-based exercise may assist HSCT survivors to meet or even surpass baseline exercise levels and improve physical functioning. There were no adverse events (ie, death or injury) during the study period. Fifty-seven percent of referred patients participated in CR, exceeding documented CR adherence in cardiac populations. The addition of CR-based exercise programming in HSCT survivorship care of patients with lymphoma is a safe and feasible intervention to assist in recovery following transplant.


Biomineralization and adaptive plasticity of the temporomandibular joint in myostatin knockout mice.
Mice lacking myostatin (GDF-8), a negative regulator of skeletal muscle growth, show a significant increase in muscle mass versus normal mice. We compared wild-type and myostatin deficient mice to assess the postnatal effect of elevated masticatory loads due to increased jaw-adductor muscle activity and greater bite forces on mandibular condyle morphology. Microcomputed tomography (microCT) was used to provide details of internal condylar morphology and quantify bone density in three condylar regions. Biomineralization levels, as well as external mandibular dimensions, were used to characterize within-slice, within-joint, within-group and between-group variation. Dimensions of the mandible and mandibular condyle were similar between the myostatin knockout and normal mice. Knockout mice exhibited significantly more biomineralization on the outer surface of the condylar subchondral bone and along the condylar neck, most notably on the buccal side of the condylar neck. The buccal side of the inner aspect of the condyle was significantly less biomineralized in knockout mice, both for the pooled data and for the posterior and anterior condylar slices. Whilst normal mice had symmetric subchondral bone surfaces, those of knockout mice were asymmetric, with a lower, less convex surface on the buccal side versus the lingual side. This appears related to the ontogenetic effects of increased masticatory stress in the mandibles of knockout mice as compared to normal mice. Significant differences in biomineralization between normal and myostatin knockout mice, coupled with the lack of significant differences in certain external dimensions, underscores a need for information on the external and internal morphology of mineralized tissues vis-à-vis altered or excessive mechanical loads.


Altered expression of CDX-2, PDX-1 and mucin core proteins in "Ulcer-associated cell lineage (UACL)" in Crohn's disease.
The ulcer-associated cell lineage (UACL) induced at the site of ileac chronic ulceration in Crohn's disease has been reported to show histological differentiation resembling gastric pyloric mucosa. To clarify the significance of homeobox gene-encoded transcription factors in the formation of the UACL in Crohn's disease, we investigated the immunohistochemical expression of gastrointestinal mucins (MUC5AC for gastric surface mucous cells; MUC6 for gastric gland mucous cells, and MUC2 for intestinal goblet cells) and homeobox gene-encoded transcription factors (CDX-2 for intestinal mucosa and PDX-1 for pyloric mucosa) in the UACL. The analysis was undertaken on ileal mucosa obtained from ileal resections performed in 19 patients with active Crohn's disease of the small bowel. The UACL was observed in nine patients. In the UACL, expression of mucous cells with a foveolar-structure showed immunoreactivity to MUC5AC, and the mucous cells with a glandular structure showed immunoreactivity to MUC6, and the expression of MUC2 was decreased. In addition, we detected the decreased expression of CDX-2 along with the increased expression of PDX-1 in the UACL. The UACL showed histological differentiation simulating gastric pylori mucosa. The down-regulation of CDX-2 and the up-regulation of PDX-1 could be an important mechanism in the induction of the UACL.


