Treatment Of Disorders Research Articles

Oxygen Transfer Effect on the Growth of Limosilactobacillus reuteri ATCC 53608 and on Its Metabolic Capacity

Limosilactobacillus reuteri is a probiotic microorganism used in the treatment of gastrointestinal disorders. The effect of oxygen transfer on cultures of L. reuteri ATCC 53608 at shake flask and stirred tank bioreactor scales was studied, using MRS and molasses-based media. At shake flask scale, in MRS medium, a maximum bacterial concentration of 2.01 ± 0.02 g L−1 was obtained; the oxygen transfer coefficient was 2.01 ± 0.04 h−1. Similarly, in a 7.5 L bioreactor, in MRS, a maximum bacterial concentration of 2.46 ± 0.16 g L−1 was achieved (kLa = 2.64 ± 0.06 h−1). In contrast, using a molasses-based medium, bacterial concentration reached 3.13 ± 0.17 g L−1 in the 7.5 L bioreactor. A progressive reduction in lactic acid concentration and yield was observed as the oxygen transfer coefficient increased, at shake flask scale. Also, the oxygen transfer coefficient strongly affected the growth of L. reuteri in shake flask and bioreactor and allowed us to successfully scale up L. reuteri culture, producing similar maximum bacterial concentrations in both scales (2.01 g L−1 and 2.46 g L−1 in MRS). This is the first study on oxygen transfer coefficients in L. reuteri, and it is a valuable contribution to the field as it provides important insights about how this organism tolerates oxygen and adapts its metabolism for larger biomass production.Graphical

An exploration of UK speech and language therapists' treatment and management of functional communication disorders: A mixed-methods online survey.

Functional Communication Disorders (FCDs) are one specific presentation of Functional Neurological Disorder (FND). FND is characterised by neurological symptoms, such as sensory and motor symptoms, which are not explained by neurological disease. Speech and language therapists (SLTs) have expertise in managing communication disorders, including FCDs, though is not known is what clinicians do in practice to treat and manage FCDs. To explore the clinical practices of SLTs who regularly manage FCDs in the UK, including the assessment and intervention approaches taken. An online survey was developed using Qualtrics software and piloted before dissemination. Participants were experienced SLTs working in the UK who managed at least three FCD referrals a year. The survey was developed with a mix of qualitative and quantitative questions. The survey was disseminated via social media and professional networks. There were 73 completed responses to the survey. Participants reported working with a range of FCDs clinically, with functional stuttering and articulation disorders seen most frequently. SLTs reported working with a wide range of multidisciplinary professionals when managing patients with FCDs, though lack of access to mental health professionals was raised as an issue. SLTs reported using a combination of formal and informal communication assessments. Interventions varied, with a wide range of psychological approaches informing treatment. Lack of specific training, evidence base and negative attitudes around functional neurological disorder (FND) were raised as ongoing issues. Therapists encountered a wide range of FCDs as part of their clinical practice, though there was a significant disparity in the service and interventions offered. SLTs feel their input can be effective, but lack the resources, training and evidence-based interventions to provide adequate care. What is already known on the subject FCDs are one manifestation of FND and can present as a wide range of communication disorders. SLTs encounter FCDs as part of clinical practice, but report feeling unsure and underprepared to manage these disorders. Consensus recommendations have provided some guidance on how to manage these disorders, though what was not known was what practising SLTs are doing in practice with FCD patients: what assessment, intervention and management strategies they use, and what they feel are the facilitators and barriers to effective management. What this study adds to the existing knowledge This is the first UK-wide survey of FCD SLT clinical practice. The survey found that SLTs are seeing a range of FCDs as part of their clinical practice. SLTs reported that they feel their input is effective, that they had confidence in their ability to provide assessment and intervention, and that SLT for FCDs should be routine. SLTs reported using a wide variety of approaches to assessment and intervention. Barriers to effective management included a lack of resources, training, negative staff attitudes towards FND, and lack of research and evidence-based interventions. What are the practical and clinical implications of this work? This survey has found that SLTs working across the UK are providing input for patients with FCDs, but frequently reported feeling isolated and lacking clinical peer support. This shows the potential for networking groups to support SLTs to learn and share resources. There is a training need for SLTs and other healthcare professionals to tackle pervasive negative attitudes towards FND. Common themes in intervention approaches were found, but there was variability in the specific approach taken. This requires further research to guide SLTs on the best evidence-based practice.

