Effects of disinfectants on Toxocara canis embryogenesis and larval establishment in mice tissues.
The objectives of this study were (i) to evaluate the effects of several different disinfectant solutions on embryonic development of Toxocara canis eggs and (ii) to investigate the potential infectivity of exposed eggs by assessing larval establishment in various tissues in a murine model. All the disinfectants tested were products routinely used in veterinary clinics, kennels, animal shelters and laboratories. Ova were obtained from gravid female T. canis uteri. Thirty samples containing 10,000 eggs were divided into five groups of six identical sample tubes per group. The treatments for the groups were as follows: Group H benzalconium chloride, Group A 70% ethanol, Group B 2-2.5% sodium hypochlorite solution, Group L 7.99% formaldehyde-based disinfectant and Group C tap water (controls). Samples were incubated at 27 ± 1°C and 80 ± 10% relative humidity. Embryonic development was evaluated on days +6, +9, +12, +15, +18, +21, +25, +28 and +36 of exposure by visual observation under light microscopy. Seventy percent ethanol degenerated all eggs within a few days and thus inhibited larval development. Sodium hypochlorite removed the external layer of the ova, but eggs harboured infective larvae for up to 2 weeks. Benzalconium chloride and formaldehyde-based disinfectants had no effect on T. canis embryogenesis according to comparison with control eggs (P > 0.05). Embryonated eggs from each of the six samples from Groups C, H and L were administered to mice as only these ova were considered viable based on in vitro trial. On day 30pi, those were euthanized and had their tissues were submitted to organ compression (brains) or acid-isolation technique (kidneys, lungs, livers and carcasses) for larval counting. The mean number of recovered larvae for Groups C, H and L were: 512.8, 393.7 and 477 respectively (P > 0.05). Larvae derived from Groups H and L eggs maintained their ability to migrate. However, larval establishment pattern differed from control. While certain disinfectants do negatively affect embryogenesis (70% ethanol) and reduce the integrity and durability (sodium hypochlorite) of infective T. canis eggs, others have no effect upon embryogenesis. Those eggs can still be a threat to human and animal health even after over a month of disinfectant exposure.


Selective Serotonin Reuptake Inhibitor Use and Hip Fracture Risk Among Patients on Hemodialysis.
Use of selective serotonin reuptake inhibitors (SSRIs) has been associated with hip fracture risk in the general population. This study examined this relationship among patients with kidney failure treated by hemodialysis, a unique high-risk subpopulation, within which the impact of SSRIs on hip fracture risk remains unexplored. Case-control study. Eligible cases of hip fracture among maintenance hemodialysis patients between January 1, 2009, and September 30, 2015, were identified using the US Renal Data System. Each case was matched on index date with 10 eligible controls. To be eligible, study participants needed to have more than 1 year of Medicare Parts A and B coverage and more than 3 years of Part D coverage. For a separate examination of new short-term SSRI exposure, we selected cases and controls with more than 18 months of Part D coverage and no prior antidepressant use for 1 year. During the 3-year Part D coverage period, use of SSRIs characterized as any (≥1 prescription filled), low, moderate, and high use (<20%, 20%-<80%, and≥80% of days covered by filled prescriptions, respectively). We selected cases using International Classification of Diseases, Ninth Revision codes 820.xx and 821.xx. In addition to 1 of these codes tied to a hospitalization, we required a corresponding surgical procedural code within 7 days of diagnosis. Conditional logistic regression to estimate unadjusted and multivariable-adjusted ORs and 95% CIs. We identified 4,912 cases and 49,120 controls. SSRI use was associated with increased hip fracture risk (adjusted OR, 1.25; 95% CI, 1.17-1.35). Risk for fracture was estimated for any, low, moderate, and high SSRI use: adjusted conditional ORs were 1.25 (95% CI, 1.17-1.35), 1.20 (95% CI, 1.08-1.32), 1.31 (95% CI, 1.18-1.43), and 1.26 (95% CI, 1.12-1.41), respectively. The association between hip fracture events and SSRI use was also seen in the examination of new short-term use (adjusted OR, 1.43; 95% CI, 1.23-1.67). Biomarkers of mineral bone disorder were not captured and accounted for in this analysis. We demonstrated an association between increased hip fracture risk and both long- and new short-term SSRI use. The stronger association with new short-term use may suggest an acute mechanism potentially related to falls.


A prospective case series on surgical treatment of circumferential and semi-circumferential defects due to peri-implantitis.
Different surgical treatment strategies for peri-implantitis with the use of graft material and membranes have been suggested without any longitudinal remarkable success rate. The present preliminary study was aimed to analyze a new clinical approach based on the disinfection of the implant connection, the disinfection of the implant surface and GBR approach in the treatment of circumferential and semi-circumferential bony defect resulting from peri-implantitis. Six consecutive patients were selected for the present study. After removal of factors that could potentially influence peri-implant pathology, the prosthetic rehabilitation was always removed and a full thickness flap was elevated to allow access to the peri-implant defect and the exposed implant surface. Once the defect was degranulated and the implant surface cleaned, a mixture (50:50) of autogenous bone and allograft was used. Guided bone regeneration technique using membranes was adopted and the flaps were closed for a submerged healing. Six months thereafter, a new re-opening procedure was performed and cleaned superstructures and crowns were repositioned. Patients were followed for one year thereafter and recalled for a customized oral hygiene every three months. Radiological and periodontal analysis was performed before surgery and every six months. The studied procedure was associated with a pronounced increase in REC and CAL with stable peri-implant conditions at 6 and 12 months. PI, BOP and PD values were significantly reduced both at 6 and 12 months. At 12 months, a mean PD gain of 4.5 mm and a bone loss reduction of 5.1 mm was obtained. Within the limitation of the present preliminary study, the proposed technique might represent a promising result for treatment of circumferential and semi-circumferential bone defects around implants affected by peri-implantitis.


Differential renal function estimation using computerized tomography based renal parenchymal volume measurement.
Nuclear renal scan is currently the gold standard imaging study to determine differential renal function. We propose helical computerized tomography as a more efficient way to gain renal function information. Renal parenchymal volume is measured and percent total renal volume is used as a surrogate marker for differential renal function. Computerized tomography and diuretic enhanced nuclear renal scan were performed in 33 patients with chronic obstruction. Computerized tomography was contrast enhanced in 23 cases and nonenhanced in 10. Diagnoses included ureteropelvic junction obstruction, ureteral stricture and extrinsic compression. Using semiautomated boundary delineation with manual editing method the parenchymal volume of each kidney was measured and percent renal volume was calculated. Percent renal volume was compared with percent renal function, as determined by nuclear renal scan. Correlations between the 2 measures were evaluated using the Spearman or Pearson coefficient. Strong correlations were observed between percent renal function and percent renal volume in all cases (r = 0.90, p <0.001), including the enhanced (r = 0.87, p <0.001) and nonenhanced (r = 0.95, p <0.001) groups. Moderately strong correlations were noted in the less than 40% (r = 0.76, p <0.001) and less than 30% (r = 0.64, p = 0.015) renal function subgroups. Differential renal volume measured from computerized tomography strongly correlates with differential renal function on nuclear renal scan for normal and chronically obstructed kidneys. Computerized tomography may serve as a single radiological diagnostic study for anatomical and functional assessment in patients in whom a poorly functioning kidney is suspected.


Microbiology of the Upper and Lower Airways in Pediatric Cystic Fibrosis Patients.
Objective To evaluate the microbiology of the upper and lower airways in pediatric cystic fibrosis (CF) patients who underwent sinus surgery. Study Design Retrospective case series with chart review. Setting Tertiary care children's hospital. Subjects and Methods A total of 201 paired sinus and pulmonary cultures from 105 CF patients were identified between 1996 and 2014. Demographics and culture results were analyzed. Results The mean age of patients was 11.2 ± 5.4 years (range, 1-27 years), and approximately one-half were female. Methicillin-sensitive Staphylococcus aureus was the most common pathogen overall. A significantly higher prevalence of Pseudomonas aeruginosa (32% for pulmonary and 37% for sinus cultures) was observed in older patients versus younger patients ( P < .001). There was low to moderate agreement between sinus and pulmonary cultures (Kappa statistic range, 0.03-0.56). The prevalence of methicillin-resistant S aureus (MRSA) increased significantly for lower respiratory tract culture (from 5% to 16%) and sinus culture (from 5% to 27%) between 1996-2004 and 2010-2014 ( P = .016 and P < .001, respectively). The prevalence of positive sinus cultures increased from 40% to 85% between 1996-2004 and 2010-2014 ( P = .018). Patients with pulmonary MRSA were more likely to be coinfected with pulmonary P aeruginosa (risk ratio, 2.4; 95% CI, 1.2-4.8; P = .015) or Aspergillus fumigatus (risk ratio, 2.2; 95% CI, 1.2-4.8; P = .035). Conclusions There is low to moderate correlation between pulmonary and sinus pathogens in CF patients. This is important to consider when treating infections. The prevalence of MRSA in sinus cultures has increased over time and warrants further investigation.


Systems Biology Analysis of Heterocellular Signaling.
Tissues comprise multiple heterotypic cell types (e.g., epithelial, mesenchymal, and immune cells). Communication between heterotypic cell types is essential for biological cohesion and is frequently dysregulated in disease. Despite the importance of heterocellular communication, most systems biology techniques do not report cell-specific signaling data from mixtures of cells. As a result, our existing perspective of cellular behavior under-represents the influence of heterocellular signaling. Recent technical advances now permit the resolution of systems-level cell-specific signaling data. This review discusses how new physical, spatial, and isotopic resolving methods are facilitating unique systems biology studies of heterocellular communication.


Concomitant TP53 Mutation Confers Worse Prognosis in EGFR-Mutated Non-Small Cell Lung Cancer Patients Treated with TKIs.
Non-small cell lung cancer (NSCLC) is the primary cause of cancer-related deaths worldwide. Epidermal Growth Factor Receptor (EGFR)-mutated patients usually benefit from TKIs treatment, but a significant portion show unresponsiveness due to primary resistance mechanisms. We investigated the role of TP53 mutations in predicting survival and response to EGFR-TKIs in EGFR-mutated NSCLC patients, to confirm, on an independent case series, our previous results. An independent retrospective cohort study was conducted, on a case series of 136 EGFR-mutated NSCLC patients receiving first or second generation TKIs as a first line therapy, and a smaller fraction of patients who acquired the T790M resistance mutation and were treated with third generation TKIs in the second or further line of treatment. TP53 mutations were evaluated in relation to disease control rate (DCR), objective response rate (ORR), progression-free survival (PFS) and overall survival (OS) of the patients. Forty-two patients (30.9%) showed a TP53 mutation. Considered together, TP53 mutations had no significant impact on time-to-event endpoints. Considering the different TP53 mutations separately, exon 8 mutations confirmed their negative effect on PFS (HR 3.16, 95% 1.59-6.28, p = 0.001). In patients who developed the T790M resistance mutation, treated with third generation TKIs, the TP53 exon 8 mutations predicted worse PFS (even though not statistically significant), and OS (HR 4.86, 95% CI: 1.25-18.90, p = 0.023). TP53 exon 8 mutations confirmed their negative prognostic impact in patients treated with first and second generation TKIs and demonstrated a role in affecting clinical outcome in patients treated with third generation TKIs.


