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Abstract Non‐alcoholic fatty liver disease (NAFLD) is projected to be the most common chronic liver disease worldwide and is closely linked to obesity, insulin resistance and type 2 diabetes. Currently, no pharmacological treatments are available to treat NAFLD, and lifestyle modification, including dietary interventions, is the only remedy. Therefore, we conducted a study to determine whether supplementation with medium‐chain triglycerides (MCTs), containing a mixture of C8 and C10 (60/40), attenuates NAFLD in obese and insulin‐resistant mice. To achieve that, we fed C57BL/6 male mice a high‐fat diet (HFD) for 12 weeks to induce obesity and hepatic steatosis, after which obese mice were assigned randomly either to remain on the HFD or to transition to an HFD supplemented with MCTs (HFD + MCTs) or a low‐fat diet (LFD) for 6 weeks as another dietary intervention model. Another group of mice was kept on an LFD throughout the study and used as a lean control group. Obese mice that transitioned to HFD + MCTs exhibited improvement in glucose and insulin tolerance tests, and the latter improvement was independent of changes in adiposity when compared with HFD‐fed mice. Additionally, supplementation with MCTs significantly reduced hepatic steatosis, improved liver enzymes and decreased hepatic expression of inflammation‐related genes to levels similar to those observed in obese mice transitioned to an LFD. Importantly, HFD + MCTs markedly lowered hepatic ceramide and diacylglycerol content and prevented protein kinase C‐ε translocation to the plasma membrane. Our study demonstrated that supplementation with MCTs formulated mainly from C8 and C10 effectively ameliorated NAFLD in obese mice.

Abstract This study investigated whether oxidative and glycolytic rat skeletal muscles respond differently to a high-fat (HF) sucrose-enriched diet with respect to diacylglycerol (DAG) and ceramides accumulation, protein kinase C (PKC) activation, glucose metabolism, and the expression of inflammatory genes. HF diet (8 weeks) suppressed insulin-stimulated glycogen synthesis and glucose oxidation in soleus (Sol), extensor digitorum longus (EDL) and epitrochlearis (Epit) muscles. However, DAG and ceramides levels increased in Sol and EDL, but not in Epit muscles of HF-fed rats. Additionally, membrane-bound PKC-delta and PKC-theta increased in Sol and EDL, whereas in Epit muscles both PKC isoforms were reduced by HF diet. In Epit muscles, HF diet also increased the expression of tumor necrosis factor-α (TNF-α) receptors (CD40 and FAS), toll-like receptor 4 (TLR4), and nuclear factor kappa light polypeptide gene enhancer in B cells (NF-kB), whereas in Sol and EDL muscles the expression of these inflammatory genes remained unchanged upon HF feeding. In conclusion, HF diet caused DAG and ceramides accumulation, PKC activation, and the induction of inflammatory pathways in a fiber type-specific manner. These findings help explain why oxidative and glycolytic muscles similarly develop insulin resistance, despite major differences in their metabolic characteristics and responsiveness to dietary lipid abundance.

Adiponectin regulates white adipose tissue (WAT) metabolism and promotes insulin-sensitizing and anti-atherosclerotic effects in vivo. In this context, small molecule adiponectin receptor agonists have become of great therapeutic value for the treatment of metabolic diseases. Here, we investigated the effects of the adiponectin mimetic compound ALY688 on WAT metabolism. To accomplish this, rat epididymal (Epid) and subcutaneous inguinal (Sc Ing) adipocytes were isolated and incubated with ALY688. Subsequently, several parameters of glucose and fat metabolism were assessed. ALY688 promoted AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC) phosphorylation, enhanced glucose oxidation, and suppressed fat oxidation in adipocytes from both fat depots. ALY688 did not affect basal and insulin-stimulated rates of glucose uptake, glucose incorporation into lipids, and AKTSer473 and p38 mitogen-activated protein kinase (MAPK) phosphorylations in either Epid or Sc Ing adipocytes. ALY688 did not alter basal lipolysis in Epid and Sc Ing adipocytes, but it enhanced isoproterenol-induced lipolysis in Epid adipocytes. Adiponectin receptor 2 (AdipoR2) mRNA was the prevalent isoform expressed in all adipocytes, and Epid adipocytes displayed significantly higher AdipoR2 mRNA expression than Sc Ing adipocytes. In conclusion, ALY688 can regulate adiposity and affect glycaemic control by altering substrate portioning in the WAT in a fat depot-specific manner.

Abstract Background: Obesity can be characterized by low-grade chronic inflammation and is associated with an excesso production of reactive oxygen species, factors that contribute to coronary heart disease and other cardiomyopathies. Objective: To verify the effects of resistance exercise training on oxidative stress and inflammatory parameters on mice with obesity induced by a high-fat diet (HFD). Methods: 24 Swiss mice were divided into 4 groups: standard diet (SD), SD + resistance exercise (SD + RE), diet-induced obesity (DIO), DIO + RE. The animals were fed SD or HFD for 26 weeks and performed resistance exercises in the last 8 weeks of the study. The insulin tolerance test (ITT) and body weight monitoring were performed to assess the clinical parameters. Oxidative stress and inflammation parameters were evaluated in the cardiac tissue. Data were expressed by mean and standard deviation (p < 0.05). Results: The DIO group had a significant increase in reactive oxygen species levels and lipid peroxidation with reduction after exercise. Superoxide dismutase and the glutathione system showed no significant changes in DIO animals, with an increase in SD + RE. Only catalase activity decreased with both diet and exercise influence. There was an increase in tumor necrosis factor-alpha (TNF-α) in the DIO group, characterizing a possible inflammatory condition, with a decrease when exposed to resistance training (DIO+RE). Conclusion: The DIO resulted in a redox imbalance in cardiac tissue, but the RE was able to modulate these parameters, as well as to control the increase in TNF-α levels.

