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Huntington's disease (HD) is an autosomal dominant inherited disease, which leads to motor, cognitive and psychiatric symptoms. The diagnosis can be confirmed by genetic testing for extended CAG repeats in the Huntingtin gene. Mental and behavioral symptoms are common in HD and can appear several years before the onset of motor symptoms. The psychiatric symptoms include apathy, depression, anxiety, obsessive-compulsive symptoms and, in some cases, psychoses and aggression. These are currently restricted to symptomatic treatment as disease-modifying treatment approaches are still under investigation. The current clinical practice is based on expert opinions as well as experience with the treatment of similar symptoms in other neurological and mental health diseases. This article provides an overview of the complex psychiatric manifestations of HD, the diagnostic options and the established pharmacological and nonpharmacological treatment approaches. [ABSTRACT FROM AUTHOR]

Inhibiting diacylglycerol acetyltransferase (DGAT1, DGAT2) enzymes (iDGAT1, iDGAT2), involved in triglyceride (TG) synthesis, improves hepatic steatosis in metabolic dysfunction-associated steatotic liver disease (MASLD) patients. However, their potential synergism in disease onset (SLD) and progression (metabolic dysfunction-associated steatohepatitis, fibrosis) has been poorly explored. We investigated iDGAT1 and iDGAT2 efficacy, alone or combined (iDGAT1/2) on fat accumulation and hepatocellular injury in hepatocytes (HepG2) and on fibrogenic processes in hepatic stellate cells (LX2). We further tested whether the addition of MitoQ antioxidant to iDGAT1/2 would enhance their effects. SLD and MASH conditions were reproduced in vitro by supplementing Dulbecco's Modified Eagle's Medium (DMEM) with palmitic/oleic acids (PAOA) alone (SLD-medium), or plus Lipopolisaccaride (LPS), fructose, and glucose (MASH-medium). In SLD-medium, iDGAT1 and iDGAT2 individually, and even more in combination, reduced TG synthesis in HepG2 cells. Markers of hepatocellular damage were slightly decreased after single iDGAT exposure. Conversely, iDGAT1/2 counteracted ER/oxidative stress and inflammation and enhanced mitochondrial Tricarboxylic acid cycle (TCA) and respiration. In HepG2 cells under a MASH-like condition, only iDGAT1/2 effectively ameliorated TG content and oxidative and inflammatory mediators, further improving bioenergetic balance. LX2 cells, challenged with SLD/MASH media, showed less proliferation and slower migration rates in response to iDGAT1/2 drugs. MitoQ combined with iDGAT1/2 improved cell viability and dampened free fatty acid release by stimulating β-oxidation. Dual DGAT inhibition combined with antioxidants open new perspectives for MASLD management. [ABSTRACT FROM AUTHOR]

Recent advancements have highlighted the crucial role of G-protein-coupled receptors (GPCRs) in dermal injuries, chronic inflammatory dermatoses, and cutaneous malignancies, revealing new therapeutic targets. Targeting transient receptor potential (TRP) channel proteins and GPCR complexes enables the regulation of calcium ion influx, which in turn modulates inflammatory responses in the skin. The utilization of cryo-electron microscopy has significantly advanced our understanding of GPCR structures and molecular binding mechanisms in skin diseases. Advances in understanding GPCR regulation in the development of skin diseases unveil therapeutic possibilities. Achieving the efficacy and specificity of G-protein-coupled receptor (GPCR) targeting-drugs in the skin remains challenging. Understanding the molecular mechanism underlying GPCR dysfunction is crucial for developing targeted therapies. Recent advances in genetic, signal transduction, and structural studies have significantly improved our understanding of cutaneous GPCR functions in both normal and pathological states. In this review, we summarize recent discoveries of pathogenic GPCRs in dermal injuries, chronic inflammatory dermatoses, cutaneous malignancies, as well as the development of potent potential drugs. We also discuss targeting of cutaneous GPCR complexes via the transient receptor potential (TRP) channel and structure elucidation, which provide new opportunities for therapeutic targeting of GPCRs involved in skin disorders. These insights are expected to lead to more effective and specific treatments for various skin conditions. [ABSTRACT FROM AUTHOR]

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Background. This article presents the results of a pilot study investigating patients' satisfaction thresholds for pharmacological outcomes versus surgical outcomes. Materials and methods. A total of 150 participants were presented with two hypothetical scenarios depicting either pharmacological therapy or surgical interventions. Each scenario described a potential outcome, from a 10% clinical improvement (value 10) to a 100% clinical improvement (value 100) and asked participants to indicate the satisfactory level they would find acceptable. Conclusions. The results revealed distinct patterns in satisfaction thresholds between the two treatment modalities. Between the 150 participants, 52,7% were male and 47,3% female. We also identified a total of 28,8% whom were healthcare workers. Overall, the results for the pharmacological therapy outcomes observed a mean of 60,88 with a standard deviation of 22,77, a median of 60 and a mode of 70; while for the surgical outcomes the mean was 67,81 with a standard deviation of 23,03, the median 85 and the mode 80. We also observed that for the pharmacological therapy outcomes healthcare workers had a lower satisfactory cut off compared to non-healthcare workers. Another interesting finding was that for pharmacological therapy outcomes individuals under 50 y/o had a higher satisfactory cut off compared to individuals over 50 y/o, while for the surgical outcomes we got opposite results. Overall, the findings of this pilot study, even if limited, demonstrated higher minimum satisfaction expectations for surgical outcomes compared to pharmacological therapy outcomes. Specifically, participants tended to require more favorable results and outcomes from surgical interventions to meet their minimum satisfaction criteria. [ABSTRACT FROM AUTHOR]

Background: This systematic review investigated the impact of familial factors on individuals aged 10–17 who have clinical signs or symptoms of eating disorders. Simultaneously, it scrutinized the involvement of the family in therapy, as well as other forms of intervention. Methods: The PsycINFO, PubMed, and Scopus databases were used to search for research material comprehensively. After applying specific criteria, 46 articles were deemed suitable and included in the systematic review. The study comprised a cohort of 4794 adolescents who received a diagnosis of either Anorexia Nervosa (AN), Bulimia Nervosa (BN), or Binge-Eating Disorder (BED). In addition, controls were utilized for 1187 adolescents, 1563 parents, 1809 siblings, and 11 other relatives. Results: The connection between family factors and eating disorders is primarily determined by the families' level of functioning, satisfaction with the family dynamic, parents' attitudes toward their children, and the role of food within the family system. Family Therapy was the most used psychotherapeutic approach in the treatment of AN. The incidence of reports in BN closely paralleled that of Cognitive–Behavioral Therapy (CBT) models. Articles about (Enhanced) CBT were exclusively associated with BED. Conclusions: Family-based approaches are crucial in comprehending, preventing, and addressing eating disorders in adolescents. Incorporating the study of family dynamics and actively engaging families in the treatment process can significantly enhance recovery rates and decrease the occurrence of relapses. [ABSTRACT FROM AUTHOR]

