Nevin Manimala

Mov Disord. 2024 Jul 4. doi: 10.1002/mds.29910. Online ahead of print.

ABSTRACT

BACKGROUND: Spinocerebellar ataxia type 8 (SCA8) is a dominantly inherited expansion disorder with highly variable penetrance. ATXN8OS/ATXN8 expanded alleles have been identified in association with other types of hereditary ataxias, pointing to a possible genetic synergism.

OBJECTIVES: We aimed to further investigate the molecular background of patients with SCA8 diagnosis.

METHODS: Patients were selected from our cohort of 346 families. A total of 14 probands with SCA8 underwent additional investigation through exome sequencing.

RESULTS: Pathogenic heterozygous STUB1 variants were found in 21.4% of SCA8 patients (3 of 14) compared to only 0.5% in the non-SCA8 group (1 of 222), indicating a statistically significant association (P < 0.05).

CONCLUSIONS: The findings reported in this study might suggest a genetic synergism between STUB1 and ATXN8OS/ATXN8 expanded alleles. Further studies are needed to validate this observation and better define the clinical impact of this genetic interaction. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

PMID:38962894 | DOI:10.1002/mds.29910

J Pediatr Gastroenterol Nutr. 2024 Jul 4. doi: 10.1002/jpn3.12283. Online ahead of print.

ABSTRACT

OBJECTIVES: We aimed to appraise the real-life efficacy of Crohn’s disease exclusion diet (CDED) coupled with partial enteral nutrition (PEN) in inducing clinical and biochemical remission at disease onset and in patients with loss of response to biologics and immunomodulators.

METHODS: We retrospectively gathered data of patients aged less than 18 years of age with a diagnosis of Crohn’s disease (CD), who received CDED coupled with PEN at a tertiary level pediatric inflammatory bowel disease center.

RESULTS: Sixty-six patients were identified. Forty (60.6%) started CDED plus PEN at disease onset and 26 (39.4%) received CDED with PEN as add-on therapy. Forty-six (69.7%) patients achieved clinical remission (weighted Pediatric Crohn’s Disease Activity Index < 12.5) at the end of Phase 1, 44 (66.7%) normalized c-reactive protein levels (<0.5 mg/dL) and 18 (27.2%) patients normalized calprotectin levels (<150 microg/g). Nine of 19 (47.3%) of patients with clinically severe disease (defined by Physician Global Assessment) achieved clinical remission at the end of Phase I. Patients with extraintestinal manifestations had statistically lower clinical response rates to the dietary regimen (p = 0.018). Among patients who received CDED + PEN as add-on treatment, a previous successful course of Exclusive Enteral Nutrition was associated with statistically higher clinical remission rates at Week 8 (p = 0.026). Clinical response at Week 4 was an independent predictor of clinical remission and fecal calprotectin normalization at Week 8 (p = 0.002).

CONCLUSION: CDED with PEN confirmed its efficacy in a real-life setting, proving to be effective also in refractory patients and those with severe disease. Early clinical response predicts clinical remission at the end of Phase 1.

PMID:38962891 | DOI:10.1002/jpn3.12283

Trop Med Int Health. 2024 Jul 4. doi: 10.1111/tmi.14029. Online ahead of print.

ABSTRACT

OBJECTIVE: The objective of this study is to analyse the epidemiological profile of global climate-related disasters in terms of morbidity and mortality, as well as to examine their temporal trends.

METHOD: This cross-sectional study analysed climate-related global disasters from 2000 to 2021, utilising definitions and criteria from the United Nations Strategy for Disaster Reduction and the Centre for Research on the Epidemiology of Disasters. Data were sourced from the EM-DAT database. The study assessed trends over the entire period and compared them with previous years (1978-2000).

RESULTS: A total of 7398 climate-related disasters were recorded, with hydrological disasters being the most frequent, followed by meteorological and climatological disasters. Statistically significant differences were noted in the average rates of affected individuals and injuries per million inhabitants. No significant trends were found in mortality rates, but the frequency trends for the entire period (1978-2021) and the subperiod (1978-2000) were increasing and statistically significant. However, the trend from 2000 onwards showed a non-significant decrease, potentially reflecting better disaster preparedness and response strategies under the Hyogo and Sendai Framework.

CONCLUSION: The study highlights hydrological disasters as the most frequent and deadliest climate-related events, with climatological disasters affecting and injuring the most people. The lack of standardised criteria for disaster inclusion in databases presents a significant challenge in comparing results and analysing trends. Establishing uniform inclusion criteria is crucial for effective data analysis and disaster management.

