Ferroptosis is a protective factor for the prognosis of cancer patients: a systematic review and meta-analysis.

BACKGROUND: Cancer is a leading global cause of death. Conventional cancer treatments like surgery, radiation, and chemotherapy have associated side effects. Ferroptosis, a nonapoptotic and iron-dependent cell death, has been identified and differs from other cell death types. Research has shown that ferroptosis can promote and inhibit tumor growth, which may have prognostic value. Given the unclear role of ferroptosis in cancer biology, this meta-analysis aims to investigate its impact on cancer prognosis. METHODS: This systematic review and meta-analysis conducted searches on PubMed, Embase, and the Cochrane Library databases. Eight retrospective studies were included to compare the impact of ferroptosis inhibition and promotion on cancer patient prognosis. The primary endpoints were overall survival (OS) and progression-free survival (PFS). Studies lacking clear descriptions of hazard ratios (HR) and 95% confidence intervals for OS and PFS were excluded. Random-effects meta-analysis and meta-regression were performed on the included study data to assess prognosis differences between the experimental and control groups. Meta-analysis results included HR and 95% confidence intervals. This study has been registered with PROSPERO, CRD 42023463720 on September 27, 2023. RESULTS: A total of 2,446 articles were screened, resulting in the inclusion of 5 articles with 938 eligible subjects. Eight studies were included in the meta-analysis after bias exclusion. The meta-analysis, after bias exclusion, demonstrated that promoting ferroptosis could increase cancer patients' overall survival (HR 0.31, 95% CI 0.21-0.44) and progression-free survival (HR 0.26, 95% CI 0.16-0.44) compared to ferroptosis inhibition. The results showed moderate heterogeneity, suggesting that biological activities promoting cancer cell ferroptosis are beneficial for cancer patient's prognosis. CONCLUSIONS: This systematic review and meta-analysis demonstrated that the promotion of ferroptosis yields substantial benefits for cancer prognosis. These findings underscore the untapped potential of ferroptosis as an innovative anti-tumor therapeutic strategy, capable of addressing challenges related to drug resistance, limited therapeutic efficacy, and unfavorable prognosis in cancer treatment. REGISTRATION: CRD42023463720.

Predictive and protective factors for failing first pass intubation in prehospital rapid sequence intubation: an aetiology and risk systematic review with meta-analysis.

BACKGROUND: Prehospital rapid sequence intubation first pass success rates vary between 59% and 98%. Patient morbidity is associated with repeat intubation attempts. Understanding what influences first pass success can guide improvements in practice. We performed an aetiology and risk systematic review to answer the research question 'what factors are associated with success or failure at first attempt laryngoscopy in prehospital rapid sequence intubation?'. METHODS: MEDLINE, EMBASE, CINAHL, and Cochrane Library were searched on March 3, 2023 for studies examining first pass success rates for rapid sequence intubation of prehospital live patients. Screening was performed via Covidence, and data synthesised by meta-analysis. The review was registered with PROSPERO and performed and reported as per Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. RESULTS: Reasonable evidence was discovered for predictive and protective factors for failure of first pass intubation. Predictive factors included age younger than 1 yr, the presence of blood or fluid in the airway, restricted jaw or neck movement, trauma patients, nighttime procedures, chronic or acute distortions of normal face/upper airway anatomy, and equipment issues. Protective factors included an experienced intubator, adequate training, use of certain videolaryngoscopes, elevating the patient on a stretcher in an inclined position, use of a bougie, and laryngeal manoeuvres. CONCLUSIONS: Managing bloody airways, positioning well, using videolaryngoscopes with bougies, and appropriate training should be further explored as opportunities for prehospital services to increase first pass success. Heterogeneity of studies limits stronger conclusions. SYSTEMATIC REVIEW PROTOCOL: PROSPERO (CRD42022353609).

Genetically predicted high serum sex hormone-binding globulin levels are associated with lower ischemic stroke risk: A sex-stratified Mendelian randomization study.

