Epidemiology and early predictors of Fabry nephropathy: evaluation of long-term outcomes from a national Fabry centre.

Background: Fabry disease is a rare genetic lysosomal storage disorder, whereby the accumulation of sphingolipids consequently leads to kidney structural damage and dysfunction. We explored the epidemiology of chronic kidney disease (CKD) among patients with Fabry disease at a major UK referral centre in Greater Manchester serving over 7 million people, to inform early predictors of kidney disease and possible treatment planning.

Methods: Data were sourced from the electronic records of registered participants from November 2020 to February 2022 of adults diagnosed with Fabry disease, with at least 1 year of follow-up.

A Case of Hyperammonemia Not Attributable to Liver Disease and Treated With IV Ammonia Scavengers.

Hyperammonemia is a serious metabolic condition marked by elevated ammonia levels in the blood, leading to neurological damage and systemic complications if untreated. While often associated with liver dysfunction, inborn metabolic errors such as fatty acid oxidation defects, pyruvate metabolism disorders, urea cycle disorders (UCDs), urea splitting bacterial infections, hemato-oncological disorders, and portosystemic shunts are less commonly recognized but significant causes, particularly outside neonatal populations. These metabolic errors, due to partial enzyme deficiencies, may present later in life with atypical symptoms.

Peripherally mediated opioid combination therapy in mouse and pig.

The concomitant epidemics of chronic pain and opioid misuse in the United States have led to a call for novel analgesics with limited abuse potential. Previously, we have shown that co-delivery of a novel combination targeting both μ- and δ-opioid receptors in the peripheral and central nervous systems can produce synergistic analgesia. Loperamide, a peripherally restricted μ-opioid agonist, and oxymorphindole, a δ-opioid receptor partial agonist, synergize in multiple mouse models of hyperalgesia.

'Hope' is the thing with feathers: Student midwifery outside the system.

Midwifery in Australia, and across other high-income countries with Westernised care arrangements, is reaching crisis point; an overrun, overworked, and underfunded maternity system causing traumatised and disenfranchised midwives to leave the profession in droves. However, there is also an underreported student midwife retention crisis negatively affecting the profession. Student midwives, becoming disempowered and disillusioned after facing the climate of collective trauma within the system, are leaving their studies at unprecedented rates.

Topical gabapentin and its relation to cutaneous innervation in symptomatic lymphocytic primary cicatricial alopecia.

In this pilot study, participants with symptomatic lymphocytic primary cicatricial alopecia applied 6% topical gabapentin solution twice daily to affected areas for 12 weeks. There was a significant reduction in symptoms, but no pronounced effect on nerve fibre density or neuropeptide expression.

Development of opioid analgesic tolerance in rat to extended-release buprenorphine formulated for laboratory subjects.

Buprenorphine in an extended-release formulation intended for use in laboratory subjects is frequently administered to rats to provide extended analgesia without repeated handling. While levels of buprenorphine may persist in serum once extended-release buprenorphine has been introduced, exposure to opioids can cause opioid tolerance or opioid-induced hypersensitivity. This work examined the analgesic duration and efficacy of a single administration of extended-release buprenorphine intended for use in laboratory subjects in models of inflammatory pain and post-operative pain and the development of opioid tolerance in rat.

Adeno-associated virus-mediated gene transfer of arginine decarboxylase to the central nervous system prevents opioid analgesic tolerance.

Agmatine, a decarboxylated form of L-arginine, prevents opioid analgesic tolerance, dependence, and self-administration when given by both central and systemic routes of administration. Endogenous agmatine has been previously detected in the central nervous system. The presence of a biochemical pathway for agmatine synthesis offers the opportunity for site-specific overexpression of the presumptive synthetic enzyme for local therapeutic effects.

Biodistribution of Agmatine to Brain and Spinal Cord after Systemic Delivery.

