Scalpel-free surgery could reduce surgeons' risk of HIV and hepatitis.
The risk of intraoperative Human Immunodeficiency Virus(HIV) infection poses a challenge to practicing surgeons worldwide, particularly in sub-Saharan Africa with its high HIV prevalence. The risk of acquiring HIV infection from one infected percutaneous exposure is 0.3-0.4%. Prior to extensive screening, blood transfusions were responsible for an estimated 5-10% of new HIV infections in sub-Saharan Africa. In this paper we describe the experience of minimally invasive techniques as alternatives to surgery in urology patients. Trans-urethral ethanol ablation of the prostate (TEAP) for prostatic enlargement, phenol sclerotherapy for hydroceles, and percutaneous aspiration and sclerotherapy for symptomatic renal cysts may result in reduced blood loss, and diminished contact with the patients' exposed tissues or body fluids compared with more invasive surgical options.


Enhancement of accuracy in shape sensing of surgical needles using optical frequency domain reflectometry in optical fibers.
We demonstrate a novel approach to enhance the precision of surgical needle shape tracking based on distributed strain sensing using optical frequency domain reflectometry (OFDR). The precision enhancement is provided by using optical fibers with high scattering properties. Shape tracking of surgical tools using strain sensing properties of optical fibers has seen increased attention in recent years. Most of the investigations made in this field use fiber Bragg gratings (FBG), which can be used as discrete or quasi-distributed strain sensors. By using a truly distributed sensing approach (OFDR), preliminary results show that the attainable accuracy is comparable to accuracies reported in the literature using FBG sensors for tracking applications (~1mm). We propose a technique that enhanced our accuracy by 47% using UV exposed fibers, which have higher light scattering compared to un-exposed standard single mode fibers. Improving the experimental setup will enhance the accuracy provided by shape tracking using OFDR and will contribute significantly to clinical applications.


Intermittent fasting may optimize intestinal microbiota, adipocyte status and metabolic health.
The aim of this review is to provide an overview of the present association between Intermittent Fasting (IF), the Gut Microbiota (GM), and the adipocyte with respect to Metabolic Health (MH). A search was carried out through Dialnet, Scielo, Web of Science, Redalyc and PubMed, using keywords such as: "intermittent fasting", "time-restricted feeding", "gut microbiota" and "Metabolic Health". Intermittent fasting (IF) regimens promote weight loss, therefore contributing to improved metabolic health. IF beneficially participates in the modulation of the intestinal microbiome, allowing a continuous interaction with nutrients to be digested and shaping the intestinal immune responses during the development of cardiovascular disease, blood pressure and diabetes mellitus through metabolic activities.


Initiation of an Inhaled Corticosteroid During a Pediatric Emergency Visit for Asthma: A Randomized Clinical Trial.
We determine whether prescribing an inhaled corticosteroid during a pediatric emergency department (ED) asthma visit increases ongoing use and improves outcomes. This randomized trial enrolled children aged 1 to 18 years, with persistent asthma not previously prescribed a controller medication, and who were being discharged after ED asthma treatment. Intervention subjects received a 1-month prescription for an inhaled corticosteroid (fluticasone or budesonide by age) in addition to standard asthma therapy and instructions given to all patients. Outcomes included filling of the intervention and subsequent inhaled corticosteroid prescriptions, asthma-related symptoms and quality of life, and follow-up rates with a primary care provider. Outcomes were assessed during telephone interviews 2 and 8 weeks after the ED visit and by review of primary care provider and pharmacy records. One hundred forty-seven children were enrolled, and baseline measures were similar between groups. In the intervention group, 53.5% of patients filled an initial ED prescription for inhaled corticosteroid. There was no important difference between groups in subsequent filling of a primary care provider prescription (21% intervention versus 17% control; relative rate=1.24; 95% confidence interval 0.63 to 2.41). During the 2 weeks after the ED visit, intervention subjects reported reduced shortness of breath while awake and cough while asleep compared with controls. Groups did not differ by rates of primary care provider follow-up, functional limitations, or asthma-related symptoms and quality of life. There was no difference in the proportion of patients who filled a primary care provider prescription after ED initiation of an inhaled corticosteroid. The intervention was associated with reduced reported symptoms but did not affect other asthma outcomes or primary care provider follow-up.


Global cerebral oxidative metabolism during hypercapnia and hypocapnia in humans: implications for BOLD fMRI.
The effect of carbon dioxide (CO(2)) on cerebral metabolism is of tremendous interest to functional imaging. In particular, mild-to-moderate hypercapnia is routinely used in calibrated blood oxygen-level dependent (BOLD)-functional magnetic resonance imaging (fMRI)-based quantification of cerebral oxidative metabolism changes (DeltaCMRO(2)), and relies on the assumption of a stable CMRO(2) during CO(2) challenges. However, this assumption has been challenged by certain animal studies, necessitating its verification in humans and under conditions customary to fMRI. We report, for the first time, on global DeltaCMRO(2) measurements made noninvasively in humans during graded hypercapnia and hypocapnia. We used computerized end-tidal CO(2) modulation to minimize undesired concurrent changes in oxygen pressure, and our findings suggest that no significant change in global CMRO(2) is expected at the levels of end-tidal CO(2) changes customary to calibrated BOLD.


[Human papilloma virus and cervical cancer].
Cervical cancer (CC) is the second most common cause of death from cancer among women worldwide and about 80% of the half of million new cases detected every year, occurs in less-developed countries. Human papillomavirus is an obligate factor for the development of CC, since some HPVtype are detected in 100% of CC. HPV16 and HPV18 are the most common viral types, accounting for about 50% and 15% of CC, respectively. HPV infection is the most common sexual transmitted infection, with an estimated prevalence of about 2-44% among sexually active young women. However, only a very small fraction of these infections evolve to CC (1-2 out of 1000), indicating that some other factors should be important in the evolution of the disease. Preventive vaccines against HPVs 16 and 18 have been developed, and in phase III clinical trials they have demonstrated 100% efficacy for prevention of persistent infection and high risk cervical squamous intraepithelial neoplasias positive for these HPV types, suggesting that these vaccines, if made widely available, will dramatically reduce the burden of CC.


Mining of caspase-7 substrates using a degradomic approach.
Caspases play critical roles in the execution of apoptosis. Caspase-3 and caspase-7 are closely related in sequence as well as in substrate specificity. The two caspases have overlapping substrate specificities with special preference for the DEVD motif. However, they are targeted to different subcellular locations during apoptosis, implying the existence of substrates specific for one or other caspase. To identify new caspase-7 substrates, we digested cell lysates obtained from the caspase-3-deficient MCF-7 cell line with purified recombinant caspase-7, and analyzed spots that disappeared or decreased by 2-DE (we refer to this as the caspase-7 degradome). Several proteins with various cellular functions underwent caspase-7- dependent proteolysis. The substrates of capase-7 identified by the degradomic approach were rather different from those of caspase-3 (Proteomics, 4, 3429-3435, 2004). Among the candidate substrates, we confirmed that Valosin-containing protein (VCP) was cleaved by both capspase-7 and caspase-3 in vitro and during apoptosis. Cleavage occurred at both DELD(307) and DELD(580). The degradomic study yielded several candidate caspase-7 substrates and their further analysis should provide valuables clues to the functions of caspase-7 during apoptosis.


What motivates open defecation? A qualitative study from a rural setting in Nepal.
Open defecation is ongoing in Nepal despite the rise in efforts for increasing latrine coverage and its use. Understanding the reasons for open defecation would complement the ongoing efforts to achieve the 'open defecation free' status in Nepal. This study aimed at exploring different motivations of people who practice open defecation in a village in Nepal. This study was conducted among the people from the Hattimudha village in Morang district of eastern Nepal, who practiced open defecation. Maximum variation sampling method was used to recruit participants for 20 in-depth interviews and 2 focus group discussions. We adopted a content analysis approach to analyze the data. We categorized different reasons for open defecation as motivation by choice and motivation by compulsion. Open defecation by choice as is expressed as a medium for socializing, a habit and an enjoyable outdoor activity that complies with spiritual and religious norms. Open defecation by compulsion include reasons such as not having a latrine at home or having an alternative use for the latrine structures. Despite having a private latrine at home or access to a public latrine, people were compelled to practice open defecation due to constraints of norms restricting latrine use and hygiene issues in general. For women the issues with privacy and issues refraining women to use the same latrine as men compelled women to look for open defecation places. Open defecation is either a voluntary choice or a compulsion. This choice is closely linked with personal preferences, cultural and traditional norms with special concerns for privacy for women and girls in different communities. The ongoing campaigns to promote latrine construction and its use needs to carefully consider these factors in order to reduce the open defecation practices and increase the use of sanitary latrines.


Dental Caries Profile and Associated Risk Factors Among Adolescent School Children in an Urban South-Indian City.
To study the dental caries experience among adolescent school children in Chennai city using the ICDAS-II scoring system. The secondary objective was to identify associated risk factors to different thresholds of dental caries defined by ICDAS. Two hundred and thirty-seven children (13-17 years) from five schools across Chennai city were included using simple random sampling. After obtaining assent to participate in the study and satisfying the selection criteria, 200 children were screened for dental caries using ICDAS-II. The population was assessed for the following risk factors: sociodemographic status, habits, diet, plaque and salivary parameters. Prevalence of dental caries was estimated at the following thresholds: normal (ICDAS-0/1), mild caries (ICDAS-2), moderate caries (ICDAS-3/4) and extensive caries (ICDAS-5/6). Backward logistic regression analysis was performed to identify risk factors at different thresholds and crude odds ratio was calculated for statistically significant risk factors. The overall prevalence of dental caries (ICDAS 3-6) was 57.5% (95% CI 48-62%). The proportions of children at different caries thresholds were: ICDAS-2 - 55% (95% CI:48-62%), ICDAS-3/4 - 51% (95% CI:44-58%) and ICDAS-5/6 - 25% (95% CI:19-31%). Reduced pH was statistically significant for moderate and extensive caries (OR 6.24, 95% CI 1.18-32.78 and 1.73, 95% CI 1.18-1.92, respectively) and the quantity of saliva was statistically significant for mild and moderate caries (OR 4.48, 95% CI 2.94-8.23 and 3.97, 95% CI 2.65-7.03, respectively). Low buffering capacity was associated with mild caries OR 5.71, 95% CI 2.82-18.2). Interobserver correlation was 0.91. A non-statistically significant value using Hosmer-Lemeshow Goodness of Fit test indicated that all three models predict the true estimate of the population. The proportions of children with mild and moderate caries were high considering their age group. The risk factors associated with mild caries were different from those associated with moderate and extensive caries.


