Short-term effects of milking frequency on milk yield, milk composition, somatic cell count and milk protein profile in dairy goats.
Goats in Canary Islands are milked once a day by tradition, but in most countries with high technology on farms, goats are milked twice a day, which is known to improve milk yield. Therefore it is important to know whether the increase of milking frequency can improve the production without impairing milk quality. The objective of this study was to investigate the short term effects of three milking frequencies on milk yield, milk composition, somatic cell count (SCC) and milk protein profile in dairy goats traditionally milked once a day. Twelve Majorera goats in early lactation (48±4 d in milk) were used. During a 5-week period, goats were milked once a day (X1) in weeks 1 and 5, twice a day (X2) in weeks 2 and 4, and three times a day (X3) in week 3. Milk recording and sampling were done on the last day of each experimental week. Milk yield increased by 26% from X1 to X2. No differences were obtained when goats were switched from X2 to X3, and from X3 to X2. The goats recovered the production level when they returned to X1. Different patterns of changes in the milk constituents due to the milking frequency effect were observed. Fat percentage increased when switched from X1 to X2, then decreased from X2 to X3, and from X3 to X2, whereas it did not show significant differences from X2 to X1. Milking frequency did not affect the protein and lactose percentages. SCC values were unaffected when goats were milked X1, X2 and X3, but then they increased slightly when milking frequency was returned to X2 and X1. Finally, quantitative analysis showed an increase in intensities of milk protein bands from X1 to X2, but the intensities of casein bands (α(S1)-CN, α(S2)-CN, β-CN, κ-CN) and major whey proteins (α-La, β-Lg) decreased from X2 to X3.


Asymmetric dimethyl arginine induces pulmonary vascular dysfunction via activation of signal transducer and activator of transcription 3 and stabilization of hypoxia-inducible factor 1-alpha.
Pulmonary hypertension (PH), associated with imbalance in vasoactive mediators and massive remodeling of pulmonary vasculature, represents a serious health complication. Despite the progress in treatment, PH patients typically have poor prognoses with severely affected quality of life. Asymmetric dimethyl arginine (ADMA), endogenous inhibitor of endothelial nitric oxide synthase (eNOS), also represents one of the critical regulators of pulmonary vascular functions. The present study describes a novel mechanism of ADMA-induced dysfunction in human pulmonary endothelial and smooth muscle cells. The effect of ADMA was compared with well-established model of hypoxia-induced pulmonary vascular dysfunction. It was discovered for the first time that ADMA induced the activation of signal transducer and activator of transcription 3 (STAT3) and stabilization of hypoxia inducible factor 1α (HIF-1α) in both types of cells, associated with drastic alternations in normal cellular functions (e.g., nitric oxide production, cell proliferation/Ca(2+) concentration, production of pro-inflammatory mediators, and expression of eNOS, DDAH1, and ICAM-1). Additionally, ADMA significantly enhanced the hypoxia-mediated increase in the signaling cascades. In summary, increased ADMA may lead to manifestation of PH phenotype in human endothelial and smooth muscle cells via the STAT3/HIF-1α cascade. Therefore this signaling pathway represents the potential pathway for future clinical interventions in PH.


Cervical cytology: an audit in a Singapore teaching hospital.
To describe the cervical cytology diagnoses and cyto-histological correlation in the Department of Pathology, National University of Singapore in 1997 and to compare the data with international figures. A database search of all cervical cytology cases diagnosed in the department in 1997 as well as follow-up biopsies was carried out. The data was then critically analysed. 10,207 cases were reviewed. 96% of the cases had a diagnosis of "negative". Under 1% of cases were labelled as "inadequate". "Atypia" was diagnosed in 1% and dysplasia and/or malignancy was diagnosed in 1%. These figures correlate well with international data. Of the dysplasia cases, 78% were followed by biopsy. Of the high-grade dysplasia cases that were biopsied, 97% of the biopsy diagnoses were within the acceptable concordance range with the cytology diagnoses and in only 3% was there a significant discrepancy. Of the cases diagnosed as atypia, 39% were subsequently biopsied at the same institution as the next procedure and only one showed high grade dysplasia. A total of six cases showed a significant discrepancy between the cervical cytology result and the subsequent biopsy diagnosis and these were reviewed to elucidate the reasons for the discrepancies. The cervical cytology service is of a high diagnostic standard. A subset of patients is probably being prematurely biopsied and may benefit from having a repeat smear instead. Specific clinical protocols regarding subsequent therapy following cytology results and closer cyto-histological correlation are two main areas where the cytology service can be improved.


The bitterness intensity of clarithromycin evaluated by a taste sensor.
The purpose of this study was to evaluate the ability of a quantitative prediction method using a taste sensor to determine the bitterness of clarithromycin powder suspensions of various concentrations and of a commercial clarithromycin dry syrup product (Clarith dry syrup, Taisho Pharmaceutical Co., Ltd., Tokyo) containing aminoalkyl methacrylate polymer as a taste-masker. The bitterness of the clarithromycin dry syrup product dissolved in various beverages was also evaluated in gustatory sensation tests and using the taste sensor. In the sensor measurements, three variables were used to predict bitterness in single and multiple regression analysis: relative sensor output (R), the change of membrane potential caused by adsorption (CPA), and CPA/R ratio. The CPA values for channel 3 of the sensor predicted well the bitterness of clarithromycin powder suspensions and their filtered solutions. For Clarith dry syrup, the sensor output was small, suggesting that aminoalkyl methacrylate polymer was successful in almost complete masking of the bitter taste of the dry syrup product. When the bitterness intensities of mixtures of 1 g of Clarith dry syrup with 25 ml of water, coffee, tea, green tea, cocoa, milk, and a sports drink were examined, a good correlation was obtained between the results from human taste tests and the predicted values calculated on the basis of multiple regression analysis using CPA data from channel 4, and the CPA/R ratio from channel 3 of the taste sensor (r(2)=0.963, p<0.005). Co-administration of 1 g of Clarith dry syrup with an acidic sports drink was found to be the most bitter using either method.


The smoker's health project: a self-determination theory intervention to facilitate maintenance of tobacco abstinence.
A previous randomized clinical trial based on self-determination theory (SDT) and consistent with the Public Health Service (PHS) Guideline for Treating Tobacco Use and Dependence demonstrated that an intensive intervention could change autonomous self-regulation and perceived competence, which in part facilitated long-term tobacco abstinence. The current article describes a pragmatic comparative effectiveness trial of three SDT-based intensive tobacco-dependence interventions. Eligible participants are randomized to one of the three treatment conditions designed to facilitate long-term maintenance of tobacco abstinence, namely, Community Care (CC), which includes the 6 month SDT-based intervention previously shown to promote autonomous self-regulation, perceived competence, medication use, and tobacco abstinence; Extended Need Support (ENS), which extends the 6 month SDT-based intervention to 12 months and trains an important other to provide support for smokers' basic psychological needs; and Harm Reduction (HR), which provides extended need support and recommends medication use for participants who do not want to stop smoking completely within 30 days but who are willing to reduce their cigarette use by half. The primary outcome is 12 month prolonged abstinence from tobacco, which is assessed one year following termination of treatment (two years post-randomization). Secondary outcomes include 7- and 30 day point prevalence tobacco abstinence, number of days using smoking-cessation medication, change in autonomous self-regulation and perceived competence, and perceived need support from important others.


Changing views on open-angle glaucoma: definitions and prevalences--The Rotterdam Study.
To create a quantitative basis for diagnostic criteria for open-angle glaucoma (OAG), to propose an epidemiologic definition for OAG based on these, and to determine the prevalence of OAG in a general white population. Of the 7983 subjects 55 years of age or older participating in the population-based Rotterdam Study, 6756 subjects participated in the ophthalmic part of this study (6281 subjects living independently and 475 in nursing homes). The criteria for the diagnosis of OAG were based on ophthalmoscopic and semiautomated Imagenet estimations of the optic disc such as vertical cup-to-disc ratio (VCDR), minimal width of neural rim, or asymmetry in VCDR between both eyes, and visual field testing with kinetic Goldmann perimetry. All criteria for the diagnosis of OAG were assessed in a masked way independently of each other. Mean VCDR on ophthalmoscopy was 0.3 and with Imagenet 0.49, and the 97.5th percentile for both was 0.7. The prevalence of glaucomatous visual field defects was 1.5%. Overall prevalence of definite OAG in the independently living subjects was 0.8% (95% confidence interval [CI] 0.6, 1.0; 50 cases). Prevalence of OAG in men was double that in women (odds ratio 2.1; 95% CI 1.2, 3.6). Different commonly used criteria for diagnosis of OAG resulted in prevalence figures ranging from 0.1% to 1.2%. The overall prevalence of OAG in the present study was comparable to most population-based studies. However, prevalence figures differed by a factor of 12 when their criteria for OAG were applied to this population. A definition for definite OAG is proposed: a glaucomatous optic neuropathy in eyes with open angles in the absence of history or signs of secondary glaucoma characterized by glaucomatous changes based on the 97.5 percentile for this population together with glaucomatous visual field loss. In the absence of the latter or of a visual field test, it is proposed to speak of probable OAG based on the 99.5th or possible OAG based on the 97.5th percentiles of glaucomatous disc changes for a population under study.


Comparisons among ten models of acoustic backscattering used in aquatic ecosystem research.
Analytical and numerical scattering models with accompanying digital representations are used increasingly to predict acoustic backscatter by fish and zooplankton in research and ecosystem monitoring applications. Ten such models were applied to targets with simple geometric shapes and parameterized (e.g., size and material properties) to represent biological organisms such as zooplankton and fish, and their predictions of acoustic backscatter were compared to those from exact or approximate analytical models, i.e., benchmarks. These comparisons were made for a sphere, spherical shell, prolate spheroid, and finite cylinder, each with homogeneous composition. For each shape, four target boundary conditions were considered: rigid-fixed, pressure-release, gas-filled, and weakly scattering. Target strength (dB re 1 m(2)) was calculated as a function of insonifying frequency (f = 12 to 400 kHz) and angle of incidence (θ = 0° to 90°). In general, the numerical models (i.e., boundary- and finite-element) matched the benchmarks over the full range of simulation parameters. While inherent errors associated with the approximate analytical models were illustrated, so were the advantages as they are computationally efficient and in certain cases, outperformed the numerical models under conditions where the numerical models did not converge.


