Enhanced reconstruction of rat calvarial defects achieved by plasma-treated electrospun scaffolds and induced pluripotent stem cells.
Tissue engineering with a combination of stem cells and nanofibrous scaffolds has attracted interest with regard to bone regeneration applications. In the present study, human induced pluripotent stem cells (iPSCs) were cultured on polymeric nanofibrous polyethersulfone (PES) with and without plasma treatment. The capacity of PES and plasma-treated PES (Plasma-PES) scaffolds to support the proliferation and osteogenic differentiation of iPSCs was investigated by MTT assay and for common osteogenic markers such as alkaline phosphatase activity, calcium mineral deposition and bone-related genes. Plasma-PES scaffolds with or without iPSCs were subsequently used to evaluate bone regeneration of critical-size defects in the rat by digital mammography, multislice spiral-computed tomography imaging and histological analysis. The results of in vitro analysis showed that plasma treatment significantly enhanced iPSC proliferation and osteogenesis. After 8 weeks of iPSC-loaded Plasma-PES implantation, no mortality or complication was observed in animals or at the site of surgery. Imaging analysis revealed more extensive bone reconstruction in rats receiving nanofibers compared with untreated control groups. Moreover, Plasma-PES seeded with iPSCs induced the highest regeneration of bone defects among all groups. These findings were confirmed by histological staining. Affective osseointegration was observed in implanted scaffolds. Thus, plasma-treated nanofibrous scaffolds are suitable tissue-engineered matrices for supporting the proliferation and osteogenic differentiation of iPSCs and might also be appropriate for the reconstruction of bone defects.


Muscarinic agonist binding in rat brain following chronic nicotine treatment.
Carbamylcholine binding was determined from competition experiments with [3H] quinuclidinyl benzilate in the rat brain chronically treated with nicotine. The nicotine group exhibited about two-fold lower affinity for the agonist binding toward a high-affinity site (or state) in the cerebral cortex, as compared with the control group. However, no alteration in the agonist binding was observed in the hypothalamus/thalamus and brainstem after chronic nicotine treatment.


Unexpected death due to gestational choriocarcinoma: a report of two cases.
We report two cases of unexpected death due to metastatic gestational choriocarcinoma and provide a review of the literature regarding these neoplasms. Our cases illustrate the extreme importance of medical follow-up of patients after an ectopic pregnancy or therapeutic abortion.


Abomasal ulcers in slaughtered cattle in Austria.
In this preliminary study, the prevalence of abomasal ulcers in cattle in Austria was evaluated for the first time. Furthermore, possible management factors contributing to the formation of abomasal ulcers and the diagnostic ability of faecal occult blood tests were evaluated. Abomasa of 91 calves, 33 cows and 91 bulls were examined for abomasal ulcers after slaughter. The ulcers were recorded, abomasal content pH was measured and faeces were examined for occult blood. The carcass classification was recorded and the owners were presented with a voluntary questionnaire targeted at health-, management- and feeding-practices that could influence gastric health. The median abomasal pH was 3.0 in calves, 3.6 in bulls and 3.9 in cows. More than 50% of all animals had abomasal ulcers, all of which belonged to the slightest kind of lesion. Faecal occult blood tests proved not to be suitable for detecting these ulcers. From the questionnaire no clear tendencies as far as causative factors for abomasal ulcers could be determined. It can be assumed that cattle management systems in Austria contribute to the formation of low-grade abomasal ulcers. Due to the lack of a suitable in vivo model to research the formation of abomasal ulcers in cattle all further speculations must remain elusive. Further influencing factors, such as bacterial ulcer colonization, and the true economic and animal welfare impact of these findings need further investigation. The results of this study should be corroborated in a larger, prospective trial.


SARS-CoV-2 vaccination and infection in ozanimod-treated participants with relapsing multiple sclerosis.
To investigate the serologic response, predictors of response, and clinical outcomes associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination and infection in ozanimod-treated participants with relapsing multiple sclerosis (RMS) from DAYBREAK. DAYBREAK (ClinicalTrials.gov-NCT02576717), an open-label extension study of oral ozanimod 0.92 mg, enrolled participants aged 18-55 years with RMS who completed phase 1-3 ozanimod trials. Participants who were fully vaccinated against SARS-CoV-2 with mRNA or non-mRNA vaccines, were unvaccinated, and/or had COVID-19-related adverse events (AEs, with or without vaccination) and postvaccination serum samples were included (n = 288). Spike receptor binding domain (RBD) antibody levels (seroconversion: ≥0.8 U/mL) and serologic evidence of SARS-CoV-2 infection (nucleocapsid IgG: ≥1 U/mL) were assessed (Roche Elecsys/Cobas e411 platform). In fully vaccinated participants (n = 148), spike RBD antibody seroconversion occurred in 90% (n = 98/109) of those without serologic evidence of prior SARS-CoV-2 exposure (100% [n = 80/80] seroconversion after mRNA vaccination) and in 100% (n = 39/39) of participants with serologic evidence of viral exposure. mRNA vaccination predicted higher spike RBD antibody levels, whereas absolute lymphocyte count (ALC), age, body mass index, and sex did not. COVID-19-related AEs were reported in 10% (n = 15/148) of fully vaccinated participants-all were nonserious and not severe; all participants recovered. Most ozanimod-treated participants with RMS mounted a serologic response to SARS-CoV-2 vaccination and infection, regardless of participant characteristics or ALC levels. In this analysis, all COVID-19-related AEs post-full vaccination in participants taking ozanimod were nonserious and not severe.


AYUSH digital initiatives: Harnessing the power of digital technology for India's traditional medical systems.
The incorporation of digital technologies is recognized as one of the inevitable factors to achieve better health care services. Recently, Indian Ministry of AYUSH (MoA) embraced digitalization extensively for development, education and research in AYUSH. In this context, we describe India's digital initiatives for AYUSH systems of medicine for information, research, and academia at various levels. We reviewed the websites and documents available from the MoA and its research councils/institutes along with the plan documents. We described the identified digital initiatives under categories of (1) Health information system (2) Research database/library (3) Academic (4) Information Education and Communication (IEC). We specified the purpose and target group of the identified digital initiatives. We identified 19 key digital initiatives. The AYUSH hospital management information system (A-HMIS), National AYUSH Morbidity and Standardized Terminologies Electronic Portal (NAMASTE), AYUSH Suraksha, e-Aushadhi, e-Charak, Triskandha Kosha, SiddAR APP were categorized under health information system. The Traditional Knowledge Digital Library (TKDL), AYUSH research portal, DHARA, e-CHLAS, Research Management Information system (RMIS), e-Granthasamuccaya and AYUSH Sanjivani App were categorized under research database/library. The Ayurveda e-learning and Ayurvedic Inheritance of India were categorized as the academic initiatives. The Siddha-NIS App, Yoga locator, and Naturopathy-NIN App were categorized as Information, education and communication (IEC) initiatives. The digital initiatives from the MoA were a key to reform the traditional systems of medicines and could improve the education, quality of research and accessibility of the AYUSH healthcare services.


Effect of directional migration on Lotka-Volterra system with desert.
Migration is observed across many species. Several authors have studied ecological migration by applying cellular automaton (CA). In this paper, we present a directional migration model with desert on a one-dimensional lattice where a traffic CA model and a lattice Lotka-Volterra system are connected. Here predators correspond to locomotive animals while prey is immobile plants. Predators migrate between deserts and fertile lands repeatedly. Computer simulations reveal the two types of phase transition: coexistence of both species and prey dominance, which is caused by both benefit and cost of migration. In the coexistence phase, the steady-state density of predators usually increases by migration as long as the desert size is small and their mortality rate is low. In contrast, the prey density increases, even if the desert size becomes large. Such a paradox comes from the indirect effect: predators go extinct by the increase of desert size, so that the plant density can increase. Moreover, we find several self-organized spatial patterns: 1) predators form a stripe pattern; namely swarms. 2) The velocity of predators is high on deserts, but very low on fertile land. 3) Predators give birth only on fertile lands.


Nonlinear association between body mass index and overall survival in advanced NSCLC patients treated with immune checkpoint blockade.
We investigated the association of body mass index (BMI) modeled as a continuous variable with survival outcomes in advanced non-small cell lung cancer (NSCLC) patients treated with immune checkpoint inhibitors (ICI). We performed a single-institution retrospective analysis of consecutively diagnosed locally advanced or metastatic NSCLC patients treated with single-agent ICI in the first line or recurrent setting. The primary outcome was overall survival (OS). Secondary outcomes were progression-free survival (PFS) and objective response rate (ORR). BMI was modeled using a four-knot restricted cubic spline. Multiple Cox regression was used for survival analysis. Two hundred patients were included (female 54%; never smoker 12%). Adenocarcinoma was the most common histology (61%). Median age was 67 years, median BMI was 25.9 kg/m2, and 65% of patients had Eastern Cooperative Oncology Group performance status (ECOG PS) of 0-1. On multivariable analysis, only BMI and ECOG PS were independently associated with OS (p < 0.01). Mortality risk decreased as the BMI increased from 20 to 30 kg/m2 (HR 0.49, 95% CI 0.28-0.84); however, it was reversed as the BMI surpassed ~ 30 kg/m2. Compared to ECOG PS ≥ 2, patients with ECOG PS of 0-1 had a longer OS (HR 0.42, 95% CI 0.28-0.63). Similar trends were observed with PFS and ORR, but the strength of the association was weaker. We observed a nonlinear association between BMI and OS following treatment with ICI in advanced NSCLC. Risk of death increases at both extremes of BMI with a nadir that exists around 30 kg/m2.


Y-family DNA polymerases and their role in tolerance of cellular DNA damage.
The past 15 years have seen an explosion in our understanding of how cells replicate damaged DNA and how this can lead to mutagenesis. The Y-family DNA polymerases lie at the heart of this process, which is commonly known as translesion synthesis. This family of polymerases has unique features that enable them to synthesize DNA past damaged bases. However, as they exhibit low fidelity when copying undamaged DNA, it is essential that they are only called into play when they are absolutely required. Several layers of regulation ensure that this is achieved.