OBJECTIVE: Cross-sectional and cohort studies have found insufficient evidence of a causal relationship between sex hormone-binding globulin and ischemic stroke, only associations. Here, we performed a sex-stratified, bidirectional, two-sample Mendelian randomization analysis to evaluate whether a causal relationship exists between sex hormone-binding globulin and ischemic stroke. METHODS: Single-nucleotide polymorphisms associated with sex hormone-binding globulin and ischemic stroke were screened from genome-wide association studies summary data as instrumental variables to enable a bidirectional, two-sample Mendelian randomization study design. Inverse-variance weighted analysis was used as the main method to evaluate potential causality, and additional methods, including the weighted median and MR-Egger tests, were used to validate the Mendelian randomization results. Cochran's Q statistic, MR-Egger intercept test, and Mendelian Randomization-Pleiotropy Residual Sum and Outlier global test were used as sensitivity analysis techniques to assure the reliability of the results. Multivariable analysis was used to show the robustness of the results with key theorized confounders. RESULTS: Inverse-variance weighted analysis showed that genetically predicted higher serum sex hormone-binding globulin levels were associated with significantly decreased risk of ischemic stroke in males (odds radio = 0.934, 95 % confidence interval = 0.885-0.985, P = 0.012) and females (odds radio = 0.924, 95 % confidence interval = 0.868-0.983, P = 0.013). In an analysis of ischemic stroke subtypes, genetically predicted higher serum sex hormone-binding globulin levels were also associated with significantly decreased risk of small-vessel occlusion in both males (odds radio = 0.849, 95 % confidence interval = 0.759-0.949, P = 0.004) and females (odds radio = 0.829, 95 % confidence interval = 0.724-0.949, P = 0.006). The association remained in sensitivity analyses and multivariable analyses. The reverse analysis suggested an association between genetically predicted risk of cardioembolism and increased serum sex hormone-binding globulin in females (Beta = 0.029 nmol/L, Standard Error = 0.010, P = 0.003). CONCLUSION: Our findings provide new insight into the etiology of ischemic stroke and suggest that modulating serum sex hormone-binding globulin may be a therapeutic strategy to protect against ischemic stroke.

The discovery of GGT1 as a novel gene for ischemic stroke conferring protection against disease risk in non-smokers and non-abusers of alcohol.

OBJECTIVES: Increased plasma gamma-glutamyl transferase (GGT1) has been identified as a robust and independent risk factor for ischemic stroke (IS), but the molecular mechanisms of the enzyme-disease association are unclear. The present study investigated whether polymorphisms in the GGT1 gene contribute to IS susceptibility. MATERIALS AND METHODS: DNA samples obtained from 1288 unrelated individuals (600 IS patients and 688 controls) were genotyped for common single nucleotide polymorphisms of GGT1 using the MassArray-4 platform. RESULTS: The rs5751909 polymorphism was significantly associated with decreased risk of ischemic stroke regardless sex and age (Pperm ≤ 0.01, dominant genetic model). The haplotype rs4820599A-rs5760489A-rs5751909A showed strong protection against ischemic stroke (OR 0.53, 95 %CI 0.36 - 0.77, Pperm ≤ 0.0001). The protective effect of SNP rs5751909 in the stroke phenotype was successfully replicated in the UK Biobank, SiGN, and ISGC cohorts (P ≤ 0.01). GGT1 polymorphisms showed joint (epistatic) effects on the risk of ischemic stroke, with some known IS-associated GWAS loci (e.g., rs4322086 and rs12646447) investigated in our population. In addition, SNP rs5751909 was found to be strongly associated with a decreased risk of ischemic stroke in non-smokers (OR 0.54 95 %CI 0.39-0.75, Pperm = 0.0002) and non-alcohol abusers (OR 0.43 95 %CI 0.30-0.61, Pperm = 2.0 × 10-6), whereas no protective effects of this SNP against disease risk were observed in smokers and alcohol abusers (Pperm < 0.05). CONCLUSIONS: We propose mechanisms underlying the observed associations between GGT1 polymorphisms and ischemic stroke risk. This pilot study is the first to demonstrate that GGT1 is a novel susceptibility gene for ischemic stroke and provides additional evidence of the genetic contribution to impaired redox homeostasis underlying disease pathogenesis.

To what extent are psychological variables considered in the study of risk and protective factors for suicidal thoughts and behaviours in individuals with cancer? A systematic review of 70 years of research.

Psychological variables substantially shape the risk of suicidal thoughts and behaviours (STBs). However, it is unclear to what extent they are considered in individuals with cancer. We synthesized the quantitative research landscape concerning psychological risk/protective factors of STBs in the (psycho-) oncological context. This pre-registered review (PROSPERO-ID CRD42022331484) systematically searched the databases PubMed/Medline, CINAHL, PsycInfo, Cochrane Library, and Web of Science (as well as the grey literature and preprints). Risk of bias (RoB) was estimated using the ROBINS-I tool. Of 11,159 retrieved records, 319 studies were eligible for inclusion. Of those, 163 (51.1%) had investigated psychological factors (affective: n = 155; social: n = 65; cognitive: n = 63; personality/individual differences: n = 37; life events: n = 6), in a combined 3,561,741 participants. The most common STBs were suicidal ideation (n = 107) or death wishes (n = 20) rather than behaviour (suicide deaths: n = 26; attempts: n = 14). Most studies had a serious RoB. Thus, a large body of research investigated STBs in cancer patients/survivors, but it rarely aligned with the theoretical or clinical developments in suicide research. We propose a conceptual model of STBs in cancer delineating moderation and mediation effects to advance the integration of the fields, and to inform future research and practice.

The single nucleotide polymorphism rs4986790 (c.896A>G) in the gene TLR4 as a protective factor in corona virus disease 2019 (COVID-19).

