Injecting drug use: A vector for the introduction of new hepatitis C virus genotypes.
Hepatitis C virus (HCV) genotypes' monitoring allows real-time insight into the dynamic changes that occur in the global epidemiological picture of HCV infection. Intravenous drug use is currently the primary driver for HCV transmission in developed and developing countries. The distribution of HCV genotypes/subtypes differs significantly between people who inject drugs (PWID) and the general population. HCV genotypes that previously exhibited a limited geographical distribution (3a, 4) are becoming more prevalent in this high-risk group. Immigration from HCV-endemic countries and the evolving networks of HCV transmission in PWID influence HCV genotypes distribution in Europe. Social vulnerabilities (e.g., unemployment, homelessness, and limited access to social and healthcare insurances systems) are important triggers for illicit drug use, which increases the associated risks of HCV infection and the frequent emergence of less prevalent genotypes. Genotype/subtype determination bears important clinical consequences in the progression of liver disease, susceptibility to antiviral therapies and the emergence of resistance-associated variants. An estimated half of the chronically HCV-infected PWID are unaware of their infection, and only one in ten of those diagnosed enter treatment. Nevertheless, PWID exhibit high response rates to new antiviral regimens, and the level of HCV reinfection is unexpectedly low. The focus of the healthcare system must be on the early detection and treatment of infection, to avoid late presentations that are associated with high levels of viremia and liver fibrosis, which may diminish the therapeutic success rate.


Phylogenetic distribution of the euryarchaeal archaellum regulator EarA and complementation of a Methanococcus maripaludis ∆earA mutant with heterologous earA homologues.
Archaella are the swimming organelles in the Archaea. Recently, the first archaellum regulator in the Euryarchaeota, EarAMma, was identified in Methanococcus maripaludis, one of the model organisms used for archaellum studies. EarAMma binds to 6 bp consensus sequences upstream of the fla promoter to activate the transcription of the fla operon, which encodes most of the proteins required for archaella synthesis. In this study, synteny analysis showed that earA homologues are widely distributed in the phylum of Euryarchaeota, with the notable exception of extreme halophiles. We classified Euryarchaeota species containing earA homologues into five classes based on the genomic location of the earA genes relative to fla and chemotaxis operons. EarA homologues from Methanococcus vannielii, Methanothermococcus thermolithotrophicus and Methanocaldococcus jannaschii successfully complemented the function of EarAMma in a ΔearAMma mutant, demonstrated by the restoration of FlaB2 expression in Western blot analysis and the appearance of archaella on the cell surface in complemented cells. Furthermore, the 6 bp consensus sequence was also found in the fla promoter region in these methanogens, indicating that the EarA homologues ly use a similar mechanism to activate transcription of the fla operons in their own hosts. Attempts to demonstrate complementation of the function of EarAMma in a ΔearAMma mutant by the EarA homologue of Pyrococcus furiosus were unsuccessful, despite the presence of a copy of the 6 bp consensus EarA-binding sequence upstream of the fla promoter in the P. furiosus genome.


Fludarabine phosphate: a synthetic purine antimetabolite with significant activity against lymphoid malignancies.
Fludarabine phosphate is the 2-fluoro, 5'-monophosphate derivative of vidarabine (ara-A) with the advantages of resistance to deamination by adenosine deaminase (ADA) and improved solubility. The mechanism of cytotoxic action of the compound appears to involve metabolic conversion to the active triphosphate. Fludarabine phosphate has substantial activity against lymphoid malignancies, particularly chronic lymphocytic leukemia (CLL) and low-grade non-Hodgkin's lymphoma (NHL). Its single-agent activity in CLL appears at least comparable to those of other conventional combination regimens. Its activity in Hodgkin's disease, mycosis fungoides, and macroglobulinemia, although suggestive, needs to be further defined and clinical trials are warranted in hairy cell leukemia, prolymphocytic leukemia, and previously untreated myeloma. The compound does not appear active against most common solid tumors. Early clinical trials indicated significant myelosuppression and the potential for severe neurotoxicity. Toxicity on the currently used low-dose schedules includes transient and reversible myelosuppression, nausea and vomiting, diarrhea, somnolence/fatigue, and elevations of liver enzymes and/or serum creatinine. Possible pulmonary toxicity has been suggested in several patients. The currently used low-doses of fludarabine phosphate, even with repeated administration, are well tolerated and appear safe with a negligible risk for severe neurotoxicity. Based on its single-agent activity and tolerability, the Food and Drug Administration recently granted group C designation of the drug for the treatment of patients with refractory CLL outside the clinical trials setting. The use of fludarabine phosphate in combination regimens and its impact on the natural history of the lymphoid malignancies is yet to be determined. Fludarabine phosphate may well occupy a pivotal role in the management of CLL and low-grade NHL.


Imaging of activated microglia with PET and [11C]PK 11195 in corticobasal degeneration.
Positron emission tomography (PET) using [(11)C]PK 11195, a ligand for peripheral benzodiazepine receptor binding sites, offers the opportunity to image activated microglia in vivo. This tool may therefore be used to display the occurrence of microglial activation in the course of neurodegeneration. A patient with the clinical diagnosis of corticobasal degeneration (CBD) and left-sided symptoms was studied using fluorodeoxyglucose (FDG) and [(11)C]PK 11195 PET. We found a marked right hemispheric hypometabolism and asymmetric microglial activation in corresponding areas of the basal ganglia and right temporal and parietal cortex. [(11)C]PK 11195 PET suggests involvement of microglial activation in the pathogenesis of CBD.


Tightly Bound Double-Caged [60]Fullerene Derivatives with Enhanced Solubility: Structural Features and Application in Solar Cells.
A series of novel highly soluble double-caged [60]fullerene derivatives were prepared by means of lithium-salt-assisted [2+3] cycloaddition. The bispheric molecules feature rigid linking of the fullerene spheres through a four-membered cycle and a pyrrolizidine bridge with an ester function CO2 R (R=n-decyl, n-octadecyl, benzyl, and n-butyl; compounds 1 a-d, respectively), as demonstrated by NMR spectroscopy and X-ray diffraction. Cyclic voltammetry studies revealed three closely overlapping pairs of reversible peaks owing to consecutive one-electron reductions of fullerene cages, as well as an irreversible oxidation peak attributed to abstraction of an electron from the nitrogen lone-electron pair. Owing to charge delocalization over both carbon cages, compounds 1 a-d are characterized by upshifted energies of frontier molecular orbitals, a narrowed bandgap, and reduced electron-transfer reorganization energy relative to pristine C60 . Neat thin films of the n-decyl compound 1 a demonstrated electron mobility of (1.3±0.4)×10-3 cm2 V-1 s-1 , which was comparable to phenyl-C61 -butyric acid methyl ester (PCBM) and thus potentially advantageous for organic solar cells (OSC). Application of 1 in OSC allowed a twofold increase in the power conversion efficiencies of as-cast poly(3-hexylthiophene-2,5-diyl) (P3HT)/1 devices relative to the as-cast P3HT/PCBM ones. This is attributed to the good solubility of 1 and their enhanced charge-transport properties - both intramolecular, owing to tightly linked fullerene cages, and intermolecular, owing to the large number of close contacts between the neighboring double-caged molecules. Test P3HT/1 OSCs demonstrated power-conversion efficiencies up to 2.6 % (1 a). Surprisingly low optimal content of double-caged fullerene acceptor 1 in the photoactive layer (≈30 wt %) favored better light harvesting and carrier transport owing to the greater content of P3HT and its higher degree of crystallinity.


Tricuspid Regurgitation Peak Gradient (TRPG)/Tricuspid Annulus Plane Systolic Excursion (TAPSE) - A Novel Parameter for Stepwise Echocardiographic Risk Stratification in Normotensive Patients With Acute Pulmonary Embolism.
Patients with intermediate-risk acute pulmonary embolism (APE) are a heterogeneous group with an early mortality rate of 2-15%. The tricuspid annulus plane systolic excursion (TAPSE) and tricuspid regurgitation peak gradient (TRPG) can be used for risk stratification, so we analyzed the prognostic value of a new echo parameter (TRPG/TAPSE) for prediction of APE-related 30-day death or need for rescue thrombolysis in initially normotensive APE patients.Methods and Results:The study group consists of 400 non-high-risk APE patients (191 men, age: 63.1±18.9 years) who had undergone echocardiography within the first 24 h of admission. The TRPG/TAPSE parameter was calculated. The clinical endpoint (CE) was a combination of 30-day APE-related death and/or rescue thrombolysis. The CE occurred in 8 (2%) patients. All patients with TAPSE ≥20 mm (n=193, 48.2%) had a good prognosis. Among 206 patients with TAPSE <20 mm, 8 cases of the CE occurred (3.9%). NPV and PPV for TRPG/TAPSE >4.5 were 0.2 and 0.98, respectively. The CE was significantly more frequent in 19 (9.2%) patients with TRPG/TAPSE >4.5 than in 188 (90.8%) with TRPG/TAPSE ≤4.5 (4 (21.1%) vs. 4 (2.1%), P=0.0005). Among normotensive APE patients with TAPSE <20 mm, TRPG/TAPSE >4.5 was associated with 21.1% risk of APE-related death or rescue thrombolysis. TRPG/TAPSE, a novel echocardiographic parameter, may be useful for stepwise echocardiographic risk stratification in normotensive patients with APE, and it identifies patients with a poor prognosis.


Individual and combined effects of postharvest dip treatments with water at 50 degrees C, soy lecithin and sodium carbonate on cold stored cactus pear fruits.
Objective of this study was to evaluate the effect of prestorage dip treatments at 20 degrees C or 50 degrees C alone or with sodium carbonate (SC) and soy lecithin (LEC), either individually or in combination, on weight losses, peel disorders, overall appearance and decay of cactus pears. Fruits were subjected to a simulated Mediterranean fruit fly (medfly) disinfestation by cold quarantine at 2 degrees C for 21 days followed by one week of shelf-life at 20 degrees C. Hot water alone was very effective in reducing peel disorders and decay both during cold storage and shelf-life. SC applied at 20 degrees C showed a weak control of decay and chilling injury, while its effectiveness significantly increased when the solution temperature was set to 50 degrees C. LEC was more effective in preserving freshness during cold storage, but after shelf-life decay incidence in fruit dipped in LEC at 20 degrees C or 50 degrees C was higher than in those dipped in water at 20 degrees C or 50 degrees C, respectively. Significant but moderate differences were detected among treatments in weight loss. After shelf-life, fruit dipped in the heated mixture of SC and LEC showed the lowest incidence of peel disorders and the highest percentage of marketable fruit, although decay incidence was slightly higher than in fruit treated with SC at 50 degrees C. SC and LEC used in combination at 50 degrees C improved fruit tolerance to chilling injury and reduced decay.


