Miracle-dz/UniFAR-FTUs huggingface dataset:
Bridging the gap: an integrated paediatric to adult clinical service for young adults with kidney failure

Problem Transition from paediatric to adult care of young adults with chronic diseases is poorly coordinated, often delayed, and usually managed through a single referral letter. About 35% of young adults lose a successfully functioning kidney transplant within 36 months of transfer from paediatric to adult services. Design Before and after study of the impact of a new integrated paediatric-adult clinical service for patients with kidney failure. Setting Adult renal centre in Oxford and two paediatric renal centres in London. Strategies for change An integrated paediatric-young adult joint transition clinic and care pathway was established in 2006, in conjunction with a young adult clinical service with regular community based clinics. Previously, young adult transplant recipients were transferred by a single referral letter to an adult renal consultant and managed in a conventional adult clinic. Key measures for improvement Rates of acute rejection and loss of kidney transplants five years before and five years after the introduction of the integrated young adult care pathway. Effects of the change Nine young adult kidney transplant recipients were transferred directly to adult care between 2000 and 2006 (group 1). From 2006 to 2010, 12 young adult transplant recipients underwent integrated transition into the new young adult service (group 2). Six transplants were lost in group 1 (67%) compared with no transplant losses in group 2. Lessons learnt Implementing an integrated transition clinic, coupled with improving young adults’ healthcare experience through a young adult clinic, improved patient adherence to regular medication and engagement with healthcare providers, as judged by reduced transplant failure rates. This model may be applicable to other young adult populations with chronic disease transferring to adult healthcare.
Human IgG3 with extended half-life does not improve Fc-gamma receptor-mediated cancer antibody therapies in mice

Background Current anti-cancer therapeutic antibodies that are used in the clinic are predominantly humanized or fully human immunoglobulin G1 (IgG1). These antibodies bind with high affinity to the target antigen and are efficient in activating the immune system via IgG Fc receptors and/or complement. In addition to IgG1, three more isotypes are present in humans, of which IgG3 has been found to be superior compared to human IgG1 in inducing antibody dependent cell cytotoxicity (ADCC), phagocytosis or activation of complement in some models. Nonetheless, no therapeutic human IgG3 mAbs have been developed due to the short in vivo half-life of most known IgG3 allotypes. In this manuscript, we compared the efficacy of V-gene matched IgG1 and IgG3 anti-tumour mAb (TA99) in mice, using natural variants of human IgG3 with short- or long half-life, differing only at position 435 with an arginine or histidine, respectively. Results In vitro human IgG1 and IgG3 did not show any differences in opsonisation ability of B16F10-gp75 mouse melanoma cells. IgG1, however, was superior in inducing phagocytosis of tumour cells by mouse macrophages. Similarly, in a mouse peritoneal metastasis model we did not detect an improved effect of IgG3 in preventing tumour outgrowth. Moreover, replacing the arginine at position 435 for a histidine in IgG3 to enhance half-life did not result in better suppression of tumour outgrowth compared to wild type IgG3 when injected prior to tumour cell injection. Conclusion In conclusion, human IgG3 does not have improved therapeutic efficacy compared to human IgG1 in a mouse tumour model.
CYP1A1 gene polymorphism and risk of endometrial hyperplasia and endometrial carcinoma

The cytochrome P4501A1 (CYP1A1) is involved in the metabolism of environmental carcinogens and estrogen. We hypothesized that CYP1A1 genetic polymorphism may be a susceptibility factor for endometrial hyperplasia (EH) and endometrial carcinoma (ECa). We therefore evaluated this hypothesis in patients with EH and ECa and control subjects using allele-specific polymerase chain reaction–based method in a Turkish population. The patients with CYP1A1 Ile/Val genotype had a fivefold higher risk of having EH than those with Ile/Ile. In contrast, a higher frequency of any Val genotype (Ile/Val and Val/Val) was found in patients with EH, indicating that persons carrying any Val allele are at increased risk for developing EH. In the ECa group, patients were also more likely to have CYP1A1 Ile/Val allele, with an adjusted odds ratio of 3.0. Moreover, there was a statistically significant increase in relative risk association with any Val genotype between patients and controls, suggesting that individuals carrying any Val genotype are at increased risk for developing ECa. We concluded that variant alleles of the CYP1A1 gene might be associated with EH and ECa susceptibility. Further studies with a large sample size should be considered to address issues of interactions between CYP1A1 and other risk factors.
Effect of platelet concentration on clinical improvement in treatment of early stage-knee osteoarthritis with platelet-rich plasma concentrations

