A molecular toolbox to study progesterone receptor signaling.
Progesterone receptor (PR) signaling is required for mammary gland development and homeostasis. A major bottleneck in studying PR signaling is the lack of sensitive assays to measure and visualize PR pathway activity both quantitatively and spatially. Here, we develop new tools to study PR signaling in human breast epithelial cells. First, we generate optimized Progesterone Responsive Element (PRE)-luciferase constructs and demonstrate that these new reporters are a powerful tool to quantify PR signaling activity across a wide range of progesterone concentrations in two luminal breast cancer cell lines, MCF7 and T47D. We also describe a fluorescent lentiviral PRE-GFP reporter as a novel tool to visualize PR signaling at the single-cell level. Our reporter constructs are sensitive to physiological levels of progesterone. Second, we show that low background signaling, and high levels of PR expression are a prerequisite for robustly measuring PR signaling. Increasing PR expression by transient transfection, stable overexpression in MCF7 or clonal selection in T47D, drastically improves both the dynamic range of luciferase reporter assays, and the induction of endogenous PR target genes as measured by qRT-PCR. We find that the PR signaling response differs per cell line, target gene and hormone concentration used. Taken together, our tools allow a more rationally designed approach for measuring PR signaling in breast epithelial cells.


Incidence of Diabetes Mellitus in Insured Swedish Cats in Relation to Age, Breed and Sex.
Diabetes mellitus (DM) is a common endocrinopathy in cats. Most affected cats suffer from a type of diabetes similar to type 2 diabetes in humans. An increasing prevalence has been described in cats, as in humans, related to obesity and other lifestyle factors. To describe the incidence of DM in insured Swedish cats and the association of DM with demographic risk factors, such as age, breed and sex. A cohort of 504,688 individual cats accounting for 1,229,699 cat-years at risk (CYAR) insured by a Swedish insurance company from 2009 to 2013. We used reimbursed insurance claims for the diagnosis of DM. Overall incidence rates and incidence rates stratified on year, age, breed, and sex were estimated. The overall incidence rate of DM in the cohort was 11.6 cases (95% confidence interval [CI], 11.0-12.2) per 10,000 CYAR. Male cats had twice as high incidence rate (15.4; 95% CI, 14.4-16.4) as females (7.6; 95% CI, 6.9-8.3). Domestic cats were at higher risk compared to purebred cats. A significant association with breed was seen, with the Burmese, Russian Blue, Norwegian Forest cat, and Abyssinian breeds at a higher risk compared to other cats. No sex predisposition was found among Burmese cats. Several breeds with a lower risk of DM were identified. Our results verify that the Burmese breed is at increased risk of developing DM. We also identified several previously unreported breeds with increased or decreased risk of DM.


Short communication: molecular epidemiology of HIV type 1 infection in Kazakhstan: CRF02_AG prevalence is increasing in the southeastern provinces.
To analyze HIV-1 genetic variants in Kazakhstan, HIV-1 sequences were obtained from 205 antiretroviral-treated (ART) and naive patients in 2009-2013. Samples were collected in the most populous cities and provinces of Kazakhstan. On the basis of phylogenetic analyses of partial pol sequences, subtype A variant intravenous drug user (IDU)-A (which is dominant in the former Soviet Union) was found in 60.0% of the individuals, followed by CRF02_AG (34.6%); the rest of the samples were subtype B, CRF03_AB, CRF63_02A1, and CRF07_BC. The proportion of CRF02_AG has increased significantly since 2001-2003, when it was less than 5%. The majority of the CRF02_AG cases were found in Almaty, the former capital and the most populous city in Kazakhstan. The IDU-A variant dominated in the industrial regions of northern and central Kazakhstan and some other regions. Both dominant HIV-1 genetic variants were almost equally represented in the two main transmission groups: IDUs and heterosexuals. The analysis of drug-resistant mutations found a low prevalence of drug resistance in 165 therapy-naive individuals (3.0%). Thus, in the beginning of the second decade of the 2000s, the HIV epidemic in Kazakhstan is driven by two main genetic variants: IDU-A and CRF02_AG.


Recommendations for lung cancer screening in Southern Africa.
Lung cancer remains the leading cause of cancer-related deaths in southern Africa. Early trials of chest radiograph-based screening in males at high risk for lung cancer found no mortality benefit of a radiograph alone, or a radiograph plus sputum cytology screening strategy. Large prospective studies, including the National Lung Screening Trial, have shown an all-cause mortality benefit when low-dose computed tomography (LDCT) was used as a screening modality in patients that are at high risk of developing lung cancer. The South African Thoracic Society, based on these findings, and those from several international guidelines, recommend that annual LDCT should be offered to patients between 55-74 years of age who are current or former smokers (having quit within the preceding 15 years), with at least a 30-pack year smoking history and with no history of lung cancer. Patients should be in general good health, fit for surgery, and willing to undergo further investigations if deemed necessary. Given the high local prevalence of tuberculosis (TB) infection and post-TB lung disease, which can radiographically mimic lung cancer, a conservative threshold (nodule size ≥6 mm) should be used to determine whether the baseline LDCT screen is positive (thus nodules <6 mm require no action until the next annual screen). If a non-calcified, solid or partly solid nodule is ≥6 mm, but <10 mm with no malignant features (e.g., distinct spiculated margins), the LDCT should be repeated in 6 months. If a solid nodule or the largest component of a non-solid nodule is ≥10 or ≥6 mm and enlarging or with additional malignant features present, definitive action to exclude lung cancer is warranted. Patients should be screened annually until 15 years have elapsed from date of smoking cessation, they turn 80, become unfit for a curative operation or significant changes are observed.


Immunological properties of the cell envelope components of Vibrio cholerae.
Several immunobiological properties of cell envelope components of Vibrio cholerae such as mitogenicity, antigenicity, adjuvanticity and toxicity were tested in mice. Killed whole bacteria, spheroplasts, lipopolysaccharide and outer membrane proteins possessed mitogenic activity as determined by [3H]thymidine uptake in spleen cell cultures. All these components predominantly stimulated murine bone-marrow derived (B) lymphocytes. The mitogenicity induced by V. cholerae lipopolysaccharide was similar in magnitude to that observed with Salmonella typhimurium lipopolysaccharide. Vibrio cholerae lipopolysaccharide was mitogenic for gut-associated lymphocytes such as those obtained from Peyer's patches and small intestine. Antibody formation at the cellular level was detected by the haemolytic plaque assay. Plaque-forming cells to V. cholerae lipopolysaccharide were only detected when mice were immunized intraperitoneally with intact cells or with spheroplasts. Among the various cell envelope components, lipopolysaccharide alone possessed adjuvant properties as it increased the number of plaque-forming cells to sheep erythrocytes fourfold in mouse spleens. Also, lipopolysaccharide was the only component found to be toxic for the mouse (LD50 0 . 5 mg). Neither spheroplasts nor outer membrane of V. cholerae showed adjuvanticity or toxicity in mice.


Circular RNAs: New layer of complexity evading breast cancer heterogeneity.
Advances in high-throughput sequencing techniques and bioinformatic analysis have refuted the "junk" RNA hypothesis that was claimed against non-coding RNAs (ncRNAs). Circular RNAs (circRNAs); a class of single-stranded covalently closed loop RNA molecules have recently emerged as stable epigenetic regulators. Although the exact regulatory role of circRNAs is still to be clarified, it has been proven that circRNAs could exert their functions by interacting with other ncRNAs or proteins in their own physiologically authentic environment, regulating multiple cellular signaling pathways and other classes of ncRNAs. CircRNAs have also been reported to exhibit a tissue-specific expression and have been associated with the malignant transformation process of several hematological and solid malignancies. Along this line of reasoning, this review aims to highlight the importance of circRNAs in Breast Cancer (BC), which is ranked as the most prevalent malignancy among females. Notwithstanding the substantial efforts to develop a suitable anticancer therapeutic regimen against the heterogenous BC, inter- and intra-tumoral heterogeneity have resulted in an arduous challenge for drug development research, which in turn necessitates the investigation of other markers to be therapeutically targeted. Herein, the potential of circRNAs as possible diagnostic and prognostic biomarkers have been highlighted together with their possible application as novel therapeutic targets.


Circulating Interleukin-6 Is Associated with Skeletal Muscle Strength, Quality, and Functional Adaptation with Exercise Training in Mobility-Limited Older Adults.
Human aging is characterized by a chronic, low-grade inflammation suspected to contribute to reductions in skeletal muscle size, strength, and function. Inflammatory cytokines, such as interleukin-6 (IL-6), may play a role in the reduced skeletal muscle adaptive response seen in older individuals. To investigate relationships between circulating IL-6, skeletal muscle health and exercise adaptation in mobility-limited older adults. Randomized controlled trial. Exercise laboratory on the Health Sciences campus of an urban university. 99 mobility-limited (Short Physical Performance Battery (SPPB) ≤9) older adults. 6-month structured physical activity with or without a protein and vitamin D nutritional supplement. Circulating IL-6, skeletal muscle size, composition (percent normal density muscle tissue), strength, power, and specific force (strength/CSA) as well as physical function (gait speed, stair climb time, SPPB-score) were measured pre- and post-intervention. At baseline, Spearman's correlations demonstrated an inverse relationship (P<0.05) between circulating IL-6 and thigh muscle composition (r = -0.201), strength (r = -0.311), power (r = -0.210), and specific force (r = -0.248), and positive association between IL-6 and stair climb time (r = 0.256; P<0.05). Although the training program did not affect circulating IL-6 levels (P=0.69), reductions in IL-6 were associated with gait speed improvements (r = -0.487; P<0.05) in "higher" IL-6 individuals (>1.36 pg/ml). Moreover, baseline IL-6 was inversely associated (P<0.05) with gains in appendicular lean mass and improvements in SPPB score (r = -0.211 and -0.237, respectively). These findings implicate age-related increases in circulating IL-6 as an important contributor to declines in skeletal muscle strength, quality, function, and training-mediated adaptation. Given the pervasive nature of inflammation among older adults, novel therapeutic strategies to reduce IL-6 as a means of preserving skeletal muscle health are enticing.


