bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phosphorylation regulates proteasomal-mediated degradation and solubility of TAR DNA binding protein-43 C-terminal fragments
Authors: Zhang Yong-Jie , Gendron Tania F , Xu Ya-Fei , Ko Li-Wen , Yen Shu-Hui , Petrucelli Leonard 
Published: August 2010

Abstract

Background
Inclusions of TAR DNA binding protein-43 (TDP-43) are the defining histopathological feature of several neurodegenerative diseases collectively referred to as TDP-43 proteinopathies. These diseases are characterized by the presence of cellular aggregates composed of abnormally phosphorylated, N-terminally truncated and ubiquitinated TDP-43 in the spinal cord and/or brain. Recent studies indicate that C-terminal fragments of TDP-43 are aggregation-prone and induce cytotoxicity. However, little is known regarding the pathways responsible for the degradation of these fragments and how their phosphorylation contributes to the pathogenesis of disease.

Results
Herein, we established a human neuroblastoma cell line (M17D3) that conditionally expresses an enhanced green fluorescent protein (GFP)-tagged caspase-cleaved C-terminal TDP-43 fragment (GFP-TDP220-414). We report that expression of this fragment within cells leads to a time-dependent formation of inclusions that are immunoreactive for both ubiquitin and phosphorylated TDP-43, thus recapitulating pathological hallmarks of TDP-43 proteinopathies. Phosphorylation of GFP-TDP220-414 renders it resistant to degradation and enhances its accumulation into insoluble aggregates. Nonetheless, GFP-TDP220-414 inclusions are reversible and can be cleared through the ubiquitin proteasome system. Moreover, both Hsp70 and Hsp90 bind to GFP-TDP220-414 and regulate its degradation.

Conclusions
Our data indicates that inclusions formed from TDP-43 C-terminal fragments are reversible. Given that TDP-43 inclusions have been shown to confer toxicity, our findings have important therapeutic implications and suggest that modulating the phosphorylation state of TDP-43 C-terminal fragments may be a promising therapeutic strategy to clear TDP-43 inclusions.
Kaposi's Sarcoma Associated-Herpes Virus (KSHV) Seroprevalence in Pregnant Women in South Africa
Authors: Malope-Kgokong Babatyi I , MacPhail Patrick , Mbisa Georgina , Ratshikhopha Edith , Maskew Mhairi , Stein Lara , Sitas Freddy , Whitby Denise 
Published: August 2010

Abstract

Background
Factors previously associated with Kaposi's sarcoma-associated herpesvirus (KSHV) transmission in Africa include sexual, familial, and proximity to river water. We measured the seroprevalence of KSHV in relation to HIV, syphilis, and demographic factors among pregnant women attending public antenatal clinics in the Gauteng province of South Africa.

Methods
We tested for antibodies to KSHV lytic K8.1 and latent Orf73 antigens in 1740 pregnant women attending antenatal clinics who contributed blood to the "National HIV and Syphilis Sero-Prevalence Survey - South Africa, 2001". Information on HIV and syphilis serology, age, education, residential area, gravidity, and parity was anonymously linked to evaluate risk factors for KSHV seropositivity. Clinics were grouped by municipality regions and their proximity to the two main river catchments defined.

Results
KSHV seropositivity (reactive to either lytic K8.1 and latent Orf73) was nearly twice that of HIV (44.6% vs. 23.1%). HIV and syphilis seropositivity was 12.7% and 14.9% in women without KSHV, and 36.1% and 19.9% respectively in those with KSHV. Women who are KSHV seropositive were 4 times more likely to be HIV positive than those who were KSHV seronegative (AOR 4.1 95%CI: 3.4 - 5.7). Although, women with HIV infection were more likely to be syphilis seropositive (AOR 1.8 95%CI: 1.3 - 2.4), no association between KSHV and syphilis seropositivity was observed. Those with higher levels of education had lower levels of KSHV seropositivity compared to those with lower education levels. KSHV seropositivity showed a heterogeneous pattern of prevalence in some localities.

