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In vitiligo, CD8+ T cells and IFN-γ production drive disease activity, representing potential targets to control depigmentation. The persistence of resident memory T cells (T RMs) in patient skin causes relapses, highlighting the significance of IL-15-targeted management strategies. Future treatment avenues potentially involve pairing oral JAK inhibitors with phototherapy and repurposing medications such as metformin and rapamycin for managing vitiligo. Local targeting of Janus kinase activity mitigates inflammation to halt CD8+ T cell activity, and nucleotide-based treatments serve as a viable option for skin conditions. IL-2 mutein preferentially targets Tregs to enhance their activity and proliferation and manage depigmentation. The autoimmune condition vitiligo, characterized by skin depigmentation, presents challenges for effective treatment design, with Janus kinase (JAK) inhibitors and other repurposed drugs offering a promising strategy for symptom management. This review explores advantages and shortcomings of current therapies, while presenting the urgent need for further innovative approaches. We emphasize the growing understanding of autoimmune involvement in vitiligo, highlighting several novel treatment avenues including relieving melanocyte stress, preventing dendritic cell activation, halting T cell migration, and suppressing inflammation and autoimmunity. Integrating psychodrama therapy to remediate stress alongside medical interventions marks a holistic approach to enhance patient well-being. The molecular underpinnings of vitiligo care are covered, emphasizing exciting advances revolutionizing vitiligo treatment and improving the quality of life for affected individuals. [ABSTRACT FROM AUTHOR]

• A variety of matrix metalloproteinases play an important role in the migration and invasion of prostate cancer. • Epigenetic modification plays an important role in prostate cancer. • Interaction between epigenetic modification and matrix metalloproteinases. • New strategies for prostate cancer diagnosis and treatment. Prostate cancer (PCa) is one of the most common tumors affecting men all over the world. PCa has brought a huge health burden to men around the world, especially for elderly men, but its pathogenesis is unclear. In prostate cancer, epigenetic inheritance plays an important role in the development, progression, and metastasis of the disease. An important role in cancer invasion and metastasis is played by matrix metalloproteinases (MMPs), zinc-dependent proteases that break down extracellular matrix. We review two important forms of epigenetic modification and the role of matrix metalloproteinases in tumor regulation, both of which may be of significant value as novel biomarkers for early diagnosis and prognosis monitoring. The author considers that both mechanisms have promising therapeutic applications for therapeutic agent research in prostate cancer, but that efforts should be made to mitigate or eliminate the side effects of drug therapy in order to maximize quality of life of patients. The understanding of epigenetic modification, MMPs, and their inhibitors in the functional regulation of prostate cancer is gradually advancing, it will provide a new technical means for the prevention of prostate cancer, early diagnosis, androgen-independent prostate cancer treatment, and drug research. [ABSTRACT FROM AUTHOR]

Back pain is, according to the World Health Organization, a widespread disease and is associated with a high disease burden. The aim of this study was to examine the effects of 50 units of rehabilitation sport (once/week) after a 3-week rehabilitation measure for patients with chronic back pain. 130 patients (75.38% female, mean age of 52,02 ± 7,44 years) were included in a prospective observational study, of which 54 (41.54%) performed rehabilitation sports in the 1.5 years between the initial measure and a 1-week refresher (rehabilitation sport group, intervention group) and 76 patients did not do sports (control group). Assessments of one's own ability to work (Work Ability Index, WAI), limitations due to back pain (Oswestry Disability Index), fear avoidance behavior (Fear Avoidance Believe) and one's own quality of life (Short Form - 36 questionnaire) were evaluated. There were no statistically significant differences in the items queried between the intervention group and the control group. The lack of significant differences between the two groups should be taken as an implication for further studies. It seems sensible to stick to general measures of rehabilitation sport until measures are designed that are effective beyond doubt. Rückenschmerzen sind laut Weltgesundheitsorganisation eine Volkskrankheit und mit einer hohen Krankheitslast verbunden. Ziel dieser Studie war es, die Wirkung von 50 Einheiten Rehabilitationssport (1x/Woche) nach einer 3-wöchigen Rehabilitationsmaßnahme bei Patienten mit chronischen Rückenschmerzen zu untersuchen. 130 Patienten (75,38% weiblich, Durchschnittsalter 52,02 ± 7,44 Jahre) wurden in eine prospektive Beobachtungsstudie eingeschlossen, von denen 54 (41,54%) in den 1,5 Jahren zwischen der Erstmaßnahme und einwöchiger Auffrischung 50 Einheiten Rehabilitationssport durchführten (Interventionsgruppe), 76 Patienten machten keinen Sport (Kontrollgruppe). Ausgewertet wurden Einschätzungen zur eigenen Arbeitsfähigkeit (Work Ability Index, WAI), zu Einschränkungen durch Rückenschmerzen (Oswestry Disability Index), zum Angstvermeidungsverhalten (Fear Vermeidung Believe) und zur eigenen Lebensqualität (Short Form – 36 Fragebogen). Es gab keine statistisch signifikanten Unterschiede in den abgefragten Items zwischen der Interventionsgruppe und der Kontrollgruppe. Das Fehlen signifikanter Unterschiede zwischen den beiden Gruppen sollte als Implikation für weitere Studien gewertet werden. Es erscheint sinnvoll, mit dem Rehabilitationssport in der derzeitigen Form fortzufahren, bis wirksamere Maßnahmen entwickelt werden. [ABSTRACT FROM AUTHOR]

[Display omitted] Neutrophilic asthma (NA) is a severe asthma phenotype associated with steroid resistance and IL-1β overproduction; however, the exact mechanism remains unclear. Moreover, the dysfunction of TNF-α signaling pathway, a regulator of IL-1β production, was associated with the deficiency of ovarian tumor protease deubiquitinase with linear linkage specificity (otulin) in autoimmune patients. We hypothesized that otulin downregulation in macrophages (Mφ) could trigger Mφ activation via the nucleotide-binding domain, leucine-rich repeat, and pyrin domain-containing protein 3 (NLRP3) inflammasome signaling pathway. We assessed the expressions of otulin in blood monocyte subsets from NA patients and in alveolar Mφ from NA mice. Additionally, we evaluated the functional consequences of otulin deficiency in bone marrow–derived Mφ. The effects of inhibiting receptor-interacting protein kinase (RIPK)-1 and RIPK-3 on neutrophils and group 3 innate lymphoid cells (ILC3s) were assessed in vitro and in vivo. When comparing nonclassical monocytes, a significant downregulation of otulin in the intracellular components was observed in NA patients compared to healthy controls (P =.005). Moreover, isolated alveolar Mφ from the NA mice exhibited lower otulin expression compared to those from control mice. After otulin knockdown in bone marrow–derived Mφ, we observed spontaneous IL-1β production depending on NLRP3 inflammasome. Moreover, the infiltrated neutrophils and ILC3s were significantly decreased by combined treatment of RIPK-1 and RIPK-3 inhibitors through blocking IL-1β release in NA. IL-1β overproduction caused by a deficiency of otulin, an upstream triggering factor, could be a promising diagnostic and therapeutic target for NA. [ABSTRACT FROM AUTHOR]

