Miracle-dz/UniFAR-FTUs huggingface dataset:
Serum protein-bound uraemic toxins and clinical outcomes in haemodialysis patients.

BACKGROUND The protein-bound uraemic toxin p-cresol is associated with immunodeficiency in haemodialysis (HD) patients. We investigated the effect of serum p-cresol, indoxyl sulphate and other variables on clinical outcomes in HD patients during a 20-month follow-up. METHODS We enrolled 100 stable HD patients from a single medical centre. The primary outcomes were infection-related hospitalization, cardiovascular events and all-cause mortality. Serum total and free p-cresol and indoxyl sulphate levels were measured using ultra-performance liquid chromatography. Biochemical data were collected concurrently. RESULTS Multivariate logistic regression analysis revealed that infection-related hospitalization correlated with free p-cresol (adjusted odds ratio: 1.70, P = 0.01) and highly sensitive C-reactive protein (hsCRP) (adjusted odds ratio: 2.07, P = 0.01); cardiovascular event was associated with free p-cresol (adjusted odds ratio: 1.78, P = 0.01) and nPCR (adjusted odds ratio: 0.01, P = 0.02); and all-cause mortality was related to albumin (adjusted odds ratio: 0.04, P = 0.01). The Kaplan-Meier method showed that free and total p-cresol were significantly associated with cardiovascular events (log-rank P < 0.01 and log-rank P < 0.01, respectively). Serum free p-cresol seemed to have a trend to correlate with infection-related hospitalization during a 20-month follow-up (log-rank P = 0.05). CONCLUSIONS Serum free and total p-cresol levels were significantly related to cardiovascular events. In addition, serum free p-cresol and hsCRP levels were also found to be associated with infection-related hospitalization.
Reduced prevalence of cardiovascular disease and metabolic syndrome-related disorders among Japanese long-term inpatients with schizophrenia

Purpose: Individuals with schizophrenia have a vastly reduced lifespan compared with the general population; comorbid cardiovascular disease (CVD) is the leading cause of death for them. Furthermore, these individuals are more likely to have metabolic syndrome-related disorders (MSDs), which increase CVD risk. We examined the medical records of long-term inpatients with schizophrenia to identify methods for preventing CVD and MSDs. Method: A retrospective survey was conducted on 56 inpatients with schizophrenia. The prevalence rates of CVD and MSDs among inpatients with schizophrenia were compared with Japanese general population data from the 2010 National Health and Nutrition Examination Survey. Then, we compared the variables influencing CVD and MSDs between first- and second-generation antipsychotic drug groups. Results: The prevalences of hyperlipidemia, diabetes mellitus, hypertension, myocardial infarction, and cerebral hemorrhage among individuals with schizophrenia were lower than those among the Japanese general population. This effect is likely attributable to the nursing care offered to individuals with schizophrenia, which includes dietary advice, moderate exercise support, and body weight and blood pressure measurement. Medication did not correlate with CVD or MSD prevalence. Discussion: Long-term hospitalization to particularly useful in and thus, to the of and MSDs among patients drugs might have only a minor influence on CVD and MSD prevalence with reliable nursing care. Japanese psychiatric personnel should attend to outpatients with schizophrenia, as this population is increasing and receives less care than do inpatients.
CGI-58 knockdown sequesters diacylglycerols in lipid droplets/ER-preventing diacylglycerol-mediated hepatic insulin resistance

