Antifungal activity of a series of 1,2-benzisothiazol-3(2H)-one derivatives.
A series of broad-spectrum antifungal agents based on the 1,2-benzisothiazol-3(2H)-one scaffold is reported. Preliminary structure-activity relationship studies have established the importance of the presence of the heterocyclic ring, a methyl group, and a phenyl ring for optimal manifestation of antifungal activity.


Fluorescent probes for nitric oxide and hydrogen peroxide in cell signaling.
Nitric oxide (NO) and hydrogen peroxide (H(2)O(2)) have emerged as essential small molecules for cellular signal transduction owing largely to their ability to mediate oxidative posttranslational modifications (PTMs). Inventing new ways to track these small, diffusible, and reactive species with spatial and temporal resolution is a key challenge in elucidating their chemistry in living systems. Recent progress in the development of fluorescent probes that respond selectively to NO and H(2)O(2) produced at cell signaling levels offers a promising approach to interrogating their physiological production, accumulation, trafficking, and function.


Inhibitory effect of PVDF tubes on biofilm formation in dental unit waterlines.
It has been reported that dental unit waterlines (DUWLs) are contaminated with bacterial biofilm, and that water discharged from a DUWL contains bacteria that might be opportunistic pathogens. This study aimed to investigate the ability of polyvinylidene fluoride (PVDF) tubing to inhibit bacterial contamination in DUWLs. Newly installed dental units were equipped with either a conventional polyurethane tube (unit A) or a PVDF tube (unit B), and the numbers of bacteria discharged from high- and low-speed handpiece lines were counted using R2A agar plates. Bacterial attachment on surfaces was observed with a scanning electron microscope (SEM) up to 185 days. Bacterial outflow during 1-day clinical service from a DUWL after 1-year usage was also examined. The surface free energy of each tube was determined based on the measurement of contact angles. The number of bacteria discharged from unit B was lower than from unit A at 80 days and thereafter. SEM examination demonstrated that the unit A tube was covered by biofilm constituting rods and filaments after 94 days, while no biofilm was observed in the unit B tube even after 185 days. After 1-year of usage, the unit B released significantly less bacteria than the unit A at every sampling period of 1-day clinic work. Surface free energies, calculated from contact angles measured, of PVDF and polyurethane tubes were 37.7 and 77.8, respectively. The present results indicate that PVDF tubes, which have lower surface free energy than the conventional tubes, were effective in inhibiting biofilm formation and reducing bacterial outflow from DUWLs.


Effectiveness and safety of switching to adalimumab biosimilar ABP 501 in Crohn's disease: the extrapolation concept.
We sincerely thank Viscido et al. for their appropriate and sharable comments on our recent study on adalimumab biosimilar ABP 501 in Crohn's disease (CD). The use of a biosimilar in inflammatory disorders is one of the current main topics, given the great opportunity to save resources that can be invested in innovative drugs and the ethical problems that non-medical switching can generate.


A mathematical model of the development of drug resistance to cancer chemotherapy.
A mathematical model incorporating descriptions of tumour growth kinetics and the effects of cytotoxic chemotherapy on established tumours, is presented. It is shown how models of this kind may be used to investigate the potential of hypothetical chemotherapy strategies, and to identify general principles for successful treatment. The model is intended to be an aid to clinicians designing new chemotherapy programmes for diseases in which progress has been disappointing.


From peptides to peptidomimetics: design of nonpeptide ligands for major histocompatibility proteins.
The ever increasing data available on antigen presentation by class I or class II histocompatibility proteins have made these glycoproteins highly interesting pharmaceutical targets for either vaccination or immunosuppressive therapy of autoimmune diseases and cancers. Herewith, we review the design and biological properties of the very first nonpeptide ligands of major histocompatibility proteins as well as their potential application in vaccination, Major Histocompatibility Complex (MHC) blockade or T cell receptor antagonism.


FGFR Family Members Protein Expression as Prognostic Markers in Oral Cavity and Oropharyngeal Squamous Cell Carcinoma.
Fibroblast growth factor receptor family member proteins (FGFR1-4) have been identified as promising novel therapeutic targets and prognostic markers in a wide spectrum of solid tumors. The present study investigates the expression and prognostic value of four FGFR family member proteins in a large multicenter oral cavity squamous cell carcinoma (OCSCC) and oropharyngeal squamous cell carcinoma (OPSCC) cohort. Protein expression of FGFR1-4 was determined by immunohistochemistry on tissue microarrays containing 951 formalin-fixed paraffin embedded OCSCC and OPSCC tissues from the University Medical Center Utrecht and University Medical Center Groningen. Protein expression was correlated to overall survival using Cox regression models, and bootstrapping was performed as internal validation. FGFR proteins were highly expressed in 39-64 % of OCSCC and 63-79 % of OPSCC. Seventy-three percent (299/412) of OCSCC and 85 % (305/357) of OPSCC highly co-expressed two or more FGFR family member proteins. FGFR1 protein was more frequently highly expressed in human papillomavirus (HPV)-negative OPSCC than HPV-positive OPSCC (82 vs. 65 %; p = 0.008). Furthermore, protein expression of FGFR family members was not related to overall survival in OCSCC or OPSCC (p > 0.05). FGFR family members are frequently highly expressed in OCSCC and OPSCC. These FGFR family member proteins are therefore potential targets for novel therapies that are urgently required to improve survival of OCSCC and OPSCC patients.


ROTAVI: simultaneous left main rotablation and transcutaneous aortic valve implantation in calcified coronaries and severe aortic stenosis - a case report.
There is a high incidence of calcified coronary artery disease in patients with severe valvular aortic stenosis (AS). With transcutaneous aortic valve replacement (TAVR) as one of the promising options for severe AS in high and intermediate surgical risk patients; we will encounter more and more patients who will require both complex percutaneous coronary intervention (PCI) with rotablation (RA) and TAVR. The timing of PCI in patients undergoing TAVR; however remains indecisive. Due to the complexity of procedures and the risks involved, very few cases of concomitant TAVR and coronary RA have been reported so far. Seventy-five years old high surgical risk female had severe AS with calcified left main (LM) distal and ostial left anterior descending (LAD) artery lesion. Successful PCI with RA to LM-LAD lesion was done followed by uneventful transfemoral TAVR in the same setting. This is probably one of the very few cases reported where PCI to LM with RA and TAVR was done successfully in the same setting. Since the calcified lesion was focal and left ventricular ejection fraction of the patient was normal, we went ahead with PCI without prior balloon dilatation of aortic valve (BAV) which was a deviation from the prior reported cases, where BAV was performed prior to complex PCI to improve the cardiac output. We herein discuss our case and thoughts about concomitant complex PCI and TAVR.


Actinic keratosis: correlation between clinical and histological classification systems.
There are several clinical and histological classification systems for grading actinic keratosis (AK) lesions. The Olsen clinical classification scheme grades AK lesions according to their thickness and degree of hyperkeratosis (grades 1-3). The Roewert-Huber histological classification system grades AK lesions based on the extent of epidermal atypical keratinocytes (AK I-III). The aim of this study was to determine whether there is a correlation between these clinical and histological AK classification schemes. One AK lesion from patients in three pivotal clinical studies and routine practice was assessed clinically and histologically. A match in grading was defined as Olsen grade 1 being classified histologically as AK I, Olsen grade 2 as AK II and Olsen grade 3 as AK III. Of the 892 lesions included, 29.0% were classified as Olsen grade 1, 59.6% as Olsen grade 2 and 11.3% as Olsen grade 3; 19.2% were histologically classified as AK I, 69.6% as AK II and 11.2% as AK III. Only 480 lesions (53.8%) had a matching clinical and histological classification. Of these matches, most were 'Olsen grade 2 = AK II' (83.1%). The Spearman's rank correlation coefficient for clinical and histological classification was r = 0.0499 (P = 0.137). Clinical classification of AK lesions using the system of Olsen does not accurately match histological classification of the same lesions using the system of Roewert-Huber. Consequently, it is not possible to draw conclusions about the histology of AK lesions from their clinical appearance. This finding reinforces the need to treat all AK lesions as well as field cancerization.


Retracted: A Study on the Impact of Basketball on the Physical Fitness and Health of Adolescents Based on the Method of Correlation Analysis.
[This retracts the article DOI: 10.1155/2022/6520518.].


Cost-effectiveness of usual general practitioner care with or without antidepressant medication for patients with minor or mild-major depression.
Minor depression is common in primary care and associated with increased health care costs. Many mildly depressed patients are prescribed antidepressants, although there is insufficient information on the cost-effectiveness of antidepressants for these patients. The objective of this study was to evaluate whether usual care without antidepressants is equivalent to (i.e. as effective as and as expensive as) usual care with antidepressants in patients with minor or mild-major depression. Severity of depression was measured using the Montgomery Asberg Depression Rating Scale (MADRS) and quality-adjusted life-years (QALYs) using the EuroQol. Resource use was measured from a societal perspective using cost diaries. Bootstrapping was used to analyze the cost-effectiveness data. Equivalence could not be shown for improvement in MADRS score or QALYs gained at 52 weeks. The mean (95% CI) difference in total costs between usual care without antidepressants and usual care with antidepressants was -euro751 (-3601; 1522). Using an equivalence margin of euro500 equivalence in costs could not be shown. In the cost-effectiveness analyses equivalence also could not be shown. This study was underpowered for economic outcomes. Another limitation was the loss-to-follow-up. Although equivalence could not be shown in the costs and cost-effectiveness analyses, 95% confidence intervals also did not show that usual care without antidepressants was vastly superior or inferior to usual care with antidepressants. Therefore, we recommend general practitioners to show restraint when prescribing antidepressants to mildly depressed patients.


Polymorphisms in SIGLEC1 contribute to susceptibility to pulmonary active tuberculosis possibly through the modulation of IL-1ß.
Siglec-1/CD169 is a sialoadhesin expressed by macrophages thought to function in cell-to-cell interactions. In the lung, the expression of Siglec-1 is specific for alveolar macrophages and single nucleotide polymorphisms (SNPs) in SIGLEC1 have been recently associated with asthma severity. Taking in account the role of alveolar macrophages in the control of M. tuberculosis and the poor literature about the contribution of SIGLEC1 genetics in M. tuberculosis susceptibility and development of pulmonary active TB, selected SNPs in SIGLEC1 were analysed in a case/control cohort from a TB endemic area of Brazil Amazon. Our findings evidenced for the first time the novel association between SIGLEC1 rs3859664 SNP and active pulmonary TB. Intriguingly, carriers of the polymorphism produced less IL-1ß than non-carriers, suggesting the possible involvement of Siglec-1 signalling pathway with inflammasome complex.