Harmful algae niche responses to environmental and community variation along the French coast.
Distribution, frequency and intensity of harmful phytoplanktonic species are impacted by changes in environmental conditions. In the Bay of Brest, Alexandrium minutum has been responsible for several harmful algal blooms (HABs) associated with toxin production causing paralytic shellfish poisoning (PSP). Additionally, Lepidodinium chlorophorum causes green water and hypoxia locally in the Bay of Biscay. Previous studies revealed that L. chlorophorum's success was related to possible competitive exclusion. Therefore, the phytoplankton composition and the environmental conditions should be taken into account. This study aims to assess the combined effect of changes in habitat conditions and community structure with the occurrence of HAB species, on a spatial-temporal scale. For the investigation we first used the Hutchinson's niche concept by means of the Outlying Mean Index (OMI) analysis. The OMI analysis enable us to observe the environmental variables defining the ecological niche of the harmful species among the community. Secondly, we used the subniche theory to highlight the environmental variables defining the subniches in cases of high and low abundance of HABs with an estimation of the biological constraint restricting the species' subniche. This was undertaken using the Within Outlying Mean indexes (WitOMI) calculated under environmental conditions promoting high (H) and low (L) abundance bloom. Thirdly, we used the Indicator Species Concept from the Indicator Species Analysis (ISA) to link the biological restriction with potential competing or indicator species. We combined a data set from the French National Phytoplankton and Phycotoxin Monitoring Network (REPHY), the Velyger network (oyster monitoring program) and satellite imagery. A total of 44 stations, over the period of 1998-2017 using 50 taxonomic units. 36 taxa had significant niche and were mostly distributed along nutrient and salinity gradients. The two species of interest L. chlorophorum and A. minutum seemed to have similar affinity for summer-like environmental conditions and both used a marginal habitat compared to the rest of the community. A. minutum had a larger niche due to a greater affinity to the estuarine-like conditions. The subniche of the two species had a similar response to the environmental variation; their respective abundance was partly caused by greater environmental restrains. Their success in abundance appeared to be linked to local hydrodynamics which increases or reduces resources. On the other hand, the biotic pressure exerted upon A. minutum and L. chlorophorum were antagonistic. A possible competitor assemblage was exposed but the analysis was inconclusive. The methodological limitations were discussed as well as a perspective for future similar studies.


CD19 monoclonal antibody HD37 inhibits anti-immunoglobulin-induced B cell activation and proliferation.
The 95 Kd CD19 antigen is the broadest lineage specific surface marker for B cells: it is present on the surface of virtually all B lymphocytes, including early B progenitor cells. In this study we have evaluated the function of the CD19 antigen by using the CD19 mAb HD37. Binding of HD37 mAb to B cells at low doses (0.5 microgram/ml) induced a strong inhibition of the proliferative response to anti-Ig. This inhibition was not mediated by the Fc portion of the antibody, since F(ab')2 fragments were as effective as the whole antibody. Both dose-response curve analysis and experiments in which a cross-linking second step anti-mouse antibody was added suggested that cross-linking of CD19 antigens was necessary for optimal inhibition. Early phases in B cell activation were affected by the HD37 mAb: it significantly reduced the number of cells that left G0 and entered the G1 phase of the cell cycle upon triggering with anti-mu. The increase in free intracellular ionized calcium [Ca2+]i that is induced by anti-mu was also consistently reduced by CD19 mAb. Cross-linking was also crucial for this effect, suggesting that a causal relationship may exist between the inhibition of anti-Ig-mediated [Ca2+]i fluxes and inhibition of proliferation. A variable but clear increase in [Ca2+]i levels followed cross-linking of CD19 antigens by specific mAb. This evidence suggests that CD19 molecules may function in the downregulation of B cell growth and proliferation.


A comprehensive study on the role of the Yersinia pestis virulence markers in an animal model of pneumonic plague.
We determined the role of Yersinia pestis virulence markers in an animal model of pneumonic plague. Eleven strains of Y. pestis were characterized using PCR assays to detect the presence of known virulence genes both encoded by the three plasmids as well as chromosomal markers. The virulence of all Y. pestis strains was compared in a mouse model for pneumonic plague. The presence of all known virulence genes correlated completely with virulence in the Balb/c mouse model. Strains which lacked HmsF initially exhibited visible signs of disease whereas all other strains (except wild-type strains) did not exhibit any disease signs. Forty-eight hours post-infection, mice which had received HmsF(-) strains regained body mass and were able to control infection; those infected with strains possessing a full complement of virulence genes suffered from fatal disease. The bacterial loads observed in the lung and other tissues reflected the observed clinical signs as did the cytokine changes measured in these animals. We can conclude that all known virulence genes are required for the establishment of pneumonic plague in mammalian animal models, the role of HmsF being of particular importance in disease progression.


Workers' Health Surveillance in the Meat Processing Industry: Work and Health Indicators Associated with Work Ability.
Workers' health surveillance (WHS) programs commonly measure a large number of indicators addressing health habits and health risks. Recently, work ability and functional capacity have been included as important risk measures in WHS. In order to address work ability appropriately, knowledge of associations with work and health measures is necessary. The objective of this study was to evaluate which of the factors measured in a WHS are independently associated with work ability in a group of meat processing workers. A cross-sectional study was performed in a large meat processing company in The Netherlands. Data were collected during a WHS between February 2012 and March 2014. Personal characteristics, health habits and health-risk indicators, functional capacity, and work-related factors were measured. Work ability was measured with the Work Ability Index and was used as dependent variable. Univariable and multivariable logistic regression analyses were conducted, a receiver operating characteristic curve was constructed and the area under the curve (AUC) was calculated. Data sets from 230 employees were used for analyses. The average age was 53 years and the average work ability index score was 39.3. In the final multivariable model age (OR 0.94), systolic blood pressure (OR 1.03), need for recovery (OR 0.56), and overhead work capacity (OR 3.95) contributed significantly. The AUC for this model was 0.81 (95% CI 0.75-0.86). Findings from the current study indicate that multifactorial outcomes (age, systolic blood pressure, need for recovery, and overhead work capacity) from a WHS were independently associated with work ability. These factors can be used to assess employees at risk for low work ability and might provide directions for interventions.


The experiences of people with liver disease of palliative and end-of-life care in the United Kingdom-A systematic literature review and metasynthesis.
Liver disease is a growing health concern and a major cause of death. It causes multiple symptoms, including financial, psychological and social issues. To address these challenges, palliative care can support people alongside active treatment, and towards the end of life, but little is known about the care experiences of individuals with liver disease in the United Kingdom. This review aimed to explore the palliative and end-of-life care experiences of people with liver disease in the United Kingdom. A systematic review was conducted using a five-stage process and following Preferred Reporting Items for Systematic Reviews and Meta Analyses guidelines. Searches were across Web of Science, Scopus, EBSCO and grey literature until 10 May 2023. The review was registered through International Prospective Register of Systematic Reviews (PROSPERO). NVivo 12.5 was used to facilitate data analysis (systematic review registration: PROSPERO CRD42022382649). Of 6035 papers (excluding duplicates) found from searches, five met the inclusion criteria of primary research related to adults with liver disease receiving palliative and/or end-of-life care in the United Kingdom, published in English. Reflexive thematic analysis of the data was conducted. The themes identified were the experiences of people with liver disease of relating to healthcare professionals, using services, receiving support, and experiences of information and communication. These were connected by an overarching concept of disempowerment versus empowerment, with the notion of person-centred care as an important feature. This review has found variations in the care experiences of people with advanced liver disease towards the end of life and an overall lack of access to specialist palliative care services. Where services are designed to be person-centred, experiences are more empowering. Further research is needed but with recognition that it is often unclear when care for people with liver disease is palliative or end-of-life. An online public involvement workshop was held on 18 April 2023 through Voice (2023). This included four people with liver disease and four carers to discuss the review findings and to design a qualitative research study to further explore the topic.


Diabetes mellitus and its association with central obesity and disability among older adults: a global perspective.
The aim of the study was to evaluate the association between various factors and diabetes type II (DM) with a particular emphasis on indicators of central obesity, and to compare the effect of DM on disability among elder populations (≥ 50 years old) in nine countries. Data were available for 52,946 people aged ≥ 18 years who participated in the WHO Study on global AGEing and adult health and the Collaborative Research on Ageing in Europe studies conducted between 2007 and 2012. DM was defined as self-report of physician diagnosis. Height, weight, and waist circumference were measured. Disability status was assessed with the WHODAS II questionnaire. The overall prevalence of DM was 7.9% and ranged from 3.8% (Ghana) to 17.6% (Mexico). A 10 cm increase in waist circumference and waist-to-height ratio of >0.5 were associated with a significant 1.26 (India) to 1.77 (Finland), and 1.68 (China, Spain) to 5.40 (Finland) times higher odds for DM respectively. No significant associations were observed in Mexico and South Africa. DM was associated with significantly higher disability status in all countries except Mexico in the model adjusted for demographics and smoking. The inclusion of chronic conditions associated with diabetes in the model attenuated the coefficients in varying degrees depending on the country. A considerable proportion of the studied older population had DM. Central obesity may be a key factor for the prevention of DM among older populations globally. Prevention of DM especially among the older population globally may contribute to reducing the burden of disability.


The two isoenzymes for yeast NAD+-dependent glycerol 3-phosphate dehydrogenase encoded by GPD1 and GPD2 have distinct roles in osmoadaptation and redox regulation.
The two homologous genes GPD1 and GPD2 encode the isoenzymes of NAD-dependent glycerol 3-phosphate dehydrogenase in the yeast Saccharomyces cerevisiae. Previous studies showed that GPD1 plays a role in osmoadaptation since its expression is induced by osmotic stress and gpd1 delta mutants are osmosensitive. Here we report that GPD2 has an entirely different physiological role. Expression of GPD2 is not affected by changes in external osmolarity, but is stimulated by anoxic conditions. Mutants lacking GPD2 show poor growth under anaerobic conditions. Mutants deleted for both GPD1 and GPD2 do not produce detectable glycerol, are highly osmosensitive and fail to grow under anoxic conditions. This growth inhibition, which is accompanied by a strong intracellular accumulation of NADH, is relieved by external addition of acetaldehyde, an effective oxidizer of NADH. Thus, glycerol formation is strictly required as a redox sink for excess cytosolic NADH during anaerobic metabolism. The anaerobic induction of GPD2 is independent of the HOG pathway which controls the osmotic induction of GPD1. Expression of GPD2 is also unaffected by ROX1 and ROX3, encoding putative regulators of hypoxic and stress-controlled gene expression. In addition, GPD2 is induced under aerobic conditions by the addition of bisulfite which causes NADH accumulation by inhibiting the final, reductive step in ethanol fermentation and this induction is reversed by addition of acetaldehyde. We conclude that expression of GPD2 is controlled by a novel, oxygen-independent, signalling pathway which is required to regulate metabolism under anoxic conditions.


