Early postoperative physical activity and function: a descriptive case series study of 53 patients after lumbar spine surgery.
The purpose of this prospective case series study was to compare changes in early postoperative physical activity and physical function between 6 weeks and 3 and 6 months after lumbar spine surgery. Fifty-three patients (mean [95% confidence interval; CI] age = 59.2 [56.2, 62.3] years, 64% female) who underwent spine surgery for a degenerative lumbar condition were assessed at 6 weeks and 3- and 6-months after surgery. The outcomes were objectively-measured physical activity (accelerometry) and patient-reported and objective physical function. Physical activity was assessed using mean steps/day and time spent in moderate to vigorous physical activity (MVPA) over a week. Physical function measures included Oswestry Disability Index (ODI), 12-item Short Form Health Survey (SF-12), Timed Up and Go (TUG), and 10-Meter Walk (10 MW). We compared changes over time in physical activity and function using generalized estimating equations with robust estimator and first-order autoregressive covariance structure. Proportion of patients who engaged in meaningful physical activity (e.g., walked at least 4400 and 6000 steps/day or engaged in at least 150 min/week in MVPA) and achieved clinically meaningful changes in physical function were compared at 3 and 6 months. After surgery, 72% of patients initiated physical therapy (mean [95%CI] sessions =8.5 [6.6, 10.4]) between 6 weeks and 3 months. Compared to 6 weeks post-surgery, no change in steps/day or time in MVPA/week was observed at 3 or 6 months. From 21 to 23% and 9 to 11% of participants walked at least 4400 and 6000 steps/day at 3 and 6 months, respectively, while none of the participants spent at least 150 min/week in MVPA at these same time points. Significant improvements were observed on ODI, SF-12, TUG and 10 MW (p < 0.05), with over 43 to 68% and 62 to 87% achieving clinically meaningful improvements on these measures at 3 and 6 months, respectively. Limited improvement was observed in objectively-measured physical activity from 6 weeks to 6 months after spine surgery, despite moderate to large function gains. Early postoperative physical therapy interventions targeting physical activity may be needed.


Staging cholangiocarcinoma by cholangioscopy.
Peroral cholangioscopy (POCS) and percutaneous transhepatic cholangioscopy (PTCS) were first developed in the 1970s, and technical developments and clinical applications have taken place gradually ever since. POCS is used to diagnose small mucosal biliary lesions in non-icteric patients and early malignant changes in patients with persistent primary sclerosing cholangitis (PSC). Although PTCS is a more invasive diagnostic procedure than POCS, it has the advantage of precise diagnosis with mapping biopsy in defining the proximal and distal extension of superficially spreading cholangiocarcinoma (CCA) or mucin-producing CCA, which is predominantly found in papillary type CCA. POCS is significantly superior to ERCP in distinguishing between malignant and benign dominant bile duct stenoses in patients with PSC. The positive rate of PTCS biopsy for CCA is 96%, while morbidity and mortality of PTCS are 9% and 0%, respectively. Although magnetic resonance (MR) cholangiography may replace PTCS in determining the longitudinal spread of infiltrating type hilar CCA, the accuracy of MR cholangiography in papillary type hilar CCA is significantly lower than that of PTCS.


The impact of stress at dressing change in patients with burns: a review of the literature on pain and itching.
Burn wounds can be particularly painful and stressful for patients, particularly during dressing change and other aspects of wound care. Research into other types of wounds has demonstrated that stress and pain at dressing change are closely linked and related to healing, since high levels of stress and pain are associated with a longer length of time for a wound to heal. Additionally, there is some evidence to suggest a similar relationship between stress and itching. This article presents a review of the literature into stress, pain, and itching in patients with burns. The review demonstrates the importance of dressing change management with these patients. Furthermore, suggestions are made for areas of research that are yet to be explored, as such research, and the findings that emerge, could have important implications for clinical practice when working with people with burns. The common focus of such studies should be the aim of minimizing stress and discomfort for people with burns and other wounds so as to improve patient well being and treatment outcomes.


Stress, Burnout, and Turnover Issues of Black Expatriate Education Professionals in South Korea: Social Biases, Discrimination, and Workplace Bullying.
The purpose of this study is to understand expatriate educators' overall teaching experiences and opinions about living in South Korea. The research study sought to explore the relationship between stressors and social biases against Black individuals and their suicidal behaviours and turnover decisions. The approach of stress, burnout, career decision, and suicide guided this study as the lens. The research method for this study included a phenomenological analysis of two sessions of semi-structured interviews with 18 Black expatriates in the field of education in South Korea. The results indicate that their experiences were impacted by unfairness against individuals based on their skin colour and nationalities. The outcomes of this study highlight the major difficulties experienced by foreign professionals living in South Korea. They can be used by human resource professionals, school administrators, and government leaders to reform their current policy and improve expatriate experiences so as to prevent turnover.


A P-glycoprotein homologue of Plasmodium falciparum is localized on the digestive vacuole.
Resistance to chloroquine in Plasmodium falciparum bears a striking similarity to the multi-drug resistance (MDR) phenotype of mammalian tumor cells which is mediated by overexpression of P-glycoprotein. We show here that the P. falciparum homologue of the P-glycoprotein (Pgh1) is a 160,000-D protein that is expressed throughout the asexual erythrocytic life cycle of the parasite. Quantitative immunoblotting analysis has shown that the protein is expressed at approximately equal levels in chloroquine resistant and sensitive isolates suggesting that overexpression of Pgh1 is not essential for chloroquine resistance. The chloroquine-resistant cloned line FAC8 however, does express approximately threefold more Pgh1 protein than other isolates which is most likely because of the increased pfmdr1 gene copy number present in this isolate. Immunofluorescence and immunoelectron microscopy has demonstrated that Pgh1 is localized on the membrane of the digestive vacuole of mature parasites. This subcellular localization suggests that Pgh1 may modulate intracellular chloroquine concentrations and has important implications for the normal physiological function of this protein.


Two new stingrays (Chondrichthyes: Dasyatidae) from the eastern Indonesian Archipelago.
Two new stingrays, Dasyatis longicauda sp. nov. and Himanturajavaensis sp. nov., are described from material collected in the eastern Indonesian Archipelago. These species, which are both relatively small stingrays (both probably smaller than 40 cm DW), have been confused with closest relatives in the region. Dasyatis longicauda sp. nov., known from West Papua, differs from its congener, the Australian endemic D. fluviorum, in having a slightly lower vertebral count, lower pectoral-radial count, a longer tail, larger and less numerous thorns along the mid-disc and tail, as well as a different CO1 Barcode. Himantura javaensis sp. nov., known only from southern Java (near Cilacap), belongs to a complex of small whiprays which also includes another Indonesian species, H. walga. Apart from major differences in squamation and a different CO1 Barcode, Himantura javaensis is more brownish in coloration, has more vertebrae, a longer tail, smaller eye and orbit, more posteriorly positioned sting, shorter adult claspers, shorter pelvic fin, and differs in various measurements around the head.


Genomic analysis of PIS1 gene expression.
The Saccharomyces cerevisiae PIS1 gene is essential and required for the final step in the de novo synthesis of phosphatidylinositol. Transcription of the PIS1 gene is uncoupled from the factors that regulate other yeast phospholipid biosynthetic genes. Most of the phospholipid biosynthetic genes are regulated in response to inositol and choline via a regulatory circuit that includes the Ino2p:Ino4p activator complex and the Opi1p repressor. PIS1 is regulated in response to carbon source and anaerobic growth conditions. Both of these regulatory responses are modest, which is not entirely surprising since PIS1 is essential. However, even modest regulation of PIS1 expression has been shown to affect phosphatidylinositol metabolism and to affect cell cycle progression. This prompted the present study, which employed a genomic screen, database mining, and more traditional promoter analysis to identify genes that affect PIS1 expression. A screen of the viable yeast deletion set identified 120 genes that affect expression of a PIS1-lacZ reporter. The gene set included several peroxisomal genes, silencing genes, and transcription factors. Factors suggested by database mining, such as Pho2 and Yfl044c, were also found to affect PIS1-lacZ expression. A PIS1 promoter deletion study identified an upstream regulatory sequence element that was required for carbon source regulation located downstream of three previously defined upstream activation sequence elements. Collectively, these studies demonstrate how a collection of genomic and traditional strategies can be implemented to identify a set of genes that affect the regulation of an essential gene.


Knowledge, attitudes and practices regarding antimicrobial use and resistance among communities of Ilala, Kilosa and Kibaha districts of Tanzania.
Antimicrobial resistance (AMR) represents one of the biggest threats to health globally. This cross-sectional study determined knowledge, attitudes and practices (KAP) regarding antimicrobial use (AMU) and AMR among communities of Ilala, Kilosa and Kibaha in Tanzania. A semi-structured questionnaire was used to collect socio-demographic and KAP data through face-to-face interviews. Responses related to the triad of KAP were assigned scores that were aggregated for each participant. Linear regression analysis was conducted to determine predictors of KAP scores. The study enrolled 828 participants from the three districts. A total of 816 (98.6%) were aware of antimicrobials, and 808 (99%, n = 816) reported to have used them. Antimicrobials were mainly used to treat cough (68.0%), urinary tract infections (53.4%), diarrhoea (48.5%) and wounds (45.2%). The most frequent sources of antimicrobials were health facility (65.0%, n = 820) and pharmacies/basic drug shops (53.7%). The median AMU knowledge score was 5 (IQR = 4, 7) and that of AMR was 26 (IQR=23, 29). The median AMU attitudes score was 32 (IQR: 29, 35) and that of AMR was 19 (IQR=17, 22). The median AMU practice score was 3 (IQR: 3, 3). The KAP scores were significantly influenced by increased participant's age (βadj=0.10; 95% CI: 0.05, 0.15) and level of education, being lower among those with primary education (βadj=5.32; 95% CI: 3.27, 7.37) and highest among those with college/university education (βadj=9.85; 95% CI: 6.04, 13.67). The study documented a moderate level of KAP regarding AMU and AMR in the study districts. The participant's age and level of education were significantly associated with participant's KAP scores. The observed inadequate knowledge, inappropriate attitude, and practices of AMU and AMR should be considered as alarming problems that require immediate actions including policy formulation and planning of community-based mitigation measures.