The paper looks into the most successful horror franchise in Philippine history. Shake, Rattle and Roll has had a successful 14-film run since its introduction in 1984, and is composed of a three-part segment, each tackling a horrific experience: ghosts and folk creatures in provincial and city settings. My paper maps out the narratives, and the social and political contexts of the series. Specif ically, the period beginning 1984 marks a series of national transition: the political crisis of the Marcoses, People Power 1, the rise of Corazon Aquino, the economic crises in 1997 and 2007, the ousting of Joseph Estrada, the rise of neoliberalism, the coming of Noynoy Aquino, and the incarceration of Gloria Arroyo. How might these films also be read as analog of the anxieties of the nation?

Impaired angiogenesis is a hallmark of metabolically dysfunctional adipose tissue in obesity. However, the underlying mechanisms restricting angiogenesis within this context remain ill-defined. Here, we demonstrate that induced endothelial-specific depletion of the transcription factor Forkhead Box O1 (FoxO1) in male mice led to increased vascular density in adipose tissue. Upon high-fat diet feeding, endothelial cell FoxO1-deficient mice exhibited even greater vascular remodeling in the visceral adipose depot, which was paralleled with a healthier adipose tissue expansion, higher glucose tolerance and lower fasting glycemia concomitant with enhanced lactate levels. Mechanistically, FoxO1 depletion increased endothelial proliferative and glycolytic capacities by upregulating the expression of glycolytic markers, which may account for the improvements at the tissue level ultimately impacting whole-body glucose metabolism. Altogether, these findings reveal the pivotal role of FoxO1 in controlling endothelial metabolic and angiogenic adaptations in response to high-fat diet and a contribution of the endothelium to whole-body energy homeostasis.

In this paper, we present a novel methodology to solve the classification problem, based on sparse (data-driven) regressions, combined with techniques for ensuring stability, especially useful for high-dimensional datasets and small samples number. The sensitivity and specificity of the classifiers are assessed by a stable ROC procedure, which uses a non-parametric algorithm for estimating the area under the ROC curve. This method allows assessing the performance of the classification by the ROC technique, when more than two groups are involved in the classification problem, i.e., when the gold standard is not binary. We apply this methodology to the EEG spectral signatures to find biomarkers that allow discriminating between (and predicting pertinence to) different subgroups of children diagnosed as Not Otherwise Specified Learning Disabilities (LD-NOS) disorder. Children with LD-NOS have notable learning difficulties, which affect education but are not able to be put into some specific category as reading (Dyslexia), Mathematics (Dyscalculia), or Writing (Dysgraphia). By using the EEG spectra, we aim to identify EEG patterns that may be related to specific learning disabilities in an individual case. This could be useful to develop subject-based methods of therapy, based on information provided by the EEG. Here we study 85 LD-NOS children, divided in three subgroups previously selected by a clustering technique over the scores of cognitive tests. The classification equation produced stable marginal areas under the ROC of 0.71 for discrimination between Group 1 vs. Group 2; 0.91 for Group 1 vs. Group 3; and 0.75 for Group 2 vs. Group1. A discussion of the EEG characteristics of each group related to the cognitive scores is also presented.

This study investigated the effect of chronic AMP-kinase (AMPK) activation with 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR) on white adipose tissue (WAT) metabolism and the implications for visceral (VC) and subcutaneous (SC) adiposity, whole body-energy homeostasis, and hypothalamic leptin sensitivity. Male Wistar rats received daily single intraperitoneal injections of either saline or AICAR (0.7g/kg body weight) for 4 and 8 weeks and were pair-fed throughout the study. AICAR-treated rats had reduced adiposity with increased mitochondrial density in VC and SC fat pads, which was accompanied by reduced circulating leptin and time-dependent and depot-specific regulation of AMPK phosphorylation and FA oxidation. Interestingly, the anorectic effect to exogenous leptin was more pronounced in AICAR-treated animals than controls. This corresponded to reductions in hypothalamic AMPK phosphorylation and suppressor of cytokine signaling 3 content, whereas signal transducer and activator of transcription 3 phosphorylation was either unchanged or increased at 4 and 8 weeks in AICAR-treated rats. Ambulatory activity and whole-body energy expenditure (EE) were also increased with AICAR treatment. Altogether, chronic AICAR-induced AMPK activation increased WAT oxidative machinery, whole-body EE, and hypothalamic leptin sensitivity. This led to significant reductions in VC and SC adiposity without inducing energy-sparing mechanisms that oppose long-term fat loss.

This essay explores the trope of the vaginal economy that is proliferated in the political economy and nature of Philippine migration. The vaginal economy is both receptacle and symptom of Philippine development. It represents the discourse through cinema, and historicizes the primal debate in the Marcos and Brocka contestation for image-building of the nation. Primarily through the sex-oriented (bomba) films and their permutations in the various political life of the contemporary nation, the vaginal economy is historicized even in the after-life of the post-Marcos and post-Brocka era.

The essay examines the racial discourse of Moros and Moro-profiling by the state in piracy—sea piracy in olden times and media piracy in contemporary times. Moro piracy becomes a local cosmopolitanism in the Philippines’ attempt to integrate in various eras of global capitalism. From the analysis of media piracy, the Moro “dibidi” (pirated DVD) seller becomes the body that mediates between the Filipinos’ middle-class fantasy of a branded lifestyle and the reality that most Filipinos do not have full access to global consumerism. Using a cultural studies framework, the essay draws a connection between seemingly unlinked events and sources, allowing for a historical and social dialog, past and present, to mix, creating junctures for sites of dialog and critique.

