Miracle-dz/UniFAR-FTUs huggingface dataset:
IGF-1 and IGFBP-1 in peripheral blood and decidua of early miscarriages with euploid embryos: comparison between women with and without PCOS

Abstract This study aims to demonstrate the possible relationship between the insulin-like growth factor (IGF) system and early miscarriage in polycystic ovarian syndrome (PCOS) patients with euploid embryos. 40 pregnant women included. 9 had PCOS and miscarried; 20 had PCOS and a successful ongoing pregnancy; the remaining 11 women did not have PCOS and miscarried. An ultrasound scan was performed to prove clinical pregnancy and a blood sample was taken on day 55 ± 4 of gestation. Serum samples of IGF-1, insulin-like growth factor binding protein-1 (IGFBP-1), total testosterone, serum hormone binding protein (SHBG), leptin and soluble leptin receptor (sOb-R) were obtained. In miscarriages, samples of decidua were obtained during vaccum curettage. Embryonic chromosomes in all miscarriages were proven to be normal. The expression of IGF-1, IGFBP-1, leptin, long-form leptin receptor and androge sOb-R n receptor (AR) were examined in the decidua. We found that miscarried PCOS patients showed significantly increased free androgen index and free IGF index, as well as decreased SHBG and IGFBP-1 than other two groups in peripheral blood. In the decidua, miscarried PCOS patients showed significantly increased expression of IGF-1 and decreased IGFBP-1 when compared with non-PCOS. AR was not expressed in the decidua of either group. Our results suggest that early miscarriage is associated with increased IGF-1 and decreased IGFBP-1 in PCOS patients.
Better Results in Weight Loss after the Second Gastrectomy in Re-Sleeve Gastrectomy

Background: Sleeve gastrectomy (SG) has been rapidly accepted as a valuable bariatric procedure before its effectiveness on weight loss in the long-term is clearly demonstrated. Re-sleeve gastrectomy (RSG) has been shown to provide promising results for patients with insufficient weight loss after SG. Methods: Seven patients underwent a re-sleeve gastrectomy procedure for insufficient weight loss after a mean 30±10 month follow-up associated with a dilated gastric pouch seen in upper gastro-intestinal contrast study. Results:Before SG, mean initial weight was 151 41 kg, mean Body Mass Index (BMI) was 55.4±12.5 kg/m2, 4 had a BMI more than 60 kg/m2 and 3 had a gastric banding before their SG. At follow-up of 12 months after SG, mean weight was 131 ±31 Kg, mean BMI was 48±9 kg/m2, mean %Excess Weight Loss (EWL) was 30 5%, and mean %Excess BMI Loss (EBL) 23 ±3%. At a follow-up of 12 months after RSG, final mean weight was 92 ±10 Kg, final mean BMI was 34±4 kg/m2, and mean %EBL since the second operation (RSG) was 58±17% (mean %EBL since the first operation (SG) was 6618%), and mean %EWL since the second operation (RSG) was 4217%(mean %EWL since the first operation (SG) was 6618%). The RSG resulted in significant mean %EBL (p<0,001) and in significant mean %EWL (p=0,029), compared to the initial SG results. Conclusion:In patients with insufficient weight loss after SG, RSG resulted in successful extra weight loss.
Evaluation of Ziehl-Neelsen staining, auramine phenol staining, antigen detection enzyme linked immunosorbent assay and polymerase chain reaction, for the diagnosis of intestinal cryptosporidiosis