Photobiotreatment: influence of nitrogen and phosphorus ratio in wastewater on growth kinetics of Scenedesmus obliquus.
Nitrogen and phosphorus concentration in the effluent of a wastewater treatment plant can vary significantly, which could affect the growth kinetic and chemical composition of microalgae when cultivated in this medium. The aim of this work was to study the rate of growth, nutrient removal and carbon dioxide biofixation as well as biomass composition of Scenedesmus obliquus (S. obliquus) when it is cultivated in wastewater at different nitrogen and phosphorus ratio, from 1:1 to 35:1. A more homogeneous method for calculating productivities in batch reactors was proposed. The proper N:P ratio for achieving optimum batch biomass productivity ranged between 9 and 13 (263 and 322 mg L(-1) d(-1) respectively). This was also the ratio range for achieving a total N and P removal. Above and below this range (9-13) the maximum biomass concentration changed, instead of the specific growth rate.The maximum carbon dioxide biofixation rate was achieved at N:P ratio between 13 and 22 (553 and 557 mg CO2 L(-1) d(-1) respectively). Lipid and crude protein content, both depend on the aging culture, reaching the maximum lipid content (34%) at the lowest N:P (1:1) and the maximum crude protein content (34.2%) at the highest N:P (35:1).


Cyclometalatedgold(III)-hydride under oriented external electric fields: a new strategy to modulate its reactivity?
Selected gold complexes have been regarded as promising anti-cancer agents because they can bind with protein targets containing thiol or selenol moieties, but their clinical applications were hindered by the unbiased binding towards off-target thiol-proteins. Recently, a novel gold(III)-hydride complex (abbreviated as 1) with visible light-induced thiol reactivity has been reported as potent photo-activated anticancer agents (Angew. Chem. Int. Ed., 2020, 132, 11139). To explore new strategies to stimuli this potential antitumor drug, the effect of oriented external electric fields (OEEFs) on its geometric structure, electronic properties, and chemical reactivity was systematically investigated. Results reveal that imposing external electric fields along the Au-H bond of 1 can effectively activate this bond, which is conducive to its dissociation and the binding of Au site to potential targets. Hence, this study provides a new OEEF-strategy to activate this reported gold(III)-hydride, revealing its potential application in electrochemical therapy. We anticipate this work could promote the development of more electric field-activated anticancer agents. However, further experimental research should be conducted to verify the conclusions obtained in this work.


Intake of fatty acids and antioxidants and pancreatic cancer in a large population-based case-control study in the San Francisco Bay Area.
There are no well-established modifiable risk factors for pancreatic cancer except smoking. Some dietary factors have been associated with pancreatic cancer risk and require further study. We examined the associations among intake of specific fatty acids and antioxidants and risk of pancreatic cancer in a large population-based case-control study in the San Francisco Bay Area. Unconditional logistic regression models were used to compute odds ratios (ORs) and 95% confidence intervals (CI) as estimates of relative risk. Positive associations were observed for high levels of the 8 individual saturated fatty acids (4th vs. 1st quartile: ORs ranged from 1.6 to 2.6; all p(trend) < 0.01), monounsaturated palmitoleic and oleic fatty acids [OR = 1.6 (95% CI: 1.2-2.1) and 1.4 (95% CI: 1.1-1.9); both p(trend) < 0.01], and polyunsaturated linolenic acid [OR = 1.5 (95% CI: 1.1-2.0); p(trend) = 0.02]. Inverse associations were observed for high levels of gadolic acid [4th vs. 1st quartile: OR = 0.68 (95% CI: 0.50-0.92); p(trend) = 0.007] and omega-3 fatty acids [>or=0.85 g/day vs. 1st quartile: OR = 0.47 (95% CI: 0.25-0.90)]. An inverse association was also observed for high total intake of vitamin C [4th vs. 1st quartile: OR = 0.69 (95% CI: 0.51-0.94); p(trend) = 0.004] and of vitamin E [OR = 0.67 (95% CI: 0.49-0.92); p(trend) = 0.01]. Although similar decreased risks were also observed for high supplemental intake of these 2 vitamins (both p(trend) < 0.01), no association was observed for intake from food alone. These results support the hypotheses that a high intake of saturated and certain monounsaturated fatty acids may increase the risk of pancreatic cancer, whereas greater intake of omega-3 fatty acids, vitamins C and E may reduce the risk.


Sensitivity to the abl inhibitor STI571 in fresh leukaemic cells obtained from chronic myelogenous leukaemia patients in different stages of disease.
STI571 (CGP57148B) is an inhibitor of BCR/ABL, the cause of chronic myeloid leukaemia (CML). A difference exists between CML patients in chronic phase, in which responses to STI571are durable, and patients in blast crisis, who generally experience only transient responses. Leukaemic cells from six CML patients from whom samples could be obtained during chronic phase and at the time of blast crisis (BC) were compared for sensitivity to STI571, using an in vitro assay. BC samples showed a sensitivity similar to that obtained during chronic phase, suggesting that no substantial intrinsic resistance to STI571 was present in BC.


Mental and sexual health outcomes following sexual assault in adolescents: a prospective cohort study.
Young people are disproportionately affected by sexual assault, yet longitudinal data are sparse. This paper examines the characteristics of adolescents presenting to sexual assault services and mental and sexual health outcomes after an assault. This was a prospective cohort study in adolescents aged 13-17 years attending the Sexual Assault Referral Centres serving Greater London, UK, over 2 years. Baseline interviews (T0) were done less than 6 weeks after an assault to collect data on sociodemographic and assault characteristics and psychological symptoms, with follow-up interviews (T1) at 4-5 months after the assault. Four psychological symptom questionnaires were used at T0 and T1: The Child Revised Impact of Events Scale, the Short Mood and Feelings Questionnaire, the Screen for Child Anxiety Related Disorders, and the Strengths and Difficulties Questionnaire. The primary outcome was prevalence of any psychiatric disorder at T1, assessed using the Development and Wellbeing Assessment. Secondary outcomes at T1 were pregnancy, sexually transmitted infections, and sexual health screening since the assault. Between April 15, 2013, and April 20, 2015, 141 (29%) of 491 eligible young people were recruited to the study (134 females; mean age 15·6 years [SD 1·27]), and 106 (75%) of 141 participants had T1 interviews (99 female). At T0, psychological symptom scores showed that 115 (88%) of 130 females were at risk for depressive disorder, 90 (71%) of 126 were at risk for anxiety disorders, and 116 (91%) of 128 were at risk for post-traumatic stress disorder, with symptoms largely persisting at T1. 68 (80%) of 85 females who had a diagnostic assessment at T1 had a psychiatric disorder, with multiple disorders in 47 (55%) of 85. Anxiety, post-traumatic stress, and major depressive disorders were the commonest diagnoses. Presence of a psychiatric disorder was associated with baseline psychosocial vulnerability (previous social services involvement, mental health service use, self-harm, or sexual abuse), but not assault characteristics. At T1, four (4%) of 105 females had been pregnant since the assault, 14 (12%) of 119 had a sexually transmitted infection diagnosed between T0 and T1, and nine (8%) of 107 reported re-victimisation since the assault. Vulnerable adolescents have the double disadvantage of being at risk for both sexual assault and associated psychiatric disorders, highlighting the need for comprehensive support after an assault. Feasibility and effectiveness of prevention programmes should be investigated. National Institute for Health Research Policy Research Programme grant (115/0001).


Prospective evaluation of risk factors for mortality in patients of Fournier's gangrene: A single center experience.
Fournier's gangrene is an aggressive disease with high morbidity and mortality. The aim of this study was to assess risk factors associated with mortality among patients of Fournier's gangrene. Between May 2011 and September 2012, all patients of Fournier's gangrene treated at our center were included in the study. All patients underwent emergency surgical debridement and received broad spectrum intravenous antibiotics. Their baseline characteristics, treatment, and follow-up data were recorded and analyzed. A total of 30 patients were included in the study. Of these, six patients (20%) died during the treatment. Age <55 years, total leukocyte count <15000 cumm, extent of the area involved, septic shock at admission, visual analog scale (VAS) <7 at admission, and Fournier gangrene severity index (FGSI) score <8 at admission were significantly associated with increased mortality. In patients of Fournier's gangrene, increased age, total leukocyte count, extent of the area involved, septic shock at admission, VAS score, and FGSI score at admission have a significant association with mortality.


Mitochondrial nitric-oxide synthase stimulation causes cytochrome c release from isolated mitochondria. Evidence for intramitochondrial peroxynitrite formation.
Nitric oxide (NO) is synthesized by members of the NO synthase (NOS) family. Recently the existence of a mitochondrial NOS (mtNOS), its Ca(2+) dependence, and its relevance for mitochondrial bioenergetics was reported (Ghafourifar, P., and Richter, C. (1997) FEBS Lett. 418, 291-296; Giulivi, C., Poderoso, J. J., and Boveris, A. (1998) J. Biol. Chem. 273, 11038-11043). Here we report on the possible involvement of mtNOS in apoptosis. We show that uptake of Ca(2+) by mitochondria triggers mtNOS activity and causes the release of cytochrome c from isolated mitochondria in a Bcl-2-sensitive manner. mtNOS-induced cytochrome c release was paralleled by increased lipid peroxidation. The release of cytochrome c as well as increase in lipid peroxidation were prevented by NOS inhibitors, a superoxide dismutase mimic, and a peroxynitrite scavenger. We show that mtNOS-induced cytochrome c release is not mediated via the mitochondrial permeability transition pore because the release was aggravated by cyclosporin A and abolished by blockade of mitochondrial calcium uptake by ruthenium red. We conclude that, upon Ca(2+)-induced mtNOS activation, peroxynitrite is formed within mitochondria, which causes the release of cytochrome c from isolated mitochondria, and we propose a mechanism by which elevated Ca(2+) levels induce apoptosis.


Small GTPase RhoE/Rnd3 is a critical regulator of Notch1 signaling.
Aberrations of Notch signaling have been implicated in a variety of human cancers. Oncogenic mutations in NOTCH1 are common in human T-cell leukemia and lymphomas. However, loss-of-function somatic mutations in NOTCH1 arising in solid tumors imply a tumor suppressor function, which highlights the need to understand Notch signaling more completely. Here, we describe the small GTPase RhoE/Rnd3 as a downstream mediator of Notch signaling in squamous cell carcinomas (SCC) that arise in skin epithelia. RhoE is a transcriptional target of activated Notch1, which is attenuated broadly in SCC cells. RhoE depletion suppresses Notch1-mediated signaling in vitro, rendering primary keratinocytes resistant to Notch1-mediated differentiation and thereby favoring a proliferative cell fate. Mechanistic investigations indicated that RhoE controls a key step in Notch1 signaling by mediating nuclear translocation of the activated portion of Notch1 (N1IC) through interaction with importins. Our results define RhoE as a Notch1 target that is essential for recruitment of N1IC to the promoters of Notch1 target genes, establishing a regulatory feedback loop in Notch1 signaling. This molecular circuitry may inform distinct cell fate decisions to Notch1 in epithelial tissues, where carcinomas such as SCC arise.


