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Restricted sugar and ketogenic diets can alter energy balance/metabolism, but decreased energy intake may be compensated by reduced expenditure. In healthy adults, randomization to restricting free sugars or overall carbohydrates (ketogenic diet) for 12 weeks reduces fat mass without changing energy expenditure versus control. Free-sugar restriction minimally affects metabolism or gut microbiome but decreases low-density lipoprotein cholesterol (LDL-C). In contrast, a ketogenic diet decreases glucose tolerance, increases skeletal muscle PDK4, and reduces AMPK and GLUT4 levels. By week 4, the ketogenic diet reduces fasting glucose and increases apolipoprotein B, C-reactive protein, and postprandial glycerol concentrations. However, despite sustained ketosis, these effects are no longer apparent by week 12, when gut microbial beta diversity is altered, possibly reflective of longer-term adjustments to the ketogenic diet and/or energy balance. These data demonstrate that restricting free sugars or overall carbohydrates reduces energy intake without altering physical activity, but with divergent effects on glucose tolerance, lipoprotein profiles, and gut microbiome.

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PURPOSE: To determine the effects of dietary sugar or carbohydrate restriction on physical activity energy expenditure, energy intake, and physiological outcomes across 24 h. METHODS: In a randomized, open-label crossover design, twenty-five healthy men (n = 10) and women (n = 15) consumed three diets over a 24-h period: moderate carbohydrate and sugar content (MODSUG = 50% carbohydrate [20% sugars], 15% protein, 35% fat); low sugar content (LOWSUG = 50% carbohydrate [< 5% sugars], 15% protein, 35% fat); and low carbohydrate content (LOWCHO = 8% carbohydrate [< 5% sugars], 15% protein, 77% fat). Postprandial metabolic responses to a prescribed breakfast (20% EI) were monitored under laboratory conditions before an ad libitum test lunch, with subsequent diet and physical activity monitoring under free-living conditions until blood sample collection the following morning. RESULTS: The MODSUG, LOWSUG and LOWCHO diets resulted in similar mean [95%CI] rates of both physical activity energy expenditure (771 [624, 919] vs. 677 [565, 789] vs. 802 [614, 991] kcal·d-1; p = 0.29] and energy intake (2071 [1794, 2347] vs. 2195 [1918, 2473] vs. 2194 [1890, 2498] kcal·d-1; P = 0.34), respectively. The LOWCHO condition elicited the lowest glycaemic and insulinaemic responses to breakfast (P < 0.01) but the highest 24-h increase in LDL-cholesterol concentrations (P < 0.001), with no differences between the MODSUG and LOWSUG treatments. Leptin concentrations decreased over 24-h of consuming LOWCHO relative to LOWSUG (p < 0.01). CONCLUSION: When energy density is controlled for, restricting either sugar or total dietary carbohydrate does not modulate physical activity level or energy intake over a 24-h period (~ 19-h free-living) despite substantial metabolic changes. CLINICAL TRIALS REGISTRATION ID: NCT03509610, https://clinicaltrials.gov/show/NCT03509610.

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It is unclear whether neuromuscular electrical stimulation (NMES) has meaningful metabolic effects when users have the opportunity to self-select the intensity to one that can be comfortably tolerated. Nine healthy men aged 28 ± 9 y (mean ± SD) with a body mass index 22.3 ± 2.3 kg/m2 completed 3 trials involving a 2-h oral glucose tolerance test whilst, in a randomised counterbalanced order, (1) sitting motionless (SIT), (2) standing motionless (STAND); and (3) sitting motionless with NMES of quadriceps and calves at a self-selected tolerable intensity. The mean (95% confidence interval [CI]) total energy expenditure was greater in the NMES trial (221 [180-262] kcal/2 h) and STAND trial (178 [164-191] kcal/2 h) than during SIT (159 [150-167] kcal/2 h) (both, p < 0.05). This was primarily driven by an increase in carbohydrate oxidation in the NMES and STAND trials compared with the SIT trial (p < 0.05). Postprandial insulin iAUC was lower in both NMES and STAND compared with SIT (16.4 [7.7-25.1], 17 [7-27] and 22.6 [10.8-34.4] nmol·120 min/L, respectively; both, p < 0.05). Compared with sitting, both NMES and STAND increased energy expenditure and whole-body carbohydrate oxidation and reduced postprandial insulin concentrations in healthy men, with more pronounced effects seen with NMES. Self-selected NMES is a potential strategy for improving metabolic health. This trial is registered at ClinicalTrials.gov (ID: NCT04389736). Novelty: NMES at a comfortable intensity enhances energy expenditure and carbohydrate oxidation, and reduces postprandial insulinemia. Thus, self-selected NMES represents a potential strategy to improve metabolic health.

