Miracle-dz/UniFAR-FTUs huggingface dataset:
A novel rodent model of severe renal ischemia reperfusion injury

Abstract Renal ischemia reperfusion injury (IRI) is a major problem, currently without treatments in clinical use. This reflects the failure of animal models to mimic the severity of IRI observed in clinical practice. Most described models lack both the ability to inflict a permanent reduction in renal function and the sensitivity to demonstrate the protective efficacy of different therapies in vivo. To test novel cell-based therapies, we have developed a model of renal IRI in Fisher 344 rats. Animals were subjected to 120 min of unilateral warm ischemia, during which they underwent an intra-renal artery infusion of therapeutic agents or vehicle. At either 2 or 6 weeks post-surgery, animals underwent terminal glomerular filtration rate (GFR) studies by inulin clearance to most accurately quantify renal function. Harvested kidneys underwent histological analysis. Compared to sham operations, saline treated animals suffered a long-term reduction in GFR of ≈50%. Histology revealed short- and long-term disruption of renal architecture. Despite the injury severity, post-operative animal losses are <5%. This model produces a severe, consistent renal injury that closely replicates the pathological processes encountered in clinical medicine. Renal artery infusion mimics the route likely employed in clinical transplantation, where the renal artery is accessible. Inulin clearance characterizes GFR, allowing full assessment of therapeutic intervention. This model is useful for screening therapeutic agents prior to testing in a transplant model. This reduces animal numbers needed to test drugs for clinical transplantation and allows for refinement of dosing schedules.
MicroRNA-939 down-regulates CD2-associated protein by targeting promoter in HEK-293T cells

Abstract CD2-associated protein (CD2AP) serves as a slit diaphragm (SD) protein and plays essential roles in maintaining podocyte integrity and reducing proteinuria. MicroRNAs (miRNAs) are novel regulators of gene expression. Podocyte-specific loss of miRNAs would lead to significant proteinuria. Here, we report new evidence in which miRNAs may function to suppress CD2AP expression through a transcriptional way. By scanning human CD2AP promoter in silico for sequences complementary to known miRNAs, we chose miR-939, miR-148b*, miR-191*, miR-638 as four candidates and transfected them into HEK-293T cells. Dual-luciferase reporter assay identified that only miR-939 significantly reduced the relative luciferase activity of CD2AP promoter region. Further analysis confirmed that the mRNA and protein expressions of CD2AP were also down-regulated by miR-939. In conclusion, we have identified that miR-939 targets CD2AP promoter sequences and suppresses its gene expression. These findings suggest that miRNAs may mediate podocyte injury via reducing the expression of the SD proteins, such as CD2AP.
Maternal and Neonatal Risk Factors Associated with Vertical Transmission of Ophthalmia Neonatorum in Neonates Receiving Health Care in Blantyre, Malawi

Context: Neonatal conjunctivitis is associated with poor prenatal care worldwide. Purpose: Data on neonatal conjunctivitis is scarce in Malawi. This study describes risk factors associated with conjunctivitis in neonates born in a large tertiary care hospital in Blantyre, Malawi. Materials and Methods: Medical records of a retrospective cohort of 231 neonates diagnosed with conjunctivitis from January 2006 to December 2009 at a large tertiary hospital in Malawi were reviewed. All subjects were clinically diagnosed with ophthalmia neonatorum. Data were collected on patient demographics and clinical features. The frequencies were calculated of various risk factors in neonates with ophthalmia neonatorum and their mothers as well as the treatments administered. Results: Mean age of the mother was 23.45 years (range, 15-40 years), and the mean number of previous deliveries was 2.3 (range, 1-7) children. Nearly, 80% of mothers delivered preterm infants via spontaneous vaginal delivery. The mean birth weight of neonates was 2869.6 grams (1100-5000 grams). Among mothers, premature rupture of membranes was the leading risk factor (24%) followed by sepsis during labor (9%), and history of sexually transmitted infections (STI) (7%). Neonates presented with low Apgar scores (19%), fever (8%), and/or meconium aspiration (5%). Providers treated patients empirically with a varied combination of benzyl penicillin, gentamicin, tetracycline eye ointment, and saline eye wash. Tetracycline with a saline eyewash was used frequently (34%) compared with combinations of benzyl penicillin and gentamicin. Conclusions: Improving prenatal care to reduce sepsis, traumatic deliveries, and early diagnosis of STI with appropriate treatment may potentially reduce vertical transmission of neonatal conjunctivitis in this understudied population.
Advances in drug delivery: is triple therapy the future for the treatment of chronic obstructive pulmonary disease?