Socioeconomic status in childhood and the lifetime risk of major depression.
Major depression occurs more frequently among people of lower socioeconomic status (SES) and among females. Although the focus of considerable investigation, the development of SES and sex differences in depression remains to be fully explained. In this study, we test the hypotheses that low childhood SES predicts an increased risk of adult depression and contributes to a higher risk of depression among females. Participants were 1132 adult offspring of mothers enrolled in the Providence, Rhode Island site of the US National Collaborative Perinatal Project between 1959 and 1966. Childhood SES, indexed by parental occupation, was assessed at the time of participants' birth and seventh year. A lifetime history and age at onset of major depressive episode were ascertained via structured interviews according to diagnostic criteria. Survival analyses were used to model the likelihood of first depression onset as a function of childhood SES. Participants from lower SES backgrounds had nearly a twofold increase in risk for major depression compared to those from the highest SES background independent of childhood sociodemographic factors, family history of mental illness, and adult SES. Analyses of sex differences in the effect of childhood SES on adult depression provided modest support for the hypothesis that childhood SES contributes to adult sex differences in depression. Low SES in childhood is related to a higher risk of major depression in adults. Social inequalities in depression likely originate early in life. Further research is needed to identify the pathways linking childhood conditions to SES differences in the incidence of major depression.


First Report and Complete Genome Sequence of Alfalfa Enamovirus from Sudan.
We report the complete genome sequence of a viral pathogen detected in alfalfa samples from Sudan and provisionally named alfalfa enamovirus 2 (AEV-2). Based on high nucleotide and amino acid identities, AEV-2 represents a strain of a newly discovered alfalfa enamovirus 1 that has only been described in Argentina.


Medic Bleep.
Medic Bleep is a secure instant messaging app that enables clinicians to discuss patient care quickly, securely and legally. It looks and feels like WhatsApp, but has been designed for the healthcare market to enable staff to communicate with each other, and to help speed up conversations between clinicians to increase efficiency.


Updates in Pediatric Hospital Medicine: Six Practical Ways to Improve the Care of Hospitalized Children.
As pediatric hospital medicine continues to grow, it is important to keep abreast of the current literature. This article provides a summary of six of the most impactful articles published in 2018. The authors reviewed articles published between January 2018 and December 2018 for the 2019 Society of Hospital Medicine national conference presentation of Top Articles in Pediatric Hospital Medicine, where the top 10 articles of 2018 were presented. Six of the 10 articles are highlighted in this review based on article quality and their applicability to change practices in the hospital setting or prompt further research. Key findings from the articles include: multiple interventions aimed at providers can improve compliance with bronchiolitis guidelines; a developed calculator can improve testing for urinary tract infections in children aged 2-24 months; nonmedical costs of hospitalizations are underappreciated and disproportionately affect those with a lower socioeconomic status; a progress note template in an electronic health record can lead to higher quality and shorter notes; for febrile infants aged 60 days and younger, most blood and cerebrospinal fluid culture pathogens can be identified within 24 hours and nearly all by 36 hours; and the development of a high-value care tool can help to bring concepts of high-value care into family-centered rounds. The six selected articles highlight findings pertinent to pediatric hospital medicine.


Baseline and longitudinal patterns of brain atrophy in MCI patients, and their use in prediction of short-term conversion to AD: results from ADNI.
High-dimensional pattern classification was applied to baseline and multiple follow-up MRI scans of the Alzheimer's Disease Neuroimaging Initiative (ADNI) participants with mild cognitive impairment (MCI), in order to investigate the potential of predicting short-term conversion to Alzheimer's Disease (AD) on an individual basis. MCI participants that converted to AD (average follow-up 15 months) displayed significantly lower volumes in a number of grey matter (GM) regions, as well as in the white matter (WM). They also displayed more pronounced periventricular small-vessel pathology, as well as an increased rate of increase of such pathology. Individual person analysis was performed using a pattern classifier previously constructed from AD patients and cognitively normal (CN) individuals to yield an abnormality score that is positive for AD-like brains and negative otherwise. The abnormality scores measured from MCI non-converters (MCI-NC) followed a bimodal distribution, reflecting the heterogeneity of this group, whereas they were positive in almost all MCI converters (MCI-C), indicating extensive patterns of AD-like brain atrophy in almost all MCI-C. Both MCI subgroups had similar MMSE scores at baseline. A more specialized classifier constructed to differentiate converters from non-converters based on their baseline scans provided good classification accuracy reaching 81.5%, evaluated via cross-validation. These pattern classification schemes, which distill spatial patterns of atrophy to a single abnormality score, offer promise as biomarkers of AD and as predictors of subsequent clinical progression, on an individual patient basis.


A computer program for selection of oligonucleotide primers for polymerase chain reactions.
We have designed a computer program which rapidly scans nucleic acid sequences to select all possible pairs of oligonucleotides suitable for use as primers to direct efficient DNA amplification by the polymerase chain reaction. This program is based on a set of rules which define in generic terms both the sequence composition of the primers and the amplified region of DNA. These rules (1) enhance primer-to-target sequence hybridization avidity at critical 3'-end extension initiation sites, (2) facilitate attainment of full length extension during the 72 degrees C phase, by minimizing generation of incomplete or nonspecific product and (3) limit primer losses occurring from primer-self or primer-primer homologies. Three examples of primer sets chosen by the program that correctly amplified the target regions starting from RNA are shown. This program should facilitate the rapid selection of effective and specific primers from long gene sequences while providing a flexible choice of various primers to focus study on particular regions of interest.


Distribution of the metatarsophalangeal sesamoids in Turkish subjects.
No statistically significant pattern of metatarsophalangeal sesamoid distribution has been reported in the literature in relation to genetic pool or group, unilaterality or bilaterality, or sesamoid division. A study was undertaken to evaluate the presence and distribution of the metatarsophalangeal sesamoid bones of the foot in Turkish subjects. A total of 602 foot radiographs from 371 patients without forefoot complaints other than those of the hallux were included in the study. Absence or hypoplasia of the first-ray sesamoids was seen on 0.7% of the radiographs, and second-, third-, fourth-, and fifth-ray sesamoids were present on 2.8%, 0.5%, 1.0%, and 15.1% of the radiographs, respectively. Fifth-ray sesamoids were more prevalent in men (odds ratio, 2.71; 95% confidence interval, 1.52-4.84). The frequency of a normal foot profile (two sesamoids in the first ray) was 83.2%. Divisions of the sesamoids were seen on 4.0% of the radiographs at the first ray and on 20.9% at the fifth ray. Distribution and division of sesamoids were predominantly bilateral (kappa = 0.91, 0.91, and 0.95 for the first, second, and fifth digits, respectively; P < .001).


Chemosensory Anhedonia in Patients With Schizophrenia and Individuals With Schizotypy: A Questionnaire Study.
Anhedonia, the loss or decline of the ability to enjoy pleasure, is an important clinical characteristic of schizophrenia. Schizotypal traits refer to the appearance of subclinical symptoms of schizophrenia across normal people. Still, few studies have investigated chemosensory anhedonia in schizophrenia patients and schizotypy individuals. Seventy-one schizophrenia patients (SCZ), 162 schizotypy individuals (SCT) as selected by the Schizotypal Personality Questionnaire (SPQ), and 182 healthy controls (HC) participated in our study. We used the Positive and Negative Syndrome Scale (PANSS) to measure the clinical symptoms of schizophrenia patients. All participants completed the Chemosensory Pleasure Scale (CPS), which was used to assess participants' smell and taste hedonic capacities. We found that the three groups differed in chemosensory anhedonia. The SCZ group presented more severe chemosensory anhedonia than the SCT group, and the SCT group presented more severe chemosensory anhedonia than the HC group. We also found that chemosensory hedonic capacity was negatively correlated with negative schizotypal traits in the SCT group. Our results suggested that chemosensory anhedonia is an important characteristic of schizophrenia spectrum disorders.


TGF-beta1 maintains suppressor function and Foxp3 expression in CD4+CD25+ regulatory T cells.
Transforming growth factor (TGF)-beta1 is a major pluripotential cytokine with a pronounced immunosuppressive effect and its deficiency results in lethal autoimmunity in mice. However, mechanisms of its immunosuppressive action are not completely understood. Here, we report that TGF-beta1 supports the maintenance of Foxp3 expression, regulatory function, and homeostasis in peripheral CD4(+)CD25(+) regulatory T (T reg) cells, but is not required for their thymic development. We found that in 8-10-d-old TGF-beta1-deficient mice, peripheral, but not thymic, T reg cells are significantly reduced in numbers. Moreover, our experiments suggest that a defect in TGF-beta-mediated signaling in T reg cells is associated with a decrease in Foxp3 expression and suppressor activity. Thus, our results establish an essential link between TGF-beta1 signaling in peripheral T reg cells and T reg cell maintenance in vivo.


Energetic costs of feeding in 12 species of small-bodied primates.
There are no comparative, empirical studies of the energetic costs of feeding in mammals. As a result, we lack physiological data to better understand the selection pressures on the mammalian feeding apparatus and the influence of variables such as food geometric and material properties. This study investigates interspecific scaling of the net energetic costs of feeding in relation to body size, jaw-adductor muscle mass and food properties in a sample of 12 non-human primate species ranging in size from 0.08 to 4.2 kg. Net energetic costs during feeding were measured by indirect calorimetry for a variety of pre-cut and whole raw foods varying in geometric and material properties. Net feeding costs were determined in two ways: by subtracting either the initial metabolic rate prior to feeding or subtracting the postprandial metabolic rate. Interspecific scaling relationships were evaluated using pGLS and OLS regression. Net feeding costs scale negatively relative to both body mass and jaw-adductor mass. Large animals incur relatively lower feeding costs indicating that small and large animals experience and solve mechanical challenges in relation to energetics in different ways. This article is part of the theme issue 'Food processing and nutritional assimilation in animals'.


