Pharmacological Treatment Research Articles

Reframing pain: the power of individual and societal factors to enhance pain treatment.

The effectiveness of analgesics can be increased if synergistic behavioural, psychological, and pharmacological interventions are provided within a supportive environment.

Evaluating the Potential of Green Light Exposure on Nociception-A Mini Review.

The capacity of animals to react to unpleasant stimuli that might endanger their integrity is known as nociception. Pharmacological treatments do not show satisfactory results in response to nociception. In the recent era, light therapy emerged as a potential non-pharmacological approach for treating various diseases, including seasonal affective disorders, migraine, pain, and others. Evaluating the potential of green light exposure on nociception involves studying its effects on different types of pain and pain-related conditions and determining the optimal exposure methods. This review provides the beneficial effects of green light on the reduction in the frequency of pain. The green light exposure on nociception changes the activity of pain-related genes and proteins in cells. This review could provide insights into the underlying mechanisms by which green light modulates pain. Overall, evaluating the potential of green light exposure on nociception requires a multidisciplinary approach and should consider the safety, efficacy, optimal dose, and duration of green light exposure and the type of pain. However, few studies have been reported so far; therefore, light therapy for treating migraines require more studies on animal models to provide precise results of light effects on nociception.

Presymptomatic Testing for Huntington's Disease in Mexico: 28 Years of Experience

IntroductionHuntington's disease (HD) is a genetic neurodegenerative disorder with dominant inheritance. Our center in Mexico City has offered presymptomatic testing (PT) since 1995. ObjectiveTo describe the main clinical and demographic characteristics of at-risk HD individuals who applied to the PT program, the reasons for seeking it, and the molecular results. MethodsA cross-sectional study was conducted with sociodemographic and clinical data of all PT applicants from 1995–2023. Reasons for seeking PT were assessed using a modified questionnaire. In addition, anxiety, and depressive symptoms before and after PT were evaluated with Beck's instruments; cognitive impairment (CI) was assessed with the Mini-Mental State Examination (MMSE) and molecular results. Results214 people applied for PT (2.1% of the at-risk population identified in our center); 63% were women (mean age of 37.11 years). 204 (95.3%) were accepted and 190 received results. 70% indicated that the main reason for applying for PT was to inform their offspring about the risk of inheriting HD. Significant differences were observed in the reasons for seeking PT by age group. Although some subjects received treatment, Beck's instrument scores did not indicate special attention or pharmacological treatment. The MMSE showed probable CI in 20 subjects. Of those who received results, 37% were carriers of a full penetrance allele. ConclusionOur center has the only formal PT program for HD in Mexico. The reasons for seeking PT are varied and age-related. Although PT is offered to all subjects at risk for HD, uptake remains low.

Pharmacological Interventions for Asymptomatic Carotid Stenosis

Pharmacological Interventions for Asymptomatic Carotid Stenosis

Acupuncture for the Treatment of Diabetes Related Distal Sensory Neuropathy: A Review of Study Designs and Quality of Randomized Controlled Trials

Diabetes affects nearly every organ system in the body, including the peripheral nervous system, and leads to the development of distal sensory peripheral neuropathy (DSP) in roughly 50% of patients. Between 30% to 50% of patients with DSP experience pain and impaired quality of life. Dissatisfaction with currently available pharmacological treatments for neuropathic pain is common, primarily due to limited effectiveness and potential for adverse side effects. Acupuncture, a non-pharmacologic intervention, is often used in the management of chronic pain and is widely available and acceptable to many patients. In this narrative review, we describe clinical research related to acupuncture and diabetes related DSP management including meta-analyses, systematic reviews, and randomized controlled clinical trials (RCTs). Data from the few clinical trials available support the use of acupuncture to reduce neuropathic pain including DSP pain; however, available studies suffer from methodological weaknesses including inadequate blinding, sample size justification, lack of well-designed controls, and gaps in reporting. These limitations highlight a critical gap and an unmet need for more rigorous and robust clinical research requiring the use of Standards for Reporting Clinical Trials of Acupuncture (STRICTA) guidelines as a design, implementation, and reporting template.