Background and aims: Several factors, such as hypertension and diabetes mellitus, are known to influence the course of coronavirus disease 2019 (COVID-19). However, there is currently little information on genetic markers that influence the severity of COVID-19. In this study, we specifically investigated the single nucleotide polymorphism (SNP) rs4986790 in the TLR4 gene to identify a universal marker for preclinical prediction of COVID-19 disease progression. Methods: We analyzed the influence of demographics, pre-existing conditions, inflammatory parameters at the time of hospitalization, and TLR4 rs4986790 genotype on the outcome of COVID-19 in a comprehensive cohort (N = 1570). We performed multivariable analysis to investigate the impact of each factor. Results: We confirmed that younger patient age and absence of pre-existing conditions were protective factors against disease progression. Furthermore, when comparing patients with mild SARS-CoV-2 infection with patients who required hospitalization or intensive care or even died due to COVID-19, the AG/GG genotype of TLR4 rs4986790 was found to be a protective factor against COVID-19 disease progression (OR: 0.51, 95% CI: 0.34 - 0.77, p = 0.001). In addition, we demonstrated that low levels of interleukin-6 (IL-6) and procalcitonin (PCT) had a favorable effect on COVID-19 disease severity. In the subsequent multivariable analysis, we confirmed the absence of cardiovascular disease, low levels of IL-6 and PCT, and TLR4 rs4986790 AG/GG genotypes as independent predictors of potential hospitalization and reduction of severe or fatal disease course. Conclusion: In this study, we identified an additional genetic factor that may serve as an invariant predictor of COVID-19 outcome. The TLR4 rs4986790 AG/GG genotype reduced by half the risk of COVID-19 patients requiring hospitalization, intensive care or to have a fatal outcome. In addition, we were able to confirm the influence of previously known factors such as pre-existing conditions and inflammatory markers upon the onset of disease on the course of COVID-19. Based on these observations, we hereby provide another prognostic biomarker that could be used in routine diagnostics as a predictive factor for the severity of COVID-19 prior to SARS-CoV-2 infection.

Discrimination and Cardiovascular Health in Black Americans: Exploring Inflammation as a Mechanism and Perceived Control as a Protective Factor.

OBJECTIVE: Inflammation may be an integral physiological mechanism through which discrimination impacts cardiovascular health and contributes to racial health disparities. Limited research has examined psychosocial factors that protect against the negative effects of discrimination on inflammation. Perceived control is a promising possible protective factor, given that it has been shown to moderate the relationship between other psychosocial stressors and physiological outcomes. This study thus tested whether systemic inflammation mediated the link between discrimination and cardiovascular health and whether perceived control moderated this relationship. METHODS: Data for this project included 347 non-Hispanic/Latinx Black adults (mean [standard deviation] age = 51.64 [11.24] years; 33% female) taken from the Midlife in the United States study. Perceived control and daily discrimination were assessed via self-report, and inflammation was measured via circulating levels of C-reactive protein (CRP), interleukin-6 (IL-6), fibrinogen, and tumor necrosis factor α. Cardiovascular health was measured by morbidity of cardiovascular conditions: heart disease, hypertension, and/or stroke. RESULTS: CRP (indirect effect: b = 0.004, 95% confidence interval [CI] = 0.001-0.007) and fibrinogen (indirect effect: b = 0.002, 95% CI = 0.0003-0.005) mediated the link between discrimination and cardiovascular conditions. Perceived control moderated the relationship between discrimination and CRP ( F (1, 293) = 4.58, Δ R2 = 0.013, b = -0.02, SE = 0.01, p = .033). CRP mediated the link between discrimination and cardiovascular conditions only for those who reported low levels of perceived control (Index = -0.003, 95% CI = -0.007 to -0.0001). CONCLUSION: Findings provide empirical evidence of inflammation as a mechanism linking discrimination to cardiovascular conditions among Black Americans. Additionally, perceived control may be protective. Findings could suggest beliefs about control as a potential intervention target to help reduce the negative effects of discrimination on cardiovascular health among Black Americans.

Risk and protective factors associated with wound infection after neurosurgical procedures: A meta-analysis.

To systematically evaluate the risk factors for wound infection at the surgical site after neurosurgical craniotomy by meta-analysis, and to provide an evidence-based basis for preventing the occurrence of wound infection. A computerised search of PubMed, EMBASE, Cochrane Library, China National Knowledge Infrastructure and Wanfang database was conducted for relevant studies on risk factors for surgical site wound infection after neurosurgical craniotomy published from the database inception to November 2023. Two researchers independently screened the literature, extracted the data and performed quality assessment in strict accordance with the inclusion and exclusion criteria. STATA 17.0 software was applied for data analysis. Overall, 18 papers with 17 608 craniotomy patients were included, of which 905 patients developed wound infections. The analysis showed that underlying diseases [OR = 2.50, 95% CI (1.68, 3.72), p < 0.001] and emergency surgery [OR = 2.47, 95% CI (1.80, 3.38), p < 0.001] were the risk factors for developing wound infections after craniotomy, age < 60 years [OR = 0.72, 95% CI (0.52, 0.98), p = 0.039] was a protective factor for wound infections; whereas sex [OR = 1.11, 95% CI (0.98, 1.27), p = 0.112] and the antimicrobial use [OR = 1.30, 95% CI (0.81 2.09), p = 0.276] were not associated with the presence or absence of wound infection after craniotomy. Underlying disease and emergency surgery are risk factors for developing wound infections after craniotomy, whereas age < 60 years is a protective factor. Clinicians can reduce the occurrence of postoperative wound infections by communicating with patients in advance about the possibility of postoperative wound infections based on these factors, and by doing a good job of preventing postoperative wound infections.

