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Abstract Background Risk factors for non-communicable diseases (NCDs, cardiovascular diseases, cancers, chronic respiratory diseases, diabetes, and mental disorders) arise in adolescence but are mostly framed as relevant to health in adulthood; little is known about the relationship between co-occurring NCD risks and mental wellbeing in young people. This study aims to describe the prevalence and co-occurrence of distinct NCD risk factors, and how they relate to current mental wellbeing amongst adolescents in Indonesia, a young and populous country where NCD burden is increasing rapidly. Methods We assessed NCD risk and mental wellbeing amongst 1,331 school-based 16–18-year-olds in Jakarta (N = 609) and South Sulawesi (N = 722). Five domains of NCD risk (adiposity, substance use, physical inactivity, excess sedentary time, and diet) were either measured or self-reported. In Jakarta, we also measured blood glucose, triglycerides, cholesterol, and blood pressure. Wellbeing was assessed using three indicators: general quality of life (QoL), physical function QoL, and psychological distress. We used linear regression to estimate the associations between co-occurring risks and wellbeing, adjusted for covariates of wellbeing: province, sex, socioeconomic status, and religion. Results NCD risk clustering was common, and more than half of adolescents had co-occurring risks in 3 or more of the 5 domains (58.9% (95%CI 53.7—63.9)). Adolescents with any NCD risk were more likely to report psychological distress, with this relationship most pronounced in those with excess sedentary time spent on video gaming and computer use. A higher number of NCD risk factors was associated with poorer psychological wellbeing and decreased general and physical function QoL. In the Jakarta subsample, reduced HDL and raised blood glucose was associated with psychological distress; and a higher number of risk biomarkers was associated with lower physical function QoL. Conclusions Our analysis also shows that these NCD risks (both individual risks and co-occurring risk count) are related to poorer profiles of mental wellbeing in adolescents, after adjusting for likely confounders.

Abstract Many mammal species have declining populations, but the consequences of small population size on the genomic makeup of species remain largely unknown. We investigated the evolutionary history, genetic load and adaptive potential of the Cat Ba langur (Trachypithecus poliocephalus), a primate species endemic to Vietnam’s famous Ha Long Bay and with less than 100 living individuals one of the most threatened primates in the world. Using high-coverage whole genome data of four wild individuals, we revealed the Cat Ba langur as sister species to its conspecifics of the northern limestone langur clade and found no evidence for extensive secondary gene flow after their initial separation. Compared to other primates and mammals, the Cat Ba langur showed low levels of genetic diversity, long runs of homozygosity, high levels of inbreeding and an excess of deleterious mutations in homozygous state. On the other hand, genetic diversity has been maintained in protein-coding genes and on the gene-rich human chromosome 19 ortholog, suggesting that the Cat Ba langur retained most of its adaptive potential. The Cat Ba langur also exhibits several unique non-synonymous variants that are related to calcium and sodium metabolism, which may have improved adaptation to high calcium intake and saltwater consumption.

Abstract Alzheimer’s disease (AD) affects millions of people worldwide and represents the most prevalent form of dementia. Treatment strategies aiming to interfere with the formation of amyloid β (Aβ) plaques and neurofibrillary tangles (NFTs), the two major AD hallmarks, have shown modest or no effect. Recent evidence suggests that ferroptosis, a type of programmed cell death caused by iron accumulation and lipid peroxidation, contributes to AD pathogenesis. The existing link between ferroptosis and AD has been largely based on cell culture and animal studies, while evidence from human brain tissue is limited. Here we evaluate if Aβ is associated with ferroptosis pathways in post-mortem human brain tissue and whether ferroptosis inhibition could attenuate Aβ-related effects in human brain organoids. Performing positive pixel density scoring on immunohistochemically stained post-mortem Brodmann Area 17 sections revealed that the progression of AD pathology was accompanied by decreased expression of nuclear receptor co-activator 4 and glutathione peroxidase 4 in the grey matter. Differentiating between white and grey matter, allowed for a more precise understanding of the disease’s impact on different brain regions. In addition, ferroptosis inhibition prevented Aβ pathology, decreased lipid peroxidation and restored iron storage in human AD iPSCs-derived brain cortical organoids at day 50 of differentiation. Differential gene expression analysis of RNAseq of AD organoids compared to isogenic controls indicated activation of the ferroptotic pathway. This was also supported by results from untargeted proteomic analysis revealing significant changes between AD and isogenic brain organoids. Determining the causality between the development of Aβ plaques and the deregulation of molecular pathways involved in ferroptosis is crucial for developing potential therapeutic interventions.

