Is the Differentiated Service Delivery Model Suited to the Needs of People Living with HIV in Rwanda?

The primary goal of antiretroviral treatment is to improve the health of individuals with HIV, and a secondary goal is to prevent further transmission. In 2016, Rwanda adopted the World Health Organization's "treat-all" approach in combination with the differentiated service delivery (DSD) model. The model's goal was to shorten the time from HIV diagnosis to treatment initiation, regardless of the CD4 T-cell count. This study sought to identify perceptions, enablers, and challenges associated with DSD model adoption among PLHIV.This study included selected health centers in Kigali city, Rwanda, between August and September 2022. The patients included were those exposed to the new HIV care model (DSD) model and those exposed to the previous model who transitioned to the current model. Interviews and focus group discussions were also held to obtain views and opinions on the DSD model. The data were collected via questionnaires and audio-recorded focus group discussions and were subsequently analyzed.The study identified several themes, including participants' initial emotions about a new HIV diagnosis, disclosure, experiences with transitioning to the DSD model, the effect of peer education, and barriers to and facilitators of the DSD model. Participants appreciated reduced clinic visits under the DSD model but faced transition and peer educator mobility challenges.The DSD model reduces waiting times, educates patients, and aligns with national goals. Identified barriers call for training and improved peer educator retention. Recommendations include enhancing the DSD model and future research to evaluate its long-term impact and cost-effectiveness.

Effects of Multi-Month Dispensing on Clinical Outcomes: Retrospective Cohort Analysis Conducted in Kenya.

Multi-month dispensing (MMD) has been widely adopted by national HIV programs as a key strategy for improving the quality of HIV care and treatment services while meeting the unique needs of diverse client populations. We assessed the clinical outcomes of clients receiving MMD in Kenya by conducting a retrospective cohort study using routine programmatic data in 32 government health facilities in Kenya. We included clients who were eligible for multi-month antiretroviral therapy (ART) dispensing for ≥ 3 months (≥ 3MMD) according to national guidelines. The primary exposure was enrollment into ≥ 3MMD. The outcomes were lost to follow-up (LTFU) and viral rebound. Multilevel modified-Poisson regression models with robust standard errors were used to compare clinical outcomes between clients enrolled in ≥ 3MMD and those receiving ART dispensing for less than 3 months (< 3MMD). A total of 3,501 clients eligible for ≥ 3MMD were included in the analysis, of whom 65% were enrolled in ≥ 3MMD at entry into the cohort. There was no difference in LTFU of ≥ 180 days between the two types of care (aRR 1.1, 95% CI 0.7-1.6), while ≥ 3MMD was protective for viral rebound (aRR 0.1 95% CI 0.0-0.2). As more diverse client-focused service delivery models are being implemented, robust evaluations are essential to guide the implementation, monitor progress, and assess acceptability and effectiveness to deliver optimal people-centered care.

Methods for quantifying breast cancer-related lymphedema in patients undergoing a contralateral prophylactic mastectomy.

Patients treated for breast cancer are at risk of developing breast cancer-related lymphedema (BCRL). A significant proportion of patients treated for breast cancer are opting to undergo a contralateral prophylactic mastectomy (CPM). Currently, it remains unclear as to whether the relative volume change (RVC) equation may be used as an alternative to the weight adjusted change (WAC) equation to quantify BCRL in patients who undergo CPM. In order to simplify BCRL screening, our cohort of patients who underwent a CPM (n=310) was matched by BMI to a subset of patients who underwent unilateral breast surgery (n=310). Arm volume measurements were obtained via an optoelectronic perometer preoperatively, postoperatively, and in the follow-up setting every 6-12 months. The correlation of ipsilateral RVC and WAC values for those who underwent bilateral surgery was calculated (r=0.60). Contralateral WAC values for patients in both cohorts were compared, and there was no significant difference between the two distributions in variance (p=0.446). The RVC equation shows potential to be used to quantify ipsilateral postoperative arm volume changes for patients who undergo a CPM. However, a larger trial in which RVC and WAC values are prospectively assessed is needed.