Inhibitory Receptors and Pathways of Lymphocytes: The Role of PD-1 in Treg Development and Their Involvement in Autoimmunity Onset and Cancer Progression.
Regulatory T (Treg) cells represent a subpopulation of suppressor CD4+ T cells critically involved in the establishment of peripheral tolerance through the inhibition of effector T (Teff) cells and the suppression of the immune-mediated tissue destruction toward self-antigens. Treg generation, their suppressive properties and also Treg-Teff cell interactions could be modulated at least in part by programmed cell death-1 (PD-1) expression on their surface and through binding between PD-1 and programmed cell death ligand-1 (PD-L1). Defects involving PD-1 and Tregs can lead to the development of pathological conditions, including autoimmune disorders or promote cancer progression by favoring tumor evasion from the host immune response. At the same time, PD-1 and Tregs could represent attractive targets for treatment, as demonstrated by the therapeutic blockade of PD-L1 applied for the management of different cancer conditions in humans. In the present Review, we focus specifically the role of PD-1/PD-L1 on Treg development and activity.


Esrrg functions in early branch generation of the ureteric bud and is essential for normal development of the renal papilla.
Congenital anomalies of the kidney and urinary tract (CAKUTs) are common disorders of human development affecting the renal parechyma, renal pelvis, ureter, bladder and urethra; they show evidence of shared genetic aetiology, although the molecular basis of this remains unknown in the majority of cases. Breakpoint mapping of a de novo, apparently balanced, reciprocal translocation associated with bilateral renal agenesis has implicated the gene encoding the nuclear steroid hormone receptor ESRRG as a candidate gene for CAKUT. Here we show that the Esrrg protein is detected throughout early ureteric ducts as cytoplasmic/sub-membranous staining; with nuclear localization seen in developing nephrons. In 14.5-16.5 dpc (days post-conception) mouse embryos, Esrrg localizes to the subset of ductal tissue within the kidney, liver and lung. The renal ductal expression becomes localized to renal papilla by 18.5 dpc. Perturbation of function was performed in embryonic mouse kidney culture using pooled siRNA to induce knock-down and a specific small-molecule agonist to induce aberrant activation of Esrrg. Both resulted in severe abnormality of early branching events of the ureteric duct. Mouse embryos with a targeted inactivation of Esrrg on both alleles (Esrrg(-/-)) showed agenesis of the renal papilla but normal development of the cortex and remaining medulla. Taken together, these results suggest that Esrrg is required for early branching events of the ureteric duct that occur prior to the onset of nephrogenesis. These findings confirm ESRRG as a strong candidate gene for CAKUT.


Stress-induced multiple organ damage in rats is ameliorated by the antioxidant and anxiolytic effects of regular exercise.
Our aim was to investigate the effects of moderate load, regular swimming exercise on stress-induced anxiety, and associated oxidative organ injury. Male Sprague-Dawley rats (n = 48) were either kept sedentary or submitted to swimming exercise for 8 weeks. Rats were then divided as non-stressed, acute stress, and chronic stress groups. After acute or chronic stress (electric foot shocks) applications, rats were placed on a holeboard and the exploratory behavior was recorded to assess the anxiety. Rats were decapitated after the stress application. Acute and chronic stress induction led to increased serum cortisol levels as compared to non-stressed groups. Plasma aspartate aminotransferase levels that were elevated in sedentary rats with both stress exposures were lower in trained rats. Malondialdehyde levels and myeloperoxidase activity were increased in the cardiac muscle, liver, stomach, and brain of the stressed rats with a concomitant reduction in the glutathione levels, while stress-induced changes in malondialdehyde, myeloperoxidase, and glutathione levels were reversed in the trained animals. Exercise, which led to increased malondialdehyde and reduced glutathione levels in the skeletal muscle of the non-stressed rats, also protected against stress-induced oxidative damage. Regular exercise with its anxiolytic and antioxidant effects ameliorates stress-induced oxidative organ damage by a neutrophil-dependent mechanism.


Pneumothorax and pneumomediastinum in patients with COVID-19: A retrospective study from tertiary care institute in India.
COVID-19 is associated with rarer extra-parenchymal manifestations, namely pneumothorax (PTX) and pneumomediastinum (PM) leading to complications and increased mortality. The study aims to describe the prevalence, risk factors for mortality, radiological characteristics and outcome of PTX/PM in patients admitted with COVID-19. This was a retrospective, single-centre, observational study in patients with confirmed COVID-19 presenting with non-iatrogenic PTX/PM from April 2020 to May 2021. Details pertaining to demographics, presentation, radiological characteristics, management and outcome were collected. Cases were classified into spontaneous and barotraumatic PTX/PM and a between-group comparison was performed using Chi-square and t-test. A total of 45 cases (mean age: 53.2 years, 82% males) out of 8,294 confirmed COVID-19 patients developed PTX/PM, the calculated incidence being 0.54%. 29 cases had spontaneous PTX/PM and the remaining 17 cases were attributed to barotrauma. The most common comorbidities were diabetes-mellitus (65.3%) and hypertension (42.3%). The majority of the cases had large PTX (62.1%) with tension in 8 cases (27.5%). There were predominant right-sided pneumothoraces and five were diagnosed with bronchopleural fistula. 37.7% of cases had associated subcutaneous emphysema. The median duration of PTX/PM from symptom onset was delayed at 22.5 and 17.6 days respectively. The mean CT severity score (CTSS) was 20.5 (± 4.9) with fibrosis (53.8%), bronchiectatic changes (50%) and cystic-cavitary changes (23%). There was no statistically significant difference between the spontaneous and barotrauma cohort. 71% of cases died and the majority belonged to the barotrauma cohort. It is imperative to consider the possibility of PTX/PM in patients having COVID-19, especially in those with deterioration in the disease course, both in spontaneously breathing and mechanically ventilated patients. These patients may also have a high incidence of death, reflecting the gravity of COVID-19.


Prevalence and predictors of alcohol and drug use among secondary school students in Botswana: a cross-sectional study.
Alcohol and illicit drug use has been recognized as a growing problem among adolescents in Botswana. Little is known about factors affecting alcohol and drug use among Botswana's secondary school students. To aid the design and implementation of effective public health interventions, we sought to determine the prevalence of alcohol and drug use in secondary school students in urban and peri-urban areas of Botswana, and to evaluate risk and protective factors for substance use. We performed a 72-item cross-sectional survey of students in 17 public secondary schools in Gaborone, Lobatse, Molepolole and Mochudi, Botswana. The World Health Organization's (WHO) Alcohol Use Disorder Identification Test (AUDIT) was used to define hazardous drinking behavior. Using Jessor's Problem Behavior Theory (PBT) as our conceptual framework, we culturally-adapted items from previously validated tools to measure risk and protective factors for alcohol and drug use. Between-group differences of risk and protective factors were compared using univariate binomial and multinomial-ordinal logit analysis. Relative risks of alcohol and drug use by demographic, high risks and low protections were calculated. Multivariate ordinal-multinomial cumulative logit analysis, multivariate nominal-multinomial logit analysis, and binominal logit analysis were used to build models illustrating the relationship between risk and protective factors and student alcohol and illicit drug use. Clustered data was adjusted for in all analyses using Generalized Estimating Equations (GEE) methods. Of the 1936 students surveyed, 816 (42.1%) reported alcohol use, and 434 (22.4%) met criteria for hazardous alcohol use. Illicit drug use was reported by 324 students (16.7%), with motokwane (marijuana) being the most commonly used drug. Risk factors more strongly associated with alcohol and drug use were reported alcohol availability, individual and social vulnerability factors, and poor peer modeling. Individual and social controls protections appear to mitigate risk of student alcohol and drug use. Alcohol and illicit drug use is prevalent among secondary school students in Botswana. Our data suggest that interventions that reduce the availability of alcohol and drugs and that build greater support networks for adolescents may be most helpful in decreasing alcohol and drug use among secondary school students in Botswana.


Reduction of plasma gelsolin levels correlates with development of multiple organ dysfunction syndrome and fatal outcome in burn patients.
Depletion of the circulating actin-binding protein, plasma gelsolin (pGSN) has been described in critically ill surgical patients. We hypothesized that the extent of pGSN reduction might correlate with different outcome of burn patients. The study was performed to evaluate the prognostic implications of pGSN levels on the development of multiple organ dysfunction syndrome (MODS) and fatal outcome in a group of severely burn patients. 95 patients were included, and they were divided into three groups with different burn area: group I (n = 33), group II (n = 32) and group III (n = 30). According to whether there was development of MODS or not, patients were divided into MODS group (n = 28) and none-MODS group (n = 67); then the patients with MODS were further divided into non-survivor group (n = 17) and survivor group (n = 11). The peripheral blood samples were collected on postburn days (PBD) 1, 3, 7, 14, and 21. The levels of pGSN were determined and T cells were procured from the blood. The contents of cytokines (IL-2, IL-4 and IFN-γ) released by T cells were also measured. The related factors of prognosis were analyzed by using multivariate logistic regression analysis. The results showed that pGSN concentrations, as well as the levels of IL-2 and IFN-γ, decreased markedly on PBD 1-21, whereas, the levels of IL-4 increased markedly in all burn groups as compared with normal controls (P<0.05 or P<0.01), and there were obviously differences between group I and group III (P<0.05 or P<0.01). The similar results were found in MODS patients and the non-survivor group as compared with those without MODS and the survival group on days 3-21 postburn (P<0.05 or P<0.01). Moreover, as the pGSN levels decreased, the incidence of septic complication as well as MODS remarkably increased. pGSN levels appear to be an early prognostic marker in patients suffering from major burns.