• Evaluation of 234 patients admitted with chronic obstructive pulmonary disease exacerbation at 10 centers with 30-day follow-up. • 12% were referred to pulmonary rehabilitation at discharge, which was utilized by 1% at 30-days. • Failing to prescribe long-acting bronchodilators during admission significantly lowered their 30-day use. • Daily in-hospital respiratory physiotherapy was an independent predictor for 30-day smoking cessation. Implementing standard of care therapy for chronic obstructive pulmonary disease (COPD) has barriers. Hospitalization with an acute exacerbation of COPD (AECOPD) is a major adverse event that could also be an opportunity to improve patients' long-term care. To evaluate which in-hospital interventions during AECOPD are associated with improved 30-day care. This was a prospective study that included patients from 10 medical centers across Israel, hospitalized with AECOPD between 2017 and 2019. Patients were approached during hospitalization in internal medicine departments. A semi-structured follow-up call was performed 30 days after discharge, and six COPD areas of care were assessed. Multivariate analyses were used to analyze predictors for each area of care. 234 patients were included (mean age 69 years and 34% females). A lower 30-day readmission rate was independently associated with smoking cessation and prescription of renin-angiotensin blockers. Initiating or continuing long acting bronchodilators (LABD) during admission was an independent predictor for their 30-day use. Among patients with prior LABD treatment, only 38% continued at 30-days if it was not prescribed during admission (OR 4, 95% CI 1.98-8.08, p<0.01). In-hospital daily respiratory physiotherapy was an independent predictor for smoking cessation (AOR 5.1, 95% CI 1.1-23, p=0.04), while smoking cessation recommendation was not (p=0.28). Initiating a smoking cessation program (5%) or pulmonary rehabilitation (1%) after discharge was performed only by patients with a written referral. Routine procedures during hospitalization for AECOPD could impact patients' long-term care in areas with proven effects on disease outcomes. [ABSTRACT FROM AUTHOR]

Low back pain (LBP) may profoundly impact the quality of life across the globe, and intervertebral disc degeneration (IVDD) is the major cause of LBP; however, targeted pharmaceutical interventions for IVDD are still lacking. Ferroptosis is a novel form of iron-dependent programmed cell death. Studies have showed that ferroptosis may closely associate with IVDD; thus, targeting ferroptosis may have great potential for IVDD therapy. Non-steroidal anti-inflammatory drugs (NSAIDs) are the first-line medications for LBP, while nuclear factor-erythroid 2-related factor-2 (Nrf2) is a key inhibitory protein for ferroptosis. In the current study, we conducted a molecular docking screening between NSAIDs library and Nrf2 protein. Tinoridine was shown to have a high binding affinity to Nrf2. The in vitro study in nucleus pulposus (NP) cells showed that Tinoridine may promote the expression and activity of Nrf2, it may also rescue RSL3-induced ferroptosis in NP cells. Knockdown of Nrf2 reverses the protective effect of Tinoridine on RSL3-induced ferroptosis in NP cells, suggesting that the inhibitory effect of Tinoridine on ferroptosis is through Nrf2. In vivo study demonstrated that Tinoridine may attenuate the progression of IVDD in rats. As NSAIDs are already clinically used for LBP therapy, the current study supports Tinoridine's application from the view of ferroptosis inhibition. • Ferroptosis plays a critical role in intervertebral disc degeneration (IVDD), contributing significantly to its pathological progression. • Tinoridine, as an NSAID, can treat IVDD by inhibiting ferroptosis both in vitro and in vivo. • These findings highlight the therapeutic promise of Tinoridine in IVDD therapy. [ABSTRACT FROM AUTHOR]

Angina pectoris may arise from obstructive coronary artery disease (CAD) or in the absence of significant CAD (ischemia with nonobstructed coronary arteries [INOCA]). Therapeutic strategies for patients with angina and obstructive CAD focus on reducing cardiovascular events and relieving symptoms, whereas in INOCA the focus shifts toward managing functional alterations of the coronary circulation. In obstructive CAD, coronary revascularization might improve angina status, although a significant percentage of patients present angina persistence or recurrence, suggesting the presence of functional mechanisms along with epicardial CAD. In patients with INOCA, performing a precise endotype diagnosis is crucial to allow a tailored therapy targeted toward the specific pathogenic mechanism. In this expert opinion paper, we review the evidence for the management of angina, highlighting the complementary role of coronary revascularization, optimal medical therapy, and lifestyle interventions and underscoring the importance of a personalized approach that targets the underlying pathobiology. • Angina pectoris may arise from obstructive CAD or in the absence of significant CAD. • Functional mechanisms may be involved in determining angina both in obstructive CAD and in ischemia with nonobstructed coronary arteries. • Revascularization and medical therapy play complementary roles in achieving optimal outcomes for patients with angina. • Management of angina is shifting toward a more personalized approach, moving away from the traditional one-size-fits-all strategy. [ABSTRACT FROM AUTHOR]

The list of standard abbreviations for JDS is available at adsa.org/jds-abbreviations-24. Nonstandard abbreviations are available in the Notes. Bovine mastitis is a prevalent infectious disease in dairy herds worldwide, resulting in substantial economic losses. Staphylococcus aureus is a major cause of mastitis in animals, and its antibiotic resistance poses challenges for treatment. Recently, renewed interest has focused on the development of alternative methods to antibiotic therapy, including bacteriophages (phages), for controlling bacterial infections. In this study, 2 lytic phages, vB_SauM_JDYN (JDYN) and vB_SauM_JDF86 (JDF86), were isolated from the cattle sewage effluent samples collected from dairy farms in Shanghai. The 2 phages have a broad bactericidal spectrum against Staphylococcus of various origins. Genomic and morphological analyses revealed that the 2 phages belonged to the Myoviridae family. Moreover, JDYN and JDF86 remained stable under a wide temperature and pH range and were almost unaffected in chloroform. In this study, we prepared a phage cocktail (PHC-1) which consisted of a 1:1:1 ratio of JDYN, JDF86, and SLPW (a previously characterized phage). We found that PHC-1 showed the strongest bacteriolytic effect and the lowest frequency of emergence of bacteriophage insensitive mutants compared with monophages. Bovine mammary epithelial cells and lactating mice mastitis models were used to evaluate the effectiveness of PHC-1 in vitro and in vivo, respectively. The results demonstrated that PHC-1 treatment significantly reduced bacterial load, alleviated inflammatory response, and improved mastitis pathology. Altogether, these results suggest that PHC-1 has the potential to treat S. aureus -induced bovine mastitis and that phage cocktails can combat antibiotic-resistant S. aureus infections. [ABSTRACT FROM AUTHOR]

La fasciite à éosinophiles (FE), ou maladie de Shulman, est une pathologie rare du tissu conjonctif caractérisée par un œdème et une induration douloureuse des membres et du tronc, souvent associés à une hyperéosinophilie et une hypergammaglobulinémie. Elle provoque des arthralgies et une limitation des amplitudes articulaires induisant un important retentissement fonctionnel et une altération de la qualité de vie. Depuis sa description par Shulman en 1974, plus de 300 cas ont été rapportés. Nous présentons ici une revue des actualités diagnostiques, physiopathologiques, et thérapeutiques de cette maladie. L'imagerie par résonance magnétique est utile pour orienter le diagnostic et la biopsie. Le diagnostic repose sur la biopsie cutanée profonde comportant le fascia qui met en évidence un œdème, une scléro-fibrose du fascia musculaire et du tissu sous-cutané et un infiltrat inflammatoire parfois composé de polynucléaires éosinophiles. Des formes secondaires à l'utilisation des inhibiteurs de checkpoint ont été décrites et l'apparition d'une sclérose cutanée chez ces patients doit faire évoquer le diagnostic. La physiopathologie reste mal connue et la prise en charge mal codifiée, reposant sur des données issues de cohorte rétrospectives et cas cliniques. Le traitement de première intention consiste en corticothérapie orale, parfois associée à un immunosuppresseur, en premier lieu le méthotrexate. Une meilleure compréhension de la physiopathologie permet d'envisager de nouvelles perspectives thérapeutiques et de préciser la place de thérapies ciblées telles que les inhibiteurs de l'interleukine 5 (IL-5) et de l'IL-6. Eosinophilic fasciitis (EF) is a rare connective tissue disorder characterized by painful edema and induration of the limbs and trunk, likely associated with hypereosinophilia and hypergammaglobulinemia. EF causes arthralgia and range of motion limitation, leading to significant functional impairment and poor quality of life. Since its description by Shulman in 1974, over 300 cases have been reported. We present here a review of the latest diagnostic, pathophysiological and therapeutic developments in this disease. Magnetic resonance imaging appears useful to guide diagnosis and biopsy. Diagnosis is based on a deep skin biopsy involving the fascia, which will reveal edema, sclerofibrosis of the muscular fascia and subcutaneous tissue, and an inflammatory infiltrate sometimes composed of eosinophilic polynuclear cells. EF may occur in patients treated with immune checkpoint inhibitors and the diagnosis should be raised in case of cutaneous sclerosis in these patients. The pathophysiology of the disease remains poorly understood, and its management lacks randomized, controlled, blinded trials. First-line treatment consists in oral corticosteroid therapy, sometimes combined with an immunosuppressant, mainly methotrexate. A better understanding of the pathophysiology has opened new therapeutic perspectives and clarified the role of targeted therapies in the management of EF, such as interleukin-6 inhibitors, whose efficacy has been reported in several cases. [ABSTRACT FROM AUTHOR]

