Miracle-dz/UniFAR-FTUs huggingface dataset:
Chronic Hemodialysis Patients Without Marked Elevation of Intact Parathyroid Hormone Are Also Good Candidates for Early Intervention With Cinacalcet

Management of calcium (Ca) and phosphorus (P) metabolism is crucial in chronic hemodialysis (HD) patients. Cinacalcet is usually used for chronic kidney disease‐mineral and bone disorders (CKD‐MBD) patients with elevated intact parathyroid hormone (iPTH) levels. However, a certain number of CKD‐MBD patients have normal iPTH levels and are not subjected to cinacalcet therapy. Here, we evaluated the efficacy of a new treatment algorithm of early initiation of cinacalcet therapy in this subgroup of patients, mainly for correcting Ca and P metabolism. Seventy‐one HD patients, including 44 patients without marked elevation of iPTH (102 < iPTH ≤ 300 pg/mL), who received cinacalcet therapy, were enrolled in this study. Serum parameters relating to CKD‐MBD patient metabolism, doses of phosphate binders, and type of vitamin D sterols were compared between pre‐ and post‐cinacalcet administration retrospectively. Sixty‐four of 71 patients did not require discontinuation of cinacalcet. In these 64 patients, serum Ca (P = 0.0003), P (P = 0.0153), and iPTH (P < 0.0001) levels were significantly reduced after cinacalcet administration, even in those without marked elevation of iPTH (Ca; P < 0.0001, P; P = 0.0422, and iPTH; P = 0.0018). The proportion of patients who received vitamin D sterols was unchanged (P = 0.5930) but the proportion of patients who received maxacalcitol was significantly reduced after cinacalcet administration (P = 0.0108). The new treatment algorithm of early initiation of cinacalcet is considered to be well tolerated and effective for controlling hypercalcemia, and/or hyperphosphatemia and/or increased iPTH of CKD‐MBD patients.
ATF6 Activated by Proteolysis Binds in the Presence of NF-Y (CBF) Directly to the cis-Acting Element Responsible for the Mammalian Unfolded Protein Response

ABSTRACT Transcription of genes encoding molecular chaperones and folding enzymes in the endoplasmic reticulum (ER) is induced by accumulation of unfolded proteins in the ER. This intracellular signaling, known as the unfolded protein response (UPR), is mediated by thecis-acting ER stress response element (ERSE) in mammals. In addition to ER chaperones, the mammalian transcription factor CHOP (also called GADD153) is induced by ER stress. We report here that the transcription factor XBP-1 (also called TREB5) is also induced by ER stress and that induction of CHOP and XBP-1 is mediated by ERSE. The ERSE consensus sequence is CCAAT-N9-CCACG. As the general transcription factor NF-Y (also known as CBF) binds to CCAAT, CCACG is considered to provide specificity in the mammalian UPR. We recently found that the basic leucine zipper protein ATF6 isolated as a CCACG-binding protein is synthesized as a transmembrane protein in the ER, and ER stress-induced proteolysis produces a soluble form of ATF6 that translocates into the nucleus. We report here that overexpression of soluble ATF6 activates transcription of the CHOP and XBP-1 genes as well as of ER chaperone genes constitutively, whereas overexpression of a dominant negative mutant of ATF6 blocks the induction by ER stress. Furthermore, we demonstrated that soluble ATF6 binds directly to CCACG only when CCAAT exactly 9 bp upstream of CCACG is bound to NF-Y. Based on these and other findings, we concluded that specific and direct interactions between ATF6 and ERSE are critical for transcriptional induction not only of ER chaperones but also of CHOP and XBP-1.
Motor neurons in onuf's nucleus and its rat homologues express the p75 nerve growth factor receptor: Sexual dimorphism and regulation by axotomy