SARS-CoV-2 seroprevalence among Vancouver public school staff in British Columbia, Canada

ImportanceContact-tracing studies suggest minimal secondary transmission in schools. However, there are limited school data accounting for asymptomatic cases, particularly late in the 2020/21 school year, and in the context of uninterrupted in-person schooling and widespread community transmission. ObjectivesTo determine the SARS-CoV-2 seroprevalence in a sample of school staff, compared to the community, and to COVID-19 rates among all students and staff within the same school population. DesignIncident COVID-19 cases among students and school staff using public health data, with an embedded cross-sectional serosurvey among school staff sampled from February 10 to May 15, 2021, comparing to age, sex and geographic location-matched blood donors sampled in January 2021. SettingVancouver School District (British Columbia, Canada) from kindergarten to grade 12. ParticipantsActive school staff enrolled from February 3 to April 23, 2021. Main outcome measuresSARS-CoV-2 antibodies in a sample of school staff using spike (S)-based testing (unvaccinated staff) or N-based serology testing (vaccinated staff). ResultsThe incidence of COVID-19 cases among students attending in-person was 9.8 per 1,000 students during the 2020/21 school year (N = 47,280 students), and among staff was 13 per 1,000 since the beginning of the pandemic (N = 7,071 active school staff). In total, 1,689 school staff (64% elementary, 28% secondary, 8.3% school board staff or multiple grades) completed the questionnaire, 78.2% had classroom responsibilities, and spent a median of 17.6 hours in class per week [IQR: 5.0 - 25 hours]. Although 21.5% (363/1,686) reported close contact with a COVID-19 case, only 1.4% (24/1688) of the school staff reported having had a positive viral nucleic acid test. Of this group, five believed they acquired the infection at school. The adjusted seroprevalence in staff who gave blood (1,556/1,689, 92.1%) was 2.3% [95%CI: 1.6 - 3.2%] compared to 2.3% [95%CI: 1.7 - 3.0%] in blood donors. Conclusion and relevanceDespite high reported COVID-19 cases among students and staff, and frequent within-school exposures, we found no detectable increase in seroprevalence among school staff above the community seroprevalence. These findings corroborate claims that, with appropriate mitigation strategies, in-person schooling is not associated with significantly increased risk for school staff. Key PointsO_ST_ABSQuestionC_ST_ABSWhat was the prevalence of COVID-19 infections in school staff who maintained in-person schooling during the 2020/21 school year in Vancouver, British Columbia, and how does it compare to the risk of COVID-19 infection in the community. FindingsAs of March 4, 2021, the incidence of COVID-19 cases among school staff was 13 per 1,000 (N = 7,071 school staff) since the beginning of the pandemic. In a cross-sectional seroprevalence analysis from February 10 to May 15, 2021, the adjusted seroprevalence among a sample of school staff (N = 1,556) was 2.3% [95%CI: 1.6 - 3.2%], compared to 2.3% [95%CI: 1.7 - 3.0%] in 1:2 age, sex and geographical location (by postal code)-matched reference group of blood donors. MeaningWe found no detectable increase in seroprevalence among school staff above the community seroprevalence. These findings corroborate claims that, with appropriate mitigation strategies in place, in-person schooling is not associated with significantly higher risk for school staff.

A simple model for the total number of SARS-CoV-2 infections on a national level.

This study aimed to identify an appropriate simple mathematical model to fit the number of coronavirus disease 2019 (COVID-19) cases at the national level for the early portion of the pandemic, before significant public health interventions could be enacted. The total number of cases for the COVID-19 epidemic over time in 28 countries was analysed and fit to several simple rate models. The resulting model parameters were used to extrapolate projections for more recent data. While the Gompertz growth model (mean R2 = 0.998) best fit the current data, uncertainties in the eventual case limit introduced significant model errors. However, the quadratic rate model (mean R2 = 0.992) fit the current data best for 25 (89%) countries as determined by R2 values of the remaining models. Projection to the future using the simple quadratic model accurately forecast the number of future total number of cases 50% of the time up to 10 days in advance. Extrapolation to the future with the simple exponential model significantly overpredicted the total number of future cases. These results demonstrate that accurate future predictions of the case load in a given country can be made using this very simple model.

Multicenter Evaluation of the Clinical Performance and the Neutralizing Antibody Activity Prediction Properties of 10 High-Throughput Serological Assays Used in Clinical Laboratories.