Efficacy of antioxidants in the management of psoriasis: A case control study

Introduction: Psoriasis is a chronic, immune-mediated inflammatory dermatosis. The pathophysiology of the disease is still incompletely elucidated and multiple factors are said to be involved in its initiation and perpetuation, e.g., stressors, genetic factors, environmental factors. In the last decade, a new theory is trying to explain the pathophysiology of this disease by looking at the role played by oxidative stress and chronic inflammation in the initiation of keratinocyte proliferation and differentiation. Keeping in consideration the increased oxidative stress in the patients of psoriasis, the anti-oxidant drugs can form an important part of the therapeutic ladder of psoriasis. Materials and Methods: The aim of this study was to measure the possible role of oxidative stress in psoriasis patient by measuring SOD level and comparing it with normal individuals and administer antioxidants supplements to the patients group to see the efficacy. It was a Case- Control study (1st part) and Clinical Trial without control group (2nd part). The study was carried out in Psoriasis awareness Club from June 2023 to December 2023. Purposive sampling done who fulfill the inclusion & exclusion criteria. 23 patients with psoriasis and 23 age and sex matched control subjects were recruited for this study. Clinical severity of the disease was determined by PASI score. All patients and control subjects were examined for plasma SOD level. 23 psoriatic patients were given antioxidant therapy in the form of once daily tablet for 30 days. PASI score, DLQI and SOD (Superoxide dismutase) level were measured before therapy (day 0) and after therapy (day 30) in patients group. Statistical analysis and Results: Data were expressed as mean ± standard deviation (SD) for quantitative variables and numbers. For comparison of two means (t test) and (ANOVA "F") test were used for several means. Chi-square (χ2 ) or fisher exact test were used when appropriate, (P<0.05) was considered statistically significant. The mean age of the patients and control subjects were 37.64 (±5.89) and 33.6 (11.02) years, respectively. The mean duration of the disease was 12.43 (±8) years. No significant difference was observed between SOD level of psoriatic patients & controls. No significant correlations of SOD level with severity of psoriasis and duration of disease were found. We observed no statistically significant difference in PASI and DLQI scores before and after antioxidant therapy but there was significant increase in the level of SOD after treatment. Conclusion: It is indisputable that antioxidant supplementation can reduce the overall morbidity, enhance the prognosis of psoriasis. Notably, in most cases, antioxidants alone are not able to induce significant clinical changes in the aspect and/or course of the disease, except perhaps in mild forms. They must be used in conjunction with standard pharmacological treatments to achieve measurable results.

Exploring the kynurenine pathway in mild traumatic brain injury: A longitudinal study.

A potential source of novel biomarkers for mTBI is the kynurenine pathway (KP), a metabolic pathway of tryptophan (Trp), that is up-regulated by neuroinflammation and stress. Considering that metabolites of the KP (kynurenines) are implicated in various neuropsychiatric diseases, exploration of this pathway could potentially bridge the gap between physiological and psychological factors in the recovery process after mTBI. This study, therefore, set out to characterize the KP after mTBI and to examine associations with long-term outcome. Patients were prospectively recruited at the emergency department (ED), and blood samples were obtained in the acute phase (<24 h; N = 256) and at 1-month follow-up (N = 146). A comparison group of healthy controls (HC; N = 32) was studied at both timepoints. Trp, kynurenines, and interleukin (IL)-6 and IL-10 were quantified in plasma. Clinical outcome was measured at six months post-injury. Trp, xanthurenic acid (XA), and picolinic acid (PA) were significantly reduced in patients with mTBI relative to HC, corrected for age and sex. For Trp (d = -0.57 vs. d = -0.29) and XA (d = -0.98 vs. d = -0.32), larger effects sizes were observed during the acute phase compared to one-month follow-up, while for PA (d = -0.49 vs. d = -0.52) effect sizes remained consistent. Findings for other kynurenines (e.g., kynurenine, kynurenic acid, and quinolinic acid) were non-significant after correction for multiple testing. Within the mTBI group, lower acute Trp levels were significantly related to incomplete functional recovery and higher depression scores at 6 months post-injury. No significant relationships were found for Trp, XA, and PA with IL-6 or IL-10 concentrations. In conclusion, our findings indicate that perturbations of the plasma KP in the hyperacute phase of mTBI and 1 month later are limited to the precursor Trp, and glutamate system modulating kynurenines XA and PA. Correlations between acute reductions of Trp and unfavorable outcomes may suggest a potential substrate for pharmacological intervention.

