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Background: Over the past several years, there have been several changes affecting the available options for oral HIV preexposure prophylaxis, including approvals for tenofovir alafenamide with emtricitabine in 2019 and a generic formulation of tenofovir disoproxil fumarate with emtricitabine in 2020., Methods: In order to better understand providers' decision-making processes when deciding between these two drugs for pre-exposure prophylaxis, we conducted semi-structured in-depth interviews with resident, fellow and attending physicians in internal medicine and infectious diseases between May 2020 and March 2021. These interviews were analyzed to identify emergent codes, which were utilized in an inductive thematic analysis to identify major themes pertinent to pre-exposure prophylaxis decision-making., Results: Of 21 participants, 18 expressed a general preference for prescribing tenofovir disoproxil fumarate with emtricitabine, 2 preferred tenofovir alafenamide with emtricitabine and 1 had no specific preference. Providers perceived similar efficacy of the two formulations, and their clinical decisions were influenced primarily by whether HIV pre-exposure prophylaxis users belonged to a population with an indication for each of the two drugs (e.g. gender-related restrictions for tenofovir alafenamide), the medications' differing side effect profiles, cost and insurance considerations, prior personal and collective experience with each of these medications, and personal preferences. Respondents also noted that both providers and HIV pre-exposure prophylaxis users were influenced by external factors, including institutional prescribing guidance, advertising, and social influences, including from peers and colleagues., Conclusions: Our findings suggest that unbiased educational campaigns for both prescribers and users of HIV pre-exposure prophylaxis will be important to support evidence-based prescribing practices and cost-effective decisions among oral pre-exposure prophylaxis options., Competing Interests: The authors have read the journal’s policy and have the following competing interests: Fenway Health served as a recruitment site for this study. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2024 Merchant et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background and objectives: Fatigue is one of the most common and disabling symptoms of multiple sclerosis (MS). It can be defined as a subjective lack of physical and mental energy. The aim of this study was to evaluate the frequency and severity of fatigue in patients with MS and its relationship with overall physical activity and disease-related disability. Materials and Methods: The study included 100 patients with a clinical relapsing-remitting form of MS. Patients with severe depression were excluded. Neurological impairment was rated using the Expanded Disability Status Scale (EDSS). Fatigue was assessed using the Modified Fatigue Impact Scale (MFIS) and the Fatigue Severity Scale (FSS), with FSS scores greater than 36 indicating patients with fatigue. Physical activity was evaluated with the International Physical Activity Questionnaire (IPAQ) and categorized on three levels: low, moderate, and high, using standard metabolic equivalents (MET). Results: The average FSS and MFIS scores were (mean ± SD) 31.3 ± 15.2 and 30.1 ± 17.0, respectively. The mean EDSS score was 2.5 ± 1.5. 42%. Patients were classified as fatigued based on FSS. Fatigued patients had higher mean EDSS scores than non-fatigued (3.0 ± 1.6 vs. 2.2 ± 1.4, respectively, p = 0.002). Low, moderate, and high levels of physical activity were reported in 35%, 20%, and 45% of patients, respectively. Higher scores of fatigue in FSS and MFIS were inversely correlated with the intensity of physical activity (r = -0.38, p < 0.001 and r = -0.33, p < 0.001, respectively). Conclusions: In patients with MS, fatigue is a common symptom. Patients with lower physical activity and greater MS-related disability have a higher severity of fatigue, which negatively affects cognitive, psychosocial, and physical functioning.

