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Cells May 2024Stress is a common denominator of complex disorders and the FK-506 binding protein (FKBP)51 plays a central role in stress. Hence, it is not surprising that multiple... (Review)
Review
Stress is a common denominator of complex disorders and the FK-506 binding protein (FKBP)51 plays a central role in stress. Hence, it is not surprising that multiple studies imply the involvement of the FKBP51 protein and/or its coding gene, , in complex disorders. This review summarizes such reports concentrating on three disorder clusters-neuropsychiatric, cancer, and type 2 diabetes mellitus (T2DM). We also attempt to point to potential mechanisms suggested to mediate the effect of /FKBP51 on these disorders. Neuropsychiatric diseases considered in this paper include (i) Huntington's disease for which increased autophagic cellular clearance mechanisms related to decreased FKBP51 protein levels or activity is discussed, Alzheimer's disease for which increased FKBP51 activity has been shown to induce Tau phosphorylation and aggregation, and Parkinson's disease in the context of which FKBP12 is mentioned; and (ii) mental disorders, for which significant association with the single nucleotide polymorphism (SNP) rs1360780 of intron 7 along with decreased DNA methylation were revealed. Since cancer is a large group of diseases that can start in almost any organ or tissue of the body, FKBP51's role depends on the tissue type and differences among pathways expressed in those tumors. The FKBP51-heat-shock protein-(Hsp)90-p23 super-chaperone complex might function as an oncogene or as a tumor suppressor by downregulating the serine/threonine protein kinase (AKt) pathway. In T2DM, two potential pathways for the involvement of FKBP51 are highlighted as affecting the pathogenesis of the disease-the peroxisome proliferator-activated receptor-γ (PPARγ) and AKt.
Topics: Humans; Diabetes Mellitus, Type 2; Tacrolimus Binding Proteins; Neoplasms; Mental Disorders; Animals
PubMed: 38786025
DOI: 10.3390/cells13100801 -
Journal of Epidemiology and Community... May 2024Plans to phase out fossil fuel-powered internal combustion engine (ICE) vehicles and to replace these with electric and hybrid-electric (E-HE) vehicles represent a...
BACKGROUND
Plans to phase out fossil fuel-powered internal combustion engine (ICE) vehicles and to replace these with electric and hybrid-electric (E-HE) vehicles represent a historic step to reduce air pollution and address the climate emergency. However, there are concerns that E-HE cars are more hazardous to pedestrians, due to being quieter. We investigated and compared injury risks to pedestrians from E-HE and ICE cars in urban and rural environments.
METHODS
We conducted a cross-sectional study of pedestrians injured by cars or taxis in Great Britain. We estimated casualty rates per 100 million miles of travel by E-HE and ICE vehicles. Numerators (pedestrians) were extracted from STATS19 datasets. Denominators (car travel) were estimated by multiplying average annual mileage (using National Travel Survey datasets) by numbers of vehicles. We used Poisson regression to investigate modifying effects of environments where collisions occurred.
RESULTS
During 2013-2017, casualty rates per 100 million miles were 5.16 (95% CI 4.92 to 5.42) for E-HE vehicles and 2.40 (95%CI 2.38 to 2.41) for ICE vehicles, indicating that collisions were twice as likely (RR 2.15; 95% CI 2.05 to 2.26) with E-HE vehicles. Poisson regression found no evidence that E-HE vehicles were more dangerous in rural environments (RR 0.91; 95% CI 0.74 to 1.11); but strong evidence that E-HE vehicles were three times more dangerous than ICE vehicles in urban environments (RR 2.97; 95% CI 2.41 to 3.7). Sensitivity analyses of missing data support main findings.
CONCLUSION
E-HE cars pose greater risk to pedestrians than ICE cars in urban environments. This risk must be mitigated as governments phase out petrol and diesel cars.
PubMed: 38772699
DOI: 10.1136/jech-2024-221902 -
Molecular Psychiatry May 2024There have been conflicting reports regarding the case-fatality outcomes associated with sepsis and septic shock in patients with severe mental illness (SMI).
BACKGROUND
There have been conflicting reports regarding the case-fatality outcomes associated with sepsis and septic shock in patients with severe mental illness (SMI).
METHODS
We searched Medline®, Web of Science® and the Cochrane Library® databases (from inception to 4-July-2023) for papers reporting outcomes associated with sepsis and septic shock in adult with (cases) vs. without SMI (controls). The main study outcome was the unadjusted case-fatality rate at hospital discharge, or 30 days if unavailable. Secondary outcomes included the rates of adjusted case-fatality at hospital discharge.