As the coronavirus disease 2019 (COVID-19) pandemic second wave is emerging, it is of the upmost importance to screen the population immunity in order to keep track of infected individuals. Consequently, immunoassays for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with high specificity and positive predictive values are needed to obtain an accurate epidemiological picture. As more data accumulate about the immune responses and the kinetics of neutralizing-antibody (nAb) production in SARS-CoV-2-infected individuals, new applications are forecast for serological assays such as nAb activity prediction in convalescent-phase plasma from recovered patients. This multicenter study, involving six hospital centers, determined the baseline clinical performances, reproducibility, and nAb level correlations of 10 commercially available immunoassays. In addition, three lateral-flow chromatography assays were evaluated, as these devices can be used in logistically challenged areas. All assays were evaluated using the same patient panels in duplicate, thus enabling accurate comparison of the tests. Seven immunoassays examined in this study were shown to have excellent specificity (98 to 100%) and good to excellent positive predictive values (82 to 100%) when used in a low (5%)-seroprevalence setting. We observed sensitivities as low as 74% and as high as 95% at ≥15 days after symptom onset. The determination of optimized cutoff values through receiver operating characteristic (ROC) curve analyses had a significant impact on the diagnostic resolution of several enzyme immunoassays by increasing the sensitivity significantly without a large trade-off in specificity. We found that spike-based immunoassays seem to be better correlates of nAb activity. Finally, the results reported here will add to the general knowledge of the interlaboratory reproducibility of clinical performance parameters of immunoassays and provide new evidence about nAb activity prediction.

Relationship between enteric pathogens and acute gastroenteritis disease severity: a prospective cohort study.

OBJECTIVES: To evaluate the relationship between individual bacterial and viral pathogens and disease severity. METHODS: Children <18 years with three or more episodes of vomiting and/or diarrhoea were enrolled in two Canadian paediatric emergency departments between December 2014 and August 2016. Specimens were analysed employing molecular panels, and outcome data were collected 14 days after enrolment. The primary outcome was severe disease over the entire illness (symptom onset until 14-day follow-up), quantified employing the Modified Vesikari Scale (MVS) score. The score was additionally analysed in two other time periods: index (symptom onset until enrolment) and follow-up (enrolment until 14-day follow-up). RESULTS: Median participant age was 20.7 (IQR: 11.3, 44.2) months; 47.4% (518/1093) and 73.4% (802/1093) of participants had index and total MVS scores ≥11, respectively. The most commonly identified pathogens were rotavirus (289/1093; 26.4%) and norovirus (258/1093; 23.6%). In multivariable analysis, severe disease over the entire illness was associated with rotavirus (OR = 9.60; 95%CI: 5.69, 16.19), Salmonella (OR = 6.61; 95%CI: 1.50, 29.17), adenovirus (OR = 2.53; 95%CI: 1.62, 3.97), and norovirus (OR = 1.43; 95%CI: 1.01, 2.01). Pathogens associated with severe disease at the index visit were: rotavirus only (OR = 6.13; 95%CI: 4.29, 8.75), Salmonella (OR = 4.59; 95%CI: 1.71, 12.29), adenovirus only (OR = 2.06; 95%CI: 1.41, 3.00), rotavirus plus adenovirus (OR = 3.15; 95%CI: 1.35, 7.37), and norovirus (OR = 0.68; 95%CI: 0.49, 0.94). During the follow-up period, rotavirus (OR = 2.21; 95%CI: 1.50, 3.25) and adenovirus (OR = 2.10; 95%CI: 1.39, 3.18) were associated with severe disease. CONCLUSIONS: In children presenting for emergency department care with acute gastroenteritis, pathogens identified were predominantly viruses, and several of which were associated with severe disease. Salmonella was the sole bacterium independently associated with severe disease.

Evidence that oxidative stress is higher in replacement gilts than in multiparous sows.