For decades, scientists have known that carriers of the apolipoprotein E ε4 ( APOE ε4) allele (homozygous/heterozygous) are at respectively higher risk for developing Alzheimer's disease (AD). Although previous research reveals that the APOE ε4 variant impacts the clearance capacity and degradation of β-amyloid from the brain, as compared with APOE ε3 (wild type with normal risk) and APOE ε2 (variant with accelerated clearance and reduced risk), little has been documented about APOE ε4's dual role in cholesterol transport, both peripheral and cerebral, and the effects of sluggish APOE ε4 cholesterol transport on cerebral metabolic rate. An understanding of the connection between brain metabolism and brain fat/cholesterol transport may unlock new prevention strategies for treating patients with a comorbidity of metabolic syndrome (MetS) with cognitive impairment. Recent findings suggest that the APOE ε4 carrier impedes the shuttling of lipids from neurons and circumvents the storage of fat within the glia lipid droplets. This sluggish transport of lipids to triglyceride droplets in the glia cells can lead to dangerous reactive oxygen species and hydroxyl-free radicals as lipids are prematurely oxidized. This case study evaluates the effects of a 10-week clinically prescribed ketogenic diet (KD) with a 68-year-old male, heterozygous APOE ε4 carrier, with a dual diagnosis of mild AD and type 2 diabetes (T2DM). The patient was administering both long- and short-acting injectable insulin to mediate his T2DM for 15+ years. Clinical goals of the intervention included increased hypothalamic and peripheral insulin sensitivity as measured via blood ketones with the Abbott Precision Xtra Blood Ketone Meter to confirm metabolic flexibility; controlled plasma glucose as measured via Abbott Precision Xtra Blood Glucose Meter and HgA1c via venous draw; normalization of lipid panel via venous draw and improved memory with restoration of cognitive functionality measured via the Montreal Cognitive Assessment. The Montreal Cognitive Assessment is considered to be a gold standard assessment in the diagnosis of early AD. Physiological biomarkers for T2DM/MetS and cognitive functionality were assessed before/during/after intervention. These measures included HOMA-IR, triglycerides/HDL ratio, HgA1c, fasting glucose, fasting insulin, complete fasting lipid panel and the PEAK mobile application for real-time measurement of cognitive improvement. The results were statistically significant. The patient's baseline Montreal Cognitive Assessment improved from 23/30 (mild AD) to 29/30 (normal ≥ 26). His T2DM was reversed. Pre-intervention HgA1c was 7.8% (T2DM); post intervention HgA1c measured 5.5% (normal). Likewise, the patient achieved statistically significant improvements in the other aforementioned biomarkers of MetS. The results of this case study suggest that a clinically prescribed ketogenic diet has strong potential to restore systemic insulin sensitivity and metabolic flexibility in diabetic, APOE ε4 heterozygous carriers. Mechanisms of action point to normalization of homeostatic negative feedback loops resetting/restoring lipid synthesis/utilization and glucose (insulin)/fatty acid (glucagon) utilization/production in both the body and brain, resulting in increased cerebral metabolism, improved cognition, and reversal of T2DM via renewed cellular insulin sensitivity.

Efficacious adherence to treatment protocol predicts metabolic control among Type 2 diabetics (T2DM) [1-4]; however, few healthcare systems employ individualized strategies to mediate the comorbidity of T2DM with other chronic disease states. A clinically prescribed ketogenic diet, patient-centered nutritional education and high intensity interval training (HIIT), girded by solution-focused psychotherapy, modulate significant improvements in the clinical biomarkers associated with concurring T2DM and clinical depression [5-15]. Relevant metabolic change was noted in the following measures: HOMA-IR, triglyceride/HDL ratio, HgA1c, fasting insulin, fasting glucose, fasting triglycerides, LDL, VLDL, HDL, total cholesterol and C-reactive protein. The Patient Health Questionnaire 9 (PHQ-9) along with clinical interview and the mental status exam showed notable change in the patient's depressive symptoms; likewise, her self-efficacy score normalized, as measured by the General Self-Efficacy Questionnaire (GSE) and the Metabolic Syndrome Compliance Questionnaire (MSC). The case study highlights a 65-year old female who presented with a 26-year history of dually-diagnosed Type 2 diabetes (T2DM) and major depressive disorder (MDD). The patient was prescribed a ketogenic diet (KD), clinically formulated from her resting metabolic rate, body fat percentage and lean body mass, together with weekly nutrition education, high intensity interval training (matched to her cardiovascular conditioning), and eight 45-minute solution-focused psychotherapy sessions. Intervention goals included improved insulin sensitivity evaluated by the HOMA-IR, sustained glycemic control measured via HgA1c, reduced cardiovascular risk via the triglyceride/HDL ratio, and improved depressive symptoms with increased self-efficacy monitored by the PHQ-9 and GSE/MSC. The results of the 12-week intervention were statistically significant. The patient's HgA1c dropped out of diabetic range (8.0%) and normalized at 5.4%. Her average daily glucose measurements declined from 216 mg/dL to 96 mg/dL; the HOMA-IR and triglyceride/HDL ratios improved by 75%. Her marker for clinical depression and measurement of self-efficacy normalized. The 12-week individualized treatment intervention served to functionally reverse 26 years of T2DM, ameliorate two and half decades of chronic depressive disorder and empower/equip the patient with a new experience of hope and success., (Copyright © 2019 Diabetes India. Published by Elsevier Ltd. All rights reserved.)