RESULTS
A total of six studies were included in the systematic review, of which four provided data for meta-analysis involving 2,124,072 patients. Compared to controls, patients with SMI were younger and more frequently women. Unadjusted analyses showed that SMI patients had a lower case-fatality rate associated with sepsis and septic shock than their non-SMI counterparts (OR 0.61, 95% CI [0.58-0.65], PI 95% CI [0.49-0.77], I = 91%). Meta-regression and subgroup analyses showed that the denominator of the study population (i.e. septic shock or sepsis) was associated with the outcome with an R of 59.7%.
CONCLUSION
In conclusion, our study reveals a survival advantage of SMI patients over their non-SMI counterparts. Further research is needed to fully elucidate the mechanisms involved and to develop targeted interventions that can improve the prognosis of both SMI and non-SMI patients facing sepsis.
PubMed: 38769373
DOI: 10.1038/s41380-024-02603-8 -
PloS One 2024Understanding causes and contributors to maternal mortality is critical from a quality improvement perspective to inform decision making and monitor progress toward...
Validating the indicator "maternal death review coverage" to improve maternal mortality data: A retrospective analysis of district, facility, and individual medical record data.
BACKGROUND
Understanding causes and contributors to maternal mortality is critical from a quality improvement perspective to inform decision making and monitor progress toward ending preventable maternal mortality. The indicator "maternal death review coverage" is defined as the percentage of maternal deaths occurring in a facility that are audited. Both the numerator and denominator of this indicator are subject to misclassification errors, underreporting, and bias. This study assessed the validity of the indicator by examining both its numerator-the number and quality of death reviews-and denominator-the number of facility-based maternal deaths and comparing estimates of the indicator obtained from facility- versus district-level data.
METHODS AND FINDINGS
We collected data on the number of maternal deaths and content of death reviews from all health facilities serving as birthing sites in 12 districts in three countries: Argentina, Ghana, and India. Additional data were extracted from health management information systems on the number and dates of maternal deaths and maternal death reviews reported from health facilities to the district-level. We tabulated the percentage of facility deaths with evidence of a review, the percentage of reviews that met the World Health Organization defined standard for maternal and perinatal death surveillance and response. Results were stratified by sociodemographic characteristics of women and facility location and type. We compared these estimates to that obtained using district-level data. and looked at evidence of the review at the district/provincial level. Study teams reviewed facility records at 34 facilities in Argentina, 51 facilities in Ghana, and 282 facilities in India. In total, we found 17 deaths in Argentina, 14 deaths in Ghana, and 58 deaths in India evidenced at facilities. Overall, >80% of deaths had evidence of a review at facilities. In India, a much lower percentage of deaths occurring at secondary-level facilities (61.1%) had evidence of a review compared to deaths in tertiary-level facilities (92.1%). In all three countries, only about half of deaths in each country had complete reviews: 58.8% (n = 10) in Argentina, 57.2% (n = 8) in Ghana, and 41.1% (n = 24) in India. Dramatic reductions in indicator value were seen in several subnational geographic areas, including Gonda and Meerut in India and Sunyani in Ghana. For example, in Gonda only three of the 18 reviews conducted at facilities met the definitional standard (16.7%), which caused the value of the indicator to decrease from 81.8% to 13.6%. Stratification by women's sociodemographic factors suggested systematic differences in completeness of reviews by women's age, place of residence, and timing of death.
CONCLUSIONS
Our study assessed the validity of an important indicator for ending preventable deaths: the coverage of reviews of maternal deaths occurring in facilities in three study settings. We found discrepancies in deaths recorded at facilities and those reported to districts from facilities. Further, few maternal death reviews met global quality standards for completeness. The value of the calculated indicator masked inaccuracies in counts of both deaths and reviews and gave no indication of completeness, thus undermining the ultimate utility of the measure in achieving an accurate measure of coverage.
Topics: Humans; Female; Maternal Mortality; Retrospective Studies; Maternal Death; Ghana; Pregnancy; India; Argentina; Health Facilities; Medical Records; Adult
PubMed: 38768186
DOI: 10.1371/journal.pone.0303028 -
Health & Place Jul 2024Unsheltered homelessness is an increasingly prevalent phenomenon in major cities that is associated with adverse health and mortality outcomes. This creates a need for...
Unsheltered homelessness is an increasingly prevalent phenomenon in major cities that is associated with adverse health and mortality outcomes. This creates a need for spatial estimates of population denominators for resource allocation and epidemiological studies. Gaps in the timeliness, coverage, and spatial specificity of official Point-in-Time Counts of unsheltered homelessness suggest a role for geospatial data from alternative sources to provide interim, neighborhood-level estimates of counts and trends. We use citizen-generated data from homeless-related 311 requests, provider-based administrative data from homeless street outreach cases, and expert reports of unsheltered count to predict count and emerging hotspots of unsheltered homelessness in census tracts across the City of Los Angeles for 2019 and 2020. Our study shows that alternative data sources can contribute timely insights into the state of unsheltered homelessness throughout the year and inform the delivery of interventions to this vulnerable population.