This study was designed to investigate the effects of prolonged activation of AMP-activated protein kinase (AMPK) on lipid partitioning and the potential molecular mechanisms involved in these processes in white adipose tissue (WAT). Rat epididymal adipocytes were incubated with 5′-aminoimidasole-4-carboxamide-1-β-d-ribofuranoside (AICAR;0.5 mM) for 15 h. Also, epididymal adipocytes were isolated 15 h after AICAR was injected (i.p. 0.7 g/kg body weight) in rats. Adipocytes were utilized for various metabolic assays and for determination of gene expression and protein content. Time-dependent in vivo plasma NEFA concentrations were determined. AICAR treatment significantly increased AMPK activation, inhibited lipogenesis, and increased FA oxidation. This was accompanied by upregulation of peroxisome proliferator-activated receptor (PPAR)α, PPARδ, and PPARγ-coactivator-1α (PGC-1α) mRNA levels. Lipolysis was first suppressed, but then increased, both in vitro and in vivo, with prolonged AICAR treatment. Exposure to AICAR increased adipose triglyceride lipase (ATGL) content and FA release, despite inhibition of basal and epinephrine-stimulated hormone-sensitive lipase (HSL) activity. Here, we provide evidence that prolonged AICAR-induced AMPK activation can remodel adipocyte metabolism by upregulating pathways that favor energy dissipation versus lipid storage in WAT. Additionally, we show novel time-dependent effects of AICAR-induced AMPK activation on lipolysis, which involves antagonistic modulation of HSL and ATGL.

Slum Imaginarles and Spatial Justice in Philippine Cinema. By Katrina Macapagal. Edinburgh: Edinburgh University Press, 2021. 204 pp. The book explores contemporary urban cinema or city films in the Philippines, [...]

This study tested whether the glycogen-accumulating effect of chronic in vivo pharmacological 5'AMP-activated protein kinase (AMPK) activation could improve glycemic control under conditions of insulin deficiency. Male Wistar rats were rendered diabetic through the administration of streptozotocin (STZ) and then treated for 7 consecutive days with the AMPK activator 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR). Subsequently, glycogen content and synthesis, glucose oxidation, and fatty acid oxidation (FAO) were determined in oxidative and glycolytic skeletal muscles. Glycemia, insulinemia, glucagonemia, and circulating triglycerides (TG) and non-esterified fatty acids (NEFAs) were measured after AICAR treatment. Insulin was almost undetectable in STZ rats and these animals were severely hyperglycemic. Glycogen content was markedly low mainly in glycolytic muscles of STZ rats and AICAR treatment restored it to control values. No differences were found among all muscles studied with regards to the content and phosphorylation of Akt/protein kinase B and glycogen synthase kinase 3. Even though glycogen synthase content was reduced in all muscles from STZ rats, insulin-induced dephosphorylation/activation of this enzyme was preserved and unaffected by AICAR treatment. Glucagon and NEFAS were 2- and 7.4-fold fold higher in STZ rats than controls, respectively. AICAR did not affect hyperglycemia and hyperglucagonemia in STZ rats; however, it normalized circulating NEFAs and significantly increased FAO in glycolytic muscles. In conclusion, even though AICAR-induced AMPK activation enhanced glycogen accumulation in glycolytic muscles and normalized circulating NEFAs and TG levels, the hyperglycemic effects of glucagon likely offset the potentially glucose-lowering effects of AICAR, resulting in no improvement of glycemic control in insulin-deficient rats.

BACKGROUND: Diet-induced obesity is a rising health concern which can lead to the development of glucose intolerance and muscle insulin resistance and, ultimately, type II diabetes mellitus. This research investigates the associations between glucose intolerance or muscle insulin resistance and tissue specific changes during the progression of diet-induced obesity. METHODOLOGY: C57BL/6J mice were fed a normal or high-fat diet (HFD; 60% kcal fat) for 3 or 8 weeks. Disease progression was monitored by measurements of body/tissue mass changes, glucose and insulin tolerance tests, and ex vivo glucose uptake in intact muscles. Lipid metabolism was analyzed using metabolic chambers and ex vivo palmitate assays in intact muscles. Skeletal muscle, liver and adipose tissues were analyzed for changes in inflammatory gene expression. Plasma was analyzed for insulin levels and inflammatory proteins. Histological techniques were used on muscle and liver cryosections to assess metabolic and morphological changes. PRINCIPAL FINDINGS/CONCLUSIONS: A rapid shift in whole body metabolism towards lipids was observed with HFD. Following 3 weeks of HFD, elevated total lipid oxidation and an oxidative fiber type shift had occurred in the skeletal muscle, which we propose was responsible for delaying intramyocellular lipid accumulation and maintaining muscle's insulin sensitivity. Glucose intolerance was present after three weeks of HFD and was associated with an enlarged adipose tissue depot, adipose tissue inflammation and excess hepatic lipids, but not hepatic inflammation. Furthermore, HFD did not significantly increase systemic or muscle inflammation after 3 or 8 weeks of HFD suggesting that early diet-induced obesity does not cause inflammation throughout the whole body. Overall these findings indicate skeletal muscle did not contribute to the development of HFD-induced impairments in whole-body glucose tolerance following 3 weeks of HFD.

This study tested whether chronic systemic administration of 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR) could attenuate hyperphagia, reduce lean and fat mass losses, and improve whole-body energy homeostasis in insulin-deficient rats. Male Wistar rats were first rendered diabetic through streptozotocin (STZ) administration and then intraperitoneally injected with AICAR for 7 consecutive days. Food and water intake, ambulatory activity, and energy expenditure were assessed at the end of the AICAR-treatment period. Blood was collected for circulating leptin measurement and the hypothalami were extracted for the determination of suppressor of cytokine signaling 3 (SOCS3) content, as well as the content and phosphorylation of AMP-kinase (AMPK), acetyl-CoA carboxylase (ACC), and the signal transducer and activator of transcription 3 (STAT3). Rats were thoroughly dissected for adiposity and lean body mass (LBM) determinations. In non-diabetic rats, despite reducing adiposity, AICAR increased (∼1.7-fold) circulating leptin and reduced hypothalamic SOCS3 content and food intake by 67% and 25%, respectively. The anorexic effect of AICAR was lost in diabetic rats, even though hypothalamic AMPK and ACC phosphorylation markedly decreased in these animals. Importantly, hypothalamic SOCS3 and STAT3 levels remained elevated and reduced, respectively, after treatment of insulin-deficient rats with AICAR. Diabetic rats were lethargic and displayed marked losses of fat and LBM. AICAR treatment increased ambulatory activity and whole-body energy expenditure while also attenuating diabetes-induced fat and LBM losses. In conclusion, AICAR did not reverse hyperphagia, but it promoted anti-catabolic effects on skeletal muscle and fat, enhanced spontaneous physical activity, and improved the ability of rats to cope with the diabetes-induced dysfunctional alterations in glucose metabolism and whole-body energy homeostasis.