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Binge eating disorder (BED) is the most prevalent eating disorder. Treatment options include pharmacotherapy as well as psychotherapy, with the latter recommended as a first-line option. However, the use of psychotherapeutic interventions poses several challenges. Antidepressants are easily accessible, but they lack robust evidence-base. This systematic review aims to comprehensively examine the efficacy and safety of antidepressants for the treatment of BED. Five databases were searched for randomized controlled trials (RCTs) comparing antidepressants vs. placebo in BED until 23/11/2023. Pairwise meta-analytic evaluations were performed. The primary outcomes were remission and binge eating frequency. Secondary outcomes were response to treatment, eating psychopathology, depression, anxiety, body weight, Body Mass Index (BMI), all-cause discontinuation, discontinuation due to adverse effects and total adverse events. Sixteen RCTs with a total of 984 participants were meta-analysed. Antidepressants were more effective than placebo in achieving remission (RR: 1.39, 95 % CI: 1.04 to 1.86) and in reducing binge eating episodes (SMD: -0.29, 95 % CI: -0.51 to -0.06). Similarly, in the secondary outcomes of response and depression, antidepressants demonstrated superiority over placebo. Antidepressants appear to be effective in reducing symptoms of BED. Small samples and effect sizes hinder the generalizability and clinical utility of these results. There is a lack of follow-up findings regarding the maintenance of effects. There is a pressing need for more RCTs examining antidepressants and other types of pharmacotherapy. Future research should include larger number of participants and increase the duration of follow-up. [ABSTRACT FROM AUTHOR]

Damage to the heart can start the repair process and cause cardiac remodeling. B cells play an important role in this process. B cells are recruited to the injured place and activate cardiac remodeling through secreting antibodies and cytokines. Different types of B cells showed specific functions in the heart. Among all types of B cells, heart-associated B cells play a vital role in the heart by secreting TGFβ1. B cells participate in the activation of fibroblasts and promote cardiac fibrosis. Four subtypes of B cells in the heart revealed the relationship between the B cells' heterogeneity and cardiac remodeling. Many cardiovascular diseases like atherosclerosis, heart failure (HF), hypertension, myocardial infarction (MI), and dilated cardiomyopathy (DCM) are related to B cells. The primary mechanisms of these B cell-related activities will be discussed in this review, which may also suggest potential novel therapeutic targets. • We summarized the relationship between B cells and cardiac remodeling. • In different cardiovascular diseases, B cells express different biomarkers and play different roles in cardiac fibrosis. • According to the mechanism of B cell action, potential therapeutic targets were proposed. [ABSTRACT FROM AUTHOR]

Attention-deficit/hyperactivity disorder is a childhood-onset neurodevelopmental disorder that frequently persists into adulthood with 3% of adult women having a diagnosis of attention-deficit/hyperactivity disorder. Many women are diagnosed and treated during their reproductive years, which leads to management implications during pregnancy and the postpartum period. We know from clinical practice that attention-deficit/hyperactivity disorder symptoms frequently become challenging to manage during the perinatal period and require additional support and attention. There is often uncertainty among healthcare providers about the management of attention-deficit/hyperactivity disorder in the perinatal period, particularly the safety of pharmacotherapy for the developing fetus. This guideline is focused on best practices in managing attention-deficit/hyperactivity disorder in the perinatal period. We recommend (1) mitigating the risks associated with attention-deficit/hyperactivity disorder that worsen during the perinatal period via individualized treatment planning; (2) providing psychoeducation, self-management strategies or coaching, and psychotherapies; and, for those with moderate or severe attention-deficit/hyperactivity disorder, (3) considering pharmacotherapy for attention-deficit/hyperactivity disorder, which largely has reassuring safety data. Specifically, providers should work collaboratively with patients and their support networks to balance the risks of perinatal attention-deficit/hyperactivity disorder medication with the risks of inadequately treated attention-deficit/hyperactivity disorder during pregnancy. The risks and impacts of attention-deficit/hyperactivity disorder in pregnancy can be successfully managed through preconception counselling and appropriate perinatal planning, management, and support. [Display omitted] [ABSTRACT FROM AUTHOR]

In the second part of this Continuing Medical Education article on paraneoplastic pemphigus/paraneoplastic autoimmune multiorgan syndrome (PNP/PAMS), its diagnostic criteria, investigative work-up, and management are reviewed. PNP/PAMS is a rare autoimmune blistering disorder associated with high morbidity and mortality. Recognizing PNP/PAMS's key features and its diagnostic criteria is critical in initiating appropriate work-up. Evaluating PNP/PAMS requires knowledge of its findings on histopathology, direct immunofluorescence, indirect immunofluorescence, and enzyme-linked immunosorbent assay. Lastly, treatments for PNP/PAMS are reviewed with suggestions based on case reports and expert opinions in the literature. [ABSTRACT FROM AUTHOR]

Inflammatory skin diseases such as atopic eczema (atopic dermatitis [AD]) affect children and adults globally. In AD, the skin barrier is impaired on multiple levels. Underlying factors include genetic, chemical, immunologic, and microbial components. Increased skin pH in AD is part of the altered microbial microenvironment that promotes overgrowth of the skin microbiome with Staphylococcus aureus. The secretion of virulence factors, such as toxins and proteases, by S aureus further aggravates the skin barrier deficiency and additionally disrupts the balance of an already skewed immune response. Skin commensal bacteria, however, can inhibit the growth and pathogenicity of S aureus through quorum sensing. Therefore, restoring a healthy skin microbiome could contribute to remission induction in AD. This review discusses direct and indirect approaches to targeting the skin microbiome through modulation of the skin pH; UV treatment; and use of prebiotics, probiotics, and postbiotics. Furthermore, exploratory techniques such as skin microbiome transplantation, ozone therapy, and phage therapy are discussed. Finally, we summarize the latest findings on disease and microbiome modification through targeted immunomodulatory systemic treatments and biologics. We believe that targeting the skin microbiome should be considered a crucial component of successful AD treatment in the future. [ABSTRACT FROM AUTHOR]

To examine the effects of Cawthorne-Cooksey exercises on individuals with vestibular dysfunction symptoms. Systematic search was conducted using PubMed, EBSCO SCOPUS, Web of Science, and Google Scholar from inception to March 2023. The Physiotherapy Evidence Database (PEDro) scale was employed to evaluate the risk of bias in the included studies. Ten randomized controlled trials met the eligibility criteria. In total, 610 participants, 41.31 % of whom were men were included in this review. The PEDro scale scores ranged from 6 to 8 with a median of 6.5/10. Our findings revealed improvements in patients' vestibular dysfunction symptoms after Cawthorne-Cooksey exercises and other conventional interventions. The initial findings showed that Cawthorne-Cooksey exercises are not superior to other concurrent vestibular rehabilitation interventions in improving vestibular dysfunction symptoms. Additional trials with long-term follow-ups are strongly recommended to understand the impacts of Cawthorne-Cooksey exercises on vestibular dysfunction symptoms. [ABSTRACT FROM AUTHOR]

