Miracle-dz/UniFAR-FTUs huggingface dataset:
Risk factors for the progression or persistence of untreated mild dysplasia of the uterine cervix

To identify the factors that may predict the progression or persistence of untreated mild dysplasia of the uterine cervix, we performed a retrospective review of 118 patients with histologically verified mild dysplasia who underwent colposcopic biopsies between January 1999 and December 2003. Regression to normal occurred in 70.3%, progression to moderate dysplasia or worse occurred in 11.0%, and persistence of mild dysplasia occurred in 18.7%. In regression/progression analysis, progression of untreated mild dysplasia was 34.5% (10/29) in patients with high viral loads (≥100 relative light units/positive control [RLU/PC]) and 4.5% (3/67) in those with low viral loads (1 to <100 RLU/PC) and negative human papillomavirus (HPV) tests (P < 0.001). Women with high viral loads had a 13-fold greater chance of progression of untreated mild dysplasia than those with low viral loads and negative HPV tests (CI: 2.494–95.297; P = 0.0022). Those associated with both positive smear and positive HPV test (12/45 = 26.7%) were at a greater risk of progression of untreated mild dysplasia as compared with those with positive smear and negative HPV (0/17 = 0.0%) or those with negative smear and positive HPV test (1/18 = 5.6%). Those with high viral loads and both with positive smear and positive HPV test should be followed closely because of their increased risk of progression of untreated mild dysplasia.
Comparison of the plasma pharmacokinetics and renal clearance of didanosine during once and twice daily dosing in HIV‐1 infected individuals

Objective:To compare the plasma pharmacokinetics of didanosine during once daily (qd) and twice daily (bid) dosing. Design:Open-label, randomized, cross-over study. Methods:HIV-1 infected patients who used didanosine were randomized to either a qd or a bid dosing regimen of didanosine. The total daily dose of didanosine was identical in both regimens. Seven days after the start of the study, the pharmacokinetic profile of didanosine in plasma and urine was assessed during an 8-h period. The next day, the patient was switched to the opposite dosing regimen, and after another 7 days, the study was concluded by again assessing the plasma and urine pharmacokinetics of didanosine during 8 h. Results:A total of 19 patients completed the study. The pharmacokinetics of didanosine in plasma (with maximum plasma concentration adjusted for dose) and urine were not significantly different in the qd and bid dosing regimen (P ≥ 0.28 for all parameters). Conclusion:We conclude that qd dosing of didanosine leads to a similar exposure in plasma as bid dosing (using the same total daily dose). Since qd dosing may lead to improved compliance of patients to regimens containing didanosine, these results provide a rationale for prescribing didanosine in a qd regimen, and is reassuring when we realize that the drug is being administered in a qd dosing regimen on a large scale in clinical practice.
Variants of the adiponectin and adiponectin receptor-1 genes and posttransplantation diabetes mellitus in renal allograft recipients.

CONTEXT Posttransplantation diabetes mellitus (PTDM) is a major metabolic complication in renal transplant recipients. Adiponectin (ADIPOQ) and adiponectin receptor-1 (ADIPOR1) gene polymorphisms have been associated with type 2 diabetes. However, it is unknown whether these polymorphisms are also risk factors for PTDM. OBJECTIVE We investigated the association between PTDM and single-nucleotide polymorphisms of ADIPOQ and ADIPOR1 in a cohort of renal allograft recipients. DESIGN, SETTING, AND PARTICIPANTS Five hundred seventy-five patients (367 men and 208 women) who received kidney transplants between 1989 and 2007, without a history of diabetes and with a pretransplant fasting glucose concentration less than 5.5 mmol/liter. Patients were followed up for a median 10 yr. Genotypes included single-nucleotide polymorphisms of the following: ADIPOQ rs266729, rs822395, rs822396, rs2241766, and rs1501299 and ADIPOR1 rs2232853, rs12733285, and rs1342387. RESULTS TT-homozygotes in ADIPOQ rs1501299 [hazard ratio (HR) = 1.70, P = 0.032] had greater risk of PTDM after adjusting for age, sex, amount of weight gain, and type of immunosuppressant. There was a significant interaction between sex and ADIPOQ rs1501299 genotype (P = 0.037). In men, but not in women, TT-homozygotes in ADIPOQ rs1501299 were more likely to develop PTDM than the wild GG-homozygotes (HR = 2.50, P = 0.002), whereas GT-heterozygotes had nonsignificantly elevated risk (HR = 1.41, P = 0.128). CONCLUSION Genetic variation in ADIPOQ rs1501299 is associated with PTDM in a sex-specific manner.
Adipocytokine concentrations in children with different types of beta-thalassemia