Assessment of past results and current practice in the treatment of rheumatoid metacarpophalangeal joints. Five year review.
A new design of prosthetic finger joint for the rheumatoid patient, and the technique for its insertion is described, which has now been in use for five years. The technique includes the soft tissue correction of the ulnar deviation. Results are reported for all the cases performed in one year giving a two year follow up, assessing flexion strength, pinch strength and the degree of recurrence of ulnar drift associated with loss of pinch strength.


Hepatic bilirubin and UDP-glucuronate levels in Bolivian squirrel monkeys exhibiting fasting hyperbilirubinemia.
1. Bolivian squirrel monkeys (BoSMs), which are animal models for Gilbert's syndrome, have 40% less hepatic bilirubin UDP-glucuronyltransferase (BR-UPPG-T) activity than Brazilian squirrel monkeys (BrSMs). 2. Although fasting results in similar decreases in hepatic UDP-glucose and UDP-glucuronate levels in both simian subspecies, increased activities (55%) of BR-UDPG-T are induced only in the fasted control BrSMs, which do not exhibit the marked fasting hyperbilirubinemia (FH). 3. Total hepatic bilirubin (BR) concentrations were 50% greater in both fed and fasted BoSMs when compared to BrSMs. 4. Hepatic unconjugated BR levels increase upon fasting only in Gilbert-like BoSMs, reaching concentrations twice that observed in BrSMs. 5. Elevated hepatic BR levels in fasted BoSMs may reflect BR overproduction or inadequate glucuronidation. 6. The increased BR-UDPG-T activity induced in BrSMs during fasting could compensate in-part for the UDPGA depletion and prevent the marked FH as observed in BoSMs.


Natural autoimmunity in oligoarticular juvenile idiopathic arthritis.
Oligoarticular juvenile idiopathic arthritis (oligo-JIA) is considered as an antigen-driven lymphocyte-mediated autoimmune disease. Natural antibodies (NAbs) are pre-immune antibodies produced in the absence of exogenous antigen stimulation, participating in both, innate and adaptive immunity. Considering their major immunoregulatory role in homeostasis and autoimmune pathogenesis, we designed this study to further elucidate their role in oligo-JIA pathogenesis. Seventy children with persistent oligo-JIA and 20 healthy matched controls were enrolled in the study. Serum IgM and IgA antibodies against human G-actin, human IgG F(ab΄)2 fragments and the hapten TriNitroPhenol (TNP) as well as the total concentration of serum IgM and IgA were measured by in-house enzyme-immunoassays. Kolmogorov-Smirnov normality test, Kruskal-Wallis H and Mann-Whitney tests were used to assess data distribution, and significant differences of non-parametric data between groups of the study. Backward regression analysis was used to analyze the effect of multiple factors (age, gender, disease activity, anti-nuclear antibody positivity, presence of uveitis) on continuous dependent variables (activities and activity/ concentration ratios of IgM and IgA NAbs). The ratios of IgA anti-TNP, anti-actin and anti-F(ab΄)2 levels to total serum IgA concentration were found to be significantly increased in patients with oligo-JIA compared to healthy subjects. Significantly elevated levels of IgM anti-TNP antibodies were also found in children with inactive oligo-JIA compared to those of children with active disease and of healthy controls. In the presence of anterior uveitis, IgM anti-TNP levels were significantly higher than in patients without uveitis or in healthy controls. Backward regression analysis revealed that the disease activity and the presence of anterior uveitis independently affect IgM anti-TNP levels. Our findings are in accordance with the hypothesis that NAbs contribute to the pathogenesis of autoimmune diseases and provide additional evidence that disturbances in natural autoimmunity may contribute to the as yet unclarified pathogenesis of oligo-JIA.


BMP signalling: visualisation of the Sog protein gradient.
Extracellular inhibitors are commonly used in development to modulate the activities of signalling molecules. Direct visualisation in the Drosophila embryo of Sog, a Dpp/Scw inhibitor, has now revealed a graded distribution established by degradation and endocytosis.


Tapping into hospital champions--strategic middle managers.
A social network analysis of eighty-nine midlevel health care professionals showed that middle managers' strategic knowledge is positively associated with championing alternative ideas and synthesizing new information for upper management. In addition, the relationship between knowledge and middle management strategic activities in informal networks is moderated by the manager's social position.


Kv7/KCNQ potassium channels in cortical hyperexcitability and juvenile seizure-related death in Ank2-mutant mice.
Autism spectrum disorders (ASD) represent neurodevelopmental disorders characterized by social deficits, repetitive behaviors, and various comorbidities, including epilepsy. ANK2, which encodes a neuronal scaffolding protein, is frequently mutated in ASD, but its in vivo functions and disease-related mechanisms are largely unknown. Here, we report that mice with Ank2 knockout restricted to cortical and hippocampal excitatory neurons (Ank2-cKO mice) show ASD-related behavioral abnormalities and juvenile seizure-related death. Ank2-cKO cortical neurons show abnormally increased excitability and firing rate. These changes accompanied decreases in the total level and function of the Kv7.2/KCNQ2 and Kv7.3/KCNQ3 potassium channels and the density of these channels in the enlengthened axon initial segment. Importantly, the Kv7 agonist, retigabine, rescued neuronal excitability, juvenile seizure-related death, and hyperactivity in Ank2-cKO mice. These results suggest that Ank2 regulates neuronal excitability by regulating the length of and Kv7 density in the AIS and that Kv7 channelopathy is involved in Ank2-related brain dysfunctions.


Evaluating clinical signs in trabeculectomized eyes.
To evaluate interobserver agreement for clinical signs in trabeculectomized eyes when examined face-to-face with slit-lamp biomicroscopy (SL) or by remote examination using telemedicine (real-time remote video imaging; TM). A system for examining trabeculectomized eyes was devised and validated. A prospective randomized interobserver agreement study was then undertaken to compare standard SL biomicroscopy and TM. Remote examination was performed using a 384 kbps Sony 5100 videoconferencing system. Three ophthalmologists each examined 40 eyes of 40 patients, who had previously undergone trabeculectomy. In rotation, two examiners used SL biomicroscopy. The third examined the eye remotely by TM. Analysis was performed to determine the variability in clinical signs and the presence or absence of systematic bias between ophthalmologists and examination methods. High levels of agreement were observed for paired examinations by SL biomicroscopy (SL/SL) for bleb vascularity (score range 0-10) with no systematic bias. Paired examination by SL and TM (SL/TM) also showed good levels of agreement for bleb vascularity, although the spread of disagreement was wider (95% limits of agreement 2.57 vs 2.98 (P=0.054)). For anterior chamber depth, observers agreed within +/- 10% of anterior chamber depth for 68% of eyes (SL/SL) and 51% of eyes (SL/TM) (P=0.68). Agreement was 'good' for wall thickness (kappa=0.63 +/- 0.08), bleb height (kappa=0.67 +/- 0.1), and the existence of bleb leak (kappa=0.63 +/- 0.19), but poor for bleb morphology (kappa=0.26 +/- 0.12). For the SL/TM comparison, agreement was fair for wall thickness (kappa=0.39 +/- 0.13), poor for bleb height (kappa=0.17 +/- 0.12), good for bleb leak (kappa=0.56 +/- 0.19), and fair for bleb morphology (kappa=0.31 +/- 0.12). Microcysts were not reliably detected using either technique. SL biomicroscopy and TM telemedicine examination may permit reliable clinical assessment of trabeculectomized eyes. However, remote examination with TM is more limited with respect to assessing bleb height and bleb wall thickness. The assessment of bleb morphology and microcysts was unreliable with both instruments. We propose that TM examination of trabeculectomized eyes appears safe and appropriate in situations where face-to-face examination by an ophthalmologist is not practical.


Evaluation of transethnic fine mapping with population-specific and cosmopolitan imputation reference panels in diverse Asian populations.
There has been limited success in identifying causal variants underlying association signals observed in genome-wide association studies (GWAS). The use of 1000 Genomes Project (1KGP) allows the imputation to estimate the genetic information at untyped variants. However, long stretches of high linkage disequilibrium within the genome prevent us from differentiating between causal variants and perfect surrogates, thus limiting our ability to identify causal variants. Transethnic strategies have been proposed as a possible solution to mitigate this. However, these studies generally rely on imputing genotypes from multiple ancestries from 1KGP but not against population-specific reference panels. Here, we perform the first transethnic fine-mapping study across three Asian cohorts from diverse ancestries at the loci implicated with eye and blood lipid traits, using population-specific reference panels that have been generated by whole-genome sequencing samples from the same ancestry groups. Our study outlines several challenges faced in a fine-mapping exercise where one simply aims to meta-analyse existing GWAS that have been imputed against reference haplotypes from the 1KGP.


[Clinical analysis of orbital cysticercus cellulosae].
To investigate the clinical features, laboratory tests, medical imaging manifestations, diagnosis and treatment of orbital cysticercus cellulosae. 23 cases of orbital cysticercus cellulosae were analyzed from 1973 to 1997. Most cases had features of exophthalmos, lid swelling, limitation of ocular movement. Some of them with visual loss, optic papilledema and orbital mass. B-scan ultrasonography revealed a cystic tumor and a strong echo spot with spontaneous movement. On CT scanning, found was a well-defined hyperdensity mass in which there was a low density area. On MRI, the signal intensity of T(1)WI of cystic fluid was low or moderate and of T(2)WI was high, while the signal intensity of T(1)WI and T(2)WI of surrounding scar tissue was still low. We can make diagnosis by imaging tests and treat them with surgical operations.


Myeloproliferative Neoplasms in Children.
Myeloproliferative neoplasms (MPN) are a group of clonal hematopoietic stem cell disorders characterized by aberrant proliferation of one or more myeloid lineages often with increased immature cells in the peripheral blood. The three classical BCR-ABL-negative MPNs are: 1) polycythemia vera (PV), 2) essential thrombocythemia (ET), and 3) primary myelofibrosis (PMF), which are typically disorders of older adults and are exceedingly rare in children. The diagnostic criteria for MPNs remain largely defined by clinical, laboratory and histopathology assessments in adults, but they have been applied to the pediatric population. The discovery of the JAK2 V617F mutation, and more recently, MPL and CALR mutations, are major landmarks in the understanding of MPNs. Nevertheless, they rarely occur in children, posing a significant diagnostic challenge given the lack of an objective, clonal marker. Therefore, in pediatric patients, the diagnosis must rely heavily on clinical and laboratory factors, and exclusion of secondary disorders to make an accurate diagnosis of MPN. This review focuses on the clinical presentation, diagnostic work up, differential diagnosis, treatment and prognosis of the classical BCR-ABL-negative MPNs (PV, ET and PMF) in children and highlights key differences to the adult diseases. Particular attention will be given to pediatric PMF, as it is the only disorder of this group that is observed in infants and young children, and in many ways appears to be a unique entity compared to adult PMF.