Prevalence and risk of cancer of focal thyroid incidentaloma identified by 18F-fluorodeoxyglucose positron emission tomography for cancer screening in healthy subjects.
The aim of this study was to define the clinical prevalence and rate of malignancy of focal thyroid incidentaloma in a relatively large number of individuals with application of 18F-fluorodeoxyglucose (FDG) Positron Emission Tomography (PET) in asymptomatic individuals. The subjects consisted of 4803 physical check-up examinees (2638 men, 2165 women; mean age+/-SD, 52.8+/-9 years old) with non-specific medical history. Whole-body FDG PET was performed on all patients. Focal hypermetabolic areas of thyroid, with an intensity equal to or exceeding the level of FDG uptake in the liver, were considered abnormal and interpreted as thyroid incidentaloma. Among the 4803 FDG PET examinations, thyroid incidentaloma was present in 60 examinations, among which, 50 had further examination with ultrasound-guided fine-needle aspiration (FNA), revealing 43 benign lesions and 7 papillary carcinomas. Of 7 examinees diagnosed with cancer, 2 had lymph nodes metastasis. The mean and standard deviation of standard uptake value (SUV) in benign and carcinoma was 2.6+/-1.01 and 6.7+/-3.66, respectively. Thyroid incidentaloma identified by FDG-PET occurred with a frequency of 1.2% (60/4803). Of the thyroid incidentalomas that underwent FNA and surgery, 14% (7/50) were found to be malignant. It is possible to differentiate benign from carcinoma of thyroid incidentalomas by the increased rate of glycolysis (SUV) in the carcinoma. The small size and moderate FDG uptake of thyroid incidentalomas per se cannot guarantee low risk in incidentally found thyroid cancers.


Tryptophan-derived secondary metabolites in Arabidopsis thaliana confer non-host resistance to necrotrophic Plectosphaerella cucumerina fungi.
A defence pathway contributing to non-host resistance to biotrophic fungi in Arabidopsis involves the synthesis and targeted delivery of the tryptophan (trp)-derived metabolites indol glucosinolates (IGs) and camalexin at pathogen contact sites. We have examined whether these metabolites are also rate-limiting for colonization by necrotrophic fungi. Inoculation of Arabidopsis with adapted or non-adapted isolates of the ascomycete Plectosphaerella cucumerina triggers the accumulation of trp-derived metabolites. We found that their depletion in cyp79B2 cyp79B3 mutants renders Arabidopsis fully susceptible to each of three tested non-adapted P. cucumerina isolates, and super-susceptible to an adapted P. cucumerina isolate. This assigns a key role to trp-derived secondary metabolites in limiting the growth of both non-adapted and adapted necrotrophic fungi. However, 4-methoxy-indol-3-ylmethylglucosinolate, which is generated by the P450 monooxygenase CYP81F2, and hydrolyzed by PEN2 myrosinase, together with the antimicrobial camalexin play a minor role in restricting the growth of the non-adapted necrotrophs. This contrasts with a major role of these two trp-derived phytochemicals in limiting invasive growth of non-adapted biotrophic powdery mildew fungi, thereby implying the existence of other unknown trp-derived metabolites in resistance responses to non-adapted necrotrophic P. cucumerina. Impaired defence to non-adapted P. cucumerina, but not to the non-adapted biotrophic fungus Erysiphe pisi, on cyp79B2 cyp79B3 plants is largely restored in the irx1 background, which shows a constitutive accumulation of antimicrobial peptides. Our findings imply differential contributions of antimicrobials in non-host resistance to necrotrophic and biotrophic pathogens.


Molecular arrangement in self-assembled azobenzene-containing thiol monolayers at the individual domain level studied through polarized near-field Raman spectroscopy.
6-[4-(phenylazo)phenoxy]hexane-1-thiol self-assembled monolayers deposited on a gold surface form domain-like structures possessing a high degree of order with virtually all the molecules being identically oriented with respect to the surface plane. We show that, by using polarized near-field Raman spectroscopy, it is possible to derive the Raman scattering tensor of the ordered layer and consequently, the in-plane molecular orientation at the individual domain level. More generally, this study extends the application domain of the near-field Raman scattering selection rules from crystals to ordered organic structures.


[Topography of changes in the mucosa of the gastro-duodenal region in chronic gastritis and peptic ulcer].
Topographic studies of 789 gastro- and duodenobiopsies obtained from 493 patients with chronic gastritis and peptic ulcer and from 37 individuals without gastro-duodenal pathology obtained various regions of the stomach and the duodenum were carried out. It was found out that investigation of only one piece of the tissue not in all cases reflected a histological state of the mucosa of the certain regions of the gastro-duodenal area. An isolated gastritis in the body of the stomach in patients with chronic gastritis was found to occur 3 times as seldom as in its distal region. The mucosa of the duodenum was affected almost equally often both in peptic ulcer of this organ and in chronic gastritis. In a number of patients the clinical picture diagnosed as chronic gastritis in reality turned out to be caused by morphological changes in the mucosa of the duodenum, but not of the stomach. At the same time, in a duodenal localization of ulcer not infrequently there were observed histological changes in the gastric mucosa aggravating the course of the main pathological process.


Use of multiplexed tandem PCR to estimate the prevalence and intensity of Theileria orientalis infections in cattle.
This study employed a semi-quantitative, multiplexed tandem PCR (MT-PCR) to assess the prevalence and infection intensity of four genotypes (buffeli, chitose, ikeda and type 5) of Theileria orientalis in cattle in Australia. Genomic DNA samples from blood samples (n=448) collected from 27 to 32 dairy cows from each of 15 dairy herds with a history of recent theileriosis outbreaks (Group 1), and from blood samples available from 24 cows with or without oriental theileriosis (Group 2) were tested using MT-PCR. Results revealed that all four genotypes were present in Group 1 cattle; genotype buffeli had the highest prevalence (80.5%), followed by genotypes ikeda (71.4%), chitose (38.6%) and type 5 (20.3%). Genotype ikeda had the highest average infection intensity in the cattle (relating to 55,277 DNA copies), followed by buffeli, chitose and type 5 (6354-51,648 copies). For Group 2, results indicated that genotype ikeda had a significantly higher average intensity of infection than buffeli in symptomatic cattle (P<0.001), and symptomatic cattle had a higher intensity of ikeda than asymptomatic cattle (P=0.004). Future studies should assess the utility of the present MT-PCR assay as a diagnostic and epidemiological tool in other parts of Australasia and the world.


Emergency Department-Initiated Tobacco Control: Update of a Systematic Review and Meta-Analysis of Randomized Controlled Trials.
A 2012 systematic review and meta-analysis of randomized controlled trials on emergency department-initiated tobacco control (ETC) showed only short-term efficacy. The aim of this study was to update data through May 2015. After registering the study protocol on the international prospective register of systematic reviews (PROSPERO) in May 2015, we searched 7 databases and the gray literature. Our outcome of interest was the point prevalence of tobacco-use abstinence at 1-month, 3-month, 6-month, or 12-month follow-up. We calculated the relative risk (RR) of tobacco-use abstinence after ETC at each follow-up time separately for each study and then pooled Mantel-Haenszel RRs by follow-up time. These results were pooled with results of the 7 studies included in the previous review. We calculated the effect of ETC on the combined point prevalence of tobacco-use abstinence across all follow-up times by using generalized linear mixed models. We retrieved 4 additional studies, one published as an abstract, comprising 1,392 participants overall. The 1-month follow-up point prevalence of tobacco-use abstinence after ETC resulted in an RR of 1.49 (95% confidence interval [CI], 1.08-2.05) across 3 studies; 3-month follow-up, an RR of 1.38 (95% CI, 1.12-1.71) across 9 studies; 6-month follow-up, an RR of 1.09 (95% CI, 0.84-1.41) across 6 studies; and 12-month follow-up, an RR of 1.26 (95% CI, 1.00-1.59) across 3 studies. The effect on the combined point prevalence of abstinence was an RR of 1.40 (95% CI, 1.06-1.86) (P = .02). ETC is effective in promoting continual tobacco-use abstinence up to 12 months after intervention. ETC may be a critically important public health strategy for engaging hard-to-reach smokers in tobacco-use cessation.


Methods to evaluate cytotoxicity and immunosuppression of combustible tobacco product preparations.
Among other pathophysiological changes, chronic exposure to cigarette smoke causes inflammation and immune suppression, which have been linked to increased susceptibility of smokers to microbial infections and tumor incidence. Ex vivo suppression of receptor-mediated immune responses in human peripheral blood mononuclear cells (PBMCs) treated with smoke constituents is an attractive approach to study mechanisms and evaluate the likely long-term effects of exposure to tobacco products. Here, we optimized methods to perform ex vivo assays using PBMCs stimulated by bacterial lipopolysaccharide, a Toll-like receptor-4 ligand. The effects of whole smoke-conditioned medium (WS-CM), a combustible tobacco product preparation (TPP), and nicotine were investigated on cytokine secretion and target cell killing by PBMCs in the ex vivo assays. We show that secreted cytokines IFN-γ, TNF, IL-10, IL-6, and IL-8 and intracellular cytokines IFN-γ, TNF-α, and MIP-1α were suppressed in WS-CM-exposed PBMCs. The cytolytic function of effector PBMCs, as determined by a K562 target cell killing assay was also reduced by exposure to WS-CM; nicotine was minimally effective in these assays. In summary, we present a set of improved assays to evaluate the effects of TPPs in ex vivo assays, and these methods could be readily adapted for testing other products of interest.


Angle Class III malocclusion with anteroposterior and vertical discrepancy in the final stage of growth.
Angle Class III malocclusion is characterized by an anteroposterior dental discrepancy with or without anteroposterior and vertical skeletal changes. Patients usually seek orthodontic treatment because facial appearance is compromised in most cases. The present study describes the clinical case of a 12-year and 6-month-old girl in her final stage of pubertal growth presenting Class III malocclusion with anteroposterior and vertical discrepancies. Initial treatment consisted of maxillary expansion using a Hass expander followed by the use of a Petit facemask for a minimum of 16 hours a day. During corrective treatment, Class III elastics were used to complement protraction. At the end of the treatment, skeletal discrepancy had improved, and the ANB angle increased from 0 to 2o. Angle Class III malocclusion, anterior crossbite and open bite were corrected. This case was presented to the Committee of the Brazilian Board of Orthodontics and Facial Orthopedics (BBO) as part of the requisites to become a BBO Diplomate.


