Diversity and distribution of ectoparasite taxa associated with Micaelamys namaquensis (Rodentia: Muridae), an opportunistic commensal rodent species in South Africa.

South Africa boasts a rich diversity of small mammals of which several are commensal and harbour parasites of zoonotic importance. However, limited information is available on the parasite diversity and distribution associated with rodents in South Africa. This is particularly relevant for Micaelamys namaquensis (Namaqua rock mouse), a regionally widespread and locally abundant species that is often commensal. To address the paucity of data, the aims of the study were to record the ectoparasite diversity associated with M. namaquensis and develop distribution maps of lice and mites associated with M. namaquensis and other rodents in South Africa. Micaelamys namaquensis individuals (n = 216) were obtained from 12 localities representing multiple biomes during 2017­2018. A total of 5591 ectoparasites representing 5 taxonomic groups ­ fleas, lice, mesostigmatid mites, chiggers and ticks was recorded. These consisted of at least 57 taxa of which ticks were the most speciose (20 taxa). Novel contributions include new host and locality data for several ectoparasite taxa and undescribed chigger species. Known vector species were recorded which included fleas (Ctenocephalides felis, Dinopsyllus ellobius and Xenopsylla brasiliensis) and ticks (Haemaphysalis elliptica, Rhipicephalus appendiculatus and Rhipicephalus simus). Locality records indicate within-taxon geographic differences between the 2 louse species and the 2 most abundant mite species. It is clear that M. namaquensis hosts a rich diversity of ectoparasite taxa and, as such, is an important rodent species to monitor in habitats where it occurs in close proximity to humans and domestic animals.

Evaluation of Normothermic Machine Perfusion of Porcine Livers as a Novel Preclinical Model to Predict Biliary Clearance and Transporter-Mediated Drug-Drug Interactions Using Statins.

There is a lack of translational preclinical models that can predict hepatic handling of drugs. In this study, we aimed to evaluate the applicability of normothermic machine perfusion (NMP) of porcine livers as a novel ex vivo model to predict hepatic clearance, biliary excretion, and plasma exposure of drugs. For this evaluation, we dosed atorvastatin, pitavastatin, and rosuvastatin as model drugs to porcine livers and studied the effect of common drug-drug interactions (DDIs) on these processes. After 120 minutes of perfusion, 0.104 mg atorvastatin (n = 3), 0.140 mg pitavastatin (n = 5), or 1.4 mg rosuvastatin (n = 4) was administered to the portal vein, which was followed 120 minutes later by a second bolus of the statin coadministered with OATP perpetrator drug rifampicin (67.7 mg). After the first dose, all statins were rapidly cleared from the circulation (hepatic extraction ratio > 0.7) and excreted into the bile. Presence of human-specific atorvastatin metabolites confirmed the metabolic capacity of porcine livers. The predicted biliary clearance of rosuvastatin was found to be closer to the observed biliary clearance. A rank order of the DDI between the various systems upon coadministration with rifampicin could be observed: atorvastatin (AUC ratio 7.2) > rosuvastatin (AUC ratio 3.1) > pitavastatin (AUC ratio 2.6), which is in good agreement with the clinical DDI data. The results from this study demonstrated the applicability of using NMP of porcine livers as a novel preclinical model to study OATP-mediated DDI and its effect on hepatic clearance, biliary excretion, and plasma profile of drugs. SIGNIFICANCE STATEMENT: This study evaluated the use of normothermic machine perfusion (NMP) of porcine livers as a novel preclinical model to study hepatic clearance, biliary excretion, plasma (metabolite) profile of statins, and OATP-mediated DDI. Results showed that NMP of porcine livers is a reliable model to study OATP-mediated DDI. Overall, the rank order of DDI severity indicated in these experiments is in good agreement with clinical data, indicating the potential importance of this new ex vivo model in early drug discovery.

Altered hippocampal function in major depression despite intact structure and resting perfusion.

