Impact of aerobic fitness status, menstrual cycle phase, and oral contraceptive use on exercise substrate oxidation and metabolic flexibility in females.

The influence of menstrual cycle phase and fitness status on metabolism during high-intensity interval exercise (HIIE) was assessed. Twenty-five females (24.4 (3.6) years) were categorized by normal menstrual cycle (n = 14) vs. oral contraceptive (OC) use (n = 11) and by aerobic fitness, high-fitness females (HFF; n = 13) vs. low-fitness females (LFF; n = 12). HIIE was four sets of four repetitions with a 3 min rest between intervals on a cycle ergometer at a power output halfway between the ventilatory threshold and V̇O2peak and performed during follicular (FOL: days 2-7 or inactive pills) and luteal phases (LUT: day ∼21 or 3rd week of active pills). Substrate oxidation was assessed via indirect calorimetry, blood lactate via finger stick, and recovery of skeletal muscle oxidative metabolism (mV̇O2) via continuous-wave near-infrared spectroscopy. HFF oxidized more fat (g·kg-1) during the full session (FOL: p = 0.050, LUT: p = 0.001), high intervals (FOL: p = 0.048, LUT: p = 0.001), low intervals (FOL: p = 0.032, LUT: p = 0.024), and LUT recovery (p = 0.033). Carbohydrate oxidation area under the curve was greater in HFF during FOL (FOL: p = 0.049, LUT: p = 0.124). Blood lactate was lower in LFF in FOL (p ≤ 0.05) but not in LUT. Metabolic flexibility (Δ fat oxidation g·kg-1·min-1) was greater in HFF than LFF during intervals 2-3 in FOL and 1-4 in LUT (p ≤ 0.05). Fitness status more positively influences exercise metabolic flexibility during HIIE than cycle phase or OC use.

Comparison of a Ramp Cycle Ergometer and a Staged Assault Fitness AssaultBike Protocol for the Assessment of VO2max.

We propose a new VO2max test using a progressive staged protocol on an Assault Fitness AssaultBike. Twelve healthy males performed a traditional ramp cycle ergometer test (TRAD) and a progressively staged AssaultBike protocol (AB) in a counterbalanced order. AB elicited higher immediate post-exercise lactate, absolute and relative VO2max, and maximum heart rate than TRAD (P = 0.006, P = 0.014, P = 0.007, and P = 0.001, respectively). The protocol outlined herein may provide a more accurate assessment of VO2max due to greater skeletal muscle mass recruitment that is more representative of the whole body.

A 4-Week Pecan-Enriched Diet Improves Postprandial Lipid Peroxidation in Aging Adults.

Pecans are rich in bioactive compounds known to reduce oxidative stress and provide glucoregulatory benefits. Few studies assessing the effect of a pecan-enriched diet on such health outcomes suggest potential improvements to cardiometabolic health; however, this has not been studied in an older adult population. Thus, we aimed to examine the effect of daily pecan consumption for 4-weeks on fasting and postmeal antioxidant status, oxidative stress, and markers of glycemia in healthy aging adults. In this randomized, parallel, controlled trial, 41 healthy adults (50-75 years) either consumed 68 g of pecans/day (pecan; n = 21) or avoided all nuts (control; n = 20). At pre- (V1) and postintervention visits (V2), blood samples were obtained at fasting, and 30, 60, and 120 min following a high saturated fat meal to assess changes in malondialdehyde, which is a measure of lipid peroxidation, total antioxidant capacity (TAC), glucose, and insulin. Across the intervention, there were no differences in fasting or postprandial TAC, glucose, or insulin for pecan versus control. There was a trend for a difference in fasting lipid peroxidation from V1 to V2 by treatment (P = .06) driven by a slight reduction for pecan versus control (Δpecan: -2.0 ± 1.1 vs. Δcontrol: +0.6 ± 0.8 µM). In addition, postprandial lipid peroxidation was suppressed at V2 for pecan, and this was different from control (pecan areas under the curve (AUC): 10.6 ± 1.3 µM/h to 9.1 ± 1.2 µM/h vs. control AUC: 8.9 ± 1.3 µM/h to 9.2 ± 1.1 µM/h; P = .03). These findings suggest that a 1 month, pecan-enriched diet is protective against postmeal oxidative stress. Longer interventions or a diabetic population may be needed to observe glucoregulatory benefits. Clinical Trial Registration: NCT04385537.

