Adherence to protective measures among healthcare workers in the UK: a cross-sectional study.
Healthcare workers (HCWs) are frontline responders to emergency infectious disease outbreaks such as COVID-19. To avoid the rapid spread of disease, adherence to protective measures is paramount. We investigated rates of correct use of personal protective equipment (PPE), hand hygiene and physical distancing in UK HCWs who had been to their workplace at the start of the COVID-19 pandemic and factors associated with adherence. We used an online cross-sectional survey of 1035 UK healthcare professionals (data collected 12-16 June 2020). We excluded those who had not been to their workplace in the previous 6 weeks, leaving us with a sample size of 831. Respondents were asked about their use of PPE, hand hygiene and physical distancing in the workplace. Frequency of uptake was reported descriptively; adjusted logistic regressions were used to separately investigate factors associated with adherence to use of PPE, maintaining good hand hygiene and physical distancing from colleagues. Adherence to personal protective measures was suboptimal (PPE use: 80.0%, 95% CI 77.3 to 82.8; hand hygiene: 67.8%, 95% CI 64.6 to 71.0; coming into close contact with colleagues: 74.7%, 95% CI 71.7 to 77.7). Adherence to PPE use was associated with having received training about health and safety in the workplace for COVID-19, greater perceived social pressure to adopt the behaviour and availability of PPE. Non-adherence was associated with fatalism about COVID-19 and greater perceived difficulty of adopting protective measures. Workplace design using markings to facilitate distancing was associated with adherence to physical distancing. Uptake of personal protective behaviours among UK HCWs at the start of the pandemic was variable. Factors associated with adherence provide insight into ways to support HCWs to adopt personal protective behaviours, such as ensuring that adequate PPE is available and designing workplaces to facilitate physical distancing.


Utility of Dermatoglyphic Pattern in Prediction of Caries in Children of Telangana Region, India.
Dermatoglyphics is an extremely useful tool as a preliminary investigation method for diagnosing suspected genetic disorders. Caries being a multifactorial disease with the influence of genetic pattern, early identification of caries risk children with dermatoglyphics can help in using effective and efficient caries preventive measures. The study was undertaken to record and know the frequency of occurrence of fingerprint patterns among children with caries and in children without caries. A total of 400 schoolchildren in the age group of 5 to 12 years were selected from a private school, Warangal, Telangana, India. Of 400 schoolchildren, 200 children were with caries group and 200 children were in caries-free group. Children with dental caries in five or more teeth based on the decayed, missing, filled teeth index performed were considered as study group, and the control group was normal healthy children without any dental caries. The fingerprints of each child were recorded using stamp pad method, and type of dermatoglyphic pattern of each digit was recorded based on Cummins and Midlo method. Data obtained were put for statistical analysis; p < 0.001 was considered statistically significant. Although the frequency of whorl pattern was more prevalent in caries group, it was statistically significant on the left hand third digit of females and on the right hand third digit and the left hand fourth digit of males. Fingerprints of female caries-free group showed maximum of ulnar loop and males showed maximum of arches. There was a decrease in total ridge count in caries group, especially in males. Dermatoglyphics could be an appropriate method to explore the possibility of a noninvasive and an early predictor for dental caries. Dermatoglyphics has a future role in identifying people with or at increased risk for dental caries so that risk reduction measures or earlier therapy may be instituted.


An Overview of Additive Manufacturing Technologies-A Review to Technical Synthesis in Numerical Study of Selective Laser Melting.
Additive Manufacturing (AM) processes enable their deployment in broad applications from aerospace to art, design, and architecture. Part quality and performance are the main concerns during AM processes execution that the achievement of adequate characteristics can be guaranteed, considering a wide range of influencing factors, such as process parameters, material, environment, measurement, and operators training. Investigating the effects of not only the influential AM processes variables but also their interactions and coupled impacts are essential to process optimization which requires huge efforts to be made. Therefore, numerical simulation can be an effective tool that facilities the evaluation of the AM processes principles. Selective Laser Melting (SLM) is a widespread Powder Bed Fusion (PBF) AM process that due to its superior advantages, such as capability to print complex and highly customized components, which leads to an increasing attention paid by industries and academia. Temperature distribution and melt pool dynamics have paramount importance to be well simulated and correlated by part quality in terms of surface finish, induced residual stress and microstructure evolution during SLM. Summarizing numerical simulations of SLM in this survey is pointed out as one important research perspective as well as exploring the contribution of adopted approaches and practices. This review survey has been organized to give an overview of AM processes such as extrusion, photopolymerization, material jetting, laminated object manufacturing, and powder bed fusion. And in particular is targeted to discuss the conducted numerical simulation of SLM to illustrate a uniform picture of existing nonproprietary approaches to predict the heat transfer, melt pool behavior, microstructure and residual stresses analysis.


Carbon-Free CoO Mesoporous Nanowire Array Cathode for High-Performance Aprotic Li-O2 Batteries.
Although various kinds of catalysts have been developed for aprotic Li-O2 battery application, the carbon-based cathodes are still vulnerable to attacks from the discharge intermediates or products, as well as the accompanying electrolyte decomposition. To ameliorate this problem, the free-standing and carbon-free CoO nanowire array cathode was purposely designed for Li-O2 batteries. The single CoO nanowire formed as a special mesoporous structure, owing even comparable specific surface area and pore volume to the typical Super-P carbon particles. In addition to the highly selective oxygen reduction/evolution reactions catalytic activity of CoO cathodes, both excellent discharge specific capacity and cycling efficiency of Li-O2 batteries were obtained, with 4888 mAh gCoO(-1) and 50 cycles during 500 h period. Owing to the synergistic effect between elaborate porous structure and selective intermediate absorption on CoO crystal, a unique bimodal growth phenomenon of discharge products was occasionally observed, which further offers a novel mechanism to control the formation/decomposition morphology of discharge products in nanoscale. This research work is believed to shed light on the future development of high-performance aprotic Li-O2 batteries.


Dietary Protective Potential of Fucoxanthin as an Active Food Component on Neurological Disorders.
The prevalence of neurodegenerative, cerebrovascular, and psychiatric diseases and other neurological disorders has increased dramatically worldwide. Fucoxanthin is an algal pigment with many biological functions, and there is rising evidence that fucoxanthin plays a preventive and therapeutic role in neurological disorders. This review focuses on the metabolism, bioavailability, and blood-brain barrier penetration of fucoxanthin. Furthermore, the neuroprotective potential of fucoxanthin in neurodegenerative diseases, cerebrovascular diseases, and psychiatric diseases as well as other neurological disorders such as epilepsy, neuropathic pain, and brain tumors by acting on multiple targets will be summarized. The multiple targets include regulating apoptosis, reducing oxidative stress, activating the autophagy pathway, inhibiting Aβ aggregation, improving dopamine secretion, reducing α-synuclein aggregation, attenuating neuroinflammation, modulating gut microbiota, and activating brain-derived neurotrophic factor, etc. Additionally, we look forward to brain-targeted oral transport systems due to the low bioavailability and blood-brain barrier permeability of fucoxanthin. We also propose exploring the systemic mechanisms of fucoxanthin metabolism and transport through the gut-brain process and envision new therapeutic targets for fucoxanthin to act on the central nervous system. Finally, we propose dietary fucoxanthin delivery interventions to achieve preventive effects on neurological disorders. This review provides a reference for the application of fucoxanthin in the neural field.


Cartilage failures. Systematic literature review, critical survey analysis, and definition.
While midterm results of matrix-assisted autologous chondrocyte transplantation (MACT) are now available, less attention has been paid to the evaluation of failures of this surgical approach. Aim of this study was to analyse how "failures" are generally defined in cartilage surgery, in order to understand how the survival rate may change according to different definitions of failure. A systematic review on MACT in the knee was conducted to report failure rates as well as different failure definitions in the available literature. Afterwards, we analysed the survival curve at 8.5-year follow-up of a survey of 193 patients treated with MACT. Using different definitions to identify failures, we compared how the survival rate changed according to the different definitions of failure. The systematic review on 93 papers showed that the average failure rate reported on 3,289 patients was 5.2 % at a mean 34 months of follow-up. However, 41 studies (44.1 %) did not even consider this aspect, and failures were variously defined, thus generating confusing data that make a meta-analysis or a study comparison meaningless. The failure analysis of the MACT survey showed that the survival curve changed significantly depending on the definition applied; in fact, the failure rate ranged from 3.6 to 33.7 %. According to a critical literature and survey analysis, we proposed a combined surgical- and improvement-based definition which led to a failure rate of 25.9 % at midterm/long-term follow-up. Nowadays, failure definitions of cartilage treatments differ in scientific articles, thus generating confusion and heterogeneous data even when applied to the same cohort of patients. While the literature analysis shows a low number of failures, this study demonstrated that if properly addressed with a comprehensive definition, the real failure rate of cartilage surgical procedures in the knee is higher than previously reported. Recognizing failures would give a better understanding and a more realistic prognosis to patients and physicians seeking treatment for cartilage lesions. IV.


Temporal differences in the expression of mRNA for IL-10 and IFN-gamma in the brains and spleens of C57BL/10 mice infected with Toxoplasma gondii.
C57BL/10 Sc Sn (B10) mice infected orally with Toxoplasma gondii tissue cysts were killed at regular intervals up to day 116 post infection (p.i.) and their brains excised. These were used either to count the total number of cysts in the brain, for RNA purification or histopathological studies. Mortality levels in a parallel group of T. gondii infected B10 mice were also monitored and regular plasma samples taken to measure specific antibody production. Seventy per cent of mice died within the first 35 days of infection. Thereafter deaths were infrequent. Inflammation in the brain was apparent from day 10 onwards and by day 25 there was widespread astrocyte activation, perivascular cuffing, meningitis and extensive encephalitis. Total cyst numbers increased rapidly from day 15 to day 35 when they peaked. By day 60, however, cyst numbers had dropped dramatically and this decrease continued through to day 116. Using the polymerase chain reaction mRNA transcripts for IFN-gamma were detected from the first time point sampled, day 25 p.i., until the end of the study. Transcripts for IL-10, an inhibitor of IFN-gamma production, release and activity, were not detected until day 70. The predominant antibody detected against T. gondii was IgG2a but not IgG1. Significantly transcripts for IFN-gamma were found in the spleens of infected but not non-infected animals. Our results suggest that an inflammatory response associated with IFN-gamma production in B10 mice eventually controls T. gondii infection. After the cyst burden has dropped dramatically transcripts for IL-10 are detected in the brain, perhaps to suppress inflammation, and limit pathology.