Abstract Background. Beta-thalassemia is an inherited blood disorder. It results from the impaired production of β-globin chains, leading to a relative excess of alpha-globin chains. Clinical severity separates this disease into three main subtypes: β- thalassemia major, β-thalassemia intermedia and β-thalassemia minor, the former two being clinically more significant. Inflammatory processes may play an important role in some of the complications of thalassemia. Adipose tissue is one of the most important endocrine and secretory organs that release adipocytokines like adiponectin, resistin and visfatin. Aim. The aim of our study was to analyze adipocytokine concentrations (adiponectin, resistin and visfatin) in different types of β-thalassemia patients and determine any possible correlations with disease severity. Methods. We recruited 29 patients who were transfusion-dependent β-thalassemia-major patients, 17 patients with β-thalassemia intermedia, 30 β-thalassemia minor patients. The control group consisted of 30 healthy children. Anthropometric measurements, complete blood count, biochemical parameters, serum concentrations of adiponectin, resistin, visfatin were performed for all subjects. Results. Resistin and visfatin concentrations were significantly higher in β-thalassemia minor patients than in controls. Adiponectin, resistin and visfatin concentrations were significantly higher in both β-thalassemia intermedia and major patients than in controls. The concentrations of adiponectin, resistin and visfatin were significantly higher in both β-thalassemia intermedia and major patients than in β-thalassemia minor patients. There was no significant difference between β-thalassemia intermedia and β-thalassemia major patients for adipocytokines concentrations. Conclusion. We speculate that these adipocytokines may play a role in the development of complications in β-thalassaemia.
Obesity-induced changes in hepatic and placental clock gene networks in rat pregnancy†

Abstract Maternal obesity induces pregnancy complications and disturbs fetal development, but the specific mechanisms underlying these outcomes are unclear. Circadian rhythms are implicated in metabolic complications associated with obesity, and maternal metabolic adaptations to pregnancy. Accordingly, obesity-induced circadian dysfunction may drive adverse outcomes in obese pregnancy. This study investigated whether maternal obesity alters the rhythmic expression of clock genes and associated nuclear receptors across maternal, fetal, and placental tissues. Wistar rats were maintained on a cafeteria (CAF) diet prior to and throughout gestation to induce maternal obesity. Maternal and fetal liver and placental labyrinth zone (LZ) were collected at four-hourly time points across days 15–16 and 21–22 of gestation (term = 23 days). Gene expression was analyzed by RTqPCR. Expression of the accessory clock gene Nr1d1 was rhythmic in the maternal and fetal liver and LZ of chow-fed controls, but in each case CAF feeding reduced peak Nr1d1 expression. Obesity resulted in a phase advance (approx. 1.5 h) in the rhythms of several clock genes and Ppar-delta in maternal liver. Aside from Nr1d1, expression of clock genes was mostly arrhythmic in LZ and fetal liver, and was unaffected by the CAF diet. In conclusion, maternal obesity suppressed Nr1d1 expression across maternal, fetal, and placental compartments and phase-advanced the rhythms of maternal hepatic clock genes. Given the key role of Nr1d1 in regulating metabolic, vascular, and inflammatory processes, our data suggest that disruptions to rhythmic Nr1d1 expression in utero may contribute to programmed health complications in offspring of obese pregnancies. Summary Sentence Obesity suppresses Nr1d1 expression in maternal, fetal, and placental tissues and phase-advances the rhythms of maternal hepatic clock genes during rat pregnancy.
Structural polymorphism of the major capsid protein of rotavirus