A pecan-enriched diet reduced postprandial appetite intensity and enhanced peptide YY secretion: A randomized control trial.

BACKGROUND & AIMS: Tree nuts have been shown to have satiating qualities; however, little is known concerning the effect of pecans on measures of appetite. The purpose of this study was to examine the impact of a pecan-enriched diet on subjective, physiological, and direct measures of appetite in older adults. METHODS: This was a randomized, controlled trial in which healthy older adults (50-75 y) were randomized to either consume 68 g of pecans/day (pecan; n = 21) or avoid all nuts (control; n = 23) for 4 weeks. At pre- (V1) and post-diet (V2) visits body weight (BW) and body fat percentage (BF) were assessed and actual change in these outcomes for pecan were compared to theoretical changes if pecans were consumed without compensation. Subjective appetite was measured using visual analog scale (VAS), and blood was collected to assess changes in physiological appetite before and every 30 min for 4 h following a high-fat meal. Energy intake (EI) at a buffet meal was then assessed in the laboratory ("in-lab"). VAS assessments continued hourly for the next 7 h and EI ("at-home") was self-reported. RESULTS: BW and BF did not change for pecan or control across the intervention and theoretical change in BW (theoretical: 2.2 ± 0.1 vs. actual: 0.4 ± 0.2 kg; p < 0.0001) and BF (theoretical: 0.4 ± 0.04 vs. actual: 0.2 ± 0.2%; p < 0.0001) was significantly greater than actual change for pecan. From V1 to V2, there was an increase in fasting (pecan: 77.0 ± 4.6 to 93.5 ± 6.1 vs control: 76.0 ± 5.0 to 72.5 ± 5.0 pg/mL; p = 0.01) and postprandial peptide YY for pecan vs. control (p = 0.04); however, fasting and postprandial cholecystokinin and ghrelin did not differ (p > 0.05). There were no differences in the change in subjective appetite ratings at fasting, following the high-fat meal (in-lab), at-home, or across the full day between groups (p > 0.05 for all). However, there was a significant suppression of peak desire to eat ratings for pecan vs. control (pecan: 67.9 ± 4.6 to 57.1 ± 5.2 vs. control: 61.9 ± 4.2 to 60.6 ± 4.3 mm; p = 0.04). Combined, buffet meal, and at-home EI did not differ significantly within pecan and control; however, there was a trend (p = 0.11) for a between group difference in buffet meal EI driven by increased EI for control (+137 ± 86 kcal) vs. decreased EI for pecan (-45 ± 77 kcal). CONCLUSION: A 4-week pecan-enriched diet led to enhanced satietogenic metrics compared to a diet void of all nuts. As weight remained stable during the intervention, adding pecans to the daily diet may be beneficial to appetite control and weight maintenance in a healthy older population. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov: NCT04385537.

Training Status Impacts Metabolic Response to A High-Protein Weight Loss Diet in Recreationally Resistance-Trained Females.

