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Traumatic brain injury (TBI) is a major source of death and disability worldwide; however, its pathogenesis is no longer regarded as an immediate, irreversible process that occurs at the time of injury. Long-term alterations in personality, sensory-motor function, and cognition are common among trauma survivors. The pathophysiology of brain injury is very complex, so it is difficult to understand. Establishing models such as weight drop, controlled cortical impact, fluid percussion, Accelerationdeceleration, hydrodynamic and cell line culture, etc., to simulate the event within controlled conditions has been a critical step in better understanding traumatic brain injury and enabling improved therapy. Establishing effective in vivo and in vitro models of traumatic brain injury and mathematical models is described here as part of the discovery of neuroprotective techniques. Some models, such as weight drop, fluid percussion, and cortical impact, help us understand the pathology of brain injury and provide suitable and effective therapeutic doses of the drug. A chemical mechanism such as prolonged or toxic exposure to chemicals and gases causes toxic encephalopathy, an acquired brain injury that may or may not be reversible. This review provides a comprehensive overview of numerous in-vivo and in-vitro models and molecular pathways to advance the knowledge of TBI. It covers traumatic brain damage pathophysiology, including apoptosis, the function of chemicals and genes, and a brief discussion on putative pharmacological remedies., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Copyright of Neurologie Pro Praxi is the property of SOLEN sro and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Movement disorders are neurological conditions in which patients manifest a diverse range of movement impairments. Distinct structures within the basal ganglia of the brain, an area involved in movement regulation, are differentially affected for every disease. Among the most studied movement disorder conditions are Parkinson’s (PD) and Huntington’s disease (HD), in which the deregulation of the movement circuitry due to the loss of specific neuronal populations in basal ganglia is the underlying cause of motor symptoms. These symptoms are due to the loss principally of dopaminergic neurons of the substantia nigra (SN) par compacta and the GABAergic neurons of the striatum in PD and HD, respectively. Although these diseases were described in the 19th century, no effective treatment can slow down, reverse, or stop disease progression. Available pharmacological therapies have been focused on preventing or alleviating motor symptoms to improve the quality of life of patients, but these drugs are not able to mitigate the progressive neurodegeneration. Currently, considerable therapeutic advances have been achieved seeking a more efficacious and durable therapeutic effect. Here, we will focus on the new advances of several therapeutic approaches for PD and HD, starting with the available pharmacological treatments to alleviate the motor symptoms in both diseases. Then, we describe therapeutic strategies that aim to restore specific neuronal populations or their activity. Among the discussed strategies, the use of Neurotrophic factors (NTFs) and genetic approaches to prevent the neuronal loss in these diseases will be described. We will highlight strategies that have been evaluated in both Parkinson’s and Huntington’s patients, and also the ones with strong preclinical evidence. These current therapeutic techniques represent the most promising tools for the safe treatment of both diseases, specifically those aimed to avoid neuronal loss during disease progression.

Bin Hu,1,* Jie Zheng,2,* Qing Liu,1 Yunkuan Yang,1 Ying Zhang2 1Department of Pain Management, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 2Department of Anesthesiology, the Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, Sichuan, People’s Republic of China *These authors contributed equally to this work Introduction: We investigated the effect and safety of ozone autohemotherapy combined with pharmacological therapy in postherpetic neuralgia (PHN).Methods: Ninety-eight patients with PHN were enrolled in this study and randomly divided into a pharmacological therapy group and ozone autohemotherapy group (49 patients in each group). The PHN patients in the pharmacological therapy group were administered pharmacological therapy for 2 weeks, whereas PHN patients in the ozone autohemotherapy group were given ozone autohemotherapy (200 mL blood from patients, the concentration of medical ozone was set as 30 μg/mL using an ozone medical apparatus, 40 mL medical ozone was incubated in 200 mL autologous blood for 3–5 minutes) combined with pharmacological therapy for 2 weeks. The Visual Analog Scale (VAS), the 50% VAS reduction in the initial value, McGill Pain Questionnaire (MPQ), the Patients’ Global Impression of Change (PGIC) scale, and the World Health Organization Quality of Life (WHOQOL-BREF) instrument were used to evaluate the outcomes of all PHN patients before therapy and at 1 week, 1 month, and 3 months after therapy.Results: Forty-five patients in the pharmacological therapy group and 47 patients in the ozone autohemotherapy group completed the study. Compared with before therapy, the two groups showed significant improvements in VAS, MPQ, PGIC, and WHOQOL-BREF scores after therapy (P0.05).Conclusion: The results of this study demonstrated that ozone autohemotherapy combined with pharmacological therapy was superior to isolated pharmacological therapy in patients with PHN and was an effective and safe way to relieve PHN. Keywords: ozone autohemotherapy, pharmacological therapy, clinical trial, postherpetic neuralgia