BACKGROUND: Hippocampal volume reductions in major depression have been frequently reported. However, evidence for functional abnormalities in the same region in depression has been less clear. We investigated hippocampal function in depression using functional magnetic resonance imaging (fMRI) and neuropsychological tasks tapping spatial memory function, with complementing measures of hippocampal volume and resting blood flow to aid interpretation. METHOD: A total of 20 patients with major depressive disorder (MDD) and a matched group of 20 healthy individuals participated. Participants underwent multimodal magnetic resonance imaging (MRI): fMRI during a spatial memory task, and structural MRI and resting blood flow measurements of the hippocampal region using arterial spin labelling. An offline battery of neuropsychological tests, including several measures of spatial memory, was also completed. RESULTS: The fMRI analysis showed significant group differences in bilateral anterior regions of the hippocampus. While control participants showed task-dependent differences in blood oxygen level-dependent (BOLD) signal, depressed patients did not. No group differences were detected with regard to hippocampal volume or resting blood flow. Patients showed reduced performance in several offline neuropsychological measures. All group differences were independent of differences in hippocampal volume and hippocampal blood flow. CONCLUSIONS: Functional abnormalities of the hippocampus can be observed in patients with MDD even when the volume and resting perfusion in the same region appear normal. This suggests that changes in hippocampal function can be observed independently of structural abnormalities of the hippocampus in depression.

The interrelationship between attentional and executive deficits in major depressive disorder.

OBJECTIVE: Cognitive dysfunction is an established feature of major depressive disorder (MDD). However, it remains unclear whether deficits in different cognitive domains are relatively independent or originate from a circumscribed 'primary deficit'. This study tested the hypothesis that a deficit in attention represents a primary deficit in depression. METHOD: Neuropsychological function was assessed in 30 depressed patients with MDD and 34 control participants. Cognitive composites were derived from a minimum of three tests and included attention, executive function, visuospatial memory and verbal memory. A multivariate analysis of variance was used to assess group differences in overall cognitive performance, and multiple regression models were used to evaluate the role of attention in deficits in other domains. RESULTS: The cognitive deficit in the depressed sample was found to be characterized by poorer performance in attention and executive function. When evaluating the interrelationship between the two deficits, the attentional deficit was found to persist when variability in executive function was statistically accounted for, whilst the executive deficit was eliminated when attention was accounted for. CONCLUSION: The results demonstrated that the attentional deficit could not be explained by deficits in executive function, which provides support for a primary attention deficit in depression.

Impulsive choice predicts short-term relapse in substance-dependent individuals attending an in-patient detoxification programme.

BACKGROUND: Impulsivity is a hallmark characteristic of substance use disorders. Recently, studies have begun to explore whether increased impulsivity in substance-dependent individuals (SDIs) is associated with a greater propensity to relapse following treatment. Despite growing recognition of its multidimensional nature, however, most studies have treated impulsivity unilaterally. Accordingly, it remains unclear whether certain facets of impulsivity are more relevant to relapse than others. The aim of the current study was to examine the relationship between multiple facets of impulsivity and short-term relapse in SDIs. As a secondary aim, we explored the role of treatment retention in this relationship. METHOD: A personality-based impulsivity questionnaire (UPPS) and three neurocognitive tasks of impulsivity [stop-signal task (SST), delay discounting task (DDT) and Iowa gambling task (IGT)] were administered in a heterogeneous sample of 70 SDIs shortly following their entry in an in-patient detoxification programme. Mediation analyses were performed to explore whether the effects of impulsivity on relapse were mediated by treatment retention. RESULTS: Performance on two neurocognitive indices of impulsive choice (i.e. delay discounting and impulsive decision-making) significantly predicted short-term relapse. The effects of delay discounting and impulsive decision-making on relapse propensity were mediated by treatment retention. CONCLUSIONS: Neurocognitive indices of impulsivity may be more sensitive to the prediction of relapse than trait-based self-report questionnaires. Post-treatment relapse in SDIs may be reduced by targeting the processes involved in impulsive choice and by improving treatment retention in SDIs with inflated impulsivity.

Validity and reliability of critical power field testing.