This study investigated the effects of a novel high-protein diet template on postprandial metabolism and body composition (e.g., waist and hip circumference, body fat (%), fat mass, fat-free mass) in recreationally resistance-trained females. Fifteen females adhered to an eight-week high-protein dietary intervention (~1.5-1.6 g·kg-1·day-1) administered via template format. Pre- and post-intervention visits included anthropometrics, measurement of body composition, and an acute high-fat meal challenge. The high-fat meal challenge (61% fat) consisted of fasting postprandial blood glucose, resting metabolic rate (RMR), fat and carbohydrate oxidation assessed at 60-, 120-, and 180-minutes. Participants were split into high (HTF; 5-6 days·week-1 of resistance training; n = 8) and low-training frequency (LTF; 2-3 days·week-1 of resistance training; n = 7) groups. All metabolism data were assessed as absolute (kcal or g) and relative (kcal or g·kg·FFM-1·minutes-1) to fat-free mass. Post-intervention, there was a significant reduction in HTF waist circumference (p = 0.044), LTF body fat % (p = 0.012), and LTF fat mass (p = 0.014). Post-intervention, HTF females had significantly lower absolute RMR area under the curve (AUC) than LTF females (p = 0.036). LTF females had higher absolute fat oxidation AUC compared to HTF females' pre-intervention (p = 0.048) but a significant decrease in absolute (p = 0.050) and relative (p = 0.050) fat oxidation AUC post-intervention. LTF females had a significant increase in absolute (p = 0.032) and relative (p = 0.029) carbohydrate oxidation AUC pre- to post-intervention (p = 0.032). For blood glucose, no significant differences between groups were detected (p > 0.05). These findings suggest that a novel high-protein diet template elicits a metabolic shift favoring carbohydrate oxidation in females engaging in low-frequency resistance training but did not alter fat and carbohydrate metabolism in females engaging in HTF resistance training.

Pecan-enriched diet improves cholesterol profiles and enhances postprandial microvascular reactivity in older adults.

Pecan-enriched diets have been linked to improved lipid metabolism; however, the impact of pecans on vascular health has yet to be examined. We hypothesized that 4 weeks of a pecan-enriched diet would improve fasting and postprandial blood lipids and vascular function compared with a nut-free diet. In this randomized control study, 44 older adults (59 ± 6 years) consumed 68 g of pecans/d (pecan; n = 21) or avoided all nuts (control; n = 23) for 4 weeks. At pre- and post-diet visits, fasting and postprandial blood lipids, macrovascular (by flow-mediated dilation), and microvascular (tissue saturation index reactive hyperemia [RH] kinetics by continuous-wave near-infrared spectroscopy) function were assessed. From the pre- to post-diet visit, there were greater reductions in fasting total cholesterol (pecan: -14 ± 4.0 vs control: -0.2 ± 5.4 mg/dL; P = .04), low-density lipoprotein (LDL) cholesterol (pecan: -15 ± 3.7 vs control: +1.9 ± 4.4 mg/dL; P = .01), non-high-density lipoprotein cholesterol (pecan: -15 ± 3.6 vs control: -0.5 ± 4.8 mg/dL; P = .02), LDL particle number (pecan: -126 ± 51 vs control: +43 ± 42 nmol/L; P = .01), and LDL medium (pecan: -34 ± 13 vs control: +16 ± 11 nmol/L; P < .01), for pecan vs control. Further, postprandial triglyceride was suppressed for pecan (P = .01) compared with control (P = .78). Postprandial RH slope (P = .04) and RH time to half (P = .004) was different by group, driven by improvements in pecan vs control. However, fasting macro- and microvascular function was unaffected. Daily pecan consumption for 4 weeks improved fasting and postprandial blood lipids and microvascular reactivity in older adults. Because changes in microvascular function typically precipitate macrovascular changes, long-term pecan consumption may improve vascular health and reduce risk for cardiovascular events. This trial was registered at clinicaltrials.gov (NCT04385537).

Seasonal and diel modulation of DOM in a mangrove-dominated estuary.

Rivers and estuaries are the main links between continents and oceans. The Paraíba do Sul River is among the most important rivers of the southeastern Brazilian region, carrying an average of 0.08 Tg of dissolved organic matter (DOM) to the ocean but has been facing significant changes in river discharge. In this study, we aimed to provide insights into the sources and transformations of chromophoric dissolved organic matter (CDOM) and fluorescent dissolved organic matter (FDOM) sources across a salinity gradient under changing river discharge scenarios. Three spatial surveys were performed covering the entire salinity gradient of the main estuarine channel and surrounding mangrove waters under contrasting river discharge (178 to 1240 m3 s-1), and diel sampling was conducted in the mangrove tidal creek. The characterization of DOM through the parallel factor analysis (PARAFAC) model identified six components across the river-ocean gradient and mangrove creek: terrestrial origin (C1 - fulvic acid and C2 and C3 - humic-like), protein-like (C4), tryptophan-like (C5), and tyrosine-like (C6). Our results showed a shift in DOM composition and contribution along the salinity gradient, from terrestrial (C3) to autochthonous (C5 and C6) signatures. The October-17 dry campaign was characterized by a higher proportion of microbial protein-like component C4 and a lower contribution of humic-like components compared to February-17 and March-18 across the salinity gradient with an increase in the mixing zone. The DOM compositions of the February 17 dry and March 18 wet campaigns were similar. Additionally, the March-18 wet campaign, marked by the highest river discharge, showed higher inputs of terrestrial DOM (C1-C3 components) compared to February-17 in the estuary, which allowed DOM to be transported rather than transformed. The mangrove diel study showed that tidal fluctuations are also an important driver of carbon input to the mangrove creek with a possible impact on DOM composition in estuarine waters.

