Miracle-dz/UniFAR-FTUs huggingface dataset:
Effect of Early Post-Transplantation Tacrolimus Concentration on the Risk of Acute Graft-Versus-Host Disease in Allogenic Stem Cell Transplantation

Simple Summary Allogeneic hematopoietic stem cell transplantation is a potentially curative treatment for many hematological malignancies and disorders but is often complicated by a relapse of the underlying disease, graft-vs-host disease and infectious complications. However, despite the introduction of calcineurin inhibitors such as tacrolimus, graft-versus-host disease remains one of the major life-threatening complications of allogeneic hematopoietic stem cell transplantation. Due to a variety of factors, there is variability in tacrolimus concentrations during the early weeks post-transplantation. Since the immunologic events leading to acute GVHD also occur in the first few days post-transplantation, it is important that optimal levels be attained early after transplantation. The findings from this study will help inform the management of optimal tacrolimus levels to be attained early post-transplantation. Abstract Acute graft versus host disease (aGVHD) remains a leading cause of morbidity and mortality in allogeneic hematopoietic stem cell transplant (allo-HSCT). Tacrolimus (TAC), a calcineurin inhibitor that prevents T-cell activation, is commonly used as a GVHD prophylaxis. However, there is variability in the serum concentrations of TAC, and little is known on the impact of early TAC levels on aGVHD. We retrospectively analyzed 673 consecutive patients undergoing allo-HSCT at the Ohio State University between 2002 and 2016. Week 1 TAC was associated with a lower risk of aGVHD II–IV at TAC level ≥10.15 ng/mL (p = 0.03) compared to the lowest quartile. The cumulative incidence of relapse at 1, 3 and 5 years was 33%, 38% and 41%, respectively. TAC levels at week 2, ≥11.55 ng/mL, were associated with an increased risk of relapse (p = 0.01) compared to the lowest quartile. Subset analysis with acute myeloid leukemia and myelodysplastic syndrome patients showed significantly reduced aGVHD with TAC level ≥10.15 ng/mL at week 1 and a higher risk of relapse associated with week 2 TAC level ≥11.55 ng/mL (p = 0.02). Hence, achieving ≥10 ng/mL during the first week of HCT may mitigate the risk of aGVHD. However, levels (>11 ng/mL) beyond the first week may be associated with suppressed graft versus tumor effect and higher relapse.
A Possible Role of Video-Head Impulse Test in Detecting Canal Involvement in Benign Paroxysmal Positional Vertigo Presenting With Positional Downbeat Nystagmus.

OBJECTIVE To describe the possible diagnostic role of video-head impulse test (vHIT) in patients presenting with positional downbeat nystagmus (PDN) due to benign paroxysmal positional vertigo (BPPV) involving the anterior canal (AC) or the non-ampullary arm of the posterior canal (PC). PATIENTS Three patients presenting with positional vertigo, PDN, symmetrical cervical and ocular vestibular-evoked myogenic potentials, and selective deficit of the vestibulo-ocular reflex (VOR) gain for a single vertical canal on vHIT. INTERVENTIONS Diagnostic evaluation and rehabilitative treatment for BPPV involving the deficient canals. MAIN OUTCOME MEASURES Video-oculographic and vHIT findings before and after canalith repositioning procedures (CRP) for AC-BPPV and apogeotropic PC-BPPV. RESULTS Each patient was treated with CRP for BPPV involving the hypoactive canal. In one case, symptoms receded with physical therapy, whereas two patients developed a paroxysmal positional upbeat nystagmus consistent with BPPV involving the ampullary arm of the ipsilateral PC and were treated with Epley CRP. Posttreatment evaluation showed resolution of symptoms and signs and restitution of canal function in all cases. CONCLUSIONS PDN can be due to both peripheral and central vestibular pathologies. In case of BPPV, involvement of the non-ampullary arm of the PC is hardly distinguishable from contralateral AC canalolithiasis. In these situations, vHIT may play a key role in the differential diagnosis. Considering these findings, we propose to include vHIT in the test battery of patient with PDN, as it may provide clues to the differential diagnosis with central pathologies enabling the identification of the canal involved by BPPV.
Ciclo de vida de Alytes dickhilleni Arntzen & García-París, 1995 (Anura: Alytidae) y batracofauna acompañante en cuerpos de agua de interés para conservación en la Región de Murcia (SE España)