[A comparative analysis of current conditions of oral health between residents living in towns and those in countryside in Guangdong Province].
A sampling population of 23,665 in Guangdong Province including 4 towns and 4 countryside had been surveyed for the current situation of oral health. A comparative analysis of residents between towns and countryside had been conducted and the results indicated that the rural residents had a higher prevalence rate of dental caries (65.30%) than those who lived in towns (59.96%). The Decayed Missing Filling (DMF) of the population (4.62) and of the patients (7.08) in countryside were both significantly higher than those (2.86 and 4.78, respectively) of citizens (P < 0.001). Females had a higher rate of dental caries than males both in towns and in countryside. Citizens had a higher prevalence rate of periodontosis than rural residents. This paper also presents a comparison of jaw deformity and personal health behaviour, an age distribution of dental caries and a multiple regression analysis.


One-Center Location With Block and Euclidean Distance.
A geometrical analysis is made of the dual simplex algorithm applied to a linear programming formulation of the one-center location problem in IR (2) using block distance. A geometric rule is given, and shown to be equivalent to the minimum ratio rule of the simplex algorithm, for updating the dual basis. The geometric analysis is applied to the Euclidean distance one-center problem and yields an alternative updating procedure for the dual algorithm.


The distal radioulnar joint in rheumatoid arthritis.
Rheumatoid arthritis (RA) involves the wrist in up to 80% of cases; up to 95% of patients have signs of wrist arthritis after 12 years of disease. The distal radioulnar joint (DRUJ) is involved in 31% to 75% of these patients and is often the first compartment of the wrist involved. The inflammatory sequence of events leads to the "caput ulnae syndrome" described by Backdahl in 1963. Extensor tendon ruptures are frequently associated. The presence of the "scallop" sign on radiographs is an alerting sign for tendon attrition. The gold standard in treatment remains resection of the distal ulnar head, known as Darrach's procedure. The most frequent complication is instability of the proximal ulnar stump. In order to restore stability or to prevent instability, several stabilisation techniques have been reported with free tendon grafts, the extensor carpi ulnaris, the flexor carpi ulnaris, the joint capsule and the pronator quadratus muscle. There is no evidence that stabilisation of the proximal ulnar stump during the initial operation gives better results. Another drawback of ulnar head resection is the progression of ulnar translation of the carpus. There are however several surveys showing that this ulnar translocation is the consequence of the disease rather than the result of the Darrach procedure. Several features such as an increased radial slope (> 23 degrees) and/or destruction of the ulnar corner of the distal radial epiphysis have been mentioned as predictive elements for further ulnar slide of the carpus. The Sauvé Kapandji procedure is in these cases a useful alternative choice. Another advantage of this technique is that it provides a larger surface so that other (radial) procedures can be more easily combined (Chamay partial radiocarpal fusion, wrist prosthesis).


Physiological and transcriptomic analysis uncovers salinity stress mechanisms in a facultative crassulacean acid metabolism plant Dendrobium officinale.
Dendrobium officinale is a precious medicinal Chinese herb that employs facultative crassulacean acid metabolism (CAM) and has a high degree of abiotic stress tolerance, but the molecular mechanism underlying the response of this orchid to abiotic stresses is poorly understood. In this study, we analyzed the root microstructure of D. officinale plantlets and verified the presence of chloroplasts by transmission electron microscopy. To obtain a more comprehensive overview of the molecular mechanism underlying their tolerance to abiotic stress, we performed whole-transcriptome sequencing of the roots of 10-month-old plantlets exposed to salt (NaCl) treatment in a time-course experiment (0, 4 and 12 h). The total of 7376 differentially expressed genes that were identified were grouped into three clusters (P < 0.05). Metabolic pathway analysis revealed that the expression of genes related to hormone (such as auxins, cytokinins, abscisic acid, ethylene and jasmonic acid) biosynthesis and response, as well as the expression of genes related to photosynthesis, amino acid and flavonoid metabolism, and the SOS pathway, were either up- or down-regulated after salt treatment. Additionally, we identified an up-regulated WRKY transcription factor, DoWRKY69, whose ectopic expression in Arabidopsis promoted seed germination under salt tress. Collectively, our findings provide a greater understanding of the salt stress response mechanisms in the roots of a facultative CAM plant. A number of candidate genes that were discovered may help plants to cope with salt stress when introduced via genetic engineering.


Damselfly (Odonata: Calopterygidae) Population Decline in an Urbanizing Watershed.
Reduction of terrestrial vegetation and degradation of water quality are among the factors driving insect population decline in growing cities. In this study, we investigated the extent of habitat deterioration, behavioral and physiological responses, and fitness of a damselfly [Hetaerina americana (F.)] population in a semitropical region in central Mexico. The study population was located in a riverine area that crosses a small urban area (Tehuixtla city). We related two habitat variables (tree/shrub covered area and numbers of wastewater outlets) to presumable damselfly responses (larval and adult abundance, duration of adults exposed directly to sunlight, lipid content and muscle mass, and egg survival) over the years 2002 and 2016. We detected a reduction in terrestrial vegetation cover, an increase in wastewater outlets, and a decrease in larval and adult abundance. Adults were more exposed to sunlight in 2016 than in 2002 and showed a reduced lipid content and muscle mass in 2016. Egg survival also decreased. Although correlative, these results suggest impairment of damselfly condition (via lipid and muscle reduction) and fitness as urbanization increases.


Comparative Analysis of Neurogenesis in the Central Olfactory Pathway of Adult Decapod Crustaceans by In Vivo BrdU Labeling.
To examine the distribution of neurogenesis in the central olfactory pathway of adult decapod crustaceans, we labeled, in vivo, six species of decapod crustaceans representing most infraorders (shrimps, spiny lobsters, clawed lobsters, crayfish, hermit crabs, true crabs) with the proliferation marker 5-bromo-2'-deoxyuridine (BrdU). In all tested species a group of small, neuron-like nuclei in the lateral soma clusters of the brain was labeled; the lateral soma clusters are composed of the cell bodies of ascending olfactory projection neurons. In only a few instances did groups of BrdU-positive nuclei also occur in the other soma clusters of the central olfactory pathway. In the spiny lobster (Panulirus argus), a group of small neuron-like nuclei was labeled in the medial soma clusters containing the cell bodies of local interneurons of the olfactory deutocerebrum. In the hermit crab (Pagurus bernhardus), and the true crab (Cancer pagurus), a group of small neuron-like nuclei was labeled in soma clusters located in the eyestalks. These soma clusters probably contain the cell bodies of local interneurons of the hemiellipsoid bodies, to which the olfactory projection neurons ascend. These results indicate that neurogenesis occurs among olfactory projection neurons in the adult brain. Among the other neuronal types of the central olfactory pathway, however, neurogeneis is restricted to specific taxa. The persistence of neurogenesis among the different neuronal types of the central olfactory pathway throughout adult life suggests an enormous structural plasticity of brain circuitry that may enable the longlived decapod crustaceans to adapt to changing olfactory environments.


Possible relevance of steroid availability and breast cancer.
The as yet circumstantial evidence for a central role of estrogens in the promotion of human breast cancer is supported by many data. However, it has not been possible to identify breast cancer patients or women at risk by abnormally elevated estrogen levels in plasma. The concept of available, i.e., non-SHBG bound sex steroid seems to offer a better understanding than total serum steroid levels do. We demonstrated that sex steroid protein binding is decreased by free fatty acids. This finding may help to explain how the affluent Western diet and sedentary life style is related to high incidence rates of breast cancer. We have postulated that it is especially the central (abdominal) type of obesity which may increase sex steroid availability. This mechanism could be important already at the age of breast development when the sensitivity to promotion seems relatively great. It may also explain the increased incidence rates which are observed in Western industrialized countries after menopause. It seems likely that other endocrine-related cancer, such as endometrial or prostatic carcinomas are influenced in an analogous way.


Wounds caused by tight contact with the barrel-cylinder gap of revolvers.
A case is presented in which the recognition of a tight cylinder gap contact wound was crucial. Experiments were carried out to reproduce the wound which was noted on the hand of a robbery suspect. Tight contact with the cylinder gap of a revolver produces a characteristic, readily recognizable wound. It is characterized by an L-shaped pattern of powder residue. Along one axis a searing burn may occur which may be deep and which may lead to significant tissue destruction.


Antibody-dependent gene transduction using gammaretroviral and lentiviral vectors pseudotyped with chimeric vesicular stomatitis virus glycoprotein.
Gammaretroviral and lentiviral vectors pseudotyped with vesicular stomatitis virus glycoprotein G (VSV-G) have been used for stable gene transfer because of their broad host range and high mechanical strength. In the present study, an expression plasmid for chimeric VSV-G, consisting of a ZZ fragment derived from Staphylococcal protein A fused to the N-terminus of VSV-G (ZZ-VSV-G), was constructed to produce viral vectors capable of antibody-dependent gene transduction. Gammaretroviral (based on mouse stem cell virus, MSCV) and lentiviral (based on human immunodeficiency virus type 1, HIV-1) vectors pseudotyped with ZZ-VSV-G were produced without the loss of antibody-binding activity. The production of infectious viral particles was promoted by the addition of an expression plasmid for native VSV-G and antibody-dependent gene transduction was achieved using plates coated with antibodies. This system may be useful for the genetic transduction of cells expressing specific proteins on their surface, and for screening of antibodies specific for cell surface receptors.


Current and Future Status of Laparoscopy in Gynecologic Oncology.
Laparoscopy is playing an increasingly important role in gynecologic oncology. The benefits of minimally invasive surgery for oncology patients and the quality of this treatment are well documented. Outcomes and quality of minimally invasive surgical procedures to treat cervical cancer were evaluated based on retrospective and case-control studies; outcomes and quality after minimally invasive treatment für early-stage low-risk endometrial cancer were also assessed in prospective randomized studies. If indicated, laparoscopic lymphadenectomy is both technically feasible and oncologically safe. Adipose patients in particular benefit from minimally invasive procedures, where feasible. The potential role of laparoscopy in neoadjuvant therapy for ovarian cancer and in surgery for early-stage ovarian carcinoma is still controversially discussed and is currently being assessed in further studies. Using a minimally invasive approach in gynecologic oncology procedures demands strict adherence to oncological principles and requires considerable surgical skill.