Antidiabetic and antioxidant activities of Toddalia asiatica (L.) Lam. leaves in streptozotocin induced diabetic rats.
The leaves of Toddalia asiatica (L.) Lam. have been utilized traditionally for the cure of diabetes. The present study was aimed to assess the antidiabetic and antioxidant effects of T. asiatica leaves in Streptozotocin (STZ) induced diabetic rats. The phytochemical screening, total phenolic content, HPLC analysis, acute toxicity study and oral glucose tolerance test were carried out. Glucose lowering effect of the hexane, ethyl acetate and methanol extracts of T. asiatica leaves was studied in STZ-induced diabetic rats. The antidiabetic and antioxidant activities were studied for the ethyl acetate extract. The effects of extracts on blood glucose, body weight, plasma insulin, total protein, liver glycogen, plasma enzymes (SGOT, SGPT and ALP) and activities of SOD, CAT and GPx were analyzed. T. asiatica leaves ethyl acetate extract (TALEe) showed highly significant blood glucose lowering effect. Phytochemical evaluation of TALEe showed the presence of alkaloids, terpenoids, cumarins, flavonoids and phenolic compounds. The total phenolic content of TALEe was 126 mg of gallic acid equivalents/g extract. HPLC analysis revealed the presence of flindersine and ulopterol. Acute toxicity study of TALEe revealed no death or toxicity. The oral glucose tolerance test showed lowered area under curve (AUC(glucose)) values in TALEe treated rats. After treatment with TALEe (250 and 500 mg/kg) for 28 days there was a significant decrease in blood glucose, plasma enzymes (SGOT, SGPT and ALP) and significant increase in body weight, total protein, serum insulin and liver glycogen levels in treated diabetic rats. The activities of antioxidant enzymes SOD, CAT and GPx were reversed to near normal in treated diabetic rats. Histopathology of pancreas in TALEe treated groups showed regeneration of β-cells. The results of the experiments showed that TALEe exerted significant antidiabetic and antioxidant effects in STZ-induced diabetic rats justifying its traditional use.


Cell movements, neuronal organisation and gene expression in hindbrains lacking morphological boundaries.
Rhombomeres are segmental units of the hindbrain that are separated from each other by a specialised zone of boundary cells. Retinoic acid application to a recently segmented hindbrain leads to disappearance of posterior rhombomere boundaries. Boundary loss is preceded by changes in segmental expression of Krox-20 and Cek-8 and followed by alterations in Hox gene expression. The characteristic morphology of boundary cells, their expression of follistatin and the periodic accumulation of axons normally associated with boundaries are all lost. In the absence of boundaries, we detect no change in anteroposterior dispersal of precursor cells and, in most cases, no substantial cell mixing between former rhombomeric units. This is consistent with the idea that lineage restriction can be maintained by processes other than a mechanical barrier composed of boundary cells. Much of the early organisation of the motor nuclei appears normal despite the loss of boundaries and altered Hox expression.


Precision Oncology: 2023 in Review.
This article presents a review of recent major advances in precision oncology and the future implications of these advances, specifying the iterative progress achieved from the end of 2022 through 2023. We discuss the different classes of precision oncology drugs and associated biomarkers as well as the improvements in clinical trial design that have enabled the efficient testing of these drugs.


Expression of bone morphogenetic proteins in human metastatic prostate and breast cancer.
To analyze the expression of bone morphogenetic proteins (BMPs) in prostate and breast cancers with established metastasis in bone, where prostate cancer causes osteoblastic metastases, and breast cancer osteolytic metastases. Primary tumor specimens from 20 patients with prostate cancer and 15 with breast cancer were studied for BMP-2/4, -3, -5, -6 and -7 immunohistochemistry. All patients had multiple bone metastases proven by bone scan. We also examined BMPs expression in normal prostate and breast tissues. BMPs expression was compared with clinicopathological and biochemical parameters. Cytoplasmic BMPs immunostaining was observed in both prostate cancer and normal prostate tissue. Expression of BMP-2/4, -5, -6, and -7 proteins was detected in all normal prostate samples, with the predominance of BMP-2/4 (87.8-/+11.4% positive cells) and BMP-7 (94.6-/+0.9% positive cells). In prostate cancer tissues, we found variable expression of all BMPs. BMP-2/4 (83-/+11.6% positive cells) was predominantly expressed in prostate carcinoma, whereas the expression of BMP-7 (24.3-/+19.2% positive cells) was significantly lower than in the normal prostate. In all breast cancers tissues, we found nuclear staining only for BMP-7. In normal breast tissue, the BMP expression was not detectable. The percent of BMP-7 positive cells in breast cancer (86.4-/+7.3%) was higher than in prostatic cancer. Comparing BMP expression levels and clinicopathological parameters, we did not find statistical difference, except for serum alkaline phosphatase, which was significantly higher in patients with prostate cancer. The expression of BMPs differs between prostate and breast cancer cells. Identifying the BMP proteins in cancers may be useful for monitoring the tumor status with reference to metastases.


Facing extremes: archaeal surface-layer (glyco)proteins.
Archaea are best known in their capacities as extremophiles, i.e. micro-organisms able to thrive in some of the most drastic environments on Earth. The protein-based surface layer that envelopes many archaeal strains must thus correctly assemble and maintain its structural integrity in the face of the physical challenges associated with, for instance, life in high salinity, at elevated temperatures or in acidic surroundings. Study of archaeal surface-layer (glyco)proteins has thus offered insight into the strategies employed by these proteins to survive direct contact with extreme environments, yet has also served to elucidate other aspects of archaeal protein biosynthesis, including glycosylation, lipid modification and protein export. In this mini-review, recent advances in the study of archaeal surface-layer (glyco)proteins are discussed.


High morbidity during treatment and residual pulmonary disability in pulmonary tuberculosis: under-recognised phenomena.
In pulmonary tuberculosis (PTB), morbidity during treatment and residual pulmonary disability can be under-estimated. Among adults with smear-positive PTB at an outpatient clinic in Papua, Indonesia, we assessed morbidity at baseline and during treatment, and 6-month residual disability, by measuring functional capacity (six-minute walk test [6MWT] and pulmonary function), quality of life (St George's Respiratory Questionnaire [SGRQ]) and Adverse Events ([AE]: new symptoms not present at outset). Results were compared with findings in locally-recruited volunteers. 200 PTB patients and 40 volunteers were enrolled. 6WMT was 497m (interquartile range 460-529) in controls versus 408m (IQR 346-450) in PTB patients at baseline (p<0.0001) and 470m (IQR 418-515) in PTB patients after 6 months (p=0.02 versus controls). SGRQ total score was 0 units (IQR 0-2.9) in controls, versus 36.9 (27.4-52.8) in PTB patients at baseline (p<0.0001) and 4.3 (1.7-8.8) by 6 months (p<0.0001). Mean percentage of predicted FEV1 was 92% (standard deviation 19.9) in controls, versus 63% (19.4) in PTB patients at baseline (p<0.0001) and 71% (17.5) by 6 months (p<0.0001). After 6 months, 27% of TB patients still had at least moderate-severe pulmonary function impairment, and 57% still had respiratory symptoms, despite most achieving 'successful' treatment outcomes, and reporting good quality of life. More-advanced disease at baseline (longer illness duration, worse baseline X-ray) and HIV positivity predicted residual disability. AE at any time during treatment were common: itch 59%, arthralgia 58%, headache 40%, nausea 33%, vomiting 16%. We found high 6-month residual pulmonary disability and high AE rates. Although PTB treatment is highly successful, the extent of morbidity during treatment and residual impairment could be overlooked if not specifically sought. Calculations of PTB-related burden of disease should acknowledge that TB-related morbidity does not stop at 6 months. Early case detection and treatment are key in minimising residual impairment.


Epigenetics of chronic inflammatory diseases.
Chronic, noncommunicable, and inflammation-associated diseases remain the largest cause of morbidity and mortality globally and within the United States. This is mainly due to our limited understanding of the molecular mechanisms that underlie these complex pathologies. The available evidence indicates that studies of epigenetics (traditionally defined as the heritable changes to gene expression that are independent of changes to DNA) are significantly advancing our knowledge of these inflammatory conditions. This review will focus on epigenetic studies of three diseases, that are among the most burdensome globally: cardiovascular disease, the number one cause of deaths worldwide, type 2 diabetes and, Alzheimer's disease. The current status of epigenetic research, including the ability to predict disease risk, and key pathophysiological defects are discussed. The significance of defining the contribution of epigenetic defects to nonresolving inflammation and aging, each associated with these diseases, is highlighted, as these are likely to provide new insights into inflammatory disease pathogenesis.


Advances and analytical applications in chemiluminescence coupled to capillary electrophoresis.
The present review presents the state of the art of the developments, key strategies and analytical applications of chemiluminescence detection coupled to CE (CE-CL). Different parts considering the most common CL systems have been included, such as the tris(2,2'-bipyridine)ruthenium(II) system, the luminol and derivatives reaction, the peroxyoxalate CL or direct oxidations. New advances in homemade configurations and applications in different fields such as clinical, pharmaceutical, environmental and food analysis have been included. The focus is on studies which appeared from 2000 to the end of 2009.


Combined chemotherapy and external beam radiation for stage IE and IIE natural killer T-cell lymphoma of nasal cavity.
To evaluate the outcome of CHOP chemotherapy and radiotherapy in Stage IE and IIE nasal natural killer (NK)/T-cell lymphoma, 53 patients with stage IE and IIE nasal NK/T-cell lymphoma were studied. By the Ann Arbor Lymphoma Staging Classification, 41 patients (77%) had Stage IE disease and 12 patients (23%) had Stage IIE disease. All patients were treated curatively using chemotherapy, followed by radiotherapy. Chemotherapy consisted of up to six cycles of the standard CHOP based regimen. The median radiation dose to the tumor bed was 45 Gy for all patients. The median follow-up for all 39 surviving patients was 30.2 months (range, 6 - 104 months). Twenty-six patients had complete response after chemotherapy, and all patients who completed first line chemotherapy achieved complete response after radiotherapy. The 2-year overall survival and progression-free survival rates were 75.6% and 61.8%, respectively. Multivariate analysis revealed that perforation as a presenting symptom, elevated pretreatment serum lactate dehydrogenase level, and ECOG performance status >or=2 were significant independent prognostic factors for this group of patients. Combined chemotherapy followed by involved field radiation produced suboptimal outcome for patients with early stage nasal NK/T-cell lymphoma. Further investigations, preferably prospective clinical trials, for more efficacious treatment strategies are needed to improve the treatment outcome of this malignancy.