The recent success obtained in term of increasing the litter size of sows has not correlated with a reduction of replacement rate. There is thus an increased economic demand for gilts with optimal reproductive potential and longevity. Unfortunately, replacement gilts are known to be more susceptible to diseases and less productive than multiparous sows. Interestingly, reproductive performance, resistance to diseases and longevity could all be largely affected by oxidative stress. To investigate whether oxidative stress conditions could account for the poor longevity of gilts, three distinct groups of conventional Yorkshire × Landrace sows were formed based on their similar age and parity (gilts, second parity sows as well as fourth to fifth parity sows). All animals were slaughtered during the post-ovulatory period, and blood as well as tissue samples were collected. Biomarkers of oxidative damage to proteins (carbonyls) and DNA (8-OHdG) were analysed in samples. Specific mRNA expression of major antioxidants such as glutathione peroxidases 1, 3 and 4 (GPx1, GPx3, GPx4) as well as superoxide dismutases 1 and 2 (Sod1, Sod2) were monitored in liver and kidney samples by quantitative RT-PCR. Specific enzymatic activities of both GPx and SOD were measured by spectrophotometric assays. The plasma concentration of protein carbonyls was significantly different between the three groups with the highest concentration being observed in gilts (p ≤ 0.001). The mRNA expression levels of GPx1 and GPx4 were also significantly increased in the liver of gilts when compared to multiparous sows (p ≤ 0.05). SOD2 enzymatic activity was found to be higher in the liver of gilts than multiparous sows (p ≤ 0.05). Taken together, these results indicate that replacement gilts sustain significantly higher oxidative conditions than multiparous sows. Current findings may contribute to the design of nutritional regimens that will increase the productivity of gilts by counteracting oxidative stress.

The complex relationships between microglia, alpha-synuclein, and LRRK2 in Parkinson's disease.

The proteins alpha-synuclein (αSyn) and leucine rich repeat kinase 2 (LRRK2) are both key players in the pathogenesis of the neurodegenerative disorder Parkinson's disease (PD), but establishing a functional link between the two proteins has proven elusive. Research studies for these two proteins have traditionally and justifiably focused in neuronal cells, but recent studies indicate that each protein could play a greater pathological role elsewhere. αSyn is expressed at high levels within neurons, but they also secrete the protein into the extracellular milieu, where it can have broad ranging effects in the nervous system and relevance to disease etiology. Similarly, low neuronal LRRK2 expression and activity suggests that LRRK2-related functions could be more relevant in cells with higher expression, such as brain-resident microglia. Microglia are monocytic immune cells that protect neurons from noxious stimuli, including pathological αSyn species, and microglial activation is believed to contribute to neuroinflammation and neuronal death in PD. Interestingly, both αSyn and LRRK2 can be linked to microglial function. Secreted αSyn can directly activate microglia, and can be taken up by microglia for clearance, while LRRK2 has been implicated in the intrinsic regulation of microglial activation and of lysosomal degradation processes. Based on these observations, the present review will focus on how PD-associated mutations in LRRK2 could potentially alter microglial biology with respect to neuronally secreted αSyn, resulting in cell dysfunction and neurodegeneration.

Active and safe transportation of elementary-school students: comparative analysis of the risks of injury associated with children travelling by car, walking and cycling between home and school.

INTRODUCTION: Elementary school active transportation programs aim to address physical inactivity in children by prompting a modal shift from travel by car to walking or cycling among children living a distance from school conducive to walking or cycling. The objectives of this study are to evaluate the risk of injury related to walking, cycling and travelling by car between home and school among elementary-school students in the Montréal area and to evaluate the impact on number of injuries of a modal shift from travel by car to walking or cycling. METHODS: The risk of injury was estimated for the 2003-2007 period by calculating the average annual rate of injury in children aged 5 to 12 years walking, cycling or being driven in a car, per 100 million kms travelled during the normal hours of travel between home and school. The impact of a modal shift from travel by car was evaluated for children living a distance from school conducive to walking and cycling (under 1.6 km), that is, the targets of active transportation programs. This evaluation was done using the regional rate of injury calculated for each travel mode. RESULTS: Between 2003 and 2007, an average of 168 children aged 5 to 12 years were injured each year while walking (n = 64), cycling (n = 28) and being driven in a car (n = 76) during the normal hours of travel between home and school in the Montréal area. The rate of injury was 69 children injured per 100 million kms for travel by car (reference group), 314 pedestrians (relative risk [RR] = 4.6; 95% confidence interval [CI]: 4.3-5.1) and 1519 cyclists (RR = 22.2; 95% CI: 14.3-30.0). A shift of 20% in the distance travelled by car to walking by children living less than 1.6 km from their school is estimated to result in an increase of 2.2% (n = 3.7) in the number of children injured each year in the area. In the case of a shift to cycling, the number of resulting injuries is estimated to be 24.4, an increase of 14.5%. CONCLUSION: The risk of injury among elementary-school students during the normal hours of travel between home and school is higher for walking and cycling than for travel by car, and cyclists are at greater risk of injury than pedestrians. A modal shift from travel by car would increase the number of children injured in the area (minor injuries, for the most part) if no action were taken to reduce the risk of injury to pedestrians and cyclists.

