Outcomes after medical treatment for primary aldosteronism: an international consensus and analysis of treatment response in an international cohort.

Background: Primary aldosteronism can be treated medically but there is no standardised method to evaluate treatment outcomes. We aimed to develop criteria for assessing the outcomes of targeted medical treatment of primary aldosteronism, analyse outcomes across an international cohort, and identify factors associated with a complete treatment response.

Methods: An international panel of 31 primary aldosteronism experts used the Delphi method to reach consensus on the definition of complete, partial, or absent biochemical and clinical outcomes of medical treatment of primary aldosteronism.

Estimating the epidemiological and economic impact of providing nutritional care for tuberculosis-affected households across India: a modelling study.

Background: Approximately 20% of global tuberculosis incidence is attributable to undernutrition, increasing to more than a third in India. Targeting nutritional interventions to tuberculosis-affected households is a policy priority, but understanding of epidemiological and economic impacts is limited. We aimed to estimate the population-level epidemiological and economic effect of such an intervention.

Aspirin after completion of standard adjuvant therapy for colorectal cancer (ASCOLT): an international, multicentre, phase 3, randomised, double-blind, placebo-controlled trial.

Background: Aspirin is a simple, globally available medication that has been shown to reduce the incidence of colorectal cancer. We aimed to evaluate the safety and efficacy of aspirin in the secondary prevention of colorectal cancer.

Methods: This phase 3, randomised, double-blind, placebo-controlled trial was conducted at 66 centres across 11 countries and territories (ten in Asia-Pacific; one in the Middle East).

Bi-allelic KICS2 mutations impair KICSTOR complex-mediated mTORC1 regulation, causing intellectual disability and epilepsy.

Nutrient-dependent mTORC1 regulation upon amino acid deprivation is mediated by the KICSTOR complex, comprising SZT2, KPTN, ITFG2, and KICS2, recruiting GATOR1 to lysosomes. Previously, pathogenic SZT2 and KPTN variants have been associated with autosomal recessive intellectual disability and epileptic encephalopathy. We identified bi-allelic KICS2 variants in eleven affected individuals presenting with intellectual disability and epilepsy.

Discovery of a DNA methylation profile in individuals with Sifrim-Hitz-Weiss syndrome.

Pathogenic heterozygous variants in CHD4 cause Sifrim-Hitz-Weiss syndrome, a neurodevelopmental disorder associated with brain anomalies, heart defects, macrocephaly, hypogonadism, and additional features with variable expressivity. Most individuals have non-recurrent missense variants, complicating variant interpretation. A few were reported with truncating variants, and their role in disease is unclear.

A constitutive interferon-high immunophenotype defines response to immunotherapy in colorectal cancer.

Fewer than 50% of metastatic deficient mismatch repair (dMMR) colorectal cancer (CRC) patients respond to immune checkpoint inhibition (ICI). Identifying and expanding this patient population remains a pressing clinical need. Here, we report that an interferon-high immunophenotype locally enriched in cytotoxic lymphocytes and antigen-presenting macrophages is required for response.

Dynamic histone modification patterns coordinating DNA processes.

Significant effort has been spent attempting to unravel the causal relationship between histone post-translational modifications and fundamental DNA processes, including transcription, replication, and repair. However, less attention has been paid to understanding the reciprocal influence-that is, how DNA processes, in turn, shape the distribution and patterns of histone modifications and how these changes convey information, both temporally and spatially, from one process to another. Here, we review how histone modifications underpin the widespread bidirectional crosstalk between different DNA processes, which allow seemingly distinct phenomena to operate as a unified whole.

Programming of synthetic regulatory DNA for cell-type targeting in humans.

In a recent study in Nature, Gosai et al. introduce a framework to engineer and validate synthetic DNA regulatory elements showing cell-type-specific activity in human cell lines, closing the distance to the machine-driven design of functional regulatory sequences with therapeutic applications in humans.

Dual controls of vapour pressure deficit and soil moisture on photosynthesis in a restored temperate bog.

Despite only covering ~3 % of the land mass, peatlands store more carbon (C) per unit area than any other ecosystem. This is due to the discrepancy between C fixed by the plants (Gross primary productivity (GPP)) and decomposition. However, this C is vulnerable to frequent, severe droughts and changes in the peatland microclimate.

Neighbourhood social cohesion, loneliness and multimorbidity: Evidence from a UK longitudinal panel study.

In the context of population ageing, multimorbidity is an increasingly prevalent public health issue that has a substantial impact on both individuals and healthcare systems. Alongside the literature looking at risk factors at the individual level, there is a growing body of research examining the role of neighbourhoods in the development of multimorbidity. However, most of this work has focused on physical features of place such as air pollution and green space, while social features of place have been largely overlooked.

Towards circular desalination: A new methodology for measuring and assessing resource flows and circular actions.

There is a lack of methodologies that quantitatively measure the intrinsic circularity of desalination systems, particularly focusing on resource flow traceability and circular actions. This study proposes a novel framework for assessing the circular economy performance of desalination systems. By integrating a systemic indicator selection and calculation approach, this methodology enables a comprehensive evaluation of intrinsic circularity in desalination processes.

Protecting monoclonal antibodies via competitive interfacial adsorption of nonionic surfactants.