BACKGROUND:The effects of diet-induced obesity on skeletal muscle function are largely unknown, particularly as it relates to changes in oxidative metabolism and morphology. PRINCIPAL FINDINGS:Compared to control fed mice, mice fed a high fat diet (HFD; 60% kcal: fat) for 8 weeks displayed increased body mass and insulin resistance without overt fasting hyperglycemia (i.e. pre-diabetic). Histological analysis revealed a greater oxidative potential in the HFD gastrocnemius/plantaris (increased IIA, reduced IIB fiber-type percentages) and soleus (increased I, IIA cross-sectional areas) muscles, but no change in fiber type percentages in tibialis anterior muscles compared to controls. Intramyocellular lipid levels were significantly increased relative to control in HFD gastrocnemius/plantaris, but were similar to control values in the HFD soleus. Using a novel, single muscle fiber approach, impairments in complete palmitate and glucose oxidation (72.8+/-6.6% and 61.8+/-9.1% of control, respectively; p

Aim/Purpose: The study examined how the developed mobile courseware can be used as instructional material to improve senior high school statistics and probability learning, particularly during distance learning caused by the COVID-19 pandemic. The study also aims to assess the gamified mobile courseware's engagement, functionality, aesthetics, and information quality using the Mobile App Rating Scale (MARS) and a researcher-made Gamified Mobile Courseware Assessment Tool (GMCET). Background: The need to investigate the effectiveness of incorporating game-based elements into mathematics courses through innovative instructional materials inspired the study. The COVID-19 pandemic has made distance learning a necessity, and gamified mobile courseware is a potential solution to improve learning outcomes and engagement in mathematics courses. Methodology: The study employed a descriptive-evaluative method with quantitative and qualitative data to achieve its objectives. Five IT practitioners assessed the developed courseware using the MARS regarding engagement, functionality, aesthetics, and information. A researcher-made GMCET was also used to evaluate the app's content quality, learning objectives, content presentation, learning assessment, and usability. Five math experts and 12 math teachers rated the app using the GMCET. The study used weighted mean to analyze the quantitative data and content analysis for the qualitative data. Contribution: The study provides insights into the strengths and weaknesses of gamified mobile courseware from the perspective of IT practitioners, math experts, and math teachers. The study's findings can inform improvements in future iterations of courseware, and the study provides a valuable guide for practitioners looking to develop gamified mobile courseware for mathematics courses. Findings: The quantitative results based on the weighted mean indicate that the IT practitioners had a moderately positive perception of the developed courseware across all categories. At the same time, the math teachers and math experts showed highly positive perceptions of the gamified mobile courseware in Statistics and Probability, rating it highly across all categories. The qualitative data analysis through content analysis highlights the need for improving the user interface, usability, user experience design, user control, flexibility in interaction, data quality, reliability, and user privacy of the developed app. Recommendations for Practitioners: Practitioners can use the study's findings to improve the design of gamified mobile courseware for mathematics courses and other content areas. The study recommends that practitioners focus on improving the user interface, usability, user experience design, user control, flexibility in interaction, data quality, reliability, and user privacy of gamified mobile courseware. Recommendations for Researchers: Future research can build on this study's findings by exploring the use of gamified mobile courseware in other mathematical courses and other subject areas. Further research can also examine how gamified mobile courseware can improve learning outcomes for students with different learning needs. Impact on Society: The study's findings could improve the effectiveness of gamified mobile courseware in enhancing student learning outcomes in mathematics courses. This can lead to better student performance, improved engagement, and increased interest in mathematics courses, positively impacting society. Future Research: Future research can explore using gamified mobile courseware in other mathematics courses and other subject areas. Additionally, future studies can examine how gamified mobile courseware can improve learning outcomes for students with different learning needs. Further research can also investigate the impact of gamified mobile courseware on student motivation, interest, and performance in mathematics courses.

Molecular farming is an evolving field in Cuba; therefore, establishing the guidelines guaranteeing the quality, safety and efficacy of biopharmaceutical products is a challenge for the National Regulatory Agency (Center for State Control on the Quality of Drugs; CECMED). The methodology to elaborate guidelines for this type of products was mainly based on the revision of the legal and regulatory international framework, the evaluation of the current and prospective developmental stage of the technology in Cuba and the comparative analysis among the manufacturing process steps of a biotechnological product obtained in traditional expression systems and that derived from transgenic plants. A first draft of the regulatory document was compared to guidance drafts issued by other regulatory agencies (such as FDA and EMEA) and extensively reviewed by CECMED specialists as well as by experts of the local biotech industry. As a result, a regulation project was elaborated, and its applicability tested while the assessment of an application for scientific advisory, related to product obtained by this technology. Finally, the regulation was approved, being applicable for products generated in genetically modified plants. It is also valid for edible vaccines and other compounds which do not constitute active pharmaceutical ingredients.