Endothelial cell integrin alpha5beta1 expression is modulated by cytokines and during migration in vitro.
Alterations in endothelial cell-extracellular matrix interactions are central to the process of angiogenesis. We have investigated the effect of wound-induced two-dimensional migration, basic fibroblast growth factor (bFGF), transforming growth factor-beta1 (TGF-beta1) and leukemia inhibitory factor (LIF) on expression of the alpha5beta1 integrin in endothelial cells. In multiple-wounded monolayers of bovine microvascular endothelial (BME) cells, an increase in mRNA and total protein for both alpha5 and beta1 subunits was observed, and this could be correlated with a reduction in cell density but not proliferation, both of which are induced following wounding. Although as previously reported, the alpha5 subunit was increased when cells were exposed to TGF-beta1 alone, co-addition of bFGF and TGF-beta1 resulted in a striking synergistic induction of alpha5, with no significant changes in the expression of beta1. In contrast, the alpha5 subunit was decreased by LIF in bovine aortic endothelial but not in BME cells. These findings suggest that quantitative alterations in alpha5 and beta1 integrin subunit expression modulate the adhesive and migratory properties of endothelial cells during angiogenesis.


ABA overly-sensitive 5 (ABO5), encoding a pentatricopeptide repeat protein required for cis-splicing of mitochondrial nad2 intron 3, is involved in the abscisic acid response in Arabidopsis.
To study the molecular mechanism of abscisic acid (ABA) regulation of root development, we screened the root growth of Arabidopsis mutants for sensitivity to ABA. ABA overly-sensitive 5 (ABO5/At1g51965) was identified, and was determined to encode a pentatricopeptide repeat protein required for cis-splicing of mitochondrial nad2 intron 3 (nad2 is one subunit in complex I). Under constant light conditions (24-h light/0-h dark photoperiod), abo5 mutants exhibited various phenotypes and expressed lower transcripts of stress-inducible genes, such as RD29A, COR47 and ABF2, and photosynthesis-related genes proton gradient regulation 5 (PGR5) and PGR5-likephotosynthetic phenotype (PGRL1), but higher levels of nuclear-encoded genes alternative oxidase 1a (AOX1a) and oxidative signal-inducible 1 (OXI1). Prolonged ABA treatment increased the expression of the cox2 gene in complex IV and nad genes in complex I to a higher level than no ABA treatment in the wild type, but only to a moderate level in abo5, probably because abo5 already expressed high levels of mitochondrial-encoded cox2 and nad genes under no ABA treatment. More H(2) O(2) accumulated in the root tips of abo5 than in the wild type, and H(2) O(2) accumulation was further enhanced by ABA treatment. However, these growth phenotypes and gene-expression defects were attenuated by growing abo5 plants under short-day conditions (12-h light/12-h dark photoperiod). Our results indicate that ABO5 is important in the plant response to ABA.


Perceptions of educators of Deaf and hard-of-hearing adolescents of HIV-risk factors for these youths.
Like the general population in South Africa, adolescents with deafness or who are hard-of-hearing may be vulnerable to HIV infection. They are exposed to all known risk factors for HIV infection. Educators who work in schools for Deaf (meaning culturally deaf) and hard-of-hearing adolescents can provide valuable information about HIV-risk factors for these youths. We conducted 21 in-depth interviews and two focus group discussions with educators of Deaf and hard-of-hearing adolescents in six schools in two provinces of South Africa. We explored the participants' perceptions of the HIV-risk factors to which their learners are exposed. The educators were aware of the adolescents' vulnerability to HIV infection. All the participants believed that Deaf and hard-of-hearing adolescents are at risk of contracting HIV due to vulnerability to sexual abuse and higher-risk sexual behaviour. The participants were aware of substance abuse patterns, such as excessive alcohol use or recreational drug use, among their learners. Adolescence is a vulnerable period, and adolescents who are Deaf or hard-of-hearing are likewise exposed to the risk of HIV infection.


Myiasis caused by Dermatobia hominis in Mexico: morphological and molecular identification using the cytochrome oxidase I gene.
Myiasis caused by Dermatobia hominis , the human botfly, is frequent in the Americas, however, scarce morphological and molecular information exist regarding this dipteran. We describe three cases in urban areas of Mexico were D. hominis is not endemic. Morphological and genetic identification were performed using the cytochrome oxidase I as a molecular marker. The mitochondrial cytochrome oxidase I gene is useful for inferring the genetic divergence of D. hominis .


Thirteen years HIV-1 sentinel surveillance and indicators for behavioural change suggest impact of programme activities in south-west Tanzania.
To describe the evolution of the HIV-1 epidemic among women attending antenatal clinics in four different geographic areas within two rural regions with differing intervention intensity in south-west Tanzania. Age-specific trends in HIV-1 seroprevalence among antenatal clinic attendees in four distinct geographic areas of Mbeya region between 1988 and 2000 and in one area of Rukwa region between 1991 and 1999 were analysed and compared. In Mbeya region a comprehensive AIDS control programme has been implemented since 1988. Indicators measuring behavioural change and the attendance rate of patients with sexually transmitted diseases (STDs) were monitored through the established routine system, complemented by two Knowledge, Attitude and Practise (KAP) surveys in 1995 and 1999. Data showed an increasing HIV-1 prevalence from 1988 up to 1994/95 for women in the age group 15-24 years across all strata. Between 1994/95 and 2000 the prevalence declined significantly in all strata for this age group in Mbeya region with diverse patterns in spread of the infection accompanied by a significant decrease in the positive syphilis serology, high rate of condom use, significant delay of age for the start of sexual activity of primary school pupils and a high treatment rate for STDs. The increasing trend of the HIV-1 prevalence in Rukwa region continued. Declining trends of HIV-1 prevalence among women aged 15-24 years may correspond to a reduced incidence partially attributable to changes in behaviour and reduction of a biological factor influencing HIV-1 transmission to which the implemented programme could contribute.


[Effect of scalp-acupuncture on plasma and cerebral TNF-alpha and IL-1beta contents in acute cerebral ischemia/reperfusion injury rats].
To explore the underlying mechanism of scalp-acupuncture therapy in the treatment of acute cerebral ischemia (ACI) in the rat. A total of 140 SD female rats were randomly assigned to sham-operation (n=20), model (n=60), scalp-acupuncture (SA, n=60) groups, and the later two groups were further divided into 24 h, 48 h and 72 h subgroups separately, with 20 cases in each. Among them, 70 rats were used for cerebral tissue section, and the other 70 cases for homogenating cerebral tissue. ACI model was established by occlusion of the middle cerebral artery (MCAO) for 1 h and reperfusion. EA (2/100 Hz, 2 mA) was applied to bilateral "Dingnie Houxiexian" (MS 7) and "Dingnie Qianxiexian" (MS 6) for 20 min, once daily for 1 d, 2 d and 3 d respectively. The rat's neurological severity score (NSS) was assessed before and after EA. Blood and brain tissue were sampled for detecting TNF-alpha and IL-1beta contents respectively with enzyme-linked immunosorbent assay. Haematoxylin-eosine (H&E) staining method was used for displaying the inflammatory cells in the ischemic brain tissue. (1) After ACI, NSS at each time-point increased significantly, while compared with model group, NSS of SA group decreased apparently 72 h after ACI (P<0.01). Compared with the corresponding time-points of sham-operation group, the number of inflammatory cells, plasma and cerebral TNF-alpha and IL-1beta contents at 24 h, 48 h and 72 h in model group increased considerably (P<0.01, 0.05). In comparison with the corresponding time-points of model group, the number of inflammatory cells at 48 h and 72 h, plasma and cerebral TNF-alpha and IL-1beta contents at 72 h in SA group declined significantly (P<0.01). Scalp-acupuncture can relieve inflammatory cell infiltration, and reduce plasma and cerebral TNF-alpha and IL-1beta contents in ACI rats, which may contribute to its effect in promoting neurofunctional recovery.


Functional interactions between the estrogen receptor coactivator PELP1/MNAR and retinoblastoma protein.
PELP1 (proline-, glutamic acid-, and leucine-rich protein-1 (also referred to as MNAR, or modulator of nongenomic activity of estrogen receptor)), a recently identified novel coactivator of estrogen receptors, is widely expressed in a variety of 17 beta-estradiol (E2)-responsive reproductive tissues and is developmentally regulated in mammary glands. pRb (retinoblastoma protein), a cell cycle switch protein, plays a fundamental role in the proliferation, development, and differentiation of eukaryotic cells. To study the putative function of PELP1, we established stable MCF-7 breast cancer cell lines overexpressing PELP1. PELP1 overexpression hypersensitized breast cancer cells to E2 signaling, enhanced progression of breast cancer cells to S phase, and led to persistent hyperphosphorylation of pRb in an E2-dependent manner. Using phosphorylation site-specific pRb antibodies, we identified Ser-807/Ser-811 of pRb as a potential target site of PELP1. Interestingly, PELP1 was discovered to be physiologically associated with pRb and interacted via its C-terminal pocket domain, and PELP1/pRb interaction could be modulated by antiestrogen agents. Using mutant pRb cells, we demonstrated an essential role for PELP1/pRb interactions in the maximal coactivation functions of PELP1 using cyclin D1 as one of the targets. Taken together, these findings suggest that PELP1, a steroid coactivator, plays a permissive role in E2-mediated cell cycle progression, presumably via its regulatory interaction with the pRb pathway.


Neoadjuvant and Definitive Radiochemotherapeutic Approaches in Esophageal Cancer: A Retrospective Evaluation of 122 Cases in Daily Clinical Routine.
Esophageal cancer (EC) is a common malignant tumor entity with increasing occurrence. The incidence of esophageal adenocarcinoma (AC), particularly, is constantly rising in the Western world. The mainstays of therapy with curative intent for EC in advanced stages are neoadjuvant radiochemotherapy (neoRCT) with surgery and definitive radiochemotherapy (defRCT). We examined our internal files to identify patients suffering from EC. Palliative cases were excluded. Statistical testing was performed by χ2 test, Student's t test, Kaplan-Meier analyses, and the Mann-Whitney U test. One hundred and twenty-two cases were included. Histology revealed squamous cell carcinoma in 92 cases and AC in 23 cases. Ninety-five patients underwent defRCT, 27 underwent neoRCT, and 114 (in both therapy regimes) received simultaneous chemotherapy. There was no difference in the overall survival (OS) (p = 0.654; HR 1.145; 95% CI 0.629-2.086) or and progression-free survival (PFS) (p = 0.912) of patients who underwent neoRCT or defRCT. Median OS was 13.5 (2-197) months for defRCT patients and 19.5 (2-134) months for neoRCT patients (p = 0.751). Karnofsky index (KI) with a cut-off of 70% was strongest, but not a significant parameter for OS (p = 0.608) or PFS (p = 0.137). defRCT is a valid and an equal alternative to neoRCT for patients suffering from EC. Selection of patients for therapy is of crucial relevance. Further studies and improvements in follow-up are needed when neoRCT has been completed before surgery, in order to spare the patient undergoing operative treatment if there is complete remission. The identification of valid markers urgently needed to limit treatment side effects.