Improved Functional Performance in Individuals With Dementia After a Moderate-Intensity Home-Based Exercise Program: A Randomized Controlled Trial.
Individuals with dementia (IWDs) experience difficulties across cognitive and functional domains. Nonpharmacological interventions aimed at reducing disability are greatly needed. Exercise is a low-cost and easily implemented approach, but investigation has yielded mixed evidence to date. The purpose of the current study was to evaluate a novel and innovative moderate-intensity functional exercise intervention for IWDs, which was developed using principles from exercise science along with a Strength-Based Approach, consisting of 24 home-based sessions. A randomized, controlled intervention trial with a 2-group pretest and posttest design was used with a sample of 23 community-dwelling IWDs (intervention group: n = 13; comparison group: n = 10). Average age of participants was 73.9 years (standard deviation, 9.1) with mild to moderate cognitive impairment (Mini-Mental State Examination, Mean = 20.8; standard deviation, 5.0). A 99.0% attendance rate indicated high adherence to the moderate-intensity exercise program. Efficacy was examined using multiple linear regression. Group assignment significantly predicted performance in key outcome measures, with IWDs from the intervention group improving in lower extremity strength (B = 5.92, t = 3.26, P = .004), balance (B = 4.04, t = 4.13, P = .001), and fast gait speed (B = .32, t = 2.61, P = .02). These findings indicated IWDs are able to participate in and benefit from a moderate-intensity functional exercise program, consisting of strength and balance activities. The current intervention used a Strength-Based Approach to facilitate implementation of exercise activities that could be completed by the sample. Therefore, integration of these techniques into mainstream clinical practice and research should be feasible with this patient population. Future research directions and implications of these findings also are discussed.


Optimal duration of dual-antiplatelet therapy following drug-eluting stent implantation: a meta-analysis.
Optimal duration of dual-antiplatelet therapy (DAPT) following drug-eluting stent (DES) implantation remains uncertain. The aim of this study was to perform a meta-analysis of trials evaluating the effect of DAPT duration on long-term clinical outcomes after DES implantation. The authors searched OvidMEDLINE, EMBASE, and the Cochrane Library for both randomized controlled trials and nonrandomized studies that evaluated DAPT duration on long-term clinical outcomes after DES implantation. The end point was the cumulative incidence of the composite of all-cause death and nonfatal myocardial infarction (MI) at maximum follow-up. Quantitative analysis was performed to estimate the pooled hazard ratios (HRs) for the effect of DAPT duration. The pooled effect of DAPT discontinuation before 6 months significantly increased risk of death and nonfatal MI (HR, 1.46; 95% confidence interval, 1.18-1.80), but DAPT beyond 12 months did not reduce the incidence of the composite end point compared with drug discontinuation at 12 months (HR, 0.91; 95% confidence interval, 0.75-1.10). In conclusion, the current evidence suggests that 6 to 12 months of DAPT may be optimal after DES implantation.


Labdane and Clerodane Diterpenoids from Colophospermum mopane.
Five labdane (1-5), an isolabdane (6), and five clerodane diterpenoids (7-11), were isolated from seeds, husks, and leaves of Colophospermum mopane. Compounds 1-3 and 6-9 are new, and their structures were elucidated by means of physical data analysis (1D and 2D NMR, HRESIMS). The absolute configurations of 1, 7, and 10 were determined by single-crystal X-ray diffraction with Cu Kα radiation. For compounds 2 and 6, the absolute configurations were established by the modified Mosher's method and corroborated by comparison of experimental and calculated electronic circular dichroism spectra of their 3-p-bromobenzoate derivatives. The crude extracts and compounds were evaluated for antimicrobial activity. The leaf extract was the most active against Staphylococcus aureus (125 μg/mL). Compound 11 showed the best inhibitory activity, with minimum inhibitory values of 15.6 μg/mL against Escherichia coli and Staphylococcus aureus and 31.3 μg/mL against Enterococcus faecalis.


RavA-ViaA antibiotic response is linked to Cpx and Zra2 envelope stress systems in Vibrio cholerae.
RavA-ViaA were reported to play a role in aminoglycoside (AG) sensitivity, but the mechanisms remain elusive. Here, we performed competition and survival experiments to confirm that deletion of ravA-viaA increases tolerance of the Gram-negative pathogen Vibrio cholerae to low and high AG concentrations during aerobic growth. Using high-throughput strategies in this species, we identify Cpx and Zra2 two-component systems as new partners of RavA-ViaA. We show that the AG tolerance of ∆ravvia requires the presence of these membrane stress sensing two-component systems. We propose that deletion of the RavA-ViaA function facilitates the response AGs because of a pre-activated state of Cpx and Zra2 membrane stress response systems. We also find an impact of these genes on vancomycin resistance, and we show that simultaneous inactivation of ravvia function together with envelope stress response systems leads to outer membrane permeabilization. Vancomycin is mostly used for Gram-positive because of its low efficiency for crossing the Gram-negative outer membrane. Targeting of the ravA-viaA operon for inactivation could be a future strategy to allow uptake of vancomycin into multidrug-resistant Gram-negative bacteria.IMPORTANCEThe RavA-ViaA complex was previously found to sensitize Escherichia coli to aminoglycosides (AGs) in anaerobic conditions, but the mechanism is unknown. AGs are antibiotics known for their high efficiency against Gram-negative bacteria. In order to elucidate how the expression of the ravA-viaA genes increases bacterial susceptibility to aminoglycosides, we aimed at identifying partner functions necessary for increased tolerance in the absence of RavA-ViaA, in Vibrio cholerae. We show that membrane stress response systems Cpx and Zra2 are required in the absence of RavA-ViaA, for the tolerance to AGs and for outer membrane integrity. In the absence of these systems, the ∆ravvia strain's membrane becomes permeable to external agents such as the antibiotic vancomycin.


[Suicidal risk in endogenous, neurotic and reactive depression in advanced age].
Suicidal syndromes were analyzed in 339 patients older than 45 years. Psychiatric treatment was instituted because of endogenous, neurotic or reactive depression. Differences in the relationship between diagnosis, sex and two age groups are discussed. Violent suicide increases with age concomitantly in all forms of depression. The prevalence of suicide after the age of 45 points toward the significance of particular life events and social influences. Life events and psychodynamic leading to suicidal behaviour are discussed Characteristic arrays of symptoms correlating with suicidal behaviour in endogenous depression are outlined. Special problems in the management of suicidal behaviour in the elderly are discussed.


Continuous ambulatory right heart pressure measurements with an implantable hemodynamic monitor: a multicenter, 12-month follow-up study of patients with chronic heart failure.
We describe the performance of an implantable hemodynamic monitor (IHM) that allows continuous recording of heart rate, patient activity levels, and right ventricular systolic, right ventricular diastolic, and estimated pulmonary artery diastolic pressures. Pressure parameters derived from the implantable monitor were correlated to measurements made with a balloon-tipped catheter to establish accuracy and reproducibility over time in patients with chronic heart failure (CHF). IHM devices were implanted in 32 patients with CHF (left ventricular ejection fraction, 29% +/- 11%; range, 14%-62%) and were tested with right heart catheterization at implantation and 3, 6, and 12 months later. Hemodynamic variables were digitally recorded simultaneously from the IHM and catheter. Values were recorded during supine rest, peak response of Valsalva maneuver, sitting, peak of a 2-stage (25-50 W) bicycle exercise test, and final rest period. The median of 21 paired beat-to-beat cardiac cycles was analyzed for each intervention. A total of 217 paired data values from all maneuvers were analyzed for 32 patients at implantation and 129 paired data values for 20 patients at 1 year. The IHM and catheter values were not different at baseline or at 1 year (P >.05). Combining all interventions, correlation coefficients were 0.96 and 0.94 for right ventricular systolic pressure, 0.96 and 0.83 for right ventricular diastolic pressure, and 0.87 and 0.87 for estimated pulmonary artery diastolic pressure at implantation and 1 year, respectively. The IHM and a standard reference pressure system recorded comparable right heart pressure values in patients with CHF. This implantable pressure transducer is accurate over time and provides a means to precisely monitor the hemodynamic condition of patients with CHF in a continuous fashion.


[The effect of LPC on the pacemaker current I(f) in ischemic myocardium and the influence of ISO on it].
To observe the effect of LPC on the pacemaker current I(f) in ischemic myocardium and if the effect could be reversed by ISO. By using two microelectrode voltage clamp technique to measure and compare the amplitude of I(f) of ischemic myocardium in the presence of LPC and LPC add ISO. Ischemia decreased the amplitude of I(f) at all membrane potential levels. Adding LPC 2 x 10(-5) mol/L to the ischemia-like solution, the amplitude of I(f) decreased further (n = 5, P < 0.05), it means that LPC aggravated the inhibitory effect of "ischemia" on the pacemaker activity. Adding LPC 2 x 10(-5) mol/L and ISO 1 x 10(-6) mol/L together to the ischemia-like solution, the amplitude of I(f) increased significantly at membrane potential -90 mV to - 120 mV (n = 8, P < 0.05) compared with ischemia condition, but still did not reach the levels before ischemia. In acute myocardial ischemia condition, toxic metabolite LPC accentuated its inhibitory effect on pacemaker current I(f), a local release and accumulation of catecholamine could not completely reverse their inhibitory effect.


Longitudinal Analysis of Quality of Diabetes Care and Relational Climate in Primary Care.
To assess the influence of relational climate on quality of diabetes care. The study was conducted at the Department of Veterans Affairs (VA). The VA All Employee Survey (AES) was used to measure relational climate. Patient and facility characteristics were gathered from VA administrative datasets. Multilevel panel data (2008-2012) with patients nested into clinics. Diabetic patients were identified using ICD-9 codes and assigned to the clinic with the highest frequency of primary care visits. Multiple quality indicators were used, including an all-or-none process measure capturing guideline compliance, the actual number of tests and procedures, and three intermediate continuous outcomes (cholesterol, glycated hemoglobin, and blood pressure). The study sample included 327,805 patients, 212 primary care clinics, and 101 parent facilities in 2010. Across all study years, there were 1,568,180 observations. Clinics with the highest relational climate were 25 percent more likely to provide guideline-compliant care than those with the lowest relational climate (OR for a 1-unit increase: 1.02, p-value <.001). Among insulin-dependent diabetic veterans, this effect was twice as large. Contrary to that expected, relational climate did not influence intermediate outcomes. Relational climate is positively associated with tests and procedures provision, but not with intermediate outcomes of diabetes care.