Indigenous students faced various challenges that could hinder their academic success. The Indigenous Peoples' Rights Act (IPRA), the United Nations Declaration on the Rights of Indigenous Peoples (UNDRIP), and the Indigenous Peoples' Education (IPEd) Policy and Framework (DepEd Order No. 32, s. 2015) all contributed to strengthening the indigenous rights movement. The research sought the influence of study habits on the academic achievement of Grade 6 indigenous students in the District of San Marcelino. The goal was to improve the quality of education through effective classroom instruction. The research investigated the correlation between study habits and academic achievement in Grade 6 IPEd students in the 2022-2023 school year. Two factors were considered: individual factors such as age, gender, birth order, mother's highest educational attainment, and father's highest educational attainment, as well as instructional factors such as interest and study habits. The research was done in San Marcelino District Schools, Division of Zambales. The participants were randomly selected from eight out of the twenty-one public elementary schools in the district. The main instrument of the data was a survey questionnaire. The collected data were analyzed using simple statistical tools, including frequency count, mean, standard deviation, and inferential statistics. The hypothesis was tested using F-Test or ANOVA and Pearson R Correlation at a significance level of 0.05. The findings indicated that the participants had a diverse mix in age, gender, birth order, and their parents' education. Most participants were between 11 and 12 years old, with an almost equal number of males and females. The distribution of birth order varied, with a majority being either the first-born or fifth-born or above. Furthermore, the parents' educational background ranged from elementary education to college. The study found a correlation between the academic performance of Grade 6 IPED learners and their study habits. This correlation was moderate in strength and statistically significant, indicating that IPED learners with good study habits had a higher likelihood of achieving higher grades. [ABSTRACT FROM AUTHOR]

Abstract Background Despite rolling out publicly-funded hepatitis C virus (HCV) treatment across the province of British Columbia (BC), Canada, 35% of people returning positive HCV RNA results in 2020 did not initiate treatment. The HCV epidemic in Canada continues to disproportionately impact people who use drugs and yet, this population has the lowest proportional uptake of HCV treatment. Evidence suggests linkages to healthcare after diagnosis is one of the key factors that impacts uptake of HCV treatment among this priority population. The Hep C Connect pilot project was implemented to characterize HCV testing outcomes and linkage-to-care rates within a low-barrier supervised consumption site (SCS) in Vancouver, BC. Methods All clients (aged ≥ 19 years) attending the Hope to Health SCS in Vancouver, Canada were invited to participate in the pilot study between November 2021 and December 2022. Interviewer-led surveys were conducted and participants were offered same-day HCV point-of-care (POC) antibody (Ab) testing. Participants received a cash honorarium for sharing their time and experiences. Descriptive statistics are shared in order to describe the reach and impact of this pilot project. Results The study enrolled 186 participants including 123(66.1%) men and 59(31.7%) women, with a median age of 42 (Q1,Q3- 34,49). Forty-seven (25.3%) participants stated that they use an SCS regularly and 123(66.1%) stated that they get new rigs every day. Notably, 64(34.4%) participants reported not having a primary care provider yet more than three-quarters of the participants (144, 77.4%) reported having been ever tested for HCV. All 186 participants agreed to HCV POC Ab testing with 59.7% returning a positive HCV POC Ab result. Despite good HCV POC Ab uptake and high rates of HCV knowledge, 49(44.1%) of the HCV Ab positive participants chose not to engage in confirmatory ribonucleic acid (RNA) testing. Conclusions The Hep C Connect pilot explored the gaps evident in the HCV cascade-of-care as it pertains to people who use drugs. Findings suggest that, despite high levels of HCV knowledge, the employment of blood draw RNA testing deterred people from engaging in confirmatory testing. Improving the HCV cascade-of-care will require alternative strategies that are more acceptable to this population.

Aging leads to deterioration of the functional capacities and increases individuals’ vulnerability. This descriptive, cross-sectional study characterized older adults with cognitive impairment from the Basic Work Group No. 2 in the Ramón López Peña University Hospital, in Santiago de Cuba, between January 2022 and January 2023. The study included a sample of 124 older adults who met the established inclusion criteria. Sociodemographic and clinical variables—such as age, sex, occupation, educational level, and independence to conduct daily life activities—were analyzed using descriptive statistics techniques. The results showed that cognitive impairments were most prevalent among individuals aged 60 to 69 (49.9%), women (55.6%), married individuals (41.9%), those with higher education (41.9%), and retirees (50.8%). The most common risk factors were a sedentary lifestyle (64.5%) and malnutrition (55.6%), while high blood pressure was the most observed comorbidity (41.9%). The findings showed that cognitive impairment was particularly more prevalent among married and retired women. Although the participants’ independence in basic activities in their daily lives remained significantly unaffected by their cognitive impairment, notable difficulties were observed in instrumental activities such as washing clothes, using the telephone and managing finances.

Non‐alcoholic fatty liver disease (NAFLD) is projected to be the most common chronic liver disease worldwide and is closely linked to obesity, insulin resistance and type 2 diabetes. Currently, no pharmacological treatments are available to treat NAFLD, and lifestyle modification, including dietary interventions, is the only remedy. Therefore, we conducted a study to determine whether supplementation with medium‐chain triglycerides (MCTs), containing a mixture of C8 and C10 (60/40), attenuates NAFLD in obese and insulin‐resistant mice. To achieve that, we fed C57BL/6 male mice a high‐fat diet (HFD) for 12 weeks to induce obesity and hepatic steatosis, after which obese mice were assigned randomly either to remain on the HFD or to transition to an HFD supplemented with MCTs (HFD + MCTs) or a low‐fat diet (LFD) for 6 weeks as another dietary intervention model. Another group of mice was kept on an LFD throughout the study and used as a lean control group. Obese mice that transitioned to HFD + MCTs exhibited improvement in glucose and insulin tolerance tests, and the latter improvement was independent of changes in adiposity when compared with HFD‐fed mice. Additionally, supplementation with MCTs significantly reduced hepatic steatosis, improved liver enzymes and decreased hepatic expression of inflammation‐related genes to levels similar to those observed in obese mice transitioned to an LFD. Importantly, HFD + MCTs markedly lowered hepatic ceramide and diacylglycerol content and prevented protein kinase C‐ε translocation to the plasma membrane. Our study demonstrated that supplementation with MCTs formulated mainly from C8 and C10 effectively ameliorated NAFLD in obese mice. What is the central question of this study?Medium‐chain triglycerides (MCTs) originate from coconut oil. Variations in the types of MCT molecules and their ratios influence their hepatoprotective properties. We aimed to investigate the effects of supplementation with MCTs, consisting primarily of C8 and C10, and not C12 that is abundant in coconut oil, on hepatic steatosis.What is the main finding and its importance?Supplementation with MCTs reduced hepatic steatosis and inflammation while improving liver enzyme levels in obese mice. Moreover, supplementation with MCTs lowered hepatic lipotoxicity and enhanced glucose homeostasis independent of adiposity. [ABSTRACT FROM AUTHOR]