N-WASP involvement in dorsal ruffle formation in mouse embryonic fibroblasts.
The Wiskott-Aldrich syndrome protein (WASP) family activates the Arp2/3 complex leading to the formation of new actin filaments. Here, we study the involvement of Scar1, Scar2, N-WASP, and Arp2/3 complex in dorsal ruffle formation in mouse embryonic fibroblasts (MEFs). Using platelet-derived growth factor to stimulate circular dorsal ruffle assembly in primary E13 and immortalized E9 Scar1(+/+) and Scar1 null MEFs, we establish that Scar1 loss does not impair the formation of dorsal ruffles. Reduction of Scar2 protein levels via small interfering RNA (siRNA) also did not affect dorsal ruffle production. In contrast, wiskostatin, a chemical inhibitor of N-WASP, potently suppressed dorsal ruffle formation in a dose-dependent manner. Furthermore, N-WASP and Arp2 siRNA treatment significantly decreased the formation of dorsal ruffles in MEFs. In addition, the expression of an N-WASP truncation mutant that cannot bind Arp2/3 complex blocked the formation of these structures. Finally, N-WASP(-/-) fibroblast-like cells generated aberrant dorsal ruffles. These ruffles were highly unstable, severely depleted of Arp2/3 complex, and diminished in size. We hypothesize that N-WASP and Arp2/3 complex are part of a multiprotein assembly important for the generation of dorsal ruffles and that Scar1 and Scar2 are dispensable for this process.


HLA-E expression and its clinical relevance in human renal cell carcinoma.
The non-classical human leukocyte antigen E (HLA-E) expression is frequently overexpressed in tumor diseases, transplants and virus-infected cells and represents an immunomodulatory molecule by binding to the receptors CD94/NKG2A, -B and -C on NK and T cells. Due to its immune suppressive features HLA-E expression might represent an important mechanism of tumors to escape immune surveillance.While an aberrant expression of the non-classical HLA-G antigen in human renal cell carcinoma (RCC) has been demonstrated to be associated with a worse outcome of patients and reduced sensitivity to immune effector cell-mediated cytotoxicity, the expression and function of HLA-E has not yet been analyzed in this tumor entity.Higher levels of HLA-E transcripts were detected in all RCC cell lines and tumor lesions, which were tested in comparison to normal kidney epithelium. Immunohistochemical staining of a tissue microarray (TMA) using the HLA-E-specific monoclonal antibody TFL-033 recognizing the cytoplasmic HLA-E α-chain as monomer revealed a heterogeneous HLA-E expression in RCC lesions with the highest frequency in chromophobe RCC when compared to other RCC subtypes. HLA-E expression did not correlate with the frequency of CD3+, CD4+, CD8+ and FoxP3+ immune cell infiltrations, but showed an inverse correlation with infiltrating CD56+ cells. In contrast to HLA-G, HLA-E expression in RCCs was not statistically significant associated with a decreased disease specific survival. These data suggest that HLA-E overexpression frequently occurs in RCC and correlates with reduced immunogenicity.


Effects of flame made zinc oxide particles in human lung cells - a comparison of aerosol and suspension exposures.
Predominantly, studies of nanoparticle (NPs) toxicology in vitro are based upon the exposure of submerged cell cultures to particle suspensions. Such an approach however, does not reflect particle inhalation. As a more realistic simulation of such a scenario, efforts were made towards direct delivery of aerosols to air-liquid-interface cultivated cell cultures by the use of aerosol exposure systems.This study aims to provide a direct comparison of the effects of zinc oxide (ZnO) NPs when delivered as either an aerosol, or in suspension to a triple cell co-culture model of the epithelial airway barrier. To ensure dose-equivalence, ZnO-deposition was determined in each exposure scenario by atomic absorption spectroscopy. Biological endpoints being investigated after 4 or 24h incubation include cytotoxicity, total reduced glutathione, induction of antioxidative genes such as heme-oxygenase 1 (HO-1) as well as the release of the (pro)-inflammatory cytokine TNFα. Off-gases released as by-product of flame ZnO synthesis caused a significant decrease of total reduced GSH and induced further the release of the cytokine TNFα, demonstrating the influence of the gas phase on aerosol toxicology. No direct effects could be attributed to ZnO particles. By performing suspension exposure to avoid the factor "flame-gases", particle specific effects become apparent. Other parameters such as LDH and HO-1 were not influenced by gaseous compounds: Following aerosol exposure, LDH levels appeared elevated at both timepoints and the HO-1 transcript correlated positively with deposited ZnO-dose. Under submerged conditions, the HO-1 induction scheme deviated for 4 and 24h and increased extracellular LDH was found following 24h exposure. In the current study, aerosol and suspension-exposure has been compared by exposing cell cultures to equivalent amounts of ZnO. Both exposure strategies differ fundamentally in their dose-response pattern. Additional differences can be found for the factor time: In the aerosol scenario, parameters tend to their maximum already after 4h of exposure, whereas under submerged conditions, effects appear most pronounced mainly after 24h. Aerosol exposure provides information about the synergistic interplay of gaseous and particulate phase of an aerosol in the context of inhalation toxicology. Exposure to suspensions represents a valuable complementary method and allows investigations on particle-associated toxicity by excluding all gas-derived effects.


Transient left ventricular apical ballooning and exercise induced hypertension during treadmill exercise testing: is there a common hypersympathetic mechanism?
To describe two cases of Takotsubo like myocardial contractile pattern during exercise stress test secondary to hypertensive response. Treadmill exercise testing is known to cause sympathetic stimulation, leading to increased levels of catecholamine, resulting in alteration in vascular tone. Hypertensive response during exercise testing can cause abnormal consequences, resulting in false positive results. We present the cases of two patients experiencing apical and basal akinesis during exercise stress echocardiography, in whom normal wall motion response was observed on subsequent pharmacologic stress testing. The first patient developed transient left ventricular (LV) apical akinesis during exercise stress echocardiography. Due to high suspicion that this abnormality might be secondary to hypertensive response, pharmacologic stress testing was performed after three days, which was completely normal and showed no such wall motion abnormality. Qualitative assessment of myocardial perfusion using contrast was also performed, which showed good myocardial blood flow, indicating low probability for significant obstructive coronary artery disease. The second patient developed LV basal akinesis as a result of hypertensive response during exercise testing. Coronary angiogram was not performed in either patient due to low suspicion for coronary artery disease, and subsequently negative stress studies. Transient stress induced cardiomyopathy can develop secondary to hypertensive response during exercise stress testing. These cases provide supporting evidence to the hyper-sympathetic theory of left ventricular ballooning syndrome.


Meningitis and encephalitis management in the ICU.
Management of patients with meningitis and encephalitis oftentimes requires ICU level of care. This article is an update on management for meningitis and encephalitis with focus on clinical care in the ICU. Information provided is based on a review of recent studies with focus on studies since 2017. Advances in diagnostic and treatment approach for different pathogens are presented. Nosocomial meningitis now constitutes a major part of brain infections seen in ICUs in the developed world. Advances in ICU care of central nervous system (CNS) infections include application of newer diagnostic methods, improved understanding and delivery of antibiotics to the CNS, infection prevention for nosocomial infections, and application of neuromonitoring where indicated. Advances in diagnostics and therapeutic approach to CNS infections are continually made. For intensivists, focus on neuromonitoring and brain resuscitation in critically ill patients with CNS infections may present a path to enhance preservation of brain function and improve outcomes. VIDEO ABSTRACT: http://links.lww.com/COCC/A22.


The prospects of daytime running lights for reducing vehicle crashes in the United States.
Daytime running lights increase visual contrast between vehicles and their background, improving their noticeability and detectability. Seven countries require motor vehicles to have lights on during all daytime periods--Canada, Denmark, Finland, Hungary, Iceland, Norway, and Sweden. Studies from these and other countries have generally indicated that daytime running lights use is associated with small to moderate reductions in multiple-vehicle daytime crashes, especially those involving vehicles approaching from the front or side. There is evidence also that initial positive effects of daytime running lights do not dissipate over time, that is, there is little support for novelty or habituation effects. The bulk of the evidence suggests that running lights do not lead to increases in collisions involving pedestrians and pedalcyclists, allaying concerns that there would be negative consequences of making these road users relatively less conspicuous. Most of the studies have been conducted in countries located at latitudes that are to the north of most of the continental United States and that have longer twilight periods and generally lower ambient illumination. The concern has been expressed that running lights may lose their effectiveness in countries located at lower latitudes, such as the United States, because the lights will provide less of a contrast. General Motors Corporation and some other manufacturers are now providing running lights on new models with higher intensities than are used in Scandinavian countries. Findings in running lights studies suggest that their effect in the United States will be positive, and their introduction provides an opportunity to determine the effect. The costs of running lights are low, so even modest crash reductions would be cost effective.


Pragmatic evaluation of events and benefits of lipid lowering in older adults (PREVENTABLE): Trial design and rationale.
Whether initiation of statins could increase survival free of dementia and disability in adults aged ≥75 years is unknown. PREVENTABLE, a double-blind, placebo-controlled randomized pragmatic clinical trial, will compare high-intensity statin therapy (atorvastatin 40 mg) with placebo in 20,000 community-dwelling adults aged ≥75 years without cardiovascular disease, disability, or dementia at baseline. Exclusion criteria include statin use in the prior year or for >5 years and inability to take a statin. Potential participants are identified using computable phenotypes derived from the electronic health record and local referrals from the community. Participants will undergo baseline cognitive testing, with physical testing and a blinded lipid panel if feasible. Cognitive testing and disability screening will be conducted annually. Multiple data sources will be queried for cardiovascular events, dementia, and disability; survival is site-reported and supplemented by a National Death Index search. The primary outcome is survival free of new dementia or persisting disability. Co-secondary outcomes are a composite of cardiovascular death, hospitalization for unstable angina or myocardial infarction, heart failure, stroke, or coronary revascularization; and a composite of mild cognitive impairment or dementia. Ancillary studies will offer mechanistic insights into the effects of statins on key outcomes. Biorepository samples are obtained and stored for future study. These results will inform the benefit of statins for increasing survival free of dementia and disability among older adults. This is a pioneering pragmatic study testing important questions with low participant burden to align with the needs of the growing population of older adults.