Rotaviruses are important human pathogens with a triple‐layered icosahedral capsid. The major capsid protein VP6 is shown here to self‐assemble into spherical or helical particles mainly depending upon pH. Assembly is inhibited either by low pH (<3.0) or by a high concentration (>100 mM) of divalent cations (Ca2+ and Zn2+). The structures of two types of helical tubes were determined by electron cryomicroscopy and image analysis to a resolution of 2.0 and 2.5 nm. In both reconstructions, the molecular envelope of VP6 fits the atomic model determined by X‐ray crystallography remarkably well. The 3‐fold symmetry of the VP6 trimer, being incompatible with the helical symmetry, is broken at the level of the trimer contacts. One type of contact is maintained within all VP6 particles (tubes and virus), strongly suggesting that VP6 assemblies arise from different packings of a unique dimer of trimers. Our data show that the protonation state and thus the charge distribution are important switches governing the assembly of macromolecular assemblies.
A clinical repetitive transcranial magnetic stimulation service in Australia: 6 years on

Objective: There is considerable research evidence for the effectiveness of repetitive transcranial magnetic stimulation in the treatment of depression. However, there is little information about its acceptability and outcomes in clinical settings. Method: This naturalistic study reports on a clinical repetitive transcranial magnetic stimulation service that has been running in Adelaide, South Australia (SA), for 6 years. During this time, 214 complete acute courses were provided to patients with treatment-resistant Major Depressive Disorder. Patients received either sequential bilateral or right unilateral repetitive transcranial magnetic stimulation treatment involving either 18 or 20 sessions given over 6 or 4 weeks respectively. Data included patient demographic details, duration of depression, and medication at the beginning of their repetitive transcranial magnetic stimulation course. The Hamilton Depression Rating Scale was used to assess response to repetitive transcranial magnetic stimulation. Results: Of those undergoing a first-time acute treatment course of repetitive transcranial magnetic stimulation (N = 167), 28% achieved remission, while a further 12% met the criteria for a response to treatment. Most patients (N = 123, 77%) had previously been treated with five or more antidepressant medications, and 77 (47%) had previously received electroconvulsive therapy. Referral rates remained high over the 6 years, indicating acceptance of the treatment by referring psychiatrists. There were no significant adverse events, and the treatment was generally well tolerated. In all, 41 patients (25%) had a second course of repetitive transcranial magnetic stimulation and 6 (4%) patients had a third course; 21 patients subsequently received maintenance repetitive transcranial magnetic stimulation. Conclusion: This naturalistic study showed that repetitive transcranial magnetic stimulation was well accepted by both psychiatrists and patients, and has good efficacy and safety. Furthermore, repetitive transcranial magnetic stimulation can provide a useful treatment alternative as part of outpatient mental health services for people with depression.
Collagen/Endogenous Thrombin-Induced Platelet Aggregation in Cord versus Adult Whole Blood

Background: In previous studies, neonatal platelets have been shown to be hypoaggregable to various agonists when compared with adult platelets. Objectives: It was the aim of this study to investigate the aggregability of neonatal versus adult platelets when the physiological relevant agonist collagen/endogenous thrombin is used. Methods and Results: Whole blood (WB) aggregation experiments employing the impedance method revealed the same responsiveness of neonatal and adult platelets to collagen/endogenous thrombin. Maximum aggregation (13.5 ± 3.2 vs. 13.6 ± 3.2 Ω; p = 0.94), slope (5.8 ± 1.8 vs. 6.2 ± 2.6 Ω/min; p = 0.79) and lag time until the onset of platelet aggregation (38.7 ± 8.9 vs. 42.6 ± 16.5 s; p = 0.59) were similar in cord and adult WB. However, the rise in serotonin plasma levels due to platelet activation was significantly lower in neonates versus adults (227.57 ± 57.65 vs. 473.34 ± 155.75 ng/ml; p = 0.0001). Furthermore, we found a fast capability of cord plasma to generate (the efficient platelet agonist) endogenous thrombin: thrombin generation started significantly earlier in cord compared with adult plasma (215 ± 19 vs. 247 ± 21 s; p = 0.01). Moreover, thrombelastometry revealed significantly shorter coagulation times in cord versus adult WB activated with collagen/endogenous thrombin (229.8 ± 12.5 vs. 256.3 ± 25.3 s; p = 0.003). Conclusions: The efficient platelet aggregation in cord WB provoked by collagen/endogenous thrombin might help to explain the clinically observed well-functioning primary hemostasis of neonates.
Childhood adversity, parental vulnerability and disorder: examining inter-generational transmission of risk.