Identification of a novel mycobacterial histone H1 homologue (HupB) as an antigenic target of pANCA monoclonal antibody and serum immunoglobulin A from patients with Crohn's disease.
pANCA is a marker antibody associated with inflammatory bowel disease (IBD), including most patients with ulcerative colitis and a subset with Crohn's disease. This study addressed the hypothesis that pANCA reacts with an antigen(s) of microbial agents potentially relevant to IBD pathogenesis. Using a pANCA monoclonal antibody, we have previously identified the C-terminal basic random-coil domain of histone H1 as a pANCA autoantigen. BLAST analysis of the peptide databases revealed H1 epitope homologues in open reading frames of the Mycobacterium tuberculosis genome. Western analysis of extracts from six mycobacterial species directly demonstrated reactivity to a single, conserved approximately 32-kDa protein. Direct protein sequencing, followed by gene cloning, revealed a novel 214-amino-acid protein, an iron-regulated protein recently termed HupB. Sequence analysis demonstrated its homology with the mammalian histone H1 gene family, and recombinant protein expression confirmed its reactivity with the 5-3 pANCA monoclonal antibody. Binding activity of patient serum immunoglobulin G (IgG) to HupB did not correlate with reactivity to histone H1 or pANCA, indicating the complex character of the pANCA antigen. However, anti-HupB IgA was strongly associated with Crohn's disease (P < 0.001). These findings indicate that the 5-3 pANCA monoclonal antibody detects a structural domain recurrent among mycobacteria and cross-reactive with a DNA-binding domain of histone H1. The association of HupB-binding serum IgA with IBD provides new evidence for the association of a mycobacterial species with Crohn's disease.


Strategy for obtaining solid fusion at L5-S1 in adult spinal deformity: risk factor analysis for nonunion at L5-S1.
Maintaining lumbosacral (LS) arthrodesis and global sagittal balance after long fusion to the sacrum remains an important issue in the surgical treatment for adult spinal deformity (ASD). The importance and usefulness of LS fixation have been documented, but the optimal surgical long fusion to the sacrum remains a matter for debate. Therefore, the authors performed a retrospective study to evaluate fusion on CT scans and the risk factors for LS pseudarthrosis (nonunion) after long fusion to the sacrum in ASD. The authors performed a retrospective study of 59 patients with lumbar degenerative kyphosis (mean age 69.6 years) who underwent surgical correction, including an interbody fusion of the L5-S1, with a minimum 2-year follow-up. Achievement of LS fusion was evaluated by analyzing 3D-CT scans at 3 months, 6 months, 9 months, 1 year, and 2 years after surgery. Patients were classified into a union group (n = 36) and nonunion group (n = 23). Risk factors for nonunion were analyzed, including patient and surgical factors. The overall fusion rate was 61% (36/59). Regarding radiological factors, optimal sagittal balance at the final follow-up significantly differed between two groups. There were no significant differences in terms of patient factors, and no significant differences with respect to the use of pedicle subtraction osteotomy, the number of fused segments, the proportion of anterior versus posterior interbody fusion, S2 alar iliac fixation versus conventional iliac fixation, or loosening of sacral or iliac screws. However, the proportion of metal cages to polyetheretherketone cages and the proportion of sacropelvic fixation were significantly higher in the union group (p = 0.022 and p < 0.05, respectively). LS junction fusion is crucial for global sagittal balance, and the use of iliac screws in addition to LS interbody fusion using a metal cage improves the outcomes of long fusion surgery for ASD patients.


Sepsis associated acute kidney injury.
Sepsis is defined as organ dysfunction resulting from the host's deleterious response to infection. One of the most common organs affected is the kidneys, resulting in sepsis associated acute kidney injury (SA-AKI) that contributes to the morbidity and mortality of sepsis. A growing body of knowledge has illuminated the clinical risk factors, pathobiology, response to treatment, and elements of renal recovery that have advanced our ability to prevent, detect, and treat SA-AKI. Despite these advances, SA-AKI remains an important concern and clinical burden, and further study is needed to reduce the acute and chronic consequences. This review summarizes the relevant evidence, with a focus on the risk factors, early recognition and diagnosis, treatment, and long term consequences of SA-AKI. In addition to literature pertaining to SA-AKI specifically, pertinent sepsis and acute kidney injury literature relevant to SA-AKI was included.


Adjunctive zonisamide for weight loss in euthymic bipolar disorder patients: a pilot study.
To assess the effectiveness and tolerability of open adjunctive zonisamide in treatment of obesity in euthymic bipolar disorder (BD) patients. Zonisamide was administered to recovered, overweight BD outpatients assessed with the Systematic Treatment Enhancement Program for Bipolar Disorders (STEP-BD) Affective Disorders Evaluation and followed with the STEP-BD Clinical Monitoring Form. Weight changes (Body Mass Index (BMI) and BMI percentage changes) were assessed prospectively at four weekly visits, one bi-weekly visit, and then five monthly visits, for a maximal duration of six months. Weight loss was assessed with random effects modeling to maximize all available data for analysis. Twenty-five BD (10 BD-type I, 15 BD-type II) patients (mean age 41.0+/-10.4 years, 64% female, 96% Caucasian) on a mean of 2.8+/-1.5 prescription psychotropic and 1.3+/-1.4 prescription non-psychotropic medications received zonisamide for a mean duration of 14.2+/-8.5 weeks, with a mean final dose of 375+/-206 (range 75-800) mg/day. Slope of weight loss was 0.078 BMI points per week, and non-zero (p<0.0005). Mean weight loss was 1.2+/-1.9 BMI points (baseline BMI 34.2+/-3.1 to final BMI 33.0+/-3.5, p<0.003). Eighteen patients (72%) discontinued study participation early, 11/25 (44%) due to emergent mood symptoms (eight depression, two mania, one subsyndromal mixed symptoms) requiring treatment intervention, 5/25 (20%) due to adverse physical events, and 2/25 (8%) due to patient choice, but none due to weight loss inefficacy. Adjunctive zonisamide appeared effective and generally physically tolerated, but had high rates of mood adverse events, in obese BD patients. Controlled trials are warranted to systematically explore these preliminary naturalistic observations.


Association between Findings in Oral Health Screening and Body Mass Index: A Nation-Wide Longitudinal Study.
Oral diseases, such as periodontitis and dental caries, can cause systemic inflammation as well as local effects, which is an important contributing factor for obesity. We aimed to investigate the change in body mass index (BMI) according to the presence of periodontitis and oral hygiene indicators. This study enrolled 110,068 participants from the national health screening cohort in Korea from 2009-2010 who underwent an oral health checkup. As oral hygiene indicators, the presence of periodontitis, dental caries, tooth loss, and tooth brushing were assessed. We constructed a linear mixed model for BMI. BMI was repeatedly measured in the health examination until 2015. In the multivariate linear mixed model for BMI, the presence of periodontitis (β = 0.0687, standard error (SE) = 0.0225, p = 0.002), dental caries (β = 0.0735, SE = 0.0152, p < 0.001), and tooth loss (β = 0.1328, SE = 0.0175, p < 0.001) were positively associated with BMI. In contrast, frequent tooth brushing (≥3 times/day) was negatively associated with BMI (β = -0.2610, SE = 0.0306, p < 0.001). The presence of periodontitis, dental caries, and tooth loss may be associated with higher BMI, whereas frequent tooth brushing may be related to lower BMI. Better oral hygiene might be associated with lower BMI. Further study is needed to determine the effect of oral health behavior and dental disease on obesity.


[Selective nutrient medium for the isolation of Bacillus cereus].
A selective dried medium for the isolation of B. cereus from clinical material and foodstuffs has been developed. The medium has high selective properties which ensure the isolation of B. cereus from microbial association in pure culture, thus making it possible to accelerate further identification of the microorganisms.


SEUSS and SEUSS-LIKE 2 coordinate auxin distribution and KNOXI activity during embryogenesis.
In Arabidopsis, SEUSS (SEU) and SEUSS-LIKE 2 (SLK2) are components of the LEUNIG (LUG) repressor complex that coordinates various aspects of post-embryonic development. The complex also plays a critical role during embryogenesis, as seu slk2 double mutants have small, narrow cotyledons and lack a shoot apical meristem (SAM). Here we show that seu slk2 double mutant embryos exhibit delayed cotyledon outgrowth and that this is associated with altered PIN-FORMED1 (PIN1) expression and localisation during the early stages of embryogenesis. These observations suggest that SEU and SLK2 promote the transition to bilateral symmetry by modulating auxin distribution in the embryonic shoot. This study also shows that loss of SAM formation in seu slk2 mutants is associated with reduced expression of the class I KNOX (KNOXI) genes SHOOTMERISTEMLESS (STM), BREVIPEDICELLUS and KNAT2. Furthermore, elevating STM expression in seu slk2 mutant embryos was sufficient to restore SAM formation but not post-embryonic activity, while both SAM formation and activity were rescued when SLK2 expression was restored in either the cotyledons or boundary regions. These results demonstrate that SEU and SLK2 function redundantly to promote embryonic shoot development and likely act through a non-cell autonomous pathway to promote KNOXI activity.


The antigen-specific CD8+ T cell repertoire in unimmunized mice includes memory phenotype cells bearing markers of homeostatic expansion.
Memory T cells exhibit superior responses to pathogens and tumors compared with their naive counterparts. Memory is typically generated via an immune response to a foreign antigen, but functional memory T cells can also be produced from naive cells by homeostatic mechanisms. Using a recently developed method, we studied CD8 T cells, which are specific for model (ovalbumin) and viral (HSV, vaccinia) antigens, in unimmunized mice and found a subpopulation bearing markers of memory cells. Based on their phenotypic markers and by their presence in germ-free mice, these preexisting memory-like CD44(hi) CD8 T cells are likely to arise via physiological homeostatic proliferation rather than a response to environmental microbes. These antigen-inexperienced memory phenotype CD8 T cells display several functions that distinguish them from their CD44(lo) counterparts, including a rapid initiation of proliferation after T cell stimulation and rapid IFN-gamma production after exposure to proinflammatory cytokines. Collectively, these data indicate that the unprimed antigen-specific CD8 T cell repertoire contains antigen-inexperienced cells that display phenotypic and functional traits of memory cells.


High Triatoma brasiliensis Densities and Trypanosoma cruzi Prevalence in Domestic and Peridomestic Habitats in the State of Rio Grande do Norte, Brazil: The Source for Chagas Disease Outbreaks?
AbstractA total of 2,431 Triatoma brasiliensis were collected from 39 populations of Paraíba (PB) and Rio Grande do Norte (RN) states, Brazil. In PB, Trypanosoma cruzi infection was not detected in either peridomestic or domestic vector populations. In contrast, in RN, T. brasiliensis was detected with high parasite prevalence in these ecotopes (30.7-40.0%). Moreover, peridomicile insect population densities were more than double the average densities of all other settings evaluated (19.17 versus < 8.94 triatomine/man-hour). Genotyped parasites evidenced a mix of T. cruzi lineages circulating in both peridomestic and sylvatic populations. Although vector control efforts have dramatically decreased Chagas disease transmission to humans, recent outbreaks have been detected in four municipalities of RN state. Our results clearly evidence a worrisome proximity between infected vectors and humans in RN. Indeed, finding of infected T. brasiliensis inside homes is routinely recorded by local vector control surveillance staff around the outbreak area, challenging the current and conventional view that vector transmissions are controlled in northeastern Brazil. This scenario calls for strengthening vector control surveillance and interventions to prevent further Chagas transmission, especially in RN State.


