Munozbanks5188

A recent study has shown that acetate administration leads to a fourfold increase in the transcription of proopiomelanocortin (POMC) mRNA in the hypothalamus. POMC is cleaved to peptides, including β-endorphin, an endogenous opioid (EO) agonist that binds preferentially to the µ-opioid receptor (MOR). We hypothesised that an acetate challenge would increase the levels of EO in the human brain. We have previously demonstrated that increased EO release in the human brain can be detected using positron emission tomography (PET) with the selective MOR radioligand [

C]carfentanil. We used this approach to evaluate the effects of an acute acetate challenge on EO levels in the brain of healthy human volunteers.

Seven volunteers each completed a baseline [

C]carfentanil PET scan followed by an administration of sodium acetate before a second [

C]carfentanil PET scan. Dynamic PET data were acquired over 90 minutes, and corrected for attenuation, scatter and subject motion. Regional [

C] carfentanil



values were then calculated using the simplified reference tissue model (with the occipital grey matter as the reference region). Change in regional EO concentration was evaluated as the change in [

C]carfentanil



following acetate administration.

Following sodium acetate administration, 2.5-6.5% reductions in [

C]carfentanil regional



were seen, with statistical significance reached in the cerebellum, temporal lobe, orbitofrontal cortex, striatum and thalamus.

We have demonstrated that an acute acetate challenge has the potential to increase EO release in the human brain, providing a plausible mechanism of the central effects of acetate on appetite in humans.

We have demonstrated that an acute acetate challenge has the potential to increase EO release in the human brain, providing a plausible mechanism of the central effects of acetate on appetite in humans.

Patients with functional stroke can present with functional speech, language or swallowing symptoms, which are managed by speech and language therapists (SLTs). The aim of this study was to explore SLTs' views and experiences of working with patients with functional stroke.

Constructivist grounded theory approach was used. Semi-structured interviews were the method of data collection. Constant comparative analysis was used to analyse data. Participants were eligible if they were SLTs who thought they had experience of working with functional stroke.

12 participants were interviewed. Patients with functional stroke were a common occurrence on participants' caseloads; yet they felt patients do not receive optimum care. All participants wanted to help their patients, yet felt they were working within a multitude of barriers to effective input. These included stigma about the diagnosis, lack of pre-qualification training, quick discharge from inpatient settings, lack of access to mental health services and lack of clinical guidelines and care pathways.

As healthcare professionals, participants were keen to help their patients. However, they felt they did not have the skills or knowledge to help which caused professional turmoil. Reducing stigma and increasing awareness and knowledge of functional stroke are required to improve patient outcomes.

As healthcare professionals, participants were keen to help their patients. However, they felt they did not have the skills or knowledge to help which caused professional turmoil. Reducing stigma and increasing awareness and knowledge of functional stroke are required to improve patient outcomes.Background Progressive familial intrahepatic cholestasis (PFIC) is an ultra-rare disease with a considerable burden on pediatric patients and their caregivers, impacting quality of life (QoL). The mortality rates highlight a significant need for efficacious treatments. Real-world data on associated costs and QoL are needed to gauge the potential impact of new pharmacological treatments.Methods Clinical and socio-economic burden of PFIC on patients/caregivers, health systems, and society will be assessed. selleck products Patient/caregiver- and physician-level retrospective cross-sectional data will be collected from the US, UK, France, and Germany, for PFIC types 1, 2, 3.A representative sample of physicians will provide clinical and resource utilization information using an electronic Case Report Form (eCRF). Patient/caregiver surveys will collect socio-economic and QoL data, enabling assessment of PFIC impact on QoL. Mean costs (direct medical/non-medical, indirect) will be calculated.The study materials were reviewed by medical professionals and patient representatives and received ethical approval from the University of Chester.Discussion The study aims to reveal the unmet medical need, disease burden, resource utilization, and costs of PFIC, to raise awareness with policymakers and healthcare professionals, and provide support for the patient/caregiver community. As novel PFIC therapies recently emerged, this study will yield quantifiable data for health technology assessments.

Cardiotocography (CTG) is the main method of intrapartum fetal surveillance. In 2015 a new guideline was introduced by the International Federation of Gynecology and Obstetrics (FIGO), FIGO-15. In Sweden it was adjusted to SWE-17, replacing the previous national template, SWE-09. This study, conducted at one university hospital and one regional hospital in southern Sweden, evaluated the diagnostic validity of these three templates to detect fetal acidosis during the first stage of labor.

