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Fibromyalgia (FM) is characterized by chronic widespread pain accompanied by fatigue, poor sleep quality, and numerous accompanying conditions. Its prevalence worldwide is around 2.7%, and it is more common in women. Although its epidemiology and pathophysiology cannot be precisely explained, it is known that various factors coexist. Over the years, guidelines containing various criteria have been established for the diagnosis of the disease. The goal of treatment in FM is to improve the patient’s quality of life and minimize symptoms as much as possible. The success of treatment in FM is limited. Many patients seek alternative treatment methods, including diet and lifestyle changes. Recently, medical nutritional therapies and phytotherapy products have been at the forefront of research in this area. Phytotherapy products can be added alone or in combination with other treatment methods and can enhance the success of treatment. In this article, the epidemiology, pathophysiology, diagnostic methods, pharmacological and non-pharmacological methods used in the treatment of FM syndrome will be discussed, and the most widely used phytotherapeutic products will be addressed.

Fibromyalgia (FM) is characterized by chronic widespread pain accompanied by fatigue, poor sleep quality, and numerous accompanying conditions. Its prevalence worldwide is around 2.7%, and it is more common in women. Although its epidemiology and pathophysiology cannot be precisely explained, it is known that various factors coexist. Over the years, guidelines containing various criteria have been established for the diagnosis of the disease. The goal of treatment in FM is to improve the patient's quality of life and minimize symptoms as much as possible. The success of treatment in FM is limited. Many patients seek alternative treatment methods, including diet and lifestyle changes. Recently, medical nutritional therapies and phytotherapy products have been at the forefront of research in this area. Phytotherapy products can be added alone or in combination with other treatment methods and can enhance the success of treatment. In this article, the epidemiology, pathophysiology, diagnostic methods, pharmacological and non-pharmacological methods used in the treatment of FM syndrome will be discussed, and the most widely used phytotherapeutic products will be addressed. [ABSTRACT FROM AUTHOR]

Heart failure (HF) is a significant disease affecting 1–2% of the general population. Despite its general aspects, HF, like other cardiovascular diseases, presents various gender-specific aspects in terms of etiology, hemodynamics, clinical characteristics, therapy, and outcomes. As is well known, HF with preserved ejection fraction more frequently affects females, with diabetes and arterial hypertension representing the most critical determinants of HF. On the other hand, women are traditionally underrepresented in clinical trials and are often considered undertreated. However, it is not clear whether such differences reflect cultural behaviors and clinical inertia or if they indicate different clinical profiles and the impact of sex on hard clinical outcomes. We aimed to review the sex-related differences in patients affected by HF. [ABSTRACT FROM AUTHOR]

Chronic obstructive pulmonary disease (COPD) is a chronic respiratory disease that is associated with significant morbidity, mortality, and healthcare costs. The burden of respiratory symptoms and airflow limitation can translate to reduced physical activity, in turn contributing to poor exercise capacity, muscle dysfunction, and body composition abnormalities. These extrapulmonary features of the disease are targeted during pulmonary rehabilitation, which provides patients with tailored therapies to improve the physical and emotional status. Patients with COPD can be divided into metabolic phenotypes, including cachectic, sarcopenic, normal weight, obese, and sarcopenic with hidden obesity. To date, there have been many studies performed investigating the individual effects of exercise training programs as well as nutritional and pharmacological treatments to improve exercise capacity and body composition in patients with COPD. However, little research is available investigating the combined effect of exercise training with nutritional or pharmacological treatments on these outcomes. Therefore, this review focuses on exploring the potential additional beneficial effects of combinations of exercise training and nutritional or pharmacological treatments to target exercise capacity and body composition in patients with COPD with different metabolic phenotypes. [ABSTRACT FROM AUTHOR]

Obstructive Sleep Apnea Syndrome (OSAS) affects 13–33% of males and 6–9% of females globally and poses significant treatment challenges, including poor adherence to Continuous Positive Airway Pressure (CPAP) and residual excessive sleepiness (RES). This review aims to elucidate the emerging interest in pharmacological treatments for OSAS, focusing on recent advancements in this area. A thorough analysis of extensive clinical trials involving various drugs, including selective dopamine reuptake inhibitors, selective norepinephrine inhibitors, combined antimuscarinic agents, and orexin agonists, was conducted. These trials focused on ameliorating respiratory metrics and enhancing sleep quality in individuals affected by OSAS. The studied pharmacological agents showed potential in improving primary outcomes, notably the apnea-hypopnea index (AHI) and the Epworth sleepiness scale (ESS). These improvements suggest enhanced sleep quality and symptom management in OSAS patients. With a deeper understanding of OSAS, pharmacological interventions are emerging as a promising direction for its effective management. This review provides a comprehensive overview of the current state of drug research in OSAS, highlighting the potential of these treatments in addressing the disorder’s complex challenges.

Intracranial aneurysms (IAs) are rare vascular lesions that are more frequently found in women. The pathophysiology behind the formation and growth of IAs is complex. Hence, to date, no single pharmacological option exists to treat them. Animal models, especially mouse models, represent a valuable tool to explore such complex scientific questions. Genetic modification in a mouse model of IAs, including deletion or overexpression of a particular gene, provides an excellent means for examining basic mechanisms behind disease pathophysiology and developing novel pharmacological approaches. All existing animal models need some pharmacological treatments, surgical interventions, or both to develop IAs, which is different from the spontaneous and natural development of aneurysms under the influence of the classical risk factors. The benefit of such animal models is the development of IAs in a limited time. However, clinical translation of the results is often challenging because of the artificial course of IA development and growth. Here, we summarize the continuous improvement in mouse models of IAs. Moreover, we discuss the pros and cons of existing mouse models of IAs and highlight the main translational roadblocks and how to improve them to increase the success of translational IA research.

Simple Summary: In this study, we examined the prescription patterns and pharmaceutical costs for treatments of multiple myeloma (MM) in Catalonia's public healthcare system over the past decade. MM is a complex and costly disease for which substantial pharmacological innovation has recently been introduced, and we aimed to understand how treatment choices and expenses have evolved. We analyzed data from 4556 MM patients and found that the number of treated patients increased annually. Drugs like lenalidomide and daratumumab showed significant utilization rises, impacting overall costs. Our findings shed light on the economic burden of MM treatment, emphasizing the importance of monitoring and optimizing healthcare resources allocation for better healthcare decision making. (1) Background: Our understanding of and treatment for multiple myeloma (MM) has advanced significantly, and new pharmacological treatments have promising benefits but high price tags. This study analyzes prescription patterns and pharmaceutical expenditure for MM treatments in Catalonia's public healthcare system over eight years. (2) Methods: A retrospective observational study examined MM treatment data from 2015 to 2022 in Catalonia, using healthcare registries from the Catalan Health Service to collect information on patients, medicines used, and treatment costs. (3) Results: A total of 4556 MM patients received treatment, with a rising trend in the number of treated patients each year from 902 in 2015 to 1899 in 2022. The mean age was 68.9 years, and patients were almost evenly distributed by gender (51.5% male). Most patients were treated with bortezomib (3338 patients), lenalidomide (2952), and/or daratumumab (1093). Most drugs showed increased utilization annually, most significantly for lenalidomide and daratumumab. The total pharmacological treatment cost throughout the entire study period was EUR 321,811,249, with lenalidomide leading with the highest total cost (EUR 157,236,784), and daratumumab exhibiting the highest increase in annual expenditure. (5) Conclusions: The study reveals a progressive increase in the number of MM patients treated and rising pharmaceutical costs. Lenalidomide and daratumumab incurred the highest costs. The findings highlight MM treatment's economic impact and the need to monitor prescription patterns and expenditures to optimize healthcare resources and decision making. Understanding these trends can guide resource allocation effectively. [ABSTRACT FROM AUTHOR]

