Current and Emerging Therapies for Lysosomal Storage Disorders.

Lysosomal storage disorders (LSDs) are rare inherited metabolic disorders characterized by defects in the function of specific enzymes responsible for breaking down substrates within cellular organelles (lysosomes) essential for the processing of macromolecules. Undigested substrate accumulates within lysosomes, leading to cellular dysfunction, tissue damage, and clinical manifestations. Clinical features vary depending on the degree and type of enzyme deficiency, the type and extent of substrate accumulated, and the tissues affected.

Disentangling the neural underpinnings of response inhibition in disruptive behavior and co-occurring ADHD.

While impaired response inhibition has been reported in attention-deficit/hyperactivity disorder (ADHD), findings in disruptive behavior disorders (DBDs) have been inconsistent, probably due to unaccounted effects of co-occurring ADHD in DBD. This study investigated the associations of behavioral and neural correlates of response inhibition with DBD and ADHD symptom severity, covarying for each other in a dimensional approach. Functional magnetic resonance imaging data were available for 35 children and adolescents with DBDs (8-18 years old, 19 males), and 31 age-matched unaffected controls (18 males) while performing a performance-adjusted stop-signal task.

Magnetic Resonance-Guided Focused Ultrasound Thalamotomy in a Prospective Cohort of 52 Patients with Parkinson's Disease: A Possible Critical Role of Age and Lesion Volume for Predicting Tremor Relapse.

Background: Magnetic resonance-guided focused ultrasound (MRgFUS) thalamotomy of ventral intermediate (Vim) nucleus is useful to treat drug-resistant tremor-dominant Parkinson's disease (TdPD), but tremor relapse may occur. Predictors of relapse have been poorly investigated so far.

Objective: The aim of this study is to evaluate the role of clinico-demographic, procedural, and neuroradiological variables in determining clinical response, relapse, and adverse events (AEs) in TdPD after MRgFUS Vim-thalamotomy.

Immunotherapy-Resistant Neuropathic Pain and Fatigue Predict Quality-of-Life in Contactin-Associated Protein-Like 2 Antibody Disease.

The long-term clinical outcomes and associated prognostic factors in contactin-associated protein-like 2 (CASPR2)-antibody diseases are unknown. A total of 75 participants with CASPR2 antibodies were longitudinally assessed for disability, quality-of-life, and chronic pain. Although most symptoms improved within 6 months of treatment, neuropathic pain and fatigue were the most immunotherapy refractory, and persisted for up to 6 years.

Defining and Conceptualizing Technology-Facilitated Abuse ("Tech Abuse"): Findings of a Global Delphi Study.

Technology-facilitated abuse (TFA) describes the misuse or repurposing of digital systems to harass, coerce, or abuse. It is a global problem involving both existing and emerging technologies. Despite significant work across research, policy, and practice to understand the issue, the field operates within linguistic, conceptual, and disciplinary silos, inhibiting collaboration.

New onset refractory status epilepticus: Long-term outcomes beyond seizures.

We propose and prioritize important outcome domains that should be considered for future research investigating long-term outcomes (LTO) after new onset refractory status epilepticus (NORSE). The study was led by the international NORSE Institute LTO Working Group. First, literature describing the LTO of NORSE survivors was identified using a PubMed search and summarized to identify knowledge gaps.

Industry updates from the field of stem cell research and regenerative medicine in December 2024.

Latest developments in the field of stem cell research and regenerative medicine compiled from publicly available information and press releases from non-academic institutions in December 2024.

A contentious intervention to support the medical workforce: a case study of the policy of introducing physician associates in the United Kingdom.

Background: Health systems across Europe are facing a workforce crisis, with some experiencing severe shortages of doctors. In response, many are exploring greater task-sharing, across established professions, such as doctors, nurses, and pharmacists, with patients and carers, and with new occupational groups, in particular ones that can assist doctors and relieve their workload.

Case Presentation: In the early 2000s the United Kingdom created a new occupational role, that of physician assistant.

The association of frailty and bedside body composition tools with total body potassium and body cell mass: a pilot study in adults with cirrhosis.

The accurate assessment of body composition in cirrhosis is challenging as fluid accumulation affects most techniques. The whole-body counter is a state-of-the-art method that measures total body potassium (TBK) unbiased by fluid, from which body cell mass (BCM) is derived. This pilot study in 20 patients with cirrhosis evaluated bedside tools including the liver frailty index (LFI), bioimpedance analysis-based phase angle, calf circumference (CC), and BMI (body mass index)/edema-adjusted CC, and explored their association with TBK and BCM.

Tucatinib and trastuzumab in HER2-mutated metastatic breast cancer: a phase 2 basket trial.

Human epidermal growth factor receptor 2 (HER2, also known as ERBB2) signaling promotes cell growth and differentiation, and is overexpressed in several tumor types, including breast, gastric and colorectal cancer. HER2-targeted therapies have shown clinical activity against these tumor types, resulting in regulatory approvals. However, the efficacy of HER2 therapies in tumors with HER2 mutations has not been widely investigated.