[Purpose] To compare two platelet-rich plasma kits with different platelet concentrations for treatment of knee osteoarthritis. [Subjects and Methods] Male and female patients with knee osteoarthritis who had confirmed diagnosis with X-ray and magnetic resonance imaging were included in this retrospective study. Eligible patients were divided into two groups: Group I, which received platelet-rich plasma kit I, and Group II, which received platelet-rich plasma kit II. Platelet concentrations of both kits were measured by manual counting. For each group, platelet-rich plasma kit was injected twice with a one-month interval between injections. The Western Ontario and McMaster Universities Osteoarthritis Index and the Visual Analog Scale were applied for clinical evaluation before the first injection and one, three and six months after the second injection. [Results] Kits I and II contained 1,000,000 and 3,000,000 platelets/µl respectively. In both groups, initial Western Ontario and McMaster Universities Osteoarthritis Index and Visual Analog Scale scores were significantly higher compared to the latter evaluations. However, no significant difference was observed between groups in terms of clinical evaluations. [Conclusion] Similar clinical results were found in groups receiving different platelet concentrations, therefore, a concentration of 1,000,000 platelet/µl is considered sufficient for pain relief and functional recovery.
Local airborne particulate concentration is associated with visible tracheal mucus in Thoroughbred racehorses.

REASON FOR PERFORMING STUDY Accumulations of tracheal mucus assessed by endoscopic examination are associated with poor performance in racehorses. The air quality in horses' stalls may contribute to this visible tracheal mucus. OBJECTIVES To determine whether the concentration and number of airborne particulates in stalls are associated with visible accumulations of tracheal mucus and with the number of inflammatory cells in tracheal aspirates. METHODS We studied 107 racehorses from 3 stables, in 3 different months, and measured airborne particulate matter 3 times daily in each of the stalls. On each monthly visit, horse airways were examined endoscopically and assigned a mucus score, and tracheal lavage was performed. Bivariate procedures, general estimating equations and linear mixed models were applied to estimate the association between PM and the presence of accumulations of mucus and number of inflammatory cells. RESULTS Stable, stall, month and PM were all significantly associated with the presence of accumulations of tracheal mucus, which had an overall prevalence of 67%. The odds of horses having visible accumulation of mucus were increased when horses occupied enclosed stables or stalls with higher particulate concentrations, and when concentrations of larger particles (≤ 10 µm in diameter) were elevated. Sixty-eight percent of tracheal wash samples contained more than 20% neutrophils. Increased numbers of neutrophils were associated with the concentration of smaller particles (≤ 2.5 µm in diameter). POTENTIAL RELEVANCE Careful consideration of stable construction and management practices focused on maintaining the lowest possible dust concentrations throughout the day should reduce the prevalence of visible accumulations of tracheal mucus, potentially improving racing performance.
Comparison of intensive and low-dose atorvastatin therapy in the reduction of carotid intimal–medial thickness in patients with coronary heart disease