Background and Objectives: Cryptosporidiosis is a very important opportunistic infection and is responsible for significant morbidity and mortality in HIV/AIDS patients. The objective of this study is to evaluate Ziehl-Neelsen staining, auramine phenol staining, antigen detection enzyme linked immunosorbent assay and polymerase chain reaction, for the diagnosis of intestinal cryptosporidiosis. Materials and Methods: The study was designed to determine the efficacy of modified Ziehl-Neelsen (ZN), Auramine-Phenol (AP) staining, antigen detection enzyme linked immunosorbent assay (ELISA) and nested polymerase chain reaction (PCR) for detection of cryptosporidia in 671 HIV-seropositive patients, 353 HIV-seronegative patients including 198 children with diarrhea and 50 apparently healthy adults. Results: Cryptosporidium was detected in 26 (3.9%), 37 (5.5%), 32 (4.8%) and 40 (6%) HIV-seropositive and 8 (2.3%), 10 (2.9%), 9 (2.6%) and 9 (2.6%) HIV-seronegative patients by ZN staining, AP staining, antigen detection ELISA and PCR, respectively. None of the healthy controls were infected with Cryptosporidium. Based on criteria of ′true positive′ samples, i.e. positive by any two of the four techniques out of ZN, AP, antigen detection ELISA and PCR, sensitivity of ZN and ELISA was 79.06% and 95.35% respectively. AP and PCR were found to be 100% sensitive. Specificity of ZN and ELISA was 100% while specificity of AP and PCR was 99.59% and 99.39% respectively. Conclusions: Auramine phenol staining is a rapid, sensitive and specific technique for diagnosis of intestinal cryptosporidiosis.
Organic cation transporters and their roles in antiretroviral drug disposition

Background: Understanding metabolising processes and drug–transporter interactions is particularly crucial to the management of patients with HIV infection, given the several antiretroviral drugs that must be taken lifelong and the use of other medications for HIV-related and non-HIV-related conditions. Several interactions of antiretroviral drugs with metabolising enzymes, especially cytochrome P450 and ATP-dependent transporter P-glycoprotein, have been described but the role of the organic cation transporters (OCTs) is less clearly defined. Objective: To review the relevance of the OCTs for antiretroviral drug disposition. Methods: Interactions of OCTs with antiretroviral drugs and evidence for clinical relevance are discussed. Results/conclusion: Several antiretroviral drugs show relevant interactions with the OCTs in cell-based experiments and the OCTs are highly upregulated in HIV-infected patients. For evaluating the clinical significance, interaction studies in HIV patients and reliable in vitro models for delineation of in vivo effects are needed.
hERG-related drug toxicity and models for predicting hERG liability and QT prolongation

Background: hERG K+ channels have been recognized as a primary antitarget in safety pharmacology. Their blockade, caused by several drugs with different therapeutic indications, may lead to QT prolongation and, eventually, to potentially fatal arrhythmia, namely torsade de pointes. Therefore, a number of preclinical models have been developed to predict hERG liability early in the drug development process. Objective: The aim of this review is to outline the present state of the art on drug-induced hERG blockade, providing insights on the predictive value of in vitro and in silico models for hERG liability. Methods: On the basis of latest reports, high-throughput preclinical models have been discussed outlining advantages and limitations. Conclusion: Although no single model has an absolute value, an integrated risk assessment is recommended to predict the pro-arrhythmic risk of a given drug. This prediction requires expertise from different areas and should encompass emerging issues such as interference with hERG trafficking and QT shortening.
Inhibition of platelet activation by peptide analogs of the β3-intracellular domain of platelet integrin αIIbβ3 conjugated to the cell-penetrating peptide Tat(48–60)

Activation of the platelet integrin-receptor αIIbβ3 is the final pathway of platelet aggregation, regardless of the initiating stimulus. Many studies suggest that there are several cytoplasmic proteins such as talin and β3-endonexin that bind to N744PLY747 and N756ITY759 motif of the β3 cytoplasmic tail and play the major role in the receptor activation. In this study, we investigated the role of the membrane distal region of human β3 cytoplasmic tail and specifically the N743NPLYKEA750 and T755NITYRGT762 sequence that contains an NXXY motif, in platelet aggregation, secretion, αIIbβ3 activation (PAC-1 binding) and fibrinogen binding. We synthesized two peptides corresponding to the above sequences as well as their conjugates with the Tat(48–60) cell-penetrating peptide. The capability of conjugates to penetrate the platelet membrane was investigated with confocal laser scanning microscopy using carboxyfluorescein (CF)-labeled peptides. Our results showed that the conjugated with the Tat(48–60) sequence peptides penetrate the platelet membrane and inhibit platelet aggregation in both PRP and washed platelets in a dose-dependent manner. The Tat-β3743–750 conjugate exhibited similar inhibitory activity in PRP and in washed platelets whereas the Tat-β3755–762 conjugate was more potent inhibitor of aggregation in washed platelets than in PRP. Both conjugated peptides were also able to inhibit P-selectin membrane expression as well as PAC-1 and fibrinogen binding to the platelets, the Tat-β3755–762 conjugate being more potent than Tat-β3743–750. The Tat(48–60) peptide and the peptides β3743–750 and β3755–762, which were not conjugated to the Tat(48–60) sequence, did not exhibit any inhibitory effect on the above parameters. In conclusion, the present study shows for the first time that the peptide analogs of the intracellular domain of the β3 subunit β3743–750 and β3755–762 conjugated to the cell-penetrating peptide Tat(48–60) are capable of penetrating the platelet membrane and expressing biological activity by inhibiting the activation of αIIbβ3, the fibrinogen binding to the activated receptor as well as platelet aggregation. Further studies are necessary to support whether such conjugated peptides may be useful tools for the development of potent antiplatelet agents acting intracellularly through the platelet integrin αIIbβ3.
Valsartan/hydrochlorothiazide: pharmacology and clinical efficacy

