Distorted bcc indium cubes as structural motifs in Ca
The title compounds were prepared from the elements by reactions in water-cooled glassy carbon crucibles under an argon atmosphere in a high-frequency furnace. CaPdIn4 crystallizes with the YNiAl4-type structure: Cmcm, a=446.7(3), b=1665(1), c=754.3(5) pm, wR2=0.0465 with 646 F2 values and 24 variables. The structure is built up from a complex three-dimensional [PdIn4] polyanion in which the calcium atoms occupy distorted pentagonal tubes formed by indium and palladium atoms. CaRhIn4 and CaIrIn4 adopt the LaCoAl4-type structure: Pmma, a=867.6(1), b=422.91(8), c=745.2(1) pm, wR2=0.0583 with 468 F2 values and 24 variables for CaRhIn4; a=869.5(1), b=424.11(6), c=746.4(1) pm, wR2= 0.0614 471 F2 values with 24 variables for CaIrIn4. This structure type, too, has a three-dimensional [RhIn4] polyanion which is related to the structure of binary RhIn3. The calcium atoms fill distorted pentagonal prismatic channels formed by indium atoms. Semi-empirical band structure calculations for Ca-RhIn4 and CaPdIn4 reveal strongly bonding In-In, Rh-In and Pd-In interactions but weaker Ca-Rh, Ca-Pd and Ca-In interactions. CaRhIn4 and Ca-PdIn4 are compared with other indium-rich compounds such as YCoIn5 and Y2CoIn8, and with elemental indium. Common structural motifs of the indium-rich compounds are distorted bcc-like indium cubes.


Integrin-mediated protein kinase A activation at the leading edge of migrating cells.
cAMP-dependent protein kinase A (PKA) is important in processes requiring localized cell protrusion, such as cell migration and axonal path finding. Here, we used a membrane-targeted PKA biosensor to reveal activation of PKA at the leading edge of migrating cells. Previous studies show that PKA activity promotes protrusion and efficient cell migration. In live migrating cells, membrane-associated PKA activity was highest at the leading edge and required ligation of integrins such as alpha4beta1 or alpha5beta1 and an intact actin cytoskeleton. alpha4 integrins are type I PKA-specific A-kinase anchoring proteins, and we now find that type I PKA is important for localization of alpha4beta1 integrin-mediated PKA activation at the leading edge. Accumulation of 3' phosphorylated phosphoinositides [PtdIns(3,4,5)P(3)] products of phosphatidylinositol 3-kinase (PI3-kinase) is an early event in establishing the directionality of migration; however, polarized PKA activation did not require PI3-kinase activity. Conversely, inhibition of PKA blocked accumulation of a PtdIns(3,4,5)P(3)-binding protein, the AKT-pleckstrin homology (PH) domain, at the leading edge; hence, PKA is involved in maintaining cell polarity during migration. In sum, we have visualized compartment-specific PKA activation in migrating cells and used it to reveal that adhesion-mediated localized activation of PKA is an early step in directional cell migration.


Ultimate Control over Hydrogen Bond Formation and Reaction Rates for Scalable Synthesis of Highly Crystalline vdW MOF Nanosheets with Large Aspect Ratio.
Large-scale synthesis of van der Waals (vdW) metal-organic framework (MOF) nanosheets with controlled crystallinity and interlayer coupling strength is one of the bottlenecks in 2D materials that has limited its successful transition to large-scale applications. Here, scalable synthesis of mBDC (m = Zn and Cu) 2D MOFs at large scales through a biphase method is demonstrated. The results show replacing water molecules with pyridine eliminates hydrogen bond formation at metal cluster sites. This prohibits tight coupling across adjacent MOF layers and sustains controllable 2D vdW MOF growth. It is further shown that control over the growth speed, crystallinity, and thickness can be achieved by addition of a controlled amount of triethylamine and formic acid to achieve highly crystalline vdW MOF nanosheets with extraordinarily high aspect ratio. The described synthesis route can easily be scaled up for large-scale production either by deposition onto desired substrates or in crystalline layered powder form. Owing to its large lateral size, vdW nature, and high crystallinity, it is possible to perform atomic force microscopy, Kelvin probe force microscopy, and Raman measurements on the 2D MOFs. The results not only establish their vibrational properties and layer-dependent responses but also show striking differences from other 2D inorganic materials.


Pathological tumour diameter predicts risk of conventional subtype in small renal cortical tumours.
To examine whether pathological tumour diameter assists in predicting conventional vs other histological subtypes in renal cortical tumours (RCTs) of <or=4 cm diameter. In all, 393 patients from Columbia University's Comprehensive Urologic Oncology Database who underwent radical or partial nephrectomy between 1988 and 2005 and had RCTs of <or=4 cm were analysed. Logistic regression analysis using tumour diameter as a continuous variable was used to determine whether size predicted histological subtype. Odds ratios (ORs) were calculated to estimate the likelihood of having conventional histology based on diameter. The median patient age at surgery was 64.3 years and median tumour diameter was 3 cm, In all, 256 (65.1%) of the RCTs were conventional subtype and 137 (34.9%) were nonconventional. Logistic regression analysis showed that for every 1 cm increase in diameter up to 4 cm, the RCT was 1.27 times more likely to be conventional (P = 0.020). The ORs showed that a 4-cm RCT was 2.06 times more likely to be conventional than tumours of 0.6-1.5 cm. There was a positive association between RCT diameter and the risk of having conventional renal cell carcinoma (RCC). Given that RCC histological subtype is a prognostic indicator for outcome, these findings may be applied in the selection of treatment options. Further studies investigating tumour size and other variables predictive of tumour histology will help clinicians better predict the RCC subtype.


T cell receptor V beta gene bias in rheumatoid arthritis.
Polymerase chain reaction (PCR) technology was employed to examine peripheral blood and synovial T cells in patients with rheumatoid arthritis (RA) for biased utilization of T cell receptor (TCR) variable region (V) genes. Oligonucleotide primers specific for individual TCR V beta gene families were used to amplify TCR gene products in a semiquantitative assay of their relative utilization in unselected T cell populations. Mean V beta expression in 24 RA peripheral blood samples was very similar to that in a panel of 15 normal subjects, except for a slight decrease in V beta 13.2 expression. V beta utilization in 8 RA synovial tissue samples and 13 synovial fluid samples was compared to simultaneously obtained blood samples. Although heterogeneous patterns of skewed V beta utilization were observed, several significant trends emerged. By a number of approaches to data analysis, a statistically significant increase in expression of V beta 6 and V beta 15 in synovial T cells was documented. In addition, increased synovial expression of V beta 14 was found, but only in the synovial fluid samples. Reduced expression of V beta 1, V beta 4, V beta 5.1, V beta 10, V beta 16, and V beta 19 was also observed in synovial T cells. These results indicate that biased V beta gene utilization in different peripheral compartments of RA patients can be observed in unselected T cell populations, and are consistent with the conclusion that populations of T cells expressing these V beta gene products may be involved in the pathogenesis of the disease.


Leptospira species infection in cats: ABCD guidelines on prevention and management.
Leptospirosis is a bacterial disease affecting a variety of domestic and wild animals as well as humans worldwide. Leptospirosis has been reported in over 150 mammalian species. It is considered an emerging infectious disease in humans and in dogs. Subclinically infected wild and domestic animals serve as reservoir hosts and are a potential source of infection for incidental hosts and humans. Reports of leptospirosis in cats are rare, but the importance of cats shedding Leptospira species and serving as a source of infection has recently gained attention. Leptospira species antibodies are commonly present in the feline population, and Leptospira species shedding of cats with outdoor exposure has been demonstrated. Cats mostly become infected through transmission from hunting rodents. The role of healthy carrier cats as a source of contamination, as well as the role of leptospires as a pathogen in cats, are likely underestimated.


Beneficial effects of virgin coconut oil on lipid parameters and in vitro LDL oxidation.
The present study was conducted to investigate the effect of consumption of virgin coconut oil (VCO) on various lipid parameters in comparison with copra oil (CO). In addition, the preventive effect of polyphenol fraction (PF) from test oils on copper induced oxidation of LDL and carbonyl formation was also studied. After 45 days of oil feeding to Sprague-Dawley rats, several lipid parameters and lipoprotein levels were determined. PF was isolated from the oils and its effect on in vitro LDL oxidation was assessed. VCO obtained by wet process has a beneficial effect in lowering lipid components compared to CO. It reduced total cholesterol, triglycerides, phospholipids, LDL, and VLDL cholesterol levels and increased HDL cholesterol in serum and tissues. The PF of virgin coconut oil was also found to be capable of preventing in vitro LDL oxidation with reduced carbonyl formation. The results demonstrated the potential beneficiary effect of virgin coconut oil in lowering lipid levels in serum and tissues and LDL oxidation by physiological oxidants. This property of VCO may be attributed to the biologically active polyphenol components present in the oil.


The knottin-like Blufensin family regulates genes involved in nuclear import and the secretory pathway in barley-powdery mildew interactions.
Plants have evolved complex regulatory mechanisms to control a multi-layered defense response to microbial attack. Both temporal and spatial gene expression are tightly regulated in response to pathogen ingress, modulating both positive and negative control of defense. BLUFENSINs, small knottin-like peptides in barley, wheat, and rice, are highly induced by attack from fungal pathogens, in particular, the obligate biotrophic fungus, Blumeria graminis f. sp. hordei (Bgh), causal agent of barley powdery mildew. Previous research indicated that Blufensin1 (Bln1) functions as a negative regulator of basal defense mechanisms. In the current report, we show that BLN1 and BLN2 can both be secreted to the apoplast and Barley stripe mosaic virus (BSMV)-mediated overexpression of Bln2 increases susceptibility of barley to Bgh. Bimolecular fluorescence complementation (BiFC) assays signify that BLN1 and BLN2 can interact with each other, and with calmodulin. We then used BSMV-induced gene silencing to knock down Bln1, followed by Barley1 GeneChip transcriptome analysis, to identify additional host genes influenced by Bln1. Analysis of differential expression revealed a gene set enriched for those encoding proteins annotated to nuclear import and the secretory pathway, particularly Importin α1-b and Sec61 γ subunits. Further functional analysis of these two affected genes showed that when silenced, they also reduced susceptibility to Bgh. Taken together, we postulate that Bln1 is co-opted by Bgh to facilitate transport of disease-related host proteins or effectors, influencing the establishment of Bgh compatibility on its barley host.