Breast-feeding as protective factor against bronchopulmonary dysplasia in preterm infants.

Breast-feeding is associated with fewer comorbidities in very-low-birth-weight (VLBW) preterm infants. Bronchopulmonary dysplasia (BPD) of VLBW infants is a multifactorial pathology in which nutritional aspects may be of special importance. The aim of this study is to determine, in a cohort of VLBW infants, whether breast milk nutrition is associated with a reduced prevalence and severity of BPD. A retrospective study was conducted to record the intake of mother's own milk (MOM), pasteurised donor human milk or preterm formula milk in the first 2 weeks of postnatal life of 566 VLBW newborns at our hospital during the period January 2008-December 2021. After applying the relevant exclusion criteria, data for 489 VLBW infants were analysed; 195 developed some degree of BPD. Moderate or severe BPD is associated with less weight gain. Moreover, the preferential ingestion of breast milk in the first and second postnatal weeks had effects associated with lower OR for BPD, which were statistically demonstrable for mild (OR 0·16; 95 % CI 0·03, 0·71) and severe (OR 0·08; 95 % CI 0·009, 0·91) BPD. Breast-feeding during the first weeks of postnatal life is associated with a reduced prevalence of BPD, which is frequently associated with less weight gain as a result of greater respiratory effort with greater energy expenditure.

An L-shaped association between composite dietary antioxidant index and stroke: Evidence from NHANES 2011-2020.

OBJECTIVES: Antioxidant diets are considered to be protective factors against stroke. However, comprehensive measurement and evaluation of antioxidant diets are lacking. This study aimed to investigate the correlation between the Composite Dietary Antioxidant Index (CDAI) and stroke in adults. MATERIALS AND METHODS: In this study, based on the National Health and Nutrition Examination Survey (NHANES) 2011-2020 data, multivariate logistic regression, smoothing curve fitting, and threshold effect analysis were used to explore the relationship between CDAI and stroke. Subgroup analyses and interaction tests were conducted to assess the stability of this association within the population. RESULTS: Among 12,922 U.S. adults, there was a significant negative correlation between CDAI and the prevalence of stroke. In the fully adjusted model, the risk of stroke was reduced by 4 % for each 1-unit increase in CDAI (OR [95% CI] = 0.96 [0.93, 0.99]). Participants in the highest quartile of the CDAI had a 37 % lower risk of stroke than those in the lowest quartile (OR [95% CI] = 0.63 [0.47, 0.84]). This negative correlation remained stable across subgroups. Furthermore, the study revealed an L-shaped association between CDAI and stroke through smoothing curve fitting. The threshold effect analysis further identified the inflection point as -1.55. CONCLUSIONS: This study revealed an L-shaped relationship between CDAI and stroke. Keeping CDAI in the proper range may help prevent stroke in the general population.

Teoría de Rango Medio: Factores personales, ambientales y consumo de alcohol / Middle Range Theory: Personal, environmental factors and alcohol consumption / Teoria do Médio Alcance: Fatores pessoais, ambientais e consumo de álcool

El consumo de alcohol se considera un fenómeno complejo y multifactorial que puede estudiarse a través de diversas posturas teóricas, sin embargo, algunas teorías existentes carecen de sufi-cientes elementos para explorar y comprender dicho fenómeno. Por lo anterior, se propone una Teoría de Rango Medio que aborde los factores personales, ambientales y representaciones so-ciales del consumo de alcohol en jóvenes universitarios a partir de la Teoría Cognitiva Social de Bandura y de la conceptualización de la representación social de Moscovici. Para ello, se utilizó el método de Estructura Conceptual-Teórico-Empírico propuesto por Fawcett, compuesto por cinco pasos. La teoría derivada de este método contribuye en la identificación de un fenómeno específico para la disciplina mediante la determinación de conceptos y su relación con el con-sumo de alcohol en jóvenes universitarios. Además, de la incorporación de las representaciones sociales como elemento innovador para la profundización del fenómeno. Esta propuesta puede ser considerada en futuras investigaciones para ser probada y contribuir significativamente en el desarrollo de conocimiento sobre el consumo de alcohol