A real-world assessment of healthcare costs associated with agitation in Alzheimer's dementia.
To describe and compare clinical characteristics, healthcare costs, and institutionalization/mortality outcomes among patients with and without agitation associated with Alzheimer's dementia (AAD). Data from the Reliant Medical Group database (01/01/2016-03/31/2020) were used, including claims, electronic medical records, and clinical information/physician notes abstracted from medical charts. Patients aged ≥55 years with Alzheimer's dementia (AD) were observed during a randomly selected 12-month study period after AD diagnosis. Using information recorded in medical charts, patients were classified into cohorts based on experiencing (agitation cohort) and not experiencing (no agitation cohort) agitated behaviors during the study period. Entropy balancing was used to create reweighted cohorts with similar characteristics. Study outcomes (patient demographic and clinical characteristics, treatments received, healthcare costs, institutionalization and death events) were compared between cohorts; agitation characteristics were described for the agitation cohort only. Among 711 patients included in the study, 240 were classified in the agitation cohort and 471 in the no agitation cohort. After reweighting, several comorbidities were more frequently observed in the agitation versus no agitation cohort, including infection, depression, and altered mental status. Use of antidepressants, anticonvulsants, antipsychotics, and antianxiety medications was more common in the agitation versus no agitation cohort. Common agitated behaviors included hitting (20.8%), pacing/aimless wandering (17.5%), and cursing/verbal aggression (15.0%). Total all-cause healthcare costs were $4,287 per-patient-per-year higher in the agitation cohort versus no agitation cohort (P = 0.04), driven by higher inpatient costs. Death was more common and time to death and institutionalization were shorter in the agitation versus no agitation cohort. Results may not be generalizable to the US population with AD. Among patients with AD, agitation was associated with shorter time to death/institutionalization and increased comorbidities, medication use, and healthcare costs, highlighting the additional clinical and economic burden that agitation poses to patients and the healthcare system.


Utilization of transgenic models in the evaluation of osteogenic differentiation of embryonic stem cells.
Previous studies reported that embryonic stem cells (ESCs) can be induced to differentiate into cells showing a mature osteoblastic phenotype by culturing them under osteo-inductive conditions. It is probable that osteogenic differentiation requires that ESCs undergo differentiation through an intermediary step involving a mesenchymal lineage precursor. Based on our previous studies indicating that adult mesenchymal progenitor cells express α-smooth muscle actin (αSMA), we have generated ESCs from transgenic mice in which an αSMA promoter directs the expression of red fluorescent protein (RFP) to mesenchymal progenitor cells. To track the transition of ESC-derived MSCs into mature osteoblasts, we have utilized a bone-specific fragment of rat type I collagen promoter driving green fluorescent protein (Col2.3GFP). Following osteogenic induction in ESCs, we have observed expression of alkaline phosphatase (ALP) and subsequent mineralization as detected by von Kossa staining. After 1 week of osteogenic induction, ESCs begin to express αSMARFP. This expression was localized to the peripheral area encircling a typical ESC colony. Nevertheless, these αSMARFP positive cells did not show activation of the Col2.3GFP promoter, even after 7 weeks of osteogenic differentiation in vitro. In contrast, Col2.3GFP expression was detected in vivo, in mineralized areas following teratoma formation. Our results indicate that detection of ALP activity and mineralization of ESCs cultured under osteogenic conditions is not sufficient to demonstrate osteogenic maturation. Our study indicates the utility of the promoter-visual transgene approach to assess the commitment and differentiation of ESCs into the osteoblast lineage.


[EMI net--electronic medical record sharing in local community for home care medicine].
An electronic medical information network (EMI net) includes patient records from more than 40 facilities in Matsudo City and it is now used especially to improve the communication between doctors and nurses who visit patients' homes. This fact suggests the importance of a medical information sharing system in a local area for home care medicine. An infrastructure connecting facilities to share the database of the patient records is essential for home care medicine performed by a multidisciplinary team beyond one medical facility.


Nosema maddoxi sp. nov. (Microsporidia, Nosematidae), a Widespread Pathogen of the Green Stink Bug Chinavia hilaris (Say) and the Brown Marmorated Stink Bug Halyomorpha halys (Stål).
We describe a unique microsporidian species that infects the green stink bug, Chinavia hilaris; the brown marmorated stink bug, Halyomorpha halys; the brown stink bug, Euschistus servus; and the dusky stink bug, Euschistus tristigmus. All life stages are unikaryotic, but analysis of the consensus small subunit region of the ribosomal gene places this microsporidium in the genus Nosema, which historically has been characterized by diplokaryotic life stages. It is also characterized by having the reversed arrangement of the ribosomal gene (LSU -ITS- SSU) found in species within the "true Nosema" clade. This microsporidium is apparently Holarctic in distribution. It is present in H. halys both where it is native in Asia and where it is invasive in North America, as well as in samples of North American native C. hilaris collected prior to the introduction of H. halys from Asia. Prevalence in H. halys from mid-Atlantic, North America in 2015-2016 ranged from 0.0% to 28.3%, while prevalence in C. hilaris collected in Illinois in 1970-1972 ranged from 14.3% to 58.8%. Oral infectivity and pathogenicity were confirmed in H. halys and C. hilaris. Morphological, ultrastructural, and ecological features of the microsporidium, together with a molecular phylogeny, establish a new species named Nosema maddoxi sp. nov.


Memory nearly on a spring: a mean first passage time approach to memory lifetimes.
We study memory lifetimes in a perceptron-based framework with binary synapses, using the mean first passage time for the perceptron's total input to fall below firing threshold to define memory lifetimes. Working with the simplest memory-related model of synaptic plasticity, we may obtain exact results for memory lifetimes or, working in the continuum limit, good analytical approximations that afford either much qualitative insight or extremely good quantitative agreement. In one particular limit, we find that memory dynamics reduce to the well-understood Ornstein-Uhlenbeck process. We show that asymptotically, the lifetimes of memories grow logarithmically in the number of synapses when the perceptron's firing threshold is zero, reproducing standard results from signal-to-noise ratio analyses. However, this is only an asymptotically valid result, and we show that extending its application outside the range of its validity leads to a massive overestimate of the minimum number of synapses required for successful memory encoding. In the case that the perceptron's firing threshold is positive, we find the remarkable result that memory lifetimes are strictly bounded from above. Asymptotically, the dependence of memory lifetimes on the number of synapses drops out entirely, and this asymptotic result provides a strict upper bound on memory lifetimes away from this asymptotic regime. The classic logarithmic growth of memory lifetimes in the simplest, palimpsest memories is therefore untypical and nongeneric: memory lifetimes are typically strictly bounded from above.


Enhancing the value of digital health tools for mental health help-seeking in Canadian transitional aged youth during the pandemic: Qualitative study.
While the COVID-19 pandemic has greatly exacerbated the mental health challenges of transition-aged youth (TAY) between 17 and 29 years old, it has also led to the rapid adoption of digital tools for mental health help-seeking and treatment. However, to date, there has been limited work focusing on how this shift has impacted perceptions, needs and challenges of this population in using digital tools. The current study aims to understand their perspectives on mental health help-seeking during the pandemic and emerging issues related to digital tools (e.g., digital health equity, inclusivity). A total of 16 TAY were invited from three post-secondary institutions in the Greater Toronto Area. A total of two streams of focus groups were held and participants were invited to share their perceptions, needs and experiences. Five main themes were identified: 1) Helpfulness of a centralized resource encompassing a variety of diverse mental health supports help-seeking; 2) The impact of the shift to online mental health support on the use of informal supports; 3) Digital tool affordability and availability; 4) Importance of inclusivity for digital tools; and 5) Need for additional support for mental health seeking and digital tool navigation. Future work should examine how these needs can be addressed through new and existing digital mental health help-seeking tools for TAY.


Sonographic findings of trisomy 18 in the second trimester of pregnancy.
The purpose of this study was to examine the sonographic findings in fetuses with trisomy 18 in the second trimester of pregnancy. A retrospective review of the cytogenetic laboratory databases at 6 tertiary referral centers identified all cases of trisomy 18. The prenatal sonographic studies in fetuses at 15 to 21 weeks' gestation, done before invasive testing for the karyotype, were reviewed for anatomic and biometric findings. We defined abnormal fetal biometric findings as a biometric measurement (biparietal diameter, abdominal circumference, or femur length) below the fifth percentile in the second trimester. Of 98 fetuses with trisomy 18, 95 (97%) were detected sonographically; an anomaly was found in 92 (94%). A biometric measurement below the fifth percentile was noted in 50 (51%). Cardiac (63%) and central nervous system (34%) anomalies were most frequently detected. Although choroid plexus cysts were commonly seen, no fetuses with trisomy 18 and isolated choroid plexus cysts were found. Targeted sonography identified abnormal fetal anatomy or abnormal biometric findings in 97% of fetuses with trisomy 18 in the second trimester. A biometric measurement below the fifth percentile was noted in half of the cases in the second trimester.


Role of the central amygdala in modulating the pituitary-adrenocortical and clinical responses in experimental herpes simplex virus-1 encephalitis.
The amygdala is known to regulate neuroendocrine and behavioral responses to a variety of stimuli. Herpes simplex virus-1 (HSV-1) is the common cause of viral encephalitis, manifested by hypothalamic-pituitary-adrenal (HPA) axis activation, fever, hypermotor activity and aggression. We examined here the role of the central amygdala (cAMG) in regulating the HPA axis function, febrile and behavioral responses to HSV-1 infection in rats. Bilateral electrolytic lesions were performed in the cAMG. HSV-1 encephalitis was induced by intracerebroventricular (ICV) inoculation of purified virions. Motor activity and body temperature were examined by a biotelemetric system. ICV inoculation of HSV-1 caused a marked time-dependent increase in serum corticotropin (ACTH) and corticosterone at 4 and 24 h post-infection. These responses were attenuated in rats with bilateral lesions of the cAMG. HSV-1 infection induced fever, motor hyperactivity and aggressive behavior. These responses were also attenuated in rats with cAMG lesions. The cAMG plays an important role in mediating the neuroendocrine, febrile and behavioral responses to HSV-1 infection.


The effect of uncorrected ametropia on ocular torsion induced by changes in fixation.
Ocular torsion, the eye movements to rotating around the line of sight, has not been well investigated regarding the influence of refractive errors. The purpose of this study was to investigate the effect of uncorrected ametropia on ocular torsion induced by fixation distances. Seventy-two subjects were classified according to the type of their refractive error, and ocular torsion of the uncorrected eye was compared based on changes induced by different fixation distances. Ocular torsion was measured using a slit-lamp biomicroscope equipped with an ophthalmic camera and a half-silvered mirror. In all groups, excyclotorsion values increased as the fixation distance decreased, but the myopia and astigmatism groups had larger amounts of ocular torsion than the emmetropia group. In addition, as the amount of uncorrected myopia and astigmatism increased, the amount of ocular torsion increased. Since the amount of ocular torsion caused by a change to a shorter fixation distance was larger when the refractive error was uncorrected, we suggest that ametropia should be fully corrected in patients frequently exposed to ocular torsion due to changes in fixation distance.