Altered fMRI activation during mental rotation in those at genetic risk for Alzheimer disease.
This study was undertaken to examine differential functional MRI patterns in those at genetic risk for Alzheimer disease (AD), specifically investigating parietal lobe activation, a brain region with changes noted in the early stages of AD. This study uses functional MRI to investigate blood oxygenation level dependent changes in the parietal lobe in a high-risk sample of 18 asymptomatic offspring of autopsy-confirmed AD cases, compared to 15 matched controls. The cognitive activation paradigm was a mental rotation task, which requires individuals to rotate three-dimensional cube stimuli to judge their similarity. We found no differences in either reaction time or performance accuracy between groups. However, the at-risk individuals showed increases in activation in the right superior parietal lobule (BA 7), the right insula (BA 13), the right middle frontal gyrus (BA 10), and the right inferior frontal gyrus (BA 47). We present evidence for a compensatory mechanism for those at increased risk for Alzheimer disease (AD). This study examines and confirms parietal changes with increased risk for late-onset AD, despite normal cognitive performance. Added to the previous findings from this group, these results demonstrate the sensitivity of functional imaging measures to brain changes that are not yet reflected in cognitive performance, which may ultimately serve as an important indicator of disease.


Nutrition and resistance exercise during reconditioning from unloading.
The recovery of muscle size and function following musculoskeletal unloading has received little attention in the scientific literature. Nutritional factors such as total energy, protein intake, and the pre- and/or post-exercise consumption of amino acid-carbohydrate (AACHO) have been shown to be important for enhancing training adaptations in recreational exercisers. A preliminary study was conducted to explore the interaction between nutrition and resistance exercise during reconditioning from unloading. Muscle CSA, strength, and endurance were measured during a control period following 30 d of unilateral lower limb suspension (Post-ULLS) and after 18 d of reconditioning (ReCon). Six participants consumed either AACHO (979 kJ, 36 g carbohydrate, 22.5 g protein) or placebo (PLAC) prior to resistance exercise (3 d x wk(-1)) during reconditioning. Total daily energy and macronutrient intake were evaluated from dietary journals. From Post-ULLS to ReCon, muscle endurance increased 1.1 +/- 0.6 min in AACHO and decreased 1.3 +/- 0.7 min in PLAC. Muscle CSA (6 +/- 2 vs. 5 +/- 3 cm2) and strength (105 +/- 53 vs. 81 +/- 37 N) increased similarly in AACHO and PLAC, respectively. When groups were pooled there was a significant correlation between daily protein intake and the recovery of muscle CSA (r = 0.81). Although our findings are preliminary, timing AACHO intake during reconditioning was beneficial for muscular endurance, while overall protein intake was associated with increased muscle size. A systematic evaluation into the synergistic relationship between nutrition and exercise during muscular recovery from prolonged unloading is warranted.


Characteristics of Yersinia intermedia-like bacteria isolated from patients with diarrhea in Nigeria.
Five Yersinia strains, biochemically mimicking Yersinia intermedia, were isolated from patients with acute diarrheal diseases seen at the University of Lagos (Nigeria) Teaching Hospital between October 1979 and September 1982. The five isolates utilized citrate as their source of carbon and fermented sucrose, L-rhamnose, and alpha-methyl-D-glucoside, but unlike any other Y. intermedia biogroup, they failed to ferment D-melibiose or D-raffinose. They all belonged to serogroup O:52,53. Four autoagglutinated and were calcium dependent for growth at 37 degrees C. Three caused conjunctivitis in the guinea pig eye model, but none possessed the 42-megadalton virulence plasmid. Four of the isolates caused diarrhea in orally infected mice and rabbits but were nonlethal for these animals. These results suggest that these isolates represent yet another Yersinia species with disease-producing capabilities in humans.


Effect of acoustic wave inertia and its implication to slow light via stimulated Brillouin scattering in an extended medium.
An analytical solution of the basic coupled stimulated Brillouin scattering (SBS) equations is obtained which describes the evolution of a Stokes pulse injected into an extended Brillouin medium excited by CW pump radiation. We show that regardless of the pulse length of the input Stokes pulse the delay of the output Stokes pulse results entirely from the inertia of the acoustic wave excitation via the electrostrictive interaction of the Stokes pulse with CW pump radiation. This delay is the SBS build up time and not the SBS induced group delay normally attributed to slow light.


Functional properties and differential neuromodulation of Na(v)1.6 channels.
The voltage-gated sodium channel Na(v)1.6 plays unique roles in the nervous system, but its functional properties and neuromodulation are not as well established as for Na(V)1.2 channels. We found no significant differences in voltage-dependent activation or fast inactivation between Na(V)1.6 and Na(V)1.2 channels expressed in non-excitable cells. In contrast, the voltage dependence of slow inactivation was more positive for Na(v)1.6 channels, they conducted substantially larger persistent sodium currents than Na(v)1.2 channels, and they were much less sensitive to inhibition by phosphorylation by cAMP-dependent protein kinase and protein kinase C. Resurgent sodium current, a hallmark of Na(v)1.6 channels in neurons, was not observed for Na(V)1.6 expressed alone or with the auxiliary beta(4) subunit. The unique properties of Na(V)1.6 channels, together with the resurgent currents that they conduct in neurons, make these channels well-suited to provide the driving force for sustained repetitive firing, a crucial property of neurons.


High-performance thin-layer chromatography fingerprinting, total phenolic and total flavonoid contents and anti-platelet-aggregation activities of Prosopis farcta extracts.
Cardiovascular diseases are a leading cause of worldwide death and excessive platelet is closely related with their pathogenesis. Different plants and natural compounds have demonstrated anti-platelet effects. The aim of this study was to report the high-performance thin-layer chromatography (HPTLC) fingerprinting and anti-platelet-aggregation activities of different leaf extracts (n-hexane, chloroform, ethyl acetate, methanol and aqueous) of Prosopis farcta (Syrian mesquite) plant. The results showed a 100% inhibition of aggregation activity after plasmatic adenosine diphosphate (ADP) aggregation activation of ethyl acetate, ethanolic, methanolic and aqueous extracts, at 60 mg/mL concentration. The IC50 ADP value of these extracts ranged between 4.07 and 11.39 mg/mL. Moreover, these extracts reported the highest amounts of phenolic and flavonoid contents. In conclusion, phytochemicals present in P. farcta leaves have anti-platelet-aggregation activities. Future studies are needed to identify the compounds with anti-platelet potential present in P. farcta.


Cluster randomised controlled trial evaluating the clinical and humanistic impact of a pharmacist-led minor ailment service.
Community pharmacists are well positioned to support patients' minor ailments. The objective was to evaluate the clinical and humanistic impact of a minor ailment service (MAS) in community pharmacy compared with usual pharmacist care (UC). A cluster randomised controlled trial was conducted. Intervention patients received MAS, which included a consultation with the pharmacist. MAS pharmacists were trained in clinical pathways and communication systems mutually agreed with general practitioners and received monthly support. Control patients received UC. All patients were followed up by telephone at 14 days. Clinical and humanistic impact were defined by primary (appropriate referral rate and appropriate non-prescription medicine rate) and secondary outcomes (clinical product-based intervention rate, referral adherence, symptom resolution, reconsultation and EuroQol EQ-5D visual analogue scale (VAS)). Patients (n=894) were recruited from 30 pharmacies and 82% (n=732) responded to follow-up. Patients receiving MAS were 1.5 times more likely to receive an appropriate referral (relative rate (RR)=1.51; 95% CI 1.07 to 2.11; p=0.018) and were five times more likely to adhere to referral, compared with UC (RR=5.08; 95%CI 2.02 to 12.79; p=0.001). MAS patients (94%) achieved symptom resolution or relief at follow-up, while this was 88% with UC (RR=1.06; 95% CI 1 to 1.13; p=0.035). MAS pharmacists were 1.2 times more likely to recommend an appropriate medicine (RR 1.20, 95% CI 1.1 to 1.3; p=0.000) and were 2.6 times more likely to perform a clinical product-based intervention (RR=2.62, 95% CI 1.28 to 5.38; p=0.009), compared with UC. MAS patients had a greater mean difference in VAS at follow-up (4.08; 95% CI 1.23 to 6.87; p=0.004). No difference in reconsultation was observed (RR=0.98; 95% CI 0.75 to 1.28; p=0.89). The study demonstrates improved clinical and humanistic outcomes with MAS. National implementation is a means to manage minor ailments more effectively in the Australian health system. ACTRN12618000286246.


Eosinophilic panniculitis: a clinicopathologic study.
Study of 18 patients with biopsy diagnoses of eosinophilic panniculitis revealed diverse patterns of systemic disease, including Wells' syndrome, vasculitis, atopy, and erythema nodosum as well as localized panniculitis. Significant associated diseases included psychiatric illness, 6 (drug dependency, 4); atopy, 5 (asthma, 3); malignancies, 5; immune complex vasculitis, 4; thyroid disease, 2; Wells' eosinophilic cellulitis, 2; glomerulonephritis and sarcoidosis, 1 each. The skin lesions varied from urticarial papules and plaques to purpura, pustules, and ulcerative lesions but always included a nodular subcutaneous component, frequently as a presenting complaint. Eosinophilic panniculitis is a non-specific finding that can signify localized disease, such as an insect bite or injection lipophagic granuloma in a drug-dependent patient, or systemic lymphoma or immune reactive disease. Eosinophilic panniculitis in erythema nodosum is perhaps its most confusing presentation.