Wireless multihop backhauls for rural areas: A preliminary study.
Rural areas have very low revenue potential. The major issue in providing low-cost broadband to rural areas is to provide reliable backhaul connections that spread over tens or even hundreds of miles, connecting villages to the nearest service provider. Along with aerial networks of Google and Facebook, there has been a considerable amount of research toward long-distance terrestrial WiFi links. As a comparison, WiFi routers are easier to be deployed and maintained by non-technical people from the local communities, whereas the aerial networks require professional support to operate. Moreover, they are still in the experimentation phase. However, the long distance WiFi links require high-gain directional antennas and very expensive tall towers for high data rates. On the other hand, multihop paths with stronger links may provide better data rates without the need of tall towers. In this paper, we evaluated the concept of using such multihop WiFi links for long backhaul connections. Our simulation results show that these networks can possibly be a cost-effective and practical solution for rural connectivity. These initial results can serve as a first step to understand the comprehensive feasibility of using multihop WiFi networks for backhaul connections in rural area.


Innovative delivery of siRNA to solid tumors by super carbonate apatite.
RNA interference (RNAi) technology is currently being tested in clinical trials for a limited number of diseases. However, systemic delivery of small interfering RNA (siRNA) to solid tumors has not yet been achieved in clinics. Here, we introduce an in vivo pH-sensitive delivery system for siRNA using super carbonate apatite (sCA) nanoparticles, which is the smallest class of nanocarrier. These carriers consist simply of inorganic ions and accumulate specifically in tumors, yet they cause no serious adverse events in mice and monkeys. Intravenously administered sCA-siRNA abundantly accumulated in the cytoplasm of tumor cells at 4 h, indicating quick achievement of endosomal escape. sCA-survivin-siRNA induced apoptosis in HT29 tumors and significantly inhibited in vivo tumor growth of HCT116, to a greater extent than two other in vivo delivery reagents. With innovative in vivo delivery efficiency, sCA could be a useful nanoparticle for the therapy of solid tumors.


Breast cancer special types: why bother?
Breast cancer is a heterogeneous disease, encompassing multiple entities associated with distinct biological features and clinical behaviours. Microarray-based expression profiling analysis has been used to unravel the molecular underpinning of several characteristics of breast cancer, including its proclivity to disseminate to distant sites and the molecular basis of histological grade. Furthermore, a breast cancer molecular classification based on transcriptional analysis has been proposed. However, microarray studies have primarily analysed invasive ductal carcinomas of no special type. Histological special types of breast cancer, which account for up to 25% of all invasive breast cancers, have not been systematically studied. Despite the limited interest, in recent years it has become apparent that the histopathological characteristics of these cancers may be underpinned by distinct arrays of genetic changes, providing direct evidence for genotypic-phenotypic correlations between morphological patterns and molecular changes in breast cancer (eg t(12;15) in secretory carcinoma of the breast). Here we review the molecular characteristics of special types of breast cancer, with special emphasis on their microarray-based expression profiles and their impact on our understanding of breast cancer.


Rare earth element identification and quantification in millimetre-sized Ryugu rock fragments from the Hayabusa2 space mission.
Millimetre-sized primordial rock fragments originating from asteroid Ryugu were investigated using high energy X-ray fluorescence spectroscopy, providing 2D and 3D elemental distribution and quantitative composition information on the microscopic level. Samples were collected in two phases from two sites on asteroid Ryugu and safely returned to Earth by JAXA's asteroid explorer Hayabusa2, during which time the collected material was stored and maintained free from terrestrial influences, including exposure to Earth's atmosphere. Several grains of interest were identified and further characterised to obtain quantitative information on the rare earth element (REE) content within said grains, following a reference-based and computed-tomography-assisted fundamental parameters quantification approach. Several orders of magnitude REE enrichments compared to the mean CI chondrite composition were found within grains that could be identified as apatite phase. Small enrichment of LREE was found for dolomite grains and slight enrichment or depletion for the general matrices within the Ryugu rock fragments A0055 and C0076, respectively. The online version contains supplementary material available at 10.1186/s40623-022-01705-3.


Frequency of antibodies to Babesia bigemina, B. bovis, Anaplasma marginale, Trypanosoma vivax and Borrelia burgdorferi in cattle from the Northeastern region of the State of Pará, Brazil.
Babesiosis, anaplasmosis, and trypanosomosis are relevant diseases, potentially causing morbidity in cattle, leading to economic losses. Borreliosis is import as a potential zoonosis. The objective of this study was to determine, by indirect enzyme-linked immunosorbent assay (ELISA), the frequency of seropositive cattle to Babesia bigemina, B. bovis, Anaplasma marginale, Trypanosoma vivax and Borrelia burgdorferi in cattle from the Northeastern region of Pará, Brazil. Sera samples from 246 female adult cattle from municipalities of Castanhal and São Miguel do Guamá were used. Crude antigens ELISAs were used to detect antibodies to all agents, except to A. marginale, to which an indirect ELISA with recombinant major surface 1a protein (MSP1a) antigen was used. Overall frequencies of seropositive animals were: B. bigemina--99.2%; B. bovis--98.8%; A. marginale--68.3%; T. vivax--93.1% and B. burgdorferi--54.9%. The frequencies of seropositive cattle to B. bovis and B. bigemina suggest a high rate of transmission of these organisms by tick in the studied region, which can be classified as enzootically stable to these hemoprotozoans. The low frequency of seropositive cattle to A. marginale may be attributed to a lower sensitivity of the recombinant antigen ELISA utilized or a distinct rate of inoculation of this rickettsia by ticks, as compared with Babesia sp. transmission. The high frequency of seropositive cattle to T. vivax indicates that this hemoprotozoan is prevalent in herds from the Northeastern region of Pará. The rate of animal that showed homologues antibodies to B. burgdorferi indicates the presence of the tickborne spirochaetal agent in the cattle population in the studied region.


Urinary incontinence and quality of life in endometrial cancer patients after robotic-assisted laparoscopic hysterectomy with lymph node dissection.
To determine the long-term effects of lymph node dissection on lower urinary tract symptoms in patients treated for endometrial cancer. We conducted a retrospective cohort study of 74 patients with International Federation of Gynaecology and Obstetrics (FIGO) Stage I endometrial cancer who underwent surgical intervention with and without lymph node dissection, and evaluated them with the Urinary Distress Inventory-6 (UDI-6) and Incontinence Impact Questionnaire-7 (IIQ-7). Patients who underwent lymph node dissection reported higher but not statistically different rates of bother by lower urinary tract symptoms compared to those without lymph node dissection. The scores for the lymph node dissection group and the control group were a mean IIQ-7 score of 14.9 ± 23 and 10.5 ± 22.9 (p=.419) and a mean UDI-6 score of 30.0 ± 25.3 and 20.7 ± 22.9 (p=.104), respectively. Lymph node dissection at the time of robotic-assisted surgery did not have a significant effect on lower urinary tract symptoms nor did it affect patient responses on quality of life questionnaires. IMPACT STATEMENT What is already known on this subject? The aetiology of urinary incontinence is multifactorial and there has been debate on how a patient's surgical history affects their risk of developing urinary incontinence. Prior studies have highlighted the relationship between hysterectomy and urinary incontinence (Milsom et al. 1993 ). Additional research has also been done to elucidate the prevalence of pelvic floor disorders in patients who have been surgically treated for endometrial cancer (Erekson et al. 2009 ; Nosti et al. 2012 ). There is limited information on how robotic-assisted lymphadenectomy during surgical staging for endometrial cancer affects patients' urinary function and their quality of life. What do the results of this study add? In this manuscript, we demonstrate that patients who underwent robotic-assisted total laparoscopic hysterectomy (TLH) with lymphadenectomy neither had significant difference in lower urinary tract symptoms nor on quality of life questionnaires as compared to those who did not undergo lymphadenectomy. Worsening of quality of life in regards to urinary incontinence should not be considered a factor of long term surgical morbidity associated with lymph node dissection. What are the implications of these findings for clinical practice and/or further research? There is a need for further studies that focus on the prevalence of pelvic floor disorders in patients after undergoing surgical staging for endometrial cancer and potential interventions that may address these issues.


Enhancement of hepatocyte differentiation from human embryonic stem cells by Chinese medicine Fuzhenghuayu.
Chinese medicine, Fuzhenghuayu (FZHY), appears to prevent fibrosis progression and improve liver function in humans. Here we found that FZHY enhanced hepatocyte differentiation from human embryonic stem cells (hESC). After treatment with FZHY, albumin expression was consistently increased during differentiation and maturation process, and expression of metabolizing enzymes and transporter were also increased. Importantly, expression of mesenchymal cell and cholangiocyte marker was significantly reduced by treatment with FZHY, indicating that one possible mechanism of FZHY's role is to inhibit the formation of mesenchymal cells and cholangiocytes. Edu-labelled flow cytometric analysis showed that the percentage of the Edu positive cells was increased in the treated cells. These results indicate that the enhanced proliferation involved hepatocytes rather than another cell type. Our investigations further revealed that these enhancements by FZHY are mediated through activation of canonical Wnt and ERK pathways and inhibition of Notch pathway. Thus, FZHY not only promoted hepatocyte differentiation and maturation, but also enhanced hepatocyte proliferation. These results demonstrate that FZHY appears to represent an excellent therapeutic agent for the treatment of liver fibrosis, and that FZHY treatment can enhance our efforts to generate mature hepatocytes with proliferative capacity for cell-based therapeutics and for pharmacological and toxicological studies.


Psychological Profile of Patients with Psoriasis.
Psoriasis is a chronic inflammatory disease with a global prevalence of approximately 2% and significant psychiatric comorbidity. There is a great deal of existing literature assessing different aspects of psychology in psoriasis. We aimed to conduct an in-depth review of current evidence linking psoriasis to personality traits and psychiatric comorbidities, as well as factors that put these patients at risk of psychopathology. A search of the PubMed database identified 1632 articles. We included articles studying psychological comorbidity in patients with psoriasis, looking especially at personality characteristics, and data linking psoriasis with increased risks of psychological distress, depression, anxiety and suicidality. In particular, we also evaluated subgroups in psoriasis found to be at risk. Patients with psoriasis are more likely to be alexithymic, lack body awareness and possess a Type D personality. Alcohol, but not illicit drug use, disorders are also more common in patients with psoriasis. Patient groups who are especially at risk of psychological distress include women, younger patients, patients with a younger age of disease onset, those who self-assess their psoriasis to be severe, and those with lesions on visible or sensitive areas. Adopting motivational interviewing skills and incorporating the use of learning materials during consultations have been found to be useful. The knowledge of personality characteristics, "at-risk" groups, and early recognition of psychological distress among patients with psoriasis can help clinicians provide better holistic care and encourage a change in patients' behaviour.