Assisted hatching on assisted conception (in vitro fertilisation (IVF) and intracytoplasmic sperm injection (ICSI)).
Failure of implantation and conception may result from inability of the blastocyst to escape from its outer coat, which is known as the zona pellucida. Artificial disruption of this coat is known as assisted hatching and has been proposed as a method for improving the success of assisted conception by facilitating embryo implantation. To determine effects of assisted hatching (AH) of embryos derived from assisted conception on live birth and multiple pregnancy rates. SEARCH METHODS: We searched the Cochrane Gynaecology and Fertility Group Specialised Register (until May 2020), the Cochrane Central Register of Controlled Trials (CENTRAL; until May 2020), in the Cochrane Library; MEDLINE (1966 to May 2020); and Embase (1980 to May 2020). We also searched trial registers for ongoing and registered trials (http://www.clinicaltrials.gov - a service of the US National Institutes of Health; http://www.who.int/trialsearch/Default.aspx - The World Health Organization International Trials Registry Platform search portal) (May 2020). Two review authors identified and independently screened trials. We included randomised controlled trials (RCTs) of AH (mechanical, chemical, or laser disruption of the zona pellucida before embryo replacement) versus no AH that reported live birth or clinical pregnancy data. We used standard methodological procedures recommended by Cochrane. Two review authors independently performed quality assessments and data extraction. We included 39 RCTs (7249 women). All reported clinical pregnancy data, including 2486 clinical pregnancies. Only 14 studies reported live birth data, with 834 live birth events. The quality of evidence ranged from very low to low. The main limitations were serious risk of bias associated with poor reporting of study methods, inconsistency, imprecision, and publication bias. Five trials are currently ongoing. We are uncertain whether assisted hatching improved live birth rates compared to no assisted hatching (odds ratio (OR) 1.09, 95% confidence interval (CI) 0.92 to 1.29; 14 RCTs, N = 2849; I² = 20%; low-quality evidence). This analysis suggests that if the live birth rate in women not using assisted hatching is about 28%, the rate in those using assisted hatching will be between 27% and 34%. Analysis of multiple pregnancy rates per woman showed that in women who were randomised to AH compared with women randomised to no AH, there may have been a slight increase in multiple pregnancy rates (OR 1.38, 95% CI 1.13 to 1.68; 18 RCTs, N = 4308; I² = 48%; low-quality evidence). This suggests that if the multiple pregnancy rate in women not using assisted hatching is about 9%, the rate in those using assisted hatching will be between 10% and 14%. When all of the included studies (39) are pooled, the clinical pregnancy rate in women who underwent AH may improve slightly in comparison to no AH (OR 1.20, 95% CI 1.09 to 1.33; 39 RCTs, N = 7249; I² = 55%; low-quality evidence). However, when a random-effects model is used due to high heterogeneity, there may be little to no difference in clinical pregnancy rate (P = 0.04). All 14 RCTs that reported live birth rates also reported clinical pregnancy rates, and analysis of these studies illustrates that AH may make little to no difference in clinical pregnancy rates when compared to no AH (OR 1.07, 95% CI 0.92 to 1.25; 14 RCTs, N = 2848; I² = 45%). We are uncertain about whether AH affects miscarriage rates due to the quality of the evidence (OR 1.13, 95% CI 0.82 to 1.56; 17 RCTs, N = 2810; I² = 0%; very low-quality evidence). This update suggests that we are uncertain of the effects of assisted hatching (AH) on live birth rates. AH may lead to increased risk of multiple pregnancy. The risks of complications associated with multiple pregnancy may be increased without evidence to demonstrate an increase in live birth rate, warranting careful consideration of the routine use of AH for couples undergoing in vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI). AH may offer a slightly increased chance of achieving a clinical pregnancy, but data quality was of low grade. We are uncertain about whether AH influences miscarriage rates.


Complications and Socioeconomic Costs Associated With Falls in the Elderly Population.
To explore the incidence, characteristics, complications and socioeconomic impacts associated with falls in community-dwelling elderly. From September 1, 2015 to October 12, 2015, a questionnaire-based survey was conducted involving a total of 2,012 elderly who lived in Guro-gu (Seoul), Yeongdeungpo-gu (Seoul), Yangpyeong-gu (Gyeonggi-do), Dalseong-gu (Daegu), and Jung-gu (Daegu). The subjects were interviewed using a structured questionnaire to obtain demographic characteristics and comprehensive falling histories. The socioeconomic cost related to falls was estimated using the statistical data provided by the Health Insurance Review and Assessment Service. Falls were recorded in 666 out of the 2,012 subjects (33.1%) during the past year. Frequent falls occurred during December, in the afternoons, when the floor was slippery. The most common injuries included the low back and the most common injury type was sprain. The total direct costs related to falls involving the 2,012 subjects were 303,061,019 KRW (Korean won). The average medical cost related to falls in the 2,012 subjects was 150,627 KRW and the average medical cost of 666 subjects who experienced falls was 455,047 KRW. Estimates of the total population over the age of 60 years showed that the annual direct costs associated with falls in Korea over the age of 60 years were about 1.378 trillion KRW. This study was conducted to explore the incidence, characteristics, complications, and socioeconomic impacts of falls in community-dwelling elderly. This study is expected to be used as a source of basic data for the establishment of medical policy for the elderly and the development of a fall prevention program for the elderly in Korea.


Synthesis of long indium nitride nanowires with uniform diameters in large quantities.
Large quantities of indium nitride (InN) nanowires are synthesized by the in situ nitriding of indium oxide (In(2)O(3)) powders in an ammonia (NH(3)) flux. Tens of milligrams of nanowires are obtained in one batch. Every 100 mg of In(2)O(3) starting powder can produce up to 65 mg of InN nanowires under the optimized conditions. The synthesized nanowires grow along the [001] direction with excellent crystallinity. They are of high purity and are 30-50 microm in length with an almost uniform diameter of about 100 nm. Photoluminescence measurements of the nanowires exhibit a strong peak at 707 nm. An optical bandgap of about 1.7 eV is estimated based on the absorption spectrum. The experimental results also demonstrate that the approach of nitriding In(2)O(3) powders in situ is feasible for the synthesis of high-purity InN nanowires in large quantities, with good reproducibility and without catalyst materials. The synthesis of InN nanowires in large quantities would be of benefit to the further study and understanding of their intrinsic properties, as well as being advantageous for their potential application in nanodevices.


Non-consequentialism, the person as an end-in-itself, and the significance of status.
Recently, several outstanding discussions of the structure of non-consequentialism have appeared. Two of these are Shelly Kagan's The Limits of Morality and a pair of articles by Warren Quinn, "Actions, Intentions, and Consequences: the Doctrine of Doing and Allowing" and "Actions, Intentions, and Consequences: the Doctrine of Double Effect." I would like to examine several related issues discussed by these authors. Another outstanding work to which I will refer in this article, but not discuss at great length, is Judith Jarvis Thomson's The Realm of Rights. The general topic with which I shall be concerned is the structure of a non-consequentialist moral theory. Non-consequentialism has two important features. In a non-consequentialist moral theory, (1) there is a permission not to maximize overall best consequences (this is sometimes referred to as an option), and (2) there are constraints on promoting overall best consequences (for example, we must not kill one innocent, non-threatening person for his organs to save five others). I shall use the works by Kagan, Quinn, and Thomson to help characterize further the elements of the non-consequentialist structure and to justify them.


[Human diseases transmitted by Culicidae in southwest Indian Ocean islands].
South-West Indian Ocean islands were inhabited at the beginning and free from all kind of vector. In Madagascar, Mayotte, Moheli and Anjouan, malaria vectors were carried by the first settlements. According to epidemics, the anopheles arrived in 1867 in Mauritius, 1869 in La Reunion and 1920 in Grande Comore. Rodrigues, Saint-Brandon and the Seychelles are still free from malaria vectors in the coastal part of Madagascarcar and in Comores archipelago, malaria is stable with a permanent transmission. Unstable malaria is seasonaly transmitted in the high territories of Madagascar; it was the same in Mauritius and Reunion island before the eradication campaign. Lymphatic filariasis is quoted in Madagascar, but Comores archipelago is an area with high transmission. The incidence of the disease is moderate in La Reunion and Mauritius and very low in Chagos and Seychelles archipelagos. There is no transmission in Rodrigues and St Brandon. Epidemics of dengue were described during the second part of the XIXth century in Mauritius and La Reunion, then in 1943 in Mayotte. But the disease was controlled in the fifties by the antimalaria campaign. A new epidemy appeared in Seychelles by the end of 1976 and then in Reunion and Mauritius next year. An isolated outbreak was described in Grande Comore only in 1994.


Estimation of oxygen effective diffusion coefficient in a non-steady-state biofilm based on response time.
In wastewater treatment, oxygen effective diffusion coefficient (D eff ) is a key parameter in the study of oxygen diffusion-reaction process and mechanism in biofilms. Almost all the reported methods for estimating the D eff rely on other biokinetic parameters, such as substrate consumption rate and reaction rate constant. Then, the estimation was complex. In this study, a method independent of other biokinetic parameters was proposed for estimating the dissolved oxygen (DO) D eff in biofilms. It was based on the dynamic DO microdistribution in a non-steady-state inactive biofilm, which was measured by the oxygen transfer modeling device (OTMD) combining with an oxygen microelectrode system. A pure DO diffusion model was employed, and the expression of the DO D eff was obtained by applying the analytical solution of the model to a selected critical DO concentration. DO D eff in the biofilm from the bioreactor was calculated as (1.054 ± 0.041) × 10-9 m2/s, and it was in the same order of magnitude with the reported results. Therefore, the method proposed in this study was effective and feasible. Without measurement of any other biokinetic parameters, this method was convenient and will benefit the study of oxygen transport-reaction process in biofilms and other biofouling deposits. Graphical abstract .


Trends and results of oesophageal cancer surgery in Finland between 2004 and 2014.
Few population-based studies reporting trends in oesophageal cancer surgery exist. The aim of this study was to assess the incidence of oesophageal cancer, changes in resection rates, patient demographics and short- and long-term outcomes of oesophagectomy at the population level in Finland. All Finnish patients diagnosed with cancer of the oesophagus or gastrooesophageal junction between 1 January 2004 and 31 December 2014 identified from the nationwide registries were included. The follow-up ended on 31 December 2016. For evaluation of changes in demographics and treatment, data were divided into 2 periods: 2004-2009 and 2010-2014. For comparison of short-and long-term outcomes, adjustments for age, sex, comorbidity, tumour stage and histology were used. The number of diagnosed oesophageal cancers was 4266. Of these, 740 underwent oesophagectomy. Resection rate increased from 15.2% in 2004-2009 to 19.6% in 2010-2014. The median number of oesophagectomies in Finnish hospitals increased from 1.9 to 3.7 per hospital per year. At the same time, minimally invasive surgery became more common (6.3% vs 35.1%, P < 0.0001) and a trend for increase in neoadjuvant treatment was observed (46.8% vs 53.8%, P = 0.0582). The rate of type III anastomosis leaks and conduit necroses was 5.1% without differences in time periods. Three-year [52.4% vs 61.6%, adjusted hazard ratio (HR) 0.75, 95% confidence interval (CI) 0.59-0.95] and 5-year survival (42.1% vs 56.5%, adjusted HR 0.70, 95% CI 0.57-0.87) improved. This nationwide population-based study demonstrates an increase in resection rate, use of neoadjuvant treatment and minimally invasive surgery together with an improvement in long-term outcome after oesophageal cancer surgery.