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This study investigated whether carbohydrate-energy replacement immediately after prolonged endurance exercise attenuates insulin sensitivity the following morning, and whether exercise improves insulin sensitivity the following morning independent of an exercise-induced carbohydrate deficit. Oral glucose tolerance and whole-body insulin sensitivity were compared the morning after 3 evening conditions, involving (1) treadmill exercise followed by a carbohydrate replacement drink (200 or 150 g maltodextrin for males and females, respectively; CHO-replace); (2) treadmill exercise followed by a non-caloric, taste-matched placebo (CHO-deficit); or (3) seated rest with no drink provided (Rest). Treadmill exercise involved 90 minutes at ∼80% age-predicted maximum heart rate. Seven males and 2 females (aged 23 ± 1 years; body mass index 24.0 ± 2.7 kg·m-2) completed all conditions in a randomised order. Matsuda index improved by 22% (2.2 [0.3, 4.0] au, p = 0.03) and HOMA2-IR improved by 10% (-0.04 [-0.08, 0.00] au, p = 0.04) in CHO-deficit versus CHO-replace, without corresponding changes in postprandial glycaemia. Outcomes were similar between Rest and other conditions. These data suggest that improvements to insulin sensitivity in healthy populations following acute moderate/vigorous intensity endurance exercise may be dependent on the presence of a carbohydrate-energy deficit. Novelty: Restoration of carbohydrate balance following acute endurance exercise attenuated whole-body insulin sensitivity. Exercise per se failed to enhance whole-body insulin sensitivity. Maximising or prolonging the post-exercise carbohydrate deficit may enhance acute benefits to insulin sensitivity.

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BACKGROUND: Whilst almost 50% of heart failure (HF) patients have preserved ejection fraction (HFpEF), evidence-based treatment options for this patient group remain limited. However, there is growing evidence of the potential value of exercise-based cardiac rehabilitation. This study reports the process evaluation of the Rehabilitation Enablement in Chronic Heart Failure (REACH-HF) intervention for HFpEF patients and their caregivers conducted as part of the REACH-HFpEF pilot trial. METHODS: Process evaluation sub-study parallels to a single-centre (Tayside, Scotland) randomised controlled pilot trial with qualitative assessment of both intervention fidelity delivery and HFpEF patients' and caregivers' experiences. The REACH-HF intervention consisted of self-help manual for patients and caregivers, facilitated over 12 weeks by trained healthcare professionals. Interviews were conducted following completion of intervention in a purposeful sample of 15 HFpEF patients and seven caregivers. RESULTS: Qualitative information from the facilitator interactions and interviews identified three key themes for patients and caregivers: (1) understanding their condition, (2) emotional consequences of HF, and (3) responses to the REACH-HF intervention. Fidelity analysis found the interventions to be delivered adequately with scope for improvement in caregiver engagement. The differing professional backgrounds of REACH-HF facilitators in this study demonstrate the possibility of delivery of the intervention by healthcare staff with expertise in HF, cardiac rehabilitation, or both. CONCLUSIONS: The REACH-HF home-based facilitated intervention for HFpEF appears to be a feasible and a well-accepted model for the delivery of rehabilitation, with the potential to address key unmet needs of patients and their caregivers who are often excluded from HF and current cardiac rehabilitation programmes. Results of this study will inform a recently funded full multicentre randomised clinical trial. TRIAL REGISTRATION: ISRCTN78539530 (date of registration 7 July 2015).

