Identifying a group of factors predicting cognitive impairment among older adults

by Longgang Zhao, Yuan Wang, Eric Mishio Bawa, Zichun Meng, Jingkai Wei, Sarah Newman-Norlund, Tushar Trivedi, Hatice Hasturk, Roger D. Newman-Norlund, Julius Fridriksson, Anwar T. Merchant

Background

Cognitive impairment has multiple risk factors spanning several domains, but few studies have evaluated risk factor clusters. We aimed to identify naturally occurring clusters of risk factors of poor cognition among middle-aged and older adults and evaluate associations between measures of cognition and these risk factor clusters.

Methods

We used data from the National Health and Nutrition Examination Survey (NHANES) III (training dataset, n = 4074) and the NHANES 2011–2014 (validation dataset, n = 2510). Risk factors were selected based on the literature. We used both traditional logistic models and support vector machine methods to construct a composite score of risk factor clusters. We evaluated associations between the risk score and cognitive performance using the logistic model by estimating odds ratios (OR) and 95% confidence intervals (CI).

Results

Using the training dataset, we developed a composite risk score that predicted undiagnosed cognitive decline based on ten selected predictive risk factors including age, waist circumference, healthy eating index, race, education, income, physical activity, diabetes, hypercholesterolemia, and annual visit to dentist. The risk score was significantly associated with poor cognitive performance both in the training dataset (OR _{Tertile 3 verse tertile 1} = 8.15, 95% CI: 5.36–12.4) and validation dataset (OR _{Tertile 3 verse tertile 1} = 4.31, 95% CI: 2.62–7.08). The area under the receiver operating characteristics curve for the predictive model was 0.74 and 0.77 for crude model and model adjusted for age, sex, and race.

Conclusion

The model based on selected risk factors may be used to identify high risk individuals with cognitive impairment.

A modified rehabilitation paradigm bilaterally increased rat extensor digitorum communis muscle size but did not improve forelimb function after stroke

by Sally Caine, Mariam Alaverdashvili, Frederick Colbourne, Gillian D. Muir, Phyllis G. Paterson

Malnutrition after stroke may lessen the beneficial effects of rehabilitation on motor recovery through influences on both brain and skeletal muscle. Enriched rehabilitation (ER), a combination of environmental enrichment and forelimb reaching practice, is used preclinically to study recovery of skilled reaching after stroke. However, the chronic food restriction typically used to motivate engagement in reaching practice is a barrier to using ER to investigate interactions between nutritional status and rehabilitation. Thus, our objectives were to determine if a modified ER program comprised of environmental enrichment and skilled reaching practice motivated by a short fast would enhance post-stroke forelimb motor recovery and preserve forelimb muscle size and metabolic fiber type, relative to a group exposed to stroke without ER. At one week after photothrombotic cortical stroke, male, Sprague-Dawley rats were assigned to modified ER or standard care for 2 weeks. Forelimb recovery was assessed in the Montoya staircase and cylinder task before stroke and on days 5–6, 22–23, and 33–34 after stroke. ER failed to improve forelimb function in either task (p > 0.05). Atrophy of extensor digitorum communis (EDC) and triceps brachii long head (TBL) muscles was not evident in the stroke-targeted forelimb on day 35, but the area occupied by hybrid fibers was increased in the EDC muscle (p = 0.038). ER bilaterally increased EDC (p = 0.046), but not TBL, muscle size; EDC muscle fiber type was unchanged by ER. While the modified ER did not promote forelimb motor recovery, it does appear to have utility for studying the role of skeletal muscle plasticity in post-stroke recovery.

Knowledge, attitudes, and practices regarding antibiotic use in Bangladesh: Findings from a cross-sectional study

by Md. Abu Raihan, Md. Saiful Islam, Shariful Islam, A. F. M. Mahmudul Islam, Khandaker Tanveer Ahmed, Tania Ahmed, Md. Nahidul Islam, Shamsunnahar Ahmed, Mysha Samiha Chowdhury, Dipto Kumar Sarker, Anika Bushra Lamisa

Background

Escalating antibiotic resistance presents a notable worldwide dilemma, pointing a large involvement of general population. The objective of this study was to assess knowledge, attitudes, and practices regarding the utilization of antibiotics among Bangladeshi residents.

Methods

A cross-sectional study, conducted from January 01 to April 25, 2022, included 1,947 Bangladeshi adults with a history of antibiotic use, via online surveys and face-to-face interviews using a pretested semi-structured questionnaire. Descriptive statistics, Chi-square tests, and multivariate linear regression models were employed.