How to improve ChatGPT performance for nephrologists: a technique guide.

The integration of ChatGPT into nephrology presents opportunities for enhanced decision-making and patient care. However, refining its performance to meet the specific needs of nephrologists remains a challenge. This guide offers a strategic roadmap for advancing ChatGPT's effectiveness in nephrological applications. Utilizing the advanced capabilities of GPT-4, we customized user profiles to optimize the model's response quality for nephrological inquiries. We assessed the efficacy of chain-of-thought prompting versus standard prompting in delineating the diagnostic pathway for nephrogenic diabetes insipidus-associated hypernatremia and polyuria. Additionally, we explored the influence of integrating retrieval-augmented generation on the model's proficiency in detailing pharmacological interventions to decelerate the progression from chronic kidney disease (CKD) G3 to end-stage kidney disease (ESKD), comparing it to responses without retrieval-augmented generation. In contrast to the standard prompting, the chain-of-thought method offers a step-by-step diagnostic process that mirrors the intricate thought processes needed for diagnosing nephrogenic diabetes insipidus-related hypernatremia and polyuria. This begins with an initial assessment, notably including a water deprivation test. After evaluating the outcomes of this test, the approach continues by identifying potential causes. Furthermore, if a patient's history suggests lithium usage, the chain-of-thought model adjusts by proposing a more customized course of action. In response to "List medication treatment to help slow progression of CKD G3 to ESKD?", GPT-4 only provides a general summary of medication options. Nevertheless, a specialized GPT-4 model equipped with a retrieval-augmented generation system delivers more precise responses, including renin-angiotensin system inhibitors, sodium-glucose cotransporter-2 inhibitors, and mineralocorticoid receptor antagonists. This aligns well with the 2024 KDIGO guidelines. GPT-4, when integrated with chain-of-thought prompting and retrieval-augmented generation techniques, demonstrates enhanced performance in the nephrology domain. This guide underscores the transformative potential of chain-of-thought and retrieval-augmented generation techniques in optimizing ChatGPT for nephrology, and highlights the ongoing need for innovative, tailored AI solutions in specialized medical fields.

Early pharmacological interventions for prevention of post-traumatic stress disorder (PTSD) in individuals experiencing acute traumatic stress symptoms.

