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Abstract Recent studies have suggested that Transposable Elements (TEs) residing in introns frequently splice into and alter primary gene-coding transcripts. To re-examine the exonization frequency of TEs into protein-coding gene transcripts, we re-analyzed a Drosophila neuron circadian rhythm RNAseq dataset and a deep long RNA fly midbrain RNAseq dataset using our Transposon Insertion and Depletion Analyzer (TIDAL) program. Our TIDAL results were able to predict several TE insertions from RNAseq data that were consistent with previous published studies. However, we also uncovered many discrepancies in TE-exonization calls, such as reads that mainly support intron retention of the TE and little support for chimeric mRNA spliced to the TE. We then deployed rigorous genomic DNA-PCR (gDNA-PCR) and RT-PCR procedures on TE-mRNA fusion candidates to see how many of bioinformatics predictions could be validated. By testing a w1118 strain from which the deeper long RNAseq data was derived and comparing to an OreR strain, only 9 of 23 TIDAL candidates (

Abstract The gut microbiota and its secreted metabolites play a significant role in cardiovascular and musculoskeletal health and diseases. The dysregulation of the intestinal microbiota poses a significant threat to cardiovascular and skeletal muscle well-being. Nonetheless, the precise molecular mechanisms underlying these changes remain unclear. Furthermore, microgravity presents several challenges to cardiovascular and musculoskeletal health compromising muscle strength, endothelial dysfunction, and metabolic changes. The purpose of this review is to critically examine the role of gut microbiota metabolites on cardiovascular and skeletal muscle functions and dysfunctions. It also explores the molecular mechanisms that drive microgravity-induced deconditioning in both cardiovascular and skeletal muscle. Key findings in this review highlight that several alterations in gut microbiota and secreted metabolites in microgravity mirror characteristics seen in cardiovascular and skeletal muscle diseases. Those alterations include increased levels of Firmicutes/Bacteroidetes (F/B) ratio, elevated lipopolysaccharide levels (LPS), increased in para-cresol (p-cresol) and secondary metabolites, along with reduction in bile acids and Akkermansia muciniphila bacteria. Highlighting the potential, modulating gut microbiota in microgravity conditions could play a significant role in mitigating cardiovascular and skeletal muscle diseases not only during space flight but also in prolonged bed rest scenarios here on Earth.

Abstract Introduction Noncommunicable diseases (NCDs) are associated with high and rising burden of morbidity and mortality in sub-Saharan Africa, including Nigeria. Diabetes mellitus (DM) is among the leading causes of NCD-related deaths worldwide and is a foremost public health problem in Nigeria. As part of National policy, Nigeria has committed to implement the World Health Organization (WHO) Package of Essential Non-communicable Disease interventions for primary care. Implementing the intervention requires the availability of essential elements, including guidelines, trained staff, health management information systems (HMIS), equipment, and medications, in primary healthcare centers (PHCs). This study assessed the availability of the DM component of the WHO package, and the readiness of the health workers in these PHCs to implement a DM screening, evaluation, and management program to inform future adoption and implementation. Methods This cross-sectional formative assessment adapted the WHO Service Availability and Readiness Assessment (SARA) tool to survey 30 PHCs selected by multistage sampling for readiness to deliver DM diagnosis and care in Abuja, Nigeria, between August and October 2021. The SARA tool was adapted to focus on DM services and the availability and readiness indicator scores were calculated based on the proportion of PHCs with available DM care services, minimum staff requirement, diagnostic tests, equipment, medications, and national guidelines/protocols for DM care within the defined SARA domain. Results All 30 PHCs reported the availability of at least two full-time staff (median [interquartile range] = 5 [4–9]), which were mostly community health extension workers (median [interquartile range]) = 3 [1–4]. At least one staff member was recently trained in DM care in 11 PHCs (36%). The study also reported high availability of paper-based HMIS (100%), and DM screening services using a glucometer (87%), but low availability of DM job aids (27%), treatment (23%), and national guidelines/protocols (0%). Conclusion This formative assessment of PHCs’ readiness to implement a DM screening, evaluation, and management program in Abuja demonstrated readiness to integrate DM care into PHCs regarding equipment, paper-based HMIS, and nonphysician health workers' availability. However, strategies are needed to promote DM health workforce training, provide DM management guidelines, and supply essential DM medications.

Glioblastoma (GBM) stands as the most common primary malignant brain tumor. Despite the best standard therapies, GBM survivors have a brief survival time, about 24 months on average. The treatment is troublesome because the cancer cells may not respond well to specific therapies as they grow within an extensive network of blood vessels. Our study aims to evaluate the impact of paclitaxel 5.3 μg/mL and topotecan 0.26 μM solely and in pairwise combination on the resultant metabolic and proteomic signatures of the U87 cell line while using the precise ultra-high-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF) analytical technology. The U87 cells wear treated with DMSO, paclitaxel 5.3 μM, topotecan 0.26 μM, and their combinations. Using One-way ANOVA, we observed 14 significantly altered metabolites compared to those cells treated with DMSO. For combination treatment (paclitaxel and topotecan), 11 metabolites were significantly dysregulated. Sparse partial least squares-discriminant analysis (sPLS-DA) revealed minimal overlap, highlighting distinctions among the four groups. While for proteomics, a total of 79 proteins were significantly dysregulated among the groups. These findings can aid in identifying new biomarkers associated with the utilized drugs and creating a map for targeted therapy. EIF3F, GNB2L1, HINT2, and RPA3 were shown to be significantly upregulated in the combination group relative to the control. Moreover, ribosome, apoptosis, HIF-1 signaling, arginine and proline, glutathione, purine metabolism, apelin signaling pathway, and glycolysis were significantly altered in the combination group. Overall, this study underscores the effectiveness of multi-omics approaches in revealing the molecular mechanisms driving chemotherapy responses in cancer cells. Additionally, this work generates a comprehensive list of molecular alterations that can serve as a foundation for further investigations and inform personalized healthcare strategies to enhance patient outcomes.

Mosquitoes, like Drosophila, are dipterans, the order of “true flies” characterized by a single set of two wings. Drosophila are prime model organisms for biomedical research, while mosquito researchers struggle to establish robust molecular biology in these that are arguably the most dangerous vectors of human pathogens. Both insects utilize the RNA interference (RNAi) pathway to generate small RNAs to silence transposons and viruses, yet details are emerging that several RNAi features are unique to each insect family, such as how culicine mosquitoes have evolved extreme genomic feature differences connected to their unique RNAi features. A major technical difference in the molecular genetic studies of these insects is that generating stable transgenic animals are routine in Drosophila but still variable in stability in mosquitoes, despite genomic DNA-editing advances. By comparing and contrasting the differences in the RNAi pathways of Drosophila and mosquitoes, in this review we propose a hypothesis that transgene DNAs are possibly more intensely targeted by mosquito RNAi pathways and chromatin regulatory pathways than in Drosophila. We review the latest findings on mosquito RNAi pathways, which are still much less well understood than in Drosophila, and we speculate that deeper study into how mosquitoes modulate transposons and viruses with Piwi-interacting RNAs (piRNAs) will yield clues to improving transgene DNA expression stability in transgenic mosquitoes.