This systematic review aims to examine the effects of task-oriented (TO) training on gait function in people with multiple sclerosis (MS) and to determine the most effective TO training protocol. We searched PubMed, Web of Science, Scopus, EMBASE, REHABDATA, and PEDro for studies that examined the effects of TO on gait ability (i.e., gait velocity, gait endurance, functional mobility) in people with MS from 1971 to October 2022. The quality of the selected studies was estimated using the Physiotherapy Evidence Database (PEDro) scale. Nine studies met the eligibility criteria. A total of 199 people with MS, 58.79% of whom were women, were included. Five studies revealed "good" quality, one revealed "fair", and three exhibited "poor" quality. Four studies administered TO training alone, and five combined TO training with conventional physiotherapy. The selected studies showed varied results for the influences of TO training on gait ability in people with MS. The evidence for the impact of TO training on people with MS was limited. The optimal TO training protocol stills vague. Further studies with larger sample sizes are needed. • Task-oriented training is safe and well tolerated by the people with MS. • The evidence for the effects of task-oriented on gait ability in people with MS is limited. • The optimal treatment protocol remains unclear. [ABSTRACT FROM AUTHOR]

Schizophrenia is a leading cause of global disease burden. Current drug treatments are associated with significant side effects and have limited efficacy for many patients, highlighting the need to develop new approaches that target other aspects of the neurobiology of schizophrenia. Preclinical, in vivo imaging, postmortem, genetic, and pharmacological studies have highlighted the key role of cortical GABAergic (gamma-aminobutyric acidergic)-glutamatergic microcircuits and their projections to subcortical dopaminergic circuits in the pathoetiology of negative, cognitive, and psychotic symptoms. Antipsychotics primarily act downstream of the dopaminergic component of this circuit. However, multiple drugs are currently in development that could target other elements of this circuit to treat schizophrenia. These include drugs for GABAergic or glutamatergic targets, including glycine transporters, D-amino acid oxidase, sodium channels, or potassium channels. Other drugs in development are likely to primarily act on pathways that regulate the dopaminergic system, such as muscarinic or trace amine receptors or 5-HT 2A receptors, while PDE10A inhibitors are being developed to modulate the downstream consequences of dopaminergic dysfunction. Our review considers where new drugs may act on this circuit and their latest clinical trial evidence in terms of indication, efficacy, and side effects. Limitations of the circuit model, including whether there are neurobiologically distinct subgroups of patients, and future directions are also considered. Several drugs based on the mechanisms reviewed have promising clinical data, with the muscarinic agonist KarXT most advanced. If these drugs are approved for clinical use, they have the potential to revolutionize understanding of the pathophysiology and treatment of schizophrenia. [ABSTRACT FROM AUTHOR]

• Bile acid malabsorption (BAM) can generate functional chronic diarrhea. • Derangement of the gut-liver axis is involved in BAM. • BAM is frequently underdiagnosed but specific tests are available. • Therapies target enterohepatic BAs circulation by sequestrants and novel approaches. Bile acid malabsorption (BAM) is an important disorder of digestive pathophysiology as it generates chronic diarrhoea. This condition originates from intricate pathways involving bile acid synthesis and metabolism in the liver and gut, the composition of gut microbiota, enterohepatic circulation and key receptors as farnesoid X receptor (FXR), fibroblast growth factor receptor 4 (FGFR4), and the G-protein bile acid receptor-1 (GPBAR-1). Although symptoms can resemble those related to disorders of gut brain interaction, accurate diagnosis of BAM may greatly benefit the patient. The empiric diagnosis of BAM is primarily based on the clinical response to bile acid sequestrants. Specific tests including the 48-hour fecal bile acid test, serum levels of 7α-hydroxy-4-cholesten-3-one (C4) and fibroblast growth factor 19 (FGF19), and the 75Selenium HomotauroCholic Acid Test (SeHCAT) are not widely available. Nevertheless, lack of diagnostic standardization of BAM may account for poor recognition and delayed management. Beyond bile acid sequestrants, therapeutic approaches include the use of FXR agonists, FGF19 analogues, glucagon-like peptide-1 (GLP-1) receptor agonists, and microbiota modulation. These novel agents can best make their foray into the therapeutic armamentarium if BAM does not remain a diagnosis of exclusion. Ignoring BAM as a specific condition may continue to contribute to increased healthcare costs and reduced quality of life. Here, we aim to provide a comprehensive review of the pathophysiology, diagnosis, and management of BAM. [ABSTRACT FROM AUTHOR]

This study looked at the effect of group music therapy on dementia patients' levels of feelings of depression and anxiety. Quasi-experiment was carried out (N = 121) in which patients were randomly divided into a control (N = 61) and an experimental group (N = 60). Following a six-weeks, twelve-sessions trial involving both passive and active music therapy, it was discovered that the music group therapy intervention decreased the anxiety and depression levels of dementia patients in the experimental group as compared to the control group, which did not receive any music therapy. It was also noted that after three months of follow-up, participants in the experimental group still maintained a low level of anxiety and depression, but the control group's level remained high, therefore, substantiating the effect of music in lowering anxiety and depression among older ones. We urge the nursing descipline, medical professionals, carers, and care homes to include music therapy in the care they provide for patients with dementia. • Despite the increasing use of music therapy to treat dementia patients, studies that focused on developing nations are few. • The impact of group music therapy intervention in ameliorating depression and anxiety. • Music group therapy intervention reduced the depression and anxiety level of older ones in the experiment group. [ABSTRACT FROM AUTHOR]

Early mechanical reperfusion, primarily via percutaneous coronary intervention, combined with timely antithrombotic drug administration, constitutes the main approach for managing acute coronary syndrome (ACS). Clinicians have access to a variety of antithrombotic agents, necessitating careful selection to balance reducing thrombotic events against increased bleeding risks. This review offers a comprehensive update on current antithrombotic therapy in ACS, emphasizing the need for individualized treatment strategies. [ABSTRACT FROM AUTHOR]

TikTok is increasingly becoming a source of health information, peer support, and validation regarding mental health. The goal of this study was to analyze the content of TikTok videos related to depression and anxiety. The sample included 100 videos, each with at least a million views, discussing either depression, anxiety, or both. The videos were retrieved from hashtag searches. The videos were coded for the type of mental health condition; specific content being discussed (e.g., symptoms or treatment); video presentation (i.e., personal experience, expert information, or general discussion), and more subcategories. Engagement statistics (i.e., likes, views, reposts, and number of comments) for each video were also recorded. The engagement statistics were higher for personal experience videos than for videos from healthcare professionals. Anxiety was the subject of 57% of the videos irrespective of the search hashtags, and over two-thirds of the videos were created by females. The most discussed topics included the description or enactment of depression/anxiety symptoms (e.g., emotional displays); mention of being diagnosed by a healthcare professional was the least prevalent. These results suggest that depression and anxiety videos featuring personal experiences are prevalent on TikTok with higher engagement compared to similar videos by health professionals. The attribution of generic symptoms to these mental health conditions may result in self-diagnosis. There is a need for more strategic efforts to ensure quality of health content on TikTok and increased focus on digital health literacy to make young social media users critical consumers of online content. [ABSTRACT FROM AUTHOR]

There is no established standard of care for treating central centrifugal cicatricial alopecia (CCCA), and treatment approaches vary widely. To develop consensus statements regarding the use of various pharmacological therapies in treating adults with CCCA. We invited 27 dermatologists with expertise in hair and scalp disorders to participate in a 3-round modified Delphi study between January and March 2023. Statements met strong consensus if 75% of respondents agreed or disagreed. Statements met moderate consensus if 55% or more but less than 75% agreed or disagreed. In round 1, 5 of 33 (15.2%) statements met strong consensus, followed by 9 of 28 (32.1%) in round 2. After the final round 3 meeting, strong consensus was reached for 20 of 70 (28.6%) overall statements. Two statements achieved moderate consensus. This study included only English-speaking, US-based dermatologists and did not consider nonpharmacological therapies. Despite varying opinions among dermatologists, consensus was reached for several statements to help clinicians manage CCCA. We also highlight areas that lack expert consensus with the goal of advancing research and therapeutic options for CCCA. [ABSTRACT FROM AUTHOR]