Comparative gene identification 58 (CGI-58) is a lipid droplet-associated protein that promotes the hydrolysis of triglyceride by activating adipose triglyceride lipase. Loss-of-function mutations in CGI-58 in humans lead to Chanarin–Dorfman syndrome, a condition in which triglyceride accumulates in various tissues, including the skin, liver, muscle, and intestines. Therefore, without adequate CGI-58 expression, lipids are stored rather than used for fuel, signaling intermediates, and membrane biosynthesis. CGI-58 knockdown in mice using antisense oligonucleotide (ASO) treatment also leads to severe hepatic steatosis as well as increased hepatocellular diacylglycerol (DAG) content, a well-documented trigger of insulin resistance. Surprisingly, CGI-58 knockdown mice remain insulin-sensitive, seemingly dissociating DAG from the development of insulin resistance. Therefore, we sought to determine the mechanism responsible for this paradox. Hyperinsulinemic-euglycemic clamp studies reveal that the maintenance of insulin sensitivity with CGI-58 ASO treatment could entirely be attributed to protection from lipid-induced hepatic insulin resistance, despite the apparent lipotoxic conditions. Analysis of the cellular compartmentation of DAG revealed that DAG increased in the membrane fraction of high fat-fed mice, leading to PKCɛ activation and hepatic insulin resistance. However, DAG increased in lipid droplets or lipid-associated endoplasmic reticulum rather than the membrane of CGI-58 ASO-treated mice, and thus prevented PKCɛ translocation to the plasma membrane and induction of insulin resistance. Taken together, these results explain the disassociation of hepatic steatosis and DAG accumulation from hepatic insulin resistance in CGI-58 ASO-treated mice, and highlight the importance of intracellular compartmentation of DAG in causing lipotoxicity and hepatic insulin resistance.
Deficiency of the RIIβ subunit of PKA affects locomotor activity and energy homeostasis in distinct neuronal populations

Significance Genetic mutations in mice and humans have dramatic effects on the overall ability of the organism to regulate body weight and maintain a homeostatic balance between energy expenditure and calorie intake. We are studying mice with a null mutation in the RIIβ subunit of the cAMP-dependent protein kinase system that renders them lean and resistant to diet-induced obesity. These mice also exhibit greatly increased physical activity. Our studies show that the brain regulates all of these phenotypes, but, surprisingly, the specific neurons that determine the phenotypes are distinct and the increased physical activity is not required for the lean phenotype. Targeted disruption of RIIβ-protein kinase A (PKA) in mice leads to a lean phenotype, increased nocturnal locomotor activity, and activation of brown adipose tissue. Because RIIβ is abundantly expressed in both white and brown adipose tissue as well as the brain, the contribution of neuronal vs. peripheral PKA to these phenotypes was investigated. We used a Cre-Lox strategy to reexpress RIIβ in a tissue-specific manner in either adipocytes or neurons. Mice with adipocyte-specific RIIβ reexpression remained hyperactive and lean, but pan-neuronal RIIβ reexpression reversed both phenotypes. Selective RIIβ reexpression in all striatal medium spiny neurons with Darpp32-Cre corrected the hyperlocomotor phenotype, but the mice remained lean. Further analysis revealed that RIIβ reexpression in D2 dopamine receptor-expressing medium spiny neurons corrected the hyperlocomotor phenotype, which demonstrated that the lean phenotype in RIIβ-PKA–deficient mice does not develop because of increased locomotor activity. To identify the neurons responsible for the lean phenotype, we used specific Cre-driver mice to reexpress RIIβ in agouti-related peptide (AgRP)-, proopiomelanocortin (POMC)-, single-minded 1 (Sim1)-, or steroidogenic factor 1 (SF1)-expressing neurons in the hypothalamus, but observed no rescue of the lean phenotype. However, when RIIβ was reexpressed in multiple regions of the hypothalamus and striatum driven by Rip2-Cre, or specifically in GABAergic neurons driven by Vgat-ires-Cre, both the hyperactive and lean phenotypes were completely corrected. Bilateral injection of adeno-associated virus1 (AAV1)-Cre directly into the hypothalamus caused reexpression of RIIβ and partially reversed the lean phenotype. These data demonstrate that RIIβ-PKA deficiency in a subset of hypothalamic GABAergic neurons leads to the lean phenotype.
Prevalence and types of cognitive impairment among patients with stroke attending a referral hospital in Uganda