To date, more than 400 types of human papillomavirus (HPV) have been identified. Despite the creation of effective prophylactic vaccines against the most common genital HPVs, the viruses remain among the most prevalent pathogens found in humans. According to WHO data, they are the cause of 5% of all cancers. Even more frequent are persistent and recurrent benign lesions such as genital and common warts. HPVs are resistant to many disinfectants and relatively unsusceptible to external conditions. There is still no drug available to inhibit viral replication, and treatment is based on removing lesions or stimulating the host immune system. This paper presents the systematics of HPV and the differences in HPV structure between different genetic types, lineages, and sublineages, based on the literature and GenBank data. We also present the pathogenesis of diseases caused by HPV, with a special focus on the role played by E6, E7, and other viral proteins in the development of benign and cancerous lesions. We discuss further prospects for the treatment of HPV infections, including, among others, substances that block the entry of HPV into cells, inhibitors of viral early proteins, and some substances of plant origin that inhibit viral replication, as well as new possibilities for therapeutic vaccines. [ABSTRACT FROM AUTHOR]

AbstractDiabetic wound is one of the most challenge in healthcare, requiring innovative approaches to promote efficient healing. In recent years, lipid nanoparticle-based drug delivery systems have emerged as a promising strategy for enhancing diabetic wound repair by stimulating angiogenesis. These nanoparticles offer unique advantages, including improved drug stability, targeted delivery, and controlled release, making them promising in enhancing the formation of new blood vessels. In this review, we summarize the emerging advances in the utilization of lipid nanoparticles to deliver angiogenic agents and promote angiogenesis in diabetic wounds. Furthermore, we provide an in-depth exploration of key aspects, including the intricate design and fabrication of lipid nanoparticles, their underlying mechanisms of action, and a comprehensive overview of preclinical studies. Moreover, we address crucial considerations pertaining to safety and the translation of these innovative systems into clinical practice. By synthesizing and analyzing the available knowledge, our review offers valuable insights into the future prospects and challenges associated with utilizing the potential of lipid nanoparticle-based drug delivery systems for promoting robust angiogenesis in the intricate process of diabetic wound healing. [ABSTRACT FROM AUTHOR]

Problematic sexual arousal (PSA) is an umbrella term to describe a range of clinical presentations related to excessive sexual thinking (e.g., sexual preoccupation) and sexual behavior (e.g., hypersexuality). Although such concepts are known to affect sexual recidivism among individuals convicted of sexual offences, PSA is not routinely or directly targeted in offending behavior programs in England and Wales. However, in recent years, there have been moves to incorporate pharmacological interventions for addressing this among people with sexual offence histories. Although some work to understand the experiences of those taking SSRI medication for this purpose has emerged, little is known about the experiences of service users taking anti-androgen medication. In this study, we interviewed all individuals in prison taking anti-androgens for the treatment of problematic sexual arousal following convictions for sexual offences in England at the time of data collection (N = 10). Using a phenomenologically oriented thematic analysis, we established themes pertaining to "Differing needs: Motivations for treatment," "Medication as a risk management strategy," and how the medication helped the men in their pursuit of "Discovering a 'new me'." This work contributes important knowledge to inform the development of ethical and effective prescribing of anti-androgen medication with this population and offer recommendations for both future research and the development of clinical practice. [ABSTRACT FROM AUTHOR]

Introduction: Polycystic ovary syndrome (PCOS) is a complex endocrine condition affecting women of reproductive age. It is characterised by insulin resistance and is a risk for type 2 diabetes mellitus (T2DM). The aim of this study was to review the literature on the effect of pioglitazone and rosiglitazone in women with PCOS. Methods: We searched PubMed, MEDLINE, Scopus, Embase, Cochrane Library and the Web of Science in April 2020 and updated in March 2023. Studies were deemed eligible if they were randomised controlled trials (RCTs) reporting the effect of pioglitazone and rosiglitazone in PCOS. The study follows the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Two reviewers independently extracted data and assessed the risk of bias using the Cochrane risk of bias tool. Results: Out of 814 initially retrieved citations, 24 randomised clinical trials (RCTs) involving 976 participants were deemed eligible. Among women with PCOS, treatment with rosiglitazone compared to metformin resulted in a significant increase in the mean body weight (mean difference (MD) 1.95 kg; 95% CI 0.03–3.87, p = 0.05). Metformin treatment was associated with a reduction in mean body mass index (BMI) compared to pioglitazone (MD 0.85 kg/m2; 95% CI 0.13–1.57, p = 0.02). Both pioglitazone compared to placebo (MD 2.56 kg/m2; 95% CI 1.77–3.34, p < 0.00001) and rosiglitazone compared to metformin (MD 0.74 kg/m2; 95% CI 0.07–1.41, p = 0.03) were associated with a significant increase in BMI. Treatment with pioglitazone compared to placebo showed a significant reduction in triglycerides (MD − 0.20 mmol/L; 95% CI − 0.38 to − 0.03, p = 0.02) and fasting insulin levels (MD − 11.47 mmol/L; 95% CI − 20.20, − 2.27, p = 0.01). Rosiglitazone compared to metformin was marginally significantly associated with a reduction in the luteinising hormone (LH) (MD − 0.62; 95% CI − 1.25–0.00, p = 0.05). Conclusion: Both pioglitazone and rosiglitazone were associated with significant increases in body weight and BMI when compared with metformin or placebo. Pioglitazone significantly reduced triglycerides and fasting insulin when compared with placebo while rosiglitazone showed a modest reduction of LH when compared with metformin. PROSPERO Registration No.: CRD42020178783. [ABSTRACT FROM AUTHOR]

Aims Patients with persistent atrial fibrillation (AF) experience 50% recurrence despite pulmonary vein isolation (PVI), and no consensus is established for secondary treatments. The aim of our i-STRATIFICATION study is to provide evidence for stratifying patients with AF recurrence after PVI to optimal pharmacological and ablation therapies, through in silico trials. Methods and results A cohort of 800 virtual patients, with variability in atrial anatomy, electrophysiology, and tissue structure (low-voltage areas, LVAs), was developed and validated against clinical data from ionic currents to electrocardiogram. Virtual patients presenting AF post-PVI underwent 12 secondary treatments. Sustained AF developed in 522 virtual patients after PVI. Second ablation procedures involving left atrial ablation alone showed 55% efficacy, only succeeding in the small right atria (<60 mL). When additional cavo-tricuspid isthmus ablation was considered, Marshall-PLAN sufficed (66% efficacy) for the small left atria (<90 mL). For the bigger left atria, a more aggressive ablation approach was required, such as anterior mitral line (75% efficacy) or posterior wall isolation plus mitral isthmus ablation (77% efficacy). Virtual patients with LVAs greatly benefited from LVA ablation in the left and right atria (100% efficacy). Conversely, in the absence of LVAs, synergistic ablation and pharmacotherapy could terminate AF. In the absence of ablation, the patient's ionic current substrate modulated the response to antiarrhythmic drugs, being the inward currents critical for optimal stratification to amiodarone or vernakalant. Conclusion In silico trials identify optimal strategies for AF treatment based on virtual patient characteristics, evidencing the power of human modelling and simulation as a clinical assisting tool. [ABSTRACT FROM AUTHOR]