Results

Mean scores for knowledge, attitudes, and practices were 6.59±1.20, 8.34±1.19, and 12.74±2.59, with correct rates of 73.22%, 92.67%, and 57.91%. Positive predictors for knowledge included being unmarried (β = 0.10, p = 0.001), higher education (College: β = 0.09, p = 0.025; Bachelor: β = 0.22, p Conclusions

Participants exhibited adequate knowledge and positive attitudes but lagged behind in proper practice of antibiotic use. Proper initiatives should be tailored to enhance prudent antibiotic use and mitigate the risk of antimicrobial resistance.

Nutrient density of Bangladeshi foods and its application in planning diet for pregnant women

by Nazma Shaheen, Abira Nowar, Saiful Islam, Md. Hafizul Islam, Md. Ruhul Amin

Nutrient profiling is a method that classifies foods based on their nutrient content and identifies foods that are high in micronutrients both across and within food groups. This study aimed to identify foods that are rich sources of the seven micronutrients (iron, zinc, calcium, thiamine, riboflavin, vitamin A, and vitamin B₁₂) of public health concern for the Bangladeshi population._. This study developed a metric termed “naturally nutrient-rich score 7 (NNR₇)” specifically for third-trimester pregnant women to identify nutrient-dense foods. Further, it computed the nutrient adequacy score (NAS) of the top NNR₇-scored foods for seven micronutrients to assess the extent (percent) to which foods can meet pregnant women’s recommended dietary allowances (RDA). A linear programming technique was then used to construct a nutrient-adequate model diet for third-trimester pregnant women using the top ten NNR₇-scored foods. According to the NNR₇, food groups such as leafy vegetables, fish, meat, poultry and eggs, and vegetables are the richest sources of the problem micronutrients. Mutton liver (916.7%), soybean (39.3%), lamb liver (2160%) and duck liver (50.0%) were found to fulfill the highest percentage of the RDA of vitamin A, zinc, vitamin B_12, and iron, respectively. In the formulated nutrient-adequate diets for pregnant women, rice, potato, brown wheat flour, and soya oil were universal to all three diets and Bengal gram, orange, Ganges River sprat, and duck liver were the most common ones. The study findings highlight the need for the consumption of foods such as leafy vegetables, fish, meat, poultry, eggs, pulses and vegetables to increase the intake of problematic micronutrients. Planning a nutrient-adequate diet for pregnant women using linear programming can be an alternative approach to optimize and shape food choices to meet their nutritional requirements.

Application of in-silico drug discovery techniques to discover a novel hit for target-specific inhibition of SARS-CoV-2 Mpro’s revealed allosteric binding with MAO-B receptor: A theoretical study to find a cure for post-covid neurological disorder

by Magdi E. A. Zaki, Sami A. AL-Hussain, Aamal A. Al-Mutairi, Abdul Samad, Vijay H. Masand, Rahul G. Ingle, Vivek Digamber Rathod, Nikita Maruti Gaikwad, Summya Rashid, Pravin N. Khatale, Pramod V. Burakale, Rahul D. Jawarkar

Several studies have revealed that SARS-CoV-2 damages brain function and produces significant neurological disability. The SARS-CoV-2 coronavirus, which causes COVID-19, may infect the heart, kidneys, and brain. Recent research suggests that monoamine oxidase B (MAO-B) may be involved in metabolomics variations in delirium-prone individuals and severe SARS-CoV-2 infection. In light of this situation, we have employed a variety of computational to develop suitable QSAR model using PyDescriptor and genetic algorithm-multilinear regression (GA-MLR) models (R² = 0.800–793, Q²_LOO = 0.734–0.727, and so on) on the data set of 106 molecules whose anti-SARS-CoV-2 activity was empirically determined. QSAR models generated follow OECD standards and are predictive. QSAR model descriptors were also observed in x-ray-resolved structures. After developing a QSAR model, we did a QSAR-based virtual screening on an in-house database of 200 compounds and found a potential hit molecule. The new hit’s docking score (-8.208 kcal/mol) and _PIC₅₀ (7.85 M) demonstrated a significant affinity for SARS-CoV-2’s main protease. Based on post-covid neurodegenerative episodes in Alzheimer’s and Parkinson’s-like disorders and MAO-B’s role in neurodegeneration, the initially disclosed hit for the SARS-CoV-2 main protease was repurposed against the MAO-B receptor using receptor-based molecular docking, which yielded a docking score of -12.0 kcal/mol. This shows that the compound that inhibits SARS-CoV-2’s primary protease may bind allosterically to the MAO-B receptor. We then did molecular dynamic simulations and MMGBSA tests to confirm molecular docking analyses and quantify binding free energy. The drug-receptor complex was stable during the 150-ns MD simulation. The first computational effort to show in-silico inhibition of SARS-CoV-2 Mpro and allosteric interaction of novel inhibitors with MAO-B in post-covid neurodegenerative symptoms and other disorders. The current study seeks a novel compound that inhibits SAR’s COV-2 Mpro and perhaps binds MAO-B allosterically. Thus, this study will enable scientists design a new SARS-CoV-2 Mpro that inhibits the MAO-B receptor to treat post-covid neurological illness.