Alcohol consumption is considered a complex and multifactorial phenomenon that can be studied through various theoretical positions; however, some existing theories lack sufficient elements to explore and understand this phenomenon. Therefore, a Middle Range Theory is proposed that addresses personal, environmental, and social representations of alcohol consumption in young university students based on Bandura's Social Cognitive Theory and Moscovici's conceptualiza-tion of social representation. For this, the method of Conceptual-Theoretical-Empirical Structure proposed by Fawcett was used, consisting of five steps. The theory derived from this method con-tributes to the identification of a specific phenomenon for the discipline by determining concepts and their relationship with alcohol consumption in young university students. In addition, the incorporation of social representations as an innovative element for the deepening of the phenom-enon. This proposal can be considered in future research to be tested and contribute significantly to the development of knowledge about alcohol consumption

O consumo de álcool é considerado um fenômeno complexo e multifatorial que pode ser estu-dado por meio de vários posicionamentos teóricos, porém, algumas teorias existentes carecem de elementos suficientes para explorar e compreender esse fenômeno. Assim, propõe-se uma Teoria de Médio Alcance que aborda as representações pessoais, ambientais e sociais do consu-mo de álcool em universitários com base na Teoria Social Cognitiva de Bandura e na conceitu-ação de representação social de Moscovici. Para isso, foi utilizado o método da Estrutura Con-ceitual-Teórico-Empírica proposto por Fawcett, composto por cinco etapas. A teoria derivada desse método contribui para a identificação de um fenômeno específico da disciplina ao deter-minar conceitos e sua relação com o consumo de álcool em jovens universitários. Além disso, a incorporação das representações sociais como elemento inovador para o aprofundamento do fenômeno. Essa proposta pode ser considerada em pesquisas futuras a serem testadas e contribuir significativamente para o desenvolvimento do conhecimento sobre o consumo de álcool

Leisure time physical activity: a protective factor against metabolic syndrome development.

PURPOSE: Physical activity (PA) is a modifiable factor in preventing/treating cardiometabolic disease. However, no studies have yet compared specific moderate-to-vigorous PA (MVPA) domains with the risk of metabolic syndrome (MetS) in detail. Here, the present study was conducted to examine the impact of different MVPA domains (leisure-time PA (LTPA) vs. occupational PA (OPA) vs. total MVPA) on the risk of MetS in Korean adults. MATERIALS AND METHODS: Data from the 2014 to 2021 Korea National Health and Nutrition Examination Survey were analyzed (N = 31,558). MetS was defined according to the criteria by revised NCEP/ATP-III. The domain-specific MVPA was assessed using the K-GPAQ. The LTPA and OPA status were classified into four categories: (1) 0 min/week, (2) 1 to 149 min/week, (3) 150 to 299 min/week, and 4) ≥ 300 min/week. In addition, the present study calculated total MVPA as a sum of OPA and LTPA and further classified it into six groups; (1) 0 min/week, (2) 1 to 149 min/week, (3) 150 to 299 min/week, (4) 300 to 449 min/week, (5) 450 to 599 min/week, 6) ≥ 600 min/week. RESULTS: The ≥ 300 min/week and the 150 to 299 min/week of LTPA showed better outcomes in cardiometabolic disease risk factors and surrogate markers of insulin resistance compared with the 0 min/week of LTPA regardless of adiposity status. Risk of MetS in ≥ 300 min/week of LTPA was lower than in 0 min/week, 1 to 149 min/week, and 150 to 299. In addition, LTPA was significantly associated with a risk of the MetS in a curvilinear dose-response curve, however, no significant effects of a non-linear relationship between OPA and risk of the MetS. CONCLUSIONS: Our findings showed that LTPA was associated with a risk of MetS with a dose-response curve, whereas no significant non-linear effects were found between OPA and the risk of MetS. Therefore, the MVPA domain is an independent factor of the risk of MetS.

Sample average treatment effect on the treated (SATT) analysis using counterfactual explanation identifies BMT and SARS-CoV-2 vaccination as protective risk factors associated with COVID-19 severity and survival in patients with multiple myeloma.

Patients with multiple myeloma (MM), an age-dependent neoplasm of antibody-producing plasma cells, have compromised immune systems and might be at increased risk for severe COVID-19 outcomes. This study characterizes risk factors associated with clinical indicators of COVID-19 severity and all-cause mortality in myeloma patients utilizing NCATS' National COVID Cohort Collaborative (N3C) database. The N3C consortium is a large, centralized data resource representing the largest multi-center cohort of COVID-19 cases and controls nationwide (>16 million total patients, and >6 million confirmed COVID-19+ cases to date). Our cohort included myeloma patients (both inpatients and outpatients) within the N3C consortium who have been diagnosed with COVID-19 based on positive PCR or antigen tests or ICD-10-CM diagnosis code. The outcomes of interest include all-cause mortality (including discharge to hospice) during the index encounter and clinical indicators of severity (i.e., hospitalization/emergency department/ED visit, use of mechanical ventilation, or extracorporeal membrane oxygenation (ECMO)). Finally, causal inference analysis was performed using the Coarsened Exact Matching (CEM) and Propensity Score Matching (PSM) methods. As of 05/16/2022, the N3C consortium included 1,061,748 cancer patients, out of which 26,064 were MM patients (8,588 were COVID-19 positive). The mean age at COVID-19 diagnosis was 65.89 years, 46.8% were females, and 20.2% were of black race. 4.47% of patients died within 30 days of COVID-19 hospitalization. Overall, the survival probability was 90.7% across the course of the study. Multivariate logistic regression analysis showed histories of pulmonary and renal disease, dexamethasone, proteasome inhibitor/PI, immunomodulatory/IMiD therapies, and severe Charlson Comorbidity Index/CCI were significantly associated with higher risks of severe COVID-19 outcomes. Protective associations were observed with blood-or-marrow transplant/BMT and COVID-19 vaccination. Further, multivariate Cox proportional hazard analysis showed that high and moderate CCI levels, International Staging System (ISS) moderate or severe stage, and PI therapy were associated with worse survival, while BMT and COVID-19 vaccination were associated with lower risk of death. Finally, matched sample average treatment effect on the treated (SATT) confirmed the causal effect of BMT and vaccination status as top protective factors associated with COVID-19 risk among US patients suffering from multiple myeloma. To the best of our knowledge, this is the largest nationwide study on myeloma patients with COVID-19.