Comparison of aspartame- and sugar-sweetened soft drinks on postprandial metabolism.

Aim: We compared the impact of artificially- and sugar-sweetened beverages co-ingested with a mixed meal on postprandial fat and carbohydrate oxidation, blood glucose, and plasma insulin and triglyceride concentrations. Methods: Eight college-aged, healthy males completed three randomly assigned trials, which consisted of a mixed macronutrient meal test with 20oz of Diet-Coke (AS), Coca-Cola (NS), or water (CON). One week separated each trial and each participant served as his own control. Resting energy expenditure (REE) via indirect calorimetry, blood pressure, and blood samples were obtained immediately before, 5, 10, 30, 60, 120, and 180 min after meal and beverage ingestion. A two-way (treatment × time) repeated-measures ANOVA was conducted to assess REE, fat and carbohydrate oxidation rates, blood glucose, and plasma insulin and triglyceride concentrations. Results: There was a significant main effect of treatment on total fat oxidation (P = 0.006), fat oxidation was significantly higher after AS (P = 0.006) and CON (P = 0.001) compared to following NS. There was a significant main effect of treatment on total carbohydrate oxidation (P = 0.005), carbohydrate oxidation was significantly lower after AS (P = 0.014) and CON (P = 0.001) compared to following NS. Plasma insulin concentration AUC was significantly lower after AS (P = 0.019) and trended lower in CON (P = 0.054) compared to following NS. Conclusion: Ingestion of a mixed meal with an artificially-sweetened beverage does not impact postprandial metabolism, whereas a sugar-sweetened beverage suppresses fat oxidation and increases carbohydrate oxidation compared to artificially-sweetened beverage and water.

Centrally expressed Cav3.2 T-type calcium channel is critical for the initiation and maintenance of neuropathic pain.

Cav3.2 T-type calcium channel is a major molecular actor of neuropathic pain in peripheral sensory neurons, but its involvement at the supraspinal level is almost unknown. In the anterior pretectum (APT), a hub of connectivity of the somatosensory system involved in pain perception, we show that Cav3.2 channels are expressed in a subpopulation of GABAergic neurons coexpressing parvalbumin (PV). In these PV-expressing neurons, Cav3.2 channels contribute to a high-frequency-bursting activity, which is increased in the spared nerve injury model of neuropathy. Specific deletion of Cav3.2 channels in APT neurons reduced both the initiation and maintenance of mechanical and cold allodynia. These data are a direct demonstration that centrally expressed Cav3.2 channels also play a fundamental role in pain pathophysiology.

African American Females Are Less Metabolically Flexible Compared with Caucasian American Females following a Single High-Fat Meal: A Pilot Study.

