Elevated levels of total tau (t-tau) are a key biomarker of neurodegeneration, often seen in Alzheimer disease (AD). Identifying individuals at increased risk of AD using minimally invasive biomarkers can enable early intervention. We developed a polygenic risk score (PRS) for plasma t-tau and examined its association with the risk for developing clinical endophenotypes of AD pathology. This longitudinal cohort study used data from the Hellenic Longitudinal Investigation of Aging and Diet (HELIAD) study, involving individuals aged 65 years or older, free of AD, or amnestic mild cognitive impairment (aMCI-an AD prodrome) at baseline. Our primary exposure was PRStau, a PRS based on common genetic variants linked to plasma tau levels. The primary outcome was aMCI or AD incidence. We assessed the association between PRStau levels and aMCI/AD risk using Cox regression models adjusted for age, sex, education, APOE ε4 allele carriership, and population structure. We sought replication in a sample of UK Biobank (UKB) participants aged 60 years or older without prevalent dementia. In the HELIAD sample, among 618 cognitively healthy participants (mean age 73.37 years, 58.4% female), followed for 2.92 ± 0.80 years, 73 developed AD/aMCI. A 1 SD increase in PRStau was linked to a 29% higher AD/aMCI risk (hazard ratio [HR] 1.290, 95% CI 1.006-1.654). Stratified analyses revealed greater effect estimates in women (HR 1.451, 95% CI 1.023-2.058) and younger participants (HR 1.866, 95% CI 1.175-2.962), whereas results in men and older participants did not reach statistical significance. In the UKB sample (n = 142,637, mean age 64.2 years, 52% female), 2,737 participants developed AD over 12.9 ± 2.4 years of follow-up. Higher PRStau was also linked to increased AD risk (HR 1.046, 95% CI 1.007-1.086). These results support the potential utility of PRS for plasma t-tau in predicting AD/aMCI incidence. The relationship between genetic predisposition for elevated plasma t-tau levels and AD pathology might be influenced by sex and age, suggesting that these factors should be considered in AD genetic risk modeling. PRS could serve as an early indicator of genetic propensity for tau pathology, enhancing existing AD diagnostic and risk stratification algorithms.

We present the isolation and structural elucidation of the first (inter-)halogen polysulfates [I3]4[S4O13]2(SO3), [IBr2]2[S4O13], [ICl2][HS2O7] and [ICl2]2[S2O7]. All compounds are accessible by the reaction of I2, Br2 and ICl3 with neat SO3 in sealed glass ampoules. The novel compounds show strong donor-acceptor interactions between the oxoanionic polysulfates and the electrophilic central iodine atom of the cations. The strength of the halogen bond increases with electron withdrawal from the iodine. The electron density donation from the polysulfates into the antibonding σ*-molecular orbitals leads to a significant weakening of the X-I bond. The influence of the HaB on the bonding situation within the anions is analyzed and compared to that of Li2[S4O13], which we synthesized as a reference alkaline metal polysulfate, showing purely electrostatic cation-anion interactions. Density functional theory (DFT) investigations and resulting MEP surface plots and QTAIM and NBO analyses show the physical nature of the HaB and reveal their energetic driving force. These insights extend our view on the influence of non-covalent interactions on anions we usually call 'weakly coordinating'.

In the 1970s and 1980s, Brazil built several large dams in the Amazon rainforest and contracted the National Institute for Research of the Amazon (INPA) to study their environmental impact. The article explores the activities of INPA’s biologists and their role in the changing perception of dam-building. Based on INPA publications and archival material about dam-related conflicts it argues that science had little impact on the discursive paradigm shift from good to bad dams and that ‘hard’ science did not have more epistemic power than local grassroots knowledge produced by the anti-dam movement. The data gathered by the biologists had no practical value and could not prevent environmental damage. When the dictatorship ended in 1985, INPA changed sides and promoted the anti-dam agenda. What finally mattered was the ability to connect science to a political narrative.

Hereditary palmoplantar keratoderma (PPK) involves hyperkeratosis of the palmoplantar skin and belongs to the palmoplantar epidermal differentiation disorders (pEDDs). One causal gene is Desmoglein 1 (DSG1), which encodes a protein crucial for epidermal integrity. Monoallelic DSG1 variants cause mild, non-syndromic PPK, whereas bi-allelic DSG1 variants typically cause syndromic PPK with severe additional clinical features (SAM syndrome). Here, we report the first detection of a homozygous DSG1 variant in mild, non-syndromic PPK. Pakistani siblings presented with striate PPK, characterized by deep palmar creases and plantar fissures only. Exome sequencing revealed the homozygous DSG1 splice-site variant c.685-3T>A with familial cosegregation. In silico analyses indicated a low probability of exon 7 skipping. An exon-trap assay confirmed splicing disruption, although some wild-type (WT) transcripts were also detected. The partial retention of DSG1 WT transcripts may explain the mild phenotype. This finding highlights the phenotypic variability of DSG1-related disorders (DSG1-pEDD), related to residual DSG1 activity.

The impact of body weight disorders on outcomes of patients undergoing cardiac surgery for infective endocarditis (IE) have been poorly studied. Obesity or malnutrition may significantly influence the course and prognosis of endocarditis, driven by distinct comorbidities and microbiological profiles. Hence, we investigated the impact of preoperative body mass index (BMI) on postoperative outcomes in a large multicentric cohort of surgically treated IE patients. Data from the Clinical Multicenter Project for Analysis of Infective Endocarditis in Germany (CAMPAIGN) registry (n = 4917) was used for retrospective analysis. The patients were divided into four groups for comparison according to their BMI: (1) underweight (≤18.5 kg/m2), (2) normal-weight (18.6-24.9 kg/m2), (3) overweight (25.0-29.9 kg/m2), (4) obesity (≥30.0 kg/m2). Patients with incomplete data on body weight or height were excluded (n = 116). The primary outcomes were 30-day and 1-year mortality. The final study cohort comprised 4801 patients, including 133 underweight patients (2.8%), 1884 normal-weight patients (39.2%), 1797 patients with overweight (37.4%), and 987 patients with obesity (20.6%). The mean age in the entire cohort was 65.0 [54.0-73.0] years. Patients with obesity had more comorbidities, including hypertension (63.0%; p < 0.001), diabetes mellitus (45.7%, p < 0.001), coronary artery disease (29.5%; p < 0.001), previous cardiac surgery (32.2%, p < 0.012) and dialysis-dependent chronic kidney disease (11.6%, p < 0.001). Patients with obesity had the highest prevalence of staphylococcal endocarditis (33.4%; p < 0.001), while underweight patients had more streptococcal infection (22.0%; p < 0.001). Patients with obesity had the worst 30-day and 1-year mortality rates after surgery for IE (14.1% and 19.6%, p < 0.001 and p < 0.001 respectively). IE patients with obesity present with comorbidities, higher 30-day mortality and lower 1-year survival rates, possibly linked to more frequent staphylococcal infections and comorbidities. This emphasises the need for early risk stratification, enhanced infection prevention and improved perioperative care in patients with obesity.