Lead poisoning and the deceptive recovery of the critically endangered California condor.
Endangered species recovery programs seek to restore populations to self-sustaining levels. Nonetheless, many recovering species require continuing management to compensate for persistent threats in their environment. Judging true recovery in the face of this management is often difficult, impeding thorough analysis of the success of conservation programs. We illustrate these challenges with a multidisciplinary study of one of the world's rarest birds-the California condor (Gymnogyps californianus). California condors were brought to the brink of extinction, in part, because of lead poisoning, and lead poisoning remains a significant threat today. We evaluated individual lead-related health effects, the efficacy of current efforts to prevent lead-caused deaths, and the consequences of any reduction in currently intensive management actions. Our results show that condors in California remain chronically exposed to harmful levels of lead; 30% of the annual blood samples collected from condors indicate lead exposure (blood lead ≥ 200 ng/mL) that causes significant subclinical health effects, measured as >60% inhibition of the heme biosynthetic enzyme δ-aminolevulinic acid dehydratase. Furthermore, each year, ∼20% of free-flying birds have blood lead levels (≥450 ng/mL) that indicate the need for clinical intervention to avert morbidity and mortality. Lead isotopic analysis shows that lead-based ammunition is the principle source of lead poisoning in condors. Finally, population models based on condor demographic data show that the condor's apparent recovery is solely because of intensive ongoing management, with the only hope of achieving true recovery dependent on the elimination or substantial reduction of lead poisoning rates.


Research Trends and Hot Topics on Virtual Reality in Nursing: A Bibliometric Analysis Using CiteSpace.
This bibliometric analysis was conducted to provide a comprehensive overview of the development of virtual reality in nursing, and to identify the research trends and hot topics in this field. Data were collected from the Web of Science Core Collection database in May and June 2022, and analyses were performed using CiteSpace 6.1.R2. A total of 885 studies on virtual reality were included in the bibliometric analysis; 3570 authors from 1283 institutions and 60 countries contributed, and the studies were published in 356 different journals. It will be important for researchers and health professionals to determine the research trends, current issues, and research gaps on virtual reality in nursing.


Occupational health, mercury exposure, and environmental justice: learning from experiences in Tanzania.
Mercury is a potent neurotoxin that is used by poverty-driven miners to extract gold in more than 50 countries. This article examines efforts of the United Nations to address occupational health and environmental justice amid these challenges, focusing on a 3-year campaign in one of the fastest-growing mining communities in Tanzania. By providing an integrative analysis of environmental health risks, labor practices, public health policies, and drivers of social inequity and marginalization, this study highlights the need for interdisciplinary public health approaches that support community development by strengthening local capacities. It illustrates why, to ensure that the needs of vulnerable populations are met, environmental justice and public health paradigms have to expand beyond the conventionally narrow attention paid to toxic exposure and emissions issues.


Fructose and metabolic health: governed by hepatic glycogen status?
Fructose is a commonly ingested dietary sugar which has been implicated in playing a particularly harmful role in the development of metabolic disease. Fructose is primarily metabolised by the liver in humans, and increases rates of hepatic de novo lipogenesis. Fructose increases hepatic de novo lipogenesis via numerous mechanisms: by altering transcriptional and allosteric regulation, interfering with cellular energy sensing, and disrupting the balance between lipid synthesis and lipid oxidation. Hepatic de novo lipogenesis is also upregulated by the inability to synthesise glycogen, either when storage is inhibited in knock-down animal models or storage is saturated in glycogen storage disease. Considering that fructose has the capacity to upregulate hepatic glycogen storage, and replenish these stores more readily following glycogen depleting exercise, the idea that hepatic glycogen storage and hepatic de novo lipogenesis are linked is an attractive prospect. We propose that hepatic glycogen stores may be a key factor in determining the metabolic responses to fructose ingestion, and saturation of hepatic glycogen stores could exacerbate the negative metabolic effects of excessive fructose intake. Since physical activity potently modulates glycogen metabolism, this provides a rationale for considering nutrient-physical activity interactions in metabolic health.


Safety, pharmacokinetics, and pharmacodynamics of the DR5 antibody LBY135 alone and in combination with capecitabine in patients with advanced solid tumors.
We evaluated the safety, maximum tolerated dose (MTD), pharmacokinetics, pharmacodynamics, biologic activity, and antitumor efficacy of the DR5 antibody, LBY135 ± capecitabine. Escalating LBY135 was administered every 21 days, alone (Arm1) or with capecitabine (Arm2), to patients with advanced solid tumors. In Arm1 (n = 40), LBY135 (0.3-40 mg/kg) resulted in no dose-limiting toxicities (DLTs); adverse events (AEs) included fatigue, hypotension, abdominal pain, dyspnea, and nausea. Stable disease (SD) was observed in 21/38 (55.3 %) patients. In Arm2 (n = 33), LBY135 (1-40 mg/kg) plus capecitabine resulted in 3 DLTs (each grade 3): dehydration and mucosal inflammation (1 mg/kg), colitis (20 mg/kg), and diarrhea (40 mg/kg). AEs included fatigue, nausea, dyspnea, and vomiting. Partial response was observed in 2 patients (rectal and breast cancer) and SD in 12/27 (44.4 %) patients. Mean elimination half-life of LBY135 ± capecitabine at saturation of clearance (≥10 mg/kg) ranged between 146 h and 492 h. Immunogenicity was detected in 16/73 (22 %) patients, of which 6 patients experienced reduced LBY135 exposure with repeat dosing. M30/M65 levels were not predictive for LBY135 response. FDG-PET responses were not consistently associated with RECIST responses. LBY135 was well tolerated up to 40 mg/kg, the maximal dose administered; no MTD for LBY135 ± capecitabine was defined. Clearance was saturated at doses ≥10 mg/kg.


Characterizing and classifying neuroendocrine neoplasms through microRNA sequencing and data mining.
Neuroendocrine neoplasms (NENs) are clinically diverse and incompletely characterized cancers that are challenging to classify. MicroRNAs (miRNAs) are small regulatory RNAs that can be used to classify cancers. Recently, a morphology-based classification framework for evaluating NENs from different anatomical sites was proposed by experts, with the requirement of improved molecular data integration. Here, we compiled 378 miRNA expression profiles to examine NEN classification through comprehensive miRNA profiling and data mining. Following data preprocessing, our final study cohort included 221 NEN and 114 non-NEN samples, representing 15 NEN pathological types and 5 site-matched non-NEN control groups. Unsupervised hierarchical clustering of miRNA expression profiles clearly separated NENs from non-NENs. Comparative analyses showed that miR-375 and miR-7 expression is substantially higher in NEN cases than non-NEN controls. Correlation analyses showed that NENs from diverse anatomical sites have convergent miRNA expression programs, likely reflecting morphological and functional similarities. Using machine learning approaches, we identified 17 miRNAs to discriminate 15 NEN pathological types and subsequently constructed a multilayer classifier, correctly identifying 217 (98%) of 221 samples and overturning one histological diagnosis. Through our research, we have identified common and type-specific miRNA tissue markers and constructed an accurate miRNA-based classifier, advancing our understanding of NEN diversity.


Characterization of the purified Chlamydomonas minus agglutinin.
Chlamydomonas flagellar sexual agglutinins are responsible for the adhesion of opposite mating-type (plus and minus) gametes during the first stages of mating. Purification and partial characterization of the plus agglutinin was previously reported (Adair, W. S., C. J. Hwang, and U. W. Goodenough, 1983, Cell, 33:183-193). Here we characterize the purified minus molecule. We show it to be a high molecular weight, hydroxyproline-rich glycoprotein that migrates in the 3% stacking region of an SDS-polyacrylamide gel and is absent from two nonagglutinating minus mutants. Plus and minus agglutinins are remarkably similar, although nonidentical, in amino acid composition, molecular morphology, and reactivity in vivo and in vitro with monoclonal antibodies raised against the plus agglutinin. Moreover, the adhesiveness of both plus and minus agglutinins, when coupled to agarose beads, is abolished by thermolysin, trypsin, periodate, alkaline borohydride, reducing agents, or heat, but unaffected by exo- or endoglycosidases. The minus agglutinin, however, migrates just ahead of the plus molecule on SDS PAGE, is excluded from an anion-exchange (Mono Q) column, elutes earlier during hydrophobic interaction (Bio-gel TSK Phenyl 5PW) chromatography, and is sensitive to chymotrypsin digestion (unlike the plus agglutinin); therefore, it differs from the plus agglutinin in apparent molecular weight, net charge, relative hydrophobicity and proteolytic susceptibility. Nevertheless, our results generally demonstrate a high degree of homology between these complementary cell-cell recognition/adhesion molecules, which suggests that they are specified by genes that have a common evolutionary origin.


Prospective integration of cultural consideration in biomedical research for patients with advanced cancer: recommendations from an international conference on malignant bowel obstruction in palliative care.
In the setting of an international conference on malignant bowel obstruction as a model for randomized controlled trials (RCTs) in palliative care, we discuss the importance of incorporating prospective cultural considerations into research design. The approach commonly used in biomedical research has traditionally valued the RCT as the ultimate "way of knowing" about how to best treat a medical condition. The foremost limitation of this approach is the lack of recognition of the impact of cultural viewpoints on research outcomes. We propose that interest relevant to cultural viewpoints should be emphasized in conceptualizing and interpreting research questions, designs, and results. In addition to recognizing our cultural biases as individuals and researchers, we recommend two major shifts in designing and implementing RCTs: 1) inclusion of a multidisciplinary team of researchers to inform the diversity of perspectives and expertise brought to the research, and 2) use of mixed methods of inquiry, reflecting both deductive and inductive modes of inference.