Burnout is a significant challenge for special educators’ wellbeing, as they report higher levels of stress than general educators. Rates of burnout are highest among special educators serving youth with emotional and behavioral disorders (EBD). At a time when nearly half of all students with EBD are spending more than 20% of their school day outside of the general education classroom—and when special education researchers continue to support the need for self-contained settings for students with EBD—it is necessary to explore if and to what extent the movement toward full inclusion is having an impact on self-contained EBD classroom teachers. A focus group with three special educators provided unique insights regarding advantages and disadvantages of working in self-contained settings, as well as the extent to which working in a self-contained setting during an era of full inclusion is having deleterious effects on teachers’ feelings of personal accomplishment. Implications for research and practice are provided.

COVID-19 is a highly contagious infectious disease that has posed a global threat, leading to a widespread pandemic characterized by multi-organ complications and failures. Aims: The present study was conducted to evaluate the impact of Pfizer and Sinopharm vaccines on metabolomic changes and their correlations with immune pathways. Main methods: The study used a cross-sectional design and implemented an untargeted metabolomics-based approach. Plasma samples were obtained from three groups: non-vaccinated participants, Sinopharm-vaccinated participants, and Pfizer-vaccinated participants. Comparative metabolomic analysis was conducted using TIMS-QTOF, and multiple t-tests with a 5 % false discovery rate (FDR) were performed using MetaboAnalyst software. Key findings: Out of the 105 metabolites detected, 72 showed statistically significant changes (p-value < 0.05) across the different groups. Notably, several metabolites such as neopterin, pyridoxal, and syringic acid were markedly altered in individuals vaccinated with Pfizer. Conversely, in the Sinopharm-vaccinated group, significant alterations were observed in sphinganine, neopterin, and sphingosine. These metabolites hold potential as biomarkers for evaluating vaccine efficacy. Additionally, both Pfizer and Sinopharm vaccinations were found to influence sphingolipid and histidine metabolisms compared to the control group. The Sinopharm group also displayed changes in lysine degradation relative to the control group. When comparing the enriched pathways between the Pfizer and Sinopharm-vaccinated groups, differences were observed in purine metabolism. Furthermore, alterations in tryptophan and vitamin B6 metabolism were noted when comparing the Pfizer-vaccinated group with both the control and Sinopharm-vaccinated groups. Significance: These findings highlight the importance of metabolomics in assessing vaccine effectiveness and identifying potential biomarkers for monitoring the efficacy of newly developed vaccines in a shorter timeframe.

BackgroundMany supportive cancer care (SCC) services were teledelivered during COVID-19, but what facilitates patients’ intentions to use teledelivered SCC is unknown. ObjectiveThe study aimed to use the unified theory of acceptance and use of technology to investigate the factors associated with the intentions of breast cancer survivors (BCS) in Hong Kong to use various types of teledelivered SCC (including psychosocial care, medical consultation, complementary care, peer support groups). Favorable telehealth-related perceptions (higher performance expectancy, lower effort expectancy, more facilitating conditions, positive social influences), less technological anxiety, and greater fear of COVID-19 were hypothesized to be associated with higher intentions to use teledelivered SCC. Moreover, the associations between telehealth-related perceptions and intentions to use teledelivered SCC were hypothesized to be moderated by education level, such that associations between telehealth-related perceptions and intentions to use teledelivered SCC would be stronger among those with a higher education level. MethodsA sample of 209 (209/287, 72.8% completion rate) women diagnosed with breast cancer since the start of the COVID-19 outbreak in Hong Kong (ie, January 2020) were recruited from the Hong Kong Breast Cancer Registry to complete a cross-sectional survey between June 2022 and December 2022. Participants’ intentions to use various types of teledelivered SCC (dependent variables), telehealth-related perceptions (independent variables), and sociodemographic variables (eg, education, as a moderator variable) were measured using self-reported, validated measures. ResultsHierarchical regression analysis results showed that greater confidence using telehealth, performance expectancy (believing telehealth helps with daily tasks), social influence (important others encouraging telehealth use), and facilitating conditions (having resources for telehealth use) were associated with higher intentions to use teledelivered SCC (range: β=0.16, P=.03 to β=0.34, P

Abstract Proton pump inhibitors (PPIs) are commonly used in cancer patients, but their impact on treatment outcomes in multiple myeloma (MM) patients remains unclear. This study investigated the association of PPI use with survival and adverse effects in MM patients across three randomized-control trials initiating daratumumab, lenalidomide, or bortezomib combination treatments. Cox proportional hazard analysis and logistic regression were employed to assess the associations with treatment outcomes, while adjusting for age, sex, weight, MM international staging system stage, ECOG-performance status, comorbidity count, and presence of gastrointestinal disorders. Pooled data involving 1804 patients revealed that 557 (32%) used PPIs at baseline. PPI use was independently associated with worse overall survival (adjusted HR [95% CI] 1.32 [1.08–1.62], P = 0.007) and grade ≥ 3 adverse events (adjusted OR [95% CI] 1.39 [1.03–1.88], P = 0.030). However, the association with progression-free survival did not reach statistical significance (adjusted HR [95% CI] 1.14 [0.97–1.33], P = 0.112). Findings were consistent across trials and treatment arms. PPI use was identified as a negative prognostic factor in MM patients, potentially enhancing clinical decisions regarding its use. Further research is needed to fully comprehend the impacts and safety of PPI use in MM patients.

Background: Postnatal care (PNC) encompasses various aspects including recovery from childbirth, newborn care, breastfeeding, and family planning. Although recent guidelines on improving PNC services in low-resource settings focus on the timing and content of PNC services, there is lack of data on these services in Cross River State, Nigeria and most other low-resource settings. Objectives: To determine the pattern and utilization of PNC services among mothers attending the University of Calabar Teaching Hospital, Cross River State, Nigeria. Materials and Methods: A descriptive cross-sectional design was employed. A total of 341 mothers were selected using simple random sampling via balloting with replacement. Data were collected using a self-developed questionnaire and analyzed through descriptive statistics, Chi-square tests, and association analysis. Results: The results indicated that 23.4% of mothers initiated PNC services within 4–14 days after delivery. Mothers arriving for PNC services after receiving PNC health talks had better utilization of PNC services (OR: 1.50, 95% CI: 1.25–1.80). Conversely, postpartum mothers who were observed to be taking iron supplements (OR: 0.72, 95% CI: 0.57–0.91) and malaria drugs (OR: 0.49, 95% CI: 0.38–0.63) were linked to poorer PNC utilization. More than half (52.3%) of the mothers demonstrated poor PNC utilization. Factors negatively influencing utilization of PNC services included long distances to health facilities (OR: 1.50, 95% CI: 1.25–1.80), negative healthcare provider attitudes (OR: 0.73, 95% CI: 0.62–0.85), and lengthy waiting times (OR: 0.79, 95% CI: 0.67–0.93). Conclusion: This study highlights the need for interventions to promote timely and optimal utilization of PNC services. Addressing barriers related to distance, healthcare provider attitudes, and financial constraints are essential to encourage better access and utilization of PNC services. Targeted strategies can ultimately contribute to improved maternal and newborn health outcomes.