Abstract Background A specialist depression service (SDS) offering collaborative pharmacological and cognitive behaviour therapy treatment for persistent depressive disorder showed effectiveness against depression symptoms versus usual community based multidisciplinary care in a randomised controlled trial (RCT) in specialist mental health services in England. However, there is uncertainty concerning how specialist depression services effect such change. The current study aimed to evaluate the factors which may explain the greater effectiveness of SDS compared to Treatment as Usual (TAU) by exploring the experience of the RCT participants. Methods Qualitative audiotaped and transcribed semi-structured interviews were conducted 12–18 months after baseline with 21 service users (12 SDS, 9 TAU arms) drawn from all three sites. Inductive thematic analysis using a grounded approach contrasted the experiences of SDS with TAU participants. Results Four themes emerged in relation to service user experience: 1. Specific treatment components of the SDS: which included sub-themes of the management of medication change, explaining and developing treatment strategies, setting realistic expectations, and person-centred and holistic approach; 2. Individual qualities of SDS clinicians; 3. Collaborative team context in SDS: which included sub-themes of communication between healthcare professionals, and continuity of team members; 4. Accessibility to SDS: which included sub-themes of flexibility of locations, frequent consultation as reinforcement, gradual pace of treatment, and challenges of returning to usual care. Conclusions The study uncovered important mechanisms and contextual factors in the SDS that service users experience as different from TAU, and which may explain the greater effectiveness of the SDS: the technical expertise of the healthcare professionals, personal qualities of clinicians, teamwork, gradual pace of care, accessibility and managing service transitions. Usual care in other specialist mental health services may share many of the features from the SDS. Trial registration “Trial of the Clinical and Cost Effectiveness of a Specialist Expert Mood Disorder Team for Refractory Unipolar Depressive Disorder” was registered in www.ClinicalTrials.gov (NCT01047124) on 12–01-2010 and the ISRCTN registry was registered in www.isrctn.com (ISRCTN10963342) on 25–11-2015 (retrospectively registered).

Venous ulcers represent the most frequent ulcers and have a high clinical and socioeconomic significance. Nevertheless, pending questions remain on epidemiology, genetic and biomolecular mechanisms, contraindications and risk factors of compression therapy, role of pharmacological therapy. Overall prevalence in the range of 1-2% and point prevalence of 0.08-0.6% can be reduced if risk factors are identified and treated early. In this context, analysis of factor XIII and hemocromatosis gene polymorphisms, with the C282Y and H63D variants, may be of great importance. Also MMP12 gene polymorphism and the imbalance between matrix metalloproteinases and their tissue inhibitors are able to impair wound healing via deleterious degradation process of extra-cellular matrix. From a therapeutic point of view, conflicting recommendations exist on relative contraindications, risks and adverse events of compression therapy. Some studies showed that the administration of pentoxyphilline, Micronized purified flavonoid fraction (MPFF) and sulodexide was effective in accelerating ulcer healing, but there is no data on the duration of treatment, recurrence rates and cost-effectiveness relationship. [ABSTRACT FROM AUTHOR]