Oncobiology and treatment of breast cancer in young women.
Female breast cancer emerged as the leading cancer type in terms of incidence globally in 2020. Although mortality due to breast cancer has improved during the past three decades in many countries, this trend has reversed in women less than 40 years since the past decade. From the biological standpoint, there is consensus among experts regarding the clinically relevant definition of breast cancer in young women (BCYW), with an age cut-off of 40 years. The idea that breast cancer is an aging disease has apparently broken in the case of BCYW due to the young onset and an overall poor outcome of BCYW patients. In general, younger patients exhibit a worse prognosis than older pre- and postmenopausal patients due to the aggressive nature of cancer subtypes, a high percentage of cases with advanced stages at diagnosis, and a high risk of relapse and death in younger patients. Because of clinically and biologically unique features of BCYW, it is suspected to represent a distinct biologic entity. It is unclear why BCYW is more aggressive and has an inferior prognosis with factors that contribute to increased incidence. However, unique developmental features, adiposity and immune components of the mammary gland, hormonal interplay and crosstalk with growth factors, and a host of intrinsic and extrinsic risk factors and cellular regulatory interactions are considered to be the major contributing factors. In the present article, we discuss the status of BCYW oncobiology, therapeutic interventions and considerations, current limitations in fully understanding the basis and underlying cause(s) of BCYW, understudied areas of BCYW research, and postulated advances in the coming years for the field.


Academic self-efficacy in Bachelor-level nursing students: Development and validation of a new instrument.
An available strategy to counteract academic failure is the development and implementation of student academic self-efficacy; however, to date, there are no instruments measuring it. The aim of this study was to develop and psychometrically test an academic nurse self-efficacy scale. A longitudinal study design was used in accordance with Consensus-based Standards for the Selection of health status Measurement Instruments guidelines. A convenience sample of 1,129 nursing students attending the first year of the course were involved. The data collection began in 2014 and went on for 3 years. Data were collected at the beginning of the first (T0), at the end of the first (T1), at the end of the second (T2), and at the end of the third (T3) year. The academic nurse self-efficacy scale was evaluated for content and face validity, for construct validity with explorative, confirmative factor analysis and hypothesis testing and for reliability. The standard error and the smallest detectable difference were also evaluated. Scree plot analysis suggested a four-factor solution and confirmative factor analysis model reached a good fit. We verified the first hypothesis, partially the second and not the third. The dimensions show a Cronbach's α 0.72-0.83. The smallest detectable difference was 26%. The academic nurse self-efficacy scale had good validity and reliability and should be considered for nursing students. These findings may have an impact on universities, mainly in nursing degree programmes because nurse educators can identify nursing students with low academic self-efficacy and help them in their academic duties. Indirectly, academic self-efficacy monitoring can be used for evaluating the effect of different teaching strategies or mentorship support over time.


Projected temperature-related deaths in ten large U.S. metropolitan areas under different climate change scenarios.
There is an established U-shaped association between daily temperature and mortality. Temperature changes projected through the end of century are expected to lead to higher rates of heat-related mortality but also lower rates of cold-related mortality, such that the net change in temperature-related mortality will depend on location. We quantified the change in heat-, cold-, and temperature-related mortality rates through the end of the century across 10 large US metropolitan areas. We applied location-specific projections of future temperature from over 40 downscaled climate models to exposure-response functions relating daily temperature and mortality in 10 US metropolitan areas to estimate the change in temperature-related mortality rates in 2045-2055 and 2085-2095 compared to 1992-2002, under two greenhouse gas emissions scenarios (RCP 4.5 and 8.5). We further calculated the total number of deaths attributable to temperature in 1997, 2050, and 2090 in each metropolitan area, either assuming constant population or accounting for projected population growth. In each of the 10 metropolitan areas, projected future temperatures were associated with lower rates of cold-related deaths and higher rates of heat-related deaths. Under the higher-emission RCP 8.5 scenario, 8 of the 10 metropolitan areas are projected to experience a net increase in annual temperature-related deaths per million people by 2086-2095, ranging from a net increase of 627 (95% empirical confidence interval [eCI]: 239, 1018) deaths per million in Los Angeles to a net decrease of 59 (95% eCI: -485, 314) deaths per million in Boston. Applying these projected temperature-related mortality rates to projected population size underscores the large public health burden of temperature. Increases in the heat-related death rate are projected to outweigh decreases in the cold-related death rate in 8 out of 10 cities studied under a high emissions scenario. Adhering to a lower greenhouse gas emissions scenario has the potential to substantially reduce future temperature-related mortality.


A novel 2-cyanobenzothiazole-based (18)F prosthetic group for conjugation to 1,2-aminothiol-bearing targeting vectors.
In a bid to find an efficient means to radiolabel biomolecules under mild conditions for PET imaging, a bifunctional (18)F prosthetic molecule has been developed. The compound, dubbed [(18)F]FPyPEGCBT, consists of a 2-substituted pyridine moiety for [(18)F]F(-) incorporation and a 2-cyanobenzothiazole moiety for coupling to terminal cysteine residues. The two functionalities are separated by a mini-PEG chain. [(18)F]FPyPEGCBT could be prepared from its corresponding 2-trimethylammonium triflate precursor (100 °C, 15 min, MeCN) in preparative yields of 11% ± 2 (decay corrected, n = 3) after HPLC purification. However, because the primary radiochemical impurity of the fluorination reaction will not interact with 1,2-aminothiol functionalities, the (18)F prosthetic could be prepared for bioconjugation reactions by way of partial purification on a molecularly imprinted polymer solid-phase extraction cartridge. [(18)F]FPyPEGCBT was used to (18)F-label a cyclo-(RGDfK) analogue which was modified with a terminal cysteine residue (TCEP·HCl, DIPEA, 30 min, 43 °C, DMF). Final decay-corrected yields of (18)F peptide were 7% ± 1 (n = 9) from end-of-bombardment. This novel integrin-imaging agent is currently being studied in murine models of cancer. We argue that [(18)F]FPyPEGCBT holds significant promise owing to its straightforward preparation, 'click'-like ease of use, and hydrophilic character. Indeed, the water-tolerant radio-bioconjugation protocol reported herein requires only one HPLC step for (18)F peptide purification and can be carried out remotely using a single automated synthesis unit over 124-132 min.


Trends in colposcopy.
Concurrent with the decreasing incidence of invasive squamous cell cancer of the cervix, there has been an increase in the incidence of cervical carcinoma in situ (CIS). The incidence of CIS has reached a plateau, and the author feels that CIS will now decline as earlier stages of cervical intraepithelial neoplasia (CIN) are being detected and eradicated. Much of the treatment of this earlier CIN can be confined to an office setting with the aid of a colposcope.


Health-related quality of life in patients with acute coronary syndromes and treated with ticagrelor or clopidogrel.
Evaluation of: Levin LA, Wallentin L, Bernfort L et al. Health-related quality of life of ticagrelor versus clopidogrel in patients with acute coronary syndromes results from the PLATO trial. Value Health 16(4), 574-580 (2013). Antiplatelet therapy is considered essential treatment for acute coronary syndromes with or without ST-segment elevation and after stent procedures. The PLATelet inhibition and patient Outcomes (PLATO) trial compared ticagrelor or clopidogrel for the prevention of cardiovascular events. Prespecified substudies included a health-related quality of life (HRQL) study; the EQ-5D, a self-report, standardized, nondisease-specific utility measure with a single index value for health status, was used to assess HRQL. In the primary HRQL analysis, the mean 12-month HRQL score in 15,212 patients was reported to be 0.840 in the ticagrelor group and 0.832 in the clopidogrel group (p = 0.046). Excluding patients who died resulted in no difference in HRQL between patients treated with ticagrelor or clopidogrel (0.864 and 0.863, respectively; p = 0.69). The improved survival and reduction in cardiovascular events with ticagrelor as demonstrated in the main PLATelet inhibition and patient Outcomes trial are apparently obtained with no difference in quality of life.


Three-dimensional eco-friendly bacterial nanocellulose (BNC) scaffold for regenerative dentistry: Characterization, cytocompatibility and differentiation potential.
Regenerative dentistry (RD) is an innovative strategy for treating necrotic teeth and regenerating damaged dental tissue. Biocompatible materials are pivotal for the advancement of RD, and the rising interest in environmental sustainability drives exploration of sustainable materials for dentistry. Bacterial nanocellulose (BNC) has emerged as a promising eco-friendly option and this study aims to assess BNC's suitability as scaffolds for regenerative dentistry applications. Different in vitro methods have been utilized to characterize the properties of BNC scaffolds in regenerative dentistry, such as scanning electron microscopy (SEM) to analyse surface property and porosity, as well as examining their absorption behaviour using phosphate-buffered saline and bovine serum. Dental pulp stem cell (DPSCs) attachment, viability, and proliferation were evaluated using SEM, live and dead, and tetrazolium reduction assays. The odontogenic potential of the scaffold was evaluated using Alizarin Red staining and qPCR (14 and 21 days). Scanning electron microscopy (SEM) images and ethanol displacement method demonstrated the porous architecture of the BNC scaffold with an average porosity of 70.02 ± 4.74% and 50.26 ± 1.43% respectively. The scaffold absorbed 2846.54 ± 258.95 of BSA and 1648.63 ± 50.37% PBS after immersion in solution for 1 h, following pseudo first and second order kinetics. The biocompatibility assay indicated that cell density increased with time and that the scaffold was appropriate for cell adhesion and migration. Moreover, the BNC led to significantly higher mineralization and odontogenic expression compared to the control (BNC in conditioned media). BNC showed fast adsorption of bovine serum, allowed DPSC attachment, migration, and odontogenic differentiation. This suggests its suitability as a biocompatible scaffold for triggering in situ mineralized tissue regeneration for regenerative dental applications.