TITRE: Transport actif et sécuritaire des élèves du primaire : analyse comparée des risques de blessures associés aux déplacements des enfants en automobile, à pied et à vélo entre la maison et l'école. INTRODUCTION: Les programmes de promotion du transport actif au primaire visent à contrer la sédentarité chez les jeunes en provoquant un transfert modal des déplacements en automobile vers les déplacements à pied ou à vélo auprès des enfants demeurant à une distance de l'école propice à la marche ou au vélo. Cette étude a pour objectif d'évaluer le risque de blessures lié aux déplacements à pied, à vélo et en automobile entre la maison et l'école pour les élèves du primaire de la région de Montréal, ainsi que d'évaluer l'impact d'un transfert modal des déplacements en automobile vers les déplacements à pied ou à vélo sur le nombre d'enfants blessés dans cette région. MÉTHODOLOGIE: Le risque de blessures a été estimé pour la période 2003 à 2007 en calculant le taux annuel moyen de blessés chez les 5 à 12 ans en tant que piétons, cyclistes ou occupants d'une automobile, par 100 millions de kilomètres parcourus lors des heures habituelles de déplacements entre la maison et l'école, durant la période scolaire. L'impact d'un transfert modal des déplacements en automobile a été évalué auprès des enfants demeurant à une distance de l'école propice à lamarche et au vélo (moins de 1,6 km), soit la clientèle visée par les programmes de promotion du transport actif au primaire. Cette évaluation a été faite en utilisant le taux régional de blessures calculé pour chaque mode de déplacement. RÉSULTATS: Entre 2003 et 2007, enmoyenne, 168 enfants de 5 à 12 ansont été blessés, chaque année, comme piétons (64), cyclistes (28) et occupants d'une automobile (76), dans la région de Montréal, lors des heures habituelles de déplacement entre la maison et l'école. Le taux de blessures a été de 69 blessés par 100 millions de kilomètres pour les déplacements en automobile (groupe de référence), 314 blessés pour les piétons (risque relatif : 4,6; IC à 95%: 4,3 à 5,1) et 1 519 blessés pour les cyclistes (risque relatif : 22,2; IC à 95 % : 14,3 à 30,0). Un transfert de 20 % du kilométrage parcouru en automobile par les enfants demeurant à moins de 1,6 km de l'école aurait occasionné, dans le cas d'un transfert vers la marche, 3,7 blessés de plus par année, soit une augmentation de 2,2 % du nombre annuel moyen d'enfants blessés lors des heures habituelles de déplacement entre la maison et l'école dans la région de Montréal et, dans le cas d'un transfert vers le vélo, de 24,4 blessés, soit une augmentation de 14,5 %. CONCLUSION: Le risque de blessures chez les élèves du primaire lors des heures habituelles de déplacement entre la maison et l'école est plus élevé pour les déplacements à pied et à vélo que pour les déplacements en automobile, et les enfants se déplaçant à vélo courent plus de risques de se blesser que ceux se déplaçant à pied. Un transfert modal des déplacements en automobile augmenterait le nombre d'enfants blessés à l'échelle de la région (blessures légères pour la plupart), si aucune mesure n'était prise pour réduire le risque de blessures chez les piétons et les cyclistes.

Inhibition of apoptotic Bax translocation to the mitochondria is a central function of parkin.