Movement disorders are neurological conditions in which patients manifest a diverse range of movement impairments. Distinct structures within the basal ganglia of the brain, an area involved in movement regulation, are differentially affected for every disease. Among the most studied movement disorder conditions are Parkinson's (PD) and Huntington's disease (HD), in which the deregulation of the movement circuitry due to the loss of specific neuronal populations in basal ganglia is the underlying cause of motor symptoms. These symptoms are due to the loss principally of dopaminergic neurons of the substantia nigra (SN) par compacta and the GABAergic neurons of the striatum in PD and HD, respectively. Although these diseases were described in the 19th century, no effective treatment can slow down, reverse, or stop disease progression. Available pharmacological therapies have been focused on preventing or alleviating motor symptoms to improve the quality of life of patients, but these drugs are not able to mitigate the progressive neurodegeneration. Currently, considerable therapeutic advances have been achieved seeking a more efficacious and durable therapeutic effect. Here, we will focus on the new advances of several therapeutic approaches for PD and HD, starting with the available pharmacological treatments to alleviate the motor symptoms in both diseases. Then, we describe therapeutic strategies that aim to restore specific neuronal populations or their activity. Among the discussed strategies, the use of Neurotrophic factors (NTFs) and genetic approaches to prevent the neuronal loss in these diseases will be described. We will highlight strategies that have been evaluated in both Parkinson's and Huntington's patients, and also the ones with strong preclinical evidence. These current therapeutic techniques represent the most promising tools for the safe treatment of both diseases, specifically those aimed to avoid neuronal loss during disease progression. [ABSTRACT FROM AUTHOR]

Copyright of Pediatrie pro Praxi is the property of SOLEN sro and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

We present a case of double‐chambered right ventricle (DCRV) complicated by hypertrophic obstructive cardiomyopathy (HOCM) in KRAS mutation‐associated Noonan syndrome. The diagnosis was incidental and made during diagnostic testing for an intradural extramedullary tumour. Spinal compression, if not surgically treated, may cause paralysis of the extremities. We decided to pursue pharmacological therapy to control biventricular obstructions and reduce the perioperative complication rate. We initiated treatment with cibenzoline and bisoprolol; the doses were titrated according to the response. After 2 weeks, the peak pressure gradient of the two RV chambers decreased from 101 to 68 mmHg, and the LV peak pressure gradient decreased from 109 to 14 mmHg. Class 1A antiarrhythmic drugs and β‐blockers decreased the severe pressure gradients of biventricular obstructions caused by DCRV and HOCM. The patient was able to undergo surgery to remove the intradural extramedullary tumour, which was diagnosed as schwannoma. [ABSTRACT FROM AUTHOR]

With the 60th anniversary of the CIBA symposium, it is worth evaluating research questions that should be prioritized in the future. Coming research initiatives can be summarized in 10 main areas. (1) From epidemiology the impact of new forms of electronic cigarettes on prevalence and mortality of COPD will be sought. (2) The study of the disease endotypes and its relationship phenotypes will have to be unraveled in the next decade. (3) Diagnosis of COPD faces several challenges opening the possibility of a change in the definition of the disease itself. (4) Patients' classification and risk stratification will need to be clarified and reassessed. (5) The asthma-COPD overlap dilemma will have to be clarified and define whether both conditions represent one only chronic airway disease again. (6) Integrating comorbidities in COPD care will be key in a progressively ageing population to improve clinical care in a chronic care model. (7) Nonpharmacological management have areas for research including pulmonary rehabilitation and vaccines. (8) Improving physical activity should focus research because of the clear prognostic impact. (9). Pharmacological therapies present several challenges including efficacy and safety issues with current medications and the development of biological therapy. (10) The definition, identification, categorization and specific therapy of exacerbations will also be an area of research development. During the next decade, we have a window of opportunity to address these research questions that will put us on the path for precision medicine. [ABSTRACT FROM AUTHOR]

