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Persons with end stage kidney disease (ESKD) on dialysis are at high risk for severe COVID-19 disease. In September 2023, 2023–2024 COVID-19 vaccination was recommended in the United States for all persons aged ≥6 months. Due to possible immune dysfunction, advanced age, and high prevalence of additional underlying conditions, including immunocompromising conditions, among individuals with ESKD, reduced vaccine effectiveness (VE) is a concern. Understanding effectiveness of 2023–2024 COVID-19 vaccine among persons with ESKD can inform COVID-19 vaccine recommendations for this population. A retrospective cohort investigation was conducted among Medicare fee-for-service beneficiaries aged ≥18 years with ESKD receiving dialysis using Medicare enrollment and claims records. Follow-up began on September 17, 2023, and continued until the earliest occurrence of claim for a COVID-19–associated outcome, other censoring event, or end of follow-up. A marginal structural Cox model was used to estimate VE (calculated as [1 – hazard ratio]*100 %), interpreted as the benefit of 2023–2024 COVID-19 vaccination compared with no 2023–2024 vaccine dose. VE was estimated by presence of additional immunocompromising conditions, age group, and time since vaccination. During September 17, 2023 – April 13, 2024, 17,749/112,250 (16 %) Medicare beneficiaries aged ≥18 years with ESKD without additional immunocompromising conditions received a 2023–2024 COVID-19 vaccine dose, with a maximum 209 days of follow-up since vaccination. During the follow-up period 6539 medically attended COVID-19 events, including 3605 COVID-19-associated hospitalizations, 789 COVID-19-associated deaths, and 896 COVID-19-associated thromboembolic events, were recorded. VE against COVID-19-associated hospitalization was 55 % (95 % confidence interval [CI]: 42 % - 65 %) at 7–59 days after vaccination and 47 % (95 % CI: 35 % – 57 %) at ≥60 days after vaccination. VE against COVID-19-associated death was 71 % (95 % CI: 46 % - 84 %) at 7–59 days after vaccination and 51 % (95 % CI: 24 % – 69 %) ≥60 days after vaccination. VE against COVID-19-associated thromboembolic events was 44 % (95 % CI, 24 %, 59 %). The 2023–2024 COVID-19 vaccines provided protection against COVID-19-associated hospitalization, death, and thromboembolic events among adults with ESKD. These data support the recommendation that adults with ESKD receive the updated COVID-19 vaccine. •End stage kidney disease (ESKD) is associated with increased risk of severe COVID-19.•Uptake of 2023–2024 COVID-19 vaccination among adults with ESKD was low.•COVID-19 vaccination was effective against severe COVID-19 among adults with ESKD.•COVD-19 vaccine effectiveness among adults with ESKD waned with more time since vaccination.

Patients with acutely decompensated cirrhosis (AD) may or may not develop acute-on-chronic liver failure (ACLF). ACLF is characterized by high-grade systemic inflammation, organ failures (OF) and high short-term mortality. Although patients with AD cirrhosis exhibit distinct clinical phenotypes at baseline, they have low short-term mortality, unless ACLF develops during follow-up. Because little is known about the association of profile of systemic inflammation with clinical phenotypes of patients with AD cirrhosis, we aimed to investigate a battery of markers of systemic inflammation in these patients. Upon hospital admission baseline plasma levels of 15 markers (cytokines, chemokines, and oxidized albumin) were measured in 40 healthy controls, 39 compensated cirrhosis, 342 AD cirrhosis, and 161 ACLF. According to EASL-CLIF criteria, AD cirrhosis was divided into three distinct clinical phenotypes (AD-1: Creatinine<1.5, no HE, no OF; AD-2: creatinine 1.5-2, and or HE grade I/II, no OF; AD-3: Creatinine<1.5, no HE, non-renal OF). Most markers were slightly abnormal in compensated cirrhosis, but markedly increased in AD. Patients with ACLF exhibited the largest number of abnormal markers, indicating \"full-blown\" systemic inflammation (all markers). AD-patients exhibited distinct systemic inflammation profiles across three different clinical phenotypes. In each phenotype, activation of systemic inflammation was only partial (30% of the markers). Mortality related to each clinical AD-phenotype was significantly lower than mortality associated with ACLF ( < 0.0001 by gray test). Among AD-patients baseline systemic inflammation (especially IL-8, IL-6, IL-1ra, HNA2 independently associated) was more intense in those who had poor 28-day outcomes (ACLF, death) than those who did not experience these outcomes. Although AD-patients exhibit distinct profiles of systemic inflammation depending on their clinical phenotypes, all these patients have only partial activation of systemic inflammation. However, those with the most extended baseline systemic inflammation had the highest the risk of ACLF development and death.