Introduction: Current therapies for chronic obstructive pulmonary disease (COPD) focus on the improvement of clinical symptoms via the use of bronchodilators: β2-adrenoreceptor agonists and muscarinic (M3) acetycholine receptor antagonists. The combination of inhaled corticosteroids (ICSs) and long-acting β2 agonists (LABAs), or LABAs and anticholinergics has become an efficient alternative to single therapies. These combinations consist of a LABA and an ICS together with an anticholinergic, such as ipratropium or tiotropium. Areas covered: This review summarizes the latest thinking and findings on the usefulness of triple therapy in the treatment and management of COPD. Drawing on commercial, clinical, scientific and intellectual property data and publications, it aims to provide an overview to understand the efficacy and need for COPD triple therapy. The reader will gain an in-depth view of the triple therapy approach in managing COPD, existing molecules in the market or in development as well as new chemical entities. Clinical evidence in support of triple therapy, formulations and products are also discussed. Expert opinion: There is limited documented clinical evidence for the use of triple therapy in COPD, reflected in the lack of commercial activity in the field. The future for the management of COPD may lie with triple therapy, but may equally rest on a better understanding of the disease and subsequent development of new chemical entities, such as dimer molecules, longer-acting β-agonists and antimuscarinics.
Prevalence of Uncorrected Refractive Error and Other Eye Problems Among Urban and Rural School Children

Background: Uncorrected refractive error is an avoidable cause of visual impairment. Aim: To compare the magnitude and determinants of uncorrected refractive error, such as age, sex, family history of refractive error and use of spectacles among school children 6-15 years old in urban and rural Maharashtra, India. Study Design: This was a review of school-based vision screening conducted in 2004-2005. Materials and Methods: Optometrists assessed visual acuity, amblyopia and strabismus in rural children. Teachers assessed visual acuity and then optometrists confirmed their findings in urban schools. Ophthalmologists screened for ocular pathology. Data of uncorrected refractive error, amblyopia, strabismus and blinding eye diseases was analyzed to compare the prevalence and risk factors among children of rural and urban areas. Results: We examined 5,021 children of 8 urban clusters and 7,401 children of 28 rural clusters. The cluster-weighted prevalence of uncorrected refractive error in urban and rural children was 5.46% (95% CI, 5.44-5.48) and 2.63% (95% CI, 2.62-2.64), respectively. The prevalence of myopia, hypermetropia and astigmatism in urban children was 3.16%, 1.06% and 0.16%, respectively. In rural children, the prevalence of myopia, hypermetropia and astigmatism was 1.45%, 0.39% and 0.21%, respectively. The prevalence of amblyopia was 0.8% in urban and 0.2% in rural children. Thirteen to 15 years old children attending urban schools were most likely to have uncorrected myopia. Conclusion: The prevalence of uncorrected refractive error, especially myopia, was higher in urban children. Causes of higher prevalence and barriers to refractive error correction services should be identified and addressed. Eye screening of school children is recommended. However, the approach used may be different for urban and rural school children.
Managing the combination of non-alcoholic fatty liver disease and metabolic syndrome

We read with great interest the review by Moscatiello et al. [1] on the importance of targeting all components of the metabolic syndrome (MetS) in the treatment of non-alcoholic fatty liver disease (NAFLD). A few comments may be of interest. One of the hallmarks of MetS is the presence of too many definitions; the joint interim statement of several major organisations published in 2009 [2] attempts to overcome this issue. In this context, the selection of diagnostic criteria may influence the prevalence of MetS [3]. Apart from other cardiovascular risk factors, possible links between NAFLD and elevated serum uric acid (SUA) levels [4] or chronic kidney disease [5] have been recently proposed. Based on this concept, SUA and renal function should be monitored in NAFLD patients. The clinical significance of statin use in the treatment of both NAFLD and MetS has been reported [6,7]. Recently, in a post hoc analysis of the Greek Atorvastatin and Coronary Heart Disease Evaluation (GREACE) study [8,] statin treatment was associated with significantly less vascular events in patients with coronary heart disease (CHD) and NAFLD (68% relative risk reduction) compared with those with CHD but no NAFLD (39% relative risk reduction; p < 0.007). Furthermore, in the majority of patients with abnormal liver function tests (LFTs) (i.e., < 3 times the upper limit of normal) at baseline, statins improved LFTs, whereas these biomarkers were worsened in those patients not receiving statins [8]. These beneficial effects of statins on liver biomarkers, along with previously reported favourable changes in renal function [9], support their use in NAFLD treatment.
Parental smoking and spirometric indices in children