Cognitive impairment in patients with Parkinson's disease (PD) is one of the commonest and most disabling non-motor manifestations during the course of the disease. The clinical spectrum of PD-related cognitive impairment includes subjective cognitive decline (SCD), mild cognitive impairment (MCI) and PD dementia (PDD). As the disease progresses, cognitive decline creates a significant burden for the family members and/or caregivers of patients with PD, and has a great impact on quality of life. Current pharmacological treatments have demonstrated partial efficacy and failed to halt disease progression, and novel, effective, and safe therapeutic strategies are required. Accumulating preclinical and clinical evidence shows that several agents may provide beneficial effects on patients with PD and cognitive impairment, including ceftriaxone, ambroxol, intranasal insulin, nilotinib, atomoxetine, mevidalen, blarcamesine, prasinezumab, SYN120, ENT-01, NYX-458, GRF6021, fosgonimeton, INT-777, Neuropeptide S, silibinin, osmotin, cordycepin, huperzine A, fibroblast growth factor 21, Poloxamer 188, ginsenoside Rb1, thioredoxin-1, tangeretin, istradefylline and Eugenia uniflora. Potential underlying mechanisms include the inhibition of a-synuclein aggregation, the improvement of mitochondrial function, the regulation of synaptic plasticity, an impact on the gut–brain axis, the modulation of neuroinflammation and the upregulation of neurotrophic factors, as well as cholinergic, dopaminergic, serotoninergic and norepinephrine neurotransmission. In this updated overview, we aim to cover the clinical aspects of the spectrum of PD-related cognitive impairment and discuss recent evidence on emerging treatment approaches that are under investigation at a preclinical and clinical level. Finally, we aim to provide additional insights and propose new ideas for investigation that may be feasible and effective for the spectrum of PD-related cognitive impairment. [ABSTRACT FROM AUTHOR]

Intracranial aneurysms (IAs) are abnormal dilations of the cerebral vessels, which pose a persistent threat of cerebral hemorrhage. Inflammation is known to contribute to IA development. The nuclear factor "kappa-light-chain-enhancer" of activated B-cells (NF-κB) is the major driver of inflammation. It increases the expression of inflammatory markers and matrix metalloproteinases (MMPs), which contribute heavily to the pathogenesis of IAs. NF-κB activation has been linked to IA rupture and resulting subarachnoid hemorrhage. Moreover, NF-κB activation can result in endothelial dysfunction, smooth muscle cell phenotypic switching, and infiltration of inflammatory cells in the arterial wall, which subsequently leads to the initiation and progression of IAs and consequently results in rupture. After a systematic search, abstract screening, and full-text screening, 30 research articles were included in the review. In this systematic review, we summarized the scientific literature reporting findings on NF-κB's role in the pathogenesis of IAs. In conclusion, the activation of the NF-κB pathway was associated with IA formation, progression, and rupture. [ABSTRACT FROM AUTHOR]

Aim: Misconceptions and non‐evidence‐based practices toward childhood fever are reported worldwide. Medical students might be ideal candidates to introduce long‐lasting changes in clinical practice. However, no study has gauged the effectiveness of an educational intervention to improve fever management in this population. We conducted an educational, interventional study on childhood fever among final‐year medical students. Methods: We conducted a prospective, multicentre interventional study employing a pre/post‐test design. Participants from three Italian Universities filled in a questionnaire just before the intervention (T0), immediately after (T1) and 6 months later (T2) in 2022. The intervention was a two‐hour lecture focused on the pathophysiology of fever, recommendations for its treatment and risks associated with improper management. Results: 188 final‐year medical students (median age of 26 years, 67% females) were enrolled. Relevant improvements in the criterion for treating fever and conceptions about the beneficial effects of fever were observed at T1 and T2. Similar data were found for the reduction of physical methods advice to decrease body temperature and concerns for brain damage from fever. Conclusion: This study shows for the first time that an educational intervention is effective in changing students' conceptions and attitudes toward fever both in the short and medium term. [ABSTRACT FROM AUTHOR]

Axial spondyloarthritis (axSpA) refers to an inflammatory rheumatic disease that mainly affects the axial skeleton and leads to progressive radiographic changes of the sacroiliac joints and spine. axSpA is currently subdivided into the radiographic (r-axSpA) and non-radiographic (nr-axSpA) form. Both forms are associated with musculoskeletal pain, restriction of spinal mobility, specific extra-musculoskeletal manifestations, and overall, altered quality of life. The therapeutic management of axSpA is currently well standardized. We reviewed available literature (by using PubMed search) on non-pharmacological and pharmacological treatment options that may be used in axSpA, including r-axSpA and nr-axSpA, as well as the role of non-steroidal anti-inflammatory drugs (NSAIDs), biological agents including TNFalpha (TNFi) and IL-17 (IL-17i) inhibitors. New treatment options such as Janus kinase inhibitors are also reviewed. NSAIDs remain the mainstay of initial therapy, and subsequently, biological agents (TNFi and IL-17i) may be envisaged. Four TNFi are licensed for the treatment of both r-axSpA and nr-axSpA, while IL-17i are approved in each indication. The choice between a TNFi and an IL-17i is mainly guided by the presence of extra-articular manifestations. JAKi were more recently introduced for the treatment of r-axSpA, but their use is restricted to specific patients with a safe cardiovascular profile. [ABSTRACT FROM AUTHOR]

Objective: Apathy, a frequent neuropsychiatric symptom in aging neurocognitive disorders, has been associated with cognitive decline and functional disability. Therefore, timely provision of pharmacological interventions for apathy is greatly needed. Design: A systematical literature review of existing studies was conducted up to 30 May 2023 in several databases (PubMed, PsychInfo, Cochrane, Google Scholar, etc.) that included randomized controlled trials (RCTs) and meta-analyses assessing pharmacological treatments for apathy in aging neurocognitive disorders. The quality of the studies was appraised. Results: In patients with Alzheimer's Disease (AD), donepezil, galantamine, rivastigmine, methylphenidate, and gingko biloba were proven efficacious for apathy, while rivastigmine, cognitive enhancer IRL752 and piribedil were found to be beneficial in patients with Parkinson's Disease (PD) and agomelatine in patients with Frontotemporal Dementia (FD). The extensive proportion of RCTs in which apathy was used as a secondary outcome measure, along with the considerable methodological heterogeneity, did not allow the evaluation of group effects. Conclusions: Pharmacological interventions for apathy in aging neurocognitive disorders are complex and under-investigated. The continuation of systematic research efforts and the provision of individualized treatment for patients suffering from these disorders is vital. [ABSTRACT FROM AUTHOR]