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This study investigated metabolic, endocrine, appetite and mood responses to a maximal eating occasion in fourteen men (mean: age 28 (sd 5) years, body mass 77·2 (sd 6·6) kg and BMI 24·2 (sd 2·2) kg/m2) who completed two trials in a randomised crossover design. On each occasion, participants ate a homogenous mixed-macronutrient meal (pizza). On one occasion, they ate until 'comfortably full' (ad libitum) and on the other, until they 'could not eat another bite' (maximal). Mean energy intake was double in the maximal (13 024 (95 % CI 10 964, 15 084) kJ; 3113 (95 % CI 2620, 3605) kcal) compared with the ad libitum trial (6627 (95 % CI 5708, 7547) kJ; 1584 (95 % CI 1364, 1804) kcal). Serum insulin incremental AUC (iAUC) increased approximately 1·5-fold in the maximal compared with ad libitum trial (mean: ad libitum 43·8 (95 % CI 28·3, 59·3) nmol/l × 240 min and maximal 67·7 (95 % CI 47·0, 88·5) nmol/l × 240 min, P < 0·01), but glucose iAUC did not differ between trials (ad libitum 94·3 (95 % CI 30·3, 158·2) mmol/l × 240 min and maximal 126·5 (95 % CI 76·9, 176·0) mmol/l × 240 min, P = 0·19). TAG iAUC was approximately 1·5-fold greater in the maximal v. ad libitum trial (ad libitum 98·6 (95 % CI 69·9, 127·2) mmol/l × 240 min and maximal 146·4 (95 % CI 88·6, 204·1) mmol/l × 240 min, P < 0·01). Total glucagon-like peptide-1, glucose-dependent insulinotropic peptide and peptide tyrosine-tyrosine iAUC were greater in the maximal compared with ad libitum trial (P < 0·05). Total ghrelin concentrations decreased to a similar extent, but AUC was slightly lower in the maximal v. ad libitum trial (P = 0·02). There were marked differences on appetite and mood between trials, most notably maximal eating caused a prolonged increase in lethargy. Healthy men have the capacity to eat twice the energy content required to achieve comfortable fullness at a single meal. Postprandial glycaemia is well regulated following initial overeating, with elevated postprandial insulinaemia probably contributing.

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BACKGROUND: Caregivers frequently provide support to people living with long-term conditions. However, there is paucity of evidence of interventions that support caregivers in their role. Rehabilitation EnAblement in Chronic Heart Failure (REACH-HF) is a novel home-based, health-professional-facilitated, self-management programme for patients with heart failure (HF) and their caregivers. METHODS: Based on the random allocation of individual adult patients with reduced ejection fraction (HFrEF) and left ventricular ejection fraction <45% within the past five years, the caregiver of patients was allocated to receive the REACH-HF intervention over 12 weeks (REACH-HF group) or not (control group). Caregiver outcomes were generic health-related quality of life (EQ-5D-5L), Family Caregiver Quality of Life Scale questionnaire (FamQol), Caregiver Burden Questionnaire HF (CBQ-HF), Caregiver Contribution to Self-care of HF Index questionnaire (CC-SCHFI) and Hospital Anxiety and Depression Scale (HADS). Outcomes were compared between groups at 4, 6 and 12 months follow-up. Twenty caregivers receiving REACH-HF were purposively selected for qualitative interviews at 4 and 12 months. RESULTS: Compared with controls (44 caregivers), the REACH-HF group (53 caregivers) had a higher mean CC-SCHFI confidence score at 12 months (57.5 vs 62.8, adjusted mean difference: 9.3, 95% confidence interval: 1.8-16.8, p = 0.016). No significant between group differences were seen in other caregiver outcomes. Qualitative interviews showed that most caregivers who received the REACH-HF intervention made positive changes to how they supported the HF patient they were caring for, and perceived that they had increased their confidence in the caregiver role over time. CONCLUSION: Provision of the REACH-HF intervention for caregivers of HF patients improved their confidence of self-management and was perceived for some to be helpful in supporting their caregiver role.