Acute traumatic stress symptoms may develop in people who have been exposed to a traumatic event. Although they are usually self-limiting in time, some people develop post-traumatic stress disorder (PTSD), a severe and debilitating condition. Pharmacological interventions have been proposed for acute symptoms to act as an indicated prevention measure for PTSD development. As many individuals will spontaneously remit, these interventions should balance efficacy and tolerability. To assess the efficacy and acceptability of early pharmacological interventions for prevention of PTSD in adults experiencing acute traumatic stress symptoms. We searched the Cochrane Common Mental Disorders Controlled Trial Register (CCMDCTR), CENTRAL, MEDLINE, Embase and two other databases. We checked the reference lists of all included studies and relevant systematic reviews. The search was last updated on 23 January 2023. We included randomised controlled trials on adults exposed to any kind of traumatic event and presenting acute traumatic stress symptoms, without restriction on their severity. We considered comparisons of any medication with placebo, or with another medication. We excluded trials that investigated medications as an augmentation to psychotherapy. We used standard Cochrane methodological procedures. Using a random-effects model, we analysed dichotomous data as risk ratios (RR) and calculated the number needed to treat for an additional beneficial/harmful outcome (NNTB/NNTH). We analysed continuous data as mean differences (MD) or standardised mean differences (SMD). Our primary outcomes were PTSD severity and dropouts due to adverse events. Secondary outcomes included PTSD rate, functional disability and quality of life. We included eight studies that considered four interventions (escitalopram, hydrocortisone, intranasal oxytocin, temazepam) and involved a total of 779 participants. The largest trial contributed 353 participants and the next largest, 120 and 118 participants respectively. The trials enrolled participants admitted to trauma centres or emergency departments. The risk of bias in the included studies was generally low except for attrition rate, which we rated as high-risk. We could meta-analyse data for two comparisons: escitalopram versus placebo (but limited to secondary outcomes) and hydrocortisone versus placebo. One study compared escitalopram to placebo at our primary time point of three months after the traumatic event. There was inconclusive evidence of any difference in terms of PTSD severity (mean difference (MD) on the Clinician-Administered PTSD Scale (CAPS, score range 0 to 136) -11.35, 95% confidence interval (CI) -24.56 to 1.86; 1 study, 23 participants; very low-certainty evidence), dropouts due to adverse events (no participant left the study early due to adverse events; 1 study, 31 participants; very low-certainty evidence) and PTSD rates (RR 0.59, 95% CI 0.03 to 13.08; NNTB 37, 95% CI NNTB 15 to NNTH 1; 1 study, 23 participants; very low-certainty evidence). The study did not assess functional disability or quality of life. Three studies compared hydrocortisone to placebo at our primary time point of three months after the traumatic event. We found inconclusive evidence on whether hydrocortisone was more effective in reducing the severity of PTSD symptoms compared to placebo (MD on CAPS -7.53, 95% CI -25.20 to 10.13; I2 = 85%; 3 studies, 136 participants; very low-certainty evidence) and whether it reduced the risk of developing PTSD (RR 0.47, 95% CI 0.09 to 2.38; NNTB 14, 95% CI NNTB 8 to NNTH 5; I2 = 36%; 3 studies, 136 participants; very low-certainty evidence). Evidence on the risk of dropping out due to adverse events is inconclusive (RR 3.19, 95% CI 0.13 to 75.43; 2 studies, 182 participants; low-certainty evidence) and it is unclear whether hydrocortisone might improve quality of life (MD on the SF-36 (score range 0 to 136, higher is better) 19.70, 95% CI -1.10 to 40.50; 1 study, 43 participants; very low-certainty evidence). No study assessed functional disability. This review provides uncertain evidence regarding the use of escitalopram, hydrocortisone, intranasal oxytocin and temazepam for people with acute stress symptoms. It is therefore unclear whether these pharmacological interventions exert a positive or negative effect in this population. It is important to note that acute traumatic stress symptoms are often limited in time, and that the lack of data prevents the careful assessment of expected benefits against side effects that is therefore required. To yield stronger conclusions regarding both positive and negative outcomes, larger sample sizes are required. A common operational framework of criteria for inclusion and baseline assessment might help in better understanding who, if anyone, benefits from an intervention. As symptom severity alone does not provide the full picture of the impact of exposure to trauma, assessment of quality of life and functional impairment would provide a more comprehensive picture of the effects of the interventions. The assessment and reporting of side effects may facilitate a more comprehensive understanding of tolerability.

CSF amino acid profiles in ICV-streptozotocin-induced sporadic Alzheimer's disease in male Wistar rat: a metabolomics and systems biology perspective.

