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BACKGROUND Dengue is increasing in its global presence with an estimated 4 billion people at-risk of infection in at least 128 countries. Despite the promising results of EcoHealth and community mobilization approaches to Aedes reduction, more evidence of their efficacy on reducing dengue risk is needed. The principal research question is to determine if interventions based upon community mobilization reduce the risk of dengue virus infection among children 3 to 9 years old compared to usual dengue control practice in Fortaleza, Brazil. METHODS The present study will follow a pragmatic cluster randomized controlled trial (cRCT) design with randomization at the census tract level with equal allocation to the two arms. In each arm, there will be 34 clusters of 86 children between 3 to 9 years old for an expected total of 5848 children enrolled in the study, assuming a risk reduction of 29.5% based upon findings from a previous multi-site cRCT. The primary outcomes are rates of anti-dengue Immunoglobulin G (IgG)s of our study will provide evidence on community mobilization as an intervention for dengue control. We anticipate that if community mobilization is effective in Fortaleza, the results of this study will help develop evidence-based vector control programs in Brazil, and also in other countries struggling with Aedes-transmitted diseases. TRIAL REGISTRATION ISRCTN66131315, registration date 1 October 2018.BACKGROUND Mexico has one of the highest prevalence rates of obesity worldwide. New pharmacological strategies that focus on people with class III obesity are required. Metformin and dapagliflozin are two drugs approved for the treatment of diabetes. Beyond its effects on glucose, metformin has been suggested by some studies to result in weight loss. Therapy with dapagliflozin is associated with a mild but sustained weight loss in patients with diabetes. The primary outcome of the study is to determine if the combined treatment with dapagliflozin and metformin is more effective than monotherapy with metformin for weight loss in patients with class III obesity and prediabetes or diabetes who are awaiting bariatric surgery (including those patients who do have surgery). We also aimed to assess the effect of this combined treatment on waist circumference, triglycerides, blood pressure, and inflammatory cytokines. METHODS This randomized phase IV clinical trial will include patients with diabetes or prediabetes we recorded throughout the study. An intention-to-treat analysis will be used. DISCUSSION Forty-six percent of the patients in our Obesity Clinic have been diagnosed with prediabetes (32%) or diabetes (14%). The use of dapagliflozin in this population could improve weight loss and other cardiovascular factors. This effect could be translated into less time before undergoing bariatric surgery and better control of associated comorbidities. TRIAL REGISTRATION Clinicaltrials.gov, ID NCT03968224. Retrospectively registered on May 29, 2019.BACKGROUND Individuals affected by stroke present with changes in cardiovascular and respiratory functions. Cardiorespiratory training (CRT) is one of the classic intervention guidelines for cardiorespiratory fitness. CRT in association with the proprioceptive neuromuscular facilitation (PNF) technique for respiratory muscles could improve the quality of life, cardiorespiratory function and gait parameters of patients after stroke. OBJECTIVE To assess the effects of respiratory and trunk patterns of CRT associated with PNF on the quality of life, gait, oxygen consumption, respiratory muscle strength and thoracic volumes. METHODS/DESIGN A blind, randomized clinical trial with allocation confidentiality will be performed. Forty patients will be randomized into four groups CRT-lower limb (LL) plus PNF; CRT-LL and respiration; CRT-upper limb (UL) plus PNF; or CRT-UL and respiration. Individuals will be evaluated at three different times (pretreatment, after 20 days of treatment and 1 month after the end of treatment). The treatment protocol consists of respiratory exercises, 30 min of CRT (cycle ergometer) and then repetition of the respiratory exercises, performed three times a week over a period of 20 days. Primary outcome measures are quality of life, gait, balance, peak oxygen uptake and rib cage compartment volumes. As secondary outcomes, respiratory function and maximal inspiratory and expiratory pressures will be measured. DISCUSSION The association of PNF with CRT may be a viable and accessible alternative to increase cardiorespiratory function in patients with stroke. TRIAL REGISTRATION ClinicalTrials.gov, NCT03171012. Registered on 6 June 2017.BACKGROUND Dementia is a neurological condition that affects the cognitive and functional ability of the brain and is the leading cause of disability among those aged 65 years and above. More effective ways to manage dementia symptoms are needed because current treatment options (antidepressants and antipsychotics) can be ineffective and are associated with substantial side effects, including increased rate of mortality. Cannabinoid-based medicine (CBM) has shown an ability to inhibit some symptoms associated with dementia, and the adverse effects are often minimal; yet, little research has explored the use of CBM among this population. AIM To monitor the safety of a purified dose of CBM oil (32 delta-9-tetrahydrocannabinolcannabidiol) on behaviour symptoms, quality of life and discomfort caused by pain. METHODS/DESIGN We will carry out an 18-week, randomised, double-blind crossover trial that consists of a 2-week eligibility period, two 6-week treatment cycles, and two 2-week washout periods (between both cyoups consisting