Skeletal muscle substrate preference for fuel is largely influenced by dietary macronutrient availability. The abundance of dietary carbohydrates promotes the utilization of glucose as a substrate for energy production, whereas an abundant dietary fat supply elevates rates of fatty acid (FA) oxidation. The objective of this study was to determine whether an obesogenic, high-fat, sucrose-enriched (HFS) diet or a carbohydrate-free ketogenic diet (KD) exert distinct effects on fat, glucose, and ketone metabolism in oxidative and glycolytic skeletal muscles. Male Wistar rats were fed either a HFS diet or a KD for 16 weeks. Subsequently, the soleus (Sol), extensor digitorum longus (EDL), and epitrochlearis (Epit) muscles were extracted to measure palmitate oxidation, insulin-stimulated glucose metabolism, and markers of mitochondrial biogenesis, ketolytic capacity, and cataplerotic and anaplerotic machinery. Sol, EDL, and Epit muscles from KD-fed rats preserved their ability to elevate glycogen synthesis and lactate production in response to insulin, whereas all muscles from rats fed with the HFS diet displayed blunted responses to insulin. The maintenance of metabolic flexibility with the KD was accompanied by muscle-fiber-type-specific adaptive responses. This was characterized by the Sol muscle in KD-fed rats enhancing mitochondrial biogenesis and ketolytic capacity without elevating its rates of FA oxidation in comparison with that in HFS feeding. Conversely, in the Epit muscle, rates of FA oxidation were increased, whereas the ketolytic capacity was markedly reduced by the KD in comparison with that by HFS feeding. In the EDL muscle, the KD also increased rates of FA oxidation, although it did so without altering its ketolytic capacity when compared to HFS feeding. In conclusion, even though obesogenic and ketogenic diets have elevated contents of fat and alter whole-body substrate partitioning, these two dietary interventions are associated with opposite outcomes with respect to skeletal muscle metabolic flexibility. [ABSTRACT FROM AUTHOR]

Abstract The mesophotic zone represents one of our planet’s largest and least explored biomes. An increasing number of studies evidence the importance of macrofouling species in marine ecosystems, but information on these communities and the factors influencing their structures at mesophotic depths remain poor. This lack of understanding limits our ability to predict anthropogenic impacts or conduct restoration operations in the mesophotic and the lower boundary of the euphotic zones. In this study, we performed a 24-month experiment in a natural environment to investigate three factors influencing the macrobenthic community structure of the mesophotic and the euphotic lower boundary: depth, substrate orientation and substrate material. Using a manned submersible, several recruitment panels of two different materials were deployed at 100, 200 and 400 meters in vertical and horizontal positions. All three factors contributed to structuring the macrofouling communities, but depth and substrate orientation displayed the strongest effects. This study not only advances our understanding of lower boundary euphotic and mesophotic macrofouling communities but also establishes a foundation for future research and restoration efforts of mesophotic environments in the Madeira archipelago, where mesophotic habitats are amongst the least studied marine habitats in the Northeast Atlantic.

This study investigated the role of diacylglycerol (DAG)‐mediated protein kinase C (PKC) activation, ceramide accumulation and inflammation in insulin‐resistant female oxidative and glycolytic skeletal muscles induced by an obesogenic high‐fat sucrose‐enriched (HFS) diet. The HFS diet impaired insulin‐stimulated AKTThr308 phosphorylation and glycogen synthesis, whereas rates of fatty acid oxidation and basal lactate production were significantly elevated in soleus (Sol), extensor digitorum longus (EDL) and epitrochlearis (Epit) muscles. Insulin resistance was accompanied by increases in triacylglycerol (TAG) and DAG contents in Sol and EDL, whereas in Epit muscles only TAG content and markers of inflammation were associated with HFS diet‐induced insulin resistance. Analysis of membrane‐bound/cytoplasmic PKC fractions revealed that the HFS diet promoted activation/translocation of PKCδ and θ isoforms in Sol, EDL and Epit muscles. However, none of these muscles displayed alterations in ceramide content in response to HFS feeding. This could be explained by a significant increase in Dgat2 mRNA expression in Sol, EDL and Epit muscles, which likely diverted most of the intramyocellular acyl‐CoAs toward TAG synthesis instead of ceramides. Overall, this study helps elucidate the molecular mechanisms underlying insulin resistance caused by diet‐induced obesity in female skeletal muscles with distinct fibre type compositions. Key points: Feeding female Wistar rats a high‐fat sucrose‐enriched diet (HFS) led to diacylglycerol (DAG)‐induced PKC activation and insulin resistance in oxidative and glycolytic skeletal muscles.HFS diet‐induced toll‐like receptor 4 (Tlr4) expression did not lead to increased ceramide content in female skeletal muscles.In highly glycolytic female muscles, elevated TAG content and markers of inflammation underlay HFS diet‐induced insulin resistance.The HFS diet suppressed glucose oxidation and increased lactate production in oxidative and glycolytic female muscles.Increased Dgat2 mRNA expression likely diverted most of the intramyocellular acyl‐CoAs toward TAG synthesis and prevented ceramide formation in skeletal muscles of HFS‐fed female rats. [ABSTRACT FROM AUTHOR]