Autoimmune pancreatitis (AIP) is a steroid-responsive inflammatory disease of the pancreas. Few studies investigated pancreatic exocrine function (PEF) in patients suffering from AIP and no definitive data are available on the effect of steroids in PEF recovery. Aim of the study is the evaluation of severe pancreatic insufficiency (sPEI) prevalence in AIP at clinical onset and after steroid treatment. 312 Patients with diagnosis of AIP between January 1st, 2010 and December 31st, 2020 were identified in our prospectively maintained register. Patients with a pre-steroid treatment dosage of fecal elastase-1 (FE-1) were included. Changes in PEF were evaluated in patients with available pre- and post-treatment FE (between 3 and 12 months after steroid). One-hundred-twenty-four patients were included, with a median FE-1 of 122 (Q1-Q3: 15–379) μg/g at baseline. Fifty-nine (47.6 %) had sPEI (FE-1<100 μg/g). Univariable analysis identified type 1 AIP, radiological involvement of the head of the pancreas (diffuse involvement of the pancreas or focal involvement of the head), weight loss, age and diabetes as associated with a greater risk of sPEI. However, at multivariable analysis, only the involvement of the head of the pancreas was identified as independent risk factor for sPEI. After steroids, mean FE-1 changed from 64 (15–340) to 202 (40–387) μg/g (P = 0.058) and head involvement was the only predictor of improvement of sPEI. The inflammatory involvement of the head of the pancreas is associated with PEF severity, as well as PEF improvement after treatment with steroids in patients with AIP. [ABSTRACT FROM AUTHOR]

Effective responses against severe systemic infection require coordination between two complementary defense strategies that minimize the negative impact of infection on the host: resistance, aimed at pathogen elimination, and disease tolerance, which limits tissue damage and preserves organ function. Resistance and disease tolerance mostly rely on divergent metabolic programs that may not operate simultaneously in time and space. Due to evolutionary reasons, the host initially prioritizes the elimination of the pathogen, leading to dominant resistance mechanisms at the potential expense of disease tolerance, which can contribute to organ failure. Here, we summarize our current understanding of the role of physiological perturbations resulting from infection in immune response dynamics and the metabolic program requirements associated with resistance and disease tolerance mechanisms. We then discuss how insight into the interplay of these mechanisms could inform future research aimed at improving sepsis outcomes and the potential for therapeutic interventions. Responses to severe infection involve resistance, aimed at pathogen elimination, and disease tolerance, that limit tissue damage. These defense strategies are both essential but rely on distinct metabolic programs. Willmann and Moita review how physiology is disrupted by infection, and how this knowledge may inspire novel therapies for sepsis. [ABSTRACT FROM AUTHOR]

Liquid biopsy is rapidly gaining acceptance as a non-invasive approach for early lung cancer detection and monitoring. Cell-free (cf)DNA methylation libraries can be prepared from very low-input DNA, and robust methods are being developed at a fast pace. Methylation data of circulating tumour (ct)DNA could be used for early detection and risk stratification in lung cancer screening programmes. Several challenges need to be addressed for the successful clinical implementation of cfDNA methylation analysis for lung cancer management. Considering the evolving approaches to lung cancer management involving liquid biopsy, we recommend technical modifications of current cfDNA methylation assay methods and introduce two lung cancer screening models. The clinical use of cell-free DNA (cfDNA) methylation in managing lung cancer depends on its ability to differentiate between malignant and healthy cells, assign methylation changes to specific tissue sources, and elucidate opportunities for targeted therapy. From a technical standpoint, cfDNA methylation analysis is primed as a potential clinical tool for lung cancer screening, early diagnosis, prognostication, and treatment, pending the outcome of elaborate validation studies. Here, we discuss the current state of the art in cfDNA methylation analysis, examine the unique features and limitations of these new methods in a clinical context, propose two models for applying cfDNA methylation data for lung cancer screening, and discuss future research directions. [ABSTRACT FROM AUTHOR]

Throughout the world, burn injury is a major cause of death and disability. In resource-limited countries, burn injury is one of the leading causes of permanent disability among children who survive traumatic injuries, and burn injury is the fourth leading cause of disability worldwide. This study applied Andersen's model of health care access to evaluate if patient characteristics (predisposing factors), burn care service availability (enabling factors) and injury characteristics (need) are associated with physical impairment at hospital discharge for patients surviving burn injuries globally. Specifically, access to rehabilitation, nutrition, operating theatre, specialized burn unit services, and critical care were investigated as enabling factors. The secondary aim was to determine whether associations between burn care service availability and impairment differed by country income level. Methods: This is a cross-sectional secondary analysis of prospectively collected data from the World Health Organization, Global Burn Registry. The outcome of interest was physical impairment at discharge. Simple and multivariable logistic regressions were used to test the unadjusted and adjusted associations between the availability of burn care services and impairment at hospital discharge, controlling for patient and injury characteristics. Effect modification was analyzed with service by country income level interaction terms added to the models and, if significant, the models were stratified by income. Results: The sample included 6622 patients from 20 countries, with 11.2% classified with physical impairment at discharge. In the fully adjusted model, patients had 89% lower odds impairment at discharge if the treatment facility provided reliable rehabilitation services compared to providing limited or no rehabilitation services (OR.11, 95%CI.08,.16, p <.01). However, this effect was modified by county income with the strong and significant association only present in high/upper middle-income countries. Sophisticated nutritional services were also significantly associated with less impairment in high/upper middle-income countries (OR=.04, 95% CI 0.203, 0.05, p <.01), but significantly more impairment in lower middle/low-income countries (OR=2.01, 95% CI 1.50, 2.69, p <.01). Patients had 444% greater odds of impairment if treated at a center with specialty burn unit services (OR 5.44, 95%CI 3.71, 7.99, p <.01), possibly due to a selection effect. Discussion: Access to reliable rehabilitation services and sophisticated nutritional services were strongly associated with less physical impairment at discharge, but only in resource-rich countries. Although these findings support the importance of rehabilitation and nutrition after burn injury, they also highlight potential disparities in the quantity or quality of services available to burn survivors in poorer countries. • Patients had 89% lower odds of impairment at discharge if the facility provided reliable rehabilitation services (OR=.11, 95% CI. 08-.16, p <.01). • Reliable rehabilitation was associated with significantly lower odds of impairment at discharge in HIUM but no association in LMLI countries. • With access to sophisticated nutritional services, the odds of impairment were 96% lower in HIUM and 101% higher in LMLI countries. [ABSTRACT FROM AUTHOR]

Enterococcal Infective Endocarditis (EIE) is usually treated with the combination of penicillin/ampicillin with gentamicin or ampicillin with ceftriaxone. To enable prolonged outpatient treatment, a combination of benzylpenicillin and ceftriaxone has been suggested. This study aimed to describe the incidence and characteristics of EIE and to determine the outcome of EIE cases treated with benzylpenicillin and ceftriaxone. This was a retrospective single-center study including all patients diagnosed with infective endocarditis (IE) during 2016–2021, comparing EIE with IE caused by other pathogens. We described the outpatient treatment of patients with EIE, comparing those treated of benzylpenicillin - ceftriaxone with other regimes. Among 222 patients with IE, 44 (20%) were diagnosed with EIE. Those were older, had a male predominance (p = 0.035), and were more disabled (p = 0.004). The incidence of EIE reached 30% towards the last year, becoming the leading etiology. Twenty-six patients received outpatient treatment, five of whom were discharged with benzylpenicillin and ceftriaxone. Adding patients from this cohort to the scarce data available, revealed similar recurrence and mortality rates compared to other treatment regimes. EIE is becoming a more frequent cause of IE, involving older, more disabled patients with male predominance. Our experience and existing literature suggest that the combination of benzylpenicillin and ceftriaxone is as safe as more conventional regimes, although further research is needed. [ABSTRACT FROM AUTHOR]