Burden of congenital hemophilia A requiring treatment in Japan: The HIKOBOSHI study.
Treatment of congenital hemophilia A (HA) in Japan has greatly improved with the widespread adoption of prophylactic factor (F)VIII concentrates. However, it is unknown if this has translated into a real-world reduction in disease and treatment burden. To describe HA disease burden in Japan based on information from two medical information databases, JMDC and Real World Data Co., Ltd. (RWD). Eligible individuals were diagnosed with congenital HA and prescribed FVIII concentrates, bypassing agents, or emicizumab. Treatment patterns and disease burden data were derived from health insurance claims and electronic medical records. Data on 459 people with HA were retrospectively collected from 2005 to 2020 in the JMDC database (median [min, max] of 37 [2, 186] months of available records), and 229 people with HA from 1985 to 2020 in the RWD database (median [min, max] of 154 [0, 409] months of available records). Mean (standard deviation) ages at the time of the first record were 25.0 (16.8) years (JMDC) and 19.2 (20.3) years (RWD). In the JMDC database, mean monthly FVIII dose increased from 2201 IU in 2005 to 8239 IU in 2013 to 11,377 IU in 2019; HA-related drug costs increased accordingly. Mean (95% confidence interval) annual outpatient and out-of-hours visits decreased slightly between 2013 and 2019 (outpatient visits: from 22.9 [16.8-29.0] to 14.3 [12.6-16.1] per person; out-of-hours visits: from 1.3 [0.2-2.5] to 0.6 [0-1.4]). There was no change in mean number of hospitalizations. Challenges remain in HA, including treatment burden, outpatient visits, and hospitalizations.


Interactions of carotid sinus or aortic input with emetic signals from gastric afferents and vestibular system.
This study investigated how baro- and chemoreceptor afferents interact with emetic signals from gastric afferents and the vestibular system, and how these interactions modulate emetic and prodromal responses. We performed splanchnic denervation and abdominal vagotomy in anesthetized shrews (Suncus murinus), and then induced emetic responses by gastric distension. Next, we investigated the effects of these gastric afferent sections on cardiovascular and emetic responses induced by electrical stimulation of the aortic depressor nerve (ADN) and the carotid sinus nerve (CSN) with or without gastric distension. Splanchnic denervation abolished the prodromal response before retching and aortic baroreflex inhibition caused by gastric distension, but had no effects on the emetic response. In contrast, abdominal vagotomy abolished the emetic response induced by gastric distension with or without CSN stimulation, but without affecting gastric distension-induced or CSN stimulation-induced vascular and respiratory responses. In conscious animals, CSN denervation significantly suppressed veratrine- and motion-induced emetic responses, whereas ADN denervation had no significant effects. These results suggest that aortic baroreflex inhibition via the activation of splanchnic afferents contributes to the prodromal response before retching and circulatory homeostasis. In contrast, carotid sinus inputs, which are usually non-emetic signals, interact with vagal and vestibular inputs, and modulate the development of retching and vomiting.


Loss of heterozygosity on chromosome 9q and p53 alterations in human bladder cancer.
Somatic loss of the 9q allele as well as alteration of the tumor suppressor p53 occurs commonly in bladder cancers. Although alteration of p53 has been strongly associated with invasive stage disease, the prognostic significance of 9q loss of heterozygosity (LOH) and the relations between these alterations are less well defined. The 9q LOH was examined at five microsatellites and p53 alterations (mutation and persistent immunohistochemical staining) in a population-based case series of 271 newly diagnosed bladder cancer patients. Loss of heterozygosity was scored quantitatively and p53 mutation completed using single-strand conformation polymorphism screening followed by sequencing. Overall, allelic loss at 9q was detected in 74.5% (202/271) of cases and allele loss was associated with invasive disease (P < 0.05). Although based on small numbers, all nine in situ lesions contained 9q LOH. Age, gender, and smoking were not significantly associated with chromosome 9q allele loss. Both intense persistent p53 staining and LOH at 9q were independently associated with invasive disease (P < 10(-14) and P < 0.05, respectively). These data, using a population-based sample, suggest a relation between 9q LOH and invasive stage bladder cancer, and thereby suggests that a tumor suppressor gene at this loci, in addition to p53, may be important in the development of this more aggressive form of the disease.


Locomotor flexibility of Polypterus senegalus across various aquatic and terrestrial substrates.
Amphibious fishes show wide variation in form and function. Examination of terrestrial locomotion in fishes has largely focused on highly specialized taxa. From an evolutionary perspective we are interested in how relatively unspecialized fishes locomote when exposed to different terrestrial environments. In this study, we explore the locomotory repertoire of the basal actinopterygian Polypterus senegalus. We describe its terrestrial locomotory strategies on different surfaces and compare them with steady aquatic locomotion. Our study is the first to describe axial and appendicular-based terrestrial locomotion across a range of substrates in this species and shows two distinct terrestrial gaits in P. senegalus, each with substantial variation. One uses body undulation against complex surfaces and the other incorporates alternating, supportive pectoral fins to achieve a tetrapod-like gait. Gait use is correlated with substrate. P. senegalus uses body and pectoral fins in diverse ways, showing opportunistic and flexible strategies of navigating novel environments.


The use of direct oral anticoagulants for thromboprophylaxis or treatment of cancer-associated venous thromboembolism: a meta-analysis and review of the guidelines.
Venous thromboembolism (VTE) is a common complication among patients with cancer and is one of the most common causes of increased morbidity and mortality. The use of direct oral anticoagulants (DOACs) for thromboprophylaxis and treatment of cancer-associated venous thromboembolism (CA-VTE) has been evaluated in several randomized clinical trials (RCTs). The aim of this meta-analysis was to assess efficacy and safety of using DOACs for thromboprophylaxis and treatment of CA-VTE and provide a summary for available guidelines' recommendations. MEDLINE was searched to identify studies evaluating the use of DOACs for thromboprophylaxis or treatment in patients with cancer. Search was limited to peer-reviewed studies published in English. Studies were excluded if they were not RCTs or subgroup analyses of data derived from RCTs, if they did not report efficacy and safety data on patients with active cancer, or if they were published as an abstract. New VTE or VTE recurrence, and major or clinically relevant non-major bleeding (CRNMB) were used to assess the efficacy and safety, respectively. The Mantel-Haenszel random-effects model risk ratios (RRs) and the corresponding 95% confidence intervals (CIs) were calculated to estimate the pooled treatment effects of DOACs. Four studies evaluating DOACs use for thromboprophylaxis and four - for treatment of CA-VTE were included. Thromboprophylaxis with DOACs was associated with a significant reduction in the risk of symptomatic VTE (RR = 0.58; 95%CI 0.37,0.91) but with an incremental risk of major bleeding or CRNMB (RR = 1.57; 95%CI 1.10,2.26). CA-VTE treatment with DOACs was linked with a significant reduction in VTE recurrence (RR = 0.62; 95%CI 0.44,0.87) but with an incremental risk of CRNMB (RR = 1.58; 95%CI 1.11,2.24). The DOACs are associated with a lower risk of symptomatic VTE and VTE recurrence, but the risk of bleeding remains a considerable concern. Clinical decisions should be made by assessing individual patient's risk of VTE and bleeding.


Trends in testicular germ cell cancer incidence in Australia.
Although increasing incidence of testicular germ cell cancer has been reported in many developed nations, national estimates for Australia, with histological differentiation, are not currently available. Using data from all state and territory population-based cancer registries in Australia, this paper reports on incidence trends for seminomas and non-seminomas in Australia between 1982 and 2004 using Joinpoint and Age-Period-Cohort models. Of the 10,528 testicular germ cell cancers diagnosed during this period, 6086 (58%) were seminomas. Incidence rates have increased (2.6% per year) in Australia since 1982, with the effect stronger among seminomas (3.4% per year) rather than non-seminomas (1.4% per year). There was a strong age effect evident for both subtypes, peaking in the 25-29 year age group for non-seminomas and the 30-34 year age group for seminomas. Non-seminoma rates reflected a significant birth cohort effect, following a U-shaped pattern with the lowest risk among the 1,945 birth cohort. The differential trends observed for Australia for seminomas and non-seminomas are consistent with those reported for the United States, but slightly different to those reported for Europe. The trends may be at least partly due to changes over time in the prevalence of etiologic or protective factors around the time of birth.


The gut wall's potential as a partner for precision oncology in immune checkpoint treatment.
The gut wall is the largest immune organ and forms a barrier through which gut microbiota interact with the immune system in the rest of the body. Gut microbiota composition plays a role in the strength and timing of the anticancer immune response on immune checkpoint inhibitors (ICI). Surprisingly, the effects of gut wall characteristics, such as physical barrier integrity, permeability, and activity and composition of the intestinal immune system, on response to ICI has received little attention. Here, we provide an overview of markers to characterize the gut wall and interventions that can modulate these gut wall characteristics. Finally, we present a future perspective on how these gut wall markers and interventions might be utilized and studied to improve ICI treatment strategies.


Localized cecal zygomycosis following renal transplantation.
Zygomycosis occurs as an opportunistic infection following organ transplantation and immunosuppressive therapy. Gastrointestinal zygomycosis is an exceedingly rare and usually fatal presentation of this infection. We discuss the case of a renal transplant recipient who survived cecal perforation from zygomycosis. The successful treatment consisted of aggressive surgical resection, intensive course of antifungal therapy, and rapid withdrawal of anti-rejection medications.


Relative validity and reproducibility of food frequency questionnaire for individuals on hemodialysis (NUGE-HD study).
Adequate assessment of food intake is essential to establish the magnitude and direction of the relationship of food, nutrients, and bioactive compounds with clinical outcomes of individuals in hemodialysis. We evaluated the relative validity and reproducibility of a specific food frequency questionnaire for individuals on hemodialysis (FFQ-HD). Eighty-two participants (57.3% male, 57.5 ± 14.4 years) from the open cohort Nutrition and Genetics in Hemodialysis Outcomes participated in this study. The relative validity of the FFQ-HD was assessed using the mean of two 24-h food recall (24hR) adjusted for within-subject variability as a reference method. We also performed Pearson correlations, and agreement between tertile, kappa statistics, and Bland-Altman scatter plots were validated. Reproducibility was assessed after 1 year using intraclass correlation coefficient (ICC). Daily energy intake was not different between FFQ-HD and 24hR (mean difference of 50.1 kcal). Intake of protein, linolenic acid, fiber, phosphorus, potassium, sodium, calcium, and sugar showed a moderate correlation (r between 0.4 and 0.5) among instruments, while mean correlation coefficient was r = 0.38 to food group intake. Bland-Altman plots showed good agreement for micronutrients, phosphorus, sodium, and potassium and for the groups "flour, bread, and pasta" and "processed, canned meat, salts, and seasonings". The reproducibility of FFQ-HD for nutrients and food groups was satisfactory, reaching a maximum ICC of 0.72 and 0.59, respectively. The FFQ-HD showed moderate validity and reproducibility for calories, nutrients, and food groups of clinical and nutritional interest for HD subjects so that it can be a useful tool in epidemiological studies in this population.