BACKGROUND: Medication safety is of paramount importance in nursing practice to ensure the accurate administration of medications. MATERIALS AND METHODS: We conducted a parallel-group randomized controlled trial involving a control group (n = 119) and an intervention group (n = 119) of nursing students at the University of Calabar Teaching Hospital (UCTH). Randomization was achieved using computer-generated random numbers. The study design employed was a parallel-group randomized controlled trial. Descriptive statistics were utilized to summarize participant characteristics, and inferential statistics were employed to compare outcomes between the control and intervention groups. RESULTS: Both groups demonstrated significant improvements in knowledge and practice of medication safety. In the control group, pre-intervention knowledge was 65.9%, increasing to 82.4% post-intervention. The intervention group exhibited an increase from 66.7% to 90.6% after targeted interventions. Practice assessments also yielded positive outcomes, with high medication safety practice rising from 52.1% to 65.5% in the control group, and from 56.3% to 80.7% in the intervention group post-intervention. CONCLUSION: This study underscores the dedication of nursing students to patient safety and affirms the effectiveness of both standard curriculum-based education and targeted interventions in enhancing medication safety knowledge and practice. Even the control group displayed notable competence, indicating the strength of the existing educational framework at UCTH. To further improve conditions and benefit the beneficiaries, we propose ongoing education and training for nursing students, as well as continued adherence to established protocols in medication safety within nursing education. These efforts will ultimately contribute to heightened patient care and safety in clinical settings.

Summary: The development of hybrid compounds has been widely considered as a promising strategy to circumvent the difficulties that emerge in cancer treatment. The well-established strategy of adding acetyl groups to certain drugs has been demonstrated to enhance their therapeutic efficacy. Based on our previous work, an approach of accommodating two chemical entities into a single structure was implemented to synthesize new acetylated hybrids (HH32 and HH33) from 5-aminosalicylic acid and 4-thiazolinone derivatives. These acetylated hybrids showed potential anticancer activities and distinct metabolomic profile with antiproliferative properties. The in-silico molecular docking predicts a strong binding of HH32 and HH33 to cell cycle regulators, and transcriptomic analysis revealed DNA repair and cell cycle as the main targets of HH33 compounds. These findings were validated using in vitro models. In conclusion, the pleiotropic biological effects of HH32 and HH33 compounds on cancer cells demonstrated a new avenue to develop more potent cancer therapies.

Microgravity, in space travel and prolonged bed rest conditions, induces cardiovascular deconditioning along with skeletal muscle mass loss and weakness. The findings of microgravity research may also aid in the understanding and treatment of human health conditions on Earth such as muscle atrophy, and cardiovascular diseases. Due to the paucity of biomarkers and the unknown underlying mechanisms of cardiovascular and skeletal muscle deconditioning in these environments, there are insufficient diagnostic and preventative measures. In this study, we employed hindlimb unloading (HU) mouse model, which mimics astronauts in space and bedridden patients, to first evaluate cardiovascular and skeletal muscle function, followed by proteomics and metabolomics LC-MS/MS-based analysis using serum samples. Three weeks of unloading caused changes in the function of the cardiovascular system in c57/Bl6 mice, as seen by a decrease in mean arterial pressure and heart weight. Unloading for three weeks also changed skeletal muscle function, causing a loss in grip strength in HU mice and atrophy of skeletal muscle indicated by a reduction in muscle mass. These modifications were partially reversed by a two-week recovery period of reloading condition, emphasizing the significance of the recovery process. Proteomics analysis revealed 12 dysregulated proteins among the groups, such as phospholipid transfer protein, Carbonic anhydrase 3, Parvalbumin alpha, Major urinary protein 20 (Mup20), Thrombospondin-1, and Apolipoprotein C-IV. On the other hand, metabolomics analysis showed altered metabolites among the groups such as inosine, hypoxanthine, xanthosine, sphinganine, l-valine, 3,4-Dihydroxyphenylglycol, and l-Glutamic acid. The joint data analysis revealed that HU conditions mainly impacted pathways such as ABC transporters, complement and coagulation cascades, nitrogen metabolism, and purine metabolism. Overall, our results indicate that microgravity environment induces significant alterations in the function, proteins, and metabolites of these mice. These observations suggest the potential utilization of these proteins and metabolites as novel biomarkers for assessing and mitigating cardiovascular and skeletal muscle deconditioning associated with such conditions.

AbstractBackground Glioblastoma (GBM) is a primary malignancy of the central nervous system and is classified as a grade IV astrocytoma by the World Health Organization (WHO). Although GBM rarely metastasizes, its prognosis remains poor. Moreover, the standard treatment for GBM, temozolomide (TMZ), is associated with chemoresistance, which is a major factor behind GBM-related deaths. Investigating drugs with repurposing potential in the context of GBM is worthwhile to bypass lengthy bench-to-bedside research. The field of omics has garnered significant interest in scientific research because of its potential to delineate the intricate regulatory network underlying tumor development. In particular, proteomic and metabolomic analyses are powerful approaches for the investigation of metabolic enzymes and intermediate metabolites since they represent the functional end of the cancer phenotype.Methods We chose two of the most widely prescribed anticancer drugs, cisplatin and paclitaxel. To our knowledge, the current literature lacks studies examining their effects on metabolic and proteomic alterations in GBM. We employed the mass spectrometry technological platform ‘UHPLC-Q-TOF-MS/MS’ to examine the changes in the proteome and metabolome profiles of the U87 cell line with defined concentrations of cisplatin and/or paclitaxel via an untargeted approach.Results A total of 1,419 distinct proteins and 90 metabolites were generated, and subsequent analysis was performed. We observed that upon treatment with cisplatin (9.5 μM), U87 cells exhibited apparent efforts to cope with this exogenous stressor, understanding the effect of paclitaxel (5.3 μM) on altering the transport machinery of the cell, and how the combination of cisplatin and/or paclitaxel suggests potential interactions with promising benefits in GBM therapeutics.Conclusion Our research provides a detailed map of alterations in response to cisplatin and paclitaxel treatment, provides crucial insights into the molecular basis of their action, and paves the way for further research to identify molecular targets for this elusive malignancy.

Background and Aim: Human monkeypox is an emerging global threat. Hundreds of publications were disseminated in the last few months. This study aimed to map, analyze, and evaluate the bibliometric indicators of the global monkeypox research output. Materials and Methods: All documents published in the past 20 years were retrieved using the Scopus database. Papers published in English and peer-reviewed journals were included. VOSviewer was used to create density and network visualization maps. Results: A total of 1725 published documents were retrieved. Of these, 53% were published in 2022. The average number of authors per document was 4.2. Authors from the USA were the most active and published about 42.1% of the total documents. International collaboration was evident between the USA and both UK and Congo. Keywords mapping identified the main research lines in this field that correlate monkeypox with public health, smallpox, vaccination, and antiviral treatment. Conclusion: This study analyzed and mapped the expanding field of monkeypox research across the world. The bibliometric analysis revealed that the United States has contributed greatly in terms of both individual researchers and academic institutions. There was less cooperation on a global scale than was anticipated. Fostering international cooperation is essential for countering this worldwide danger. Additional scientific research should be conducted to investigate the link between smallpox immunization and monkeypox epidemics.

IntroductionIn temperate regions, one of the most critical determinants of present range-wide genetic diversity was the Pleistocene climate oscillations, the most recent one created by the last glacial maximum (LGM). This study aimed to describe N. luetkeana genetic structure across its entire range (Alaska to California) and test different models of population connectivity within the Salish Sea. This region was colonized after the LGM and has been under increased disturbance in recent decades.MethodsWe utilized microsatellite markers to study N. luetkeana genetic diversity at 53 sites across its range. Using higher sampling density in the Salish Sea, we employed a seascape genetics approach and tested isolation by hydrodynamic transport and environment models.ResultsAt the species distribution scale, we found four main groups of genetic co-ancestry, Alaska; Washington with Vancouver Island’s outer coast and Juan de Fuca Strait; Washington’s inner Salish Sea; and Oregon with California. The highest allelic richness (AR) levels were found in California, near the trailing range edge, although AR was also high in Alaska. The inner Salish Sea region had the poorest diversity across the species distribution. Nevertheless, a pattern of isolation by hydrodynamic transport and environment was supported in this region.DiscussionThe levels of allelic, private allele richness and genetic differentiation suggest that during the LGM, bull kelp had both northern and southern glacial refugia in the Prince of Wales Island-Haida Gwaii region and Central California, respectively. Genetic diversity in Northern California sites seems resilient to recent disturbances, whereas the low levels of genetic diversity in the inner Salish Sea are concerning.