Hypothesis: Bioengineered monoclonal antibodies (mAbs) have gained significant recognition as medical therapies. However, during processing, storage and use, mAbs are susceptible to interfacial adsorption and desorption, leading to structural deformation and aggregation, and undermining their bioactivity. To suppress antibody surface adsorption, nonionic surfactants are commonly used in formulation.

Antibiotic resistance gene levels within a highly urbanised estuary.

Antibiotic resistant bacteria are increasingly being found in aquatic environments, representing a potential threat to public health. To examine the dynamics and potential sources of antibiotic-resistant genes (ARGs) in urbanised waterways, we performed a six-month temporal study at six locations within the Sydney Harbour estuary. These locations spanned a salinity gradient from seawater at the mouth of the harbour to freshwater at the more urbanised western sites.

Self-directed violence and unclear intent presentation within a major trauma system. A multisite analysis.

Background: Determining trauma as an act of Self-directed violence (SDV) or from high risk or unclear behaviours is challenging for trauma clinicians and may be affected by patient sex and mechanism of injury. The aim of this study was to examine the differences in characteristics and outcomes between those who have intentionally directed violence towards themselves with those of unclear intent, within a regional trauma system.

Methods: Data was collected between January 2018 and December 2021 in patients who had been identified as a result of either self-directed violence (SDV) defined as any intentional act that can cause injury to one's self, including death or participated in high-risk behaviours, where the intent was unclear (UI).

Gamma knife versus linear accelerator thalamotomy for essential tremor and Parkinson's disease: A systematic review and meta-analysis.

Background: Tremor, either in patients with Essential Tremor (ET) or Parkinson's disease (PD), constitutes the most common movement disorder. Stereotactic radiosurgery using Gamma Knife (GK) and linear accelerator (LINAC) systems, is an effective, incisionless treatment modality for ET and PD. Although these technologies have been used clinically since the 1990's, most studies have focused on GK, and efficacy, safety and time to treatment effect (latency) of GK and LINAC have not been compared.

Tumour volume analysis applied to imaging and histological examinations in breast cancer.

Purpose: Response Evaluation Criteria in Solid Tumours (RECIST) determines partial response (PR) and progressive disease (PD) as a 30 % reduction and 20 % increase in the longest diameter (LD), respectively. Tumour volume analysis (TVA) utilises three diameters to calculate response parameters.

Patients And Methods: We conducted a pilot investigation of patients who underwent neoadjuvant breast cancer treatment and evaluation using RECIST with LD measurements and TVA with three diametric measurements, using the parameters PR (>30 % tumour regression), PD (>20 % tumour growth), and intermediate stable disease (SD).

Concurrent validity of skin-based motion capture systems in measuring dynamic lumbar intervertebral angles.

Spine kinematics are commonly measured by external sensors such as motion capture and accelerometers. However, these skin-based measures cannot directly capture intervertebral motion of the lumbar spine. To date, research in this area has focused on the estimation of intervertebral kinematics using static trials but no study has analyzed agreement throughout the dynamic range of motion.

Association between age at loss of ambulation and cardiac function in adults with Duchenne muscular dystrophy.

Cardiomyopathy is a common co-morbidity in individuals with Duchenne muscular dystrophy (DMD). This retrospective single centre study investigated the relationship between age at loss of ambulation (LOA) and late stage left ventricular ejection fraction (LVEF) in 84 individuals (> 16 years old) with DMD taking glucocorticoid and ACE inhibitors treatment. Regression analyses showed a positive correlation between later age at LOA and higher LVEF in adulthood (linear regression estimate 1.

Social norms relating to gender and dating and relationship violence in English secondary schools: Exploring student, staff and parent/carer accounts.

Dating and relationship violence (DRV) among young people is widespread. DRV is associated with subsequent mental ill health, substance use and sexual risk among girls and boys and is a leading cause of morbidity and mortality among girls globally. Harmful social norms are widely recognised for their role in sustaining DRV, and interventions often seek to change these.

Molecular basis of conjugation-mediated DNA transfer by gram-negative bacteria.

Bacterial conjugation is the unidirectional transfer of DNA (often plasmids, but also other mobile genetic elements, or even entire genomes), from a donor cell to a recipient cell. In Gram-negative bacteria, it requires the formation of three complexes in the donor cell: i-a large, double-membrane-embedded transport machinery called the Type IV Secretion System (T4SS), ii-a long extracellular tube, the conjugative pilus, and iii-a DNA-processing machinery termed the relaxosome. While knowledge has expanded regarding molecular events in the donor cell, very little is known about the machinery involved in DNA transfer into the recipient cell.

Diagnostic features of functional/ dissociative seizures in the first presentation of transient loss of consciousness.

Objectives: Previous studies have identified features in patient's history and seizure descriptions supporting a clinical diagnosis of functional / dissociative seizures (FDS). However, most studies involved patients with chronic seizure disorders. This study explores the value of reported features for a clinical diagnosis of FDS in an adult population with a first presentation of transient loss of consciousness (TLoC).

The management of people with epilepsy in a city wide care home service, the impact of a GP with Special Interest in epilepsy, and Enhanced Health in Care Homes Framework.

Background: The incidence of epilepsy increases with age, especially in people diagnosed with dementia. Seizures in an elderly population are likely to have a focal onset, for which sodium channel blockers are the drug of choice. This study reviews the clinical needs and care of people with epilepsy (PWE) in a city wide care home service and assessing the impact of a GP with Special Interest in epilepsy (GPwSIe).