Significant changes in endogenous retinal gene expression assessed 1 year after a single intraocular injection of AAV-CNTF or AAV-BDNF.
Use of viral vectors to deliver therapeutic genes to the central nervous system holds promise for the treatment of neurodegenerative diseases and neurotrauma. Adeno-associated viral (AAV) vectors encoding brain-derived neurotrophic factor (BDNF) or ciliary derived neurotrophic factor (CNTF) promote the viability and regeneration of injured adult rat retinal ganglion cells. However, these growth-inducing transgenes are driven by a constitutively active promoter, thus we examined whether long-term AAV-mediated secretion of BDNF or CNTF affected endogenous retinal gene expression. One year after the intravitreal injection of AAV-green fluorescent protein (GFP), bi-cistronic AAV-BDNF-GFP or AAV-CNTF-GFP, mRNA was extracted and analyzed using custom 96 well polymerase chain reaction arrays. Of 93 test genes, 56% showed significantly altered expression in AAV-BDNF-GFP and/or AAV-CNTF-GFP retinas compared with AAV-GFP controls. Of these genes, 73% showed differential expression in AAV-BDNF versus AAV-CNTF injected eyes. To focus on retinal ganglion cell changes, quantitative polymerase chain reaction was undertaken on mRNA (16 genes) obtained from fixed retinal sections in which the ganglion cell layer was enriched. The sign and extent of fold changes in ganglion cell layer gene expression differed markedly from whole retinal samples. Sustained and global alteration in endogenous mRNA expression after gene therapy should be factored into any interpretation of experimental/clinical outcomes, particularly when introducing factors into the central nervous system that require secretion to evoke functionality.


Species composition and abundance of Brevipalpus spp. on different citrus species in Mexican orchards.
We studied the abundance of Brevipalpus spp. in citrus orchards in the Mexican states of Yucatan, Quintana Roo and Campeche. Mites were collected from 100 trees containing a mixture of citrus species where sweet orange was always the main species. Eight collections were made at each location from February 2010 to February 2011. Mites from the genus Brevipalpus were separated from other mites surveyed and their abundance and relationships with the different citrus species were quantified throughout the collection period. A subsample of 25% of the total Brevipalpus mites collected were identified to species level and the interaction of mite species and citrus species were described. Brevipalpus spp. were present on all collection dates and their relative abundance was similar on all citrus species studies. The smallest number of mites collected was during the rainy season. Brevipalpus phoenicis (Geijskes) and Brevipalpus californicus (Banks) were the only two species present and they were found in all locations except Campeche, where only B. phoenicis was present. Yucatan and Campeche are at greater risk of leprosis virus transmission than Quintana Roo because the main vector, B. phoenicis, was more abundant than B. californicus. The implications of our results for the design of more accurate sampling and control methods for Brevipalpus spp. are discussed.


Adversarial interspecies relationships facilitate population suppression by gene drive in spatially explicit models.
Suppression gene drives bias their inheritance to spread through a population, potentially eliminating it when they reach high frequency. CRISPR homing suppression drives have already seen success in the laboratory, but several models predict that success may be elusive in population with realistic spatial structure due to extinction-recolonization cycles. Here, we extend our continuous space framework to include two competing species or predator-prey pairs. We find that in both general and mosquito-specific models, competing species or predators can facilitate drive-based suppression, albeit at the cost of an increased rate of drive loss outcomes. These results are robust in mosquito models with seasonal fluctuations. Our study illustrates the difficulty of predicting outcomes in complex ecosystems. However, our results are promising for the prospects of less powerful suppression gene drives to successfully eliminate target mosquito and other pest populations.


Lipoprotein profile assessed by 1H NMR, BMI and blood pressure are associated with vascular alterations in children with familial hypercholesterolaemia.
Children with familial hypercholesterolaemia (FH) have elevated low-density lipoprotein cholesterol (LDL-C) concentrations since birth, which increases the risk of cardiovascular disease in adulthood. Arterial injury and stiffness parameters, including carotid intima media thickness (cIMT), pulse wave velocity (PWV) and distensibility (DIST), can be detected early in childhood. We studied the associations between cIMT, PWV and DIST with the lipoprotein profile assessed by proton nuclear magnetic resonance (1H NMR) and with influential variables such as blood pressure (BP) or body mass index (BMI) in children with FH. In this cross-sectional study, we included 201 children (96 with FH and 105 non-FH controls). Clinical history, physical examination and standard biochemical studies were performed. FH genetic testing was performed when clinically indicated. Carotid ultrasonography and an advanced lipoprotein profile by 1H NMR were performed. Multivariate and classification methods were used. There were no differences between cIMT, PWV and DIST between FH and non-FH children. FH children presented more total LDL and large, medium and small particles. Small LDL particles, BMI and systolic BP determined the presence of pathological IMT in the FH group. LDL size, high-density lipoproteins and very low-density lipoprotein particles together with blood pressure determined the presence of pathological arterial wall elasticity. Alterations in lipoprotein parameters assessed by are associated with early structural and functional arterial characteristics in children with FH. BMI and BP act as boosting factors. Cardiovascular prevention should start early in children with FH, encompassing all components of a healthy lifestyle.