Pharmacological and molecular characterisation of SK3 channels in the TE671 human medulloblastoma cell line.
The expression of the small conductance calcium-activated potassium channels SK1, SK2 and SK3 was investigated in the TE671 human medulloblastoma cell line using RT-PCR and transcripts were detected only for SK3. Immunodetection experiments confirmed this result, demonstrating the presence of the SK3 protein. This potassium channel was characterised in TE671 cells using whole-cell patch-clamp recordings. Voltage steps to -100 mV from a holding potential of 0 mV in equimolar 140 mM intra- and extracellular K(+) (K(+)(in/out)) elicited an inward current. The reversal potential of this current shifted 56.6 mV per 10-fold increase in K(+)(out) thus suggesting K(+) selectivity. This current was dependent on the concentration of Ca(2+)(in) with an EC(50) of 104.2 nM. A pharmacological characterisation of this current revealed that it was not blocked by 1 microM charybdotoxin (ChTX), 0.3 microM iberiotoxin (IbTX) or 10 microM clotrimazole (CLT) and only modestly inhibited (<50%) by 30 nM scyllatoxin (ScTX), 200 microM dequalinium chloride (Deq) or 300 microM d-tubocurarine (d-TC). The non-selective SK blocker d-TC blocked the current with an IC(50) of 43.2 microM while apamin blocked the current to a much greater extent (87.8% at 1 microM) with an IC(50) of 4.3 nM. Furthermore, the current was significantly increased (132.6+/-5.2%, n=7) by 500 microM 1-ethyl-2-benzimidazolinone (EBIO). Collectively, these data demonstrate the presence of an endogenous SK3 channel in human TE671 cells.


Characterization of multiple type-VI secretion system (T6SS) VgrG proteins in the pathogenicity and antibacterial activity of porcine extra-intestinal pathogenic Escherichia coli.
Porcine extra-intestinal pathogenic Escherichia coli (ExPEC) causes great economic losses to the pig industry and poses a serious threat to public health worldwide. Some secreted virulence factors have been reported to be involved in the pathogenicity of the infection caused by ExPEC. Type-VI secretion system (T6SS) is discovered in many Gram-negative bacteria and contributes to the virulence of pathogenic bacteria. Valine-glycine repeat protein G (VgrG) has been reported as an important component of the functional T6SS. In our previous studies, a functional T6SS was identified in porcine ExPEC strain PCN033. Further analysis of the PCN033 genome identified two putative vgrGs genes (vgrG1 and 0248) located inside T6SS cluster and another two (vgrG2 and 1588) outside it. This study determined the function of the four putative VgrG proteins by constructing a series of mutants and complemented strains. In vitro, the VgrG1 protein was observed to be involved in the antibacterial ability and the interactions with cells. The animal model experiment showed that the deletion of vgrG1 significantly led to the decrease in the multiplication capacity of PCN033. However, the deletion of 0248 and/or the deletion of vgrG2 and 1588 had no effect on the pathogenicity of PCN033. The study of four putative VgrGs in PCN033 indicated that only VgrG1 plays an important role in the interaction between PCN033 and other bacteria or host cells. This study can provide a novel perspective to the pathogenesis of PCN033 and lay the foundation for discovering potential T6SS effectors.


A proposed signaling motif for nuclear import in mRNA processing via the formation of arginine claw.
Phosphorylation of proteins by kinases is the most commonly studied class of posttranslational modification, yet its structural consequences are not well understood. The human SR (serine-arginine) protein ASF/SF2 relies on the processive phosphorylation of the serine residues of eight consecutive arginine-serine (RS) dipeptide repeats at the C terminus by SRPK1 before it can be transported into the nucleus. This SR protein plays critical roles in spliceosome assembly, pre-mRNA splicing, and mRNA export, and the phosphorylation process of the RS repeats has been extensively studied experimentally. However, knowledge of the conformational changes associated with the phosphorylation of this simple sequence and how it triggers the importation of the SR protein is lacking. Here, we have carried out extensive molecular dynamics simulations to show that phosphorylation of the eight RS repeats significantly alters the peptide's conformation and leads to the formation of very stable structures that are likely to be involved in the recognition, binding, and transport of the SR protein. Specifically, we found an unusual symmetry-broken phase of conformations of the repetitive and quasi-symmetric phosphorylated peptide sequence. One of the main characteristics of these conformations is the exposed phosphate groups on the periphery, which possibly could serve as the recognition platform for the transport protein transportin-SR2.


SARS-CoV-2 HaploGraph: visualization of SARS-CoV-2 haplotype spread in Japan.
Since the early phase of the coronavirus disease 2019 (COVID-19) pandemic, a number of research institutes have been sequencing and sharing high-quality severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genomes to trace the route of infection in Japan. To provide insight into the spread of COVID-19, we developed a web platform named SARS-CoV-2 HaploGraph to visualize the emergence timing and geographical transmission of SARS-CoV-2 haplotypes. Using data from the GISAID EpiCoV database as of June 4, 2022, we created a haplotype naming system by determining the ancestral haplotype for each epidemic wave and showed prefecture- or region-specific haplotypes in each of four waves in Japan. The SARS-CoV-2 HaploGraph allows for interactive tracking of virus evolution and of geographical prevalence of haplotypes, and aids in developing effective public health control strategies during the global pandemic. The code and the data used for this study are publicly available at: https://github.com/ktym/covid19/.


Using National-Scale Data To Develop Nutrient-Microcystin Relationships That Guide Management Decisions.
Quantitative models that predict cyanotoxin concentrations in lakes and reservoirs from nutrient concentrations would facilitate management of these resources for recreation and as sources of drinking water. Development of these models from field data has been hampered by the high proportion of samples in which cyanotoxin concentrations are below detection limits and by the high variability of cyanotoxin concentrations within individual lakes. Here, we describe a national-scale hierarchical Bayesian model that addresses these issues and that predicts microcystin concentrations from summer mean total nitrogen and total phosphorus concentrations. This model accounts for 69% of the variance in mean microcystin concentrations in lakes and reservoirs of the conterminous United States. Mean microcystin concentrations were more strongly associated with differences in total nitrogen than total phosphorus. A general approach for assessing this and similar types of models for their utility for guiding management decisions is also described.


Recent Developments in Electrodeposition of Transition Metal Chalcogenides-based Electrode Materials for Advance Supercapacitor Applications: A Review.
High-performance supercapacitive electrode materials have received significant attention from researchers worldwide, thus aiming for comparable performance similar to the extensively used rechargeable batteries. For emerging energy storage technologies like flexible supercapacitors, transition metal chalcogenides (TMCs) have been in the spotlight due to their promising electrochemical features compared to other electrode materials. Among the synthesis techniques, electrodeposition-mediated preparation of thin films of TMCs offered an affordable binder-free approach for electrode fabrication that effectively improved the supercapacitor performance. Hence, this review mainly focussed on the electrodeposition-based syntheses of single/ multinary chalcogenides and their composites for supercapacitors applications. Further, the effects of different deposition parameters were discussed for boosting the supercapacitor performance. Finally, this review outlined the existing challenges and future perspectives in this research domain, which will assist the upcoming exploration in the energy storage field.


Role of sildenafil in neurological disorders.
Sildenafil, a phosphodiesterase-5 inhibitor commonly used for erectile dysfunction, may also have a beneficial therapeutic effect in the treatment of stroke, subarachnoid hemorrhage, dementia, learning, and neurodegenerative disorders by enhancing angiogenesis and neurogenesis. It also favorably influences the nitric oxide-cyclic guanosine monophosphate pathways, which are involved in the pathogenesis of a number of neurological diseases. Its potential therapeutic role in the treatment of the neurological disorders mentioned above is still under preclinical investigation. Sildenafil is currently being used to treat erectile dysfunction in patients with multiple sclerosis, Parkinson disease, multisystem atrophy, and spinal cord injury by improving their neurologically related erectile dysfunction. Conversely, it has been implicated in a number of neurological problems, such as intracerebral hemorrhage, migraine, seizure, transient global amnesia, nonarteritic anterior ischemic optic neuropathy, macular degeneration, branch retinal artery occlusion, and ocular muscle palsies. Thus, preclinical and very limited clinical data suggest that sildenafil may have therapeutic potential in selected neurological disorders. However, numerous reports are available regarding neurological adverse events ascribed to the drug. Although sildenafil shows some promise as a therapeutic agent in selected neurological disorders, well-designed clinical trials are needed before the agent can be recommended for use in any neurological disorder.


Design and analysis of aerodynamic force platforms for free flight studies.
We describe and explain new advancements in the design of the aerodynamic force platform, a novel instrument that can directly measure the aerodynamic forces generated by freely flying animals and robots. Such in vivo recordings are essential to better understand the precise aerodynamic function of flapping wings in nature, which can critically inform the design of new bioinspired robots. By designing the aerodynamic force platform to be stiff yet lightweight, the natural frequencies of all structural components can be made over five times greater than the frequencies of interest. The associated high-frequency noise can then be filtered out during post-processing to obtain accurate and precise force recordings. We illustrate these abilities by measuring the aerodynamic forces generated by a freely flying bird. The design principles can also be translated to other fluid media. This offers an opportunity to perform high-throughput, real-time, non-intrusive, and in vivo comparative biomechanical measurements of force generation by locomoting animals and robots. These recordings can include complex bimodal terrestrial, aquatic, and aerial behaviors, which will help advance the fields of experimental biology and bioinspired design.


The Epidemiology of Chronic Suppurative Lung Disease and Bronchiectasis in Children and Adolescents.
In the modern era, the global burden of childhood chronic suppurative lung disease (CSLD) remains poorly captured by the literature. What is clear, however, is that CSLD is essentially a disease of poverty. Disadvantaged children from indigenous and low- and middle-income populations had a substantially higher burden of CSLD, generally infectious in etiology and of a more severe nature, than children in high-income countries. A universal issue was the delay in diagnosis and the inconsistent reporting of clinical features. Importantly, infection-related CSLD is largely preventable. A considerable research and clinical effort is needed to identify modifiable risk factors and socioeconomic determinants of CSLD and provide robust evidence to guide optimal prevention and management strategies. The purpose of this review was to update the international literature on the epidemiology, etiology, and clinical features of pediatric CSLD.


[Action of benzbromarone on the renal excretion of allantoin in normouricemic and hyperuricemic humans (author's transl)].
Oral administration of benzbromarone at daily doses of 100 mg or 300 mg over a period of 3 or 6 days does not produce a significant change of the excretion rates of allantoin in the 24-h-urines of humans in a normouricemic or hyperuricemic state. Threrefore, the theroretically improbable assumption that benzbromarone may induce an increased elimination of uric acid by an enteral pathway cannot be accepted any longer. Failing additional direct effects upon purine metabolic pathways (Sorensen and Levinson, 1976) benzbromarone exerts its hypouricemic action solely by uricosuric properties.