Rosmarinic acid (RA), a natural ester phenolic compound, is known to have antioxidant and anti-inflammatory properties. RA has also been reported to exhibit a hypoglycemic effect; however, the mechanisms underlying this effect have yet to be investigated. Therefore, the present study focused on the anti-diabetic effects and mechanism of RA in INS-1 cells using in vitro model. Streptozotocin (STZ) at a concentration of 3 mM was applied to INS-1 cells for 4 h to create a diabetic model. The cells were pretreated for 24 h with various concentrations (1 and 2.5 μM) of RA. The Cell viability, glucose-stimulated insulin secretion (GSIS), glucose uptake, lipid peroxidation, reactive oxygen species (ROS), apoptosis, and protein expression of Bcl-2, NF-κB, 1L-1β, and PARP were assessed. Results showed that STZ-treated INS-1 cells exhibited reduced cell viability, insulin release, insulin content, glucose uptake, and elevated MDA and ROS levels. Cells pretreated with RA maintained the function and morphology of β-cells against STZ-induced damage. Moreover, RA sustained high protein expression levels of Bcl-2 and low expression levels of NF-κB, IL-1β, and PARP. In conclusion, RA preserved β-cells function against STZ-induced damage by altering NF-κB and Bcl-2 pathways.

Abstract The use of alternative tobacco products, particularly medwakh, has expanded among youth in the Middle East and around the world. The present study is conducted to investigate the biochemical and pathophysiological changes caused by medwakh smoking, and to examine the salivary metabolomics profile of medwakh smokers. Saliva samples were collected from 30 non-smokers and 30 medwakh smokers and subjected to metabolomic analysis by UHPLC-ESI-QTOF-MS. The CRP and Glutathione Peroxidase 1 activity levels in the study samples were quantified by ELISA and the total antioxidant capacity (TAC) by TAC assay kits. Statistical measurements and thorough validation of data obtained from untargeted metabolomics identified 37 uniquely and differentially abundant metabolites in saliva of medwakh smokers. The levels of phthalate, L-sorbose, cytosine, uridine, alpha-hydroxy hippurate, and L-nicotine were noticeably high in medwakh smokers. Likewise, 20 metabolic pathways were differentially altered in medwakh smokers. This study identified a distinctive saliva metabolomics profile in medwakh smokers associated with altered redox homeostasis, metabolic pathways, antioxidant system, and CRP levels. The impact of the altered metabolites in medwakh smokers and their diagnostic utility require further research in large cohorts.

Gold nanoparticles (GNPs) are widely searched for their usage in breast cancer research because of their unique features. For example, these particles can deliver drugs to specific sites, making imaging and photothermal therapy possible, thus rendering them suitable particles for theranostic purposes. Bibliometric research is a statistical analytical technique useful for the data systematically found in the literature. In this bibliometric study, the global research output regarding GNPs in breast cancer (BC) research was analyzed, mapped, and evaluated using bibliometric indicators.All documents related to the application of GNPs applications in BC research that were published in English-language, peer-reviewed journals over the past 20 years were retrieved from the Scopus database. Bibliometric indicators were extracted using VOSviewer and Biblioshiny. Thematic maps, conceptual maps, and visualization graphs were created.A total of 2035 published documents were retrieved. Chinese authors were the most active, having published approximately 27.5% of the total documents, while researchers from the United States (USA) had the most significant scientific impact. The study revealed weak international collaboration in this research area. Keywords mapping identified the main research themes and hotspots in this research field. Multimodal approaches in cancer treatment and diagnostics, targeted and effective cancer treatment, aptamers and biosensors, and green synthesis of GNPs were the four clusters retrieved from theme and hotspot analyses. This study analyzed and mapped the expanding field of GNPs in breast cancer research (GNP-BCR) and identified various applications of GNPs in this field. GNPs were used as drug delivery systems to target specific cancer cells and improve anticancer drug bioavailability. Different treatment and diagnostic modalities were revealed, such as photodynamic therapy (PDT) and photothermal therapy (PTT). Moreover, the development of aptamer-based biosensors using gold nanoparticles was identified as a niche theme in this research, while the green synthesis of GNPs emerged as a new and promising theme. However, clinical research is still warranted to translate this fundamental knowledge into practical and human-useable formulas.

Abstract Background Extensive studies have confirmed social support as a critical protective factor of people’s health-related quality of life (HRQoL) and subjective well-being (SWB). However, health promoting behaviors as a potential mechanism and age differences in this mechanism has received fewer attention. This study aims to examine the associations among social support, health promoting behaviors, HRQoL and SWB in older and younger persons in Hong Kong. Method A convenience sample of both younger (12–35 years old) and older persons (55 years old and above) were recruited from three non-government organizations to complete a survey. Structural Equation Model (SEM) was conducted to test both the measurement model and structural models to examine the relationship between social support, health promoting behaviors, HRQoL and SWB. Multi-group SEM was also performed and compared to test whether there were significant age differences in the pathways between the key variables. Results A final sample of 408 participants (older-persons: N = 200 (mean age: 71.63 (8.16); 180/200 female), younger-persons: N = 208 (mean age: 18.10 (5.04); 155/208 female) were included in the final analysis. Results showed that social support was positively associated with SWB directly and indirectly through health promoting behaviors for the whole sample (CFI = .95, IFI = .94, RMSEA = .07, SRMR = 0.056). Results suggested that the association between the variables differed across age samples. While social support showed a positive association with health promoting behaviors for both younger and older persons, how each of them associated with HRQoL and SWB was different. Conclusion Findings suggest that the pathway which social support linked with HRQoL and SWB might differ across age groups. Age-specific strategies should be considered when promoting HRQoL and SWB among the younger and older population.

Candida albicans is a common pathogenic fungus that presents a challenge to healthcare facilities. It can switch between a yeast cell form that diffuses through the bloodstream to colonize internal organs and a filamentous form that penetrates host mucosa. Understanding the pathogen’s strategies for environmental adaptation and, ultimately, survival, is crucial. As a complementary study, herein, a multi-omics analysis was performed using high-resolution timsTOF MS to compare the proteomes and metabolomes of Wild Type (WT) Candida albicans (strain DK318) grown on agar plates versus liquid media. Proteomic analysis revealed a total of 1793 proteins and 15,013 peptides. Out of the 1403 identified proteins, 313 proteins were significantly differentially abundant with a p-value < 0.05. Of these, 156 and 157 proteins were significantly increased in liquid and solid media, respectively. Metabolomics analysis identified 192 metabolites in total. The majority (42/48) of the significantly altered metabolites (p-value 0.05 FDR, FC 1.5), mainly amino acids, were significantly higher in solid media, while only 2 metabolites were significantly higher in liquid media. The combined multi-omics analysis provides insight into adaptative morphological changes supporting Candida albicans’ life cycle and identifies crucial virulence factors during biofilm formation and bloodstream infection.