Long-term exposure of concrete to nuclear reactor environments may enhance the ageing phenomena. An investigation concerning a possible deleterious alkali-silica reaction (ASR) in concrete containing high-density aggregates is presented in this paper. The scope of this investigation was limited to heavy aggregates that could be used for the construction of the first Polish nuclear power plant (NPP). Five different high-density aggregates were selected and tested: three barites, magnetite, and hematite. Mineralogical analysis was conducted using thin section microscopic observation in transmitted light. The accelerated mortar beam test and the long-time concrete prism test were applied to estimate the susceptibility of heavy aggregates to ASR. X-ray diffraction (XRD) and scanning electron microscopy (SEM) analyses were conducted on aggregates and mortars. The quartz size in aggregate grains was evaluated using image analysis. Application of the accelerated mortar beam method confirmed the observations of thin sections and XRD analysis of high-density aggregates. The microcrystalline quartz in hematite aggregate and cristobalite in one of barite aggregate triggered an ASR. The composition of ASR gel was confirmed by microscopic analysis. The long-term concrete test permitted the selection of innocuous high-density aggregates from among the other aggregates available, which showed practically no reactivity.

The objective of this paper is to examine the possible use of new blended cements containing calcareous fly ash in structural concrete, potentially adequate for structural elements of nuclear power plants. The investigation included five new cements made with different contents of non-clinker constituents: calcareous fly ash, siliceous fly ash, ground granulated blastfurnace slag, and a reference cement-ordinary Portland cement. The influence of innovative cements on the resistance of concrete to chloride and carbonation exposure was studied. Additionally, an evaluation of the microstructure was performed using optical microscopy on concrete thin sections. Test results revealed a substantial improvement of the resistance to chloride ion penetration into concrete containing blended cements. The resistance was higher for increased clinker replacement levels and increased with curing time. However, concrete made with blended cements exhibited higher depth of carbonation than the Portland cement concrete, except the Portland-fly ash cement with 14.3% of calcareous fly ash. The thin sections analysis confirmed the values of the carbonation depth obtained from the phenolphthalein test. Test results indicate the possible range of application for new cements containing calcareous fly ash.

The aim of the study was to generate rules for the prediction of the chloride resistance of concrete modified with high calcium fly ash using machine learning methods. The rapid chloride permeability test, according to the Nordtest Method Build 492, was used for determining the chloride ions' penetration in concrete containing high calcium fly ash (HCFA) for partial replacement of Portland cement. The results of the performed tests were used as the training set to generate rules describing the relation between material composition and the chloride resistance. Multiple methods for rule generation were applied and compared. The rules generated by algorithm J48 from the Weka workbench provided the means for adequate classification of plain concretes and concretes modified with high calcium fly ash as materials of good, acceptable or unacceptable resistance to chloride penetration.