Background: Receiving hemodialysis treatment makes end-stage renal disease (ESRD) patients highly vulnerable amidst the COVID-19 pandemic. Hence, their kidney disease quality of life (KDQOL) is affected. We aimed to examine the association between fear of COVID-19 (FCoV-19) and KDQOL, and the effect modification of Health literacy (HL) on this association.Material and Methods: A survey was conducted at 8 hospitals from July 2020 to March 2021 on 972 patients. Data collection includes socio-demographic factors, clinical parameters, HL, digital healthy diet literacy (DDL), hemodialysis diet knowledge (HDK), FCoV-19, suspected COVID-19 symptoms (S-COVID-19-S), and KDQOL.Results: Higher HL scores B = 0.13 (95% CI = 0.06–0.21, p = 0.001) and HDK scores B = 0.58 (95% CI = 0.31–0.85, p = 0.001) were associated with higher KDQOL scores. Whereas, S-COVID-19-S B = −6.12 (95% CI = −7.66 to – 4.58, p = 0.001) and FCoV-19 B = −0.91 (95% CI = −1.03 to – 0.80, p = 0.001) were associated with lower KDQOL scores. Notably, higher HL scores significantly attenuate the negative impact of FCoV-19 on overall KDQOL and the kidney disease component summary.Conclusions: In hemodialysis patients, FCoV-19 and S-COVID-19-S were associated with a lower KDQOL. Health literacy significantly mitigates the negative impact of FCoV-19 on KDQOL. Strategic public health interventions to improve HL are suggested to protect patient’s KDQOL during the pandemic.

Background: Determining the clinical and subclinical characteristics related to the recurrence status in patients with a thyroid carcinoma has great significance for prognosis, prediction of recurrence and monitoring of treatment outcomes. This study aimed to determine the association between recurrence rate and some characteristics in patients with thyroid carcinoma. Patients and Methods: The study was conducted by descriptive method with longitudinal follow-up on 102 thyroid carcinoma patients at 103 Military Hospital, Hanoi, Vietnam, from July 2013 to December 2016. Results: Univariate analysis showed that there was a relationship between the recurrence characteristics in the studied patients and the characteristics of lymph node metastasis (P = 0.026; OR = 15; 95% CI = 1.4–163.2) and BRAF V600E mutation status (P = 0.01; OR = 3.41; 95% CI = 1.31–8.88). When analysing the multivariable Logistic regression model, there was a positive correlation between the occurrence of BRAF V600E gene mutation (P = 0.032; OR = 17.649; 95% CI = 1.290–241.523) and male sex (P = 0.036; OR = 12.788; 95% CI = 1.185–137.961) and the occurrence of recurrence in study patients. The mean time to relapse was earlier in male patients than in female patients (P = 0.02). The mean time to relapse in patients with the BRAF V600E mutation (31.81 ± 1.14 months) was shorter than the mean time to relapse in the group without the mutation (57.82 ± 2.08 months) (P = 0.01). The group of patients with mutations in the BRAF V600E gene increased the risk of recurrence compared with the group without the mutation (HR = 9.14, P = 0.04). Conclusion: There is a positive correlation between recurrence and masculinity, lymph node metastasis and the occurrence of BRAF V600E mutations in thyroid carcinoma patients.

BaTiO3 thin films with different annealing times were grown on LSMO/STO (001) substrates by pulsed laser deposition. An interesting phenomenon of loss-and-reappearance of the interfacial layer in BaTiO3 was detected in the x-ray diffraction results, and the ordered–unordered–ordered lattice transformation caused by oxygen vacancies’ filling was thought to be the reason. The ferroelectric domain was also confirmed to form during such an annealing process according to the piezoresponse force microscopy, transmission electron microscopy, and phase-field simulation. A Ti-displacement-rotation region considered an intermediate structure during the domain formation was observed at the interfacial layer of the 5.5-min-annealing film. Because of the oxygen deficiency and the effect of ferroelectric domain modulation of the built-in barrier height, a good memristive behavior with a resistive switching ratio of 1916 was obtained in the 10-min-annealing BaTiO3 (BTO) film, offering an avenue toward the application of oxygen-deficient BTO in neural network applications.