Musculoskeletal disorders are characterized by several impairments, including pain, affecting muscles, bones, joints and adjacent connective tissue, resulting in temporary or permanent functional limitations and disability. Musculoskeletal pain is particularly prevalent worldwide and greatly impacts the quality of life, social participation and economic burden. To date, several issues persist about the classification of musculoskeletal pain and its management strategies and resources. The treatment of musculoskeletal pain conditions is complex and often requires a multimodal approach, including pharmacological and non-pharmacological therapy that might be ineffective in many cases, resulting in poor patient satisfaction and controversial expectations about the potential benefits of available interventions. This manuscript provides an overview of unmet needs in managing musculoskeletal pain, particularly focusing on pharmacotherapeutic pitfalls in this context. [ABSTRACT FROM AUTHOR]

Treatment-resistant depression (TRD) is a complex disorder. Although no standardized definition has been established to date, there are promising and well-established treatment options for the condition. Looking at the current pharmacological and neuromodulatory strategies, there is an urgent need for fast-acting and well-tolerated treatment options. The search for new mechanisms of action goes beyond the monoamine hypothesis. For example, esketamine is already an established treatment method that is fast-acting and well tolerated, while psychedelics or esmethadone are currently still undergoing clinical trials. Compounds that can be used off-label, such as dextromethorphan or anti-inflammatory strategies are also presented. Pharmacological approaches that focus on the modulation of the glutamatergic system or belong to the class of psychedelics, appear to be of particular importance for current research and development. These particularly include substances that rapidly exert clinical effects and have a favorable side-effect profile. [ABSTRACT FROM AUTHOR]

This document is an editorial published in the journal Frontiers in Psychiatry that discusses the topic of schizophrenia and the ongoing research efforts to understand and treat the disorder. The editorial emphasizes the diverse nature of schizophrenia and its relationship with other psychiatric disorders. It highlights the importance of identifying factors that can aid in accurate diagnosis and appropriate treatment. The document also mentions several reviews that explore non-pharmacological treatment options, such as virtual reality and cognitive remediation therapy, as well as alternative pharmacological treatments like palmitoylethanolamide (PEA). The editorial concludes by mentioning other reviews that investigate the symptoms and comorbidities of schizophrenia. Overall, the document suggests that a comprehensive and integrated approach to schizophrenia treatment is necessary, and further research is needed in areas that have received less attention. [Extracted from the article]

Binge eating disorder (BED) is the most common eating disorder categorized in the DSM-V, but it is often not diagnosed in patients with obesity because it can be difficult to detect in these patients who often have altered eating patterns. In this narrative review, we have highlighted the most recent findings in the screening, diagnosis, and treatment of patients with BED and obesity. The results of our search showed that many BED patients are not obese, and most people with obesity do not have binge behavior. In the diagnostic assessment of these patients, it is important to evaluate not only the clinical and nutritional status and the presence of medical comorbidities, but also the psychological signs and symptoms related to psychiatric comorbidities to define the appropriate diagnosis and the consequent level of treatment. Well-tolerated drugs with action on both body weight and binges can be useful as a second-line complement to cognitive behavioral therapy (CBT). Specific guidelines are needed to obtain consensus on appropriate recommendations in patients with obesity and BED approaching bariatric surgery, taking into account not only weight reduction and clinical data, but also eating behaviors. Identification of BED is important for targeting individuals at high risk of obesity, adverse metabolic patterns, and cardiovascular disease. The challenge is to also achieve lasting weight loss in patients with BED and concomitant obesity.

Binge eating disorder (BED) is the most common eating disorder categorized in the DSM-V, but it is often not diagnosed in patients with obesity because it can be difficult to detect in these patients who often have altered eating patterns. In this narrative review, we have highlighted the most recent findings in the screening, diagnosis, and treatment of patients with BED and obesity. The results of our search showed that many BED patients are not obese, and most people with obesity do not have binge behavior. In the diagnostic assessment of these patients, it is important to evaluate not only the clinical and nutritional status and the presence of medical comorbidities, but also the psychological signs and symptoms related to psychiatric comorbidities to define the appropriate diagnosis and the consequent level of treatment. Well-tolerated drugs with action on both body weight and binges can be useful as a second-line complement to cognitive behavioral therapy (CBT). Specific guidelines are needed to obtain consensus on appropriate recommendations in patients with obesity and BED approaching bariatric surgery, taking into account not only weight reduction and clinical data, but also eating behaviors. Identification of BED is important for targeting individuals at high risk of obesity, adverse metabolic patterns, and cardiovascular disease. The challenge is to also achieve lasting weight loss in patients with BED and concomitant obesity. [ABSTRACT FROM AUTHOR]

Obesity, marked by abnormal fat accumulation, poses significant health risks, necessitating effective therapeutic interventions. The focus of this review is to elucidate the importance of glucagon-like peptide 1 (GLP-1) receptor-binding medications in addressing obesity-related health deteriorations. Exploring the mechanisms, efficacy, and safety profiles, this review comprehensively assesses medications selectively or non-selectively binding the GLP-1 receptor for obesity treatment. A meticulous analysis of phase 2 and phase 3 data positions retatrutide, CagriSema, survudotide, tirzepatide, semaglutide, and liraglutide in order of effectiveness. While showcasing their efficacy and safety, the review acknowledges the ongoing phase 3 studies, highlighting the need for further exploration of contraindications, dosage, and potential adverse effects to inform personalized treatment decisions. The ongoing anticipation of long-term benefits, particularly sustained weight loss and cardiovascular outcomes, underscores the significance of future treatment algorithms for addressing the disease of obesity. [ABSTRACT FROM AUTHOR]

The heart is the most energy-demanding organ throughout the whole body. Perturbations or failure in energy metabolism contributes to heart failure (HF), which represents the advanced stage of various heart diseases. The poor prognosis and huge economic burden associated with HF underscore the high unmet need to explore novel therapies targeting metabolic modulators beyond conventional approaches focused on neurohormonal and hemodynamic regulators. Emerging evidence suggests that alterations in metabolic substrate reliance, metabolic pathways, metabolic by-products, and energy production collectively regulate the occurrence and progression of HF. In this review, we provide an overview of cardiac metabolic remodeling, encompassing the utilization of free fatty acids, glucose metabolism, ketone bodies, and branched-chain amino acids both in the physiological condition and heart failure. Most importantly, the latest advances in pharmacological interventions are discussed as a promising therapeutic approach to restore cardiac function, drawing insights from recent basic research, preclinical and clinical studies. [ABSTRACT FROM AUTHOR]