The present study establishes that populations of neurons in the lumbosacral cord, which innervate pelvic striated muscles, express p75NGFR throughout their life spans. These neuronal groups comprise the Onuf's nucleus in humans and its principal rat homologues, dorsolateral (DL) and dorsomedial (DM) nuclei, as well as the cremasteric (CRE) nucleus. The p75NGFR in these neurons is localized in the rough endoplasmic reticulum, Golgi complex, and lysosomes. Almost all neurons that project to striated perineal muscles in the male rat express p75NGFR; very low levels of p75NGFR are detected in neurons that innervate perineal sphincters of the female. In the female rat, p75NGFR expression is masculinized with perinatal androgen treatment. In addition, the expression of p75NGFR in DM and DL neurons in the adult is up‐regulated by injury (i. e., pudendal axotomy) but is not influenced by gonadectomy. The results of this study establish that neurons of Onuf s nucleus and its rat homologues differ from general somatic motor neurons in that they express p75NGFR from early postnatal life (i. e., when all motor neurons express p75NGFR) into the adult (when the former, but not the latter, express the receptor). In view of growing evidence for the role of neurotrophins in the physiology of motor neurons, the above differentiating feature between general somatic and sexually dimorphic motor neurons suggests that p75NGFR may be involved in motor neuron plasticity and may participate in mechanisms by which neurons can protect themselves from degenerative insults. © 1994 Wiley‐Liss, Inc.
Altered phenotypes associated with ampD mutations in Enterobacter cloacae

A study was done to determine the genetic locus responsible for altered expression of AmpC beta-lactamase in Enterobacter cloacae 1194E and several mutants derived from E. cloacae 029. These phenotypes were defined by units of enzyme activity found in sonic extracts of cells before and after induction with cefoxitin and included (units uninduced/units induced) the wild-type (7/219), high-level constitutive (10,911/10,862), temperature-sensitive (at 30 degrees C 82/706 and at 42 degrees C 5,031/6,020), and hyperinducible (19/1,688) phenotypes. When the ampD region of each E. cloacae strain was cloned and introduced into an ampD mutant Escherichia coli strain, the altered phenotypes were found to reside within this locus. Furthermore, transformants containing wild-type ampD were poorly inducible at 42 degrees C while those with high-level constitutive or hyperinducible ampD were unaffected by temperature. Since the source of ampD was the only variable in these E. coli transformants, these results suggested that ampD encodes a protein that is involved in sensing the inducer. To test this possibility, the responses to different inducers of E. coli transformants containing various ampD regions were assessed. In the presence of wild-type ampD, transformants responded equally to cefoxitin and cefotetan, regardless of temperature. In the presence of temperature-sensitive ampD, induction by cefotetan was similar to that by cefoxitin at 30 degrees C but greater than that by cefoxitin at 42 degrees C. These results suggest that ampD encodes a protein involved in induction of AmpC beta-lactamase in E. cloacae.
Role of melatonin on electromagnetic radiation-induced oxidative stress and Ca2+ signaling molecular pathways in breast cancer

Aims: Exposure to electromagnetic radiation (EMR) may increase breast cancer risk by inducing oxidative stress and suppressing the production of melatonin. Aim of the present review is to discuss the mechanisms and risk factors of EMR and oxidative stress-induced breast cancer, to summarize the controlled studies evaluating measures for prevention, and to conclude with evidence-based strategies for prevention. Materials: Review of the relevant literature and results from our recent basic studies, as well as critical analyses of published systematic reviews were obtained from the Pubmed and the Science Citation Index. Results: It has been proposed that chronic exposure to EMR may increase the risk of breast cancer by suppressing the production of melatonin; this suppression may affect the development of breast cancer either by increasing levels of circulation of estrogen or through over production of free oxygen radicals. Most epidemiological studies have also indicated overall effect of EMR exposure in premenopausal women, particularly for estrogen receptor positive breast tumors. Enhanced voltage-dependent Ca2+ current and impaired inhibitory G-protein function, and derangement of intracellular organelles with a Ca2+ buffering effect, such as endoplasmic reticulum and mitochondria have been also shown to contribute to disturbed Ca2+ signaling in breast cancer. Conclusion: Melatonin may modulate breast cancer through modulation of enhanced oxidative stress and Ca2+ influx in cell lines. However, there is not enough evidence on increased risk of breast cancer related to EMR exposure.
The relationship of Helicobacter pylori infection and colon neoplasia, on the basis of meta-analysis