François’ langur is an Endangered colobine inhabiting limestone habitats in southern China and northern Vietnam. Its global population has been estimated to be just more than 2000 mature individuals. Populations in Vietnam are highly fragmented with reportedly fewer than 200 adults in total and 50 in a single location. Although the François’ langur in Vietnam is highly imperiled as remnant populations persist in only three to four sites, little research has been carried out to provide a reliable estimate of its remaining population. In this study, we conducted field surveys in Lam Binh District, Tuyen Quang Province, northeastern Vietnam. In total, we recorded at least 16 groups of François’ langurs, with 156 individuals, raising the total number of individuals by approximately 10% compared to a previous study. The group structure, group size, activity budget, and density of the Lam Binh population resemble those reported in François’ langurs in China and other limestone langur species. The results show that the behavior ecology of limestone langurs significantly differs from that of forest langurs probably because they occupy separate habitats with distinctly different environmental variables. During our surveys, we detected a number of direct threats to this population, namely illegal logging, hunting, firewood collecting, hydropower development, grazing, and mining. It is recommended that the protection forest be elevated to the nature reserve status to better protect the most important population of the François’ langur in Vietnam.

The current decline in global biodiversity is most evident in amphibians with 41% percent of all species worldwide classified as threatened with extinction. Hence, a major challenge in amphibian conservation is the high number of threatened species, leading to a common approach of identifying priority species and regions for conservation efforts. As a part of one of 36 globally designated biodiversity hotspots, Vietnam is considered to be of particular importance for conservation action. To improve amphibian conservation in Vietnam, this study provides an updated species list and assesses their threat status by compiling data from a variety of sources. Furthermore, a Zoological Information Management System (ZIMS) analysis was conducted to determine the representation of extant amphibians from Vietnam in zoos worldwide. The batrachofauna of Vietnam is characterized by a high level of species richness and local endemism as well as a high rate of new discoveries, with more than half of the endemic species reported exclusively from their type locality, making them especially vulnerable to extinction. Up to 18% of all amphibians extant in Vietnam and 28% of endemic species are classified as threatened with extinction by the IUCN. In many cases, the IUCN Red List status is either missing or outdated, highlighting the urgent need of action. Around 14% of endemic amphibian species have been recorded exclusively from unprotected areas, suggesting prioritization for further research and conservation measures. The continuing decline in many species remains an unresolved problem. As a guide for future research and conservation measures, a list of the top 57 species was compiled. In addition, according to the ZIMS analysis, only 8% of threatened and 3% of endemic amphibian taxa from Vietnam are currently kept in zoos worldwide, and a richness analysis revealed that the highest density of husbandries is found in Europe and North America. To achieve maximum outcome for the conservation of threatened species, this study recommends a general shift by zoos towards maintaining species in greater need of captive assurance populations and breeding programs to support integrative strategies that combine in situ and ex situ conservation efforts following the IUCN’s One Plan Approach.

Resistance to endocrine therapies remains a major clinical hurdle in breast cancer. Mutations to estrogen receptor alpha (ERα) arise after continued therapeutic pressure. Next generation selective estrogen receptor modulators and degraders/downregulators (SERMs and SERDs) show clinical efficacy, but responses are often non-durable. A tyrosine to serine point mutation at position 537 in the ERα ligand binding domain (LBD) is among the most common and most pathogenic alteration in this setting. It enables endocrine therapy resistance by superceding intrinsic structural-energetic gatekeepers of ER hormone-dependence, it enhances metastatic burden by enabling neomorphic ER-dependent transcriptional programs, and it resists SERM and SERD inhibiton by reducing their binding affinities and abilities to antagonize transcriptional coregulator binding. However, a subset of SERMs and SERDs can achieve efficacy by adopting poses that force the mutation to engage in a new interaction that favors the therapeutic receptor antagonist conformation. We previously described a chemically unconventional SERM, T6I-29, that demonstrates significant anti-proliferative activities in Y537S ERα breast cancer cells. Here, we use a comprehensive suite of structural-biochemical, in vitro, and in vivo approaches to better T6I-29's activities in breast cancer cells harboring Y537S ERα. RNA sequencing in cells treated with T6I-29 reveals a neomorphic downregulation of DKK1, a secreted glycoprotein known to play oncogenic roles in other cancers. Importantly, we find that DKK1 is significantly enriched in ER + breast cancer plasma compared to healthy controls. This study shows how new SERMs and SERDs can identify new therapeutic pathways in endocrine-resistant ER + breast cancers. [ABSTRACT FROM AUTHOR]