Stroke results in local neural disconnection and brain-wide neuronal network dysfunction leading to neurological deficits. Beyond the hyper-acute phase of ischaemic stroke, there is no clinically-approved pharmacological treatment that alleviates sensorimotor impairments. Functional recovery after stroke involves the formation of new or alternative neuronal circuits including existing neural connections. The type-5 metabotropic glutamate receptor (mGluR5) has been shown to modulate brain plasticity and function and is a therapeutic target in neurological diseases outside of stroke. We investigated whether mGluR5 influences functional recovery and network reorganization rodent models of focal ischaemia. Using multiple behavioural tests, we observed that treatment with negative allosteric modulators (NAMs) of mGluR5 (MTEP, fenobam and AFQ056) for 12 days, starting 2 or 10 days after stroke, restored lost sensorimotor functions, without diminishing infarct size. Recovery was evident within hours after initiation of treatment and progressed over the subsequent 12 days. Recovery was prevented by activation of mGluR5 with the positive allosteric modulator VU0360172 and accelerated in mGluR5 knock-out mice compared with wild-type mice. After stroke, multisensory stimulation by enriched environments enhanced recovery, a result prevented by VU0360172, implying a role of mGluR5 in enriched environment-mediated recovery. Additionally, MTEP treatment in conjunction with enriched environment housing provided an additive recovery enhancement compared to either MTEP or enriched environment alone. Using optical intrinsic signal imaging, we observed brain-wide disruptions in resting-state functional connectivity after stroke that were prevented by mGluR5 inhibition in distinct areas of contralesional sensorimotor and bilateral visual cortices. The levels of mGluR5 protein in mice and in tissue samples of stroke patients were unchanged after stroke. We conclude that neuronal circuitry subserving sensorimotor function after stroke is depressed by a mGluR5-dependent maladaptive plasticity mechanism that can be restored by mGluR5 inhibition. Post-acute stroke treatment with mGluR5 NAMs combined with rehabilitative training may represent a novel post-acute stroke therapy. [ABSTRACT FROM AUTHOR]

Pyrin is a cytosolic protein encoded by the MEFV gene, predominantly expressed in innate immune cells. Upon activation, it forms an inflammasome, a multimolecular complex that enables the activation and secretion of IL-1β and IL-18. In addition, the Pyrin inflammasome activates Gasdermin D leading to pyroptosis, a highly pro-inflammatory cell death. Four autoinflammatory syndromes are associated with Pyrin inflammasome dysregulation: familial Mediterranean fever, hyper IgD syndrome/mevalonate kinase deficiency, pyrin-associated autoinflammation with neutrophilic dermatosis, and pyogenic arthritis, pyoderma gangrenosum, and acne syndrome. In this review, we discuss recent advances in understanding the molecular mechanisms regulating the two-step model of Pyrin inflammasome activation. Based on these insights, we discuss current pharmacological options and identify a series of existing molecules with therapeutic potential for the treatment of pyrin-associated autoinflammatory syndromes. [ABSTRACT FROM AUTHOR]

Abstract The social impact of glaucoma is worth of note: primary open-angle glaucoma (POAG) is one of the leading causes of irreversible blindness worldwide, affecting some 68.56 million people with overall prevalence of 2.4%. Since one of the main risk factors for the development of POAG is the increase of intraocular pressure (IOP) causing retinal ganglion cells death, the medical treatment of POAG consists in the use of drugs endowed with neuroprotective effect and able to reduce IOP. These drugs include beta-blockers, prostaglandin analogues, carbonic anhydrase inhibitors, alpha or cholinergic agonists and rho kinase inhibitors. However, not all the patients respond to the same extent to the therapy in terms of efficacy and safety. Genetics and genome wide association studies have highlighted the occurrence of mutations and polymorphisms influencing the predisposition to develop POAG and its phenotype, as well as affecting the response to pharmacological treatment. The present systematic review and meta-analysis aims at identifying genetic variants and at verifying whether these can influence the responsiveness of patients to therapy for efficacy and safety. It follows the most updated Preferred Reporting Items for Systematic reviews and Meta-Analyses 2020 recommendations. The literature search was conducted consulting the most relevant scientific databases, i.e. PubMed/MEDLINE, Scopus, Web of Science and Public Health Genomics and Precision Health Knowledge Base up to June 14th, 2023. The search retrieved 1026 total records, among which eight met the eligibility criteria for inclusion in the analysis. The results demonstrated that the most investigated pharmacogenetic associations concern latanoprost and timolol, and that efficacy was studied more in depth than safety. Moreover, the heterogeneity of design and paucity of studies prompt further investigation in randomized clinical trials. In fact, adequately powered and designed pharmacogenetic association studies are needed to provide body of evidence with good certainty for a more appropriate use of medical therapy in POAG. PROSPERO registration: CRD42023434867.

Inhibiting diacylglycerol acetyltransferase (DGAT1, DGAT2) enzymes (iDGAT1, iDGAT2), involved in triglyceride (TG) synthesis, improves hepatic steatosis in metabolic dysfunction-associated steatotic liver disease (MASLD) patients. However, their potential synergism in disease onset (SLD) and progression (metabolic dysfunction-associated steatohepatitis, fibrosis) has been poorly explored. We investigated iDGAT1 and iDGAT2 efficacy, alone or combined (iDGAT1/2) on fat accumulation and hepatocellular injury in hepatocytes (HepG2) and on fibrogenic processes in hepatic stellate cells (LX2). We further tested whether the addition of MitoQ antioxidant to iDGAT1/2 would enhance their effects. SLD and MASH conditions were reproduced in vitro by supplementing Dulbecco’s Modified Eagle’s Medium (DMEM) with palmitic/oleic acids (PAOA) alone (SLD-medium), or plus Lipopolisaccaride (LPS), fructose, and glucose (MASH-medium). In SLD-medium, iDGAT1 and iDGAT2 individually, and even more in combination, reduced TG synthesis in HepG2 cells. Markers of hepatocellular damage were slightly decreased after single iDGAT exposure. Conversely, iDGAT1/2 counteracted ER/oxidative stress and inflammation and enhanced mitochondrial Tricarboxylic acid cycle (TCA) and respiration. In HepG2 cells under a MASH-like condition, only iDGAT1/2 effectively ameliorated TG content and oxidative and inflammatory mediators, further improving bioenergetic balance. LX2 cells, challenged with SLD/MASH media, showed less proliferation and slower migration rates in response to iDGAT1/2 drugs. MitoQ combined with iDGAT1/2 improved cell viability and dampened free fatty acid release by stimulating β-oxidation. Dual DGAT inhibition combined with antioxidants open new perspectives for MASLD management.

To date, more than 400 types of human papillomavirus (HPV) have been identified. Despite the creation of effective prophylactic vaccines against the most common genital HPVs, the viruses remain among the most prevalent pathogens found in humans. According to WHO data, they are the cause of 5% of all cancers. Even more frequent are persistent and recurrent benign lesions such as genital and common warts. HPVs are resistant to many disinfectants and relatively unsusceptible to external conditions. There is still no drug available to inhibit viral replication, and treatment is based on removing lesions or stimulating the host immune system. This paper presents the systematics of HPV and the differences in HPV structure between different genetic types, lineages, and sublineages, based on the literature and GenBank data. We also present the pathogenesis of diseases caused by HPV, with a special focus on the role played by E6, E7, and other viral proteins in the development of benign and cancerous lesions. We discuss further prospects for the treatment of HPV infections, including, among others, substances that block the entry of HPV into cells, inhibitors of viral early proteins, and some substances of plant origin that inhibit viral replication, as well as new possibilities for therapeutic vaccines.