Uso inconsistente del preservativo masculino en hombres VIH negativos que tienen sexo con hombres / Inconsistent use of male condoms among HIV-negative men who have sex with other men / Uso inconsistente do preservativo masculino entre homens HIV negativos que fazem sexo com homens

Objetivo: analizar los factores asociados con el uso inconsistente del preservativo masculino en hombres VIH negativos que tienen sexo con hombres. Método: estudio transversal, analítico, nacional realizado de forma online en todas las regiones de Brasil, en 2020, a través de redes sociales y sitios de citas. El uso inconsistente del preservativo se definió como el uso ocasional o no usarlo nunca. Se realizaron análisis estadísticos descriptivos, pruebas de asociación y regresión logística binaria. Resultados: 1222 (85%) de los 1438 participantes informaron uso inconsistente del preservativo. Las variables "homosexuales" (ORA: 2,03; IC 95%: 1,14-3,59; p = 0,016), "tener pareja estable" (ORA: 2,19; IC 95%: 1,55-3,09; p<0,001), "sexo oral" (ORA: 2,41; IC 95%: 1,31-4,43; p = 0,005), "anal insertivo" (ORA: 1,98; IC 95%: 1,10-3,58; p = 0,023) y "diagnóstico de ITS" (ORA: 1,59; IC 95%: 1,13-2,24; p = 0,007) se asociaron de forma independiente con el uso inconsistente del preservativo masculino. Las variables "recibió consejo de un amigo sobre la prueba del VIH" (ORA: 0,71; IC 95%: 0,52-0,96; p = 0,028) y "trabajador sexual" (ORA: 0,26; IC 95%: 0,11-0,60; p = 0,002) fueron factores protectores. Conclusión: las variables estudiadas indicaron que hay una fuerte relación entre las parejas estables y el aumento de la confianza y la baja adherencia al uso del preservativo, lo que coincide con otros estudios.

Objective: to analyze the factors associated with inconsistent use of male condoms among HIV-negative men who have sex with other men. Method: a cross-sectional, analytical and nationwide study conducted online in all the Brazilian regions in 2020, via networks and in dating websites. Inconsistent condom use was defined as occasional use or as never using it. Descriptive statistical analyses were performed, as well as association and binary logistic regression tests. Results: inconsistent condom use was reported by 1,222 (85%) of all 1,438 participants. The "homosexuals" (ORAdj: 2.03; 95% CI: 1.14-3.59; p=0.016), "having a fixed partner" (ORAdj: 2.19; 95% CI: 1.55-3.09; p<0.001), "oral sex" (ORAdj: 2.41; 95% CI: 1.31-4.43; p=0.005), "insertive anal" (ORAdj: 1.98; 95% CI: 1.10-3.58; p=0.023) and "STI diagnosis" (ORAdj: 1.59; 95% CI: 1.13-2.24; p=0.007) variables were independently associated with inconsistent use of male condoms. The "receiving advice on HIV test from a friend" (ORAdj: 0.71; 95% CI: 0.52-0.96; p=0.028) and "sex worker" (ORAdj: 0.26; 95% CI: 0.11-0.60; p=0.002) variables were protective factors. Conclusion: the variables under study pointed to a strong relationship between steady partners and increased trust and low adherence to condom use, corroborating other studies.