Takagi-Sugeno fuzzy-model-based fault detection for networked control systems with Markov delays.
A Takagi-Sugeno (T-S) model is employed to represent a networked control system (NCS) with different network-induced delays. Comparing with existing NCS modeling methods, this approach does not require the knowledge of exact values of network-induced delays. Instead, it addresses situations involving all possible network-induced delays. Moreover, this approach also handles data-packet loss. As an application of the T-S-based modeling method, a parity-equation approach and a fuzzy-observer-based approach for fault detection of an NCS were developed. An example of a two-link inverted pendulum is used to illustrate the utility and viability of the proposed approaches.


Experimental inoculation of cattle with bovine herpesvirus-4: evidence for a lymphoid-associated persistent infection.
A strain of bovine herpesvirus-4 isolated from cows with mammary pustular dermatitis was used for experimental inoculation of cattle. This strain is serologically indistinguishable from the group prototype Movar 33/63 and from strain DN-599. Seronegative cattle were inoculated IV or by simultaneous intranasal, IV, intramammary (via teat channel), and intradermal inoculations. All inoculated cattle seroconverted. Clinical signs of disease or lesions were not evident, except for a dermal lesion corresponding with one intradermal inoculation site. Virus was recovered from the dermal lesion and was excreted in the milk for 17 days. Virus was recovered from esophagopharyngeal fluid at 9 and 13 days after inoculation. At different times of euthanasia (2 to 14 months after inoculation), virus was recovered from cocultures with bovine lung cells and/or explant cultures of lymph nodes, spleen, tonsils, and, in one case, kidney. In 2 animals, the virus was recovered repeatedly during 1 year from peripheral blood leukocytes by cocultivation with bovine lung cells. The number of infectious leukocytes, as determined by infectious center assay, ranged from less than 1 to 6 infectious cells/10(7) leukocytes.


Ultrasound scalpel in thyroidectomy. Prospective randomized study.
The ultrasonic scalpel is a surgical shear that uses high-frequency mechanical energy to enable simultaneous vessel sealing and tissue coagulation at the same time. We conducted a prospective randomized study to compare the outcome of total thyroidectomy using the ultrasonic scalpel versus standard clamp and tie (CT) procedure in terms of safety, operative time, overall drainage volume, complications, hospital stay. Between January 2008 and December 2010, 200 patients (130 women, 70 men; mean age 46 years) undergoing thyroidectomy were randomized into two groups: group A, where CT technique were used, and group B, where the ultrasonic device was used. There was no significant differences between the two groups in terms of age, gender, indication for thyroidectomy, thyroid gland weight and diameter, histopathologic diagnosis, preoperative and postoperative serum calcium levels, postoperative complications and reoperative thyroid surgery. In group B there is a statistically significant reduction of the operative times (63 ± 9' vs 85 ± 15', P<0.001) and overall drainage volume (50 ± 20cc vs 70 ± 25cc, P<0.001) . The ultrasonic scalpel is safe, effective, useful, and time-saving alternative to the traditional suture ligation technique for thyroid surgery. They simplified total thyroidectomy, eliminating the need for clamp-and-tie maneuvers while achieving efficient hemostasis. Our study shows that the use of ultrasound in thyroid surgery reduces significantly surgical time and overall drainage volume. Furthermore, we also verified a decrease in hospitalization time, postoperative pain and blood loss, without increasing complication rates, for patients who underwent total thyroidectomy with the ultrasonically activated shear.


A randomized trial of the effects of rosiglitazone and metformin on inflammation and subclinical atherosclerosis in patients with type 2 diabetes.
Metformin and rosiglitazone both improve glycemic control in type 2 diabetes mellitus, however may possess different anti-inflammatory and anti-atherosclerotic properties. We investigated the effects of these medications on high-sensitivity C-reactive protein (hsCRP) and carotid artery intima-media thickness (CIMT) to determine their relative potential to reduce cardiovascular risk independent of their antihyperglycemic actions. Ninety-two subjects with suboptimally controlled diabetes mellitus (hemoglobin A1c [HbA1c] >7.0%) were assigned to therapy with either rosiglitazone 4 mg once daily or metformin 850 mg twice daily for 24 weeks. The primary end point was the change in hsCRP after 24 weeks. The change in CIMT was prespecified as a secondary end point. Metformin and rosiglitazone treatment led to similar significant improvements in glycemic control (HbA1c -1.08% in the rosiglitazone group and -1.18% in the metformin group, P = nonsignificant). High-sensitivity C-reactive protein levels decreased by an average of 68% in the rosiglitazone group (5.99 +/- 0.88 to 1.91 +/- 0.28 mg/L, P < .001), compared with a nonsignificant 4% reduction in hsCRP with metformin (5.69 +/- 0.83 to 5.46 +/- 0.92 mg/L; P = nonsignificant). Maximal CIMT progressed in the metformin group (+0.084 +/- 0.038 mm), whereas regression of maximal CIMT was observed in the rosiglitazone group (-0.037 +/- 0.031 mm; P = .02 for the between group comparison). Similar changes were observed for mean CIMT. The change in hsCRP and maximal CIMT were related in a multivariable model controlling for changes in HbA1c and lipid parameters (r = .31; P = .01). Rosiglitazone, compared to metformin, induced a prompt and profound reduction in hsCRP levels independent of its effect on glycemia. This change was associated with regression of CIMT after 24 weeks.


Differentiation of tracheal epithelium during fetal lung maturation in the rhesus monkey Macaca mulatta.
Of the eight categories of epithelial cells identified in pulmonary conducting airways, four are found in the trachea of adult primates: basal, mucous goblet, intermediate, and ciliated cells. While their ultrastructure is well characterized, little is understood about their origin or differentiation. This study describes the pattern of differentiation of the tracheal luminal epithelium in a species of nonhuman primate, the rhesus monkey, Macaca mulatta. Tracheas of 57 fetal and postnatal rhesus were fixed with glutaraldehyde/paraformaldehyde: ten at 29-54 days gestational age (GA), ten at 59-80 days GA (pseudoglandular stage), sixteen at 82-130 days GA (canalicular stage), ten at 141-168 days GA (saccular stage), eight at 1-134 days postnatal, and three adults (2 yr 11 months to 11 yr 11 months). Slices taken proximal to the carina were processed for electron microscopy by a selective embedding procedure. In the youngest fetuses, essentially one population of cells lined the tracheal epithelial surface. These cells were columnar in shape with a central nucleus, few organelles, and large amounts of cytoplasmic glycogen. At 46 days GA, ciliated cells were observed on the membranous side of the trachea. Some nonciliated cells had concentrations of organelles in the most apical portion of their cytoplasm. At 59 days GA, membrane-bound cored granules were intermixed with organelles in the apices of some glycogen-filled cells. They were observed first on the cartilaginous side. Between 59 and 100 days GA, a large number of cell forms which appeared to be transitional between ciliated, secretory, basal, and undifferentiated cells were present. These included ciliated cells with electron-lucent inclusions resembling mucous granules. Mucous secretory cells were more numerous and had more granules and less glycogen in older fetuses. By 105 days GA, few of the secretory cells had significant amounts of glycogen and the cytoplasm was condensed. Secretory granules were very abundant in some cells and minimal in others. The Golgi apparatus was prominent. In animals 120 days GA and older, small mucous granule cells and basal cells resembling these cells in adults were present. By 134 days postnatal age, the epithelium resembled that in adults. We conclude that most of the differentiation of tracheal epithelium in the rhesus monkey occurs prior to birth; the cells differentiate in the following sequences: ciliated, mucous goblet, small mucous granule, basal; and basal and small mucous granule cells do not play a role in ciliated and mucous cell formation in the fetus.


A meta-analysis on the association between bladder cancer and occupation.
To date, many epidemiological studies have been conducted to examine the association between occupation and bladder cancer incidence. However, results from these studies often have been inconsistent, and significant associations have rarely been found, possibly owing to the lack of adequate statistical power in these studies. This meta-analysis summarizes the relevant literature regarding occupation and bladder cancer incidence to increase the statistical power to detect associations. The Medline and Embase databases were searched to retrieve epidemiological studies published up until May 2008. Individual risk estimates for subjects with an employment history in the occupation of interest were extracted from each included publication. For each occupation, a summary relative risk (SRR) was calculated by means of a random effects model. Significantly increased risks with an SRR greater than 1.20 were identified for miners [SRR=1.31, 95% confidence interval (CI) 1.09-1.57], bus drivers (SRR=1.29, 95% CI 1.08-1.53), rubber workers (SRR=1.29, 95% CI 1.06-1.58), motor mechanics (SRR=1.27, 95% CI 1.10-1.46), leather workers (SRR=1.27, 95% CI 1.07-1.49), blacksmiths (SRR=1.27, 95% CI 1.02-1.58), machine setters (SRR=1.24, 95% CI 1.09-1.42), hairdressers (SRR=1.23, 95% CI 1.11-1.37) and mechanics (SRR=1.21, 95% CI 1.12-1.31). In conclusion, the studies reviewed provide consistent support for a small but significant increased risk of bladder cancer among workers in these nine occupations. Although the relative risk of bladder cancer associated with these occupations is small, the public health impact may be significant, considering the substantial number of people who were and are employed in these occupations.


Short-term evaluation of dorsal acetabular augmentation in 10 canine total hip replacements.
To report the use of dorsal acetabular augmentation (DAA) in canine total hip arthroplasty (THA) and to evaluate the clinical and radiographic outcome after a minimum of 1 year follow-up. Clinical study. Nine dogs that had THA. Ten hips requiring acetabular augmentation for optimum acetabular cup implantation for THA were evaluated retrospectively. The excised femoral head and neck was used as the corticocancellous bone graft for index THA surgeries, and the dorsal crest of the ipsilateral ilial wing was used as the bone graft in 1 dog that had a revision surgery. Clinical and radiographic follow-up examinations were performed at approximately 8 weeks and 1 year postoperatively. Long-term radiographic examinations included use of a standing dorsal acetabular rim (DAR) projection for assessment of graft-recipient boundary. Functional clinical outcome was assessed using direct patient evaluation and telephone interview. One dog failed to regain limb function after surgery. Suspected aseptic loosening of the acetabular cup was observed on radiographs approximately 12 weeks postoperatively. Excluding this single explantation, follow-up physical and radiographic examinations indicated good implant and graft positioning and normal function for all dogs. Acetabular augmentation permitted implantation of an appropriately sized acetabular cup while maintaining complete DAR coverage of the prosthesis. Nine out of 10 hips had a successful outcome with minimal radiographic and no functional abnormalities. Further follow-up is necessary to determine the long-term outcome of DAR augmentation in canine THA. Acetabular augmentation with an autogenous corticocancellous bone graft constructed from the femoral head and neck can provide complete DAR coverage to permit use of an appropriately sized acetabular cup in THA.