Parkinson's disease (PD) is the second most prevalent neurodegenerative disorder, affecting 1-3% of the population over 65. Mutations in the ubiquitin E3 ligase parkin are the most common cause of autosomal recessive PD. The parkin protein possesses potent cell-protective properties and has been mechanistically linked to both the regulation of apoptosis and the turnover of damaged mitochondria. Here, we explored these two functions of parkin and the relative scale of these processes in various cell types. While biochemical analyses and subcellular fractionation were sufficient to observe robust parkin-dependent mitophagy in immortalized cells, higher resolution techniques appear to be required for primary culture systems. These approaches, however, did affirm a critical role for parkin in the regulation of apoptosis in primary cultured neurons and all other cells studied. Our prior work demonstrated that parkin-dependent ubiquitination of endogenous Bax inhibits its mitochondrial translocation and can account for the anti-apoptotic effects of parkin. Having found a central role for parkin in the regulation of apoptosis, we further investigated the parkin-Bax interaction. We observed that the BH3 domain of Bax is critical for its recognition by parkin, and identified two lysines that are crucial for parkin-dependent regulation of Bax translocation. Last, a disease-linked mutation in parkin failed to influence Bax translocation to mitochondria after apoptotic stress. Taken together, our data suggest that regulation of apoptosis by the inhibition of Bax translocation is a prevalent physiological function of parkin regardless of the kind of cell stress, preventing overt cell death and supporting cell viability during mitochondrial injury and repair.

Evaluation of two new surrogate indices including parameters not using insulin to assess insulin sensitivity/resistance in non-diabetic postmenopausal women: a MONET group study.

AIM: The study evaluated and compared, with other surrogate indices of insulin sensitivity/resistance (IS/R), the relevance of the TyG index, a product of fasting glucose and triglyceride (TG) levels, and the EGIR index, which includes TG, high-density lipoprotein cholesterol (HDL-c) and waist circumference in its formula to estimate IS/R, in non-diabetic postmenopausal women. METHODS: A secondary analysis was performed using the baseline data for 163 non-diabetic postmenopausal women from the Montreal-Ottawa New Emerging Team (MONET) population database. The subjects participated in hyperinsulinaemic-euglycaemic (HIEG) clamp and oral glucose tolerance (OGTT) tests. Correlations and comparisons between surrogate indices were performed in addition to inter-rater agreement tests. The optimal value of surrogate indices for diagnosis of IS/R was established on a receiver operating characteristic (ROC) scatter plot. RESULTS: A significant correlation was found between the HIEG clamp and all IS/R surrogate indices tested [r=-0.370 (TyG index) to 0.608 (SIisOGTT index); P<0.001]. On ROC curve analysis, a higher AUROC was found for SIisOGTT (0.791) than for TyG and EGIR (0.706 and 0.675, respectively; P=0.07 and P<0.05, respectively). CONCLUSION: The TyG and EGIR IS/R indices were only relatively modestly related to the HIEG clamp. In contrast, both fasting- and OGTT-derived IS/R surrogate indices, which include insulin values in their formulae, appeared to be more accurate in estimating IS/R in our study population. Thus, the TyG and EGIR IS/R indices need to be tested and validated more extensively in different populations before being put to large-scale clinical use.

The role of drinking water in the transmission of antimicrobial-resistant E. coli.

To determine whether drinking water contaminated with antimicrobial-resistant E. coli is associated with the carriage of resistant E. coli, selected households sending water samples to Ontario and Alberta laboratories in 2005-2006 were asked to participate in a cross-sectional study. Household members aged ≥12 years were asked to complete a questionnaire and to submit a rectal swab. In 878 individuals, 41% carried a resistant strain of E. coli and 28% carried a multidrug-resistant strain. The risk of carriage of resistant E. coli was 1·26 times higher for users of water contaminated with resistant E. coli. Other risk factors included international travel [prevalence ratio (PR) 1·33], having a child in nappies (PR 1·33), being male (PR 1·33), and frequent handling of raw red meats (PR 1·10). Protecting private water sources (e.g. by improving systems to test and treat them) may help slow the emergence of antimicrobial resistance in E. coli.

Characterizing the profile of obese patients who are metabolically healthy.