Background: This systematic review investigated the impact of familial factors on individuals aged 10–17 who have clinical signs or symptoms of eating disorders. Simultaneously, it scrutinized the involvement of the family in therapy, as well as other forms of intervention. Methods: The PsycINFO, PubMed, and Scopus databases were used to search for research material comprehensively. After applying specific criteria, 46 articles were deemed suitable and included in the systematic review. The study comprised a cohort of 4794 adolescents who received a diagnosis of either Anorexia Nervosa (AN), Bulimia Nervosa (BN), or Binge-Eating Disorder (BED). In addition, controls were utilized for 1187 adolescents, 1563 parents, 1809 siblings, and 11 other relatives. Results: The connection between family factors and eating disorders is primarily determined by the families’ level of functioning, satisfaction with the family dynamic, parents’ attitudes toward their children, and the role of food within the family system. Family Therapy was the most used psychotherapeutic approach in the treatment of AN. The incidence of reports in BN closely paralleled that of Cognitive–Behavioral Therapy (CBT) models. Articles about (Enhanced) CBT were exclusively associated with BED. Conclusions: Family-based approaches are crucial in comprehending, preventing, and addressing eating disorders in adolescents. Incorporating the study of family dynamics and actively engaging families in the treatment process can significantly enhance recovery rates and decrease the occurrence of relapses.

Background: Chronic pain is one of the most challenging diseases for physicians as its etiology and manifestations can be extremely varied. Many guidelines have been published and many therapeutic options are nowadays available for the different types of pain. Given the enormous amount of information that healthcare providers must handle, it is not always simple to keep in mind all the phases and strategies to manage pain. We here present the acronym PATIENT (P: patient's perception; A: assessment; T: tailored approach; I: iterative evaluation; E: education; N: non-pharmacological approach; T: team), a bundle which can help to summarize all the steps to follow in the management of chronic pain. Methods: We performed a PubMed search with a list of terms specific for every issue of the bundle; only English articles were considered. Results: We analyzed the literature investigating these topics to provide an overview of the available data on each bundle's issue; their synthesis lead to an algorithm which may allow healthcare providers to undertake every step of a patient's evaluation and management. Discussion: Pain management is very complex; our PATIENT bundle could be a guide to clinicians to optimize a patient's evaluation and treatment. [ABSTRACT FROM AUTHOR]

This prospectively registered systematic review and meta-analysis examines whether exercise (EX) training has an additive effect to osteoanabolic and/or antiresorptive pharmacological therapy (PT) in people with osteoporosis on bone mineral density (BMD), bone turnover markers (BTMs), fracture healing, and fractures. Four databases (inception to 6 May 2022), 5 trial registries, and reference lists were searched. Included were randomized controlled trials comparing the effect of EX + PT vs. PT with regard to BMD, BTM, fracture healing, and fractures. Risk of bias was assessed using the Cochrane RoB2 and certainty of evidence by the GRADE approach. Random-effects meta-analysis with Hartung-Knapp-Sidik-Jonkman adjustment was used to estimate standardized mean differences and 95% confidence intervals. Out of 2593 records, five RCTs with 530 participants were included. Meta-analysis showed with very low certainty evidence and wide confidence intervals that EX + PT compared to PT had larger effect sizes for BMD at 12 months at the hip (SMD [95%CI]: 0.18 [− 1.71; 2.06], n = 3 studies), tibia (0.25 [− 4.85; 5.34], n = 2), lumbar spine (0.20 [− 1.15; 1.55], n = 4), and forearm (0.05 [− 0.35; 0.46], n = 3), but not femoral neck (− 0.03 [− 1.80; 1.75], n = 3). Furthermore, no improvement was revealed for BTM such as bone ALP (− 0.68 [− 5.88; 4.53], n = 3), PINP (− 0.74 [− 10.42; 8.93], n = 2), and CTX-I (− 0.69 [− 9.61; 8.23], n = 2), but with very wide confidence intervals. Three potentially relevant ongoing trials were identified via registries. No data were found for fracture healing or fracture outcomes. It remains unclear whether EX has an additive impact to PT in people with osteoporosis. High-quality, adequately powered, targetted RCTs are required. Protocol Registration: PROSPERO CRD42022336132. [ABSTRACT FROM AUTHOR]

The social impact of glaucoma is worth of note: primary open-angle glaucoma (POAG) is one of the leading causes of irreversible blindness worldwide, affecting some 68.56 million people with overall prevalence of 2.4%. Since one of the main risk factors for the development of POAG is the increase of intraocular pressure (IOP) causing retinal ganglion cells death, the medical treatment of POAG consists in the use of drugs endowed with neuroprotective effect and able to reduce IOP. These drugs include beta-blockers, prostaglandin analogues, carbonic anhydrase inhibitors, alpha or cholinergic agonists and rho kinase inhibitors. However, not all the patients respond to the same extent to the therapy in terms of efficacy and safety. Genetics and genome wide association studies have highlighted the occurrence of mutations and polymorphisms influencing the predisposition to develop POAG and its phenotype, as well as affecting the response to pharmacological treatment. The present systematic review and meta-analysis aims at identifying genetic variants and at verifying whether these can influence the responsiveness of patients to therapy for efficacy and safety. It follows the most updated Preferred Reporting Items for Systematic reviews and Meta-Analyses 2020 recommendations. The literature search was conducted consulting the most relevant scientific databases, i.e. PubMed/MEDLINE, Scopus, Web of Science and Public Health Genomics and Precision Health Knowledge Base up to June 14th, 2023. The search retrieved 1026 total records, among which eight met the eligibility criteria for inclusion in the analysis. The results demonstrated that the most investigated pharmacogenetic associations concern latanoprost and timolol, and that efficacy was studied more in depth than safety. Moreover, the heterogeneity of design and paucity of studies prompt further investigation in randomized clinical trials. In fact, adequately powered and designed pharmacogenetic association studies are needed to provide body of evidence with good certainty for a more appropriate use of medical therapy in POAG. PROSPERO registration: CRD42023434867. [ABSTRACT FROM AUTHOR]

Persistent, acute, chronic pain. The healthcare system must face a considerable challenge in addressing pain, which affects a large portion of patients. The therapies and protocols applied very often lack effectiveness for the patient, and the health system tries to find a solution that can adequately treat the pain. At the moment, we cannot reverse and definitively treat this major problem. The debate within the health system and outside it is permanent. [ABSTRACT FROM AUTHOR]

Background: Knee osteoarthritis is a degenerative and inflammatory disease causing pain and worsening patients’ quality of life. Various conservative treatment options exist, but a gap between scientific evidence and clinical practice is still present. The aim of this prospective multicenter observational study is to describe the real outpatient territorial management of patients with knee osteoarthritis and to analyze the correlation between the anthropometric and clinical characteristics of the population of patients suffering from symptomatic knee osteoarthritis who were screened in the national survey. Methods: The educational national project was divided into three modules: the first and the last through webinars; and the second held in daily practice. The participants had to register structured observations, which were then stored in a national database and analyzed in order to identify correlations. The subgroups were stratified by body composition, radiological severity of knee osteoarthritis, pain, and functional ability. Results: The project has been joined by 155 physicians, and 2.656 observations about real-world outpatients being treated for knee osteoarthritis in Italy were collected. Data relating to real-world pharmacological and rehabilitation therapies in correlation with body composition, the radiological severity of knee osteoarthritis, pain, and functional ability were reported. Conclusions: Currently, there are no standardized protocols using effective combinations of therapeutic exercises, physical agents, and medications to control the progression of knee osteoarthritis. This real-word national survey proved to be useful for describing the current state of the art of therapeutic management of knee osteoarthritis and for emphasizing the need to fill the gap between scientific evidence and clinical practice.

