Miracle-dz/UniFAR-FTUs huggingface dataset:
Complementary therapies for acute pain management: What does the evidence say?

Pain is a condition that affects more Americans than heart disease, cancer, and diabetes combined, cumulatively impacting 25 million American adults daily. The prevalence of acute pain among inpatients varies greatly from 30% to 84%. Pain can be diffi cult to treat given its subjective nature. Uncontrolled pain has a signifi cant effect on mood, sleep, and overall enjoyment in life. Additionally, acute pain may interfere with recovery from injury, may lead to thrombolytic events and prolonged hospital stays, and can progress to chronic pain. In our current times of transparency, patient satisfaction is often linked to effective pain management in the inpatient setting. As providers combating the opioid epidemic and attempting to provide high-quality patient care, it is imperative we consider complementary pain management options to deliver opioid sparing and effective treatment. Traditional interventions for pain management have relied on pharmaceutical therapies; in an effort to decrease the use of opioid medications, multimodal treatments have been implemented with success. Complementary therapies may serve as an additional opioid sparing multimodal adjunct, further improving acute pain management and preventing postoperative complications as well as onset of chronic pain. This brief review will outline additional therapeutic options providers may consider when treating acute pain in the inpatient setting. A search strategy was developed after consultation with a reference librarian in July 2019 at Vanderbilt University Medical Center. Inclusion criteria were as follows: use of complementary therapies to treat acute pain, human studies, and review articles published in English within the past 5 years. We identifi ed seven complementary therapies reported to be supportive when used in combination with pharmacologic interventions in acute care settings (see Supportive complementary therapies in the acute care setting). The search terms included in the search were: acute pain, complementary therapies, complementary treatments, alternative therapies, nonpharmacologic therapies, and nonpharmacologic treatments. These terms were entered into CINAHL and PubMed databases, and duplicate research publications were removed. The retrieved publications’ reference lists were also appraised for comprehensive review studies. All titles and abstracts were examined for pertinence to the study aim of this review, and inclusion criteria were applied. Initially, 369 articles were retrieved, and after review of abstracts, this number was reduced to 34 full-text publications for evaluation.
The biophysics of superoxide dismutase-1 and amyotrophic lateral sclerosis

Abstract Few proteins have come under such intense scrutiny as superoxide dismutase-1 (SOD1). For almost a century, scientists have dissected its form, function and then later its malfunction in the neurodegenerative disease amyotrophic lateral sclerosis (ALS). We now know SOD1 is a zinc and copper metalloenzyme that clears superoxide as part of our antioxidant defence and respiratory regulation systems. The possibility of reduced structural integrity was suggested by the first crystal structures of human SOD1 even before deleterious mutations in the sod1 gene were linked to the ALS. This concept evolved in the intervening years as an impressive array of biophysical studies examined the characteristics of mutant SOD1 in great detail. We now recognise how ALS-related mutations perturb the SOD1 maturation processes, reduce its ability to fold and reduce its thermal stability and half-life. Mutant SOD1 is therefore predisposed to monomerisation, non-canonical self-interactions, the formation of small misfolded oligomers and ultimately accumulation in the tell-tale insoluble inclusions found within the neurons of ALS patients. We have also seen that several post-translational modifications could push wild-type SOD1 down this toxic pathway. Recently we have come to view ALS as a prion-like disease where both the symptoms, and indeed SOD1 misfolding itself, are transmitted to neighbouring cells. This raises the possibility of intervention after the initial disease presentation. Several small-molecule and biologic-based strategies have been devised which directly target the SOD1 molecule to change the behaviour thought to be responsible for ALS. Here we provide a comprehensive review of the many biophysical advances that sculpted our view of SOD1 biology and the recent work that aims to apply this knowledge for therapeutic outcomes in ALS.
Getting to Zero San Francisco: A Collective Impact Approach.