Neuronal Kir3.1/Kir3.2a channels coupled to serotonin 1A and muscarinic m2 receptors are differentially modulated by the "short" RGS3 isoform.
"Regulators of G protein signaling" (RGS proteins) have profound effects on ion channels regulated by G protein-coupled receptor (GPCR) signaling, including the G protein-gated inwardly rectifying K+ (GIRK) channels that inhibit excitability of neuronal, endocrine, and cardiac cells. Here we describe the effects of an alternatively spliced "short" RGS3 isoform (RGS3s) in comparison to RGS4, on the temporal and steady-state gating properties of neuronal GIRK channels (Kir3.1/Kir3.2a) activated by either serotonin 1A (5-HT(1A)) receptors or muscarinic m2 receptors expressed in Chinese hamster ovary (CHO-K1) cells. RGS3s is abundantly expressed in brain and contains a unique short N-terminus via alternative splicing that distinguishes it from other RGS3 isoforms as well as other members of the B/R4 RGS gene subfamily. Our results indicate that RGS3s and RGS4 similarly affect the temporal and steady-state gating properties of 5-HT(1A) receptor-coupled Kir3.1/Kir3.2a channels, but differentially modulate muscarinic m2 receptor-coupled channels. RGS3s caused a significant approximately 45% reduction in the maximal acetylcholine (ACh)-evoked GIRK current amplitude and a marked shift in the steady-state ACh dose-response relation indicative of a reduction in functionally coupled m2 receptor-GIRK channel complexes. Yet RGS3s still accelerated the m2 receptor-dependent GIRK activation, deactivation, and acute desensitization time course consistent with the RGS-enhanced GAP activity that was also observed with RGS4. Several mechanisms that may contribute to the receptor-dependent effects of RGS3s are discussed with particular attention to the role of the distinct N-terminal domain. Our findings highlight the potential impact of selective RGS-GPCR interactions on neuronal GIRK channel function that may affect the properties of inhibitory postsynaptic potentials activated by different GPCR-GIRK channel complexes.


Optimizing the implementation of a forest fuel break network.
Methods and models to design, prioritize and evaluate fuel break networks have potential application in many fire-prone ecosystems where major increases in fuel management investments are planned in response to growing incidence of wildfires. A key question facing managers is how to scale treatments into manageable project areas that meet operational and administrative constraints, and then prioritize their implementation over time to maximize fire management outcomes. We developed and tested a spatial modeling system to optimize the implementation of a proposed 3,538 km fuel break network and explore tradeoffs between two implementation strategies on a 0.5 million ha national forest in the western US. We segmented the network into 2,766 treatment units and used a spatial optimization model to compare linear versus radial project implementation geometries. We hypothesized that linear projects were more efficient at intercepting individual fire events over larger spatial domains, whereas radial projects conferred a higher level of network redundancy in terms of the length of the fuel break exposed to fires. We simulated implementation of the alternative project geometries and then examined fuel break-wildfire spatial interactions using a library of simulated fires developed in prior work. The results supported the hypothesis, with linear projects exhibiting substantially greater efficiency in terms of intercepting fires over larger areas, whereas radial projects had a higher interception length given a fire encountered a project. Adding economic objectives made it more difficult to obtain alternative project geometries, but substantially increased net revenue from harvested trees. We discuss how the model and results can be used to further understand decision tradeoffs and optimize the implementation of planned fuel break networks in conjunction with landscape conservation, protection, and restoration management in fire prone regions.


Factors associated with fatal outcome of children with enterovirus A71 infection: a case series.
Enterovirus A-71 (EV-A71) may be fatal, but the natural history, symptoms, and signs are poorly understood. This study aimed to examine the natural history of fatal EV-A71 infection and to identify the symptoms and signs of early warning of deterioration. This was a clinical observational study of fatal cases of EV-A71 infection treated at five Chinese hospitals between 1 January 2010 and 31 December 2012. We recorded and analysed 91 manifestations of EV-A71 infection in order to identify early prognosis indicators. There were 54 fatal cases. Median age was 21.5 months (Q1-Q3: 12-36). The median duration from onset to death was 78.5 h (range, 6 to 432). The multilayer perceptron analysis showed that ataxia respiratory, ultrahyperpyrexia, excessive tachycardia, refractory shock, absent pharyngeal reflex, irregular respiratory rhythm, hyperventilation, deep coma, pulmonary oedema and/or haemorrhage, excessive hypertension, tachycardia, somnolence, CRT extension, fatigue or sleepiness and age were associated with death. Autopsy findings (n = 2) showed neuronal necrosis, softening, perivascular cuffing, colloid and neuronophagia phenomenon in the brainstem. The fatal cases of enterovirus A71 had neurologic involvement, even at the early stage. Direct virus invasion through the neural pathway and subsequent brainstem damage might explain the rapid progression to death.


Toxicity of spike fragments SARS-CoV-2 S protein for zebrafish: A tool to study its hazardous for human health?
Despite the significant increase in the generation of SARS-CoV-2 contaminated domestic and hospital wastewater, little is known about the ecotoxicological effects of the virus or its structural components in freshwater vertebrates. In this context, this study evaluated the deleterious effects caused by SARS-CoV-2 Spike protein on the health of Danio rerio, zebrafish. We demonstrated, for the first time, that zebrafish injected with fragment 16 to 165 (rSpike), which corresponds to the N-terminal portion of the protein, presented mortalities and adverse effects on liver, kidney, ovary and brain tissues. The conserved genetic homology between zebrafish and humans might be one of the reasons for the intense toxic effects followed inflammatory reaction from the immune system of zebrafish to rSpike which provoked damage to organs in a similar pattern as happen in severe cases of COVID-19 in humans, and, resulted in 78,6% of survival rate in female adults during the first seven days. The application of spike protein in zebrafish was highly toxic that is suitable for future studies to gather valuable information about ecotoxicological impacts, as well as vaccine responses and therapeutic approaches in human medicine. Therefore, besides representing an important tool to assess the harmful effects of SARS-CoV-2 in the aquatic environment, we present the zebrafish as an animal model for translational COVID-19 research.


Glucocorticoid hormones inhibit DNA synthesis in glial cells cultured in chemically defined medium.
Primary cultures of glial cells from 2-day-old rat cerebellum were used to examine the growth control properties of steroid hormones. Immunocytochemical staining with antiglial fibrillary acidic protein (anti-GFAP) demonstrated that the cultures were highly enriched for astrocytes (90%). In an effort to avoid the potential influence of serum-borne steroids, cultures were switched from serum-supplemented to serum-free, chemically defined medium prior to experimentation. Assays for DNA synthesis used [3H]thymidine incorporation with either liquid scintillation counting of TCA-insoluble material or light microscopic autoradiography. Glial cells grown in serum-free, chemically defined medium (F12 basal medium supplemented with putrescine, selenium, insulin, transferrin, and BSA) replicated their DNA to a limited extent even in the absence of serum mitogens. When the glial cells were shifted to defined medium supplemented with various steroid hormones (corticosterone, dexamethasone, hydrocortisone, 17 beta-estradiol, progesterone, or testosterone) at a concentration of 10(-7) M, it was found that the glucocorticoids, corticosterone and dexamethasone inhibited synthesis of DNA by 49.6 and 56.9%, respectively. Hydrocortisone, another glucocorticoid, caused only a small reduction in DNA synthesis. The growth-controlling activity of the glucocorticoids was dose-dependent with concentrations of 10(-7) -10(-6) M showing maximal effect on DNA synthesis. These results suggest that physiological concentrations of glucocorticoid hormones may exert negative control over DNA synthesis of glial cells in the developing or injured central nervous system.


Biosynthesis of factor XIII B subunit by human hepatoma cell lines.
The plasma transglutaminase, factor XIIIa (FXIIIa), circulates as a zymogen containing two proteins, A and B, arranged in a noncovalent tetrameric complex, A2B2. Biosynthesis of plasma FXIII has not previously been demonstrated. In the present study, direct evidence has been obtained that two human hepatoma cell lines, Hep G2 and PLC/PRF/5, synthesize and secrete FXIII B protein. Secretion of the B subunit of FXIII by Hep G2 was demonstrated by immunoblotting. De novo synthesis by Hep G2 was confirmed in 35S-methionine-labeled cultures. Radiolabeled conditioned medium was concentrated, mixed (1:1) with purified B protein, and examined by crossed immunoelectrophoresis with antiserum to the B subunit. The single protein precipitin arc of purified B protein comigrated with the radiolabeled FXIII from Hep G2 visualized by autoradiography, indicating both electrophoretic and antigenic identity. The data presented here represent the first demonstrations of biosynthesis of FXIII B protein by any cell type and suggest that the liver is the site of synthesis of FXIII B protein. Further analysis of concentrated Hep G2 serum-free conditioned medium (SFCM) and cell lysate by immunoblotting following nondenaturing agarose gel electrophoresis demonstrated the FXIII A protein as well as the B protein and also revealed synthesis and secretion of the A and B proteins by PLC/PRF/5. Crossed immunoelectrophoresis studies of Hep G2 SFCM and cell lysate suggest that Hep G2 cells also synthesize and secrete the plasma FXIII zymogen. With a specific radioimmunoassay for B protein, FXIII was found in Hep G2 SFCM at approximately 4 ng/mL; with an amplified rocket immunoelectrophoresis technique the level was approximately 5 ng/mL.


Imaging and manipulation of cytosolic ions and messengers during cell activation.
Optical methods have recently become available for continuously imaging the free concentrations of important ions and second messengers such as calcium, sodium and hydrogen inside living cells. These ion levels are found to undergo remarkable changes upon stimulation of quiescent cells with growth factors known to stimulate phosphoinositide breakdown. In serum-starved REF-52 fibroblasts, growth factors such as serum, vasopressin, or PDGF (platelet-derived growth factor) cause intracellular [Na+] to increase from about 4 mM to 8 mM. If mitogen treatment is combined with pharmacological depolarization of the membrane potential, repetitive [Ca2+]i spikes result in these rat fibroblasts. The mechanism of this oscillation has been investigated by light-flash release of intracellular messengers such as inositol 1,4,5-trisphosphate (Ins(1,4,5)P3), Ca2+, and diacylglycerol, as well as more traditional biochemical techniques. The key feedback pathway appears to be Ca2(+)-stimulation of phospholipase C production of Ins(1,4,5)P3.