Selective Lymphatic Duct Embolization for Treatment of Thoracic Lymphatic Flow Disorders in Children: Technical Aspects and Comparison with Thoracic Duct Embolization

PurposeTo assess effectiveness of selective lymphatic duct embolization (SLDE) for treatment of thoracic lymphatic flow disorders, performed to maintain patency of the thoracic duct (TD), compared to thoracic duct embolization (TDE). Materials and MethodsRecords of 39 patients (mean age 7.6±7.1 years) with thoracic lymphatic flow disorders who underwent 43 SLDE procedures were analyzed and compared to a cohort of 104 patients (7.8±7.6 y) who underwent TDE. Relevant clinical and imaging data were collated.All patients presented with chylous effusion and/or plastic bronchitis. For the SLDE cohort, etiology of disorders included single-ventricle heart disease palliation in 28 patients (72%) and vascular malformation/aneuploidy in 8 (21%). For the TDE cohort, 92/104(88%) had single-ventricle heart disease palliation. ResultsSLDE was performed with glue via microcatheter in 35 procedures, and dextrose flood technique was used in 26. SLDE via direct needle access was performed in 11.After SLDE, presenting symptoms resolved in 33/39 patients (85%), improved in 5 (13%), and were unchanged in 1 (3%) (mean follow-up 693±523 days). The TD remained patent in all cases. There was a significant difference in outcomes (P=0.001) with the TDE cohort—symptoms resolved or improved in 75/104 patients (72%), were unchanged in 15 (14%); and new leak (e.g., ascites, protein-losing enteropathy) developed in 14 TDE patients (13%) (follow-up 1041±879 d). ConclusionSLDE was effective for treatment of thoracic lymphatic flow disorders, and outcomes were comparable to TDE. Selective techniques preserve the patency of the TD and may have potential benefits that warrant further study.

Metformin acts on miR-181a-5p/PAI-1 axis in stem cells providing new strategies for improving age-related osteogenic differentiation decline.

A general decline in the osteogenic differentiation capacity of human bone marrow mesenchymal stem cells (hBMSCs) in the elderly is a clinical consensus, with diverse opinions on the mechanisms. Many studies have demonstrated that metformin (MF) significantly protects against osteoporosis and reduces fracture risk. However, the exact mechanism of this effect remains unclear. In this study, we found that the decreased miR-181a-5p expression triggered by MF treatment plays a critical role in recovering the osteogenic ability of aging hBMSCs (derived from elderly individuals). Notably, the miR-181a-5p expression in hBMSCs was significantly decreased with prolonged MF (1000 μM) treatment. Further investigation revealed that miR-181a-5p overexpression markedly impairs the osteogenic ability of hBMSCs, while miR-181a-5p inhibition reveals the opposite result. We also found that miR-181a-5p could suppress the protein translation process of plasminogen activator inhibitor-1 (PAI-1), as evidenced by luciferase assays and western blots. Additionally, low PAI-1 levels were associated with diminished osteogenic ability, whereas high levels promoted it. These findings were further validated in human umbilical cord mesenchymal stem cells (hUCMSCs). Finally, our in vivo experiment with a bone defects rat model confirmed that the agomiR-181a-5p (long-lasting miR-181a-5p mimic) undermined bone defects recovery, while the antagomiR-181a-5p (long-lasting miR-181a-5p inhibitor) significantly promoted the bone defects recovery. In conclusion, we found that MF promotes bone tissue regeneration through the miR-181a-5p/PAI-1 axis by affecting MSC osteogenic ability, providing new strategies for the treatment of age-related bone regeneration disorders.

Sleep medicine education in the United States advanced dental education programs.