Background: Intensive statin therapy has been shown to improve prognosis in patients with coronary heart disease (CHD). It is unknown whether such benefit is mediated through the reduction of atherosclerotic plaque burden. Aim: To examine the efficacy of high-dose atorvastatin in the reduction of carotid intimal–medial thickness (IMT) and inflammatory markers in patients with CHD. Design: Randomised trial. Setting: Single centre. Patients: 112 patients with angiographic evidence of CHD. Interventions: A high dose (80 mg daily) or low dose (10 mg daily) of atorvastatin was given for 26 weeks. Main outcome measures: Carotid IMT, C-reactive protein (CRP) and proinflammatory cytokine levels were assessed before and after therapy. Results: The carotid IMT was reduced significantly in the high-dose group (left: mean (SD), 1.24 (0.48) vs 1.15 (0.35) mm, p = 0.02; right: 1.12 (0.41) vs 1.01 (0.26) mm, p = 0.01), but was unchanged in the low-dose group (left: 1.25 (0.55) vs 1.20 (0.51) mm, p = NS; right: 1.18 (0.54) vs 1.15 (0.41) mm, p = NS). The CRP levels were reduced only in the high-dose group (from 3.92 (6.59) to 1.35 (1.83) mg/l, p = 0.01), but not in the low-dose group (from 2.25 (1.84) to 3.36 (6.15) mg/l, p = NS). A modest correlation was observed between the changes in carotid IMT and CRP (r = 0.21, p = 0.03). Conclusions: In patients with CHD, intensive atorvastatin therapy results in regression of carotid atherosclerotic disease, which is associated with reduction in CRP levels. On the other hand, a low-dose regimen only prevents progression of the disease.
Familial chronic myeloproliferative disorders: the state of the art

Familial chronic myeloproliferative disorders are defined when in the same pedigree at least two relatives have a chronic myeloproliferative disorder (CMD) as polycythemia vera (PV), essential thrombocythemia (ET) or primary myelofibrosis (PMF). This condition should be distinguished from inherited disorders with Mendelian transmission and single haematopoietic lineage proliferation, named hereditary erythrocytosis and thrombocytosis. The recently discovered mutations in patients with CMD (V617F and exon 12 of JAK2 gene, MPL gene), and those identified in hereditary erythrocytosis and in hereditary thrombocytosis have improved our ability to discriminate these conditions. In familial CMD, the JAK2 mutations are acquired and occur as secondary genetic events. As both mutations of the JAK2 gene have been reported in the same pedigree, a genetic predisposition to the acquisition of the JAK2 mutations is supposed to be inherited. The prevalence of familial cases within CMD is at least 7.6%. The inheritance pattern of familial CMD is consistent with an autosomal dominant trait with decreased penetrance. The clinical presentation at diagnosis of patients with familial CMD does not differ from that of patients with sporadic CMD. In addition, patients with familial CMD develop the same type of complications (thrombosis and haemorrhage) and disease evolution (post‐PV myelofibrosis, post‐ET myelofibrosis and leukaemia) observed in patients with sporadic CMD. The 10‐year survival is 83% for patients with familial PV, 100% for those with familial ET, and 30% for those with familial PMF. The aim of this review is to focus the state of the art of familial CMD and to offer an overview of inherited conditions causing erythrocytosis and thrombocytosis. Copyright © 2008 John Wiley & Sons, Ltd.
Acute Changes in Cardiac Synchrony and Output According to RV Pacing Sites in Koreans with Normal Cardiac Function

Introduction: The synchrony of the pacing heart can be affected by the right ventricular (RV) pacing site and is crucial to cardiac function in pacemaker recipients. We evaluated the acute changes in cardiac synchrony according to the RV pacing sites in normal systolic functioning subjects with normal QRS. Methods: We conducted this study with 30 patients with the pacing in the RV apex (RVA), RV septum (RVS), and RV outflow tract (RVOT) in a sequential manner . Transthoracic echocardiography was conducted at rest and during pacing in order to measure interventricular and intraventricular dyssynchrony in all patients. Results: QRS duration (148.1 ± 12.8 ms) of RVA pacing was significantly shorter than that of RVS pacing (154.4 ± 14.1 ms, P < 0.01) and RVOT pacing (160.6 ± 15.7 ms, P < 0.001). We noted no statistically significant difference in cardiac output according to the pacing sites. The interventricular dyssynchrony with M‐mode and Doppler echocardiography in RVOT pacing was increased to an insignificant degree as compared with those with RVS pacing or RVA pacing. The intraventricular dyssynchrony with tissue Doppler echocardiography in RVA pacing was reduced significantly as compared with that of RVS pacing or RVOT (RVA = 60.3 ± 32.7 ms, RVS = 82.1 ± 33.8 ms, RVOT = 79.1 ± 33.3 ms; RVA vs RVS = P < 0.05, RVA vs RVOT = P < 0.01, RVS vs RVOT = P = NS). Conclusion: RVA pacing is superior to RVS and RVOT pacing with regard to intraventricular synchrony in normal systolic functioning subjects with normal QRS. Cardiac output at RVA pacing is not inferior to other sites. (ECHOCARDIOGRAPHY, Volume 26, July 2009)
Obesity and incremental hospital charges among patients with and without diabetes in the United States.