The entire joint gradually wears down incoxofemoral degenerative joint disease, albeit the articular cartilage of the femoral head and acetabulum is affected the most. Coxofemoral degenerative joint disease's prevalence is increasing due to the elderly population's life expectancy increase, thus making these patients compelled to resort to pain relief medication. This medication includes nonsteroidalanti-inflammatory drugs, taken orally or topically, whose efficacy has been shown by various studies as high, but only during the first weeks, thereafter becoming futile. Chronic pain experienced by the elderly population due to coxofemoral degenerative joint disease has a negative impact on their quality of life. Given the high risk of comorbidities and toxicity to medication, we have hypothesized that kinetic treatment of the coxofemoral degenerative joint disease is, if not an alternative to pharmacological therapy, at least a way to reduce the nonsteroidal anti-inflammatory and anti-rheumatic drugs taken, which would then lead to high pain relief/prevention and maintaining independence in carrying out the physical activities of daily living in the old age patients affected by this joint disease. We conducted a comparative study on patients with stage one and stage two coxofemoral degenerative joint disease, evaluating the results of two batches of female patients: an experimental one (who followed a kinetic programme we proposed) and a control group (who did not follow a kinetic program, but agreed to participate in assessments). Due to the high risk of toxic reactions: gastro-intestinal, hepatic, renal, cardio-circulatory, cerebrovascular etc. the elderly patients are prone to have to the drugs in the nonsteroidal anti-inflammatory and anti-rheumatic drugs pharmacological group, as well as low effectiveness in the disease's late stages, the optimal pain management for joint pain in the coxofemoral degenerative joint disease is non-pharmacological, using kinesiotherapy or hip replacement. In designing the kinetic programme, we inserted predominantly proprioceptive neuromuscular facilitation techniques and stretching, as their therapeutic value is recognized. The operational strategy proposed, carried out based on the patient's functional capacities and permanently adapted to the progress made by them, both in terms of content, and dosage, at the same time considering the continuous evolution of degenerative processes led to a favourable outcome, demonstrating a significant decrease of joint pain, an enhancement of the possibilities to perform most of the domestic activities, but also a significant reduction of medication use; this verified our hypothesis. [ABSTRACT FROM AUTHOR]

Nonalcoholic steatohepatitis (NASH) is the second leading cause of liver transplantation in the US with a high risk of liver-related morbidities and mortality. Given the global burden of NASH, development of appropriate therapeutic strategies is an important clinical need. Where applicable, lifestyle modification remains the primary recommendation for the treatment of NASH, even though such changes are difficult to sustain and even insufficient to cure NASH. Bariatric surgery resolves NASH in such patients where lifestyle modifications have failed, and is recommended for morbidly obese patients with NASH. Thus, pharmacotherapies are of high value for NASH treatment. Though no drug has been approved by the US Food and Drug Administration for treatment of NASH, substantial progress in pharmacological development has been made in the last few years. Agents such as vitamin E and pioglitazone are recommended in patients with NASH, and yet concerns about their side effects remain. Many agents targeting various vital molecules and pathways, including those impacting metabolic perturbations, inflammatory cascades, and oxidative stress, are in clinical trials for the treatment of NASH. Some agents have shown promising results in phase II or III clinical trials, but more studies are required to assess their long-term effects. Herein, we review the potential strategies and challenges in therapeutic approaches to treating NASH. [ABSTRACT FROM AUTHOR]