Determination of cocaine in human urine, plasma and red blood cells by gas-liquid chromatography.
This paper describes a sensitive and reliable method for the determination of cocaine in human urine, plasma and red blood cells. Cocaine is extracted into cyclohexane from the biological materials at slightly alkaline pH, reduced with lithium aluminium hydride, acylated with pentafluoropropionic anhydride and detected by an electron capture detector. When compared with a gas chromatography-mass spectrometry method the results of cocaine determination correlated highly (r = 0.986). When cocaine was given intravenously to volunteer subjects only 0.2-1.4% of the administered dose was excreted as unmetabolized cocaine in the first 9 h after administration. Plasma and red blood cell levels of cocaine were also determined by this method after intravenous administration.


Drug-naïve first-episode schizophrenia spectrum disorders: Pharmacological treatment practices in inpatient units in Hunan Province, China.
This study describes antipsychotic prescription patterns for drug-naïve inpatients diagnosed with first-episode schizophrenia-spectrum (FES) disorders and factors associated with practices deviating from China's current guidelines. All inpatients aged 7 to 45 years experiencing a first episode of schizophrenia-spectrum disorder with a duration of untreated illness of less than 18 months and admitted between 1 August 2016 and 1 August 2017 to one of eight psychiatric hospitals in Hunan were included. Demographics, clinical characteristics and prescriptions at discharge were collected from electronic medical records. Logistic regression and random forest methods were used to model relationships between demographic and clinical factors and deviations from China's guidelines. Of the 602 inpatients included in the study, 598 (99.3%) were prescribed antipsychotics, and no patients were discharged on long-acting injectable antipsychotics. Polypharmacy (more than one antipsychotic prescribed) was present in 121 (20.2%) participants. Clozapine was prescribed to 45 (7.5%) patients. Adults receiving polypharmacy were more likely to be prescribed high-dose antipsychotics than those receiving a single antipsychotic. Minors under 13 years of age were more likely to receive polypharmacy and unapproved antipsychotics than those older than 13 years. Our findings suggest that most of the inpatients were prescribed a single antipsychotic at discharge, consistent with China's guidelines. Minors with FES and patients discharged on polypharmacy and clozapine may require more intense monitoring and management. With the current implementation of China's National Mental Health Working Plan, these results will assist decision-makers in allocating resources and conducting reforms to facilitate best practice treatment for FES.


Long-term effect of elevated temperatures on SSPE virus expression in persistently infected rat glial cells.
Cultivation of measles virus (SSPE virus, Lec strain) persistently infected C6 rat glioma cells at 39 degrees C resulted in the loss of detectable expression of measles virus proteins. Temperature shift-back led to reactivation of measles virus even after maintenance of the cells at 39 degrees C for 15 days. In Northern blot analysis viral mRNA disappeared at 3 days after shift-up whereas 50 S viral genome-sized RNA was detectable until 6 days. The 50 S RNA decreased in quantity in rough correlation with dilution by cell passage at 39 degrees C. The 50 S viral RNA was found in the nucleocapsid fraction. On day 9 after shift-down of persistently infected cells, maintained at 39 degrees C for 15 days, 50 S viral RNA reappeared although mRNAs were not yet detected. Infectious center assays showed that the number of cells in the population at 39 degrees C, which contained an SSPE virus genome that could be reactivated, declined after temperature shift. Moreover, cell cloning experiments, in which single cells of cultures maintained for various lengths of time at 39 degrees C were incubated at 35 degrees C and examined by immunofluorescence, reconfirmed the above results. This indicates that the reactivation of SSPE virus described here was due to re-infection of virus-antigen negative cells with progeny virus produced by a few latently infected cells in the population. The biological significance of this phenomenon in the central nervous system virus infection is discussed.