Objective This study aims to investigate the interrelationship of risk factors for suicidal behaviour and their influence on attempt severity in a sample of adolescents who have recently attempted suicide. For it a network analyse was performed. Method Data from a sample of adolescents from 12 to 17 years of age with documented suicide attempts were collected and analysed in the context of a larger study conducted in Spain called SURVIVE. Several factors were examined including age, sex, depression, trauma, impulsivity, and substance abuse. Graph analysis was performed to identify relationships and centrality measures among these factors. Results A total of 267 participants were enrolled: 233 females and 34 males with a mean age of 15.00 years (SD = 1.52). The results indicate that age and sex do not have a notable relationship with attempt severity in adolescents. Emotional and behavioural difficulties, measured by the Strengths and Difficulties Questionnaire (SDQ), have the greatest influence on other variables. Depression and childhood trauma show varying degrees of association with suicidal behaviour, as does motor impulsivity. Substance use does not appear to be strongly related to suicide attempt severity. The number of suicide attempts is strongly correlated with emotional and behavioural difficulties, depression, and childhood trauma. Lethality of suicide attempts and intensity of suicidal ideation do not show significant associations with the other variables. Conclusion This study identifies significant risk factors for adolescent suicide. Emotional and behavioural symptoms, depression, and childhood trauma are strongly linked to suicidal behaviour. However, age, sex, and substance abuse show minimal correlation. Assessing emotional difficulties and depressive symptoms using specific questionnaires could be crucial in evaluating suicidal behaviour in adolescents.

The expression of facial asymmetries has been recurrently related with poverty and/or disadvantaged socioeconomic status. Departing from the developmental instability theory, previous approaches attempted to test the statistical relationship between the stress experienced by individuals grown in poor conditions and an increase in facial and corporal asymmetry. Here we aim to further evaluate such hypothesis on a large sample of admixed Latin Americans individuals by exploring if low socioeconomic status individuals tend to exhibit greater facial fluctuating asymmetry values. To do so, we implement Procrustes analysis of variance and Hierarchical Linear Modelling (HLM) to estimate potential associations between facial fluctuating asymmetry values and socioeconomic status. We report significant relationships between facial fluctuating asymmetry values and age, sex, and genetic ancestry, while socioeconomic status failed to exhibit any strong statistical relationship with facial asymmetry. These results are persistent after the effect of heterozygosity (a proxy for genetic ancestry) is controlled in the model. Our results indicate that, at least on the studied sample, there is no relationship between socioeconomic stress (as intended as low socioeconomic status) and facial asymmetries.

The current genetic makeup of Latin America has been shaped by a history of extensive admixture between Africans, Europeans and Native Americans, a process taking place within the context of extensive geographic and social stratification. We estimated individual ancestry proportions in a sample of 7,342 subjects ascertained in five countries (Brazil, Chile, Colombia, México and Perú). These individuals were also characterized for a range of physical appearance traits and for self-perception of ancestry. The geographic distribution of admixture proportions in this sample reveals extensive population structure, illustrating the continuing impact of demographic history on the genetic diversity of Latin America. Significant ancestry effects were detected for most phenotypes studied. However, ancestry generally explains only a modest proportion of total phenotypic variation. Genetically estimated and self-perceived ancestry correlate significantly, but certain physical attributes have a strong impact on self-perception and bias self-perception of ancestry relative to genetically estimated ancestry.

We report a genome-wide association scan in >6,000 Latin Americans for pigmentation of skin and eyes. We found eighteen signals of association at twelve genomic regions. These include one novel locus for skin pigmentation (in 10q26) and three novel loci for eye pigmentation (in 1q32, 20q13 and 22q12). We demonstrate the presence of multiple independent signals of association in the 11q14 and 15q13 regions (comprising the GRM5/TYR and HERC2/OCA2 genes, respectively) and several epistatic interactions among independently associated alleles. Strongest association with skin pigmentation at 19p13 was observed for an Y182H missense variant (common only in East Asians and Native Americans) in MFSD12 , a gene recently associated with skin pigmentation in Africans. We show that the frequency of the derived allele at Y182H is significantly correlated with lower solar radiation intensity in East Asia and infer that MFSD12 was under selection in East Asians, probably after their split from Europeans. Pigmentation variation in humans is influenced by complex genetic architecture in different populations. Here, the authors perform a genome-wide association analysis involving > 6,000 Latin Americans for pigmentation of skin and eyes, and identify known and novel genetic associations.