An immunochromatographic serological assay for the diagnosis of Mycobacterium tuberculosis.
A rapid serological test for tuberculosis (TB) infection was designed using antigens specific to Mycobacterium tuberculosis. Tuberculosis infection, TB vaccination and exposure to environmental Mycobacteria cannot be distinguished using skin tests based on tuberculin protein derivatives. The standard diagnostic techniques such as skin tests, X-rays and DNA techniques are time consuming, expensive, and not practical for screening large populations. We used the 38, 63, 64, 14, 59-kDa antigens of M. tuberculosis to develop a rapid immunochromatographic test kit. This study evaluates the diagnostic potential of the rapid test kit using TB positive and TB negative serum samples from various hospitals in India. The samples were obtained from patients infected with or exposed to bacteria and viral pathogens. The results demonstrated that the combination of antigens improved the diagnostic specificity and sensitivity. The specificity of the test was 99.42% with sensitivity of 98.52% (n = 241). In case of multiple infections, the specificity was 93.15% with a low sensitivity of 73.52% n = 141). The test kit may offer an improved alternative to purified protein derivative (PPD). This rapid TB test kit may be a useful tool for first-line testing of suspected cases, epidemiological studies and in designing a quality health system to reduce health hazards in resource-poor countries.


Optimal two-stage designs for phase II clinical trials.
The primary objective of a phase II clinical trial of a new drug or regimen is to determine whether it has sufficient biological activity against the disease under study to warrant more extensive development. Such trials are often conducted in a multi-institution setting where designs of more than two stages are difficult to manage. This paper presents two-stage designs that are optimal in the sense that the expected sample size is minimized if the regimen has low activity subject to constraints upon the size of the type 1 and type 2 errors. Two-stage designs which minimize the maximum sample size are also determined. Optimum and "minimax" designs for a range of design parameters are tabulated. These designs can also be used for pilot studies of new regimens where toxicity is the endpoint of interest.


Changes in alcohol intake over time found to affect disease risk.
Post-menopausal woman who drank two extra alcoholic drinks a day over a five-year period increased their risk of breast cancer, but reduced their chance of developing coronary heart disease, a new study suggests.


Molecular miscibility of phosphatidylcholine and phosphatidylethanolamine in binary mixed bilayers with acidic phospholipids studied by 2H- and 31P-NMR.
The intermolecular interactions and microscopic miscibility of the lipid bilayers of single component and binary mixtures with high content of saturated fatty acids were investigated by 2H- and 31P-NMR for phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylglycerol (PG) and cardiolipin (CL). Their glycerol backbones were selectively deuterated by biosynthesis and chemical synthesis. Deuterium quadrupole splittings and phosphorus chemical shift anisotropies provided the consistent information for the molecular miscibility of each phospholipids. PE was found to be completely miscible with PG and CL. Since deuterium quadrupole splittings and phosphorus chemical shift anisotropy are identical for two components in the mixed bilayer, the dynamic structure from the glycerol backbone to phosphate group should be uniform in the binary mixture of these phospholipids. In contrast to PE, PC was not fully miscible with PG and CL at molecular resolution. The dynamic structure from the glycerol backbone to phosphate group is different for two components in the binary mixed bilayers. In the case of the mixed bilayers of PC and PE, both phospholipids are microscopically immiscible with each other. Thus, while PE, PG and CL can adapt to a new situation to form a uniform dynamic structure in mixed bilayers, PC has no ability for adaptation. The molecular miscibility in lipid bilayers was shown to depend on the molecular species and the nature of the molecular interactions. The biological significance of this result was discussed.


Impacts of Working From Home During COVID-19 Pandemic on Physical and Mental Well-Being of Office Workstation Users.
To understand impacts of social, behavioral and physical factors on well-being of office workstation users during COVID-19 work from home (WFH). A questionnaire was deployed from April 24 to June 11, 2020 and 988 responses were valid. Linear regression, multinomial logistic regression and chi-square tests were used to understand factors associated with overall physical and mental health statuses and number of new physical and mental health issues. Decreased overall physical and mental well-being after WFH were associated with physical exercise, food intake, communication with coworkers, children at home, distractions while working, adjusted work hours, workstation set-up and satisfaction with workspace indoor environmental factors. This study highlights factors that impact workers' physical and mental health well-being while WFH and provides a foundation for considering how to best support a positive WFH experience.


Electroencephalography-Derived Functional Connectivity in Sensorimotor Networks in Post Stroke Fatigue.
Poor suppression of anticipated sensory information from muscle contractions is thought to underlie high fatigue. Such diminished task-related sensory attenuation is reflected in resting state connectivity. Here we test the hypothesis 'altered electroencephalography (EEG)-derived functional connectivity in somatosensory network in the beta band, is a signature of fatigue in post-stroke fatigue'. In non-depressed, minimally impaired stroke survivors (n = 29), with median disease duration of 5 years, resting state neuronal activity was measured using 64-channel EEG. Graph theory-based network analysis measure of functional connectivity via small-world index (SW) was calculated focusing on right and left motor (Brodmann areas 4, 6, 8, 9, 24 and 32) and sensory (Brodmann areas 1, 2, 3, 5, 7, 40 and 43) networks, in the beta (13-30 Hz) frequency range. Fatigue was measured using Fatigue Severity Scale - FSS (Stroke), with scores of > 4, defined as high fatigue. Results confirmed the working hypothesis, with high fatigue stroke survivors showing higher small-worldness in the somatosensory networks when compared to low fatigue. High levels of small-worldness in somatosensory networks indicates altered processing of somesthetic input. Such altered processing would explain high effort perception within the sensory attenuation model of fatigue.


Histopathological and combinatorial effects of the metalloprotease InhA1 and Cry proteins of Bacillus thuringiensis against Spodoptera littoralis.
The zinc metalloprotease (InhA) of Bacillus thuringiensis specifically hydrolyzes cecropins and attacins, two antibacterial peptides in the immune hemolymph of insects, leading to a high resistance of the bacteria to the humoral defense system of its host. In the present study, the inhA gene of B. thuringiensis strain BUPM28 was cloned and the nucleotide sequence analysis revealed that it was identical to that of B. thuringiensis 8010. The expressed InhA1 protein in Escherichia coli showed toxicity to neonate Spodoptera littoralis larvae with a LC50 of 2.07±0.72μg/cm(2). Study of the effect of combining Cry proteins with InhA1 showed that one improves the toxicity of the other one against S. littoralis. Investigation of the histopathological effect of this metalloprotease showed an extensive damage of S. littoralis epithelium tissue. These results provide an insight to the use of InhA as supplement to Cry toxins to improve the efficacy of B. thuringiensis formulations and to overcome possible resistance problems.


Neuroendocrine carcinoma of the uterus.
Neuroendocrine carcinomas of the cervix and endometrium were reviewed. They have been variously designated as carcinoid, argyrophil cell carcinoma, apudoma, small cell carcinoma, oat cell carcinoma, endocrine carcinoma, and neuroendocrine carcinoma, the last-mentioned term being preferred in this chapter. Adenocarcinomas with neuroendocrine cells are occasionally encountered in the cervix and endometrium. It is generally questioned whether they should be included in the spectrum of neuroendocrine carcinomas, although differential diagnosis between some such tumors of the gastrointestinal tract and neuroendocrine carcinoma is reported to be difficult. Since the majority of neuroendocrine carcinomas of the cervix are highly aggressive, it is important to establish the neuroendocrine nature in the cervical carcinomas. In addition to the characteristic histologic features and argyrophil stainability, immunohistochemical demonstration of several neuroendocrine markers may be helpful in diagnosing neuroendocrine carcinoma of the cervix. Ultrastructural demonstration of neurosecretory granules is almost decisive in establishing the tumor's neuroendocrine nature, but it is not applicable in all cases. Neuroendocrine carcinomas of the cervix have been treated by surgery, radiation therapy, and chemotherapy, but optimal treatment methods have not yet been established because of the rarity of the tumor. Finally, we have described a typical neuroendocrine carcinoma of the cervix and reported some data regarding its experimental study.


Anatomical Connections of the Functionally Defined "Face Patches" in the Macaque Monkey.
The neural circuits underlying face recognition provide a model for understanding visual object representation, social cognition, and hierarchical information processing. A fundamental piece of information lacking to date is the detailed anatomical connections of the face patches. Here, we injected retrograde tracers into four different face patches (PL, ML, AL, AM) to characterize their anatomical connectivity. We found that the patches are strongly and specifically connected to each other, and individual patches receive inputs from extrastriate cortex, the medial temporal lobe, and three subcortical structures (the pulvinar, claustrum, and amygdala). Inputs from prefrontal cortex were surprisingly weak. Patches were densely interconnected to one another in both feedforward and feedback directions, inconsistent with a serial hierarchy. These results provide the first direct anatomical evidence that the face patches constitute a highly specialized system and suggest that subcortical regions may play a vital role in routing face-related information to subsequent processing stages.


Effects of organic matter fraction and compositional changes on distribution of cadmium and zinc in long-term polluted paddy soils.
Soil particulate organic matter (POM) has rapid turnover and metal enrichment, but the interactions between organic matter (OM) and metals have not been well studied. The present study aimed to investigate changes in the OM concentration and composition of the POM fraction and their corresponding effects on metal distribution and extractability in long-term polluted paddy soils. Soil 2000-53 μm POM size fractions had higher contents of C-H and C=O bonds, C-H/C=O ratios and concentrations of fulvic acid (FA), humic acid (HA), cadmium (Cd) and zinc (Zn) than the bulk soils. Cadmium and Zn stocks in soil POM fractions were 24.5-27.9% and 7.12-16.7%, respectively, and were more readily EDTA-extractable. Compared with the control soil, the 2000-250 μm POM size fractions had higher organic carbon concentrations and C/N ratios in the polluted soils. However, there were no significant differences in the contents in C-H and C=O bonds or C-H/C=O ratios of POM fractions among the control, slightly and highly polluted soils. In accordance with the lower contents of C=O bonds and FA and HA concentrations, the Cd and Zn concentrations in 250-53 μm POM size fractions were lower than those in 2000-250 μm POM size fractions. Enrichment of Cd in POM fractions increased with increasing soil pollution level. These results support the view that changes in the OM concentration and the size and composition of POM fractions play a key role in determining the distribution of Cd and Zn in paddy soils.