Preference of juvenile tiger puffer for light spectrum and tank colours based on different body size and breeding background.
As important environmental factors, the light spectra and tank colours have not received sufficient attention. Most fishes have the ability to perceive environment, distinguish colours, and exhibit preferences or aversions towards different environments, which can provide a reference for the design of their rearing environment. Tiger puffer (Takifugu rubripes) is an important mariculture species in China and East Asia, but its preference for illumination spectra and tank colours is unclear. This study focuses on the preferences of juvenile tiger puffers for different spectra and tank background colours in different rearing backgrounds and body sizes. The experiments were conducted in a preference testing device, and the behavioural videos were recorded and analysed using a motion behaviour tracking system (EthoVision XT 12). The results show that the puffers showed preference for short-wavelength lights ((i.e., cyan, green, etc.), avoidance of long-wavelength light (i.e., red) and less stay time in the full light spectrum and dark. For tank colours, the puffers showed a preference for light background colours (i.e., white), and avoidance of deep background colours (i.e., dark, red, etc.). Fish body sizes and original breeding environment could significantly affect the selective preference of juvenile puffer (P < 0.05). Large puffers preferred green tank colour than small ones, while small ones preferred grey and red. The puffers reared in green light and grey tank for 3 months preferred green light spectrum and green tank colour compared with those reared in full spectrum and grey tank, while the fish reared in full spectrum preferred grey tank colour and area without light. It was also found that the movement rate of juvenile puffers was affected by the light spectra and tank colours and was positively correlated with light wavelength (P < 0.05). Therefore, for tiger puffer breeding, short-wavelength light spectrums (cyan, green, etc.) and light-coloured tank backgrounds (white) are recommended. Long-wavelength Light-emitting diodes and dark tank colours should be avoided in breeding. This study would provide a reference basis for fish light spectra and background colour preference studies, as well as for the improvement of breeding welfare and production efficiency of juvenile tiger puffer.


Diosgenin, a Novel Aldose Reductase Inhibitor, Attenuates the Galactosemic Cataract in Rats.
To seek efficient aldose reductase inhibitors (ARIs) with excellent in vitro and in vivo biological activities against rat galactosemic cataract. The method was firstly optimized to screen strong ARIs from nonoriented synthetic compounds and natural extracts. Then, diosgenin was assessed on osmotic expansion of primarily cultured lens epithelial cells (LECs) induced by galactose (50 mM). Diosgenin was administered to galactosemic rats by oral (100 and 200 mg/kg) or direct drinking (0.1%) to evaluate its anticataract effects. Diosgenin was found as the strongest ARI with IC50 of 4.59 × 10-6 mol/L. Diosgenin (10 μM) evidently inhibited the formation of tiny vacuoles and upregulation of AR mRNA in LECs. In vivo, diosgenin delayed lens opacification, inhibited the increase of ratio of lens weight to body weight, and decreased AR activity, galactitol level, and AR mRNA expression, especially in the diosgenin drinking (0.1%) group. Diosgenin was an efficient ARI, which not only significantly decreased the LECs' osmotic expansion in vitro but also markedly delayed progression of rat galactosemic cataract in vivo. Thus, diosgenin rich food can be recommended to diabetic subjects as dietary management to postpone the occurrence of sugar cataract, and diosgenin deserves further investigation for chronic diabetic complications.


A narrative review of facilitators and barriers to smoking cessation and tobacco-dependence treatment in patients with tuberculosis in low- and middle-income countries.
Smoking is a substantial cause of premature death in patients with tuberculosis (TB), particularly in low- and middle-income countries (LMICs) with high TB prevalence. The importance of incorporating smoking cessation and tobacco-dependence treatment (TDT) into TB care is highlighted in the most recent TB care guidelines. Our objective is to identify the likely key facilitators of and barriers to smoking cessation for patients with TB in LMICs. A systematic search of studies with English-language abstracts published between January 2000 and May 2019 was undertaken in the EMBASE, MEDLINE, EBSCO, ProQuest, Cochrane and Web of Science databases. Data extraction was followed by study-quality assessment and a descriptive and narrative synthesis of findings. Out of 267 potentially eligible articles, 36 satisfied the inclusion criteria. Methodological quality of non-randomized studies was variable; low risk of bias was assessed in most randomized controlled studies. Identified facilitators included brief, repeated interventions, personalized behavioural counselling, offer of pharmacotherapy, smoke-free homes and a reasonable awareness of smoking-associated risks. Barriers included craving for a cigarette, low level of education, unemployment, easy access to tobacco in the hospital setting, lack of knowledge about quit strategies, and limited space and privacy at the clinics. Findings show that the risk of smoking relapse could be reduced through consistent follow-up upon completion of TB therapy and receiving a disease-specific smoking cessation message. Raising awareness of smoking-related health risks in patients with TB and implementing guideline-recommended standardized TDT within national TB programmes could increase smoking cessation rates in this high-risk population.


Free groin flap to the hand with end-to-side vessel anastomosis.
A single case of successful free groin flap transfer to the hand is presented. Its use demonstrates a distinct advantage of free flap transfer, preventing dependent edema and enforced immobilization of the hand necessitated by conventional technics. It also demonstrates a successful end-to-side microarterial anastomosis, thus allowing a continued normal blood supply to the hand.


De novo mapping of α-helix recognition sites on protein surfaces using unbiased libraries.
The α-helix is one of the most common protein surface recognition motifs found in nature, and its unique amide-cloaking properties also enable α-helical polypeptide motifs to exist in membranes. Together, these properties have inspired the development of α-helically constrained (Helicon) therapeutics that can enter cells and bind targets that have been considered "undruggable", such as protein-protein interactions. To date, no general method for discovering α-helical binders to proteins has been reported, limiting Helicon drug discovery to only those proteins with previously characterized α-helix recognition sites, and restricting the starting chemical matter to those known α-helical binders. Here, we report a general and rapid screening method to empirically map the α-helix binding sites on a broad range of target proteins in parallel using large, unbiased Helicon phage display libraries and next-generation sequencing. We apply this method to screen six structurally diverse protein domains, only one of which had been previously reported to bind isolated α-helical peptides, discovering 20 families that collectively comprise several hundred individual Helicons. Analysis of 14 X-ray cocrystal structures reveals at least nine distinct α-helix recognition sites across these six proteins, and biochemical and biophysical studies show that these Helicons can block protein-protein interactions, inhibit enzymatic activity, induce conformational rearrangements, and cause protein dimerization. We anticipate that this method will prove broadly useful for the study of protein recognition and for the development of both biochemical tools and therapeutics for traditionally challenging protein targets.


Heterogeneity in the Antibody Response to Foot-and-Mouth Disease Primo-vaccinated Calves.
Foot-and-mouth disease (FMD) vaccines are routinely used as effective control tools in large regions worldwide and to limit outbreaks during epidemics. Vaccine-induced protection in cattle has been largely correlated with the FMD virus (FMDV)-specific antibodies. Genetic control of cattle immune adaptive responses has been demonstrated only for peptide antigens derived from FMDV structural proteins. Here, we quantify the heterogeneity in the antibody response of cattle primo-vaccinated against FMD and study its association with the genetic background in Holstein and Jersey sires. A total of 377 FMDV-seronegative calves (122 and 255 calves from 16 and 15 Holstein and Jersey sires, respectively) were included in the study. Samples were taken the day prior to primo-vaccination and 45 days post-vaccination (dpv). Animals received commercial tetravalent FMD single emulsion oil vaccines formulated with inactivated FMDV. Total FMDV-specific antibody responses were studied against three viral strains included in the vaccine, and antibody titres were determined by liquid-phase blocking ELISA. Three linear hierarchical mixed regression models, one for each strain, were formulated to assess the heterogeneity in the immune responses to vaccination. The dependent variables were the antibody titres induced against each FMDV strain at 45 dpv, whereas sire's 'breed' was included as a fixed effect, 'sire' was included as a random effect, and 'farm' was considered as a hierarchical factor to account for lack of independence of within herd measurements. A significant association was found between anti-FMDV antibody responses and sire's breed, with lower immune responses found in the Jersey sires' offspring compared with those from Holstein sires. No significant intrabreed variation was detected. In addition, farm management practices were similar in this study, and results of the serological assays were shown to be repeatable. It therefore seems plausible that differences in the immune response may be expected in the event of a mass vaccination campaigns.


Protein, DNA, and virus crystallography with a focused imaging proportional counter.
A set of programs has been developed for rapid collection of x-ray intensity data from protein and virus crystals with a commercially available two-dimensional focused geometry electronic detector. The detector is compact and portable, with unusually high spatial resolution comparable to that used in oscillation photography. It has allowed x-ray data collection on weakly diffracting crystals with large unit cells, as well as more conventional "diffractometer-quality" crystals. The quality of the data is compared with that from oscillation photography and automated diffractometry in the range of unit cells from 96.3 to 383.2 angstroms. Isomorphous and anomalous difference Pattersons, based on detector data, are shown for a variable surface glycoprotein mercury derivative and for a repressor-DNA bromine derivative, which has been solved at 7 angstroms with detector data only.


Does perceptual learning suffer from retrograde interference?
In motor learning, training a task B can disrupt improvements of performance of a previously learned task A, indicating that learning needs consolidation. An influential study suggested that this is the case also for visual perceptual learning. Using the same paradigm, we failed to reproduce these results. Further experiments with bisection stimuli also showed no retrograde disruption from task B on task A. Hence, for the tasks tested here, perceptual learning does not suffer from retrograde interference.


Biofilm monitoring by photoacoustic spectroscopy.
The use of photoacoustic spectroscopy (PAS) as a new biofilm monitoring technique is presented. Growth and detachment of biofilms at three different positions inside a flow channel were monitored by photoacoustic measurements in the visible spectral range (lambda = 532 nm). The experimental approach allows the investigation of the influence of various process parameters (e.g. pH or flow conditions) on growth and detachment of biofilms. In addition, the distribution of the attached biomass can be monitored by depth-resolved photoacoustic measurements.


Placental transfer as a function of uterine blood flow.
The effect of variations of uterine blood flow (F) on placental transfer was examined in six chronic sheep preparations by measuring the placental clearances of ethanol (CE) and antipyrine (CA) at different levels of F. Norepinephrine infusion, hemorrhage, and occlusion of the terminal aorta were used to reduce F below normal. The reduction of F had no appreciable effect on umbilical blood flow (f). In each ewe, CE significantly correlated with F. The CE vs. F relationship at constant f was curvilinear with convexity toward the clearance axis. Regression analysis showed that the equation 1/CE = 1/.911 F + 1/.831 f could account for most of the CE variance (r2 = 0.97). Implicit in this relation is the concept that, given a certain level of placental perfusion, an F/f ratio congruent to 1 is optimal for the exchange of highly diffusible inert molecules between mother and fetus [CE/(F + f) was maximum at F/f = 0.955]. CA was not significantly different from CE at low clearance level but became smaller than CE at clearance values greater than 300 ml/min. This suggests that a high rates of perfusion placental permeability was a factor in limiting CA.


