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The function of many DNA metabolism proteins depends on their ability to coordinate an iron-sulfur (Fe-S) cluster. Biogenesis of Fe-S proteins is a multistep process that takes place in mitochondria and the cytoplasm, but how it is linked to nuclear Fe-S proteins is not known. Here, we demonstrate that MMS19 forms a complex with the cytoplasmic Fe-S assembly (CIA) proteins CIAO1, IOP1, and MIP18. Cytoplasmic MMS19 also binds to multiple nuclear Fe-S proteins involved in DNA metabolism. In the absence of MMS19, a failure to transfer Fe-S clusters to target proteins is associated with Fe-S protein instability and preimplantation death of mice in which Mmsl9 has been knocked out. We propose that MMS19 functions as a platform to facilitate Fe-S cluster transfer to proteins critical for DNA replication and repair.

Background An increased risk of cardiovascular (CV) complications has been described in patients with rheumatoid arthritis (RA). It is the result of the combined effect of classic CV risk factors and others that are specific to the disease. Methods We assessed data from 448 early arthritis (EA) patients: 79% women, age (median [p25-p75]) at onset: 55 [44–67] years and disease duration at study entry 5 [3–8] months; and 72% fulfilled the 1987 RA criteria at 2 years of follow-up. Rheumatoid factor was positive in 54% of patients and anti-citrullinated peptide antibodies in 50%. The follow-up of patients ranged from 2 to 5 years with more than 1400 visits with lipoprotein measurements available (mean 2.5 visits/patient). Demographic- and disease-related variables were systematically recorded. Total cholesterol (TC), high-density lipoprotein (HDL-C), and low-density lipoprotein (LDL-C) levels were obtained from routine laboratory tests. Oxidized-LDL (oxLDL-C) levels were assessed using a commercial ELISA kit. We fitted population-averaged models nested by patient and visit to determine the effect of independent variables on serum levels of TC, its fractions, and oxLDL-C. Results After adjustment for several confounders, high-disease activity was significantly associated with decreased TC, HDL-C, and LDL-C levels and increased oxLDL-C levels. Standardized coefficients showed that the effect of disease activity was greater on oxLDL-C and HDL-C. Interestingly, we observed that those patients with lower levels of LDL-C showed higher oxLDL-C/LDL-C ratios. Conclusions High-disease activity in EA patients results in changes in the HDL-C and oxLDL-C levels, which in turn may contribute to the increased risk of CV disease observed in these patients.

Cancer is the leading cause of death among Hispanics/Latinos, who represent the largest racial/ethnic minority group in the United States, accounting for 17.8% (57.5 million) of the total population in the continental United States and Hawaii in 2016. In addition, more than 3 million Hispanic Americans live in the US territory of Puerto Rico. Every 3 years, the American Cancer Society reports on cancer occurrence, risk factors, and screening for Hispanics in the United States based on data from the National Cancer Institute, the North American Association of Central Cancer Registries, and the Centers for Disease Control and Prevention. For the first time, contemporary incidence and mortality rates for Puerto Rico, which has a 99% Hispanic population, are also presented. An estimated 149,100 new cancer cases and 42,700 cancer deaths will occur among Hispanics in the continental United States and Hawaii in 2018. For all cancers combined, Hispanics have 25% lower incidence and 30% lower mortality compared with non‐Hispanic whites, although rates of infection-related cancers, such as liver, are up to twice as high in Hispanics. However, these aggregated data mask substantial heterogeneity within the Hispanic population because of variable cancer risk, as exemplified by the substantial differences in the cancer burden between island Puerto Ricans and other US Hispanics. For example, during 2011 to 2015, prostate cancer incidence rates in Puerto Rico (146.6 per 100,000) were 60% higher than those in other US Hispanics combined (91.6 per 100,000) and 44% higher than those in non-Hispanic whites (101.7 per 100,000). Prostate cancer is also the leading cause of cancer death among men in Puerto Rico, accounting for nearly 1 in 6 cancer deaths during 2011-2015, whereas lung cancer is the leading cause of cancer death among other US Hispanic men combined. Variations in cancer risk are driven by differences in exposure to cancer-causing infectious agents and behavioral risk factors as well as the prevalence of screening. Strategies for reducing cancer risk in Hispanic populations include targeted, culturally appropriate interventions for increasing the uptake of preventive services and reducing cancer risk factor prevalence, as well as additional funding for Puerto Rico-specific and subgroup-specific cancer research and surveillance.

Most physical and other natural systems are complex entities that are composed of a large number of interacting individual elements. It is a surprising fact that they often obey the so-called scaling laws that relate an observable quantity to a measure of the size of the system. Here, we describe the discovery of universal superlinear metabolic scaling laws in human cancers. This dependence underpins increasing tumour aggressiveness, owing to evolutionary dynamics, that leads to an explosive growth as the disease progresses. We validated this dynamic using longitudinal volumetric data of different histologies from large cohorts of patients with cancer. To explain our observations we tested complex, biologically inspired mathematical models that describe the key processes that govern tumour growth. Our models predict that the emergence of superlinear allometric scaling laws is an inherently three-dimensional phenomenon. Moreover, the scaling laws that we identified allowed us to define a set of metabolic metrics with prognostic value, which adds clinical utility to our findings. The authors investigate the relationship between the volume of malignant tumours and their metabolic processes using a large dataset of patients with cancer. They find that cancers follow a superlinear metabolic scaling law, which implies that the proliferation of cancer cells accelerates with increasing volume.