The role of pH in the intracellular acetylcholine receptor ligand processing.
Previous studies have shown that the internalized AChRs are transported through many vesicular compartments: Golgi associated vesicles, coated vesicles, smooth vesicles, endosome-like structures and lysosomes. These compartments have an acidic pH ranging from 4.5 to 6.5. The pH differences between organelles suggests that these differences may influence the sorting and final expression of AChRs. To test this hypothesis, we measured the number of counts of 125I-alpha BTX or 125I-Mab35 dissociated from myotube membranes containing AChRs as a function of pH. Neither the 125I-alpha BTX nor 125I-Mab35 showed an enhanced dissociation in the pH range 4.0-7.0, whereas lowering the pH to 6.0 or below enhanced the dissociation of 125I-alpha 2-macroglobulin from myotubes. In other experiments using Torpedo membrane we showed that neither 125I-alpha BTX nor 125I-Mab35 appreciably dissociated from the AChR unless the pH was less than 4 or above 11. Double-label studies using a novel membrane permeable acidotropic molecule DAMP (3-(2,4 nitroanilino) 3'amino-N-methyl-dipropylamine), facilitated mapping the pH of the intracellular compartments containing internalized AChRs. This molecule accumulates inside acidic compartments in the cell and has a dinitrophenol (DNP) group recognized by DNP specific antibodies. Cells were treated with 30 micrograms DAMP for 30 min and allowed to internalize Mab35-gold (15 nm) for various periods (0-15 h). At each time point we fixed and washed the cells, and incubated with anti-DNP monoclonal antibodies followed by incubation with anti-mouse IgG and protein A colloidal gold (5 nm). Different sized gold particles allowed us to simultaneously identify the AChR compartments and estimate their pH. Sister cultures were exposed to acidotropic drugs to destroy pH gradients. Under those conditions, AChR delivery to lysosomes was blocked. Our studies show that AChRs are transported through acidic compartments ranging from pH 4.5 to 6.5 and in contrast to other ligands they do not dissociate from the intracellular membranes at low pH.


Major hepatectomy for colorectal metastases: is preoperative portal occlusion an oncological risk factor?
This study investigates oncological risks and benefits of portal occlusion (PO) in major resection for colorectal liver metastases (CLM). Between 1995 and 2004, 107 patients were scheduled for major hepatectomy for CLM. Of these, 53 patients were selected for PO due to insufficient future liver remnant (FLR), and 54 patients had straightforward hepatectomy. Associations of clinicopathologic factors with resectability, and outcome after PO were analyzed. 21 of 53 patients (39.6%) after PO were unresectable. These patients had a significant smaller volume of the FLR than the 32 resected patients after PO (P = .029). In total, 17 patients (80.9%) did not undergo resection due to cancer progression. Among these, 11 patients (52.4%) exhibited either a progression of known metastases located in the occluded lobes, or new metastases in the nonoccluded portion of the liver. In another 4 individuals (19%), the decision against resection resulted from insufficient hypertrophy of the FLR. Following major hepatectomy, the 5-year survival was 43.66%. Although there was a significantly higher rate of extended hepatectomies versus formal hepatectomies (P < .001), more bilobar distributed metastases versus unilobar manifestations (P = .015), and a smaller resection margin (P = .01) in patients who had PO, no adverse effect on mortality, morbidity, recurrence and survival was observed. Unresectability after PO is a major problem that warrants multidisciplinary improvements, and randomization to resection with or without PO remains ethically problematic. However, following adequate patient selection, PO may provide a significant survival benefit for patients with prior unresectable CLM.


Genome-wide identification of microsatellite markers from cultivated peanut (Arachis hypogaea L.).
Microsatellites, or simple sequence repeats (SSRs), represent important DNA variations that are widely distributed across the entire plant genome and can be used to develop SSR markers, which can then be used to conduct genetic analyses and molecular breeding. Cultivated peanut (A. hypogaea L.), an important oil crop worldwide, is an allotetraploid (AABB, 2n = 4× = 40) plant species. Because of its complex genome, genomic marker development has been very challenging. However, sequencing of cultivated peanut genome allowed us to develop genomic markers and construct a high-density physical map. A total of 8,329,496 SSRs were identified, including 3,772,653, 4,414,961, and 141,882 SSRs that were distributed in subgenome A, B, and nine scaffolds, respectively. Based on the flanking sequences of the identified SSRs, a total of 973,984 newly developed SSR markers were developed in subgenome A (462,267), B (489,394), and nine scaffolds (22,323), with an average density of 392.45 markers per Mb. In silico PCR evaluation showed that an average of 88.32% of the SSR markers generated only one in silico-specific product in two tetraploid A. hypogaea varieties, Tifrunner and Shitouqi. A total of 39,599 common SSR markers were identified among the two A. hypogaea varieties and two progenitors, A. duranensis and A. ipaensis. Additionally, an amplification effectiveness of 44.15% was observed by real PCR validation. Moreover, a total of 1276 public SSR loci were integrated with the newly developed SSR markers. Finally, a previously known leaf spot quantitative trait locus (QTL), qLLS_T13_A05_7, was determined to be in a 1.448-Mb region on chromosome A05. In this region, a total of 819 newly developed SSR markers were located and 108 candidate genes were detected. The availability of these newly developed and public SSR markers both provide a large number of molecular markers that could potentially be used to enhance the process of trait genetic analyses and improve molecular breeding strategies for cultivated peanut.


Predicting venous insufficiency in flaps raised on the deep inferior epigastric system using computed tomography (CT) angiography.
Computed Tomography Angiogram (CTA) has become a routine part of pre-operative assessment of vascular anatomy and design in perforator flaps. We conducted a retrospective cohort study of flap raised on the deep inferior epigastric system (DIES) at our institution in order to identify CTA signs that might predict venous congestion in these flaps. 98 consecutive patients who had 124 DIES flaps raised from 2008 to 2012 were studied. Of these 124 flaps, four (3.2%) developed venous congestion. Our results showed that a Superficial Inferior Epigastric Vein (SIEV) that is larger than the DIEV at origin is highly predictive of congestion (5.2 vs 3.5 mm, p = 0.007). The findings of an axial non-arborising superficial system (96.7% vs 0, p < 0.001), without connection to deep system perforators (38.1 vs 88.8%, p < 0.001) and a type I pedicle were also predictive (75 vs 64.2%, p = 0.22). These results show the importance of CTAs as a pre-operative study for the identification of risk factors for venous compromise, and their use should prompt a robust discussion of the risk of flap failure with patients, and contingency planning to augment venous drainage with the superficial system if required.


Interaction between carbamazepine and propoxyphene in man.
This investigation was carried out because of a clinical suspicion of drug interaction between Propoxyphene (PRX) hydrochloride and Carbamazepine (CBZ). Seven out-patients, six suffering from epilepsy and one from trigeminal neuralgia, treated with CBZ alone or in combination with phenobarbitone, received PRX hydrochloride capsules, 65 mg three times a day. Two patients stopped the PRX intake after 2 days due to severe side effects. Three of the remaining patients had symptoms and signs of drug intoxication. Blood samples were examined by thin-layer chromatography. A marked increase (45-77 per cent) in CBZ plasma level was found in all patients on combined treatment of CBZ and PRX. There were no significant changes in CBZ-10,11-epoxide level. The results suggest an inhibition of CBZ metabolism when CBZ and PRX are administered simultaneously.


Vein ablation is an effective treatment for patients with bleeding varicose veins.
Bleeding is a rare but potentially life-threatening complication of varicose veins. There is paucity of literature about patients with varicose veins that present with bleeding and the effectiveness of vein ablation as therapy to prevent recurrent bleeding. This study compares patients treated with vein ablation for bleeding varicose veins with patients treated for venous symptoms other than bleeding. We hypothesize that vein ablation is safe and effective in preventing recurrence of bleeding from varicose veins. A retrospective single-centre review of consecutive patients undergoing vein ablation using radiofrequency in an outpatient office was performed. Patients presenting with bleeding were identified. A random (3:1) group of patients undergoing vein ablation for other venous symptoms and no bleeding was selected as a comparative group (control). The medical records were reviewed for patient characteristics and outcomes. A telephone survey inquiring about intensity of symptoms on a numeric rating scale of 0 to 10 prior and after treatment as well as recurrence of bleeding was also conducted. Patient characteristics and outcomes were compared between the two groups. The incidence of patients with bleeding varicose veins was 3.6% (13/362) of all patients undergoing vein ablation at our center. A total of 26 ablations and 60 ablations were performed in patients with bleeding (n = 13) and controls (n = 39), respectively. There was no difference in age and race, but there was a trend for bleeding to occur more commonly in male patients (61.5% vs 33.3%; P = .073). Patients with bleeding from varicose veins were more likely to have congestive heart failure (P = .013) and present with more advanced venous disease based on CEAP classification (P = .005) compared with the control group. There was no difference between the 2 groups in vein closure (P = .246) or complications (P = .299) after vein ablation. With mean follow-up of 2.26 ± 1.17 years, 85% of patients (n = 11) remained free from bleeding episodes. One patient with recurrent bleeding required additional vein ablation and the second patient had a concomitant ulcer that was treated with compression therapy. Bleeding from varicose veins is rare and more common in patients with congestive heart failure. Bleeding affects patients with higher CEAP scores. Vein ablation is a safe and effective treatment to prevent the recurrence of bleeding.


Experimental studies defining omega-3 fatty acid antiinflammatory mechanisms and abrogation of tumor-related syndromes.
Clinical and experimental evidence has supported a benefit for the inclusion of fish oils (a primary source of omega-3 fatty acids) as a component of a normal healthy diet. Polyunsaturated omega-3 fatty acids have been demonstrated to be of benefit in a number of inflammation-associated disease states, including atherosclerosis, autoimmune disorders, malignancy, and sepsis. The beneficial effects of omega-3 fatty acids are thought to occur through the postulated antiinflammatory actions of omega-3 fats; however, the specific mechanism(s) of action has not been completely defined. In this review, we discuss the recent progress made in our laboratory on defining the mechanisms of omega-3 fatty acids activity.