Erectile dysfunction (ED) is the inability to get and maintain an adequate penile erection for satisfactory sexual intercourse. Due to its negative impacts on men's life quality and increase during aging (40% of men between 40 and 70 years), ED has always attracted researchers of different disciplines, from urology, andrology and neuropharmacology to regenerative medicine, and vascular and prosthesis implant surgery. Locally and/or centrally acting drugs are used to treat ED, e.g., phosphodiesterase 5 inhibitors (first in the list) given orally, and phentolamine, prostaglandin E1 and papaverine injected intracavernously. Preclinical data also show that dopamine D4 receptor agonists, oxytocin and α-MSH analogues may have a role in ED treatment. However, since pro-erectile drugs are given on demand and are not always efficacious, new strategies are being tested for long lasting cures of ED. These include regenerative therapies, e.g., stem cells, plasma-enriched platelets and extracorporeal shock wave treatments to cure damaged erectile tissues. Although fascinating, these therapies are laborious, expensive and not easily reproducible. This leaves old vacuum erection devices and penile prostheses as the only way to get an artificial erection and sexual intercourse with intractable ED, with penile prosthesis used only by accurately selected patients. [ABSTRACT FROM AUTHOR]

Spinal cord injury brings devastating consequences and huge economic burden. Different authoritative organizations have developed different guidelines for pharmacological treatments of spinal cord injury, but there is a lack of a critical appraisal of them. To systematically review and appraise guidelines regarding their recommendations for pharmacological treatments for spinal cord injury. Systematic review. We searched Medline, Embase, Cochrane, and Web of Science from January 2000 to January 2022 as well as guideline-specific databases (eg, Congress of Neurological Surgeons) and Google Scholar. We included the most updated guideline containing evidence-based recommendations or consensus-based recommendations developed by specific authoritative organizations if multiple versions were available. We appraised guidelines through the Appraisal of Guidelines for Research and Evaluation, 2nd edition instrument consisting of six domains (eg, applicability). With supporting evidence, recommendations were classified as: for, against, neither for nor against. We utilized an evidence assessment system to categorize the quality of supporting evidence as poor, fair, or good. Eight guidelines developed from 2008 to 2020 were included, but all of them scored lowest in the domain of applicability among all six domains. Twelve pharmacological agents (eg, methylprednisolone) were studied. For methylprednisolone, three guidelines (3/8=37.5%) recommended for (one evidence-based and two consensus-based), three (3/8=37.5%) recommended against (all evidence-based), and two (2/8=25%) recommended neither for nor against. For monosialotetrahexosylganglioside (GM-1), one guideline (1/4=25%) recommended for (consensus-based), one (1/4=25%) recommended against (evidence-based), and two (2/4=50%) recommended neither for nor against. For other agents (eg, minocycline), most guidelines (3/5=60%) recommended neither for nor against, one (1/5=20%) recommended against naloxone (evidence-based) and nimodipine (evidence-based), and one (1/5=20%) recommended for neural growth factor (consensus-based). The quality of most of the supporting evidence was poor, and the rest was fair. There were inconsistencies among recommendations for methylprednisolone and GM-1. Evidence-based recommendations tended to recommend against, whereas consensus-based recommendations tended to recommend for. [ABSTRACT FROM AUTHOR]

Chronic obstructive pulmonary disease (COPD) is a chronic respiratory disease that is associated with significant morbidity, mortality, and healthcare costs. The burden of respiratory symptoms and airflow limitation can translate to reduced physical activity, in turn contributing to poor exercise capacity, muscle dysfunction, and body composition abnormalities. These extrapulmonary features of the disease are targeted during pulmonary rehabilitation, which provides patients with tailored therapies to improve the physical and emotional status. Patients with COPD can be divided into metabolic phenotypes, including cachectic, sarcopenic, normal weight, obese, and sarcopenic with hidden obesity. To date, there have been many studies performed investigating the individual effects of exercise training programs as well as nutritional and pharmacological treatments to improve exercise capacity and body composition in patients with COPD. However, little research is available investigating the combined effect of exercise training with nutritional or pharmacological treatments on these outcomes. Therefore, this review focuses on exploring the potential additional beneficial effects of combinations of exercise training and nutritional or pharmacological treatments to target exercise capacity and body composition in patients with COPD with different metabolic phenotypes.

Celiac disease (CD) is a common autoimmune disease affecting around 1% of the population. It consists of an immune-mediated enteropathy, triggered by gluten exposure in susceptible patients. All patients with CD, irrespective of the presence of symptoms, must endure a lifelong gluten-free diet (GFD). This is not an easy task due to a lack of awareness of the gluten content in foods and the extensive incorporation of gluten in processed foods. Furthermore, a GFD imposes a sense of limitation and might be associated with decreased quality of life in CD patients. This results in gluten contamination in the diet of four out of five celiac patients adhering to a GFD. Furthermore, one in three adult patients will report persistent symptoms and two in three will not achieve full histological recovery when on a GFD. In recent years, there has been extensive research conducted in the quest to find the holy grail of pharmacological treatment for CD. This review will present a concise description of the current rationale and main clinical trials related to CD drug therapy. [ABSTRACT FROM AUTHOR]

The postacute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection (PASC), also known as post‐acute coronavirus disease 19 (COVID‐19) or the long COVID syndrome (long COVID) is an emerging public health concern. A substantial proportion of individuals may remain symptomatic months after initial recovery. An updated review of published and ongoing trials focusing on managing long COVID will help identify gaps and address the unmet needs of patients suffering from this potentially debilitating syndrome. A comprehensive literature search was conducted on the international databases and clinical trial registries from inception to 31 July 2022. This review included 6 published trials and 54 trial registration records. There is significant heterogeneity in the characterization of long COVID and ascertainment of primary outcomes. Most of the trials are focused on individual symptoms of long COVID or isolated organ dysfunction, classified according to cardiovascular, respiratory and functional capacity, neurological and psychological, fatigue, and olfactory dysfunction. Most of the interventions are related to the mechanisms causing the individual symptoms. Although the six published trials showed significant improvement in the symptoms or organ dysfunction studied, these initial studies lack internal and external validity limiting the generalizability. This review provides an update of the pharmacological agents that could be used to treat long COVID. Further standardization of the diagnostic criteria, inclusion of participants with concomitant chronic cardiometabolic diseases and standardization of outcomes will be essential in future clinical trials. [ABSTRACT FROM AUTHOR]