Nudel binds Cdc42GAP to modulate Cdc42 activity at the leading edge of migrating cells.
Cdc42GAP promotes inactivation of Cdc42, a small GTPase whose activation at the leading edge by guanine nucleotide exchange factors is critical for cell migration. How Cdc42GAP is regulated to ensure proper levels of active Cdc42 is poorly understood. Here we show that Nudel, a cytoplasmic dynein regulator, competes with Cdc42 for binding Cdc42GAP. Consequently, Nudel can inhibit Cdc42GAP-mediated inactivation of Cdc42 in a dose-dependent manner. Both Nudel and Cdc42GAP exhibit leading-edge localization in migrating cells. The localization of Nudel requires its phosphorylation by Erk1/2. Depleting Nudel by RNAi or overexpression of a nonphosphorylatable mutant abolishes Cdc42 activation and cell migration. Our data thus uncover Nudel as a regulator of Cdc42 during cell migration. Nudel facilitates cell migration by sequestering Cdc42GAP at the leading edge to stabilize active Cdc42 in response to extracellular stimuli. Excess active Cdc42 may in turn control its own activity by recruiting Cdc42GAP from Nudel.


Feeding activity of the northern bat Eptesicus nilssoni during pregnancy and lactation.
Female northern bats emerged at dusk to feed when aerial insect density was 0.1 m-3 or higher. A model suggests that this is the threshold level above which foraging may be energetically profitable. Insect density was determined mainly by air temperature, and reached the threshold level at 6-10°C. Mean temperature during early summer in six years was correlated with the date of parturition. This suggests that periods when foraging was not energetically profitable were spent in torpor.


Synthesis and characterization of Ce0.5Bi0.5VO4/rGO nanocomposite by sonochemical method for photocatalytic desulfurization of petroleum derivatives.
In order to improve the desulfurization efficiency of petroleum derivatives, Ce0.5Bi0.5VO4/rGO nanocomposite was synthesized by sonochemical method. The prepared nanocomposites were characterized by XRD, FESEM, EDS, FT-IR, BET, and DRS analyses. XRD analysis shows that the synthesized nanocomposite is amorphous. FESEM images showed that nanostructures with a smaller particle size distribution were synthesized under optimal conditions, i.e. controlling the synthesis temperature between 0 and 5 °C. The results of desulfurization showed that nanocomposites containing reduced graphene oxide (rGO) have higher photocatalytic efficiency than pure samples, the main reason of which can be better charge separation in the samples through the π electron in the rGO structure. The highest amount of desulfurization of CeVO4/rGO, BiVO4/rGO, and Ce0.5Bi0.5VO4/rGO nanocomposites was 95.62, 91.25, and 96.38%, respectively, after exposure to UV light for 40 min. The enhancement of photocatalytic activity of Ce0.5Bi0.5VO4/rGO composite could be attributed to the efficient separation of electron-hole pairs and the inhibition of recombination. Desulfurization in the presence of hydrochloric acid and hydrogen peroxide increased the efficiency by 12%, which is a significant amount.


The organization of inputs establishes two functional and morphologically identifiable classes of ganglion cells in the retina of the turtle.
Analyses of the photoresponses and morphologies of ganglion cells in the turtle retina suggests that these cells are of two types: type A ganglion cells receive predominantly bipolar inputs, while type B ganglion cells receive a mixture of inputs from bipolar and amacrine cells. According to these classification criteria, ganglion cells may reflect either activities of the outer or of the inner plexiform layer, respectively. To corroborate the validity of this classification a number of basic properties of ganglion cells were analysed. It was found that double colour opponency was characteristic of type A cells and directional selectivity was performed only by type B cells. In addition, the absolute sensitivity and the firing rate of type A cells were significantly higher than those of type B cells.