Background Helicobacter pylori is an important causative factor in gastric carcinogenesis. However, its role in extragastric gastrointestinal malignancies, such as colon neoplasia, is controversial. Aim The aim of this study was to explore the relationship of H. pylori infection with colon neoplasia by meta-analysis of all relevant studies. Materials and methods Pooled estimates were obtained using fixed or random-effects models as appropriate. Heterogeneity between studies was evaluated using the Cochran Q-test, whereas the likelihood of publication bias was assessed by constructing funnel plots. Results Among 238 potentially relevant studies, 210 were rejected as unsuitable and 28 studies were finally eligible for meta-analysis, including a total of 33 sets of data (17 on colon cancer and 16 on colon polyps). There was evidence of heterogeneity (I2=57.37%); thus, the random-effects model of meta-analysis was chosen, showing pooled odds ratio (OR) equal to 1.41 [95% confidence interval 1.24–1.60, P=0.000]. The subgroup meta-analyses showed a significant relationship between H. pylori and colon cancer as well as colon polyps [OR 1.3 (1.07–1.59), P=0.01 and OR 1.5 (1.26–1.79), P=0.000, respectively]. Conclusion The results of this meta-analysis showed a modest statistically significant relationship of H. pylori infection with both colon cancer and polyps.
Importance of enteric adenoviruses 40 and 41 in acute gastroenteritis in infants and young children

In a prospective 1-year study of acute infantile gastroenteritis, adenoviruses were detected in the stools or by seroconversions, or both, in 56 of 416 (13.5%) ill children. By use of DNA restriction enzyme analysis, enzyme immunoassay, and culture techniques, 33 of 56 (59%) adenovirus specimens were identified as enteric adenoviruses 40 and 41 (Ad40 and Ad41). They were found as the sole recognizable cause of diarrhea in 30 of 416 (7.2%) ill children and in 0 of 200 controls. Three additional ill children had enteric adenoviruses as a part of a dual infection. Evidence for established adenoviruses (Ad1 through Ad39) in gastroenteritis was found in 15 of 416 (3.6%) ill children but also in 3 of 200 (1.5%) controls. Eight adenovirus specimens remained untyped. Seroconversions were demonstrated in 17 of 18 (94%) paired serum samples from patients shedding enteric adenoviruses. The predominant symptom of infections with enteric adenoviruses was diarrhea, with a mean duration of 8.6 days (Ad40) and 12.2 days (Ad41). One-third of the children with Ad41 infections had prolonged symptoms (greater than or equal to 14 days). The frequency of respiratory symptoms was low (21%). The established adenoviruses presented a different clinical picture, characterized by diarrhea of shorter duration, higher fever, and significantly increased occurrence of respiratory symptoms (79%). In conclusion, enteric adenoviruses appear to be an important cause of acute infantile gastroenteritis, second only to rotaviruses in this study.
Prevalence and factors associated with it, of birds dead on arrival at the slaughterhouse and other rejection conditions in broiler chickens

1. Standardised data on husbandry were recorded for a flock of birds in one house on each of 150 broiler farms in the UK during the 4 d prior to slaughter. 2. For each flock, the incidence of birds found dead on arrival (DoAs) and the Meat Hygiene Service carcase rejection records were recorded at the slaughterhouse. 3. The mean percentage of birds in each flock found DoA was 0·12% (range 0–0·64%) and the mean percentage of Total Carcase Rejects (TCRs) for each flock was 1·23% (range 0·07–5·51%). 4. A general linear model was developed to examine factors associated with flock percentage DoAs. Assuming a linear relationship, all other factors remaining the same, a one percentage point (PP) increase in small/emaciated birds will result in a 0·155 PP increase in DoAs and a 1 PP increase in wheat in diet 4 will result in a 0·003 PP decrease. An increase by one in the total number of vaccines administered will cause a 0·029 PP decrease in DoAs, a 1 g increase in live weight at slaughter will be associated with a 0·000043 PP increase and a 1 PP increase in mortality on farm would be associated with a 0·000044 PP increase. A 1 PP increase in Ross birds decreases DoAs by 0·0004 PPS: there is also a seasonal effect. 5. The model developed for flock percentage TCRs found that a 1 PP increase in wheat in diet 3 will result in a 0·052 PP decrease in TCRs and a 1 PP increase in Ross birds will cause a 0·009 PP decrease. A 1 PP increase in birds culled on farm will be associated with a 0·03 PP increase in TCRs and the diagnosis of disease during the flock cycle increases TCRs by 0·397 PPs. A one day increase in age at slaughter will result in a 0·046 PP increase in TCRs.
Mandatory versus Voluntary Consent for Newborn Screening?