Epidemiology and Predictors of Long-Stays in Medical ICU: A Retrospective Cohort Study.
Prolonged stays in ICU have been associated with overconsumption of resources but little is known about their epidemiology. We aimed to identify predictors and prognostic factors of extended stays, studying a long-stay population. We present a retrospective cohort study between July 2000 and December 2013 comparing patients hospitalized in a medical ICU for ≥30 days (long-stay patients-LSP) with patients hospitalized for <30 days (short-stay patients-SSP). Admission characteristics were collected from the local database for every patient and evolution during the ICU stay was retrieved from LSP files. Among 8906 patients hospitalized in the ICU, 417 (4.7%) were LSP. At admission, male sex (adjusted odds-ratio (aOR) 1.4 [1.1; 1.7]), inpatient (aOR 2.0 [1.6; 2.4]) and in-ICU hospitalizations for respiratory (aOR 2.9 [1.6; 3.5]) or infectious diseases (aOR 1.6 [1.1; 2.5]) were all independently associated with a long stay in the ICU, while hospitalizations for metabolic (aOR 0.2 [0.1; 0.5]) or cardiovascular diseases (aOR 0.3 [0.2; 0.5]) were in favor of a short stay. In-ICU and in-hospital LSP mortality were 38.8% and 48.2%. Age (aOR 1.02 [1.00-1.04]), catecholamines (aOR 3.9 [1.9; 8.5]), renal replacement therapy (aOR 2.4 [1.3; 4.3]), primary disease-related complications (aOR 2.5 [1.4; 4.6]) and nosocomial infections (aOR 4.1 [1.8; 10.1]) were independently associated with mortality in LSP. LSP were highly comorbid patients mainly hospitalized for respiratory diseases. Their mortality was mostly related to nosocomial infections but the majority were discharged alive from the hospital.


Phenotypic mixing between different hepadnavirus nucleocapsid proteins reveals C protein dimerization to be cis preferential.
Hepadnaviruses encode a single core (C) protein which assembles into a nucleocapsid containing the polymerase (P) protein and pregenomic RNA during viral replication in hepatocytes. We examined the ability of heterologous hepadnavirus C proteins to cross-oligomerize. Using a two-hybrid assay in HepG2 cells, we observed cross-oligomerization among the core proteins from hepatitis B virus (HBV), woodchuck hepatitis virus, and ground squirrel hepatitis virus. When expressed in Xenopus oocytes, in which hepadnavirus C proteins form capsids, the C polypeptides from woodchuck hepatitis virus and ground squirrel hepatitis virus, but not duck hepatitis B virus, can efficiently coassemble with an epitope-tagged HBV core polypeptide to form mixed capsids. However, when two different core mRNAs are coexpressed in oocytes the core monomers show a strong preference for forming homodimers rather than heterodimers. This holds true even for coexpression of two HBV C proteins differing only by an epitope tag, suggesting that core monomers are not free to diffuse and associate with other monomers. Thus, mixed capsids result from aggregation of different species of homodimers.


Oral verruciform xanthoma and erythroplakia associated with chronic graft-versus-host disease: a rare case report and review of the literature.
Oral verruciform xanthoma is an uncommon benign lesion. Although oral verruciform xanthoma occurs in healthy individuals, it has been also reported in association with some inflammatory conditions. The aim of this study is to report a case of oral verruciform xanthoma associated with chronic graft-versus-host disease and to review the literature on this topic. A 47-year-old Caucasian male presented to the Sector of Oral Medicine "V. Margiotta", University Policlinic "P. Giaccone" of Palermo complaining of a mass on the gingiva. He first noticed the painless mass 1 year ago. He reported to have undergone allogenic hematopoietic stem cell transplantation 15 years ago for acute lymphoblastic leukaemia. Intraoral examination revealed a well-circumscribed, sessile yellowish and verrucous nodule upon canine, multiple yellowish and verrucous nodules on the hard palate, yellowish and verrucous nodules on left buccal mucosa. In addiction an area of white striae in a reticular pattern with erythema and ulceration was present on the dorsum of the tongue. This lesion was consistent with a known history of oral chronic graft versus host disease. Moreover, we observed a suspected area of oral erythroplakia yet on the dorsum of the tongue. In biopsy specimen of hard palate histopathological examination revealed a diagnosis of verrucous xanthoma of the oral cavity; in addiction in biopsy specimen of the dorsum of the tongue revealed the presence of erythroplakia with high grade dysplasia. Verruciform xanthoma of the oral cavity associated with chronic graft-versus-host disease is a rare condition with a usually benign clinical course but malignant transformation has been described in association with oral potential malignant disorder (e.g. chronic graft versus host disease, erythroplakia). Very rare cases showed association with oral chronic graft versus-host-disease. To date, only eight cases were published in the world literature. Therefore it could be important follow up patients also for oral verruciform xanthoma onset.


Polymer-Mediated Inhibition of Pro-invasive Nucleic Acid DAMPs and Microvesicles Limits Pancreatic Cancer Metastasis.
Nucleic acid binding polymers (NABPs) have been extensively used as vehicles for DNA and RNA delivery. More recently, we discovered that a subset of these NABPs can also serve as anti-inflammatory agents by capturing pro-inflammatory extracellular nucleic acids and associated protein complexes that promote activation of toll-like receptors (TLRs) in diseases such as lupus erythematosus. Nucleic-acid-mediated TLR signaling also facilitates tumor progression and metastasis in several cancers, including pancreatic cancer (PC). In addition, extracellular DNA and RNA circulate on or within lipid microvesicles, such as microparticles or exosomes, which also promote metastasis by inducing pro-tumorigenic signaling in cancer cells and pre-conditioning secondary sites for metastatic establishment. Here, we explore the use of an NABP, the 3rd generation polyamidoamine dendrimer (PAMAM-G3), as an anti-metastatic agent. We show that PAMAM-G3 not only inhibits nucleic-acid-mediated activation of TLRs and invasion of PC tumor cells in vitro, but can also directly bind extracellular microvesicles to neutralize their pro-invasive effects as well. Moreover, we demonstrate that PAMAM-G3 dramatically reduces liver metastases in a syngeneic murine model of PC. Our findings identify a promising therapeutic application of NABPs for combating metastatic disease in PC and potentially other malignancies.


Laminar and columnar organization of immunoreactivity for calcineurin, a calcium- and calmodulin-regulated protein phosphatase, in monkey striate cortex.
Protein phosphorylation and dephosphorylation play an important role in neuronal signal transduction. In this study the distribution of calcineurin, a calcium/calmodulin-dependent protein phosphatase, was investigated in the striate cortex of two Old World monkeys, Macaca fascicularis and Papio anubis, using a well-characterized, affinity-purified polyclonal antibody to calcineurin. In order to relate the calcineurin distributions to established cytochemical markers, adjacent sections were processed for the visualization of cytochrome oxidase. The staining patterns obtained from the two species were remarkably similar. The results indicate that (1) monkey striate cortex exhibits strong calcineurin-like immunoreactivity that is present both in the neuropil and in neurons, most of which have characteristics of pyramidal cells; (2) the distribution of calcineurin is laminar specific; and (3) it is complementary to that of cytochrome oxidase activity with respect to both its laminar and its tangential pattern. In sections perpendicular to the cortical lamination calcineurin immunoreactivity is high in layers II and III, reduced in layer IVA, nearly as dense as in supragranular layers in layer IVB, minimal in layer IVC, and again enhanced, but not as much as in supragranular layers, in layers V and VI. In addition to these lamina-specific variations, the density of calcineurin-like immunoreactivity exhibits a periodic modulation along trajectories parallel to the pial surface that is most marked in layer III but also discernable in infragranular layers. Accordingly, in tangential sections through supragranular layers the calcineurin distribution is mosaic-like with patches of high density corresponding to cytochrome-poor regions (interblob regions) and zones of low density corresponding to areas of high cytochrome oxidase activity (blobs).


[Characteristics of systemic hemodynamics in relation to the emotional state of animals prior to experimentation].
Initial hemodynamics and reflex changes in the circulation were studied in acute experiments on cats at varying emotional states of the animals before experiment. In the cats not exposed to emotional stress, the initial parameters of the circulation and reflex mechanisms of hemodynamic control differed from those in controls. It is concluded that emotional stress provokes sustained changes in the central mechanisms of hemodynamic control.


Early-Life Microbiota Exposure Restricts Myeloid-Derived Suppressor Cell-Driven Colonic Tumorigenesis.
Gut microbiota and their metabolites are instrumental in regulating homeostasis at intestinal and extraintestinal sites. However, the complex effects of prenatal and early postnatal microbial exposure on adult health and disease outcomes remain incompletely understood. Here, we showed that mice raised under germ-free conditions until weaning and then transferred to specific pathogen-free (SPF) conditions harbored altered microbiota composition, augmented inflammatory cytokine and chemokine expression, and were hyper-susceptible to colitis-associated tumorigenesis later in adulthood. Increased number and size of colon tumors and intestinal epithelial cell proliferation in recolonized germ-free mice were associated with augmented intratumoral CXCL1, CXCL2, and CXCL5 expression and granulocytic myeloid-derived suppressor cell (G-MDSC) accumulation. Consistent with these findings, CXCR2 neutralization in recolonized germ-free mice completely reversed the exacerbated susceptibility to colitis-associated tumorigenesis. Collectively, our findings highlight a crucial role for early-life microbial exposure in establishing intestinal homeostasis that restrains colon cancer in adulthood.


[A population-based study on types of viral hepatitis].
The epidemiological features of various types of acute viral hepatitis in 5 regions of Sichuan Province (211,639 population) from Feb. 16, 1987 to Feb. 15, 1988 were studied. The results of the study showed that the incidence of acute viral hepatitis was 167.74 per 100,000 and the proportion of HA, HB, NANBH, HEB, HCM, MIXED infection in all the patients was 24.51%, 38.31%, 24.51%, 3.38%, 3.38%, and 5.92 respectively. There was an incidence of 14.93% for multiple infections. Large incidence differences in these regions (from 110.30 per 100,000 to 299.95 per 100,000) were noted. The sex ratio (male: female) for acute viral hepatitis was 1.75:1. There was a peak attack rate of HA in 0-19 age group. The incidence of HB in 20-39 age group was obviously higher than those in other age groups. For NANBH, attack rate was relatively high in 5-19 age groups. There were no significant age-differences for HEB, HCM and mixed infections.


Formation of the Drosophila ovarian ring canal inner rim depends on cheerio.
In Drosophila oogenesis, the development of a mature oocyte depends on having properly developed ring canals that allow cytoplasm transport from the nurse cells to the oocyte. Ring canal assembly is a step-wise process that transforms an arrested cleavage furrow into a stable intercellular bridge by the addition of several proteins. Here we describe a new gene wc named cheerio that provides a critical function for ring canal assembly. Mutants in cheerio fail to localize ring canal inner rim proteins including filamentous actin, the ring canal-associated products from the hu-li tai shao (hts) gene, and kelch. Since hts and kelch are present but unlocalized in cheerio mutant cells, cheerio is likely to function upstream from each of them. Examination of mutants in cheerio places it in the pathway of ring canal assembly between cleavage furrow arrest and localization of hts and actin filaments. Furthermore, this mutant reveals that the inner rim cytoskeleton is required for expansion of the ring canal opening and for plasma membrane stabilization.