Classifying the health of Connecticut streams using benthic macroinvertebrates with implications for water management.
Bioassessments have formed the foundation of many water quality monitoring programs throughout the United States. Like many state water quality programs, Connecticut has developed a relational database containing information about species richness, species composition, relative abundance, and feeding relationships among macroinvertebrates present in stream and river systems. Geographic Information Systems can provide estimates of landscape condition and watershed characteristics and when combined with measurements of stream biology, provide a useful visual display of information that is useful in a management context. The objective of our study was to estimate the stream health for all wadeable stream kilometers in Connecticut using a combination of macroinvertebrate metrics and landscape variables. We developed and evaluated models using an information theoretic approach to predict stream health as measured by macroinvertebrate multimetric index (MMI) and identified the best fitting model as a three variable model, including percent impervious land cover, a wetlands metric, and catchment slope that best fit the MMI scores (adj-R (2) = 0.56, SE = 11.73). We then provide examples of how modeling can augment existing programs to support water management policies under the Federal Clean Water Act such as stream assessments and anti-degradation.


Bacterial type III secretion systems are ancient and evolved by multiple horizontal-transfer events.
Type III secretion systems (TTSS) are unique bacterial mechanisms that mediate elaborate interactions with their hosts. The fact that several of the TTSS proteins are closely related to flagellar export proteins has led to the suggestion that TTSS had evolved from flagella. Here we reconstruct the evolutionary history of four conserved type III secretion proteins and their phylogenetic relationships with flagellar paralogs. Our analysis indicates that the TTSS and the flagellar export mechanism share a common ancestor, but have evolved independently from one another. The suggestion that TTSS genes have evolved from genes encoding flagellar proteins is effectively refuted. A comparison of the species tree, as deduced from 16S rDNA sequences, to the protein phylogenetic trees has led to the identification of several major lateral transfer events involving clusters of TTSS genes. It is hypothesized that horizontal gene transfer has occurred much earlier and more frequently than previously inferred for TTSS genes and is, consequently, a major force shaping the evolution of species that harbor type III secretion systems.


Genetic abnormalities in adolescents and young adults with neuroblastoma: A report from the Italian Neuroblastoma group.
Less than 5% of neuroblastomas (NB) occur in adolescents and young adults (AYA), in whom the disease has an indolent and fatal course. We studied the genomic profile and histological characteristics of 34 NBs from AYA patients enrolled in the Italian Neuroblastoma Registry (INBR) between 1979 and 2009. Disease was disseminated in 20 patients and localized in 14; 30/34 tumors were classified as NB and 4/34 as nodular ganglioneuroblastoma (nGNB). Segmental Chromosome Aberrations (SCAs) were observed in 29 tumors (85%) namely 1p imbalance (58%), 17q gain (52%), 9p loss (32%), 11q loss (30%), 1q gain (17%), 7q gain (17%), 2p gain (14%), 3p loss (14%), and 4p loss (7%). MYCN amplification and MYCN gain were detected in 3 (10%) and 2 cases (7%) respectively. An anaplastic lymphoma receptor tyrosine kinase (ALK) gene mutation study on the available cases from this cohort revealed 4/25 (16%) mutated cases. In parallel, alpha thalassaemia/mental retardation syndrome X linked (ATRX) gene mutations were also sought, a novel mutation being detected in 1/21 (4,7%) cases. This study confirmed the low incidence of MYCN amplification in AYA and recorded a high frequency of 17q gain and 9p and 11q loss independently from the stage of the disease. The presence of 1q gain, which identifies patients with particularly aggressive disease, relapse and poor survival, was also detected. Furthermore, the frequency of ALK mutations suggests that a target-based therapy with ALK inhibitors might be effective in this subset of patients.


Psychological impacts of COVID-19 on Vietnamese health workers over the prolonged restricted COVID-19 responses: a cross-sectional study.
We assessed the psychological impact posed by COVID-19 and its associated factors on the healthcare workforce nationwide during the peak of Vietnam's fourth outbreak. A cross-sectional study. Our study was conducted in 61 provinces of Vietnam. A total of 2814 healthcare professionals in 61/63 provinces of Vietnam. An online questionnaire using Patient Health Questionnaire-9 (PHQ-9), Perceived Stress Scale-4 (PSS-4) and Generalised Anxiety Disorder-7 (GAD-7) scales was distributed randomly to a subgroup of 503 respondents. To determine the impact of COVID-19 on the psychological of health workers, we conducted analyses to test a primary hypothesis related to participants based on three main scales including PHQ-9, PSS-4 and GAD-7 scales. Nearly half (49.7%) of healthcare workers experienced mild depression symptoms, 34.0% underwent moderate anxiety symptoms and 49.3% reported high-stress levels. Respondents who had a monthly income below 5 million VND (~US$212) and had more than 3 days of duty per week had a higher score on the anxiety scales. Compared with medical doctors, nurses/midwives had lower PHQ-9 (Coef=-2.53; 95% CI=-3.71 to -1.36) and GAD-7 scores (Coef=-2.36; 95% CI=-3.56 L to -1.16). Increased workload and work time was the harmful factor that increase the PHQ-9, GAD-7 or PSS-4 scores. More than half (53.9%) of respondents stated no demand for mental healthcare services. Health workers who gained less financial rewards are reported to have higher levels of mental distress than others, implying the need for a raise in basic salary as well as compensation and encouragement schemes. To tackle hesitancy in seeking mental help, integrating online mental health therapy with e-health consultations via social media can be strategically implemented to augment service delivery, and simultaneously enhance the standard of mental health services.


Spectrophotometric-chemometrics study of the effect of solvent composition and temperature on the spectral shape and shift of copper and nickel phthalocyanines in different aqueous-nonaqueous mixed solvents.
Phthalocyanines (Pcs) are green-blue colored aromatic macrocyclic compounds used extensively in the dyeing industry. The assembly phenomenon for dye molecules is directly traceable by most of the spectroscopic methods. In this investigation, the monomer-dimer equilibria of copper and nickel phthalocyanines tetra sulfonic acid tetrasodium salts (CuPcTS, NiPcTS) have been investigated by spectrophotometric and chemometrics methods in binary mixtures of H2O-DMSO and H2O-CH3CN. The dimerization constants, (KD), enthalpies and entropies of CuPcTS and NiPcTS have been calculated by studying the UV-Vis spectra at different concentrations of dyes (10-6 to 10-4molL) and in the temperature range 298-343 K and in some samples up to 353 K by multivariate curve resolution (mcr) methods. By increasing the temperature, the value of KD decreases. The inverse temperature dependence of KD (van't Hoff equation) was used for determination of ΔH 0 and ΔS 0and following that ΔG 0of the dimerization reactions. As a result, upon aggregation, an increase in the intensity of the new shoulder at (~600 nm) and the Q-band at (662-670 nm) and concomitant decrease of the dimer band at (630-624 nm) are observed for all of the samples in different solvents composition. Therefore, the H-dimer type of these pigments was notable, in studied binary solvents. The effect of the solvent composition, concentration dye, and temperature on the spectral responses, the exciton parameters and concentration distribution diagrams of the two pigments were studied and discussed. The density functional theory (DFT) calculations were done in the aqueous and gas phase that they were included the HOMO-LUMO energies and the simulated UV-Vis spectrum. These calculations were beneficial for studying the UV-Vis spectrum of it in the aqueous phase for checking experimental data.


Comparison of cold-hardening bending and direct electric resistance heat treatment on the mechanical properties and transformation temperature of NiTi archwire: An in vitro study.
The aim of this investigation was (1) to compare the effects of cold-hardening bending and direct electric resistance heat treatment (DERHT) methods; and (2) to compare the effects of offsets and angulations on the mechanical properties and thermal analysis of NiTi alloy archwire. Nickel-titanium (NiTi) archwires (Ormco, Glendora, CA), 0.016×0.022-inch, were bent by cold-hardening bending and DERHT methods into 1-mm, 2-mm, or 3-mm offset for a 3-point bending test, and at angles of 30°, 45°, or 60° to the horizontal plane for testing the change in transformation temperature (Af) measured by differential scanning calorimetry (DSC). The data were analysed using ANOVA followed by the Scheffe post-hoc test. The 3-point bending test results of the cold-hardening bending and DERHT methods were not significantly different between the 1-mm, 2-mm and 3-mm offset groups (95% CI: -0.05 to 0.97; P=0.082, 95% CI: -0.65 to 0.74; P=0.983 and 95% CI: -0.61 to 0.98; P=0.813, respectively). Increasing the offset resulted in a significantly decreased force in the 3-point bending test (P<0.001). The Af temperatures of the cold-hardening bending and DERHT methods were not significantly different for the 30°, 45°, and 60° bending angulations (95% CI: -1.93 to 1.39; P=0.876, 95% CI: -1.2 to 0.87; P=0.878, 95% CI: -2.24 to 1.18; P=0.636, respectively). Af temperatures were not influenced by different bending angulations. NiTi archwire shape can be modified by using both cold-hardening and DERHT bending methods, because the mechanical properties and Af temperature are not affected. However, the bending distance has an effect on the mechanical properties.


Contribution of dehydroepiandrosterone sulfate and progesterone to in vitro regulation of tolerogenic activity of IFN-α-induced dendritic cells.
Dehydroepiandrosterone sulfate and progesterone exhibited an immunomodulatory effect on the tolerogenic characteristics of IFN-α-induced dendritic cells. The hormone effects depended on the initial level of allostimulatory activity of dendritic cells in mixed lymphocyte culture. However, dehydroepiandrosterone sulfate significantly more often stimulated allostimulatory activity by attenuating the tolerogenic properties of dendritic cells, while progesterone potentiated their tolerogenic potential. The capacity of the hormones (dehydroepiandrosterone sulfate and progesterone) to attenuate tolerogenic activity of dendritic cells was associated with reduction of FasL expression on these cells, while the increase in tolerogenic activity was associated with the increase in the percentage of CD123(+) dendritic cells, and under conditions of modification with dehydroepiandrosterone sulfate it was associated with increased B7-H1 expression. Possible contribution of indolamine-2,3-dioxygenase and prostaglandin E2 to stimulation of tolerogenic characteristics of dendritic cells modified with dehydroepiandrosterone sulfate and progesterone, respectively, was demonstrated.


The thermal biology of Geolycosa godeffroyi and other burrow inhabiting Lycosidae (Araneae) in Australia.
Using both field and laboratory data a detailed examination of behavioural thermoregulation is presented for Geolycosa godeffroyi (Koch), a burrow inhabiting Australian wolf spider; comparative data are given for Schizocosa leuckartii (Thorell), Venatrix fuscus (Hogg), Lycosa speciosa Koch, and two undescribed species of Lycosa. Egg sac and spider body temperatures were recorded either by implanted thermocouples or biotelemetry. The burrows permitted the spiders access to a wide range of temperature throughout the day but the spiders maintained temperatures above the upper limit of this range except in the middle of the day in summer. In winter the burrows protected the spiders from extreme cold. G. godeffroyi thermoregulated throughout the year and could achieve temperatures of 38°C when the global radiation exceeded about 260 mW cm-2 d-1. The activity regimes deduced from temperature recording were in accord with those derived using field actographs and photographic recording. The spiders thermoregulated in a manner similar to that used by behaviourally thermoregulating lizards and did so whenever conditions were suitable. They maintained temperatures between 32 and 36°C but the preferred temperature was reduced by lack of food or water, in egg sacs or females carrying egg sacs and in mature males to about 30°C. The data do not support the concept of a refractory zone but suggest two or more set points required for specific physiological or ecological purposes.