Vitreous surgery for retinal detachment associated with choroidal coloboma.
We report the results of vitreous surgery in seven eyes with retinal detachments caused by retinal breaks at the margin of, or within, a choroidal coloboma. All seven eyes (100%) were reattached; visual acuities in five (71%) of the seven eyes improved from preoperative levels. Vitrectomy was combined with air-fluid exchange and endodrainage through preexisting retinal breaks or planned retinotomies in all but one of the cases. Part or all of the rim of the choroidal coloboma in six eyes underwent endophotocoagulation. The two eyes that did not experience postoperative visual improvement underwent intraoperative endolaser treatment 360 degrees around the optic nerve. If peripapillary endophotocoagulation is performed, especially through the papillomacular bundle, nerve fiber damage may occur and prevent visual recovery, despite retinal reattachment. For eyes with retinal detachment associated with choroidal colobomas involving the optic nerve, postoperative laser treatment through the papillomacular bundle may be preferable.


Structural analysis and chromosomal localization of the mouse Psmb5 gene coding for the constitutively expressed beta-type proteasome subunit.
The proteasome is a multi-subunit protease responsible for the production of peptides presented by major histocompatibility complex class I molecules. Accumulated evidence indicates that, upon stimulation with interferon-gamma (IFN-gamma), three beta-type subunits, designated LMP2, LMP7, and PSMB10, are incorporated into the 20S proteasome by displacing the housekeeping beta-type subunits designated PSMB6, PSMB5, and PSMB7, respectively. These changes in the subunit composition appear to facilitate class I-mediated antigen presentation, presumably by altering the cleavage specificities of the proteasome. In the present study, we determined the organization of the mouse gene Psmb5, coding for the PSMB5 subunit. Psmb5 is made up of three exons, spanning approximately 5 kilobases. Its exon-intron organization differs radically from those of the other IFN-gamma-regulated, beta-type subunit genes including Lmp7 with which Psmb5 is believed to share an immediate common ancestor. The structure of the mouse Psmb5 gene is identical to that of its recently characterized human counterpart. Thus, the unique organization of the gene coding for the PSMB5 subunit appears to have been established before mammalian radiation. As well as the Psmb5 gene, the mouse genome contains a processed pseudogene designated Psmb5-ps. Interspecific backcross mapping showed that Psmb5 maps close to the Gtrgal2 locus on chromosome 14 and that Psmb5-ps is located in the vicinity of the Psme3 locus on chromosome 11. These results were confirmed by fluorescent in situ hybridization analysis that localized Psmb5 to band C2 to proximal D1 of chromosome 14 and Psmb5-ps to band D of chromosome 11.


Acupuncture for dysmenorrhoea.
Primary dysmenorrhoea is the most common form of period pain and affects up to three-quarters of women at some stage of their reproductive life. Primary dysmenorrhoea is pain in the absence of any organic cause and is characterised by cramping pain in the lower abdomen, starting within the first eight to 72 hours of menstruation.This review examines the currently available evidence supporting the use of acupuncture (stimulation of points on the body using needles) and acupressure (stimulation of points on the body using pressure) to treat primary dysmenorrhoea. To determine the effectiveness and safety of acupuncture and acupressure in the treatment of primary dysmenorrhoea when compared with a placebo, no treatment, or conventional medical treatment. We searched the following databases: the Cochrane Menstrual Disorders and Subfertility Group Trials Register (to September 2015), Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library), MEDLINE, EMBASE, PsycINFO, CINAHL and Chinese databases including Chinese Biomedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI), VIP database and registers of ongoing trials. We included all published and unpublished randomised controlled trials (RCTs) comparing acupuncture with sham acupuncture or placebo control, usual care, pharmacological treatment or no treatment. We included the following modes of treatment: acupuncture, electro-acupuncture, and acupressure. Participants were women of reproductive age with primary dysmenorrhoea during the majority of the menstrual cycles or for three consecutive menstrual cycles, and moderate to severe symptoms. We calculated odds ratios (ORs) for dichotomous outcomes and mean differences (MDs) or standardised mean differences (SMDs) for continuous outcomes, with 95% confidence intervals (CIs). We pooled the data where appropriate. Our primary outcomes was pain. Secondary outcomes included menstrual symptoms, quality of life, and adverse effects. We included 42 RCTs (4640 women). Acupuncture or acupressure was compared with a sham/placebo group, medication, no treatment or other treatment. Many of the continuous data were not suitable for calculation of means, mainly due to evidence of skew.1. Acupuncture studies Acupuncture versus sham or placebo control (6 RCTs)Findings were inconsistent and inconclusive. However, the only study in the review that was at low risk of bias in all domains found no evidence of a difference between the groups at three, six or 12 months. The overall quality of the evidence was low. No studies reported adverse events. Acupuncture versus NSAIDs Seven studies reported visual analogue scale (VAS) pain scores, but were unsuitable for pooling due to extreme heterogeneity (I² = 94%). In all studies the scores were lower in the acupuncture group, with the mean difference varying across studies from 0.64 to 4 points on a VAS 0 - 10 scale (low-quality evidence). Four RCTs reported rates of pain relief, and found a benefit for the acupuncture group (OR 4.99, 95% CI 2.82 to 8.82, 352 women, I² = 0%, low-quality evidence). Adverse events were less common in the acupuncture group (OR 0.10, 95% CI 0.02 to 0.44, 4 RCTs, 239 women, 4 trials, I² = 15%, low-quality evidence). Acupuncture versus no treatment Data were unsuitable for analysis, but pain scores were lower in the acupuncture group in all six studies reporting this outcome. The quality of the evidence was low. No studies reported adverse events.2. Acupressure studiesNo studies of acupressure reported adverse events. Acupressure versus sham or placebo controlData were unsuitable for pooling, but two studies reported a mean benefit of one to three points on a 0 - 10 VAS pain scale. Another four studies reported data unsuitable for analysis: all found that pain scores were lower in the acupuncture group. No studies reported adverse events. The quality of the evidence was low. Acupressure versus NSAIDsOne study reported this outcome, using a 0 - 3 pain scale. The score was higher (indicating more pain) in the acupressure group (MD 0.39 points, 95% CI 0.21 to 0.57, 136 women, very low-quality evidence). Acupressure versus no treatmentThere was no clear evidence of a difference between the groups on a VAS 0 - 10 pain scale (MD -0.96 points, 95% CI -2.54 to 0.62, 2 trials, 140 women, I² = 83%, very low-quality evidence). There is insufficient evidence to demonstrate whether or not acupuncture or acupressure are effective in treating primary dysmenorrhoea, and for most comparisons no data were available on adverse events. The quality of the evidence was low or very low for all comparisons. The main limitations were risk of bias, poor reporting, inconsistency and risk of publication bias.


Electrospinning of polyaniline: effect of different raw sources.
Nanofibers of conducting polymers, as polyaniline (PANI), have received a great deal of attention by the scientific community for their potential applications (electronic, magnetic, biomedical, optical fields). Recently the electrospinning has emerged as a promising technique to produce wires and fibers of polymers with diameters ranging from 10 nm to 10 microm. PANI shows poor processability by electrospinning due to its low solubility in common solvents. However, it is possible to spin polyaniline nanofibers adding another polymer to the organic solutions, generally an insulator, necessary to increase the viscosity of the polymeric solution to be spun. Unfortunately, the presence of an insulator copolymer decreases the fibers conductivity. The key factor to obtain fibers of good quality (high conductivity and a narrow distribution of the diameters) is to reduce the amount of insulator copolymer in the spun process. Accordingly, we prepared raw PANI following different synthetic methods to be compared, aiming at the best optimized protocol in terms of easy solubility and enhanced spinning behavior of the polymers achieved. All the materials have been characterized by FT-IR and UV-VIS spectroscopies. The spun samples obtained have been characterized by SEM to evaluate the fiber morphology and complex impedance spectroscopy (EIS) in order to measure the electrical conductivity.


Combined in Vitro Cell-Based/in Silico Screening of Naturally Occurring Flavonoids and Phenolic Compounds as Potential Anti-Alzheimer Drugs.
Alzheimer's disease (AD) is the main cause of dementia in people over 65 years. One of the major culprits in AD is the self-aggregation of amyloid-β peptide (Aβ), which has stimulated the search for small molecules able to inhibit Aβ aggregation. In this context, we recently reported a simple, but effective in vitro cell-based assay to evaluate the potential antiaggregation activity of putative Aβ aggregation inhibitors. In this work this assay was used together with docking and molecular dynamics simulations to analyze the anti-Aβ aggregation activity of several naturally occurring flavonoids and phenolic compounds. The results showed that rosmarinic acid, melatonin, and o-vanillin displayed zero or low inhibitory capacity, curcumin was found to have an intermediate inhibitory potency, and apigenin and quercetin showed potent antiaggregation activity. Finally, the suitability of the combined in vitro cell-based/in silico approach to distinguish between active and inactive compounds was further assessed for an additional set of flavonols and dihydroflavonols.


Progressive mitochondrial protein lysine acetylation and heart failure in a model of Friedreich's ataxia cardiomyopathy.
The childhood heart disease of Friedreich's Ataxia (FRDA) is characterized by hypertrophy and failure. It is caused by loss of frataxin (FXN), a mitochondrial protein involved in energy homeostasis. FRDA model hearts have increased mitochondrial protein acetylation and impaired sirtuin 3 (SIRT3) deacetylase activity. Protein acetylation is an important regulator of cardiac metabolism and loss of SIRT3 increases susceptibility of the heart to stress-induced cardiac hypertrophy and ischemic injury. The underlying pathophysiology of heart failure in FRDA is unclear. The purpose of this study was to examine in detail the physiologic and acetylation changes of the heart that occur over time in a model of FRDA heart failure. We predicted that increased mitochondrial protein acetylation would be associated with a decrease in heart function in a model of FRDA. A conditional mouse model of FRDA cardiomyopathy with ablation of FXN (FXN KO) in the heart was compared to healthy controls at postnatal days 30, 45 and 65. We evaluated hearts using echocardiography, cardiac catheterization, histology, protein acetylation and expression. Acetylation was temporally progressive and paralleled evolution of heart failure in the FXN KO model. Increased acetylation preceded detectable abnormalities in cardiac function and progressed rapidly with age in the FXN KO mouse. Acetylation was also associated with cardiac fibrosis, mitochondrial damage, impaired fat metabolism, and diastolic and systolic dysfunction leading to heart failure. There was a strong inverse correlation between level of protein acetylation and heart function. These results demonstrate a close relationship between mitochondrial protein acetylation, physiologic dysfunction and metabolic disruption in FRDA hypertrophic cardiomyopathy and suggest that abnormal acetylation contributes to the pathophysiology of heart disease in FRDA. Mitochondrial protein acetylation may represent a therapeutic target for early intervention.


