Regarding stakeholders within investigation goal placing a new scoping assessment

Tourette syndrome (TS) is a neurodevelopmental condition characterized by multiple tics. Sensory symptoms play a key role in the clinical phenomenology and pathophysiology of TS, as most patients report premonitory urges driving tic expression. Interestingly, sensory symptoms have also been reported in other conditions characterized by repeated behaviors. This review explores the nature of sensory symptoms reported by patients with body focused repetitive behaviors (BFRBs, especially trichotillomania and skin picking disorder) and restless legs syndrome (RLS) in comparison to TS. A sense of mounting inner tension and reinforcement mechanisms driven by gratification and relief on expression of the tic or repetitive behavior appear to be implicated across all conditions. Subjective urges can be temporarily suppressed by patients with TS and selected BFRBs, whereas patients with RLS tend to report dysesthesia more frequently than a suppressible urge to move. The observed similarities in the phenomenology of sensory symptoms across these conditions raise the possibility of a comparable underlying pathophysiology. Preliminary findings suggest an overlap of neural pathways encompassing the insula, basal ganglia (putamen), and posterior cingulate cortex.Breast cancer diagnosis, surgery, adjuvant therapies and survivorship can all be extremely stressful. In women, concerns about body image are common as a result of the disease and can affect interpersonal relationships, possibly leading to social isolation, increasing the likelihood for mood disorders. This is particularly relevant as women are at greater risk to develop anxiety and depressive symptoms in response to highly stressful situations. Here we address the mechanisms and the pathways activated as a result of stress and contributing to changes in the pathophysiology of breast cancer, as well as the potential of stress management factors and interventions in buffering the deleterious effects of chronic stress in a gender perspective. An improved understanding of the biological mechanisms linking stress-management resources to health-relevant biological processes in breast cancer patients could reveal novel therapeutic targets and help clarifying which psychosocial interventions can improve cancer outcomes, ultimately offering a unique opportunity to improve contemporary cancer treatments.The critical problem of space exploration is the effect of long-term space travel on brain functioning. Current information concerning the effects of actual spaceflight on the brain was obtained on rats and mice flown on five missions of Soviet/Russian biosatellites, NASA Neurolab Mission STS90, and International Space Station (ISS). The review provides converging lines of evidence that 1) long-term spaceflight affects both principle regulators of brain neuroplasticity - neurotransmitters (5-HT and DA) and neurotrophic factors (CDNF, GDNF but not BDNF); 2) 5-HT- (5-HT2A receptor and MAO A) and especially DA-related genes (TH, MAO A, COMT, D1 receptor, CDNF and GDNF) belong to the risk neurogenes; 3) brain response to spaceflight is region-specific. Substantia nigra, striatum and hypothalamus are highly sensitive to the long-term spaceflight in these brain areas spaceflight decreased the expression of both DA-related and neurotrophic factors genes. Since DA system is involved in the regulation of movement and cognition the data discussed in the review could explain dysfunction of locomotion and behavior of astronauts and direct further investigations to the DA system.The phytocannabinoid Δ9-tetrahydrocannabinol (THC) was isolated and synthesized in the 1960s. Since then, two synthetic cannabinoids (SCBs) targeting the cannabinoid 1 (CB1R) and 2 (CB2R) receptors were approved for medical use based on clinical safety and efficacy data dronabinol (synthetic THC) and nabilone (synthetic THC analog). To probe the function of the endocannabinoid system further, hundreds of investigational compounds were developed; in particular, agonists with (1) greater CB1/2R affinity relative to THC and (2) full CB1/2R agonist activity. This pharmacological profile may pose greater risks for misuse and adverse effects relative to THC, and these SCBs proliferated in retail markets as legal alternatives to cannabis (e.g., novel psychoactive substances [NPS], "Spice," "K2"). These SCBs were largely outlawed in the U.S., but blanket policies that placed all SCB chemicals into restrictive control categories impeded research progress into novel mechanisms for SCB therapeutic development. There is a concerted effort to develop new, therapeutically useful SCBs that target novel pharmacological mechanisms. This review highlights the potential therapeutic efficacy and safety considerations for unique SCBs, including CB1R partial and full agonists, peripherally-restricted CB1R agonists, selective CB2R agonists, selective CB1R antagonists/inverse agonists, CB1R allosteric modulators, endocannabinoid-degrading enzyme inhibitors, and cannabidiol. We propose promising directions for SCB research that may optimize therapeutic efficacy and diminish potential for adverse events, for example, peripherally-restricted CB1R antagonists/inverse agonists and biased CB1/2R agonists. Together, these strategies could lead to the discovery of new, therapeutically useful SCBs with reduced negative public health impact.
The management of non-operable chronic thromboembolic pulmonary hypertension (CTEPH) has evolved with the availability of balloon pulmonary angioplasty (BPA) and pulmonary vasodilators. We launched the BPA program in 2011. The aim was to analyze the survival and treatment efficacy of our CTEPH treatment program in the modern management era.