A scoping review of the structuring of questions about sexual orientation and gender identity.
The purpose of this scoping review is to map the extent of the current research on how to best structure questions asking respondents to self-identify their sexual orientation and gender identity and to ascertain what further issues about measurement need to be explored. Using the Arksey and O'Malley framework for scoping reviews, 52 articles describing primary research about how to structure sexual orientation and gender identity (SOGI) questions, published in the years 2000-2021, were identified and analyzed. The domain of sexuality being asked about (e.g., self-label vs. behavior) needs to be clarified, and gender identity should be asked through a multipart item differentiating current identity from the sex assigned at birth. The terms used in the response options should be defined and may vary based on the study population or context. Contrary to expectations given the wide range of question formats currently being used in the field, there is considerable consensus around the basic tenets for structuring questions designed to assess SOGI dimensions.


Detection of A-to-I RNA Editing in SARS-COV-2.
ADAR1-mediated deamination of adenosines in long double-stranded RNAs plays an important role in modulating the innate immune response. However, recent investigations based on metatranscriptomic samples of COVID-19 patients and SARS-COV-2-infected Vero cells have recovered contrasting findings. Using RNAseq data from time course experiments of infected human cell lines and transcriptome data from Vero cells and clinical samples, we prove that A-to-G changes observed in SARS-COV-2 genomes represent genuine RNA editing events, likely mediated by ADAR1. While the A-to-I editing rate is generally low, changes are distributed along the entire viral genome, are overrepresented in exonic regions, and are (in the majority of cases) nonsynonymous. The impact of RNA editing on virus-host interactions could be relevant to identify potential targets for therapeutic interventions.


Risk assessment in patients with unstable angina/non-ST-elevation myocardial infarction and normal N-terminal pro-brain natriuretic peptide levels by N-terminal pro-atrial natriuretic peptide.
To compare the accuracy of the N-terminal fragment of its pro-hormone (Nt-proBNP) and N-terminal pro-atrial natriuretic peptide (Nt-proANP) in the prediction of the 2 year mortality and to investigate whether additional measurement of Nt-proANP to troponin I (TnI) could improve risk assessment in the subgroups of patients with unstable coronary artery disease (UCAD) and normal Nt-proBNP. Plasma levels of the TnI, Nt-proANP, and Nt-proBNP were determined in 120 consecutive patients with UCAD without ST-segment elevations and normal left ventricular function. In multivariable logistic regression analysis, TnI and Nt-proBNP were independent predictors of mortality (P=0.01 and P=0.02, respectively). However, in the group of patients with normal Nt-proBNP levels, only Nt-proANP and TnI were independently associated with mortality (P=0.007 and P=0.03, respectively). Accordingly, patients with elevated Nt-proANP levels in this group of patients had significantly higher mortality rate than patients with normal Nt-proANP levels (P=0.003). Our results suggest that determination of Nt-proANP might improve risk assessment in patients with UCAD, especially when Nt-proBNP is in the normal range.


Surface mixing and biological activity in the North-West African upwelling.
Near-shore water along the North-West African margin is one of the world's major upwelling regions. It is associated with physical structures of oceanic fronts which influence the biological productivity. The study of these coherent structures in connection with chlorophyll concentration data is of fundamental importance for understanding the spatial distributions of the plankton. In this work, we study the horizontal stirring and mixing in different upwelling areas using Lagrangian coherent structures (LCSs). These LCSs are calculated using the recent geodesic theory of LCSs. We use these LCSs to study the link between the chlorophyll fronts concentrations and surface mixing, based on 10 years of satellite data. These LCSs move with the flow as material lines, thus the horizontal mixing is calculated from the intersection of these LCSs with the finite time Lyapunov exponent maps. We compare our results with those of a recent study conducted over the same area, but based on finite size Lyapunov exponents (FSLEs), whose output is a plot of scalar distributions. We discuss the differences between FSLE and geodesic theory of LCS. The latter yields analytical solutions of LCSs, while FSLEs can only provide LCSs for sharp enough ridges of nearly constant height.


Optimizing low loss negative index metamaterial for visible spectrum using differential evolution.
A novel negative index metamaterial design methodology for the visible spectrum with low losses was presented in this paper. A robust differential evolution (DE) was employed to optimize the metamaterial design to achieve a desired set of values for the index of refraction. By using numerical simulation of a wedge-shaped model and S-parameter retrieval method, we found that the DE-designed optimal solution can exhibit a low loss LH frequency band with simultaneously negative values of effective permittivity and permeability at the violet-light wavelength of 408 nm, and the figure of merit is 15.2, that means it may have practical applications because of its low loss and high transmission. Therefore, the design methodology presented in this paper is a very convenient and efficient way to pursue a novel metamaterial with desired electromagnetic characteristics in the visible spectrum.


A novel pressor area at the medullo-cervical junction that is not dependent on the RVLM: efferent pathways and chemical mediators.
Chemical stimulation of a region extending from the most caudal ventrolateral medulla into the upper cervical spinal cord evoked large sympathetically mediated pressor responses. These responses were not dependent on the integrity of the rostral ventrolateral medulla (RVLM) and may be mediated by glutamatergic neurons embedded in the white matter that project to the thoracic spinal cord. We term this new region the medullo-cervical pressor area (MCPA). This region is distinct from the caudal pressor area, because blockade of the RVLM with muscimol inhibited this pressor response but not that evoked from the MCPA. This is the first study to provide functional evidence for a cardiovascular role for neurons in the cervical spinal cord white matter that innervate sympathetic preganglionic neurons (Jansen and Loewy, 1997). Using retrograde tracing, in combination with immunohistochemistry and in situ hybridization, we identified two groups of spinally projecting neurons in the region. Approximately 50% of neurons in one group were excitatory because they contained vesicular glutamate transporter 1 (VGluT1)/VGluT2 mRNA, whereas the other contained a mixed population of neurons, some of which contained either VGluT1/VGluT2 or GAD67 (glutamic acid decarboxylase 67) mRNA. Despite the fact that activation of the MCPA causes potent sympathoexcitation, it does not act to restore arterial pressure after chemical lesion of the RVLM so that a role for this novel descending sympathoexcitatory region remains to be elucidated.


Construction of recombinant human type 5 adenoviruses expressing rodent IL-6 genes. An approach to investigate in vivo cytokine function.
The majority of biologic functions assigned to cytokines have been characterized by in vitro assay systems which may not necessarily reflect cytokine roles in vivo. Recently, recombinant virus approaches have allowed tissue-specific expression of foreign gene products in experimental animal models. We have constructed recombinant human type 5 adenoviruses, deficient in the E3 region of the genome, with incorporated rodent IL-6 cDNA that express significant levels of biologically active IL-6 on infection both in vitro and in vivo. After i.p. injection, the liver, spleen, and peritoneum appear to be primary sites of expression, whereas the lung and bronchus are the main sites of expression after intratracheal instillation. Injection i.p. of BALB/c mice with the murine rIL-6 virus causes an increase in serum levels of bioactive IL-6 for up to 6 days post-infection, whereas similar changes are not seen in animals infected with control viruses. Coincident with enhanced plasma levels of IL-6, we detect raised serum levels of hepatic-derived acute phase proteins. Associated with the expression of IL-6 in the liver and spleen, at 7 days we note a fourfold splenomegaly with expansion of B and T cell compartments, as well as the presence of lymphoid aggregates in the liver. These morphologic changes had resolved by 16 days. Our findings demonstrate that recombinant human type 5 adenoviruses expressing cDNA for various cytokines could be used as a transient pseudo-transgenic animal model to investigate the biologic function of cytokines in vivo.


Radial head subluxation in an 8-year-old girl with joint hypermobility.
An 8-year-old girl attended the children's emergency department after having been play-fighting with her younger brother. Her arm had been pushed away by her father during the fight. The girl immediately complained of pain in her arm and refused to move it. Following analgesia and investigation with a plain radiograph of the elbow it was decided to attempt a manipulation procedure with the possibility that this could represent a 'pulled elbow' in an unusual age group. Soon after the manipulation the child was completely pain-free and moving her arm fully at the elbow, suggesting a diagnosis of radial head subluxation. The patient demonstrated hypermobility of several joints and she was able to hyperextend her unaffected elbow by >10°. This case highlights the association between radial head subluxation and joint hypermobility.


Biomolecule detection using a silicon nanoribbon: accumulation mode versus inversion mode.
Silicon nanoribbons were fabricated using standard optical lithography from silicon on insulator material with top silicon layer thicknesses of 100, 60 and 45 nm. Electrically these work as Schottky-barrier field-effect transistors and, depending on the substrate voltage, electron or hole injection is possible. The current through the nanoribbon is extremely sensitive to charge changes at the oxidized top surface and can be used for biomolecule detection in a liquid. We show that for detection of streptavidin molecules the response is larger in the accumulation mode than in the inversion mode, although not leading to higher detection sensitivity due to increased noise. The effect is attributed to the location in depth of the conducting channel, which for holes is closer to the screened surface charges of the biomolecules. Furthermore, the response increases for decreasing silicon thickness in both the accumulation mode and the inversion mode. The results are verified qualitatively and quantitatively through a two-dimensional simulation model on a cross section along the nanoribbon device.


Association of Food Insecurity with Nutrient Intake and Depression among Korean and US Adults: Data from the 2014 Korea and the 2013-2014 US National Health and Nutrition Examination Surveys.
The purpose of this study is to understand the current status of food insecurity in Korea and the US and to compare the relationship of food insecurity with nutrient intake and depression. Data from the 2014 Korea and the 2013-2014 US National Health and Nutrition Examination Surveys were analyzed, and a total of 3102 Korean and 3234 American adults aged 20-64 years were included. Study subjects were classified into three groups according to degree of food insecurity assessed by the 18-item Household Food Security Survey Module: food secure (FS), mildly food insecure (FI 1), and moderately-to-severely food insecure (FI 2) groups. Energy and nutrient intake were assessed using a 24-h dietary recall. Depression was measured using the Patient Health Questionnaire-9 (PHQ-9) screener. The prevalence of food insecurity was 17.2% in Korea and 26.4% in the US. In both countries, the people in the FI 2 group had lower incomes and education levels and were mostly single. Energy and nutrient intake differed by food insecurity status. In both Korea and the US, adults with moderate-to-severe food insecurity (FI 2) consumed fewer proteins, fiber, potassium, and vitamin C. Additionally, the FI 2 groups had higher proportions of people not meeting the Dietary Reference Intake for protein, potassium, niacin, and vitamin C than the FS groups in Korea and the US. FI 2 people were three times more likely to be depressed than FS group; this difference was stronger in Korea than the US. We found that the prevalence of food insecurity was higher in the US than in Korea, and food insecurity was associated with reduced nutrient intake and increased odds of depression in both Korean and US adults. Therefore, food insecurity is an important public health issue at both the individual and national levels. Continuous monitoring and new intervention activities to promote food security are needed.