Background Cognitive impairment is associated with short and long term adverse outcomes in stroke patients that may impair functional recovery during their rehabilitative process. Aims This study determined the prevalence, grades and demographic factors associated with cognitive impairment among patients with stroke attending Mulago National Referral Hospital in Uganda, a teaching hospital for Makerere University College of Health Sciences. Methods This was a cross-sectional descriptive study conducted from Mulago National Referral Hospital between June 2006 and March 2007. Eighty five patients with stroke confirmed by brain computed tomography scan, consenting either by themselves or by their guardians, were consecutively recruited from the Medical wards, Neurology clinic and the Physiotherapy department. A standardized questionnaire was interviewer administered, to obtain demographic and clinical data, and the Mini-Mental State Examination instrument was used to screen and grade cognitive impairment. Results Of the 85 patients evaluated, 70 (82.4%) had infarct and 15 (17.6%) hemorrhagic stroke. Fifty-four (63%, 95% confidence interval (CI): 53 - 73) had cognitive impairment; of which 23 (27%) and 14 (16%) had mild and moderate cognitive impairment respectively accounting for 43% of the cognitively impaired but with no dementia, and 17 (20%) had severe cognitive impairment (dementia). The only socio-demographic factor associated with cognitive impairment was age . 40 years (odds ratio (OR) 4, 95% CI 1.2 - 13.4, P = 0.024). Conclusions The prevalence of cognitive impairment among patients with stroke is high. Increasing age is significantly associated with cognitive impairment. There is need for neurocognitive assessment programs among stroke patients and the introduction of rehabilitation services should target to maximize their functional recovery.
Two novel recessive mutations in KRT14 identified in a cohort of 21 Spanish families with epidermolysis bullosa simplex

Background Basal epidermolysis bullosa simplex (EBS) is a group of blistering genodermatoses mostly caused by mutations in the keratin genes, KRT5 and KRT14. Recessive mutations represent about 5% of all EBS mutations, being common and specific in populations with high consanguinity, where affected patients show severe phenotypes.
Alcohol and Energy Drinks in NSW

Energy drinks and energy ‘shots’ have become increasingly popular in recent years. Many people consume them with the belief that the beverage will assist in endurance, concentration and stamina. To better understand any potential for harm when young people drink alcohol and energy drinks together, NSW Health commissioned independent research. The Turning Point Drug and Alcohol Centre in Victoria led a research consortium which comprised Australia’s top researchers. The research study included:  an online survey of 16-35 year olds in NSW to determine how common consumption of combined alcohol and energy drink is, target group most affected, characteristics of use and harms of use  a street intercept face-to-face survey of 16-35 year olds in NSW conducted at night times in several Sydney metropolitan sites and Orange and Newcastle  a lab-based experiment to test the effects of combining alcohol and energy drinks on the body, coordination and risk-taking behaviour. The outcome was a good first step in looking at this issue in the Australian setting. The lab-based research undertaken by the consortium has added real knowledge about the body’s response to combined alcohol and energy drinks. Use of alcohol and energy drinks is an emerging issue and a very difficult area to research effectively. As a consequence, caution is needed in interpreting and acting on any findings. The surveys, while containing some unavoidable methodological constraints, provide some consistent social findings. Given the difficult nature of research in this area, these findings cannot easily be generalised to the NSW population and cannot be solely used as a basis for regulatory or other interventions
Overcoming drug-resistant herpes simplex virus (HSV) infection by a humanized antibody

Despite the availability of antiviral chemotherapy, herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) infections remain a severe global health problem. Of particular concern is the growing incidence of drug resistance in immunocompromised patients, which stresses the urgency to develop new effective treatment alternatives. We have developed a humanized monoclonal antibody (mAb hu2c) that completely abrogates viral cell-to-cell spread, a key mechanism by which HSV-1/2 escapes humoral immune surveillance. Moreover, mAb hu2c neutralized HSV fully independent of complement and/or immune effector cell recruitment in a highly efficient manner. Prophylactic and therapeutic administration of mAb hu2c completely prevented infection-related mortality of severely immunodeficient mice being challenged with a lethal dose of HSV-1. The high neutralization capacity of mAb hu2c was fully maintained toward clinical HSV isolates being multiresistant to standard antiviral drugs, and infection was fully resolved in 7/8 nonobese diabetic/SCID mice being infected with a multidrug resistant HSV-1 patient isolate. Immunohistochemical studies revealed no significant cross-reactivity of the antibody toward human tissues. These features warrant further clinical development of mAb hu2c as an immunotherapeutic compound for the management of severe and particularly drug-resistant HSV infections.
The five most cited NDT papers from 2005 to 2009.