PURPOSE: To test the validity and reliability of field critical power (CP). METHOD: Laboratory CP tests comprised three exhaustive trials at intensities of 80, 100 and 105 % maximal aerobic power and CP results were compared with those determined from the field. Experiment 1: cyclists performed three CP field tests which comprised maximal efforts of 12, 7 and 3 min with a 30 min recovery between efforts. Experiment 2: cyclists performed 3 × 3, 3 × 7 and 3 × 12 min individual maximal efforts in a randomised order in the field. Experiment 3: the highest 3, 7 and 12 min power outputs were extracted from field training and racing data. RESULTS: Standard error of the estimate of CP was 4.5, 5.8 and 5.2 % for experiments 1-3, respectively. Limits of agreement for CP were -26 to 29, 26 to 53 and -34 to 44 W for experiments 1-3, respectively. Mean coefficient of variation in field CP was 2.4, 6.5 and 3.5 % for experiments 1-3, respectively. Intraclass correlation coefficients of the three repeated trials for CP were 0.99, 0.96 and 0.99 for experiments 1-3, respectively. CONCLUSIONS: Results suggest field-testing using the different protocols from this research study, produce both valid and reliable CP values.

Medical students' views on selection tools for medical school--a mixed methods study.

It is important to ensure that the tools used in Medical School selection are acceptable to students and applicants. A questionnaire was administered to year 1 medical students in 2010 to determine the suitability of a variety of selection tools and the acceptability of HPAT-Ireland in particular. There were 291 respondents a 77% response rate representing approximately one third of all school leaver entrants that year. While the majority 285 (98%) were in favour of using school leaving examinations there was also support for the use of interviews 215 (74%) and other tools. Three quarters of Irish respondents 159 (76%) agreed that HPAT-Ireland is a fair test overall however section 3 (non-verbal reasoning) appeared less acceptable and relevant than other sections. A little over half had taken a preparatory HPAT-Ireland course 112 (54%). Medical school applicants appear to accept the use of non-traditional tools in the selection process.

Efficacy of neuromuscular exercises to promote movement quality and reduce musculoskeletal injury during initial military training in Royal Navy recruits.

INTRODUCTION: Musculoskeletal injuries (MSKIs) are a significant problem in the Royal Navy, contributing to 48% of all medical discharges from service between 2019 and 2020. The objective of the study was to assess efficacy of implementing a neuromuscular training intervention to improve movement quality and reduce MSKIs in Royal Navy recruits undertaking initial military training. METHODS: Neuromuscular training (pre-activation exercises, focusing on hip control) was integrated into the warm-up exercise regimen preceding physical training during the 10-week initial naval training (recruits) programme (January-March 2020) at HMS Raleigh (intervention group; n=162). A control group comprised (n=90) of recruits entering training from January 2019, who completed the standard warm-up programme prior to physical training. Movement control of the intervention group (intervention) was assessed before and after the 10-week programme using the Hip and Lower-Limb Movement Screen (HLLMS). Injury incidence proportion for both groups was determined retrospectively by review of medical notes. RESULTS: The control group's MSKI incidence proportion was 31%, which was higher (p<0.05) than the 8% reported in the intervention group. The majority of MSKIs were of the lower limb, and were reported in weeks 1, 2 and 5 of the 10-week training programme. Movement control, as assessed by the HLLMS score, improved (pretraining (week 1) and post-training (week 10) HLLMS score (mean (SD) pre: 11.2 (5.6); post: 8.4 (3.9); t=5.829, p<0.001) following the neuromuscular training in the intervention group but was not assessed in the control group. CONCLUSION: A neuromuscular control intervention was successfully implemented during the initial military training in the Royal Navy. The cohort undertaking the intervention demonstrated lower injury incidence compared with an equivalent cohort of recruits who undertook standard training. Movement control improved following the intervention, indicating better movement quality. Continued use of the programme may reduce military training attrition in the Royal Navy.

Ex vivo gut-hepato-biliary organ perfusion model to characterize oral absorption, gut-wall metabolism, pre-systemic hepatic metabolism and biliary excretion; application to midazolam.