Cognitive impairment in patients with Parkinson’s disease (PD) is one of the commonest and most disabling non-motor manifestations during the course of the disease. The clinical spectrum of PD-related cognitive impairment includes subjective cognitive decline (SCD), mild cognitive impairment (MCI) and PD dementia (PDD). As the disease progresses, cognitive decline creates a significant burden for the family members and/or caregivers of patients with PD, and has a great impact on quality of life. Current pharmacological treatments have demonstrated partial efficacy and failed to halt disease progression, and novel, effective, and safe therapeutic strategies are required. Accumulating preclinical and clinical evidence shows that several agents may provide beneficial effects on patients with PD and cognitive impairment, including ceftriaxone, ambroxol, intranasal insulin, nilotinib, atomoxetine, mevidalen, blarcamesine, prasinezumab, SYN120, ENT-01, NYX-458, GRF6021, fosgonimeton, INT-777, Neuropeptide S, silibinin, osmotin, cordycepin, huperzine A, fibroblast growth factor 21, Poloxamer 188, ginsenoside Rb1, thioredoxin-1, tangeretin, istradefylline and Eugenia uniflora. Potential underlying mechanisms include the inhibition of a-synuclein aggregation, the improvement of mitochondrial function, the regulation of synaptic plasticity, an impact on the gut–brain axis, the modulation of neuroinflammation and the upregulation of neurotrophic factors, as well as cholinergic, dopaminergic, serotoninergic and norepinephrine neurotransmission. In this updated overview, we aim to cover the clinical aspects of the spectrum of PD-related cognitive impairment and discuss recent evidence on emerging treatment approaches that are under investigation at a preclinical and clinical level. Finally, we aim to provide additional insights and propose new ideas for investigation that may be feasible and effective for the spectrum of PD-related cognitive impairment.

Growing evidence supports the presence of social cognition deficits and social behavior alterations in major and minor neurocognitive disorders (NCDs). Even though the ability to identify socio-emotional changes has significantly improved in recent years, there is still no specific treatment available. Thus, we explored evidence of drug therapies targeting social cognition alterations in NCDs. Papers were selected according to PRISMA guidelines by searching on the PubMed and Scopus databases. Only papers reporting information on pharmacological interventions for the treatment of social cognition and/or social behavioral changes in major and/or minor NCDs were included. Among the 171 articles entered in the paper selection, only 9 papers were eligible for the scope of the review. Trials testing pharmacological treatments for socio-emotional alterations in NCDs are poor and of low-medium quality. A few attempts with neuroprotective, psychoactive, or immunomodulating drugs have been made. Oxytocin is the only drug specifically targeting the social brain that has been tested with promising results in frontotemporal dementia. Its beneficial effects in long-term use have yet to be evaluated. No recommendation can currently be provided. There is a long way to go to identify and test effective targets to treat social cognition changes in NCDs for the ultimate benefit of patients and caregivers. [ABSTRACT FROM AUTHOR]

In insects, the emergence of mating behavior requires the interplay among sexdetermination hierarchy mechanisms that regulate sex-specific differentiation, perception and integration of different sensory cues, and precisely patterned behavioral outputs. Biogenic amines, including octopamine (OA), dopamine (DA), tyramine (TA), serotonin and histamine, have been identified and proposed as putative neurotransmitters, neurohormones and/or neuromodulators in the central nervous system of insects to influence multiple physiologies and behaviors. The current study provides the physiological roles and pharmacology of these biogenic amines in the mating performance of Bactrocera dorsalis. Silencing gene expressions coding for biosynthetic enzymes of DA and serotonin in male flies could decrease mating rates, while OA, TA and histamine had no such effects on mating. Furthermore, injection of DA or the DA receptor antagonist chlorpromazine could affect mating rate, as well as injection of serotonin. Pharmacological treatments with other biogenic amines or their receptor antagonists in male flies have no roles in regulating mating performance. We conclude that DA and its receptors are involved in regulating male mating behaviors in B. dorsalis, while changes in serotonin levels in male flies could also affect mating rates. In the current study, the modulatory effects of these biogenic amines on mating performance were investigated, and these results will be helpful in providing a new strategy for controlling B. dorsalis. [ABSTRACT FROM AUTHOR]

Neuropathic pain, a debilitating condition, remains challenging to manage effectively. An insight into neuropharmacological mechanisms is critical for optimizing treatment strategies. This systematic review aims to evaluate the role of neuropharmacological agents based on their efficacy, involved neurotransmitters, and receptors. A manual literature search was undertaken in PubMed including Medline, Cochrane Library, Google Scholar, Plos One, Science Direct, and clinicaltrials.gov from 2013 until 2023. Out of the 13 included studies, seven evaluated the role of gabapentinoids. Two main drugs from this group, gabapentin and pregabalin, function by binding voltage-gated calcium channels, lowering neuronal hyperexcitability and pain signal transmission, thereby relieving neuropathic pain. Four of the pooled studies reported the use of tricyclic antidepressants (TCAs) including amitriptyline and nortriptyline which work by blocking the reuptake of norepinephrine and serotonin, their increased concentration is thought to be central to their analgesic effect. Three articles assessed the use of serotonin-norepinephrine reuptake inhibitors (SNRIs) and reported them as effective as the TCAs in managing neuropathic pain. They work by augmenting serotonin and norepinephrine. Three studies focused on the use of selective serotonin reuptake inhibitors (SSRIs), modulating their effect by increasing serotonin levels; however, they were reported as not a highly effective treatment option for neuropathic pain. One of the studies outlined the use of cannabinoids for neuropathic pain by binding to cannabinoid receptors with only mild adverse effects. It is concluded that gabapentinoids, TCAs, and SNRIs were reported as the most effective therapy for neuropathic pain; however, for trigeminal neuralgia, anticonvulsants like carbamazepine were considered the most effective. Opioids were considered second-line drugs for neuropathic pain as they come with adverse effects and a risk of dependence. Ongoing research is exploring novel drugs like ion channels and agents modulating pain pathways for neuropathic pain management. Our review hopes to inspire further research into patient stratification by their physiology, aiding quicker and more accurate management of neuropathic pain while minimizing inadvertent side effects., Competing Interests: Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Mian et al.)

Background: Many women with endometriosis experience chronic abdominal pain. Clinical guidelines recommend treatment with analgesics, contraceptive hormones, gonadotropin-releasing hormone analogs, and surgery. Treatment patterns in women with endometriosis are not well characterized. Methods: Data from the IBM® MarketScan® Commercial Database were accessed from 2009 to 2017. One-year baseline and follow-up periods were defined around the date of the first claim with a diagnosis of endometriosis (the index date). Women 18–49 years of age on the index date with a diagnosis of endometriosis, continuous enrollment during baseline and follow-up, and pharmacy benefits were included. The following outcomes were analyzed descriptively: baseline comorbidities; medication use and surgeries; and sequence of treatment utilization in the baseline and the follow-up period. Results: A total of 190,921 women were included. The mean ± (standard deviation) age was 39.0 ± (7.3), and abdominal/pelvic pain (36.0%) and excessive or frequent menstruation (32.0%) were the most prevalent comorbidities. In the baseline period, the utilization of pharmacological treatment was: estrogen/progestin 42.5%, opioids 41.5%, and nonsteroidal anti-inflammatory drugs (NSAIDs) 37.5%. In the follow-up period, utilization of opioids and NSAIDs increased to 68.9% and 51.1%, respectively, whereas the use of estrogen/progestin dropped to 23.8%. Surgeries were infrequent in the baseline period (6.3%). However, in the follow-up period, 27.9% of women underwent laparoscopy and 29.7% had a hysterectomy, with a total of 68.1% of the study population undergoing surgical treatment. Conclusions: A diagnosis of endometriosis is accompanied by an increase in the use of analgesics and surgical procedures. The diversity of treatments suggests a lack of clarity in management guidelines. [ABSTRACT FROM AUTHOR]

