Miracle-dz/UniFAR-FTUs huggingface dataset:
Effectiveness of Salmon Calcitonin Nasal Spray in the Treatment of Lumbar Canal Stenosis: A Double-Blind, Randomized, Placebo-Controlled, Parallel Group Trial

Study Design. Double-blind, randomized, placebo-controlled study to assess the effectiveness of calcitonin nasal spray on symptoms and function in patients with lumbar canal stenosis. Objective. To compare effectiveness of calcitonin administered by nasal spray with placebo in patients with clinically symptomatic lumbar canal stenosis. Summary of Background Data. Lumbar canal stenosis is the most common reason for spine surgery in individuals over 65 years of age. Nonoperative approaches have been not well studied and limited primarily to physical therapy exercises. Several small trials in the past have suggested that subcutaneous and intramuscular calcitonin is an effective nonsurgical option in treating the symptoms of spinal stenosis patients. Only three trials were randomized and placebo-controlled. Methods. Fifty-five patients with clinical lumbar canal stenosis (pseudoclaudication), confirmatory MR imaging, and pain intensity index (VAS) of ≥6 were randomized to either placebo or intranasal calcitonin daily for 6 weeks, followed by an open label 6-week extension, during which all patients received active drug. Outcome parameters performed at baseline, 6 weeks, and 12 weeks, included pain intensity index, walking time and distance to pain, SF-36, and Oswestry disability index. Results. Thirty-six patients received calcitonin, and 19 placebo. Eight (14.54%) calcitonin and 4 (7.27%) placebo patients withdrew from the study. The mean baseline pain score for calcitonin group was 7.8 and 7.5 for placebo. Comparisons at week 6 showed no statistically significant difference in the change in pain intensity (VAS) between calcitonin group (−2.9) and placebo (−2.4) (P = 0.4382) from baseline. There was no significant difference in walking time to pain (calcitonin −10.0 seconds; placebo +32.2 seconds; P = 0.5136). Walking distance to pain showed a mean improvement of +91.4 ft in the calcitonin group and +254.7 ft in the placebo group (P = 0.4948). Nosignificant difference was observed in the SF-36 score between the treatment groups. Using a threshold of at least 50% reduction in pain from baseline to 6 weeks, 12 of 29 (41.37%) of calcitonin patients were considered responders versus 7 of 18 (38.88%) of placebo patients (P = 0.4238) Conclusions. In this first ever largest randomized placebo-controlled parallel group trial of nasal calcitonin in spinal stenosis, nasal calcitonin was not superior to placebo in treating the symptoms of spinal stenosis at 6 weeks. Based on this study, nasal calcitonin does not appear to have a role in nonoperative treatment of lumbar canal stenosis.
Private Intergenerational Transfers, Family Structure, and Health in a sub-Saharan African Context.

CFP acknowledges funding from the David E. Bell fellowship and the ANU Futures Scheme. Funding for the MLSFH has been provided by the NICHD (grants R01 HD053781, R01 HD/MH041713, R01 HD37276, R01 HD044228, R21 HD050652, R03 HD058976, R21 HD071471, R01 HD087391), and the Swiss Programme for Research on Global Issues for Development (SNF r4d grant 400640_160374). The MLSFH also acknowledges support through pilot grants from the Population Studies Center (PSC), Population Aging Research Center (PARC), the Boettner Center for Pensions and Retirement Security, the Institute on Aging, and the Center for AIDS Research (CFAR), all at the University of Pennsylvania, and supported by NIH grants NICHD R24 HD044964, NIA P30 AG12836, NIAID AI 045008. NICHD R01HD053781 and R01 HD087391 are the only grants that provided direct support for the writing of this manuscript.
DNA prime/protein boost vaccine strategy in neonatal macaques against simian human immunodeficiency virus

Newborn macaques were vaccinated against a chimeric simian human immunodeficiency (SHIV) virus, SHIV‐vpu+, by DNA priming and boosting with homologous HIV‐1 gp160. Following SHIV‐vpu+ challenge, containment of infection was observed in 4 of 15 animals given DNA priming/protein boost vaccination and in three of four animals given gp160 boosts only. Rechallenge with homologous virus of six animals that contained the first challenge virus resulted in rapid viral clearance or low viral loads. Upon additional rechallenge with heterologous, pathogenic SHIV89.6P, four of these six animals maintained normal CD4+ T‐cell counts with no or limited SHIV89.6P infection. Our data suggest that humoral and cellular immune mechanisms may have contributed to the containment of SHIV89.6P; however, viral interference with SHIV‐vpu+ could also have played a role. Our results indicate that immunogenicity and efficacy of candidate AIDS vaccines are not affected when vaccination is initiated during infancy as compared with later in life.
A modelling approach to estimate the sensitivity of pooled faecal samples for isolation of Salmonella in pigs