Feasibility and metabolic outcomes of a well-formulated ketogenic diet as an adjuvant therapeutic intervention for women with stage IV metastatic breast cancer: The Keto-CARE trial

by Alex Buga, David G. Harper, Teryn N. Sapper, Parker N. Hyde, Brandon Fell, Ryan Dickerson, Justen T. Stoner, Madison L. Kackley, Christopher D. Crabtree, Drew D. Decker, Bradley T. Robinson, Gerald Krystal, Katherine Binzel, Maryam B. Lustberg, Jeff S. Volek

Purpose

Ketogenic diets may positively influence cancer through pleiotropic mechanisms, but only a few small and short-term studies have addressed feasibility and efficacy in cancer patients. The primary goals of this study were to evaluate the feasibility and the sustained metabolic effects of a personalized well-formulated ketogenic diet (WFKD) designed to achieve consistent blood beta-hydroxybutyrate (βHB) >0.5 mM in women diagnosed with stage IV metastatic breast cancer (MBC) undergoing chemotherapy.

Methods

Women (n = 20) were enrolled in a six month, two-phase, single-arm WFKD intervention (NCT03535701). Phase I was a highly-supervised, ad libitum, personalized WFKD, where women were provided with ketogenic-appropriate food daily for three months. Phase II transitioned women to a self-administered WFKD with ongoing coaching for an additional three months. Fasting capillary βHB and glucose were collected daily; weight, body composition, plasma insulin, and insulin resistance were collected at baseline, three and six months.

Results

Capillary βHB indicated women achieved nutritional ketosis (Phase I mean: 0.8 mM (n = 15); Phase II mean: 0.7 mM (n = 9)). Body weight decreased 10% after three months, primarily from body fat. Fasting plasma glucose, plasma insulin, and insulin resistance also decreased significantly after three months (p Conclusions

Women diagnosed with MBC undergoing chemotherapy can safely achieve and maintain nutritional ketosis, while improving body composition and insulin resistance, out to six months.

“High blood pressure comes from thinking too much”: Understandings of illness among couples living with cardiometabolic disorders and HIV in Malawi

by Jane Jere, Allison Ruark, Julie T. Bidwell, Rita M. Butterfield, Torsten B. Neilands, Sheri D. Weiser, Nancy Mulauzi, James Mkandawire, Amy A. Conroy

Cardiometabolic disorders (CMD) such as hypertension and diabetes are increasingly prevalent in sub-Saharan Africa, placing people living with HIV at risk for cardiovascular disease and threatening the success of HIV care. Spouses are often the primary caregivers for people living with CMD, and understanding patients’ and partners’ conceptions of CMD could inform care. We conducted semi-structured interviews with 25 couples having a partner living with HIV and either hypertension or diabetes. Couples were recruited from HIV clinics in Malawi and were interviewed on beliefs around symptoms, causation, prevention, and treatment for CMD. Data were analyzed at the individual and dyadic levels using framework analysis and Kleinman’s theory of explanatory models as a lens. On average, participants were 51 years old and married for 21 years. Approximately 57%, 14%, and 80% had hypertension, diabetes, and HIV. Couples endorsed a combination of biomedical explanatory models (beliefs around physical and mental health) and traditional explanatory models (beliefs around religion and natural remedies), although tended to emphasize the biomedical model. Half of couples believed stress was the main cause of hypertension. For diabetes, diet was believed to be a common cause. In terms of prevention, dietary changes and physical activity were most frequently mentioned. For disease management, medication adherence and diet modifications were emphasized, with some couples also supporting herbal remedies, stress reduction, and faith in God as strategies. Participants were generally more concerned about CMD than HIV due to poor access to CMD medications and beliefs that CMD could lead to sudden death. Within couples, partners often held many of the same beliefs but diverged around which etiological or preventive factors were most important (e.g., stress versus diet) and the best diet for CMD. Health education programs should involve primary partners to build knowledge of CMD and address overlap with HIV, and reinforce accurate information on lifestyle factors for the prevention and treatment of CMD.