Initial weight loss and early intervention adherence predict long-term weight loss during the Promoting Successful Weight Loss in Primary Care in Louisiana lifestyle intervention.
This study tested whether initial weight change (WC), self-weighing, and adherence to the expected WC trajectory predict longer-term WC in an underserved primary-care population with obesity. Data from the intervention group (n = 452; 88% women; 74% Black; BMI 37.3 kg/m2 [SD: 4.6]) of the Promoting Successful Weight Loss in Primary Care in Louisiana trial were analyzed. Initial (2-, 4-, and 8-week) percentage WC was calculated from baseline clinic weights and daily at-home weights. Weights were considered adherent if they were on the expected WC trajectory (10% at 6 months with lower [7.5%] and upper [12.5%] bounds). Linear mixed-effects models tested whether initial WC and the number of daily and adherent weights predicted WC at 6, 12, and 24 months. Percentage WC during the initial 2, 4, and 8 weeks predicted percentage WC at 6 (R2 = 0.15, R2 = 0.28, and R2 = 0.50), 12 (R2 = 0.11, R2 = 0.19, and R2 = 0.32), and 24 (R2 = 0.09, R2 = 0.11, and R2 = 0.16) months (all p < 0.01). Initial daily and adherent weights were significantly associated with WC as individual predictors, but they only marginally improved predictions beyond initial weight loss alone in multivariable models. These results highlight the importance of initial WC for predicting long-term WC and show that self-weighing and adherence to the expected WC trajectory can improve WC prediction.


Randomized controlled clinical trial of beta irradiation as an adjunct to trabeculectomy in open-angle glaucoma.
To assess the effect of a single intraoperative application of 750 cGy of beta irradiation on the outcome of trabeculectomy for uncontrolled open-angle glaucoma. A prospective, randomized, double-blind, placebo-controlled clinical trial. Sixty-one eyes of 61 Caucasian patients at low risk of filtering surgery failure, with poorly controlled primary or secondary open-angle glaucoma undergoing routine trabeculectomy. Patients were randomly assigned to control or beta irradiation groups. All patients underwent standard trabeculectomy with fornix-based conjunctival incision. Eyes assigned to beta irradiation received 750 cGy of beta irradiation directly over the sclerostomy site on completion of conjunctival suturing. An identical but inactive applicator was applied to control eyes, delivering no radiation. Both operator and patient remained masked to the assignment for the 12-month follow-up period. The main outcome measure was intraocular pressure (IOP) control. Complete success of IOP control was defined as an IOP less than 21 mmHg at 12 months without need for additional medication. Qualified success was defined as an IOP less than 21 mmHg at 12 months where additional medication was required. Complete success of IOP control was achieved in 19 (86%) control eyes and 35 (90%) irradiated eyes (P = 1.0). Qualified success of IOP control was achieved in 21 (95%) control eyes and 39 (100%) irradiated eyes at 12 months follow-up (P = 1.0) We experienced a very high success rate of filtration surgery in this select population without adjunctive irradiation. Our sample size was too small to show any improvement in success with use of beta irradiation in this group. Other studies would have to be done to determine whether it may have measurable benefit in cases with a high risk of filtration failure.


The role of radiotherapy in the management of progressive glioblastoma : a systematic review and evidence-based clinical practice guideline.
Can re-irradiation (by using conventional radiotherapy, fractionated radiosurgery, or single fraction radiosurgery) be used in patients with progressive glioblastoma multiforme after the first adjuvant combined multimodality treatment with radiation and chemotherapy? These recommendations apply to adult patients with progressive glioblastoma after first line combined multimodality treatment with chemotherapy and radiation. When the target tumor is amenable for additional radiation, re-irradiation is recommended as it provides improved local tumor control, as measured by best imaging response. Such re-irradiation can take the form of conventional fractionation radiotherapy, fractionated radiosurgery, or single fraction radiosurgery. Re-irradiation is recommended in order to maintain or improve a patient's neurological status and quality of life prior to any further tumor progression.