Risk factors for bulk milk somatic cell counts and total bacterial counts in smallholder dairy farms in the 10th region of Chile.
We investigated the principal management factors that influenced bulk milk somatic cell count (BMSCC) and total bacterial count (TBC) of smallholder dairy farms in the 10th region of Chile. One hundred and fifty smallholder milk producers were selected randomly from 42 milk collection centres (MCCs). In April and May of 2002, all farms were visited and a detailed interview questionnaire on dairy-cow management related to milk quality was conducted. In addition, the BMSCC and TBC results from the previous 2 months' fortnightly tests were obtained from the MCCs. The mean BMSCC and TBC were used as the dependent variables in the analyses and were normalised by a natural-logarithm transformation (LN). All independent management variables were categorised into binary outcomes and present (=1) was compared with absent (=0). Biserial correlations were calculated between the LNBMSCC or LNTBC and the management factors of the smallholder farms. Management factors with correlations with P</=0.20 were entered into the linear multiple regression models and backward elimination was used to exclude non-significant (P>0.05) factors. A random MCC effect was included in the models to investigate the importance of clustering of herds within MCC. In the null model for mean LNTBC, the random effect of MCCs was highly significant. It was explained by: milk collected once a day or less compared with collection twice a day, not cleaning the bucket after milking mastitic cows versus cleaning the bucket and cooling milk in a vat of water versus not cooling milk or using ice or a bulk tank to cool milk. Other factors that increased the LNTBC were a waiting yard with a soil or gravel floor versus concrete, use of plastic buckets for milking instead of metal, not feeding California mastitis test (CMT)-positive milk to calves and cows of dual-purpose breed. The final model explained 35% of the variance. The model predicted that a herd that complied with all the management practices had a mean predicted TBC of 105 colony forming units (cfu)/ml, whereas a herd that did not comply with any of these management factors had a predicted TBC of 59 x 10(9)cfu/ml. The model of mean LNBMSCC explained 18% of the variance; the random effect of MCC was not significant. Management factors that decreased the mean LNBMSCC were: using the CMT for 1 year versus using the test for more than 1 year or not at all, absence of a concrete waiting yard, not filtering the milk or using filters other than a plastic sieve to filter the milk, milking cows with mastitis last, and sometimes or always examining the udder before milking. A herd that complied with all of these management factors had a BMSCC of approximately 46,166 cells/ml, whereas a herd that did not comply with any of the management practices above had a mean BMSCC of 2 x 10(6)cells/ml.


Investigating the pertussis resurgence in England and Wales, and options for future control.
In 2012 England and Wales experienced a resurgence of pertussis and an increase in infant deaths. This occurred 8 years after acellular pertussis (aP) vaccine replaced whole cell (wP) primary vaccine despite continued high coverage for the primary series and pre-school aP booster. We developed a mathematical model to describe pertussis transmission dynamics in England and Wales since the 1950s and used it to investigate the cause of the resurgence and the potential impact of additional vaccination strategies. An age-structured, compartmental, deterministic model of the pertussis transmission dynamics was fitted to 60 continuous years of age-stratified pertussis notification data in England and Wales. The model incorporated vaccine-induced and natural immunity and differentiated between vaccine-induced protection against clinical disease and infection. The degree of protection of wP vaccine against infection was estimated to be higher than that of aP vaccine. Furthermore, the duration of protection for natural and wP-induced immunity was likely to be at least 15 years, but for aP vaccine it could be as low as 5 years. Model results indicated that the likely cause of the resurgence was the replacement of wP by less efficacious aP vaccine and that an elevated level of pertussis would continue. The collapse in wP vaccine coverage in the 1970s and resultant outbreaks in the late 1970s and early 1980s could not explain the resurgence. Addition of an adolescent or toddler booster was predicted to have little impact on the disease in infants. Our findings support the recent recommendation by the World Health Organisation that countries currently using wP vaccine for primary immunisation should not change to aP vaccine unless additional strategies to control infant disease such as maternal immunisation can be assured. Improved pertussis vaccines that provide better protection against infection are needed.


Umbilical cord-derived mesenchymal stem cell sheets transplanted subcutaneously enhance cell retention and survival more than dissociated stem cell injections.
Human umbilical cord-derived mesenchymal stem cell (hUC-MSC) sheets have recently attracted attention as an alternative approach to injected cell suspensions for stem cell therapy. However, cell engraftment and cytokine expression levels between hUC-MSC sheets and their cell suspensions in vivo have not yet been compared. This study compares hUC-MSC in vivo engraftment efficacy and cytokine expression for both hUC-MSC sheets and cell suspensions. hUC-MSC sheets were prepared using temperature-responsive cell culture; two types of hUC-MSC suspensions were prepared, either by enzymatic treatment (trypsin) or by enzyme-free temperature reduction using temperature-responsive cell cultureware. hUC-MSC sheets and suspensions were transplanted subcutaneously into ICR mice through subcutaneous surgical placement and intravenous injection, respectively. hUC-MSC sheet engraftment after subcutaneous surgical transplantation was investigated by in vivo imaging while intravenously injected cell suspensions were analyzing using in vitro organ imaging. Cytokine levels in both transplant site tissues and blood were quantified by enzyme-linked immunosorbent assay. After subcutaneous transplant, hUC-MSC sheets exhibited longer engraftment duration than hUC-MSC suspensions. This was attributed to extracellular matrix (ECM) and cell-cell junctions retained in sheets but enzymatically altered in suspensions. hUC-MSC suspensions harvested using enzyme-free temperature reduction exhibited relatively long engraftment duration after intravenous injection compared to suspensions prepared using trypsin, as enzyme-free harvest preserved cellular ECM. High HGF and TGF-β1 levels were observed in sheet-transplanted sites compared to hUC-MSC suspension sites. However, no differences in human cytokine levels in murine blood were detected, indicating that hUC-MSC sheets might exert local paracrine rather than endocrine effects. hUC-MSC sheet transplantation could be a more effective cell therapeutic approach due to enhanced engraftment and secretion of therapeutic cytokines over injected hUC-MSC suspensions.


Computer analysis of the optic cup in glaucoma.
This paper describes two complementary methods for computer analysis of the optic disc in glaucoma. The objective of both techniques is to detect and monitor changes in the optic disc through the use of digital image processing techniques that allow user intervention. In the first method, optic disc photographs from successive years are digitized, scaled and registered (aligned) with each other, and are then displayed in rapid sequence on a television monitor. Changes in the optic cup thus appear as localized movement on the display, while stable regions of the optic cup appear stationary. Both monocular and stereo photographs can be processed by this technique. In the second method, stereo optic disc photographs are digitized and processed by a new, robust, photogrammetric computer algorithm that quantifies optic cup depth information. Together, these two techniques may be valuable for both clinical and research purposes in the detection and monitoring of glaucomatous optic cupping.


TCR transgenes and transgene cassettes for TCR gene therapy: status in 2008.
The genetic introduction of T cell receptor genes into T cells has been developed over the past decade as a strategy to induce defined antigen-specific T cell immunity. With the potential value of TCR gene therapy well-established in murine models and the feasibility of infusion of TCR-modified autologous T cells shown in a first phase I trial, the next key step will be to transform TCR gene transfer from an experimental technique into a robust clinical strategy. In this review, we discuss the different properties of the TCR transgene and transgene cassette that can strongly affect both the efficacy and the safety of TCR gene transfer.


A Pilot Study of a Standardized Smoking Cessation Intervention for Patients with Vascular Disease.
The goal of this study is to evaluate the efficacy of a smoking cessation intervention performed by a vascular surgery provider compared with current smoking cessation practices. Patients with peripheral arterial and aneurysmal disease who presented to the vascular surgery service at a tertiary care center over a 9-month period were randomized to either control or intervention group. Both control and intervention groups received 2 weeks of free nicotine patches and referral to an outpatient smoking-cessation program. The intervention group additionally received a brief presentation by a vascular surgeon regarding the benefits of smoking cessation, with a focus on vascular complications. At enrollment and at follow-up, patients underwent carbon monoxide breath testing and completed a survey. The primary outcome was smoking cessation or reduction among control and intervention groups in patients who underwent medical management, endovascular procedures, or open surgical procedures. Fisher's exact test was used to assess the primary outcome among groups. Fifty-nine patients were enrolled in the trial initially, but 55 had 1-month follow-up (control n = 28, intervention n = 27) and 52 had long-term follow-up (control n = 28, intervention n = 24). By long-term follow-up, 40 patients (77%) had reduced smoking by at least 50% and 16 patients (31%) had quit completely. At long-term follow-up, 88% of patients in the intervention group and 68% of patients in the control group reduced smoking (P = 0.1). A large proportion of vascular patients who received 2 weeks of nicotine replacement with or without the addition of brief smoking cessation counseling delivered by a vascular surgery provider were able to reduce smoking and maintain reduction after 6 months. Delivery of a brief standardized smoking cessation counseling session by a vascular surgery provider is safe and feasible. Additional randomized controlled trials with large enrollment periods and long follow-up are needed to determine the efficacy of this intervention in comparison to standard care.


Neuraminidase increases DNA synthesis of spleen cells induced by native and asialylated erythropoietin.
The uptake of 3H-thymidine by a suspension of spleen cells, obtained from mice made anemic by phenylhydrazine injections, is increased above the values obtained with native human or mouse erythropoietin (Ep) if the hormone is enzymatically asialylated. Preparations of human Ep asialylated by mild acid hydrolysis stimulated DNA synthesis to a lesser extent than the native hormone; however, when neuraminidase was added to the culture medium, the stimulation exhibited by the asialylated Ep was not significantly different from the stimulation shown by the native hormone. The DNA synthesis of these cells is increased even more if neuraminidase and the asialylated hormone are added to the cell suspension. The asialylated Eps are not biologically active in vivo. The sialic acid moieties of Ep and of the cells responding to Ep are involved in the in vitro response of spleen cells to the hormone, possibly by making Ep receptors available to interact with the hormone.