Somatic CAG repeat expansion in blood associates with biomarkers of neurodegeneration in Huntington's disease decades before clinical motor diagnosis.

Huntington's disease (HD) is an autosomal dominant neurodegenerative disease with the age at which characteristic symptoms manifest strongly influenced by inherited HTT CAG length. Somatic CAG expansion occurs throughout life and understanding the impact of somatic expansion on neurodegeneration is key to developing therapeutic targets. In 57 HD gene expanded (HDGE) individuals, ~23 years before their predicted clinical motor diagnosis, no significant decline in clinical, cognitive or neuropsychiatric function was observed over 4.

Examining memory reconsolidation as a mechanism of nitrous oxide's antidepressant action.

There is an ongoing need to identify novel pharmacological agents for the effective treatment of depression. One emerging candidate, which has demonstrated rapid-acting antidepressant effects in treatment-resistant groups, is nitrous oxide (NO)-a gas commonly used for sedation and pain management in clinical settings and with a range of pharmacological effects, including antagonism of NMDA glutamate receptors. A growing body of evidence suggests that subanaesthetic doses of NO (50%) can interfere with the reconsolidation of maladaptive memories in healthy participants and across a range of disorders.

The role of host plants, land cover and bioclimate in predicting the invasiveness of Aromia bungii on a global scale.

Aromia bungii is an invasive Cerambycidae of major concern at the global scale because of the damage caused to Rosaceae. Given the major phytosanitary relevance of A. bungii, predicting its spread in invaded areas and identifying possible new suitable regions worldwide remains a key action to develop appropriate management practices and optimise monitoring and early detection campaigns.

Association between herpes simplex virus infection and Alzheimer's disease biomarkers: analysis within the MAPT trial.

In vitro and animal studies have suggested that inoculation with herpes simplex virus 1 (HSV-1) can lead to amyloid deposits, hyperphosphorylation of tau, and/or neuronal loss. Here, we studied the association between HSV-1 and Alzheimer's disease biomarkers in humans. Our sample included 182 participants at risk of cognitive decline from the Multidomain Alzheimer Preventive Trial who had HSV-1 plasma serology and an amyloid PET scan.

Comprehensive benefits evaluation of low impact development using scenario analysis and fuzzy decision approach.

The comprehensive benefit evaluation of LID based on multi-criteria decision-making methods faces technical issues such as the uncertainties and vagueness in hybrid information sources, which can affect the overall evaluation results and ranking of alternatives. This study introduces a multi-indicator fuzzy comprehensive benefit evaluation approach for the selection of LID measures, aiming to provide a robust and holistic framework for evaluating their benefits at the community level. The proposed methodology integrates quantitative environmental and economic indicators with qualitative social benefit indicators, combining the use of the Storm Water Management Model (SWMM) and ArcGIS for scenario-based analysis, and the use of hesitant fuzzy language sets and Technique for Order of Preference by Similarity to Ideal Solution (TOPSIS) for decision-making.

Soil Nitrogen Supply Exerts Largest Influence on Leaf Nitrogen in Environments with the Greatest Leaf Nitrogen Demand.

Accurately representing the relationships between nitrogen supply and photosynthesis is crucial for reliably predicting carbon-nitrogen cycle coupling in Earth System Models (ESMs). Most ESMs assume positive correlations amongst soil nitrogen supply, leaf nitrogen content, and photosynthetic capacity. However, leaf photosynthetic nitrogen demand may influence the leaf nitrogen response to soil nitrogen supply; thus, responses to nitrogen supply are expected to be the largest in environments where demand is the greatest.

Diabetic foot ulcer in the Western Pacific Region: Current data on ulceration rates and microbial profiles, gaps and charting strategies.

The Western Pacific Region hosts the largest proportion of people with diabetes. Despite being a key diabetes-related complication, diabetic foot ulcer has been neglected in both prevention and treatment efforts. This narrative review highlights available data on the burden (either prevalence or incidence), as well as microbial profiles of diabetic foot ulcers in the Western Pacific Region, identifies data gaps, and discusses strategies to address these gaps.

Sex and Cardiac Operations: Are We Being Fair to Our Female Patients?

Background: Research suggests that although men have a higher cardiovascular disease (CVD) rate, women with CVD are more likely to experience a poorer prognosis, possibly owing to incorrect diagnosis and poorer treatment. A question not yet addressed is whether some of this inequality could be due to sex bias when selecting patients for operation.

Method: The participants were from the Scottish Heart Health Extended Cohort who had been admitted to hospital with a cardiovascular diagnosis over the study period.

Simplified acid extraction and quantification of histones in human tumor cells.

Histones are essential nuclear proteins that package eukaryotic DNA into chromosomes, play a vital role in gene regulation, DNA replication, DNA repair and chromosome condensation. Understanding histone modifications is crucial for grasping biological and disease-related processes. Specific alterations in histone modifications serve as sensitive and selective biomarkers for conditions like cancer, impacting both tumor and immune cells and affecting their interactions.