Dental sleep medicine is an emerging field within dentistry. While limited education in sleep medicine has been reported among US predoctoral dental schools, no study has been conducted among postgraduate dental programs. This study compared the extent and exposure to sleep medicine education among US postgraduate programs in orthodontics, pediatric dentistry, orofacial pain (OFP), general practice residency (GPR), and advanced education in general dentistry (AEGD). A REDCap survey was distributed among N=391 US postgraduate programs investigating the nature, content, and modality of sleep education during the 2023-24 academic year. Among 68 responding programs (43.1% GPR, 18.5% AEGD, 18.5% orthodontics, 12.3% pediatric dentistry, and 7.7% OFP), faculty with sleep training constituted 7.5%, with 2.6% being board certified in sleep medicine. Approximately 41.8% of programs offered sleep medicine courses, with differences among specialties (100% OFP, 42.9% GPR, 37.5% pediatric dentistry, 33.3% orthodontics, 16.7% AEGD; p=0.032). Didactic teaching comprised 7.8±14.6h/year (range 0h/year in 21.5% to 80h/year in 1.5%), with differences across programs (OFP=44.0±17.7, orthodontics=8.7±11.0, GPR=5.0±8.0, pediatric dentistry=2.1±1.9, and AEGD=2.9±5.4; p<0.001), and constituted the primary modality of instruction (mainly obstructive sleep apnea, bruxism, sleep physiology). Screening and treatment for sleep-related disorders were provided by 35.9% and 37.9% of programs, respectively, with variations among specialties (p=0.004). Our findings revealed an average of 7.8h/year of didactic sleep medicine instruction, which differed across specialties. OFP offered the highest level of didactic and clinical training. These findings emphasize the need for increased dental sleep medicine education to address the increasing involvement of dental professionals in managing sleep-related disorders.

Evaluating the potential for psilocybin as a treatment for post-traumatic stress disorder.

Post-traumatic stress disorder (PTSD) is a debilitating psychiatric condition that develops following exposure to a traumatic event. Individuals with this condition experience numerous physiological and behavioral alterations, including intrusive memories, avoidance of trauma-related stimuli, heightened anxiety, hypervigilance, impaired cognition, elevated resting heart rate and blood pressure, and altered neuroendocrine function, to name a few. In most patients, currently available pharmacological and psychological treatments are insufficient to alleviate the array of symptoms associated with the disorder. Thus, novel treatment options that can more effectively target the core etiology of PTSD are desperately needed. Recent work demonstrating the psychoplastogenic effects of psychedelics has reinvigorated research to examine their therapeutic potential in psychiatric conditions. Psilocybin, one psychedelic found in the Psilocybe genus of mushrooms, has exhibited promising antidepressant and anxiolytic effects in preclinical and clinical studies. The purpose of this review is to summarize the existing research that has examined the behavioral effects of psilocybin and link it to potential efficacy in treating PTSD-related symptoms. The proposed mechanisms for psilocybin's effects are then explored, as are the benefits and drawbacks for the agent's therapeutic use. Finally, the challenges faced by investigators aiming to study psilocybin as a therapeutic aid in future studies are discussed in order to shed light on this budding area of research. Significance Statement Current pharmacotherapy for PTSD is insufficient. Traditional antidepressants and anxiolytics help reduce symptom severity, but nonresponse rates often reach levels greater than 50%, emphasizing the need for more effective treatment options. The goal of this review is to summarize the existing evidence for and the potential mechanisms of the antidepressant and anxiolytic effects of psilocybin, a psychedelic compound found in the Psilocybe genus of mushrooms. We then relate the observed effects to psilocybin's potential use as a treatment for PTSD.

Assessment of Cup Placement Impact on Functional Outcomes in Total Hip Replacement: A Retrospective Analysis of 20 Patients

Introduction:Total hip replacement surgery is gaining popularity as a treatment for hip disorders, replacing alternative treatments like excisional arthroplasty, osteotomy, arthrodesis, and hemiarthroplasty. This research aims to evaluate the effect of the acetabular cup on functional outcomes, particularly in younger patients with hip arthritis and femur neck fractures.Materials And Methods:This study aimed to evaluate the placement of the acetabular cup and its association with functional outcomes in total hip replacement (THR). 20 patients were randomly selected from the MRD department and underwent pelvic CT scans postoperatively. Functional results have been analyzed using the Harris Hip Score. The acceptable cup version range was 15 ± 10 degrees, and patients outside this range were closely examined for rotational movements. Results: A study of 20 patients with a neck or femur fracture found that 11 patients had a right knee injury, while 9 had a left knee injury. After a year postoperatively, 18 patients reported no pain, while 2 had mild pain. Functional assessment depicted better outcomes in 17 patients, good outcomes in 2 patients, and fair outcomes in 1 patient. Radiological analysis revealed a mean cup version of 17.77 degrees, with complications including one dislocation and three limb length discrepancies. None of the patients developed an infection.Conclusion:The study found that 90% of patients had excellent functional outcomes, with only 10% exhibiting excessive anteversion. CT scan-based measurements of cup placement provided reliable predictions, consistent with intraoperative assessment of cup positioning.