Objective: To assess the comparative efficacy and safety of both pharmacological and non-pharmacological therapies for the behavioral and psychological symptoms of dementia, using direct and indirect evidence from randomized data. Method: A systematic review and Bayesian network meta-analysis was conducted on only randomized controlled trials (RCTs) of all the available interventions for BPSD. RCTs were selected from Pubmed, EMBASE, the Cochrane library, and CINAHL. The efficacy outcomes were Neuropsychiatric Inventory (NPI) and Cohen–Mansfield Agitation Inventory (CMAI). The outcomes of safety were total adverse events (AEs), diarrhea, dizziness, headache, falls, nausea, vomiting, and cerebrovascular diseases. Result: 146 RCTs comprising 44,873 patients with BPSD were included in this study. On NPI, aripiprazole (MD − 3.65, 95% credible interval (CrI) = − 6.92 to − 0.42), escitalopram (MD − 6.79, 95% CrI − 12.91 to − 0.60), donepezil (MD − 1.45, 95% CrI − 2.70 to − 0.20), galantamine (MD − 1.80, 95% CrI − 3.29 to − 0.32), memantine (MD − 2.14, 95% CrI − 3.46 to − 0.78), and risperidone (MD − 3.20, 95% CrI − 6.08 to − 0.31) were superior to placebo. On CMAI, aripiprazole (MD − 4.00, 95% CrI − 7.39 to − 0.54) and risperidone (MD − 2.58, 95% CrI − 5.20 to − 0.6) showed superiority to placebo. On the risk of total AEs, donepezil (OR 1.27, 95% CrI 1.07–1.50), galantamine (OR 1.91, 95% CrI 1.58–2.36), risperidone (OR 1.47, 95% CrI 1.13–1.97), and rivastigmine (OR 2.02, 95% CrI 1.53–2.70) owned higher risk than placebo. Conclusion: Pharmacological therapies should be the first choice for BPSD. Aripiprazole, haloperidol, quetiapine, and risperidone of antipsychotics showed the significant efficacy, while memantine, galantine, and donepezil may provide the modest effectiveness. The safety of all was thought to be acceptable. [ABSTRACT FROM AUTHOR]

Objective  We assessed if the initial response to medical nutritional therapy (MNT) can help predict the need for pharmacological therapy in women with gestational diabetes mellitus (GDM). Study Design  We identified 1,174 women with GDM who underwent standardized dietary counseling and reported glucose values from the first week of MNT. We compared women who required pharmacological therapy with those who did not use bivariate statistics, and used multivariable logistic regression modeling to assess for factors predicting the need for pharmacological therapy. Results  We identified 819 women (69.8%) who needed pharmacological therapy. They had higher prepregnancy body mass index, higher rates of GDM diagnosis before 24 weeks, and higher oral glucose tolerance test values. After adjustment for covariates, age (odds ratio [OR]: 1.04; 95% confidence interval [CI]: 1.01–1.08), obesity (OR: 2.49; 95% CI: 1.70–3.66), and ≥33% of abnormal glucose values from the first week of MNT (OR: 13.84; 95% CI: 9.4–20.20) were associated with the need for pharmacological therapy. Area under the curve of the regression model was 0.83, with a sensitivity of 72.2%, a specificity of 86.8%, and a positive predictive value of 92.5%. Conclusion  Glucose values from the first week of MNT were the strongest predictor of needing pharmacological therapy. Further studies are needed to define metabolic predictors of response to MNT in women with GDM. [ABSTRACT FROM AUTHOR]

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. • The RANK/RANKL pathway plays a pivotal role in osteoarthritis (OA) pathogenesis by regulating osteoclast differentiation. • Advanced gene-based strategies hold promise for precisely targeting and modulating RANK/RANKL signaling in OA. • Biomaterials-based approaches enable localized delivery of RANK/RANKL-targeting therapeutics to affected joints. [ABSTRACT FROM AUTHOR]