Virtually every infant in the United States undergoes a heel stick within the first week of life to test for a variety of metabolic, endocrine, and hematological conditions as part of state-run universal newborn screening (NBS) programs. The history of this mandatory public health program is examined, as well as whether the policy was morally justifiable. Three changes in NBS practice necessitate a re-evaluation of the mandatory nature of NBS. First is the adoption of NBS for hemoglobinopathies in the 1980s that led to the identification of many sickle cell carriers and carriers of other hemoglobin variants. In all other contexts, carrier testing requires consent, and there is no moral rationale why NBS ought to be exceptional. Second is the application of tandem mass spectrometry (MS/MS) to NBS in the 1990s that led to the identification of many metabolic conditions and variants, some of which were not treatable and others of which had unknown clinical relevance. To the extent that the conditions do not need emergent diagnosis and treatment, there is less justification for mandatory screening. Third, there is great interest in using residual blood spots for research, and the cornerstone of research ethics is the voluntary consent of the participant (or his or her proxy). These three changes support revising mandatory NBS with a tiered consent process to best balance respect for parental autonomy and the promotion of children’s health.
Effects on alcohol related fatal crashes of a community based initiative to increase substance abuse treatment and reduce alcohol availability

Objective: This analysis tested whether comprehensive community interventions that focus on reducing alcohol availability and increasing substance abuse treatment can reduce alcohol related fatal traffic crashes. Intervention: Five of 14 communities awarded Fighting Back grants by The Robert Wood Johnson Foundation to reduce substance abuse and related problems attempted to reduce availability of alcohol and expand substance abuse treatment programs (FBAT communities). Program implementation began on 1 January 1992. Design: A quasi-experimental design matched each program community to two or three other communities of similar demographic composition in the same state. Main outcome measures: The ratio of fatal crashes involving a driver or pedestrian with a blood alcohol concentration of 0.01% or higher, 0.08% or higher, or 0.15% or higher were examined relative to fatal crashes where no alcohol was involved for 10 years preceding and 10 years following program initiation. Results: Relative to their comparison communities, the five FBAT communities experienced significant declines of 22% in alcohol related fatal crashes at 0.01% BAC or higher, 20% at 0.08% or higher, and 17% at 0.15% or higher relative to fatal crashes not involving alcohol. Conclusions: Community interventions to reduce alcohol availability and increase substance abuse treatment can reduce alcohol related fatal traffic crashes.
Association between chronic obstructive pulmonary disease and lung cancer: the missing link.

OBJECTIVE This review focuses on current knowledge of specific processes that drive chronic airway inflammation which are important in the pathogenesis of both chronic obstructive pulmonary disease (COPD) and lung cancer. DATA SOURCES The data used in this review were obtained mainly from studies reported in the PubMed database (1997 - 2012) using the terms of COPD and lung cancer. STUDY SELECTION Data from published articles about prevalence of COPD-lung cancer overlap and mechanism involved in lung cancer development in COPD were identified, retrieved and reviewed. RESULTS COPD prevalence, morbidity and mortality vary and are directly related to the prevalence of tobacco smoking except in developing countries where air pollution resulting from the burning of biomass fuels is also important. COPD is characterized by a chronic inflammation of lower airway and, importantly, the presence of COPD increases the risk of lung cancer up to 4.5 fold among long-term smokers. COPD is by far the greatest risk factor for lung cancer amongst smokers and is found in 50% - 90% of patients with lung cancer. CONCLUSIONS Both COPD and lung cancer are tobacco smoking-associated chronic diseases that cluster in families and aggravate with age, and 50% - 70% of patients diagnosed with lung cancer have declined spirometric evidence of COPD. Understanding and targeting common pathogenic mechanisms for lung cancer and COPD would have potential diagnostic and therapeutic implications for patients with these lung diseases and for people at risk.
Biochemical identification of new species and biogroups of Enterobacteriaceae isolated from clinical specimens

In 1972 there were only 11 genera and 26 species in the family Enterobacteriaceae. Today there are 22 genera, 69 species, and 29 biogroups or Enteric Groups. This paper is a review of all of the new organisms. It has a series of differential charts to assist in identification and a large chart with the reactions of 98 different organisms for 47 tests often used in identification. A simplified version of this chart gives the most common species and tests most often used for identification. The sources of the new organisms are listed, and their role in human disease is discussed. Fourteen new groups of Enterobacteriaceae are described for the first time. These new groups are biochemically distinct from previously described species, biogroups, and Enteric Groups of Enterobacteriaceae. The new groups are Citrobacter amalonaticus biogroup 1, Klebsiella group 47 (indole positive, ornithine positive), Serratia marcescens biogroup 1, and unclassified Enteric Groups 17, 45, 57, 58, 59, 60, 63, 64, 68, and 69.
Greater increase in urinary hepcidin predicts protection from acute kidney injury after cardiopulmonary bypass.