The relationship between metabolic flexibility (MF) and components of metabolic disease has not been well-studied among African American (AA) females and may play a role in the higher incidence of chronic disease among them compared with Caucasian American (CA) females. This pilot study aimed to compare the metabolic response of AA and CA females after a high-fat meal. Eleven AA (25.6 (5.6) y, 27.2 (6.0) kg/m2, 27.5 (9.7) % body fat) and twelve CA (26.5 (1.5) y, 25.7 (5.3) kg/m2, 25.0 (7.4) % body fat) women free of cardiovascular and metabolic disease and underwent a high-fat meal challenge (55.9% fat). Lipid oxidation, insulin, glucose, and interleukin (IL)-8 were measured fasted, 2 and 4 h postprandial. AA females had a significantly lower increase in lipid oxidation from baseline to 2 h postprandial (p = 0.022), and trended lower at 4 h postprandial (p = 0.081) compared with CA females, indicating worse MF. No group differences in insulin, glucose or HOMA-IR were detected. IL-8 was significantly higher in AA females compared with CA females at 2 and 4 h postprandial (p = 0.016 and p = 0.015, respectively). These findings provide evidence of metabolic and inflammatory disparities among AA females compared with CA females that could serve as a predictor of chronic disease in individuals with a disproportionately higher risk of development.

Effect of Prior Exercise on Postprandial Lipemia: An Updated Meta-Analysis and Systematic Review.

The purpose of this systematic review was to synthesize the results from current literature examining the effects of prior exercise on the postprandial triglyceride (TG) response to evaluate current literature and provide future direction. A quantitative review was performed using meta-analytic methods to quantify individual effect sizes. A moderator analysis was performed to investigate potential variables that could influence the effect of prior exercise on postprandial TG response. Two hundred and seventy-nine effects were retrieved from 165 studies for the total TG response and 142 effects from 87 studies for the incremental area under the curve TG response. There was a moderate effect of exercise on the total TG response (Cohen's d = -0.47; p < .0001). Moderator analysis revealed exercise energy expenditure significantly moderated the effect of prior exercise on the total TG response (p < .0001). Exercise modality (e.g., cardiovascular, resistance, combination of both cardiovascular and resistance, or standing), cardiovascular exercise type (e.g., continuous, interval, concurrent, or combined), and timing of exercise prior to meal administration significantly affected the total TG response (p < .001). Additionally, exercise had a moderate effect on the incremental area under the curve TG response (Cohen's d = -0.40; p < .0001). The current analysis reveals a more homogeneous data set than previously reported. The attenuation of postprandial TG appears largely dependent on exercise energy expenditure (∼2 MJ) and the timing of exercise. The effect of prior exercise on the postprandial TG response appears to be transient; therefore, exercise should be frequent to elicit an adaptation.

Dietary Intake of Adults Who Participate in CrossFit® Exercise Regimens.

Background: The combination of high-intensity aerobic and high-load resistance training, as in CrossFit®, exerts similar or superior benefits to other exercise modalities. This study aimed to assess dietary habits and characterize the nutritional goals, exercise habits, and clinical health outcomes of individuals who participate in CrossFit®. Methods: Adults who are 19 y or older, with >6 mo of CrossFit® participation, completed an electronic survey and the dietary health questionnaire III. In separate models, multiple stepwise linear regressions were performed to detect the associations between (i) dietary intake, (ii) exercise habits, (iii) clinical measures, and a priori selected predictors (sex, weight status, age, and exercise frequency) in each case. Odds ratios were detected between nutritional and fitness goals, clinical outcomes, and predictors. Results: In total, 449 respondents completed both questionnaires. Of these, 443 respondents were used for relative macronutrients assessment due to not reporting body weight. Dietary intake was associated with sex, weight status, age, exercise frequency, and nutritional goals. Nutritional and fitness goals and clinical outcomes were associated with sex, weight status, age, and exercise frequency. Conclusion: Nutritional goals are underlying factors that affect eating behaviors in non-competitive CrossFit® participants. It is imperative to consider the sex, age, exercise habits, and nutritional goals of CrossFit® participants when investigating and prescribing dietary outcomes.

Prophylactic nipple-sparing mastectomy with immediate breast reconstruction: results of a French prospective trial.