To date, characterization of the first-pass effect of orally administered drugs consisting of local intestinal absorption and metabolism, portal vein transport and hepatobiliary processes remains challenging. Aim of this study was to explore the applicability of a porcine ex-vivo perfusion model to study oral absorption, gut-hepatobiliary metabolism and biliary excretion of midazolam. Slaughterhouse procured porcine en bloc organs (n = 4), were perfused via the aorta and portal vein. After 120 min of perfusion, midazolam, atenolol, antipyrine and FD4 were dosed via the duodenum and samples were taken from the systemic- and portal vein perfusate, intestinal faecal effluent and bile to determine drug and metabolite concentrations. Stable arterial and portal vein flow was obtained and viability of the perfused organs was confirmed. After intraduodenal administration, midazolam was rapidly detected in the portal vein together with 1-OH midazolam (EG-pv of 0.16±0.1) resulting from gut wall metabolism through oxidation. In the intestinal faecal effluent, 1-OH midazolam and 1-OH midazolam glucuronide (EG-intestine 0.051±0.03) was observed resulting from local gut glucuronidation. Biliary elimination of midazolam (0.04±0.01 %) and its glucuronide (0.01±0.01 %) only minimally contributed to the enterohepatic circulation. More extensive hepatic metabolism (FH 0.35±0.07) over intestinal metabolism (FG 0.78±0.11) was shown, resulting in oral bioavailability of 0.27±0.05. Ex vivo perfusion demonstrated to be a novel approach to characterize pre-systemic extraction of midazolam by measuring intestinal as well as hepatic extraction. The model can generate valuable insights into the absorption and metabolism of new drugs.

Household model of Chagas disease vectors (Hemiptera: Reduviidae) considering domestic, peridomestic, and sylvatic vector populations.

ABSTRACT Disease transmission is difficult to model because most vectors and hosts have different generation times. Chagas disease is such a situation, where insect vectors have 1-2 generations annually and mammalian hosts, including humans, can live for decades. The hemataphagous triatominae vectors (Hemiptera: Reduviidae) of the causative parasite Trypanosoma cruzi (Kinetoplastida: Trypanosomatidae) usually feed on sleeping hosts, making vector infestation of houses, peridomestic areas, and wild animal burrows a central factor in transmission. Because of difficulties with different generation times, we developed a model considering the dwelling as the unit of infection, changing the dynamics from an indirect to a direct transmission model. In some regions, vectors only infest houses; in others, they infest corrals; and in some regions, they also infest wild animal burrows. We examined the effect of sylvatic and peridomestic vector populations on household infestation rates. Both sylvatic and peridomestic vectors increase house infestation rates, sylvatic much more than peridomestic, as measured by the reproductive number R0. The efficacy of manipulating parameters in the model to control vector populations was examined. When R0 > 1, the number of infested houses increases. The presence of sylvatic vectors increases R0 by at least an order of magnitude. When there are no sylvatic vectors, spraying rate is the most influential parameter. Spraying rate is relatively unimportant when there are sylvatic vectors; in this case, community size, especially the ratio of houses to sylvatic burrows, is most important. The application of this modeling approach to other parasites and enhancements of the model are discussed.

Portion weights of food served in English schools: have they changed following the introduction of nutrient-based standards?

BACKGROUND: Mandatory food-based and nutrient-based standards for the food provided in English schools were introduced in 2008 (primary) and 2009 (secondary) and have had a positive impact on pupils' food choice and nutrient intake at school. There are no recommendations for portion sizes in England, although anecdotal evidence suggests that portions of food and drink sold in schools have decreased since the standards were introduced. METHODS: Data were collected from 136 primary and 80 secondary schools in 2009 and 2010/11, respectively. All food and drink items provided at lunchtime were weighed on five consecutive days at each school. The mean and median weight, SD, and 25th and 75th centile for each individual food were calculated. Data were compared with the results obtained from similar surveys in 2004 and 2005, as well as with portion size recommendations for Scottish schools. RESULTS: The proportion of food items that differed in weight since 2004/05 varied from 13% in primary schools to 29% in secondary schools. Changes in weight were equally likely to be positive or negative, with the exception of portions of fruit and vegetables, which had decreased. Primary schools were more likely to meet portion size recommendations than secondary schools. CONCLUSIONS: Of the items that were directly comparable over time, a limited number showed a significant change in portion size since the standards for school food were introduced. Portion weight recommendations are based on a balanced healthy diet, and pupils should eat all the components of meals offered by schools to meet dietary recommendations.

"It's always hard being a mom, but the pandemic has made everything harder": A qualitative exploration of the experiences of perinatal women during the COVID-19 pandemic.