S.P.O.R.R.T.-A Comprehensive Approach to the Assessment and Non-Operative Management of Overuse Knee Conditions in Youth Athletes.
The evaluation of a young athlete with an overuse injury to the knee involves a comprehensive approach. There are a number of elements to consider including assessments of skeletal maturity (biologic maturation), workload (training load + competition load), sport specialization status, and biomechanics. The type of injury and treatment, as well as future prognosis, may be influenced by these and other factors. Calculating the percentage of predicted adult height (PPAH) is a valuable tool in assessing overuse injury patterns and diagnoses in youth athletes. Modifiable and non-modifiable overuse injury risk factors require monitoring from clinicians as young athletes mature and develop over time. Training and rehabilitation programs should be adapted to account for these. In this manuscript, we seek to introduce a novel, comprehensive approach: S.P.O.R.R.T. (Skeletal Maturity, Prior Injury Risk, One Sport Specialization, Rehabilitation, Return to Play, Training Recommendations) (Fig. 1). Overuse, non-traumatic injuries to the knee in youth athletes will be presented in a case-based and evidence-based model to provide a framework for a comprehensive approach to the assessment and treatment of youth athletes with overuse injuries.


A kinematic analysis of the upper limb during the topspin double-handed backhand stroke in tennis.
The purpose of this study was to compare double-handed backhand kinematics of the non-dominant wrist of tennis players using either an eastern or continental grip position with the non-dominant hand. Trajectory data were captured using sixty reflective markers on sixteen sub-elite right-handed tennis players using a 12-camera VICON motion capture system (250 Hz). Participants executed double-handed backhands using two non-dominant grip positions (Eastern [E] and Continental [C]), aiming for two crosscourt zones (Deep [D] and Short [S]), totalling to four conditions (ED, CD, ES and CS). Three successful attempts from each condition were selected for analysis. The eastern grip demonstrated faster horizontal racket head velocity compared to the continental grip. However, no differences were observed in accuracy or spin rate between grips (p > 0.05). In the non-dominant upper limb, elbow flexion was smaller in the continental condition throughout the swing, whilst wrist extension and ulnar deviation was larger. Collectively, these data suggest that the continental grip may place the wrist in a position vulnerable to overuse injury. Future research into the kinetics of the double-handed backhand would help better understand the onset of ulnar-side wrist pain in tennis.


Chromatography purification of canine adenoviral vectors.
Canine adenovirus vectors (CAV2) are currently being evaluated for gene therapy, oncolytic virotherapy, and as vectors for recombinant vaccines. Despite the need for increasing volumes of purified CAV2 preparations for preclinical and clinical testing, their purification still relies on the use of conventional, scale-limited CsCl ultracentrifugation techniques. A complete downstream processing strategy for CAV2 vectors based on membrane filtration and chromatography is reported here. Microfiltration and ultra/diafiltration are selected for clarification and concentration of crude viral stocks containing both intracellular and extracellular CAV2 particles. A DNase digestion step is introduced between ultrafiltration and diafiltration operations. At these early stages, concentration of vector stocks with good recovery of viral particles (above 80%) and removal of a substantial amount of protein and nucleic acid contaminants is achieved. The ability of various chromatography techniques to isolate CAV2 particles was evaluated. Hydrophobic interaction chromatography using a Fractogel propyl tentacle resin was selected as a first chromatography step, because it allows removal of the bulk of contaminating proteins with high CAV2 yields (88%). An anion-exchange chromatography step using monolithic supports is further introduced to remove the remaining contaminants with good recovery of CAV2 particles (58-69%). The main CAV2 viral structural components are visualized in purified preparations by electrophoresis analyses. Purified vector stocks contained intact icosahedral viral particles, low contamination with empty viral capsids (10%), and an acceptable total-to-infectious particle ratio (below 30). The downstream processing strategy that was developed allows preparation of large volumes of high-quality CAV2 stocks.


Effects of using a nursing crisis intervention program on psychosocial responses and coping strategies of infertile women during in vitro fertilization.
Infertility and its treatment may cause life crises in infertile women. The purpose of this study is to evaluate the effects of a crisis intervention program on improving psychosocial responses and enhancing coping strategies for infertile women attending different stages of an In-Vitro Fertilization V Embryo Transfer (IVF-ET) treatment program. Using an experimental study design, infertile women attending an IVF-ET treatment program were randomly assigned to experimental and control groups. In the experimental group, infertile women completed and answered a questionnaire and received nursing crisis intervention at the initial stage of treatment (day 3). This included (1). viewing a video explaining the therapeutic process of IVF-ET, (2). self-hypnosis and muscle relaxation training, and (3). provision of cognitive-behavioral counseling. The same questionnaire was used again for subjects at the stage of embryo transfer and before taking a pregnancy test. The women in the control group were only interviewed using the same questionnaire and at the same times as the experimental group. Analysis by repeated measurement ANOVA demonstrated that there was a reduction in psychosocial response in terms of interpersonal relationships, and there was an interaction between intervention effects and stage of treatment. However, there was no statistically significant difference in the level of psychosocial responses between the experimental and control groups although some meaningful findings were made. However, in terms of state of anxiety, confrontational problems, and isolated mind/body relaxation, there were significant differences between the two groups of infertile women at some stages of IVF-ET treatment. The women in the experimental group perceived a positive effect of the nursing intervention in relieving their psychosocial responses. The results of this nursing crisis intervention could be helpful in nursing practice when dealing with infertile women attending IVF treatment programs.


Flow cytometric assessment of drug susceptibility in Leishmania infantum promastigotes.
Flow cytometry can be a valuable tool for parasitology in studies of parasite-drug interaction and cellular toxicity. This unit presents protocols for assessment of Leishmania promastigote proliferation, viability, and cellular protein content. The cytometric approach permits one to detect, differentiate, and quantify cellular changes in these parasites resulting from drug treatment, in this case allopurinol, as well as demonstrate differences in drug susceptibility between promastigote forms. Rapid and relatively simple flow cytometry replaces incorporation of [3H]-thymidine, hitherto the most common method for determining cell division.


COVID-Transformer: Interpretable COVID-19 Detection Using Vision Transformer for Healthcare.
In the recent pandemic, accurate and rapid testing of patients remained a critical task in the diagnosis and control of COVID-19 disease spread in the healthcare industry. Because of the sudden increase in cases, most countries have faced scarcity and a low rate of testing. Chest X-rays have been shown in the literature to be a potential source of testing for COVID-19 patients, but manually checking X-ray reports is time-consuming and error-prone. Considering these limitations and the advancements in data science, we proposed a Vision Transformer-based deep learning pipeline for COVID-19 detection from chest X-ray-based imaging. Due to the lack of large data sets, we collected data from three open-source data sets of chest X-ray images and aggregated them to form a 30 K image data set, which is the largest publicly available collection of chest X-ray images in this domain to our knowledge. Our proposed transformer model effectively differentiates COVID-19 from normal chest X-rays with an accuracy of 98% along with an AUC score of 99% in the binary classification task. It distinguishes COVID-19, normal, and pneumonia patient's X-rays with an accuracy of 92% and AUC score of 98% in the Multi-class classification task. For evaluation on our data set, we fine-tuned some of the widely used models in literature, namely, EfficientNetB0, InceptionV3, Resnet50, MobileNetV3, Xception, and DenseNet-121, as baselines. Our proposed transformer model outperformed them in terms of all metrics. In addition, a Grad-CAM based visualization is created which makes our approach interpretable by radiologists and can be used to monitor the progression of the disease in the affected lungs, assisting healthcare.


A direct interaction between the Utp6 half-a-tetratricopeptide repeat domain and a specific peptide in Utp21 is essential for efficient pre-rRNA processing.
The small subunit (SSU) processome is a ribosome biogenesis intermediate that assembles from its subcomplexes onto the pre-18S rRNA with yet unknown order and structure. Here, we investigate the architecture of the UtpB subcomplex of the SSU processome, focusing on the interaction between the half-a-tetratricopeptide repeat (HAT) domain of Utp6 and a specific peptide in Utp21. We present a comprehensive map of the interactions within the UtpB subcomplex and further show that the N-terminal domain of Utp6 interacts with Utp18 while the HAT domain interacts with Utp21. Using a panel of point and deletion mutants of Utp6, we show that an intact HAT domain is essential for efficient pre-rRNA processing and cell growth. Further investigation of the Utp6-Utp21 interaction using both genetic and biophysical methods shows that the HAT domain binds a specific peptide ligand in Utp21, the first example of a HAT domain peptide ligand, with a dissociation constant of 10 muM.


Synergistic effect of triiodothyronine and dexamethasone on male and female fetal rat lung surfactant synthesis.
It has previously been reported that morphologic and functional indices of fetal lung maturation are delayed in male rabbit fetuses, and these differences cannot be overcome by glucocorticoid treatment. Since thyroid hormone also stimulates surfactant production we have studied the effects of triiodothyronine (T3) and dexamethasone on saturated phosphatidylcholine (SPC) synthesis by day 20 male and female rat lung. Control male lung slices incorporated significantly less 3H-choline into SPC than females; surgery on day 17 markedly stimulated 3H-choline incorporation into SPC by both sexes, but the sex difference persisted. The optimal dose of T3 inhibited SPC synthesis by both sexes while dexamethasone was stimulatory. When T3 and dexamethasone were given together they had a greater effect than that of dexamethasone or T3 alone. Based on these results we conclude that the male deficit in pulmonary surfactant production may be overcome by the synergistic effects of T3 and dexamethasone.


Dynasore inhibits rapid endocytosis in bovine chromaffin cells.
Vesicle recycling is vital for maintaining membrane homeostasis and neurotransmitter release. Multiple pathways for retrieving vesicles fused to the plasma membrane have been reported in neuroendocrine cells. Dynasore, a dynamin GTPase inhibitor, has been shown to specifically inhibit endocytosis and vesicle recycling in nerve terminals. To characterize its effects in modulating vesicle recycling and repetitive exocytosis, changes in the whole cell membrane capacitance of bovine chromaffin cells were recorded in the perforated-patch configuration. Constitutive endocytosis was blocked by dynasore treatment, as shown by an increase in membrane capacitance. The membrane capacitance was increased during strong depolarizations and declined within 30 s to a value lower than the prestimulus level. The amplitude, but not the time constant, of the rapid exponential decay was significantly decreased by dynasore treatment. Although the maximal increase in capacitance induced by stimulation was significantly increased by dynasore treatment, the intercepts at time 0 of the curve fitted to the decay phase were all approximately 110% of the membrane capacitance before stimulation, regardless of the dynasore concentration used. Membrane depolarization caused clathrin aggregation and F-actin continuity disruption at the cell boundary, whereas dynasore treatment induced clathrin aggregation without affecting F-actin continuity. The number of invagination pits on the surface of the plasma membrane determined using atomic force microscopy was increased and the pore was wider in dynasore-treated cells. Our data indicate that dynamin-mediated endocytosis is the main pathway responsible for rapid compensatory endocytosis.