Abstract In recent years, emphasis has shifted from preventing and treating chronic obstructive pulmonary disease (COPD) to early prevention, early treatment, and disease stabilization, with the main goal of improving patients’ quality of life and reducing the frequency of acute exacerbations. This review summarizes pharmacological therapies for stable COPD.

Abstract The pharmacological management of nonspecific chronic low back pain (NCLBP) aims to restore patients’ daily activities and improve their quality of life. The management of NCLBP is not well codified and extremely heterogeneous, and residual symptoms are common. Pharmacological management should be considered as co-adjuvant to non-pharmacological therapy, and should be guided by the symptoms reported by the patients. Depending on the individual severity of NCLPB, pharmacological management may range from nonopioid to opioid analgesics. It is important to identify patients with generalized sensory hypersensitivity, who may benefit from dedicated therapy. This article provides an evidence-based overview of the principles of pharmacological management of NCLPB.

Introduction: Houttuynia cordata Thunb, a perennial plant indigenous to East Asia and the northeastern region of India, belongs to the Saururaceae family. Thriving in shaded environments, this plant is commonly harvested from moist habitats and local markets for research purposes, while also serving as a valuable resource in various sectors, including food, medicine, and commerce. This study aims to comprehensively explore the plant's morphology, distribution, traditional uses, nutritional composition, pharmacological characteristics, prominent bioactive compounds, therapeutic applications, and potential future prospects. Methods: The study involves an extensive review of existing literature and research findings concerning H. cordata. Information regarding its botanical characteristics, geographical distribution, and historical utilization is collected from diverse sources. Results: The research findings reveal that H. cordata possesses a wide range of therapeutic applications, including antibacterial, antifungal, antimicrobial, antiviral, anticancer, antimutagenic, anti-obesity, anti-corona, antioxidative, and anti-inflammatory activities. Notably, the significant bioactive compounds extracted from this plant, such as quercetin, quercitrin, and isoquercitrin, exhibit diverse and promising applications. Discussion: The study underscores the importance of H. cordata as a valuable natural resource with a rich history of traditional use and a burgeoning recognition for its diverse applications. Its therapeutic properties, ranging from combating infections to addressing chronic diseases like cancer, highlight its significance in modern medicine. The presence of major bioactive compounds, particularly flavonoids, further accentuates its potential in pharmaceutical and nutritional industries. Looking ahead, future research should prioritize in vitro and in vivo clinical experiments to advance our understanding of this plant's mechanisms of action and enhance its contribution to human healthcare.

Osteoarthritis (OA) is a chronic degenerative disease afflicting millions globally. Despite the development of numerous pharmacological treatments for OA, a substantial unmet need for effective therapies persists. The RANK/RANKL signaling pathway has emerged as a promising therapeutic target for OA, owing to its pivotal role in regulating osteoclast differentiation and activity. In this comprehensive review, we aim to elucidate the relevant mechanisms of OA mediated by RANK/RANKL signaling, including bone remodeling, inflammation, cartilage degradation, osteophyte formation, and pain sensitization. Furthermore, we discuss and summarize the cutting-edge strategies targeting RANK/RANKL signaling for OA therapy, encompassing approaches such as gene-based interventions and biomaterials-aided pharmacotherapy. In addition, we highlight the prevailing challenges associated with pharmacological OA treatments and explore potential future directions, approached through a clinical-translational lens.

Dystrophinopathies are x-linked muscular disorders which emerge from mutations in the Dystrophin gene, including Duchenne and Becker muscular dystrophy, and dilated cardiomyopathy. However, Duchenne muscular dystrophy interconnects with bone loss and osteoporosis, which are exacerbated by glucocorticoids therapy. Procedures for diagnosing dystrophinopathies include creatine kinase assay, haplotype analysis, Southern blot analysis, immunological analysis, multiplex PCR, multiplex ligation-dependent probe amplification, Sanger DNA sequencing, and next generation DNA sequencing. Pharmacological therapy for dystrophinopathies comprises glucocorticoids (prednisone, prednisolone, and deflazacort), vamorolone, and ataluren. However, angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), and β-blockers are the first-line to prevent dilated cardiomyopathy in dystrophinopathy patients. Duchenne muscular dystrophy gene therapy strategies involve gene transfer, exon skipping, exon reframing, and CRISPR gene editing. Eteplirsen, an antisense-oligonucleotide drug for skipping exon 51 from the Dystrophin gene, is available on the market, which may help up to 14% of Duchenne muscular dystrophy patients. There are various FDA-approved exon skipping drugs including ExonDys-51 for exon 51, VyonDys-53 and Viltolarsen for exon 53 and AmonDys-45 for exon 45 skipping. Other antisense oligonucleotide drugs in the pipeline include casimersen for exon 45, suvodirsen for exon 51, and golodirsen for exon 53 skipping. Advances in the diagnosis and therapy of dystrophinopathies offer new perspectives for their early discovery and care. [ABSTRACT FROM AUTHOR]

Background Clinician adherence to guideline recommendations in the pharmacological therapy of schizophrenia is important for favorable patient outcomes. To evaluate whether prescriptions followed the guidelines for pharmacological therapy of schizophrenia, we recently developed a summary indicator of multiple quality indicators: the individual fitness score (IFS). It is unclear whether adherence to the guidelines is related to patient outcomes. Here, we investigated correlations between the IFS values and psychotic symptoms in patients with schizophrenia. Methods We assessed whether patients' current prescriptions adhered to the guideline recommendations using the IFS in 47 patients with treatment-resistant schizophrenia (TRS) and 353 patients with non-TRS (total n = 400), respectively. We investigated correlations between the IFS and total scores and scores on the 5 subscales of the Positive and Negative Syndrome Scale (PANSS). Furthermore, we explored correlations between over 2-year longitudinal changes in IFS values and changes in psychotic symptoms in some patients (n = 77). Results We found significant negative correlation between the IFS and PANSS total score in all patients with schizophrenia (β = −0.18, P  = 9.80 × 10−5). The IFS was significantly and nominally negatively correlated with the PANSS total score in patients with non-TRS (Spearman's rho = −0.15, P  = 4.40 × 10−3) and patients with TRS (rho = −0.37, P  = .011), respectively. The IFS was also significantly and nominally negatively correlated with several factors, such as the negative and depressed factors, in patients with non-TRS and patients with TRS, respectively (P < .05). Furthermore, the change in IFS values was marginally negatively correlated with the changes in PANSS total scores and scores on the positive and depressed factors (P < .05). Conclusions These findings suggest that efforts to improve clinician adherence to guideline recommendations for pharmacological therapy of schizophrenia, as assessed by the IFS, may lead to better outcomes in patients with schizophrenia. [ABSTRACT FROM AUTHOR]