Purpose – Ticketing system is common in Technical Support in Information Technology Industry. At present time, even management is using it. It serves as a way to connect the company and the client, end to end. Support Industry used this also to monitor and log all solutions and processes that come up to resolve the ticket. Client and the resources that will troubleshoot this, use the ticket to have an idea for what is the problem, when the client encountered it, and even the business impact. The researchers conducted research entitled “Impact of Critical and Auto Ticket’s: Analysis for Management and Workers Productivity in using Ticketing System" where it aims to come up with a solution on how we are going to prevent, troubleshoot, and give insight for possible business impact to those everyday issues. This will help the management’s business process to have an analysis to prevent critical issues that will affect the live production as well as give time to their resource to focus on their tasks. Method – Researchers used data collection to gather data from management, support workers, and Service Now’s open-source ticketing system to visualize the ticketing system application. Also, a purposive sampling type of survey has been used to highly represent the data. Results – Critical ticket gives a lot of pressure to the resources as they needed to resolve the incident in accordance with the service level agreement. It affects their productivity to maximize their time to resolve other escalated incidents as they need to focus with critical ones. Instead of maximizing time management and prioritizing employee’s welfare like work and life balance, auto ticket’s affects it because of continuous re-occurring and sometimes needed to be escalated as it will affect the live production. Having knowledge management helps resource to find references on how to deal with the incident. It helps them to execute workaround quickly and think of a way on how to resolve it permanently. Conclusion – It is concluded that critical and auto ticket’s affects the everyday productivity of the worker especially teaching new employees despite ongoing critical incidents. Researchers provided solutions such as knowledge Management and Dashboard to document all the solutions encountered and monitor the SLA’s and incoming tickets. Recommendation – It is recommended to have further research on how critical and auto ticket affects the mental health of resources and its direct impact to businesses. It is also recommended to have a study on how knowledge management work and help resources to identify correct workaround despite of having a lot of troubleshooting guides. Practical Implication – This research benefits data warehousing companies that can be used as a third-party application to connect support team, management, and clients. Management can create a dashboard and identify how their support team provides good quality of service with their response and resolution time. Support team can have a reference to quickly fix escalated incidents and provide ticket number to the client for easily follow up an update.

Purpose – This study aims to shed light on the rise of play-to-earn games in the Philippines alongside cryptocurrency. The lack of research and public understanding of its benefits and drawbacks prompted the researchers to investigate its market. As such, the study tried to look into the risks and benefits of crypto gaming if it would be regulated by the government, and how market volatility influences the churn rate of crypto games. Method – The research used a descriptive study to determine the perception of people who are engaged in playing “Axie Infinity”. The research also used non-probability sampling using the snowball method. The only tool used to collect data was Google Forms. Furthermore, the study used Statistical Package for Social Science (SPSS) to analyze the descriptive data. Result – The results showed that most players spend their time playing Axie Infinity for about 1 to 4 hours a day. Predominantly, the return of investments for playing the game will take about 1 to 3 months. It also showed that these players agreed that there is a possible financial instability in a volatile market. With this, they have a high trust issue in terms of price manipulation, privacy and security, and its design and usability. Conclusion – Understanding the cryptocurrency market requires comprehending the perspective of the people who are engaged in a play-to-earn game, and their concerns are critical for any government actions aimed at regulating self-employed income earners playing (Non-fungible Tokens) NFT games in the Philippines. Recommendations – It is suggested that further research must be conducted to understand how self-employed Filipino income earners comprehend NFT gaming and cryptocurrency, impacting their level of interest and participation. Research Implications – Taxing NFT games without sound regulatory frameworks may result in the disarray of this alternative income source. Therefore, the government must tread carefully to avoid a market collapse or other unfavorable outcomes.

IntroductionDuring the holy month of Ramadan, adult healthy Muslims are mandated to abstain from dawn to sunset, with free eating at night hours that may extend up to 12 h. The current work was designed to investigate the metabolomics changes incurred upon the observance of Ramadan diurnal intermittent fasting (RDIF).MethodsTwenty-five metabolically healthy participants with overweight and obesity (7 females and 18 males, with a mean age of 39.48 ± 10.0 years) were recruited for the study and were followed before and at the end of RDIF month. Dietary, anthropometric, biochemical, and physical activity assessments were performed before and at the end of the fasting month. The metabolomic assay was performed using liquid chromatography-mass spectrometry for the two-time points.Results and discussionMetabolomics assay revealed a significant reduction in a few metabolites. The analysis revealed that 27 metabolites differed significantly (P < 0.05) between pre-and post-RDIF. Among the differentially abundant metabolites, 23 showed a decrease with fasting, these included several amino acids such as aspartame, tryptophan, phenylalanine, histidine, and other metabolites including valeric acid, and cortisol. On the other hand, only four metabolites showed increased levels after RDIF including traumatic acid, 2-pyrrolidinone, PC[18:1(9Z)/18:1(9Z)], and L-sorbose. The MetaboAnalyst® platform reported that the top enriched metabolic pathways included: (1) histidine metabolism; (2) folate biosynthesis (3) phenylalanine, tyrosine, and tryptophan biosynthesis; (4) aminoacyltRNA biosynthesis; (5) caffeine metabolism; (6) vitamin B6 metabolism; and several other pathways relating to lipid metabolisms such as arachidonic acid metabolism, glycerophospholipid metabolism, and linoleic acid metabolism. In conclusion, RDIF entails significant changes in various metabolic pathways that reflect different dietary and lifestyle behaviors practiced during the fasting month.

Increased levels of 17-β estradiol (E2) due to pregnancy in young women or to hormonal replacement therapy in postmenopausal women have long been associated with an increased risk of yeast infections. Nevertheless, the effect underlying the role of E2 in Candida albicans infections is not well understood. To address this issue, functional, transcriptomic, and metabolomic analyses were performed on C. albicans cells subjected to temperature and serum induction in the presence or absence of E2. Increased filament formation was observed in E2 treated cells. Surprisingly, cells treated with a combination of E2 and serum showed decreased filament formation. Furthermore, the transcriptomic analysis revealed that serum and E2 treatment is associated with downregulated expression of genes involved in filamentation, including HWP1, ECE1, IHD1, MEP1, SOD5, and ALS3, in comparison with cells treated with serum or estrogen alone. Moreover, glucose transporter genes HGT20 and GCV2 were downregulated in cells receiving both serum and E2. Functional pathway enrichment analysis of the differentially expressed genes (DEGs) suggested major involvement of E2 signaling in several metabolic pathways and the biosynthesis of secondary metabolites. The metabolomic analysis determined differential secretion of 36 metabolites based on the different treatments’ conditions, including structural carbohydrates and fatty acids important for hyphal cell wall formation such as arabinonic acid, organicsugar acids, oleic acid, octadecanoic acid, 2-keto-D-gluconic acid, palmitic acid, and steriacstearic acid with an intriguing negative correlation between D-turanose and ergosterol under E2 treatment. In conclusion, these findings suggest that E2 signaling impacts the expression of several genes and the secretion of several metabolites that help regulate C. albicans morphogenesis and virulence.