BACKGROUND Building on several decades of innovative HIV prevention and treatment programming in San Francisco, in 2014, a small group of academic, civic, and community leaders launched Getting to Zero San Francisco, a city-wide consortium focused on getting to zero HIV infections, zero HIV-related deaths, and zero HIV stigma and discrimination. SETTING San Francisco city and county. METHODS The consortium operates under the principles of collective impact composed of 5 components: a common agenda, shared measurement, mutually reinforcing activities, continuous communication, and organization backbone. Two flagship initiatives are described: citywide scale-up of pre-exposure prophylaxis and rapid antiretroviral therapy upon diagnosis. RESULTS The number of new HIV diagnoses declined by over 50% from 399 to 197 from 2013 to 2018; the time from diagnosis to viral suppression decreased from 134 to 62 days during that period. However, continued racial/ethnic disparities in new HIV diagnoses and viral suppression rates point to the need for the Getting to Zero San Francisco committees to focus on racial/ethnic equity as a primary focus. Cisgender and transgender women, people who inject drugs, and people who are homeless also have lower viral suppression rates; ongoing initiatives are attempting to address these disparities. CONCLUSION A collective impact implementation strategy that operates by unifying municipal organizations toward a common goal was associated with citywide gains in reducing new HIV diagnosis and time to viral suppression in San Francisco. Formal evaluation of this strategy will help elucidate under which conditions this approach is most likely to succeed.
The lived experience of adults with cystic fibrosis: what they would tell their younger selves about the gut

Abstract Background Little is known about adults’ experience of living with cystic fibrosis (CF) specifically in relation to the gut. However, their unique perspectives may be meaningful to children with CF and inform the understanding and practice of dietitians. The present study aimed to explore adults’ lived experience of the CF gut and how they learnt to manage the gut as they were growing up. Methods Semi‐structured interviews were conducted with adult inpatients (n = 10). Interviews were audio‐recorded, transcribed verbatim and accounts analysed using interpretative phenomenological analysis. Results Three super‐ordinate themes were identified: taking Creon, the learning process and this much I (now) know. Participants accounts of how CF affects the gut predominantly focused on taking Creon (pancreatin, Mylan). Various strategies were employed for coping with peer responses to taking Creon at school. Several participants reached adulthood before they understood and/or accepted that taking Creon consistently needed to be normal for them. Knowledge and understanding developed over time, with ‘CF experience’ and was shaped by family, CF care teams and other children with CF. All had unmet information needs when growing up. Having key explanations earlier, to make connections between eating, taking Creon, gaining weight and growth, did or would have helped most participants. Participants urged children to be assertive, ask questions and not only be involved in managing their diet and gut, but also begin to take control of this aspect of their CF. Conclusions Supporting development of knowledge, skills and confidence to manage diet and the gut needs to be integral to care throughout childhood.
The role of propolis against paclitaxel‐induced oligospermia, sperm abnormality, oxidative stress and DNA damage in testes of male rats

Paclitaxel (taxol) is one of the most powerful anticancer drugs but it possesses toxic effects on male reproductive system. Propolis, from folkloric remedy, have antioxidant, anti‐inflammatory and anticancer effects. The present study established to examine the protective impact of Propolis against malformation of semen induced by taxol. Twenty‐four male rats equally divided into four groups. Group I (normal control); group II, administrated Propolis alone; group III, taxol‐treated group received taxol; group IV, co‐administered of taxol and Propolis extract. After 4 weeks of treatment, the semen were collected and testis 24 hr after the last treatment. Sperm count, motility, viability and sperm morphology were assayed. Tissue supernatants were isolated for oxidative stress, cell energy parameters and 8‐OHdG. DNA damage was evaluated using Comet assay in testes. Our results confirmed that taxol‐induced significant reduction in sperm count, motility, viability and recorded marked elevation in sperm abnormalities. Also, taxol caused increased in 8‐OHdG and DNA damage versus that recorded in control group. Treatment with Propolis improving semen quality and protected testis from detrimental effects of taxol and minimises its toxicity. In conclusions, Oral administration of Propolis modulates the toxic impact of taxol by amelioration semen quality, diminishing oxidation state, DNA damage and preserving cell energy.
Aging alters cerebrovascular endothelial GPCR and K+ channel function: Divergent role of biological sex.