A brief measure of high nicotine dependence for busy clinicians and large epidemiological surveys.
It is important to perform a routine screening of nicotine dependence in psychiatric patients. The Fagerstrom Test for Nicotine Dependence (FTND) is a widely used six-item questionnaire. The Heavy Smoking Index (HSI) is a briefer measure including only two FTND items (time to first cigarette of day and number of daily cigarettes). In a prior study comparing HSI with FTND, a high HSI (score > or = 4) was a good and briefer alternative for detecting high nicotine dependence. The goals of this study were: (i) to compare the effectiveness of the HSI with the effectiveness of Items 1 and 4 alone for the screening of high nicotine dependence; (ii) to investigate the optimality of 4 as a cut-off score for the HSI so that the HSI can be used as a binary indicator of high nicotine dependence; and (iii) to compare the sensitivity and specificity of four indexes of high nicotine dependence, namely 'High HSI', 'Very Early Smoking', 'Heavy Smoking' and 'High in Either Item'. The FTND was administered to 819 current daily smokers from a general population survey. As in a prior study, an FTND score > or = 6 was considered the reference or 'gold standard' test for detecting high nicotine dependence. Receiver-operating characteristic analyses were performed. This new study using more sophisticated statistical methodology verified that a cut-off of 4 for the HSI is appropriate and that the 'high' HSI has good sensitivity and specificity even across different population subclassifications. With four questions (smoking, daily smoking, time to first cigarette of day and number of daily cigarettes) and minimal calculations, it may be possible to screen whether a smoker has high nicotine dependence. If other studies in other populations and settings verify this finding, this brief measure might be an ideal screening instrument for busy clinicians, epidemiologists developing questionnaires for health surveys and psychiatric researchers.


A comparison of furazolidone and doxorubicin enhanced free radical chemistry.
Furazolidone and doxorubicin induce dilative cardiomyopathies but are not structurally similar. In order to determine if these drugs might share a common mechanism of action, the free radical based chemistry of these drugs were compared. Furazolidone like doxorubicin stimulates lipid peroxidation in the presence of added iron. However, while furazolidone (50 microM) stimulated lipid peroxidation 2.4 fold, doxorubicin (50 microM) increased lipid peroxidation 10 fold in the presence of iron (50 microM). In contrast, furazolidone was more potent than doxorubicin at stimulating the oxidation of epinephrine and the reduction of cytochrome c when incubated with cardiac sarcosomes. These data demonstrate that while both drugs stimulate free radical chemistry, they differ in their propensity to stimulate iron-dependent (lipid peroxidation) versus iron-independent reactions. Thus differences in the expression of these drugs pathology may be due to differences in their redox chemistry.


Overview of the changing epidemiology of candidemia.
Candida spp. are currently the fourth most common cause of bloodstream infections in US hospitals, and the third most common cause of bloodstream infections in the intensive care unit. Over the last 2 decades there has been a shift towards a greater involvement of non-Candida albicans spp. as the cause of candidemia. Several of these non-albicans spp. (e.g., C. glabrata and C. krusei ) exhibit resistance to traditional triazole antifungals like fluconazole, and cross-resistance with newer triazoles, focusing attention on the first-line use of antifungals such as the echinocandins, which possess improved activity against fluconazole-resistant strains. Recent treatment guidelines from the Infectious Diseases Society of America (IDSA) recommend an echinocandin as primary therapy for nonneutropenic or neutropenic patients with moderately severe to severe candidiasis and for patients at risk for infection with a triazole-resistant strain. However, further improvement in candidemia-associated mortality will only be attainable with the development and validation of new diagnostic tools that will allow earlier detection, discrimination, and treatment of invasive candidiasis. Clinicians should remain vigilant to wider emergence of Candida spp. with echinocandin resistance.


Honey in modern wound care: a systematic review.
Honey, known for centuries as a topical treatment for a wide range of wounds, has recently known a revival in modern wound care. The objective of this systematic review is to evaluate the available evidence and the role of honey in contemporary wound care. The search strategy was developed in the databases PubMed and ISI Web of Science. Fifty-five studies of any design, evaluating the use of honey in human burns, ulcers and other wounds, written in English, French, German or Dutch were eligible for inclusion. In all three wound categories honey seems to be a dressing with wound healing stimulating properties. In burns there is also evidence for its antibacterial capacity. In general, honey is also been mentioned to have deodorizing, debridement, anti-inflammatory and wound pain reducing properties, although the evidence for these properties is rather limited. Many of the included studies have methodological problems, and the quality of certain studies is low, making it difficult to formulate conclusive guidelines. This review reveals several gaps in the research of honey in modern wound care, and recommendations are suggested for future research.


Atrial fibrillation burden and cognitive decline in elderly patients undergoing continuous monitoring.
To study the relationship between subclinical atrial fibrillation (AF) and changes in cognitive function in a large cohort of individuals with stroke risk factors. Individuals with no prior AF diagnosis but with risk factors for stroke were recruited to undergo annual cognitive assessment with the Montreal Cognitive Assessment (MoCA) along with implantable loop recorder (ILR) monitoring for AF for 3 years. If AF episodes lasting ≥6 minutes were detected, oral anticoagulation (OAC) treatment was initiated. A total of 1194 participants (55.2 % men, mean age 74.5 (±3.9)) had a combined duration of heart rhythm monitoring of ≈1.3 million days. Among these, 339 participants (28.3%) had adjudicated AF, with a median AF burden of 0.072% (0.02, 0.39), and 324 (96%) initiated OAC. When stratifying the participants into AF burden groups (No AF, AFlow (AF burden <0.25%), and AFhigh, (AF burden >0.25%)), only participants in the AFlow group had a decrease in MoCA score over time (P = .03), although this was not significant after adjustment for stroke risk factors. A subgroup analysis of 175 participants (14.6%) with a MoCA <26 at 3 years found no association to AF diagnosis or burden. In a high-risk population, subclinical AF detected by continuous monitoring and subsequently treated with OAC was not associated with a significant change in MoCA score over a 3-year period.


Neuroepigenetic Editing.
Studies of the mammalian nervous system have revealed widespread epigenetic regulation underlying gene expression intrinsic to basic neurobiological function as well as neurological disease. Over the past decade, a critical role has emerged for the neural regulation of chromatin-modifying enzymes during both development and adulthood, and in response to external stimuli. These biochemical data are complemented by numerous next generation sequencing (NGS) studies that quantify the extent of chromatin and DNA modifications in neurons. Neuroepigenetic editing tools can be applied to distinguish between the mere presence and functional relevance of such modifications to neural transcription and animal behavior. This review discusses current advances in neuroepigenetic editing, highlighting methodological considerations pertinent to neuroscience, such as delivery methods and the spatiotemporal specificity of editing. Although neuroepigenetic editing is a nascent field, the studies presented in this review demonstrate the enormous potential of this approach for basic neurobiological research and therapeutic application.


Comparison of quality of life measures in heart failure.
Although numerous health-related quality-of-life instruments are available to measure patients' quality of life, few studies have compared these measures directly to determine how they function in the same group of patients. The purpose of this study was to empirically compare psychometric properties of the Chronic Heart Failure Questionnaire (CHQ), the Minnesota Living with Heart Failure Questionnaire (LHFQ), and the General Health Survey Short-form-12 (SF-12). A convenience sample of 211 patients with heart failure completed baseline questionnaires; 165 patients completed the entire 26-week study. Patients completed telephone interviews at baseline and at 4, 8, and 26 weeks after baseline. To compare mode of administration, a subset of patients (n = 173) completed face-to-face and telephone interviews. Patients reported low-to-moderate health-related quality-of-life overall. Reliability of the three instruments was satisfactory. Responsiveness to changing condition, as evaluated by analysis of variance, receiver operating curve characteristics, and the minimal clinically important difference method, indicated that the CHQ and LHFQ were more responsive to changing conditions than the SF-12. No major differences were noted between the scores of the face-to-face interviews and the baseline telephone interviews. The LHFQ and SF-12 were easier and took less time to administer than the CHQ. While all three instruments were reliable and valid, the CHQ and LHFQ were more sensitive than the SF-12 in detecting clinically important changes over time.


The polygenic and reactive nature of observed parenting.
In Wertz et al. (2019), parents' polygenic scores of educational attainment (PGS-EA) predicted parental sensitive responses to the child's needs for support, as observed in a dyadic task (i.e., observed sensitivity). We aimed to replicate and expand these findings by combining longitudinal data, child genotype data and several polygenic scores in the Generation R Study. Mother-child dyads participated in two developmental periods, toddlerhood (14 months old; n = 648) and early childhood (3-4 years old, n = 613). Higher maternal PGS-EA scores predicted higher observed sensitivity in toddlerhood (b = 0.12, 95% CI 0.03, 0.20) and early childhood (b = 0.16, 95% CI 0.08, 0.24). Child PGS-EA was significantly associated with maternal sensitivity in early childhood (b = 0.11, 95% CI 0.02, 0.21), and the effect of maternal PGS-EA was no longer significant when correcting for child PGS-EA. A latent factor of PGSs based on educational attainment, intelligence (IQ) and income showed similar results. These polygenic scores might be associated with maternal cognitive and behavioral skills that help shape parenting. Maternal PGSs predicted observed sensitivity over and above the maternal phenotypes, showing an additional role for PGSs in parenting research. In conclusion, we replicated the central finding of Wertz et al. (2019) that parental PGS-EA partially explains parental sensitivity. Our findings may be consistent with evocative gene-environment correlation (rGE), emphasizing the dynamic nature of parenting behavior across time, although further research using family trios is needed to adequately test this hypothesis.


Congenital amusia in speakers of a tone language: association with lexical tone agnosia.
Congenital amusia is a neurogenetic disorder that affects the processing of musical pitch in speakers of non-tonal languages like English and French. We assessed whether this musical disorder exists among speakers of Mandarin Chinese who use pitch to alter the meaning of words. Using the Montreal Battery of Evaluation of Amusia, we tested 117 healthy young Mandarin speakers with no self-declared musical problems and 22 individuals who reported musical difficulties and scored two standard deviations below the mean obtained by the Mandarin speakers without amusia. These 22 amusic individuals showed a similar pattern of musical impairment as did amusic speakers of non-tonal languages, by exhibiting a more pronounced deficit in melody than in rhythm processing. Furthermore, nearly half the tested amusics had impairments in the discrimination and identification of Mandarin lexical tones. Six showed marked impairments, displaying what could be called lexical tone agnosia, but had normal tone production. Our results show that speakers of tone languages such as Mandarin may experience musical pitch disorder despite early exposure to speech-relevant pitch contrasts. The observed association between the musical disorder and lexical tone difficulty indicates that the pitch disorder as defining congenital amusia is not specific to music or culture but is rather general in nature.