Sex/Gender Differences in Esophageal Motility Disorders

Esophageal motility disorders are relatively rare and are attributed to an imbalance between the excitatory and inhibitory nerves that innervate the esophagus. These disorders include achalasia, distal esophageal spasms, and jackhammer esophagus. The prevalence of achalasia is equal in men and women; however, lower esophageal hypermotility disorders are slightly more common in women. Women with achalasia experience chest pain more frequently, whereas men tend to have high lower esophageal sphincter pressure. Additionally, women with achalasia respond better to pneumatic balloon dilatation than men. However, research on sex and gender differences in the outcomes of peroral endoscopic myotomy remains insufficient. Future studies should investigate the differences in outcomes, complications, and long-term effects to ensure optimal treatment in men and women with esophageal motility disorders. This research will be useful to develop sex-tailored treatments for esophageal motility disorders.

The Role of ACE2 in Neurological Disorders: From Underlying Mechanisms to the Neurological Impact of COVID-19

Angiotensin-converting enzyme 2 (ACE2) has become a hot topic in neuroscience research in recent years, especially in the context of the global COVID-19 pandemic, where its role in neurological diseases has received widespread attention. ACE2, as a multifunctional metalloprotease, not only plays a critical role in the cardiovascular system but also plays an important role in the protection, development, and inflammation regulation of the nervous system. The COVID-19 pandemic further highlights the importance of ACE2 in the nervous system. SARS-CoV-2 enters host cells by binding to ACE2, which may directly or indirectly affect the nervous system, leading to a range of neurological symptoms. This review aims to explore the function of ACE2 in the nervous system as well as its potential impact and therapeutic potential in various neurological diseases, providing a new perspective for the treatment of neurological disorders.

Drug problems and treatment services at the community level: findings from a national sample of key informants in Nigeria

ABSTRACT Aims This study aimed to provide community-level perspectives on substance use, related health and social harms and utilization of treatment for substance use disorders in Nigeria. Methods The study is based on descriptive-qualitative data from semi-structured interviews with a purposive sample of 2,787 key informants (e.g. police officers, health workers) from the 36 states of Nigeria. Results The findings highlight social, economic, legal, academic, occupational and health problems linked to drug consumption. Drug-related problems extended beyond individuals who consume drugs to impact close relations and local communities. Government-funded facilities (e.g. general hospitals, specialist psychiatric facilities) were thought to be more available, accessible and acceptable to people seeking treatment for substance use disorders than other types of facilities (e.g. faith-based facilities, NGO treatment centers). The provision and uptake of services in these facilities are constrained by financial cost and inadequate specialist services for drug use owing to shortage of skilled professionals. Conclusion There exist a need to improve access to substance use disorder treatment through development of skilled manpower, expansion of health service coverage and strengthening of community-based services. Further, prioritizing healthcare services and combating stigma against people who use drugs could contribute to uptake of services.

VEGF, but Not BDNF, Prevents the Downregulation of KCC2 Induced by Axotomy in Extraocular Motoneurons

The potassium–chloride cotransporter KCC2 is the main extruder of Cl- in neurons. It plays a fundamental role in the activity of the inhibitory neurotransmitters (GABA and glycine) since low levels of KCC2 promote intracellular Cl- accumulation, leading to the depolarizing activity of GABA and glycine. The downregulation of this cotransporter occurs in neurological disorders characterized by hyperexcitability, such as epilepsy, neuropathic pain, and spasticity. KCC2 is also downregulated after axotomy. If muscle reinnervation is allowed, the KCC2 levels recover in motoneurons. Therefore, we argued that target-derived neurotrophic factors might be involved in the regulation of KCC2 expression. For this purpose, we performed the axotomy of extraocular motoneurons via the monocular enucleation of adult rats, and a pellet containing either VEGF or BDNF was chronically implanted in the orbit. Double confocal immunofluorescence of choline acetyl-transferase (ChAT) and KCC2 was carried out in the brainstem sections. Axotomy led to a KCC2 decrease in the neuropil and somata of extraocular motoneurons, peaking at 15 days post-lesion, with the exception of the abducens motoneuron somata. VEGF administration prevented the axotomy-induced KCC2 downregulation. By contrast, BDNF either maintained or reduced the KCC2 levels following axotomy, suggesting that BDNF is involved in the axotomy-induced KCC2 downregulation in extraocular motoneurons. The finding that VEGF prevents KCC2 decrease opens up new possibilities for the treatment of neurological disorders coursing with neuronal hyperactivity due to KCC2 downregulation.