Background: Despite available and effective prevention and treatment strategies for substance use disorders (SUD), drug overdose deaths in the US remain high. Further, limited public knowledge of SUD pharmacotherapies may contribute to increased stigmatization toward SUD medications and a lack of willingness to help people with SUD. Objectives: This study evaluated knowledge and attitudes about SUD pharmacotherapies and willingness to help people with SUD among a sample of U.S. adults. Method: Participants recruited through Amazon's Mechanical Turk (N = 314; 62.1% male) completed online surveys evaluating knowledge, attitudes, and willingness to help by various demographic factors, history of substance use, and experience with someone with SUD. Results: Results revealed a significant difference in attitudes by race/ethnicity (F(1,307) = 11.85, p <.001). Participants with a personal history of substance use exhibited greater knowledge (F(1,312) = 31.94, p <.001) and willingness to help someone with a SUD (F(1,312) = 7.84, p =.005). Participants with experience with someone with a SUD also exhibited greater knowledge (F(1,311) = 19.42, p <.001) and willingness to help (F(1,311) = 13.63, p <.001). Conclusion: Results emphasize the importance of targeted education to bridge gaps in knowledge, enhance public attitudes, and promote willingness to help individuals with SUD. Utilizing public health strategies that promote empathy, willingness to help, and increase accessibility and acceptance of SUD treatment options, could be potential avenues that ultimately improve outcomes for individuals with SUD. [ABSTRACT FROM AUTHOR]

Abstract Background In 2016, we conducted a systematic review to assess the feasibility of treatment monitoring for people living with HIV (PLHIV) receiving antiretroviral therapy (ART) in low and middle-income countries (LMICs), in line with the 90-90-90 treatment target. By 2020, global estimates suggest the 90-90-90 target, particularly the last 90, remains unattainable in many LMICs. This study aims to review the progress and identify needs for public health interventions to improve viral load monitoring and viral suppression for PLHIV in LMICs. Methods A literature search was conducted using an update of the initial search strategy developed for the 2016 review. Electronic databases (Medline and PubMed) were searched to identify relevant literature published in English between Dec 2015 and August 2021. The primary outcome was initial viral load (VL) monitoring (the proportion of PLHIV on ART and eligible for VL monitoring who received a VL test). Secondary outcomes included follow-up VL monitoring (the proportion of PLHIV who received a follow-up VL after an initial elevated VL test), confirmation of treatment failure (the proportion of PLHIV who had two consecutive elevated VL results) and switching treatment regimen rates (the proportion of PLHIV who switched treatment regimen after confirmation of treatment failure). Results The search strategy identified 1984 non-duplicate records, of which 34 studies were included in the review. Marked variations in initial VL monitoring coverage were reported across study settings/countries (range: 12–93% median: 74% IQR: 46–82%) and study populations (adults (range: 25–96%, median: 67% IQR: 50–84%), children, adolescents/young people (range: 2–94%, median: 72% IQR: 47–85%), and pregnant women (range: 32–82%, median: 57% IQR: 43–71%)). Community-based models reported higher VL monitoring (median: 85%, IQR: 82-88%) compared to decentralised care at primary health facility (median: 64%, IRQ: 48-82%). Suboptimal uptake of follow-up VL monitoring and low regimen switching rates were observed. Conclusions Substantial gaps in VL coverage across study settings and study populations were evident, with limited data availability outside of sub-Saharan Africa. Further research is needed to fill the data gaps. Development and implementation of innovative, community-based interventions are required to improve VL monitoring and address the “failure cascade” in PLHIV on ART who fail to achieve viral suppression.