BACKGROUND: Understanding the psychosocial impacts of the COVID-19 pandemic in vulnerable groups, such as pregnant and parenting women, is a critical research and clinical imperative. Although many survey-based perinatal health studies have contributed important information about mental health, few have given full voice about the experiences of pregnant and postpartum women during the prolonged worldwide pandemic using a qualitative approach. OBJECTIVE: The purpose of this study is to explore the lived experience of pregnant and postpartum women in the United States during the ongoing COVID-19 pandemic. DESIGN: Qualitative phenomenological study. SETTING: This study was conducted in the community, by recruiting women throughout the U.S. PARTICIPANTS: Fifty-four pregnant and postpartum women participated in qualitative interviews. METHODS: Data from one-on-one semi-structured interviews were analyzed using a team-based phenomenological qualitative approach. RESULTS: Two key themes were apparent: the pandemic has shined a light on the many typical struggles of motherhood; and, there is a lack of consistent, community-based or healthcare system resources available to address the complex needs of pregnant and postpartum women, both in general and during the pandemic. CONCLUSIONS: Going forward, as the world continues to deal with the current pandemic and possible future global health crises, health care systems and providers are encouraged to consider the suggestions provided by these participants: talk early and often to women about mental health; help pregnant and postpartum women create and institute a personal plan for early support of their mental health needs and create an easily accessible mental health network; conceptualize practice methods that enhance coping and resilience; practice in community-based and interdisciplinary teams (e.g., midwives, doulas, perinatal social workers/ psychotherapists) to ensure continuity of care and to foster relationships between providers and pregnant/ postpartum women; and consider learning from other countries' successful perinatal healthcare practices. REGISTRATION: Number (& date of first recruitment): not applicable. TWEETABLE ABSTRACT: Pregnant and postpartum women insist that mental health care must be overhauled, stating the pandemic has highlighted inherent cracks in the system.

The contribution of school meals and packed lunch to food consumption and nutrient intakes in UK primary school children from a low income population.

BACKGROUND: The Low Income Diet and Nutrition Survey described the food consumption and nutrient intake of UK children in low income households in 2003-2005. METHODS: To describe food consumption and nutrient intake associated with school meals and packed lunches, based on a cross-sectional analysis of 680, 24-h dietary recalls from 311 school children aged 4-11 years. RESULTS: In children from low income households, pupils who took a packed lunch consumed more white bread, fats and oils, crisps and confectionery and fewer potatoes (cooked with or without fat) at lunchtime compared to other pupils. Many of these differences persisted when diet was assessed over the day. For younger pupils (4-7 years), packed lunches provided the least amount of folate, the highest amount of sodium, and the highest average percentage of food energy from fat and saturated fatty acids (SFA) compared to free school meals (FSMs). Over the whole day, in both younger (4-7 years) and older (8-11 years) children, there were no notable differences in energy or nutrient intake between those eating a packed lunch or a school meal. Older children's packed lunches contributed a significantly higher proportion of fat, SFA, calcium and sodium to the day's nutrient intake compared to a FSM. CONCLUSIONS: In children from low income households, packed lunches are less likely to contribute towards a 'healthier' diet compared to a school meal. The difference was more apparent in younger children. Key differences were the high consumption of sodium, SFA and non-milk extrinsic sugars by pupils who had packed lunches.

Inhaled vs subcutaneous effects of a dual IL-4/IL-13 antagonist in a monkey model of asthma.

BACKGROUND: Pitrakinra is a recombinant protein derived from human interleukin-4 (IL-4) that binds to IL-4Ralpha and acts as a competitive antagonist of IL-4 and IL-13. The studies reported here compare the dose-ranging effects of pitrakinra on allergen-induced airway hyperresponsiveness (AHR) and airway eosinophilia when administered subcutaneously (s.c.) or by inhalation to the Ascaris suum-sensitive cynomolgus monkey for the purpose of elucidating the primary site of pitrakinra's anti-asthmatic action. METHODS: Airway responsiveness to inhaled methacholine and bronchoalveolar lavage cell composition was determined before and after three allergen exposures with a 1-week course of twice-daily (b.i.d.) s.c. or inhaled pitrakinra or placebo treatment. RESULTS: Treatment with s.c. pitrakinra significantly reduced allergen-induced AHR, with a maximum effect of a 2.8- to 3.8-fold increase in methacholine PC(100) relative to control (P < 0.05) observed at b.i.d. s.c. doses of 0.05-0.5 mg/kg. Inhaled pitrakinra also significantly reduced AHR with a similar maximum effect of a 2.8- to 3.2-fold increase in methacholine PC(100) relative to control (P < 0.05) at nominal b.i.d. doses of 3-100 mg. The maximal effect on AHR following inhalation was observed at a plasma concentration which exhibited no efficacy via the subcutaneous route. The effect of pitrakinra on lung eosinophilia was not statistically significant following either route of administration, although lung eosinophil count was reduced in all studies relative to control. CONCLUSION: Local administration of pitrakinra to the lung is sufficient to inhibit AHR, one of the cardinal features of asthma, indicating the therapeutic potential of inhaled pitrakinra in the treatment of atopic asthma.