Youth with Attention-Deficit Hyperactivity Disorder (ADHD) may suffer from comorbid difficulties, such as anxiety–depressive symptoms, social withdrawal, and somatic complaints. Although stimulants remain the ADHD cornerstone treatment, mental fatigue, school problems and low self-esteem may persist, often being the most unacceptable symptoms for these patients. We present two cases of adolescents (14 and 15 years old) with methylphenidate-treated ADHD, where cognitive fatigability, depressive thoughts, anxiety, irritability, and poor social relationships remained. Based on clinical observation and the completion of parent and child rating scales, the aforementioned manifestations appeared to progressively reduce by the time of the subsequent control visits planned 1, 3, and 5 months after, following the use of vortioxetine (up to 10 mg/day) as add-on therapy to methylphenidate. No significant side effects were reported in both cases in a follow-up period of 3 months, also supporting the stability of the observed clinical improvement. Vortioxetine monotherapy has already been tested for the treatment of anxiety–depressive symptoms in youth, as well as ADHD in adulthood. The cases presented here suggest that vortioxetine could also be an effective option for ADHD treatment in childhood and adolescence, warranting further investigation of its potential benefits as both a monotherapy and adjunctive therapy to stimulants.

The rate of syncope in the Emergency Department ranges between 0.9 and 1.7%. Syncope is mostly related to a underlying reflex or orthostatic mechanism. A bradycardic or a hypotensive phenotype, may be identified. The latter is the most common and could be constitutional or drug induced. Consequently, obtaining an accurate drug history is an important step of the initial assessment of syncope. As anti-hypertensive medication might be responsible for orthostatic hypotension, managing hypertension in patients with syncope requires finding an ideal balance between hypotensive and cardiovascular risks. The choice of anti-hypertensive molecule as well as the therapeutic regimen and dosage, influences the risk of syncope. Not only could anti-hypertensive drugs have a hypotensive effect but opioids and psychoactive medications may also be involved in the mechanism of syncope. Proper drug management could reduce syncope recurrences and their consequences.

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., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Extracellular vesicles (EV) are at the center of an intense activity of investigation, both for their possible employment as biomarkers of ongoing pathologic processes and for their broad range of biological activities. EV can promote tissue repair in very different pathologic settings, including hindlimb and myocardial ischemia. Importantly, the exact mode of action of EV is still partly understood, since they may act by modulating growth factors and cytokines, signaling pathways, and by transferring non-coding RNAs to target cells. However, the term EV identifies cell derived, enveloped particles very heterogeneous in size, composition, and biogenesis. Therefore, part of the controversies on the biological effects exerted by EV is a consequence of differences in methods of separation that result in the enrichment of different entities. Since technical challenges still hamper the highly specific sorting of different EV subpopulations, up to now only few investigators have tried to verify differences in the biological effects of specific EV subtypes. This review summarizes the current state of the art on the comprehension of mechanisms involved in EV biogenesis and release, which is a prerequisite for understanding and investigating the impact that pathology and drug therapy may exert on the secretion and composition of EV. Finally, we described both the mechanism involved in the modulation of EV secretion by drugs commonly used in patients affected by heart failure, and how pathophysiological mechanisms involved in heart disease modify EV secretion.

Copyright of Rheuma Plus is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

In recent decades, pharmacotherapy for depression has undergone dramatic changes. In contrast to the formerly relatively small number of available preparations, the entire range of antidepressants is now practically available to clinicians. Many of them have been launched only in recent years, with the market demand for these preparations constantly increasing, further initiating research in this area. On the eve of the epidemic of depression, the issues of nosology, etiology, prevention, and treatment of this disorder become a priority for anyone who tries to help their loved ones. Pharmacological therapy of depression requires physicians to make the right choice according to world guidelines, close monitoring of the patient , and to control side effects and interactions. Due to the overload of psychiatrists and the high prevalence of depression, patients suffering from depression are often marginalized, stigmatized and inadequately cared for. Therefore, a Master of Pharmacy, through an interdisciplinary approach and practice in pharmaceutical care, can contribute to a rational approach to patient treatment through: monitoring patient compliance, counseling on side effects and drug interactions, and finally supporting a patient with depression to help improve quality of life. [ABSTRACT FROM AUTHOR]