Are the cardiac effects of anabolic steroid abuse in strength athletes reversible?
To investigate the reversibility of adverse cardiovascular effects after chronic abuse of anabolic androgenic steroids (AAS) in athletes. Doppler echocardiography and cycle ergometry including measurements of blood pressure at rest and during exercise were undertaken in 32 bodybuilders or powerlifters, including 15 athletes who had not been taking AAS for at least 12 months (ex-users) and 17 currently abusing AAS (users), as well as in 15 anabolic-free weightlifters. Systolic blood pressure was higher in users (mean (SD) 140 (10) mm Hg) than in ex-users (130 (5) mm Hg) (p < 0.05) or weightlifters (125 (10) mm Hg; p < 0.001). Left ventricular muscle mass related to fat-free body mass and the ratio of mean left ventricular wall thickness to internal diameter were not significantly higher in users (3.32 (0.48) g/kg and 42.1 (4.4)%) than in ex-users (3.16 (0.53) g/kg and 40.3 (3.8)%), but were lower in weightlifters (2.43 (0.26) g/kg and 36.5 (4.0)%; p < 0.001). Left ventricular wall thickness related to fat-free body mass was also lower in weightlifters, but did not differ between users and ex-users. Left ventricular wall thickness was correlated with a point score estimating AAS abuse in users (r = 0.49, p < 0.05). In all groups, systolic left ventricular function was within the normal range. The maximum late transmitral Doppler flow velocity (Amax) was higher in users (61 (12) cm/s) and ex-users (60 (12) cm/s) than in weightlifters (50 (9) cm/s; p < 0.05 and p = 0.054). Several years after discontinuation of anabolic steroid abuse, strength athletes still show a slight concentric left ventricular hypertrophy in comparison with AAS-free strength athletes.


Neurotrophic Factors In Cannabis-Induced Psychosis: An Update.
Cannabis is the most widely used illicit substance. Numerous scientific evidence confirm the strong association between cannabis and psychosis. Exposure to cannabis can induce the development of psychosis and schizophrenia in vulnerable individuals. However, the neurobiological processes underlying this relationship are unknown. Neurotrophins are a class of proteins that serve as survival factors for central nervous system (CNS) neurons. In particular, nerve growth factor (NGF) plays an important role in the survival and function of cholinergic neurons while brain-derived neurotrophic factor (BDNF) is involved in synaptic plasticity and the maintenance of midbrain dopaminergic and cholinergic neurons. Glial Cell Derived Neurotrophic Factor (GDNF) promotes the survival of midbrain dopaminergic neurons and Neuregulin 1 (NrG-1) contributes to glutamatergic signals regulating the N-methyl-D-aspartate (NMDA). They have a remarkable influence on the neurons involved in the Δ-9-THC (tethra-hydro-cannabinol) action, such as dopaminergic and glutamatergic neurons, and can play dual roles: first, in neuronal survival and death, and, second, in activity-dependent plasticity. In this brief update, reviewing in a narrative way the relevant literature, we will focus on the effects of cannabis on this class of proteins, which may be implicated, at least in part, in the mechanism of the psychostimulant-induced neurotoxicity and psychosis. Since altered levels of neurotrophins may participate in the pathogenesis of psychotic disorders which are common in drug users, one possible hypothesis is that repeated cannabis exposure can cause psychosis by interfering with neurotrophins synthesis and utilization by CNS neurons.


Targeted anti-colon cancer activities of a millet bran-derived peroxidase were mediated by elevated ROS generation.
Foxtail millet (Setaria italica) is the sixth most important cereal in the world. In particular, the millet-derived active components play important roles in disease prevention. In this study, we found that a peroxidase from foxtail millet bran, named FMBP, displayed profound inhibitory effects on the growth of human colon cancer cells, but not on that of the normal colon epithelial cells. Mechanistic investigations suggested that the selective anti-cancer effects of FMBP were mainly achieved by inducing more accumulation of reactive oxygen species (ROS) in colon cancer cells than normal cells. The preferential ROS accumulation in cancer cells by FMBP appears to be partially attributed to the down-regulation of NF-E2-related factor 2 (Nrf2) expression, and the reduction of catalase activities and glutathione contents. The increased ROS accumulation is speculated to block the STAT3 signaling pathway, which results in the anti-proliferative effects on colon cancer cells. Therefore, these results suggest that the millet bran-derived peroxidase has a therapeutic potential in the management of colon cancer.


[Spectroscopic characterization analysis on Cr (VI) removal mechanism by low-cost adsorbent of rice husk ash].
Analyzing methods of Fourier transform infrared spectroscopy (FTIR), scanning electron microscope (SEM), X-ray photoelectron spectroscopy (XPS), X-ray diffraction analysis (XRD) and X-ray fluorescence spectroscopy (XRF) were used to reveal the adsorption mechanism of Cr(VI) by low-cost adsorbent of rice husk ash. Results of FTIR showed that amide II band, Si--O--Si, and (O--Si--O were important for Cr(VI) removal. SEM micrographs suggested that series of needle-shaped precipitation appeared on cell surface, and inorganic precipitation mechanism and redox mechanism might work in the test. XPS spectra showed that main elements of rice husk ash were C, N, O, P and Si, existing state of C was mainly aldoketones groups, coordi nation reaction existed between C functional groups and Cr(VI); N element, --NH2 in chief, could remove Cr(VI) in the way of physical adsorption based on electrostatic interaction; Si--O might be useful in adsorption process. XRD data suggested representative characteristic adsorption band of SiO2, and the increasing crystallinity of rice husk ash showed metallic compound formed between Cr(VI) and rice husk ash. XRF results indicated that the content of K, Na, Mg and Ca changed, and two new elements were detected, the evidence of ion exchange mechanism. The functional groups played different roles in Cr(VI) adsorption process, and inorganic precipitation mechanism, redox mechanism, surf-complexation mechanism and ion exchange mechanism were important ways in Cr(VI) removal, which could provide theoretical support in further application.


CTLA4 expression is an indicator and regulator of steady-state CD4+ FoxP3+ T cell homeostasis.
The presence of FoxP3(+) regulatory T cells (Tregs) is necessary for control of deleterious immune responses in the steady state; however, mechanisms for maintaining the frequency and quality of endogenous Tregs are not well defined. In this study, we used in vivo modulators of the CD28 and CTLA4 pathways administered to intact mice to reveal mechanisms controlling the homeostasis and phenotype of endogenous Tregs. We demonstrate that expression of the negative costimulatory regulator CTLA4 on FoxP3(+) Tregs in vivo is a direct consequence of their rapid, perpetual homeostasis. Up-regulation of CTLA4 expression occurs only on FoxP3(+) Tregs undergoing extensive proliferation and can be abrogated by inhibiting the CD28 pathway, coinciding with a reduction in FoxP3(+) Treg proliferation and frequency. We further demonstrate that CTLA4 negatively regulates steady-state Treg homeostasis, given that inhibiting CTLA4 signaling with an anti-CTLA4 blocking Ab greatly enhances Treg proliferation and overall Treg frequency. Our findings provide new insight into the origin and role of CTLA4 expression on natural FoxP3(+) Tregs and reveal opposing effects of costimulation modulators on the steady-state level and quality of Tregs, with implications regarding their effects on endogenous Tregs in patients receiving immunotherapy.


Spatial Analysis of Incidence of Diagnosed Type 2 Diabetes Mellitus and Its Association With Obesity and Physical Inactivity.
To investigate the spatial distribution of 10-year incidence of diagnosed type 2 diabetes mellitus (T2DM) and its association with obesity and physical inactivity at a reginal level breakdown. Demographic, behavioral, medical and pharmaceutical and diagnosed T2DM incidence data were collected from a cohort of 232,064 participants who were free of diabetes at enrolment in the 45 and Up Study, conducted in the state of New South Wales (NSW), Australia. We examined the geographical trend and correlation between obesity prevalence, physical inactivity rate and age-and-gender-adjusted cumulative incidence of T2DM, aggregated based on geographical regions. The T2DM incidence, prevalence of obesity and physical inactivity rate at baseline were 6.32%, 20.24%, and 18.7%, respectively. The spatial variation of T2DM incidence was significant (Moran's I=0.52; p<0.01), with the lowest incidence of 2.76% in Richmond Valley-Coastal and the highest of 12.27% in Mount Druitt. T2DM incidence was significantly correlated with the prevalence of obesity (Spearman r=0.62, p<0.001), percentage of participants having five sessions of physical activities or less per week (r=0.79, p<0.001) and percentage of participants walked to work (r=-0.44, p<0.001). The geographical variations in obesity prevalence and physical inactivity rate resembled the geographical variation in the incidence of T2DM. The spatial distribution of T2DM incidence is significantly associated with the geographical prevalence of obesity and physical inactivity rate. Regional campaigns advocating the importance of physical activities in response to the alarming T2DM epidemic should be promoted.


Adipose Stem Cell Function Maintained with Age: An Intra-Subject Study of Long-Term Cryopreserved Cells.
The progressive decline in tissue mechanical strength that occurs with aging is hypothesized to be due to a loss of resident stem cell number and function. As such, there is concern regarding use of autologous adult stem cell therapy in older patients. To abrogate this, many patients elect to cryopreserve the adipose stromal-vascular fraction (SVF) of lipoaspirate, which contains resident adipose stem cells (ASC). However, it is not clear yet if there is any clinical benefit from banking cells at a younger age. We performed a comparative analysis of SVF composition and ASC function from cells obtained under GMP conditions from the same three patients with time gap of 7 to 12 years. SVF, cryobanked under good manufacturing practice (GMP) conditions, was thawed and cell yield, viability, and cellular composition were assessed. In parallel, ASC proliferation and efficiency of tri-lineage differentiation were evaluated. The results showed no significant differences existed in cell yield and SVF subpopulation composition within the same patient between harvest procedures 7 to 12 years apart. Further, no change in proliferation rates of cultured ASCs was found, and expanded cells from all patients were capable of tri-lineage differentiation. By harvesting fat from the same patient at two time points, we have shown that despite the natural human aging process, the prevalence and functional activity of ASCs in an adult mesenchymal stem cell, is highly preserved. 5.


Ensuring Comprehensive Care and Support for Transgender and Gender-Diverse Children and Adolescents.
As a traditionally underserved population that faces numerous health disparities, youth who identify as transgender and gender diverse (TGD) and their families are increasingly presenting to pediatric providers for education, care, and referrals. The need for more formal training, standardized treatment, and research on safety and medical outcomes often leaves providers feeling ill equipped to support and care for patients that identify as TGD and families. In this policy statement, we review relevant concepts and challenges and provide suggestions for pediatric providers that are focused on promoting the health and positive development of youth that identify as TGD while eliminating discrimination and stigma.


[Research on spatially modulated Fourier transform imaging spectrometer data processing method].
Fourier transform imaging spectrometer is a new technic, and has been developed very rapidly in nearly ten years. The data catched by Fourier transform imaging spectrometer is indirect data, can not be used by user, and need to be processed by various approaches, including data pretreatment, apodization, phase correction, FFT, and spectral radicalization calibration. No paper so far has been found roundly to introduce this method. In the present paper, the author will give an effective method to process the interfering data to spectral data, and with this method we can obtain good result.