Alzheimer's disease (AD) is an increasingly important public health concern due to the increasing proportion of older individuals within the general population. The impairment of processes responsible for adequate brain energy supply primarily determines the early features of the aging process. Restricting brain energy supply results in brain hypometabolism prior to clinical symptoms and is anatomically and functionally associated with cognitive impairment. The present study investigated changes in metabolic profiles induced by intracerebroventricular-streptozotocin (ICV-STZ) in an AD-like animal model. To this end, male Wistar rats received a single injection of STZ (3 mg·kg-1) by ICV (2.5 μL into each ventricle for 5 min on each side). In the second week after receiving ICV-STZ, rats were tested for cognitive performance using the Morris Water Maze test and subsequently prepared for positron emission tomography (PET) to confirm AD-like symptoms. Tandem Mass Spectrometry (MS/MS) analysis was used to detect amino acid changes in cerebrospinal fluid (CFS) samples. Our metabolomics study revealed a reduction in the concentrations of various amino acids (alanine, arginine, aspartic acid, glutamic acid, glycine, isoleucine, methionine, phenylalanine, proline, serine, threonine, tryptophane, tyrosine, and valine) in CSF of ICV-STZ-treated animals as compared to controls rats. The results of the current study indicate amino acid levels could potentially be considered targets of nutritional and/or pharmacological interventions to interfere with AD progression.

Will Tirzepatide become a game-changer in the pharmacological treatment of obesity? - literature review

Introduction and objective: Obesity has become an important public health issue in Poland. Furthermore, it is one of the most common preventable causes of diseases and mortality. Pharmacological methods of treating obesity have been developing significantly in recent years.Tirzepatide is a new dual incretin receptor agonist that activates both GIP (glucose-dependent insulinotropic polypeptide) and GLP-1 (glucagon-like peptide-1) receptors. The aim of this review is to assess the effectiveness of this medication in reducing body weight. Current state of knowledge: According to data from the Central Statistical Office (GUS) in Poland, 65% of men and 49% of women are struggling with the issue of excessive body weight [1]. Obesity in Polish society is steadily increasing in every age group. However, it affects most significantly children aged 7-13 years and adolescents. In 2022, the novel dual GLP and GIP-1 agonist has been registered for the treatment of type 2 diabetes which is not satisfactorily controlled. It can be also used together with diet and physical activity in patients diagnosed with obesity (BMI of 30 kg/m2 or more) or who are overweight (BMI 27-30 kg/m2) and have weight-related health problems such as hypertension, metabolic syndrome, dislipidaemia and diabetes mellitus [2]. Summary: The increasing prevalence of obesity leads to a dynamic search for the most effective pharmacological methods of treating obesity. The combined activation of GLP-1 and GIP receptors by Tirzepatide has been shown to have additional benefits beyond satisfying glucose control. The biological mechanism of action of this medication additionally causes decreased food intake, slowed gastric emptying and enhanced insulin secretion, all of which can contribute to weight reduction.

Liver Fibrosis Amelioration by Macrophage-Biomimetic Polydopamine Nanoparticles via Synergistically Alleviating Inflammation and Scavenging ROS.

The progression of liver fibrosis is determined by the interaction of damaged hepatocytes, active hepatic stellate cells, and macrophages, contributing to the development of oxidative stress and inflammatory environments within the liver. Unfortunately, the current pharmacological treatment for liver fibrosis is limited by its inability to regulate inflammation and oxidative stress concurrently. In this study, we developed a cell membrane biomaterial for the treatment of liver fibrosis, which we designated as PM. PM is a biomimetic nanomaterial constructed by encapsulating polydopamine (PDA) with a macrophage membrane (MM). It is hypothesized that PM nanoparticles (NPs) can successfully target the site of inflammation, simultaneously inhibit inflammation, and scavenge reactive oxygen species (ROS). In vitro experiments demonstrated that PM NPs exhibited strong antioxidant properties and the ability to neutralize pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β). Moreover, the capacity of PM NPs to safeguard cells from oxidative stress and their anti-inflammatory efficacy in an inflammatory model were validated in subsequent cellular experiments. Additionally, PM NPs exhibited a high biocompatibility. In a mouse model of hepatic fibrosis, PM NPs were observed to aggregate efficiently in the fibrotic liver, displaying excellent antioxidant and anti-inflammatory properties. Notably, PM NPs exhibited superior targeting, anti-inflammatory, and ROS scavenging abilities in inflamed tissues compared to MM, PDA, or erythrocyte membrane-encapsulated PDA. Under the synergistic effect of anti-inflammation and antioxidant, PM NPs produced significant therapeutic effects on liver fibrosis in mice. In conclusion, the synergistic alleviation of inflammation and ROS scavenging by this specially designed nanomaterial, PM NPs, provides valuable insights for the treatment of liver fibrosis and other inflammatory- or oxidative stress-related diseases.