Reliable Industry 4.0 Based on Machine Learning and IoT for Analyzing, Monitoring, and Securing Smart Meters.
The modern control infrastructure that manages and monitors the communication between the smart machines represents the most effective way to increase the efficiency of the industrial environment, such as smart grids. The cyber-physical systems utilize the embedded software and internet to connect and control the smart machines that are addressed by the internet of things (IoT). These cyber-physical systems are the basis of the fourth industrial revolution which is indexed by industry 4.0. In particular, industry 4.0 relies heavily on the IoT and smart sensors such as smart energy meters. The reliability and security represent the main challenges that face the industry 4.0 implementation. This paper introduces a new infrastructure based on machine learning to analyze and monitor the output data of the smart meters to investigate if this data is real data or fake. The fake data are due to the hacking and the inefficient meters. The industrial environment affects the efficiency of the meters by temperature, humidity, and noise signals. Furthermore, the proposed infrastructure validates the amount of data loss via communication channels and the internet connection. The decision tree is utilized as an effective machine learning algorithm to carry out both regression and classification for the meters' data. The data monitoring is carried based on the industrial digital twins' platform. The proposed infrastructure results provide a reliable and effective industrial decision that enhances the investments in industry 4.0.


Detection of functional connectivity in the brain during visuo-guided grip force tracking tasks: A functional near-infrared spectroscopy study.
The functional connectivity (FC) between multiple brain regions during tasks is currently gradually being explored with functional near-infrared spectroscopy (fNIRS). However, the FC present during grip force tracking tasks performed under visual feedback remains unclear. In the present study, we used fNIRS to measure brain activity during resting states and grip force tracking tasks at 25%, 50%, and 75% of maximum voluntary contraction (MVC) in 11 healthy subjects, and the activity was measured from four target brain regions: the left prefrontal cortex (lPFC), right prefrontal cortex (rPFC), left sensorimotor cortex (lSMC), and right sensorimotor cortex (rSMC). We determined the FC between these regions utilizing three different methods: Pearson's correlation method, partial correlation method, and a pairwise maximum entropy model (MEM). The results showed that the FC of lSMC-rSMC and lPFC-rPFC (interhemispheric homologous pairs) were significantly stronger than those of other brain region pairs. Moreover, FC of lPFC-rPFC was strengthened during the 75% MVC task compared to the other task states and the resting states. The FC of lSMC-lPFC and rSMC-rPFC (intrahemispheric region pairs) strengthened with a higher task load. The results provided new insights into the FC between brain regions during visuo-guided grip force tracking tasks.


Evaluation of Load-Velocity Relationships and Repetitions-to-Failure Equations in the Presence of Male and Female Spotters.
Nickerson, BS, Williams, TD, Snarr, RL, Garza, JM, and Salinas, G. Evaluation of load-velocity relationships and repetitions-to-failure equations in the presence of male and female spotters. J Strength Cond Res 34(9): 2427-2433, 2020-The purpose of this study was 2 fold: (a) to determine whether differences in mean concentric velocity (MCV), repetitions-to-failure (RTF), measured 1 repetition maximum (1RM), and 1RM prediction methods vary between lifter and spotter sex and (b) determine the accuracy of velocity-based 1RM (MCV1RM) and repetitions-to-failure-based 1RM (RTF1RM) prediction equations in the presence of either a male or female spotter. Twenty resistance-trained individuals (50% men) participated in this study. The initial 2 visits involved measuring 1RM for the bench press with a male or female spotter. Visits 3 and 4 required subjects to lift loads at 30 (5-repetitions), 50 (5-repetitions), and 70% 1RM (RTF) in the presence of a male or female spotter. Velocity-based 1RM was determined through individual regression equations using the submaximal loads (MCV30, MCV50, and MCV70). Repetitions-to-failure-based 1RM was determined through the RTF at 70% 1RM using Wathen (Wathen1RM), Mayhew (Mayhew1RM), and Epley (Epley1RM) equations. There were significant interactions when assessing Wathen1RM and Mayhew1RM (p < 0.05). Female lifters produced significantly higher estimated 1RM values during the male spotter condition using Wathen1RM and Mayhew1RM than the female spotter condition (p = 0.032 and 0.033, respectively). MCV1RM and Epley1RM produced smaller mean differences than Wathen1RM and Mayhew1RM when compared with measured 1RM. However, MCV1RM produced the largest standard error of estimate, whereas Epley1RM produced the lowest values. Epley1RM should be used over MCV1RM, Wathen1RM, and Mayhew1RM when loads up to 70% 1RM are implemented. Also, spotter sex only seems to impact female lifters when using the RTF1RM prediction equations of Wathen1RM and Mayhew1RM.


Australian women's needs and preferences for information about human papillomavirus in cervical screening.
The role of human papillomavirus (HPV) in cervical cancer and developments in medical technology to prevent cervical cancer has changed information needs for women participating in cervical screening. Qualitative face-to-face interviews were conducted with 19 women diagnosed with HPV infection on their Pap smear following routine cervical screening. Family planning clinics, general practice and specialist gynaecologist practices in Sydney and the surrounding area, Australia. Women's information needs, preferences and experiences of HPV diagnosis. Women wanted further information on different HPV viral types, transmission, implications for sexual partners, prevalence, latency and regression of HPV, their management options and the implications of infection for cancer risk and fertility. Uncertainty about the key aspects of HPV, the style in which the clinician communicated the result and the mode of delivering the result (letter, telephone or consultation) influenced women's psychological response to the diagnosis of HPV. The delivery of results by letter alone was linked to considerable anxiety among the women interviewed. Women's experience of searching the Internet for further information about HPV was reported as difficult, anxiety provoking and contributing to the stigma of the infection because information was often located in the context of other sexually transmitted infections, with multiple sexual partners highlighted as a risk factor for infection. Women participating in cervical screening need high-quality information about HPV and its role in cervical cancer prior to screening rather than afterwards, when they face an abnormal result. The clinician potentially plays an important role in moderating the effects of diagnosis through the manner and mode in which an HPV diagnosis is delivered. Revision of cervical screening policy and practice in light of the changes in the understanding of HPV is recommended.


Recent progress in understanding pediatric pulmonary hypertension.
Pulmonary artery hypertension (PAH) in children contributes significantly to morbidity and mortality in diverse pediatric cardiac, lung, hematologic and other diseases. Advances in pulmonary vascular biology over the past few decades have significantly expanded therapeutic strategies; however, many unique issues persist regarding our understanding of pediatric PAH. Recent studies of pediatric PAH include those that highlight gaps in our understanding of pediatric diseases associated with PAH from those of adult onset, emphasizing the strong need for specific studies regarding unique aspects of the pathogenesis and treatment of children with PAH. Registries have begun to provide new data showing differences in physiology, course, and genetics between adult and pediatric forms of PAH. Unfortunately, therapeutic strategies in pediatric pulmonary hypertension are often limited to small observational studies in children and are dependent on results from larger adult studies. In addition, clinical endpoints for studies and care remain poorly defined in infants and children. Despite many advances, long-term outcomes for children with PAH remain guarded and substantial challenges persist, especially with regard to understanding mechanisms and approach to severe PAH. Future studies are needed to develop novel biomarkers, clinical endpoints and interventions for young children with diverse causes of PAH.


A suction thrombectomy technique: a rapid and effective method for intra-arterial thrombolysis.
During mechanical thrombolysis, to reduce procedure-related complications and time, the authors have performed a simple suction thrombectomy technique. In this article, the authors describe the technical details and clinical outcomes of this technique. From January 2013 to December 2013, 14 consecutive acute ischemic stroke (AIS) patients with large cerebral arterial occlusions in the middle cerebral artery (MCA; n = 7), internal cerebral artery (ICA; n = 5), basilar artery (BA; n = 1), and a tandem lesion (ICA and MCA; n = 1) were treated using this technique. The proximal part of the occluding clot was aspirated or captured and retrieved as one piece using a large bored microcatheter by applying negative suction pressure using a 50 mL syringe. Overall recanalization rate was 85.7% (12 patients). In the 8 patients in whom this technique was used alone, the recanalization rate was 87.5% (7 patients). The median procedural duration was 30 minutes (range 17-112) in these 7 patients. Distal embolism did not occur. Two patients developed post-procedural intracerebral hemorrhages and one was symptomatic. His modified Rankin Scale (mRS) score at 90 days was 4. This technique is a feasible, fast, and safe method for treatment of AIS.


A study to enhance clinical end-user MEDLINE search skills: design and baseline findings.
To determine if a preceptor and timely, individualized feedback improves the performance of physicians in searching MEDLINE using GRATEFUL MED in clinical settings. Randomized controlled trial. A 300 bed primary to tertiary care teaching hospital. Computers were installed in wards and clinics of 6 major clinical services, and the emergency room, intensive care and neonatal intensive care units. All physicians and physicians-in-training from the departments of Medicine, Family Medicine, Surgery, Psychiatry, Pediatrics, and Obstetrics and Gynecology were included if they made patient care decisions for at least 8 weeks during the study period. All participants were given a 1-hour training class and 1 hour of individualized searching with 1 of the 2 study librarians. After training, participants were randomized to a control group who received no further intervention or to an intervention group in which each person chose a clinical preceptor experienced in MEDLINE searching and received individualized feedback by a study librarian on their first 10 searches, indicating search quality and providing suggestions for improvement. Feedback was mailed the first week day after the search was done. Baseline characteristics by study group, department and level of training, study participation rates, and searching rates. 308 of 392 eligible physicians joined the study. Participation was almost 80% with some variation by department and level of training. Excellent balance in the baseline characteristics was achieved for the 2 groups, as well as for the number who did first searches. Intervention group participants searched MEDLINE more often than did controls (3.5 searches per month vs 2.5 per month for controls, P = 0.046). The recall and precision for first searches for both groups was significantly less than that of librarians. The analysis of study data will be completed by September 1991. Clinicians are willing to do self-service searching of MEDLINE in clinical settings but their precision and recall are less than a trained librarian at baseline. Search skills enhancements are needed and the effect of feedback and preceptors is being tested. U.S. National Library of Medicine and Ontario Ministry of Health.