Extensive expansion of A1 family aspartic proteinases in fungi revealed by evolutionary analyses of 107 complete eukaryotic proteomes.
The A1 family of eukaryotic aspartic proteinases (APs) forms one of the 16 AP families. Although one of the best characterized families, the recent increase in genome sequence data has revealed many fungal AP homologs with novel sequence characteristics. This study was performed to explore the fungal AP sequence space and to obtain an in-depth understanding of fungal AP evolution. Using a comprehensive phylogeny of approximately 700 AP sequences from the complete proteomes of 87 fungi and 20 nonfungal eukaryotes, 11 major clades of APs were defined of which clade I largely corresponds to the A1A subfamily of pepsin-archetype APs. Clade II largely corresponds to the A1B subfamily of nepenthesin-archetype APs. Remarkably, the nine other clades contain only fungal APs, thus indicating that fungal APs have undergone a large sequence diversification. The topology of the tree indicates that fungal APs have been subject to both "birth and death" evolution and "functional redundancy and diversification." This is substantiated by coclustering of certain functional sequence characteristics. A meta-analysis toward the identification of Cluster Determining Positions (CDPs) was performed in order to investigate the structural and biochemical basis for diversification. Seven CDPs contribute to the secondary structure of the enzyme. Three other CDPs are found in the vicinity of the substrate binding cleft. Tree topology, the large sequence variation among fungal APs, and the apparent functional diversification suggest that an amendment to update the current A1 AP classification based on a comprehensive phylogenetic clustering might contribute to refinement of the classification in the MEROPS peptidase database.


Incidence of central nervous system tumors in Gironde, France.
The incidence of CNS tumors is subject to geographical and temporal variations which are poorly understood. The incidence of these tumors was studied in Gironde, a department of southwestern France with 1,058,911 inhabitants older than 16 years. We recorded any malignant or benign central nervous system (CNS) tumor diagnosed between May 1999 and April 2001 in adults living in Gironde. Three hundred and twenty-nine CNS tumors were diagnosed during the study period. The incidence of CNS tumors in adults was therefore 15.5 per 100,000. Overall, the incidence according to sex was 14.7 for males and 16.2 per 100,000 for females. The incidence rate increased according to age up to 80 years (3.7 per 100,000 for 20-29 years of age to 33.4 per 100,000 for 70-79 years of age) and reduced thereafter for gliomas. Our estimation of the incidence of CNS tumors ranks high among the earlier reports. Further analytic studies are ongoing.


Exploring factors in fear of COVID-19 and its GIS-based nationwide distribution: the case of Bangladesh.
The COVID-19 pandemic is a public health threat of international concern, intensifying peoples' psychological risk and vulnerability by strengthening mental health stressors such as fear, panic and uncertainty. The unexpected fear of COVID-19 has been reported to be associated with suicide occurrences, similar to prior pandemics. Identifying the factors associated with fear of COVID-19 could help us to develop better mental health strategy and practice to improve the situation here in Bangladesh. This was the first attempt to present a Geographic Information System (GIS)-based distribution of fear of COVID-19 across the country's administrative districts in a nationwide sample. Data for a total of 10 067 individuals were collected by an online survey during the first wave of the pandemic (1 to 10 April 2020); data for 10 052 participants were finally analysed after excluding 15 transgender individuals. The survey questionnaire included items concerning sociodemographic, behavioural and health-related variables, COVID-19-related issues, and the Bangla Fear of COVID-19 Scale. The mean fear of COVID-19 scores was 21.30 ± 6.01 (out of a possible 35) in the present sample. Female gender, highly educated, non-smoker, non-alcohol consumer, having chronic diseases, using social media, and using social media and not using newspapers as COVID-19 information sources were associated with a higher level of fear of COVID-19. Higher levels of fear of COVID-19 were found in districts of Magura, Panchagarh, Tangail, Sunamganj and Munshiganj; by contrast, Kushtia, Pirojpur, Chapainawabganj, Jhalokathi and Naogaon districts had lower fear of COVID-19. Based on the GIS-distribution, fear of COVID-19 was significantly associated with the district as well as in respect to its gender-based and education-level-based associations. However, fear of COVID-19 and COVID-19 cases were heterogeneously distributed across the districts; that is, no consistent association of higher COVID-19 cases with higher fear of COVID-19 was found. This study being exploratory in nature may help to facilitate further studies, as well as directing governmental initiatives for reducing fear of COVID-19 in at-risk individuals. Providing adequate resources and mental health services in the administrative regions identified as highly vulnerable to fear of COVID-19 is recommended.


Construction of a Festuca pratensis BAC library for map-based cloning in Festulolium substitution lines.
Introgression in Festulolium is a potentially powerful tool to isolate genes for a large number of traits which differ between Festuca pratensis Huds. and Lolium perenne L. Not only are hybrids between the two species fertile, but the two genomes can be distinguished by genomic in situ hybridisation and a high frequency of recombination occurs between homoeologous chromosomes and chromosome segments. By a programme of introgression and a series of backcrosses, L. perenne lines have been produced which contain small F. pratensis substitutions. This material is a rich source of polymorphic markers targeted towards any trait carried on the F. pratensis substitution not observed in the L. perenne background. We describe here the construction of an F. pratensis BAC library, which establishes the basis of a map-based cloning strategy in L. perenne. The library contains 49,152 clones, with an average insert size of 112 kbp, providing coverage of 2.5 haploid genome equivalents. We have screened the library for eight amplified fragment length polymorphism (AFLP) derived markers known to be linked to an F. pratensis gene introgressed into L. perenne and conferring a staygreen phenotype as a consequence of a mutation in primary chlorophyll catabolism. While for four of the markers it was possible to identify bacterial artificial chromosome (BAC) clones, the other four AFLPs were too repetitive to enable reliable identification of locus-specific BACs. Moreover, when the four BACs were partially sequenced, no obvious coding regions could be identified. This contrasted to BACs identified using cDNA sequences, when multiple genes were identified on the same BAC.


Physical Exercise or Activity and Energy Balance or Metabolism in the Context of Health and Diseases.
Regular long-lasting physical exercise demands a tremendous amount of metabolic energy [...].


[Meningiomas. Histopathological aspects and recurrence].
The authors assessed 246 cases of meningiomas that were classified as typical, atypical, anaplastic and papillary, according to previously defined criteria. Among the criteria used to define non-typical tumours, brain invasion was predominant in 62.3%. Meningiomas were typical in 75.22%, atypical in 19.1%, anaplastic in 5.68% of the cases. There was recurrence in 3.78% of typical, 42.55% of atypical and 45.45% of anaplastic. The authors conclusion was that the criteria used to define typical and non-typical were adequate to predict a higher chance to tumour recurrences


RAPPORT: running scientific high-performance computing applications on the cloud.
Cloud computing infrastructure is now widely used in many domains, but one area where there has been more limited adoption is research computing, in particular for running scientific high-performance computing (HPC) software. The Robust Application Porting for HPC in the Cloud (RAPPORT) project took advantage of existing links between computing researchers and application scientists in the fields of bioinformatics, high-energy physics (HEP) and digital humanities, to investigate running a set of scientific HPC applications from these domains on cloud infrastructure. In this paper, we focus on the bioinformatics and HEP domains, describing the applications and target cloud platforms. We conclude that, while there are many factors that need consideration, there is no fundamental impediment to the use of cloud infrastructure for running many types of HPC applications and, in some cases, there is potential for researchers to benefit significantly from the flexibility offered by cloud platforms.


A study on prevalence, profile, and risk factors of developing fungal infection in patients with diabetic foot ulcer.
Many chronic nonhealing diabetic foot ulcers (DFUs) with increased rates of amputation are frequently associated with fungal infections. To evaluate the prevalence, profile, and risk factors of developing a fungal infection in patients with DFU. This prospective observational study was carried out from October 2018 to July 2020. All adult patients with DFUs admitted to the surgery ward were recruited. Patients on antifungal therapy or who received such therapy within 6 weeks prior to admission were excluded. Three deep tissue samples were sent for bacterial culture, fungal culture, and histopathological examination of fungal elements. A total of 251 patients were enrolled in the study. Of the 23.3% of patients with positive fungal growth (n = 47/202), 2% (n = 4/202) had pure fungal growth and 21.3% (n = 43/202) had mixed growth with bacteria in their ulcers (ie, non-contaminated samples). A significant association was found between wound grade (P = .027), ulcer duration (P = .028), and positive fungal growth in DFUs. In this study, the prevalence of fungal infection in DFUs was 23.3%; Candida tropicalis (27.08%) was the most common isolate, followed by C. albicans (20.83%). The rate of fungal infections was high in patients with mild diabetic foot infection or DFU of 7 to 14 days' duration.


The Incidence and Nature of Allergic and Anaphylactic Reactions During Pediatric Procedural Sedation: A Report From the Pediatric Sedation Research Consortium.
Anaphylaxis is rare but life-threatening. Its incidence during pediatric procedural sedation outside of the operating room is unknown. We used data from the Pediatric Sedation Research Consortium (PSRC) to determine the incidence and nature of allergic and anaphylactic reactions in this practice. A retrospective observational study of prospectively collected information in the PSRC's multicenter database was performed. Cases of allergic reaction were identified. Because anaphylaxis is not a listed complication in the PSRC database, all cases for which allergic reaction was noted were reviewed for the occurrence of other complications or interventions that would suggest at least 2 organ system derangements consistent with anaphylaxis as well as for practitioner commentary stating the occurrence of anaphylaxis. Descriptive analyses of demographic information and summary statistics were performed, and multiple logistic regression analysis was used to evaluate associations between the occurrence of allergic reactions and medications. During the study period, 227 833 cases were entered into the PSRC database. There were 54 cases of allergic reaction (incidence 1:4219); 6 were consistent with anaphylaxis (incidence 1:37 972). A significant association between the development of allergic reaction and 4 sedative and/or analgesic medications was noted: midazolam (odds ratio [OR] 2.2; confidence interval [CI] 1.2-3.9), ketamine (OR 3.8; CI 2.1-7.1), methohexital (OR 48.8; CI 14.9-159.9), and morphine (OR 4.4; CI 1.04-18.2). There were no mortalities. Allergic reactions and anaphylaxis during pediatric procedural sedation are rare. In this study, the development of allergic reactions was significantly associated with the use of midazolam, ketamine, methohexital, and morphine.