A total of 73 neonates with pH <7.1 in umbilical cord artery or vein at cesarean delivery during the first stage of labor were identified retrospectively. For each acidotic neonate, three non-acidemic neonates, with a pH ≥7.2 in cord artery and vein, and Apgar scores ≥9 at five and ten minutes, in all 219 neonates, were selected. The CTG tracings before birth in acidemic neonates, and tracings at the same cervical dilatation in the non-acidemic neonates, were independently assessed by three professionals from the obsteith acidemia, agreement for three independent assessors was strong (κ 0.85) with SWE-09, and weak for FIGO-15 (κ 0.47), and SWE-17 (κ 0.51). For tracings from neonates without acidemia, the agreement was almost perfect for FIGO-15 (κ 0.91), strong withSWE-17 (κ 0.90) and moderate with SWE-09 (κ 0.78).

The ability of FIGO-15 and SWE-17 to identify fetal acidosis is considered insufficient. The combination of a high sensitivity and a high specificity makes SWE-09 the most discriminatory template during the first stage of labor.

The ability of FIGO-15 and SWE-17 to identify fetal acidosis is considered insufficient. The combination of a high sensitivity and a high specificity makes SWE-09 the most discriminatory template during the first stage of labor.Introduction Treatment of osteoporosis with the available drug formulations is still challenging due to multiple associated limitations such as chronic treatment, off-target side effects, poor bone targeting, and low bioavailability. Adopting advanced bone-targeted drug delivery strategies like liposomes is one of the safe and effective approaches for osteoporosis treatment.Areas covered This review summarizes the applications of liposomes in gene delivery, bone regeneration, bone-targeted delivery, and as a carrier for drug encapsulation in the treatment of osteoporosis. Details of all the supportive studies are discussed here and the bone-specific roles of the strategies like new generation liposomes in osteoporosis are elaborated. The future scope of performing in-depth research on the bone-targeted liposomes is discussed.Expert opinion Liposomes-based bone-targeted delivery of therapeutics seems to be a promising approach for the effective treatment of osteoporosis. But till date, the tremendous in vitro and in vivo research on liposomes has failed to attain significant progress in their clinical translation. From bench to bedside success of the research an interdisciplinary collaboration between the preclinical and clinical experts engaged at different stages of liposomes development is required.

To assess the long-term cost-effectiveness of an atrial fibrillation disease management program (i.e. the SAFETY program) from the Australian healthcare system perspective.

A multistate Markov model was developed based on patient-level data from the SAFETY randomized controlled trial. Predicted long-term survival, dependent on hospital admission history, was estimated by extrapolating parametric survival models. Quality-adjusted life years (QALY) and life years (LY) were the primary and secondary outcome measures used to estimate the incremental cost-utility/effectiveness ratio (ICUR/ICER). Both deterministic and probabilistic sensitivity analyses (PSA) were undertaken.

The SAFETY program was associated with both higher costs ($94,953 vs. $78,433) and benefits [QALY (3.99 vs 3.60); LY (5.86 vs 5.24)], with an ICUR of $42,513/QALY or ICER of $26,356/LY, compared to standard care. Due to the extended survival, the SAFETY was associated with a greater number of hospitalizations (14.85 vs 11.65) and higher costs for medications ($25,084 vs $22,402) and outpatient care ($12,904 vs $11,524). The cost per hospitalization for an average length of stay, analytical time horizon, and cost of medication are key determinants of ICUR. The PSA showed that the intervention has a 70.4% probability of being cost-effective at a threshold of $50,000/QALY.

The SAFETY program has a high probability of being cost-effective for patients with atrial fibrillation. It is associated with uncertainty that further research could potentially eliminate; implementation with further evidence collection is recommended.

The SAFETY program has a high probability of being cost-effective for patients with atrial fibrillation. It is associated with uncertainty that further research could potentially eliminate; implementation with further evidence collection is recommended.The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes the coronavirus disease 2019 (COVID-19) has infected millions of individuals and has claimed hundreds of thousands of human lives worldwide. Patients with underlying cardiovascular conditions are at high risk for SARS-CoV-2 infection, and COVID-19 patients have high incidence of cardiovascular complications such as acute cardiac injury, arrhythmias, heart failure, and thromboembolism. The disease has no approved proven effective therapy and hence repurposing of existing approved drugs has been considered as the fastest treatment approach. Statins have been shown to exhibit lipid lowering dependent and independent cardiovascular protective effects as well as favorable effects in various other pathophysiological states. These beneficial properties of statins are a result of their multiple pleotropic effects that include, anti-inflammatory, immunomodulatory, antithrombotic and antimicrobial properties. In this review, we provide a comprehensive description of the mechanisms of the pleotropic effects of statins, the relevant pre-clinical and clinical data pertinent to their role in infections and acute lung injury, the possible cardiovascular benefits of statins in COVID-19, and the implications of the therapeutic potential of statins in COVID-19 disease. We conclude with the rationale for conducting randomized controlled trials of statins in COVID-19 disease.