Defective in cullin neddylation 1 domain containing 1 (DCUN1D1) is an E3 ligase for the neddylation, a post-translational process similar to and occurring in parallel to ubiquitin proteasome pathway. Although established as an oncogene in a variety of squamous cell carcinomas, the precise role of DCUN1D1 in prostate cancer (PCa) has not been previously explored thoroughly. Here, we investigated the role of DCUN1D1 in PCa and demonstrated that DCUN1D1 is upregulated in cell lines as well as human tissue samples. Inhibition of DCUN1D1 significantly reduced PCa cell proliferation and migration and remarkably inhibited xenograft formation in mice. Applying both genomics and proteomics approaches, we provide novel information about the DCUN1D1 mechanism of action. We identified CUL3, CUL4B, RBX1, CAND1 and RPS19 proteins as DCUN1D1 binding partners. Our analysis also revealed the dysregulation of genes associated with cellular growth and proliferation, developmental, cell death and cancer pathways and the WNT/β-catenin pathway as potential mechanisms. Inhibition of DCUN1D1 leads to the inactivation of β-catenin through its phosphorylation and degradation which inhibits the downstream action of β-catenin, reducing its interaction with Lef1 in the Lef1/TCF complex that regulates Wnt target gene expression. Together our data point to an essential role of the DCUN1D1 protein in PCa which can be explored for potential targeted therapy.

Metastasis is a serious and often life-threatening condition, representing the leading cause of death among women with breast cancer (BC). Although the current clinical classification of BC is well-established, the addition of minimally invasive laboratory tests based on peripheral blood biomarkers that reflect pathological changes in the body is of utmost importance. In the current study, the serum proteome and lipidome profiles for 50 BC patients with (25) and without (25) metastasis were studied. Targeted proteomic analysis for concertation measurements of 125 proteins in the serum was performed via liquid chromatography–multiple reaction monitoring mass spectrometry (LC–MRM MS) using the BAK 125 kit (MRM Proteomics Inc., Victoria, BC, Canada). Untargeted label-free lipidomic analysis was performed using liquid chromatography coupled to tandem mass-spectrometry (LC–MS/MS), in both positive and negative ion modes. Finally, 87 serum proteins and 295 lipids were quantified and showed a moderate correlation with tumor grade, histological and biological subtypes, and the number of lymph node metastases. Two highly accurate classifiers that enabled distinguishing between metastatic and non-metastatic BC were developed based on proteomic (accuracy 90%) and lipidomic (accuracy 80%) features. The best classifier (91% sensitivity, 89% specificity, AUC = 0.92) for BC metastasis diagnostics was based on logistic regression and the serum levels of 11 proteins: alpha-2-macroglobulin, coagulation factor XII, adiponectin, leucine-rich alpha-2-glycoprotein, alpha-2-HS-glycoprotein, Ig mu chain C region, apolipoprotein C-IV, carbonic anhydrase 1, apolipoprotein A-II, apolipoprotein C-II and alpha-1-acid glycoprotein 1.

We present an exploratory study of differences in international students' adjustment and social-emotional outcomes based on key demographic variables. Drawing on a sample of 558 international students attending 14 colleges and universities in the United States, we examined students' belonging, social support, academic stress and confidence, COVID-19-related stress, and social integration by students' gender, graduate level, and region of origin as well as by combinations of gender, graduate level, and region of origin. Key findings include that graduate and undergraduate female students as well as graduate male students reported better social-emotional experiences compared with undergraduate male students and that students' region of origin accounted for a range of differences in student outcomes. Findings are discussed both in relation to the current literature and with respect to opportunities for methodological development in the field of international student engagement and global student mobility.

Dengue fever (DF), caused by the dengue virus (DENV), is the most burdensome arboviral disease in the world, with an estimated 400 million infections each year. The Aedes aegypti mosquito is the main vector of DENV and transmits several other human pathogens, including Zika, yellow fever, and chikungunya viruses. Previous studies have shown that the pathogen infection of mosquitoes can alter reproductive fitness, revealing specific vector-pathogen interactions that are key determinants of vector competence. However, only a handful of studies have examined the effect of DENV infection in A. aegypti, showing a reduction in lifespan and fecundity over multiple blood meals. To provide a more comprehensive analysis of the impact of DENV infection on egg laying and fecundity, we assessed egg laying timing in DENV-2 blood-fed mosquitoes (infected group) compared to mock blood-fed mosquitoes (control group). We confirmed a significant decrease in fecundity during the first gonadotrophic cycle. To further investigate this phenotype and the underlying DENV-2 infection-dependent changes in gene expression, we conducted a transcriptomic analysis for differentially expressed genes in the ovaries of A. aegypti infected with DENV-2 vs. mock-infected mosquitoes. This analysis reveals several DENV-2-regulated genes; among them, we identified a group of 12 metabolic genes that we validated using reverse transcription-quantitative PCR (RT-qPCR). Interestingly, two genes found to be upregulated in DENV-infected mosquito ovaries exhibited an antiviral role for DENV-2 in an Aedes cell line. Altogether, this study offers useful insights into the virus-vector interface, highlighting the importance of gene expression changes in the mosquito’s ovary during DENV-2 infection in the first gonadotrophic cycle, triggering antiviral responses that may possibly interfere with mosquito reproduction. This information is extremely relevant for further investigation of A. aegypti’s ability to tolerate viruses since virally infected mosquitoes in nature constitute a powerful source of supporting viruses during intra-epidemic periods, causing a huge burden on the public health system.

Water monitor lizards (WMLs) reside in unhygienic and challenging ecological surroundings and are routinely exposed to various pathogenic microorganisms. It is possible that their gut microbiota produces substances to counter microbial infections. Here we determine whether selected gut bacteria of water monitor lizards (WMLs) possess anti-amoebic properties using Acanthamoeba castellanii of the T4 genotype. Conditioned media (CM) were prepared from bacteria isolated from WML. The CM were tested using amoebicidal, adhesion, encystation, excystation, cell cytotoxicity and amoeba-mediated host cell cytotoxicity assays in vitro. Amoebicidal assays revealed that CM exhibited anti-amoebic effects. CM inhibited both excystation and encystation in A. castellanii. CM inhibited amoebae binding to and cytotoxicity of host cells. In contrast, CM alone showed limited toxic effects against human cells in vitro. Mass spectrometry revealed several antimicrobials, anticancer, neurotransmitters, anti-depressant and other metabolites with biological functions. Overall, these findings imply that bacteria from unusual places, such as WML gut, produce molecules with anti-acanthamoebic capabilities.

Recently, aflatoxin exposure especially through maize and groundnuts has been associated with growth impairment in children. Infants and children are considered to be more susceptible to toxins because of their lower body weight, higher metabolic rate, and lower ability to detoxify. On the other hand, for women of reproductive age, aflatoxin exposure may not only affect their health but also that of their foetus in the case of pregnancy. This study focused on investigating AFB1 contamination in maize and groundnut from respondent households, exposure among women of reproductive age and associations of aflatoxin contamination with growth retardation among children in Mtwara region, Tanzania. The highest maximum AFB1 contamination levels from all samples obtained were in maize grain (2351.5 μg/kg). From a total of 217 maize samples collected, aflatoxins were above European Union (EU) and East African Community (EAC) tolerable limits in 76.0% and 64.5% of all samples. Specifically, maize grain had the highest proportion of samples contaminated above tolerable limits (80.3% and 71.1% for EU and EAC limits). Groundnut had 54.0% and 37.9% of samples above EU and EAC maximum tolerable limits. The lowest proportion of contaminated samples on the other hand was for bambara nut (37.5% and 29.2% for EU and EAC limits, respectively). Aflatoxin exposure in our surveyed population was much higher than previous observations made in Tanzania and also higher than those observed in Western countries such as Australia and the USA. Among children, AFB1 concentration was associated with lower weight for height z scores and weight for age z scores in the univariate model (p < 0.05). In summary, these results indicate the seriousness of aflatoxin contamination in foods commonly consumed in the vulnerable population assessed. Strategies both from the health, trade, and nutrition sectors should therefore be designed and implemented to address aflatoxin and mycotoxin contamination in diets.