PMID:38962808 | DOI:10.1111/tmi.14029

J Drug Target. 2024 Jul 4:1-16. doi: 10.1080/1061186X.2024.2374037. Online ahead of print.

ABSTRACT

The discovery of novel targeted agents for non-small cell lung cancer (NSCLC) remains an important research landscape due to the limited efficacy, side effects and drug resistance of current treatment options. Among many repurposed drugs, disulfiram (DSF) has shown the potential to target tumors. However, its unpleasant neurotoxicity greatly limits its use. A DSF derivative, S-(N,N-diethyldithiocarbamoyl)-N-acetyl-L-cysteine (DS-NAC), was synthesized against NSCLC. The therapeutic effects, mechanism, and toxicities of DS-NAC were evaluated in A549 and H460 cells and the mouse model of in-situ lung cancer. The in-vitro results exhibited that DS-NAC had potent anti-proliferation, apoptotic, anti-metastasis, and epithelial-mesenchymal transition (EMT) inhibition effects. In the orthotopic lung cancer mouse model, therapeutic effects of DS-NAC were better than that of DSF and were similar to docetaxel (DTX). Also, results from western blot and immunohistochemistry showed that DS-NAC in combination with copper exerted the therapeutic effects via regulating NF-κB signaling pathway and ROS-related proteins such as HIF-1α, Nrf2, and PKC-δ rather than regulating ROS level directly. Moreover, the safety evaluation study showed that DS-NAC had low hematologic and hepatic toxicities in comparision with DTX as well as low neurological toxicity compared with DSF. DS-NAC could be a promising anti-lung cancer agent with a favorable safety profile.

PMID:38962807 | DOI:10.1080/1061186X.2024.2374037

Sleep Biol Rhythms. 2024 Mar 15;22(3):353-362. doi: 10.1007/s41105-024-00516-1. eCollection 2024 Jul.

ABSTRACT

There is limited research on the circadian rhythm and sleep state in patients with acute cerebral infarction (ACI) accompanied by sleep-breathing disorders (SDB). This study aims to provide a scientific basis for individualized diagnosis and treatment for stroke-related SDB patients. The SC-500 sleep monitor was used to continuously monitor 1367 ACI patients over 5 days. Based on the apnea-hypopnea index (AHI), patients were divided into non-SDB group (normal) and SDB group (mild, moderate, severe, fluctuating). Interdaily stability (IS) and intradaily variability (IV) were calculated through heart rate monitoring, and sleep states and their correlations were analyzed. Compared to the non-SDB group, patients with moderate-to-severe ACI accompanied by SDB showed decreased IS, increased IV, and sleep fragmentation. Significant statistical differences were observed in total sleep time (TST), rapid eye movement latency (REML), sleep efficiency (SE), non-rapid eye movement stages 1-2 (NREM stages1-2), non-rapid eye movement stages 3-4 (NREM stages 3-4), proportion of non-rapid eye movement (NREM%), wake after sleep onset (WASO), and number of awakenings (NOA) between the SDB group and the non-SDB group (P < 0.05). AHI showed a strong negative correlation with IS and a strong positive correlation with IV. AHI was positively correlated with sleep latency (SL), REML, NREM stages1-2, NREM%, proportion of rapid eye movement (REM%), WASO, time out of bed (TOB), and NOA, and negatively correlated with TST, SE, NREM stages 3-4, and rapid eye movement (REM), all with statistical significance (P < 0.05). There were significant statistical differences in the Mini-Mental State Examination (MMSE) between patients with and without SDB, and among mild, moderate, severe, and fluctuating groups (P < 0.05). Patients with moderate-to-severe ACI accompanied by SDB are more likely to experience changes in circadian rhythm and sleep states, which in turn affect cognitive functions.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s41105-024-00516-1.

PMID:38962800 | PMC:PMC11217207 | DOI:10.1007/s41105-024-00516-1

Sleep Biol Rhythms. 2024 Feb 12;22(3):333-341. doi: 10.1007/s41105-024-00511-6. eCollection 2024 Jul.