Conclusions
The association between KSHV and HIV seropositivity and a lack of common association with syphilis, suggests that KSHV transmission may involve geographical and cultural factors other than sexual transmission.
High anorectal malformation in a five-month-old boy: a case report
Authors: Pandey Anand , Gangopadhyay Ajay N , Kumar Vijayendra , Sharma Shiv P 
Published: August 2010

Abstract

Introduction
Anorectal malformation, one of the most common congenital defects, may present with a wide spectrum of defects. Almost all male patients present within first few days of life.

Case presentation
A five-month-old baby boy of Indian origin and nationality presented with anal atresia and associated rectourethral prostatic fistula. The anatomy of the malformation and our patient's good condition permitted a primary definitive repair of the anomaly. A brief review of the relevant literature is included.

Conclusion
Delayed presentation of a patient with high anorectal malformation is rare. The appropriate treatment can be rewarding.
Anti-tumor effects of CIK combined with oxaliplatin in human oxaliplatin-resistant gastric cancer cells in vivo and in vitro
Authors: Zhao Qun , Zhang Hui , Li Yong , Liu Jun , Hu Xiaojie , Fan Liqiao 
Published: August 2010

AbstractBackgroundDrug resistance remains a great challenge in the treatment of gastric cancer. The goal of this study was to explore the anti-tumor effects and mechanism of cytokine-induced killer (CIK) cell combined with oxaliplatin (L-OHP) in human oxaliplatin-resistant gastric cancer cells.MethodsAfter producing oxaliplatin-resistant gastric cancer cells, cell morphology, growth and doubling time were observed, followed by detection of cell cycle distribution and apoptosis, drug sensitivity (e.g., L-OHP) and expression of P-gp and livin. MTT assay, in vivo pharmacodynamics and pathomorphology experiments were used to detect killing activities of CIK combined with L-OHP.ResultsCompared with parental gastric cancer cells, oxaliplatin-resistant gastric cancer cells in S phase were reduced and cell apoptosis rate was increased (P < 0.05), the inhibition rate of 10 chemotherapeutics on oxaliplatin-resistant gastric cancer cells was significantly lower and the expression of P-gp was significantly higher (P < 0.05). However, there was no significant difference in livin expression between parental gastric cancer cells and oxaliplatin-resistant gastric cancer cells (P > 0.05). The in vitro killing activity of CIK combined with L-OHP on parental cells and oxaliplatin-resistant cells were significantly enhanced compared with L-OHP or CIK alone. And it showed greater synergetic effects against oxaliplatin-resistant cells compared with parental cells (P < 0.05). In addition, survival rate, abdominal circumference and pathomorphology results revealed stronger in vivo anti-tumor effects when the two therapies were combined.ConclusionsThe mechanism of oxaliplatin-resistant cell secondary multidrug resistance was correlated with the variation of cell cycle distribution, extension of doubling time and upregulation of P-gp expression. The synergistic effect of CIK in combination with L-OHP on killing activity against oxaliplatin-resistant cells was shown in vivo and in vitro.
Are probiotics a feasible intervention for prevention of diarrhoea in the developing world?
Authors: Hajela Neerja , Nair Gopinath B , Ganguly Nirmal K 
Published: August 2010

Abstract
With more than 1.4 million of the 9 million child deaths being attributed to diarrhoea in 2008 and 49% of them occurring in five countries namely, India, Nigeria, Democratic Republic of the Congo, Pakistan and China, there is an urgent need for intervention to prevent and control diarrhoeal diseases. Of the various interventions, probiotics offer immense potential. The past decade has witnessed the validation of their utility for the prevention, treatment and management of a variety of infective and non infective disorders. The most investigated field continues to remain infectious diarrhoea and compelling evidence comes from randomized placebo controlled trials. While results from these studies are encouraging most of them reflect the outcomes of the developed world. Developing countries like India continue to struggle with nutritional and health challenges and bear the greatest burden of diarrhoea. A paucity of data from the developing countries limits the definite recommendation of probiotics. In these countries curd, often confused for a probiotic, is practiced as an integral part of the culture. While the nutritional benefits of these products cannot be understated, it is still uncertain whether these products can be classified as a probiotic. The emergence of probiotic foods which are scientifically validated for their efficacy and impart defined health benefits offer an excellent opportunity to improve public health. A recent randomized controlled trial conducted by the National Institute of Cholera and Enteric Diseases in Kolkata, India demonstrated a protective efficacy of 14% in preventing diarrhoea among children who received a probiotic. For the developing world however the vision for probiotics would mean a fundamental change in perception and developing a well planned strategy to allow interventions like probiotics to permeate to impoverished settings, where the assault of micro organisms is on a daily basis. This would mean that probiotics are ingrained into the public health system without being seen as a medicine.
Testing for illicit drug use in mental health services
Authors: Abraham Abu , Luty Jason 
Published: August 2010