Microvascular pericytes in brain-associated vascular disease.
Pericytes, as mural cells of microvessels, are important regulators of vascular structure formation and function maintenance in the process of cerebrovascular maturation, cerebrovascular homeostasis and disease. In the recent years, they have gradually become the hot spot of the research. In fact, pericytes are not isolated cells. Their functions can't be played without the cooperation with surrounding cells. In the neurovascular unit (NVU), they communicate with other cells by direct contact or through signaling pathways to regulate cerebral vascular function and the state of blood vessels in response to changes in neural activity. Pericytes are closely related to the cerebrovascular and central nervous system disease. Currently, a large number of clinical and animal studies have confirmed that pericytes biological function is related to cerebral blood flow, blood-brain barrier permeability, cerebral vascular formation maintenance, and neuroinflammation. The objective of this review is to highlight the role of pericytes in cerebral microvessels as well as their relationships with stroke, dementia, and brain tumor disease. The possible pathogenic mechanisms between pericytes and these diseases will also be described. As a matter of fact, the role of pericytes in the brain-associated vascular disease may provide new ideas for clinical treatment.


CPNE1 silencing inhibits cell proliferation and accelerates apoptosis in human gastric cancer.
Gastric cancer is a heterogeneous disease accompanied by the alteration of various causative genes. The discovery of molecular targets and potential mechanisms of gastric cancer is valuable. Here we explored the biological function of CPNE1 and its molecular mechanisms in gastric cancer. Immunohistochemistry and Kaplan-Meier plotter database were used to identify that CPNE1 was upregulated in human gastric cancer and high expression of CPNE1 suggested a worse prognosis. Silencing CPNE1 could effectively suppress tumor proliferation, accelerate cell apoptosis and arrest cell cycle in vitro. CPNE1 knockdown mediating apoptosis by PARP-1 cleavage via caspase-3 and -7 activation through cytochrome c release from mitochondria in gastric cancer cells. Xenograft mouse model showed that targeted inhibition of CPNE1 slowed down the rate of tumor growth in vivo. We also verified that CPNE1 knockdown inhibited the activation of MAPK pathway mediated by DDIT3-FOS-MKNK2 axis. Specific inhibitor of DDIT3-FOS-MKNK2 axis could suppress gastric cancer cell proliferation, concomitant with knockdown of CPNE1. In conclusion, CPNE1 silencing inhibited gastric cancer growth via deactivating DDIT3-FOS-MKNK2 axis, which indicated that CPNE1 might serve as a therapeutic target for gastric cancer.


No evidence for an association between G protein beta3 subunit gene C825T polymorphism and tardive dyskinesia in schizophrenia.
Tardive dyskinesia (TD) is a long-term adverse effect of antipsychotic. We evaluated candidate functional polymorphism of the G protein beta3 subunit (GNB3) gene for association with drug-induced TD in the Korean schizophrenic patients. We investigated whether the C825T polymorphism of the GNB3 gene is associated with the TD in a Korean sample of schizophrenic patients with (n = 83) and without TD (n = 126), matched for antipsychotic drug exposure and other relevant variables. The distribution of genotypes and allele frequencies of GNB3 were not different between schizophrenic patients with TD and without TD (p > 0.05). Within the limitations imposed by the size of the clinical sample, these findings suggest that the GNB3 825 C/T single nucleotide polymorphism (SNP) does not contribute significantly to risk for TD.


Methylene blue dye removal on silver nanoparticles reduced by Kyllinga brevifolia.
Silver nanoparticles (AgNPs) were prepared by reacting Kyllinga brevifolia extract (KBE) with AgNO3 aqueous solution at room temperature (22 ± 3 °C). The phytochemical constituents in KBE responsible for the reduction process were identified as carbohydrate, protein, and plant sterols (stigmasterol and campesterol). KBE was also found to function as a capping agent for stabilization of AgNPs. The AgNPs were stable at room temperature and had a quasi-spherical shape with an average particle size 22.3 nm. The use of KBE offers not only eco-friendly and non-pathogenic path for AgNPs formation, it also induced rapid formation of the AgNPs. Methylene blue (MB) removal was then done on the AgNPs in the presence of either KBE or NaBH4. Ninety-three percent removal of MB was achieved with a rate of reaction 0.2663 min-1 in the solution with KBE+AgNPs (pH 2). However, in NaBH4+AgNPs system, 100% MB removal was achieved at pH 8-10. The reaction rate was 2.5715 min-1 indicating a fast removal rate of MB dye. The process of reduction occurs via electron relay effect whereas in KBE+AgNPs system, sedimentation occurred along with the reduction process. Nevertheless, the use of KBE+AgNPs system is preferred as the reducing agent is more benign to the environment.


Green synthesis and characterization of zirconium oxide nanoparticles by using a native Enterobacter sp. and its antifungal activity against bayberry twig blight disease pathogen Pestalotiopsis versicolor.
Pestalotiopsis versicolor is a most destructive fungal pathogen that causes twig blight disease in bayberry. For the last seven years, it is difficult to control this pathogen due to its latent infestation mode and its control through chemical fungicides is environmentally corrosive in addition to being costly. In this study, we reported the fungicidal potential of biologically synthesized zirconium oxide nanoparticles (ZrONPs) against P. versicolor for the first time. The strain used for green synthesis of ZrONPs was taxonomically identified as Enterobacter sp. strain RNT10. The production of ZrONPs in reaction mixture was confirmed through UV-vis spectroscopy analysis. Moreover, FTIR, XRD, SEM and TEM analysis showed the presence of capping proteins and crystalline nature of spherical shaped ZrONPs with particle size ranging from 33 to 75 nm. EDX spectra revealed an elemental profile of ZrONPs comprising of Zr (54.40%) and oxygen (43.49%). Biogenic ZrONPs showed substantial antifungal inhibition zones (25.18 ± 1.52 mm) at 20 μg mL-1 concentration against P. versicolor strain XJ27. Moreover, the treatment of 20 μg mL-1 ZrONPs significantly inhibited twig blight in detached leaf assay. Furthermore, imaging through SEM and TEM showed the adverse effects of ZrONPs against P. versicolor in terms of extracellular leakage of DNA and proteins. Overall, this study suggested that biogenic ZrONPs could substitute chemically synthesized antifungal agents with the specific application towards control of twig blight disease in bayberry.


Anthocyanins and colonic metabolites of dietary polyphenols inhibit platelet function.
Maintenance and achievement of an optimal platelet function by dietary solutions might be considered an interesting target to influence cardiovascular health. Polyphenol-rich foods such as vegetables and fruits have been shown to significantly improve platelet function in ex vivo studies in humans. However, until yet, it still remains unclear if polyphenols itself, their metabolites or a mixture of both are responsible for the beneficial effects observed so far. Our study aims to evaluate the effect of anthocyanins, in vivo metabolites of different polyphenols from colonic origin and a representative mixture of both at physiological concentrations on platelet aggregation and activation function. Some anthocyanins [1 microM], colonic metabolites [10 microM] and a mixture (4 phenolic acid [1 microM], 4 anthocyanin [0.1 microM] showed significant platelet sedating and desensitizing effects. Activation of the platelets (P-selectin expression) was significantly reduced by 10-40% in resting platelets, TRAP-activated and hydrogen peroxide-stressed platelets and epinephrine pre-activated platelets relative to controls. The dose-response curve of the weak agonist TRAP was also significantly altered resulting in a >0.8 microM increase of threshold concentration to induce aggregation. The representative mixture was active despite ten times lower concentrations of the individual components, which showed no activity when tested individually at that concentration, indicating synergism of the different components. Platelet reactivity to strong agonists such as collagen and ADP was not influenced. These results show that anthocyanins and in vivo metabolites of polyphenols have anti-thrombotic properties, suggesting themselves as well as their dietary sources and precursors as potential cardiovascular health promoters.


The dilemma of trauma-focused therapy: effects of imagery rescripting on voluntary memory.
Trauma-focused imagery-based interventions are suspected to alter or even distort declarative voluntary memory of a traumatic event, especially if they involve the active modification of imagery, e.g., as used in imagery rescripting (ImRs). However, systematic research is lacking so far. To investigate whether ImRs modifies voluntary memory of a standardized autobiographical aversive event (Trier Social Stress Test) (Session 1), healthy participants (N = 100) were randomly assigned to either an intervention condition receiving one session of ImRs or to a no-intervention control condition (NIC) (Session 2). Voluntary memory was examined using a free recall (Sessions 2 and 3) and a cued recall (Sessions 3 and 4). Although voluntary memory tended to deteriorate over time, contrary to expectations, this effect was not associated with ImRs. Remarkably, the number of correct details in free recall even improved in ImRs but not in NIC. This challenges the view that ImRs alters voluntary memory.


Vegetarianism, low meat consumption and the risk of lung, postmenopausal breast and prostate cancer in a population-based cohort study.
The few prospective studies that examined lung, female breast and prostate cancer risk in vegetarians have yielded mixed results, whereas none have studied the effects of low meat diets. Moreover, little is known about the explanatory role of (non-) dietary factors associated with these diets. The Netherlands Cohort Study-Meat Investigation Cohort (NLCS-MIC)- is an analytical cohort of 11 082 individuals including 1133 self-reported vegetarians (aged 55-69 years at baseline). At baseline (1986), subjects completed a questionnaire on dietary habits and other risk factors for cancer and were classified into vegetarians (n=691), pescetarians (n=389), 1 day per week (n=1388), 2-5 days per week (n=2965) and 6-7 days per week meat consumers (n=5649). After 20.3 years of follow-up, 279 lung, 312 postmenopausal breast and 399 prostate cancer cases (including 136 advanced) were available for analyses. After adjustment for confounding variables, we found no statistically significant association between meat consumption groups and the risk of lung cancer. As well, no significant associations were observed for postmenopausal breast and overall prostate cancer. After adjustment for confounders, individuals consuming meat 1 day per week were at a 75% increased risk of advanced prostate cancer compared with 6-7 days per week meat consumers (95%CI 1.03-2.97). Vegetarians, pescetarians and 1 day per week meat consumers did not have a reduced risk of lung, postmenopausal breast and overall prostate cancer compared with individuals consuming meat on a daily basis after taking confounders into account.