Association between toll-like receptor 4 gene polymorphism and biopsy-proven giant cell arteritis.
Dendritic cells localized at the adventitia-media border of the normal medium-sized arteries play a pivotal role in the initiation of giant cell arteritis (GCA). These cells express a singular surface receptor profile, including a series of Toll-like receptors (TLR). Ligands of TLR-4 promote activation and differentiation of adventitial dendritic cells and are directly implicated in the pathogenesis of GCA. We aimed to assess the potential implication of the TLR4-(+896 A/G) gene polymorphism in the susceptibility to GCA. A total of 210 patients diagnosed with biopsy-proven GCA and 678 matched controls were included in our study. DNA from patients and controls was obtained from peripheral blood. Samples were genotyped for the TLR4-(+896 A/G) (rs4986790) gene polymorphism by polymerase chain reaction, using a predesigned TaqMan allele discrimination assay. The TLR4 +896 G allele was significantly increased in biopsy-proven GCA patients compared to controls [p = 0.01; odds ratio (OR) 1.65; 95% confidence interval (CI) 1.08-2.52]. The increase was due to a significantly increased frequency of heterozygosity for the TLR4 -896 A/G genotype in the group of patients with biopsy-proven GCA compared to controls (TLR4 -896 A/G heterozygous in patients with GCA 18.1% compared to 11.4% in controls: p = 0.01; OR 1.72; 95% CI 1.10-2.69). However, no significant differences were observed when patients with GCA were stratified according to the presence of specific clinical features of the disease. Our results show for the first time an association of TLR4-(+896 A/G) gene polymorphism with susceptibility to biopsy-proven GCA.


Multivariate Analysis of Electrophysiological Signals Reveals the Temporal Properties of Visuomotor Computations for Precision Grips.
The frontoparietal networks underlying grasping movements have been extensively studied, especially using fMRI. Accordingly, whereas much is known about their cortical locus much less is known about the temporal dynamics of visuomotor transformations. Here, we show that multivariate EEG analysis allows for detailed insights into the time course of visual and visuomotor computations of precision grasps. Male and female human participants first previewed one of several objects and, upon its reappearance, reached to grasp it with the thumb and index finger along one of its two symmetry axes. Object shape classifiers reached transient accuracies of 70% at ∼105 ms, especially based on scalp sites over visual cortex, dropping to lower levels thereafter. Grasp orientation classifiers relied on a system of occipital-to-frontal electrodes. Their accuracy rose concurrently with shape classification but ramped up more gradually, and the slope of the classification curve predicted individual reaction times. Further, cross-temporal generalization revealed that dynamic shape representation involved early and late neural generators that reactivated one another. In contrast, grasp computations involved a chain of generators attaining a sustained state about 100 ms before movement onset. Our results reveal the progression of visual and visuomotor representations over the course of planning and executing grasp movements.SIGNIFICANCE STATEMENT Grasping an object requires the brain to perform visual-to-motor transformations of the object's properties. Although much of the neuroanatomic basis of visuomotor transformations has been uncovered, little is known about its time course. Here, we orthogonally manipulated object visual characteristics and grasp orientation, and used multivariate EEG analysis to reveal that visual and visuomotor computations follow similar time courses but display different properties and dynamics.


Liver Stiffness Measurement and Risk Prediction of Hepatocellular Carcinoma After HCV Eradication in Veterans with Cirrhosis.
Patients with cirrhosis secondary to chronic hepatitis C (HCV) are at risk for hepatocellular carcinoma (HCC) despite a sustained virological response (SVR). We examined whether post-SVR liver stiffness measurement (LSM) could be used to stratify HCC risk. This was a retrospective cohort study of 1,850 participants identified from the Veterans Health Administration, with HCV cirrhosis and SVR, followed up over 5099 person-years, from the time of post-SVR elastography until death, HCC, or the end of the study. The risk of HCC increased by 3% with every 1 kPa increase in LSM (adjusted Hazard Ratio [aHR] 1.03, 95% confidence interval [CI] 1.01-1.04, p<0.001) and decreased with the number of years from SVR (aHR 0.79, 0.70-0.90, p=0.0003). The adjusted annual risk of HCC was 2.03% among participants with post-SVR LSM <10 kPa, 2.48% in LSM 10-14.9 kPa (aHR 1.71, 95% CI 1.01-2.88, p=0.046), 3.22% for LSM 15-19.9 kPa (aHR 1.59, 95% CI 0.78-3.20, p=0.20), 5.07% among LSM 20-24.9 kPa (aHR 2.55, 95% CI 1.30-5.01, p=0.01), and 5.44% in LSM≥25 kPa (aHR 3.03, 95% CI 1.74-5.26, p<0.0001). The adjusted annual risk of HCC was < 0.4% in participants with LSM< 5 kPa and without diabetes mellitus. LSM predicts rates of HCC in patients with HCV cirrhosis after SVR at multiple cutoff levels and offers a single test to predict portal hypertension-related complications and HCC. Patients with LSM <5 kPa in the absence of diabetes mellitus had a low risk of HCC where surveillance could be discontinued.


Novel DSP Spectrin 6 Region Variant Causes Neonatal Erythroderma, Failure to Thrive, Severe Herpes Simplex Infections and Brain Lesions.
Desmoplakin (DSP) and Desmoglein 1 (DSG1) variants result in skin barrier defects leading to erythroderma, palmoplantar keratoderma and variable [AQ4] other features. Some DSG1 variant carriers present with SAM syndrome (Severe dermatitis, multiple Allergies, Metabolic wasting) and a SAM-like phenotype has been reported in 4 subjects with different heterozygous DSP variants. We report here a patient with a novel DSP spectrin region (SR) 6 variant c.1756C>T, p.(His586Tyr), novel features of brain lesions and severe recurrent mucocutaneous herpes simplex virus infections, with a favourable response to ustekinumab. Through a review of reported cases of heterozygous variants in DSP SR6 (n = 15) and homozygous or compound heterozygous variants in DSG1 (n = 12) and SAM-like phenotype, we highlight phenotypic variability. Woolly hair, nail abnormalities and cardiomyopathy characterize patients with DSP variants, while elevated immunoglobulin E and food allergies are frequent in patients with DSG1 variants. Clinicians should be aware of the diverse manifestations of desmosomopathies.


SGI-4 in Monophasic Salmonella Typhimurium ST34 Is a Novel ICE That Enhances Resistance to Copper.
A multi drug resistant Salmonella enterica 4,[5],12:i- of sequence type 34 (monophasic S. Typhimurium ST34) is a current pandemic clone associated with livestock, particularly pigs, and numerous outbreaks in the human population. A large genomic island, termed SGI-4, is present in the monophasic Typhimurium ST34 clade and absent from other S. Typhimurium strains. SGI-4 consists of 87 open reading frames including sil and pco genes previously implicated in resistance to copper (Cu) and silver, and multiple genes predicted to be involved in mobilization and transfer by conjugation. SGI-4 was excised from the chromosome, circularized, and transferred to recipient strains of S. Typhimurium at a frequency influenced by stress induced by mitomycin C, and oxygen tension. The presence of SGI-4 was associated with increased resistance to Cu, particularly but not exclusively under anaerobic conditions. The presence of silCBA genes, predicted to encode an RND family efflux pump that transports Cu from the periplasm to the external milieu, was sufficient to impart the observed enhanced resistance to Cu, above that commonly associated with S. Typhimurium isolates. The presence of these genes resulted in the absence of Cu-dependent induction of pco genes encoding multiple proteins linked to Cu resistance, also present on SGI-4, suggesting that the system effectively limits the Cu availability in the periplasm, but did not affect SodCI-dependent macrophage survival.


Evaluation of Mineral Trioxide Aggregate and Biodentine as pulpotomy agents in immature first permanent molars with carious pulp exposure: A randomised clinical trial.
There is insufficient evidence on the outcome of pulpotomies in carious exposed young permanent molars with newer biomaterials. This study aimed to compare Mineral Trioxide Aggregate (MTA) and Biodentine as pulpotomy materials in carious exposed vital immature mandibular first permanent molars. Study design: Sixty immature first mandibular permanent molars, with carious exposure were randomly assigned to an MTA or Biodentine group in a split-mouth design. After the amputation of the coronal pulp, the pulp stumps were covered with one of the study materials and coronal restorations placed. Blinded clinical and radiographic evaluations were performed at baseline. Following this there were evaluations at 6, 12 and 18 months where comparisons between and within the two groups were made. A high success was observed in both groups for all outcome measures for clinical success, with no significant difference between them. The mean survival time for the Biodentine and MTA groups was (17.8 and 18 months) with 95% confidence interval (17.4-18.2) and (18 .0-18.0) months respectively. Similarly, there were no significant differences between the Biodentine and MTA groups for radiographic success (P<0.001) with an increase in root length and increasing apical closure observed in both groups. Both materials were equally effective in the treatment of cariously exposed vital immature mandibular first permanent molars.


Mechanism and influencing factors of proximal fibular osteotomy for treatment of medial compartment knee osteoarthritis: A prospective study.
Objectives This study was performed to explore the mechanism of proximal fibular osteotomy (PFO) for treatment of medial compartment knee osteoarthritis (OA) and evaluate the relevant factors influencing the treatment outcome. Methods Fifty-two patients with medial compartment knee OA with varus deformities were prospectively selected. Radiographs were obtained preoperatively and postoperatively. Knee function and OA severity were evaluated using the Hospital for Special Surgery (HSS) knee score and the Kellgren-Lawrence (KL) score. Multivariable linear regression models were used to examine associations between increases in the HSS score and selected factors influencing knee OA. Results Sixty-seven knee joints of 45 patients undergoing PFO were included. The HSS scores were significantly better at the final follow-up than preoperatively. Regression analysis identified five factors influencing changes in the HSS score: the change in the vertical distance between the fibular head and tibial plateau, the KL score for tibiofibular joint arthritis, the body mass index, the inclination of the tibiofibular joint, and the preoperative HSS score. Conclusions PFO is a simple and effective procedure for medial compartment knee OA. Greater distal displacement of the fibular head suggests greater range of motion of the tibiofibular joint and more evident improvement of postoperative OA symptoms.