Alzheimer’s disease (AD) and Parkinson’s disease (PD) represent the most prevalent neurodegenerative disorders severely impacting life expectancy and quality of life of millions of people worldwide. AD and PD exhibit both a very distinct pathophysiological disease pattern. Intriguingly, recent researches, however, implicate that overlapping mechanisms may underlie AD and PD. In AD and PD, novel cell death mechanisms, encompassing parthanatos, netosis, lysosome-dependent cell death, senescence and ferroptosis, apparently rely on the production of reactive oxygen species, and seem to be modulated by the well-known, “old” second messenger cAMP. Signaling of cAMP via PKA and Epac promotes parthanatos and induces lysosomal cell death, while signaling of cAMP via PKA inhibits netosis and cellular senescence. Additionally, PKA protects against ferroptosis, whereas Epac1 promotes ferroptosis. Here we review the most recent insights into the overlapping mechanisms between AD and PD, with a special focus on cAMP signaling and the pharmacology of cAMP signaling pathways.

Kras is frequently mutated in lung cancer and two isoforms are generated via alternative splicing. Here, the authors show that the two isoforms have divergent roles in cancer stem cells and the main tumour cell population, which are regulated by hypoxia and endoplasmic reticulum stress.

Background: Risk factors for non-communicable diseases (NCDs, cardiovascular diseases, cancers, chronic respiratory diseases, diabetes, and mental disorders) arise in adolescence but are mostly framed as relevant to health in adulthood; little is known about the relationship between co-occurring NCD risks and mental wellbeing in young people. This study aims to describe the prevalence and co-occurrence of distinct NCD risk factors, and how they relate to current mental wellbeing amongst adolescents in Indonesia, a young and populous country where NCD burden is increasing rapidly. Methods: We assessed NCD risk and mental wellbeing amongst 1,331 school-based 16–18-year-olds in Jakarta (N = 609) and South Sulawesi (N = 722). Five domains of NCD risk (adiposity, substance use, physical inactivity, excess sedentary time, and diet) were either measured or self-reported. In Jakarta, we also measured blood glucose, triglycerides, cholesterol, and blood pressure. Wellbeing was assessed using three indicators: general quality of life (QoL), physical function QoL, and psychological distress. We used linear regression to estimate the associations between co-occurring risks and wellbeing, adjusted for covariates of wellbeing: province, sex, socioeconomic status, and religion. Results: NCD risk clustering was common, and more than half of adolescents had co-occurring risks in 3 or more of the 5 domains (58.9% (95%CI 53.7—63.9)). Adolescents with any NCD risk were more likely to report psychological distress, with this relationship most pronounced in those with excess sedentary time spent on video gaming and computer use. A higher number of NCD risk factors was associated with poorer psychological wellbeing and decreased general and physical function QoL. In the Jakarta subsample, reduced HDL and raised blood glucose was associated with psychological distress; and a higher number of risk biomarkers was associated with lower physical function QoL. Conclusions: Our analysis also shows that these NCD risks (both individual risks and co-occurring risk count) are related to poorer profiles of mental wellbeing in adolescents, after adjusting for likely confounders. [ABSTRACT FROM AUTHOR]

Background: Receiving hemodialysis treatment makes end-stage renal disease (ESRD) patients highly vulnerable amidst the COVID-19 pandemic. Hence, their kidney disease quality of life (KDQOL) is affected. We aimed to examine the association between fear of COVID-19 (FCoV-19) and KDQOL, and the effect modification of Health literacy (HL) on this association. Material and Methods: A survey was conducted at 8 hospitals from July 2020 to March 2021 on 972 patients. Data collection includes socio-demographic factors, clinical parameters, HL, digital healthy diet literacy (DDL), hemodialysis diet knowledge (HDK), FCoV-19, suspected COVID-19 symptoms (S-COVID-19-S), and KDQOL. Results: Higher HL scores B = 0.13 (95% CI = 0.06–0.21, p = 0.001) and HDK scores B = 0.58 (95% CI = 0.31–0.85, p = 0.001) were associated with higher KDQOL scores. Whereas, S-COVID-19-S B = −6.12 (95% CI = −7.66 to – 4.58, p = 0.001) and FCoV-19 B = −0.91 (95% CI = −1.03 to – 0.80, p = 0.001) were associated with lower KDQOL scores. Notably, higher HL scores significantly attenuate the negative impact of FCoV-19 on overall KDQOL and the kidney disease component summary. Conclusions: In hemodialysis patients, FCoV-19 and S-COVID-19-S were associated with a lower KDQOL. Health literacy significantly mitigates the negative impact of FCoV-19 on KDQOL. Strategic public health interventions to improve HL are suggested to protect patient's KDQOL during the pandemic. [ABSTRACT FROM AUTHOR]