Brown adipose tissue (BAT) is rich in mitochondria containing uncoupling protein 1 (UCP1), and dissipates energy through thermogenesis. However, even though BAT mass and its UCP1 content increase in rodents chronically fed a high‐fat sucrose‐enriched (HFS) diet, marked expansion of adiposity still occurs in these animals, suggesting insufficient BAT‐mediated HFS diet‐induced thermogenesis. Thus, the objective of this study was to investigate the metabolic and molecular mechanisms that regulate BAT thermogenesis in HFS‐induced obesity. To accomplish this, rats were fed either a standard chow or HFS diet for 8 weeks. Subsequently, glucose and fatty acid metabolism and the molecular mechanisms underlying these processes were assessed in freshly isolated primary BAT adipocytes. Despite increasing BAT mass and its UCP1 content, the HFS diet reduced uncoupled glucose and palmitate oxidation in BAT adipocytes. It also markedly diminished tyrosine hydroxylase content and lipolysis in these cells. Conversely, glucose uptake, lactate production, glycerol incorporation into lipids, palmitate incorporation into triacylglycerol (TAG), phosphoenolpyruvate carboxykinase and glycerol kinase levels, and lipoprotein lipase and cluster of differentiation 36 gene expression were increased. In summary, a HFS diet enhanced glyceroneogenesis and shifted BAT metabolism toward TAG synthesis by impairing UCP1‐mediated substrate oxidation and by enhancing fatty acid esterification in intact brown adipocytes. These adaptive metabolic responses to chronic HFS feeding attenuated BAT thermogenic capacity and favoured the development of obesity. Key points: Despite increasing brown adipose tissue (BAT) mass and levels of thermogenic proteins such as peroxisome proliferator‐activated receptor γ coactivator 1α, carnitine palmitoyltransferase 1B and uncoupling protein 1 (UCP1), an obesogenic high‐fat sucrose‐enriched (HFS) diet attenuated uncoupled glucose and fatty acid oxidation in brown adipocytes.Brown adipocytes diverted glycerol and fatty acids toward triacylglycerol (TAG) synthesis by elevating the cellular machinery that promotes fatty acid uptake along with phosphoenolpyruvate carboxykinase and glycerol kinase levels.The HFS diet increased glucose uptake that supported lactate production and provided substrate for glyceroneogenesis and TAG synthesis in brown adipocytes.Impaired UCP‐1‐mediated thermogenic capacity and enhanced TAG storage in BAT adipocytes were consistent with reduced adipose triglyceride lipase and tyrosine hydroxylase levels in HFS diet‐fed animals. [ABSTRACT FROM AUTHOR]

Aim/Purpose: The study examined how the developed mobile courseware can be used as instructional material to improve senior high school statistics and probability learning, particularly during distance learning caused by the COVID-19 pandemic. The study also aims to assess the gamified mobile courseware's engagement, functionality, aesthetics, and information quality using the Mobile App Rating Scale (MARS) and a researcher-made Gamified Mobile Courseware Assessment Tool (GMCET). Background: The need to investigate the effectiveness of incorporating game-based elements into mathematics courses through innovative instructional materials inspired the study. The COVID-19 pandemic has made distance learning a necessity, and gamified mobile courseware is a potential solution to improve learning outcomes and engagement in mathematics courses. Methodology: The study employed a descriptive-evaluative method with quantitative and qualitative data to achieve its objectives. Five IT practitioners assessed the developed courseware using the MARS regarding engagement, functionality, aesthetics, and information. A researcher-made GMCET was also used to evaluate the app's content quality, learning objectives, content presentation, learning assessment, and usability. Five math experts and 12 math teachers rated the app using the GMCET. The study used weighted mean to analyze the quantitative data and content analysis for the qualitative data. Contribution: The study provides insights into the strengths and weaknesses of gamified mobile courseware from the perspective of IT practitioners, math experts, and math teachers. The study's findings can inform improvements in future iterations of courseware, and the study provides a valuable guide for practitioners looking to develop gamified mobile courseware for mathematics courses. Findings: The quantitative results based on the weighted mean indicate that the IT practitioners had a moderately positive perception of the developed courseware across all categories. At the same time, the math teachers and math experts showed highly positive perceptions of the gamified mobile courseware in Statistics and Probability, rating it highly across all categories. The qualitative data analysis through content analysis highlights the need for improving the user interface, usability, user experience design, user control, flexibility in interaction, data quality, reliability, and user privacy of the developed app. Recommendations for Practitioners: Practitioners can use the study's findings to improve the design of gamified mobile courseware for mathematics courses and other content areas. The study recommends that practitioners focus on improving the user interface, usability, user experience design, user control, flexibility in interaction, data quality, reliability, and user privacy of gamified mobile courseware. Recommendations for Researchers: Future research can build on this study's findings by exploring the use of gamified mobile courseware in other mathematical courses and other subject areas. Further research can also examine how gamified mobile courseware can improve learning outcomes for students with different learning needs. Impact on Society: The study's findings could improve the effectiveness of gamified mobile courseware in enhancing student learning outcomes in mathematics courses. This can lead to better student performance, improved engagement, and increased interest in mathematics courses, positively impacting society. Future Research: Future research can explore using gamified mobile courseware in other mathematics courses and other subject areas. Additionally, future studies can examine how gamified mobile courseware can improve learning outcomes for students with different learning needs. Further research can also investigate the impact of gamified mobile courseware on student motivation, interest, and performance in mathematics courses. [ABSTRACT FROM AUTHOR]

The use of routinely collected administrative health data for research can provide unique insights to inform decision-making and, ultimately, support better public health outcomes. Yet, since these data are primarily collected to administer healthcare service delivery, challenges exist when using such data for secondary purposes, namely epidemiologic research. Many of these challenges stem from the researcher's lack of control over the quality and consistency of data collection, and - furthermore - a lessened understanding of the data being analyzed. That said, we assert that these challenges can be partly mitigated through careful, systematic use of these data in epidemiologic research. This article presents considerations derived from experiences analyzing administrative health data (e.g., healthcare practitioner billings, hospitalizations, and prescription medication data) in the Canadian province of British Columbia (population of over 5 million in 2024), though we believe the underlying principles generalize beyond this region. Key considerations were organized around four themes: 1) Know the data and their primary use (understand their scope and limitations); 2) Understand classification and coding systems (appreciate the nuances regarding classification systems, versions, how they are employed in the primary uses of the data, and querying the values); 3) Transform data into meaningful forms (process data and apply identification algorithms, when necessary); 4) Recognize the importance of validity when defining analytic variables (make meaningful inferences based on data/algorithms). Although this article is not an exhaustive list of all considerations, we believe that it will provide pragmatic insights for those interested in leveraging administrative health data for epidemiologic research.