The Effects of a Nonpharmacological Intervention Practice for Older Adults with Mild Cognitive Impairment and Their Family Caregivers in China

ABSTRACT Mild cognitive impairment (MCI) marks a critical phase in the progression to dementia. In our study, social workers utilized the Multicomponent Nonpharmacological Intervention Approach (MCNIA) to aid MCI participants (N = 52) and their caregivers, dividing into intervention and control groups. The intervention group underwent an additional regimen of non-pharmacological therapies besides pharmacological treatment. Our findings highlighted that: 1) MCNIA significantly enhanced cognitive and daily living abilities in the intervention group; 2) Caregivers experienced reduced burdens and improved social support; 3) Correlation analyses involving biomarkers indicated that MCNIA was particularly effective in alleviating depression in those with slightly more severe cognitive impairment.

Pharmacotherapy for alcohol use disorder among adults with medical disorders in Sweden

BackgroundAlcohol-attributable medical disorders are prevalent among individuals with alcohol use disorder (AUD). However, there is a lack of research on prescriptions of pharmacological treatment for AUD in those with comorbid conditions. This study aims to investigate the utilization of pharmacological treatment (acamprosate, disulfiram and naltrexone) in specialist care among patients with AUD and comorbid medical diagnoses.MethodsThis was a descriptive register-based Swedish national cohort study including 132,728 adults diagnosed with AUD (N = 270,933) between 2007 and 2015. The exposure was alcohol-attributable categories of comorbid medical diagnoses. Odds ratios (OR) were calculated using mixed-effect logistic regression analyses for any filled prescription of acamprosate, disulfiram or oral naltrexone within 12 months post AUD diagnosis.ResultsIndividuals with comorbid alcohol-attributable medical diagnoses had lower odds of filling prescriptions for any type of AUD pharmacotherapy compared to those without such comorbidities. Cardiovascular (OR = 0.41 [95% CI: 0.39–0.43]), neurological (OR = 0.52 [95% CI: 0.48–0.56]) and gastrointestinal (OR = 0.57 [95% CI: 0.54–0.60]) diseases were associated with the lowest rates of prescription receipt. The presence of diagnoses which are contraindications to AUD pharmacotherapy did not fully explain the low prescription rate.ConclusionThere is a substantial underutilization of AUD pharmacotherapy in patients with AUD and comorbid medical disorders in specialist care. Increasing the provision of pharmacotherapy to this group of patients is essential and may prevent morbidity and mortality. There is a need to further understand barriers to medical treatment both from the patient and prescriber perspective.

Everolimus alleviates CD4+ T cell inflammation by regulating autophagy and cellular redox homeostasis.

Aging is associated with the onset and progression of multiple diseases, which limit health span. Chronic low-grade inflammation in the absence of overt infection is considered the simmering source that triggers age-associated diseases. Failure of many cellular processes during aging is mechanistically linked to inflammation; however, the overall decline in the cellular homeostasis mechanism of autophagy has emerged as one of the top and significant inducers of inflammation during aging, frequently known as inflammaging. Thus, physiological or pharmacological interventions aimed at improving autophagy are considered geroprotective. Rapamycin analogs (rapalogs) are known for their ability to inhibit mTOR and thus regulate autophagy. This study assessed the efficacy of everolimus, a rapalog, in regulating inflammatory cytokine production in T cells from older adults. CD4+ T cells from older adults were treated with a physiological dose of everolimus (0.01µM), and indices of autophagy and inflammation were assessed to gain a mechanistic understanding of the effect of everolimus on inflammation. Everolimus (Ever) upregulated autophagy and broadly alleviated inflammatory cytokines produced by multiple T cell subsets. Everolimus's ability to alleviate the cytokines produced by Th17 subsets of T cells, such as IL-17A and IL-17F, was dependent on autophagy and antioxidant signaling pathways. Repurposing the antineoplastic drug everolimus for curbing inflammaging is promising, given the drug's ability to restore multiple cellular homeostasis mechanisms.