Surgical treatment of craniopharyngioma often leads to a rapid and dramatic weight gain, leading to hypothalamic obesity. Treatment focused on the diet, physical activity, and different types of drugs have very often provided unsatisfactory results. To date, no data have been reported on hypothalamic obesity (HO) regarding the use of semaglutide, a novel type 1 receptor glucagon-like peptide-1 agonist, to limit body weight gain after surgical removal of a neoplasm, despite its already documented efficacy in obesity treatment. In this case report, we tested semaglutide in an 18-year-old patient with HO induced by a surgical intervention for craniopharyngioma. A very favorable treatment response was found in terms of body weight reduction and improvement in metabolic parameters. Our patient lost more than than 30 kg after only 6 months of therapy, which has never been reported before in the literature on HO. [ABSTRACT FROM AUTHOR]

Although pulmonary endarterectomy (PEA) is the treatment of choice for chronic thromboembolic pulmonary hypertension (CTEPH), many patients have inoperable disease, and some have persistent or recurrent pulmonary hypertension (PH) after surgery. Alternative options (balloon pulmonary angioplasty (BPA) and PH-targeted medical therapy) are, therefore, required. Studies of medical therapies for CTEPH have evolved since Aerosolized Iloprost Randomized (AIR), the first randomized, controlled study of a PH-targeted therapy (inhaled iloprost) to include patients with CTEPH. Key learnings from these studies include the need to evaluate CTEPH separately from other types of PH, the importance of prospective operability adjudication as part of the protocol, and the need for sufficient duration to allow treatment benefits to become apparent. The 16-week Chronic Thromboembolic Pulmonary Hypertension Soluble Guanylate Cyclase-Stimulator Study 1 (CHEST-1) study was the first to operationalize these learnings, demonstrating a significant mean improvement in 6-minute walk distance (+46 m) and improvements in hemodynamic endpoints with riociguat versus placebo. Findings from previous studies will inform the design of future studies to address key issues related to combination medical therapy. Data on combinations of macitentan with phosphodiesterase type 5 inhibitors or oral prostanoids are available from MERIT, the first study to allow such regimens. No data on combinations including riociguat, the only licensed medical therapy for CTEPH, are available. Studies are also needed for multimodality treatment, including medical therapy plus BPA, and medical therapy as a bridge to PEA in selected operable patients. To address these issues and improve patient outcomes, it is vital that we learn from current studies to improve future trial design.

Introduction/Objective. Mild cognitive impairment (MCI) is a state of progressive cognitive decline, rarely recognized by general practitioners (GPs), which is a reason of late treatment and fast progression towards more serious conditions. The main obstacles for the timely treatment of MCI are lack of diagnostic protocols and clinical guidelines as well as lack of knowledge and disbelief in the pharmacological therapeutic possibilities. The aim of this investigation was to assess level of recognition of MCI symptoms by GPs, and to estimate their perception of distinct risk factors significance for MCI development. Methods. Participants of the “Days of General Medicine” Conference (Serbia, March 2018), n = 340, completed 12 items questionnaire about recognition and treatment of the MCI patients. We have used descriptive statistics, χ2, Mann–Whitney U tests, binary logistic regression analysis for results presentation, sub-groups comparison, to assess predictors of drug therapy selection, respectively. Results. Study showed GPs recognize diabetes as most important factor for MCI, then hypercholesterolemia, smoking and sedentary behavior, while hypertension and obesity are perceived as less important. Those GPs who estimated diabetes and hypercholesterolemia as more important for all patients are significantly more prone to prescribe symptomatic therapy (pentoxifylline and vinpocetine), p < 0.05 according to χ2 test. Logistic regression analysis regarding therapy predictions showed that years of GP experience is the most important predictor of drug therapy selection (p < 0.01). Conclusion. Results of this investigation pointed a need for MCI education for young physicians, in order to improve diagnosis and treatment of these patients.

Background and objective: Vascular cognitive impairment with no dementia (VCIND) is considered to be the prodromal stage of vascular dementia, characterized by insidious onset. Although acupuncture and drug therapies are effective, the optimal therapy for VCIND remains to be further determined. Therefore, we conducted a network meta-analysis to compare the effectiveness of acupuncture therapies and current common medicines for VCIND. Methods: We searched eight electronic databases to identify eligible randomized controlled trials of patients with VCIND treated by acupuncture or drug therapies. The primary outcome was Montreal Cognitive Assessment, and the secondary outcome was Mini-Mental State Examination. We conducted the network meta-analysis within a Bayesian framework. Weighted mean difference with 95% confidence intervals were applied as effect sizes to continuous data for all outcomes. Sensitivity analysis was done to assess the robustness of the findings, and we also carried out a subgroup analysis based on age. We assessed the risk of bias using the Risk of Bias 2.0 tool and applied the Grade of Recommendation Assessment, Development and Evaluation (GRADE) to assess the quality of the outcomes. This study was registered with PROSPERO, number CRD42022331718. Results: A total of 33 studies with 14 interventions were included, including 2603 participants. In terms of the primary outcome, manual acupuncture plus herbal decoction was considered to be the most effective intervention (P = 91.41%), followed by electroacupuncture (P = 60.77%) and manual acupuncture plus piracetam (P = 42.58%), whereas donepezil hydrochloride ranked the least efficacious intervention (P = 54.19%). For the secondary outcome, electroacupuncture plus nimodipine was considered to be the most effective intervention (P = 42.70%), followed by manual acupuncture plus nimodipine (P = 30.62%) and manual acupuncture (P = 28.89%), whereas nimodipine ranked the least efficacious intervention (P = 44.56%). Conclusion: Manual acupuncture plus herbal decoction might be the most effective intervention for VCIND. The combination of acupuncture and drug therapy had a tendency to perform better than monotherapy in terms of clinical outcomes. [ABSTRACT FROM AUTHOR]

The pharmacological management of nonspecific chronic low back pain (NCLBP) aims to restore patients' daily activities and improve their quality of life. The management of NCLBP is not well codified and extremely heterogeneous, and residual symptoms are common. Pharmacological management should be considered as co-adjuvant to non-pharmacological therapy, and should be guided by the symptoms reported by the patients. Depending on the individual severity of NCLPB, pharmacological management may range from nonopioid to opioid analgesics. It is important to identify patients with generalized sensory hypersensitivity, who may benefit from dedicated therapy. This article provides an evidence-based overview of the principles of pharmacological management of NCLPB. [ABSTRACT FROM AUTHOR]