Generation and characterisation of a semi-synthetic siderophore-immunogen conjugate and a derivative recombinant triacetylfusarinine C-specific monoclonal antibody with fungal diagnostic application.
Invasive pulmonary aspergillosis (IPA) is a severe life-threatening condition. Diagnosis of fungal disease in general, and especially that caused by Aspergillus fumigatus is problematic. A. fumigatus secretes siderophores to acquire iron during infection, which are also essential for virulence. We describe the chemoacetylation of ferrated fusarinine C to diacetylated fusarinine C (DAFC), followed by protein conjugation, which facilitated triacetylfusarinine C (TAFC)-specific monoclonal antibody production with specific recognition of the ferrated form of TAFC. A single monoclonal antibody sequence was ultimately elucidated by a combinatorial strategy involving protein LC-MS/MS, cDNA sequencing and RNAseq. The resultant murine IgG2a monoclonal antibody was secreted in, and purified from, mammalian cell culture (5 mg) and demonstrated to be highly specific for TAFC detection by competitive ELISA (detection limit: 15 nM) and in a lateral flow test system (detection limit: 3 ng), using gold nanoparticle conjugated- DAFC-bovine serum albumin for competition. Overall, this work reveals for the first time a recombinant TAFC-specific monoclonal antibody with diagnostic potential for IPA diagnosis in traditional and emerging patient groups (e.g., COVID-19) and presents a useful strategy for murine Ig sequence determination, and expression in HEK293 cells, to overcome unexpected limitations associated with aberrant or deficient murine monoclonal antibody production.


Compatibility of Tanshinone IIA and Astragaloside IV in attenuating hypoxia-induced cardiomyocytes injury.
Herbal medicines including Tanshinone IIA (TanIIA) and Astragaloside IV (AsIV) are widely used in Asia as therapeutic agents for cardiovascular diseases, due to their complementary roles and shared properties based on the theory of traditional Chinese medicine and pharmacological researches. However, the underlying pathological mechanisms for their efficacy are still unclear. In addition, the compatibility or incompatibility of the herbal medicines when administered with other herbal remedies or with prescription drugs is unknown. We aimed to investigate the compatibility of TanIIA and AsIV in protecting cardiomyocytes against hypoxia-induced injury. Cultured cardiomyocytes were stimulated in hypoxia condition, in the absence or presence of the two herbal compounds, TanIIA and AsIV. Indicators were determined by cytotoxicity assay, quantitative PCR, ELISA, flow cytometry assay, immunofluorescence staining and western blot. Either TanIIA alone or the combined herbal compounds inhibited hypoxia-triggered chemokines production including CCL2/5/19, CXCL2 and Transwell assay-indicated monocyte/macrophage recruitment, cytokines production including TNF-α and IL-6. While AsIV alone or the combined herbal compounds attenuated hypoxia-induced cell apoptosis indicated by decreased Annexin V+ cells and the ratio of Bax/Bcl-2, but no significant effect of the herbal compounds was observed in modulating cell apoptosis following both hypoxia and TNF-α stimulation. As an anti-apoptotic factor, stress granule formation was further enhanced by AsIV alone or the combined herbal compounds in hypoxia or heat shock stress. Moreover, immunoblotting analysis indicated that stress-responsive mitogen-activated protein kinases (MAPK) pathways including the phosphorylation of ERK1/2, p38 and JNK were inhibited while the phosphorylation of Akt in phosphatidylinositol 3-kinase (PI3K) -Akt pathway for cell survival was restored by the herbal compounds. Among these results, the combination of TanIIA and AsIV comprised most of the beneficial properties tested, although their combination did not improve the maximal effects achieved by any of the compounds alone. Taken together, these data suggest a compatibility of TanIIA and AsIV in protecting cardiomyocyte against hypoxia-induced injury.


The reactions to macro-economic crises in Nordic health system policies: Denmark, Finland and Sweden, 1980-2013.
Denmark, Finland and Sweden have experienced two major recessions during the last 25 years. The adjustments to the earlier crisis in the late 1980s (Denmark) and early 1990s (Finland and Sweden) resembled the policies in many other European countries during the present crisis. The analysis of relationship of deep economic crises and growth period between them to the health system policies and institutions in the three countries from the 1980s to 2013 is based on a categorisation of reactions to external shocks as path conforming or path breaking. The results of the empirical long-term trends show that the reactions to deep recessions have been mainly temporary adjustments and acceleration of changes already prepared before economic crisis. The economic crisis in the three countries has not been 'good enough' to enable paradigmatic changes in the Nordic public, decentralised and equity-oriented health systems. Changes such as the slow privatisation in care funding and production and the adoption of new management practices indicate an ongoing paradigmatic change related to longer-term societal, ideological and political developments rather than directly to economic crises or growth.


A comparison between emergency diagnostic and treatment unit and inpatient care in the management of acute asthma.
Emergency diagnostic and treatment units (EDTUs) may provide an alternative to hospitalization for patients with reversible diseases, such as asthma, who fail to adequately respond to emergency department therapy. To evaluate the medical and cost-effectiveness, patient satisfaction, and quality of life of patients receiving EDTU care for acute asthma compared with inpatient care. A prospective, randomized clinical trial performed at 2 urban public hospitals enrolled patients with acute asthma (age range, 18-55 years) not meeting discharge criteria after 3 hours of emergency department therapy. Patients were treated with inhaled adrenergic agonists and steroids in an EDTU for up to 9 hours after randomization or with routine therapy in a hospital ward. Patients were followed up for 8 weeks. Discharge rate from the EDTU, length of stay, relapse rates, days missed from work or school, days incapacitated during waking hours, symptom-free days and nights, nocturnal awakenings, direct medical costs, patients satisfaction, and patient quality of life. The study consisted of 222 patients with asthma. Sixty-five patients (59%) treated in an EDTU were discharged home; the remainder were admitted to the hospital. There were no differences during the follow-up period in relapse rates (P = .74) or in any other morbidities between the EDTU and inpatient groups. There were significant differences in the length of stay, patient satisfaction, and quality of life favoring EDTU care. The mean (+/-SD) cost per patient in the EDTU group was $1202.79 +/- $1343.96, compared with $2247.32 +/- $1110.18 for the control group (P < .001). Treatment of selected patients with asthma in an EDTU results in the safe discharge of most such patients. This study suggests that quality gains and cost-effective measures can be achieved by the use of such units.


Longitudinal Associations Between Bullying and Emotions in Deaf and Hard of Hearing Adolescents.
In hearing adolescents, emotions play important roles in the development of bullying and victimization. Yet, it is unclear whether this also applies to adolescents who are deaf or hard of hearing (DHH). The present study examines the longitudinal associations of anger, fear, guilt, and shame with bullying/victimization in DHH adolescents. Overall, 80 DHH and 227 hearing adolescents (Mage = 11.7; 103 males) completed self-reports on two occasions with a 9-month interval. Outcomes show that DHH adolescents reported fewer bullying behaviors, but more victimization compared to hearing adolescents. Longitudinal relations between emotions and bullying/victimization did not differ between DHH and hearing adolescents. More anger and less guilt predicted increased bullying, and more bullying predicted increased anger and decreased guilt. Higher levels of anger, fear, and shame predicted increased victimization, and more victimization predicted increased anger, fear, and shame. These findings emphasize that emotions are involved in both the emergence and maintenance of bullying and victimization. These outcomes have clinical implications for the prevention of bullying.


New-Onset Atrial Fibrillation in Patients Hospitalized With COVID-19: Results From the American Heart Association COVID-19 Cardiovascular Registry.
New-onset atrial fibrillation (AF) in patients hospitalized with COVID-19 has been reported and associated with poor clinical outcomes. We aimed to understand the incidence of and outcomes associated with new-onset AF in a diverse and representative US cohort of patients hospitalized with COVID-19. We used data from the American Heart Association COVID-19 Cardiovascular Disease Registry. Patients were stratified by the presence versus absence of new-onset AF. The primary and secondary outcomes were in-hospital mortality and major adverse cardiovascular events (MACE; cardiovascular death, myocardial infarction, stroke, cardiogenic shock, and heart failure). The association of new-onset AF and the primary and secondary outcomes was evaluated using Cox proportional-hazards models for the primary time to event analyses. Of the first 30 999 patients from 120 institutions across the United States hospitalized with COVID-19, 27 851 had no history of AF. One thousand five hundred seventeen (5.4%) developed new-onset AF during their index hospitalization. New-onset AF was associated with higher rates of death (45.2% versus 11.9%) and MACE (23.8% versus 6.5%). The unadjusted hazard ratio for mortality was 1.99 (95% CI, 1.81-2.18) and for MACE was 2.23 (95% CI, 1.98-2.53) for patients with versus without new-onset AF. After adjusting for demographics, clinical comorbidities, and severity of disease, the associations with death (hazard ratio, 1.10 [95% CI, 0.99-1.23]) fully attenuated and MACE (hazard ratio, 1.31 [95% CI, 1.14-1.50]) partially attenuated. New-onset AF was common (5.4%) among patients hospitalized with COVID-19. Almost half of patients with new-onset AF died during their index hospitalization. After multivariable adjustment for comorbidities and disease severity, new-onset AF was not statistically significantly associated with death, suggesting that new-onset AF in these patients may primarily be a marker of other adverse clinical factors rather than an independent driver of mortality. Causality between the MACE composites and AF needs to be further evaluated.


Mechanically-evoked C-fiber activity in painful alcohol and AIDS therapy neuropathy in the rat.
While altered activities in sensory neurons were noticed in neuropathic pain, caused by highly diverse insults to the peripheral nervous system, such as diabetes, alcohol ingestion, cancer chemotherapy and drugs used to treat AIDS, other infections and autoimmune diseases, as well as trauma, our understanding of how these various peripheral neuropathies manifest as altered neuronal activity is still rudimentary. The recent development of models of several of those neuropathies has, however, now made it possible to address their impact on primary afferent nociceptor function. We compared changes in mechanically-evoked C-fiber activity, in models of painful peripheral neuropathy induced by drinking ethanol (alcohol) or administering 2',3'-dideoxycytidine (ddC), a nucleoside reverse transcriptase inhibitor for AIDS therapy, two co-morbid conditions in which pain is thought to be mediated by different second messenger signaling pathways. In C-fiber afferents, ddC decreased conduction velocity. In contrast, alcohol but not ddC caused enhanced response to mechanical stimulation (i.e., decrease in threshold and increase in response to sustained threshold and supra-threshold stimulation) and changes in pattern of evoked activity (interspike interval and action potential variability analyses). These marked differences in primary afferent nociceptor function, in two different forms of neuropathy that produce mechanical hyperalgesia of similar magnitude, suggest that optimal treatment of neuropathic pain may differ depending on the nature of the causative insult to the peripheral nervous system, and emphasize the value of studying co-morbid conditions that produce painful peripheral neuropathy by different mechanisms.