Topics: Humans; Ill-Housed Persons; Los Angeles; Male; Female; Geographic Information Systems; Adult; Neighborhood Characteristics; Spatial Analysis; Middle Aged; Residence Characteristics
PubMed: 38763049
DOI: 10.1016/j.healthplace.2024.103267 -
Current Opinion in Genetics &... Jun 2024Recent advances have highlighted the significant roles of post-transcriptional modifications in rRNA in various cancers. Evidence suggests that dysregulation of rRNA... (Review)
Review
Recent advances have highlighted the significant roles of post-transcriptional modifications in rRNA in various cancers. Evidence suggests that dysregulation of rRNA modifications acts as a common denominator in cancer development, with alterations in these modifications conferring competitive advantages to cancer cells. Specifically, rRNA modifications modulate protein synthesis and favor the specialized translation of oncogenic programs, thereby contributing to the formation of a protumorigenic proteome in cancer cells. These findings reveal a novel regulatory layer mediated by changes in the deposition of rRNA chemical modifications. Moreover, inhibition of these modifications in vitro and in preclinical studies demonstrates potential therapeutic applications. The recurrence of altered rRNA modification patterns across different types of cancer underscores their importance in cancer progression, proposing them as potential biomarkers and novel therapeutic targets. This review will highlight the latest insights into how post-transcriptional rRNA modifications contribute to cancer progression and summarize the main developments and ongoing challenges in this research area.
Topics: Humans; Neoplasms; RNA, Ribosomal; RNA Processing, Post-Transcriptional; Animals; Gene Expression Regulation, Neoplastic; Protein Biosynthesis
PubMed: 38759459
DOI: 10.1016/j.gde.2024.102204 -
Archives of Sexual Behavior Jun 2024Latin America comprises 20 countries and 14 dependent territories throughout the Western Hemisphere. It is a diverse and plural region in terms of its geography,...
Latin America comprises 20 countries and 14 dependent territories throughout the Western Hemisphere. It is a diverse and plural region in terms of its geography, cultures, languages, and historical experiences, with fifteenth-century colonialism as a common denominator. Two areas in which the lingering effects of coloniality seem clearly ever-present are the realms of gender and sexuality. The latter encompasses sexual fantasies, a subject of focus in this article. The examination of sexual fantasies remains a ripe area for future research, particularly throughout the Global South, where its linkages to coloniality should be explored in detail. To contribute to this larger and long-term goal, we implemented an online qualitative study designed to document the sexual fantasies of Spanish-speaking individuals living in the Latin American region. We developed a data-gathering form that included open-ended questions to document sexual fantasies. The form was available through the JotForm online platform that was linked to the study webpage entitled "A Calzón Quita'o." We conducted a thematic analysis to identify response patterns. Three main categories emerged from: (1) spatiotemporal references, (2) multiple partners, and (3) power, control, and rough sex. We relied on perspectives linked to ongoing discussions about coloniality to analyze the thematic content in the participants' responses regarding their sexual fantasies. The findings highlight the existing tensions between the reproduction of-and resistance to-the norms associated with gender roles and their embodiment within the framework of the gender binary inherited from coloniality.
Topics: Humans; Latin America; Male; Female; Colonialism; Sexual Behavior; Adult; Erotica; Fantasy; Middle Aged; Sexual Partners; Imagination; Young Adult; Qualitative Research
PubMed: 38755505
DOI: 10.1007/s10508-024-02870-0 -
ACS Pharmacology & Translational Science May 2024The value of connected devices and health apps with features such as adherence trackers, dosing reminders, and remote communication tools for users and healthcare...
The value of connected devices and health apps with features such as adherence trackers, dosing reminders, and remote communication tools for users and healthcare providers has been assessed to support home-based subcutaneous administration. A comprehensive survey was conducted with 605 participants, including users and caregivers, from eight countries. Medical conditions encompassed ankylosing spondylitis, asthma, cerebral palsy, cluster headaches, Crohn's disease, hemophilia, lupus, migraine, multiple sclerosis, Parkinson's disease, plaque psoriasis, psoriatic arthritis, rheumatoid arthritis, spasticity, spondyloarthritis, and ulcerative colitis. Utilizing a maximum difference scaling methodology, the survey gauged participant preferences regarding specific attributes and features of connected drug delivery devices. Irrespective of demographic factors like age, gender, nationality, or the specific medical condition, the device's ability to verify a successful injection stood out as universally valued. The second and third most valued attributes pertained to temperature-related indicators or warnings. These features do not necessitate the use of a connected device and can be integrated into existing autoinjector platforms. The survey findings support the development of a universal adherence tool for at-home subcutaneous dosing, independent of a specific medical condition. This tool may be gradually improved with disease-specific features. Once established as a platform, manufacturers can launch any subcutaneous medication and later integrate real-world evidence for enhanced educational, treatment, and diagnostic capabilities. This approach is crucial for advancing connected adherence tools in decentralized healthcare, aligning with user and healthcare system needs while translating scientific innovation into practical solutions.