The five most cited NDT articles from 2005 through 2009 Grobner T. Gadolinium—a specific trigger for the development of nephrogenic fibrosing dermopathy and nephrogenic systemic fibrosis? NDT 2006; 21 (4): 1104–1108 (258 citations, end 2009) Vanholder R, Massy Z, Argiles A et al. for the European Uraemic Toxin Work Group (EUTox) Chronic kidney disease as cause of cardiovascular morbidity and mortality. NDT 2005; 20 (6): 1048–1056 (90 citations, end 2009) Uehlinger DE, Jakob SM, Ferrari P et al. Comparison of continuous and intermittent renal replacement therapy for acute renal failure. NDT 2005; 20 (8): 1630–1637 (70 citations, end 2009) Cirillo M, Anastasio P, De Santo NG. Relationship of gender, age, and body mass index to errors in predicted kidney function. NDT 2005; 20 (9): 1791–1798 (62 citations, end 2009) Schiffmann R, Ries M, Timmons M et al. Long-term therapy with agalsidase alfa for Fabry disease: safety and effects on renal function in a home infusion setting. NDT 2006; 21 (2): 345–354 (60 citations, end 2009)
Dynamics of internal pore opening in KV channels probed by a fluorescent unnatural amino acid

Atomic-scale models on the gating mechanism of voltage-gated potassium channels (Kv) are based on linear interpolations between static structures of their initial and final state derived from crystallography and molecular dynamics simulations, and, thus, lack dynamic structural information. The lack of information on dynamics and intermediate states makes it difficult to associate the structural with the dynamic functional data obtained with electrophysiology. Although voltage-clamp fluorometry fills this gap, it is limited to sites extracellularly accessible, when the key region for gating is located at the cytosolic side of the channels. Here, we solved this problem by performing voltage-clamp fluorometry with a fluorescent unnatural amino acid. By using an orthogonal tRNA-synthetase pair, the fluorescent unnatural amino acid was incorporated in the Shaker voltage-gated potassium channel at key regions that were previously inaccessible. Thus, we defined which parts act independently and which parts act cooperatively and found pore opening to occur in two sequential transitions.
Long Term Follow-up of Morbidity and Quality of Life Associated with Isolated Gastroschisis

Gastroschisis is a birth defect in which an opening in the abdominal wall allows herniation of the viscera. Prenatal counseling regarding gastroschisis typically discusses that, although these infants often endure a difficult neonatal course, they experience few long-term complications. However, information regarding long-term outcomes is based on limited studies that lack specificity. Therefore, we aimed to study the long-term morbidity and quality of life in children born with gastroschisis in a large and diverse population drawn from the Texas Birth Defects Registry (TBDR). Study packets with informed consent, a questionnaire, and the Pediatric Quality of Life Inventory Generic Core Scale 4.0 (PedsQL 4.0) in English and Spanish were mailed to 1,112 parents of children born with isolated gastroschisis in Texas between 1999 and 2008 via the TBDR. Information was abstracted from the TBDR for 58 mothers of children with gastroschisis who returned study materials. Three hundred fifty five packets were returned to sender, giving a response rate of 7.7%. Children born with gastroschisis had quality of life scores that were not significantly different than expected (p = 0.981). However, factors such as having a learning disability (p = 0.001) and missing school due to gastrointestinal issues (p = 0.020) were found to significantly decrease quality of life. Overall, children with gastroschisis had a significantly increased risk for learning disabilities regardless of whether they were preterm (p = 0.021) or full term (p = 0.021). Additionally, there appeared to be an increased risk for auditory impairment in Caucasian children (p < 0.0001). Therefore, while overall long-term quality of life is not significantly altered for children born with gastroschisis, the previously unreported increased risk for learning disabilities and possible association with hearing impairment are important findings that should be conveyed to prospective parents.
MicroRNAs as novel players in skin development, homeostasis and disease

MicroRNAs (miRNAs) are a group of newly discovered small (∼19–24 nucleotides), noncoding RNAs that modulate gene expression by interacting with the 3′ untranslated region of the corresponding target gene messenger RNA (mRNA). miRNAs have been estimated to regulate more than one‐third of protein‐encoding mRNAs. As a consequence, cellular protein expression and a large number of biological processes are influenced by miRNA‐mediated post‐transcriptional regulation of gene expression. The severe phenotype of mice lacking key enzymes of the miRNA biogenesis pathway (Dgcr8 and Dicer) in the skin confirmed the essential function of miRNAs in this tissue. In addition, a growing number of reports has identified miRNAs as regulators of the morphogenesis and homeostasis of the skin and its appendages, and miRNA deregulation was shown to be associated or even causally related to several skin diseases. Profiling studies have identified numerous differentially regulated miRNAs associated with physiological (e.g. keratinocyte differentiation) and pathological (e.g. psoriasis, melanoma) processes. These data bear enormous potential for further studies. Because of the easy accessibility of the skin, it is plausible to anticipate that, once efficient and safe methods for the topical delivery of substances mimicking or modulating miRNA activity become available, skin diseases will be among the first to be approached with miRNA‐based therapies. This review article gives a short introduction to miRNA biology and summarizes and discusses existing evidence for a role of these molecules in the skin.
Malassezia, dandruff and seborrhoeic dermatitis: an overview