Congenital heart disease (CHD) is the most common inborn defect. Due to advances in paediatric care, surgical, and catheter procedures the number of adults with CHD has grown remarkably in recent years. Most of these patients, however, have residua from their original operation/s and require life-long care, many of them are subjected to further haemodynamic and electrophysiological interventions during adulthood. While such re-do surgical or catheter interventions together with device therapy and transplantation play a key therapeutic role, increasingly, adults with CHD require drug therapy for late complications namely heart failure (HF), arrhythmias, pulmonary and systemic hypertension, thromboembolic events, etc. Unlike other cardiovascular areas, drug therapy in adult CHD is based on scarce clinical data and remains largely empiric. Consequently, pharmacological therapies are individualized to ameliorate patients' symptoms and/or degree of haemodynamic impairment. Thus far, recommendations have been difficult to make and formalized guidelines on drug therapy are lacking. We review herewith the rationale, limited evidence and knowledge gaps regarding drug therapy in this growing cardiovascular field and discuss pharmacotherapy options in specific conditions namely HF, arrhythmias, thrombosis, pulmonary arterial hypertension, contraception, and pregnancy. [ABSTRACT FROM AUTHOR]

While implantable cardioverter defibrillators decrease mortality in high risk groups of patients who have ventricular arrhythmias, antiarrhythmic drugs are still required to reduce the burden of both benign and life-threatening arrhythmias. This review will address the available medical therapy for ventricular arrhythmias in Australia and their use in different clinical situations. [ABSTRACT FROM AUTHOR]

Rationale: Pulmonary arterial hypertension (PAH) is a devastating disease characterized by progressive vasoconstriction and obliterative vascular remodeling that leads to right heart failure (RHF) and death. Current therapies do not target vascular remodeling and RHF, and result in only modest improvement of morbidity and mortality.Objectives: To determine whether targeting HIF-2α (hypoxia-inducible factor-2α) with a HIF-2α-selective inhibitor could reverse PAH and RHF in various rodent PAH models.Methods: HIF-2α and its downstream genes were evaluated in lung samples and pulmonary arterial endothelial cells and smooth muscle cells from patients with idiopathic PAH as well as various rodent PAH models. A HIF-2α-selective inhibitor was used in human lung microvascular endothelial cells and in Egln1Tie2Cre mice, and in Sugen 5416/hypoxia- or monocrotaline-exposed rats.Measurements and Main Results: Upregulation of HIF-2α and its target genes was observed in lung tissues and isolated pulmonary arterial endothelial cells from patients with idiopathic PAH and three distinct rodent PAH models. Pharmacological inhibition of HIF-2α by the HIF-2α translation inhibitor C76 (compound 76) reduced right ventricular systolic pressure and right ventricular hypertrophy and inhibited RHF and fibrosis as well as obliterative pulmonary vascular remodeling in Egln1Tie2Cre mice and Sugen 5416/hypoxia PAH rats. Treatment of monocrotaline-exposed PAH rats with C76 also reversed right ventricular systolic pressure, right ventricular hypertrophy, and pulmonary vascular remodeling; prevented RHF; and promoted survival.Conclusions: These findings demonstrate that pharmacological inhibition of HIF-2α is a promising novel therapeutic strategy for the treatment of severe vascular remodeling and right heart failure in patients with PAH. [ABSTRACT FROM AUTHOR]

Copyright of Der Hautarzt is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The objective of this study is to know the influence of religious/spiritual elements on the adherence to pharmacological therapy. The descriptors used for this literature review were “medicine, medication, drug, or treatment,” “adherence to treatment,” and “religion or spirituality or faith or prayer” in different databases (CINAHL, PsycINFO, PubMed). Finally, 23 articles were selected. Articles available in full text, published between 2010 and 2017, in English or Spanish were included. The results showed that some studies relate positively the R/S and therapeutic adherence, but others determine an opposite or even mixed effect, mainly addressing pathologies such as HIV and other chronic diseases. The influence of religiosity/spirituality on therapeutic adherence requires that health professionals acquire sensitivity and competence to address these issues with their patients. [ABSTRACT FROM AUTHOR]