Enzymatically modified LDL, atherosclerosis and beyond: paving the way to acceptance.
The eLDL (enzymatically modified LDL) hypothesis proposes that modification of LDL during atherogenesis occurs through the action of ubiquitous hydrolytic enzymes. eLDL is recognized by multiple macrophage receptors. Following cellular uptake, eLDL triggers atherosclerotic lesion initiation with reversion or progression depending on the balance between cholesterol insudation and depletion. The effects of eLDL on cellular constituents of the atherosclerotic lesion comprise both pro- and anti-inflammatory mechanisms. eLDL triggered complement activation is centrally involved in atherosclerosis with the first CRP (C-reactive protein)-dependent activation step to prevail at the early stages of atherogenesis (lesion initiation with reversion), and the second situation to gain dominance as local concentrations of eLDL surpass a critical threshold (lesion initiation with progression). Thus, CRP-mediated lipoprotein removal likely underlies the regression of early lesions, which occurs continuously through life. Perhaps CRP should be considered as an antiatherogenic agent and the question whether it is an innocent bystander or proatherogenic culprit is not really to the point. The observed association between CRP and atherosclerosis might simply be reverse causation: atherosclerotic disease progression induces CRP.


hKSR-2, a vitamin D-regulated gene, inhibits apoptosis in arabinocytosine-treated HL60 leukemia cells.
Ras signaling can be modulated by the scaffolding activity of kinase suppressor of Ras-1 (KSR-1) and by the hKSR-2 protein, resulting in diverse phenotypic outcomes. The mitogen-activated protein kinase cascade downstream from Ras and KSRs includes Raf-1 and extracellular signal-regulated kinase 1/2 kinases, known to enhance survival potential of a range of cell types. Because the molecular events that increase survival of HL60 cells induced to differentiate toward monocytic phenotype by 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] are not known, we investigated if KSR proteins provide a survival function in these cells. We found that whereas kinase suppressor of Ras-1 had no detectable effect on cell survival in the system studied here, 1,25-(OH)2D3-induced up-regulation of hKSR-2 enhanced the resistance of HL60 cells to arabinocytosine. Knockdown of hKSR-2 by either small interfering RNA or antisense oligonucleotides increased arabinocytosine-induced apoptosis, which was accompanied by reduced Bcl-2/Bax and Bcl-2/Bad ratios, and increased caspase-3 activating cleavage. In contrast, up-regulation of Mcl-1 was not abrogated by anti-sense (AS) AS-hKSR-2, pointing to a specific role of Bcl-2 in control of 1,25-(OH)2D3-induced increased cell survival. These findings are consistent with the previously shown lack of fully differentiated monocytic cells in HL60 cultures exposed to 1,25-(OH)2D3 in which hKSR-2 was knocked down, suggesting that optimal differentiation of these cells requires enhanced antiapoptotic mechanisms provided, at least in part, by hKSR-2. Collectively, these results suggest that hKSR-2 may offer a new target for novel therapies of acute myelogenous leukemia.


A qualitative examination of barriers and solutions to renal transplantation in Malaysia: Key-informants' perspective.
End-stage renal disease (ESRD) is increasing globally, and renal transplantation (RT) is the preferred renal replacement therapy to treat ESRD. Internationally, there are only a few countries with RT rates above 50 per million population (pmp), while most of the countries have RT rates between 30-40 pmp. The low- and middle-income countries (LMIC) makes up the majority for the RT rates below 20 pmp in which Malaysia belongs to despite its increasing ESRD rates. There is a need to explore the barriers to access RT with targeted solutions to improve the RT rates and service in LMIC. Thus, a qualitative study was undertaken in Malaysia to address this issue. A qualitative methodological approach was performed between March-May 2018. Semi-structured interviews were used to explore current RT policy and service availability. Key-informants were identified from a detailed stakeholder analysis of RT system in Malaysia. Interviews were digitally audio-recorded, transcribed verbatim, coded with ATLAS.ti software and underwent thematic analysis thoroughly. Eight key-informants participated in the study. Barriers and related solutions were classified using the socio-ecological model (SEM). As reported, the barriers and solutions of RT in Malaysia are the results of a complex interplay of personal, cultural, and environmental factors. Key barriers are linked to public's attitude and perception towards RT and the unaccommodating practices in the healthcare fraternity for RT. Key-informants provided a systematic solution that shed light on how RT could be improved at each SEM level via effective communication, education and inter-agency collaboration. The SEM provided a framework to foster a better understanding of current practice, barriers, and solutions to RT in Malaysia. This study is the first to explore the barriers and related solutions to RT comprehensively as a whole. Implications of these findings could prompt a policy change for a better RT service delivery model not just for Malaysia but also for other LMIC. Further stakeholder engagement and evaluation of the systems are required to provide insight into best practices that will help to improve the RT rates and service in Malaysia.


[Method to increase efficiency of irradiation of biological objects by electron beams].
The method has been proposed for active control of distribution of the dose caused by an electron beam passed through the medium. The method is based on the influence of magnetic field on charged particles and it allows concentrating of the absorbed dose in the prescribed area. To investigate this method the Monte-Carlo simulations were carried out for 20-70 MeV electrons in 0.5-3 T magnetic field using GEANT program. From the obtained results it follows that in the uniform magnetic field the maximum in distribution of the electron beam dose appears and its shape is similar to Bregg's peak for heavy charged particles. The location of the maximum may be changed by varying beam energy and magnetic fields configuration. For 60-70 MeV beam the maximum may be obtained at the depth of 10-15 cm that is convenient for radiotherapeutic usage.


Influence of IL17A polymorphisms on the aberrant methylation of DAPK and CDH1 in non-cancerous gastric mucosa.
CpG island aberrant methylation is shown to be an important mechanism in gene silencing. The important role of IL-17 in inflammatory response to H. pylori colonization has been indicated. We investigated the influence of IL17A polymorphisms, -197 G > A (rs2275913) and *1249 C > T (rs3748067), on the methylation of DAPK and CDH1. Gastric mucosal samples were obtained from 401 subjects without malignancies. Methylation status of gene was determined by MSP. The genotyping of IL17A was performed by PCR-SSCP. Methylations of DAPK and CDH1 were seen in 196 and 149 of all 401 subjects, respectively. Overall, *1249 T carrier was associated with a decreased risk for DAPK methylation, whereas -197 G > A was not. In the subjects older than 60 years old, *1249 T carrier was more strongly associated with gene methylation and -197 A carrier tended to be associated with an increased risk for CDH1 methylation. When evaluating by inflammation promoting haplotype (-197 mutant carrier with *1249 homozygote), this haplotype had a more strongly increased risk for both DAPK and CDH1 methylations in comparatively older subjects. Both atrophy and metaplasia scores were significantly increased with age in -197 A carrier or *1249 CC homozygote, whereas were not in -197 GG homozygote or *1249 T carrier. PG I/II ratio was more significantly decreased in -197 A carrier than in GG homozygote under influence of H. pylori infection. In -197 A allele carrier with *1249 CC homozygote, the methylations of both DAPK and CDH1 may be increased gradually, but more rapidly than the other genotypes, with age and altered gastric mucosal structure induced by H. pylori infection.


Development of Y-axon innervation of cortical area 18 in the cat.
1. Geniculocortical Y-axons (n = 38) in the optic radiations of 4-5-week-old kittens (n = 20) and adult cats (n = 18) were studied both physiologically and morphologically. Axons were recorded from intracellularly and subsequently filled ionophoretically with horseradish peroxidase (HRP). The HRP filled the axons' terminal arborizations in visual cortex (particularly well for those innervating area 18). Fourteen axons appeared to be completely filled with HRP (n = 8 in kitten, n = 6 in adult) and served as the basis for the quantitative analysis of the terminal arborizations reported in this study. 2. The distribution and correspondence of the axonal boutons to presynaptic elements in cortical layer 4A was analysed at both the light and electron microscope level using computerized three-dimensional analysis and serial section reconstruction, respectively. Compared to adult axons, the boutons of the kitten axons were smaller (means = 0.75 vs. 1.75 microns length, P less than 0.001) and more densely spaced both along individual axon branches (means = 6.60 vs. 11.20 microns interbouton interval, P less than 0.001) and between neighbouring branches of the same axon (means = 4.7 vs. 6.4 microns nearest-neighbour distance, P less than 0.01). 3. Most kitten boutons made a single Gray's type 1 synapse on a cortical neurone, unlike adult boutons which usually contacted two or more postsynaptic targets. Both kitten and adult axons had dendritic spines as their major target. Occasionally, HRP reaction-product was observed in cortical neurones postsynaptic to the labelled geniculocortical axon, which gave some estimate of the number of synaptic contacts between a single geniculocortical axon and target cell (about five). 4. The kitten Y-axons innervated the visual cortex in a pattern similar to that of the adult, with the richest terminal branching and bouton density in layer 4A with some additional boutons distributed in layers 3, 4B and 6. The extent of the terminal arborizations primarily in layer 4A (as measured in surface views) of kitten Y-axons in area 18 was significantly less than that of adult Y-axons in area 18 (means = 0.9 mm2 vs. means = 1.2 mm2, P = 0.04). 5. We conclude that between 4 and 5 postnatal weeks and 1 year, geniculocortical Y-axons projecting to cortical area 18 undergo four major changes. These include a reduction in synaptic bouton density (both in three-dimensional space and along individual branches), a concomitant moderate expansion in the surface area of cortex innervated, an increase in bouton size and an increase in the number of synaptic contacts made by each bouton. A general proportional growth of the individual axons' terminal arborization together with fusion and/or separation of neighbouring boutons is sufficient to explain this development.


Structural elements in the Girk1 subunit that potentiate G protein-gated potassium channel activity.
G protein-gated inwardly rectifying K(+) (Girk/K(IR)3) channels mediate the inhibitory effect of many neurotransmitters on excitable cells. Girk channels are tetramers consisting of various combinations of four mammalian Girk subunits (Girk1 to -4). Although Girk1 is unable to form functional homomeric channels, its presence in cardiac and neuronal channel complexes correlates with robust channel activity. This study sought to better understand the potentiating influence of Girk1, using the GABA(B) receptor and Girk1/Girk2 heteromer as a model system. Girk1 did not increase the protein levels or alter the trafficking of Girk2-containing channels to the cell surface in transfected cells or hippocampal neurons, indicating that its potentiating influence involves enhancement of channel activity. Structural elements in both the distal carboxyl-terminal domain and channel core were identified as key determinants of robust channel activity. In the distal carboxyl-terminal domain, residue Q404 was identified as a key determinant of receptor-induced channel activity. In the Girk1 core, three unique residues in the pore (P) loop (F137, A142, Y150) were identified as a collective potentiating influence on both receptor-dependent and receptor-independent channel activity, exerting their influence, at least in part, by enhancing mean open time and single-channel conductance. Interestingly, the potentiating influence of the Girk1 P-loop is tempered by residue F162 in the second membrane-spanning domain. Thus, discontinuous and sometime opposing elements in Girk1 underlie the Girk1-dependent potentiation of receptor-dependent and receptor-independent heteromeric channel activity.