The Role of Sonic Hedgehog in Craniofacial Patterning, Morphogenesis and Cranial Neural Crest Survival.
Craniofacial defects (CFD) are a significant healthcare problem worldwide. Understanding both the morphogenetic movements which underpin normal facial development, as well as the molecular factors which regulate these processes, forms the cornerstone of future diagnostic, and ultimately, preventative therapies. The soluble morphogen Sonic hedgehog (Shh), a vertebrate orthologue of Drosophila hedgehog, is a key signalling factor in the regulation of craniofacial skeleton development in vertebrates, operating within numerous tissue types in the craniofacial primordia to spatiotemporally regulate the formation of the face and jaws. This review will provide an overview of normal craniofacial skeleton development, and focus specifically on the known roles of Shh in regulating the development and progression of the first pharyngeal arch, which in turn gives rise to both the upper jaw (maxilla) and lower jaw (mandible).


[Leadership in the nursing context].
Leadership is one of the most indispensable tools for nursing work. This study is aimed at making a bibliographical survey about leadership in the nursing context and characterizing the scientific production on the topic based on year and place of publication and theme categorization. An online literature review, carried out using LILACS data, considered periodical material, dissertations and theses available in Portuguese and Spanish from the past twenty years. From the 31 selected works, 17 (54.8%) have been published in international nursing magazines, 10 (32.2%) have been published in Brazilian nursing periodicals, 3 (9.8%) were Master's Degree theses, and one (3.2%) was a teaching thesis, with publication concentrated between 1997 and 1998 (22.6%). When categorizing the references, the numbers were: 14 (45.2%) dealt with nurse leadership styles, 15 (48.5%) were reflections upon leadership, and 2 (6.4%) discussed leadership and communication.


A unique approach toward near-infrared fluorescent probes for bioimaging with remarkably enhanced contrast.
Near-infrared (NIR) fluorescent probes are attractive molecular tools for bioimaging because of their low autofluorescence interference, deep tissue penetration, and minimal damage to sample. However, most previously reported NIR probes exhibit small Stokes shift, typically less than 30 nm, and low fluorescence quantum yield, strictly limited contrast and spatial resolution for bioimaging. Herein, by expanding the π-conjugated system of rhodamine B, while, at the same time, keeping its rigid and planar structure, we reported an efficient NIR dye, HN7, with large stokes shift of 73 nm and fluorescence quantum yield as high as 0.72 in ethanol, values superior to those of such traditional cyanine NIR dyes as Cy5. Using HN7, living cells, tissues and mice were imaged, and the results showed significantly enhanced contrast, improved spatial resolution, and satisfactory tissue imaging depth when compared to Cy5. Moreover, the nonfluorescent spirocyclic structure of rhodamine B is an inherent component of HN7; therefore, our strategy provided a universal platform for the design of efficient NIR turn-on bioimaging probes for various targets. As a proof-of-concept, two different NIR probes, HN7-N2 and HN7-S for NO and Hg2+, respectively, were designed, synthesized, and successfully applied for the imaging of NO and Hg2+ in living cells, tissues and mice, respectively, demonstrating the potential bioimaging applications of the new probes. In sum, this new type of dye may present new avenues for the development of efficient NIR fluorescent probes for contrast-enhanced imaging in biological applications.


Integrating behavioural health and primary care: qualitative findings on contextual factors that influence integration.
Integrating behavioural health care into primary care practices may increase patients' access to behavioural health services and improve health outcomes. However, few studies have explored factors that influence integration processes. We sought to better understand contextual factors that support or impede behavioural health integration in primary care practices. We conducted 71 semi-structured interviews with providers, staff, and leaders from eight primary care practices in the United States with integrated behavioural health services, which were participating in a randomized control, pragmatic trial: Integrating Behavioural Health and Primary Care. Practices were selected for diversity on geographic location, size, ownership, and experience with integration. We conducted a thematic analysis of the qualitative data derived from the interviews. We identified four categories of contextual factors influencing behavioural health integration: leadership commitment to integration, financial considerations, workflow and communication systems, and providers' perspectives on integration and team-based healthcare. Supportive factors included leaders' commitment to integration, adequate staffing, customized communication and workflow systems, collaborative practice culture, and healthy working relationships amongst providers. Impediments included staffing issues and payment models that do not reimburse for activities required to support integrated care. Interviewees described various benefits of integration, including providers feeling better equipped to address patients' needs due to collaboration between medical and behavioural providers and resulting interdisciplinary learning. Given concerns about provider burnout, this finding warrants further study.


Injury to the pre-pubertal vas deferens. I. Histological analysis of pre-pubertal human vas.
There is very little information in the literature on the development of the human vas deferens. Therefore, the age at which the pre- or para-pubertal vas deferens becomes large enough for a vasovasostomy to be technically feasible is unknown. To determine the age or degree of sexual maturity at which a microscopic vasovasostomy is technically feasible, we collected surgical or autopsy vasa from 34 young males over a three year period, and correlated vasal size to age and Tanner stage (degree of sexual maturity ranging from 1-childhood to 5-adult). The specimens were embedded and sectioned transversely in glycol methacrylate. Using image analysis, the total transverse area and diameter, and luminal area and diameter was determined for each specimen. Surprisingly, there was no change in vasal size from birth up through 11 years. From age 15 years and on, the vas was adult in size. The vas develops to adult size between Tanner stages 2 and 3. The average external and luminal diameters of pre-midpuberty specimens (Tanner stages 1 and 2) were 1.0 and 0.19 (mm.) and the diameters of post-midpuberty specimens were 2.1 and 0.43 (mm.), respectively. These results suggest that, in the event of a recognized iatrogenic injury to the vas deferens after midpuberty, a repair by a traditional microsurgical vasovasostomy is possible. If the vas is injured before midpuberty it may be technically difficult to repair by traditional microsurgical methods.


Purulent otitis media in adults.
While the bacterial origin of otitis media has been studied extensively in children, there are few data regarding adults with this disease. We undertook this study to identify the incidence, prevalence, and bacteriologic origin of purulent otitis media in adults. This was accomplished through a review of the English-language literature on adult otitis media and a retrospective review of adult patients with this disease who were hospitalized at our institution. Results of literature review indicate that Streptococcus pneumoniae and Haemophilus influenzae are the most common causes of otitis media in ambulatory adults, but this illness is uncommon, with an incidence of only 0.25%. Hospitalized patients in whom this diagnosis was established suffered a variety of serious suppurative complications such as mastoiditis, meningitis, or brain abscess. Otalgia and fever were the most common symptoms noted in this patient population. Further studies of adult otitis media need to be performed to determine bacteriologic, symptomatic, and high-risk patient groups.


[The methods of traditional medicine in outpatient polyclinic practice].
Some 7950 patients have been treated at the traditional medicine department of the Consulting and Diagnostic Center N52, 2/3rds of them came after long and unsuccessful medicamental treatment. Psychotherapy, manual therapy and acupuncture-reflex methods were successful in 86-93% of cases. They are recommended for local clinics provided that the latter are properly equipped and stuffed.


Monopolar-probe monitoring during spinal surgery with expandable prosthetic ribs.
Intraoperative monitoring (IOM) has been proven to decrease the risk of neurological injury during scoliosis surgery. The vertical expandable prosthetic titanium rib (VEPTR) is a device that allows spinal growth. However, injuries to the spinal cord and brachial plexus have been reported after VEPTR implantation in 2 and 5% of patients, respectively. Simultaneous monitoring of these two structures requires the use of multiple time-consuming and complex methods that are ill-suited to the requirements of paediatric surgery, particularly when repeated VEPTR lengthening procedures are needed. We developed a monopolar stimulation method derived from Owen's monitoring technique. This method is easy to implement, requires only widely available equipment, and allows concomitant monitoring of the spinal cord and brachial plexus. The primary objective of this study was to assess the reliability of our technique for brachial plexus monitoring by comparing the stability of neurogenic mixed evoked potentials (NMEPs) at the upper and lower limbs. We hypothesised that the coefficients of variation (CVs) of NMEPs were the same at the upper and lower limbs. Twelve VEPTR procedures performed in 6 patients between 1st January 2012 and 1st September 2014 were monitored using a monopolar stimulating probe. NMEPs were recorded simultaneously at the upper and lower limbs, at intervals of 150 s. The recording sites were the elbow over the ulnar nerve and the popliteal fossa near the sciatic nerve. Wilcoxon's test for paired data was used to compare CVs of the upper and lower limb NMEPs on the same side. Mean CV of NMEP amplitude at the lower limbs was 16.34% on the right and 16.67% on the left; corresponding values for the upper limbs were 18.30 and 19.75%, respectively. Mean CVs of NMEP latencies at the lower limbs were 1.31% on the right and 1.19% on the left; corresponding values for the upper limbs were 1.96 and 1.73%. The risk of type I error for a significant difference between the upper and lower limbs was 0.5843 on the right and 0.7312 on the left for NMEP amplitudes and 0.7618 on the right and 0.4987 on the left for NMEP latencies. Using an epidural active electrode and a sternal return electrode allows simultaneous stimulation of the cervical spinal cord and brachial plexus roots. The NMEPs thus obtained are as stable (reliable) at the upper limbs as at the lower limbs. This easy-to-implement method allows simultaneous monitoring of the upper and lower limbs. It seems well suited to VEPTR procedures. IV, retrospective single-centre non-randomised study.