The Hispanic/Latino population is the second largest racial/ethnic group in the continental United States and Hawaii, accounting for 18% (60.6 million) of the total population. An additional 3 million Hispanic Americans live in Puerto Rico. Every 3 years, the American Cancer Society reports on cancer occurrence, risk factors, and screening for Hispanic individuals in the United States using the most recent population-based data. An estimated 176,600 new cancer cases and 46,500 cancer deaths will occur among Hispanic individuals in the continental United States and Hawaii in 2021. Compared to non-Hispanic Whites (NHWs), Hispanic men and women had 25%-30% lower incidence (2014-2018) and mortality (2015-2019) rates for all cancers combined and lower rates for the most common cancers, although this gap is diminishing. For example, the colorectal cancer (CRC) incidence rate ratio for Hispanic compared with NHW individuals narrowed from 0.75 (95% CI, 0.73-0.78) in 1995 to 0.91 (95% CI, 0.89-0.93) in 2018, reflecting delayed declines in CRC rates among Hispanic individuals in part because of slower uptake of screening. In contrast, Hispanic individuals have higher rates of infection-related cancers, including approximately two-fold higher incidence of liver and stomach cancer. Cervical cancer incidence is 32% higher among Hispanic women in the continental US and Hawaii and 78% higher among women in Puerto Rico compared to NHW women, yet is largely preventable through screening. Less access to care may be similarly reflected in the low prevalence of localized-stage breast cancer among Hispanic women, 59% versus 67% among NHW women. Evidence-based strategies for decreasing the cancer burden among the Hispanic population include the use of culturally appropriate lay health advisors and patient navigators and targeted, community-based intervention programs to facilitate access to screening and promote healthy behaviors. In addition, the impact of the COVID-19 pandemic on cancer trends and disparities in the Hispanic population should be closely monitored.

Background The relationship between obesity and risk of complications described during the 2009 influenza pandemic is poorly defined for seasonal influenza and other viral causes of influenza‐like illness (ILI). Methods An observational cohort of hospitalized and outpatient participants with ILI was conducted in six hospitals in Mexico. Nasopharyngeal swabs were tested for influenza and other common respiratory pathogens. Results A total of 4778 participants were enrolled in this study and had complete data. A total of 2053 (43.0%) had severe ILI. Seven hundred and seventy‐eight (16.3%) were positive for influenza, 2636 (55.2%) were positive for other viral respiratory pathogens, and 1364 (28.5%) had no respiratory virus isolated. Adults with influenza were more likely to be hospitalized if they were underweight (OR: 5.20), obese (OR: 3.18), or morbidly obese (OR: 18.40) compared to normal‐weight adults. Obese adults with H1N1 had a sixfold increase in odds of hospitalization over H3N2 and B (obese OR: 8.96 vs 1.35, morbidly obese OR: 35.13 vs 5.58, respectively) compared to normal‐weight adults. In adults with coronavirus, metapneumovirus, parainfluenza, and rhinovirus, participants that were underweight (OR: 4.07) and morbidly obese (OR: 2.78) were more likely to be hospitalized as compared to normal‐weight adults. All‐cause influenza‐like illness had a similar but less pronounced association between underweight or morbidly obesity and hospitalization. Conclusions There is an increased risk of being hospitalized in adult participants that are underweight or morbidly obese, regardless of their viral pathogen status. Having influenza, however, significantly increases the odds of hospitalization in those who are underweight or morbidly obese.

Rheumatoid arthritis (RA) has a negative impact on bone that is partly mediated by anti-citrullinated proteins antibodies (ACPA). These antibodies are associated with erosions, and with juxta-articular and systemic bone loss. Other RA autoantibodies, the anti-carbamylated protein antibodies (anti-CarPA), are independently associated with erosions. However, we do not know if they are also associated with juxta-articular and systemic bone loss. Here, we have addressed this question with data from 548 early arthritis (EA) patients. Bone mineral density (BMD) was assessed by dual-energy x-ray absorptiometry at the lumbar spine (LS), total hip (TH) and metacarpophalangeal joints (MCP). The 25.9% anti-CarPA positive patients did not show significant differences in BMD Z-scores with the negative patients. Nevertheless, this result was due to the similarity between negative and low-positive (below the median of the positive) patients, whereas the high-positive patients showed significant decrease of BMD at LS (β = -0.39, p = 0.01) and TH (β = -0.30, p = 0.02); but not at the juxta-articular bone of MCP. Given the overlap between anti-CarPA and ACPA, we included the two autoantibodies in an analysis that showed significantly lower BMD Z-scores at LS and TH (p< 0.01) only in the ACPA positive/anti-CarPA high-positive subgroup. However, the similar coefficients of regression between the ACPA positive/anti-CarPA high-positive and the ACPA negative/anti-CarPA high-positive subgroups (β = -0.50 vs. -0.52 at LS, and β = -0.37 vs. -0.30 at TH) suggested an independent association. Overall, these results support a contribution of anti-CarPA to systemic bone loss in EA patients.