Agmatine, an endogenous polyamine, has been shown to reduce chronic pain behaviors in animal models and in patients. This reduction is due to inhibition of the GluN2B subunit of the N-methyl-D-aspartate receptor (NMDAR) in the central nervous system (CNS). The mechanism of action requires central activity, but the extent to which agmatine crosses biologic barriers such as the blood-brain barrier (BBB) and intestinal epithelium is incompletely understood.

Clinical, biochemical and molecular analysis in a cohort of individuals with gyrate atrophy.

Background: Gyrate atrophy of the choroid and retina is a rare autosomal recessive metabolic disorder caused by biallelic variants in the OAT gene, encoding the enzyme ornithine δ-aminotransferase. Impaired enzymatic activity leads to systemic hyperornithinaemia, which in turn underlies progressive chorioretinal degeneration. In this study, we describe the clinical and molecular findings in a cohort of individuals with gyrate atrophy.

A Text-Mining Analysis to Examine Dominant Sources of Online Information and Content on Continuous Glucose Monitors.

Purpose: The purpose of this study is to use text-mining methods to examine the dominant sources of online information and content about continuous glucose monitors (CGMs). Because the internet is the most popular source for health information, it is important to understand what is being said about CGMs in online sources of information.

Methods: A text miner, algorithmic-driven statistical program was used to identify the main sources of online information and topics on CGMs.

COVID-19 topics and emotional frames in vaccine hesitation: A social media text and sentiment analysis.

Objective: Addressing gaps in COVID-19 vaccine-hesitancy research, the current study aimed to add depth and nuance to the exploratory research examining vaccine-hesitant groups. Using a larger, but more focused conversation occurring on social media, the results can be used by health communicators to frame emotionally resonant messaging to improve COVID-19 vaccine advocacy while also mitigating negative concerns for vaccine-hesitant individuals.

Methods: Social media mentions were collected using a social media listening software, Brandwatch, to examine topics and sentiments in COVID-19 hesitancy discourse during a period of September 1, 2020, through December 31, 2020.

Clinical Reasoning: A Missing Piece for Improving Evidence-Based Assessment in Psychology.

Clinical reasoning is a foundational component of conducting evidence-based psychological assessments. In spite of its importance, limited attention has been paid to the teaching or measurement of clinical reasoning skills relative to psychological assessment, as well as how clinical reasoning develops or how its efficacy can be measured. Improving clinical reasoning throughout the assessment process, from initial case conceptualization to hypotheses testing, to recommendation writing, has the potential to address commonly noted concerns regarding diagnostic accuracy, as well as the accessibility and utility of psychological reports and recommendations, and will, ultimately, lead to improved outcomes for clients.

Web-Based Conversations Regarding Fathers Before and During the COVID-19 Pandemic: Qualitative Content Analysis.

Background: Studies of new and expecting parents largely focus on the mother, leaving a gap in knowledge about fathers.

Objective: This study aimed to understand web-based conversations regarding new and expecting fathers on social media and to explore whether the COVID-19 pandemic has changed the web-based conversation.

Methods: A social media analysis was conducted.

The Tourette OCD Alberta Network: Development of a Continuing Professional Development Program for Community Based Mental Health Therapists.

The Tourette OCD Alberta Network (TOAN) supports mental health therapists to improve the delivery of care to patients with Tourette syndrome (TS) and OCD in Alberta. We evaluated the professional development needs of health care workers to develop a continuing professional development (CPD) webinar series. Health care workers demonstrated an urgent need to access a CPD program grounded in evidenced based knowledge about TS and OCD.

Long-term reversal of chronic pain behavior in rodents through elevation of spinal agmatine.

Chronic pain remains a significant burden worldwide, and treatments are often limited by safety or efficacy. The decarboxylated form of L-arginine, agmatine, antagonizes N-methyl-d-aspartate receptors, inhibits nitric oxide synthase, and reverses behavioral neuroplasticity. We hypothesized that expressing the proposed synthetic enzyme for agmatine in the sensory pathway could reduce chronic pain without motor deficits.