Leadership through a gender lens: Disparities in Dental Research.
This study aimed to analyze the 100 most-cited papers in Dentistry, with a focus on female leadership in dental research. Papers were retrieved from the Web of Science Core Collection (WoS- CC) in the category 'Dentistry, Oral Surgery & Medicine'. Gender was assessed through WoS-CC, Scopus, ResearchGate, social media, institutional websites, and software that assigns gender according to first names (https://genderapi.io). Characteristics of authors in leadership roles were retrieved, such as affiliation, publication history, citations, H factor, and i500. The 100 most-cited papers in Dentistry were authored by 394 researchers, 326 (82.7%) men, and 68 (17.3%) women - there were 4.8 male authors for each female. Among the lead authors, there were 11.3 males for each female. Among female senior authors, there were 7 males for each female. Among lead/senior authors of the 100 most-cited papers (first and last authors, respectively), 18 were women. There was an increase in the participation of women in the top cited papers regardless of authorship role across the six decades, with a peak of two female authors in the first decade of the 21st century. For female authors in leadership roles, their publication history shows the time between their first and last papers in WoS-CC ranged from 4 to 42 years for lead authors and 1 to 39 years for senior authors. Women were found to be largely underrepresented as leaders of the 100 most-cited papers, highlighting pervasive gender inequalities in dental research publications.


"DOMINO - Stop Domestic Violence". An Educational Mobile Application.
Domestic violence affects people of all socioeconomic backgrounds and education levels and can happen to anyone. It is a public health issue that needs to be addressed with health and social care professionals playing an essential role in prevention and early intervention. These professionals need to be prepared through proper education. A European funded project developed "DOMINO - Stop domestic violence" educational mobile application which was piloted among 99 social and/or health care students and professionals. Most of the participants (n= 59, 59.6%) indicated that the DOMINO mobile application was easy to install and over half of them (n=61, 61.6%) would recommend the app. They found it easy to use, and quick access to useful materials and tools. Participants found case studies and the checklist good and useful tools for them. The DOMINO educational mobile application is available open access, in English, Finnish, Greek, Latvian, Portuguese and Swedish, for any stakeholder worldwide who is interested to learn more about domestic violence prevention and intervention.


A moisture balanced antibacterial dressing loaded with lysozyme possesses antibacterial activity and promotes wound healing.
Wound moisture management is very important in wound healing. Previous wound management has included dry healing and moist healing, and the theory of wound moisture balance is currently generally accepted. However, current studies have not reported which humidity is suitable for wound healing and how to appropriately use antibacterial compounds when the humidity is suitable. Our study explored the moisture balance of polyurethane foam dressings through a moisture balance test and constructed a safe and effective moisture balanced antibacterial dressing by loading lysozyme onto a polyurethane foam dressing. Wound healing experiments showed that the wound healing speed was the fastest when the humidity was 25%. In vivo and in vitro antibacterial experiments showed the superior antibacterial performance of the dressing after lysozyme loading. We loaded lysozyme on moisture balanced polyurethane dressings by means of dopamine adsorption, and the modified dressings were named PU/DA-LYS (polyurethane/dopamine-lysozyme). Experiments on wound healing in infected mice indicated that PU/DA-LYS helps fight infection while promoting wound healing. Cytotoxicity experiments and in vivo biological safety experiments indicated that PU/DA-LYS was safe for use. Our study found that the lysozyme loaded polyurethane dressing can provide appropriate wound moisture and prevent bacterial infection, which is a future developmental direction for wound dressings.


Different mechanisms of acute versus long-term antihypertensive effects of soluble epoxide hydrolase inhibition: studies in Cyp1a1-Ren-2 transgenic rats.
Recent studies have shown that the long-term antihypertensive action of soluble epoxide hydrolase inhibition (sEH) in angiotensin-II (AngII)-dependent hypertension might be mediated by the suppression of intrarenal AngII levels. To test this hypothesis, we examined the effects of acute (2 days) and chronic (14 days) sEH inhibition on blood pressure (BP) in transgenic rats with inducible AngII-dependent hypertension. AngII-dependent malignant hypertension was induced by 10 days' dietary administration of indole-3-carbinol (I3C), a natural xenobiotic that activates the mouse renin gene in Cyp1a1-Ren-2 transgenic rats. BP was monitored by radiotelemetry. Acute and chronic sEH inhibition was achieved using cis-4-(4-(3-adamantan-1-yl-ureido)cyclohexyloxy) benzoic acid, given at doses of 0.3, 3, 13, 26, 60 and 130 mg/L in drinking water. At the end of experiments, renal concentrations of epoxyeicosatrienoic acids, their inactive metabolites dihydroxyeicosatrienoic acids and AngII were measured. Acute BP-lowering effects of sEH inhibition in I3C-induced rats was associated with a marked increase in renal epoxyeicosatrienoic acids to dihydroxyeicosatrienoic acids ratio and acute natriuresis. Chronic treatment with cis-4-(4-(3-adamantan-1-yl-ureido)cyclohexyloxy) benzoic acid in I3C-induced rats elicited dose-dependent persistent BP lowering associated with a significant reduction of plasma and kidney AngII levels. Our findings show that the acute BP-lowering effect of sEH inhibition in I3C-induced Cyp1a1-Ren-2 transgenic rats is mediated by a substantial increase in intrarenal epoxyeicosatrienoic acids and their natriuretic action without altering intrarenal renin-angiotensin system activity. Long-term antihypertensive action of cis-4-(4-(3-adamantan-1-yl-ureido)cyclohexyloxy) benzoic acid in I3C-induced Cyp1a1-Ren-2 transgenic rats is mediated mostly by suppression of intrarenal AngII concentration.


Rifamycin Derivatives Are Effective Against Staphylococcal Biofilms In Vitro and Elutable From PMMA.
Local antimicrobial delivery through polymethylmethacrylate beads (PMMA), commonly vancomycin, is used for the treatment of contaminated open fractures but has limited activity against Staphylococcus aureus biofilms, which occur commonly in such fractures. Rifamycins have activity against biofilms and are an effective treatment for osteoarticular infections involving staphylococcal biofilms, but there are limited studies evaluating the activity of rifamycin derivatives, other than rifampin, against biofilms of S. aureus and evaluating incorporation of these drugs into PMMA for treatment of contaminated open fractures. (1) Are rifamycin derivatives effective against established biofilms of clinical isolates of S. aureus? (2) Can PMMA be used as a carrier for rifamycin derivatives? Biofilms were developed and evaluated for susceptibility to a panel of antimicrobials in vitro using the minimum biofilm eradication concentration high-throughput model. Susceptibility was assessed by measuring bacterial recovery at 6 and 24 hours after antimicrobial treatment. Activity of rifamycin derivatives against intracellular bacteria was also evaluated using a gentamicin protection assay. Evaluation of PMMA as a carrier for rifampin and rifamycin derivatives was determined by assessing the curing time subsequent to loading of rifamycins and characterizing the release kinetics of rifamycins at daily intervals for 14 days from PMMA by performing bioassays. Rifamycin derivatives between 1 and 8 µg/mL reduced bacteria within biofilms 5- to 9-logs and prevented bacterial recovery up to 24 hours post-treatment, indicating near to complete eradication of biofilms. Rifamycin derivatives at 32 µg/mL had activity against intracellular staphylococci, significantly reducing the number of internalized bacteria with limited effects on osteoblast viability. Rifampin was the only rifamycin observed to have a suitable release profile from PMMA, releasing 49% of the total antibiotic and maintaining a sustained released profile up to 14 days at a mean 28 ± 6 μg/mL. Rifampin can be incorporated into PMMA and eluted at concentrations effective against biofilms and intracellular staphylococci. Our in vitro findings suggest that local delivery of rifampin may be an effective strategy for the prevention and/or treatment of open fractures where S. aureus biofilms might develop. Clinical studies are needed to characterize what role this approach might have in the prevention and treatment of infections involving biofilms.


Rheology of sickle cells and its role in microcirculatory dynamics.
The alterations in the viscoelastic properties of the hemoglobin S solution following deoxygenation can be correlated, on the one hand, with the gelation of the HbS molecules and, on the other hand, with changes in the rheological behavior of the deoxygenated SS erythrocytes. The abnormal rheology of SS erythrocytes forms the basis of their altered flow behavior through filter pores in vitro and microcirculation in vivo. The results support the notion that the rheological behavior of sickle cells is an important link between the molecular events in hemoglobin S following deoxygenation and the behavior of the cell in the microcirculation. Although recent advances have shed considerable lights on the rheology of sickle cells in a variety of conditions, further studies are needed in order to elucidate the pathophysiological role of cell rheology in this disease, especially in terms of the influence of individual SS cells in the heterogeneous populations and the correlation between in vitro and in vivo behavior of SS cells.


Anti-inflammatory effects of water extract of Taraxacum mongolicum hand.-Mazz on lipopolysaccharide-induced inflammation in acute lung injury by suppressing PI3K/Akt/mTOR signaling pathway.
Taraxacum mongolicum Hand.-Mazz is a famous medicinal plant in China, has been listed in the Pharmacopoeia of the People's Republic of China and used to treat infection, fever, upper respiratory tract infection, pneumonia, and other infectious diseases. This study aims to evaluate the possible mechanisms responsible for the anti-inflammation effects of water extract of T. mongolicum Hand.-Mazz (WETMHM) on lipopolysaccharide (LPS)-induced inflammatory in acute lung injury. Female BALB/c mice were randomly divided into five groups with 10 mice in each group: (1) control group (saline), (2) LPS group, (3) LPS+dexamethasone (LPS+Dex, 2mg/kg, administered by gavage), (4) LPS+WETMHM (5 g/kg, administered by gavage), (5) LPS+WETMHM (10 g/kg, administered by gavage). The cell counting in the bronchoalveolar lavage fluid (BALF) was measured. The animal lung edema degree was evaluated by wet/dry weight (W/D) ratio. The superoxidase dismutase (SOD) activity and myeloperoxidase (MPO) activity were assayed by SOD and MPO kits, respectively. The levels of inflammation mediators including tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, and IL-6 were assayed by an enzyme-linked immunosorbent assay method. Pathological changes of lung tissues were observed by hematoxylin and eosin (HE) staining. The levels of P-PI3K, PI3K, P-Akt, Akt, P-mTOR and mTOR were measured by Western blotting. The data showed that treatment with the WETMHM inhibited LPS-induced inflammation: (1) WETMHM attenuated inflammation cell numbers in the BALF, (2) decreased protein levels of lung PI3K/Akt/mTOR, and (3) improved SOD activity and (4) inhibited MPO activity; (5) histological studies demonstrated that WETMHM substantially inhibited LPS-induced neutrophils in lung tissue. The results indicated that the WETMHM had a protective effect on LPS-induced ALI in mice.