Age-related dementia entails impaired blood flow to and throughout the brain due, in part, to reduced endothelial nitric oxide signaling. However, it is unknown whether sex impacts cerebrovascular Gq-protein-coupled receptors (GPCRs) and K+ channels underlying endothelium-derived hyperpolarization (EDH) during progressive aging. Thus, we simultaneously evaluated intracellular Ca2+ ([Ca2+]i) and membrane potential (Vm) of intact endothelial tubes freshly isolated from posterior cerebral arteries of young (4-6 mo), middle-aged (12-16 mo), and old (24-28 mo) male and female C57BL/6 mice. Purinergic receptor function (vs. muscarinic) was dominant and enhanced for [Ca2+]i increases in old females vs. old males. Although, Ca2+-sensitive K+ channel function as defined by NS309-evoked Vm hyperpolarization, was mildly impaired in females vs. males during old age. This sex-based contrast in declined function of GPCRs and K+ channels to produce EDH may support a greater ability for physiological endothelial GPCR function to maintain optimal cerebral blood flow in females vs. males during old age. As reflective of the pattern of cerebral blood flow decline in human subjects, KIR channel function decreased with progressive age regardless of sex. Combined age-related analyses masked male vs. female aging and, contrary to expectation, hydrogen peroxide played a minimal role. Altogether, we conclude a sex-based divergence in cerebrovascular endothelial GPCR and K+ channel function while highlighting a previously unidentified form of age-related endothelial dysfunction as reduced KIR function.
Carbetocin vs oxytocin for prevention of postpartum hemorrhage after vaginal delivery

Abstract Objective: To evaluate the efficacy and safety of carbetocin for prevention of postpartum hemorrhage in women undergoing vaginal delivery compared with oxytocin. Methods: We conducted a systemic literature search in PubMed, the Cochrane Library, and Embase without language restrictions from inception of each of database to November 18th, 2018. Randomized controlled trials with outcome measure of blood loss ≥500 ml were eligible if they compared carbetocin with oxytocin to prevent postpartum hemorrhage during the third stage of labor in women undergoing vaginal delivery. Results: This meta-analysis of 5 randomized controlled trials (30,314 women) indicated that there was no significant difference between carbetocin and oxytocin in blood loss ≥500 ml in women undergoing vaginal delivery (relative risks (RRs), 0.52; 95% confidence intervals (CIs), 0.24 to 1.15; P = . 11; I2 = 69%). Sensitivity analyses showed the same results. No significant differences were found in blood loss ≥1000 ml, use of additional uterotonic agents, blood transfusion, uterine massage, flushing, vomiting, abdominal pain, nausea, dizziness, headache, palpitation, itching, and shivering. Conclusions: This meta-analysis showed that carbetocin was as effective and safe as oxytocin for prevention of postpartum hemorrhage in women undergoing vaginal delivery, and the choice of carbetocin for routine prophylaxis will depend on cost-effectiveness.
MITOCHONDRIAL DYSFUNCTION IS ASSOCIATED WITH AN IMMUNE PARALYSIS PHENOTYPE IN PEDIATRIC SEPSIS.

OBJECTIVE Immune dysregulation is a defining feature of sepsis, but the role for mitochondria in the development of immunoparalysis in pediatric sepsis is not known. We sought to determine if mitochondrial dysfunction measured in peripheral blood mononuclear cells (PBMCs) is associated with immunoparalysis and systemic inflammation in children with sepsis. DESIGN Prospective observational study SETTING:: Single academic pediatric intensive care unit (PICU) PATIENTS:: 161 children with sepsis/septic shock and 18 non-infected PICU controls MEASUREMENTS AND MAIN RESULTS:: Mitochondrial respiration in PBMCs, markers of immune function, and plasma cytokines were measured on days 1-2 (T1), 3-5 (T2), and 8-14 (T3) after sepsis recognition, and once for controls. Immunoparalysis was defined as whole-blood ex vivo lipopolysaccharide (LPS)-induced tumor necrosis factor-alpha (TNF-α) ≤200 pg/mL or monocyte human leukocyte antigen (mHLA)-DR ≤30%. Mitochondrial respiration was lower in children with versus without immunoparalysis measured at the same timepoint. Mitochondrial respiration measured early (at T1 and T2) was also lower in those with immunoparalysis at T2 and T3, respectively. Although most patients with immunoparalysis exhibited low mitochondrial respiration, this metabolic finding was not specific to the immunoparalysis phenotype. Plasma cytokines, including IL-8, IL-10, TNF-α, and MCP-1 were highest in the subset of sepsis patients with immune paralysis or low mitochondrial respiration at T1. CONCLUSIONS Children with sepsis had lower PBMC mitochondrial respiration when immunoparalysis was present compared to those without immunoparalysis. The subsets with immune paralysis and low mitochondrial respiration exhibited the highest levels of systemic inflammation.
Detecting antimicrobial peptides by exploring the mutual information of their sequences