espanolSe ha estudiado el ciclo de vida durante un periodo anual (diciembre 2016–noviembre 2017) de los anfibios en dos cuerpos de agua artificiales en el limite oriental de la distribucion de la especie amenazada Alytes dickhilleni Arntzen y Garcia-Paris, 1995. En ambos sistemas, se reproduce la especie objetivo y dos mas, Bufo spinosus Daudin, 1803, y Pelophylax perezi (LopezSeoane, 1885). Los ciclos reproductivos de A. dickhilleni y P. perezi muestran semejanzas con lo descrito en medios naturales y artificiales en la Region de Murcia; por el contrario, B. spinosus presento un adelanto significativo. Este estudio pone de manifiesto el importante papel de los cuerpos de agua artificiales ligados a practicas ganaderas tradicionales para la conservacion de A. dickhilleni en el sureste iberico semiarido. EnglishLife cycle of amphibian community inhabiting two artificial ponds on the eastern edge of the native distribution of the endangered species Alytes dickhilleni Arntzen and Garcia- Paris, 1995, was studied over a complete annual cycle (from December 2016 to November 2017). We confirm the breeding status of the target species and two more, Bufo spinosus Daudin, 1803 and Pelophylax perezi (Lopez-Seoane, 1885). Breeding cycles of A. dickhilleni and P. perezi showed similar phenology to available data from other natural and manmade ponds on Region of Murcia; conversely, B. spinosus showed a slightly advanced cycle. This study highlights the important role of artificial and traditional livestock ponds to conservation of A. dickhilleni population in Iberian southeast.
A sophisticated antibiotic-loading protocol in articulating cement spacers for the treatment of prosthetic joint infection

Objectives The optimal protocol for antibiotic loading in the articulating cement spacers for the treatment of prosthetic joint infection (PJI) remains controversial. The objective of the present study was to investigate the effectiveness of articulating cement spacers loaded with a new combination of antibiotics. Methods A retrospective cohort study involving 114 PJI cases treated with implantation of an articulating cement spacer between 2005 and 2016 was performed. The treatment outcomes of the conventional protocol (i.e. gentamicin and vancomycin (GV protocol)) were compared with those reported using the sophisticated antibiotic-loading protocol (i.e. vancomycin, meropenem, and amphotericin (VMA protocol)). Results There were 62 and 52 PJI cases treated with the GV and VMA protocols, respectively. Antimicrobial susceptibility testing revealed that 22/78 of all isolates (28.2%) in this series were resistant to gentamicin, whereas there were no vancomycin-, meropenem-, or amphotericin-resistant strains. The overall infection recurrence rates were 17.7% (11/62) and 1.9% (1/52), respectively (p = 0.006). In patients with a negative preoperative culture, there was no infection recurrence reported in the VMA cohort (0/45 (0%) vs 10/54 (18.5%) in the GV cohort; p = 0.002). Multivariate analysis indicated that the VMA protocol correlated with a decreased risk of infection recurrence compared with the GV protocol (p = 0.025). Conclusion The sophisticated VMA protocol for the loading of antibiotics in articulating cement spacers, as part of a two-stage exchange, was associated with a reduced rate of infection recurrence. This proposed protocol appears to be safe and effective, especially in patients with negative culture results prior to the first-stage operation. Cite this article: Bone Joint Res 2019;8:526–534.
Changes in leukocyte profile and C-reactive protein concentration in overweight and obese adolescents after reduction of body weight

Aim of the study To assess the changes in the leukocyte profile and C-reactive protein (CRP) concentration in adolescents with excess fat mass after 6-12 months of dietary intervention. Material and methods The retrospective study included 99 overweight and obese adolescents, aged from 10.0 to 17.5 years, 82 of whom were re-hospitalized 6 to 12 months after dietary counseling. The control group consisted of 42 normal weight peers. Anthropometric measurements and laboratory tests were performed, homeostasis model assessment – insulin resistance (HOMA-IR) and triglycerides/high-density lipoprotein cholesterol (TG/HDL-C) ratio were calculated. Results Obese and overweight adolescents had higher white blood cells (WBC), neutrophil, monocyte counts and CRP concentration. In the backward stepwise regression analysis, body mass index standard deviation score (BMI SDS) and fasting insulin concentration were independent predictors of WBC and neutrophil counts at the baseline. At the follow-up visit in 45 (54.8%) children, who had lost weight, decreases in WBC, neutrophil and monocyte counts and CRP, fasting insulin, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG) concentrations were observed. Changes in WBC and neutrophil counts were dependent on changes in HOMA-IR and TG/HDL ratio. Changes in HOMA-IR had a significant impact on changes in the monocyte count. Conclusions Adipose tissue promotes systemic inflammation and its intensity depends on the degree of obesity and insulin resistance. This state is reversible. Changes in HOMA-IR were independent predictors of changes in WBC, neutrophil and monocyte counts after reduction of body weight.
Exploring cyberchondria and worry about health among individuals with no diagnosed medical condition.