The objective of this study was to develop and parametrize a mathematical model of the sensitivity of pooled sampling of faeces to detect Salmonella infection in pigs. A mathematical model was developed to represent the effect of pooling on the probability of Salmonella isolation. Parameters for the model were estimated using data obtained by collecting 50 faecal samples from each of two pig farms. Each sample was tested for Salmonella at individual sample weights of 0.1, 0.5, 1, 10 and 25 g and pools of 5, 10 and 20 samples were created from the individual samples. The highest test sensitivity for individual samples was found at 10 g (90% sensitivity), with the 25 g test sensitivity equal to 83%. For samples of less than 10 g, sensitivity was found to reduce with sample weight. Incubation for 48 h was found to produce a more sensitive test than incubation for 24 h. Model results found increasing sensitivity with more samples in the pool, with the pools of 5, 10 and 20 being more sensitive than individual sampling, and the pools of 20 being the most sensitive of those considered.
Vasopressin 1a receptor partial agonism increases sodium excretion and reduces portal hypertension and ascites in cirrhotic rats

Patients and rats with cirrhosis and ascites have portal hypertension and circulatory dysfunction. Synthetic arginine vasopressin (AVP) receptor agonists able to induce systemic and mesenteric vasoconstriction have shown their usefulness in reducing portal pressure (PP) in this condition. We assessed the potential therapeutic value of a new V1a‐AVP receptor partial agonist with a preferential splanchnic vasoconstrictor effect (FE 204038) in rats with cirrhosis and ascites. The hemodynamic effects of cumulative intravenous doses of FE 204038, terlipressin, or vehicle were investigated. Mean arterial pressure and PP were continuously recorded and cardiac output and systemic vascular resistance (SVR) assessed at 30‐minute intervals for 90 minutes. Urine volume, urine osmolality, and urinary excretion of sodium and creatinine were measured in basal conditions and following twice‐daily subcutaneous doses of FE 204038 or vehicle. PP, mean arterial pressure, cardiac output, SVR, and ascites volume were also measured after 6 days. The expression of an array of vasoactive genes was assessed in the thoracic aorta and the mesenteric circulation of control rats and rats with cirrhosis and ascites. FE 204038 dose‐dependently decreased PP, did not modify mean arterial pressure, and increased SVR. The effect of the V1a‐AVP receptor partial agonist on PP was associated with an improvement in urine volume and urinary excretion of sodium during the first day of treatment. SVR was higher and cardiac output and ascites volume were lower in rats with cirrhosis and ascites treated with FE 204038. V1a‐AVP receptor expression in rats with cirrhosis and ascites was markedly enhanced in the mesenteric circulation compared to the thoracic aorta. Conclusion: FE 204038 increases sodium excretion and reduces portal hypertension and ascites in experimental cirrhosis. V1a‐AVP receptor partial agonism could be a useful pharmacological treatment in decompensated patients with cirrhosis. (Hepatology 2016;63:207–216)
Immunoregulation in onchocerciasis: predominance of Th1‐type responsiveness to low molecular weight antigens of Onchocerca volvulus in exposed individuals without microfilaridermia and clinical disease

Chronic and generalized onchocerciasis is associated with suppression of the parasite‐specific cellular responsiveness, while exposed individuals without parasitological and clinical evidence of infection (endemic normals) display prominent cellular reactivity to Onchocerca volvulus antigens (OvAg). In order to identify those parasite antigens which may account for this differential cellular responsiveness, total adult worm‐derived OvAg were fractionated by means of preparative SDS–PAGE and blot‐elution into 22 antigen fractions of continuously decreasing molecular weight. Peripheral blood mononuclear cells (PBMC) from microfilariae (mf)‐positive onchocerciasis patients (n = 18) proliferated weakly in response to all OvAg fractions. In contrast, in vitro reactivity of PBMC from endemic normals (n = 9) was depressed in response to OvAg of mol. wt 200–30 kD only, while antigens of mol. wt <30 kD induced vigorous proliferation in these individuals compared with the microfilaridermic patients (P < 0.05). Highest proliferative reactivity of cells from endemic normals was observed in response to OvAg of mol. wt 15–11 kD. Furthermore, these low mol. wt antigen fractions induced substantial production of IL‐2 and interferon‐gamma (IFN‐γ) in PBMC from endemic normals, but not in those from onchocerciasis patients. Cells from individuals of both groups secreted similar amounts of IL‐5 in response to all OvAg fractions, with highest production again being induced by low mol. wt OvAg. In contrast, PBMC from onchocerciasis patients clearly produced more IL‐10 than did cells from endemic normals. This augmented IL‐10 production by PBMC from mf‐positive individuals was not only observed after stimulation with OvAg fractions, but was measured in unstimulated control cultures as well. IFN‐γ‐specific mRNA in antigen‐stimulated PBMC from endemic normals appeared to be more prominent than in cells from onchocerciasis patients. However, mRNA transcripts of IL‐10 and IL‐13 were clearly present in patients, but were absent or inconsistently observed in endemic normals. Our results suggest that vigorous Th1‐type cellular responsiveness encountered in endemic normals is restricted to low mol. wt antigens of O. volvulus, while such reactivity will not be present in mf‐positive individuals. Furthermore, spontaneous production of high levels of IL‐10 in onchocerciasis patients is likely to suppress Th1‐type immunity, and thus may favour manifestation of chronic onchocerciasis. These traits of cellular immunity may contribute to the differential outcome of O. volvulus infection, the manifestation of clinical disease, and may also regulate the build up of acquired immunity in humans.
Expression and clinical significance of the programmed cell death 5 gene and protein in laryngeal squamous cell carcinoma