Cardiovascular risk modification in participants with coronary disease screened by the Kidney Early Evaluation Program.

BACKGROUND: Coronary artery disease (CAD) identifies the need for intensive treatment of risk factors among individuals with chronic kidney disease (CKD), a high-risk, complex cardiovascular risk state. METHODS: An estimated glomerular filtration rate<60 mL/min/1.73 m2 or a urine albumin:creatinine ratio (ACR)≥30 mg/g (3.4 mg/mmol) defined CKD. RESULTS: Of 70,454 volunteers screened the mean age was 53.5±15.7 years and 68.3% were female. A total of 5410 (7.7%) had a self-reported history of CAD; 1295 (1.8%) had a history of prior percutaneous coronary intervention (PCI); and 1124 (1.6%) had a prior history of coronary artery bypass surgery (CABG). Multivariate analysis for the outcome of suboptimal CAD risk management (composite of systolic blood pressure≥130 mmHg, glucose≥125 mg/dL (6.9 mmol/L) for diabetics, total cholesterol≥200 mg/dL (5.2 mmol/L), or current smoking; n=38,746/53,403, 72.5%) revealed older age (per year) (odds ratio (OR)=1.04, 95% confidence interval (CI) 1.03-1.04, P<0.0001), male gender (OR=1.40, 95% CI 1.34-1.47, P<0.0001), ACR≥30 mg/g (3.4 mg/mmol) (OR=1.66, 95% CI 1.55-1.79, P<0.0001), body mass index (per kg/m2) (OR=1.06, 95% CI 1.06-1.06, P<0.0001), CAD without a history of revascularization (OR=1.14, 95% CI 1.02-1.28, P=0.02) and care received by a nephrologist (OR=1.49, 95% CI 1.22-1.83, P<0.0001) were associated with worse risk factor control. Prior coronary revascularization and being under the care of a cardiologist were not associated with either improved or suboptimal risk factor control. CONCLUSIONS: Chronic kidney disease is associated with overall poor rates of CAD risk factor control.

Bioring® gastric banding for obesity in a private South African hospital.

BACKGROUND: Obesity is a significant health problem in South Africa. Surgery is the most effective means of durable weight loss for the morbidly obese. Of the surgical options, laparoscopic adjustable gastric banding is the most controversial. We aimed to assess a single surgeon's experience with a specific band. METHODS: A retrospective observational study of a continuous cohort of laparoscopic adjustable gastric Cousin Bioring® band placements from a single private South African hospital was conducted. Three hundred and fifty bands were placed in 347 patients, 75% were female. Variables analysed were BMI obesity class, comorbidities, weight loss, diabetes resolution, adherence to aftercare, patient satisfaction, complications and death. RESULTS: Outcomes were assessed in 343 patients (4 patients lost to follow-up). The mean follow-up was 39 months (IQR 29-66 months). The mean preoperative BMI was 43.3 kg/m2 (IQR 37.4-47.6 kg/m2). Most weight loss occurred in the first year, and 66% achieved > 40% excess weight loss. Resolution of type 2 diabetes and prediabetes occurred in 56.4% and 89.8% of patients respectively. Increasing age (p = 0.002), class 3 obesity (p < 0.001) and suboptimal aftercare (p < 0.001) were associated with failure. One patient developed band erosion and 40 developed band slippage, 34 of whom underwent secondary surgery (32 removals, 2 revisions). All complications were grade I-III. There was no high grade complication, and no death. CONCLUSIONS: Bioring® gastric banding achieved moderately good weight loss and resolution of type 2 diabetes with a low complication rate. BMI > 60 and suboptimal aftercare predicted poor outcome.

Allergen dose dependency of the early- and late-phase cutaneous response in the cynomolgus monkey.