SummaryTesting for illicit drug use is used in pre-employment checks, the criminal justice system, sports medicine and for screening and confirmatory purposes in patients with physical and mental illnesses. The types of drugs tested for and the methods used vary depending on the indication. This article focuses primarily on blood, urine and oral fluids, which are specimens more commonly used in mental health settings, although hair and sweat are increasingly used in medico-legal cases and in child protection issues. The main drugs and their metabolism are discussed to gain a better understanding of the methods used and for accurate interpretation. Methods to ensure validity during sample collection are explored. False-positive and false-negative tests are common and possible confounders are discussed.
Efficacy of antidepressants in treating the negative symptoms of chronic schizophrenia: meta-analysis
Authors: Singh Surendra P. , Singh Vidhi , Kar Nilamadhab , Chan Kelvin 
Published: August 2010

BackgroundTreatment of negative symptoms in chronic schizophrenia continues to be a major clinical issue.AimsTo analyse the efficacy of add-on antidepressants for the treatment of negative symptoms of chronic schizophrenia.MethodSystematic review and meta-analysis of randomised controlled trials comparing the effect of antidepressants and placebo on the negative symptoms of chronic schizophrenia, measured through standardised rating scales. Outcome was measured as standardised mean difference between end-of-trial and baseline scores of negative symptoms.ResultsThere were 23 trials from 22 publications (n = 819). The antidepressants involved were selective serotonin reuptake inhibitors, mirtazapine, reboxetine, mianserin, trazodone and ritanserin; trials on other antidepressants were not available. The overall standardised mean difference was moderate (–0.48) in favour of antidepressants and subgroup analysis revealed significant responses for fluoxetine, trazodone and ritanserin.ConclusionsAntidepressants along with antipsychotics are more effective in treating the negative symptoms of schizophrenia than antipsychotics alone.
Psychotic symptoms in the general population – an evolutionary perspective
Authors: Kelleher Ian , Jenner Jack A. , Cannon Mary 
Published: August 2010

SummaryOur ideas about the intrinsically pathological nature of hallucinations and delusions are being challenged by findings from epidemiology, neuroimaging and clinical research. Population-based studies using both self-report and interview surveys show that the prevalence of psychotic symptoms is far greater than had been previously considered, prompting us to re-evaluate these psychotic symptoms and their meaning in an evolutionary context. This non-clinical phenotype may hold the key to understanding the persistence of psychosis in the population. From a neuroscientific point of view, detailed investigation of the non-clinical psychosis phenotype should provide novel leads for research into the aetiology, nosology and treatment of psychosis.
Awareness of the cost of psychotropic medication among doctors: a service evaluation
Authors: Singh Dhananjay Kumar , Khawaja Shakil , Pala Ishaq , Khaja Jaleel , Krishnanu Ray , Walker Heather , Bustin Julian 
Published: August 2010

Aims and methodCost-effective prescribing is an increasingly important aspect of our practice. A service evaluation was carried out to assess the level of awareness and knowledge of different aspects of cost-effective prescribing among doctors working in the North East London Foundation Trust. A semi-structured questionnaire was used to benchmark knowledge against six standards.ResultsThe survey was completed by 71% of doctors working in adult or old age psychiatry. A total of 2% of doctors stated that they should always take into consideration the price of the drug when prescribing and only 5% of doctors claimed to know the price of medications they prescribe most frequently.Clinical implicationsStrategies to improve the poor level of knowledge and awareness in this area of clinical practice would be of benefit in making the best use of limited financial resources without any detriment to patient care.
Thinking about cost – undermining trust
Authors: Oyebode Femi 
Published: August 2010