Impact of varying stages of endometriosis on the outcome of in vitro fertilization-embryo transfer.
The impact of severity of endometriosis on the outcome of in vitro fertilization (IVF) was analyzed in an uncontrolled, retrospective study in an academic IVF program. Sixty-one patients with a primary diagnosis of endometriosis undergoing 85 cycles of IVF were included in the study. Patients were divided according to the severity of disease based on the revised American Fertility Society (AFS) classification into groups A (stages I/II, or minimal/ mild) and B (stages III/IV, or moderate/severe). Group A included 32 patients undergoing 45 IVF-embryo transfer (ET) cycles; group B included 29 patients undergoing 40 IVF cycles. Exclusion criteria were age older than 40 years, basal day 3 follicle stimulating hormone (FSH) greater than 20 IU/L, male-factor infertility, assisted hatching, and gamete intrafallopian transfer cases. Stimulation for IVF cycles was standard using pituitary down-regulation with gonadotropin-releasing hormone agonist in a midluteal protocol. Controlled ovarian hyperstimulation (COH) was achieved using a combination of FSH and human menopausal gonadotropin. Outcomes assessed included response to COH and number, maturity, and quality of oocytes retrieved. Fertilization, implantation, and pregnancy rates after IVF-ET were also analyzed. The response to COH and the number, maturity, and quality of the oocytes was comparable between patients with varying severity of endometriosis. Fertilization rates for oocytes of patients in group B (stages III/IV) were significantly impaired compared to those in group A (stages I/II) (P = 0.004). The rates for implantation, clinical pregnancy, and miscarriage were comparable between the two groups. The reduced fertilization potential of the oocytes obtained from patients with severe endometriosis in the absence of male-factor infertility suggests an adverse biological impact of the advanced disease on the oocytes. The outcome of IVF-ET, however, is unaffected by increasing severity of endometriosis. This suggests that IVF may compensate for or overcome this reduction in the biological potential of the oocytes associated with severe disease, thus accounting for a comparable outcome irrespective of the severity of endometriosis.


The concept of motherhood among three generations of African American women.
To provide an understanding of the experiences of three generations of African American women in the transition to motherhood. Hermeneutic phenomenology from an Afrocentric feminist perspective is the methodological approach used in this study. Using the snowball technique, a purposive sample of 18 African American women from three generations who were mostly middle class, partnered, and educated was recruited. Individual open-ended interviews were used to identify information-rich cases that would provide an in-depth understanding of the phenomenon. Generation 1 included seven women, between the ages of 65 and 83 years, who became mothers between 1950 and 1970, prior to the Civil Rights Movement. Generation 2 included five women, between the ages of 51 and 58 years, who became mothers between 1971 and 1990, after the Civil Rights Movement. There were six women in Generation 3, between the ages of 30 and 41 years, who became mothers between 1991 and 2003. Three constitutive patterns and their associated themes were identified. The first pattern, It Took Me a Minute, had three themes: Finding Out, Realizing What Mothers Do, and Way Tricked! The second pattern, Preserving Our Home, had four themes: Mothering Within the isms: Racism, Classism, and Sexism, I Did the Best I Could, Mothers and Others, and Spiritual Mothers. Eat the Meat, Throw Away the Bone, the third pattern, had two themes: The Ways in Which We Learn and Someone Who Looks Like Me. The results of this study reveal some consistency with current descriptions of maternal identity and becoming a mother and add to our understanding of the complexities that racism, classism, and sexism play in the lives of African American mothers and their families. The data from this study also suggest that future development of theoretical frameworks and analytical tools, used to assess the effects of stress and other psychosocial factors on health, need to be grounded in a historic understanding of the African American experience and of the African influence on family and cultural knowledge. Additionally, this study demonstrated the impact that the media, both professional and mass media outlets, have in defining and perpetuating our beliefs and feelings of the "good mother-bad mother" dualism. The description of motherhood for this group of African American women illustrates that motherhood is a source of power and provides significant meaning, satisfaction, and respect within the family and the larger community. It also highlighted the communal role that "othermothers" and spiritual mothers have in facilitating the transition to motherhood and providing strong social support. Analysis of the stories in this study adds to the current literature on becoming a mother and Black feminist descriptions of motherhood. This study adds to our understanding of how negative portrayals of African American mothers and the lack of representation in the media perpetuate negative stereotypes of African American motherhood. The stories, told by the 18 women in this study, provide a positive description of African American motherhood.


Liposome-camouflaged iodinated mesoporous silica nanoparticles with high loading capacity, high hemodynamic stability, high biocompatibility and high radiopacity.
Due to their low osmolality and high tolerability, the highly water-soluble nonionic iodinated contrast agents, such as Ioversol (IV), are widely used as clinical agents for CT imaging. However, their clinical applications still are severely limited by the rapid renal excretion, serious adverse effects especially contrast-induced nephropathy and inefficient targetability. Various nanocarriers have demonstrated tremendous potential for achieving high imaging efficiency and low side effects. However, few nanoparticulate contrast agents can simultaneously integrate the desirable functions for imaging, including high loading capacity of iodine, high structure stability for systemic circulation, high biocompatibility and high radiopacity. Herein, we designed and prepared a kind of new radiopaque liposome-camouflaged iodinated mesoporous silica nanoparticles (OIV-MSNs@Liposomes) as contrast agents in CT imaging. Their composition, structure, morphology, biocompatibility and physicochemical properties as well as in vitro radiopacity were investigated in detail. The results indicated that OIV-MSNs@Liposomes can integrate their individual advantages of liposomes and MSNs, thus exhibiting great potential for use in the CT imaging. Considering the simple preparation process and readily available starting materials as well as enhanced biosafety and high performance in X-ray attenuation, the strategy reported here offers a versatile route to efficiently deliver highly water-soluble nonionic iodinated contrast agents for enhanced CT imaging, which are unattainable by traditional means.


[Complications of wound healing after appendectomy. Medical and economic aspects].
The incidence of hospital and posthospital wound complications was studied in 236 patients, residents of Zelonograd, who underwent operation for acute appendicitis. The material was collected at City Hospital No. 3 and four out-patient clinics of Zelenograd. The incidence of suppuration of the surgical wound in the hospital period was 13.1%, that of nonpurulent complications was 9.3%, and the total incidence of the wound complications was 22.4%. In the posthospital period additional suppuration of wounds was encountered in 23.3% of patients, nonsuppurative wound complications in 17.1%, and the total incidence of posthospital wound complications was 40.3%. The frequency of rehospitalization was 5.5%, the incidence of postoperative hernias was 0.9%. The economical loss due to the development of wound complications in 236 patients operated on for acute appendicitis came up to 56,120 roubles.


The antiproteinuric action of angiotensin-converting enzyme is dependent on kinin.
Converting enzyme inhibitors (CEI) reduce proteinuria in nephrotic humans and animals, but the mediator(s) of this effect has not been identified definitively. To determine whether enhanced kinin activity contributes to the antiproteinuric action of CEI, rats with passive Heymann nephritis were treated with the B2 kinin receptor antagonist HOE 140, 300 micrograms/kg per day, for 3 days and then the CEI enalapril (ENAL), 35 mg/kg per day, was given for another 4 days while HOE 140 was continued (HOE/ENAL). Additional groups of nephrotic rats were untreated (CON), received HOE 140 only (HOE), or received ENAL only. ENAL alone produced a > 60% decrease in albuminuria after 4 days, whereas HOE 140 alone had no effect on albuminuria. In HOE/ENAL, pretreatment with HOE 140 prevented the decrease in albuminuria observed in ENAL. GFR increased significantly over time in all groups but was not different among the groups on any day. The clearance of albumin decreased significantly in ENAL (P < 0.001) and was significantly lower than in CON, HOE, or HOE/ENAL on Day 10. The fractional clearance of albumin decreased in all groups as a result of the increase in GFR but was significantly lower in ENAL compared with the other three groups at Day 10 and was not different between CON, HOE, and HOE/ENAL. Plasma renin activity and concentration were increased significantly in both ENAL and HOE/ENAL, indicating that converting enzyme was effectively inhibited in both groups. It was concluded that enhanced kinin activity contributes to the antiproteinuric action of CEI in this model of nephrotic syndrome.


Functional evolution of the vertebrate Myb gene family: B-Myb, but neither A-Myb nor c-Myb, complements Drosophila Myb in hemocytes.
The duplication of genes and genomes is believed to be a major force in the evolution of eukaryotic organisms. However, different models have been presented about how duplicated genes are preserved from elimination by purifying selection. Preservation of one of the gene copies due to rare mutational events that result in a new gene function (neofunctionalization) necessitates that the other gene copy retain its ancestral function. Alternatively, preservation of both gene copies due to rapid divergence of coding and noncoding regions such that neither retains the complete function of the ancestral gene (subfunctionalization) may result in a requirement for both gene copies for organismal survival. The duplication and divergence of the tandemly arrayed homeotic clusters have been studied in considerable detail and have provided evidence in support of the subfunctionalization model. However, the vast majority of duplicated genes are not clustered tandemly, but instead are dispersed in syntenic regions on different chromosomes, most likely as a result of genome-wide duplications and rearrangements. The Myb oncogene family provides an interesting opportunity to study a dispersed multigene family because invertebrates possess a single Myb gene, whereas all vertebrate genomes examined thus far contain three different Myb genes (A-Myb, B-Myb, and c-Myb). A-Myb and c-Myb appear to have arisen by a second round of gene duplication, which was preceded by the acquisition of a transcriptional activation domain in the ancestral A-Myb/c-Myb gene generated from the initial duplication of an ancestral B-Myb-like gene. B-Myb appears to be essential in all dividing cells, whereas A-Myb and c-Myb display tissue-specific requirements during spermatogenesis and hematopoiesis, respectively. We now report that the absence of Drosophila Myb (Dm-Myb) causes a failure of larval hemocyte proliferation and lymph gland development, while Dm-Myb(-/-) hemocytes from mosaic larvae reveal a phagocytosis defect. In addition, we show that vertebrate B-Myb, but neither vertebrate A-Myb nor c-Myb, can complement these hemocyte proliferation defects in Drosophila. Indeed, vertebrate A-Myb and c-Myb cause lethality in the presence or absence of endogenous Dm-Myb. These results are consistent with a neomorphic origin of an ancestral A-Myb/c-Myb gene from a duplicated B-Myb-like gene. In addition, our results suggest that B-Myb and Dm-Myb share essential conserved functions that are required for cell proliferation. Finally, these experiments demonstrate the utility of genetic complementation in Drosophila to explore the functional evolution of duplicated genes in vertebrates.