Objetivo: analisar os fatores associados ao uso inconsistente do preservativo masculino entre homens HIV negativos que fazem sexo com homens. Método: estudo transversal, analítico, de abrangência nacional realizado on-line em todas as regiões do Brasil, em 2020, por meio de redes sociais e em sites de relacionamento. O uso inconsistente do preservativo foi definido como uso ocasional ou nunca ter usado. Foram realizadas análises estatísticas descritivas, testes de associação e regressão logística binária. Resultados: o uso inconsistente do preservativo foi relatado por 1222 (85%) dos 1438 participantes. As variáveis "homossexuais" (ORA: 2,03; IC 95%: 1,14- 3,59; p = 0,016), "ter parceiro fixo" (ORA: 2,19; IC 95%: 1,55-3,09; p<0,001), "sexo oral" (ORA: 2,41; IC 95%: 1,31-4,43; p = 0,005), "anal insertivo" (ORA: 1,98; IC 95%: 1,10-3,58; p = 0,023) e "diagnóstico de IST" (ORA: 1,59; IC 95%: 1,13-2,24; p = 0,007) foram independentemente associadas ao uso inconsistente do preservativo masculino. As variáveis "recebeu aconselhamento de amigo sobre teste de HIV" (ORA: 0,71; IC 95%: 0,52-0,96; p = 0,028) e "profissional do sexo" (ORA: 0,26; IC 95%: 0,11-0,60; p = 0,002) foram fatores de proteção. Conclusão: as variáveis estudadas apontaram uma forte relação das parcerias fixas com o aumento da confiança e uma baixa adesão ao uso do preservativo, o que corrobora com outros estudos.

Interaction of Fabry Disease and Diabetes Mellitus: Suboptimal Recruitment of Kidney Protective Factors.

Fabry disease is a lysosomal disease characterized by globotriaosylceramide (Gb3) accumulation. It may coexist with diabetes mellitus and both cause potentially lethal kidney end-organ damage. However, there is little information on their interaction with kidney disease. We have addressed the interaction between Fabry disease and diabetes in data mining of human kidney transcriptomics databases and in Fabry (Gla-/-) and wild type mice with or without streptozotocin-induced diabetes. Data mining was consistent with differential expression of genes encoding enzymes from the Gb3 metabolic pathway in human diabetic kidney disease, including upregulation of UGCG, the gene encoding the upstream and rate-limiting enzyme glucosyl ceramide synthase. Diabetic Fabry mice displayed the most severe kidney infiltration by F4/80+ macrophages, and a lower kidney expression of kidney protective genes (Pgc1α and Tfeb) than diabetic wild type mice, without a further increase in kidney fibrosis. Moreover, only diabetic Fabry mice developed kidney insufficiency and these mice with kidney insufficiency had a high expression of Ugcg. In conclusion, we found evidence of interaction between diabetes and Fabry disease that may increase the severity of the kidney phenotype through modulation of the Gb3 synthesis pathway and downregulation of kidney protective genes.

Older adults' awareness of modifiable risk and protective factors for dementia and interest in eHealth interventions for brain health: a comparison between the Netherlands and Germany.

BACKGROUND: Evidence on modifiable risk factors for dementia is accumulating rapidly, including e.g. smoking, hypertension, and diabetes. Comparing knowledge of risk factors for dementia and factors associated with knowledge and motivation to learn about dementia risk reduction in different countries may support the design of tailored public health campaigns. We investigated (1) differences in knowledge of risk and protective factors for dementia between the Netherlands and Germany, and interest in (2) information on brain health and (3) eHealth for brain health. MATERIALS AND METHODS: Population-based telephone (Germany) or web-based surveys (Netherlands) were conducted among adults aged 60-75 (ntotal=614; Germany: n = 270; Netherlands: n = 344), assessing sociodemographic factors, knowledge of risk and protective factors for dementia, interest in information on brain health and respective eHealth-tools. Correlates of knowledge, interest in information on brain health and eHealth for brain health were analyzed using multivariable regression, by country and in pooled analyses. RESULTS: In the total sample (Mage: 67.3 (SD: 4.3) years; %female: 48.6), knowledge of risk and protective factors (sum score assessing number of correctly identified factors) was higher among German participants (M (SD) = 7.6 (2.5) vs. 6.0 (4.3), p < .001). This was confirmed using linear regression analyses, controlling for sociodemographic covariates (b = 1.51; 95% CI: 1.00; 2.01). High education was linked to better knowledge of risk and protective factors (b = 1.61; 95% CI: 0.89; 2.34). Controlling for covariates, interest in information on brain health (OR: 0.05, 95% CI: 0.02; 0.09) and eHealth for brain health (OR: 0.40, 95% CI: 0.25; 0.65) was lower in German participants. Widowed participants were less interested in information on brain health, while widowed and single participants expressed less interest in eHealth for brain health in pooled analyses. Further associations between sociodemographic factors, interest in information on brain health and eHealth for brain health by country were detected. DISCUSSION: Engaging older adults in the design of eHealth interventions and cooperation with trusted sources, e.g., general practitioners, might enhance appreciation of eHealth for brain health. Education on risk and protective factors for dementia is warranted in both countries. However, differences in recruitment and assessment need to be acknowledged.

An updated meta-analysis investigating the association between DNMTs gene polymorphism andgastric cancer risk.