BACKGROUND A systematic quantitative review was conducted of the evidence relating parental smoking to spirometric indices in children. METHODS An electronic search of the Embase and Medline databases was completed in April 1997 and identified 692 articles from which we included four studies in neonates, 42 cross-sectional studies in school aged children (22 were included in a meta-analysis), and six longitudinal studies of lung function development. RESULTS In a pooled analyses of 21 surveys of school aged children the percentage reduction in forced expiratory volume in one second (FEV1) in children exposed to parental smoking compared with those not exposed was 1.4% (95% CI 1.0 to 1.9). Effects were greater on mid expiratory flow rates (5.0% reduction, 95% CI 3.3 to 6.6) and end expiratory flow rates (4.3% reduction, 95% CI 3.1 to 5.5). Adjustment for potential confounding variables had little effect on the estimates. A number of studies reported clear evidence of exposure response. Where exposure was explicitly identified it was usually maternal smoking. Two studies in neonates have reported effects of prenatal exposure to maternal smoking. Of five cross sectional studies that compared effects of perinatal exposure (retrospectively assessed) with current exposure to maternal smoking in later childhood, the three largest concluded that the major effect was in utero or neonatal exposure. Longitudinal studies suggest a small effect of current exposure on growth in lung function, but with some heterogeneity between studies. CONCLUSIONS Maternal smoking is associated with small but statistically significant deficits in FEV1 and other spirometric indices in school aged children. This is almost certainly a causal relationship. Much of the effect may be due to maternal smoking during pregnancy.
The Treatment of Retinoblastoma with Four-Drug Regimen Including Cisplatin, Etoposide, Vincristine, and Cyclophosphamide

Over an 11-year period, 59 patients (83 eyes) were treated with four-drug chemotherapy (cisplatin, etoposide, cyclophosphamide, and vincristine) at Hacettepe University, Departments of Ophthalmology and Pediatric Oncology. We evaluated the clinical features, treatment modalities, and outcome of these patients with a median follow-up of 55 months (range 9–130 months). Enucleation was performed as a first-line treatment for 30 eyes due to iris neovascularization and neovascular glaucoma, tumor in the anterior chamber regardless of the tumor stage, and for the patients with the Reese–Ellsworth (RE) group Vb. Chemotherapy was given regardless of tumor stages according to the RE groups in all 59 patients (83 eyes). Fifty-three eyes were treated with chemoreduction (CRD) and focal treatment. The rates of globe preservation were 87% for bilateral tumors and 35% for unilateral tumors in the CRD group. The 5-year overall (OS) and enucleation-free survival (EnFS) was 86.9% and 40%, respectively, for the whole group. At 3rd year, ocular survival rate for the eyes with vitreal or subretinal seeding was 58% and without seeding was 66% (P = .78). Seeding or subretinal collection may not indicate poor prognosis under intensive chemotherapy. The intensive four-drug chemotherapy protocol might have satisfactory results in the retinoblastoma (RBL) patients.
Typically Unobserved Variables (Tuvs) and Selection into Prenatal Inputs: Implications for Estimating Infant Health Production Functions