Serotonergic transmission at Merkel discs: modulation by exogenously applied chemical messengers and involvement of Ih currents.
The Merkel disc is a main type of tactile end organ consisting of Merkel cells and Aβ-afferent endings that responds to tactile stimulation with slowly adapting type 1 (SA1) afferent impulses. Our recent study has shown that Merkel discs in whisker hair follicles are serotonergic synapses using endogenous serotonin to transmit tactile signals from Merkel cells to Aβ-afferent endings. In this study, we hypothesize that tactile sensitivity of Merkel discs can be modulated by chemical messengers. We tested this hypothesis by determining whether and how SA1 responses of mouse whisker hair follicles may be affected by exogenously applied chemical messengers. We found that SA1 responses were potentiated by serotonin at low concentration (10 μM) but almost completely occluded by serotonin at high concentration (2 mM). In contrast, SA1 responses were not significantly affected by ATP and its metabolically stable analog α,β-methylene-ATP, glutamate, γ-aminobutyric acid (GABA), and histamine. SA1 responses were also not affected by antagonists for P2X receptors, ionotropic glutamate receptors, and ionotropic GABA and glycine receptors. Whole-cell patch-clamp recordings reconfirm the presence of both ionotropic and metabotropic 5-HT receptors on afferent neurons and their terminals innervating whisker hair follicles. All whisker afferent neurons expressed hyperpolarization-activated inward currents (Ih ), which are potentiated by serotonin through the activation of metabotropic 5-HT receptors. Taken together, the findings substantiate the serotonergic mechanism of tactile transmission at Merkel discs and identify the involvement of Ih currents in postsynaptic excitatory actions of serotonin. In addition, the findings do not favor any significant involvement of ATP, glutamate, histamine, GABA, or glycine in tactile transmission at the Merkel discs of whisker hair follicles.


Transplantation of Menstrual Blood-Derived Mesenchymal Stem Cells Promotes the Repair of LPS-Induced Acute Lung Injury.
Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are associated with high morbidity and mortality. Menstrual blood-derived stem cells (MenSCs) have been shown to be good therapeutic tools in diseases such as ovarian failure and cardiac fibrosis. However, relevant studies of MenSCs in ALI have not yet proceeded. We hypothesized that MenSC could attenuate the inflammation in lipopolysaccharide (LPS)-induced ALI and promote the repair of damaged lung. ALI model was induced by LPS in C57 mice, and saline or MenSCs were administered via tail vein after four hours. The MenSCs were subsequently detected in the lungs by a live imaging system. The MenSCs not only improved pulmonary microvascular permeability and attenuated histopathological damage, but also mediated the downregulation of IL-1β and the upregulation of IL-10 in bronchoalveolar lavage fluid (BALF) and the damaged lung. Immunohistochemistry revealed the increased expression of proliferating cell nuclear antigen (PCNA) and the reduced expression of caspase-3 indicating the beneficial effect of MenSCs. Keratinocyte growth factor (KGF) was also upregulated after MenSCs administrated. As shown using transwell co-culture, the MenSCs also could improve the viability of BEAS-2B cells and inhibit LPS-induced apoptosis. These findings suggest that MenSC-based therapies could be promising strategies for treating ALI.


Familial risks for migraine and other headaches among siblings based on hospitalizations in Sweden.
Migraine and other headaches are common disabling conditions, reducing the quality of life in the affected individuals. The unambiguous definition of familial risk for subtypes of migraine and other headaches will advance the search for the heritable causes of these conditions and their underlying mechanisms. We aim at defining familial risks for siblings to be hospitalized because of migraine or other headaches. An ad hoc migraine database was constructed by linking the Multigeneration Register on 0- to 69-year-old siblings to the Hospital Discharge Register for data on migraines of all hospitalized patients in Sweden from years 1987 to 2001. Standardized incidence ratios (SIRs) were calculated for affected sibling pairs by comparison with those whose siblings had no migraine. Among a total of 14,123 hospitalized patients, 205 affected siblings were identified, with a familial SIR of 2.84. SIRs for migraine with and without aura were 3.08 and 2.67, respectively. The highest familial risk of 3.71 was noted for unspecified migraine. The risk tended to be higher for concordant (both siblings sharing the migraine subtype, ranging from 4.0 to 6.0) than discordant subtypes, but even many discordant SIRs were significant. The SIR for spouse correlation was 1.14 for husbands and 1.22 for wives, far from being significant. All subtypes of hospitalized migraines and other headaches show an increased familial risk, at least in specific age groups. The different subtypes appear to share susceptibility, which may imply common disease mechanisms.


Within- and Between-Session Reliability of the Isometric Midthigh Pull in Young Female Athletes.
Moeskops, S, Oliver, JL, Read, PJ, Cronin, JB, Myer, GD, Haff, GG, and Lloyd, RS. Within- and between-session reliability of the isometric midthigh pull in young female athletes. J Strength Cond Res 32(7): 1892-1901, 2018-To investigate the within- and between-session reliability of the isometric midthigh pull (IMTP) in pre- and post-peak height velocity (PHV) female athletes. Nineteen pre- and 19 post-PHV athletes performed bilateral IMTPs using a custom-designed isometric testing system. Participants attended 3 separate testing sessions and performed 3 trials within each session. Peak force, relative peak force, force at 30, 50, 90, 100, 150, 200, and 250 ms, rate of force development (RFD) within time-specific bands, time to peak force (TPF), and time to peak RFD were obtained for analysis. Within- and between-session reliability for each variable was calculated from repeated-measures analysis of variance, intraclass correlation coefficients (ICCs), and coefficients of variation (CV) with 95% confidence intervals. Within- and between-session measures of absolute and relative peak force were found to be reliable for both pre-PHV (CV ≤ 9.4%, ICC ≥ 0.87) and post-PHV (CV ≤ 7.3%, ICC ≥ 0.92), but systematic bias was evident between sessions in the pre-PHV group, from session 1 to 2. Analyses of force at the specific time points revealed CVs between 19-37% and 5-24% for pre-PHV and post-PHV athletes, respectively. Greater variability was evident in TPF, and all RFD-related variables for pre-PHV (CV ≥ 38%) and post-PHV (CV ≥ 27%) athletes, respectively. The IMTP appears a reliable and safe method for evaluating peak force in young female athletes. Overall, post-PHV athletes were more reliable than pre-PHV athletes, with pre-PHV athletes needing additional familiarization to minimize the influence of systematic bias.


High pressure in bioscience and biotechnology: pure science encompassed in pursuit of value.
A fundamental factors, pressure (P), is indispensable to develop and support applications in the field of bioscience and biotechnology. This short sentence describes an example how high pressure bioscience and biotechnology, which started from applied science, stimulates challenges of basic science and pure science in the biology-related fields including not only food science, medicine, and pharmacology but also biochemistry, molecular biology, cell biology, physical chemistry, and engineering.


Discrete and Balanced Spectral Clustering With Scalability.
Spectral Clustering (SC) has been the main subject of intensive research due to its remarkable clustering performance. Despite its successes, most existing SC methods suffer from several critical issues. First, they typically involve two independent stages, i.e., learning the continuous relaxation matrix followed by the discretization of the cluster indicator matrix. This two-stage approach can result in suboptimal solutions that negatively impact the clustering performance. Second, these methods are hard to maintain the balance property of clusters inherent in many real-world data, which restricts their practical applicability. Finally, these methods are computationally expensive and hence unable to handle large-scale datasets. In light of these limitations, we present a novel Discrete and Balanced Spectral Clustering with Scalability (DBSC) model that integrates the learning the continuous relaxation matrix and the discrete cluster indicator matrix into a single step. Moreover, the proposed model also maintains the size of each cluster approximately equal, thereby achieving soft-balanced clustering. What's more, the DBSC model incorporates an anchor-based strategy to improve its scalability to large-scale datasets. The experimental results demonstrate that our proposed model outperforms existing methods in terms of both clustering performance and balance performance. Specifically, the clustering accuracy of DBSC on CMUPIE data achieved a 17.93% improvement compared with that of the SOTA methods (LABIN, EBSC, etc.).


Localization of synapsin-I and PSD-95 in developing postnatal rat cerebellar cortex.
The comparative localization of two prominent synaptic proteins, synapsin-I (Syn-I) and PSD-95, was investigated in slices of developing (P3-P21) rat cerebellar cortex using double- or triple-label fluorescence immunohistochemistry and confocal microscopy. During the first postnatal week, Syn-I and PSD-95 immunoreactive (IR) puncta were strongly concentrated in the Purkinje cell layer (PCL) where they circumscribed irregularly shaped PC somata, forming pericellular nests that likely correspond to early climbing fiber synapses. PSD-95 and Syn-I puncta also were found along the shafts and at the tips of growing PC dendrite branches labeled with calbindin. During the second postnatal week, synaptic puncta were lost from the PC layer, while many new puncta were added to the molecular layer (ML). At P10, about half of the PCs were circumscribed by PSD-95 or Syn-I puncta, whereas at P14 no PCs were circumscribed. By P14, PSD-95 and Syn-I became most strongly localized to many small puncta in the ML and to large clusters at mossy fiber rosettes in the glomerular layer (GL) where PSD-95 often encircled Syn-I clusters. Some large clusters in the GL contained only PSD-95 or Syn-I, but not both, suggesting differential growth or remodeling of pre- and post-synaptic structures. No PSD-95 staining of pre-synaptic terminal pinceau was observed during the first 3 weeks of postnatal development. Thus, in relation to PCs, there is a developmental shift in PSD-95 localization whereby, first, it is concentrated on PC cell bodies and short dendrites (P3-P7), then it is lost on PC cell bodies (P7-14) and becomes localized almost exclusively to PC dendrites (P14-P21).


The southernmost myco-heterotrophic plant, Arachnitis uniflora: root morphology and anatomy.
Root morphology and anatomy of the myco-heterotrophic Arachnitis uniflora (Corsiaceae) were studied in relation to their association with a Glomus species (Glomeromycota). The mycorrhizal features were studied in three distinctive stages of development: (i) shoot and flower restricted to a small, underground bud; (ii) shoot and flower bud up to 1.5 cm; and (iii) shoot and flower already withered. The hyphae penetrate through and between the epidermal and exodermal cells; the exodermis and outer cortical cells become colonized in an inter- and intracellular manner, with some coils being formed in these layers. The fungi colonize the middle cortex, where intracellular vesicles in bundles are abundant. Arbuscules are formed profusely at very early stages of development, while in older stages they almost disappear and abundant vesicles are formed. Except for some details, the pattern of root colonization corresponds to a Paris-type. Presence of storage substances (starch and oil) also was recorded. Starch is produced and stored within root cells, mainly in the outer and inner root cortex. In senescent stages, plant and fungal tissues collapse.