Gastric cancer (GC) is a prominent global health issue, as it ranks as the fifth most prevalent type of cancer and the fourth most significant cause of cancer-related mortality worldwide. Although H. pylori is known to play a role in the development of GC, genetic factors also play a role in its onset and progression. Recent studies have shown that genetic polymorphisms are strongly associated with the development of GC and that certain single nucleotide polymorphisms (SNPs) can be used as biomarkers for early diagnosis and prevention. Epigenetic disturbances, such as DNA methylation, are involved in the development of GC, and mutations in the DNA methyltransferase (DNMT) gene have been found to increase the risk of GC. However, previous findings on the association between DNMTs SNPs and GC risk have been inconsistent. In this study, an updated meta-analysis of three well-studied and controversial DNMTs polymorphic loci, DNMT1 rs16999593, DNMT3A rs1550117 and DNMT3B rs1569686, was performed to provide more reliable results. It was found that DNMT1 rs16999593 was not associated with GC, DNMT3A rs1550117 may have a positive association with GC risk, and DNMT3B rs1569686 may be a protective factor for GC. These findings may provide valuable information for early diagnosis and prevention of GC, but further studies are needed to confirm these results.

Association of lncRNA SOX2OT rs9839776 polymorphism with gastric cancer risk in Korean: Case-control study.

Aberrant regulation of the long non-coding RNA SRY-box transcription factor 2 overlapping transcript (SOX2OT) has been reported in various diseases including gastric cancer (GC). However, an association between the well-studied rs9839776 single nucleotide polymorphism in SOX2OT and GC susceptibility has not been reported. This study aimed to evaluate the association between the rs9839776 single nucleotide polymorphism in SOX2OT and GC risk. Genotyping of rs9839776 was conducted using TaqMan genotyping assay for 460 patients with GC and 386 controls. We found that the dominant model (CT+TT) and rs9839776 T allele were significantly associated with decreased GC risk (P = .046, adjusted odds ratio [AOR] = 0.72, 95% confidence interval [CI] = 0.52-1.00 and P = .044, AOR = 0.74, 95% CI = 0.56-0.99, respectively). In addition, stratified analysis revealed that the dominant model (CT+TT) and rs9839776 T allele were significantly associated with decreased risk of lymph node metastasis-negative (P = .039, AOR = 0.67, 95% CI = 0.46-0.98 and P = .049, AOR = 0.71, 95% CI = 0.51-1.00, respectively) and tumor stage I (A+B)/II (A+B+C) (P = .028, AOR = 0.66, 95% CI = 0.50-0.96 and P = .041, AOR = 0.71, 95% CI = 0.52-0.99, respectively) GC. Our findings suggest that the rs9839776 T allele may be a protective factor against GC susceptibility. Further research is needed to clarify whether rs9839776 affects SOX2OT expression.

Unveiling adcyap1 as a protective factor linking pain and nerve regeneration through single-cell RNA sequencing of rat dorsal root ganglion neurons.

BACKGROUND: Severe peripheral nerve injury (PNI) often leads to significant movement disorders and intractable pain. Therefore, promoting nerve regeneration while avoiding neuropathic pain is crucial for the clinical treatment of PNI patients. However, established animal models for peripheral neuropathy fail to accurately recapitulate the clinical features of PNI. Additionally, researchers usually investigate neuropathic pain and axonal regeneration separately, leaving the intrinsic relationship between the development of neuropathic pain and nerve regeneration after PNI unclear. To explore the underlying connections between pain and regeneration after PNI and provide potential molecular targets, we performed single-cell RNA sequencing and functional verification in an established rat model, allowing simultaneous study of the neuropathic pain and axonal regeneration after PNI. RESULTS: First, a novel rat model named spared nerve crush (SNC) was created. In this model, two branches of the sciatic nerve were crushed, but the epineurium remained unsevered. This model successfully recapitulated both neuropathic pain and axonal regeneration after PNI, allowing for the study of the intrinsic link between these two crucial biological processes. Dorsal root ganglions (DRGs) from SNC and naïve rats at various time points after SNC were collected for single-cell RNA sequencing (scRNA-seq). After matching all scRNA-seq data to the 7 known DRG types, we discovered that the PEP1 and PEP3 DRG neuron subtypes increased in crushed and uncrushed DRG separately after SNC. Using experimental design scRNA-seq processing (EDSSP), we identified Adcyap1 as a potential gene contributing to both pain and nerve regeneration. Indeed, repeated intrathecal administration of PACAP38 mitigated pain and facilitated axonal regeneration, while Adcyap1 siRNA or PACAP6-38, an antagonist of PAC1R (a receptor of PACAP38) led to both mechanical hyperalgesia and delayed DRG axon regeneration in SNC rats. Moreover, these effects can be reversed by repeated intrathecal administration of PACAP38 in the acute phase but not the late phase after PNI, resulting in alleviated pain and promoted axonal regeneration. CONCLUSIONS: Our study reveals that Adcyap1 is an intrinsic protective factor linking neuropathic pain and axonal regeneration following PNI. This finding provides new potential targets and strategies for early therapeutic intervention of PNI.