Filament formation and robust strand exchange activities of the rice DMC1A and DMC1B proteins.
The DMC1 protein, a meiosis-specific DNA recombinase, catalyzes strand exchange between homologous chromosomes. In rice, two Dmc1 genes, Dmc1A and Dmc1B, have been reported. Although the Oryza sativa DMC1A protein has been partially characterized, however the biochemical properties of the DMC1B protein have not been defined. In the present study, we expressed the Oryza sativa DMC1A and DMC1B proteins in bacteria and purified them. The purified DMC1A and DMC1B proteins formed helical filaments along single-stranded DNA (ssDNA) and double-stranded DNA (dsDNA), and promoted robust strand exchange between ssDNA and dsDNA over five thousand base pairs in the presence of RPA, as a co-factor. The DMC1A and DMC1B proteins also promoted strand exchange in the absence of RPA with long DNA substrates containing several thousand base pairs. In contrast, the human DMC1 protein strictly required RPA to promote strand exchange with these long DNA substrates. The strand-exchange activity of the Oryza sativa DMC1A protein was much higher than that of the DMC1B protein. Consistently, the DNA-binding activity of the DMC1A protein was higher than that of the DMC1B protein. These biochemical differences between the DMC1A and DMC1B proteins may provide important insight into their functional differences during meiosis in rice.


Nutritional physiology and ecology of wildlife in a changing world.
Over the last century, humans have modified landscapes, generated pollution and provided opportunities for exotic species to invade areas where they did not evolve. In addition, humans now interact with animals in a growing number of ways (e.g. ecotourism). As a result, the quality (i.e. nutrient composition) and quantity (i.e. food abundance) of dietary items consumed by wildlife have, in many cases, changed. We present representative examples of the extent to which vertebrate foraging behaviour, food availability (quantity and quality) and digestive physiology have been modified due to human-induced environmental changes and human activities. We find that these effects can be quite extensive, especially as a result of pollution and human-provisioned food sources (despite good intentions). We also discuss the role of nutrition in conservation practices, from the perspective of both in situ and ex situ conservation. Though we find that the changes in the nutritional ecology and physiology of wildlife due to human alterations are typically negative and largely involve impacts on foraging behaviour and food availability, the extent to which these will affect the fitness of organisms and result in evolutionary changes is not clearly understood, and requires further investigation.


Tunable recognition of the steroid alpha-face by adjacent pi-electron density.
We report a previously unknown recognition motif between the alpha-face of the steroid hydrocarbon backbone and pi-electron-rich aromatic substrates. Our study is based on a systematic and comparative analysis of the solid-state complexation of four steroids with 24 aromatic molecules. By using the solid state as a medium for complexation, we circumvent solubility and solvent competition problems that are inherent to the liquid phase. Characterization is performed using powder and single crystal X-ray diffraction, infrared solid-state spectroscopy and is complemented by a comprehensive cocrystal structure prediction methodology that surpasses earlier computational approaches in terms of realism and complexity. Our combined experimental and theoretical approach reveals that the alpha...pi stacking is of electrostatic origin and is highly dependent on the steroid backbone's unsaturated and conjugated character. We demonstrate that the alpha...pi stacking interaction can drive the assembly of molecules, in particular progesterone, into solid-state complexes without the need for additional strong interactions. It results in a marked difference in the solid-state complexation propensities of different steroids with aromatic molecules, suggesting a strong dependence of the steroid-binding affinity and even physicochemical properties on the steroid's A-ring structure. Hence, the hydrocarbon part of the steroid is a potentially important variable in structure-activity relationships for establishing the binding and signaling properties of steroids, and in the manufacture of pharmaceutical cocrystals.


Pickering emulsions: wetting and colloidal stability of hairy particles--a self-consistent field theory.
The assembly of sterically stabilized colloids at liquid-liquid interfaces is studied with the self-consistent field (SCF) theory using the discretization scheme that was developed by Scheutjens, Fleer, and co-workers. The model is based on a poly(methyl methacrylate) (pMMA) particle with poly(isobutylene) (pIB) grafted to the surface. The stabilizing groups on the particle surface have a significant effect on the interfacial assembly and, therefore, also on the formation and properties of Pickering emulsions. The wetting behavior of the particle is altered by the presence of the stabilizing groups, which affects the equilibrium position of the particles at the interface. The stabilizing groups can also lead to an activation barrier before interfacial adsorption, analogous to the steric repulsion between two particles. These effects are numerically solved with the SCF theory. It is commonly known that flocculating conditions enhance the interfacial adsorption and yield stable Pickering emulsions, which is confirmed in this work. Additionally, it is concluded that those conditions are not an absolute requirement. There is a window of stabilizer concentrations Γ(pIB), 2.2-3.3 mg/m(2) pIB, that shows both partial wetting and colloidal stability. The activation barrier for interfacial assembly is 140-550 k(B)T and is an order of magnitude higher than the colloidal stability. The difference can be attributed to the unfavorable interaction of pIB with water and a difference in geometry (plate-sphere vs sphere-sphere). This study demonstrates the interplay and provides a quantitative comparison between the wetting behavior and the colloidal stability, and it gives a better understanding of the colloidal assembly at soft interfaces and formation of Pickering emulsions in general.


Enhanced Recovery After Surgery for Noncolorectal Surgery?: A Systematic Review and Meta-analysis of Major Abdominal Surgery.
To evaluate the impact of enhanced recovery after surgery (ERAS) protocols across noncolorectal abdominal surgical procedures. ERAS programs have been studied extensively in colorectal surgery and adopted at many centers. Several studies testing such protocols have shown promising results in improving postoperative outcomes across various surgical procedures. However, surgeons performing major abdominal procedures have been slower to adopt these ERAS protocols. A systematic review was performed using "enhanced recovery after surgery" or "fast track" as search terms and excluded studies of colorectal procedures. Primary endpoints for the meta-analysis include length of stay (LOS) and complication rate. Secondary endpoints were time to first flatus, readmission rate, and costs. A total of 39 studies (6511 patients) met inclusion and exclusion criteria. Among them 14 studies were randomized trials, and the remaining 25 studies were cohort studies. Meta-analysis showed a decrease in LOS of 2.5 days (95% confidence interval, CI: 1.8-3.2, P < 0.001) and a complication rate of 0.70 (95% CI: 0.56-0.86, P = 0.001) for patient treated in ERAS programs. There was also a significant reduction in time to first flatus of 0.8 days (95% CI: 0.4-1.1, P < 0.001) and cost reduction of $5109.10 (95% CI: $4365.80-$5852.40, P < 0.001). There was no significant increase in readmission rate (OR 1.03, 95% CI: 0.84-1.26, P = 0.80) in our analysis. ERAS protocols decreased length of stay and cost by not increasing complications or readmission rates. This study adds to the evidence that ERAS protocols are safe to implement and are beneficial to surgical patients and the healthcare system across multiple abdominal procedures.


Nanomechanical Contribution of Collagen and von Willebrand Factor A in Marine Underwater Adhesion and Its Implication for Collagen Manipulation.
Recent works on mussel adhesion have identified a load bearing matrix protein (PTMP1) containing von Willebrand factor (vWF) with collagen binding capability that contributes to the mussel holdfast by manipulating mussel collagens. Using a surface forces apparatus, we investigate for the first time, the nanomechanical properties of vWF-collagen interaction using homologous proteins of mussel byssus, PTMP1 and preCollagens (preCols), as collagen. Mimicking conditions similar to mussel byssus secretion (pH < 5.0) and seawater condition (pH 8.0), PTMP1 and preCol interact weakly in the "positioning" phase based on vWF-collagen binding and strengthen in "locked" phase due to the combined effects of electrostatic attraction, metal binding, and mechanical shearing. The progressive enhancement of binding between PTMP1 with porcine collagen under the aforementioned conditions is also observed. The binding mechanisms of PTMP1-preCols provide insights into the molecular interaction of the mammalian collagen system and the development of an artificial extracellular matrix based on collagens.


Teleost luteinizing hormone-releasing hormone: action on bullfrog sympathetic ganglia is consistent with role as neurotransmitter.
Bullfrog sympathetic ganglion neurons have a "late, slow" excitatory postsynaptic potential (EPSP) that is mediated by a peptide similar to mammalian luteinizing hormone-releasing hormone (M-LHRH) (Jan, Y. N., L. Y. Jan, and S. W. Kuffler (1979) Proc. Natl. Acad. Sci. U. S. A. 76: 1501-1505). On biochemical evidence (Eiden, L. E., E. Loumaye, N. Sherwood, and R. L. Eskay (1982) Peptides 3:323-327) the endogenous LHRH-like peptide in the ganglion may be identical to teleost LHRH (T-LHRH; [Trp7,Leu8]M-LHRH) (Sherwood, N., L. Eiden, M. Brownstein, J. Speiss, J. Rivier, and W. Vale (1983) Proc. Natl. Acad. Sci. U. S. A. 80: 2794-2798). We have found that T-LHRH acts qualitatively like M-LHRH on bullfrog ganglion cells, but it is quantitatively more potent. As for M-LHRH, the primary action of T-LHRH under single-electrode voltage clamp is to inhibit the M-current, a voltage-dependent potassium current that is active in the region between rest and threshold in these cells. The M-current is also inhibited during the late, slow EPSP. Both T-LHRH and the late, slow EPSP can also induce an additional inward current, associated with an increased conductance, in some cells. An LHRH antagonist is effective against both T-LHRH and the late, slow EPSP. These results are consistent with a role for T-LHRH as the natural transmitter for the late, slow EPSP in bullfrog sympathetic ganglia.


Skeletal muscle regeneration during aging and after long-term denervation.
Data accumulated in recent years strongly suggest that the basis for at least part of the muscle atrophy seen in old age is related to the diminution of motor innervation in normal muscle and a decreased effectiveness of reinnervation of regenerating muscle fibers. Thus, attempts to stabilize reverse the decline of the skeletal musculature during aging must take into account both the effects of aging on the peripheral nervous system and the presence of populations of denervated muscle fibers in the aging muscles. Of considerable importance is the question of how long muscle fibers in old animals can remain denervated before they begin to lose their capacity for restoration if they ultimately become reinnervated. The experimental studies reviewed here have shown that normal muscles in old animals are capable of a high degree of restoration as long as their motor nerve supply remains undamaged. After a certain period of time, denervated muscle in young animals steadily loses the capacity to restore or repair itself. To date, so little information is available on the properties of denervated muscle in old animals that meaningful comparisons cannot be made. Ultimately, ensuring that normal or injured muscle in old individuals is supplied by an effective motor innervation may be a real key to the problems of muscle loss in old age, but if such could be provided, it will be important that the old musculature, whether normal or injured, is capable of adequately responding to the innervation.