An auxiliary factor for increasing the retention of short abutments.
Retention is an essential factor in the sustainability of the prosthesis, especially for short abutment. Despite, the availability of several auxiliary applications, achieving a clinically good retention for cast crowns in prepared short teeth remains a major challenge for the practicing dentist. This study tests a new method for applying frustum-shaped grooves on short prepared abutments and compares them with traditional setting grooves. Forty-eight copper machine-milled short dies with 3.5 mm length and 12o conversion with a chamfer finish line of 0.7 mm were prepared to mimic short prepared molars and distributed into 4 groups. A control group with two opposing setting grooves and two groups with dual opposing frustums, one of which was prepared to receive two integrated metal protrusions inside the casting that fit the frustums. Frustums were prepared with Komet bur No. 807 with dimensions 0.9 mm at the base and 0.7 mm at the occlusal surface. A direct wax-up was carried out on all dies and all castings were cemented with zinc phosphate cement. A pull-off test was applied until separation. Data were analysed to compare the correlation of the four groups using one-way ANOVA and Bonferroni test (p ≤ 0.05). The mean retentive values in Newton were as follows: the control group, 457.80; the setting grooves group, 461.07; the frustum group, 597.59; and the frustum group with the two metal protrusions, 919.80. The retention was increased by 65% in frustum group and doubled in frustum group with the metal protrusions. The results showed a statistical significance in retention in the frustum groups with and without metal protrusion over the retention of the control and the setting grooves groups.


Psychiatric comorbidity among terminally ill patients in general practice in the Netherlands: a comparison between patients with cancer and heart failure.
It is unclear whether psychiatric disorders are specifically related to the terminal phase of cancer, or independent of the underlying disease. To investigate the rate of psychiatric comorbidity and psychotropic drugs prescription in terminally ill patients in the GP setting, comparing both patients with terminal cancer and heart failure. Retrospective cohort study using the Utrecht General Practitioner Research Network. Equally-sized groups of patients with terminal cancer and heart failure were randomly selected from the database of four general practices over the years 2005-2009. Psychiatric comorbidities were determined using the International Classification for Primary Care (ICPC) codes and psychotropic drugs prescriptions using the Anatomical Therapeutic Chemical (ATC) Classification System codes. A total of 191 terminally ill patients were included in the study (111 with cancer and 80 with heart failure). The mean age for patients with terminal cancer (70.8 years, standard deviation [SD] = 12.8) was 15 years younger than that of patients with heart failure (85.6 years, SD = 9.2). Half of the terminally ill patients (50.3 %) were prescribed psychotropics, but only 13.6% of them had obtained a psychiatric diagnosis. There were no significant differences in prevalence of psychiatric disease and psychotropic drug prescription between patients with terminal cancer and heart failure. The results demonstrate a high use of psychotropic drugs in terminally ill patients, often in the absence of a formal diagnosis of a psychiatric disorder. The absence of differences between patients with cancer and heart failure suggests that psychiatric diagnoses and increased psychotropic prescriptions are primarily related to the terminal stage of the disease and not to the background of cancer or heart failure.


Electrocatalytic Hydrogen Production Trilogy.
H2 production via water electrolysis is of great significance in clean energy production, which, however, suffers from the sluggish kinetics of the anodic oxygen evolution reaction (OER). Moreover, the anode product, O2 , which is of rather low value, may lead to dangerous explosions and the generation of membrane-degrading reactive oxygen species. Herein, to address these issues of electrocatalytic H2 production, we summarize the most recent advances in three stages based on the benefit increments and various electron donation routes, which are: 1) electron donation by traditional OER: developing efficient catalysts for water oxidation to promote H2 production; 2) electron donation by the oxidation of sacrificial agents: using sacrificial agents to assist H2 production; 3) electron donation by electrosynthesis reaction: achieving electrosynthesis in parallel with cathodic H2 production. Present challenges and related prospects will also be discussed, hopefully to benefit the further progress of electrocatalytic H2 generation.


Flapless CAD/CAM-guided surgery for staged transition from failing dentition to complete arch implant rehabilitation: a 3-year clinical report.
The transition of patients from failing dentition to complete arch implant rehabilitation often requires that the patient be rendered edentulous and has to wear a complete removable dental prosthesis for varying periods of time. This is objectionable to many patients. A staged treatment approach allows a fixed interim restoration, patient comfort, and prosthodontic control throughout the rehabilitation process. CAD/CAM-guided flapless implant surgery has the advantage of prosthetically driven implant placement and minimal postoperative sequelae. A patient with a failing dentition was treated with this combined protocol and was followed up for 3 years after loading. Implant and prosthesis survival rates were 100%, with no technical complications encountered up to the last recall. The purpose of this clinical report is to describe a combination of CAD/CAM-guided flapless surgery and a staged treatment approach, thereby giving the patient a tooth-supported or implant-supported fixed interim prosthesis during the entire rehabilitation process. The various surgical, laboratory, and prosthetic stages are illustrated for the complete arch prosthetic rehabilitation, and the 3-year follow-up outcome is reported.


Endosymbionts and mitochondrial origins.
The possibility is put forth that the mitochondrion did not originate from an endosymbiosis, 1-2 billion years ago, involving an aerobic bacterium. Rather, it arose by endosymbiosis in a much early, anaerobic period, and was initially a photosynthetic organelle, analogous to the modern chloroplast. This suggestion arises from a reconsideration of the nature of endosymbiosis. It explains the remarkable diversity in mitochondrial information storage and processing systems.


Fluorescence histochemical demonstration of dopa thioethers by condensation with gaseous formaldehyde.
The usefulness of the formaldehyde (FA) and glyoxylic acid (GA) methods for the fluorescence histochemical demonstration of dopa thioethers has been tested using protein droplet models. Similar fluorescence intensities were recorded from these compounds after either FA or GA treatment. Cysteinyldopa gave a high fluorescence yield similar to that obtained from dopamine and dopa in the FA reaction, whereas gluatitodopa showed a lower, although clearly visible fluorescence. Since the FA method seemed to be the most useful one for demonstration of catechol thioethers, the FA-induced fluorophores of these compounds were further characterized by microspectrofluorometry. The spectral characteristics of the thioether fluorophores (excitation maxima at 420 nm and emission maxima at 480-485 nm) distinguish these substances from dopa and other compounds fluorogenic in the Falck-Hillarp method. Dopa thioethers are proposed to form fluorophores with FA in a manner analogous to that of the primary catecholamines i.e. via low-fluorescent tetrahydroisoquinolines, along two different pathways, to strongly fluorescent 3,4-dihydroisoquinolines and 2-methyl-dihydroisoquinolinium compounds. These dihydroisoquinolines are in a pH-dependent tautomeric equilbrium with their quinoidal forms as reflected by a characteristic spectral shift upon acidification. The results of this study provide the guide-lines for the characterization of fluorogenic compounds in pigment-forming cells.


Anopheles vector distribution and malaria transmission dynamics in Gbêkê region, central Côte d'Ivoire.
A better understanding of vector distribution and malaria transmission dynamics at a local scale is essential for implementing and evaluating effectiveness of vector control strategies. Through the data gathered in the framework of a cluster randomized controlled trial (CRT) evaluating the In2Care (Wageningen, Netherlands) Eave Tubes strategy, the distribution of the Anopheles vector, their biting behaviour and malaria transmission dynamics were investigated in Gbêkê region, central Côte d'Ivoire. From May 2017 to April 2019, adult mosquitoes were collected monthly using human landing catches (HLC) in twenty villages in Gbêkê region. Mosquito species wereidentified morphologically. Monthly entomological inoculation rates (EIR) were estimated by combining the HLC data with mosquito sporozoite infection rates measured in a subset of Anopheles vectors using PCR. Finally, biting rate and EIR fluctuations were fit to local rainfall data to investigate the seasonal determinants of mosquito abundance and malaria transmission in this region. Overall, Anopheles gambiae, Anopheles funestus, and Anopheles nili were the three vector complexes found infected in the Gbêkê region, but there was a variation in Anopheles vector composition between villages. Anopheles gambiae was the predominant malaria vector responsible for 84.8% of Plasmodium parasite transmission in the area. An unprotected individual living in Gbêkê region received an average of 260 [222-298], 43.5 [35.8-51.29] and 3.02 [1.96-4] infected bites per year from An. gambiae, An. funestus and An. nili, respectively. Vector abundance and malaria transmission dynamics varied significantly between seasons and the highest biting rate and EIRs occurred in the months of heavy rainfall. However, mosquitoes infected with malaria parasites remained present in the dry season, despite the low density of mosquito populations. These results demonstrate that the intensity of malaria transmission is extremely high in Gbêkê region, especially during the rainy season. The study highlights the risk factors of transmission that could negatively impact current interventions that target indoor control, as well as the urgent need for additional vector control tools to target the population of malaria vectors in Gbêkê region and reduce the burden of the disease.


catena-Poly[[(2,2'-bi-pyridine-κ2 N,N')manganese(II)]-di-μ-bromido].
In the polymeric title complex, [MnBr2(C10H8N2)] n , the MnII ion, situated on a twofold axis of symmetry, is six-coordinated in a distorted octa-hedral coordination geometry defined by two N atoms from the chelating 2,2'-bi-pyridine ligand and four bridging Br- anions. The crystal reveals a one-dimensional Br-bridged chain along the c-axis direction with a zigzag topology. In the crystals, contacts between chains include π-π inter-actions between pyridyl rings [inter-centroid separation = 4.082 (1) Å].


Immunological evaluation of the mycotoxin patulin in female B6C3F1 mice.
Patulin is a mycotoxin produced by many fungal species of the genera Penicillium, Aspergillus and Bryssochamys. Previous literature reports have suggested that patulin is toxic to the immune system. The studies presented were conducted to provide a comprehensive assessment of the effects of patulin on the immune system. Unlike previous reports, the doses of patulin used (0.08, 0.16, 0.32, 0.64, 1.28 and 2.56 mg/kg) were based on predicted human exposure levels. Female B6C3F1 mice were exposed orally to patulin for 28 days. Effects were not observed on final body weight or body weight gain. Relative weight of the liver, spleen, thymus, kidneys with adrenals, and lungs was not affected. Peripheral blood leucocyte and lymphocyte counts were decreased by approximately 30% in the two highest dose groups. The leucocyte differential was not altered. Total spleen cell, total T-cell (CD3+), helper T-cell (CD4+CD8-), B-cell (surface immunoglobulin+) and monocyte (MAC-3+) counts were not changed. Cytotoxic T-cell (CD8+CD4-) counts were increased 50% only by the highest dose. Natural killer cell (NK1.1+CD3-) and monocyte (MAC-1+) counts were increased 30% and 24%, respectively, only in the 0.08 mg/kg group. Humoral immune function as assessed by antibody-forming cell response and serum IgM titre to sheep erythrocytes, and cell-mediated immune function evaluated utilizing natural killer cell activity and the mixed lymphocyte reaction were not altered. Oral exposure to patulin for 28 days did not alter the ability of female B6C3F1 mice to mount either a cell-mediated or humoral immune response.