The human T cell receptor beta-chain gene complex contains at least 57 variable gene segments. Identification of six V beta genes in four new gene families.
The human TCR beta-chain gene complex includes at least 57 variable (V) gene segments, a number estimated using a combination of Southern blots of conventional and pulsed field gels, sequence analysis of cDNA clones, and from the analysis of genomic cosmid and phage clones. This number includes six TCR beta-chain V genes in four new families identified here by sequence analysis of clones derived from a human TCR beta-chain specific cDNA library. Comparison of the sequences of the new V beta genes with previously reported V beta sequences reveals predicted similarities but less than 75% nucleic acid identity that establishes them as new V beta families. One of the new V beta gene families includes three genes and the other three are single member families. Identification of these six new V beta genes falling into four V beta families brings the total number of transcribed human V beta families to 24 and makes it possible to refine the estimate of the total number of human TCR V beta genes to 57.


A Reliable Method Based on Liquid Chromatography-Tandem Mass Spectrometry for the Simultaneous Quantification of Neurotransmitters in Caenorhabditis elegans.
Neurotransmitters like dopamine (DA), serotonin (SRT), γ-aminobutyric acid (GABA) and acetylcholine (ACh) are messenger molecules that play a pivotal role in transmitting excitation between neurons across chemical synapses, thus enabling complex processes in the central nervous system (CNS). Balance in neurotransmitter homeostasis is essential, and altered neurotransmitter levels are associated with various neurological disorders, e.g., loss of dopaminergic neurons (Parkinson's disease) or altered ACh synthesis (Alzheimer's disease). Therefore, it is crucial to possess adequate tools to assess precise neurotransmitter levels, and to apply targeted therapies. An established in vivo model to study neurotoxicity is the model organism Caenorhabditis elegans (C. elegans), as its neurons have been well characterized and functionally are analogous to mammals. We have developed a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method including a sample preparation assuring neurotransmitter stability, which allows a simultaneous neurotransmitter quantification of DA, SRT, GABA and ACh in C. elegans, but can easily be applied to other matrices. LC-MS/MS combined with isotope-labeled standards is the tool of choice, due to its otherwise unattainable sensitivity and specificity. Using C. elegans together with our analytically validated and verified method provides a powerful tool to evaluate mechanisms of neurotoxicity, and furthermore to identify possible therapeutic approaches.


A metapopulation network model for the spreading of SARS-CoV-2: Case study for Ireland.
We present preliminary results on an all-Ireland network modelling approach to simulate the spreading the Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2), commonly known as the coronavirus. In the model, nodes correspond to locations or communities that are connected by links indicating travel and commuting between different locations. While this proposed modelling framework can be applied on all levels of spatial granularity and different countries, we consider Ireland as a case study. The network comprises 3440 electoral divisions (EDs) of the Republic of Ireland and 890 superoutput areas (SOAs) for Northern Ireland, which corresponds to local administrative units below the NUTS 3 regions. The local dynamics within each node follows a phenomenological SIRX compartmental model including classes of Susceptibles, Infected, Recovered and Quarantined (X) inspired from Science 368, 742 (2020). For better comparison to empirical data, we extended that model by a class of Deaths. We consider various scenarios including the 5-phase roadmap for Ireland. In addition, as proof of concept, we investigate the effect of dynamic interventions that aim to keep the number of infected below a given threshold. This is achieved by dynamically adjusting containment measures on a national scale, which could also be implemented at a regional (county) or local (ED/SOA) level. We find that - in principle - dynamic interventions are capable to limit the impact of future waves of outbreaks, but on the downside, in the absence of a vaccine, such a strategy can last several years until herd immunity is reached.


Ferulic acid relaxed rat aortic, small mesenteric and coronary arteries by blocking voltage-gated calcium channel and calcium desensitization via dephosphorylation of ERK1/2 and MYPT1.
Ferulic acid, a natural ingredient presents in several Chinese Materia Medica such as Radix Angelicae Sinensis, has been identified as an important multifunctional and physiologically active small molecule. However, its pharmacological activity in different blood vessel types and underlying mechanisms are unclear. The present study was to investigate the vascular reactivity and the possible action mechanism of FA on aorta, small mesenteric arteries and coronary arteries isolated from Wistar rats. We found FA dose-dependently relieved the contraction of aorta, small mesenteric arteries and coronary arteries induced by different contractors, U46619, phenylephrine (Phe) and KCl. The relaxant effect of FA was not affected by L-NAME (eNOS inhibitor), ODQ (soluble guanylate cyclase inhibitor), and mechanical removal of endothelium in thoracic aortas. The contraction caused by 60mM KCl (60K) was concentration-dependently hindered by FA pretreatment in all three types of arteries. In Ca2+-free 60K solution, FA weakened Ca2+-related contraction in a concentration dependent manner. And FA relaxed both fluoride and phorbol ester which were PKC, ERK and Rho-kinase activators induced contraction in aortic rings with or without Ca2+ in krebs solution. Western blotting experiments in A7r5 cells revealed that FA inhibited calcium sensitization via dephosphorylation of ERK1/2 and MYPT1. Furthermore, the relaxation effect of FA was attenuated by verapamil (calcium channel blocker), ERK inhibitor, and fasudil (ROCK inhibitor). These results provide evidence that FA exhibits endothelium-independent vascular relaxant effect in different types of arteries. The molecular mechanism of vasorelaxation activity of FA probably involved calcium channel inhibition and calcium desensitization.


Clinical aspects of X-linked hypohidrotic ectodermal dysplasia.
Boys with X-linked hypohidrotic ectodermal dysplasia and their families were studied. Many suffered severe illness in early childhood and nearly 30% died; many had feeding problems, severe fever, atopic disease, and recurrent respiratory infections. Some infants failed to thrive. We found no consistent common endocrine or immunological abnormality, although, most had abnormal immunoglobulin production. This may be related to the abnormal mucosa of the gastrointestinal and respiratory tracts which exacerbates the chronic obstructive airways disease found later in life in those who smoke. Mental handicap was not a feature, although convulsions sometimes occurred during fever. Early diagnosis is important to avoid attacks of severe fever and so that rational management may be planned for other problems that arise. Dental advice should be sought before school age and genetic counselling may also be required. Many female carriers may be recognised at clinical examination: their affected sons can then be diagnosed more readily.


Non-invasive fetal RHD genotyping in the first trimester of pregnancy.
Hemolytic disease of the fetus and newborn (HDN) is caused primarily by feto-maternal RhD incompatibility. Although all RhD negative pregnant women undergo routine antenatal RhD prophylaxis at 28 weeks of gestation, and following delivery if the newborn is RhD positive, HDN has not been eradicated. Here, we investigated fetal Rhesus D (RHD) genotype in maternal plasma during the first trimester of pregnancy in our area. Plasma samples were obtained from 111 RhD negative pregnant women, between 9 and 13 weeks of gestation. DNA from maternal plasma containing cell-free fetal DNA (cffDNA) was analyzed by quantitative PCR (qPCR) to detect RHD exons 5 and 7. A beta-globin (HBB) sequence was quantified to estimate total DNA concentration. qPCR results were compared with newborn RhD determined in cord blood serum. The influence of several gestational parameters on DNA concentration was also analyzed. The specificity and sensitivity of the assay was 93% and 100%, respectively, with 97% diagnostic accuracy. Cell-free DNA concentrations during the first trimester of pregnancy were not affected by the gestational parameters studied (free-beta fraction of human chorionic gonadotropin and pregnancy-associated plasma protein A concentrations, fetal sex, materno-fetal ABO blood group incompatibility, maternal weight and gestational age). Non-invasive fetal RHD genotyping during the first trimester of pregnancy can be determined with a high specificity, thus representing a valuable tool for improving the management of RhD negative pregnant women. As a high percentage of pregnant women participate in the routine first trimester combined screening program for aneuploidies, the fetal RHD study could be of immediate implementation, since the same blood collection could be used.


Evaluation of antibacterial properties of lactic acid bacteria from traditionally and industrially produced fermented sausages from Germany.
With regards to the frequently reported findings of spoilage bacteria and pathogens in various foods there is a need to explore new ways to control hazards in food production and to improve consumer safety. Fermented sausages from traditional and industrial production in Germany were screened for lactic acid bacteria with antibacterial effects towards important foodborne pathogens (Escherichia coli DSM 1103, Listeria innocua DSM 20649, Listeria monocytogenes DSM 19094, Pseudomonas aeruginosa DSM 939, Staphylococcus aureus DSM 799 and Salmonella Typhimurium DSM 19587). The obtained isolates and their cell-free supernatants were tested for their antibacterial activity by agar well diffusion assay. Isolates with an inhibitory effect were examined for the underlying antibacterial mechanism. Among the 169 collected isolates, 12.4% showed antibacterial effects only against Listeria innocua DSM 20649 and Listeria monocytogenes DSM 19094. In 6.5% of the isolates, bacteriocins were responsible for the effect. On the remaining test strains, the lactic bacteria isolates exerted no antibacterial effect. Two isolates were selected based on their antibacterial potential against Listeria spp. and the thermostability of the deriving cell free supernatants, traditional product: Pediococcus pentosaceus LMQS 331.3, industrial product: Pediococcus acidilactici LMQS 154.1, were investigated further and confirmed for the presence of bacteriocin structural genes by real-time PCR. Enriched crude bacteriocin preparations were obtained by ammonium sulfate precipitation and were found to remain stable under different pH milieus and to be active towards an extended set of Listeria spp. strains. Fermented meat products from German production are a promising source for bacteriocin-producing lactic acid bacteria. Two bacteriocin-producing isolates were identified which have the potential to contribute to product and consumer safety.


The behavioral consequences of terrorism: a meta-analysis.
Effective postterrorism public health interventions require the recognition that behavioral consequences are, in fact, the intent of terrorists. The authors searched published and unpublished post-1980 studies that documented population-level behavioral and psychological consequences of terrorist incidents, focusing on posttraumatic stress disorder (PTSD). Results were tabulated, and random effects models were used to calculate overall effect sizes. The analysis indicates that in the year following terrorist incidents, the prevalence of PTSD in directly affected populations varies between 12% and 16%. The review also shows that this prevalence can be expected to decline 25% over the course of that year. These prevalence estimates mask great variability, depending on who is being studied, who is conducting the study, and where the event occurred. Higher rates of disease are reported for survivors and rescue workers, and higher overall rates are also reported from studies conducted in Western Europe compared with studies conducted in North America. Prior psychiatric diagnoses are strongly associated with subsequent PTSD and may be a useful triage factor, particularly when considered together with factors such as female gender and direct exposure to events as either a survivor or rescuer. The review indicates that these associations are consistent across study types and environments and represent important variables to consider when developing triage, outreach, and treatment programs.