We examine the extent to which infant health production functions are sensitive to model specification and measurement error. We focus on the importance of typically unobserved but theoretically important variables (TUVs), other non-standard covariates (NSCs), input reporting, and characterization of infant health. The TUVs represent wantedness, taste for risky behavior, and maternal health endowment. The NSCs include father and family structure characteristics. We estimate effects of prenatal drug use, prenatal cigarette smoking, and first trimester prenatal care on birth weight, low birth weight, and a measure of abnormal infant health conditions. We compare estimates using self-reported inputs versus input measures that combine information from medical records and self-reports. We find that TUVs and NSCs are significantly associated with both inputs and outcomes, but that excluding them from infant health production functions does not appreciably affect the input estimates. However, using self-reported inputs leads to overestimated effects of inputs, particularly prenatal care, on outcomes, and using a direct measure of infant health does not always yield input estimates similar to those when using birth weight outcomes. The findings have implications for research, data collection, and public health policy.
Impacted canines: Etiology, diagnosis, and orthodontic management

Impaction of maxillary and mandibular canines is a frequently encountered clinical problem, the treatment of which usually requires an interdisciplinary approach. Surgical exposure of the impacted tooth and the complex orthodontic mechanisms that are applied to align the tooth into the arch may lead to varying amounts of damage to the supporting structures of the tooth, not to mention the long treatment duration and the financial burden to the patient. Hence, it seems worthwhile to focus on the means of early diagnosis and interception of this clinical situation. In the present article, an overview of the incidence and sequelae, as well as the surgical, periodontal, and orthodontic considerations in the management of impacted canines is presented.
Candesartan plus hydrochlorothiazide: an overview of its use and efficacy

Introduction: The 2007 European Society of Cardiology/ European Society of Hypertension guidelines suggests that among the therapeutic possibilities, the use of angiotensin receptor blockers as an important component of antihypertensive combination therapy. Thiazide-type diuretics are usually added in order to increase the therapeutic efficacy in lowering blood pressure (BP). Many authors have demonstrated how effective is a fixed-dose combination of candesartan cilexetil/hydrochlorothiazide in lowering BP, even when compared with other antihypertensive drugs belonging to the same therapeutic category. Moreover, this combination showed good compliance and tolerability and few adverse reactions. Areas covered: The authors analyze the importance of the combination therapy of candesartan cilexetil plus hydrochlorothiazide in the treatment of hypertension. Many authors explain how effective BP control is often achieved only with the combination of drugs with different mechanisms of action, in particular in high risk patients or in those affected with diabetes mellitus or chronic renal disease; in fact, these patients need a more intensive BP control. Expert opinion: The fixed-dose combination drug candesartan/hydrochlorothiazide turned out to be a significant alternative in the treatment of hypertension, both for its high efficacy in BP reduction and in prevention of target organ damage, both for its tolerability and patient compliance.
Leishmaniasis: an update of current pharmacotherapy

Introduction: Leishmaniasis broadly manifests as visceral leishmaniasis (VL), cutaneous leishmaniasis (CL) and mucocutaneous leishmaniasis (MCL). The treatment of VL is challenging. The duration of treatment is long, and drugs are toxic thereby needing monitoring and hospitalization. Areas covered: Novel therapies such as single dose of liposomal amphotericin B (L-AmB) and multidrug therapy are important breakthrough for VL in the Indian subcontinent and have been recommended as the treatment of choice in this region. African Leishmania donovani is less susceptible to L-AmB, miltefosine and paromomycin as compared to the Indian strains, and the treatment of choice remains a 17-day combination therapy of pentavalent antimonials (SBv) and paromomycin. L-AmB at a total dose of 18 – 21 mg/kg is the recommended regimen in the Mediterranean region and South America. It is also the treatment of choice for HIV–VL coinfection. Treatment of CL should be decided by the clinical lesions, etiological species and its potential to develop into mucosal leishmaniasis. A literature search on treatment of leishmaniasis was done on PubMed and through Google. Expert opinion: There is an urgent need for exploratory studies with short course, highly efficient regimens such as single dose L-AmB or combination therapy for all the endemic regions of VL. Shorter and more acceptable regimens are needed for the treatment of post–kala-azar dermal leishmaniasis. Treatment of CL remains one of the neglected areas of leishmaniasis as data are scarce and drawn from uncontrolled studies.
Efficacy and Safety of Human Umbilical Cord Derived Mesenchymal Stem Cell Therapy in Children with Severe Aplastic Anemia Following Allogeneic Hematopoietic Stem Cell Transplantation: A Retrospective Case Series of 37 Patients