Background: The inappropriate use of pharmacological treatments for insomnia may increase patients' risk of serious adverse events. However, few epidemiological studies on the use of medications for insomnia in China have been conducted to date. Objective: We aimed to investigate the current pharmacological treatments for insomnia and guide the rational use of drugs. Methods: The prescription data of outpatients with insomnia between 2015 and 2019 in Zhejiang province were extracted from the Hospital Prescription Analysis Cooperative Project of China and evaluated. The demographic characteristics of insomnia and the proportion and prescription trends of different drugs were analyzed along with multidrug combinations for insomnia. Results: The number of patients with insomnia who were prescribed medications for insomnia increased from 2,385 in 2015 to 3,919 in 2019, with an increase of 64.32%, whereas the mean age of these patients decreased from 64.07 years to 60.94 years. There were nearly 1.42 times as many female patients prescribed medications for insomnia as male patients, and female patients tended to be younger than male patients. Benzodiazepines (53.99%) were the most common type of medicine for insomnia. The incidence of benzodiazepine usage decreased significantly yearly (P < 0.01), whereas the incidences of non-benzodiazepine receptor agonist (nBZRA) and antidepressant usage increased (P < 0.05). The most common benzodiazepine, nBZRA, antidepressant, and antipsychotic were estazolam, zolpidem, trazodone, and olanzapine, respectively. A total of 13.97%of outpatients with insomnia were prescribedmultiple drugs for insomnia, even though nearly half of the drug combinations had similar pharmacological mechanisms. Conclusions: Benzodiazepines remained the most common medication for insomnia, but the prescription rates of nBZRAs and antidepressants increased. Attention should be paid to multidrug combinations for insomnia, which may lead to an increased risk of serious adverse effects. [ABSTRACT FROM AUTHOR]

Non-alcoholic fatty liver disease (NAFLD) is categorised into simple steatosis, termed nonalcoholic fatty liver (NAFL) and nonalcoholic steatohepatitis (NASH). Nonalcoholic steatohepatitis is characterized by steatosis, hepatocyte damage, inflammation and liver fibrosis, which through cirrhosis leads to organ failure, including hepatocellular carcinoma. Development of effective non-alcoholic fatty liver disease therapies depends on basic biomedical research on liver metabolism or the body's response to factors of the metabolic syndrome. In this article, we present important information on in vitro experimental models (including multilayer co-cultures of cells, spheroids, microprocessor technologies, bioprinting) and animal models (diet-induced models, genetic models and models of combinations of various interventions) of non-alcoholic fatty liver disease enabling refinement of therapeutic targets that can accelerate drug development. We also discuss the emerging targets for drug development intended to stop or reverse disease progression. We present research on the reduction of fibrosis in the course of non-alcoholic fatty liver disease and the optimization of brown adipose function (BAT) for mitigating of metabolic syndrome and nonalcoholic steatohepatitis. The development of nonalcoholic steatohepatitis is also associated with the appearance of chronic inflammation. Thus, pro-inflammatory pathways involving inflammatory mediators represent potential therapeutic targets. Weight loss caused by diet and lifestyle changes, as a result reduces the supply of metabolic substrates to the liver, which in turn slows the progression of non-alcoholic fatty liver disease and reduces the process of liver fibrosis. Therefore, the therapy has also focused on metabolic pathways that can be used to treat non-alcoholic fatty liver disease by limiting the supply of metabolic substrates to the liver or to facilitate their degradation. We also discuss different strategies that involve combination therapies.

Erectile dysfunction (ED) is the inability to get and maintain an adequate penile erection for satisfactory sexual intercourse. Due to its negative impacts on men’s life quality and increase during aging (40% of men between 40 and 70 years), ED has always attracted researchers of different disciplines, from urology, andrology and neuropharmacology to regenerative medicine, and vascular and prosthesis implant surgery. Locally and/or centrally acting drugs are used to treat ED, e.g., phosphodiesterase 5 inhibitors (first in the list) given orally, and phentolamine, prostaglandin E1 and papaverine injected intracavernously. Preclinical data also show that dopamine D4 receptor agonists, oxytocin and α-MSH analogues may have a role in ED treatment. However, since pro-erectile drugs are given on demand and are not always efficacious, new strategies are being tested for long lasting cures of ED. These include regenerative therapies, e.g., stem cells, plasma-enriched platelets and extracorporeal shock wave treatments to cure damaged erectile tissues. Although fascinating, these therapies are laborious, expensive and not easily reproducible. This leaves old vacuum erection devices and penile prostheses as the only way to get an artificial erection and sexual intercourse with intractable ED, with penile prosthesis used only by accurately selected patients.

Objectives: As healthcare systems continue to respond to the COVID-19 pandemic, cost-effectiveness evidence will be needed to identify which tests and treatments for COVID-19 offer value for money. We sought to review economic evaluations of diagnostic tests and treatments for COVID-19, critically appraising the methodological approaches used and reporting cost-effectiveness estimates, using a "living" systematic review approach.Methods: Key databases (including MEDLINE, EconLit, Embase) were last searched on July 12, 2021. Gray literature and model repositories were also searched. Only full economic evaluations published in English were included. Studies were quality assessed and data were extracted into standard tables. Results were narratively summarized. The review was completed by 2 reviewers independently, with disagreements resolved through discussion with a senior reviewer.Results: Overall, 3540 records were identified, with 13 meeting the inclusion criteria. After quality assessment, 6 were excluded because of very severe limitations. Of the 7 studies included, 5 were cost-utility analyses and 2 were cost-effectiveness analyses. All were model-based analyses. A total of 5 evaluated treatments (dexamethasone, remdesivir, hypothetical) and 2 evaluated hypothetical testing strategies. Cost-effectiveness estimates were sensitive to the treatment effect on survival and hospitalization, testing speed and accuracy, disease severity, and price.Conclusions: Presently, there are few economic evaluations for COVID-19 tests and treatments. They suggest treatments that confer a survival benefit and fast diagnostic tests may be cost effective. Nevertheless, studies are subject to major evidence gaps and take inconsistent analytical approaches. The evidence may improve for planned updates of this "living" review. [ABSTRACT FROM AUTHOR]