Pharmacologic and Nutritional Interventions for Early Alzheimer's Disease: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials.

Early intervention is essential for meaningful disease modification in Alzheimer's disease (AD). We aimed to determine the efficacy and safety of pharmacologic and nutritional interventions for early AD. PubMed, Embase, the Cochrane Library, and ClinicalTrials.gov were searched from database inception until 1 September 2023. We included randomized controlled trials that evaluated the efficacy of interventions in early AD. Only interventions that demonstrated efficacy compared to placebo were included in the network meta-analysis (NMA). Then we performed frequentist fixed-effects NMA to rank the interventions. GRADE criteria were used to evaluate the level of evidence. Fifty-eight trials including a total of 33,864 participants and 48 interventions were eligible for inclusion. Among the 48 interventions analyzed, only 6 (12.5%) treatments- ranging from low to high certainty- showed significant improvement in cognitive decline compared to placebo. High certainty evidence indicated that donanemab (standardized mean difference [SMD] -0.239, 95% confidence interval [CI] -0.343 to -0.134) and lecanemab (SMD -0.194, 95% CI -0.279 to -0.108) moderately slowed the clinical progression in patients with amyloid pathology. Additionally, methylphenidate, donepezil, LipiDiDiet, and aducanumab with low certainty showed significant improvement in cognitive decline compared to placebo. However, there was no significant difference in serious adverse events as reported between the six interventions and placebo. Only 12.5% of interventions studied demonstrated efficacy in reducing cognitive impairment in early AD. Donanemab and lecanemab have the potential to moderately slow the clinical progression in patients with amyloid pathology. Further evidence is required for early intervention in AD.

O15 Transcriptomic profiling reveals regulators of dermal fibroblast state switching

Abstract Introduction and aims Fibroblasts, the major cell population in connective tissue, are the guardians of the extracellular matrix homeostasis. In adult tissue they exist in a quiescent state that can persist for years, but upon tissue injury, they become rapidly activated and re-enter the cell cycle, followed by deposition and reorganization of the dermal matrix. The fundamental mechanism by which fibroblasts can maintain quiescence and be primed for prompt activation is currently unknown. Deregulations of this process in the skin and other organs is associated with several pathologies including fibrosis or chronic wounds. Notably, rapid fibroblast state switching is also observed during skin development, where a tightly controlled change from a highly proliferative state to a quiescent state promotes extracellular matrix deposition and maturation of the dermal architecture. Understanding the shared mechanisms and differences between development and wound healing will help in the development of tissue regenerative therapies. Methods Using dermal development as a model for fibroblast state switching, we integrated several single-cell RNA-Seq and assay for transposase-accessible chromatin-Seq datasets of whole skin during embryonic and postnatal growth. Our novel integrated multiomics single-cell dataset can recapitulate skin developmental changes observed in vivo and reveal the major regulatory networks. Results We identified the activating protein (AP)-1 member cJun as the key regulator of fibroblast state switching in skin development and wound repair. Mechanistically, in quiescent adult fibroblasts cJun is highly transcribed, but the protein is constantly ubiquitinated and degraded, priming fibroblasts for rapid activation when needed. Upon injury cJun ubiquitination is reduced, allowing an accumulation of cJun leading to a change in AP-1 dimer composition at the chromatin level, inhibiting fibroblast quiescence and promoting proliferation and activation. Conclusions In normal wounds cJun accumulation is inhibited during the advanced (remodelling) wounding phase; however, chronic wounds and fibrotic disease conditions show a continuous and pathological cJun stabilization, which can be targeted through pharmacological intervention.