OBJECTIVE The purpose of this study was to estimate the association between obesity and diabetes among inpatients in the United States as well as to investigate the incremental hospital charges attributable to obesity or morbid obesity. METHODS We analyzed the Nationwide Inpatient Sample 2005, a nationally representative probability sample that includes nearly 8 million inpatient records from US community hospitals. RESULTS During the past decade, the obesity among inpatients has steeply increased. In 2005, nearly 1.87 million hospitalizations were made by obese or morbidly obese patients. Both patients with type 1 and type 2 diabetes were considerably more likely to be obese or morbidly obese compared with inpatients without diabetes (P < 0.01). The proportions of hospitalizations with obese or morbidly obese conditions were 4.5% among patients without diabetes, 6.5% among patients with type 1, and 12.2% among patients with type 2 diabetes. The hospital charges for obese and morbidly obese patients were 6.1% (P < 0.01) and 18.7% (P < 0.01) higher than that of the nonobese patients when diabetes status, sex, age, race, hospital admission type, and length of hospital stays were the same. CONCLUSIONS Following a parallel rise in obesity among the general population, hospital admissions of obese and morbidly obese inpatients are continuously increasing. Morbidly obese patients consumed substantially more hospital resources regardless of the presence or type of diabetes. Under the current price-per-case reimbursement system, additional hospital resource use by this growing number of morbidly obese inpatients could be a burden to hospital financial systems.
No Evidence of Association of CTLA-4 -318 C/T, 159 C/T, 3′ STR and SUMO4 163 AG Polymorphism with Autoimmune Diabetes

Autoimmune diabetes is an organ specific and multifactorial disorder including insulin dependent diabetes mellitus (Type 1 Diabetes) and latent autoimmune diabetes in adults (LADA), which progresses to insulin dependency because of the beta cells destruction. Several polymorphisms in different genes have been associated with diabetes. The CTLA4 gene is considered a down regulator of T cell function, and the SUMO4 gene encodes a small ubiquitin-like modifier implicated in the intensity and duration of the immune response. We selected 62 LADA patients, 123 patients with Type 1 diabetes patients and 136 unrelated volunteers to study CTLA4 -318 C/T, 159 C/T, 3′ STR and SUMO4 163 A/G polymorphisms by PCR. There was a statistical difference significant in the frequency of the allele 209pb for the 3′STR between LADA and Type 1 diabetes patients but not with respect the normal group, the frequencies were found to be 6.9%, 1.0% and 1.9%, respectively. However, no association with either of the polymorphisms has been found in the studied population. The knowledge of the several susceptibility loci in autoimmune diabetes will enhanced the prediction of individuals at high risk of developing the disease in order to establish the best treatment and the prevention of autoimmune diabetes.
Does Dsm-III-r diagnose Depression in Non-Western Patients?

The author reports the cases of three non-Western patients with impaired function ing due to symptoms of major depression. Their characteristic style of symptom expression was different from the usual manifestations, emphasizing vegetative rather than cognitive and affective aspects of depression. Non-Western patients may be either misdiagnosed or overdiagnosed, which may complicate their assessment and treatment, because the diagnostic criteria used reflect Western values of behaviour. To improve the treatment of non-Western patients who seek therapy for depressive symptomatology in Western countries, therapists should seek broader understan ding and deeper appreciation of non-Western belief systems and cultural differences.
Kinetic analysis of the effects of mutagenesis of W501 and V432 of the hepatitis C virus NS3 helicase domain on ATPase and strand-separating activity.