Sulfite exposure-induced hepatocyte death is not associated with alterations in p53 protein expression.
Although sulfite (SO3(2-)) is commonly used as an antimicrobial agent and preservative in foods, medicines and wine, it has also been listed as an important risk factor for the initiation and progression of liver diseases due to oxidative damage. In general, apoptosis that is induced by oxidative stress is triggered by increases in p53 and alterations in Mdm2 and Bcl-2. However, the level of involvement of the p53 signaling pathway, which has been shown to be upregulated in some animal studies, in hepatocyte death remains unclear. To examine the response of the p53 signaling pathway to stimulation with different concentrations of sulfite, a time course study of p53, Mdm2, and Bcl-2 expression was conducted in an immortalized hepatic cell line, HL-7702. When the HL-7702 cells were cultured in the presence of Na2SO3, the cell viability was significantly decreased after 24h compared to that of the control group (0mmol/L) (p<0.05). Meanwhile, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels in the supernatants of HL-7702 cells were significantly increased following Na2SO3 administration. Interestingly, the expression of p53 and p-p53 (Ser15) remained unchanged. In addition, no obvious alterations in Mdm2 and Bcl-2 expression were observed in HL-7702 cells that had been stimulated with various concentrations of sulfite. To further investigate the detailed mechanism underlying sulfite toxicity, caspase-3, PCNA and RIP1 expression in HL-7702 cells was studied. The expression levels of caspase-3 and PCNA were unchanged, but RIP1 expression was increased significantly after 24h of exposure. In light of this evidence, we propose that sulfite is cytotoxic to hepatocytes, but this cytotoxicity is not achieved by direct interruption of the p53 signaling pathway. In addition, we propose that an alternative necrotic process underlies hepatocellular death following sulfite exposure.


The generation of simulated data in the form of industrial cohorts.
A computer program INDCOGEN, which generates data in the form of industrial cohorts, is being made available to interested users. Values for variables which include selection effects, dose-response effects, length of study, staff turnover, plant exposure levels, and underlying rates of mortality are defined by the user. The program can be used to estimate the likelihood of detecting a cancer "hazard" given the parameters of a field study cohort, the likely size of selection effects, and an assumed form of dose-response.


Prenatal diagnosis of persistent common cloaca with prune belly and anencephaly in the second trimester.
We report the prenatal diagnosis of a fetus with persistent cloaca, prune belly sequence, and anencephaly. This fetus resembles the recently reported patient with prune belly and anencephaly. A syndromic diagnosis was not possible in either case, but the likelihood of a chance association also has to be regarded as low.


Identification of novel HLA-DQA1*03:02:03 allele using next-generation sequencing.
The HLA-DQA1*03:02:03 allele differs from HLA-DQA1*03:02:01:01 allele by a single nucleotide in codon 42.


Invasion and dissemination of Yersinia enterocolitica in the mouse infection model.
Yersinia enterocolitica is one of the most common causes of food borne gastrointestinal disease. After oral uptake yersiniae replicate in the small intestine, invade Peyer's patches of the distal ileum and disseminate to spleen and liver. In these tissues and organs yersiniae replicate extracellularly and form exclusively monoclonal microabscesses. Only very few yersiniae invade Peyer's patches and establish just a very few monoclonal microabscesses. This is due to both Yersinia and host specific factors.


Ultrastructural evidence for a functional unit between nerve fibers and type II cerebral mast cells in the cerebral vascular wall.
By histofluorescence microscopic examinations of pial arteries from rats and rabbits, we have observed that the routes of adrenergic fibers were apparently organized along successive sites of granular autofluorescent cells present in the adventitia. Subsequent electron microscopic studies showed that these cells were often situated in close apposition (80 to 200 nm) to the adventitial nerve bundles. The granular cells and nerve varicosities were frequently enclosed within the same basement membrane, with a membrane-to-membrane distance as small as 20 nm. However, no clear membrane differentiation was seen. These granular cells were identified histochemically by staining with Sudan Black, Oil Red O, Toluidine Blue, Alcian Blue, together with ultrastructural and pharmacological methods (48/80 compound and carbachol intracarotid infusions). The cells, many of which contained large amounts of lipids, showed morphological ultrastructural and pharmacological similarities to peripheral mast cells. Nerve bundles contained two types of varicosities: some of them degenerated after superior cervical ganglionectomy and were thus of sympathetic origin, whereas the others contained small clear vesicles (probably cholinergic) and/or large dense-cored vesicles (probably peptidergic). As we have shown that cholinomimetics induce exocytosis of these granular cells, the close relationship between these cells and the nerve fibers may indicate a neurogenic control of the cerebrovascular mast cell secretion. As these cells contain potent vasoactive substances, this relationship may be of importance in the genesis of physiological or pathological cerebrovascular events which are, as yet, poorly understood.