From their original description, fungi of the genus Malassezia (previously Pityrosporum) have been associated with dandruff and seborrhoeic dermatitis. The principle evidence on which this connection was based was that the organisms were present, often in high numbers, on the skin in these conditions and that both responded to treatment that inhibited or destroyed Malassezia yeasts. The availability of new tools such as genomic and proteomic analyses has begun to provide a new insight into the pathogenetic mechanisms involved. New evidence shows the production of specific phospholipases on affected skin sites in dandruff and signalling molecules such as malassezin in seborrhoeic dermatitis. It is still not clear why those individuals and skin sites, prone to either disease, are particularly associated with the presence of these marker molecules but these studies are providing clues to the different ways in which organisms, which are normally commensals, interact with human skin.
Renoprotective effect of erythropoietin against ischaemia-reperfusion injury in a non-human primate model.

BACKGROUND The renoprotective effect of erythropoietin (Epo) against ischaemia-reperfusion injury (IR/I) was evaluated in a non-human primate model. METHODS Crab-eating macaques were divided into two groups: Control (n = 10), treated with saline, and EPO (n = 10), treated with Epo. Epo was injected intravenously at a dose of 12,000 units, 5 min before clamping the renal pedicle and 5 min before declamping. Renal IR/I was created by clamping the left renal artery for 90 min following right nephrectomy. Haemoglobin (Hb), haematocrit (Ht), creatinine (Cr), blood urea nitrogen (BUN), cystatin C and interleukin-6 (IL-6) were measured before (Pre) and after (Day 0) the operation, and on post-operative days: Day 1, Day 3, Day 5 and Day 7. Apoptotic cells were counted on Day 1. RESULTS There were no differences in Hb and Ht between the two groups. Cr, BUN, cystatin C and IL-6 levels in the EPO group were lower than those in the Control group at most of the observation points. The number of apoptotic cells in the Control was significantly higher than that of and EPO group. CONCLUSIONS Epo significantly ameliorates renal IR/I in this non-human primate model. Our findings justify the clinical application of Epo, not only for acute renal failure, but also in transplantation.
A meta-analysis of the clinical remission rate and long-term efficacy of tonsillectomy in patients with IgA nephropathy.

BACKGROUND We wished to evaluate the clinical remission rate and long-term efficacy of tonsillectomy for patients with IgA nephropathy. METHODS We searched a number of databases, including PubMed, CNKI, Wanfang and others, for clinical case-control studies of tonsillectomy in patients with IgA nephropathy. We then performed a meta-analysis of these studies. After evaluating total clinical remission rates, we compared the remission rates for specific treatments: tonsillectomy plus steroid pulse, tonsillectomy plus normal-dose steroid, and general treatment using neither tonsillectomy nor steroids. We also compared the rates of end-stage renal failure (ESRF) at last follow-up to estimate the long-term renal survival rate associated with each treatment. RESULTS Seven retrospective studies met the inclusion criteria and were included. These included a total of 858 patients, in which 534 underwent tonsillectomy and 324 did not. The total clinical remission rate was higher in the operative group, while the ESRF rate was higher in the non-operative group. The clinical remission rate in patients who underwent tonsillectomy remained higher than in the non-operative group at both 5- and 10-year follow-up. The clinical remission rate in patients who underwent tonsillectomy plus steroid pulse was higher than in those treated with steroid pulse alone, normal-dose steroids or general treatment alone (P < 0.05). However, the clinical remission rate of simple tonsillectomy was not higher than that of general treatment (P > 0.05). CONCLUSIONS Whereas neither tonsillectomy nor steroid treatment alone increased remission rates in patients with IgA nephropathy, tonsillectomy combined with either normal steroid or steroid pulse treatment resulted in higher remission rates with favourable long-term efficacy.