BACKGROUND An investigation of intergenerational factors associated with psychiatric disorder in late adolescence/early adulthood was undertaken to differentiate influences from maternal disorder, maternal poor psychosocial functioning and poor parenting, on offspring. METHOD The sample comprised an intensively studied series of 276 mother-offspring pairs in a relatively deprived inner-city London area with high rates of lone parenthood and socio-economic disadvantage. The paired sample was collected over two time periods: first a consecutively screened series of mothers and offspring in 1985-90 (n = 172 pairs) and second a 'vulnerable' series of mothers and offspring in 1995-99 (n = 104 pairs). The vulnerable mothers were selected for poor interpersonal functioning and/or low self-esteem and the consecutive series were used for comparison. Rates of childhood adversity and disorder in the offspring were examined in the two groups. Maternal characteristics including psychosocial vulnerability and depression were then examined in relation to risk transmission. RESULTS Offspring of vulnerable mothers had a fourfold higher rate of yearly disorder than those in the comparison series (43% vs. 11%, p < .001). They were twice as likely as those in the comparison series to have experienced childhood adversity comprising either severe neglect, physical or sexual abuse before age 17. Physical abuse, in particular, perpetrated either by mother or father/surrogate father was significantly raised in the vulnerable group. Analysis of the combined series showed that maternal vulnerability and neglect/abuse of offspring provided the best model for offspring disorder. Maternal history of depression had no direct effect on offspring disorder; its effects were entirely mediated by offspring neglect/abuse. Maternal childhood adversity also had no direct effect. CONCLUSIONS Results are discussed in relation to psychosocial models of risk transmission for disorder. Maternal poor psychosocial functioning needs to be identified as a factor requiring intervention in order to stem escalation of risk across generations.
The Latest Treatment Interventions Improving Mental Health Outcomes for Women, Following Gender-Based Violence in Low-and-Middle-Income Countries: A Mini Review

Gender-based violence (GBV), specifically violence against women, is a worldwide pandemic. Prevalence is further escalated in low-and-middle-income countries and in humanitarian crises. Survivors are left with a combination of post-traumatic stress disorder, depression and anxiety. These mental health disorders lead to further morbidity and mortality. Despite its high prevalence and co-morbidities, gender disparities and mental health stigma globally lead to few interventions developed for this population. The aim of this review is to highlight the mental health interventions developed in the past 5 years, for women following GBV in low-and-middle-income countries. It aims to discuss their efficacy and controversies when implemented into healthcare systems, understand the gaps that remain in the field and suggest future research developments. A thorough literature search revealed 16 new interventions available for improving mental health outcomes for women following GBV in low-and-middle-income countries. Following an in-depth evaluation of the papers, one intervention was successful in effectively implementing treatment into healthcare systems—“PM+. ” However, it proved only to be effective in the short term. Further research must be done for improving long-term mental health outcomes. Results demonstrated poor follow-up for women engaging in group therapy. The review also highlights community workers were used in service delivery to reduce barriers accessing care. No interventions proved effective in humanitarian crises, despite GBV escalated in these settings. There are very few interventions available in comparison to the prevalence of this global health issue. Therefore, this review encourages further research and improvements in mental healthcare interventions following GBV.
Social Media, Text Messaging, and Email—Preferences of Asthma Patients between 12 and 40 Years Old

Background. Electronic media such as social media (Facebook, Twitter, MySpace), email, and text messaging could be useful in the management of asthma. However, patient use and preferences for electronic media in asthma management is currently unknown. Methods. A survey was sent to asthma patients between 12–40 years of age. The survey collected demographic information, use of electronic media, interest in using electronic media to receive asthma information, and interest in using electronic media to communicate with a health care provider about asthma. Free text entries were encouraged. Results. 145 completed surveys were returned. Text messaging, email, and Facebook were used at least weekly by a majority of respondents (82%, 77%, and 65%, respectively). Email was clearly the most preferred method to receive asthma information and to communicate with a physician. There was some interest in using Facebook or text messaging, whereas Myspace and Twitter had minimal interest. On logistic regression analysis, female and Black or Hispanic participants were more likely to have an interest in the use of electronic media for asthma care. Frequent users (>1X/week) of each electronic media type had greater enthusiasm for their incorporation into asthma care. Free text entries revealed that many participants felt social media sites were for connecting with friends rather than for health care, and privacy concerns were also raised. Conclusion. Electronic media offers a novel way to improve asthma care. Email was the most preferred method, though text messaging and social media sites like Facebook may be appropriate for certain patients.
Interaction between human natural anti-alpha-galactosyl immunoglobulin G and bacteria of the human flora