Abstract Background Being diagnosed with cancer, irrespective of type initiates a serious psychological concern. The increasing rate of detection of indolent prostate cancers is a source of worry to public health. Digital rectal examination and prostate-specific antigen tests are the commonly used prostate cancer screening tests. Understanding the diagnostic accuracies of these tests may provide clearer pictures of their characteristics and values in prostate cancer diagnosis. This review compared the sensitivities and specificities of digital rectal examination and prostate-specific antigen test in detection of clinically important prostate cancers using studies from wider population. Main body We conducted literature search in PubMed, Medline, Science Direct, Wiley Online, CINAHL, Scopus, AJOL and Google Scholar, using key words and Boolean operators. Studies comparing the sensitivity and specificity of digital rectal examination and prostate-specific antigen tests in men 40 years and above, using biopsy as reference standard were retrieved. Data were extracted and analysed using Review manager (RevMan 5.3) statistical software. The overall quality of the studies was good, and heterogeneity was observed across the studies. The result comparatively shows that prostate-specific antigen test has higher sensitivity (P

The profound effects of and distress caused by the global COVID-19 pandemic highlighted what has been known in the health sciences a long time ago: that bacteria, fungi, viruses, and parasites continue to present a major threat to human health. Infectious diseases remain the leading cause of death worldwide, with antibiotic resistance increasing exponentially due to a lack of new treatments. In addition to this, many pathogens share the common trait of having the ability to modulate, and escape from, the host immune response. The challenge in medical microbiology is to develop and apply new experimental approaches that allow for the identification of both the microbe and its drug susceptibility profile in a time-sensitive manner, as well as to elucidate their molecular mechanisms of survival and immunomodulation. Over the last three decades, proteomics has contributed to a better understanding of the underlying molecular mechanisms responsible for microbial drug resistance and pathogenicity. Proteomics has gained new momentum as a result of recent advances in mass spectrometry. Indeed, mass spectrometry-based biomedical research has been made possible thanks to technological advances in instrumentation capability and the continuous improvement of sample processing and workflows. For example, high-throughput applications such as SWATH or Trapped ion mobility enable the identification of thousands of proteins in a matter of minutes. This type of rapid, in-depth analysis, combined with other advanced, supportive applications such as data processing and artificial intelligence, presents a unique opportunity to translate knowledge-based findings into measurable impacts like new antimicrobial biomarkers and drug targets. In relation to the Research Topic “Proteomic Approaches to Unravel Mechanisms of Resistance and Immune Evasion of Bacterial Pathogens,” this review specifically seeks to highlight the synergies between the powerful fields of modern proteomics and microbiology, as well as bridging translational opportunities from biomedical research to clinical practice.

Due to an increase in the overuse of antimicrobials and accelerated incidence of drug resistant pathogens, antimicrobial resistance has become a global health threat. In particular, bacterial antimicrobial resistance, in both hospital and community acquired transmission, have been found to be the leading cause of death due to infectious diseases. Understanding the mechanisms of bacterial drug resistance is of clinical significance irrespective of hospital or community acquired since it plays an important role in the treatment strategy and controlling infectious diseases. Here we highlight the advances in mass spectrometry-based proteomics impact in bacterial proteomics and metabolomics analysis- focus on bacterial drug resistance. Advances in omics technologies over the last few decades now allows multi-omics studies in order to obtain a comprehensive understanding of the biochemical alterations of pathogenic bacteria in the context of antibiotic exposure, identify novel biomarkers to develop new drug targets, develop time-effectively screen for drug susceptibility or resistance using proteomics and metabolomics.

Despite the growing number of the vaccinated population, COVID-19, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), remains a global health burden. Obesity, a metabolic syndrome affecting one-third of the population, has proven to be a major risk factor for COVID-19 severe complications. Several studies have identified metabolic signatures and disrupted metabolic pathways associated with COVID-19, however there are no reports evaluating the role of obesity in the COVID-19 metabolic regulation. In this study we highlight the involvement of obesity metabolically in affecting SARS-CoV-2 infection and the consequent health complications, mainly cardiovascular disease. We measured one hundred and forty-four (144) metabolites using ultra high-performance liquid chromatography-quadrupole time of flight mass spectrometry (UHPLC-QTOF-MS) to identify metabolic changes in response to SARS-CoV-2 infection, in lean and obese COVID-19 positive (n=82) and COVID-19 negative (n=24) patients. The identified metabolites are found to be mainly correlating with glucose, energy and steroid metabolisms. Further data analysis indicated twelve (12) significantly yet differentially abundant metabolites associated with viral infection and health complications, in COVID-19 obese patients. Two of the detected metabolites, n6-acetyl-l-lysine and p-cresol, are detected only among the COVID-19 cohort, exhibiting significantly higher levels in COVID-19 obese patients when compared to COVID-19 lean patients. These metabolites have important roles in viral entry and could explain the increased susceptibility of obese patients. On the same note, a set of six metabolites associated with antiviral and anti-inflammatory functions displayed significantly lower abundance in COVID-19 obese patients. In conclusion, this report highlights the plasma metabolome of COVID-19 obese patients as a metabolic feature and signature to help improve clinical outcomes. We propose n6-acetyl-l-lysine and p-cresol as potential metabolic markers which warrant further investigations to better understand their involvement in different metabolic pathways in COVID-19.

Genetic mechanisms that repress transposable elements (TEs) in young animals decline during aging, as reflected by increased TE expression in aged animals. Does increased TE expression during aging lead to more genomic TE copies in older animals? To address this question, we quantified TE Landscapes (TLs) via whole genome sequencing of young and aged Drosophila strains of wild-type and mutant backgrounds. We quantified TLs in whole flies and dissected brains and validated the feasibility of our approach in detecting new TE insertions in aging Drosophila genomes when small RNA and RNA interference (RNAi) pathways are compromised. We also describe improved sequencing methods to quantify extra-chromosomal DNA circles (eccDNAs) in Drosophila as an additional source of TE copies that accumulate during aging. Lastly, to combat the natural progression of aging-associated TE expression, we show that knocking down PAF1, a conserved transcription elongation factor that antagonizes RNAi pathways, may bolster suppression of TEs during aging and extend lifespan. Our study suggests that in addition to a possible influence by different genetic backgrounds, small RNA and RNAi mechanisms may mitigate genomic TL expansion despite the increase in TE transcripts during aging. Author summary Transposable elements, also called transposons, are genetic parasites found in all animal genomes. Normally, transposons are compacted away in silent chromatin in young animals. But, as animals age and transposon-silencing defense mechanisms break down, transposon RNAs accumulate to significant levels in old animals like fruit flies. An open question is whether the increased levels of transposon RNAs in older animals also correspond to increased genomic copies of transposons. This study approached this question by sequencing the whole genomes of young and old wild-type and mutant flies lacking a functional RNA interference (RNAi) pathway, which naturally silences transposon RNAs. Although the wild-type flies with intact RNAi activity had little new accumulation of transposon copies, the sequencing approach was able to detect several transposon accumulation occurrences in some RNAi mutants. In addition, we found that some fly transposon families can also accumulate as extra-chromosomal circular DNA copies. Lastly, we showed that genetically augmenting the expression of RNAi factors can counteract the rising transposon RNA levels in aging and promote longevity. This study improves our understanding of the animal host genome relationship with transposons during natural aging processes.