A high-fat and fructose diet in dogs mirrors insulin resistance and β-cell dysfunction characteristic of impaired glucose tolerance in humans

by Justin M. Gregory, Guillaume Kraft, Chiara Dalla Man, James C. Slaughter, Melanie F. Scott, Jon R. Hastings, Dale S. Edgerton, Mary C. Moore, Alan D. Cherrington

This study examined the impact of a hypercaloric high-fat high-fructose diet (HFFD) in dogs as a potential model for human impaired glucose tolerance (IGT) and type 2 diabetes mellitus (T2DM). The HFFD not only led to weight gain but also triggered metabolic alterations akin to the precursors of human T2DM, notably insulin resistance and β-cell dysfunction. Following the HFFD intervention, the dogs exhibited a 50% decrease in insulin sensitivity within the first four weeks, paralleling observations in the progression from normal to IGT in humans. Calculations of the insulinogenic index using both insulin and C-peptide measurements during oral glucose tolerance tests revealed a significant and sustained decrease in early-phase insulin release, with partial compensation in the later phase, predominantly stemming from reduced hepatic insulin clearance. In addition, the Disposition Index, representing the β-cell’s capacity to compensate for diminished insulin sensitivity, fell dramatically. These results confirm that a HFFD can instigate metabolic changes in dogs akin to the early stages of progression to T2DM in humans. The study underscores the potential of using dogs subjected to a HFFD as a model organism for studying human IGT and T2DM.

Dietary magnesium, C-reactive protein and interleukin-6: The Strong Heart Family Study

by Nandana D. Rao, Rozenn N. Lemaitre, Colleen M. Sitlani, Jason G. Umans, Karin Haack, Veronica Handeland, Ana Navas-Acien, Shelley A. Cole, Lyle G. Best, Amanda M. Fretts

Objectives

To examine the associations of dietary Mg intake with inflammatory biomarkers (C-reactive protein (CRP) and interleukin 6 (IL-6)), and the interaction of dietary Mg intake with single nucleotide polymorphism (SNP) rs3740393, a SNP related to Mg metabolism and transport, on CRP and IL-6 among American Indians (AIs).

Methods

This cross-sectional study included AI participants (n = 1,924) from the Strong Heart Family Study (SHFS). Mg intake from foods and dietary supplements was ascertained using a 119-item Block food frequency questionnaire, CRP and IL-6 were measured from blood, and SNP rs3740393 was genotyped using MetaboChip. Generalized estimating equations were used to examine associations of Mg intake, and the interaction between rs3740393 and dietary Mg, with CRP and IL-6.

Results

Reported Mg intake was not associated with CRP or IL-6, irrespective of genotype. A significant interaction (p-interaction = 0.018) was observed between Mg intake and rs3740393 on IL-6. Among participants with the C/C genotype, for every 1 SD higher in log-Mg, log-IL-6 was 0.04 (95% CI: -0.10 to 0.17) pg/mL higher. Among participants with the C/G genotype, for every 1 SD higher in log-Mg, log-IL-6 was 0.08 (95% CI: -0.21 to 0.05) pg/mL lower, and among participants with the G/G genotype, for every 1 SD higher in log-Mg, log-IL-6 was 0.19 (95% CI: -0.38 to -0.01) pg/mL lower.

Conclusions

Mg intake may be associated with lower IL-6 with increasing dosage of the G allele at rs3740393. Future research is necessary to replicate this finding and examine other Mg-related genes that influence associations of Mg intake with inflammation.

An agent-based nested model integrating within-host and between-host mechanisms to predict an epidemic

by Yuichi Tatsukawa, Md. Rajib Arefin, Kazuki Kuga, Jun Tanimoto

The COVID-19 pandemic has remarkably heightened concerns regarding the prediction of communicable disease spread. This study introduces an innovative agent-based modeling approach. In this model, the quantification of human-to-human transmission aligns with the dynamic variations in the viral load within an individual, termed “within-host” and adheres to the susceptible–infected–recovered (SIR) process, referred to as “between-host.” Variations in the viral load over time affect the infectivity between individual agents. This model diverges from the traditional SIR model, which employs a constant transmission probability, by incorporating a dynamic, time-dependent transmission probability influenced by the viral load in a host agent. The proposed model retains the time-integrated transmission probability characteristic of the conventional SIR model. As observed in this model, the overall epidemic size remains consistent with the predictions of the standard SIR model. Nonetheless, compared to predictions based on the classical SIR process, notable differences existed in the peak number of the infected individuals and the timing of this peak. These nontrivial differences are induced by the direct correlation between the time-evolving transmission probability and the viral load within a host agent. The developed model can inform targeted intervention strategies and public health policies by providing detailed insights into disease spread dynamics, crucial for effectively managing epidemics.