Anti-alpha-galactosyl immunoglobulin G (anti-Gal) is a natural antibody present in unusually high amounts in human sera. It constitutes as much as 1% of circulating immunoglobulin G in humans and displays a distinct specificity for the carbohydrate epitope galactosyl alpha(1----3) galactosyl (Gal alpha 1----3Gal). Recently, it has been suggested by various investigators that anti-Gal may be related to some autoimmune phenomena, since marked elevation of its titer was found in sera of patients with autoimmune thyroid disorders, rheumatoid arthritis, glomerulonephritis, and Chagas' disease. In view of the ubiquitous presence of anti-Gal in high titers in humans, throughout life, we hypothesized that, analogous with synthesis of anti-blood group antibodies against bacterial antigens, bacteria within normal intestinal flora may provide constant antigenic stimulation for the synthesis of anti-Gal. This hypothesis would imply that anti-Gal may bind to a variety of bacterial strains of human flora. In the present study, the interaction between affinity chromatography-purified anti-Gal and various bacterial strains was studied. By the use of a direct immunostaining assay and an enzyme-linked immunosorbent assay, anti-Gal was found to interact with a variety of Escherichia coli, Klebsiella, and Salmonella strains, some of which were isolates from normal stool. Furthermore, the anti-Gal-binding sites in some strains were found to be present on the carbohydrate portion of bacterial lipopolysaccharides. It is thus suggested that Gal alpha 1----3Gal epitopes in the outer membranes of normal flora enterobacteria may provide a continuous source for antigenic stimulation. Since there is no immune tolerance to the Gal alpha 1----3Gal carbohydrate structure in humans, anti-Gal seems to be constantly produced in response to these enterobacteria. In addition, bacteria which express Gal alpha----3Gal epitopes and which may adhere to various cells mediated binding of anti-Gal to human cell lines. These findings raise the possibility that anti-Gal may damage normal human tissues via inflammatory processes facilitated by bacterial Gal alpha 1----3Gal epitopes.
Inhibition of the organic anion-transporting polypeptide 1B1 by quercetin: an in vitro and in vivo assessment.

AIM To investigate the effect of quercetin on organic anion transporting polypeptide 1B1 (OATP1B1) activities in vitro and on the pharmacokinetics of pravastatin, a typical substrate for OATP1B1 in healthy Chinese-Han male subjects. METHODS Using human embryonic kidney 293 (HEK293) cells stably expressing OATP1B1, we observed the effect of quercetin on OATP1B1-mediated uptake of estrone-3-sulphate (E3S) and pravastatin. The influence of quercetin on the pharmacokinetics of pravastatin was measured in 16 healthy Chinese-Han male volunteers receiving a single dose of pravastatin (40 mg orally) after co-administration of placebo or 500 mg quercetin capsules (once daily orally for 14 days). RESULTS Quercetin competitively inhibited OATP1B1-mediated E3S uptake with a K(i) value of 17.9 ± 4.6 µm and also inhibited OATP1B1-mediated pravastatin uptake in a concentration dependent manner (IC(50) , 15.9 ± 1.4 µm). In healthy Chinese-Han male subjects, quercetin increased the pravastatin area under the plasma concentration - time curve (AUC(0,10 h) and the peak plasma drug concentration (C(max)) to 24% (95% CI 15, 32%, P < 0.001) and 31% (95% CI 20, 42%, P < 0.001), respectively. After administration of quercetin, the elimination half-life (t(1/2) ) of pravastatin was prolonged by 14% (95% CI 4, 24%, P = 0.027), with no change in the time to reach C(max) (t(max) ). Moreover, quercetin decreased the apparent clearance (CL/F) of pravastatin by 18% (95% CI 75, 89%, P < 0.001). CONCLUSIONS These findings suggest that quercetin inhibits the OATP1B1-mediated transport of E3S and pravastatin in vitro and also has a modest inhibitory influence on the pharmacokinetics of pravastatin in healthy Chinese-Han male volunteers. The effects of quercetin on other OATP1B1 substrate drugs deserve further investigation.