SummaryThis commentary argues that decisions about the distribution of resources in a healthcare system paid out of taxation such as the NHS is best dealt with at arm's length from the doctor-patient encounter within the clinic. Thus, the role of the National Institute of Health and Clinical Excellent (NICE) that is to take a population perspective is appropriate, whereas any attempt by individual doctors to be influenced by costs and to base their judgements on the relative costs of interventions is likely to undermine the trust that exists within the doctor-patient relationship.
Multivitamin Use Is Not Associated With Cancer Recurrence or Survival in Patients With Stage III Colon Cancer: Findings From CALGB 89803
Authors: Ng Kimmie , Meyerhardt Jeffrey A. , Chan Jennifer A. , Niedzwiecki Donna , Hollis Donna R. , Saltz Leonard B. , Mayer Robert J. , Benson Al B. , Schaefer Paul L. , Whittom Renaud , Hantel Alexander , Goldberg Richard M. , Fuchs Charles S. 
Published: August 2010

Purpose Multivitamin use is widespread in the United States, especially among patients with cancer. However, the influence of multivitamin supplementation on cancer recurrence and death after a curative resection of colon cancer is unknown. Patients and Methods We conducted a prospective, observational study of 1,038 patients with stage III colon cancer enrolled in a randomized adjuvant chemotherapy trial. Patients reported on multivitamin use during and 6 months after adjuvant chemotherapy. Patients were observed until March 2009 for disease recurrence and death. To minimize bias by occult recurrence, we excluded patients who recurred or died within 90 days of their multivitamin assessment. Results Among 1,038 patients, 518 (49.9%) reported multivitamin use during adjuvant chemotherapy. Compared with nonusers, the multivariate hazard ratio (HR) for disease-free survival was 0.94 (95% CI, 0.77 to 1.15) for patients who used multivitamins. Similarly, multivitamin use during adjuvant chemotherapy was not significantly associated with recurrence-free survival (multivariate HR, 0.93; 95% CI, 0.75 to 1.15) or overall survival (multivariate HR 0.92; 95% CI, 0.74 to 1.16). Multivitamin use reported 6 months after completion of adjuvant chemotherapy was also not associated with improved patient outcome, and consistent use both during and following adjuvant therapy conferred no benefit. Neither an increasing number of tablets nor increasing duration of use before cancer diagnosis was associated with cancer recurrence or mortality. Multivitamin use also did not improve the rates of grade 3 and higher GI toxicity. Conclusion Multivitamin use during and after adjuvant chemotherapy was not significantly associated with improved outcomes in patients with stage III colon cancer.
Anaemia and Long Term Mortality in Heart Failure Patients: A Retrospective Study
Authors: Charlot Mette , Torp-Pedersen Christian , Valeur Nana , Seibæk Marie , Weeke Peter , Køber Lars 
Published: August 2010

Background:
Anaemia has been demonstrated as a risk factor in patients with heart failure over periods of a few years, but long term data are not available. We examined the long-term risk of anaemia in heart failure patients during 15 years of follow-up.

Methods:
We evaluated survival data for 1518 patients with heart failure randomized into the Danish Investigations of Arrhythmia and Mortality on Dofetilide (DIAMOND) trial. The follow-up time was from 13 to 15 years. After 15 years 11.5% of the patients were still alive.

Results:
Anaemia was present in 34% of the patients. 264 (17%) had mild, 152 (10%) had moderate and 98 (7%) had severe anaemia. Hazard ratio of death for patients with mild anaemia compared with patients with no anaemia was 1.27 (1.11-1.45, p<0.001), for moderate anaemia 1.48 (1.24-1.77, p<0.001) and for severe anaemia 1.82 (1.47-2.24, p<0.001), respectively. In multivariable analyses anaemia was still associated with increased mortality with hazard ratios of 1.19 (1.04–1.37, p=0.014) for mild anaemia, 1.23 (1.03–1.48, p=0.024) for moderate anaemia and 1.33 (1.07–1.66, p=0.010) for severe anaemia, respectively. In landmark analysis the increased mortality for mild anaemia was only significant during the first 2 years, while moderate anaemia remained significant for at least 5 years. There were too few patients left with severe anaemia after 5 years to evaluate the importance on mortality beyond this time.