of the aged-care staff and next of kin. DISCUSSION The study design has been informed by medical professionals and key stakeholders, including those working in the residential aged-care industry to ensure patient safety, collection of non-invasive measures, and methodological rigor and study feasibility. TRIAL REGISTRATION Australian New Zealand Clinical Trials Registry, ACTRN12619000474156. Registered on 21 March 2019.BACKGROUND The optimal management of PDA in very low birth weight (VLBW) infants is still controversial. Aim of our study was to investigate the management of PDA in the Italian neonatal intensive care units (NICU). METHODS We conducted an on-line survey study from June to September 2017. A 50-items questionnaire was developed by the Italian Neonatal Cardiology Study Group and was sent to Italian NICUs. RESULTS The overall response rate was 72%. Diagnosis of PDA was done by neonatologists, cardiologists or both (62, 12 and 28% respectively). PDA significance was assessed by a comprehensive approach in all centers, although we found a heterogeneous combination of parameters and cut-offs used. None used prophylactic treatment. 19% of centers treated PDA in the first 24 h, 60% after the first 24 h, following screening echocardiography or clinical symptoms, 18% after the first 72 h and 2% after the first week. In the first course of treatment ibuprofen, indomethacin and paracetamol were used in 87, 6 and 7% of centers respectively. Median of surgical ligation was 3% (1-6%). CONCLUSIONS Significant variations exist in the management of PDA in Italy. Conservative strategy and targeted treatment to infants older than 24 h with echocardiographic signs of hemodynamic significance seemed to be the most adopted approach.Toll-like receptor 4 (TLR4) is a crucial receptor in neuroinflammation and apoptotic neuronal death, and increasing evidences indicated that β2-microglobulin (B2M) is thought to be a major contributor to age-related cognitive decline. In present study, we designed to investigate the effects of TLR4 on B2M-induced age-related cognitive decline. Wild-type (WT) C57BL/6, TLR4 knockout (TLR4 -KO) mice and hippocampal neurons from the two type mice were respectively divided into two groups (1) Veh group; (2) B2M-treated group. The behavioral responses of mice were measured using Morris Water Maze. Hippocampal neurogenesis and neuronal damage, inflammatory response, apoptosis, synaptic proteins and neurotrophic factors, and TLR4/MyD88/NF-κB signaling pathway proteins were examined using molecular biological or histopathological methods. The results showed that WT mice received B2M in the DG exhibited age-related cognitive declines, increased TLR4 mRNA expression and high levels of interleukin-1β (IL-1β), tumor necrosis factor-alpha (TNF-α) and apoptotic neuronal death in the hippocampus, which were partially attenuated in TLR4-KO mice. Moreover, in absence of TLR4, B2M treatment improved hippocampus neurogenesis and increased synaptic related proteins. Our cell experiments further demonstrated that deletion of TLR4 could significantly increase synaptic related protein, decrease neuroinflammatory fators, inhibited apoptotic neuronal death, and regulated MyD88/NF-κB signal pathway after B2M treatment. In summary, our results support the TLR4 contributes to B2M-induced age-related cognitive decline due to neuroinflammation and apoptosis through TLR4/MyD88/NF-κB signaling pathway via a modulation of hippocampal neurogenesis and synaptic function. This may provide an important neuroprotective mechanism for improving age-related cognitive decline.BACKGROUND Informal caregivers report substantial burden and depressive symptoms which predict higher rates of patient institutionalization. While caregiver education interventions may reduce caregiver distress and decrease the use of long-term institutional care, evidence is mixed. Inconsistent findings across studies may be the result of reporting average treatment effects which do not account for how effects differ by participant characteristics. We apply a machine-learning approach to randomized clinical trial (RCT) data of the Helping Invested Family Members Improve Veteran's Experiences Study (HI-FIVES) intervention to explore how intervention effects vary by caregiver and patient characteristics. METHODS We used model-based recursive partitioning models. Caregivers of community-residing older adult US veterans with functional or cognitive impairment at a single VA Medical Center site were randomized to receive HI-FIVES (n = 118) vs. usual care (n = 123). The outcomes included cumulative days not in the community and caregiver depressive symptoms assessed at 12 months post intervention. Potential moderating characteristics were veteran age, caregiver age, caregiver ethnicity and race, relationship satisfaction, caregiver burden, perceived financial strain, caregiver depressive symptoms, and patient risk score. RESULTS The effect of HI-FIVES on days not at home was moderated by caregiver burden (p  less then  0.001); treatment effects were higher for caregivers with a Zarit Burden Scale score ≤ 28. Caregivers with lower baseline Center for Epidemiologic Studies Depression Scale (CESD-10) scores (≤ 8) had slightly lower CESD-10 scores at follow-up (p  less then  0.001). CONCLUSIONS Family caregiver education interventions may be less beneficial for highly burdened and distressed caregivers; these caregivers may require a more tailored approach that involves assessing caregiver needs and developing personalized approaches. https://www.selleckchem.com/products/e-64.html TRIAL REGISTRATION ClinicalTrials.gov, IDNCT01777490. Registered on 28 January 2013.

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