Long-term follow up and predictive factors for successful outcome of transurethral incision of the bladder neck in women with detrusor underactivity.
Detrusor underactivity (DU) is a common urologic problem. Our previous study revealed the transurethral incision of the bladder neck (TUI-BN) improves short-term voiding efficiency (VE) in female patients with DU. This study focused on the long-term outcomes of TUI-BN and identified the predictive factors of satisfactory outcomes. A total 50 women with DU for whom medical treatment failed underwent TUI-BN. The urodynamic parameters at baseline and follow-up visits were analyzed. Patients with VEs >50% were considered to have satisfactory outcomes. Baseline urodynamic parameters were analyzed as factors predictive of outcomes. After a mean follow up of 61.8 months, 26 of 50 patients had satisfactory outcomes. The mean VE, maximum flow rate, voided volume, detrusor pressure, and postvoid residual volume significantly improved after TUI-BN. A higher intravesical pressure [Pves, odds ratio (OR) = 1.023, p = 0.013] and smaller first sensation of bladder filling (OR = 0.990, p = 0.020) at baseline were predictive factors for satisfactory outcomes. The multivariate analysis revealed that only baseline Pves was a significant predictor of satisfactory outcomes (OR = 1.024, p = 0.038). The receiver operating characteristic curve analysis of baseline Pves showed that the area under the curve was 0.767 (95% confidence interval = 0.624-0.876). The optimal cutoff value of Pves for a satisfactory outcome was 45 cmH2O, which had a specificity of 78.26% and acceptable sensitivity of 73.08%. TUI-BN improved VE in women with DU over the long term. A higher Pves compared to a lower Pves was predictive of satisfactory surgical outcomes.


Intravenous immunoglobulin (i.v. IgG) for previously treated acute or for chronic idiopathic thrombocytopenic purpura (ITP) in childhood: a prospective multicenter study.
In a prospective multicenter study 42 thrombocytopenic (less than 30 X 10(9) platelets/l) children with chronic idiopathic thrombocytopenic purpura (ITP) or with acute ITP, dependent on or refractory to corticosteroids, were given 0.4 g i.v. IgG/kg body weight/day on 5 consecutive days and thereafter once a week if the platelet count fell to less than 20 X 10(9)/l or if the patient bled. After the initial 5 days of i.v. IgG the platelets rose within a mean of 7-8 days to greater than 30 X 10(9)/l in all and to greater than 150 X 10(9)/l in 33 of 42 patients (79%). After a mean observation time of 26.6 months 26 of 42 patients (62%) showed a satisfactory long-term effect, i.e. no need for treatment for at least 6 months without bleeding and with no platelet counts below 20 X 10(9)/l. No difference in response rate was found between children with chronic and those with previously treated acute ITP. These results indicate that i.v. IgG could be used to control emergency situations, e.g. to stop bleeding or to prepare a patient for surgery. I.v. IgG also represents a good alternative to treatment modalities, such as splenectomy and/or the administration of cytostatic immunosuppressants with potentially serious side effects. In addition to the expected transient rise in serum IgG levels, i.v. IgG induced a more prolonged elevation of serum IgM. Platelet associated IgG, elevated before therapy, was correlated with the clinical long-term outcome.


Pressure eye: In-bed contact pressure estimation via contact-less imaging.
Computer vision has achieved great success in interpreting semantic meanings from images, yet estimating underlying (non-visual) physical properties of an object is often limited to their bulk values rather than reconstructing a dense map. In this work, we present our pressure eye (PEye) approach to estimate contact pressure between a human body and the surface she is lying on with high resolution from vision signals directly. PEye approach could ultimately enable the prediction and early detection of pressure ulcers in bed-bound patients, that currently depends on the use of expensive pressure mats. Our PEye network is configured in a dual encoding shared decoding form to fuse visual cues and some relevant physical parameters in order to reconstruct high resolution pressure maps (PMs). We also present a pixel-wise resampling approach based on Naive Bayes assumption to further enhance the PM regression performance. A percentage of correct sensing (PCS) tailored for sensing estimation accuracy evaluation is also proposed which provides another perspective for performance evaluation under varying error tolerances. We tested our approach via a series of extensive experiments using multimodal sensing technologies to collect data from 102 subjects while lying on a bed. The individual's high resolution contact pressure data could be estimated from their RGB or long wavelength infrared (LWIR) images with 91.8% and 91.2% estimation accuracies in PCSefs0.1 criteria, superior to state-of-the-art methods in the related image regression/translation tasks.


[A case of complete androgen insensitivity syndrome with special family history and its genetic analysis].
To report a case of complete androgen insensitivity syndrome with a special family history and its genetic analysis. We studied the medical history, diagnosis and treatment of a case of complete androgen insensitivity syndrome, collected blood samples from the patient and his mother for whole exome sequencing, and analyzed the genetic etiology. The patient presented with "primary amenorrhea" and diagnosed with male pseudohermaphroditism, with the karyotype as 46, XY. Surgery confirmed undescended testes in the abdominal cavity. The androgen level was higher than normal. Whole exome sequencing of the patient and his mother found c.2678C>T (p.P893L) but no other abnormalities, which was considered as a suspected pathogenic mutation of complete androgen insensitivity syndrome. The patient had a "sister" with a similar medical history. c.2678C>T (p.P893L) is a suspected pathogenic mutation of complete androgen insensitivity syndrome, which usually cannot be detected until puberty, making it easy to delay the diagnosis.


Sex Differences in Outcomes After Transcatheter Aortic Valve Replacement: A POPular TAVI Subanalysis.
Stroke and bleeding are complications after transcatheter aortic valve replacement (TAVR). A higher incidence of bleeding and stroke has been reported in women, but the role of antithrombotic management pre- and post-TAVR has not been studied. The study sought to compare bleeding and ischemic complications after TAVR between women and men stratified by antiplatelet and oral anticoagulant (OAC) regimen. The POPular TAVI (Antiplatelet Therapy for Patients Undergoing Transcatheter Aortic Valve Implantation) trial was a randomized clinical trial to test the hypothesis that monotherapy with aspirin or OAC after TAVR is safer than the addition of clopidogrel. The primary endpoints of interest of this post hoc subanalysis were: 1) all bleeding; and 2) a composite of ischemic events consisting of stroke and myocardial infarction. Secondary endpoints were: 1) nonprocedural bleeding; 2) major or life-threatening bleeding; 3) minor bleeding; 4) stroke; 5) myocardial infarction; and 6) all-cause death. A total of 978 patients (466 [47.6%] women) were included in this study. All bleeding and the composite of myocardial infarction and stroke rates were similar between sexes (all bleeding: 106 [22.8%] women vs 121 [23.6%] men; P = 0.815; ischemic events: 26 [5.6%] vs 36 [7.0%]; P = 0.429). However, major or life-threatening bleeding occurred more often in women (58 [12.5%]) vs men (38 [7.4%]) (P = 0.011), most of which were access site bleedings. The use of aspirin pre- and post-TAVR increased major or life-threatening bleeding in women but not in men. After TAVR, overall bleeding and ischemic outcomes were similar between women and men. However, women had more major or life-threatening bleedings, especially those receiving aspirin pre- and post-TAVR.


Analysis of interactions between intraflagellar transport proteins.
Intraflagellar transport (IFT) involves the movement of large proteinaceous particles or trains along the length of ciliary and flagellar axonemal microtubules. The particles contain multiple copies of two protein complexes. As isolated from the flagellated model organism, Chlamydomonas reinhardtii, IFT A contains 6 distinct gene products while IFT B contains at least 13 distinct gene products. To better understand the architecture of these two complexes, a multifaceted approach has been employed to identify subcomplexes and specific protein-protein interactions. The high biochemical yields afforded with Chlamydomonas preparations have allowed traditional biochemical approaches including chemical cross-linking and disruption of native complexes, which, in the case of IFT B, have revealed a core subcomplex retaining nine of the B subunits. Complementing these results are molecular approaches including two-hybrid screenings and heterologous expression that have identified specific protein-protein interactions. Lastly, genetic approaches utilizing Chlamydomonas IFT mutants have shown how the loss of specific subunits perturb the complexes and, in the case of IFT A, they have revealed a core subcomplex containing half of the A subunits.


Scoping Review on Risk Factors and Methods for the Prevention of Bovine Respiratory Disease Applicable to Cow-Calf Operations.
The presented scoping review summarizes the available research evidence and identifies gaps in knowledge for bovine respiratory disease (BRD) prevention. Published literature on BRD from 1990 to April 2021 was searched in online databases, including Medline, CAB Abstracts, Scopus, Biosis, and Searchable Proceedings of Animal Conferences. Citations were systematically evaluated in a three-stage approach using commercial software and summarized in a scoping review format. A total of 265 publications were included in this review with herd/farm management (27.9%) as the most prevalent factors studied, followed by metaphylaxis (24.5%), vaccinations (24.1%), diet formulations, and nutritional supplementations (17.7%), animal characteristics (10.2%), and less common interventions and risk factors (6.4%). A high proportion of studies under herd/farm management (73%), metaphylaxis (86%), vaccinations (70%), animal characteristics (78%), and less common interventions and risk factors (59%) showed either significant effects on reducing BRD morbidity or significant differences of BRD between treatments. However, diet and nutritional supplementations reduced BRD only in 30% of research publications. Most studies on BRD were performed in feedlot populations, and more studies in cow-calf populations are needed. We further suggest meta-analyses on the use of yeast and trace mineral supplementation, and nitric oxide-releasing solution for BRD prevention.


The impact of chronic disease management on primary care doctors in Switzerland: a qualitative study.
Patient-centeredness and therapeutic relationship are widely explored as a means to address the challenge of chronic disease and multi-morbidity management, however research focusing on the perspective of doctors is still rare. In this study, we aimed to explore the impact of the patient's chronic disease(s) on their healthcare provider. A qualitative approach was taken using semi-structured interviews with general practitioners working in outpatient clinics either in individual practices or in a hospital setting in Geneva, Switzerland. Codes were developed through an iterative process and using grounded theory an inductive coding scheme was performed to identify the key themes. Throughout the analysis process the research team reviewed the analysis and refined the coding scheme. Twenty interviews, 10 in each practice type, allowed for saturation to be reached. The following themes relevant to the impact of managing chronic diseases emerge around the issue of feeling powerless as a doctor; facing the patient's socio-economic context; guidelines versus the reality of the patient; time; and taking on the patient's burden. Primary care practitioners face an emotional burden linked with their powerlessness and work conditions, but also with the empathetic bond with their patients and their circumstances. Doctors seem poorly prepared for this emotional strain. The health system is also not facilitating this with time constraints and guidelines unsuitable for the patient's reality. Chronic disease and multi-morbidity management is a challenge for healthcare providers. This has its roots in patient characteristics, the overall health system and healthcare providers themselves. Structural changes need to be implemented at different levels: medical education; health systems; adapted guidelines; leading to an overall environment that favors the development of the therapeutic relationship.