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Hepatitis C virus (HCV) serotypes are important in the epidemiology and pathogenesis of HCV-related disease, but little is known of this connection in West Africa. Coinfection with human immunodeficiency virus (HIV) is associated with significant morbidity and mortality. This study aims to determine the prevalence of HCV and its serotypes associated with HIV in The Gambia. A total of 1500 individuals referred to the Royal Victoria Teaching Hospital for HIV serology between July and December, 2002 were screened for antibodies to HIV and subsequently for HCV, and seropositive samples were typed. This study shows HIV and HCV prevalence of 6.7% and 1.6%, respectively, with a co-infection rate of 0.6%. Serotype 2 showed the highest prevalence (58.1%), followed by serotype 1 (19.4%). Prevalence of HCV serotype 3 was 6.5% and five samples were untypeable. Co-infection of HIV-1 with HCV serotype 1 showed a prevalence of 44.4%, and with HCV serotype 2 of 33.3%. The findings support the evidence to suggest the West African subregion as the origin of HCV serotype 2. It also demonstrates the need for routine HCV screening of HIV-infected persons and blood donations, and calls for further studies to elucidate the sources of the HCV virus.

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BACKGROUND: In most West African countries, the distribution and risk factors for co-infection with Human Immunodeficiency Virus (HIV) and Hepatitis C Virus (HCV) is unknown despite the current HIV epidemic and evidence of increasing prevalence of HCV in the region. OBJECTIVE: This study aimed to evaluate the distribution and the risk factors for the transmission of co-infection between HIV and HCV in The Gambia. METHODS: A total of 1500 persons referred for HIV serology at the Royal Victoria teaching Hospital were interviewed following informed consent to obtain information on their demographic variables, knowledge of sexually transmitted diseases and their prevention, and patterns of risk behavior. Blood was collected and tested for anti-HIV and anti-HCV antibodies by Enzyme Linked Immunosorbent Assay (ELISA). RESULTS: In the general population, the prevalence of HIV was 6.7%, while that of HCV was 2.1%. Both infections occurred more frequently in males than in females. HIV and HCV coinfection rate was 0.6%. Co-infection was significantly more common in males than females. All types of infection--HIV, HCV and HIV/HCV co-infections occurred much more in polygamous settings than in monogamy. CONCLUSION: This study has demonstrated the extent of coinfection with HIV and HCV in The Gambia. The prevalence of female circumcision may be a contributory occurrence factor in the transmission of HIV but not in that of HCV.

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OBJECTIVES: This study was undertaken to monitor the CD4+ lymphocyte count in individuals infected with Human Immunodeficiency Virus (HIV) and/or co-infected with Hepatitis C Virus (HCV) and to compare this with the counts in normal individuals in The Gambia. METHODS: Blood samples were taken from 1500 individuals referred for HIV serology at the Royal Victoria Teaching Hospital (RVTH) following informed consent. Samples were tested for antibodies to HIV by the Murex ELISA, antibodies to HCV by the Ortho ELISA, and CD4 counts determined by the Dynalimmunomagnetic cell isolation method RESULTS: Of the 1500 patients screened for HIV and HCV antibodies, 6.7% (101/1500) were infected with HIV, 0.6 % (9/1500) were co-infected with HCV and 1.5 % (22/1500) were infected with HCV alone. Almost half (44.6%; 25/56) of HIV-1 infected patients had a CD4+ lymphocyte count at diagnosis of 200 cells/microl or less as compared to 41.7 % (10/24) of HIV-2 and 75% (6/8) of HIV-D infected patients. The rate of CD4 decline was higher among HIV/HCV co-infected persons than individuals infected with HIV or HCV. The rate of decline was higher among men than women. These differences did not reach statistical significance due in large part to the small number of participants who completed the programme. The CD4+ lymphocyte count of apparently healthy Gambian male and females was 489 cells/microl and 496 cells/microl respectively. This rate is lower than that reported for Caucasians, but in agreement with the global range. CONCLUSION: A significant progressive decline in CD4+ lymphocyte count was observed among the female control group who were negative for HIV and HCV. This finding is unclear and calls for a longitudinal study involving a cohort of women in this region.