ABSTRACT

The aim was to investigate brain responses to non-painful tactile stimuli applied to the non-dominant hand during sleep. 21 healthy subjects participated in the study (11 female, mean age ± SD: 20.67 ± 1.91 years). A 40-channel polysomnography system and a pneumatic tactile stimulator unit were used. Stimuli were applied to the participants’ non-dominant hand. Evoked potential components of the C_Z electrode were examined in four sleep stages (N1, N2, N3, and REM). Repeated measures ANOVA was used in statistical analyses. Brain responses, categorized as early (P50, N100, and P200), mid-early (N300, P450, and N550), and late (P900 and Nlate), were detected all sleep stages. No notable variances were found in the amplitude and latency of early brain responses when analyzed across different sleep stages. Differences in both amplitude and latency were observed across different sleep stages for the N300, P450, P900, and Nlate response components. This study presents a pioneering exploration into the responses of the non-dominant hand throughout all sleep stages, encompassing eight distinct response components. This novel investigation contributes to the existing literature by shedding light on previously unexplored aspects. The observed early responses are identified as sensory, while middle to late responses align with cognitive processes within the realm of sleep research. Notably, N300, P450, P900, and Nlate components display variations across diverse sleep stages, marked by alterations in both amplitude and latency. These findings offer valuable insights into the dynamic nature of hand responses throughout the sleep continuum.

PMID:38962787 | PMC:PMC11217254 | DOI:10.1007/s41105-024-00511-6

Front Public Health. 2024 Jun 19;12:1390780. doi: 10.3389/fpubh.2024.1390780. eCollection 2024.

ABSTRACT

INTRODUCTION: Globally, air pollution is the leading environmental cause of disease and premature death. Raising awareness through environmental education and adequate communication on air quality could reduce the adverse effects. We aimed to assess the knowledge, attitudes, and practices (KAP) regarding air pollution and health and determine the factors associated with these KAP in children and adolescents.

METHODS: In 2019-2020, a cross-sectional study was conducted on 6th-11th grade high school students in five municipalities in Colombia. Variables collected included: age, sex, private or public school, any medical history, emergency room visits due to respiratory symptoms in the last year, and whether students played sports. The main exposure was the School Environmental Project. The outcomes were the KAP scale [0% (the lowest score) to 100% (the highest score)]. The factors associated with KAP levels were evaluated with independent mixed regressions due to the multilevel structure of the study (level 1: student; level 2: school), and the exponential coefficients (95% confidence interval-CI) were reported.

RESULTS: Among 1,676 students included, 53.8% were females. The median knowledge score about air pollution and its health effects was 33.8% (IQR: 24.0-44.9), 38.6% knew the air quality index, 30.9% knew the air quality alerts that occurred twice a year in these municipalities and 5.3% had high self-perceived knowledge. Positive attitudes, pro-environmental practices, being female, grade level, attending a private school, having respiratory diseases, and the school environmental project importance were associated with higher knowledge scores. The median attitudes score was 78.6% (IQR: 71.4-92.9). Pro-environmental attitudes were associated with knowledge-increasing, being female, attending a private school, and the school environmental project. The median pro-environmental practices score was 28.6% (IQR: 28.6-42.9). During air quality alerts, 11.6% had worn masks, 19% had reduced the opening time of windows and 15.9% avoided leaving home. Pro-environmental practices were associated with knowledge-increasing and attitudes-increasing, and lower practices with higher grade levels, visiting a doctor in the last year, and practicing sports.

DISCUSSION: Children and adolescents have low knowledge scores and inadequate pro-environmental practices scores regarding air pollution. However, they demonstrate positive attitudes towards alternative solutions and express important concerns about the planet’s future.

PMID:38962783 | PMC:PMC11221384 | DOI:10.3389/fpubh.2024.1390780

Front Public Health. 2024 Jun 19;12:1365657. doi: 10.3389/fpubh.2024.1365657. eCollection 2024.

ABSTRACT

PURPOSE: The present study examines how the coronavirus disease 2019 (COVID-19) experience affected values and priorities.

METHODS: This cross-sectional study collected data between January and April 2023, from 1,197 individuals who are chronically ill or part of a general population sample. Using open-ended prompts and closed-ended questions, we investigated individuals’ perceptions about COVID-19-induced changes in what quality of life means to them, what and who are important, life focus, and changes in norms and stressors. Data analyses included content and psychometric analysis, leading to latent profile analysis (LPA) to characterize distinct groups, and analysis of variance and chi-squared to compare profile groups’ demographic characteristics.