Identification of colony-forming activities of various hemopoietic cells in the serum-free culture medium of a human embryo fibroblast cell strain.
Ralph et al. reported that human cell lines for the production of colony stimulating factor cannot secrete the factor in serum-free media (Blood 68, 633-639, 1986). However, we found various colony-forming activities to be present in the serum-free culture medium of a human embryo fibroblast cell strain (YH-1). When a soy bean trypsin inhibitor was added to the serum-free media, semisolid cultures of mouse and human bone marrow cells exhibited a considerable degree of colony formation by macrophages and to a lesser extent by other cells. A difference in apparent molecular weights in macrophage colony-forming activities by YH-1 cells from serum-free and serum-containing cultures was observed. The physiological significance of these findings is discussed in terms of regulation of hemopoietic cell differentiation by human embryo fibroblasts.


Integrated Comparative Transcriptome and circRNA-lncRNA-miRNA-mRNA ceRNA Regulatory Network Analyses Identify Molecular Mechanisms Associated with Intramuscular Fat Content in Beef Cattle.
Intramuscular fat content (IMF), one of the most important carcass traits in beef cattle, is controlled by complex regulatory factors. At present, molecular mechanisms involved in regulating IMF and fat metabolism in beef cattle are not well understood. Our objective was to integrate comparative transcriptomic and competing endogenous RNA (ceRNA) network analyses to identify candidate messenger RNAs (mRNAs) and regulatory RNAs involved in molecular regulation of longissimus dorsi muscle (LDM) tissue for IMF and fat metabolism of 5 beef cattle breeds (Angus, Chinese Simmental, Luxi, Nanyang, and Shandong Black). In total, 34 circRNAs, 57 lncRNAs, 15 miRNAs, and 374 mRNAs were identified by integrating gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Furthermore, 7 key subnets with 16 circRNAs, 43 lncRNAs, 7 miRNAs, and 237 mRNAs were detected through clustering analyses, whereas GO enrichment analysis of identified RNAs revealed 48, 13, and 28 significantly enriched GO terms related to IMF in biological process, molecular function, and cellular component categories, respectively. The main metabolic-signaling pathways associated with IMF and fat metabolism that were enriched included metabolic, calcium, cGMP-PKG, thyroid hormone, and oxytocin signaling pathways. Moreover, MCU, CYB5R1, and BAG3 genes were common among the 10 comparative groups defined as important candidate marker genes for fat metabolism in beef cattle. Contributions of transcriptome profiles from various beef breeds and a competing endogenous RNA (ceRNA) regulatory network underlying phenotypic differences in IMF provided novel insights into molecular mechanisms associated with meat quality.


[Clinical, bacteriological and pharmacokinetic study of Sisomicin in the newborn infant].
A study of the efficiency and tolerance of sisomicin in 19 children with severe bacterial infections led to the following conclusions: -sisomicin was efficient, particularly in association with beta-lactamin; -the local and systemic tolerance was good. The susceptibility of various bacterial strains was studied. The half-life of sisomicin given intramuscularly was : 4,0 +/- 1,8 hours in the new-borns under 10 days and 2,0 +/- 0,3 hours in older infants, when creatininemia was below 10 mg/l. No accumulation was found. The recommended daily dose of sisomicin by intramuscular route is 3 to 6 mg/kg, i.e. 1 to 2 mg every 8 hours in infants an 1,5 to 3 mg every 12 hours in new-borns.


Changes in the Serum Levels of Trace Elements Before and After the Operation in Thyroid Cancer Patients.
The present study aims to examine the changes in the serum levels of trace elements before and after the operation in thyroid cancer patients. The study registered 50 individuals, of whom 25 were female and 25 were male. The patients were allocated to four groups: group 1: male thyroid cancer patients group (n = 15), group 2: female thyroid cancer patients group (n = 15), group 3: male control group (n = 10), group 4: female control group (n = 10). The subjects in groups 1 and 2 were the patients who were post-operatively diagnosed with a pathological malignancy in the thyroid tissue samples. Blood samples were collected from all subjects before the operation, immediately after the operation, and on the post-operative day 15. Additionally, thyroid tissue samples were taken from all subjects post-operatively. Some elements in the blood and tissue samples were determined using the atomic emission method. Zinc and selenium levels of groups 1 and 2 in the pre- and post-operative measurements were significantly lower than those in the control groups (p < 0.05), but were higher in the thyroid tissue (p < 0.05). Serum zinc and selenium levels measured in the subjects on the post-operative day 15 were similar to those measured in the controls. Our study show that changes in the serum and thyroid tissue levels of trace elements like zinc and selenium, which play a critical role in thyroid function, might be associated with the pathogenesis of thyroid cancer.


Multidetector computed tomography angiography in the evaluation of potential living donors for liver transplantation: single-center experience in China.
To evaluate relevant arterial, hepatic, and portal venous anatomy using multidetector computed tomography (CT) angiography in potential living liver donors at a single liver transplantation center in China. One hundred two consecutive potential liver donors underwent CT angiography in the arterial, portal, and hepatic venous phases with a 16-row CT scanner. All source and reconstructed images were evaluated for hepatic vasculature anatomy by an experienced radiologist and a surgeon in consensus. The anatomic variants of arterial system, portal venous system, and hepatic veins were characterized according to the classification system of Michels, Akgul, and Nakamura respectively. In 42 donors of right hepatic lobectomy, CT findings were compared with the results of surgery. Of 102 candidates, 63 had type I, 8 type II, 12 type III, 3 type IV, 11 type V, 2 type VI, 2 type VIII, and 1 type IX hepatic arterial anatomy. According to the classification of the portal venous system created by Akgul, type A was seen in 81 subjects. Type B, type C, and type E were revealed in 15, 4, and 2 subjects, respectively. According to the classification of the right hepatic drainage pattern by Nakamura, type 1 drainage was seen in 71 subjects (69.6%), type 2 in 22 candidates (21.6%), and type 3 in 9 subjects (8.8%). Forty five right inferior hepatic veins were identified in 41 potential donors, and 68.9% of these veins were larger than 5 mm in diameter. CT angiography findings were confirmed in all donors who underwent operations. Multidetector CT angiography can successfully show the relevant hepatic vascular anatomy in potential liver donors.


Virtualization of Cross-Border Labor Migration.
Under virtual labor migration, or telemigration, in the expert community it is customary to understand remote work or the provision of services that are carried out in a cross-border format. The presence of the word migration in this term logically prompts us to consider the designated process in a migration context. From the standpoint of the concept of migration transition, the spread of virtual migration can be interpreted as a new link in the chain of mobility transformations generated by multifaceted digital transformations. With this kind of migration, a person crosses only virtual borders of states and, without leaving the country of residence, actually works outside it and performs the tasks of a foreign customer in a remote electronic mode. The short duration and rapid turnover of most jobs in cyberspace makes this process extremely circulatory, uncharacteristic of traditional labor relations. So far, this employment model has been limited in scope, but it is rapidly developing, having gained great momentum in the context of the COVID-19 pandemic, and may become significant in the future. While paying dividends to workers and employers interacting in global digitalized labor markets, virtual migration simultaneously exacerbates chronic imbalances and generates new sources of social tension. They are connected, among other things, with the global asymmetry of socioeconomic and digital development, the emergence of new factors and areas of competition for workers in the labor market, and insufficient social protection of the workers. Optimization of the development of virtual migration could be facilitated by comprehensive regulatory measures at the level of international organizations, states, and companies.


A novel biologically active selenoorganic compound. VIII. Biotransformation of ebselen.
1. The metabolism of ebselen, a Se-containing heterocyclic compound, in rats, pigs and human volunteers has been investigated. 2. Unchanged ebselen is not present in urine, plasma or bile. All metabolites of ebselen have in common that the isoselenazolone ring is opened. 3. Both in pigs and human, the dominant metabolite in plasma and urine is a Se-glucuronide. This is the major metabolite in rats as well but, additionally, some selenomethyl-derivatives of ebselen can be detected.


Multimodal imaging for detecting metamorphopsia after successful retinal detachment repair.
To investigate the etiologies of metamorphopsia after successful retinal detachment repair. In this retrospective study, we included patients who underwent pars plana vitrectomy (PPV) for macula-off rhegmatogenous retinal detachment (RRD). Patients were reviewed after 3 to 6 weeks. Best-corrected visual acuity (BCVA), fundus biomicroscopy, Amsler grid test, spectral-domain optical coherence tomography (SD-OCT), and fundus autofluorescence images (FAF) were obtained from all patients to visualize abnormalities in retinal layers and retinal rotation. A total of 50 eyes from 49 consecutive patients were included, of whom 12 (24%) complained of postoperative metamorphopsia. The main cause of metamorphopsia was retinal shift after RRD repair (p < 0.001). Distorted vision after macula-off RRD is a common and retinal shift was found to be the main reason patients experience metamorphopsia after a successful macula-off RRD repair.


[Associated severe head injury].
Rarely do head and spinal cord injuries occur as isolated injuries. The associated injuries are well known. Multitraumatized patients are assessed and treated on a priority principle, based on the nature of injuries and stability of vital signs. Neurosurgeons are frequently faced with diagnosing and treating head injury in multitraumatized patients. The authors studied the incidence, diagnosis and treatment of patients with head injuries in cases with multiple trauma. The authors conducted a retrospective review of 45 patients with severe head injuries in cases with multiple trauma. All patients were assessed after the GCS and GOS scoring system. All had CT scan. 32 patients were operated in our department. 29 patients died, 4 developed vegetative state and in 8 achieved a complete recovery. The highest rate of mortality was observed in patients with severe head injury, associated with pulmonary injury. Associated injuries constitute a serious problem with progressively increasing car accident traumatism. Being familiar with the assessment and management protocols for multitrauma patients gives neurosurgeons a better appreciation of the interrelationship in multisystem injury and an effective sequence of diagnostics and treatment of associated head injuries.