Neural encoding with unsupervised spiking convolutional neural network.
Accurately predicting the brain responses to various stimuli poses a significant challenge in neuroscience. Despite recent breakthroughs in neural encoding using convolutional neural networks (CNNs) in fMRI studies, there remain critical gaps between the computational rules of traditional artificial neurons and real biological neurons. To address this issue, a spiking CNN (SCNN)-based framework is presented in this study to achieve neural encoding in a more biologically plausible manner. The framework utilizes unsupervised SCNN to extract visual features of image stimuli and employs a receptive field-based regression algorithm to predict fMRI responses from the SCNN features. Experimental results on handwritten characters, handwritten digits and natural images demonstrate that the proposed approach can achieve remarkably good encoding performance and can be utilized for "brain reading" tasks such as image reconstruction and identification. This work suggests that SNN can serve as a promising tool for neural encoding.


Antimicrobial Selection for Transurethral Procedures Across the United States: A State-by-State Antibiogram Evaluation.
To evaluate optimal regimens for perioperative antimicrobial prophylaxis in transurethral procedures by examining antimicrobial susceptibility patterns in the United States. Through several methods, we attempted to attain an antibiogram for each state. We focused on microbes known to cause infections after transurethral surgeries and antibiotics referred to in current or prior recommendations and compared susceptibility rates across states using Kruskal Walis tests and the Dwass, Steel, Critchlow-Fligner tests. We also examined susceptibility to (non-ceftazidime) third generation cephalosporins. Data is included from 40 states. For each microbe studied, there was significant variability in sensitivity to antibiotics studied. Current first line recommendations for antimicrobial prophylaxis include first generation cephalosporins with 82%, 80%, and 87% mean coverage for E coli, Proteus, and Klebsiella respectively and trimethoprim-sulfamethoxazole with 74%, 80%, and 93% coverage, respectively. Susceptibility to aminoglycosides is 91%, 92%, and 96%, respectively and to third generation cephalosporin, it is 92%, 99%, and 94%. Current first line recommended antimicrobials for prophylaxis in transurethral procedures provide overall poor predicted coverage based on our database of antibiograms. Alternatives exist that have higher predicted susceptibility, though clinical significance of this and risk of resultant antimicrobial resistance is unknown. Urologists should consider local patterns when selecting antimicrobial prophylaxis for their patients.


Pharmacokinetics, Safety, and Tolerability of Imipenem/Cilastatin/Relebactam in Children with Confirmed or Suspected Gram-Negative Bacterial Infections: A Phase 1b, Open-Label, Single-Dose Clinical Trial.
Imipenem/cilastatin/relebactam is approved for the treatment of serious gram-negative bacterial infections in adults. This study assessed the pharmacokinetics (PK), safety, and tolerability of a single dose of imipenem/cilastatin/relebactam (with a fixed 2:1 ratio of imipenem/cilastatin to relebactam, and with a maximum dose of 15 mg/kg imipenem and 15 mg/kg cilastatin [≤500 mg imipenem and ≤500 mg cilastatin] and 7.5 mg/kg relebactam [≤250 mg relebactam]) in children with confirmed/suspected gram-negative bacterial infections receiving standard-of-care antibacterial therapy. In this phase 1, noncomparative study (ClinicalTrials.gov identifier, NCT03230916), PK parameters from 46 children were analyzed using both population modeling and noncompartmental analysis. The PK/pharmacodynamic (PD) target for imipenem was percent time of the dosing interval that unbound plasma concentration exceeded the minimum inhibitory concentration (%fT>MIC) of ≥30% (MIC = 2 mcg/mL). For relebactam, the PK/PD target was a free drug area under the plasma concentration-time curve (AUC) normalized to MIC (at 2 mcg/mL) of ≥8.0 (equivalent to an AUC from time zero extrapolated to infinity of ≥20.52 mcg·h/mL). Safety was assessed up to 14 days after drug infusion. For imipenem, the ranges for the geometric mean %fT>MIC and maximum concentration (Cmax ) across age cohorts were 56.5%-93.7% and 32.2-38.2 mcg/mL, respectively. For relebactam, the ranges of the geometric mean Cmax and AUC from 0 to 6 hours across age cohorts were 16.9-21.3 mcg/mL and 26.1-55.3 mcg·h/mL, respectively. In total, 8/46 (17%) children experienced ≥1 adverse events (AEs) and 2/46 (4%) children experienced nonserious AEs that were deemed drug related by the investigator. Imipenem and relebactam exceeded plasma PK/PD targets; single doses of imipenem/cilastatin/relebactam were well tolerated with no significant safety concerns identified. These results informed imipenem/cilastatin/relebactam dose selection for further pediatric clinical evaluation.


Integrating angiogenesis signature and tumor mutation burden for improved patient stratification in immune checkpoint blockade therapy for muscle-invasive bladder cancer.
Muscle-invasive bladder cancer (MIBC) patients have benefitted greatly from immune checkpoint blockade (ICB) therapy. However, there is a pressing need to identify factors underlying the heterogeneity of clinical responses to ICB. We conducted a study on 848 MIBC patients from 4 independent cohorts to investigate the key biological characteristics affecting ICB responses. The IMvigor210 cohort (n = 234) was used to identify the key factor, followed by exploration of the correlation between tumor angiogenesis and immune suppression in the IMvigor210, TCGA (n = 391), and UNC-108 (n = 89) cohorts. The ZSHS cohort (n = 134) was used for validation. Additionally, we integrated angiogenesis signature with tumor mutation burden (TMB) to decipher the heterogeneity of clinical outcomes to ICB in MIBC patients. Our analysis revealed that nonresponders to PD-L1 blockade were enriched with angiogenesis signature. Furthermore, we observed a correlation between angiogenesis signature and decreased neoantigen load, downregulated T-cell antigen recognition, and noninflamed immunophenotype. We identified a subgroup of patients resistant to ICB, characterized by high angiogenesis signature and low tumor mutation burden (TMB), and found the activation of TGF-β signaling and downregulation of T-cell cytolytic signatures in this subgroup. The study concluded that angiogenesis signature is closely associated with an immunosuppressive microenvironment, leading to resistance to ICB therapy in MIBC patients. The study further suggested that the combination of angiogenesis signature and TMB can serve as an integrated biomarker for better stratification of patients' clinical outcomes to ICB therapy.


Development of gellan gum containing formulations for transdermal drug delivery: Component evaluation and controlled drug release using temperature responsive nanogels.
Enhancing skin permeation is important for development of new transdermal drug delivery formulations. This is particularly relevant for non-steroidal anti-inflammatory drugs (NSAIDs). To address this, semisolid gel and solid hydrogel film formulations containing gellan gum as a gelling agent were developed and the effects of penetration enhancers (dimethyl sulfoxide, isopropyl alcohol and propylene glycol) on transport of the NSAID diclofenac sodium was quantified. A transwell diffusion system was used to accelerate formulation development. After 4h, diclofenac flux from a superior formulation of the semisolid gel or the solid hydrogel film was 130±11μg/cm(2)h and 108±7μg/cm(2)h, respectively, and significantly greater than that measured for a currently available diclofenac sodium topical gel (30±4μg/cm(2)h, p<0.05) or solution formulation (44±6μg/cm(2)h, p<0.05) under identical conditions. Over 24h diclofenac transport from the solid hydrogel film was greater than that measured for any new or commercial diclofenac formulation. Entrapment of temperature-responsive nanogels within the solid hydrogel film provides temperature-activated prolonged release of diclofenac. Diclofenac transport was minimal at 22°C, when diclofenac is entrapped within temperature-responsive nanogels incorporated into the solid hydrogel film, but increased 6-fold when the temperature was increased to skin surface temperature of 32°C. These results demonstrate the feasibility of the semisolid gel and solid hydrogel film formulations that can include thermo-responsive nanogels for development of transdermal drug formulations with adjustable drug transport kinetics.


Overexpressed GRP78 affects EMT and cell-matrix adhesion via autocrine TGF-β/Smad2/3 signaling.
Glucose-regulated protein of 78kD (GRP78) is a multifunctional protein belonging to the heat shock protein 70 family. Overexpression of GRP78 triggered by environmental and physiological stresses is positively correlated with the occurrence and progression of various tumors, but the molecular mechanisms have not been well established. The present study indicated that overexpression of GRP78 in colon cancer cells could promote cell-matrix adhesion through the upregulation of fibronectin, integrin-β1 and phosphorylated FAK. Meanwhile, it resulted in a visible epithelial-mesenchymal transition in DLD1 cells, and the Snail-2 played the key role during the process. More importantly, the data indicated that GRP78 overexpression facilitated the expression and secretion of TGF-β1, which further activated the downstream Smad2/3 signaling module to effectuate the cell-matrix adhesion and epithelial-mesenchymal transition. Taken together, this study provides a novel molecular mechanism involving in the effects of GRP78 on colon cancer metastasis.


Difficulties Facing Junior Physicians and Solutions Toward Delivering End-of-Life Care for Patients with Cancer: A Nationwide Survey in Japan.
Junior physicians' perceived difficulty in end-of-life care of patients with cancer has not been structurally investigated; therefore, current challenges and solutions in this area remain unknown. To identify some difficulties junior physicians face in delivering end-of-life care for patients with cancer and to clarify the support required to reduce these difficulties. A nationwide survey was conducted in over 300 institutions selected randomly from 1037 clinical training hospitals in Japan. From each of these institutions, two resident physicians of postgraduate year (PGY) 1 or 2, two clinical fellows of PGY 3-5, and an attending physician were requested to respond to the survey. The survey investigated issues regarding end-of-life care using the palliative care difficulties scale with two additional domains ("discussion about end-of-life care" and "death pronouncement"). Items related to potential solutions for alleviating the difficulties as well were investigated. A total of 198 resident physicians, 134 clinical fellows, and 96 attending physicians responded to the survey (response rate: 33.0%, 22.3%, and 32.0%). The results revealed that junior physicians face difficulties within specific domains of end-of-life care. The most challenging domain comprised communication and end-of-life discussion with patients and family members, symptom alleviation, and death pronouncement. The most favored supportive measure for alleviating these difficulties was mentorship, rather than educational opportunities or resources regarding end-of-life care. The findings of this study reveal the need for further effort to enrich the mentorship and support systems for junior physicians delivering end-of-life care.