The presence of obesity-related metabolic disturbances varies widely among obese individuals. Accordingly, a unique subset of obese individuals has been described in the medical literature, which seems to be protected or more resistant to the development of metabolic abnormalities associated with obesity. These individuals, now known as 'metabolically healthy but obese' (MHO), despite having excessive body fatness, display a favorable metabolic profile characterized by high levels of insulin sensitivity, no hypertension as well as a favorable lipid, inflammation, hormonal, liver enzyme and immune profile. However, recent studies have indicated that this healthier metabolic profile may not translate into a lower risk for mortality. Mechanisms that could explain the favorable metabolic profile of MHO individuals are poorly understood. However, preliminary evidence suggests that differences in visceral fat accumulation, birth weight, adipose cell size and gene expression-encoding markers of adipose cell differentiation may favor the development of the MHO phenotype. Despite the uncertainty regarding the exact degree of protection related to the MHO status, identification of underlying factors and mechanisms associated with this phenotype will eventually be invaluable in helping us understand factors that predispose, delay or protect obese individuals from metabolic disturbances. Collectively, a greater understanding of the MHO individual has important implications for therapeutic decision making, the characterization of subjects in research protocols and medical education.

Assessing the impact of non-dilating the eye on full-field electroretinogram and standard flash response.

We investigated the possibility of performing electroretinography (ERG) in non-pharmacologically dilated eyes using brighter flash (time-integrated) luminance. Photopic (N = 26; background 25.5 cd·m(-2), white LED flashes) and scotopic ERG (N = 23, green LED flashes) luminance response functions were obtained simultaneously in a dilated (DE) and non-dilated eye (NDE). In the NDE, photopic V (max) b-wave amplitude was reduced by 14% (P < 0.0001), implicit time prolonged (P < 0.0001), and retinal sensitivity (log K) decreased by 0.38 log units (P < 0.0001) with no effect on a-wave. Using a xenon strobe light (N = 6) to increase flash luminance, V (max) remained lower by about 12% in the NDE (P = 0.02). V (max) with LED and xenon was achieved at 3.9 ± 1.0 cd·s·m(-2) and 3.3 ± 0.81 cd·s·m(-2) in the DE and 10.6 ± 1.2 cd·s·m(-2) and 12.3 ± 1.90 cd·s·m(-2) in the NDE, that is an increase of 0.43 and 0.57 log unit (P < 0.0001), respectively. Increasing background luminance by 0.50 log units (80 cd·m(-2), N = 4) resulted in implicit time normalization but not V (max) amplitude. Rod V (max) was decreased by 7% in NDE (P < 0.05) and sensitivity reduced by 0.40 log units (P < 0.0001), but our data suggest that the luminance may have not been sufficient to reach V (max) in all participants in the NDE and that the sensitivity change may have been due to an inadequate inter-stimulus interval. For the photopic ERG, increasing flash luminance is not sufficient to compensate for the smaller pupil size, whereas for the scotopic ERG, more data are needed to establish proper inter-stimulus interval to perform recordings in a non-pharmacologically dilated.

Association between physical activity energy expenditure and inflammatory markers in sedentary overweight and obese women.

OBJECTIVE: Chronic subclinical inflammation and regular physical activity have opposing relationships to obesity-related metabolic diseases. Yet, the association between chronic inflammation and physical activity has rarely been examined in obese subjects. We examined the association between physical activity energy expenditure (PAEE), total (TEE) and resting energy expenditure (REE) and cardiorespiratory fitness (VO(2)peak) with inflammatory markers in overweight/obese women. DESIGN: Cross-sectional study. METHODS: The study included 152 overweight/obese postmenopausal women who were sedentary and free of chronic/inflammatory diseases (mean age: 57.5 (95% confidence interval (CI) 56.7-58.3) years, body mass index (BMI): 32.5 (95% CI 31.8-33.2) kg m(-2)). The following parameters were measured: TEE (doubly labeled water), REE (indirect calorimetry), PAEE (as (TEE x 0.90)-REE), VO(2)peak (ergocycle) and serum high-sensitive C-reactive protein (hsCRP), haptoglobin, soluble tumor necrosis factor-α receptor 1 (sTNFR1), interleukin-6, orosomucoid and white blood cells. RESULTS: Sedentary women with the highest tertile of PAEE (1276 (1233-1319) kcal day(-1)) had lower concentrations of hsCRP and haptoglobin than those in the lowest tertile (587 (553-621) kcal day(-1)) after adjustment for fat mass (P<0.05). Soluble TNFR1 was positively correlated with VO(2)peak, TEE and REE (P<0.05), and hsCRP and orosomucoid were positively associated with REE (P<0.01), whereas haptoglobin was negatively associated with PAEE (P<0.05). In stepwise regression analyses that examined the concomitant associations of components of energy expenditure with inflammatory markers, PAEE remained the only predictor of hsCRP and haptoglobin (P<0.05), explaining 14 and 5%, respectively, of their variation,whereas REE was the only predictor of orosomucoid (r (2) = 0.05, P = 0.02) after adjustment for fat mass. Adding leptin to the regression models results in similar relationships between inflammatory markers and components of energy expenditure. CONCLUSION: PAEE is an independent predictor of hsCRP and haptoglobin in sedentary overweight/obese postmenopausal women free of chronic disease. Our data support the role of physical activity in reducing subclinical inflammation and risk of metabolic and cardiovascular diseases.