Background: Valsartan/hydrochlorothiazide is a combination of an angiotensin II receptor antagonist and diuretic indicated for hypertensive patients as initial therapy and those not controlled on monotherapy. Objective: To evaluate the pharmacokinetic, pharmacodynamic and clinical efficacy of valsartan/hydrochlorothiazide in hypertension therapy and other cardiovascular outcomes. Methods: Review of current literature. Results: Valsartan/hydrochlorothiazide has been shown to be superior to its individual components in randomized controlled studies of patients with moderate-to-severe hypertension and in patients who did not respond to monotherapy. When compared to amlodipine, valsartan/hydrochlorothiazide was shown to have a similar rate of the combined outcome of morbidity and mortality. Valsartan/hydrochlorothiazide has also been studied in specific patient populations, such as diabetics, obese, elderly, black hypertensives and hypertensives with further cardiovascular risk factors, and has been shown to be efficacious in such populations. Conclusion: Valsartan/hydrochlorothiazide has been shown to be an efficacious fixed-dose combination antihypertensive agent that is well tolerated with few side effects.
Pediatric Neurotrauma

Traumatic brain injury (TBI) is the leading cause of death and disability in children over 1 year of age. Knowledge about the age-specific types of injury and how to manage children with neurotrauma is essential to understanding and recognizing the extent and degree of injury and to optimize outcomes. In this article, we review the epidemiology, pathophysiology, and clinical management of pediatric neurotrauma.
An uncommon pulmonary embolism

Objectives: To report an unusual case of suicide attempt secondary complicated of pulmonary and systemic embolisms. Data Source: A 49-year-old-woman, with a factor V Leiden mutation and a notion of chronic depression, admitted to our intensive care unit for a suicide attempt by ingestion ofmepronizine and lormetazepam. Data Extraction: We report the rare evolution of this patient with a persistent alteration of consciousness associating a respiratory degradation. Despite the drug intoxication and possibility of aspiration, we performed a computed tomography (CT) angiography which confirmed the presence of a bilateral, proximal, pulmonary embolism suspected on transthoracic echocardiography. A cerebral CT showed left sylvian and cerebellar infarctions complicated of perilesional edema. Association of stroke and pulmonary embolism led us to suspect a patent foramen ovale (PFO). There was also a context of genetical perturbation of hemostasis. Transesophageal echocardiography confirmed the presence of a PFO undiagnosed by transthoracic echography. The PFO was complicated by an entrapped thrombus. The thrombotic complications were treated by unfractionated heparin. Data Synthesis: Neurological and respiratory degradation following voluntary drug intoxication led to the discovery of both a pulmonary and cerebral embolism secondary to a PFO entrapped thrombus. Conclusions: An entrapped thrombus in a PFO is a rare and dangerous situation, associated with many complications. Association of systemic and pulmonary embolisms should lead to PFO detection to guide therapeutic interventions.
Bimodal targeting of microsomal cytochrome P450s to mitochondria: implications in drug metabolism and toxicity