Nebulized tranexamic acid for recurring hemoptysis in critically ill patients: case series.
Hemoptysis is a clinical condition encountered in the emergency department (ED) and must be managed and investigated urgently to maintain the patient's hemostasis. The management of hemoptysis depends on treating the underlying cause. Tranexamic acid (TXA) is an anti-fibrinolytic drug used to systemically control bleeding. There are a few studies available that investigate the use of nebulized tranexamic acid for hemoptysis with contradictory results. Our paper demonstrates three cases where patients presented with significant hemoptysis and had significant improvement in symptoms following the administration of nebulized tranexamic acid. The overall need for blood transfusion was reduced. Three patients presented to the emergency room for evaluation of hemoptysis. All three patients had different underlying pathologies resulting in their hemoptysis and were monitored in the ICU. Initial conventional medical therapies including the correction of coagulopathy and discontinuing offending agents were utilized for treatment. After persistent symptoms, nebulized TXA at a dose of 500 mg three times a day was administered. The patients were all discharged from the hospital with improvement in their symptoms. Tranexamic acid may be considered in the treatment of hemoptysis regardless of the underlying cause. This may be utilized pending further workup and investigation into the underlying source of the bleeding.


Interfacial tension effects on the properties of PLGA microparticles.
Many types of long-acting injectables, including in situ forming implants, preformed implants, and polymeric microparticles, have been developed and ultimately benefited numerous patients. The advantages of using long-acting injectables include greater patient compliance and more steady state drug plasma levels for weeks and months. However, the development of long-acting polymeric microparticles has been hampered by the lack of understanding of the microparticle formation process, and thus, control of the process. Of the many parameters critical to the reproducible preparation of microparticles, the interfacial tension (IFT) effect is an important factor throughout the process. It may influence the droplet formation, solvent extraction, and drug distribution in the polymer matrix, and ultimately drug release kinetics from the microparticles. This mini-review is focused on the IFT effects on drug-loaded poly(lactic-co-glycolic acid) (PLGA) microparticles.


Retention and stability--taking various treatment parameters into account.
In order to assess stability after orthodontic treatment, 132 patients who had been treated by one orthodontist in private practice were examined 6 years on average after completion of their treatment. Therapeutically induced movements and post-therapeutic changes were measured using dental casts, and the number of cases which had relapsed was calculated as a percentage of the individual measurements. The extent of post-therapeutic changes in patients with and without long-term retention was analyzed together with possible correlations with retention time and retainer type. Furthermore, the influence of gender, Angle classification, treatment-induced changes, initiation, type and duration of therapy, and extraction of premolars on the development of relapse was also investigated. Some degree of relapse was recorded in 13% of the measurements on average, even in patients with some form of long-term retention. However, it may be possible to reduce the relapse rate by taking account of the following criteria: Retention time should be increased in cases of short-term therapy, since relapse was found to occur more often on average (19%) when the treatment time was less than 3 years than when it was longer than 4 years (13%). As the highest relapse rate registered was 24% when therapy was started between the ages of 9 and 12 years, but was up to 42% in younger and older patients, there should be more extensive retention in these latter cases. Where there is a risk of relapse in the anterior arch, fixed lingual retainers should be given preference over removable ones. This is especially applicable to male patients and to non-extraction patients, as relapses in the anterior segment occurred more often or were more marked in these cases. The use of removable retainers is necessary when the transverse stability of the buccal segment is at risk. When only fixed retainers were used in the anterior area, relapses were recorded 6-31% more frequently in the interpremolar distance in the maxilla (21%) and the mandible (35%), and in the lower intermolar distance (27%). In particular, the use of a removable mandibular retainer should not be dispensed with after bicuspid extractions, transverse expansion and, in female patients, in the lower jaw, as relapse in the buccal segment was more marked or more common in such cases. On the basis of our clinical findings and of earlier studies, the retention time should be at least 2 years. The retainer type used has been found to be just as important as the retention time. If optimum relapse prevention is aimed at, fixed maxillary and mandibular retainers in the anterior region should be combined with a removable retainer and worn until the patients reach their late twenties.


The amino acid/auxin:proton symport permease family.
Amino acids and their derivatives are transported into and out of cells by a variety of permease types which comprise several distinct protein families. We here present a systematic analysis of a group of homologous transport proteins which together comprise the eukaryotic-specific amino acid/auxin permease (AAAP) family (TC #2. 18). In characterizing this family, we have (1) identified all sequenced members of the family, (2) aligned their sequences, (3) identified regions of striking conservation, (4) derived a family-specific signature sequence, and (5) proposed a topological model that appears to be applicable to all members of the family. We have also constructed AAAP family phylogenetic trees and dendrograms using six different programs that allow us to trace the evolutionary history of the family, estimate the relatedness of proteins from dissimilar organismal phyla, and evaluate the reliability of the different programs available for phylogenetic studies. The TREE and neighbor-joining programs gave fully consistent results while CLUSTAL W gave similar but non-identical results. Other programs gave less consistent results. The phylogenetic analyses reveal (1) that many plant AAAP family proteins arose recently by multiple gene duplication events that occurred within a single organism, (2) that some plant members of the family with strikingly different specificities diverged early in evolutionary history, and (3) that AAAP family proteins from fungi and animals diverged from the plant proteins long ago, possibly when animals, plants and fungi diverged from each other. The Neurospora protein nevertheless exhibits overlapping specificity with those found in plants. Preliminary evidence is presented suggesting that proteins of the AAAP family are distantly related to proteins of the large ubiquitous amino acid/polyamine/choline family (TC #2.3) as well as to those of two small bacterial amino acid transporter families, the ArAAP family (TC #2.42) and the STP family (TC #2.43).


Molecular cloning and characterization of cDNAs encoding cinnamoyl CoA reductase (CCR) from barley (Hordeum vulgare) and potato (Solanum tuberosum).
Cinnamoyl CoA reductase catalyzes the reduction of cinnamic acid CoA esters into their corresponding aldehydes, the first step of the phenylpropanoid pathway specifically dedicated to monolignol biosynthesis. Two cDNA clones encoding cinnamoyl CoA reductase (CCR) have been isolated from Hordeum vulgare (HvCCR) and Solanum tuberosum (StCCR1). Amino acid sequence alignment revealed the motif, NWYCY, representing the active site of CCR, conserved in both the encoded HvCCR and StCCR1 amino acid sequences. The HvCCR encoded protein possesses substantial homology with CCRs isolated and cloned form other sources; the highest identity (89%) was observed with CCR from fescue (Festuca arundicinea). Expression analysis by RT-PCR demonstrated that the HvCCR gene is expressed in barley stem and root tissue while no expression is detected in leaves and flowers. This expression pattern suggests that HvCCR is involved in constitutive lignification. Transcripts of StCCR1 were detected in potato root, leaf and also in stem although at a very low level.


Synaptic strength regulated by palmitate cycling on PSD-95.
Dynamic regulation of AMPA-type glutamate receptors represents a primary mechanism for controlling synaptic strength, though mechanisms for this process are poorly understood. The palmitoylated postsynaptic density protein, PSD-95, regulates synaptic plasticity and associates with the AMPA receptor trafficking protein, stargazin. Here, we identify palmitate cycling on PSD-95 at the synapse and find that palmitate turnover on PSD-95 is regulated by glutamate receptor activity. Acutely blocking palmitoylation disperses synaptic clusters of PSD-95 and causes a selective loss of synaptic AMPA receptors. We also find that rapid glutamate-mediated AMPA receptor internalization requires depalmitoylation of PSD-95. In a nonneuronal model system, clustering of PSD-95, stargazin, and AMPA receptors is also regulated by ongoing palmitoylation of PSD-95 at the plasma membrane. These studies suggest that palmitate cycling on PSD-95 can regulate synaptic strength and regulates aspects of activity-dependent plasticity.


Counting Kmers for Biological Sequences at Large Scale.
Counting the abundance of all the distinct kmers in biological sequence data is a fundamental step in bioinformatics. These applications include de novo genome assembly, error correction, etc. With the development of sequencing technology, the sequence data in a single project can reach Petabyte-scale or Terabyte-scale nucleotides. Counting demand for the abundance of these sequencing data is beyond the memory and computing capacity of single computing node, and how to process it efficiently is a challenge on a high-performance computing cluster. As such, we propose SWAPCounter, a highly scalable distributed approach for kmer counting. This approach is embedded with an MPI streaming I/O module for loading huge data set at high speed, and a counting bloom filter module for both memory and communication efficiency. By overlapping all the counting steps, SWAPCounter achieves high scalability with high parallel efficiency. The experimental results indicate that SWAPCounter has competitive performance with two other tools on shared memory environment, KMC2, and MSPKmerCounter. Moreover, SWAPCounter also shows the highest scalability under strong scaling experiments. In our experiment on Cetus supercomputer, SWAPCounter scales to 32,768 cores with 79% parallel efficiency (using 2048 cores as baseline) when processing 4 TB sequence data of 1000 Genomes. The source code of SWAPCounter is publicly available at https://github.com/mengjintao/SWAPCounter.


Haemorrhagic adrenal pseudocyst: a case report.
A case of a non-functioning adrenal pseudocyst is reported herein. The key role of sonography and abdominal CT in the diagnosis of this rare retroperitoneal cystic lesion is highlighted. A possible etiological relationship with the trauma of parturition is proposed in our patient.


The UDP-GalNAcA biosynthesis genes gna-gne2 are required to maintain cell envelope integrity and in vivo fitness in multi-drug resistant Acinetobacter baumannii.
Acinetobacter baumannii infects a wide range of anatomic sites including the respiratory tract and bloodstream. Despite its clinical importance, little is known about the molecular basis of A. baumannii pathogenesis. We previously identified the UDP-N-acetyl-d-galactosaminuronic acid (UDP-GalNAcA) biosynthesis genes, gna-gne2, as being critical for survival in vivo. Herein, we demonstrate that Gna-Gne2 are part of a complex network connecting in vivo fitness, cell envelope homeostasis and resistance to antibiotics. The ∆gna-gne2 mutant exhibits a severe fitness defect during bloodstream infection. Capsule production is abolished in the mutant strain, which is concomitant with its inability to survive in human serum. In addition, the ∆gna-gne2 mutant was more susceptible to vancomycin and unable to grow on MacConkey plates, indicating an alteration in cell envelope integrity. Analysis of lipid A by mass spectrometry showed that the hexa- and hepta-acylated species were affected in the gna-gne2 mutant. Finally, the ∆gna-gne2 mutant was more susceptible to several classes of antibiotics. Together, this study demonstrates the importance of UDP-GalNAcA in the pathobiology of A. baumannii. By interrupting its biosynthesis, we showed that this molecule plays a critical role in capsule biosynthesis and maintaining the cell envelope homeostasis.