Dynamic phase-locking states and personality in sub-acute mild traumatic brain injury: An exploratory study

by Harm J. van der Horn, Myrthe E. de Koning, Koen Visser, Marius G. J. Kok, Jacoba M. Spikman, Myrthe E. Scheenen, Remco J. Renken, Vince D. Calhoun, Victor M. Vergara, Joana Cabral, Andrew R. Mayer, Joukje van der Naalt

Research has shown that maladaptive personality characteristics, such as Neuroticism, are associated with poor outcome after mild traumatic brain injury (mTBI). The current exploratory study investigated the neural underpinnings of this process using dynamic functional network connectivity (dFNC) analyses of resting-state (rs) fMRI, and diffusion MRI (dMRI). Twenty-seven mTBI patients and 21 healthy controls (HC) were included. After measuring the Big Five personality dimensions, principal component analysis (PCA) was used to obtain a superordinate factor representing emotional instability, consisting of high Neuroticism, moderate Openness, and low Extraversion, Agreeableness, and Conscientiousness. Persistent symptoms were measured using the head injury symptom checklist at six months post-injury; symptom severity (i.e., sum of all items) was used for further analyses. For patients, brain MRI was performed in the sub-acute phase (~1 month) post-injury. Following parcellation of rs-fMRI using independent component analysis, leading eigenvector dynamic analysis (LEiDA) was performed to compute dynamic phase-locking brain states. Main patterns of brain diffusion were computed using tract-based spatial statistics followed by PCA. No differences in phase-locking state measures were found between patients and HC. Regarding dMRI, a trend significant decrease in fractional anisotropy was found in patients relative to HC, particularly in the fornix, genu of the corpus callosum, anterior and posterior corona radiata. Visiting one specific phase-locking state was associated with lower symptom severity after mTBI. This state was characterized by two clearly delineated communities (each community consisting of areas with synchronized phases): one representing an executive/saliency system, with a strong contribution of the insulae and basal ganglia; the other representing the canonical default mode network. In patients who scored high on emotional instability, this relationship was even more pronounced. Dynamic phase-locking states were not related to findings on dMRI. Altogether, our results provide preliminary evidence for the coupling between personality and dFNC in the development of long-term symptoms after mTBI.

Analysis of uterine evacuation methods in postabortion care after implementation of a surveillance network (CLAP MUSA-Network) at a university hospital

by Nelio N. Veiga-Junior, Caroline Eugeni, Beatriz D. Kajiura, Priscilla B. F. Dantas, Caroline B. Trabach, Aline A. Junqueira, Carina C. Nunes, Luiz F. Baccaro

Background

Management of uterine evacuation is essential for increasing safe abortion care. Monitoring through surveillance systems tracks changes in clinical practice and provides information to improve equity in abortion care quality.

Objective

This study aimed to evaluate the frequency of manual vacuum aspiration (MVA) and medical abortion (MA), and identify the factors associated with each uterine evacuation method after surveillance network installation at a Brazilian hospital.

Methods

This cross-sectional study included women admitted for abortion or miscarriage to the University of Campinas Women’s Hospital, Brazil, between July 2017 and November 2020. The dependent variables were the use of MVA and MA with misoprostol. The independent variables were the patients’ clinical and sociodemographic data. The Cochran–Armitage, chi-square, and Mann–Whitney U tests, as well as multiple logistic regression analysis, were used to compare uterine evacuation methods.

Results

We enrolled 474 women in the study, 91.35% of whom underwent uterine evacuation via uterine curettage (78.75%), MVA (9.46%), or MA (11.54%). MVA use increased during the study period (Z = 9.85, p Conclusion

MVA use increased following the installation of a surveillance network for good clinical practice. Being part of a network that encourages the use of evidence-based methods provides an opportunity for healthcare facilities to increase access to safe abortions.

Towards a pan marsupial sero-immunological tool in the demanding field of wildlife serology: Marsupial immunoglobulin-binding capability with protein A/G, protein L and anti-kangaroo antibody

by K. L. D. Tharaka D. Liyanage, Paola K. Vaz, Abdul Jabbar, Jasmin Hufschmid

Detection of infections in wildlife species is increasingly important to reduce the risk of spreading zoonotic and economically important parasites, understand disease epidemiology and promote the conservation of wildlife species. Serological tests are key in disease diagnosis and surveillance by detecting immunoglobulins against infectious agents. However, the need for species-specific reagents has limited the application of serological tests in wildlife species. This study evaluated the serum immunoglobulin-binding capability of polyclonal anti-kangaroo antibody and two non-species-specific reagents, including protein A/G and protein L, with the largest range of Australian marsupial species so far, including 32 species representing three major marsupial orders. Immunoglobulin-binding capability was assessed using immunoblotting, enzyme-linked immunosorbent assay and Western blot techniques. Variation in immunoglobulin-binding capability was observed between the three reagents and across the species tested, both across but also within taxonomic groups. Taxonomic distance was thus not always a good predictor of immunoglobulin-binding affinity, emphasizing the need to validate these reagents for each species separately. However, all three reagents bound with the serum immunoglobulins of most marsupial species tested. The findings of this study provide a valuable reference for species differences in affinity to protein A/G, protein L and anti-kangaroo antibody, assisting in the selection of appropriate reagents and the development of sero-immunological assays in Australian marsupials.