Objective To study the phenomenon of cyberchondria and related worries about health among individuals without any diagnosed medical condition. METHODS The survey-based, cross-sectional study was conducted from January to July 2018 in the twin cities of Rawalpindi and Islamabad, Pakistan, and comprised graduates of either gender aged at least 35 years with access to internet and means of use, and with no current diagnosed medical condition. The self-reporting Cyberchondria Severity Scale was used data-collection along with a demographic sheet. SPSS 21 was used for data analysis. RESULTS Of the 150 subjects, 90(60%) were men and 60(40%) were women. A total of 40(26.6%) subjects had low level of cyberchondria, while 35(23.3%) experienced a higher level of it. Mean scores of men on total CSS were slightly higher than those of women (p>0.05). Men also scored higher on compulsion, distress, excessiveness and reassurance subsclaes (p>0.05 each), whereas women scored slightly higherthan men on 'mistrust of medical profession' subscale (p>0.05). No significant gender differences werefound on cyberchondria and its subscales (p>0.05 each). CONCLUSIONS Doctors / health professionals may benefit from the findings by focussing on their patients who use internet as a major source of medical information.
Colonoscopy Findings: A Single Institution Study from Pakistan

Introduction Colonoscopy is a diagnostic procedure used not only for screening and assessment but also for therapeutic management of various diseases such as removal of polyps, flat lesions, etc. In this study, we determine various outcomes of colonoscopy done in the gastroenterology unit of Ghulam Muhammad Mahar Medical College and Teaching Hospital in Pakistan. Methods and Materials This retrospective cross-sectional review was carried out at the colonoscopy unit of Ghulam Muhammad Mahar Medical College and Teaching Hospital in Sukkur, Pakistan. Data was gathered from medical records of patients and by calling their physicians if necessary from July 1 to December 31, 2018. Results In our study, the most common site for colonoscopy was a rectosigmoid colon (37.85%, n=134), almost parallel to the anal canal (37.57%, n=133). Normal colonoscopy was reported in 25.42% (n=90). The most common pathology was hemorrhoids (32.48%, n=115), followed by ulcers (17.79%, n=63). Conclusion Colonoscopic detection of hemorrhoids was the most common finding in colonoscopy. Normal colonoscopy was less compared to other literature, suggesting physicians are carefully screening patients in advising colonoscopies.
Using Mobile Health Tools to Assess Physical Activity Guideline Adherence and Smoking Urges: Secondary Analysis of mActive-Smoke

Background Rates of cigarette smoking are decreasing because of public health initiatives, pharmacological aids, and clinician focus on smoking cessation. However, a sedentary lifestyle increases cardiovascular risk, and therefore, inactive smokers have a particularly enhanced risk of cardiovascular disease. Objective In this secondary analysis of mActive-Smoke, a 12-week observational study, we investigated adherence to guideline-recommended moderate-to-vigorous physical activity (MVPA) in smokers and its association with the urge to smoke. Methods We enrolled 60 active smokers (≥3 cigarettes per day) and recorded continuous step counts with the Fitbit Charge HR. MVPA was defined as a cadence of greater than or equal to 100 steps per minute. Participants were prompted to report instantaneous smoking urges via text message 3 times a day on a Likert scale from 1 to 9. We used a mixed effects linear model for repeated measures, controlling for demographics and baseline activity level, to investigate the association between MVPA and urge. Results A total of 53 participants (mean age 40 [SD 12] years, 57% [30/53] women, 49% [26/53] nonwhite, and 38% [20/53] obese) recorded 6 to 12 weeks of data. Data from 3633 person-days were analyzed, with a mean of 69 days per participant. Among all participants, median daily MVPA was 6 min (IQR 2-13), which differed by sex (12 min [IQR 3-20] for men vs 3.5 min [IQR 1-9] for women; P=.004) and BMI (2.5 min [IQR 1-8.3] for obese vs 10 min [IQR 3-15] for nonobese; P=.04). The median total MVPA minutes per week was 80 (IQR 31-162). Only 10% (5/51; 95% CI 4% to 22%) of participants met national guidelines of 150 min per week of MVPA on at least 50% of weeks. Adjusted models showed no association between the number of MVPA minutes per day and mean daily smoking urge (P=.72). Conclusions The prevalence of MVPA was low in adult smokers who rarely met national guidelines for MVPA. Given the poor physical activity attainment in smokers, more work is required to enhance physical activity in this population.
Polygenic risk scores predict diabetic complications and their response to therapy