Stroke patients' knowledge of stroke. Influence on time to presentation.
New treatments for acute stroke will likely have to be given soon after stroke onset. Little is known about stroke patients' general knowledge about stroke, their interpretation of stroke symptoms, and how these factors influence the timing of their decision to seek medical attention. We interviewed consecutive stroke patients within 72 hours of stroke onset to define factors influencing time of arrival to the emergency department. Data recorded included demographic information, method of transportation, type of stroke symptoms, the patient's interpretation of the symptoms, previous stroke, and knowledge of stroke warning signs. Stroke severity was measured with the Barthel Index. Early arrival was defined as within 3 hours of awareness of symptoms. Sixty-seven patients were interviewed; 96% had an ischemic stroke and 4% a cerebral hemorrhage. Although 38% of patients professed to know the warning signs of stroke, only 25% correctly interpreted their symptoms. Patients with prior stroke were more likely to correctly interpret their symptoms (45% versus 16%; P = .03) but were not more likely to present early (19% versus 39%; P = .35). Eighty-six percent of patients presenting more than 3 hours after stroke onset thought that their symptoms were not serious. The 24% (n = 16) of early arrivals were more likely to arrive by ambulance (81% versus 38%; P = .003) and had more severe stroke (Barthel Index score of 49 versus 72; P = .01) than late arrivals. Arrival by ambulance was independently associated with early arrival (odds ratio, 5.55; 95% confidence interval, 1.37 to 22.6). Approximately one quarter of stroke patients correctly interpret their symptoms as representing a stroke. This knowledge is not associated with early presentation to the emergency department. Ambulance transport is independently associated with early arrival at the emergency department. Even when patients know that they are having a stroke, most present late because they perceive their symptoms as "not serious." Widespread public education of stroke-prone individuals may increase the proportion of patients eligible for new acute stroke treatments.


[Balloon assisted kyphoplasty: new technique for treatment of vertebral compression fractures].
Balloon assisted kyphoplasty and vertebroplasty are minimally invasive procedures with established value in the management of osteoporotic and neoplastic vertebral compression fractures. Kyphoplasty, a variation of vertebroplasty, is a technique with indications and therapeutic particularities that require validation.


Understanding the motivations of long-term care insurance owners: the importance of retirement planning.
This article is based on two recent reports by the American Council of Life Insurers (ACLI) that illuminate the reasons why individuals purchase private long-term care insurance in both the group and individual markets. This information suggests that a younger and more diverse group of individuals are becoming increasingly interested in private long-term care insurance and that workplace education linkage the purchase of long-term care insurance to retirement planning may promote coverage.


Strain softening is not present during axial extensions of rat intact right ventricular trabeculae in the presence or absence of 2,3-butanedione monoxime.
Recent studies of passive myocardial mechanics have shown that strain softening behavior is present during both inflation of isolated whole rat hearts and shearing of tissue blocks taken from the left ventricular free wall in pigs. Strain softening is typically manifested by a stiffer force-extension relation in the first deformation cycle relative to subsequent cycles and is distinguished from viscoelasticity by a lack of recovery of stiffness, even after several hours of rest. The causes of this behaviour are unknown. We investigated whether strain softening is observed in uniaxial extensions of intact, viable, rat right ventricular (RV) cardiac trabeculae. Stretch and release cycles of 5%, 10%, and 15% muscle length were applied at a constant velocity at 26 degrees C. Muscles were tested in random order in the presence and absence of 50 mM 2,3-butanedione monoxime (BDM). Whereas strain softening was displayed by nonviable trabeculae, it was not observed in viable preparations undergoing physiologically relevant extensions whether in the presence or absence of BDM. BDM also had no effect on passive compliance. There was a reversible increase of muscle compliance between the first and subsequent cycles, with recovery after 30 s of rest, independent of the presence of BDM. We conclude that strain softening is neither intrinsic to viable rat RV trabeculae nor influenced by BDM and that passive trabeculae compliance is not altered by the addition of BDM.


Corticosteroid increases gastrointestinal luminal proteolysis in suckling rats.
Although stress during the perinatal period may influence a number of enzymes in the gastrointestinal tract, the resulting effects on digestive processes are not completely understood. In suckling rats, corticosteroid administration increases levels of proteases in gastric mucosa and pancreas, but previous studies of unstimulated luminal fluid proteolytic activity suggest no effect. To re-evaluate this phenomenon, we injected suckling rats with cortisone acetate (5 mg/100 g body weight) subcutaneously daily on days 9-11 followed by sacrifice on day 12; littermates served as controls. Luminal fluid from stomach and small intestine was analyzed for proteolytic activity by a sensitive assay in which incubation in vitro with 125I-bovine casein was followed by measurement of radioactivity soluble in trichloroacetic acid. Cortisone acetate produced significant increases in luminal proteolytic activity in all gastrointestinal segments with the most dramatic effect observed in the ileum; this segment showed a more than 10-fold enhancement of proteolysis with steroid treatment. Analysis of acid-precipitable reaction products by electrophoresis in polyacrylamide gels containing sodium dodecyl sulfate also revealed enhancement of casein degradation by luminal fluid in all segments from steroid-treated animals. We conclude that corticosteroid increases luminal proteolysis in the gastrointestinal tract of the suckling rat. This phenomenon may have implications for steroid-induced premature closure to macromolecular absorption and protein digestive capacity during the perinatal period.


Antioxidant, phenolic and antifungal profiles of Acanthus mollis (Acanthaceae).
Acanthus mollis is used as ornamental and medicinal plant. The ethnopharmacology reports indicate that extracts have anti-inflammatory activity. Phytoconstituents profile was evaluated by estimating the content of anthraquinones, flavonoids and phenols. In addition, the antioxidant activity was evaluated using four methods: Hydrogen atoms transfer (TRAP, ORAC and DPPH assays), and single electron transfer (FRAP assay). Finally, antifungal activity was determined by the M27-A2 test. The results shown that ethanol extracts have the highest concentration of phenols, anthraquinones and flavonoids. Total antioxidant capacity, extracts of ethyl acetate and ethanol are those with the highest activity, which correlates strongly with the presence of phenols. The antifungal activity measured in various strains of Candida is concentrated in ethyl acetate extracts of flower and leaf ethanol, a phenomenon may be related to antioxidant activity.


Locality of contacts determines the subdiffusion exponents in polymeric models of chromatin.
Loop extrusion by motor proteins mediates the attractive interactions in chromatin on the length scale of megabases, providing the polymer with a well-defined structure and at the same time determining its dynamics. The mean-square displacement of chromatin loci varies from a Rouse-like scaling to a more constrained subdiffusion, depending on cell type, genomic region, and time scale. With a simple polymeric model, we show that such a Rouse-like dynamics occurs when the parameters of the model are chosen so that contacts are local along the chain, while in the presence of nonlocal contacts we observe subdiffusion at short time scales with exponents smaller than 0.5. Such exponents are independent of the detailed choice of the parameters and build a master curve that depends only on the mean locality of the resulting contacts. We compare the loop-extrusion model with a polymeric model with static links, showing that also in this case only the presence of nonlocal contacts can produce low-exponent subdiffusion. We interpret these results in terms of a simple analytical model.


CHCHD2 mediates glioblastoma cell proliferation, mitochondrial metabolism, hypoxia‑induced invasion and therapeutic resistance.
Glioblastoma (GBM) is the most common and malignant primary brain tumor affecting adults and remains incurable. The mitochondrial coiled‑coil‑helix‑coiled‑coil‑helix domain‑containing protein 2 (CHCHD2) has been demonstrated to mediate mitochondrial respiration, nuclear gene expression and cell migration; however, evidence of this in GBM is lacking. In the present study, it was hypothesized that CHCHD2 may play a functional role in U87 GBM cells expressing the constitutively active epidermal growth factor receptor variant III (EGFRvIII). The amplification of the CHCHD2 gene was found to be associated with a decreased patient overall and progression‑free survival. The CHCHD2 mRNA levels were increased in high‑vs. low‑grade glioma, IDH‑wt GBMs, and in tumor vs. non‑tumor tissue. Additionally, CHCHD2 protein expression was greatest in invasive, EGFRvIII‑expressing patient‑derived samples. The CRISPR‑Cas9‑mediated knockout of CHCHD2 in EGFRvIII‑expressing U87 cells resulted in an altered mitochondrial respiration and glutathione status, in decreased cell growth and invasion under both normoxic and hypoxic conditions, and in an enhanced sensitivity to cytotoxic agents. CHCHD2 was distributed in both the mitochondria and nuclei of U87 and U87vIII cells, and the U87vIII cells exhibited a greater nuclear expression of CHCHD2 compared to isogenic U87 cells. Incubation under hypoxic conditions, serum starvation and the reductive unfolding of CHCHD2 induced the nuclear accumulation of CHCHD2 in both cell lines. Collectively, the findings of the present study indicate that CHCHD2 mediates a variety of GBM characteristics, and highlights mitonuclear retrograde signaling as a pathway of interest in GBM cell biology.


A thieno-2H-chromene alpha-amino acid derivative: synthesis and photochromic properties.
[structure: see text] A new photochromic thieno-2H-chromene alpha-amino acid derivative was prepared by C-N palladium-catalyzed cross-coupling of a bromothieno-2H-chromene with the aminated aromatic side chain of the methyl ester of a N,N-diprotected amino acid. Its good photochromic properties demonstrated by flash photolysis and continuous irradiation indicate a possible application in ophthalmic lenses. It may also be inserted into peptides to give photoinduced reversible structural changes.


The V-ATPase B1-subunit promoter drives expression of Cre recombinase in intercalated cells of the kidney.
The collecting duct of the kidney is composed of two morphologically and physiologically distinct cell types, principal and intercalated cells. To better understand intercalated cell function we generated a transgenic mouse expressing Cre recombinase under the control of a cell type- specific promoter. We used 7 kb of the ATP6V1B1 5' untranslated region (B1 promoter), a gene found in the intercalated cells of the kidney and the male reproductive tract. We first crossed these B1-Cre transgenic mice with the ROSA26-loxP-stop-loxP-yellow fluorescent protein reporter mice to assess the specificity of Cre expression. Immunohistochemistry and confocal fluorescence microscopy showed that Cre is selectively active in all intercalated cells (type A, type B, and non-A/B cells) within the collecting duct and most cells of the connecting segment. About half of the principal cells of the connecting segment also expressed Cre, a pattern also seen in B1-driven enhanced green fluorescent protein transgenic mice. Cre was found to be active in the male reproductive tract and at a low level in limited non-ATP6V1B1 expressing tissues. The B1-Cre transgenic mice are healthy, breed normally, produce regular sized litters, and transmit the transgene in Mendelian fashion. This new cell-specific Cre expressing mouse should prove useful for the study of intercalated cell physiology and development.