An auxiliary diagnostic tool for common fundus diseases based on fundus color photography and light-weight classification models.
To evaluate the performance of two lightweight neural network models in the diagnosis of common fundus diseases and make comparison to another two classical models. A total of 16,000 color fundus photography were collected, including 2000 each of glaucoma, diabetic retinopathy (DR), high myopia, central retinal vein occlusion (CRVO), age-related macular degeneration (AMD), optic neuropathy, and central serous chorioretinopathy (CSC), in addition to 2000 normal fundus. Fundus photography was obtained from patients or physical examiners who visited the Ophthalmology Department of Beijing Tongren Hospital, Capital Medical University. Each fundus photography has been diagnosed and labeled by two professional ophthalmologists. Two classical classification models (ResNet152 and DenseNet121), and two lightweight classification models (MobileNetV3 and ShufflenetV2), were trained. Area under the curve (AUC), sensitivity, specificity, accuracy, positive predictive value, and negative predictive value were used to evaluate the performance of the four models. Compared with the classical classification model, the total size and number of parameters of the two lightweight classification models were significantly reduced, and the classification speed was sharply improved. Compared with the DenseNet121 model, the ShufflenetV2 model took 50.7% less time to make a diagnosis on a fundus photography. The classical models performed better than lightweight classification models, and Densenet121 showed highest AUC in five out of the seven common fundus diseases. However, the performance of lightweight classification models is satisfying. The AUCs using MobileNetV3 model to diagnose AMD, diabetic retinopathy, glaucoma, CRVO, high myopia, optic atrophy, and CSC were 0.805, 0.892, 0.866, 0.812, 0.887, 0.868, and 0.803, respectively. For ShufflenetV2model, the AUCs for the above seven diseases were 0.856, 0.893, 0.855, 0.884, 0.891, 0.867, and 0.844, respectively. The training of light-weight neural network models based on color fundus photography for the diagnosis of common fundus diseases is not only fast but also has a significant reduction in storage size and parameter number compared with the classical classification model, and can achieve satisfactory accuracy.


Autonomic responses during Gambling: the Effect of Outcome Type and Sex in a large community sample of young adults.
Psychological theories consider autonomic arousal to be a reinforcer for problem gambling. Structural characteristics such as near-misses, which are non-win events that come close to a real win, have been shown to elicit win-like responses while increasing motivation and gambling persistence. This study investigated the autonomic and subjective responses of young adults to different gambling outcomes. This study also investigated sex differences in autonomic and subjective responses to different gambling outcomes.Participants from Sweden (n = 270) performed a computerized slot machine task that produced wins, near-misses (before and after payline) and full-misses. Phasic measurements of heart rate (HR) and skin conductance responses (SCR) were recorded during gambling performance and ratings of perceived chance of winning, pleasure and motivation to play were collected following each gambling outcome.Autonomic responses differed across slot machine outcomes as indicated by HR and SCR. Compared with other gambling outcomes, near-misses elicited the largest HR accelerations, and they also elicited larger HR decelerations and SCRs relative to full-misses. Near-misses before and after payline elicited differential psychophysiological responses and subjective reports, suggesting different emotional processing of near-miss subtypes. Females showed increased SCRs and motivation following win outcomes compared with males.In conclusion, wins, near-misses and full-misses generate differential physiological and subjective responses among young adults. Autonomic responses to wins differed between male and female players, emphasizing the need to consider sex differences when investigating the role of autonomic arousal in gambling.


A case report of compensation in daily life of a person with memory problems: detailed functional use of memory aids over a five-year period.
Numerous studies have been conducted on memory aids for memory-impaired people. However, it is not known how they use these memory aids in a functional, practical way. A 20-year-old patient (MH) was monitored for five years to identify what memory aids or other means she used and how she used them to compensate for her memory problems, e.g., forgetting what was said by others in a few minutes and getting lost or turning in the wrong direction on a walk or in a building. Results indicated MH did not necessarily always use memory aids such as a notebook or calendar to compensate for her memory problems, although MH and her mother reported that she frequently used them in daily life. She coped with memory problems by using various "resources" besides the memory aid. These facts suggest that it may be necessary to redefine functionally useful compensations, which include both memory aids and resources in daily life.


Indomethacin and diclofenac sodium increase sodium and water excretion after extracellular volume expansion in the rabbit.
The renal effects of an acute extracellular fluid volume expansion (50 ml Ringer/kg body weight/60 min) were studied in aldosterone-treated (100 microgram/kg), anesthetized rabbits with and without pretreatment with either indomethacin (3.0 mg/kg) or diclofenac sodium (3.0 mg/kg), two different inhibitors of renal prostaglandin (PG) biosynthesis. In controls (n = 7), the volume expansion increased urine flow from 1.5 +/- 0.24 to 6.1 +/- 0.5 (S.E.) ml/min/100 g kidney weight and sodium excretion from 0.15 +/- 0.03 to 0.99 +/- 0.10 mmol/min/100 g. PAH and inulin clearance increased by 42 and 58%, respectively, while plasma renin activity and urinary excretion of PGF2 alpha-like immunoreactivity were reduced (P less than 0.05). In animals pretreated with indomethacin (n = 6) or diclofenac sodium (n = 6), the diuresis and the natriuresis following volume expansion were significantly increased about two-fold over controls, whereas PAH and inulin clearance, plasma renin activity and hematocrit did not differ from controls. Both drugs were found to reduce urinary excretion of PGF2 alpha-like immunoreactivity by 75--95% througout the experiment. The results indicate that diclofenac sodium, indomethacin and extracellular volume expansion enhance sodium and water excretion partly by suppression of a PG sensitive reabsorption process in the kidney.


Efficient removal of organophosphate esters by ligand functionalized MIL-101 (Fe): Modulated adsorption and DFT calculations.
Organophosphate esters (OPEs) are a new class of flame retardants present in diverse waters. The study focused on the removal of aqueous OPEs using functionalized MIL-101(Fe), which was a representative of the metal-organic frameworks (MOFs). Adsorption kinetics of tris(2-chloroethyl) phosphate (TCEP), tributyl phosphate (TnBP), and triphenyl phosphate (TPhP) were investigated. Additionally, TCEP was selected as the model contaminant to study the adsorption isotherms, thermodynamics, and effect of solution matrix properties. Adsorption mechanisms obtained from the experiments were confirmed using density functional theory (DFT) calculations. Adsorption kinetics indicated that functionalized MOFs provided a significant enhancement to the removal of TCEP. The maximum adsorption capacities qm of MIL-101(Fe), MIL-101(Fe)-NH2, MIL-101(Fe)-OH, and MIL-101(Fe)-CH3 at 298 K for TCEP were 76.040, 282.940, 119.680, and 181.274 μmol/g, respectively. By comparing the adsorption behavior of functionalized MOFs, MIL-101(Fe)-NH2 was proved to be most efficient for TCEP removal. Based on the adsorption experiments and DFT calculations, TCEP removal was dominated by physical adsorption. The van der Waals (vdW) interactions and hydrogen bonding were assumed to be involved in the adsorption. This work proves that appropriate ligand functionalization is promising for the removal of aqueous OPEs, which also provides a new insight for the control of OPEs pollution.


Anterograde and retrograde labelling of CNS pathways with unconjugated lectins using the unlabelled antibody enzyme method.
A method for demonstrating the anterograde and retrograde transport of unconjugated lectins in the CNS is given using the labelled antibody enzyme technique. Successful labelling of a variety of pathways is demonstrated using wheat germ agglutinin (WGA) and concanavalin A (Con A). Exceptionally large numbers of neurones labelled by retrograde transport were detected in each area. Using this method afferents to the mediodorsal thalamus are reported from prefrontal, cingulate and perirhinal cortex, substantia innominata, magnocellular and lateral preoptic area, ventral pallidum and diagonal band of Broca. In addition it is shown that large numbers of neurones of the periventricular hypothalamus and periaqueductal central grey of the mesencephalon techniques and further applications of the method are outlined.


Simultaneous determination of PCBs, OCPs and PAHs in mussel by ultrasound-assisted cloudy extraction and gas chromatography-tandem mass spectrometry.
A method for the simultaneous determination in mussel of 8 polychlorinated biphenyls (PCBs), 23 organochlorine pesticides (OCPs), and 35 polycyclic aromatic hydrocarbons (PAHs), including alkyl-PAHs, was optimised using ultrasound-assisted cloudy extraction and gas chromatography-tandem mass spectrometry (GC-MS/MS). Optimal selection of the extraction solvent and the dispersing solvent contributed to a high extraction yield and a clean extract. The ranges of the lower limits of detection of PCBs, OCPs and PAHs were 0.012-0.058, 0.01-0.29 and 0.01-0.5 μg kg-1, respectively. The feasibility of the proposed method was validated by analysing standard reference materials of mussel with satisfactory results. The precision achieved by this method was in the range of 0.677-2.69% (PCBs), 1.14-6.60% (OCPs) and 0.694-7.46% (PAHs), and its accuracy was in the range of 101-104% (PCBs), 99.6-106% (OCPs) and 101-110% (PAHs). The advantages of the method include the simultaneous measurement of 66 analytes and the simplicity, low cost and high sensitivity of the procedure. When the proposed method was used to analyse the target compounds in 11 mussel samples, the analytical results displayed a concentration range of 0.41-0.45 µg kg-1 for PCBs, 0.26-6.49 µg kg-1 for OCPs, and 3.48-30.69 µg kg-1 for PAHs.


Hydrolytic Metabolism of Withangulatin A Mediated by Serum Albumin Instead of Common Esterases in Plasma.
The oral bioavailability of withangulatin A (WA) is low and may undergo first-pass metabolism because of the presence of two esters bonds. This study aimed to identify the hydrolysis behavior and mechanism of WA, thus enriching its structure-pharmacokinetic relationship. The in vivo pharmacokinetic studies of WA in rats were first investigated, followed by in vitro assays including metabolic stability, phenotyping identification and metabolic kinetics assays. After screening out the responsible enzymes with higher catalytic capacity, molecular docking study was performed to demonstrate the interaction mode between WA and metabolic enzymes. Then, metabolites in human serum albumin (HSA) were identified by LC-TOF-MS/MS. In rats, the oral bioavailability of WA was only 2.83%. In vitro, WA was hydrolyzed in both rat and human plasma and could not be inhibited by selective esterase inhibitors. Physiologic concentration of HSA not recombinant human carboxylesterases (rhCES) could significantly hydrolyze WA, and it had a similar hydrolytic capacity with human plasma to WA. Furthermore, WA could stably bind to HSA by forming hydrogen bonds with Lys199 and Arg410, accompanied by the metabolic reaction of the lactone ring opening. The study showed that WA underwent obvious hydrolysis in rat and human plasma, which implied a strong first-pass effect. Serum albumin rather than common esterases primarily contributed to the hydrolytic metabolism of WA in plasma.