Glycaemic status influences the nature and severity of coronary artery disease.

AIMS/HYPOTHESIS: We sought to understand the relationships between glycaemic status and both severity and progression of coronary artery disease (CAD), the leading cause of death in diabetes. METHODS: Baseline fasting blood glucose (FBG) and HbA1c (%)were measured in 426 patients with known or suspected stable CAD, who underwent coronary artery intravascular ultrasound(IVUS) at baseline and after a mean follow-up period of 664 days (range 257 to 961). The patients were categorised as normoglycaemic (n=226, 53%), or as having impaired fasting glucose (n=118, 28%) or diabetes (n=82, 19%). RESULTS: The maximum percentage coronary atheroma area at baseline was greater in diabetic patients (73.33+/-8.86%) than in those with normoglycaemia (69.08+/-10.43%; p=0.001) and impaired fasting glucose (69.32+/-9.59%; p=0.0031). In averaged IVUS measurements of the 30-mm target segment(n=332 participants), change in percentage atheroma area during follow-up was also greater in the diabetes (1.86+/-3.90%) than in other groups (0.28+/-3.32% and 0.56+/-2.96%,p=0.0047 global). FBG correlated with maximum percentage atheroma area at baseline (r=0.17; p=0.0003). HbA1c also correlated with maximum percentage atheroma area at baseline (r=0.26; p=0.0001) and with change in maximum plaque area (r=0.16; p=0.016). A similar pattern of results occurred with plaque volume. The relationships between diabetes or HbA1c and both IVUS measurements of plaque burden and remodelling persisted after adjustment. CONCLUSIONS/INTERPRETATION: Fasting blood glucose, HbA1c and the presence of diabetes are associated with the severity and progression of coronary atherosclerosis. These observations support the hypothesis that better glycaemic control may favourably influence CAD in patients with abnormal glucose tolerance or diabetes.

Circadian variation in the electroretinogram and the presence of central melatonin.

The light/dark cycle is the most important circadian clock synchronizer for mammals and humans. Circadian rhythms of dopamine and melatonin production in the retina have been reported to follow the light and dark cycle, but their impact on rod and cone functioning is not clear. The purpose of this study was to assess diurnal variations (morning vs. evening) in retinal function as measured with the photopic and scotopic electroretinogram (ERG). We also tried to correlate our results with the presence or absence of melatonin secretion in the saliva. Photopic and scotopic luminance-response functions were obtained in 29 participants at 11:00 (when melatonin should not be present) and 23:00 (when melatonin should be present). From the luminance-response function, Vmax, log K and slope parameters were derived. In scotopic condition, a significant increase of 6% in Vmax amplitude was observed in evening compared to morning (P = 0.03) along with a prolonged b-wave implicit time of 8% (P = 0.01) and an increase in rod sensitivity in evening compared to morning (P = 0.02). As expected, these changes in rod function were accompanied by a higher concentration of melatonin in saliva samples in the evening (P = 0.01). In photopic condition, only a prolonged a-wave implicit time of 5% was observed in evening when compared to morning (P = 0.02). Our findings suggest that the rod system is favored during night time, when circulating melatonin is present. Although statistically significant changes were observed, the day vs. night difference observed in the present study appears to be too small to impact significantly upon clinical assessment of retinal function.