Development of an enhanced analytical method utilizing pepper matrix as an analyte protectant for sensitive GC‒MS/MS detection of dimethipin in animal-based food products

by Jae-Han Shim, Md. Musfiqur Rahman, Tuba Esatbeyoglu, Fatih Oz, A. M. Abd El-Aty

Herein, an analytical method using gas chromatography-tandem mass spectrometry (GC‒MS/MS) was devised to detect the presence of the troublesome pesticide dimethipin in various animal-based food products, including chicken, pork, beef, eggs, and milk. The injection port was primed with a matrix derived from pepper leaves that acts as an analyte protectant (AP) to safeguard the target compound from thermal degradation during gas chromatography. The presence of AP resulted in a remarkable limit of quantification of 0.005 mg/kg for dimethipin in five matrices. Three different versions (original, EN, and AOAC) of the QuEChERS (Quick, Easy, Cheap, Effective, Rugged, and Safe) method were compared for dimethipin extraction, with a double-layer solid-phase extraction (SPE) cartridge utilized for matrix purification. A seven-point external calibration curve was established for dimethipin in the five matrices, demonstrating excellent linearity with determination coefficients (R²) ≥ 0.998. The developed quantitative method was validated by fortifying each matrix with three different concentrations of standard dimethipin, and the average recovery fell within the acceptable range outlined in the CODEX guidelines (ranging from 88.8% to 110.0%), with a relative standard deviation (RSD) of ≤ 11.97%. This method effectively addresses the challenge of analyzing dimethipin and can therefore be used as a routine monitoring tool for dimethipin across various matrices.

Downscaling epidemiological time series data for improving forecasting accuracy: An algorithmic approach

by Mahadee Al Mobin, Md. Kamrujjaman

Data scarcity and discontinuity are common occurrences in the healthcare and epidemiological dataset and often is needed to form an educative decision and forecast the upcoming scenario. Often to avoid these problems, these data are processed as monthly/yearly aggregate where the prevalent forecasting tools like Autoregressive Integrated Moving Average (ARIMA), Seasonal Autoregressive Integrated Moving Average (SARIMA), and TBATS often fail to provide satisfactory results. Artificial data synthesis methods have been proven to be a powerful tool for tackling these challenges. The paper aims to propose a novel algorithm named Stochastic Bayesian Downscaling (SBD) algorithm based on the Bayesian approach that can regenerate downscaled time series of varying time lengths from aggregated data, preserving most of the statistical characteristics and the aggregated sum of the original data. The paper presents two epidemiological time series case studies of Bangladesh (Dengue, Covid-19) to showcase the workflow of the algorithm. The case studies illustrate that the synthesized data agrees with the original data regarding its statistical properties, trend, seasonality, and residuals. In the case of forecasting performance, using the last 12 years data of Dengue infection data in Bangladesh, we were able to decrease error terms up to 72.76% using synthetic data over actual aggregated data.

Feasibility, enablers and challenges of using timeliness metrics for household contact tracing and TB preventive therapy in Pakistan

by Bushra Jamil, Divya Nair, Pruthu Thekkur, Neelofar Laeeq, Anum Adil, Mohammed Khogali, Rony Zachariah, Selma Dar Berger, Srinath Satyanarayana, Ajay M. V. Kumar, Aaron Bochner, Amanda McClelland, Razia Fatima, Anthony D. Harries

Introduction

Screening household contacts of TB patients and providing TB preventive therapy (TPT) is a key intervention to end the TB epidemic. Global and timely implementation of TPT in household contacts, however, is dismal. We adapted the 7-1-7 timeliness metric designed to evaluate and respond to infectious disease outbreaks or pandemics, and assessed the feasibility, enablers and challenges of implementing this metric for screening and management of household contacts of index patients with bacteriologically-confirmed pulmonary TB in Karachi city, Pakistan.

Methods

We conducted an explanatory mixed methods study with a quantitative component (cohort design) followed by a qualitative component (descriptive design with focus group discussions).

Results

From January-June 2023, 92% of 450 index patients had their household contacts line-listed within seven days of initiating anti-TB treatment (“first 7”). In 84% of 1342 household contacts, screening outcomes were ascertained within one day of line-listing (“next 1”). In 35% of 256 household contacts eligible for further evaluation by a medical officer (aged ≤5 years or with chest symptoms), anti-tuberculosis treatment, TPT or a decision for no drugs was made within seven days of symptom screening (“second 7”). The principal reason for not starting anti-tuberculosis treatment or TPT was failure to consult a medical officer: only 129(50%) of 256 contacts consulted a medical officer. Reasons for poor performance in the “second 7” component included travel costs to see a medical officer, loss of daily earnings and fear of a TB diagnosis. Field staff reported that timeliness metrics motivated them to take prompt action in household contact screening and TPT provision and they suggested these be included in national guidelines.