Phenotypic differences among clinically isolated mucoid Pseudomonas aeruginosa strains.
Mucoid strains of Pseudomonas aeruginosa isolated from patients with cystic fibrosis or urinary tract infections displayed many phenotypic differences. The ratios of D-mannuronosyl to L-guluronosyl moieties of the extracellular alginate-like polysaccharides produced by the 19 strains examined varied from 99 to 0.8; the acetyl content of the polymers varied from 0.38 to 0.02 mol per mole of uronosyl residue. The strains also differed with regard to the stability of the mucoid phenotype. Of 15 isolates from patients with cystic fibrosis, 7 displayed stable mucoid phenotypes; 8 isolates were unstable and reverted to the nonmucoid phenotype at high frequency. The four strains isolated from patients with urinary tract infections were also unstable. Strains from urinary tract infections expressed the mucoid phenotype on six different media, both minimal and complex, whereas cystic fibrosis-associated strains varied widely with regard to medium-dependent expression of the mucoid phenotype. Of 15 cystic fibrosis strains, 5 were mucoid on each of six different media, 4 were mucoid on five media, 1 was mucoid on four media, 4 were mucoid on three media, and 1 yielded mucoid colonies on only one of the six media tested. There was no obvious correlation among polysaccharide structure, stability of the mucoid phenotype, and medium-dependent expression of the mucoid phenotype for any of the 19 strains investigated. These data suggest that although mucoid strains of P. aeruginosa must share some common property related to their ability to colonize their host, this property seems to be unrelated to polysaccharide composition, medium-dependent expression of the mucoid phenotype, or stability of the mucoid phenotype.


The problems of deformity and disability in cerebral palsy.
The relationship of deformity and dysfunction has been studied on 67 children with spastic hemiplegia. The usual treatment of conditions resulting from polioencephalitis acuta infantum consists in improving both achievements and skills or in taking measures aimed at reducing the deformity. At best, both of these therapeutical approaches may be used. Quite often, however, it is necessary to decide which of the two approaches is the best one for the patient in question. Also perhaps by improving the patient's achievements, while the deformity is increased. What is also of great consequence in this particular respect is a skillful and responsible psychotherapeutical treatment of the patient.


Relative biological effectiveness of 103Pd and 125I photons for continuous low-dose-rate irradiation of Chinese hamster cells.
Monolayers of Chinese hamster lung cells (CCL-16) in a polystyrene phantom were irradiated in vitro by 103Pd and 125I sources at dose rates of 6 to 72 cGy/h. Cell survival curves for acute high-dose-rate irradiation (over 30 Gy/h) were also measured using nearly monoenergetic X-ray beams which were designed to simulate the mean energies of photons emitted by 125I and 103Pd and also using a clinical 250 kVp X-ray beam. A profound dose-rate effect is observed over the dose-rate range of 6 to 20 cGy/h. An inverse dose-rate effect was observed for both radionuclides, with its onset occurring at a dose rate of about 20-30 cGy/h. The average RBE of 103Pd relative to 125I was determined to be 1.45 +/- 0.07, 1.41 +/- 0.07, 0.70 +/- 0.07 and 1.49 +/- 0.07 at dose rates of 6.9, 12.6, 19.0 and 26.7 cGy/h, respectively. Because 103Pd implants are generally prescribed at a higher initial dose rate (21 cGy/h) than the corresponding 125I implants (7 cGy/h), the effects of both dose rate and photon energy on biological response must be considered together. For the CCL-16 cells, the RBE of 103Pd at 19.0 cGy/h relative to that of 125I at 6.9 cGy/h was estimated to be 2.3 +/- 0.5.


Correction and verification of AECL Bonner Sphere response matrix based on mono-energetic neutron calibration performed at NPL.
The AECL Bonner Sphere Spectrometer (BSS) was taken to National Physical Laboratory (NPL) for calibration in mono-energetic neutron fields and bare (252)Cf neutron fields. The mono-energetic radiations were performed using ISO-8529 prescribed neutron energies: 0.071, 0.144, 0.565, 1.2, 5 and 17 MeV. A central SP9 proportional counter was also evaluated at the NPL thermal neutron calibration facility in order to assess an effective pressure of (3)He inside the counter, i.e. number density of (3)He atoms. Based on these measurements and methods outlined by Thomas and Soochak, a new BSS response matrix was generated. The response matrix is then verified by unfolding spectra corresponding to various neutron fields. Those are NPL bare (252)Cf source, National Institute of Standards and Technology bare and heavy water moderated (252)Cf source and (241)AmBe calibration source located at National Research Council. A good agreement was observed with expected neutron fluence rates, as well as derived dosimetric quantities, such as International Commission on Radiological Protection-74 ambient dose equivalent.


Aedes polynesiensis in the Society Islands: environmental correlates of isoenzyme differentiation.
Isoenzyme genetic differentiation of Aedes polynesiensis mosquitoes in Raiatea island, French Polynesia, was evaluated by two models of population structure based on seven gene-enzyme systems: Ak, Est, Got, Gpi, Hk, Mdh and Pgm. The ecological model tested whether genetic differentiation is congruent with habitat differences. The isolation model evaluated whether genetic differentiation is proportional to geographical distribution. The ecological model found no significant differentiation between populations of Ae.polynesiensis from beach and forest ecotopes, whereas the isolation model was consistent with the data. However, incipient speciation is opposed by the source-sink system of population dynamics in such small neighbouring islands, where Ae.polynensiensis extinction is readily followed by reinvasion causing considerable gene flow between island populations.


Effects of nitric oxide synthase inhibition on phospholipid fatty acid composition of brown adipose tissue.
We investigated the effects of nitric oxide synthase inhibition on the phospholipid fatty acid composition of brown adipose tissue by administering chronic N omega-nitro-L-arginine methyl ester (L-NAME) (0.01%) to rats via drinking water. L-NAME caused a significant decrease in C14:0, C16:0, C16:1 and C18:1, with a concomitant increase in C18:0 and C18:2, L-NAME treatment elicited an increase in the unsaturation index. There were no significant changes in other fatty acids including the polyunsaturated fatty acids docosahexaenoate (DHA, C22:6) and arachidonate (C20:4). Polyunsaturated fatty acid linoleate (C18:2) was increased and the arachidonate index decreased in the L-NAME-treated group, suggesting a diminished conversion of C18:2 to C20:4.


[Diffusion tensor imaging and tractography of central pontine myelinolysis].
To illustrate the value of diffusion tensor imaging and tractography in the diagnosis and follow-up of central pontine myelinolysis. We report a case of central pontine myelinolysis in a 29 year old woman, also anorexic, studied using MR Diffusion Tensor Imaging (DTI) and Fibre Tracking (FT) focused on the pons, and compared with the studies of 5 normal volunteers. Tractography showed a swollen aspect of the right corticospinal fiber tract correlating with mild left lower extremity deficit at clinical evaluation. The pontine fibers were posteriorly displaced but intact. The sensory tracts were also intact. Apparent Diffusion Coefficient values were increased and Fractional Anisotropy was decreased in the lesions. Follow up imaging showed persistent abnormal ADC and FA values in the pons although the left cortico-spinal tract returned to normal, consistent with the clinical outcome. Diffusion Tensor Imaging MR and Fiber tractography are a new method to analyse white matter tracts. It can be used to prospectively evaluate the location of white matter tract lesions at the acute phase of central pontine myelinolysis and follow up.


Imaging of P glycoprotein function in vivo with PET.
P glycoprotein (Pgp) is expressed on cell membranes of various organs in the body, such as the capillary endothelial cells of the brain. Furthermore, Pgp can also be expressed on the cell membrane of tumour cells. Because of Pgp-mediated efflux, tissue levels of several Pgp substrates are lower than in Pgp-negative tissues. Drug levels in Pgp-expressing organs may be increased by modulation of this Pgp-facilitated transport with several compounds, such as cyclosporin A. Up to now, the presence of drug efflux pumps in tissues could only be examined at the mRNA and protein level. However, this gives no insight into the important question of the functionality of these drug efflux pumps. Information about the transport function of Pgp and the effect of modulating this function may improve the therapeutic treatment of these patients. Positron emission tomography (PET) gives us a unique opportunity to study non-invasively (patho)physiological dynamic processes in vivo. We have therefore developed and validated a method for studying Pgp-mediated transport and its modulation in vivo with PET.


Readout-segmented EPI for rapid high resolution diffusion imaging at 3 T.
Readout mosaic segmentation has been suggested as an alternative approach to EPI for high resolution diffusion-weighted imaging (DWI). In the readout-segmented EPI (RS-EPI) scheme, segments of k-space are acquired along the readout direction. This reduces geometric distortions due to the decrease in readout time. In this work, further distortion reduction is achieved by combining RS-EPI with parallel imaging (PI). The performance of the PI-accelerated RS-EPI scheme is assessed in volunteers and patients at 3T with respect to both standard EPI and PI-accelerated EPI. Peripherally cardiac gated and non-gated RS-EPI images are acquired to assess whether motion due to brain pulsation significantly degrades the image quality. Due to the low off-resonance of PI-driven RS-EPI, we also investigate if the eddy currents induced by the diffusion gradients are low enough to use the Stejskal-Tanner diffusion preparation instead of the twice-refocused eddy-current compensated diffusion preparation to reduce TE. It is shown that non-gated phase corrected DWI performs equally as well as gated acquisitions. PI-driven DW RS-EPI images with substantially less distortion compared with single-shot EPI are shown in patients-allowing the delineation of structures in the lower parts of the brain. A twice-refocused diffusion preparation was found necessary to avoid blurring in the DWI data. This paper shows that the RS-EPI scheme may be an important alternative sampling strategy to EPI to achieve high resolution T2-weighted and diffusion-weighted images.


VIRUSBreakend: Viral Integration Recognition Using Single Breakends.
Integration of viruses into infected host cell DNA can cause DNA damage and disrupt genes. Recent cost reductions and growth of whole genome sequencing has produced a wealth of data in which viral presence and integration detection is possible. While key research and clinically relevant insights can be uncovered, existing software has not achieved widespread adoption, limited in part due to high computational costs, the inability to detect a wide range of viruses, as well as precision and sensitivity. Here, we describe VIRUSBreakend, a high-speed tool that identifies viral DNA presence and genomic integration. It utilizes single breakends, breakpoints in which only one side can be unambiguously placed, in a novel virus-centric variant calling and assembly approach to identify viral integrations with high sensitivity and a near-zero false discovery rate. VIRUSBreakend detects viral integrations anywhere in the host genome including regions such as centromeres and telomeres unable to be called by existing tools. Applying VIRUSBreakend to a large metastatic cancer cohort, we demonstrate that it can reliably detect clinically relevant viral presence and integration including HPV, HBV, MCPyV, EBV and HHV-8. VIRUSBreakend is part of the Genomic Rearrangement IDentification Software Suite (GRIDSS). It is available under a GPLv3 license from https://github.com/PapenfussLab/VIRUSBreakend. Supplementary data are available at Bioinformatics online.