Cognitive Remediation (CR) is an evidence-based therapy targeting cognitive difficulties in people with psychosis to promote functional recovery, but it is rarely implemented routinely. To reach more individuals, CR is beginning to be delivered remotely, but there is limited evidence to support the acceptability of this method. To evaluate the acceptability and feasibility of remote therapist-supported CR in people with psychosis and estimate its cost and potential benefits. A case-series with all participants assessed before and after therapy with measures of personal goal attainment (main outcome), cognition, functioning and symptoms. Acceptability was assessed with post-therapy interviews. Feasibility was assessed using proportions and confidence intervals on pre-specified parameters. Indication of benefits was assessed with exploratory analyses comparing baseline and post-therapy scores on the pre-specified outcomes. The cost of providing remote CR was assessed from both healthcare and societal perspectives. Twenty-nine participants started therapy with two dropping out; on average participants attended 25.5 sessions. Interviews suggested that remote CR had good acceptability and led to perceived benefits. Significant and large improvements were observed on goal attainment. Cost analyses suggest that remote CR has the same health care cost as face-to-face therapy but a lower societal cost. Our results support the use of remote CR in psychosis services as an alternative delivery modality. This method may improve adherence, attendance and be more convenient for service users. Possible barriers such as poor digital literacy or appropriate device ownership should be addressed before starting therapy. [ABSTRACT FROM AUTHOR]

Carbapenem-resistant Klebsiella pneumoniae (CRKP) poses a substantial healthcare challenge. This study assessed the in vitro efficacy of selected antibiotic combinations against CRKP infections. Our research involved the evaluation of 40 clinical isolates of CRKP, with half expressing Klebsiella pneumoniae carbapenemase (KPC) and half producing Metallo-β-lactamase (MBL), two key enzymes contributing to carbapenem resistance. We determined the minimum inhibitory concentrations (MICs) of four antibiotics: eravacycline, tigecycline, polymyxin-B, and ceftazidime/avibactam. Synergistic interactions between these antibiotic combinations were examined using checkerboard and time-kill analyses. We noted significant differences in the MICs of ceftazidime/avibactam between KPC and MBL isolates. Checkerboard analysis revealed appreciable synergy between combinations of tigecycline (35%) or eravacycline (40%) with polymyxin-B. The synergy rates for the combination of tigecycline or eravacycline with polymyxin-B were similar among the KPC and MBL isolates. These combinations maintained a synergy rate of 70.6% even against polymyxin-B resistant isolates. In contrast, combinations of tigecycline (5%) or eravacycline (10%) with ceftazidime/avibactam showed significantly lower synergy than combinations with polymyxin-B (P < 0.001 and P = 0.002, respectively). Among the MBL CRKP isolates, only one exhibited synergy with eravacycline or tigecycline and ceftazidime/avibactam combinations, and no synergistic activity was identified in the time-kill analysis for these combinations. The combination of eravacycline and polymyxin-B demonstrated the most promising synergy in the time-kill analysis. This study provides substantial evidence of a significant synergy when combining tigecycline or eravacycline with polymyxin-B against CRKP strains, including those producing MBL. These results highlight potential therapeutic strategies against CRKP infections. [ABSTRACT FROM AUTHOR]

The global antibiotic resistance crisis poses critical needs for alternative sustainable solutions in which predatory bacteria are considered promising candidates. Diverse predatory bacteria are available as potential biocontrol agents that employ different predation strategies. Bdellovibrio bacteriovorus showed great potential as a living antibiotic, as demonstrated in relevant animal models in vivo. Myxobacteria and Bdellovibrio and like organisms (BALOs) predate broadly upon plant and animal pathogens, making them promising biocontrol applications in agriculture and aquaculture. The cell lysis ability of predatory bacteria enables a variety of applications in environmental engineering systems. Exploiting predatory bacteria as living antibiotics and biocontrol agents demands thorough understanding of predation mechanisms and impact of predation on community dynamics. Future advances in exploring the application potentials of bacterial predation rely on integrating the power of emerging culture-independent technologies with classic culture-based methodology that can disentangle predator ecophysiology and ecogenomics in high throughput. Predatory bacteria have been increasingly known for their ubiquity in environments and great functional potentials in controlling unwanted microorganisms. Fundamental understanding of the predation mechanisms, population dynamics, and interaction patterns underlying bacterial predation is required for wise exploitation of predatory bacteria for enhancing ecoenvironmental, animal, and human health. Here, we review the recent achievements on applying predatory bacteria in different systems as biocontrol agents and living antibiotics as well as new findings in their phylogenetic diversity and predation mechanisms. We finally propose critical issues that deserve priority research and highlight the necessity to combine classic culture-based and advanced culture-independent approaches to push research frontiers of bacterial predation across ecosystems for promising biocontrol and therapy strategies towards a sustainable ecoenvironment and health. [ABSTRACT FROM AUTHOR]

Translational reprogramming enables swift adaptation of breast cancer cells in the metastatic cascade. Cancer cells strategically manipulate translation machinery and mRNA attributes to selectively translate mRNAs for specific functional requirements. tRNAs and other trans -acting RNAs significantly shape the translational landscape in the progression of breast cancer. Advances in comprehending translational adaptation in breast cancer metastasis unveil therapeutic possibilities. Breast cancer's tendency to metastasize poses a critical barrier to effective treatment, making it a leading cause of mortality among women worldwide. A growing body of evidence is showing that translational adaptation is emerging as a key mechanism enabling cancer cells to thrive in the dynamic tumor microenvironment (TME). Here, we systematically summarize how breast cancer cells utilize translational adaptation to drive metastasis, highlighting the intricate regulation by specific translation machinery and mRNA attributes such as sequences and structures, along with the involvement of tRNAs and other trans -acting RNAs. We provide an overview of the latest findings and emerging concepts in this area, discussing their potential implications for therapeutic strategies in breast cancer. [ABSTRACT FROM AUTHOR]

Evidence is lacking to guide the management of infective native aortic aneurysm (INAA). The aim of this study was to establish expert consensus on surgical and antimicrobial treatment and follow up, and to define when an INAA is considered cured. Delphi methodology was used. The principal investigators invited 47 international experts (specialists in infectious diseases, radiology, nuclear medicine, and vascular and cardiothoracic surgery) via email. Four Delphi rounds were performed, three weeks each, using an online questionnaire with initially 28 statements. The panellists rated the statements on a five point Likert scale. Comments on statements were analysed, statements were revised and added or deleted, and the results were presented in the iterative rounds. Consensus was defined as ≥ 75% of the panel rating a statement as strongly agree or agree on the Likert scale, and consensus on the final assessment was defined as Cronbach's alpha > 0.80. All 49 panellists completed all four rounds, resulting in 100% participation. One statement was added based on the results and comments of the panel, resulting in 29 final statements: three on need for consensus, 20 on treatment, five on follow up, and one on definition of cure. All 29 statements reached agreement of ≥ 86%. Cronbach's alpha increased for each consecutive round; round 1, 0.85; round 2, 0.90; round 3, 0.91; and round 4, 0.94. Thus, consensus was reached for all statements. INAAs are rare, and high level evidence to guide optimal management is lacking. This consensus document was established with the aim of helping clinicians manage these challenging patients, as a supplement to current guidelines. The presented consensus will need future amendments in accordance with newly acquired knowledge. [ABSTRACT FROM AUTHOR]

• A patient-centered approach was implemented to define comprehensive behavioral intervention for tics (CBIT) research priorities. • Priorities related to treatment access and improving broad functional outcomes. • Our approach efficiently identified actionable priorities for CBIT research. To establish a patient-centered agenda for research that will lead to effective, widespread availability, adoption, and utilization of evidence-based behavioral treatment of Tourette syndrome and other tic disorders (TDs), we planned and executed a multistage, collaborative "Treating Tourette Together" research planning project with researchers, clinicians, patients, families, and other interested parties. Priorities for future behavioral treatment research were solicited from these parties via anonymous community surveys, a 2-day research planning summit with 46 individuals representing key stakeholder groups, and community response to summit reports. Four high-priority research domains were identified: (a) expanding treatment access, (b) improving treatment outcomes, (c) optimizing treatment within a broader care model, and (d) evaluating outcomes beyond tic severity. Community-engaged participatory research models can efficiently delineate clear and actionable priorities for clinical research. This approach holds promise for improving the impact of clinical research in TDs and other neuropsychiatric disorders. [ABSTRACT FROM AUTHOR]