Temperature Drives Contrasting Alternaria Leaf Spot Epidemic Development in Canola and Mustard Rape from Alternaria japonica and A. brassicae.
Recent surveys of canola (Brassica napus) crops across southern Australia highlighted that Alternaria leaf spot on canola is not solely caused by Alternaria brassicae but that other Alternaria spp. are also involved, including A. japonica. Studies were undertaken into the effects of different temperatures (14 and 10°C [day and night] or 22 and 17°C [day and night]) on development of Alternaria leaf spot caused by A. japonica as compared with A. brassicae in cotyledons (embryonic leaves) and true leaves (first leaves) of canola (B. napus 'Thunder TT') and mustard rape (B. juncea 'Dune'). Both pathogens expressed less disease at lower temperatures of 14 and 10°C with percent disease index (%DI) of 19.1 for A. japonica and 41.8 for A. brassicae, but expressed significantly more disease at higher temperatures of 22 and 17°C with %DI of 80.8 and 88.2 for the same pathogens, respectively. At 14 and 10°C, mustard rape cotyledons showed less disease (percent cotyledons disease index [%CDI] = 18.1) from A. japonica but showed more disease (%CDI = 75.0) from A. brassicae. However, at 22 and 17°C, cotyledons and true leaves of both canola and mustard rape showed significantly more disease and varied in expressing the disease severity to the two pathogens; true leaves of mustard rape showed less disease (percent true leaf disease index [%TDI] = 48.4) from A. japonica but showed more disease (%TDI = 92.0) from A. brassicae. At 22 and 17°C, cotyledons of canola expressed more disease from A. japonica (%CDI = 99.1) than from A. brassicae (%CDI = 70.7). At the lower temperature, both host species showed the least disease, with mean %DI of 27.3 and 33.5 for canola and mustard rape, respectively, as compared with the higher temperatures, where there was a greater DI, with %DI values of 87.9 and 81.2 for these same host species, respectively. We believe that these are the first studies to highlight the critical role played by temperature for A. japonica as compared with A. brassicae in Alternaria leaf spot disease development and severity. These findings explain how temperature affects Alternaria leaf spot severity caused by A. japonica as compared with A. brassicae on different foliage components of canola and mustard rape.


A multifunctional, reconfigurable pulse generator for high-frequency ultrasound imaging.
High-frequency (>20 MHz) ultrasound (HFUS) imaging systems have made it possible to image small structures with fine spatial resolution. They find a variety of biomedical applications in dermatology, ophthalmology, intravascular imaging, and small-animal imaging. One critical technical challenge of HFUS is to generate high-voltage, high-frequency pulsed signals to effectively excite the transducer for a high SNR. This paper presents the development of a multifunctional, reconfigurable pulse generator for HFUS imaging. The pulse generator can produce a high-voltage unipolar pulse, a bipolar pulse, or arbitrary pulses for B-mode imaging, Doppler measurement, and modulated excitation imaging. The characteristics of the pulses, such as timing, waveform, and frequency are reconfigurable by a high-speed field-programmable gate array (FPGA). Customized software was developed to interface with the FPGA through a USB connector for pulse selection, and easy, flexible, real-time pulse management. The hardware was implemented in a compact, printed circuit board (PCB)-based scheme using state-of-the-art electronics for costeffectiveness and fully digital control. Testing results show that the unipolar pulse can reach over 165 Vpp with a 6-dB bandwidth of 70 MHz, and the bipolar pulse and arbitrary pulses can reach 150 and 60 Vpp with central frequencies of 60 and 120 MHz, respectively.


Temperature can shape a cline in polyandry, but only genetic variation can sustain it over time.
Multiple mating by females (polyandry) is a widespread behavior occurring in diverse taxa, species, and populations. Polyandry can also vary widely within species, and individual populations, so that both monandrous and polyandrous females occur together. Genetic differences can explain some of this intraspecific variation in polyandry, but environmental factors are also likely to play a role. One environmental factor that influences many fundamental biological processes is temperature. Higher temperatures have been shown to directly increase remating in laboratory studies of insects. In the longer term, high temperature could also help to drive the evolution of larger-scale patterns of behavior by changing the context-dependent balance of costs and benefits of polyandry across environments. We examined the relative influence of rearing and mating temperatures on female remating in populations of Drosophila pseudoobscura that show a latitudinal cline in polyandry in nature, using a range of ecologically relevant temperatures. We found that females of all genotypes remated more at cooler temperatures, which fits with the observation of higher average frequencies of polyandry at higher latitudes in this species. However, the impact of temperature was outweighed by the strong genetic control of remating in females in this species. It is likely that genetic factors provide the primary explanation for the latitudinal cline in polyandry in this species.


Developmental pathways of dendritic cells in vivo: distinct function, phenotype, and localization of dendritic cell subsets in FLT3 ligand-treated mice.
We have recently shown that Flt3 ligand administration dramatically increases dendritic cell (DC) numbers in various mouse tissues. This has enabled the identification of distinct mature DC subpopulations. These have been designated: population C (CD11c(bright) CD11b(bright)), D (CD11c(bright) CD11b(dull)), and E (CD11c(bright) CD11b(negative)) This report demonstrates that the mature DC subsets (C, D, and E) from Flt3 ligand-treated mice differ with respect to phenotype, geographic localization, and function. The myeloid Ags CD11b, F4/80, and Ly-6C are predominantly expressed by population C, but not D or E. In addition, a subset of population C-type DC expresses 33D1 and CD4. In contrast, DC within population D and E selectively express the lymphoid-related DC markers CD8alpha, DEC 205, CD1d, as well as CD23, elevated levels of CD117 (c-kit), CD24 (HSA), CD13, and CD54. Immunohistology indicates that the different DC subsets reside in distinct microenvironments, with populations D and E residing in the T cell areas of the white pulp, while DC within population C localize in the marginal zones. These DC subpopulations showed different capacities to phagocytose FITC-zymosan and to secrete IL-12 upon stimulation with Staphylococcus aureus cowan I strain + IFN-gamma + granulocyte-macrophage-CSF. Population C-type DC were more phagocytic but secreted little inducible IL-12 while population D- and E-type DC showed poor phagocytic capacity and secreted considerably higher levels of IL-12. These results underscore the importance of viewing DC development in vivo, as an interplay between distinct lineages and a maturational dependence on specific microenvironmental signals.


[Work and health of the Cordoba National University teachers: medicaments/legal drugs use and infantile-maternal plan].
This study aimed to investigate university teachers in reproductive age--life conditions, work and health process and medicaments use. Beside, aimed research the use, opinions and suggestions of Infantile-Maternal Plan of the University Social Assistance clients. In dialectic and historic materialism theory and method way, this is a social research developed by a strategic and correlative-descriptive fieldwork with 50 persons sample. The results showed degraded work and life conditions, affecting the teachers' health profile and medicaments use. The Infantile-Maternal Plan is good or very good and demands best information accord the teachers in high percent opinion.


WT1 is differentially expressed in serous, endometrioid, clear cell, and mucinous carcinomas of the peritoneum, fallopian tube, ovary, and endometrium.
The Wilms' tumor gene WT1 plays complex roles in the development of the organs of the genitourinary tract and mesothelium, as well as Wilms' tumors. Although its biologic role is still unclear, most serous carcinomas of the ovary and peritoneum, mesotheliomas, and Wilms' tumor have been shown to express WT1. A recent study, however, found no WT1 expression in serous carcinomas of the endometrium, suggesting that WT1 could be useful in identifying the primary site of serous carcinomas. We examined the expression of WT1 and p53 by immunohistochemistry in 69 cases of endometrial carcinoma (35 endometrioid, 18 clear cell, 16 serous), 68 cases of ovarian carcinoma (28 serous, 11 endometrioid, 18 clear cell, and 11 mucinous), 14 fallopian tube carcinomas (12 serous, 2 endometrioid), and 20 primary peritoneal serous carcinomas. WT1 nuclear reactivity of any extent and intensity was considered positive. Immunohistochemical stains were evaluated semiquantitatively using a four-tiered scale. Among endometrial carcinomas, WT1 immunoreactivity was seen in 10 of 16 serous, but in none of 35 endometrioid or 18 clear cell carcinomas. Among ovarian tumors, WT1 expression was seen in 24 of 28 serous and 4 of 18 clear cell carcinomas, but in none of 11 endometrioid and 11 mucinous tumors. All 12 serous carcinomas but none of 2 endometrioid carcinomas of the fallopian tube were positive for WT1. WT1 expression was seen in 19 of 20 serous primary peritoneal carcinomas. The difference in WT1 expression was highly significant between serous and other types of tumors in all sites (p<0.0001, chi-square test), although the level of WT1 expression was significantly different among serous carcinomas arising at different sites (p<0.0001, Kruskal-Wallis test). A significant positive correlation was found between the level of p53 and WT1 expression in all carcinomas combined (r = 0.3935, p<0.0001, Spearman test), but when only serous carcinomas were analyzed, the correlation between p53 and WT1 expression levels did not reach statistical significance. Our results suggest that WT1 expression in epithelial tumors of the female genital tract may be related to cell differentiation and histologic subtypes of carcinomas, rather than to primary site of origin.


Cystic echinococcosis of the liver: A primer for hepatologists.
Cystic echinococcosis (CE) is a complex, chronic and neglected disease with a worldwide distribution. The liver is the most frequent location of parasitic cysts. In humans, its clinical spectrum ranges from asymptomatic infection to severe, potentially fatal disease. Four approaches exist in the clinical management of CE: surgery, percutaneous techniques and drug treatment for active cysts, and the "watch and wait" approach for inactive cysts. Allocation of patients to these treatments should be based on cyst stage, size and location, available clinical expertise, and comorbidities. However, clinical decision algorithms, efficacy, relapse rates, and costs have never been properly evaluated. This paper reviews recent advances in classification and diagnosis and the currently available evidence for clinical decision-making in cystic echinococcosis of the liver.


Reinventing the neural crest: direct reprogramming makes iNCCs.
Aberrant neural crest (NC) development is at the origin of many congenital diseases. Given the limitations in human NC cell isolation and expansion, the development of new strategies for NC generation is crucial. In this issue of Cell Stem Cell, Kim et al. (2014) report the direct reprogramming of postnatal fibroblasts into multipotent NC cells.