Conclusion:
Anaemia at the time of diagnosis of heart failure is an independent factor for mortality during the following years but loses its influence on mortality over time.
Diabetic Neuropathy
Authors: Gibbons Christopher H. , Freeman Roy , Veves Aristidis 
Published: August 2010

OBJECTIVE
To determine the relationships among large, small, and autonomic fiber neurophysiological measures in a cross-sectional study of patients with diabetes.

RESEARCH DESIGN AND METHODS
We assessed 130 individuals: 25 healthy subjects and 105 subjects with diabetes. Subjects were classified by the presence or absence of neuropathy by physical examination. All subjects underwent autonomic testing, nerve conduction studies, quantitative sensory testing, and nerve-axon reflex vasodilation in addition to quantifiable neurological examination and symptom scores. Correlation and cluster analysis were used to determine relationships between and among different neurophysiological testing parameters.

RESULTS
Results of neurophysiological tests were abnormal in patients with clinical evidence of diabetic neuropathy compared with results in healthy control subjects and in those without neuropathy (P &lt; 0.01, all tests). The correlations among individual tests varied widely, both within (r range &lt;0.5–&gt;0.9, NS to &lt;0.001) and between test groups (r range &lt;0.2–&gt;0.5, NS to &lt;0.01). A two-step hierarchical cluster analysis revealed that neurophysiological tests do not aggregate by typical “small,” “large,” or “autonomic” nerve fiber subtypes.

CONCLUSIONS
The modest correlation coefficients seen between the different testing modalities suggest that these techniques measure different neurophysiological parameters and are therefore not interchangeable. However, the data suggest that only a small number of neurophysiological tests are actually required to clinically differentiate individuals with neuropathy from those without. The natural clustering of both patients and healthy control subjects suggests that variations in the population will need to be considered in future studies of diabetic neuropathy.
Racial/Ethnic Differences in Association of Fasting Glucose–Associated Genomic Loci With Fasting Glucose, HOMA-B, and Impaired Fasting Glucose in the U.S. Adult Population
Authors: Yang Quanhe , Liu Tiebin , Shrader Peter , Yesupriya Ajay , Chang Man-huei , Dowling Nicole F. , Ned Renée M. , Dupuis Josée , Florez Jose C. , Khoury Muin J. , Meigs James B. ,   the MAGIC Investigators
Published: August 2010

OBJECTIVE
To estimate allele frequencies and the marginal and combined effects of novel fasting glucose (FG)-associated single nucleotide polymorphisms (SNPs) on FG levels and on risk of impaired FG (IFG) among non-Hispanic white, non-Hispanic black, and Mexican Americans.

RESEARCH DESIGN AND METHODS
DNA samples from 3,024 adult fasting participants in the National Health and Nutrition Examination Survey (NHANES) III (1991–1994) were genotyped for 16 novel FG-associated SNPs in multiple genes. We determined the allele frequencies and influence of these SNPs alone and in a weighted genetic risk score on FG, homeostasis model assessment of β-cell function (HOMA-B), and IFG by race/ethnicity, while adjusting for age and sex.

RESULTS
All allele frequencies varied significantly by race/ethnicity. A weighted genetic risk score, based on 16 SNPs, was associated with a 0.022 mmol/l (95% CI 0.009–0.035), 0.036 mmol/l (0.019–0.052), and 0.033 mmol/l (0.020–0.046) increase in FG levels per risk allele among non-Hispanic whites, non-Hispanic blacks, and Mexican Americans, respectively. Adjusted odds ratios for IFG were 1.78 for non-Hispanic whites (95% CI 1.00–3.17), 2.40 for non-Hispanic blacks (1.07–5.37), and 2.39 for Mexican Americans (1.37–4.14) when we compared the highest with the lowest quintiles of genetic risk score (P = 0.365 for testing heterogeneity of effect across race/ethnicity).

CONCLUSIONS
We conclude that allele frequencies of 16 novel FG-associated SNPs vary significantly by race/ethnicity, but the influence of these SNPs on FG levels, HOMA-B, and IFG were generally consistent across all racial/ethnic groups.