The crosstalk of joint pathology with local lymph nodes in osteoarthritis (OA) is poorly understood. We characterized the change in T cells in lymph nodes following load-induced OA and established the association of the presence and migration of T cells to the onset and progression of OA. We used an in vivo model of OA to induce mechanical load-induced joint damage. After cyclic tibial compression of mice, we analyzed lymph nodes for T cells using flow cytometry and joint pathology using histology and microcomputed tomography. The role of T-cell migration and the presence of T-cell type was examined using T-cell receptor (TCR)α−/− mice and an immunomodulatory drug, Sphingosine-1-phosphate (S1P) receptor inhibitor-treated mice, respectively. We demonstrated a significant increase in T-cell populations in local lymph nodes in response to joint injury in 10, 16, and 26-week-old mice, and as a function of load duration, 1, 2, and 6 weeks. T-cell expression of inflammatory cytokine markers increased in the local lymph nodes and was associated with load-induced OA progression in the mouse knee. Joint loading in TCRα−/− mice reduced both cartilage degeneration (Osteoarthritis Research Society International (OARSI) scores: TCRα 0.568, 0.981-0.329 confidence interval (CI); wild type (WT) 1.328, 2.353-0.749 CI) and osteophyte formation. Inhibition of T-cell egress from lymph nodes attenuated load-induced cartilage degradation (OARSI scores: Fingolimod: 0.509, 1.821-0.142 CI; Saline 1.210, 1.932-0.758 CI) and decreased localization of T cells in the synovium. These results establish the association of lymph node-resident T cells in joint damage and suggest that the S1P receptor modulators and T-cell immunotherapies could be used to treat OA. [ABSTRACT FROM AUTHOR]

• Despite the increasing use of music therapy to treat dementia patients, studies that focused on developing nations are still in their embryonic stage. • This study examined the impact of group music therapy intervention in ameliorating depression levels among older people. • Music group therapy intervention reduced the depression level of older ones in the experiment group. • The music therapy session also influenced the salivary cortisol of the patients as it was shown to reduce their salivary cortisol levels. Despite the increasing use of music therapy to treat patients with dementia, studies focused on developing nations are still in their embryonic stages. In this view, this study examined the impact of group music therapy intervention in ameliorating depression levels among older people in two care homes. A randomized control trial (RCT) was carried out in which a total of 121 patients were randomly divided into control 61 and experimental group 60. After 6 weeks, 12-session experiment which involved passive and active music therapy, it was found that music group therapy intervention reduced the depression level of older persons in the experimental group, compared to those who were not exposed to the music therapy; control group. The music therapy session also influenced the salivary cortisol of the patients as it was shown to reduce their salivary cortisol levels. It was also observed that after three months of follow-up, participants in the experimental group still maintained a low level of depression and salivary cortisol level, but the control group's level was still high, thus, substantiating the effect of music in reducing depression among older people. We encouraged clinicians, nursing practitioners and care homes in Nigeria to incorporate music therapy as part of the treatment offered to patients with dementia. [ABSTRACT FROM AUTHOR]

The outcomes of the best medical treatment (BMT) and intervention treatment (INT) in a single-center experience were reported in type B intramural hematoma (IMH). From February 2015 to February 2021, a total of 195 consecutive patients with type B IMH were enrolled in the study. The primary end point was mortality, and the secondary end points included clinical and imaging outcomes. The clinical outcomes were aortic-related death, retrograde type A aortic dissection, stent graft-induced new entry tear, endoleak, and reintervention. The imaging outcome was evaluated through the latest follow-up computed tomography angiography, which included aortic rupture, aortic dissection, aortic aneurysm, rapid growth of aortic diameter, newly developed or enlarged penetrating aortic ulcer or ulcer-like projection (ULP) and increased aortic wall thickness. Kaplan-Meier curves were used to assess the association between different treatments. Among the enrolled patients, 115 received BMT, and 80 received INT. There was no significant difference in early (1.7% vs 2.5%; P = 1.00) and midterm all-cause death (8.3% vs 5.2%; P =.42) between the BMT and INT groups. However, patients who underwent INT were at risk of procedure-related complications such as stent graft-induced new entry tear and endoleaks. The INT group was associated with a profound decrease in the risk of ULP, including newly developed ULP (4.3% vs 26.9%; P <.05), ULP enlargement (6.4% vs 31.3%; P <.05), and a lower proportion of high-risk ULP (10.9% vs 45.6%; P <.05). Although there was no significant difference in the incidence of IMH regression between the two groups, the maximum diameter of the descending aorta in patients receiving INT was larger compared with those treated with BMT. Based on our limited experience, patients with type B IMH treated with BMT or INT shared similar midterm clinical outcome. Patients who underwent INT may have a decreased risk of ULPs, but a higher risk of procedure-related events and patients on BMT should be closely monitored for ULP progression. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is one of the most common gastrointestinal malignancies, characterized by insidious onset and high propensity for metastasis and recurrence. Apart from surgical resection, there are no effective curative methods for HCC in recent years, due to resistance to radiotherapy and chemotherapy. Heat shock proteins (HSP) play a crucial role in maintaining cellular homeostasis and normal organism development as molecular chaperones for intracellular proteins. Both basic research and clinical data have shown that HSPs are crucial participants in the HCC microenvironment, as well as the occurrence, development, metastasis, and resistance to radiotherapy and chemotherapy in various malignancies, particularly liver cancer. This review aims to discuss the molecular mechanisms and potential clinical value of HSPs in HCC, which may provide new insights for HSP-based therapeutic interventions for HCC. [Display omitted] • Heat shock proteins (HSP) plays an important role in the tumor microenvironment of Hepatocellular carcinoma. • In highly suspicious cases, HSP helps in differential diagnosis. • HSP related inhibitors and HSP based tumor vaccines have broad prospects in the treatment of HCC. [ABSTRACT FROM AUTHOR]

Vascular smooth muscle cells (VSMCs) have emerged as pivotal contributors throughout all phases of atherosclerotic plaque development, effectively dispelling prior underestimations of their prevalence and significance. Recent lineage tracing studies have unveiled the clonal nature and remarkable adaptability inherent to VSMCs, thereby illuminating their intricate and multifaceted roles in the context of atherosclerosis. This comprehensive review provides an in-depth exploration of the intricate mechanisms and distinctive characteristics that define VSMCs across various physiological processes, firmly underscoring their paramount importance in shaping the course of atherosclerosis. Furthermore, this review offers a thorough examination of the significant strides made over the past two decades in advancing imaging techniques and therapeutic strategies with a precise focus on targeting VSMCs within atherosclerotic plaques, notably spotlighting meticulously engineered nanoparticles as a promising avenue. We envision the potential of VSMC-targeted nanoparticles, thoughtfully loaded with medications or combination therapies, to effectively mitigate pro-atherogenic VSMC processes. These advancements are poised to contribute significantly to the pivotal objective of modulating VSMC phenotypes and enhancing plaque stability. Moreover, our paper also delves into recent breakthroughs in VSMC-targeted imaging technologies, showcasing their remarkable precision in locating microcalcifications, dynamically monitoring plaque fibrous cap integrity, and assessing the therapeutic efficacy of medical interventions. Lastly, we conscientiously explore the opportunities and challenges inherent in this innovative approach, providing a holistic perspective on the potential of VSMC-targeted strategies in the evolving landscape of atherosclerosis research and treatment. [Display omitted] [ABSTRACT FROM AUTHOR]

To highlight some important findings from osteoarthritis (OA) epidemiology and therapy research undertaken over the past year. Search of MEDLINE and EMBASE databases between April 1, 2022 to March 3, 2023 using "exp *Osteoarthritis/" as the preliminary search term. The search was limited to articles published in English and including human subjects. Final inclusions were based on perceived importance and results that may inform improved identification of risk factors or OA treatments, as well as OA subgroups of potential relevance to risk factors or treatment approaches. 3182 studies were screened, leaving 208 eligible for inclusion. This narrative review of thirty-three selected studies was arranged into: a) OA predictors – population-based studies, b) Specific predictors of OA and OA outcome; c) Intra-articular injections, and d) OA phenotypes. There was some suggestion of sex differences in predictors of incidence or outcomes. Body mass index changes appear largely to affect knee OA outcomes. Evidence points to a lack of benefit of viscosupplementation in knee OA; findings were variable for other injectables. Studies of OA phenotypes reveal potentially relevant clinical and pathophysiological differences. Identifying risk factors for the incidence/progression of OA represents an ongoing and important area of OA research. Sex may play a role in this understanding and bears consideration and further study. For knee injectables other than viscosupplementation, additional high-quality trials appear warranted. Continued investigation and application of phenotyping across the OA disease, illness and care spectrum may be key to developing disease-modifying agents and their appropriate selection for individuals. [ABSTRACT FROM AUTHOR]