Reconstruction of defects of the mandible.
A series of 14 mandibular reconstruction in 13 patients with chips of autogenous, cancellous bone and marrow supported by a titanium mesh tray is presented. The mandibular defects were the results either of operation for carcinoma of the tongue and the floor of the mouth or trauma. Satisfactory rehabilitation was accomplished in 11 patients. The advantages of this technique are ease of accomplishment, ability to replace long and awkardly shaped segments, less shrinkage due to bone resorption, and shorter intermaxillary fixation.


Differential effects of approach bias and eating style on unhealthy food consumption in overweight and normal weight women.
The current study aimed to examine the effects of approach bias for unhealthy food and trait eating style on consumption of unhealthy food in overweight and normal weight individuals. Participants were 245 undergraduate women aged 17 - 26 years. They completed an Approach-Avoidance Task, the Dutch Eating Behaviour Questionnaire (to assess restrained, emotional, and external eating), and a taste test to measure consumption of unhealthy food. An external eating style predicted increased consumption of unhealthy food. Among overweight participants, external and emotional eating style individually moderated the relationship between approach bias for unhealthy food and subsequent consumption. Specifically, approach bias was positively related to consumption in high external and emotional eaters, but negatively related to consumption in low emotional eaters. These interactions were not observed among normal weight participants. Practically, the results suggest that overweight individuals who are external or emotional eaters may benefit from interventions that aim to modify approach bias towards unhealthy food cues to reduce problematic eating behaviour.


Green Synthesis of Silver Nanoparticles with Antimicrobial Properties Using Phyla dulcis Plant Extract.
Foodborne illnesses caused by the consumption of food contaminated with foodborne pathogens at infectious doses are becoming a common health issue throughout the world. Metal nanoparticles with potential antimicrobial properties are an area that can be explored to discover novel antimicrobial agents. The traditional synthesis methods of metal nanoparticles involve the use of toxic chemicals and the generation of harmful byproducts. In this study, a greener method to synthesize silver nanoparticles (AgNPs) with potential antimicrobial properties was investigated. The aqueous extract of the medicinal plant Phyla dulcis Trev. (verbenaceae) was used as the reducing and stabilizing agent to synthesize AgNPs using microwave irradiation. The formation of AgNPs was confirmed using ultraviolet-visible spectroscopy by the appearance of characteristic surface plasmon resonance peaks in the 430-440 nm wavelength range. The size and stability of the AgNPs were studied using Zetasizer nano-series for 5 weeks after synthesis. The average particle size remained between 63 and 76 nm during the first 4 weeks and increased to 114 nm in the fifth week showing possible aggregation after the fourth week. The zeta potential remained between -20 and -24 mV throughout the 5 weeks showing relatively good stability. Scanning electron microscopy/energy dispersive X-ray spectroscopy showed the association of phytoconstituents with the AgNPs. X-ray photoelectron spectroscopy analysis confirmed the formation of metallic nanoparticles starting from silver nitrate. Finally, the AgNPs were tested to be effective against Escherichia coli O157:H7 (ATCC 43888), Salmonella Typhimurium (novobiocin and nalidixic acid resistant strain), Listeria monocytogenes (4b; ATCC 19115), and Staphylococcus aureus (ATCC 6538) strains, which are known to be common foodborne pathogens.


Precise excision of plastid DNA by the large serine recombinase Bxb1.
Marker genes are essential for the selection and identification of rarely occurring transformation events generated in biotechnology. This includes plastid transformation, which requires that multiple copies of the modified chloroplast genome be present to obtain genetically stable transplastomic plants. However, the marker gene becomes dispensable when homoplastomic plants are obtained. Here, we demonstrate the precise excision of attP- and attB-flanked DNA from the plastid genome mediated by the large serine recombinase Bxb1. We transformed the tobacco plastid genome with the pTCH-PB vector containing a stuffer fragment of DNA flanked by directly oriented nonhomologous attP and attB recombinase recognition sites. In the absence of the Bxb1 recombinase, the transformed plastid genomes were stable and heritable. Nuclear-transformed transgenic tobacco plants expressing a plastid-targeted Bxb1 recombinase were crossed with transplastomic pTCH-PB plants, and the T₁ hybrids exhibited efficient excision of the target sequence. The Bxb1-att system should prove to be a useful tool for site-specifically manipulating the plastid genome and generating marker-free transplastomic plants.


Medical Management of Ovarian Endometriomas: A Systematic Review and Meta-analysis.
To estimate the effect of medical management on the size of ovarian endometriomas. Online databases were searched from inception to October 2022, including Ovid MEDLINE, Ovid EMBASE, PubMed, EBM Reviews-Cochrane Central Register of Controlled Trials (CENTRAL), ClinicalTrials.gov , and Web of Science. Following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, we included all English-language, full-text articles that reported on change in endometrioma size (either diameter or volume) after medical interventions. Studies evaluating surgical interventions or postoperative recurrence were excluded. All screening and data extraction were performed independently by two authors. Risk of bias assessment was performed with either the Cochrane Risk of Bias Tool for randomized controlled trials or a modified Newcastle-Ottawa Scale for observational studies. After removal of duplicates, 9,332 studies were screened, with 33 full-text articles deemed eligible for inclusion. In the meta-analysis, dienogest showed significant reduction in cyst diameter (reduction 1.32 cm, 95% CI, 0.91-1.73, eight studies, n=418 cysts) and volume (mean difference of log-transformed volume 1.35, 95% CI, 0.87-1.83, seven studies, n=282 cysts). Similarly, significant reductions were seen with the oral contraceptive pill (OCP) (1.06 cm, 95% CI, 0.59-1.53, nine studies, n=455), gonadotropin-releasing hormone (GnRH) agonists (1.17 cm, 95% CI, 0.42-1.92, four studies, n=128 cysts), norethindrone acetate (0.6 cm, 95% CI, 0.27-0.94, two studies, n=88 cysts), and danazol (1.95 cm, 95% CI, 1.18-2.73, two studies, n=34 cysts). Norethindrone acetate with aromatase inhibitor was also effective in reducing endometrioma volume (mean difference of log-transformed volume 1.47, 95% CI, 0.16-2.78, two studies, n=34 cysts). Medical management with dienogest, OCPs, GnRH agonists, norethindrone acetate, norethindrone acetate with aromatase inhibitor, or danazol can reduce the size of ovarian endometriomas. PROSPERO, CRD 42022363319.


Late infertile days in early postpartum cycles.
Luteal phase abnormalities in early menstrual cycles after pregnancy have been shown to cause confusion in the practice of natural family planning (NFP) for some patients and to restrict severely the number of late infertile days available to others. The cause of the abnormalities is uncertain but appears to be related to the nursing status of the patient.


Genomic characterization of severe acute respiratory syndrome-related coronavirus in European bats and classification of coronaviruses based on partial RNA-dependent RNA polymerase gene sequences.
Bats may host emerging viruses, including coronaviruses (CoV). We conducted an evaluation of CoV in rhinolophid and vespertilionid bat species common in Europe. Rhinolophids carried severe acute respiratory syndrome (SARS)-related CoV at high frequencies and concentrations (26% of animals are positive; up to 2.4×10(8) copies per gram of feces), as well as two Alphacoronavirus clades, one novel and one related to the HKU2 clade. All three clades present in Miniopterus bats in China (HKU7, HKU8, and 1A related) were also present in European Miniopterus bats. An additional novel Alphacoronavirus clade (bat CoV [BtCoV]/BNM98-30) was detected in Nyctalus leisleri. A CoV grouping criterion was developed by comparing amino acid identities across an 816-bp fragment of the RNA-dependent RNA polymerases (RdRp) of all accepted mammalian CoV species (RdRp-based grouping units [RGU]). Criteria for defining separate RGU in mammalian CoV were a >4.8% amino acid distance for alphacoronaviruses and a >6.3% distance for betacoronaviruses. All the above-mentioned novel clades represented independent RGU. Strict associations between CoV RGU and host bat genera were confirmed for six independent RGU represented simultaneously in China and Europe. A SARS-related virus (BtCoV/BM48-31/Bulgaria/2008) from a Rhinolophus blasii (Rhi bla) bat was fully sequenced. It is predicted that proteins 3b and 6 were highly divergent from those proteins in all known SARS-related CoV. Open reading frame 8 (ORF8) was surprisingly absent. Surface expression of spike and staining with sera of SARS survivors suggested low antigenic overlap with SARS CoV. However, the receptor binding domain of SARS CoV showed higher similarity with that of BtCoV/BM48-31/Bulgaria/2008 than with that of any Chinese bat-borne CoV. Critical spike domains 472 and 487 were identical and similar, respectively. This study underlines the importance of assessments of the zoonotic potential of widely distributed bat-borne CoV.


Effect of gemfibrozil in vitro on fat-mobilizing lipolysis in human adipose tissue.
Fat-mobilizing lipolysis was studied in rat and human adipose tissue during incubation in vitro by following the release of glycerol into the incubation medium. Gemfibrozil as well as clofibrate consistently and readily inhibited basal as well as noradrenaline-stimulated fat-mobilizing lipolysis in rat fat. With human adipose tissue no effect was observed with gemfibrozil and clofibrate on basal lipolysis. This may be due to the comparatively low rate of the nonstimulated fat-mobilizing lipolysis in human tissue incubated in vitro. When lipolysis was stimulated with noradrenaline as well as isoprenaline, however, both gemfibrozil and clofibrate significantly reduced the fat-mobilizing lipolysis. This inhibition of lipolysis was however not observed in all studies. When lipolysis had been stimulated with theophylline, no inhibition of lipolysis was obtained with either compound. The possibility that reduced fat-mobilizing lipolysis in adipose tissue may cause a lowering of plasma triglycerides by reducing the flow of FFA to the liver is discussed in some detail. It is also suggested that inhibition of lipolysis may be accompanied by increased activity of lipoprotein lipase as well as an increase in the FIAT process. However, the pharmacological implication of the above-mentioned findings, particularly for gemfibrozil, must await further studies, as fairly large doses, around 1 mg/ml of incubation medium, were needed to obtain inhibition of fat-mobilizing lipolysis.