Design and implementation of a Type-2 hybrid, prospective randomized trial of opioid agonist therapies integration into primary care clinics in Ukraine

IntroductionUkraine has high HIV prevalence, concentrated among people who inject drugs (PWID), mostly of opioids. Maintenance on opioid agonist therapies (OAT) is the most effective evidence-based treatment for opioid use disorder. As PWID experience high morbidity and mortality from preventable and treatable non-communicable diseases, international agencies recommend integrating OAT into primary care centers (PCC). MethodsA randomized, type-2 hybrid implementation trial was carried out to compare outcomes of OAT integration in PCC to OAT delivery at specialty treatment centers (STC) – standard-of-care. Tele-education supporting PCC providers in managing OAT, HIV, tuberculosis and non-communicable diseases along with pay-for-performance incentives were used to facilitate implementation. Consenting patients underwent 1:2 randomization to either STC or PCC. Quality health indicators (QHIs), a composite percentage of recommended primary and specialty services accessed by patients (blood/urine tests, cancer screenings, etc.), were defined as efficacy outcomes and were assessed by participant self-report at baseline and every 6 months over 24 months and electronic chart reviews after the completion of the follow-up. The primary outcome is defined as the difference in composite QHI scores at 24 months, in which a repeated measures likelihood-based mixed model with missing at random assumptions will be used. Providers at PCC completed surveys at baseline, 12 and 24 months to assess implementation outcomes including changes in stigma and attitudes towards OAT and PWID. Preliminary resultsAmong the 1459 participants allocated to STC (N = 509) or PCC (N = 950), there were no differences in clinical and demographic characteristics. Self-reported prevalences were available for HIV (42 %), HCV (57 %), and prior tuberculosis (17 %). Study retention at 6, 12, 18, and 24 months was as 91 %, 85 %, 80 %, and 74 %, respectively. ConclusionPWID have a high prevalence of medical comorbidities and integrating OAT into primary care settings has the potential to improve the health of PWID. Findings from this study can help guide implementation of integrated care in Ukraine and throughout similar low-resource, high-burden countries in the Eastern European and Central Asian region.

The effects of alfalfa powder combined with health education on patients with dyslipidemia: A randomized controlled trial

BackgroundCardiovascular diseases (CVDs) remain the leading cause of global mortality, with dyslipidemia recognized as a significant risk factor. Dyslipidemia, characterized by elevated levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG), is associated with an increased lifetime risk of CVD. Although alfalfa’s cholesterol-lowering effects have been demonstrated in animal models, clinical trial data supporting its efficacy in human dyslipidemia treatment are limited. MethodsA randomized controlled trial was conducted from September 20, 2021, to January 12, 2023, involving patients diagnosed with dyslipidemia. Approved by the China Ethics Committee of Registering Clinical Trials, the study included multiple sites in China. Eligible participants were adults aged 18 years or older, meeting criteria from the Chinese Guidelines for the Prevention and Treatment of Adult Blood Lipid Disorders. Participants were randomly assigned to either a health education-only group or a combined alfalfa powder supplementation and health education group for a three-month intervention period. ResultsA total of 160 eligible patients were enrolled and randomized into two groups: the Alfalfa group (n = 80) and the Education group (n = 80). The intervention resulted in significant improvements in key lipid parameters in the Alfalfa group, including reductions in TC, LDL-C, and Apo A1 levels. Although changes in HDL-C levels were not significantly different between the groups, the Alfalfa group exhibited a larger increase. Serum lipid metabolomics analysis using liquid chromatography-tandem mass spectrometry (LC-MS/MS) indicated that the combined intervention did not significantly alter the overall blood lipid metabolome but identified fifteen regulated differential metabolites, with the glycerophospholipid metabolism pathway significantly affecting lipid metabolism levels. ConclusionSupplementation with alfalfa powder combined with health education significantly reduced TC, LDL-C, and Apo A1 levels in patients with dyslipidemia. KEGG pathway analysis suggests an association between the glycerophospholipid metabolism pathway and dyslipidemia. Further research is warranted to validate these findings and explore the underlying mechanisms.