Background: Central post-stroke pain (CPSP) is a type of neuropathic pain caused by dysfunction in the spinothalamocortical pathway. However, no animal studies have examined comorbid anxiety and depression symptoms. Whether the typical pharmacological treatments for CPSP, which include antidepressants, selective serotonin reuptake inhibitors (SSRIs), and anticonvulsants, can treat comorbid anxiety and depression symptoms in addition to pain remains unclear? The present study ablated the ventrobasal complex of the thalamus (VBC) to cause various CPSP symptoms. The effects of the tricyclic antidepressants amitriptyline and imipramine, the SSRI fluoxetine, and the anticonvulsant carbamazepine on pain, anxiety, and depression were examined. Results: The results showed that VBC lesions induced sensitivity to thermal pain, measured using a hot water bath; mechanical pain, assessed by von Frey test; anxiety behavior, determined by the open-field test, elevated plus-maze test, and zero-maze test; and depression behavior, assessed by the forced swim test. No effect on motor activity in the open-field test was observed. Amitriptyline reduced thermal and mechanical pain sensitivity and anxiety but not depression. Imipramine suppressed thermal and mechanical pain sensitivity, anxiety, and depression. Fluoxetine blocked mechanical but not thermal pain sensitivity, anxiety, and depression. However, carbamazepine did not affect pain, anxiety, or depression. Conclusion: In summary, antidepressants and SSRIs but not anticonvulsants can effectively ameliorate pain and comorbid anxiety and depression in CPSP. The present findings, including discrepancies in the effects observed following treatment with anticonvulsants, antidepressants, and SSRIs in this CPSP animal model, can be applied in the clinical setting to guide the pharmacological treatment of CPSP symptoms. [ABSTRACT FROM AUTHOR]

Abstract Background Lymphangioleiomyomatosis (LAM) is a rare, low-grade multisystem neoplastic disease. Most LAM patients are at a high risk of losing lung function at an accelerated rate and developing progressive dyspnea. Recently, several studies have reported their experience with pharmacological treatments for LAM. Therefore, we conducted a systematic review and meta-analysis to assess the efficacy and safety of these therapies. Methods PubMed (Medline), EMBASE, Cochrane Library, Web of Science and EBSCO Host were searched (until March 31, 2019) for eligible prospective studies regarding LAM patients treated with pharmacological treatments. Random effect models were used for quantitative analysis. Results Fourteen prospective studies regarding five pharmacological treatments (including sirolimus, everolimus, doxycycline, triptorelin, and a combination therapy of sirolimus and hydroxychloroquine) were enrolled in our systematic review, and ten of them were used for the meta-analysis. Seven prospective studies reported that sirolimus was effective at improving or stabilizing lung function and alleviating renal angiomyolipoma (AML) in LAM patients. Subsequent quantitative analyses showed that during sirolimus treatment, the pooled values of lung function and 6-min walk distance (6MWD) were not significantly changed (P > 0.05), with the pooled response rate of AML being 0.62 (95% confidence intervals [CIs]: 0.43 to 0.82, I 2 = 65%). Regarding everolimus, three prospective studies reported similar effects to those of sirolimus with regard to preserving lung function and reducing AMLs. The meta-analysis showed that the changes in lung function during everolimus treatment were not statistically significant (P > 0.05), while the pooled response rate of AML was 0.78 (95% CI: 0.68 to 0.88, I 2 = 8%). Neither the qualitative nor the quantitative results confirmed the benefits of doxycycline or triptorelin treatment, and the effects of the combination therapy were unclear in LAM patients. Most of the adverse events during pharmacological treatments were low or moderate grade and tolerable. Conclusions Overall, sirolimus and everolimus were recommended for the treatment of LAM because they could stabilize lung function and alleviate renal AML. Doxycycline and triptorelin were not recommended for the treatment of LAM because no beneficial outcomes were consistently observed. The efficacy and safety of combination therapy remain to be further explored.

Celiac disease (CD) is a common autoimmune disease affecting around 1% of the population. It consists of an immune-mediated enteropathy, triggered by gluten exposure in susceptible patients. All patients with CD, irrespective of the presence of symptoms, must endure a lifelong gluten-free diet (GFD). This is not an easy task due to a lack of awareness of the gluten content in foods and the extensive incorporation of gluten in processed foods. Furthermore, a GFD imposes a sense of limitation and might be associated with decreased quality of life in CD patients. This results in gluten contamination in the diet of four out of five celiac patients adhering to a GFD. Furthermore, one in three adult patients will report persistent symptoms and two in three will not achieve full histological recovery when on a GFD. In recent years, there has been extensive research conducted in the quest to find the holy grail of pharmacological treatment for CD. This review will present a concise description of the current rationale and main clinical trials related to CD drug therapy.

This systematic review evaluates the efficacy and safety of contemporary migraine treatments, synthesizing evidence from recent randomized controlled trials (RCTs). The focus is on both pharmacological interventions, such as calcitonin gene-related peptide (CGRP) monoclonal antibodies and non-specific oral migraine preventives, and non-pharmacological approaches like myofascial release. Through a detailed examination of the studies, this review identifies superior strategies for acute and preventive migraine management, assessing their impact on patient-reported outcomes and determining the prevalence of associated adverse events. Findings suggest that while CGRP monoclonal antibodies show promise as first-line treatments due to their efficacy and safety, myofascial release offers considerable benefits for pain and disability in tension-type and cervicogenic headaches. Challenges such as the variability in individual response and potential side effects emphasize the need for personalized treatment plans. This review underscores the importance of integrating new therapeutic discoveries into clinical practice to enhance the quality of care for migraine sufferers., Competing Interests: Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Achiatar et al.)

Cardiovascular diseases (CVDs), including ischemic heart disease and stroke, are the leading cause of mortality worldwide, causing nearly 20 million deaths annually. Traditional therapies, while effective, have not curbed the rising prevalence of CVDs driven by aging populations and lifestyle factors. This review highlights innovative therapeutic strategies that show promise in improving patient outcomes and transforming cardiovascular care. Emerging pharmacological treatments, such as proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors and sodium-glucose co-transporter 2 (SGLT2) inhibitors, introduce novel mechanisms to complement existing therapies, significantly reducing cardiovascular events and mortality. These advancements emphasize the necessity of ongoing clinical trials and research to discover new therapeutic targets. Advanced biological therapies, including gene therapy, stem cell therapy, and RNA-based treatments, offer groundbreaking potential for repairing and regenerating damaged cardiovascular tissues. Despite being in various stages of clinical validation, early results are promising, suggesting these therapies could fundamentally change the CVD treatment landscape. Innovative medical devices and technologies, such as implantable devices, minimally invasive procedures, and wearable technology, are revolutionizing CVD management. These advancements facilitate early diagnosis, continuous monitoring, and effective treatment, driving care out of hospitals and into homes, improving patient outcomes and reducing healthcare costs. Personalized medicine, driven by genetic profiling and biomarker identification, allows for tailored therapies that enhance treatment efficacy and minimize adverse effects. However, the adoption of these emerging therapies faces significant challenges, including regulatory hurdles, cost and accessibility issues, and ethical considerations. Addressing these barriers and fostering interdisciplinary collaboration are crucial for accelerating the development and implementation of innovative treatments. Integrating emerging therapeutic strategies in cardiovascular care holds immense potential to transform CVD management. By prioritizing future research and overcoming existing challenges, a new era of personalized, effective, and accessible cardiovascular care can be achieved., Competing Interests: Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Singh et al.)