US Evaluation of Axillary Lymphadenopathy Following COVID-19 Vaccination: A Prospective Longitudinal Study.
Background Both temporal changes in imaging characteristics of lymphadenopathy on US scans after COVID-19 vaccination and expected duration of radiologically evident lymphadenopathy remain uncertain. Purpose To longitudinally evaluate COVID-19 vaccine-associated lymphadenopathy on axillary US scans at various time intervals in both messenger (mRNA) and vector vaccine recipients. Materials and Methods This prospective cohort study was conducted between March 2021 and January 2022. The participants were asymptomatic women without breast cancer who had received COVID-19 vaccination. Serial follow-up US was performed in women with lymphadenopathy. The following variables were assessed: cortical thickness, number of lymph nodes, morphologic characteristics, and Doppler signal. Temporal changes in cortical thickness and number of lymph nodes during follow-up were assessed using a linear mixed model. Results Ninety-one women with lymphadenopathy in the vaccinated arm had undergone a total of 215 serial US examinations (mean age, 44 years ± 13 [SD]). Fifty-one participants had received a vector vaccine (ChAdOx1 nCoV-19 vaccine) and 40 had received an mRNA vaccine (BNT162b2 vaccine [n = 37] and mRNA-1273 vaccine [n = 3]). Three of the 91 women were lost to follow-up; thus, 88 women underwent serial US. Complete resolution of axillary lymphadenopathy was observed at a median of 6 weeks after vaccination (range, 4-7 weeks) in 26% of women (23 of 88). Among 49 women with follow-up US at a median of 12 weeks after vaccination (range, 8-14 weeks), persistent lymphadenopathy was observed in 25 (51%). During the follow-up period, the cortical thickness gradually decreased (P < .001) over time regardless of vaccine type; however, values were higher in recipients of the mRNA vaccine than in recipients of the vector vaccine (P = .02). Conclusion COVID-19 vaccine-associated axillary lymphadenopathy frequently persisted for more than 6 weeks on US scans. Lymphadenopathy should be interpreted considering vaccine type and time elapsed since vaccination. Follow-up US examination at least 12 weeks after vaccination may be reasonable, particularly for recipients of the messenger RNA vaccine. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Moy and Kim in this issue.


Dissecting the unique role of the retinoblastoma tumor suppressor during cellular senescence.
The RB protein family (RB, p107, and p130) has overlapping and compensatory functions in cell-cycle control. However, cancer-associated mutations are almost exclusively found in RB, implying that RB has a nonredundant role in tumor suppression. We demonstrate that RB preferentially associates with E2F target genes involved in DNA replication and is uniquely required to repress these genes during senescence but not other growth states. Consequently, RB loss leads to inappropriate DNA synthesis following a senescence trigger and, together with disruption of a p21-mediated cell-cycle checkpoint, enables extensive proliferation and rampant genomic instability. Our results identify a nonredundant RB effector function that may contribute to tumor suppression and reveal how loss of RB and p53 cooperate to bypass senescence.


UV but not gamma-irradiation induces specific transcriptional activity of p53 in primary hepatocytes.
The mechanisms are poorly understood by which p53 can stimulate different downstream events, including growth arrest, DNA repair, and apoptosis, after DNA damage. Changes in protein levels do not predict a particular p53 response, but it is possible that differences in functional activities such as transactivation are important. The present report describes the successful use of a specific p53 reporter plasmid transfected into primary murine hepatocytes to evaluate p53 transactivation activity over time after two different genotoxic injuries (gamma-irradiation, 15 Gy and UV-c irradiation, 10 J/m2) known to produce p53-dependent growth arrest in this cell type. The results show that UV injury to hepatocytes was followed by a transient increase in transcriptional activation of the reporter plasmid by p53 and that this response preceded changes in p53 protein levels, as assessed by immunocytochemistry. By contrast, gamma-irradiation injury failed to induce detectable changes in either transactivation activity or hepatocyte p53 protein levels. The data show that p53 responses to DNA damage are dependent on both cell and injury type and suggest that in hepatocytes they can be independent of protein concentration and specific transcriptional activity. The results have implications for how particular dysfunctional p53 mutations in carcinogenesis could alter hepatocyte responses to different DNA injuries.


Pharmacists' role in ensuring safe and effective hospital use of insulin.
To highlight the potential errors that may occur with insulin use in the inpatient setting and to describe how pharmacists can be part of the solution by implementing practices that reduce the likelihood of insulin-related medication errors. Insulin is a drug with a low therapeutic index, and it bears a heightened risk of causing significant patient harm when used in error, making it a high-alert medication. Both underdosing and overdosing of insulin may be associated with adverse outcomes. The use of standard insulin order sets for scheduled subcutaneous insulin administration and standard concentrations for i.v. insulin are recommended to ensure the safe use of this medication. Any ambiguous insulin therapy orders should be clarified in writing prior to administration. Preparation of all insulin infusions should occur within the pharmacy. Pharmacists should be aware of possible medication errors related to inappropriate use of abbreviations such as U for units. Safe insulin storage practices are recommended to reduce the risk for insulin error. Insulin pen delivery devices may be used in hospitals, but safe use depends on ongoing oversight by a multidisciplinary committee, introduction of one device at a time, and initial and regular follow-up education of nurses, including agency nurses and those who work part-time. In addition, ongoing monitoring is needed to assure ongoing safety. The use of sliding-scale insulin can lead to hyperglycemia and hypoglycemia and is confusing and prone to error; it is not recommended. Pharmacists can contribute to the safe use of insulin in the inpatient setting by minimizing the likelihood of medication errors related to prescribing, transcription, dispensing, administration, storage, and communication.


1,25-Dihydroxyvitamin D3 and muscle strength in the elderly: a randomized controlled trial.
An unexplained loss of muscle strength occurs with aging. Vitamin D deficiency can cause myopathy and administration of 1,25-dihydroxyvitamin D3 [1,25-(OH2)D3] to persons with low serum concentrations can improve strength. To test the hypothesis that the weakness associated with aging is in part due to inadequate serum concentrations of [1,25-(OH2)D3], we conducted a randomized, controlled, double blinded trial in 98 men and women volunteers over 69 yr old. Treatment consisted of 0.25 micrograms 1,25-(OH)2D3, orally, twice per day or identical placebo for 6 months. Leg muscle strength of the quadriceps was measured with an isokinetic dynamometer. There was no difference between the two groups at 1 week, 1 month, or 6 months of treatment in any of the measures of muscle strength. We conclude that oral administration of 0.5 micrograms 1,25-(OH)2D3/day does not improve muscle strength in older persons. Further research is needed to determine the etiology of the decline in muscle strength associated with aging.


Interruption of continuous opioid exposure exacerbates drug-evoked adaptations in the mesolimbic dopamine system.
Drug-evoked adaptations in the mesolimbic dopamine system are postulated to drive opioid abuse and addiction. These adaptations vary in magnitude and direction following different patterns of opioid exposure, but few studies have systematically manipulated the pattern of opioid administration while measuring neurobiological and behavioral impact. We exposed male and female mice to morphine for one week, with administration patterns that were either intermittent (daily injections) or continuous (osmotic minipump infusion). We then interrupted continuous morphine exposure with either naloxone-precipitated or spontaneous withdrawal. Continuous morphine exposure caused tolerance to the psychomotor-activating effects of morphine, whereas both intermittent and interrupted morphine exposure caused long-lasting psychomotor sensitization. Given links between locomotor sensitization and mesolimbic dopamine signaling, we used fiber photometry and a genetically encoded dopamine sensor to conduct longitudinal measurements of dopamine dynamics in the nucleus accumbens. Locomotor sensitization caused by interrupted morphine exposure was accompanied by enhanced dopamine signaling in the nucleus accumbens. To further assess downstream consequences on striatal gene expression, we used next-generation RNA sequencing to perform genome-wide transcriptional profiling in the nucleus accumbens and dorsal striatum. The interruption of continuous morphine exposure exacerbated drug-evoked transcriptional changes in both nucleus accumbens and dorsal striatum, dramatically increasing differential gene expression and engaging unique signaling pathways. Our study indicates that opioid-evoked adaptations in brain function and behavior are critically dependent on the pattern of drug administration, and exacerbated by interruption of continuous exposure. Maintaining continuity of chronic opioid administration may, therefore, represent a strategy to minimize iatrogenic effects on brain reward circuits.


Butyrylcholinesterase inhibitory activity of testosterone and some of its metabolites.
Testosterone and ten of its metabolites were examined as inhibitors of butyrylcholinesterase. A significant enzyme inhibition activity (IC(50) = 1.55 microM) was observed for androst-4-en-3,7-dione. The kinetic parameters of butyrylcholinesterase inhibition were determined and molecular docking was carried out in order to develop a better understanding of the inhibitor-enzyme interactions. The results showed that the inhibition was non-competitive, stabilized mainly by hydrogen bonds and hydrophobic interactions between the inhibitor and butyrylcholinesterase.


Neurotoxicity Associated With Dimethyl Sulfoxide Used in Allogeneic Stem Cell Transplantation.
Dimethyl sulfoxide (DMSO) is a cryoprotective agent used in storage of frozen stem cells in stem cell transplantation. Central nervous system side effects of DMSO such as epileptic seizures, stroke, transient global amnesia, and temporary leucoencephalopathy are rarely seen. Here, we report a pediatric patient who developed seizures after DMSO-cryopreserved stem cell infusion and whose magnetic resonance imaging of the brain demonstrated parietal and occipital focal cortical T2-signal intensity increase. DMSO toxicity should be kept in mind in patients who received cryopreserved stem cell infusion and magnetic resonance imaging may be helpful in differential diagnosis of central nervous system involvement.


Male breast cancer: an 11 year review of 66 patients.
A review was conducted of 66 men with carcinoma of the breast seen at this institution between 1981 and 1992. The results of the study suggest that there are many similarities between breast cancer in men and women. The most common clinical presentation was a lump in the breast. The majority of tumors were T1 or T2, and infiltrating ductal carcinoma was the predominant histological type. Axillary nodal status and histological grade were predictive of survival. The pattern of recurrence and survival rates were similar to those seen in women. Some differences, however, were evident. Tumors were centrally located in the majority of patients and there was a high frequency of nipple involvement. The hormone receptor positivity rate was high and the median age at presentation was older. In comparison to a previous report of the same disease from this institution 10 years ago, fewer patients underwent radical surgical procedures and more patients received adjuvant systemic therapy. These approaches are justified since there are many biological similarities between breast cancer in men and women.