Long-term follow-up of the Bergen 4-day treatment for panic disorder during the COVID-19 pandemic

Long-term follow-up of the Bergen 4-day treatment for panic disorder during the COVID-19 pandemic

Early-stage implementation of peer-led interventions for emergency department patients with substance use disorder: Findings from a formative qualitative evaluation

IntroductionEmergency department (ED)-based peer recovery coach (PRC) programs can improve access to substance use disorder treatment (SUD) for ED patients. As literature on early stages of PRC implementation is limited, we conducted a qualitative assessment of ED PRC program implementation from several US-based PRC programs focusing on barriers and facilitators for implementation and providing recommendations based on the findings. MethodsWe collected qualitative data from 39 key informants (peer recovery coaches, PRC program managers, ED physicians and staff, representatives of community-based organizations) via 6 focus groups and 21 interviews in February–December 2023. We transcribed audio-recordings and analyzed data using codebook thematic analysis. ResultsWe identified the following major themes related to specific barriers and recommendations to address them. To facilitate timely linkage to PRCs, programs would regularly inform ED staff about the program and its linkage procedures, establish trust between PRC and ED staff, streamline the linkage procedures, and choose an “opt-out” linkage approach. To address barriers related to external referrals, programs use “warm handoff” and “warm line” strategies, maintain and update a comprehensive catalog of resources, and familiarize peer coaches with local service providers. Telehealth services implementation requires addressing logistical barriers, ensuring patients' privacy, and training peer coaches on building trust and rapport online. Peer coaches' wellness and quality of services can be improved by limiting PRC's workload, prioritizing quality over quantity, facilitating self-, peer- and professional care to mitigate stress and burnout; and, importantly, by providing supportive supervision and training to peer coaches and advocating for PRC team as an equal partner in the ED settings. To facilitate PRC program adoption and sustainment program managers engage local communities and program champions, seek diverse sources of funding, and advocate for structural changes to accommodate recruitment and retention of peer recovery coaches. ConclusionsWe compiled a wealth of best practices used by PRC programs to address numerous implementation barriers and challenges. These recommendations are intended for PRC program planners, managers and champions, hospital leadership, and state and local public health agencies leading SUD epidemic response.

Automatic 3D pelvimetry framework in CT images and its validation

In the field of spinal pathology, sagittal balance of the spine is usually judged by the spatial structure and morphology of pelvis, which can be represented by pelvic parameters. Pelvic parameters, including pelvic incidence, pelvic tilt and sacral slope, are therefore essential for the diagnosis and treatment of spinal disorders, however, it is a time-consuming and laborious procedure to measure these parameters by traditional methods. In this paper, an automatic measurement framework for pelvic CT images was proposed to calculate three-dimensional (3D) pelvic parameters with the support of deep learning technology. Pelvic images were first preprocessed, and 3D reconstruction was then performed to obtain 3D pelvic model by the Visualization Toolkit. DRINet was trained to segment the femoral head region in the pelvic images, and 3D sphere fitting was performed to locate the femoral heads. In addition, VGG16 was adopted to recognize images containing superior sacral endplate, and the plane growth algorithm was used to fit the plane so that the midpoint and normal vector of the superior sacral endplate could be obtained. Finally, 3D pelvic parameters were automatically calculated, and compared with manual measurements for 15 patients. The proposed framework automatically generated 3D pelvic models, and calculated two-dimensional (2D) and 3D pelvic parameters from continuous CT images. Experiments demonstrated that the framework can greatly speed up the calculation of pelvic parameters, and these parameters are accurate when compared with the manual measurements. In conclusion, the proposed framework demonstrates good performance on automatic pelvimetry measurement by incorporating deep learning technology, and can well replace the traditional methods for pelvic parameter measurement.

Anxiolytic and sedative effects of sodium valproate with different experimental paradigms in male and female rats.

Valproic acid or sodium valproate is a widely used drug in the treatment of epilepsy, although it also appears to have anxiolytic and sedative properties derived from its agonistic action on the GABAergic system. To analyze these potential effects of the drug, we conducted three experiments with rats using procedures designed to assess anxiety in rodents. In the first experiment, with a fear conditioning procedure, three groups of male rats were included that received either 100 mg/kg or 300 mg/kg of valproate or an equivalent volume of saline solution. In Experiment 2, recording spontaneous activity in an open field, we compared the effects of valproic acid (300 mg/kg) on male and female rats. In the third experiment, we analyzed the effect of valproic acid using a novelty-induced hypophagia test and tested again for potential differences as a function of the sex of the animals. The results showed an anxiolytic effect restricted to the 300 mg/kg dose of the drug in Experiment 1. Such an effect was restricted to the female sample in Experiment 2, but in the third experiment affected both sexes. As for the sedative effect, it was observed in all experiments irrespective of the sex of the rats. These findings hold significant implications for the treatment of anxiety disorders since valproate may offer a novel therapeutic approach for anxiety-related conditions with distinct benefits and fewer side effects. However, clinical studies are needed to validate the translation of these findings from animal models to human patients.