Primary stenting in the treatment of focal atherosclerotic abdominal aortic stenoses.
To evaluate the results of primary stent placement in focal atherosclerotic aortic stenoses using balloon expandable stents. Twenty-six primary balloon expandable stent placements in the abdominal aorta were performed and reviewed. All the aortic stenoses were atherosclerotic. Patients were followed up by ankle/brachial pressure indices (ABPI) and Doppler ultrasound (US) at 24h after procedure and at 12 and 24 months. Follow-up angiograms were performed at 12 months. Twenty-six stents in 26 patients were placed in the infrarenal aorta. All procedures were technically successful and immediate clinical success was obtained. The mean ABPI significantly improved from 0.52+/-0.10 to 0.94+/-0.09 within 24h after procedure, and remained at 0.90+/-0.12 between 12 and 24 months follow-up (mean 18 months). There was full haemodynamic success at hospital discharge and at 12 and 24 months after the procedure. Clinical success at 12 and 24 months (mean 18 months) was defined as an improvement in the Fontaine classification by at least one class compared with the pre-procedure class and was shown to be 100%. In summary, we report that primary stenting is a safe and effective alternative to surgery in cases of symptomatic stenosis of the infrarenal abdominal aorta. The excellent intermediate term results suggested that we would recommend primary stenting as the treatment of choice for focal atherosclerotic stenoses of the infrarenal aorta in selected patients.


Anorectic activity of NG-nitro-L-arginine, an inhibitor of brain nitric oxide synthase, in obese Zucker rats.
We investigated the effects of NG-nitro-L-arginine (L-NO Arg) administration (12.5, 25 and 50 mg/kg i.p.) on food consumption and body weight of male obese Zucker rats (fa/fa) and in their lean age-matched controls (FA/?; FA/FA), both groups aged 14 weeks. Acute or repeated administration of L-NO Arg reduced food intake and body weight in both obese and lean rats. However the lean rats showed tolerance to the L-NO Arg effects after 5 days of treatment. L-NO Arg anorexia was suppressed by pretreatment with metergoline. These results suggest that L-NO Arg may represent a new anorectic drug.


Regulation of miRNA-21 by reactive oxygen species-activated ERK/NF-κB in arsenite-induced cell transformation.
After acute exposure of cells to arsenic, reactive oxygen species mediate changes in cell behavior, including activation of proliferative signaling. For chronic exposure to arsenic, however, the function of reactive oxygen species in cell transformation remains poorly understood. Although microRNA-21 (miR-21) has been implicated in various aspects of carcinogenesis, its functions and molecular mechanisms in carcinogen-induced tumorigenesis are unclear. The purpose of this study was to determine if miR-21 is involved in arsenite-induced malignant transformation and to characterize the associated signaling pathways. During arsenite-induced transformation of human embryo lung fibroblast (HELF) cells, miR-21 was upregulated, and the extracellular signal-regulated kinase (ERK)/nuclear factor-κB (NF-κB) signal pathway was activated. Moreover, superoxide radical dismutase (a scavenger of superoxide) and catalase (a scavenger of hydroperoxides) blocked the arsenite-induced effects in HELF cells and mouse embryonic fibroblasts. Blockage of ERK by the inhibitor U0126 or inhibition of NF-κB p65 by siRNA or Bay 11-7082 prevented the increases in miR-21 and the decreases in Spry1, Pten, and Pdcd4, the target proteins of miR-21, induced by arsenite. As determined by a ChIP-qPCR assay, NF-κB p65 regulated miR-21 expression by binding directly to the promoter of miR-21. Further, anti-miR-21 downregulated miR-21 expression and prevented the arsenite-induced activation of ERK via the increase in Spry1, indicating that miR-21 has a feedback effect in regulating ERK activation. Overexpression of miR-21 with an miR-21 mimic and feedback activation of ERK and NF-κB via the decrease in Spry1 promoted the malignancy of HELF cells exposed to arsenite, but knockdown of miR-21 with anti-miR-21 and feedback blockage of ERK and NF-κB activation through an increase in Spry1 decreased anchorage-independent growth of arsenite-transformed cells. Thus, the transformation of HELF cells induced by chronic exposure to arsenite is mediated by increased miR-21 expression, which, in turn, is mediated by reactive oxygen species activation of the ERK/NF-κB pathway.


Real-time analysis of the effects of toxic, therapeutic and sub-therapeutic concentrations of digitoxin on lung cancer cells.
Digitoxin belongs to a naturally occurring class of cardiac glycosides (CG); digitoxin is clinically approved for heart failure and known for its anti-cancer effects against non-small lung cancer cells (NSCLC). However, concerns associated with its narrow therapeutic index and its concentration-dependent mechanism of action are rising. Thus, before digitoxin implementation in designing and developing safer and more effective CG-based anti-cancer therapies, its pharmacological and safety profiles need to be fully elucidated. In this research we used a combinatorial approach to evaluate the anti-cancer mechanisms of digitoxin in real-time. Our approach employed a non-invasive electric cell impedance sensing technique as a proxy to monitor NSCLC behavior post-exposure to toxic, therapeutic and sub-therapeutic concentrations of the drug. By developing structure-function combinatorial relations we showed that digitoxin targets cancer cells in a time and dose-dependant manner by activating pro-apoptotic and anti-proliferative signaling cascades that results in strengthening cellular adhesion and sequestration of key regulatory proliferation protein from the nucleus.


Toxic effects of fluridone on early developmental stages of Japanese Medaka (Oryzias latipes).
The herbicide fluridone is intensively applied to control invasive aquatic plants globally, including in the Sacramento and San Joaquin Delta (the Delta), California, USA. Our previous study revealed that the adult stage of Delta Smelt showed acute and sub-lethal adverse effects following 6 h of exposure to environmentally relevant concentrations of fluridone. To further investigate mechanisms of toxicity of fluridone and to assess its toxicity to early life stages of fish, we performed additional exposures using the fish model Japanese Medaka (Oryzias latipes). Male and female Medaka embryos were exposed to concentrations of fluridone for 14 d and showed reduced hatching success in a dose dependent manner. The half maximal effective concentration for the hatching success was 2.3 mg L-1. In addition, male and female Medaka larvae were acute exposed to fluridone for 6 h to assess their swimming behavior and gene expression patterns. Fish exposed to fluridone at 4.2 mg L-1 or higher became lethargic and showed abnormal swimming behavior. The response to the stimuli was significantly impaired by fluridone at 21 mg L-1 and above in males, and at 104 mg L-1 in females. Transcriptome analysis identified a total of 799 genes that were significantly differentially expressed, comprising 555 up-regulated and 244 down-regulated genes in males exposed to 21 mg L-1 of fluridone. The gene set enrichment analysis indicated a number of biological processes altered by fluridone. Among the genes involved in those biological processes, the expression of the genes, acetylcholinesterase, retinoic acid receptor, insulin receptor substrate, glutathione reductase, and glutathione S transferase, exhibited dose- and sex-dependent responses to fluridone. The study indicated that fluridone exposure led to detrimental toxic effects at early developmental stages of fish, by disturbing the biological processes of growth and development, and the nervous system, inducing oxidative stress and endocrine disruption.


Prevalence and Clinical Characteristics of Bacterial Pneumonia in Neurosurgical Emergency Center Patients: A Retrospective Study Spanning 13 Years at a Tertiary Center.
Patients with brain injuries are at a heightened susceptibility to bacterial pneumonia, and the timely initiation of empiric antibiotic treatment has been shown to substantially reduce mortality rates. Nevertheless, there is a need for knowledge regarding the resistance and prevalence of pulmonary bacterial infections in this patient population. To address this gap, a retrospective study was conducted at a neurosurgical emergency center, focusing on patients with brain injuries. Among the entire patient population, a total of 739 individuals (18.23%) were identified as having bacterial pneumonia, consisting of 1489 strains of Gram-negative bacteria and 205 strains of Gram-positive bacteria. The resistance of Klebsiella pneumoniae to imipenem exhibited a significant increase, rising from 21.74% in 2009 to 96.67% in 2018, and subsequently reaching 48.47% in 2021. Acinetobacter baumannii displayed resistance rates exceeding 80.0% against multiple antibiotics. The resistance profile of Pseudomonas aeruginosa was relatively low. The proportion of Staphylococcus aureus reached its peak at 18.70% in 2016, but experienced a decline to 7.83% in 2021. The abundance of Gram-negative bacteria exceeded that of Gram-positive bacteria by a factor of 5.96. Klebsiella pneumoniae, Acinetobacter baumannii, and Staphylococcus aureus are prominent pathogens characterized by limited antibiotic choices and scarce treatment alternatives for the isolated strains.


Response to comments on "A comparison of different physical stomach models and an analysis of shear stresses and strains in these system" by Wu and Chen (2020).
Physical stomach (in-vitro) models have considerable potential for answering questions about the dissolution and delivery of tablets, as well as answering fundamental questions about the hydrodynamics of the stomach and ultimately investigating diseases of the human gastrointestinal system. Physical gastrointestinal models have been compared in terms of their advantages and disadvantages. The structures of the produced stomach parts have been compared among the in-vitro models. The possible materials to manufacture the stomach models have also been summarized. This letter to the editor responds to the correspondence by Wu and Chen (2020) about our paper, aiming to further check and describe the substance in our paper.


[The choice of the uterine-contraction agent in managing the placental period of labor based on our data].
Every obstetrician is acquainted with the existing risk during the placental stage. The danger of a greater blood loss is always present. The use of uterotonic medicines reduces the post-delivery bleeding. The authors have carried out observations over 422 delivery cases. In 153 of them ergotamine has been applied in the placental stage, in 121 oxytocine, and in 148 delivery cases the placental stage has passed without uterotonic drugs. The authors have concluded that the application of contracting medicines reduces the blood loss, but their usage has to be selective and after delivery of the fore shoulder of the foetus.


MicroRNA-378 regulates neural stem cell proliferation and differentiation in vitro by modulating Tailless expression.
Previous studies have suggested that microRNAs (miRNAs) play an important role in regulating neural stem cell (NSC) proliferation and differentiation. However, the precise role of miRNAs in NSC remains largely unexplored. In this study, we showed that miR-378 can target Tailless (TLX), a critical regulator of NSC, to regulate NSC proliferation and differentiation. By bioinformatic algorithms, miR-378 was found to have a predicted target site in the 3'-untranslated region of TLX, which was verified by a dual-luciferase reporter assay. The expression of miR-378 was increased during NSC differentiation and inversely correlated with TLX expression. qPCR and Western blot analysis also showed that miR-378 negatively regulated TLX mRNA and protein expression in neural stem cells (NSCs). Intriguingly, overexpression of miR-378 increased NSC differentiation and reduced NSC proliferation, whereas suppression of miR-378 led to decreased NSC differentiation and increased NSC proliferation. Moreover, the downstream targets of TLX, including p21, PTEN and Wnt/β-catenin were also found to be regulated by miR-378. Additionally, overexpression of TLX rescued the NSC proliferation deficiency induced by miR-378 overexpression and abolished miR-378-promoted NSC differentiation. Taken together, our data suggest that miR-378 is a novel miRNA that regulates NSC proliferation and differentiation via targeting TLX. Therefore, manipulating miR-378 in NSCs could be a novel strategy to develop novel interventions for the treatment of relevant neurological disorders.