There are few published data on long-term treatment with sirolimus in lymphangioleiomyomatosis (LAM). The objective of this study was to describe the long-term effect of sirolimus in a series of LAM patients followed up in a referral centre, focusing on pulmonary function. We retrospectively reviewed a series of 48 patients with LAM diagnosed, followed up and treated with sirolimus in a single centre. Response to sirolimus was evaluated at 1 and 5 years. A negative sirolimus response was defined as an FEV 1 decline greater than − 75 ml/year. A mixed-effects model was used to estimate the longitudinal changes in FEV 1 (average slope), both as absolute (ml/year) and as predicted values (%predicted/year). From a total of 48 patients, 9 patients underwent lung transplantation and 4 died during the study. Mean (95% CI) FEV 1 slope over 5 years was − 0.14 (− 26.13 to 25.85) ml/year in the whole LAM group, 42.55 (14.87 to 70.22) ml/year in the responder group, − 54.00 (− 71.60 to − 36.39) ml/year in the partial responder group and − 84.19 (− 113.5 to − 54.0) ml/year in the non-responder group. After 5 years of sirolimus treatment 59% had a positive response, 30% had a partial response and 11% had a negative response. Our study found that sirolimus treatment had a positive long-term effect on most LAM patients.

We report a genome-wide association scan for facial features in ∼6,000 Latin Americans. We evaluated 14 traits on an ordinal scale and found significant association ( P values<5 × 10 −8 ) at single-nucleotide polymorphisms (SNPs) in four genomic regions for three nose-related traits: columella inclination (4q31), nose bridge breadth (6p21) and nose wing breadth (7p13 and 20p11). In a subsample of ∼3,000 individuals we obtained quantitative traits related to 9 of the ordinal phenotypes and, also, a measure of nasion position. Quantitative analyses confirmed the ordinal-based associations, identified SNPs in 2q12 associated to chin protrusion, and replicated the reported association of nasion position with SNPs in PAX3 . Strongest association in 2q12, 4q31, 6p21 and 7p13 was observed for SNPs in the EDAR , DCHS2 , RUNX2 and GLI3 genes, respectively. Associated SNPs in 20p11 extend to PAX1 . Consistent with the effect of EDAR on chin protrusion, we documented alterations of mandible length in mice with modified Edar funtion. Humans show great diversity in facial appearance and this variation is highly heritable. Here, Andres Ruiz-Linares and colleagues examined facial features in admixed Latin Americans and identify genome-wide associations for 14 facial traits, including four gene loci ( RUNX2 , GLI3 , DCHS2 and PAX1 ) influencing nose morphology.

•A chimeric protein GP64-prM-E-NS1-VSVG was designed and an rBV was produced.•The rBV expresses the E protein in western blot, IFI and virometry studies.•Mice immunized with rBV showed induction of specific immune responses.•Mice immunized with rBV were protected after challenge with YFV. Yellow fever (YF) is a disease caused by the homonymous flavivirus that can be prevented by a vaccine containing attenuated viruses. Since some individuals cannot receive this vaccine, the development of alternatives is desirable. Here, we developed a recombinant baculovirus (rBV) surface display platform utilizing a chimeric E-NS1 protein as a vaccine candidate. A pBacPAK9 vector containing the baculoviral GP64 signal peptide, the YFV prM, E, NS1 and the ectodomain of VSV-G sequences was synthesized. This transfer plasmid and the bAcGOZA bacmid were cotransfected into Sf9 cells, and an rBV-E-NS1 was obtained, which was characterized by PCR, WB, IFI and FACS analysis. Mice immunized with rBV-E-NS1 elicited a specific humoral and cellular immune response and were protected after YFV infection. In summary, we have developed an rBV that expresses YFV major antigen proteins on its surface, which opens new alternatives that can be tested in a mouse model.

We report a genome-wide association scan in over 6,000 Latin Americans for features of scalp hair (shape, colour, greying, balding) and facial hair (beard thickness, monobrow, eyebrow thickness). We found 18 signals of association reaching genome-wide significance ( P values 5 × 10 −8 to 3 × 10 −119 ), including 10 novel associations. These include novel loci for scalp hair shape and balding, and the first reported loci for hair greying, monobrow, eyebrow and beard thickness. A newly identified locus influencing hair shape includes a Q30R substitution in the Protease Serine S1 family member 53 ( PRSS53 ). We demonstrate that this enzyme is highly expressed in the hair follicle, especially the inner root sheath, and that the Q30R substitution affects enzyme processing and secretion. The genome regions associated with hair features are enriched for signals of selection, consistent with proposals regarding the evolution of human hair. By examining Latin American individuals of mixed European, Native American and African ancestry, Adhikari et al . identify novel loci influencing various features of facial and scalp hair. The study also provides experimental evidence that one of the implicated genes (PRSS53) is expressed in the hair follicle and that the top associated variant alters processing of this enzyme.