Extracellular vesicles (EV) are at the center of an intense activity of investigation, both for their possible employment as biomarkers of ongoing pathologic processes and for their broad range of biological activities. EV can promote tissue repair in very different pathologic settings, including hindlimb and myocardial ischemia. Importantly, the exact mode of action of EV is still partly understood, since they may act by modulating growth factors and cytokines, signaling pathways, and by transferring non-coding RNAs to target cells. However, the term EV identifies cell derived, enveloped particles very heterogeneous in size, composition, and biogenesis. Therefore, part of the controversies on the biological effects exerted by EV is a consequence of differences in methods of separation that result in the enrichment of different entities. Since technical challenges still hamper the highly specific sorting of different EV subpopulations, up to now only few investigators have tried to verify differences in the biological effects of specific EV subtypes. This review summarizes the current state of the art on the comprehension of mechanisms involved in EV biogenesis and release, which is a prerequisite for understanding and investigating the impact that pathology and drug therapy may exert on the secretion and composition of EV. Finally, we described both the mechanism involved in the modulation of EV secretion by drugs commonly used in patients affected by heart failure, and how pathophysiological mechanisms involved in heart disease modify EV secretion. [ABSTRACT FROM AUTHOR]

Primary mitochondrial diseases (PMD) refer to a group of severe, often inherited genetic conditions due to mutations in the mitochondrial genome or in the nuclear genes encoding for proteins involved in oxidative phosphorylation (OXPHOS). The mutations hamper the last step of aerobic metabolism, affecting the primary source of cellular ATP synthesis. Mitochondrial diseases are characterized by extremely heterogeneous symptoms, ranging from organ-specific to multisystemic dysfunction with different clinical courses. The limited information of the natural history, the limitations of currently available preclinical models, coupled with the large variability of phenotypical presentations of PMD patients, have strongly penalized the development of effective therapies. However, new therapeutic strategies have been emerging, often with promising preclinical and clinical results. Here we review the state of the art on experimental treatments for mitochondrial diseases, presenting “one-size-fits-all” approaches and precision medicine strategies. Finally, we propose novel perspective therapeutic plans, either based on preclinical studies or currently used for other genetic or metabolic diseases that could be transferred to PMD.

Minakuchi H, Fujisawa M, Abe Y, Iida T, Oki K, Okura K, Tanabe N, Nishiyama A. Managements of sleep bruxism in adult: A systematic review. Jpn Dent Sci Rev. 2022; 58:124-36. None was reported. Systematic review. [ABSTRACT FROM AUTHOR]

The review concerns modern pharmacological methods of Parkinson's disease treatment. The basic drugs used in practice are levodopa, dopamine receptor agonists, MAO-B inhibitors, anticholinergics, COMT inhibitors, and amantadine drugs. The article considers main features, assessment methods and targets of the differentiated therapy, presents benefits and drawbacks of each drug, and describes the problem of generics. According to the study, there is a preferences to use long-acting drugs. The choice of a drug for Parkinson's disease treatment depends on such characteristics as the patient's age, the character of Parkinson's disease, the severity of movement disorder, concomitant diseases, the drug price, the patient's individual sensitivity to different drugs. Finally, the article presents recommendations on initial treatment of Parkinson's disease.

Osteoporosis is the most common bone disease affecting millions of people worldwide, particularly in elderly or in post-menopausal women. The pathogenesis is useful to understand the possible mechanism of action of anti-osteoporotic drugs. Early diagnosis, possible with several laboratory and instrumental tests, allows a major accuracy in the choice of anti-osteoporosis drugs. Treatment of osteoporosis is strictly related to severity of pathology and consists on prevention of fragility fractures with a correct lifestyle and adequate nutritional supplements, and use of pharmacological therapy, started in patients with osteopenia and history of fragility fracture of the hip or spine. The purpose of this review is to focus on main current pharmacological products to treat osteoporotic patients.