PubMed: 38751643
DOI: 10.1021/acsptsci.3c00377 -
Trends in severity of work-related traumatic injury and musculoskeletal disorder, Ontario 2004-2017.American Journal of Industrial Medicine Jul 2024Traumatic injury surveillance can be enhanced by describing injury severity trends. This study reports trends in work-related injury severity for males and females over...
OBJECTIVES
Traumatic injury surveillance can be enhanced by describing injury severity trends. This study reports trends in work-related injury severity for males and females over the period 2004-2017 in Ontario, Canada.
METHODS
A weighted measure of workers' compensation benefit expenditures was used to define injury severity, obtained from the linkage of workers' compensation claims to emergency department (ED) records where the main injury or illness was attributed to work. Denominator counts were obtained from Statistics Canada's Labor Force Survey. Trends in the annual incidence of injury, classified as low, moderate, or high severity, were examined using regression modeling, stratified by age and sex.
RESULTS
Over a 14-year observation period, there were 1,636,866 ED records included in the analyses. Overall, 57.6% of occupational injury records were classified as low severity, 29.5% as moderate severity, and 12.8% as high severity conditions. There was an increase in the incidence of high severity injuries among females (annual percent change (APC): 1.52%; 95% CI: 0.77, 2.28), while the incidence of low and moderate severity injuries generally declined for males and females. Among females, injuries attributed to animate mechanical forces and assault increased as causes of low, moderate, and high severity injuries. The incidence of concussion increased for both males (APC: 10.51%; 95% CI: 8.18, 12.88) and females (APC: 16.37%; 95% CI: 13.37, 19.45).
CONCLUSION
The incidence of severe work-related injuries increased among females in Ontario between 2004 and 2017. The methods applied in this surveillance study of traumatic injury severity are plausibly generalizable to applications in other jurisdictions.
Topics: Humans; Ontario; Male; Female; Occupational Injuries; Adult; Middle Aged; Workers' Compensation; Incidence; Musculoskeletal Diseases; Young Adult; Adolescent; Emergency Service, Hospital; Injury Severity Score
PubMed: 38751170
DOI: 10.1002/ajim.23614 -
Annals of Epidemiology Jul 2024The U.S. Virgin Islands (USVI) receives an updated population count once every 10 years and used 2010 decennial census population counts to estimate COVID-19 vaccination...
PURPOSE
The U.S. Virgin Islands (USVI) receives an updated population count once every 10 years and used 2010 decennial census population counts to estimate COVID-19 vaccination coverage during the COVID-19 emergency response. We investigated whether using outdated (2010) or modeled (2020 international database [IDB]) population counts biased vaccination coverage estimates used to inform public health priorities during the 2020-2022 COVID-19 response.
METHODS
We estimated percentage of USVI residents with a completed primary COVID-19 vaccination series during December 16, 2020-September 20, 2022. Vaccination coverage was calculated as number of persons who completed the vaccination series divided by 2010 and 2020 decennial census population counts and 2020 IDB intercensal estimate.
RESULTS
COVID-19 vaccination coverage using the 2020 population count was 12 % points higher than coverage using 2010 denominator (2010 denominator: 51 %; 2020 denominator: 63 %). Vaccination coverage estimated using 2020 IDB was approximately equal with the 2010 decennial census estimate (52 %).
CONCLUSIONS
Using 2010 and modeled population counts underestimated 2020 USVI COVID-19 vaccination coverage given the 18 % population decline during 2010-2020, potentially limiting USVI's ability to assess vaccination progress. Identifying mechanisms for more reliable population enumeration or improved estimate modeling are essential for accurately guiding USVI public health decision-making.
Topics: Humans; COVID-19; Vaccination Coverage; COVID-19 Vaccines; SARS-CoV-2; United States Virgin Islands; Female; Adult; Male; Middle Aged; Aged; Adolescent; Vaccination; Bias; Young Adult
PubMed: 38740077
DOI: 10.1016/j.annepidem.2024.05.006