Importance of the field: Microsomal CYPs are critical for drug metabolism and toxicity. Recent studies show that these CYPs are also present in the mitochondrial compartment of human and rodent tissues. Mitochondrial CYP1A1 and 2E1 show both overlapping and distinct metabolic activities compared to microsomal forms. Mitochondrial CYP2E1 also induces oxidative stress. The mechanisms of mitochondria targeting of CYPs and their role in drug metabolism and toxicity are important factors to consider while determining the drug dose and in drug development. Areas covered in this review: This review highlights the mechanisms of bimodal targeting of CYP1A1, 2B1, 2E1 and 2D6 to mitochondria and microsomes. The review also discusses differences in structure and function of mitochondrial CYPs. What the readers will gain: A comprehensive review of the literature on drug metabolism in the mitochondrial compartment and their potential for inducing mitochondrial dysfunction. Take home message: Studies on the biochemistry, pharmacology and pharmacogenetic analysis of CYPs are mostly focused on the molecular forms associated with the microsomal membrane. However, the mitochondrial CYPs in some individuals can represent a substantial part of the tissue pool and contribute in a significant way to drug metabolism, clearance and toxicity.
Leisure-Time Internet Use Does Not Correlate with Physical Activity or Physical Fitness Level of Ninth Grade African-American Girls

We assessed leisure-time Internet use (IU) and its relationship to physical fitness (PF) and leisure-time physical activity (PA) among 295 adolescent African-American girls. In addition, scales measuring variables in the Theory of Reasoned Action (TRA) were administered to elucidate PA data. Based on responses to the IU Questionnaire, participants were placed into either an Internet Nonuser (n = 184) or Internet User (n = 111) group. PF was assessed using body mass index (BMI) and AAHPERD Youth Fitness Tests. There were no correlations found between the fitness test scores and IU, PA, or BMI. No correlation was found between IU and PA, and similar findings were noted between PA and each variable constituting the TRA. As expected, within the TRA variables studied, significant moderate to high correlations were found between both Attitude to Exercise and Subjective Norm with Intention to Exercise, r = . 43 and r = . 53, respectively. The remarkably low scores among participants on the fitness tests and TRA sc.
An increase of granulosa cell apoptosis mediates aqueous neem (Azadirachta indica) leaf extract-induced oocyte apoptosis in rat

Objective: Neem plant (Azadirachta indica) has been extensively used in Ayurvedic system of medicine for female fertility regulation for a long time, but its mechanism of action remains poorly understood. Hence, the present study was aimed to determine whether an increase of granulosa cell apoptosis is associated with aqueous neem leaf extract (NLE)-induced oocyte apoptosis. Materials and Methods: Sexually immature female rats of 20 days old were fed NLE (50 mg/day) for 10 days and then subjected to superovulation induction protocol. The morphological changes in cumulus oocyte complexes (COCs), rate of oocyte apoptosis, hydrogen peroxide (H2O2), total nitrite, and cytochrome c concentrations, inducible nitric oxide synthase (iNOS), cytochrome c, p53, Bcl2 and Bax expressions, deoxyribonucleic acid (DNA) fragmentation, and estradiol 17β level in granulosa cells collected from preovulatory COCs were analyzed. Results: Aqueous NLE increased H2O2 concentration and decreased catalase activity, increased iNOS expression and total nitrite concentration, increased p53, Bax, and p53 expressions but decreased Bcl2 expression, increased cytochrome c concentration and induced DNA fragmentation in granulosa cells. An increased granulosa cell apoptosis resulted in reduced estradiol 17β concentration and induced apoptosis in ovulated oocytes. Conclusion: We conclude that aqueous NLE-induced granulosa cell apoptosis through the mitochondria-mediated pathway, reduced estradiol 17β concentration and induced apoptosis in ovulated oocytes. Thus, granulosa cell apoptosis mediates NLE-induced oocyte apoptosis during female fertility regulation in rat.
Pharmacokinetics and metabolism update for some recent antipsychotics