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High breast density as measured on mammograms is a strong risk factor for breast cancer in the general population, but its effect in carriers of germline BRCA1 and BRCA2 mutations is unclear. We obtained mammograms from 206 female carriers of BRCA1 or BRCA2 mutations, 96 of whom were subsequently diagnosed with breast cancer and 136 relatives of carriers who were themselves noncarriers. We compared the mammographic densities of affected carriers (cases) and unaffected carriers (controls), and of mutation carriers and noncarriers, using a computer-assisted method of measurement and visual assessment by two observers. Analyses were adjusted for age, parity, body mass index, menopausal status, and hormone replacement therapy use. There was no difference in the mean percent density between noncarriers and carriers. Among carriers, increasing mammographic density was associated with an increased risk of breast cancer (P(trend) = 0.024). The odds ratio (OR; 95% confidence interval) for breast cancer associated with a density of > or =50% was 2.29 (1.23-4.26; P = 0.009). The OR did not differ between BRCA1 and BRCA2 carriers or between premenopausal and postmenopausal carriers. The results suggest that the distribution of breast density in BRCA1 and BRCA2 carriers is similar to that in non-carriers. High breast density in carriers is associated with an increased risk of breast cancer, with the relative risk being similar to that observed in the general population. Use of mammographic density could improve individual risk prediction in carriers.

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OBJECTIVES: Hepatocellular Carcinoma is the commonest form of cancer in The Gambia, and although Hepatitis B and Hepatitis C are known risk factors, accurate baseline data on Hepatitis B and Hepatitis C distribution in the region are limited. Similarly data including information on the involvement of the viruses in HCC remains unknown. The current study was undertaken to estimate the risk of HCC in relation to HCV and HBV in The Gambia. METHODS: Thirteen patients with histological proven history of HCC and 39 healthy controls were enrolled in the study. Each subject blood was screened individually for anti-HCV using ORTHO HCV 3.0 ELISA test system (Ortho-Clinical Diagnostics, Inc, U.S.A) and for HBsAg using QUADRATECH CHECK 4-HBs one step generation hepatitis B surface antigen test kit (VEDALAB, France) following the manufacturers instructions. RESULTS: HBsAg and anti-HCV was detected in 38.5 % (5/13) and 7.7% (1/39) of the persons with a history of HCC respectively. HBsAg but not anti-HCV was detected in 12.8% (5/39 of the case control subjects. HBsAg and HCV rates among the HCC patients were higher in men than women. Rates were highest in patients 48 years and above (37.5%; 3/8). No patient was found with anti-HCV and anti-HBV. CONCLUSION: These results indicate that the involvement of HBV and HCV in HCC in the country is in a ratio of 5:1 and that these two viruses might be independently involved in the pathogenesis of the disease. The study revealed a statistically significant association (p = 0.04) between HBsAg and HCC patients. The results also indicate that up to 50% of HCC cases in the country may be due to non viral factors and calls for further studies in this regard. These findings call for provision of diagnostic facilities for these viruses in hospitals and for their routine screening in blood banks while intervention programmes should be put in place.

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This study evaluates the seroprevalence and risk factors for hepatitis C (HCV) antibodies in asymptomatic first-time blood donors in The Gambia. The study population includes 460 blood donors (age range: 18-40 years [mean: 27.5]) who attended the Royal Victoria Teaching Hospital from July to December 2002. Antibodies to hepatitis C are determined using and enzyme-linked immunosorbent assay (ELISA) test system. The prevalence of hepatitis C found in this study was 1.1% (95% CI, 0.16-1.12). Previous history of sexually transmitted disease, married men in polygamous relationships, and hospital or clinic-based workers were determined to be at risk of acquiring hepatitis C. The study shows that seroprevalence of hepatitis C in The Gambia is low compared to other countries in the region.

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