Therapeutic efficacy of intracerebral hematopoietic stem cell gene therapy in an Alzheimer’s disease mouse model

The conditions supporting the generation of microglia-like cells in the central nervous system (CNS) after transplantation of hematopoietic stem/progenitor cells (HSPC) have been studied to advance the treatment of neurodegenerative disorders. Here, we explored the transplantation efficacy of different cell subsets and delivery routes with the goal of favoring the establishment of a stable and exclusive engraftment of HSPCs and their progeny in the CNS of female mice. In this setting, we show that the CNS environment drives the expansion, distribution and myeloid differentiation of the locally transplanted cells towards a microglia-like phenotype. Intra-CNS transplantation of HSPCs engineered to overexpress TREM2 decreased neuroinflammation, Aβ aggregation and improved memory in 5xFAD female mice. Our proof of concept study demonstrates the therapeutic potential of HSPC gene therapy for Alzheimer’s disease.

Population pharmacokinetic analysis of zastaprazan (JP-1366), a novel potassium-competitive acid blocker, in patients and healthy volunteers.

Zastaprazan (JP-1366) is a novel potassium-competitive acid blocker for the treatment of acid-related disorders. We aimed to establish a population pharmacokinetic (PK) model of zastaprazan, thereby characterizing the PK of zastaprazan in patients with gastroesophageal reflux disease (GERD) as well as evaluating the impact of various covariates, including CYP2C19 phenotypes, on zastaprazan PK. This population PK analysis included zastaprazan plasma concentration-time data from 92 patients with erosive GERD and 68 healthy volunteers without any gastrointestinal disorders and was performed using nonlinear mixed-effect modeling. Simulations were conducted to predict zastaprazan PK under various dosing regimens in patients with GERD. The plasma PK of zastaprazan was adequately described by a two-compartment model with Erlang-type absorption (six sequential compartments) and first-order elimination. CYP2C19 phenotypes had no significant effect on zastaprazan PK. The disease status was identified as a significant covariate on apparent clearance of zastaprazan, showing lower values in patients with GERD compared to healthy volunteers. However, the model-based simulation indicated that the impact of disease status on zastaprazan exposure was not clinically meaningful. Overall, the current population PK model successfully characterized the observed zastaprazan PK in both patients with GERD and healthy volunteers.

The preliminary study of the effects of individual musculoskeletally stable position in the treatment of temporomandibular disorders

BackgroundTemporomandibular Disorders (TMD) is the dysfunction of group of muscles and bones in the joint area, the main symptoms of TMD are the pain of the chewing muscles and (or) the temporomandibular joints, mandibular movement disorders and joint noise. This study was designed to explore the therapeutic effects following Individual Musculoskeletally Stable (IMS) position stabilization splint therapy for TMD patients using Fricton index, cone beam computed tomography (CBCT) and surface-Electromyogram (sEMG).MethodsIn this study, we enrolled 31 TMD patients (ranging from 18 to 26 years old, including 7 males and 24 females), first Fricton index was used to evaluate the clinical curative effect of TMD with the treatment of IMS stabilization splint; then CBCT was used to observe the TMJ condylar position changes of TMD before and after the treatment of IMS stabilization splint; finally sEMG was used to observe the changes of electromyography of anterior temporalis (AT) and masseter muscles (MM) of TMD before and after the treatment of IMS stabilization splint.ResultsThe course of treatment was 6–8 months, with an average of 7.6 months. After the IMS stabilization splint treatment, TMD symptoms relieved, especially in pain, mandibular movement disorder, but still slightly inferior in the treatment of joint noise. And there was a statistically significant difference in the anterior and inner joint space, the condyle had the tendency of moving forward and outward. AT presented reduction significantly of EMG value at rest position after treatment.ConclusionsIMS stabilization splint is a therapeutic reversible treatment for TMD, especially for pain and mandibular movement disorder; it produces effects of forward and outward condylar movement and elimination of the masticatory muscles antagonism.