The treatment of pediatric severe aplastic anemia (SAA) with allogeneic hematopoietic stem cell transplantation (allo-HSCT), presents major challenges including the risks of graft failure, septic complications, and graft-versus-host disease (GVHD). Additive infusions of human umbilical cord derived mesenchymal stem cell (hUC-MSC) may be administered to improve patient survival. We retrospectively examined 37 pediatric patients with SAA who received allo-HSCT and subsequent infusions of hUC-MSC suspension at a dose of 1.0 × 106 /kg. The times and doses of hUC-MSC infusions were increased in patients with severe GVHD. All patients received hUC-MSC infusions. The median time to post-transplantation neutrophil count of greater than 0.5 × 109 /L was 14 days (range, 11–20 days) and time to post-transplantation platelet count of greater than 20 × 109 /L was 19 days (14–29 days). The overall frequency of acute GVHD (aGVHD) was 45.9% (17/37). These aGVHD episodes occurred at a median time of post-transplantation 47 days (15–83 days). The frequency of chronic GVHD (cGVHD) was 18.9% (7/37); cGVHD developed from aGVHD in 10.8% (4/37) of patients. The GVHD-associated mortality rate was 18.9% (7/37) and aGVHD-specific mortality rate was 8.1% (3/37). The median overall survival time was 35 months (9—67 months) and the three-year overall survival rate was 74.2% (28/37). Seven patients died of GVHD, one patient died of a severe invasive fungal infection, and one patient died of renal failure. In conclusion, post-transplantation hUC-MSC infusions seemed to be safely infused in children with SAA who have previously received allo-HSCT.
Understanding Physician Perspectives on Hospice: A Framework for Effective Communication and Patient Advocacy

Hospice in its present form is a new therapy based on an old concept. Physicians' unfamiliarity with the dying process has limited the expansion and acceptance of palliative medicine at this point. Communication between hospice and physicians is paramount to improve the care of the terminally ill and to advance hospice both from a business and educational standpoint. The role of hospice in medical care may be treated as a specialty consultation service. Using the "three As" of specialty consultation—availability, affability, and ability—hospice can provide exceptional care for the patient as well as individualized service for the physician.
Metabolic regulation: effects of natriuretic peptide interactions

In addition to their well-established effects on blood pressure and volume homeostasis, natriuretic peptides have complex effects on carbohydrate and lipid metabolism. In vivo, pharmacological and physiological concentrations of atrial natriuretic peptides induce lipolysis in a concentration-dependent manner and increase the lipid oxidation rate. The response appears to be mediated through the stimulation of natriuretic peptide receptor-A. More recent studies suggest that natriuretic peptides also affect the production of several adipokines. These mechanisms may be relevant, as natriuretic peptide availability is altered in numerous physiological and pathological conditions, including physical exercise, congestive heart failure and obesity.
Skin Necrosis and Purpura Fulminans in Children With and Without Thrombophilia—A Tertiary Center's Experience

Purpura fulminans (PF) is a very rare clinicopathologic skin disorder comprising dermal microvascular thrombosis associated with perivascular hemorrhage of multiple origins. It may occur as the presenting symptom of severe congenital deficiency of protein C (PC) or protein S (PS) during the newborn period, or later in life following oral anticoagulant therapy with vitamin K antagonists, or of sepsis that may be associated with disseminated intravascular coagulation. Treatment consists of anticoagulants and PC concentrates during acute episodes. We report our experience in the diagnosis and management of pediatric PF. The medical records of the 6 children aged 2–16 years (median: 5 years) who presented with PF to our tertiary care center between 1996 and 2013 were studied. The thrombophilia workup revealed either the presence of congenital homozygous PC deficiency, prothrombotic polymorphisms (factor V Leiden and FIIG20210A heterozygosity), acquired PC/PS deficiency, or no discernible thrombophilia. The skin necrosis resolved following conservative fresh-frozen plasma/anticoagulant therapy in 2 cases, whereas 3 children required interventional plastic surgery. The sixth case, a 10-year-old child with severe PC deficiency, heterozygous factor V Leiden, and FIIG20210A, received recombinant activated PC. PF in childhood is rare and has multiple etiologies. Understanding of the variable pathogenesis and risk factors will facilitate diagnosis and appropriate clinical management.