A multi-layered Fe2O3/graphene composite with mesopores as a catalyst for rechargeable aprotic lithium-oxygen batteries.
Aprotic Li-O2 batteries have attracted a huge amount of interest in the past decade owing to their extremely high energy density. However, identifying a desirable cathodic catalyst for this promising battery system is one of the biggest challenges at present. In this work, a multi-layered Fe2O3/graphene nanosheets (Fe2O3/GNS) composite with sandwich structure was synthesized using an easy thermal casting method, and served as a cathodic catalyst for aprotic Li-O2 batteries. The aprotic Li-O2 cell with the Fe2O3/GNS catalyst demonstrated a better reversibility, lower overpotential for oxygen evolution, and a higher Coulombic efficiency (close to 100%) than those of pure GNS. An excellent rate performance and good cycle stability were also confirmed. The results, characterized by ex and in situ methods, revealed that the dominant discharge product Li2O2 was decomposed below 4.35 V. This superior electrochemical performance is mainly attributed to the unique sandwich structure of the Fe2O3/GNS catalyst with mesopores, which can provide substantially more catalytic sites and prevent direct contact between carbon and Li2O2.


Asymptomatic wild-type poliovirus infection in India among children with previous oral poliovirus vaccination.
Mucosal immunity induced by oral poliovirus vaccine (OPV) is imperfect and potentially allows immunized individuals to participate in asymptomatic wild-type poliovirus transmission in settings with efficient fecal-oral transmission of infection. We examined the extent of asymptomatic wild-type poliovirus transmission in India by measuring the prevalence of virus in stool samples obtained from 14,005 healthy children who were in contact with 2761 individuals with suspected poliomyelitis reported during the period 2003-2008. Wild-type poliovirus serotypes 1 and 3 were isolated from the stool samples of 103 (0.74%) and 104 (0.74%) healthy contacts, respectively. Among contacts of individuals with laboratory-confirmed poliomyelitis, 27 (12.7%) of 213 and 29 (13.9%) of 209 had serotypes 1 and 3, respectively, isolated from their stool samples. The odds ratio of excreting serotype 1 wild-type poliovirus was 0.13 (95% confidence interval, 0.02-0.87) among healthy children reporting 6 doses of OPV, compared with children reporting 0-2 doses. However, two-thirds of healthy children who excreted this virus reported >or=6 doses, and the prevalence of this virus did not decrease with age over the sampled range. Although OPV is protective against infection with poliovirus, the majority of healthy contacts who excreted wild-type poliovirus were well vaccinated. This is consistent with a potential role for OPV-vaccinated children in continued wild-type poliovirus transmission and requires further study.


The role of phosphate in the secretion of parathyroid hormone in man.
In man, oral administration of 1 g of phosphorus resulted in a 60-125% increase in serum immunoassayable parathyroid hormone (PTH) concentration. Peak PTH levels were attained in 1 hr, and PTH returned to base line levels in 2 hr. This increase in PTH appeared to be initiated by a very small decrease of total and ionized calcium and was abolished by a calcium infusion. There was no correlation between serum phosphorus and PTH. The experiments show that oral phosphorus administration initiates a calcium-mediated control system for PTH secretion and that this system operates very sensitively in man.


Autoreactivity is highly prevalent in patients with multiple intolerances to NSAIDs.
A subset of drug-allergic patients show a marked propensity to react against several, chemically unrelated nonsteroidal anti-inflammatory drugs (NSAIDs). The pathogenesis of such multiple drug reactions is unclear. Approximately 30% of patients with chronic idiopathic urticaria, a condition frequently characterized by autoreactivity on autologous serum skin test (ASST), experience flares of hives after taking chemically unrelated NSAIDs. To detect whether a clinically unapparent autoreactivity may represent the nonspecific mechanism facilitating drug-induced histamine release in patients with a history of urticaria/angioedema induced by several, chemically unrelated NSAIDs. Thirty-six adults with a history of acute NSAID-induced urticaria (22 with multiple NSAID sensitivity [MNS]; 14 with single NSAID sensitivity [SNS]; and 20 atopic controls without a history of drug allergy) underwent ASST. Sera from 14 MNS and 4 SNS subjects (all ASST-positive) underwent histamine release assay with basophils from normal donors. Sera from five MNS patients were tested on autologous basophils as well. Twenty of 22 (91%) MNS subjects versus 5 of 14 (36%) SNS subjects were positive on ASST (P < 0.01). No atopic control was ASST-positive. Sera from 4 of 14 (29%) MNS patients versus 0/4 SNS subjects (P = NS) induced significant histamine release from basophils of normal donors. The use of autologous basophils did not significantly change these results. Most patients with multiple NSAID intolerance and approximately one-third of those with single NSAID hypersensitivity are characterized by the presence of circulating histamine-releasing factors. Their nature is still unclear, but the fact that only a minority of sera from ASST+ subjects were able to induce histamine release from normal basophils in vitro suggests that these factors might not differ from those involved in most patients with chronic urticaria. These factors might play a relevant pathogenic role in NSAID-induced urticaria reactions.


Imaging Features of Early Diffuse Idiopathic Skeletal Hyperostosis (pre-DISH): Analysis of Progression of Ligament Ossification over 5 Years by Computed Tomography.
Some patients who have not been diagnosed with diffuse idiopathic skeletal hyperostosis (DISH) (patients in the preclinical stage of DISH [pre-DISH]) may develop DISH in the future. However, there are currently no clearly defined diagnostic criteria for pre-DISH. This study aims to define pre-DISH by analyzing the change in the ossification extent in each intervertebral space in the thoracic and lumbar spines over time using computed tomography (CT). Of the patients who underwent CT of the thoracic to pelvic region at least twice from 2009 to 2018, 188 who underwent CT at an interval of 5 years to 5 years and 2 months were enrolled. The prevalence of DISH during the first and second CT scans was investigated. The pre-DISH feature was defined, and the prevalence of pre-DISH on the first CT and the change after 5 years in patients with pre-DISH was investigated. Of the 188 patients, 37 (19.7%) and 48 (25.5%) were diagnosed with DISH on the first and second CT scans, respectively. Pre-DISH was defined as the ossification characterized by the modified Mata score of three contiguous intervertebral spaces with a score of ≥2 points (222; 2 points, ligament ossification of half or more of the intervertebral disc height but incomplete fusion), and 52 patients were diagnosed with pre-DISH. Of the 52 patients with a score of ≥(222), 11 (21.2%) were diagnosed with DISH 5 years later. Patients who have three contiguous intervertebral spaces with a modified Mata score of 2 or 3 points should be considered pre-DISH.


Variation in the cost of 5 common operations in the United States.
Health care costs are an important policy focus in the United States. The magnitude and drivers of variation in the costs of common operative procedures are not well understood. We sought to characterize variation in costs across hospitals. We used data from the Nationwide Inpatient Sample from 2001-2011 for 5 elective operations: colectomy, coronary artery bypass graft, total knee arthroplasty, cesarean section, and lung resection. Hospitals were benchmarked for each using hierarchical risk- and reliability-adjustment methods to generate an observed-to-expected cost ratio, which was adjusted for patient demographics, comorbidity, wage index, and procedure complexity. Hospitals were divided into quintiles. Characteristics of high- and low-quintile hospitals and their adjusted outcomes were examined. Cost observed-to-expected ratios ranged widely for all 5 procedures: 14.9-fold for colectomy, 5.5-fold for coronary artery bypass graft, 12.5-fold for lung resection, 10.6-fold for total knee arthroplasty, and 28.0-fold for cesarean section. Comparing highest to lowest cost quintiles of hospitals, high-cost hospitals were more likely to serve minority and Medicaid patients. Mortality was elevated significantly in high-cost hospitals for colectomy, coronary artery bypass graft, and lung resection (adjusted odds ratio 1.99, 1.32, 2.57; respectively). Service lines were correlated at low-cost hospitals. There was a significant association between greater procedure volume and low-cost hospitals for colectomy, coronary artery bypass graft, and total knee arthroplasty. Despite robust adjustment, there is wide cost variation for common operative procedures in the United States. High-cost hospitals may need to focus on cost reduction at the hospital level to reduce cost across service lines. Benchmarking costs may identify significant opportunities to promote value, or the balance between cost and quality, in operative care in the United States.


Effective gene delivery into human stem cells with a cell-targeting Peptide-modified bioreducible polymer.
Stem cells are poorly permissive to non-viral gene transfection reagents. In this study, we explored the possibility of improving gene delivery into human embryonic (hESC) and mesenchymal (hMSC) stem cells by synergizing the activity of a cell-binding ligand with a polymer that releases nucleic acids in a cytoplasm-responsive manner. A 29 amino acid long peptide, RVG, targeting the nicotinic acetylcholine receptor (nAchR) was identified to bind both hMSC and H9-derived hESC. Conjugating RVG to a redox-sensitive biodegradable dendrimer-type arginine-grafted polymer (PAM-ABP) enabled nanoparticle formation with plasmid DNA without altering the environment-sensitive DNA release property and favorable toxicity profile of the parent polymer. Importantly, RVG-PAM-ABP quantitatively enhanced transfection into both hMSC and hESC compared to commercial transfection reagents like Lipofectamine 2000 and Fugene. ∼60% and 50% of hMSC and hESC were respectively transfected, and at increased levels on a per cell basis, without affecting pluripotency marker expression. RVG-PAM-ABP is thus a novel bioreducible, biocompatible, non-toxic, synthetic gene delivery system for nAchR-expressing stem cells. Our data also demonstrates that a cell-binding ligand like RVG can cooperate with a gene delivery system like PAM-ABP to enable transfection of poorly-permissive cells.