BACKGROUND Acute kidney injury (AKI) is a common and serious complication of cardiopulmonary bypass (CPB) surgery. Hepcidin, a peptide hormone that regulates iron homeostasis, is a potential biomarker of AKI following CPB. METHODS We investigated the association between post-operative changes in serum and urinary hepcidin and AKI in 93 patients undergoing CPB. RESULTS Twenty-five patients developed AKI based on the Risk, Injury, Failure, Loss, End-stage kidney disease (RIFLE) criteria in the first 5 days. Serum hepcidin, urine hepcidin concentration, the urinary hepcidin:creatinine ratio and fractional excretion of hepcidin in urine rose significantly after surgery. However, urine hepcidin concentration and urinary hepcidin:creatinine ratio were significantly lower at 24 h in patients with RIFLE-Risk, Injury or Failure compared to those without AKI (P = 0.0009 and P < 0.0001, respectively). Receiver operator characteristic analysis showed that lower 24-h urine hepcidin concentration and urinary hepcidin:creatinine ratio were sensitive and specific predictors of AKI. The urinary hepcidin:creatinine ratio had an area under the curve for the diagnosis of RIFLE ≥ risk at 24 h of 0.77 and of 0.84 for RIFLE ≥ injury. Urinary hepcidin had similar predictive accuracy. Such predictive ability remained when patients with early creatinine increases were excluded. CONCLUSIONS Urinary hepcidin and hepcidin:creatinine ratio are biomarkers of AKI after CPB, with an inverse association between its increase at 24 h and risk of AKI in the first five post-operative days. Measuring hepcidin in the urine on the first day following surgery may deliver earlier diagnosis and interventions.
Eating Habits and Appetite Control in the Elderly: The Anorexia of Aging

Although a high prevalence of overweight is present in elderly people, the main concern in the elderly is the reported decline in food intake and the loss of the motivation to eat. This suggests the presence of problems associated with the regulation of energy balance and the control of food intake. A reduced energy intake causing body weight loss may be caused by social or physiological factors, or a combination of both. Poverty, loneliness, and social isolation are the predominant social factors that contribute to decreased food intake in the elderly. Depression, often associated with loss or deterioration of social networks, is a common psychological problem in the elderly and a significant cause of loss of appetite. The reduction in food intake may be due to the reduced drive to eat (hunger) resulting from a lower need state, or it arises because of more rapidly acting or more potent inhibitory (satiety) signals. The early satiation appears to be predominantly due to a decrease in adaptive relaxation of the stomach fundus resulting in early antral filling, while increased levels and effectiveness of cholecystokinin play a role in the anorexia of aging. The central feeding drive (both the opioid and the neuropeptide Y effects) appears to decline with age. Physical factors such as poor dentition and ill-fitting dentures or age-associated changes in taste and smell may influence food choice and limit the type and quantity of food eaten in older people. Common medical conditions in the elderly such as gastrointestinal disease, malabsorption syndromes, acute and chronic infections, and hypermetabolism often cause anorexia, micronutrient deficiencies, and increased energy and protein requirements. Furthermore, the elderly are major users of prescription medications, a number of which can cause malabsorption of nutrients, gastrointestinal symptoms, and loss of appetite. There is now good evidence that, although age-related reduction in energy intake is largely a physiologic effect of healthy aging, it may predispose to the harmful anorectic effects of psychological, social, and physical problems that become increasingly frequent with aging. Poor nutritional status has been implicated in the development and progression of chronic diseases commonly affecting the elderly. Protein-energy malnutrition is associated with impaired muscle function, decreased bone mass, immune dysfunction, anemia, reduced cognitive function, poor wound healing, delayed recovery from surgery, and ultimately increased morbidity and mortality. An increasing understanding of the factors that contribute to poor nutrition in the elderly should enable the development of appropriate preventive and treatment strategies and improve the health of older people.