BACKGROUND: Cutaneous administration of allergen provides a means to confirm an allergic status, investigate the pathogenesis of allergic diseases, and/or provide a mechanism to evaluate the benefit of new potential therapeutics. OBJECTIVE: Studies were performed to characterize the allergen-induced cutaneous early- and late-phase response (EPR and LPR) in the cynomolgus monkey. METHODS: Following intradermal injections of Ascaris suum allergen, the cutaneous weal and flare EPR was measured 15 min post-injection, and skin biopsies were collected at 8-24 h to determine the optimal time of LPR occurrence. Biopsies were analysed for epidermal and dermal inflammatory changes. RESULTS: The EPR was dose related with a reproducible, measurable response at 1 : 10 000 and maximal at a 1 : 100 allergen dilution. In contrast, the threshold dose required for a reproducible LPR was much greater requiring a dilution of 6 : 100, suggesting independent mechanisms for the EPR and LPR. The LPR 20 h post-allergen injection induced an inflammatory response in the upper and deep dermis. The response was characterized by a moderate perivascular to diffuse inflammation consisting of mononuclear cells, neutrophils and eosinophils. Dexamethasone, while having no effect on the EPR, reduced dermal inflammation (upper dermis, P=0.004; deep dermis, P=0.03). Similarly, dermal eosinophilia was also reduced (upper dermis, P<0.001; deep dermis, P=0.02). CONCLUSION: Collectively, the results indicate the dose dependency of the EPR and LPR. Furthermore, our observations indicate the value of the LPR response in the cynomolgus monkey to evaluate new therapeutics for the treatment of allergic diseases such as atopic dermatitis.

O-GlcNAcylation, an original modulator of contractile activity in striated muscle.

There is growing evidence that O-linked N-acetyl-D-glucosaminylation, more simply termed O-GlcNAcylation or O-GlcNAc, is a post-translational modification involved in many cellular processes from transcription to modulation of protein properties. O-GlcNAc is a dynamic and reversible glycosylation and therefore quite similar to the phosphorylation/dephosphorylation process, with which O-GlcNAc can interplay. Since O-GlcNAc serves as a glucose sensor by the way of hexosamine biosynthesis pathway, this glycosylation is often associated with glucose toxicity and development of insulin resistance. In this way, O-GlcNAc could be involved in muscle pathological consequences of diabetes. Nevertheless, in regards of several studies performed in healthy striated muscles, O-GlcNAc seems to exert protective effects against different types of injuries. Recent new insights suggest a key implication of O-GlcNAc in skeletal and cardiac muscles contractile activity, in particular by O-GlcNAc modification of motor as well as regulating contractile proteins. While evidence linked O-GlcNAc to the regulation of calcium activation properties, its exact role remains to be defined as well as the existence of potential interference with phosphorylation. The better understanding of the exact function of OGlcNAc in this physiological process could contribute to the determination of newly markers of skeletal dysfunctions.

Microorganism mediated reproductive isolation in flour beetles (genus Tribolium).

Reproductive isolation is induced by microorganisms in diverse geographic strains of the flour beetle Tribolium confusum (Coleoptera:Tenebrionidae). The incompatibility between populations is due to nongenetic cytoplasmically inherited factors. Males of infected strains produce no progeny when crossed with females of noninfected strains; however, they produce "normal" numbers of progeny when crossed with infected females. Males from noninfected strains show no reproductive isolation. Infected strains of T. confusum can be cured when tetracycline or other antibiotics are added to the flour medium. "Cured" strains become partially reproductively isolated from all noncured strains including the source strain

Low birth weight is associated with chronic kidney disease only in men.

The association of low birth weight and chronic kidney disease was examined in a screened volunteer population by the National Kidney Foundation's Kidney Early Evaluation Program. This is a free, community-based health program enrolling individuals aged 18 years or older with diabetes, hypertension, or a family history of kidney disease, diabetes, or hypertension. Self-reported birth weight was categorized and chronic kidney disease defined as an estimated glomerular filtration rate less than 60 ml per min per 1.73 m(2) or a urine albumin/creatinine ratio >or=30 mg/g. Among 12 364 participants, 15% reported a birth weight less than 2500 g. In men, significant corresponding odds ratios were found after adjustment for demographic characteristics and health conditions to this low birth weight and chronic kidney disease, but there was no association among women. There was no significant interaction between birth weight and race for either gender. Efforts to clinically understand the etiology of this association and potential means of prevention are essential to improving public health.