NOTCH3 is a Prognostic Factor and Is Correlated With Immune Tolerance in Gastric Cancer.
Although traditional treatments confer survival benefits to patients with gastric cancer (GC), many patients experience relapse soon after postoperative adjuvant therapy. Immune-related mechanisms play an important role in GC, and immunotherapeutic strategies are considered to be a promising direction for the treatment of GC. Thus, our study aimed to investigate the expression and prognostic significance of immune-related genes in GC. Formalin-fixed, paraffin-embedded samples were collected from 48 resectable GC patients. The transcriptome data of the tumor immune microenvironment were assessed using an immuno-oncology 395-gene panel RNA sequencing platform. The prognostic value of the 395 genes was analyzed and validated in the KM plotter and GEPIA databases. The data from The Cancer Genome Atlas (TCGA, downloaded from UCSC Xena repository) and Tumor IMmune Estimation Resource (TIMER) were used to evaluate the correlations between prognostic factors and immune signatures. Among the 395 genes, NOTCH3 was identified as a good prognostic factor for GC patients. Its prognostic value was also suggested in both our GC cohort from Zhongshan Hospital and the public databases (KM plotter and GEPIA database). Mechanistically, high NOTCH3 expression correlated with a lower infiltration of activated CD8+ T cells and a higher infiltration of immunosuppressive cells including Tregs and M2 macrophages in the tumor microenvironment. Moreover, high NOTCH3 expression was accompanied by the increased expression of a series of immune checkpoint inhibitors, resulting in a dampened immune response. Interestingly, NOTCH3 expression had a negative association with well-documented predictive biomarkers of immune checkpoint blockade (ICB) immunotherapy, including tumor mutation burden (TMB), gene expression profiling (GEP) score and innate anti-PD-1 resistance (IPRES) signature. These findings uncovered a new mechanism by which NOTCH3 participates in the immune tolerance of GC, implying the potential of NOTCH3 as a therapeutic target or predictive marker for GC patients.


Effects of a health behavior change model--based HIV/STI prevention intervention on condom use among heterosexual couples: a randomized trial.
This study examines an intervention for heterosexual couples to prevent human immunodeficiency virus/sexually transmitted infections. It also evaluates the effect of the intervention, which is based on current models of health behavior change, on intermediate outcomes (individual and relationship factors) and consistency of condom use. Eligible couples were administered a baseline interview and randomized to either a 3-session theory-based intervention or a 1-session standard of care comparison condition. Men and women completed 3-month interviews; only women completed 6-month interviews. No significant intervention effect on condom use was found among couples at 3 months (n = 212) or among women (n = 178) at 6 months. However, condom use increased significantly between baseline and 3 months and baseline and 6 months for participants in both treatment conditions. Intervention effects on condom use self-efficacy were found at 3 months and 6 months and on health-protective communication at 3 months. These findings provide valuable information for the design of future studies to help disentangle the effects of intervening with couples.


[Proatherogenic and hemodynamic risk factors of occupational arterial hypertension in sailing personel].
The article demonstrates reliably increased risk of arterial hypertension under exposure to general vibration. Lipid metabolism disorders in vibration disease patients were proved to increase risk of atherosclerosis. Recommendations include studies of limbs macrohemodynamics in prophylactic medical examinations among sailing personnel.


A dual origin of the Xist gene from a protein-coding gene and a set of transposable elements.
X-chromosome inactivation, which occurs in female eutherian mammals is controlled by a complex X-linked locus termed the X-inactivation center (XIC). Previously it was proposed that genes of the XIC evolved, at least in part, as a result of pseudogenization of protein-coding genes. In this study we show that the key XIC gene Xist, which displays fragmentary homology to a protein-coding gene Lnx3, emerged de novo in early eutherians by integration of mobile elements which gave rise to simple tandem repeats. The Xist gene promoter region and four out of ten exons found in eutherians retain homology to exons of the Lnx3 gene. The remaining six Xist exons including those with simple tandem repeats detectable in their structure have similarity to different transposable elements. Integration of mobile elements into Xist accompanies the overall evolution of the gene and presumably continues in contemporary eutherian species. Additionally we showed that the combination of remnants of protein-coding sequences and mobile elements is not unique to the Xist gene and is found in other XIC genes producing non-coding nuclear RNA.


Uncovering the behaviors of individual cells within a multicellular microvascular community.
Although individual cells vary in behavior during the formation of tissues, the nature of such variations are largely uncharacterized. Here, we tracked the morphologies and motilities of ~300 human endothelial cells from an initial dispersed state to the formation of capillary-like structures, distilling the dynamics of tissue morphogenesis into an array of ~36,000 numerical phenotypes. Quantitative analysis of population averages revealed two previously unidentified phases in which the cells spread before forming connections with neighboring cells and where the microvascular plexus stabilized before spatially reorganizing. Analysis at the single-cell level showed that in contrast to the population-averaged behavior, most cells followed distinct temporal patterns that were not reflected in the bulk average. Interestingly, some of these behavioral patterns correlated to the cells' final structural role within the plexus. Knowledge of how individual cells or groups of cells behave enhances our understanding of how native tissues self-organize and could ultimately enable more precise approaches for engineering tissues and synthesizing multicellular communities.


Intra-uterine fetal death and thrombosis of the umbilical vessels.
Intra-uterine fetal death associated with thrombosis of the umbilical cord vessels is a rarely described condition. Three cases are now reported and the possible genesis of the thrombosis is discussed, with particular regard to the significance of disturbances in the fetal circulation.


Pediatric glioma histone H3.3 K27M/G34R mutations drive abnormalities in PML nuclear bodies.
Point mutations in histone variant H3.3 (H3.3K27M, H3.3G34R) and the H3.3-specific ATRX/DAXX chaperone complex are frequent events in pediatric gliomas. These H3.3 point mutations affect many chromatin modifications but the exact oncogenic mechanisms are currently unclear. Histone H3.3 is known to localize to nuclear compartments known as promyelocytic leukemia (PML) nuclear bodies, which are frequently mutated and confirmed as oncogenic drivers in acute promyelocytic leukemia. We find that the pediatric glioma-associated H3.3 point mutations disrupt the formation of PML nuclear bodies and this prevents differentiation down glial lineages. Similar to leukemias driven by PML mutations, H3.3-mutated glioma cells are sensitive to drugs that target PML bodies. We also find that point mutations in IDH1/2-which are common events in adult gliomas and myeloid leukemias-also disrupt the formation of PML bodies. We identify PML as a contributor to oncogenesis in a subset of gliomas and show that targeting PML bodies is effective in treating these H3.3-mutated pediatric gliomas.


Validation of PAMFix, A Novel Platelet Stabilization Product, for Use on Flow Cytometric Analysis of Pigtailed Macaque (Macaca nemestrina) Blood.
Quantification of platelet activation can be important for patients suffering from prothrombotic states, bleeding diatheses, cardiovascular disease, and other diseases in which platelets play a role. The analysis of platelet activation ex vivo typically requires blood processing immediately after venipuncture; this requirement can create problematic situations for both medical and research personnel. Flow cytometry is one method used to quantify platelet activation by measuring the expression of platelet surface markers with fluorescent antibodies. PAMFix is a fixative that stabilizes platelet activation markers, including P-selectin (CD62P), in whole blood. PAMFix has already been validated for use in humans and canines for stabilization of whole blood, thus allowing flow cytometry to be performed up to 28 and 22 d, respectively, after venipuncture and reducing the need for expensive equipment and highly trained personnel at the location of venipuncture. Pigtailed macaques (Macaca nemestrina) are frequently used in infectious disease research that may require containment conditions that preclude immediate processing of samples. In this study, we tested the efficacy of PAMFix on whole blood from pigtailed macaques to determine the short- and long-term effects of PAMFix on platelet P-selectin expression as analyzed by flow cytometry.


SLC38A5 Modulates Ferroptosis to Overcome Gemcitabine Resistance in Pancreatic Cancer.
Pancreatic cancer is characterized by a poor prognosis, with its five-year survival rate lower than that of any other cancer type. Gemcitabine, a standard treatment for pancreatic cancer, often has poor outcomes for patients as a result of chemoresistance. Therefore, novel therapeutic targets must be identified to overcome gemcitabine resistance. Here, we found that SLC38A5, a glutamine transporter, is more highly overexpressed in gemcitabine-resistant patients than in gemcitabine-sensitive patients. Furthermore, the deletion of SLC38A5 decreased the proliferation and migration of gemcitabine-resistant PDAC cells. We also found that the inhibition of SLC38A5 triggered the ferroptosis signaling pathway via RNA sequencing. Also, silencing SLC38A5 induced mitochondrial dysfunction and reduced glutamine uptake and glutathione (GSH) levels, and downregulated the expressions of GSH-related genes NRF2 and GPX4. The blockade of glutamine uptake negatively modulated the mTOR-SREBP1-SCD1 signaling pathway. Therefore, suppression of SLC38A5 triggers ferroptosis via two pathways that regulate lipid ROS levels. Similarly, we observed that knockdown of SLC38A5 restored gemcitabine sensitivity by hindering tumor growth and metastasis in the orthotopic mouse model. Altogether, our results demonstrate that SLC38A5 could be a novel target to overcome gemcitabine resistance in PDAC therapy.


Metatranscriptomic outlook on green and brown food webs in acid mine drainage.
Acid mine drainages (AMDs), metal-rich acidic effluents generated by mining activities, are colonized by prokaryotic and eukaryotic microorganisms widely distributed among different phyla. We compared metatranscriptomic data from two sampling stations in the Carnoulès AMD and from a third station in the nearby Amous River, focussing on processes involved in primary production and litter decomposition. A synergistic relationship between the green and brown food webs was favoured in the AMD sediments by the low carbon content and the availability of mineral nutrients: primary production of organic matter would benefit C-limited decomposers whose activity of organic matter mineralization would in turn profit primary producers. This balance could be locally disturbed by heterogeneous factors such as an input of plant debris from the riparian vegetation, strongly boosting the growth of Tremellales which would then outcompete primary producers. In the unpolluted Amous River on the contrary, the competition for limited mineral nutrients was dominated by the green food web, fish and bacterivorous protists having a positive effect on phytoplankton. These results suggest that in addition to direct effects of low pH and metal contamination, trophic conditions like carbon or mineral nutrient limitations also have a strong impact on assembly and activities of AMDs' microbial communities.