Variations in coping stages for individuals with chronic kidney disease: Results from an exploratory study with patient navigators.
Using a cross-sectional design, we examined coping stages (Kübler-Ross) among patients with end-stage renal disease at nephrology practices incorporating professional social workers as patient navigators, providing person-centered education and support (N = 420). We evaluated associations with behavioral counseling constructs (assess-advise-agree-assist-arrange). Coping stages comprised denial = 35.24 percent, acceptance = 24.05 percent, depression = 21.43 percent, bargaining = 12.86 percent, and anger = 6.43 percent. Compared to denial, other coping stages showed increased odds ratios for transplant referral agreement, transplant referral evaluations, understanding treatments, understanding donation procedures, plans to recruit donors, active donor recruitment, and potential living donor(s). Assessment of coping stages, and strategies to influence these, may be key factors in guiding patients to living donor kidney transplantation.


Influence of different positive emotions on persuasion processing: a functional evolutionary approach.
Much research has found that positive affect facilitates increased reliance on heuristics in cognition. However, theories proposing distinct evolutionary fitness-enhancing functions for specific positive emotions also predict important differences among the consequences of different positive emotion states. Two experiments investigated how six positive emotions influenced the processing of persuasive messages. Using different methods to induce emotions and assess processing, we showed that the positive emotions of anticipatory enthusiasm, amusement, and attachment love tended to facilitate greater acceptance of weak persuasive messages (consistent with previous research), whereas the positive emotions of awe and nurturant love reduced persuasion by weak messages. In addition, a series of mediation analyses suggested that the effects distinguishing different positive emotions from a neutral control condition were best accounted for by different mediators rather than by one common mediator. These findings build upon approaches that link affective valence to certain types of processing, documenting emotion-specific effects on cognition that are consistent with functional evolutionary accounts of discrete positive emotions.


The influence of inulin on the absorption of nitrogen and the production of metabolites of protein fermentation in the colon.
In the present study, the production and fate of bacterial metabolites in the colon were investigated in a direct way using two substrates labelled with stable isotopes: lactose [(15)N,(15)N]ureide as a source of labelled ammonia and egg proteins intrinsically labelled with [(2)H4]tyrosine as a precursor of [(2)H4]p-cresol. Both ammonia and phenolic compounds are believed to be carcinogenic. Stimulation of carbohydrate fermentation in order to prevent accumulation of these toxic metabolites was induced by inclusion of inulin in a test meal or by addition of inulin to the daily diet, allowing us to distinguish between changes induced by the actual presence of a fermentable carbohydrate and effects caused by a long-term dietary intervention. When a single dose of inulin was administered together with the labelled substrates, a significant increase in faecal (15)N excretion, accompanied by a proportional decrease in urinary (15)N excretion was observed, probably reflecting an enhanced uptake of ammonia for bacterial biosynthesis, since an increased concentration of labelled N in bacterial pellets was found. A statistically significant reduction of urinary [(2)H4]p-cresol excretion was also noted. Upon supplementation of inulin to the daily diet during 4 weeks, however, only a tendency towards decreased urinary excretion of both labelled and unlabelled p-cresol was noted. Further studies are warranted to confirm these results in a larger cohort.


Cross-Adversarial Learning for Molecular Generation in Drug Design.
Molecular generation is an important but challenging task in drug design, as it requires optimization of chemical compound structures as well as many complex properties. Most of the existing methods use deep learning models to generate molecular representations. However, these methods are faced with the problems of generation validity and semantic information of labels. Considering these challenges, we propose a cross-adversarial learning method for molecular generation, CRAG for short, which integrates both the facticity of VAE-based methods and the diversity of GAN-based methods to further exploit the complex properties of Molecules. To be specific, an adversarially regularized encoder-decoder is used to transform molecules from simplified molecular input linear entry specification (SMILES) into discrete variables. Then, the discrete variables are trained to predict property and generate adversarial samples through projected gradient descent with corresponding labels. Our CRAG is trained using an adversarial pattern. Extensive experiments on two widely used benchmarks have demonstrated the effectiveness of our proposed method on a wide spectrum of metrics. We also utilize a novel metric named Novel/Sample to measure the overall generation effectiveness of models. Therefore, CRAG is promising for AI-based molecular design in various chemical applications.


[Angiokeratomas. Apropos of 8 cases].
Eight patients with angiokeratomas are reported; three of them with angiokeratoma circumscriptum present at birth, three angiokeratoma Fordyce type with vulvar location, another one with scrotum location all these appeared by the third decade and the other one a solitary angiokeratoma which age of onset was forty-one years. The clinical and histopathological aspects of the angiokeratoma are studied.


Recent Pathophysiological Aspects of Peyronie's Disease: Role of Free Radicals, Rationale, and Therapeutic Implications for Antioxidant Treatment-Literature Review.
Peyronie's disease (PD) is a chronic inflammation of tunica albuginea of the corpora cavernosa that causes an inelastic plaque resulting in penis deformation. Although its etiology is not completely known, there is general consensus that PD is genetically transmitted and secondary to penile trauma. In recent years, numerous studies demonstrated the role played by oxidative stress in PD pathogenesis, and other studies have described successful use of antioxidants in PD treatment. Oxidative stress is an integral part of this disease, influencing its progression. In the early stages of PD, the inflammatory infiltrate cells produce high quantities of free radicals and proinflammatory and profibrotic cytokines, with consequent activation of transcription factor NF-κB. While conservative therapies commonly used in the early stages of PD include oral substances (Potaba, tamoxifen, colchicine, and vitamin E), intralesional treatment (verapamil, interferon, steroids, and more recently collagenase clostridium histolyticum-Xiaflex), and local physical treatment (iontophoresis, extracorporeal shock wave therapy, and penile extender), the significant results obtained by emerging treatments with the antioxidants cited in this article suggest these therapeutic agents interfere at several levels with the disease's pathogenetic mechanisms. Antioxidants therapy outcomes are interesting for good clinical practice and also confirm the fundamental role played by oxidative stress in PD.


Inherited thrombophilia: undetected comorbidity complicating COVID-19 infection.
The relation between the severity of COVID-19 and coexisting undiagnosed underlying thrombophilic conditions is not yet established. It may be possible that undiagnosed thrombophilia exaggerates an already pro-thrombotic state in COVID-19 patients and may be responsible for severe disease in absence of any known co-morbidity. The aim was to analyze the association of underlying thrombophilia with the severity of COVID-19 infection in post-COVID patients after a minimum of 6 weeks of recovery and to compare thrombophilia profile in severe versus non-severe COVID-19 patients. Forty severe and 40 non-severe COVID patients at least 6 weeks post recovery were selected for thrombophilia profile and complete blood count evaluation. The data were analyzed using Stata software, USA; version 13. The Chi-square test and Student's t-test were used to compare proportions and mean respectively. A total of 14/80 (17.5%) were positive for the thrombophilia screen. Protein C deficiency was noted in 6/40 (15%) severe COVID patients but not in the non-severe group. The Protein S deficiency was seen in 7/40 (17.5%) severe patients and only 1 patient was deficient in the non-severe group (2.5%). The mean Protein C and Protein S levels of severe and non-severe COVID patients were statistically significant (P-0.002) and (P-0.007) respectively. The difference in mean anti-COVID IgG antibody titer of severe and non-severe COVID patients was also statistically significant (P-0.0001). To Conclude, Protein C & S deficiencies were the commonest abnormalities detected in severe COVID patients. Positive thrombophilia profile and higher titers of anti-IgG COVID-19 antibodies were seen in a significant number of patients who had suffered from Severe COVID-19 than in non-severe infection, even after 6 weeks of recovery. Thereby, suggesting that underlying thrombophilia might have affected the severity of the disease.


Management of behavioral and psychological symptoms of dementia in long-term care facilities in Japan.
An increasing number of old people, and their medical requirements, cannot be managed by their families in their homes, which has been the traditional and prevalent practice in Japan. The number of people with dementia is increasing and behavioral and psychological symptoms of dementia (BPSD) make care difficult. In the present study, we investigated management techniques for BPSD in long-term care facilities in Japan by using the data mining method, which looks at the reported behaviors of care providers. First, interviews were conducted with 15 care providers to develop items for a questionnaire. These data were analyzed qualitatively and synthesized with criteria from the professional literature. The resulting self-report questionnaire on techniques used to manage different symptoms of dementia was completed by 275 care providers. We applied the association rule as a data mining method examining 15 management techniques related to 13 BPSD. Analysis identified four types of management techniques: (i) emotional and behavior-concordance techniques; (ii) acceptance and supportive techniques; (iii) restraining techniques; and (iv) avoidance techniques. Different management techniques, and combinations of techniques, were found to vary in use and effectiveness with different BPSD. Good management techniques for many BPSD have been developed and are being implemented by care providers. The present study has the potential to inform researchers and care providers in Japan about the types of management techniques in current use, as well as areas of potential need for staff training.


The possible role of GABAA receptors and gephyrin in epileptogenesis.
The term epileptogenesis refers to a dynamic alteration in neuronal excitability that promotes the appearance of spontaneous seizures. Temporal lobe epilepsy, the most common type of acquired epilepsy, often develops after an insult to the brain such as trauma, febrile seizures, encephalitis, or status epilepticus. During the pre-epileptic state (also referred as latent or silent period) there is a plethora of molecular, biochemical, and structural changes that lead to the generation of recurrent spontaneous seizures (or epilepsy). The specific contribution of these alterations to epilepsy development is unclear, but a loss of inhibition has been associated with the increased excitability detected in the latent period. A rapid increase in neuronal hyperexcitability could be due, at least in part, to a decline in the number of physiologically active GABAA receptors (GABAAR). Altered expression of scaffolding proteins involved in the trafficking and anchoring of GABAAR could directly impact the stability of GABAergic synapses and promote a deficiency in inhibitory neurotransmission. Uncovering the molecular mechanisms operating during epileptogenesis and its possible impact on the regulation of GABAAR and scaffolding proteins may offer new targets to prevent the development of epilepsy.