RESULTS: About 75% of the study sample noted changes in values and/or priorities, particularly in the greater prominence of family and friends. LPA yielded a four-profile model that fit the data well. Profile 1 (Index group; 64% of the sample) had relatively average scores on all indicators. Profile 2 (COVID-Specific Health & Resignation to Isolation Attributable to COVID-19; 5%) represented COVID-19-specific preventive health behaviors along with noting the requisite isolation and disengagement entailed in the social distancing necessary for COVID-19 prevention. Profile 3 (High Stress, Low Trust; 25%) represented high multi-domain stress, with the most elevated scores both on focusing on being true to themselves and perceiving people to be increasingly uncivil. Profile 4 (Active in the World, Low Trust; 6%) was focused on returning to work and finding greater meaning in their activities. These groups differed on race, marital status, difficulty paying bills, employment status, number of times they reported having had COVID-19, number of COVID-19 boosters received, whether they had Long COVID, age, BMI, and number of comorbidities.

CONCLUSION: Three years after the beginning of the worldwide COVID-19 pandemic, its subjective impact is notable on most study participants’ conceptualization of quality of life, priorities, perspectives on social norms, and perceived stressors. The four profile groups reflected distinct ways of dealing with the long-term effects of COVID-19.

PMID:38962781 | PMC:PMC11221197 | DOI:10.3389/fpubh.2024.1365657

Front Public Health. 2024 Jun 19;12:1348755. doi: 10.3389/fpubh.2024.1348755. eCollection 2024.

ABSTRACT

BACKGROUND: Despite prior progress and the proven benefits of optimal feeding practices, improving child dietary intake in developing countries like Ethiopia remains challenging. In Ethiopia, over 89% of children fail to meet the minimum acceptable diet. Understanding the geographical disparity and determinants of minimum acceptable diet can enhance child feeding practices, promoting optimal child growth.

METHODS: Spatial and multiscale geographically weighted regression analysis was conducted among 1,427 weighted sample children aged 6-23 months. ArcGIS Pro and SatScan version 9.6 were used to map the visual presentation of geographical distribution failed to achieve the minimum acceptable diet. A multiscale geographically weighted regression analysis was done to identify significant determinants of level of minimum acceptable diet. The statistical significance was declared at P-value <0.05.

RESULTS: Overall, 89.56% (95CI: 87.85-91.10%) of children aged 6-23 months failed to achieve the recommended minimum acceptable diet. Significant spatial clustering was detected in the Somali, Afar regions, and northwestern Ethiopia. Children living in primary clusters were 3.6 times more likely to be unable to achieve the minimum acceptable diet (RR = 3.61, LLR =13.49, p < 0.001). Mother’s with no formal education (Mean = 0.043, p-value = 0.000), family size above five (Mean = 0.076, p-value = 0.005), No media access (Mean = 0.059, p-value = 0.030), home delivery (Mean = 0.078, p-value = 0.002), and no postnatal checkup (Mean = 0.131, p-value = 0.000) were found to be spatially significant determinants of Inadequate minimum acceptable diet.

CONCLUSION: Level of minimum acceptable diet among children in Ethiopia varies geographically. Therefore, to improve child feeding practices in Ethiopia, it is highly recommended to deploy additional resources to high-need areas and implement programs that enhance women’s education, maternal healthcare access, family planning, and media engagement.

PMID:38962777 | PMC:PMC11221355 | DOI:10.3389/fpubh.2024.1348755

Front Public Health. 2024 Jun 19;12:1366327. doi: 10.3389/fpubh.2024.1366327. eCollection 2024.

ABSTRACT

INTRODUCTION: Enhancing the efficiency of primary healthcare services is essential for a populous and developing nation like China. This study offers a systematic analysis of the efficiency and spatial distribution of primary healthcare services in China. It elucidates the fundamental landscape and regional variances in efficiency, thereby furnishing a scientific foundation for enhancing service efficiency and fostering coordinated regional development.

METHODS: Employs a three-stage DEA-Malmquist model to assess the efficiency of primary healthcare services across 31 provincial units in mainland China from 2012 to 2020. Additionally, it examines the spatial correlation of efficiency distribution using the Moran Index.

RESULTS: The efficiency of primary healthcare services in China is generally suboptimal with a noticeable declining trend, highlighting significant potential for improvement in both pure technical efficiency and scale efficiency. There is a pronounced efficiency gap among provinces, yet a positive spatial correlation is evident. Regionally, efficiency ranks in the order of East > Central > West. Factors such as GDP per capita and population density positively influence efficiency enhancements, while urbanization levels and government health expenditures appear to have a detrimental impact.

DISCUSSION: The application of the three-stage DEA-Malmquist model and the Moran Index not only expands the methodological framework for researching primary healthcare service efficiency but also provides scientifically valuable insights for enhancing the efficiency of primary healthcare services in China and other developing nations.

PMID:38962768 | PMC:PMC11220123 | DOI:10.3389/fpubh.2024.1366327