Abstract Background Mobile health clinics serve an important role in the health care system, providing care to some of the most vulnerable populations. Mobile Health Map is the only comprehensive database of mobile clinics in the United States. Members of this collaborative research network and learning community supply information about their location, services, target populations, and costs. They also have access to tools to measure, improve, and communicate their impact. Methods We analyzed data from 811 clinics that participated in Mobile Health Map between 2007 and 2017 to describe the demographics of the clients these clinics serve, the services they provide, and mobile clinics’ affiliated institutions and funding sources. Results Mobile clinics provide a median number of 3491 visits annually. More than half of their clients are women (55%) and racial/ethnic minorities (59%). Of the 146 clinics that reported insurance data, 41% of clients were uninsured while 44% had some form of public insurance. The most common service models were primary care (41%) and prevention (47%). With regards to organizational affiliations, they vary from independent (33%) to university affiliated (24%), while some (29%) are part of a hospital or health care system. Most mobile clinics receive some financial support from philanthropy (52%), while slightly less than half (45%) receive federal funds. Conclusion Mobile health care delivery is an innovative model of health services delivery that provides a wide variety of services to vulnerable populations. The clinics vary in service mix, patient demographics, and relationships with the fixed health system. Although access to care has increased in recent years through the Affordable Care Act, barriers continue to persist, particularly among populations living in resource-limited areas. Mobile clinics can improve access by serving as a vital link between the community and clinical facilities. Additional work is needed to advance availability of this important resource.

Background: Protein energy malnutrition (PEM) and iron deficiencies (ID) are of major public health concern in Tanzania including among school-aged children. PEM and ID in early childhood have serious, long-term consequences because they impede motor, sensory, social and emotional development, growth retardation, poor cognitive development, learning disability of children, lowered resistance to infectious diseases, and reduced physical work capacity. The objective of this study was to elucidate the drivers of pigeon pea consumption among school-aged children in Dodoma district, Central Tanzania. Understanding these drivers would be useful in promoting pigeon pea consumption among school-aged children as one of the strategies to increase dietary protein and iron intake.Methods: This study was a cross-sectional study in which data were collected using a questionnaire based on a combination of the Theory of Planned Behavior and Health Belief Model. The data were collected from caregivers (n = 138) in four villages in Kongwa district, Dodoma region, Central Tanzania. We used correlations and multiple regressions to assess associations between constructs and identify predictive constructs. Mann–Whitney U tests were used for score comparisons with a significant p-value set at

Despite the availability of effective drug treatment, Mycobacterium tuberculosis (Mtb), the causative agent of TB disease, kills ~1. 5 million people annually, and the rising prevalence of drug resistance increasingly threatens to worsen this plight. We previously showed that sublethal exposure to the frontline anti-TB drug, rifampicin, resulted in substantial adaptive remodeling of the proteome of the model organism, Mycobacterium smegmatis, in the drug-sensitive mc2155 strain [wild type (WT)]. In this study, we investigate whether these responses are conserved in an engineered, isogenic mutant harboring the clinically relevant S531L rifampicin resistance-conferring mutation (SL) and distinguish the responses that are specific to RNA polymerase β subunit- (RpoB-) binding activity of rifampicin from those that are dependent on the presence of rifampicin alone. We verified the drug resistance status of this strain and observed no phenotypic indications of rifampicin-induced stress upon treatment with the same concentration as used in WT (2.5 μg/ml). Thereafter, we used a cell wall-enrichment strategy to focus attention on the cell wall proteome and observed 253 proteins to be dysregulated in SL bacteria in comparison with 716 proteins in WT. We observed that decreased abundance of ATP-binding cassette (ABC) transporters and increased abundance of ribosomal machinery were conserved in the SL strain, whereas the upregulation of transcriptional machinery and the downregulation of numerous two-component systems were not. We conclude that the drug-resistant M. smegmatis strain displays some of the same proteomic responses observed in WT and suggest that this evidence supports the hypothesis that rifampicin exercises effects beyond RpoB-interaction alone and that mycobacteria recognise rifampicin as a signaling molecule in an RpoB-independent manner at sublethal doses. Taken together, our data indicates mixed RpoB-independent and RpoB-dependent proteomic remodeling in WT mycobacteria, with evidence for RpoB-independent ABC transporter downregulation, but drug activity-based transcriptional upregulation and two-component system downregulation.

Background: Iron and zinc deficiency are common public health problems in low-income countries largely due to poor consumption of iron and zinc rich foods. It has previously been observed that 57% of school aged children (SAC) in Tanzania suffer from anemia. In addition, estimates indicate that over 25% of the population have inadequate zinc intake. Pearl millet is an example of a nutrient dense, resilient cereal crop, that can be promoted to diversify diets and combat iron and zinc deficiency. This study overall aim was to increase pearl millet consumption among school aged (5 – 12 years) children. As part of the study, we investigated, the drivers of food choice relating to pearl millet consumption.Methods: The study was a cross-sectional study of randomly selected households in Kongwa district, Dodoma region of Tanzania. In total, 128 women of reproductive age (20 – 49 years) were randomly selected for the study. A study questionnaire consisting of 66 items, was developed and validated. The constructs in the questionnaire were categorized in two groups: internal and external factors. Respondents were asked to indicate their level of agreement or disagreement with statements read to them by interviewers. The scores on intention and behavior constructs were based on the number of times caregivers intended to, or had fed their school going children with pearl millet in the referent month. Intention was considered high if it was higher than the median intention score of the group, and low if it was equal to or lower than the median scores. Correlations and multiple linear regressions were performed to measure association between constructs and to identify predictive constructs. The Mann-Whitney U test was used for score comparison.Results: There was a significant difference between intention and behavior among those who did not consume pearl millet (P = 0.003), and those who consumed pearl millet two or more times a week, in the same month (P = 0.01). Knowledge was significantly correlated with behavior identity (ρ = 0.58, P = 0.001), while health behavior identity was significantly correlated with intention (ρ = 0.31, P = 0.001). Intention of caregivers was significantly and positively correlated (ρ = 0.44, P = 0.001) with and predicted consumption of pearl millet (ρ = 0.87, P = 0.067).Conclusion: Increasing knowledge or awareness on nutritional benefits of pearl millet among caregivers may increase consumption of pearl millet by children of school going age.

Diabetic kidney disease (DKD) is a severe irreversible complication of diabetes mellitus that further disturbs glucose metabolism. Identifying metabolic changes in the blood may provide early insight into DKD pathogenesis. This study aims to determine blood biomarkers differentiating DKD from non-diabetic kidney disease in the Emirati population utilizing the LC-MS/MS platform. Blood samples were collected from hemodialysis subjects with and without diabetes to detect indicators of pathological changes using an untargeted metabolomics approach. Metabolic profiles were analyzed based on clinically confirmed diabetic status and current HbA1c values. Five differentially significant metabolites were identified based on the clinically confirmed diabetic status, including hydroxyprogesterone and 3,4-Dihydroxymandelic acid. Similarly, we identified seven metabolites with apparent differences between Dialysis Diabetic (DD) and Dialysis non-Diabetic (DND) groups, including isovalerylglycine based on HbA1c values. Likewise, the top three metabolic pathways, including Tyrosine metabolism, were identified following the clinically confirmed diabetic status. As a result, nine different metabolites were enriched in the identified metabolic pathways, such as 3,4-Dihydroxymandelic acid. As a result, eleven different metabolites were enriched, including Glycerol. This study provides an insight into blood metabolic changes related to DKD that may lead to more effective management strategies.