Prediction of acute in vivo toxicity of some amine and amide drugs to rats by multiple linear regression, partial least squares and an artificial neural network.
The oral acute in vivo toxicity of 32 amine and amide drugs was related to their structural-dependent properties. Genetic algorithm-partial least-squares and stepwise variable selection was applied to select of meaningful descriptors. Multiple linear regression (MLR), artificial neural network (ANN) and partial least square (PLS) models were created with selected descriptors. The predictive ability of all three models was evaluated and compared on a set of five drugs, which were not used in modeling steps. Average errors of 0.168, 0.169 and 0.259 were obtained for MLR, ANN and PLS, respectively.


The world-wide waste web.
Countries globally trade with tons of waste materials every year, some of which are highly hazardous. This trade admits a network representation of the world-wide waste web, with countries as vertices and flows as directed weighted edges. Here we investigate the main properties of this network by tracking 108 categories of wastes interchanged in the period 2001-2019. Although, most of the hazardous waste was traded between developed nations, a disproportionate asymmetry existed in the flow from developed to developing countries. Using a dynamical model, we simulate how waste stress propagates through the network and affects the countries. We identify 28 countries with low Environmental Performance Index that are at high risk of waste congestion. Therefore, they are at threat of improper handling and disposal of hazardous waste. We find evidence of pollution by heavy metals, by volatile organic compounds and/or by persistent organic pollutants, which are used as chemical fingerprints, due to the improper handling of waste in several of these countries.


Effect of Acute Static Stretching on Lower Limb Movement Performance Using STABL Virtual Reality System.
The effect of acute static stretching (ASS) on the lower limb reaction time (RT) has been recently questioned to decrease the risk of falling and injuries in situations requiring a rapid reaction, as in the cases of balance disturbance. The main purpose of this study was to detect the effect of ASS on the lower limb RT using a virtual reality device. Two-group control group design. Research laboratory. The control and experimental groups were formed randomly from 60 female university students. Each participant in the experimental group was tested before and after ASS for the quadriceps, hamstrings, and planter flexor muscles, and compared with the control group with warming-up exercise alone. The stretching program involved warming up in the form of circular running inside the lab for 5 minutes followed by stretching of each muscle group three times, to the limit of discomfort of 45 seconds, with resting period of 15 seconds between stretches. The measurements included the RT of the dominant lower-extremity using the dynamic stability program STABL Virtual Reality System (model no. DIZ 2709; Motekforce Link). There was a statistically significant reduction (F = 162, P < .05) in posttest RT between the 2 groups and significant decrease in RT after stretching in the experimental group (7.5%; P < .05). ASS of the lower limb muscles tends to decrease the lower limb RT and improve movement performance.


Efficacy of Rectal Systemic Administration of Mesenchymal Stem Cells to Injury Sites via the CXCL12/CXCR4 Axis to Promote Regeneration in a Rabbit Skeletal Muscle Injury Model.
Mesenchymal stem cells (MSCs) have been transplanted directly into lesions or injected intravenously. The administration of MSCs using these delivery methods requires specialized knowledge, techniques, and facilities. Here, we describe intrarectal systemic administration of MSCs, a simple, non-invasive route for homing to the injury sites to promote the regeneration of skeletal muscle injuries. Using a cardiotoxin (CTX)-induced rabbit skeletal muscle injury model, homing to the site of muscle injury was confirmed by intrarectal administration of MSCs; the time required for homing after intrarectal administration was approximately 5 days. In addition, the C-X-C chemokine ligand 12 (CXCL12)/C-X-C chemokine receptor-4 (CXCR4) axis was found to be involved in the homing process. Histopathological examinations showed that skeletal muscle regeneration was promoted in the MSCs-administered group compared to the CTX-only group. Myosin heavy polypeptide 3 (Myh3) expression, an indicator of early muscle regeneration, was detected earlier in the intrarectal MSCs group compared to the CTX-only group. These findings indicate that intrarectal administration of MSCs is effective in homing to the injured area, where they promote injury repair. Since intrarectal administration is a simple and non-invasive delivery route, these findings may be valuable in future research on stem cell therapy.


Successful management of lower extremity distal embolization following percutaneous atherectomy with the JetStream G3 device.
There has been a resurgence of atherectomy as a strategy to treat peripheral atherosclerosis. Distal embolization occurs frequently during peripheral endovascular interventions but is of particular concern during atherectomy. We describe a case of distal embolization following atherectomy with the Pathway JetStream system successfully managed with aspiration thrombectomy and infrapopliteal angioplasty. A detailed review of the incidence, treatment, and prevention of DE in this context are presented.


Effects of adding cocoa fermentation medium on cigar leaves in agricultural fermentation stage.
Background and Objective: With the development of the world economy and the integration of cultures, the Chinese cigar market has shown a significant upward trend. However, high-quality cigar leaves are mostly produced in Dominica, Cuba, Nicaragua and other places. In contrast, Chinese cigar leaves have problems such as insufficient aroma, which has become one of the main factors restricting the development of Chinese cigars. Adding medium to ferment is a traditional method in the cigar industry. At present, it mostly relies on manual experience, and lacks systematic and scientific research. At the same time, the addition of medium fermentation is mainly concentrated in the industrial fermentation process, and has not yet begun to be applied in the agricultural fermentation process. In this study, the medium was added to the agricultural fermentation process for the first time to explore the possibility of the application. The effects of adding cocoa medium to ferment on the chemical composition, sensory quality and surface microbial diversity of eggplant core cigar leaves were investigated.wrapper. Method: With Dexue 7' as the experimental material, the changes of main chemical components of wrapper fermented with water and cocoa medium were determined, and microbial community structure on the surface and relative abundance of cigar leaves at different turning periods were analyzed, and the functional genes were predicted. The results of the study were as follows: 1) The results of sensory evaluation showed that the addition of cocoa medium could highlight the aroma of bean, cocoa and coffee, improve the sweetness and fluency and the combustibility of cigar leaves. 2) The addition of cocoa medium increased the contents of proline and malic acid which were positively correlated with sensory quality, and decreased the contents of citric acid, linoleic acid, basic amino acids and aromatic amino acids which were negatively correlated with sensory quality. 3) The addition of cocoa medium increased the total amount of aroma components in cigar leaves, especially carotenoid degradation products, and changed the structural composition of some aroma substances in wrappercigar leaves. 4) The similarity of species composition between the water-added group and the cocoa-added group was higher, but the dominant microorganisms were more concentrated. Staphylococcus and Arthrobacter maintained a high relative abundance throughout the fermentation process, which may be the key microorganisms in the agricultural fermentation stage. 5) The addition of cocoa medium increased the expression abundance of related functional genes in cigar leaves, accelerated the fermentation process of cigar leaves, and bacteria played a major role in the fermentation process. Conclusion: Adding cocoa medium in the agricultural fermentation stage, the changes of bacterial community and dominant flora on the surface of cigar leaves are the main factors affecting their internal chemical components, and the addition of media has a positive effect on tobacco fermentation.


Glutathione-S-transferases genes-promising predictors of hepatic dysfunction.
One of the most commonly known genes involved in chronic diffuse liver diseases pathogenesis are genes that encodes the synthesis of glutathione-S-transferase (GST), known as the second phase enzyme detoxification system that protects against endogenous oxidative stress and exogenous toxins, through catalisation of glutathione sulfuric groups conjugation and decontamination of lipid and deoxyribonucleic acid oxidation products. The group of GST enzymes consists of cytosolic, mitochondrial and microsomal fractions. Recently, eight classes of soluble cytoplasmic isoforms of GST enzymes are widely known: α-, ζ-, θ-, κ-, μ-, π-, σ-, and ω-. The GSTs gene family in the Human Gene Nomenclature Committee, online database recorded over 20 functional genes. The level of GSTs expression is considered to be a crucial factor in determining the sensitivity of cells to a broad spectrum of toxins. Nevertheless, human GSTs genes have multiple and frequent polymorphisms that include the complete absence of the GSTM1 or the GSTT1 gene. Current review supports the position that genetic polymorphism of GST genes is involved in the pathogenesis of various liver diseases, particularly non-alcoholic fatty liver disease, hepatitis and liver cirrhosis of different etiology and hepatocellular carcinoma. Certain GST allelic variants were proven to be associated with susceptibility to hepatological pathology, and correlations with the natural course of the diseases were subsequently postulated.


Serum microRNA profiling and bioinformatics analysis of patients with type 2 diabetes mellitus in a Chinese population.
Type 2 diabetes mellitus (T2DM) is characterized by islet β-cell dysfunction and insulin resistance, which leads to an inability to maintain blood glucose homeostasis. Circulating microRNAs (miRNAs) have been suggested as novel biomarkers for T2DM prediction or disease progression. However, miRNAs and their roles in the pathogenesis of T2DM remain to be fully elucidated. In the present study, the serum miRNA expression profiles of T2DM patients in Chinese cohorts were examined. Total RNA was extracted from serum samples of 10 patients with T2DM and five healthy controls, and these was used in reverse-transcription‑quantitative polymerase chain reaction analysis with the Exiqon PCR system of 384 serum/plasma miRNAs. A total of seven miRNAs were differentially expressed between the two groups (fold change >3 or <0.33; P<0.05). The serum expression levels of miR‑455‑5p, miR‑454‑3p, miR‑144‑3p and miR‑96‑5p were higher in patients with T2DM, compared with those of healthy subjects, however, the levels of miR‑409‑3p, miR‑665 and miR‑766‑3p were lower. Hierarchical cluster analysis indicated that it was possible to separate patients with T2DM and control individuals into their own similar categories by these differential miRNAs. Target prediction showed that 97 T2DM candidate genes were potentially modulated by these seven miRNAs. Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed that 24 pathways were enriched for these genes, and the majority of these pathways were enriched for the targets of induced and repressed miRNAs, among which insulin, adipocytokine and T2DM pathways, and several cancer‑associated pathways have been previously associated with T2DM. In conclusion, the present study demonstrated that serum miRNAs may be novel biomarkers for T2DM and provided novel insights into the pathogenesis of T2DM.