Conclusions

Field staff found “7-1-7” timeliness metrics to be feasible and useful. Integration of these metrics into national guidelines could improve timeliness of diagnosis, treatment and prevention of TB within households of index patients.

A medium-chain fatty acid analogue prevents hepatosteatosis and decreases inflammatory lipid metabolites in a murine model of parenteral nutrition-induced hepatosteatosis

by Bennet S. Cho, Scott C. Fligor, Gillian L. Fell, Jordan D. Secor, Savas T. Tsikis, Amy Pan, Lumeng J. Yu, Victoria H. Ko, Duy T. Dao, Lorenzo Anez-Bustillos, Thomas I. Hirsch, Jenny Lund, Arild C. Rustan, David A. Fraser, Kathleen M. Gura, Mark Puder

Background

Parenteral (intravenous) nutrition is lifesaving for patients with intestinal failure, but long-term use of parenteral nutrition often leads to liver disease. SEFA-6179 is a synthetic medium-chain fatty acid analogue designed to target multiple fatty acid receptors regulating metabolic and inflammatory pathways. We hypothesized that SEFA-6179 would prevent hepatosteatosis and lipotoxicity in a murine model of parenteral nutrition-induced hepatosteatosis.

Methods

Two in vivo experiments were conducted. In the first experiment, six-week-old male mice were provided an ad lib fat-free high carbohydrate diet (HCD) for 19 days with orogastric gavage of either fish oil, medium-chain triglycerides, or SEFA-6179 at a low (0.3mmol/kg) or high dose (0.6mmol/kg). In the second experiment, six-week-old mice were provided an ad lib fat-free high carbohydrate diet for 19 days with every other day tail vein injection of saline, soybean oil lipid emulsion, or fish oil lipid emulsion. Mice then received every other day orogastric gavage of medium-chain triglyceride vehicle or SEFA-6179 (0.6mmol/kg). Hepatosteatosis was assessed by a blinded pathologist using an established rodent steatosis score. Hepatic lipid metabolites were assessed using ultra-high-performance liquid chromatography-mass spectrometry. Effects of SEFA-6179 on fatty acid oxidation, lipogenesis, and fatty acid uptake in human liver cells were assessed in vitro.

Results

In the first experiment, mice receiving the HCD with either saline or medium-chain triglyceride treatment developed macrovesicular steatosis, while mice receiving fish oil or SEFA-6179 retained normal liver histology. In the second experiment, mice receiving a high carbohydrate diet with intravenous saline or soybean oil lipid emulsion, along with medium chain triglyceride vehicle treatment, developed macrovescular steatosis. Treatment with SEFA-6179 prevented steatosis. In each experiment, SEFA-6179 treatment decreased arachidonic acid metabolites as well as key molecules (diacylglycerol, ceramides) involved in lipotoxicity. SEFA-6179 increased both β- and complete fatty oxidation in human liver cells, while having no impact on lipogenesis or fatty acid uptake.

Conclusions

SEFA-6179 treatment prevented hepatosteatosis and decreased toxic lipid metabolites in a murine model of parenteral nutrition-induced hepatosteatosis. An increase in both β- and complete hepatic fatty acid oxidation may underlie the reduction in steatosis.

Cumulative violence exposures among men who have sex with men living with HIV in India: Psychosocial correlates of HIV care continuum outcomes

by Bushra Sabri, Chakra Budhathoki, Allison M. McFall, Shruti H. Mehta, David D. Celentano, Sunil S. Solomon, Aylur K. Srikrishnan, Santhanam Anand, Canjeevaram K. Vasudevan, Gregory M. Lucas

Lifetime exposures to violence among men who have sex with men (MSM) are associated with multiple psychosocial health risks and can affect engagement and outcomes of HIV treatment. This study a) explored relationships between levels of exposures to violence and HIV care continuum outcomes among MSM living with HIV in India, and b) identified psychosocial correlates of HIV care continuum outcomes among MSM living with HIV and those with lifetime cumulative exposures to violence (CVE). CVE referred to exposures to violence in both childhood and adulthood. This cross-sectional analysis used survey data collected between August 2016 and May 2017 from 1763 men who have sex with men living with HIV across 10 cities in India, using respondent-driven sampling. We found that higher levels of violence exposure were significantly associated with lower awareness of HIV positive status, and lower likelihood of initiating antiretroviral therapy. Compared with MSM living with HIV that had no CVE, those with CVE were more likely to report perpetration of interpersonal violence, alcohol misuse, depressive symptoms, and HIV transmission risk behaviors and to have two to four co-occurring psychosocial problems. In multivariable analysis with the subset of MSM with CVE, psychosocial correlates significantly associated with at least one HIV care continuum outcome were HIV transmission risk behaviors, perpetration of interpersonal violence, depression, and alcohol misuse. The findings highlight the need for integrating care for lifetime violence exposures and associated behavioral problems in HIV care settings for men who have sex with men living with HIV in India.