Congenital cataracts affect the retinal visual cycle and mitochondrial function: A multi-omics study of GJA8 knockout rabbits.
Congenital cataracts are a threat to visual development in children, and the visual impairment persists after surgical treatment; however, the mechanisms involved remain unclear. Previous clinical studies have identified the effect of congenital cataracts on retinal morphology and function. To further understand the molecular mechanisms by which congenital cataracts affect retinal development, we analyzed retina samples from 7-week-old GJA8-knockout rabbits with congenital cataracts and controls by four-dimensional label-free quantification proteomics and untargeted metabolomics. Bioinformatics analysis of proteomic data showed that retinol metabolism, oxidative phosphorylation, and fatty acid degradation pathways were downregulated in the retinas of rabbits with congenital cataracts, indicating that their visual cycle and mitochondrial function were affected. Additional validation of differentially abundant proteins related to the visual cycle and mitochondrial function was performed using Parallel reaction monitoring and western blot experiments. Untargeted metabolome analysis showed significant upregulation of the antioxidant glutathione and ascorbic acid in the retinas of rabbits with congenital cataracts, indicating that their oxidative stress balance was not dysregulated. SIGNIFICANCE: Congenital cataracts in children can alter retinal structure and function, yet the mechanisms are uncertain. Here is the first study to use proteomics and metabolomics approaches to investigate the effects of congenital cataracts on retinal development in the early postnatal period. Our findings suggest that congenital cataracts have an impact on the retinal visual cycle and mitochondrial function. These findings give insight on the molecular pathways behind congenital cataract-induced visual function impairment in the early postnatal period.


Measuring Productivity in Primary Care Behavioral Health: A Delphi Study.
High productivity by behavioral health consultants (BHC) is a defining aspect of the primary care behavioral health (PCBH) model to maximize access to care and is often measured by patient volume. Studies of productivity in health care settings suggest a single productivity target may not be optimal. We used a Delphi method to obtain expert consensus on an operational definition of high productivity by BHCs in the PCBH model. Clinicians, managers, and researchers in PCBH were recruited to participate in a multi-round survey using a modified Delphi technique and develop consensus on PCBH productivity metrics. Ten participants completed all three survey rounds and rated 28 metrics. After three rounds, two direct metrics (average number of billable BHC visits each day; number of patients seen per day) received at least 80% consensus as "Essential", two received at least 50%, and five received less than 50%. One influencer (level of integration at the practice) received at least 80% consensus as "Very Much" influential, 19 received at least 50%, and eight items received less than 50%. Several themes arose from participant comments. PCBH productivity can be interpreted as being high volume. Numerous practice factors influence how productive a BHC may be. Future studies should determine the feasibility of our metrics in clinical practice, establish productivity expectations based on patient needs and clinic resources, and identify patient-, clinician-, or practice-level moderators of productivity.


Role of activation of calcium-sensitive K+ channels in NO- and hypoxia-induced pial artery vasodilation.
It has been previously observed that nitric oxide (NO) contributes to hypoxic pial artery dilation and that both sodium nitroprusside (SNP), a releaser of NO, and hypoxia elicit dilation via activation of ATP-sensitive K+ channels in the newborn pig. Other studies, however, have shown that NO activates calcium-sensitive K+ (K(Ca)) channels. The present study, therefore, was designed to investigate the role of K(Ca)-channel activation in NO and hypoxic dilation and to relate this mechanism to the previously observed role of NO in hypoxic dilation in newborn pigs equipped with closed cranial windows. SNP (10(-8) and 10(-6) M) elicited pial artery dilation that was unchanged in the presence of the K(Ca)-channel antagonist iberiotoxin (10(-7) M; 10 +/- 1 and 20 +/- 1 vs. 9 +/- 1 and 20 +/- 2% for 10(-8) and 10(-6) M SNP in the absence and presence of iberiotoxin, respectively). Responses to S-nitroso-N-acetylpenicillamine and 8-bromoguanosine 3',5'-cyclic monophosphate were similarly unchanged by iberiotoxin. In contrast, iberiotoxin attenuated the dilation resulting from moderate and severe hypoxia (arterial PO2 approximately 35 and 25 mmHg, respectively; 27 +/- 1 vs. 21 +/- 2 and 34 +/- 1 vs. 16 +/- 2% for moderate and severe hypoxia in the absence and presence of iberiotoxin, respectively). Iberiotoxin blocked responses to the K(Ca)-channel agonist NS-1619, whereas responses to the ATP-sensitive K+ agonist cromakalim were unchanged (8 +/- 1 and 15 +/- 1 vs. 1 +/- 1 and 1 +/- 1% for 10(-8) and 10(-6) M NS-1619 in the absence and presence of iberiotoxin, respectively). These data show that NO and guanosine 3',5'-cyclic monophosphate do not elicit dilation via K(Ca)-channel activation. However, activation of K(Ca) channels does contribute to hypoxic pial dilation. Finally, these data suggest that substances other than NO are involved in the contribution of K(Ca)-channel activation to hypoxic pial artery dilation.


Intention to Receive the Second Round of COVID-19 Vaccine Among Healthcare Workers in Eastern Ethiopia.
COVID-19 pandemic has remained one of the leading causes of death which claimed the lives of many well-trained and experienced healthcare professionals. Vaccination is the most effective way of controlling infectious diseases, while success is challenged by individuals and groups who choose to delay or refuse vaccines. The objective of the present study was to assess the intention of healthcare workers in Eastern Ethiopia to receive the second round of COVID-19 vaccine. Institution-based cross-sectional survey research design was used to collect quantitative data from a representative sample of healthcare workers in Dire Dawa, Haramaya, and Harar towns of Eastern Ethiopia. The correctly filled questionnaires were selected and entered into SPSS software for further analysis, where frequency tables, percentages, mean, and multinomial logistic regression analysis were used in the process. The findings revealed that most (61.6%) of the research participants are willing to receive the second round of COVID-19 vaccine, and 10.3% reported that they have not decided yet. Moreover, the main reason for respondents' lack of intention to receive the second round of COVID-19 vaccine is the belief that the first round of COVID-19 vaccine is sufficient to prevent infection (27.8%) followed by concern over the safety or side effects of the vaccine (26.6%). Above all, the healthcare workers' intention of taking the second round of COVID-19 vaccine is significantly associated to having children (OR=0.362, P<0.05; 95% CI: 3.279-5465.189), previous interaction with someone infected by COVID-19 (OR=1.480, P<0.05; 95% CI: 3.949-0.055), the perception that COVID-19 causes a severe illness (OR=0.018, P<0.05, 95% CI: 13.489-196.391), and experience of receiving the first round of COVID-19 vaccine (OR=50431.104, P<0.01; 95% CI: 408.789-626.00). The present study has shown that healthcare workers in Eastern Ethiopia have a good intention of receiving the second round of COVID-19 vaccine. Nevertheless, the findings have also made it clear that there are still issues to be addressed as far as both willingness to receive the second round of the vaccine and experience of taking the first round of the vaccine are concerned. It is, therefore, important that sufficient training should be given to the healthcare workers in the area in order to raise their level of awareness and enhance their willingness to receive the second round of the vaccine.


Vaginal microecological changes of different degrees of cervical lesions in Hakka women in Meizhou City.
Research shows an association between vaginal microbiota and the development of cervical cancer, but the role of altered microbiota in cancer development remains controversial. In this study, we attempted to reveal the vaginal microecological changes in cervical lesions by 16S rRNA gene sequencing. Vaginal secretions were collected from Hakka women in Meizhou City, Guangdong Province, China. The diversity, composition and the correlations among species of the vaginal microbiota were determined by sequencing the bacterial 16S rRNA gene. The microbial functional abundance was detected via KEGG and COG (Clusters of Orthologous Groups). The results showed that the Cancer group was characterised by evident changes in the composition of the vaginal microbiota, increased alpha diversity, and altered community structure distribution and microbial interaction network. Linear discriminant analysis (LDA) effect size showed that 21 bacterial species were abundant in the Cancer group. In addition, the loss of Lactobacillus stimulated other flora proliferation, resulting in a microecological disturbance. KEGG and COG analysis indicated the cancer group is mainly concentrated in energy metabolism. In short, the vaginal microecology of Hakka women in Meizhou City presents with different degrees of cervical lesions, and the flora imbalance is an important factor in the development of cervical cancer.IMPACT STATEMENTWhat is already known on this subject? Cervical cancer is one of the most common gynecological malignancies worldwide and has become a prominent public health problem.What the results of this study add? Our study showed that the type of vaginal community status of Hakka women in Meizhou area was characterised by L. Iners predominates, and the gradual loss of Lactobacillus dominance in vaginal bacteria is key to microecological imbalance.What the implications are of these findings for clinical practice and/or further research? Disturbances in vaginal microecology can stimulate energy metabolism and lipid metabolism to induce cervical cancer development.


Dietary Echinacea purpurea during murine pregnancy: effect on maternal hemopoiesis and fetal growth.
The medicinal benefits of Echinacea sp. plants in several disease conditions, including insect bites, respiratory ailments, and even cancer and AIDS, have been touted for decades. Echinacea sp.-based phytoceuticals are among the top selling herbals in the Western marketplace today. However, evidence is very scant concerning the effects of using Echinacea species herbals during pregnancy. While available data indicates that fetal malformations do not occur during pregnancy in humans consuming this herb, there are no formal studies aimed at assessing the possibility that consuming Echinacea herbals may promote spontaneous abortions, thereby reducing the number of live births upon which to assess the presence or absence of malformations. We undertook a study in which pregnant mice were fed daily Echinacea purpurea from pregnancy onset until gestational days 10, 11, 12, 13, and 14. Maternal spleen and bone marrow were taken for enumeration of cells in each of five separate hemopoietic lineages/organ, and fetal status was recorded. The data indicate that the significant, pregnancy-induced elevation in splenic lymphocytes and nucleated erythroid cells was all but eliminated in those females which consumed E. purpurea daily throughout their pregnancy. Moreover, consuming E. purpurea during pregnancy reduced the number of viable fetuses. The data may be extrapolated to suggest that in humans, abstention from consuming Echinacea products during the early/mid stages of pregnancy, may be prudent.


Diagnosis and characterization of fetal sacrococcygeal teratoma with prenatal MRI.
The purpose of this study was to determine whether prenatal MRI provides additional information about fetal sacrococcygeal teratoma compared with prenatal sonography. Twenty-two pregnant women with fetal sacrococcygeal teratoma underwent prenatal MRI (mean gestational age, 23 weeks). The size, location, mass characteristics, and compressive effects of the tumors were determined and correlated with sonography and postnatal findings. Based on the MRI findings, the following American Academy of Pediatrics, Surgical Section classifications were assigned: type I in six patients, type II in 12, and type III in four. No type IV tumors were found. The sacrococcygeal teratoma appeared entirely cystic in five fetuses, microcystic in one, mixed cystic and solid in 12, and solid in four. The diagnosis of sacrococcygeal teratoma was accurate in all cases assessed at our center using both MRI and sonography. Two additional patients initially referred with the diagnosis of sacrococcygeal teratoma had a different diagnosis at reevaluation at our institution (healthy, n = 1; myelomeningocele, n = 1). MRI was superior to sonography for detecting displacement of the colon (n = 11), urinary tract dilatation (n = 9), hip dislocation (n = 4), intraspinal extension (n = 2), and vaginal dilation (n = 1). In fetuses with sacrococcygeal teratoma types II and III, MRI better showed the cephalic extent of the tumor compared with sonography. MRI findings were confirmed at surgery or autopsy in all patients. Three fetuses with high output cardiac physiology underwent open fetal resection of the tumor at 21-, 24-, and 26-weeks' gestational age with two surviving. Our results show that ultrafast fetal MRI is a useful adjunct to the prenatal evaluation of fetal sacrococcygeal teratoma. Compared with sonography, MRI more accurately characterized the intrapelvic and abdominal extent of the tumors and provided more information on compression of adjacent organs. The additional anatomic resolution provided by MRI resulted in more accurate prenatal counseling and improved preoperative planning for surgical resection.