The monitoring, prevention and treatment of sub-acute ruminal acidosis (SARA): a review.
Sub-acute ruminal acidosis (SARA) has become an increasing problem in well-managed, high yielding dairy herds and the monitoring of groups of cows for signs of the condition is now crucial. Rumenocentesis may be ethically questionable but the technique remains the most reliable means of diagnosing SARA. Continuous measurement of ruminal pH may however be possible in the future. Parameters reflecting the metabolic acidosis caused by SARA are also promising tools, and measurement of milk fat content may be useful in individual mid-lactation cows although it is less valuable for bulk tank milk samples. The prevention of SARA includes the establishment of feeding and management guidelines seeking to minimize rumen acidotic load. Regular monitoring may facilitate early recognition of the condition and limit economic losses. Some degree of SARA may however be inevitable and presents a challenge to the dairy industry as consumers become increasingly concerned about the welfare of production animals.


Health-related quality of life 90 days after stroke assessed by the International Consortium for Health Outcome Measurement standard set.
Stroke has detrimental effects in multiple health domains not captured by routine scales. The International Consortium for Health Outcome Measurement has developed a standardized set for self-reported assessment to overcome this limitation. The aim was to assess this set in acute stroke care. Consecutive patients with acute ischaemic stroke, transient ischaemic attack or intracerebral hemorrhage were enrolled. Demographics, living situation and cardiovascular risk factors were collected from medical records and interviews. The Patient-reported Outcomes Measurement Information System 10-Question Short Form (PROMIS-10) and the Patient Health Questionnaire-4 (PHQ-4) were conducted 90 days after admission. Linear and logistic regression analyses were used to identify predictors of outcome. The study is registered at ClinicalTrials.gov, NCT03795948. In all, 1064 patients were enrolled; mean age was 71.6 years, 51% were female, and median National Institutes of Health Stroke Scale (NIHSS) on admission was 3. Diagnosis was acute ischaemic stroke in 74%, transient ischaemic attack in 20% and intracerebral hemorrhage in 6%. 673 patients were available for outcome evaluation at 90 days; of these 90 (13%) had died. In survivors, t scores of PROMIS-10 physical and mental health were 40.3 ± 6.17 and 44.3 ± 8.63, compared to 50 ± 10 in healthy populations. 16% reported symptoms indicating depression or anxiety on the PHQ-4. Higher NIHSS, prior stroke and requiring help pre-stroke predicted lower values in physical and mental health scores. Higher NIHSS and diabetes were associated with anxiety or depression. Integrated in the routine of acute stroke care, systematic assessment of patient-reported outcomes reveals impairments in physical and mental health. Main predictors are severity of stroke symptoms and comorbidities such as hypertension and diabetes.


Establishment of correlation between in-silico and in-vitro test analysis against Leishmania HGPRT to inhibitors.
Hypoxanthine Phosphoribosyltransferase (HGPRT; EC 220.127.116.11) is a central enzyme in the purine recycling pathway of all protozoan parasites. Protozoan parasites cannot synthesize purine bases (DNA/RNA) which is essential for survival as lack of de-novo pathway. Thus its good target for drug design and discovery as inhibition leads to cessation of replication. PRTase (transferase enzyme) has common PRTase type I folding pattern domain for its activities. Genomic studies revealed the sequence pattern and identified highly conserved residues that catalyzed the reaction in protozoan parasites. A recombinant protein has 24 kDa molecular mass (rLdHGPRT) was cloned, expressed and purified for testing of guanosine monophosphate (GMP) analogous compounds in-vitro by spectroscopically to the rLdHGPRT, lysates protein and MTT assay on Leishmania donovani. The predicted inhibitors of different libraries were screen into FlexX. The reported inhibitors were tested in-vitro. The 2'-deoxyguanosine 5'-diphosphate (DGD) (IC50 value 12.5 μM) is two times more effective when compared to guanosine-5'-diphosphate sodium (GD). Interestingly, LdHGPRT complex has shown stable after 24 ns in molecular dynamics simulation with interacting amino acids are Glu125, Ile127, Lys87 and Val186. QSAR studies revealed the correlation between predicted and experimental values has shown R2 0.998. Concludes that inversely proportional to their docked score with activities.


Treatment of angioblastoma with recombinant interferon-alpha 2.
Interferon-alpha 2 has been used successfully to treat angiomatous lesions such as Kaposi sarcoma and life-threatening hemangiomas, possibly by its antiangiogenetic activity. We report the successful use of this agent in a child with an angioblastoma of the right leg.


[Atypical onset of Churg and Strauss syndrome in a child].
We report the case of a 13-year-old boy who had been treated since the age of 6 for moderate asthma. Except asthma, his past medical history was uneventful. The patient was referred for the sudden onset of bilateral leg edemas with peripheral purpuric lesions. Blood tests showed increased blood eosinophilia (9000/mm(3)) with no fever. The antineutrophil cytoplasmic antibodies (ANCA) were negative. The skin biopsy showed extensive ischemic subcutaneous necrosis related to necrotizing vasculitis. The general secondary symptoms occurred with multiorgan involvement (pulmonary infiltrates, peripheral neuropathy, gastrointestinal tract symptoms, and arthralgia). Genital infiltration was also noted. The child's general health was preserved. Neither cardiac nor renal involvement were found. The patient showed favorable clinical progression after oral prednisone therapy.


[Cause and regulation of pain during root canal therapy].
In stomatology, root canal therapy is a commonly used and effective treatment for dental pulp diseases and periapical diseases. However, pain may occur during or after treatment and may severely affect patients. This article aimed to analyze the mechanism and cause of pain during root canal therapy, which may reduce or relieve pain.


Fatigue in patients with cancer.
This paper reviews current knowledge regarding cancer-related fatigue assessment, prevalence, mechanisms and management. Most quality of life questionnaires contain at least some items pertaining to fatigue and a number of more specific self-assessment tools have now also been developed. As a results, there is a growing body of literature which documents the extent and severity of fatigue in cancer populations. Unfortunately most of these studies are uncontrolled and do not, therefore, provide an accurate estimate of the prevalence or severity of cancer fatigue relative to that found in the general population. Data from controlled studies are limited and the results are conflicting. Cross-sectional studies suggest that fatigue is the result of a combination of physical and psychological causes. Although no one treatment is proven to alleviate cancer-related fatigue a number of strategies show therapeutic promise.


Computational study of energetic nitrogen-rich derivatives of 1,4-bis(1-azo-2,4-dinitrobenzene)-iminotetrazole.
The heats of formation (HOFs), electronic structure, energetic properties, and thermal stabilities for a series of 1,4-bis(1-azo-2,4-dinitrobenzene)-iminotetrazole derivatives with different substituents and substitution positions and numbers of nitrogen atoms in the nitrobenzene rings were studied using the DFT-B3LYP method. All the substituted compounds have higher HOFs than their parent compounds. As the number of nitrogen atoms in the nitrobenzene ring increases, the HOFs of the derivatives with the same substituent rise gradually. Replacing carbon atoms in the nitrobenzene with nitrogen atoms to form N-N bonds is very helpful in improving their HOFs. Most of the substituted compounds have higher HOMO-LUMO gaps than the corresponding unsubstituted compounds. Substitution of the -NO₂, -NF₂, or -ONO₂ group and an increase in the number of nitrogen atoms in the nitrobenzene rings are useful for enhancing their detonation performance. The substituents' substitution is not favorable for improving thermal stability. Considering detonation performance and thermal stability, five compounds may be considered potential candidates for high energy density compounds (HEDCs).


A single LC-MS/MS validated method for tulathromycin quantification in plasma, seminal plasma, and urine to be applied in a pharmacokinetic study in bull.
Tulathromycin is a macrolide antibiotic generally used for the treatment of respiratory diseases in cattle and swine. This work proposes an improvement of a previously published LC-MS/MS method for tulathromycin determination in pig serum, here validated in three different bull matrices: plasma, seminal plasma, and urine. The approach is based on a quick protein precipitation with acetonitrile, filtration, and sample dilution before injection, allowing to rapidly process large batches of samples. Analytes separation was obtained using a BEH C18 (50 × 2.1 mm, 1.7 μm) column, maintained at 40°C with a chromatographic run of 5 min. The method was fully validated over concentration ranges suitable for field levels of tulathromycin found in each matrix (0.01-1 μg/ml for plasma, 0.05-5 μg/ml for seminal plasma, and 0.1-10 μg/ml for urine), showing good linearity during each day of testing (R2 always >0.99). Accuracy and precision were within ±15% at all QC concentrations in all the three matrices. Furthermore, the use of tulathromycine-d7 as internal standard mitigated the potential impacts of matrix effect. The validated technique was successfully applied to samples collected during a pharmacokinetic study in bulls, allowing to monitor tulathromycin concentrations over time in the three matrices. To our knowledge, this is the first validated approach for LC-MS/MS quantification of tulathromycin in seminal plasma and urine.


Obsessive-compulsive disorder.
Obsessive-compulsive disorder is a heterogeneous cluster of syndromes that share aspects of both anxiety and affective disorders. Obsessive-compulsive disorder is epidemiologically and phenomenologically distinct from the compulsive character. Although both genetic and neuropsychological data suggest some biologic basis to obsessive-compulsive disorder, there is still insufficient information in both of these areas. Treatment with clomipramine, a tricyclic antidepressant, has proved useful for obsessional patients either as an adjunct to behavior therapy or as a primary treatment for patients who are not amenable to behavioral interventions.


Harmonizing Ethno-Regionally Diverse Datasets to Advance the Global Epidemiology of Dementia.
Understanding dementia and cognitive impairment is a global effort needing data from multiple sources across diverse ethno-regional groups. Methodological heterogeneity means that these data often require harmonization to make them comparable before analysis. We discuss the benefits and challenges of harmonization, both retrospective and prospective, broadly and with a focus on data types that require particular sorts of approaches, including neuropsychological test scores and neuroimaging data. Throughout our discussion, we illustrate general principles and give examples of specific approaches in the context of contemporary research in dementia and cognitive impairment from around the world.