More than a hundred genetic loci have been associated with atrial fibrillation (AF). But the exact mechanism remains unclear and the treatment needs to be improved. This study aimed to investigate the mechanism and potential treatment of NPPA mutation–associated AF. Nppa knock-in (KI, p.I137T) rats were generated, and cardiac function was evaluated. Blood pressure was recorded using a tail-cuff system. The expression levels were measured using real-time polymerase chain reaction, enzyme-linked immunosorbent assay or Western blot analysis, and RNA-sequence analysis. Programmed electrical stimulation, patch clamp, and multielectrode array were used to record the electrophysical characteristics. Mutant rats displayed downregulated expression of atrial natriuretic peptide but elevated blood pressure and enlarged left atrial end-diastolic diameter. Further, gene topology analysis suggested that the majority of differently expressed genes in Nppa KI rats were related to inflammation, electrical remodeling, and structural remodeling. The expression levels of C-C chemokine ligand 5 and galectin-3 involved in remodeling were higher, while there were declined levels of Na v 1.5, Ca v 1.2, and connexin 40. AF was more easily induced in KI rats. Electrical remodeling included abbreviated action potentials, effective refractory period, increased late sodium current, and reduced calcium current, giving rise to conduction abnormalities. These electrophysiological changes could be reversed by the late sodium current blocker ranolazine and the Na v 1.8 blocker A-803467. Our findings suggest that structural remodeling related to inflammation and fibrosis and electrical remodeling involved in late sodium current underly the major effects of the Nppa (p.I137T) variant to induce AF, which can be attenuated by the late sodium current blocker and Na v 1.8 blocker. [Display omitted] [ABSTRACT FROM AUTHOR]

Nerve transfer surgery is commonly used to treat patients with brachial plexus injuries. However, guidelines on postoperative rehabilitation are not clearly established. Nerve transfers require the patient to relearn how to recruit newly innervated muscle(s), which may not occur naturally or intuitively. Supervised therapy is a valuable resource to guide patients through their lengthy recovery (often >12 months) because target muscle strength is both obtained and functionally used in daily life. This article highlights 10 key principles that provide the foundation for rehabilitation following nerve transfer surgery after a brachial plexus injury. Due to the shortcomings of the current evidence base for nerve transfer rehabilitation, we have included our anecdotal experience to augment the existing literature. It is important to have a collaborative surgeon–therapist relationship to communicate regarding operative details, expected timelines for reinnervation, patient needs, and realistic expectations. We provide examples of how to tailor the exercise program to synergistically recruit both the donor and target muscle action, including how to appropriately advance exercises based on the current level of nerve return. We also discuss the role that fatigue plays in denervated muscle and how fatigue may affect the exercise demands placed on the target muscle during specific stages of recovery. [ABSTRACT FROM AUTHOR]

Nanoscale extracellular vesicles (EVs), consisting of exomers, exosomes and microvesicles/ectosomes, have been extensively investigated in the last 20 years, although their biological role is still something of a mystery. EVs are involved in the transfer of lipids, nucleic acids and proteins from donor to recipient cells or distant organs as well as regulating cell-cell communication and signaling. Thus, EVs are important in intercellular communication and this is not limited to sister cells, but may also mediate the crosstalk between different cell types even over long distances. EVs play crucial functions in both cellular homeostasis and the pathogenesis of diseases, and since their contents reflect the status of the donor cell, they represent an additional valuable source of information for characterizing complex biological processes. Recent advances in isolation and analytical methods have led to substantial improvements in both characterizing and engineering EVs, leading to their use either as novel biomarkers for disease diagnosis/prognosis or even as novel therapies. Due to their capacity to carry biomolecules, various EV-based therapeutic applications have been devised for several pathological conditions, including eye diseases. In the eye, EVs have been detected in the retina, aqueous humor, vitreous body and also in tears. Experiences with other forms of intraocular drug applications have opened new ways to use EVs in the treatment of retinal diseases. We here provide a comprehensive summary of the main in vitro , in vivo , and ex vivo literature-based studies on EVs' role in ocular physiological and pathological conditions. We have focused on age-related macular degeneration, diabetic retinopathy, glaucoma, which are common eye diseases leading to permanent blindness, if not treated properly. In addition, the putative use of EVs in retinitis pigmentosa and other retinopathies is discussed. Finally, we have reviewed the potential of EVs as therapeutic tools and/or biomarkers in the above-mentioned retinal disorders. Evidence emerging from experimental disease models and human material strongly suggests future diagnostic and/or therapeutic exploitation of these biological agents in various ocular disorders with a good possibility to improve the patient's quality of life. [Display omitted] [ABSTRACT FROM AUTHOR]

Randomized controlled trials comparing the effectiveness of 5-fluorouracil cream, methylaminolevulinate photodynamic therapy (MAL-PDT) and surgical excision in patients with Bowen's disease are lacking. In this multicenter noninferiority trial, patients with a histologically proven Bowen's disease of 4-40 mm were randomly assigned to excision with 5 mm margin, 5% 5-fluorouracil cream twice daily for 4 weeks, or 2 sessions of MAL-PDT with 1 week interval. The primary outcome was the proportion of patients with sustained clearance at 12 months after treatment. A noninferiority margin of 22% was used. Between May 2019 and January 2021, 250 patients were randomized. The proportion of patients with sustained clearance was 97.4% (75/77) after excision, 85.7% (66/77) after 5-fluorouracil, and 82.1% (64/78) after MAL-PDT. Absolute differences were −11.7% (95% CI −18.9 to −4.5; P =.0049) for 5-fluorouracil versus excision and −15.4% (95% CI −23.1 to −7.6; P =.00078) for MAL-PDT versus excision. Both noninvasive treatments significantly more often led to good or excellent cosmetic outcome. Based on our predefined noninferiority margin of 22%, 5-fluorourcail is noninferior to excision and associated with better cosmetic outcome. For MAL-PDT noninferiority to excision cannot be concluded. Therefore, 5-fluorouracil should be preferred over excision and MAL-PDT in treatment of Bowen's disease. [ABSTRACT FROM AUTHOR]

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Extracellular vesicles (EVs), encompassing exosomes, microvesicles (MVs), and apoptotic bodies (ABs), are cell-derived heterogeneous nanoparticles with a pivotal role in intercellular communication. EVs are enclosed by a lipid-bilayer membrane to escape enzymatic degradation. EVs contain various functional molecules (e.g., nucleic acids, proteins, lipids and metabolites) which can be transferred from donor cells to recipient cells. EVs provide many advantages including accessibility, modifiability and easy storage, stability, biocompatibility, heterogeneity and they readily penetrate through biological barriers, making EVs ideal and promising candidates for diagnosis/prognosis biomarkers and therapeutic tools. Recently, EVs were implicated in both physiological and pathophysiological settings of cardiovascular system through regulation of cell-cell communication. Numerous studies have reported a role for EVs in the pathophysiological progression of cardiovascular diseases (CVDs) and have evaluated the utility of EVs for the diagnosis/prognosis and therapeutics of CVDs. In this review, we summarize the biology of EVs, evaluate the perceived biological function of EVs in different CVDs along with a consideration of recent progress for the application of EVs in diagnosis/prognosis and therapies of CVDs. [Display omitted] • Extracellular vesicles (EVs) regulate diverse pathological process via transporting various bioactive molecules. • The content alteration of EVs plays a pivotal role in regulating the development of various cardiovascular diseases. • EVs with specific content combinations are promising tools for early diagnosis of cardiovascular diseases. • EVs have potential therapeutic applications in various cardiovascular diseases. [ABSTRACT FROM AUTHOR]