We retrospectively reviewed data from 143 consecutive CTEPH patients diagnosed from January 2011 (i.e. after the availability of BPA) to December 2019. Of forty-one patients who underwent pulmonary endarterectomy (PEA), 25 underwent additional BPA (Combination group) and the others were treated with only PEA (PEA group). Ninety patients underwent BPA (BPA group). The remaining 12 patients did not undergo any interventional treatments. The 1- and 5-year survival rates of operated patients (n=41) were 97.4% and 90.0%, compared to 96.9% and 86.9% in not-operated patients (n=102), respectively (p=0.579). There was no mortality in the Combination group. Mean pulmonary artery pressure after treatments in the PEA only, Combination, and BPA only groups was 20.5±6.7, 17.9±4.9, and 20.7±4.6mmHg, respectively (p=0.067, one-way ANOVA). Percent decrease of pulmonary vascular resistance in each treatment groups was -73.7±11.3%, -74.3±11.8%, and-54.9±22.5%, respectively (p<0.01, one-way ANOVA).
There was no significant difference in long-term survival between operated and not-operated CTEPH. Moreover, the Combination approach might have the potential to introduce notable improvements in the prognosis of CTEPH. BPA and PEA appear to be mutually complementary therapies in the modern management era.
There was no significant difference in long-term survival between operated and not-operated CTEPH. Moreover, the Combination approach might have the potential to introduce notable improvements in the prognosis of CTEPH. BPA and PEA appear to be mutually complementary therapies in the modern management era.
Chronic heart failure (CHF) is a serious complication and a major cause of mortality in patients with Takayasu arteritis (TA). We aimed to explore the clinical features and long-term outcomes in TA patients with CHF.
Adult TA patients admitted to our hospital between January 2009 to April 2018 were classified as HF and non-HF group. The adverse events were defined as a composite of all-cause mortality and hospitalization for HF. The outcome of the HF-group was further analyzed. A total of 61 HF patients and 102 non-HF patients were identified. In the HF group, the median age at assessment was 41.9years, and female was predominant (82.0%). The multivariable logistic regression model revealed that pulmonary hypertension, aortic regurgitation, mitral regurgitation, level albumin, and uric acid were independently associated with CHF. After a median follow-up of 1347days, 25 adverse events occurred in HF patients, and the 5-year event-free rate was 54.7%. The Cox model showed that coronary artery involvement, aortic regurgitation, without interventional treatment were related to adverse events.
The 5-year event-free rate was not satisfying. Aggressive intervention may decreased the likelihood of adverse events in patients with CHF.
The 5-year event-free rate was not satisfying. Aggressive intervention may decreased the likelihood of adverse events in patients with CHF.The endogenous free radical nitric oxide (NO) plays a pivotal role in the immunological system. NO has already been reported as a potential candidate for use in the treatment of human coronavirus infections, including COVID-19. In fact, inhaled NO has been used in clinical settings for its antiviral respiratory action, and in the regulation of blood pressure to avoid clot formation. In this mini-review, we discuss recent progress concerning the antivirus activity of NO in clinical, pre-clinical and research settings, and its beneficial effects in the treatment of clinical complications in patients infected with coronaviruses and other respiratory viral diseases, including COVID-19. selleck products We also highlight promising therapeutic effects of NO donors allied to nanomaterials to combat COVID-19 and other human coronavirus infections. Nanomaterials can be designed to deliver sustained, localized NO release directly at the desired application site, enhancing the beneficial effects of NO and minimizing the side effects. Challenges and perspectives are presented to open new fields of research.Dimethyl cardamonin (DMC) has been isolated from diverse plants, notably from Cleistocalyx operculatus. We have reviewed the pharmacological properties of this natural product which displays anti-inflammatory, anti-hyperglycemic and anti-cancer properties. The pharmacological activities essentially derive from the capacity of DMC to interact with the protein targets HMGB1 and AMPK. Upon binding to HMGB1, DMC inhibits the nucleocytoplasmic transfer of the protein and its extracellular secretion, thereby blocking its alarmin function. DMC also binds to the AMP site of AMPK to activate phospho-AMPK and then to trigger downstream signals leading to the anti-inflammatory and anti-hyperglycemic effects. AMPK activation by DMC reinforces inhibition of HMGB1, to further reduce the release of the alarmin protein, likely contributing to the anticancer effects. The characterization of a tight control of DMC over the AMPK-HMGB1 axis not only helps to explain the known activities of DMC but also suggests opportunities to use this chalcone to treat other pathological conditions such as the acute respiratory distress syndrome (which affects patients with COVID-19). DMC structural analogues are also evoked.As the most common form of arthritis, osteoarthritis (OA) has become a major cause of severe joint pain, physical disability, and quality of life impairment in the affected population. To date, precise pathogenesis of OA has not been fully clarified, which leads to significant obstacles in developing efficacious treatments such as failures in finding disease-modifying OA drugs (DMOADs) in the last decades. Given that diarthrodial joints primarily display the weight-bearing and movement-supporting function, it is not surprising that mechanical stress represents one of the major risk factors for OA. However, the inner connection between mechanical stress and OA onset/progression has yet to be explored. Mitochondrion, a widespread organelle involved in complex biological regulation processes such as adenosine triphosphate (ATP) synthesis and cellular metabolism, is believed to have a controlling role in the survival and function implement of chondrocytes, the singular cell type within cartilage. Mitochondrial dysfunction has also been observed in osteoarthritic chondrocytes.