This study investigated the molecular mechanisms by which a high-fat diet (HFD) dysregulates lipolysis and lipid metabolism in mouse epididymal (visceral, VC) and inguinal (subcutaneous, SC) adipocytes. Eight-weeks of HFD feeding increased adipose triglyceride lipase (ATGL) content and comparative gene identification-58 (CGI-58) expression, whereas hormone-sensitive lipase (HSL) phosphorylation and perilipin content were severely reduced. Adipocytes from HFD mice elicited increased basal but blunted epinephrine-stimulated lipolysis and increased diacylglycerol content in both fat depots. Consistent with impaired adrenergic receptor signaling, HFD also increased adipose-specific phospholipase Az expression in both fat depots. Inhibition of E-prostanoid 3 receptor increased basal lipolysis in control adipocytes but failed to acutely alter the effects of HFD on lipolysis in both fat depots. In HFD visceral adipocytes, activation of adenylyl cyclases by forskolin increased HSL phosphorylation and surpassed the lipolytic response of control cells. However, in HFD subcutaneous adipocytes, forskolin induced lipolysis without detectable HSL phosphorylation, suggesting activation of an alternative lipase in response to HFD-induced suppression of HSL in VC and SC adipocytes. HFD also powerfully inhibited basal, epinephrine-, and forskolin-induced AMP kinase (AMPK) activation as well peroxisome proliferator-activated receptor gamma coactivator-1[alpha] expression, citrate synthase activity, and palmitate oxidation in both fat depots. In summary, novel evidence is provided that defective adrenergic receptor signaling combined with upregulation of ATGL and suppression of HSL and AMPK signaling mediate HFD-induced alterations in lipolysis and lipid utilization in VC and SC adipocytes, which may play an important role in defective lipid mobilization and metabolism seen in diet-induced obesity. adipose tissue; adipose triglyceride lipase; hormone-sensitive lipase; AMP kinase doi: 10.1152/ajpcell.00547.2009.

Obesity‐associated insulin resistance plays a major role in the pathogenesis of non‐alcoholic fatty liver disease (NAFLD). The accumulation of diacylglycerol (DAG), ceramides and inflammation are key factors that cause NAFLD. In recent years, the ketogenic diet (KD) has emerged as an effective non‐pharmacological intervention for the treatment of NAFLD and other obesity‐related metabolic disorders. What remains undetermined is how the KD affects DAG and ceramide content and insulin sensitivity in the liver. Thus, this research was designed to assess these variables, as well as glucose and fat metabolism and markers of inflammation in livers of rats exposed for 8 weeks to one of the following diets: standard chow (SC), obesogenic high‐fat, sucrose‐enriched diet (HFS) or a KD. Despite having a higher fat content than the HFS diet, the KD did not cause steatosis and preserved hepatic insulin signalling. The KD reduced DAG content and protein kinase C‐ε activity, but markedly increased liver ceramide content. However, whereas the KD increased ceramide synthase 2 (CerS2) expression, it suppressed CerS6 expression, an effect that promoted the production of beneficial very long‐chain ceramides instead of harmful long‐chain ceramides. The KD also enhanced the liver expression of key genes involved in mitochondrial biogenesis and fatty acid oxidation (Pgc‐1α and Fgf21), suppressed inflammatory genes (Tnfα, Nf‐kb, Tlr4 and Il6), and shifted substrate away from de novo lipogenesis. Thus, through multiple mechanisms the KD exerted anti‐steatogenic and insulin‐sensitizing effects in the liver, which supports the use of this dietary intervention to treat NAFLD. Key points: The accumulation of diacylglycerol (DAG), ceramides and inflammation are key factors that cause insulin resistance and non‐alcoholic fatty liver disease (NAFLD). This study provides evidence that a ketogenic diet (KD) rich in fat and devoid of carbohydrate reduced DAG content and preserved insulin signalling in the liver.The KD shifted metabolism away from lipogenesis by enhancing genes involved in mitochondrial biogenesis and fatty acid oxidations in the liver.The KD also promoted the production of beneficial very long‐chain ceramides instead of potentially harmful long‐chain ceramides.Through multiple mechanisms, the KD exerted anti‐steatogenic and insulin‐sensitizing effects in the liver, which supports the use of this dietary intervention to treat NAFLD. [ABSTRACT FROM AUTHOR]

Background Hospitalizations are a resource-intensive form of healthcare use, particularly for persons with chronic conditions such as those with HIV. Interhospital transfers typically appear as separate records in Canadian databases; misclassifying transfers as independent hospitalizations can bias key metrics such as readmission rates. We examined approaches of combining sequential, related records into hospitalization episodes of care (HEoCs) among persons with and without HIV (PWH; PWoH) in British Columbia (BC), Canada. Methods BC hospitalization records (1992 to 2020) were sourced from the Comparative Outcomes and Service Utilization Trends (COAST) study, a data linkage that includes samples of PWH and PWoH. We constructed 8 HEoC definitions that varied by the: a) time gap between records, and b) transfer indication. Comparisons were informed by the proportion of multi-record HEoCs (mHEoCs; episodes with multiple hospitalization records) generated, and feasibility given data quality. Results We analyzed 98,553 hospitalization records from 13,498 PWH, and 1,874,507 hospitalization records from 385,011 PWoH. Across the definitions, the proportion of mHEoCs varied from 2.46% to 5.27% for PWH and 2.73% to 4.18% for PWoH. Definitions requiring no transfer indication yielded the highest proportion of mHEoCs, whereas those requiring two-way agreement of hospital identifiers yielded the lowest proportion of mHEoCs. Patterns were comparable among PWH and PWoH. A pragmatic approach to defining HEoCs can be a reasonable option for general purposes – requiring at least one populated hospital identifier field, and ≤ 1 day gap between hospitalizations. Conclusions Various approaches can be employed to combine sequential, related hospitalization records into HEoCs to help provide less biased estimates of hospitalization-related metrics.