Introduction: The search for drugs that reduce psychotic symptoms, with minimal adverse effects, has led to the development of new agents that act somewhat differently from their older antipsychotic counterparts. These agents, which include aripiprazole, lurasidone and perospirone, act by targeting both D2 and 5-HT1A receptors, in addition to other characteristic receptors. Areas covered: This article covers the pharmacokinetics and metabolism of aripiprazole, perospirone, lurasidone and cariprazine. The review also describes the effects of physiological and pathological variables on these drugs as well as potential drug interactions. The author provides the reader with knowledge of the fundamental pharmacokinetic characteristics and metabolic pathways of these new antipsychotics, emphasizing the clinically important common features and differences compared to other older agents. Expert opinion: Aripiprazole, perospirone, lurasidone and cariprazine share some of the pharmacokinetic characteristics of older, lipophilic antipsychotics and, like these, each has some distinct pharmacokinetic features that are clinically beneficial and some that are not. We await the results of future practical effectiveness trials of these new antipsychotics and their follow-on derivatives to learn more about their benefit/risk profile compared with established antipsychotics. It is hoped that some of these newer antipsychotics will not only increase the range of pharmacotherapeutic options, but decisively improve the expectations of psychotherapy for schizophrenia.
Tibial cortical thickness: A dependable tool for assessing osteoporosis in the absence of dual energy X-ray absorptiopmetry

Background and Objective: Bone mineral density measurements with absorptiometry dual-energy X-ray absorptiometry (DXA) is the gold standard for diagnosing low bone mass and risk for fragility fractures. DXA is not available at every center, and physicians require an alternative method of diagnosis before referring patients. We conducted this study to assess and compare total cortical thickness (TCT) and its relation to the T score by DXA and its correlation-ship in the diagnosis of osteoporosis. Patients and Methods: Total cortical thickness was carried out in 50 Saudi Arabian females ≥ 45 years with DXA scans and 25 patients with age of ≤ 35 years whose radiographs of the upper tibia were available for analysis. Postero-medial cortical thickness of the tibia was measured 13 cm from the joint line and an average was calculated. The average T score of the spine and the hip was taken. A comparison was made between age, T score, and the TCT. Inter cortical distance (ICD) was measured and compared in both groups. Data were analyzed for predictive value for diagnosis of osteopenia and osteoporosis. Results: There was a significant association between the T score and the TCT and age. As the age advanced the T score and TCT was very low (<0.05, 95% confidence interval [CI] <0.2). Forty patients were osteopenic and 10 osteoporotic. The T score in the former was − 1.33 ± 0.71 and the later was − 3.22 ± 0.56 (P < 0.0001 95% CI: <−1.67) and the TCT was 0.655 ± 0.06 versus 0.51 ± 0.05 (P < 0.0001 95% CI: <−0.17). In women ≤35 years the average TCT was 0.804 ± 0.155 cm and IMD was 3.34 ± 0.45 cm. Conclusions: We conclude that if TCT is less than the threshold value of ≤ 0.5 cm, patients should be referred for further investigations with DXA. We believe that further studies are needed to confirm our findings and in areas where DXA is not available, based on the TCT measurement anti-osteoporotic therapy could be initiated when other risk factors for osteoporosis is present.
Ferric carboxymaltose: A revolution in the treatment of postpartum anemia in Indian women

Objectives: The objective of the present study is to compare the safety and efficacy of ferric carboxymaltose (FCM), intravenous (IV) iron sucrose and oral iron in the treatment of post = partum anemia (PPA). Materials and Methods: A total of 366 women admitted to SCB Medical College, Cuttack between September 2010 and August 2012 suffering from PPA hemoglobin (Hb) <10 g/dL were randomly assigned to receive either oral iron or IV FCM or iron sucrose. FCM, IV iron sucrose, and oral iron were given as per the protocol. Changes in hemoglobin (Hb) and serum ferritin levels at 2 and 6 weeks after treatment were measured and analyzed using ANOVA. Adverse effects to drug administration were also recorded. Results: A statistically significant increase in Hb and serum ferritin level were observed in all three groups, but the increase in FCM group was significantly higher (P < 0.0001) than conventional iron sucrose and oral iron group. The mean increase in Hb after 2 weeks was 0.8, 2.4, and 3.2 g/dL and 2.1, 3.4, and 4.4 g/dL at 6 weeks in oral iron, iron sucrose and FCM groups, respectively. The mean increase in serum ferritin levels after 2 weeks was 2.5, 193.1, and 307.1 and 14.2, 64, and 106.7 ng/mL after 6 weeks in oral iron, iron sucrose and FCM groups, respectively. Adverse drug reactions were significantly less (P < 0.001) in FCM group when compared with other two groups. Conclusion: Ferric carboxymaltose elevates Hb level and restores iron stores faster than IV iron sucrose and oral iron, without any severe adverse reactions. There was better overall satisfaction reported by the patients who received FCM treatment.