Context: Polycystic ovary syndrome (PCOS) is a complex endocrine disease that affects women of reproductive age and is characterised by biochemical and clinical androgen excess. Aim: To evaluate the efficacy of pharmacological interventions used to decrease androgen hormones in women with PCOS. Data source: We searched PubMed, MEDLINE, Scopus, Embase, Cochrane library and the Web of Science from inception up to March 2021. Data synthesis: Two reviewers selected eligible studies and extracted data, and the review is reported according to the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Results: Of the 814 randomised clinical trials (RCTs) located in the search, 92 met the eligibility criteria. There were significant reductions in total testosterone level with metformin versus (vs) placebo (SMD: − 0.33; 95% CI − 0.49 to − 0.17, p < 0.0001, moderate grade evidence) and dexamethasone vs placebo (MD:-0.86 nmol/L; 95% CI − 1.34 to − 0.39, p = 0.0004, very low-grade evidence). Significant reductions in the free testosterone with sitagliptin vs placebo (SMD: − 0.47; 95% CI − 0.97 to 0.04, p = 0.07, very low-grade evidence), in dehydroepiandrosterone sulphate (DHEAS) with flutamide vs finasteride (MD: − 0.37 µg/dL; 95% CI − 0.05 to − 0.58, p = 0.02, very low-grade evidence), a significant reduction in androstenedione (A4) with rosiglitazone vs placebo (SMD: − 1.67; 95% CI − 2.27 to − 1.06; 59 participants, p < 0.00001, very low-grade evidence), and a significant increase in sex hormone-binding globulin (SHBG) with oral contraceptive pill (OCP) (35 µg Ethinyl Estradiol (EE)/2 mg cyproterone acetate (CPA)) vs placebo (MD: 103.30 nmol/L; 95% CI 55.54–151.05, p < 0.0001, very low-grade evidence) were observed. Conclusion: Metformin, OCP, dexamethasone, flutamide, and rosiglitazone use were associated with a significant reduction in biochemical hyperandrogenemia in women with PCOS, though their individual use may be limited due to their side effects. PROSPERO registration No: CRD42020178783. [ABSTRACT FROM AUTHOR]

Arrhythmogenic substrate, modulating factors, and triggering factors (the so-called Coumel's triangle concept) play a primary role in atrial fibrillation (AF) pathophysiology. Several years have elapsed since Coumel and co-workers advanced the concept of the relevance of autonomic nervous system (ANS) influences on atrial cells' electrophysiological characteristics. The ANS is not only associated with cardiac rhythm regulation but also exerts an important role in the triggering and maintenance of atrial fibrillation. This review aims to describe in detail the autonomic mechanisms involved in the pathophysiology of atrial fibrillation (AF), starting from the hypothesis of an "Autonomic Coumel Triangle" that stems from the condition of the fundamental role played by the ANS in all phases of the pathophysiology of AF. In this article, we provide updated information on the biomolecular mechanisms of the ANS role in Coumel's triangle, with the molecular pathways of cardiac autonomic neurotransmission, both adrenergic and cholinergic, and the interplay between the ANS and cardiomyocytes' action potential. The heterogeneity of the clinical spectrum of the ANS and AF, with the ANS playing a relevant role in situations that may promote the initiation and maintenance of AF, is highlighted. We also report on drug, biological, and gene therapy as well as interventional therapy. On the basis of the evidence reviewed, we propose that one should speak of an "Autonomic Coumel's Triangle" instead of simply "Coumel's Triangle". [ABSTRACT FROM AUTHOR]

Cardiovascular diseases (CVDs), the leading cause of death worldwide, share in common mitochondrial dysfunction, in specific a dysregulation of Ca2+ uptake dynamics through the mitochondrial Ca2+ uniporter (MCU) complex. In particular, Ca2+ uptake regulates the mitochondrial ATP production, mitochondrial dynamics, oxidative stress, and cell death. Therefore, modulating the activity of the MCU complex to regulate Ca2+ uptake, has been suggested as a potential therapeutic approach for the treatment of CVDs. Here, the role and implications of the MCU complex in CVDs are presented, followed by a review of the evidence for MCU complex modulation, genetically and pharmacologically. While most approaches have aimed within the MCU complex for the modulation of the Ca2+ pore channel, the MCU subunit, its intra‐ and extra‐ mitochondrial implications, including Ca2+ dynamics, oxidative stress, post‐translational modifications, and its repercussions in the cardiac function, highlight that targeting the MCU complex has the translational potential for novel CVDs therapeutics. [ABSTRACT FROM AUTHOR]

Ferroptosis is a novel form of cell death, manifested by iron-dependent, non-apoptotic manner resulting from the intracellular accumulation of large clusters of reactive oxygen species (ROS) and lipid peroxides due to abnormal iron metabolism. Since the liver is the main organ of human body for storing iron, it is essential to perform in-depth investigation on the role and mechanistic basis of ferroptosis in the context of divergent liver diseases. We previously summarized the emerging role of ferroptosis among various liver diseases, however, the past few years have been a surge in research establishing ferroptosis as the molecular basis or treatment option. This review article concentrated on the accumulating research progress of ferroptosis in a range of liver diseases such as acute liver injury/failure (ALI/ALF), immune-mediated hepatitis, alcoholic liver disease (ALD), nonalcoholic fatty liver disease and liver fibrosis. Ferroptosis may be a promising target for the prevention and treatment of various liver diseases, providing a strategy for exploring new therapeutic avenues for these entities. [ABSTRACT FROM AUTHOR]

Aim: The aim of the study is to compare the effects of vestibular rehabilitation and pharmacological treatment in benign paroxysmal positional vertigo (BPPV). Materials and methods: Thirty patients (40.93 ± 8.66 years old) diagnosed with BPPV were recruited. Patients were equally divided into pharmacological control group and vestibular rehabilitation group. The pharmacological control group was further divided into Group A (n = 8, 2 doses/day, 24 mg betahistine) and Group B (n = 7, 1 dose/day, 50 mg dimenhydrinate in addition to betahistine). Patients in the rehabilitation group underwent repeated head and eye movements, and Epley or Barbecue Roll Maneuvers were applied for 4 weeks. Subjective assessment of vertigo was measured with the visual analog scale. Static balance parameters were measured with the tandem, one-legged stance, and Romberg tests. Dynamic visual acuity was measured with a Snellen chart, and vestibular dysfunction was measured with the Unterberger (Fukuda stepping) test. All parameters were evaluated before and after treatment. Results: Vestibular rehabilitation resulted in greater improvement in severity of vertigo, balance parameters except Romberg test, and vestibular dysfunction than pharmacological therapy (p < 0,001). There was no significant difference in dynamic visual acuity between groups (p = 0,24). The effects of medication with the active ingredients betahistine and dimenhydrinate were similar (p > 0,05). Conclusion: The vestibular rehabilitation method can positively change the severity of vertigo, balance ability, and vestibular dysfunction compared to pharmacological therapy. Dimenhydrinate administered in combination with betahistine was not superior to betahistine alone but can be recommended for its antiemetic effect. [ABSTRACT FROM AUTHOR]