Neuropathic pain poses a significant challenge due to its complex mechanisms, necessitating specific treatments. In recent decades, significant progress has been made in the clinical research of neuropathic pain, marking a shift from empirical strategies to evidence-based medicine in its management. This review outlines both pharmacological and non-pharmacological interventions. Antidepressants (tricyclic and serotonin-noradrenaline reuptake inhibitors), antiepileptics (gabapentin, pregabalin), and topical agents constitute the main pharmacological treatments. These approaches target peripheral or central mechanisms associated with neuropathic pain. Noninvasive neurostimulation, including transcutaneous electrical nerve stimulation (TENS) and repetitive transcranial magnetic stimulation (rTMS), provides non-pharmacological alternatives. However, challenges persist in effectively targeting existing medications and developing drugs that act on novel targets, necessitating innovative therapeutic strategies., Competing Interests: Declaration of competing interest Over the past 3 years, Nadine Attal has received fees for advisory boards or speakers bureau from Pfizer, Viatris, Novartis, Grunenthal, Upsa, Merz, Biogen outside the submitted work. Annachiara Spagna has nothing to disclose., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Growing evidence supports the presence of social cognition deficits and social behavior alterations in major and minor neurocognitive disorders (NCDs). Even though the ability to identify socio-emotional changes has significantly improved in recent years, there is still no specific treatment available. Thus, we explored evidence of drug therapies targeting social cognition alterations in NCDs. Papers were selected according to PRISMA guidelines by searching on the PubMed and Scopus databases. Only papers reporting information on pharmacological interventions for the treatment of social cognition and/or social behavioral changes in major and/or minor NCDs were included. Among the 171 articles entered in the paper selection, only 9 papers were eligible for the scope of the review. Trials testing pharmacological treatments for socio-emotional alterations in NCDs are poor and of low-medium quality. A few attempts with neuroprotective, psychoactive, or immunomodulating drugs have been made. Oxytocin is the only drug specifically targeting the social brain that has been tested with promising results in frontotemporal dementia. Its beneficial effects in long-term use have yet to be evaluated. No recommendation can currently be provided. There is a long way to go to identify and test effective targets to treat social cognition changes in NCDs for the ultimate benefit of patients and caregivers.

The behavioural responses to nicotine involve appetite-regulatory hormones; however, the effects of the anorexigenic hormone amylin on reward-related behaviours induced by nicotine remain to be established. Previous studies have shown that the amylinergic pathway regulates behavioural responses to alcohol, amphetamine and cocaine. Here, we evaluated the effects of salmon calcitonin (sCT), an amylin and calcitonin receptor (CTR) agonist, on nicotine-induced locomotor stimulation and sensitisation as well as dopamine release in the nucleus accumbens (NAc) shell. Moreover, we investigated the effects of sCT on the acquisition and expression of nicotine-induced reward in the conditioned place preference (CPP) paradigm. Finally, we performed Western Blot experiments in an attempt to identify the levels of the amylin receptor components CTRa, CTRb, and RAMP1 in reward-related areas of mice responding differently to repeated injections of sCT and nicotine in the locomotor sensitisation test. We found that sCT blocked nicotine’s stimulatory and dopamine-releasing effects and prevented its ability to cause locomotor sensitisation. On the other hand, sCT did not alter nicotine-induced acquisition and expression of CPP. Lastly, sCT-nicotine treated mice from the locomotor sensitisation experiment displayed higher levels of total CTR, i.e. CTRa and CTRb together, in the reward-processing laterodorsal tegmental area (LDTg) of the brain compared to mice treated with vehicle-nicotine. Overall, the present data reveal that activation of CTR or/and amylin receptors attenuates certain nicotine-induced behaviours in male mice, further contributing to the understanding of appetite-regulatory peptides in reward regulation.

The behavioural responses to nicotine involve appetite-regulatory hormones; however, the effects of the anorexigenic hormone amylin on reward-related behaviours induced by nicotine remain to be established. Previous studies have shown that the amylinergic pathway regulates behavioural responses to alcohol, amphetamine and cocaine. Here, we evaluated the effects of salmon calcitonin (sCT), an amylin and calcitonin receptor (CTR) agonist, on nicotine-induced locomotor stimulation and sensitisation as well as dopamine release in the nucleus accumbens (NAc) shell. Moreover, we investigated the effects of sCT on the acquisition and expression of nicotine-induced reward in the conditioned place preference (CPP) paradigm. Finally, we performed Western Blot experiments in an attempt to identify the levels of the amylin receptor components CTRa, CTRb, and RAMP1 in reward-related areas of mice responding differently to repeated injections of sCT and nicotine in the locomotor sensitisation test. We found that sCT blocked nicotine's stimulatory and dopamine-releasing effects and prevented its ability to cause locomotor sensitisation. On the other hand, sCT did not alter nicotine-induced acquisition and expression of CPP. Lastly, sCT-nicotine treated mice from the locomotor sensitisation experiment displayed higher levels of total CTR, i.e. CTRa and CTRb together, in the reward-processing laterodorsal tegmental area (LDTg) of the brain compared to mice treated with vehicle-nicotine. Overall, the present data reveal that activation of CTR or/and amylin receptors attenuates certain nicotine-induced behaviours in male mice, further contributing to the understanding of appetite-regulatory peptides in reward regulation. [ABSTRACT FROM AUTHOR]

The sea lice control regulations on salmon farms in Chile require weekly monitoring of Caligus rogercresseyi populations and specifically recording the number of gravid females, mobile adult (male and female without eggs strings) and attached chalimus stages. The sea lice threshold to trigger treatment has been established to maintain the number of gravid females <3 per fish after the application of any antiparasitic treatment. However, because the non-gravid females are not considered in the count, this generates an underestimation of the real abundance of the total females on the fish and also an underestimation of the fecundity rate. This study shows that the number of females was higher than the number of males after the application of an anti-sea lice treatment, with the lowest sex ratio (1.2:1) for emamectin benzoate and the highest sex ratio (14.9:1) for azamethiphos. There were no significant differences in the proportion of females after an anti-sea lice treatment for the different products (p = 0.609) and the same for males (p = 0.864). The percentage of non-gravid females in the total females ranged from 11.2 to 51.7% and the non-gravid component of the mobile adults ranged from 15.0 to 77.6% after an anti-sea lice treatment. • To ignore the abundance of non-gravid females in the sea lice monitoring generate an underestimation of the fecundity rate. • To ignore the abundance of non-gravid females, cause an underestimation of the abundance of females on the fish. • To ignore the abundance of non-gravid females, cause an underestimation of the real epidemiological situation of sea lice. [ABSTRACT FROM AUTHOR]

Non-alcoholic steatohepatitis (NASH) develops from non-alcoholic fatty liver disease (NAFLD). Currently, around 25% of the population is estimated to have NAFLD, and 25% of NAFLD patients are estimated to have NASH. NASH is typically characterized by liver steatosis inflammation, and fibrosis driven by metabolic disruptions such as obesity, diabetes, and dyslipidemia. NASH patients with significant fibrosis have increased risk of developing cirrhosis and liver failure. Currently, NASH is the second leading cause for liver transplant in the United States. More importantly, the risk of developing hepatocellular carcinoma from NASH has also been highlighted in recent studies. Patients may have NAFLD for years before progressing into NASH. Although the pathogenesis of NASH is not completely understood, the current “multiple-hits” hypothesis suggests that in addition to fat accumulation, elevated oxidative and ER stress may also drive liver inflammation and fibrosis. The development of clinically relevant animal models and pharmacological treatments for NASH have been hampered by the limited understanding of the disease mechanism and a lack of sensitive, non-invasive diagnostic tools. Currently, most pre-clinical animal models are divided into three main groups which includes: genetic models, diet-induced, and toxin + diet-induced animal models. Although dietary models mimic the natural course of NASH in humans, the models often only induce mild liver injury. Many genetic and toxin + diet-induced models rapidly induce the development of metabolic disruption and serious liver injury, but not without their own shortcomings. This review provides an overview of the “multiple-hits” hypothesis and an evaluation of the currently existing animal models of NASH. This review also provides an update on the available interventions for managing NASH as well as pharmacological agents that are currently undergoing clinical trials for the treatment of NASH.