[Neurotoxic workshop materials: II. Organic substances--a review of the years 1970 to 1982].
This paper summarizes the knowledge and recent research of some organic neurotoxic substances at the workplace concerning peripheral nervous system. The review covers the substances: acrylamide, n-hexane, methyl-n-butylketone, n-pentane, n-heptane, carbondisulfide, styrene, toluene, trichloroethylene, tri-ortho-cresylphosphate and other organophosphorus compounds, polyhalogenated and complex organic compounds and solvent-mixtures. First the chemical and physical properties, the toxicokinetic and biotransformation as well as possibilities of exposure at the workplace are given. Following the characteristics after acute and chronic intoxications. The effects to the peripheral nervous systems due to short- and longtime exposure of the substance are described. Field studies in exposed workers and neurophysiological investigations with evaluation of dose-effect-relationships are reviewed especially. Each section is discussed and evaluated in respect to occupational medicine.


Degradation of Total Petroleum Hydrocarbon (TPH) in Contaminated Soil Using Bacillus pumilus MVSV3.
A study on bioremediation of soil contaminated with petroleum sludge was performed using Bacillus pumilus/MVSV3 (Accession number JN089707). In this study, 5 kg of agricultural soil was mixed well with 5% oil sludge and fertilizers containing nitrogen, phosphorus and potassium (N:P:K). The treatment resulted in 97% removal of total petroleum hydrocarbon (TPH) in 122 d in bacteria mixed contaminated soil when compared to 12% removal of TPH in uninoculated contaminated soil. The population of the microorganism remained stable after introduced into the oil environment. The physical and chemical parameters of the soil mixed with sludge showed variation indicating improvement and the pH level decreased during the experiment period. Elemental analysis and Gas Chromatography-Mass Spectroscopy (GC-MS) analysis revealed the bacterial ability to degrade oil sludge components. Growth experiments with Trigonellafoenumgraecum (Fenugreek) showed the applicability of bioremediated soil for the production.


Improvement of saccadic functions after dosing with methadone in opioid addicted individuals.
In the current experiment, we used the saccadometric test to study the effect of a single therapeutic dose of methadone on the integrity of cortico-subcortical brain functioning. In this prospective study, we used the Saccadometer System (Advanced Clinical Instrumentation, Cambridge, UK). The saccadometric test was performed before and 1.5 hours after methadone dosing. We analyzed the following saccadic parameters: latency, duration, amplitude, average and peak velocity, and processing performance (promptness) as well as a number of different types of saccades (like correct/incorrect, under/overshoot, and left-sided/right-sided). The sample consists of 40 subjects with an average 18 years of opioid addiction. The mean age is 35.3 ± 7 (80% males and 20% females). The mean period of heroin dependence is 15.3 ± 6.3 years. The mean daily dose of methadone in substitution therapy is 90 ± 26.5 mg. After administration of a single therapeutic dose of methadone, there were statistically significant differences in the values of saccade duration and latency when compared to the values before the drug administration. Average duration of saccade was significantly longer [51.40 ± 8.75 ms versus 48.93 ± 6.91 ms, z = 2.53, p = .01] and average latency was significantly longer [198.85 ± 52.57 ms versus 183.05 ± 30.95 ms, z = 2.09 p < .03]. This is the first study to test the therapeutic effect of daily methadone dosing on the integrity of the cortico-subcortical brain functions as measured by the saccadometry. More research is needed to explore the effect of illicit opioid use on the integrity of brain structures and functions, and the protective effect of opioid agonist therapy on reversing the damaging effects of illicit opioid use.


Epidermal CD147 expression plays a key role in IL-22-induced psoriatic dermatitis.
Psoriasis is a chronic inflammatory skin disease characterized by abnormal keratinocyte proliferation and terminal differentiation. Interleukin-22 (IL-22) and the transcription factor Stat3 play pivotal roles in the pathogenesis of psoriasis. CD147 is a transmembrane glycosylation protein that belongs to the immunoglobulin superfamily. Our previous studies have shown that CD147 is a marker of high keratinocyte proliferation and poor keratinocyte differentiation as well as a psoriasis susceptibility gene. The current study demonstrates that CD147 is highly expressed in psoriatic skin lesions. Specific CD147 over-expression in the epidermis of K5-promoter transgenic mice promotes imiquimod (IMQ)-induced psoriasis-like inflammation characterized by acanthosis, granular layer loss and inflammatory cell infiltration. We also found that IL-22 increases CD147 transcription in vitro and in vivo and that Stat3 binds directly to the CD147 promoter between positions -854 and -440, suggesting that CD147 expression is up-regulated in patients with psoriasis through Stat3 activation. In addition, CD147 knockdown dramatically blocks IL-22-mediated Stat3 activation as well as IL-22-induced cytokine, chemokine and antimicrobial factor expression. Together, these findings show that CD147 is a novel and key mediator of IL-22-induced psoriatic alterations in the epidermis and might be a therapeutic target in patients with psoriasis.


[Cell types of respiratory epithelium: morphology, molecular biology and clinical significance].
The epithelium of the human lower airways is composed of several different cell types. In the proximal parts of the lower airways, the basal cell, the goblet cell, and the ciliated cell are the principal cell types. In the distal airways, the Clara cell and the ciliated cell are present. Serous and mucous cells are the secretory cell types of the glands which are found in the wall of the large airways. In the last few years, several cell- and molecular-biological characteristics of these cell types have been investigated and their importance to physiological and pathological processes has been clarified. The products of secretory cell types are essential for the mucociliary clearance and thus play an important part in defense. In many diseases, such as asthma or cystic fibrosis, the structure and function of these cells are altered in a characteristic way. Another defence mechanism is represented by the ciliated cells. Their function can be impaired by inborn or acquired diseases. Knowledge about cell differentiation and cell proliferation is important to understand both the physiological regeneration as well as pathological conditions, such as wound repair or neoplasms. Further, the development of gene-therapeutical approaches depends on the investigation of the molecular biology of the airway cells. It is the aim of this article to describe the morphology of the relevant cell types and molecular biological aspects of their function.


Novel drugs in pediatric gliomas.
Astrocytomas (gliomas) are the most common primary brain tumors among adults and second most frequent neoplasm among children. New ideas and novel approaches are being explored world over with aim to devise better management strategeies for this deadly pathological state. We searched the electronic database PubMed for pre-clinical as well as clinical controlled trials reporting importance of various therapeutic drugs against gliomas. It was observed clearly that this approach of using therapeutic drugs is clearly evolving and has been observed to be promising future therapeutic avenue against gliomas. The searched literature on whole revealed that although gliomas are treated aggressively with surgery, chemotherapy and radiation, treatment resistance, drug toxicity and poor response rates among pediatric glioma patients, continue to drive the need to discover new and more effective chemotherapeutic agents. The present review is focused on the latest updates in therapeutic drugs against gliomas in pediatric patients. The important chemo-therapeutics discussed in this review included alkylating agents like temoxolomide, derivatives of platinum, nitrosoureas, topoisomerases, angiogenesis inhibitors and cytomegalovirus as therapeutic agents.


Molecular basis for the selective interaction of synthetic agonists with the human histamine H1-receptor compared with the guinea pig H1-receptor.
Previous studies revealed that phenylhistamines and histaprodifens possess higher potency and affinity at guinea pig histamine H(1)-receptor (gpH(1)R) than at human histamine H(1)-receptor (hH(1)R). However, we recently identified an imidazolylpropylguanidine [N(1)-(3-cyclohexylbutanoyl)-N(2)-[3-(1H-imidazol-4-yl)-propyl]guanidine (UR-AK57)] with higher potency and efficacy at hH(1)R compared with gpH(1)R. The aim of this study was to reveal the molecular basis for the species differences of synthetic ligands. We studied 11 novel phenylhistamines and phenoprodifens. H(1)R species isoforms were expressed in Sf9 insect cells, and [(3)H]mepyramine competition binding and GTPase assays were performed. We identified bulky phenylhistamines with higher potency and affinity at hH(1)R compared with gpH(1)R. Molecular dynamics simulations of ligand-H(1)R interactions revealed four potential binding modes for phenylhistamines possessing an additional histamine moiety; the terminal histamine moiety showed a high flexibility in the binding pocket. There are striking similarities in ligand properties in bulky phenylhistamines and UR-AK57. Comparison of bulky phenylhistamine binding mode with binding mode of UR-AK57 suggests that only one of these four binding modes should be established. The higher potency is explained by more effective van der Waals interaction of the compounds with Asn(2.61) (hH(1)R) relative to Ser(2.61) (gpH(1)R). In addition, two stable binding modes for phenoprodifens with different orientations in the binding-pocket were identified. Depending on phenoprodifen orientation, the highly conserved Trp(6.48), part of the toggle switch involved in receptor activation, was found in an inactive or active conformation, respectively. We identified the first phenylhistamines with higher potency at hH(1)R than at gpH(1)R and obtained insight into the binding mode of bulky phenylhistamines and imidazolylpropylguanidines.


Animals models of spinal cord contusion injury.
Spinal cord contusion injury is one of the most serious nervous system disorders, characterized by high morbidity and disability. To mimic spinal cord contusion in humans, various animal models of spinal contusion injury have been developed. These models have been developed in rats, mice, and monkeys. However, most of these models are developed using rats. Two types of animal models, i.e. bilateral contusion injury and unilateral contusion injury models, are developed using either a weight drop method or impactor method. In the weight drop method, a specific weight or a rod, having a specific weight and diameter, is dropped from a specific height on to the exposed spinal cord. Low intensity injury is produced by dropping a 5 g weight from a height of 8 cm, moderate injury by dropping 10 g weight from a height of 12.5-25 mm, and high intensity injury by dropping a 25 g weight from a height of 50 mm. In the impactor method, injury is produced through an impactor by delivering a specific force to the exposed spinal cord area. Mild injury is produced by delivering 100 ± 5 kdyn of force, moderate injury by delivering 200 ± 10 kdyn of force, and severe injury by delivering 300 ± 10 kdyn of force. The contusion injury produces a significant development of locomotor dysfunction, which is generally evident from the 0-14th day of surgery and is at its peak after the 28-56th day. The present review discusses different animal models of spinal contusion injury.