Two hydrophobic residues, W501 and V432, in the nucleic acid (NA) binding pocket of the HCV helicase domain (E) were mutagenized in an effort to investigate contributions of these residues to substrate affinities and to enzymatic activities. The affinities of wild-type [hE(wt)] and mutant enzymes [hE(W501F), hE(W501A), and hE(V432A)] for NA and ATP were determined by monitoring changes in the intrinsic protein fluorescence, in the fluorescence of fluorescently tagged nucleic acid, and in the enzymatic activity. The steady-state kinetic parameters of the mutant enzymes for ATP hydrolysis (at saturating concentrations of NA) were similar to those of hE(wt). hE(W501F), hE(W501A), and hE(V432A) had strand-separating activities that were 136%, 3.8%, and 3.1% of that of hE(wt). The processivities of hE(W501F), hE(W501A), and hE(V432A) were reduced relative to that of hE(wt). The reduced processivities of hE(W501F) and hE(W501A) were primarily due to an increase in the rate of dissociation of E. ATP from E.ATP. NA. The reduced processivity of hE(V432A) was primarily due to a reduction in the intrinsic forward rate constant for strand separation. This result suggested that V432 may constitute part of the forward "stepping" motor of E. hE(W501A) and hE(V432A) did not display a dominant negative phenotype in a steady-state helicase assay with hE(wt). hE(wt) stored in the presence of beta-mercaptoethanol was covalently modified at three cysteinyl residues. The biological significance of the potential reactivity of these cysteinyl residues on hE(wt) is unknown.
Structures of human primase reveal design of nucleotide elongation site and mode of Pol α tethering

Significance DNA synthesis during duplication of the genome depends on primase, the DNA-dependent RNA polymerase that initiates nucleotide polymerization by assembling short RNA primers on the unwound template DNA. The mechanism of DNA priming remains poorly understood, principally because of lack of high-resolution structural information. Our study begins to fill the gap in our knowledge by reporting crystal structures of human primase in unliganded form and bound to UTP. We exploit the atomic model of primase to map amino acids that are important for the catalytic function of the enzyme. In addition, we describe crystallographically the interaction between primase and DNA polymerase α, which keeps primase tethered to the replication fork. Initiation of DNA synthesis in genomic duplication depends on primase, the DNA-dependent RNA polymerase that synthesizes de novo the oligonucleotides that prime DNA replication. Due to the discontinuous nature of DNA replication, primase activity on the lagging strand is required throughout the replication process. In eukaryotic cells, the presence of primase at the replication fork is secured by its physical association with DNA polymerase α (Pol α), which extends the RNA primer with deoxynucleotides. Our knowledge of the mechanism that primes DNA synthesis is very limited, as structural information for the eukaryotic enzyme has proved difficult to obtain. Here, we describe the crystal structure of human primase in heterodimeric form consisting of full-length catalytic subunit and a C-terminally truncated large subunit. We exploit the crystallographic model to define the architecture of its nucleotide elongation site and to show that the small subunit integrates primer initiation and elongation within the same set of functional residues. Furthermore, we define in atomic detail the mode of association of primase to Pol α, the critical interaction that keeps primase tethered to the eukaryotic replisome.
Effects of Oxidative Stress on Growth Performance, Nutrient Digestibilities and Activities of Antioxidative Enzymes of Weanling Pigs

This study was undertaken to investigate the effects of oxidative stress on growth performance, nutrient digestibilities and activities of antioxidant enzymes of weanling pigs. In the experiment, 24 male LandrancexYorkshire weanling pigs were allotted to three groups of 8 animals each. Pigs were fed individually. According to a single factorial arrangement, pigs received diets with 5% of either fresh (group 1 and group 3) or oxidized fish oil (peroxide value was 786.50 meq O 2 /kg before inclusion in the diet, group 2). At the beginning of the experiment, pigs in group 3 received an intraperitoneal injection of diquat at 12 mg/kg of body weight. The trial lasted for 26 d. A metabolism test was carried out during the last 4 days of the second week. The results showed that feeding diets containing oxidized fish oil or injection with diquat depressed the growth performance and nutrient digestibilities of weanling pigs, decreased activities of antioxidant enzymes and increased concentration of malondialdehyde in plasma and liver. Intraperitoneal injection of diquat would induce more serious oxidative stress than oral intake of oxidized fish oil in the diet. In conclusion, administration of oxidized fish oil or diquat could induce oxidative stress in weanling pigs, and oxidative stress could depress growth performance and impact anti-oxidative ability of young pigs.