BACKGROUND: Nipple-sparing mastectomy (NSM) with immediate breast reconstruction (IBR) is used increasingly when performing a prophylactic mastectomy. Few prospective studies have reported on complication rates. This complementary trial to the French prospective multicentre MAPAM trial aimed to evaluate the nipple-areola complex (NAC) necrosis rate in prophylactic NSM with IBR. METHODS: Patient characteristics and surgical data were recorded. Morbidity after prophylactic NSM with a focus on NAC necrosis was analysed. RESULTS: Among 59 women undergoing prophylactic NSM, 19 (32 per cent) of the incisions were partly on the NAC. Reconstructions were performed with 46 definitive implants and 13 expanders. The crude rate of postoperative complications was 25 per cent (15 patients). Complete NAC necrosis was reported in two women (3 per cent) and partial or total necrosis in nine (15 per cent). No NAC resection was necessary. Median BMI was lower in women with total or partial NAC necrosis compared with the others (20.0 versus 21.3 kg/m2 respectively; P = 0.034). CONCLUSION: Results of this prospective study confirm that prophylactic NSM with IBR is associated with a low risk of total NAC necrosis.

The patient advisor, an organizational resource as a lever for an enhanced oncology patient experience (PAROLE-onco): a longitudinal multiple case study protocol.

BACKGROUND: Quebec is one of the Canadian provinces with the highest rates of cancer incidence and prevalence. A study by the Rossy Cancer Network (RCN) of McGill university assessed six aspects of the patient experience among cancer patients and found that emotional support is the aspect most lacking. To improve this support, trained patient advisors (PAs) can be included as full-fledged members of the healthcare team, given that PA can rely on their knowledge with experiencing the disease and from using health and social care services to accompany cancer patients, they could help to round out the health and social care services offer in oncology. However, the feasibility of integrating PAs in clinical oncology teams has not been studied. In this multisite study, we will explore how to integrate PAs in clinical oncology teams and, under what conditions this can be successfully done. We aim to better understand effects of this PA intervention on patients, on the PAs themselves, the health and social care team, the administrators, and on the organization of services and to identify associated ethical and legal issues. METHODS/DESIGN: We will conduct six mixed methods longitudinal case studies. Qualitative data will be used to study the integration of the PAs into clinical oncology teams and to identify the factors that are facilitators and inhibitors of the process, the associated ethical and legal issues, and the challenges that the PAs experience. Quantitative data will be used to assess effects on patients, PAs and team members, if any, of the PA intervention. The results will be used to support oncology programs in the integration of PAs into their healthcare teams and to design a future randomized pragmatic trial to evaluate the impact of PAs as full-fledged members of clinical oncology teams on cancer patients' experience of emotional support throughout their care trajectory. DISCUSSION: This study will be the first to integrate PAs as full-fledged members of the clinical oncology team and to assess possible clinical and organizational level effects. Given the unique role of PAs, this study will complement the body of research on peer support and patient navigation. An additional innovative aspect of this study will be consideration of the ethical and legal issues at stake and how to address them in the health care organizations.

High-fat meal increases peripheral blood mononuclear cell pro-inflammatory cytokine expression in African-American women.

African-American (AA) women have elevated predominance of inflammatory diseases concurrent with local inflammation resulting in compromised metabolic function. The purpose of the study was 2-fold: 1) to examine the gene and protein expression of pro- and anti-inflammatory cytokine secretion by peripheral blood mononuclear cells (PBMC) obtained from AA and Caucasian-American (CA) women in response to an acute high-fat meal; and 2) to explore the influence of race (AA vs. CA) on PBMC reactivity. Ten AA and 11 CA women consumed a high-fat meal with baseline and 4 h postprandial venous blood draws. PBMCs were incubated for 3 h then messenger RNA expression and supernatant protein concentration was used to examine inflammatory profiles. All women had a postprandial increase in interleukin (IL)-8 gene expression, IL-8 protein concentration, and tumor necrosis factor alpha (TNF-α) protein concentration (P < 0.05). AA women had a postprandial increase in IL-6, IL-8, and TNF-α protein concentration (P < 0.05). AA women had higher postprandial IL-1ß protein concentration and IL-8 gene expression compared with CA women (P < 0.05). Our data uncovers the specific impact of race and time on pro-inflammatory PBMC (IL-1ß, IL-6, IL-8, and TNF-α) expression profiles in response to an acute high-fat meal challenge. Novelty: African Americans have higher predominance of inflammatory disease. We explored the potential race impact on peripheral blood mononuclear cell reactivity in response to a meal. A pro-inflammatory response to an acute high-fat meal with race impact was observed possibly contributing to health disparities impacting African-American women.