Hydrido copper clusters supported by dithiocarbamates: oxidative hydride removal and neutron diffraction analysis of [Cu7(H){S2C(aza-15-crown-5)}6].
Reactions of Cu(I) salts with Na(S(2)CR) (R = N(n)Pr(2), NEt(2), aza-15-crown-5), and (Bu(4)N)(BH(4)) in an 8:6:1 ratio in CH(3)CN solution at room temperature yield the monocationic hydride-centered octanuclear Cu(I) clusters, [Cu(8)(H){S(2)CR}(6)](PF(6)) (R = N(n)Pr(2), 1(H); NEt(2), 2(H); aza-15-crown-5, 3(H)). Further reactions of [Cu(8)(H){S(2)CR}(6)](PF(6)) with 1 equiv of (Bu(4)N)(BH(4)) produced neutral heptanuclear copper clusters, [Cu(7)(H){S(2)CR}(6)] (R = N(n)Pr(2), 4(H); NEt(2), 5(H); aza-15-crown-5, 6(H)) and clusters 4-6 can also be generated from the reaction of Cu(BF(4))(2), Na(S(2)CR), and (Bu(4)N)(BH(4)) in a 7:6:8 molar ratio in CH(3)CN. Reformation of cationic Cu(I)(8) clusters by adding 1 equiv of Cu(I) salt to the neutral Cu(7) clusters in solution is observed. Intriguingly, the central hydride in [Cu(8)(H){S(2)CN(n)Pr(2)}(6)](PF(6)) can be oxidatively removed as H(2) by Ce(NO(3))(6)(2-) to yield [Cu(II)(S(2)CN(n)Pr(2))(2)] exploiting the redox-tolerant nature of dithiocarbamates. Regeneration of hydride-centered octanuclear copper clusters from the [Cu(II)(S(2)CN(n)Pr(2))(2)] can be achieved by reaction with Cu(I) ions and borohydride. The hydride release and regeneration of Cu(I)(8) was monitored by UV-visible titration experiments. To our knowledge, this is the first time that hydride encapsulated within a copper cluster can be released as H(2) via chemical means. All complexes have been fully characterized by (1)H NMR, FT-IR, UV-vis, and elemental analysis, and molecular structures of 1(H), 2(H), and 6(H) were clearly established by single-crystal X-ray diffraction. Both 1(H) and 2(H) exhibit a tetracapped tetrahedral Cu(8) skeleton, which is inscribed within a S(12) icosahedron constituted by six dialkyl dithiocarbamate ligands in a tetrametallic-tetraconnective (μ(2), μ(2)) bonding mode. The copper framework of 6(H) is a tricapped distorted tetrahedron in which the four-coordinate hydride is demonstrated to occupy the central site by single crystal neutron diffraction. Compounds 1-3 exhibit a yellow emission in both the solid state and in solution under UV irradiation at 77 K, and the structureless emission is assigned as a (3)metal to ligand charge transfer (MLCT) excited state. Density functional theory (DFT) and time-dependent density functional theory (TDDFT) calculations on model compounds match the experimental structures and provide rationalization of their bonding and optical properties.


Measurement of cumulative radiation exposure to children and adolescents in contact with outpatients treated with low dose radioactive iodine (131I).
Radiation exposure from patients treated with radioactive iodine (131I) represents a radiation hazard to children and adolescents, representing the most vulnerable group of household contacts. Our aim was to calculate the cumulative radiation exposure (CRE) figures to children and adolescents sharing the same home with outpatients treated with low-dose 131I. The secondary aim was to study the demographic and educational factors that may significantly affect radiation exposure to them. The whole number of household contacts less than 18 years was 99, out of them 49 ≤ 12 years. CRE level to children and adolescents ranged from 79 to 934 uSv. The mean, median, and 75th percentile figures were 284 ± 178 uSv, 215 uSv, and 334 uSv, respectively. The compliance of this group of contacts to radiation exposure constraint (1 mSv) was 100%. All CRE values were below this figure with 75% of them below half of this constraint. Thirteen adolescents from 12 to 18 years and 17 mothers of 23 household contacts ≤ 12 years got radiation safety instructions (RSI) directly from a radiation safety officer (RSO). This group had a significantly lower mean CRE value (184 ± 93 uSv) compared to those who got RSI from the patient or from other family members (298 ± 185 uSv) with a significant p value. The compliance of adolescents and children to the 1-mSv radiation exposure constraint is 100%. It is advised for adolescents and mothers of children in contact with 131I-treated patients to get direct RSI from the RSO, which is the only factor associated with significantly lower radiation exposure figures.


Pigmented ganglioglioma in a patient with chronic epilepsy and cortical dysplasia.
We report a rare case of a 22-year-old woman with biopsy-proven pigmented ganglioglioma. The patient initially underwent a right temporal lobectomy for intractable seizures at the age of 9 and remained seizure free for several years but subsequently developed complex partial seizures. Due to enhancement of a left mesial occipital lesion on preoperative MRI of the brain, the patient underwent a left subdural electrode placement and simultaneous biopsy of the left mesial occipital lesion. Biopsy results revealed a rare pigmented ganglioglioma, World Health Organization Grade I. The seizure focus was identified in the left mesial occipital lobe and the patient underwent tumor resection. An extensive literature search revealed that our patient is the fourth case of pigmented ganglioglioma described in the literature and was positive for BRAF V600E mutation by molecular studies.


Isolation of alpha-toxin, theta-toxin and kappa-toxin mutants of Clostridium perfringens by Tn916 mutagenesis.
Clostridium perfringens is the causative agent of clostridial myonecrosis or gas gangrene and mediates infection and disease by producing numerous extracellular toxins, including alpha-toxin, theta-toxin and kappa-toxin. Tn916-mutagenesis was used to isolate mutants defective in their ability to produce either alpha-toxin or theta-toxin. Nine independently derived mutants were isolated. In four of these mutants Tn916 had inserted at sites located 193 bp or 198 bp upstream of the theta-toxin structural gene, pfoA. Four mutants contained large deletions, three in regions which encompassed the theta-toxin structural and regulatory genes pfoA and pfoR, respectively, and the kappa-toxin structural gene, colA, and one in a region encompassing the alpha-toxin structural gene, plc. These mutants should prove to be invaluable for further genetic studies aimed at determining the role of these toxins in virulence.


Protein changes in the albedo of citrus fruits on postharvesting storage.
In this work, major protein changes in the albedo of the fruit peel of Murcott tangor (tangerine x sweet orange) during postharvest ageing were studied through 2D PAGE. Protein content in matured on-tree fruits and in fruits stored in nonstressing [99% relative humidity (RH) and 25 degrees C], cold (99% RH and 4 degrees C), and drought (60% RH and 25 degrees C) conditions was initially determined. Protein identification through MS/MS determinations revealed in all samples analyzed the occurrence of manganese superoxide dismutase (Mn SOD), actin, ATP synthase beta subunit (ATPase), citrus salt-stress associated protein (CitSap), ascorbate peroxidase (APX), translationally controlled tumor protein (TCTP), and a cysteine proteinase (CP) of the papain family. The latter protein was identified in two different gel spots, with different molecular mass, suggesting the simultaneous presence of the proteinase precursor and its active form. While Mn SOD, actin, ATPase, and CitSap were unchanged in the assayed conditions, TCTP and APX were downregulated during the postharvest ageing process. Ageing-induced APX repression was also reversed by drought. CP contents in albedo, which were similar in on- and off-tree fruits, were strongly dependent upon cold storage. The active/total CP protein ratio significantly increased after cold exposure. This proteomic survey indicates that major changes in protein content in the albedo of the peel of postharvest stored citrus fruits are apparently related to the activation of programmed cell death (PCD).


Benefits and limitations of antidepressants and traditional mood stabilizers for treatment of bipolar depression.
The aim of this paper was to review the rationales, risks, and benefits for using standard antidepressants versus mood stabilizing agents and/or atypical antipsychotics to treat bipolar depression. A selective literature review was conducted using key terms and by reference known to the authors. Bibliographies of articles and book chapters were further scrutinized for relevant literature. The strengths and limitations of current studies are described and critically reviewed in order to present optimal strategies for effective pharmacotherapy. Clinical factors that can mitigate or confound simple bivariate relationships between antidepressant use and outcome have seldom been examined using multivariate statistical techniques. For many of the key questions there is a paucity of informative literature and randomized clinical trials are of limited value in addressing some of the issues. Clinicians and investigators should be aware of the methodological shortcomings of existing studies. Decisions about the relative merits versus contraindications for antidepressant use should be made via more individualized, case-by-case profiling rather than by rigid prescribing practices.


Endogenous IL-17 does not play a significant role in the development of experimental murine allergic conjunctivitis.
Endogenous IL-17 is needed for the Ag sensitization that results in murine allergic asthma, a Th2-mediated disease. Here, we aimed to investigate the role IL-17 plays in the development of murine experimental allergic conjunctivitis (EC) which is also a Th2-mediated disease. To induce EC, wild-type (WT) and IL-17-deficient (IL-17 KO) mice on the BALB/c and C57BL/6 backgrounds were immunized with ragweed (RW) in alum and challenged with RW in eye drops. Alternatively, EC was induced by adoptively transferring RW-primed splenocytes followed by challenge with RW-containing eye drops. Twenty-four hours after the RW challenge, the conjunctivas and spleens were harvested for histological analyses and cytokine assays, respectively. The WT and IL-17 KO mice on both backgrounds did not differ in terms of the severity of actively induced EC, as evaluated by the conjunctival eosinophil infiltration. They also did not differ with regard to the phenotypes of the inflammatory cells infiltrating the conjunctivas, although primed IL-17 KO splenocytes stimulated in vitro with RW extract did produce significantly higher amounts of IL-4, IL-13 and IFN-gamma than WT splenocytes. Reciprocal adoptive transfer experiments also demonstrated that the IL-17 from both the donor splenocytes and the recipient mice is not involved in the development of EC. Endogenous IL-17 does not appear to play a significant role in the development of EC.


Studies of the human sex ratio and factors influencing family size in Botucatu, Brazil.
During 1974--75, data on sex and family size were obtained from approximately 500 Brazilian college students and their parents. Sex ratios for the immediate and parental generations were 107:100 and 106:100, respectively. Correlation coefficients were calculated between sexes of various children in families of the immediate generation. A significant positive relationship was found between sexes of the first two children in families of two or more children. The overall correlation between sexes of successive births was positive but not significant. Correlation coefficients between sexes separated by one or more births were not significant. The observed frequencies of combinations of sexes within the various family sizes did not differ from expected frequencies. Average numbers of children per family were 4.39 and 6.80 for the immediate and parental generations, respectively. Average family sizes decreased as the formal educational level of the parents increased. If the parents' desired both sexes of children, such preferences had no measurable influence on family size.


Malignant Melanoma of Anorectum: Two Case Reports.
Malignant melanoma of the anorectum is a rare disorder. Patients often present with local symptoms similar to benign diseases. The prognosis is very poor, and almost all patients die because of metastases. We report 2 female patients with unremarkable histories. Both of them received previous operations before visiting our center after they were diagnosed with anorectal malignant melanoma. One case underwent abdominoperineal resection and postoperative chemotherapy. The other had been treated with ultralow anterior resection followed by immunotherapy.