Pregnancy after kidney and kidney-pancreas transplantation under tacrolimus: a single center's experience.
Chronic renal failure leads to amenorrhea, and successful pregnancy is rare. The aim of the present report is to examine the outcome of pregnancies under tacrolimus after kidney transplantation (KTx) and simultaneous kidney-pancreas transplantation (SPKTx). All pregnancies under tacrolimus after KTx or SPKTx from 1993 to April 2002 were retrospectively examined. Renal function and the mother's survival were followed until December 2002. Thirteen mothers after KTx delivered 19 babies, and 2 mothers after SPKTx delivered 3 babies. All mothers survived the pregnancy and retained allograft function. One mother had a stillborn baby from an unrecognized amniotic fluid leak and a small ischemic placenta. The mean gestational period was 34.4 +/- 5.1 weeks. Mean birth weight was 2373 +/- 1001 g. Birth-weight percentile to gestational period was 40 +/- 28. None of the mothers experienced rejection during the pregnancy. Three pregnancies in mothers with KTx experienced toxemia of pregnancy, and one mother with SPKTx developed pre-eclampsia during both pregnancies. Five mothers (6 deliveries, 27.3%) required caesarian section. During the follow-up period, one mother died from a cerebrovascular accident. Another five mothers returned to dialysis 55.6 +/- 32.4 months after the last delivery and 99.4+28.5 months after the last KTx. Both SPKTx mothers have maintained normal renal and pancreatic allograft function 42 and 62 months postdelivery. All mothers survived the pregnancy. One baby was stillborn. Forty-one percent of babies were either preterm or premature, and 27% of babies were delivered by caesarean section. Toxemia of pregnancy or pre-eclampsia was observed in 23% of pregnancies postKTx and SPKTx. None of the mothers experienced rejection during their pregnancy.


How effective are health messages/warnings in improving knowledge and awareness of alcohol-related harm? The Slovenian case on using a mobile app.
Consumers generally lack access to information on alcoholic beverages, in spite of it being readily available for food and non-alcoholic beverages. Given the rights of consumers, and as with other products harmful to the population, there have been increasing calls for health warnings to be placed on alcoholic beverages, similar to those implemented on tobacco products. The aim of our research was to assess whether knowledge and awareness of the risks and harms associated with alcohol can be improved with a mobile app. Intervention was conducted using VKJ mobile app, which enables users to scan the barcode of an alcoholic beverage and receive feedback on its labelled alcohol content and estimated energy value. At each search, eleven different health messages/warnings about the risks and harms of alcohol are also displayed randomly, rotating on the screen. A survey was conducted before and after the intervention, to assess the knowledge and awareness of the risks and harms associated with drinking alcohol. Significant differences were found for eight of the twelve tested statements. The improvement was seen to a greater extent in the group of high-risk drinkers. The results also showed that the vast majority of participants (78%) who were exposed to the health messages supported mandatory labelling of alcoholic beverages with information on ingredient listing and energy value, and 72% would like to have health warnings on alcohol products. The use of a mobile app can be an option to improve knowledge and raise awareness of the risks and harms related to alcohol.


Electrochemical detection of glycan and protein epitopes of glycoproteins in serum.
Aberrant protein glycosylation is associated with a range of pathological conditions including cancer and possesses diagnostic importance. Translation of glycoprotein biomarkers will be facilitated by the development of a rapid and sensitive analytical platform that simultaneously interrogates both the glycan and protein epitopes of glycoproteins in body fluids such as serum or saliva. To this end, we developed an electrochemical biosensor based on the immobilization of a lectin on the gold electrode surface to recognize/capture a target glycan epitope conjugated to glycoproteins, followed by detection of the protein epitope using a target protein-specific antibody. Electrochemical signals are generated by label-free voltammetric or impedimetric interrogation of a ferro/ferricyanide redox couple (e.g. [Fe(CN)6](3-/4-)) on the sensing surface, where the change in voltammetric current or interfacial electron transfer resistance was measured. The detection system was demonstrated using the model glycoprotein chicken ovalbumin with Sambucus nigra agglutinin type I (SNA lectin), and exhibits femtomolar sensitivity in the background of diluted human serum. The results obtained in this proof-of-concept study demonstrate the possibility of using electrochemical detection for developing cheap point-of-care diagnostics with high specificity and sensitivity for blood glycoprotein biomarkers.


Serum antioxidant concentrations and metabolic syndrome are associated among U.S. adolescents in recent national surveys.
Specific micronutrients, including retinol, retinyl esters, carotenoids [α-carotene, β-carotene (cis+trans), β-cryptoxanthin, lutein+zeaxanthin, and total lycopene], vitamin E, and vitamin C have antiinflammatory and antioxidant effects, properties shown to reduce oxidative stress, a process that accompanies the pathogenesis of many chronic diseases. It is still largely unknown whether they are associated with the occurrence of metabolic syndrome (MetS) in the adolescent U.S. population. MetS was defined by the International Diabetes Federation (IDF) criteria. Other non-MetS outcomes relying on blood measurements were elevated HOMA-IR, C-reactive protein (CRP), and hyperuricemia. We tested associations between serum antioxidants and MetS outcomes among adolescents aged 12-19 y using cross-sectional data from NHANES 2001-2006 (n = 782-4285). IDF MetS prevalence was estimated at 7% among boys and 3% among girls. In adjusted models, adolescents with MetS had consistently lower carotenoid concentrations compared with their counterparts without MetS. Total carotenoids were also inversely related to HOMA-IR and CRP. Vitamin C was inversely related to uric acid level and MetS binary outcome. Retinol+retinyl esters exhibited an inverse relationship with CRP and a positive relationship with uric acid and HOMA-IR as well as MetS binary outcome. Vitamin E had no association with MetS, particularly after controlling for serum cholesterol and TG. In conclusion, among U.S. adolescents, serum carotenoid concentrations were inversely associated with MetS status, HOMA-IR, and CRP, whereas serum vitamin C was inversely related to MetS status and serum uric acid. Vitamin E had no consistent association with MetS, whereas retinol+retinyl esters had a positive relationship with HOMA-IR, uric acid, and MetS, while being inversely related to CRP. These associations need further study.


Glycation in food and metabolic transit of dietary AGEs (advanced glycation end-products): studies on the urinary excretion of pyrraline.
Pyrraline [epsilon-(2'-formyl-5'-hydroxymethyl-pyrrolyl)-L-norleucin] belongs to the group of AGEs (advanced glycation end-products) formed in the final stage of the Maillard reaction in foods and in vivo. As it is generally accepted that AGEs are pathophysiologically relevant in aging and in diseases such as diabetes and uraemia, physiological consequences resulting from the ingestion of dietary AGEs are discussed, but balance studies for well defined AGEs are still lacking. The aim of our study was to investigate the influence of nutrition on the urinary excretion of pyrraline. After the first day without dietary restrictions, seven healthy volunteers were asked, starting on the morning of day 2, to ingest a diet virtually free of Maillard compounds (i.e. no cooked or roasted foods, no bakery products, no coffee, etc.). Dietary control was stopped on the morning of day 5. We collected 24 h urine samples for these 5 days, which were analysed for free pyrraline by reverse-phase HPLC with UV detection at 297 nm. We found that urinary excretion of free pyrraline was directly affected by the composition of the diet, decreasing from 4.8+/-1.1 mg/day on day 1 to levels of 1.6, 0.4 and 0.3 mg/day on days 2, 3 and 4 respectively, followed by a significant increase to 3.2+/-1.4 mg/day on the 5th day. The results of this work prove, for the first time, that urinary excretion of pyrraline is strongly dependent on its dietary intake. Thus the influence of nutrition should be taken into consideration in studies directed to the physiological role of glycation compounds.


The response of clinical balanitis xerotica obliterans to the application of topical steroid-based creams.
The aim of this study was to assess the effectiveness of using topical steroid-based creams in the management of clinically diagnosed balanitis xerotica obliterans (BXO) in boys. The response in 56 boys to locally applied steroid-based creams was studied retrospectively. All had been referred by their general practitioners with symptoms of penile pathology and then subsequently had a clinical diagnosis of BXO made. The boys were initially assessed after 3 months of treatment and then at various intervals depending on their response. The mean age at presentation of the boys was 8.9 (4 to 15) years. After the initial 3-month assessment, 10 (17.9%) boys had complete resolution. When the treatment period was prolonged by an average of 14 months, the total number of boys showing resolution increased to 17 (30.4%). All boys showing resolution had clinically mild BXO limited to the prepuce only. Those patients with established scar formation on the foreskin showed no significant improvement. Topical steroids seem to offer a reliable option only in the management of mild BXO limited to the prepuce in boys with minimal scar formation. Steroid-based creams can be offered to such patients provided they and their families are realistic as to the likelihood of success. This treatment is ineffective in the face of established scarring.


Applying Multi-Theory Model (MTM) of Health Behavior Change to Predict Water Consumption Instead of Sugar-Sweetened Beverages.
A substantial proportion of college students to not drink enough water and consume sugar-sweetened beverages (SSBs). Consumption of SSBs is associated with weight gain, obesity, type 2 diabetes mellitus, dental carries, and increased risk for cardiovascular disease. Hence, the purpose of this study was to use the multi-theory model (MTM) in predicting initiation and sustenance of plain water consumption instead of sugar-sweetened beverages among college students. A cross-sectional study. In this cross-sectional study, a 37-item valid and reliable MTM-based survey was administered to college students in 2016 via Qualtrics at a large public university in the Southeastern United States. Overall, 410 students responded to the survey; of those, 174 were eligible for the study and completed it. Stepwise multiple regression analysis revealed that 61.8% of the variance in the initiation of drinking plain water instead of SSBs was explained by behavioral confidence (P<0.001) and changes in the physical environment (P<0.001). Further, 58.3% of the variance in the sustenance of drinking plain water instead of SSBs was explained by emotional transformation (P<0.001) and practice for change (P=0.001). Multi-theory model of health behavior change is a robust theory for predicting plain water consumption instead of SSBs in college students. Interventions should be developed based on this theory for this target population.


Prediction of parturition date in the bitch and queen.
Assessment of gestational age and parturition date prediction is a challenging, yet common task in clinical management of the pregnant bitch or queen. Knowing the approximate parturition date is essential for a thorough pregnancy monitoring. Radiographic and ultrasonographic methods are suitable in bitches and queens. In the bitch, moreover, ovulation timing by means of LH or progesterone assay, determination of onset of vaginal dioestrus by means of examination of vaginal cytology, and recognition of impending parturition by monitoring prepartal progesterone levels and body temperature variation are practical methods. A combination of different methods increases the accuracy of parturition date prediction.