HPV types, cervical high-grade lesions and risk factors for oncogenic human papillomavirus infection among 3416 Tanzanian women.
The objective of the present study was to assess the prevalence and type-specific distribution of cervical high-risk (HR) human papillomavirus (HPV) among women with normal and abnormal cytology, and to describe risk factors for HR HPV among HIV-positive and HIV-negative women in Tanzania. A cross-sectional study was conducted in existing cervical cancer screening clinics in Kilimanjaro and Dar es Salaam. Cervical specimens were obtained from women aged 25-60 years. Samples were shipped to Denmark for cytological examination, and to Germany for HR HPV testing (using Hybrid Capture 2) and genotyping (using LiPaExtra). Risk factors associated with HPV were assessed by multivariable logistic regression analysis. Altogether, 4080 women were recruited with 3416 women contributing data for the present paper, including 609 HIV-positive women and 2807 HIV-negative women. The overall HR HPV prevalence was 18.9%, whereas the HR HPV prevalence in women with high-grade squamous intraepithelial lesions (HSILs) was 92.7%. Among HPV-positive women with HSIL, HPV16 (32.5%) and HPV58 (19.3%) were the the most common types followed by HPV18 (16.7%) and HPV52 (16.7%). Factors associated with HR HPV included younger age, increasing number of partners and early age at first intercourse. Similar risk factors were found among HIV-positive and HIV-negative women. In addition, among HIV-positive women, those with CD4 counts <200 cells/mm3 had an increased risk of HR HPV (OR 2.2; 95% CI 1.2 to 4.8) compared with individuals with CD4 count ≥500 cells/mm3. Given the HPV distribution among Tanzanian women, the current HPV vaccination in Tanzania using quadrivalent vaccine may be considered replaced by the nonavalent vaccine in the future. In addition, appropriate antiretroviral treatment management including monitoring of viremia may decrease the burden of HR HPV in HIV-positive women.


[Activity of 5-aminolevulinate synthase in rat liver during degradation of cytochrome P-450 caused by administration of cadmium chloride].
The 5-aminolevulinate synthase, tryptophan-2,3-dioxygenase activities and cytochrome P-450 content in the rat liver was studied in different terms after CdCl2 administration and after administration of metal salt against a background of 2-hours action of alpha-tocopherol. The lowering of activity of 5-aminolevulinate synthase in 2 h with the consequent increase of the enzyme activity in 6 h and 24 h was detected. The holoenzyme activity and heme saturation of tryptophan-2,3-dioxygenase increased 6 h after CdCl2 administration. The holoenzyme activity and the total activity of tryptophan-2,3-dioxygenase rised in 24 h. The level of cytochrome P-450 lowered. Preliminary administration of alpha-tocopherol prevented changes of studied parameters 24 h after CdCl2 administration. The relationship between decrease of cytochrome P-450 level and 5-aminolevulinate synthase activation are discussed.


[Sport as a profession: medical and social aspects].
The author analyses possible use of methods and achievements of industrial medicine in solving problems of acme in sports. The article covers theoretic, methodologic and practical basis for possible integration of industrial medicine and sports medicine. Mechanisms of such interdisciplinary integration include current legal basis, scientific research (mostly, concept of occupational risk, norm and pathology concept, doctrine of preventive medicine, etc), practical experience accumulated in this country and abroad. Some aspects of public health preservation in contemporary Russia are also tackled.


Triage of patients and remote consultations in primary care facilities during the COVID-19 pandemic in France (PRICOV-19 study)
PRICOV-19 is a European cross-sectional study based on an online questionnaire, describing the impact of the pandemic on primary care structures (PCS). In France, PCS are solo practices (SP), single or multi-professional group practices (GP), coordinated practice structures (CPS): health houses and health centers. Triage, whether it is digital (TD), by telephone (TT) or at the reception (TR), is essential to reduce the risk of infection, and is part of recommended organizational practices. Based on French data from the PRICOV-19 study, the objective is to describe the frequency and factors associated with triage in PCSs during the COVID 19 pandemic. 1100 structures responded to the survey. The TD was implemented in 64% of PCSs (53.3% of SPs, 64.9% of GPs, 73.2% of CPSs). The TT was implemented in 76% of structures (72.7% of SPs, 75.4% of GPs and 81% of CPSs). Finally, TR was implemented in 52% of structures (37.7% of SPs, 52% of GPs and 67% of CPSs). The other positively associated factors are the urban territory and the lower workload for the TD, and the presence of a receptionist for the TR. Triage practices seem to be clearly associated with the organization and working conditions in the PCSs, and first and foremost with the type of structure.


Terrestrial adult stages of freshwater insects are sensitive to insecticides.
Terrestrial adult stages of freshwater insects may be exposed to pesticides by wind drift, over-spray, contact or feeding. However, studies addressing insecticide effects on freshwater invertebrates focus primarily on the impact of pesticides reaching the streams and potentially harming the aquatic juvenile stages. This is also reflected in the current risk assessment procedures, which do not include testing of adult freshwater insects. In order to assess the potential impact of insecticides on adult stages of freshwater insects, we exposed six common species to the insecticides Karate (lambda-cyhalothrin) and Confidor (imidacloprid). Dose-response relations were established, and LD50 estimates were compared to those of the honey bee, Apis mellifera L. (Hymenoptera: Apidae), which is the standard terrestrial test insect when pesticides are evaluated prior to commercial release. Generally, the tested species were more sensitive to the studied insecticides than the honey bee. In order to examine whether the sensitivity of adult stages of freshwater insects corresponds with the sensitivity of the juvenile stages of the same species, the ranking of the two life stages with respect to the toxicity of Karate was compared, revealing some correspondence, but also some dissimilarities. Our results strongly indicate that terrestrial adult stages of aquatic insects are not adequately protected by current risk assessment procedures.


Plaque Wall Distribution Pattern of the Atherosclerotic Middle Cerebral Artery Associates With the Circle of Willis Completeness.
Objective: Investigating the relevance of the incomplete circle of Willis (COW) to the plaque wall distribution in the atherosclerotic middle cerebral arteries (MCAs) through utilizing high-resolution magnetic resonance imaging (HR-MRI), and its potential clinical impact. Methods: This hospital-based study enrolled consecutive adult patients with acute ischemic stroke or transient ischemic attack, who received a 3.0T Achieva MR system scanning. The COW completeness was evaluated on MR angiography imaging, including anterior (A) and posterior (P)-COW sections. The MCA plaque wall distribution was assessed on HR-MRI. The occurrence of perforator infarction was detected on diffusion-weighted imaging. Results: Among 87 patients (mean age = 62.39 ± 11.64 years old) with atherosclerotic plaques in the MCA M1 segments, the incomplete COW types were more prevalent than the complete COW type (incomplete P-COW, 83.9%; incomplete A-COW, 36.8%; complete COW, 8.1%). The incomplete A-COW had more inferior but fewer ventral plaques of MCA atherosclerosis than the complete A-COW, while the incomplete P-COW had fewer inferior MCA plaques than the complete P-COW. Moreover, symptomatic MCA plaques causing perforator infarctions were more likely to locate on the superior wall. Conclusion: Our findings suggested that the COW completeness could influence the vessel wall distribution of the MCA plaques, among which the superior plaques of symptomatic MCA atherosclerosis was associated with branch occlusive disease.


[Inflammatory diseases of the external auditory passage and methods for their treatment].
Inflammatory diseases of the external auditory passage may be of immune or infectious origin. In both cases, the main manifestations are erythema, swelling, and pruritus of the skin of the external auditory passage. The treatment with ointments is restricted by the difficulty of their application. The use of ear drops containing neomycyn sulfate, polymyxin B sulfate, and dexamethasone (polydexa) appears more reasonable. The two antibiotics have a synergistic effect when acting on various pathogenic microorganisms whereas dexamethasone acts as a universal anti-inflammatory agent.


Contrasting relationships between biogeochemistry and prokaryotic diversity depth profiles along an estuarine sediment gradient.
Detailed depth profiles of sediment geochemistry, prokaryotic diversity and activity (sulphate reduction and methanogenesis) were obtained along an estuarine gradient from brackish to marine, at three sites on the Colne estuary (UK). Distinct changes in prokaryotic populations [Archaea, Bacteria, sulphate-reducing bacteria (SRB) and methanogenic archaea (MA)] occurred with depth at the two marine sites, despite limited changes in sulphate and methane profiles. In contrast, the brackish site exhibited distinct geochemical zones (sulphidic and methanic) yet prokaryotic depth profiles were broadly homogenous. Sulphate reduction rates decreased with depth at the marine sites, despite nonlimiting sulphate concentrations, and hydrogenotrophic methanogenic rates peaked in the subsurface. Sulphate was depleted with depth at the brackish site, and acetotrophic methanogenesis was stimulated. Surprisingly, sulphate reduction was also stimulated in the brackish subsurface; potentially reflecting previous subsurface seawater incursions, anaerobic sulphide oxidation and/or anaerobic oxidation of methane coupled to sulphate reduction. Desulfobulbaceae, Desulfobacteraceae, Methanococcoides and members of the Methanomicrobiales were the dominant SRB and MA. Methylotrophic Methanococcoides often co-existed with SRB, likely utilising noncompetitive C1-substrates. Clear differences were found in SRB and MA phylotype distribution along the estuary, with only SRB2-a (Desulfobulbus) being ubiquitous. Results indicate a highly dynamic estuarine environment with a more complex relationship between prokaryotic diversity and sediment geochemistry, than previously suggested.


A review of omega-3 ethyl esters for cardiovascular prevention and treatment of increased blood triglyceride levels.
The two marine omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), prevalent in fish and fish oils, have been investigated as a strategy towards prophylaxis of atherosclerosis. While the results with fish and fish oils have been not as clear cut, the data generated with the purified ethyl ester forms of these two fatty acids are consistent. Although slight differences in biological activity exist between EPA and DHA, both exert a number of positive actions against atherosclerosis and its complications. EPA and DHA as ethyl esters inhibit platelet aggregability, and reduce serum triglycerides, while leaving other serum lipids essentially unaltered. Glucose metabolism has been studied extensively, and no adverse effects were seen. Pro-atherogenic cytokines are reduced, as are markers of endothelial activation. Endothelial function is improved, vascular occlusion is reduced, and the course of coronary atherosclerosis is mitigated. Heart rate is reduced, and heart rate variability is increased by EPA and DHA. An antiarrhythmic effect can be demonstrated on the supraventricular and the ventricular level. More importantly, two large studies showed reductions in clinical endpoints like sudden cardiac death or major adverse cardiac events. As a consequence, relevant cardiac societies recommend using 1 g/day of EPA and DHA for cardiovascular prevention, after a myocardial infarction and for prevention of sudden cardiac death.