Effects of gamma irradiation on the survival of Listeria monocytogenes and on its growth at refrigeration temperature in poultry and red meat.
Gamma irradiation sensitivity of a strain of Listeria monocytogenes was determined in trypticase soy broth supplemented with yeast extract (TSB-YE), in a slurry of chicken breast meat and in raw ground beef. D10 values in these different media were 0.364, 0.599, and 0.699 kGy, respectively. This organism appeared most sensitive in TSB-YE, more resistant in minced fresh chicken breast meat, and most resistant in fresh minced beef. It was found that irradiation at 2.5 kGy prior to refrigeration is an efficient way for the preservation of meat products contaminated at 10(3) to 10(4) per gram initial load of L. monocytogenes for about 7 d. However, with this initial load, the injured cells might repair themselves and cause a health hazard during storage at 4 C in the presence of air after 7 d.


[Effects of wheat and soybean stubbles on soil microbial ecological characteristics in cucumber field].
The study with traditional dilution plate method and BIOLOG ECO system indicated that under wheat and soybean stubbles, the amounts of soil fungi, bacteria and actinomyces in cucumber field increased, while that of Fusarium oxysporum f. sp. cucumerinum decreased (P <0.05). The Shannon-Wiener index, evenness index, Simpson index, and McIntosh index of soil microbial communities as well as soil microbial biomass C increased (P <0.05), basal respiration and metabolic quotient qCO2 decreased (P <0.05), and soil microbe's sole-carbon-source utilization enhanced. In addition, the contents of soil available P and K and the cucumber yields were also increased markedly. All of these illustrated that wheat and soybean stubbles improved the ecological environment of soil microbes.


Electromyography: its potential as an adjunct to other monitored parameters during conscious sedation in children receiving dental treatment.
The purpose of this study was to evaluate the effect of a combination of a low dose of chloral hydrate and hydroxyzine on the frontalis muscle electromyogram in addition to other physiologic parameters in pediatric dental patients. A double blind, two-appointment cross-over design was used. Either a placebo or a combination of chloral hydrate and hydroxyzine was given to children during the first visit with the sequence of placebo/drug conditions being randomly determined. During the second visit, the children received that agent not given during the first visit. Baseline physiologic data was obtained at the beginning of each visit and the physiologic measures were again recorded during topical and local anesthesia administration, high-speed tooth preparation, and at the end of the dental appointment. The results indicated that the frontalis muscle activity and cardiovascular parameters were significantly affected by the drug and dental procedures. Oxygen saturation was least affected. The frontalis muscle appears to be a sensitive physiologic parameter to monitor during conscious sedation as an index of the amount of patient relaxation.


Incidence and growth pattern of vestibular schwannomas in a Danish county, 1977-98.
During a period of 21 years 162 acoustic neuromas or vestibular schwannomas (VS) were diagnosed in the county of Aarhus. During this period the incidence increased gradually, probably due to improvement of the quality of computed tomography imaging (CTI), and more widely available access to magnetic resonance imaging (MRI). Sixty-four patients were followed up by repeated CTI or MRI, whereas the remaining patients were referred for immediate operation. Six of the observed patients had their tumours removed after demonstration of continuous tumour growth. The observation of 64 tumours over periods between 5 months and 15 years provided useful information on the natural history of sporadic VS. Our results showed that 14 VS (22%) regressed, 35 VS (55%) did not grow or had only minimal growth (growth rate up to 1 mm/year), whereas 15 VS (23%) grew > 1 mm/year. All VS with positive growth had regular growth patterns.


Contextual modulation of substantia nigra pars reticulata neurons.
Neurons in the substantia nigra pars reticulata (SNr) are known to encode saccadic eye movements within some, but not all, behavioral contexts. However, the precise contextual factors that effect the modulations of nigral activity are still uncertain. To further examine the effect of behavioral context on the SNr, we recorded the activity of 72 neurons while monkeys made saccades during a delayed saccade task and during periods of free viewing. We quantified and compared the movement fields of each neuron for saccades made under three different conditions: 1) spontaneous saccades, which shifted gaze during periods of free viewing when no stimuli were presented and no reinforcements were delivered; 2) fixational saccades, which brought gaze into alignment with a fixation target at the start of a delayed saccade trial, were necessary for trial completion, but were not directly followed by reinforcement; and 3) terminal saccades, which brought gaze into alignment with a visual target at the end of a delayed saccade trial and were directly followed by reinforcement. For three of the four SNr neuron classes, saccade-related modulations were only present before terminal saccades. For the fourth class, discrete pausers, saccade-related modulations were substantially larger for terminal saccades than for fixational saccades, and modulations were absent for spontaneous saccades. These results and other recent work on the basal ganglia suggest that some saccade-related signals in the SNr may be influenced by the reinforcement associated with a particular saccadic eye movement.


Is genetic amniocentesis warranted when isolated choroid plexus cysts are found?
Our aim was to evaluate the prevalence of trisomy 18 in the setting of isolated fetal choroid plexus cysts and then to consider the risk of trisomy 18 versus the risks of genetic amniocentesis. Fetuses with choroid plexus cysts were prospectively obtained from a total mid-trimester population of 18861 fetuses with known outcomes. If the fetuses had trisomy 18, they were part of the study group and part of the control group if they had normal karyotypes. Scans were retrospectively reviewed for the characterization of cysts according to size, laterality, and appearance (simple or complex echo patterns). Chi-square analysis of contingency tables of results was performed. 208/18861 (1.1 per cent) fetuses had choroid plexus cysts. 201/208 (96.6 per cent) were normal fetuses or newborns, while 7/208 (3.4 per cent) of the fetuses with choroid plexus cysts had trisomy 18. Overall, 16 fetuses had trisomy 18 and seven (44 per cent) of these had choroid plexus cysts. 0/16 fetuses had choroid plexus cysts as the only sonographic finding. Although laterality or complexity of the cysts did not correlate with the presence or absence of a cytogenetic abnormality, cysts > or = 10 mm were more often associated with trisomy 18 than with a normal karyotype (P < 0.01). We conclude that the discovery of choroid plexus cysts in otherwise normal fetuses in the late second trimester does not by itself justify the risks of genetic amniocentesis.


Developmental effects of heatwave conditions on the early life stages of a coral reef fish.
Marine heatwaves, which are increasing in frequency, duration and intensity owing to climate change, are an imminent threat to marine ecosystems. On coral reefs, heatwave conditions often coincide with periods of peak recruitment of juvenile fishes and exposure to elevated temperature may affect their development. However, whether differences in the duration of high temperature exposure have effects on individual performance is unknown. We exposed juvenile spiny damselfish, Acanthochromis polyacanthus, to increasing lengths of time (3, 7, 30 and 108 days post-hatching) of elevated temperature (+2°C). After 108 days, we measured escape performance at present-day control and elevated temperatures, standard length, mass and critical thermal maximum. Using a Bayesian approach, we show that 30 days or more exposure to +2°C leads to improved escape performance, irrespective of performance temperature, possibly owing to developmental effects of high temperature on muscle development and/or anaerobic metabolism. Continued exposure to elevated temperature for 108 days caused a reduction in body size compared with the control, but not in fish exposed to high temperature for 30 days or less. By contrast, exposure to elevated temperatures for any length of time had no effect on critical thermal maximum, which, combined with previous work, suggests a short-term physiological constraint of ∼37°C in this species. Our study shows that extended exposure to increased temperature can affect the development of juvenile fishes, with potential immediate and future consequences for individual performance.


Fluor determination in toothpaste-extracts with fluoride-selectrode based on the kinetics of hydrolysis of sodiummonofluorophosphate.
The Sodiummonofluorophosphate is used in a large number of toothpastes, s, while clinical research proved that application of fluoride has an important contribution in caries prevention. This prevention is almost due to the reconstitution of the by acids disappeared hydroxylapatite Ca10 (PO4)6 (OH)2 in the toothsurface, which process goes two to three times faster in the presence of F- by sedimentation of hydroxyfluorapatite Ca10 (PO4)6 (OH)2-xFx, with a higher chemical resistance for acids. Therefore, the F- must been released from the FPO3-- during the application of the pasta, e.g. by hydrolysis in the mouth. Solutions of Na2FPO3 seem to release an important amount of free F- ions, without addition of acid, and as a function of concentration, time and temperature. The hydrolysis of FPO3-- is pH-dependent and can be studied as a pseudo-first-order reaction. The dependence of the pH is found in the kinetic expression: -dC/dt = k. [H2PO3F] [H+] = k1.C, where C is the total formal concentration of all monofluorophosphate species at time t. The Arrhenius energy of activation is 16.42 +/- 0.1 Kcal/mole. The hydrolysis of monofluorophosphoric acid has already been studied before. In the present work additional F(-)-determinations are performed with a specific F(-)-selectrode, without any interference of the monofluorophosphate species, which was warned for by other authors. More recent investigation showed that in samples of controlled ionic strength little interference occurs, and phosphates in particular do not interfere. Fresh prepared solutions of Na2FPO3 were used at different pH and different temperature.(ABSTRACT TRUNCATED AT 250 WORDS)


The oligomeric state of CtBP determines its role as a transcriptional co-activator and co-repressor of Wingless targets.
C-terminal-binding protein (CtBP) is a well-characterized transcriptional co-repressor that requires homo-dimerization for its activity. CtBP can both repress and activate Wingless nuclear targets in Drosophila. Here, we examine the role of CtBP dimerization in these opposing processes. CtBP mutants that cannot dimerize are able to promote Wingless signalling, but are defective in repressing Wingless targets. To further test the role of dimerization in repression, the positions of basic and acidic residues that form inter-molecular salt bridges in the CtBP dimerization interface were swapped. These mutants cannot homo-dimerize and are compromised for repression. However, their co-expression leads to hetero-dimerization and consequent repression of Wingless targets. Our results support a model where CtBP is a gene-specific regulator of Wingless signalling, with some targets requiring CtBP dimers for inhibition while other targets utilize CtBP monomers for activation of their expression. Functional interactions between CtBP and Pygopus, a nuclear protein required for Wingless signalling, support a model where monomeric CtBP acts downstream of Pygopus in activating some Wingless targets.