Cohort profile: Genetic data in the German Socio-Economic Panel Innovation Sample (SOEP-G)

by Philipp D. Koellinger, Aysu Okbay, Hyeokmoon Kweon, Annemarie Schweinert, Richard Karlsson Linnér, Jan Goebel, David Richte, Lisa Reiber, Bettina Maria Zweck, Daniel W. Belsky, Pietro Biroli, Rui Mata, Elliot M. Tucker-Drob, K. Paige Harden, Gert Wagner, Ralph Hertwig

The German Socio-Economic Panel (SOEP) serves a global research community by providing representative annual longitudinal data of respondents living in private households in Germany. The dataset offers a valuable life course panorama, encompassing living conditions, socioeconomic status, familial connections, personality traits, values, preferences, health, and well-being. To amplify research opportunities further, we have extended the SOEP Innovation Sample (SOEP-IS) by collecting genetic data from 2,598 participants, yielding the first genotyped dataset for Germany based on a representative population sample (SOEP-G). The sample includes 107 full-sibling pairs, 501 parent-offspring pairs, and 152 triads, which overlap with the parent-offspring pairs. Leveraging the results from well-powered genome-wide association studies, we created a repository comprising 66 polygenic indices (PGIs) in the SOEP-G sample. We show that the PGIs for height, BMI, and educational attainment capture 22∼24%, 12∼13%, and 9% of the variance in the respective phenotypes. Using the PGIs for height and BMI, we demonstrate that the considerable increase in average height and the decrease in average BMI in more recent birth cohorts cannot be attributed to genetic shifts within the German population or to age effects alone. These findings suggest an important role of improved environmental conditions in driving these changes. Furthermore, we show that higher values in the PGIs for educational attainment and the highest math class are associated with better self-rated health, illustrating complex relationships between genetics, cognition, behavior, socio-economic status, and health. In summary, the SOEP-G data and the PGI repository we created provide a valuable resource for studying individual differences, inequalities, life-course development, health, and interactions between genetic predispositions and the environment.

The burden of non-disabled frailty and its associated factors among older adults in Bangladesh

by Sabuj Kanti Mistry, A. R. M. Mehrab Ali, Uday Narayan Yadav, Saruna Ghimire, Afsana Anwar, Md. Nazmul Huda, Fouzia Khanam, Rashidul Alam Mahumud, Ateeb Ahmad Parray, Shovon Bhattacharjee, David Lim, Mark Fort Harris

Objective

The present study aims to measure the prevalence of non-disabled frailty and its associated factors among Bangladeshi older adults.

Methods

This cross-sectional study was conducted during September and October 2021 among 1,045 Bangladeshi older adults (≥60 years). Telephone interviews, using a semi-structured questionnaire, were undertaken to collect data on participants’ characteristics and level of frailty. The non-disabled frailty was measured using the ‘Frail Non-Disabled (FiND)’ questionnaire. A multinomial logistic regression model assessed the factors associated with frailty among the participants.

Results

Around a quarter of the participants (24.8%) were frail. The multinomial regression analysis showed that older participants aged ≥80 years (RRR = 3.23, 95% CI: 1.41–7.37) were more likely to be frail compared to participants aged 60–69 years. Likewise, the participants living in a large family with ≥4 members (RRR = 1.39, 95% CI: 1.01–1.92) were more likely to be frail compared to those living in smaller families. Also, participants having memory or concentration problems (RRR = 1.56, 95% CI: 1.12–2.17) were more likely to be frail compared to those who were not suffering from these problems. Moreover, participants whose family members were non-responsive to their day-to-day assistance (RRR = 1.47, 95% CI: 1.06–2.03) were more likely to be frail compared to those whose family members were responsive. Furthermore, participants who were feeling lonely (RRR = 1.45, 95% CI: 1.07–1.98) were more likely to be frail than their counterparts who were not feeling lonely.

Conclusions

The findings of the present study suggest developing tailored interventions to address the burden of frailty among the older populations in Bangladesh. In particular, providing long-term care and health promotion activities can be of value in preventing frailty and reducing adverse health outcomes among this vulnerable population group.