Abstract The rise of antibiotic resistance in pathogenic bacteria is a growing concern for every part of the world. The present study shows the prediction efficiency of mutual information for the classification of antimicrobial peptides. The proven role of antimicrobial peptides (AMPs) to fight against multidrug-resistant pathogens and AMP’s low toxic properties laid the foundation of computational methods to play their role in detecting AMPs from non-AMPs. Mutual information vectors (MIV) were created for AMP/non-AMP sequences and then fed to different machine learning classifiers out of which a random forest (RF) classifier showed best results for predicting AMPs. Random forest classifiers were evaluated on benchmark datasets by 10-fold cross-validation. The proposed MIV-RF method showed better prediction accuracy, MCC (Matthews correlation coefficient), and AUC-ROC (Area Under The Curve-Receiver Operating Characteristics) than available methods for detecting AMPs. Communicated by Ramaswamy H. Sarma
Allogeneic Cardiosphere-derived Cells for the Treatment of Heart Failure with Reduced Ejection Fraction: Results of the Dilated cardiomYopathy iNtervention with Allogeneic Myocardially-regeneratIve Cells (DYNAMIC) trial.

AIMS The DYNAMIC trial assessed the safety and explored the efficacy of multivessel intracoronary infusion of allogeneic cardiosphere-derived cells (CDCs) in patients with heart failure and reduced ejection fraction (HFrEF). METHODS AND RESULTS We enrolled 14 patients with EF≤35% and NYHA III-IV despite maximal medical- and device-based therapy in this single-center, open-label trial. Intracoronary catheterization delivered four escalating doses (totaling 37.5-75 million cells) by sequential non-occlusive technique to all three major coronary arteries. The primary safety endpoint was a composite of post-infusion TIMI flow, ventricular tachycardia/fibrillation, sudden death, major adverse cardiac events or acute myocarditis within 72 hours. Twelve patients were male and EF averaged 23.0% (±4.5%). No primary safety endpoints were observed. Two patients died of HFrEF progression 9- and 12-months following infusion. Compared to baseline, there was an improvement in EF (26.8% vs. 22.9%, p=0.023) and left ventricular end-systolic volume (139.5 vs. 177.8, p=0.03) at 6 months. Quality of life (QoL) scores and NYHA class (p=0.006) improved at 6 months. At 12 months, the improvement in EF and QoL remained significant. CONCLUSIONS Global intracoronary infusion of allogeneic CDCs is safe and feasible. The efficacy of allogeneic CDCs in HFrEF needs to be tested in larger randomized trials.
Defining raft domains in the plasma membrane