Type 2 diabetes increases the risk of cardiovascular and renal complications, but early risk prediction can lead to timely intervention and better outcomes. Through summary statistics of meta-analyses of published genome-wide association studies performed in over 1.2 million of individuals, we combined 9 PRS gathering genomic variants associated to cardiovascular and renal diseases and their key risk factors into one logistic regression model, to predict micro- and macrovascular endpoints of diabetes. Its clinical utility in predicting complications of diabetes was tested in 4098 participants with diabetes of the ADVANCE trial followed during a period of 10 years and replicated it in three independent non-trial cohorts. The prediction model adjusted for ethnicity, sex, age at onset and diabetes duration, identified the top 30% of ADVANCE participants at 3.1-fold increased risk of major micro- and macrovascular events (p=6.3×10−21 and p=9.6×10−31, respectively) and at 4.4-fold (p=6.8×10−33) increased risk of cardiovascular death compared to the remainder of T2D subjects. While in ADVANCE overall, combined intensive therapy of blood pressure and glycaemia decreased cardiovascular mortality by 24%, the prediction model identified a high-risk group in whom this therapy decreased mortality by 47%, and a low risk group in whom the therapy had no discernable effect. Patients with high PRS had the greatest absolute risk reduction with a number needed to treat of 12 to prevent one cardiovascular death over 5 years. This novel polygenic prediction model identified people with diabetes at low and high risk of complications and improved targeting those at greater benefit from intensive therapy while avoiding unnecessary intensification in low-risk subjects.
The Role of Dot1l in Prenatal and Postnatal Murine Chondrocytes and Trabecular Bone

Osteoarthritis and osteoporosis are widely prevalent and have far‐reaching public health implications. There is increasing evidence that epigenetics, in particular, histone 3 lysine 79 methyltransferase DOT1L, plays an important role in the cartilage and bone biology. In this study, we evaluated the role of Dot1l in the articular cartilage, growth plate, and trabecular bone utilizing conditional KO mouse models. We generated chondrocyte‐specific constitutive and inducible conditional Dot1l KO mouse lines using Col2a1‐Cre and Acan‐CreER systems. Prenatal deletion of Dot1l in mouse chondrocytes led to perinatal mortality, accelerated ossification, and dysregulation of Col10a1 expression. Postnatal deletion of Dot1l in mouse chondrocytes resulted in trabecular bone loss decreased extracellular matrix production, and disruption of the growth plate. In addition, pharmacological inhibition of DOT1L in a progeria mouse model partially rescued the abnormal osseous phenotype. In conclusion, Dot1l is important in maintaining the growth plate, extracellular matrix production, and trabecular bone. © 2019 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.
The Role of Resveratrol in the Inflammatory Bowel Diseases

Cite this article: Lima TA, Marton LT, Marqui SV, Neto FC, Goulart RA, Barbalho SM. The Role of Resveratrol in the Inflammatory Bowel Diseases. Pharmacog Rev. 2019;13(26):36-44. ABSTRACT Resveratrol is a polyphenol that possesses several biological functions that are usually related to its modulating actions against inflammatory and oxidative processes. Hence, the objective of this review was to evaluate the effects of these substances in UC and CD. This review used studies published in the MEDLINE-PubMed (National Library of Medicine) following the PRISMA guidelines (Preferred Reporting Items for a Systematic Review and Meta-Analysis). The use of resveratrol in animal and human models has led to an improvement in disease activity indices, reduction of weight loss and improvement of diarrhea and rectal bleeding. It also led to serum reduction of inflammatory markers such as Interleukin (IL)-1α, IL-6, IL-8, Tumor Necrosis Factor (TNF)-α, Interferon (IFN)-γ and COX-2 and a significant decrease in OS. It promotes the reversal of dysbiosis and stimulates the expression of Tight Junctionassociated proteins, including Claudin-1, Occludin and ZO-1. Resveratrol is effective in the treatment of IBD by reducing the production of free radicals and increasing antioxidant enzymes. Besides, this polyphenol is capable of reducing the expression of inflammatory markers characteristic of UC and CD.
TCB2, a new anti-human interleukin-2 antibody, facilitates heterodimeric IL-2 receptor signaling and improves anti-tumor immunity