Modifying quantitative sensory testing to investigate behavioral reactivity in a pediatric global developmental delay sample: Relation to peripheral innervation and chronic pain outcomes.

Early tactile and nociceptive (pain) mechanisms in children with global developmental delay at risk for intellectual and developmental disability are not well understood. Sixteen children with global developmental delay (mean age = 5.1 years, SD = 1.

Neurocognitive outcome and mental health in children with tyrosinemia type 1 and phenylketonuria: A comparison between two genetic disorders affecting the same metabolic pathway.

Tyrosinemia type 1 (TT1) and phenylketonuria (PKU) are both inborn errors of phenylalanine-tyrosine metabolism. Neurocognitive and behavioral outcomes have always featured in PKU research but received less attention in TT1 research. This study aimed to investigate and compare neurocognitive, behavioral, and social outcomes of treated TT1 and PKU patients.

Telehealth adoption during the COVID-19 pandemic: A social media textual and network analysis.

Objective: The telemedicine industry has rapidly grown during the COVID-19 pandemic, and telemedicine has become a common form of care. The present study looks at the online conversation regarding telemedicine at the beginning of the pandemic and one year later. The Technology Acceptance Model is utilized to explain the findings.

Targeted Interventions in Tourette's using Advanced Neuroimaging and Stimulation (TITANS): study protocol for a double-blind, randomised controlled trial of transcranial magnetic stimulation (TMS) to the supplementary motor area in children with Tourette's syndrome.

Introduction: Tourette's syndrome (TS) affects approximately 1% of children. This study will determine the efficacy and safety of paired comprehensive behavioural intervention for tics (CBIT) plus repetitive transcranial magnetic stimulation (rTMS) treatment in children with Tourette's syndrome. We hypothesise that CBIT and active rTMS to the supplementary motor area (SMA) will (1) decrease tic severity, and (2) be associated with changes indicative of enhanced neuroplasticity (eg, changes in in vivo metabolite concentrations and TMS neurophysiology measures).

Mental health diagnoses in adults with phenylketonuria: a retrospective systematic audit in a large UK single centre.

Background: Recently published European Society for Phenylketonuria (ESPKU) guidelines have recommended a lifelong diet with phenylalanine (Phe) control ≤ 600 μmol/L for phenylketonuria (PKU) patients. This study aimed to identify whether PKU adult patients are at a higher risk of mental health diagnoses if their 2-year average Phe level is higher than the ESPKU European guidelines. Published studies identified by a literature review showed that related studies have been published in American and European PKU study populations but not in the United Kingdom (UK) study populations.

A non-interventional observational study to identify and validate clinical outcome assessments for adults with phenylketonuria for use in clinical trials.

Introduction: Current clinical outcome assessments (COAs) are not effectively capturing the complex array of symptoms of adults with phenylketonuria (PKU). This study aimed to identify concepts of interest relevant to adults with PKU. Based on these concepts, COAs for patient-reported outcomes (PROs), observer-reported outcomes (ObsROs), and clinician-reported outcomes (ClinROs) were selected or developed and content validity was assessed.

Central Nervous System Distribution of an Opioid Agonist Combination with Synergistic Activity.

Novel combinations of specific opioid agonists like loperamide and oxymorphindole targeting the - and -opioid receptors, respectively, have shown increased potency with minimized opioid-associated risks. However, whether their interaction is pharmacokinetic or pharmacodynamic in nature has not been determined. This study quantitatively determined whether these drugs have a pharmacokinetic interaction that alters systemic disposition or central nervous system (CNS) distribution.

Expression of and correlational patterns among neuroinflammatory, neuropeptide, and neuroendocrine molecules from cerebrospinal fluid in cerebral palsy.

Background: The underlying pathogenesis of cerebral palsy (CP) remains poorly understood. The possibility of an early inflammatory response after acute insult is of increasing interest. Patterns of inflammatory and related biomarkers are emerging as potential early diagnostic markers for understanding the etiologic diversity of CP.