Lupus-specific antibodies reveal an altered pattern of somatic mutation.
The F4 idiotype is a heavy chain determinant expressed almost exclusively on IgG immunoglobulins and is highly associated with specificity for double-stranded DNA. Since high-titered F4 expression is present predominantly in sera of patients with systemic lupus erythematosus (SLE), we thought F4+ IgG antibodies might constitute a useful subset of immunoglobulins in which to investigate lupus-specific alterations in variable (V) region gene expression or in the process of somatic mutation. This molecular analysis of F4+ B cell lines generated from lupus patients demonstrates that despite the strong association of F4 reactivity with specificity for native DNA, there is no apparent VH gene restriction. Furthermore, VH gene segments encoding these antibodies are also used in protective immune responses. An examination of the process of somatic mutation in F4+ antibodies showed no abnormality in frequency of somatic mutation nor in the distribution of mutations in complementarity-determining regions or framework regions. However, there was a decrease in targeting of mutations to putative mutational hot spots. This subtle difference in mutations present in these antibodies may reflect an intrinsic defect in mutational machinery or, more likely, altered state of B cell activation that affects the mutational process and perhaps also negative selection.


Activation of K+ channels induces apoptosis in vascular smooth muscle cells.
Intracellular K+ plays an important role in controlling the cytoplasmic ion homeostasis for maintaining cell volume and inhibiting apoptotic enzymes in the cytosol and nucleus. Cytoplasmic K+ concentration is mainly regulated by K+ uptake via Na+-K+-ATPase and K+ efflux through K+ channels in the plasma membrane. Carbonyl cyanide p-trifluoromethoxyphenylhydrazone (FCCP), a protonophore that dissipates the H+ gradient across the inner membrane of mitochondria, induces apoptosis in many cell types. In rat and human pulmonary artery smooth muscle cells (PASMC), FCCP opened the large-conductance, voltage- and Ca2+-sensitive KK+ (maxi-K) channels, increased K+ currents through maxi-K channels [I(K(Ca))], and induced apoptosis. Tetraethylammonia (1 mM) and iberiotoxin (100 nM) decreased I(K(Ca)) by blocking the sarcolemmal maxi-K channels and inhibited the FCCP-induced apoptosis in PASMC cultured in media containing serum and growth factors. Furthermore, inhibition of K+ efflux by raising extracellular K+ concentration from 5 to 40 mM also attenuated PASMC apoptosis induced by FCCP and the K+ ionophore valinomycin. These results suggest that FCCP-mediated apoptosis in PASMC is partially due to an increase of maxi-K channel activity. The resultant K+ loss through opened maxi-K channels may serve as a trigger for cell shrinkage and caspase activation, which are major characteristics of apoptosis in pulmonary vascular smooth muscle cells.


Survey for Salmonellae in porcine bile and cecums and on equipment surfaces in an Ohio abattoir.
Porcine bile samples and cecal swabbings and environmental swabbings collected from an abattoir in Columbus, Oh, were examined for salmonellae. Of 40 cecal swabbings, 6 were culture-positive for Salmonella choleraesuis and 2 of 25 swabbings of surfaces that were in contact with edible products were culture-positive for Salmonella typhimurium. All of 500 bile samples were Salmonella-free.


Interoceptive impairments do not lie at the heart of autism or alexithymia.
Quattrocki and Friston (2014) argued that abnormalities in interoception-the process of representing one's internal physiological states-could lie at the heart of autism, because of the critical role interoception plays in the ontogeny of social-affective processes. This proposal drew criticism from proponents of the alexithymia hypothesis, who argue that social-affective and underlying interoceptive impairments are not a feature of autism per se, but of alexithymia (a condition characterized by difficulties describing and identifying one's own emotions), which commonly co-occurs with autism. Despite the importance of this debate for our understanding of autism spectrum disorder (ASD), and of the role of interoceptive impairments in psychopathology, more generally, direct empirical evidence is scarce and inconsistent. Experiment 1 examined in a sample of 137 neurotypical (NT) individuals the association among autistic traits, alexithymia, and interoceptive accuracy (IA) on a standard heartbeat-tracking measure of IA. In Experiment 2, IA was assessed in 46 adults with ASD (27 of whom had clinically significant alexithymia) and 48 NT adults. Experiment 1 confirmed strong associations between autistic traits and alexithymia, but yielded no evidence to suggest that either was associated with interoceptive difficulties. Similarly, Experiment 2 provided no evidence for interoceptive impairments in autistic adults, irrespective of any co-occurring alexithymia. Bayesian analyses consistently supported the null hypothesis. The observations pose a significant challenge to notions that interoceptive impairments constitute a core feature of either ASD or alexithymia, at least as far as the direct perception of interoceptive signals is concerned. (PsycINFO Database Record


Bioinspired kirigami metasurfaces as assistive shoe grips.
Falls and subsequent complications are major contributors to morbidity and mortality, especially in older adults. Here, by taking inspiration from claws and scales found in nature, we show that buckling kirigami structures applied to footwear outsoles generate higher friction forces in the forefoot and transversally to the direction of movement. We identified optimal kirigami designs capable of modulating friction for a range of surfaces, including ice, by evaluating the performance of the dynamic kirigami outsoles through numerical simulations and in vitro friction testing, as well as via human-gait force-plate measurements. We anticipate that lightweight kirigami metasurfaces applied to footwear outsoles could help mitigate the risk of slips and falls in a range of environments.


Changes in appearance of silicone elastomers for maxillofacial prostheses as a result of aging.
The purpose of this study was to investigate the influence of certain defined variables on color and opacity of silicone elastomers for maxillofacial prostheses. Three condensation-type and five addition-type silicone elastomers were tested for their changes in color and opacity as a result of aging. The specimens were aged under a xenon light source, dry or wet, and in darkness, also dry (control specimens) or wet. The aging times were 24, 96, 168, 336, 504, 840, 1176, and 1512 hours. The changes in appearance were measured with a spectrophotometer. The condensation-type polymers increased in opacity in an aqueous environment, while the addition-type polymers, as a group, showed the smallest color changes. Although the addition-type polymers generally had a higher filler content than the condensation types, they had a lower opacity. However, because of their higher viscosity, the condensation-type polymers offer better possibilities for intrinsic coloring of the prosthesis. Under the experimental conditions studied, significant differences between the silicone elastomers regarding color and opacity changes were demonstrated. However, for a proper choice of material in a given case, these factors have to be related to biologic and mechanical properties of the material.


A universal protocol for photochemical covalent immobilization of intact carbohydrates for the preparation of carbohydrate microarrays.
A universal photochemical method has been established for the immobilization of intact carbohydrates and their analogues, and for the fabrication of carbohydrate microarrays. The method features the use of perfluorophenyl azide (PFPA)-modified substrates and the photochemical reaction of surface azido groups with printed carbohydrates. Various aldoses, ketoses, nonreducing sugars such as alditols, and their derivatives can be directly arrayed on the PFPA-modified chips. The lectin-recognition ability of arrayed mannose, glucose, and their oligo- and polysaccharides were confirmed using surface plasmon resonance imaging and laser-induced fluorescence imaging.


Systematic Reviews and Meta-analyses in Regional Anesthesia and Pain Medicine (Part II): Guidelines for Performing the Systematic Review.
In Part I of this series, we provide guidance for preparing a systematic review protocol. In this article, we highlight important steps and supplement with exemplars on conducting and reporting the results of a systematic review. We suggest how authors can manage protocol violations, multiplicity of outcomes and analyses, and heterogeneity. The quality (certainty) of the evidence and strength of recommendations should follow the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. It is our goal that Part II of this series provides valid guidance to authors and peer reviewers who conduct systematic reviews to adhere to important constructs of transparency, structure, reproducibility, and accountability. This will likely result in more rigorous systematic reviews being submitted for publication to the journals like Regional Anesthesia & Pain Medicine and Anesthesia & Analgesia.


Dispersal of Lycorma delicatula (Hemiptera: Fulgoridae) Nymphs Through Contiguous, Deciduous Forest.
Spotted lanternfly (Lycorma delicatula) is a recently introduced pest in the United States, where it threatens the wine, timber, and ornamentals industries. Knowledge of the dispersal ability of L. delicatula is key to developing effective management strategies for this invasive pest. We conducted a mark, release, re-sight study, marking nymphs with fluorescent powders and observing dispersal distances from a central release point at three time points over 7 d following release. To examine how dispersal patterns changed over the course of nymphal development, we repeated this process for each of L. delicatula's four instars. All releases were conducted in contiguous, deciduous forest, which is a widespread habitat type within L. delicatula's invaded range and a habitat where this pest may have negative ecological and economic impacts. We found that nymphs displayed clear directionality in their movement following release, apparently preferring to move uphill on the modest 6° grade at our release site. Most nymphs remained near the release location, while some moved tens of meters. The maximum displacement we observed was 65 m from the release point, 10 d after release. Nymphs were re-sighted singly and in small groups on a variety of trees, shrubs, and understory vegetation. All four instars had similar dispersal distances over time, though third instar nymphs moved farthest on average, with estimated median displacement of 16.9 m 7 d after release. Further studies are needed to provide additional information on what factors influence spotted lanternfly dispersal.


Genetic characterization of a MUT locus mutation discriminating heterogeneity in mut0 and mut- methylmalonic aciduria by interallelic complementation.
Genetic complementation of fibroblasts from patients with methylmalonic aciduria (MMA) defines a unique class of allelic mutations arising from mutations at the locus encoding the methylmalonyl coenzyme A (CoA) mutase apoenzyme. Various phenotypes of MMA have been delineated including complete absence of enzyme activity (mut0) and abnormal enzyme activity with an elevated Km for adenosylcobalamin (mut-). We describe genetic studies on a cell line (WG1130) from a patient with mut0 MMA which exhibited an unusual complementation phenotype, complementing with three of nine mut0 cell lines and four of five mut- cell lines. This suggests that interallelic complementation occurs between mutant alleles in WG1130 and subsets of alleles associated with both mut0 and mut- phenotypes. The methylmalonyl CoA mutase cDNA was cloned from WG1130 and found to contain a G354----A (Arg93----His) mutation. Gene transfer of this mutant clone into primary fibroblasts from patients with MMA confirms that this mutation expresses a mut0 phenotype when transferred into a mut0 cell line with low levels of mRNA but can contribute to apoenzyme function when transferred into mut cell lines which show correction with WG1130 by somatic cell complementation. These results point to further heterogeneity within both mut0 and mut- and may enable identification of mutations affecting discrete components of apoenzyme function.