Pediatric obsessive-compulsive disorder (OCD) clusters around three major symptom dimensions: contamination/cleaning, symmetry/ordering, and disturbing thoughts/checking. The Obsessive-Compulsive Inventory-Child Version (OCI-CV) is a self-report questionnaire that provides scores along six theory-based OCD dimensions, but no study has evaluated how well OCI-CV identifies clinically significant symptoms within each of the three major symptom dimensions of OCD. We examined this question using data from 197 Swedish and Spanish youth with OCD. All youth completed the OCI-CV and clinically significant symptom severity within each major OCD dimension was established with a validated interview-based measure. Results showed that a score ≥ 3 on the OCI-CV washing scale excellently captured those with clinically significant contamination/cleaning symptoms (AUC = 0.85 [0.80–0.90], 79% accuracy). A score ≥ 4 on the obsessing scale adequately captured those with disturbing thoughts/checking symptoms (AUC = 0.71 [0.64–0.78], 67% accuracy) and a score ≥ 3 on the ordering scale adequately captured those with symmetry/ordering symptoms (AUC = 0.72 [0.65–0.79], 70% accuracy). Similar accuracy of the breakpoints was found in the Swedish and Spanish samples. OCI-CV works well to identify youth with pediatric OCD that have clinically significant contamination/cleaning symptoms. The measure can also with adequate precision identify those with clinically significant disturbing thoughts/checking and symmetry/ordering symptoms. The breakpoints provided in this study can be used to examine differences in clinical presentation and treatment outcome for youth with different types of OCD.

Mistreatment is a complex problem that impacts people's quality of life, morbidity, and mortality. In aged people, it has been associated with female sex, poor general health, depression, functional and cognitive decline, and increased dependence levels, all of which are well-recognized characteristics of patients with rheumatic diseases (RMDs). The objective was to describe the mistreatment phenomenon in Mexican patients with RMDs. We additionally report the adaptation and validation of the Geriatric Mistreatment Scale (GMS) in the target population. This cross-sectional study was developed in two phases (June 28, 2023-February 2, 2024), and three convenience samples were used: S-1 (n = 30), S-2 (n = 260), and S-3 (n = 372). Phase 1 consisted of adapting the GMS to RMDs (RMD-MS) (experts' agreement), followed by RMD-MS face validity (pilot testing, S-1), content validity (experts' agreement), concurrent criterion validity (family APGAR score ≤3, S-2), construct validity (exploratory factor analysis and convergent validity, S-2), reliability (internal consistency and temporal stability, S-2) and feasibility (in S-1). Phase 2 consisted of the mistreatment description in S-3. Patients represented typical RMD outpatients with substantial disease duration. There were 187 (50.3%) patients with overall mistreatment, and psychological was the most frequent in 142 (75.9%) patients, followed by neglect mistreatment in 96 (51.3%), sexual in 30 (16%), physical in 23 (12.3%), and economic mistreatment in 20 (10.7%) patients. Patients' perceived mistreatment was related to the underlying RMD in 13.3% of sexual mistreatment and 53.3% of psychological mistreatment. The number of \"I do not want to answer\" responses raised to 21.7%-67.7% for abusers' sex and 40%-72.9% for the abusers' relationship with the participant. The RMD-MS was valid, reliable, and feasible. Half of the Mexican patients with RMDs perceived some mistreatment, most frequently psychological mistreatment, which is also often perceived as related to the underlying RMD.

Glioblastoma (GBM) is the most aggressive primary brain tumor, with a median survival at diagnosis of 16–20 months. Metabolism represents a new attractive therapeutic target; however, due to high intratumoral heterogeneity, the application of metabolic drugs in GBM is challenging. We characterized the basal bioenergetic metabolism and antiproliferative potential of metformin (MF), dichloroacetate (DCA), sodium oxamate (SOD) and diazo-5-oxo-L-norleucine (DON) in three distinct glioma stem cells (GSCs) (GBM18, GBM27, GBM38), as well as U87MG. GBM27, a highly oxidative cell line, was the most resistant to all treatments, except DON. GBM18 and GBM38, Warburg-like GSCs, were sensitive to MF and DCA, respectively. Resistance to DON was not correlated with basal metabolic phenotypes. In combinatory experiments, radiomimetic bleomycin exhibited therapeutically relevant synergistic effects with MF, DCA and DON in GBM27 and DON in all other cell lines. MF and DCA shifted the metabolism of treated cells towards glycolysis or oxidation, respectively. DON consistently decreased total ATP production. Our study highlights the need for a better characterization of GBM from a metabolic perspective. Metabolic therapy should focus on both glycolytic and oxidative subpopulations of GSCs.