Exploring Shared Delusions among Three Sisters in Folie à Trois: A Case Report

In this case report we present the case of three sisters experiencing shared psychotic disorder (SPD), or folie à trois, characterized by the transmission of delusional beliefs within close familial relationships. The primary patient presented aggressive behaviors and paranoid delusions, leading to hospitalization, while the other two siblings displayed similar beliefs but with less severe symptoms. Treatment involved physical separation and pharmacological intervention, resulting in significant improvement, particularly in the induced siblings. The case underscores the importance of a comprehensive approach to managing SPD, combining pharmacotherapy and psychosocial interventions. Further research is needed to improve understanding and optimize treatment strategies for shared delusions. Documenting and sharing such cases can contribute to improved outcomes for patients and their families.

Osteoporosis management in adults with schizophrenia following index hip fracture event: a 10-year population-based retrospective cohort study, Ontario, Canada.

Evidence suggests that individuals with schizophrenia may be more likely to experience hip fractures than the general population; however, little is known about osteoporosis management in this disadvantaged subpopulation. Our study objective was to compare bone mineral density (BMD) testing and pharmacologic treatment in hip fracture patients with versus without schizophrenia. This was a retrospective population-based cohort study leveraging health administrative databases, and individuals aged 66-105 years with hip fracture between fiscal years 2009 and 2018 in Ontario, Canada. Schizophrenia was ascertained using a validated algorithm. The outcome was a composite measure of (1) pharmacologic prescription for osteoporosis; or (2) a BMD test. Inferential analyses were conducted using Fine-Gray subdistribution hazard regression, with mortality as the competing event. A total of 52,722 individuals aged 66 to 105 years who sustained an index hip fracture in Ontario during the study period were identified, of whom 1890 (3.6%) had schizophrenia. Hip fracture patients with vs without schizophrenia were more likely to be long-term care residents (44.3% vs. 18.1%; standardized difference, 0.59), frail (62.5% vs. 36.5%; standardized difference, 0.54) and without a primary care provider (9.2% vs. 4.8%; standardized difference, 0.18). In Fine-Gray models, schizophrenia was associated with a lower incidence of testing or treatment (0.795 (0.721, 0.877)). In this population-based retrospective cohort study, a schizophrenia diagnosis among hip fracture patients was associated with a lower incidence of testing or treatment, after accounting for mortality, and several enabling and predisposing factors. Further research is required to investigate barriers to osteoporosis management in this disadvantaged population.

Effects of gender-affirming hormone therapy on body fat: a retrospective case‒control study in Chinese transwomen

BackgroundThere is insufficient research on how gender-affirming hormone therapy (GAHT) affects body fat modifications in transwomen from China. It is unclear whether hormone therapy affects the prevalence of obesity and blood lipid levels within this population. The current research aimed to assess how GAHT and treatment duration had an impact on the change in and redistribution of body fat in Chinese transwomen.MethodsThis study included 40 transwomen who had not received GAHT and 59 who had. Body fat, blood lipid, and blood glucose levels were measured. GAHT is mainly a pharmacologic (estrogen and anti-androgen) treatment. The study also stratified participants based on the duration of GAHT to assess its impact on body fat distribution. The duration of GAHT was within one year, one to two years, two to three years, or more than three years.ResultsAfter receiving GAHT, total body fat increased by 19.65%, and the percentage of body fat increased by 17.63%. The arm, corrected leg, and leg regions showed significant increases in fat content (+ 24.02%, + 50.69%, and + 41.47%, respectively) and percentage (+ 25.19%, + 34.90%, and + 30.39%, respectively). The total visceral fat content decreased (-37.49%). Based on the diagnostic standards for a body mass index ≥ 28 or total body fat percentage ≥ 25% or 30%, the chance of developing obesity did not change significantly. Blood glucose levels significantly increased (+ 12.31%). Total cholesterol levels (-10.45%) decreased significantly. Fat changes in those who received GAHT for one to two years were significantly different from those who did not receive GAHT.ConclusionAfter receiving GAHT, total body fat and regional fat increased in Chinese transwomen, and the body fat distribution changed from masculine to feminine, especially during the first two years. However, neither the increase in total body fat percentage nor the decrease in visceral fat content didn’t bring about significant changes in the incidence of obesity, nor did triglycerides or low-density lipoprotein-cholesterol.