Many plasma membrane (PM) functions depend on the cholesterol concentration in the PM in strikingly nonlinear, cooperative ways: fully functional in the presence of physiological cholesterol levels (35~45 mol%), and nonfunctional below 25 mol% cholesterol; namely, still in the presence of high concentrations of cholesterol. This suggests the involvement of cholesterol‐based complexes/domains formed cooperatively. In this review, by examining the results obtained by using fluorescent lipid analogs and avoiding the trap of circular logic, often found in the raft literature, we point out the fundamental similarities of liquid‐ordered (Lo)‐phase domains in giant unilamellar vesicles, Lo‐phase‐like domains formed at lower temperatures in giant PM vesicles, and detergent‐resistant membranes: these domains are formed by cooperative interactions of cholesterol, saturated acyl chains, and unsaturated acyl chains, in the presence of >25 mol% cholesterol. The literature contains evidence, indicating that the domains formed by the same basic cooperative molecular interactions exist and play essential roles in signal transduction in the PM. Therefore, as a working definition, we propose that raft domains in the PM are liquid‐like molecular complexes/domains formed by cooperative interactions of cholesterol with saturated acyl chains as well as unsaturated acyl chains, due to saturated acyl chains' weak multiple accommodating interactions with cholesterol and cholesterol's low miscibility with unsaturated acyl chains and TM proteins. Molecules move within raft domains and exchange with those in the bulk PM. We provide a logically established collection of fluorescent lipid probes that preferentially partition into raft and non‐raft domains, as defined here, in the PM.
Coronally advanced flap with connective tissue graft or xenogeneic acellular dermal matrix in the treatment of multiple gingival recessions: A split-mouth randomized clinical trial.

OBJECTIVE To evaluate the clinical efficacy of xenogeneic acellular dermal matrix (XADM) or connective tissue graft (CTG) combined with modified-coronally advanced flap (M-CAF) in the treatment of multiple gingival recessions. MATERIALS AND METHODS Twelve participants with bilateral MGRs (multiple gingival recession) (82 gingival recessions) randomly received XADM (test group, 41 teeth) on one side and subepithelial CTG (control group, 41 teeth) on the other side in conjunction with M-CAF in the same session and completed the 18-months study period. Recession depth (RD), recession width (RW), keratinized tissue width (KTW), probing depth (PD), and clinical attachment level (CAL) were recorded at baseline, and 6-, 18-months postoperatively. RESULTS PD was significantly higher in the test group at 18-months (P < .05). PD in the test group was also significantly higher at 6- and 18-months compared to baseline (P < .05). RD and RW were significantly lower at 6- and 18-months compared to baseline in both groups (P < .05) and both parameters were significantly higher in the test group at 18-months (P < .05). Percentage of teeth with complete root coverage in the test and control groups were similar at 6-months (78% and 70.7%, respectively) and at 18-months (both 87.8%) (P > .05). CONCLUSION Within the limits of the study, M-CAF combined with XADM or CTG seems to be similarly effective in RD reduction of class I and II MGRs at least in the short term. Soft tissue shrinkage and increase in PD may be observed with XADM, while; CTG seems to provide stable clinical outcomes for 18-months follow-up. CLINICAL SIGNIFICANCE Even though the CTG and XADM in conjunction with M-CAF may provide similar RD reduction in class I and II multiple gingival recessions in the short term. CTGs may be superior in terms of soft tissue shrinkage and PD values.
The impact of a higher eating frequency on the diet quality and nutritional status of women with breast cancer undergoing chemotherapy

Abstract The present study investigated the association between eating frequency (EF), diet quality and nutritional status of fifty-five women with breast cancer (BC) undergoing chemotherapy (CT), with three follow-ups, before the first cycle (T0), after the intermediate cycle (T1) and after the last cycle of CT (T2). Dietary data were obtained by nine 24-h dietary recalls (24HR), and the Brazilian Healthy Eating Index Revised (BHEI-R) was used for qualitative analysis of diet. The average EF was established by adding the number of daily eating episodes in the three 24HR of each time. Anthropometric variables were obtained at three times. Women who reported higher EF (equal to or above median value (T0 and T1: 4·67; T2: 4·33 eating episodes)) presented better anthropometric parameters, in T0 and T1, as well as higher scores for BHEI-R specific groups and BHEI-R Total score in T1 and T2. In generalised linear models, the continuous variable EF was negatively associated with all the anthropometric variables in T0 and with the waist:height ratio in T1. There were positive associations for the BHEI-R groups at the three times: Total Fruit; Whole Fruit; Total Vegetables; Dark Green and Orange Vegetables and Legumes. At T1 and T2 the EF was positively associated with the BHEI-R Total score, and also with Whole Grains in T1. The results suggest that a higher EF was associated with a better diet quality during CT in women with BC. In contrast, an inverse association was observed between EF and anthropometric parameters before the first cycle of treatment.