Anti-retroviral therapy after "Treat All" in Harare, Zimbabwe: What are the changes in uptake, time to initiation and retention?

Background: In Zimbabwe, Harare was the first province to implement "Treat All" for people living with human immunodeficiency virus (PLHIV). Since its roll out in July 2016, no study has been conducted to assess the changes in key programme indicators. We compared antiretroviral therapy (ART) uptake, time to ART initiation from diagnosis, and retention before and during "Treat All". Methods: We conducted an ecological study to assess ART uptake among all PLHIV newly diagnosed before and during "Treat All". We conducted a cohort study to assess time to ART initiation and retention in care among all PLHIV newly initiated on ART from all electronic patient management system-supported sites (n=50) before and during "Treat All". Results: ART uptake increased from 65% (n=4619) by the end of quarter one, 2014 to 85% (n=5152) by the end of quarter four, 2018.  A cohort of 2289 PLHIV were newly initiated on ART before (April-June 2015) and 1682 during "Treat all" (April-June 2017). Their age and gender distribution was similar. The proportion of PLHIV in early stages of disease was significantly higher during "Treat all" (73.2% vs. 55.6%, p<0.001). The median time to ART initiation was significantly lower during "Treat All" (31 vs. 88 days, p<0.001). Cummulative retention at three, six and 12 months was consistently lower during "Treat all" and was significant at six months (74.9% vs.78.1% p=0.022). Conclusion: Although there were benefits of early ART initiation during "Treat All", the programme should consider strategies to improve retention.

Clinical and experimental insight into pathophysiology, comorbidity and therapy of absence seizures.

Absence seizures in children and teenagers are generally considered relatively benign because of their non-convulsive nature and the large incidence of remittance in early adulthood. Recent studies, however, show that 30% of children with absence seizures are pharmaco-resistant and 60% are affected by severe neuropsychiatric comorbid conditions, including impairments in attention, cognition, memory and mood. In particular, attention deficits can be detected before the epilepsy diagnosis, may persist even when seizures are pharmacologically controlled and are aggravated by valproic acid monotherapy. New functional MRI-magnetoencephalography and functional MRI-EEG studies provide conclusive evidence that changes in blood oxygenation level-dependent signal amplitude and frequency in children with absence seizures can be detected in specific cortical networks at least 1 min before the start of a seizure, spike-wave discharges are not generalized at seizure onset and abnormal cortical network states remain during interictal periods. From a neurobiological perspective, recent electrical recordings and imaging of large neuronal ensembles with single-cell resolution in non-anaesthetized models show that, in contrast to the predominant opinion, cortical mechanisms, rather than an exclusively thalamic rhythmogenesis, are key in driving seizure ictogenesis and determining spike-wave frequency. Though synchronous ictal firing characterizes cortical and thalamic activity at the population level, individual cortico-thalamic and thalamocortical neurons are sparsely recruited to successive seizures and consecutive paroxysmal cycles within a seizure. New evidence strengthens previous findings on the essential role for basal ganglia networks in absence seizures, in particular the ictal increase in firing of substantia nigra GABAergic neurons. Thus, a key feature of thalamic ictogenesis is the powerful increase in the inhibition of thalamocortical neurons that originates at least from two sources, substantia nigra and thalamic reticular nucleus. This undoubtedly provides a major contribution to the ictal decrease in total firing and the ictal increase of T-type calcium channel-mediated burst firing of thalamocortical neurons, though the latter is not essential for seizure expression. Moreover, in some children and animal models with absence seizures, the ictal increase in thalamic inhibition is enhanced by the loss-of-function of the astrocytic GABA transporter GAT-1 that does not necessarily derive from a mutation in its gene. Together, these novel clinical and experimental findings bring about paradigm-shifting views of our understanding of absence seizures and demand careful choice of initial monotherapy and continuous neuropsychiatric evaluation of affected children. These issues are discussed here to focus future clinical and experimental research and help to identify novel therapeutic targets for treating both absence seizures and their comorbidities.