ABSTRACT IL-2 is a pleiotropic cytokine that plays an essential role in the survival, expansion, and function of CD8 T cells, regulatory T cells (Tregs), and natural killer (NK) cells. Previous studies showed that binding IL-2 with an anti-IL-2 monoclonal antibody (mAb) with a particular specificity could block its interaction with IL-2Rα, which is mainly expressed on Tregs. This selectivity can enhance the anti-tumor effects of IL-2 by activating CD8 T and NK cells, while disfavoring Treg stimulation. Based on this, we newly developed a series of anti-human IL-2 (hIL-2) mAbs (TCB1-3) that selectively stimulate CD8 T and NK cells without overtly activating Tregs. Among them, the hIL-2/TCB2 complex (hIL-2/TCB2c) exerted the best efficacy by inducing a prodigious expansion of host memory phenotype (MP) CD8 T (60-fold) and NK cells (18-fold) with less efficient Treg proliferation (5-fold). As a result, there was an average eightfold increase in the ratio of MP CD8 to Tregs. Accordingly, hIL-2/TCB2c strongly inhibited the growth of B16F10, MC38, and CT26 tumors. More remarkably, hIL-2/TCB2c showed synergy with checkpoint inhibitors such as anti-CTLA-4 or PD1 antibodies, and resulted in almost complete regression of implanted tumors and resistance to secondary tumor challenge. For direct clinical use, we generated a humanized form of TCB2 that had equal immunostimulatory and anti-tumor efficacy as a murine one. Collectively, these results show that TCB2 can provide a potent immunotherapeutic modality either alone or together with checkpoint inhibitors in cancer patients.
Effect of ultrasound-assisted debridement on wound healing and infection outcomes in diabetic foot

Objective The objective of this study was to determine the efficacy of low-frequency ultrasound (LFU) in chronic wound healing and infection outcome in diabetic foot ulcers. Background Around 15% of patients with diabetes will develop foot ulcers at some point in their life, making them 30–40 times more likely to undergo amputation due to a nonhealing foot ulcer than the nondiabetic population. Debridement plays a significant role in the healing of diabetic foot ulcers. Patient and methods This randomized clinical trial was conducted on 46 patients with diabetes, recruited from the Diabetic Foot Clinic at Mansoura and Menoufia Universities, Egypt. All patients with diabetes (type I and type II) who had chronic diabetic foot ulcers without severe arterial insufficiency, with ankle brachial indices of at least 0.6, and without severe limb-threatening infections were included. Results Patients were divided into two groups – group 1 received ultrasound-assisted wound (UAW) therapy in conjunction with standard wound care (n = 23), and the other group received only standard wound care. Patients were followed-up for 3 months. The complete healing rate in the present study population was 30.34% (control group = 17.39%, UAW group = 43.47%). The mean wound size reduction was significantly higher in the UAW group only in the second-week and third-month follow-ups. The number of infected ulcers was reduced by ultrasound debridement more than surgical debridement (control group = 5, UAW group = 11) at the end of the study, but with no significant difference (P = 0.148). A significant difference in healing ratio was found in patients with ultrasound debridement and initial wound culture (P = 0.01). Conclusion In diabetic foot ulcers, LFU debridement accompanied by standard wound care has a beneficial effect on wound healing and wound infection. LFU debridement can initially accelerate ulcer healing; however, there was no significant difference between the two modalities in the healing rate after 3 months.
Dual-energy contrast-enhanced spectral mammography (CESM) for breast cancer screening.

Dual-energy contrast-enhanced spectral mammography (CESM) is a novel imaging modality. It enables anatomical and functional imaging of the breast (1). At CESM two images of each view are obtained, at two energy levels. The first is a low-energy image depicting breast morphology. This image is equivalent to standard 2D mammography. The second image is a subtracted image highlighting areas of contrast uptake that can indicate malignant neovascularization (2).