Day-to-day care: the interplay of CNAs' views of residents & nursing home environments.
This qualitative study identified certified nursing assistants' (CNAs') perspectives of nursing home residents and how these perspectives translate into care practices. Data included observations of and interviews with 27 CNAs in three dissimilar nursing homes. All participants were people of color, and all but 3 were immigrants. CNAs constructed three views of residents: as fictive kin, as a commodity, and as an autonomous person. Although individual CNAs held one primary view of residents in general, select residents were viewed from an alternative perspective, resulting in variations in care practices. These findings suggest that such distinctions, in tandem with structural, organizational, and cultural differences in nursing homes, present opportunities for nursing leadership to affect the visible, everyday practice of nursing CNAs. To target interventions, further research is needed on how CNAs come to differentially view residents and how these differences influence CNAs' care relationships with residents.


Dissociation of local and global skeletal muscle oxygen transport metrics in type 2 diabetes.
Exercise capacity is impaired in type 2 diabetes, and this impairment predicts excess morbidity and mortality. This defect appears to involve excess skeletal muscle deoxygenation, but the underlying mechanisms remain unclear. We hypothesized that reduced blood flow, reduced local recruitment of blood volume/hematocrit, or both contribute to excess skeletal muscle deoxygenation in type 2 diabetes. In patients with (n=23) and without (n=18) type 2 diabetes, we recorded maximal reactive hyperemic leg blood flow, peak oxygen utilization during cycling ergometer exercise (VO2peak), and near-infrared spectroscopy-derived measures of exercise-induced changes in skeletal muscle oxygenation and blood volume/hematocrit. We observed a significant increase (p<0.05) in skeletal muscle deoxygenation in type 2 diabetes despite similar blood flow and recruitment of local blood volume/hematocrit. Within the control group skeletal muscle deoxygenation, local recruitment of microvascular blood volume/hematocrit, blood flow, and VO2peak are all mutually correlated. None of these correlations were preserved in type 2 diabetes. These results suggest that in type 2 diabetes 1) skeletal muscle oxygenation is impaired, 2) this impairment may occur independently of bulk blood flow or local recruitment of blood volume/hematocrit, and 3) local and global metrics of oxygen transport are dissociated.


Effectiveness, Good Tolerability, and High Compliance of Doses of Risperidone Long-Acting Injectable Higher Than 75 mg in People With Severe Schizophrenia: A 3-Year Follow-Up.
Tolerability and effectiveness of antipsychotics are important to increase treatment compliance in people with schizophrenia. The aim of this study was to evaluate effectiveness, tolerability, and adherence to treatment with high doses of risperidone long-acting injectable (RLAI) in patients with severe schizophrenia.It is a 3-year prospective, observational study of patients with severe (Clinical Global Impression Severity scale [CGI-S] score of ≥5) schizophrenia according to International Classification of Diseases (ICD-10) criteria. Subjects were the consecutive 60 who first underwent treatment with RLAI with doses of 75 mg or higher every 14 days to get clinical stabilization.Assessment included the following: CGI-S, World Health Organization Disability Assessment Schedule, Camberwell Assessment of Need (CAN), Medication Adherence Rating Scale, laboratory tests, weight, and hospital admissions.The mean (SD) dose of RLAI was 111.2 (9.1) mg per 14 days. Tolerability was good and there were almost no interruptions due to adverse effects or to relevant biological parameters alterations. Also, weight gain was not significant.Retention rate in treatment after 3 years was 95%. Clinical Global Impression Severity (P < 0.01) and Camberwell Assessment of Need (P < 0.01) decreased and also Disability Assessment Schedule in the 4 areas (P < 0.01). Medication Adherence Rating Scale score increased from 3.6 (0.7) to 8.9 (0.9) (P < 0.001). There were significantly few hospital admissions than during the previous 36 months (1.9 [1.3] vs 0.31 [0.2], P < 0.001).As a conclusion, we highlight that the effectiveness and tolerability of 75 mg or higher every 14 days of RLAI were high, being useful in improving treatment adherence in patients with severe schizophrenia, getting good clinical and functional outcomes.


Transdermal clonidine: therapeutic considerations.
Transdermal clonidine was approved by the US Food and Drug Administration in 1984 for the treatment of mild-to-moderate hypertension alone or in combination with a diuretic. Clonidine is released from the patch at a constant rate and thus displays a pharmacokinetic pattern not dissimilar to that of infusion therapy. Transdermal clonidine, like oral clonidine, is effective first- or second-line therapy for most forms of hypertension. More recently, transdermal clonidine has found alternative uses in the areas of smoking cessation, posttraumatic stress disorder, menopausal hot flashes, and alcohol and opiate withdrawal syndromes. The not infrequent development of a dermatitis, together with a substantially greater cost than oral clonidine, have been the major undoings for transdermal clonidine.


Enhanced control of Mycobacterium tuberculosis extrapulmonary dissemination in mice by an arabinomannan-protein conjugate vaccine.
Currently there are a dozen or so of new vaccine candidates in clinical trials for prevention of tuberculosis (TB) and each formulation attempts to elicit protection by enhancement of cell-mediated immunity (CMI). In contrast, most approved vaccines against other bacterial pathogens are believed to mediate protection by eliciting antibody responses. However, it has been difficult to apply this formula to TB because of the difficulty in reliably eliciting protective antibodies. Here, we developed capsular polysaccharide conjugates by linking mycobacterial capsular arabinomannan (AM) to either Mtb Ag85b or B. anthracis protective antigen (PA). Further, we studied their immunogenicity by ELISA and AM glycan microarrays and protection efficacy in mice. Immunization with either Abg85b-AM or PA-AM conjugates elicited an AM-specific antibody response in mice. AM binding antibodies stimulated transcriptional changes in Mtb. Sera from AM conjugate immunized mice reacted against a broad spectrum of AM structural variants and specifically recognized arabinan fragments. Conjugate vaccine immunized mice infected with Mtb had lower bacterial numbers in lungs and spleen, and lived longer than control mice. These findings provide additional evidence that humoral immunity can contribute to protection against Mtb.


New ventilated isolation cage.
A multifunction lid has been developed for a commercially available transparent animal cage which permits feeding, watering, viewing, long-term holding, and local transport of laboratory rodents on experiment while isolating the surrounding environment. The cage is airtight except for its inlet and exhaust high-efficiency particulate air filters, and it is completely steam-sterilizable. Opening of the cage's feed and water ports causes an inrush of high velocity air which prevents back-migration of aerosols and permits feeding and watering while eliminating need for chemical vapor decontamination. Ventilation system design permits the holding in adjacent cages of animals infected with different organisms without danger of cross-contamination; leaves the animal room odor-free; reduces required bedding changes to twice a month or less, and provides investigators with capability to control precisely individual cage ventilation rates. Forty-eight cages can be conveniently placed on a standard NIH "shoebox" cage rack (60 inches wide x 28 inches deep x 74 inches high) fitted with a simple manifold exhaust system. The entire system is mobile, requiring only an electrical power outlet. Principal application of the caging system is in the area of preventing exposure of animal caretakers to pathogenic substances associated with the animal host, and in reducing handling of animals and their exposure to extraneous contamination.


Focusing on transitions of care: A change is here.
Transitions of care have emerged as an important point of vulnerability in the health care system where medical errors and clinical deterioration can occur. Most research in the area has focused on non-neurologically ill patients in the postdischarge transition from the inpatient to outpatient clinical environment in part due to the emergence of hospital readmissions reduction programs. A multidisciplinary strategy that addresses several common opportunities for improvement can mitigate the risk to patients during these periods and can serve as an opportunity for neurologists to take the lead in developing systems-based solutions that can ultimately enhance the quality of care for our patients.


Role of visceral pleural invasion and tumor sizing at CT of resected NSCLC in clinical-radiological and pathological T agreement.
To describe in non-small cell lung cancer (NSCLC) the impact of visceral pleural invasion (VPI) and of tumor sizing assessed at computed tomography (CT) on the agreement between clinical-radiological and pathological T staging and its prognostic value. Patients affected by NSCLC treated by surgery in the period from January 2017 to September 2020 were retrospectively evaluated. Exclusion criteria were: (1) baseline CT not performed in our hospital; (2) failure of software segmentation at CT of the primary lesion. Clinical-radiological T (cT) was assessed at baseline CT, evaluating in particular T size by semi-automatic tool and VPI (cVPI) visually. Pathological T (pT) and VPI (pVPI) were recorded by pathological report and obtained after formalin-fixation and eventual elastic stain on surgical specimen. The agreement between cT and pT was evaluated by calculating the weighted kappa by Cohen (κw); the association between progression free survival (PFS) with both cT and pT was assessed by the Cox regression analysis. The study included 84 NSCLC in 82 patients (median age 71 years, IQR 63-76 years; females 22/82, 27%). The agreement between cT and pT was poor (κw 0.302, 95%CI 0.158-0.447). The main causes of disagreement were CT oversizing (21%) and false positive cVPI (29%). A significant association was found between PFS and pT2-T3 (HR 2.75, 95%CI 1.21-6.25, p=0.015) but not with cT2-T3 (not retained in the model). False positive cVPI and oversizing at CT are causes of disagreement between cT and pT in around one-third of resected NSCLC. PFS was significantly associated with pT but not with cT.


In vitro and in vivo Evaluation of New Topical Anaesthetic Cream Formulated with Palm Oil Base.
Topical local anaesthetic cream was reported to be useful for pain relief for cutaneous procedures such as minor surgery and venipuncture. The aim of this study was to evaluate the effectiveness of new formulation of lidocaine topical anaesthetic using palm oil base, HAMIN® and to determine how fast this new formulation produces adequate numbness compared to the currently used EMLA cream, in the University of Malaya Medical Centre (UMMC) set-up. The skin permeation test was conducted by using Franz type diffusion cell and pain assessment was carried out in healthy subject by using Verbal Rating Score (VRS) and Visual Analogue Score (VAS) evaluation. Result of permeation test demonstrated that the cumulative amount of lidocaine released from HAMIN® cream was increased with time and slightly higher than EMLA cream. The clinical study showed that HAMIN® single lidocaine cream can produces numbness through venepuncture procedure and comparable with EMLA cream which is a combination therapy for local anaesthetic (lidocaine and prilocaine). It can be concluded that HAMIN® Lidocaine cream is suitable for cream preparation especially for topical application and it can be regarded as an achievement in palm oil and medical industries.