Introduction: Autism spectrum disorder (ASD) is a neurodevelopmental disorder affecting approximately 3% of school-age children. The core symptoms are deficits in social communication and restricted and repetitive patterns of behavior. Associated problems in cognition, language, behavior, sleep and mood are prevalent. Currently, no established pharmacological treatment exists for core ASD symptoms. Risperidone and aripiprazole are used to manage associated irritability, but their effectiveness is limited and adverse events are common., Areas Covered: This mini-review summarizes existing scientific literature and ongoing clinical trials concerning cannabinoid treatment for ASD. Uncontrolled case series have documented improvements in both core ASD symptoms and related behavioral challenges in children treated with cannabis extracts rich in cannabidiol (CBD). Placebo-controlled studies involving CBD-rich cannabis extracts and/or pure CBD in children with ASD have demonstrated mixed efficacy results. A similar outcome was observed in a placebo-controlled study of pure CBD addressing social avoidance in Fragile X syndrome. Importantly, these studies have shown relatively high safety and tolerability., Expert Opinion: While current clinical data suggest the potential of CBD and CBD-rich cannabis extract in managing core and behavioral deficits in ASD, it is prudent to await the results of ongoing placebo-controlled trials before considering CBD treatment for ASD.

Obstructive Sleep Apnea Syndrome (OSAS) affects 13-33% of males and 6-9% of females globally and poses significant treatment challenges, including poor adherence to Continuous Positive Airway Pressure (CPAP) and residual excessive sleepiness (RES). This review aims to elucidate the emerging interest in pharmacological treatments for OSAS, focusing on recent advancements in this area. A thorough analysis of extensive clinical trials involving various drugs, including selective dopamine reuptake inhibitors, selective norepinephrine inhibitors, combined antimuscarinic agents, and orexin agonists, was conducted. These trials focused on ameliorating respiratory metrics and enhancing sleep quality in individuals affected by OSAS. The studied pharmacological agents showed potential in improving primary outcomes, notably the apnea-hypopnea index (AHI) and the Epworth sleepiness scale (ESS). These improvements suggest enhanced sleep quality and symptom management in OSAS patients. With a deeper understanding of OSAS, pharmacological interventions are emerging as a promising direction for its effective management. This review provides a comprehensive overview of the current state of drug research in OSAS, highlighting the potential of these treatments in addressing the disorder's complex challenges., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Liu, Yang, Li and Liu.)

Human neurodegenerative diseases, such as Alzheimer’s disease (AD), are not easily modeled in vitro due to the inaccessibility of brain tissue and the level of complexity required by existing cell culture systems. Three-dimensional (3D) brain organoid systems generated from human pluripotent stem cells (hPSCs) have demonstrated considerable potential in recapitulating key features of AD pathophysiology, such as amyloid plaque- and neurofibrillary tangle-like structures. A number of AD brain organoid models have also been used as platforms to assess the efficacy of pharmacological agents in disease progression. However, despite the fact that stem cell-derived brain organoids mimic early aspects of brain development, they fail to model complex cell-cell interactions pertaining to different regions of the human brain and aspects of natural processes such as cell differentiation and aging. Here, we review current advances and limitations accompanying several hPSC-derived organoid methodologies, as well as recent attempts to utilize them as therapeutic platforms. We additionally discuss comparative benefits and disadvantages of the various hPSC-derived organoid generation protocols and differentiation strategies. Lastly, we provide a comparison of hPSC-derived organoids to primary tissue-derived organoids, examining the future potential and advantages of both systems in modeling neurodegenerative disorders, especially AD.

Abstract Background A growing number of pharmacological and nonpharmacological trials have been performed to test the efficacy of approved or experimental treatments in Alzheimer disease (AD) and mild cognitive impairment (MCI). In this context, functional magnetic resonance imaging (fMRI) may be a good candidate to detect brain changes after a short period of treatment. Main body This critical review aimed to identify and discuss the available studies that have tested the efficacy of pharmacological and nonpharmacological treatments in AD and MCI cases using task-based or resting-state fMRI measures as primary outcomes. A PubMed-based literature search was performed with the use of the three macro-areas: ‘disease’, ‘type of MRI’, and ‘type of treatment’. Each contribution was individually reviewed according to the Cochrane Collaboration’s tool for assessing risk of bias. Study limitations were systematically detected and critically discussed. We selected 34 pharmacological and 13 nonpharmacological articles. According to the Cochrane Collaboration’s tool for assessing risk of bias, 40% of these studies were randomized but only a few described clearly the randomization procedure, 36% declared the blindness of participants and personnel, and only 21% reported the blindness of outcome assessment. In addition, 28% of the studies presented more than 20% drop-outs at short- and/or long-term assessments. Additional common shortcomings of the reviewed works were related to study design, patient selection, sample size, choice of outcome measures, management of drop-out cases, and fMRI methods. Conclusion There is an urgent need to obtain efficient treatments for AD and MCI. fMRI is powerful enough to detect even subtle changes over a short period of treatment; however, the soundness of methods should be improved to enable meaningful data interpretation.

Since December 2019 SARS-Cov-2 was found responsible for the disease COVID-19, which has spread worldwide. No specific therapies/vaccines are yet available for the treatment of COVID-19. Drug repositioning may offer a strategy and a number of drugs have been repurposed, including lopinavir/ritonavir, remdesivir, favipiravir and tocilizumab. This paper describes the main pharmacological properties of such drugs administered to patients with COVID-19, focusing on their antiviral, immune-modulatory and/or anti-inflammatory actions. Where available, data from clinical trials involving patients with COVID-19 are reported. Preliminary clinical trials seem to support their benefit. However, such drugs in COVID-19 patients have peculiar safety profiles. Thus, adequate clinical trials are necessary for these compounds. Nevertheless, while waiting for effective preventive measures i.e. vaccines, many clinical trials on drugs belonging to different therapeutic classes are currently underway. Their results will help us in defining the best way to treat COVID-19 and reducing its symptoms and complications. LINKED ARTICLES: This article is part of a themed issue on The Pharmacology of COVID-19. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v177.21/issuetoc. [ABSTRACT FROM AUTHOR]