Objective To determine the expression of the gene programmed cell death 5 (PDCD5) and its protein PDCD5 in laryngeal squamous cell carcinoma and to analyse possible correlations with clinicopathological parameters. Methods PDCD5 mRNA expression was assessed using reverse transcription–polymerase chain reaction and expression of PDCD5 protein was studied using Western blot analysis and immunohistochemistry in laryngeal squamous cell carcinoma and morphologically normal para-carcinoma tissue. Results A total of 41 laryngeal squamous cell carcinoma and 29 normal para-carcinoma tissue specimens were examined. Expression of both PDCD5 mRNA and PDCD5 protein was significantly reduced in laryngeal squamous cell carcinoma compared with normal tissue. Expression was correlated with clinical stage and histological grade, but was not associated with age, sex, location of primary tumour or the presence of lymph node metastases. Conclusion The expression of PDCD5 and its protein were shown to be reduced in laryngeal squamous cell carcinoma. The functional importance of PDCD5 as a regulating agent in cell apoptosis suggests that it may play a key role in tumour pathogenesis and development.
Comprehensive proteomic and transcriptomic characterization of hepatic expression signatures affected in p14 liver conditional knockout mice

Scaffold proteins regulate intracellular MAP kinase signaling by providing critical spatial and temporal specificities. We have shown previously that the scaffold protein MEK1 partner (MP1) is localized to late endosomes by the adaptor protein p14. Using conditional gene disruption of p14 in livers of mice (p14Δhep) we analyzed protein and transcript signatures in tissue samples. Further biological network analysis predicted that the differentially expressed transcripts and proteins are involved in cell cycle progression and regulation of cellular proliferation. Although some of the here identified signatures were previously linked to phospho‐ERK activity, most of them were novel targets of the late endosomal p14/MP1/MEK/ERK signaling module. Finally, the proliferation defect was confirmed in a chemically induced liver regeneration model in p14Δhep knockout mice.
Effect of Helicobacter pylori eradication therapy in rosacea patients.

OBJECTIVE The causal relation between rosacea and Helicobacter pylori infection is discussed. We evaluated the clinical evolution of rosacea after infection eradication. PATIENTS AND METHODS We have prospectively studied 44 patients diagnosed with rosacea. Helicobacter pylori infection was determined, and infected patients were treated with eradication therapy. The evolution of dermatological symptoms in a subgroup of 29 infected patients in whom eradication had been achieved was followed during 16.8 (+/- 17.8) months. Median age was 50.6 (+/- 14.1) years for 22 women (75.9%) and 7 men (24.1%). Clinical response according to gender and clinical subtype of rosacea was evaluated. RESULTS Complete improvement was observed in 10 patients (34.5%; 95% CI: 18.6-54.3%), relevant improvement in 9 (31.1%; 95% CI: 16-51%), poor improvement in 5 (17.2%; 95% CI: 6.5-36.4%), and absence of improvement in 5 cases (17.2%; 95% CI: 6.5-36.4%). No significant differences in dermatological evolution according to sex were observed. Regarding subtype of rosacea there was a relevant improvement in 83.3% (95% CI: 64.1-93.8%) of cases with papulopustular type as opposed to 36.5% (95% CI: 20-56.1%) of cases with erythematous predominance, p = 0.02. CONCLUSIONS Based on these results, the relation between Helicobacter pylori and rosacea is supported, and infection should be investigated in these patients because an appreciable percentage of patients diagnosed with rosacea and Helicobacter pylori infection can benefit from eradication therapy, mainly in the papulopustular subtype.
The spectrum of biopsy sites for the diagnosis of sarcoidosis.

BACKGROUND The diagnosis of sarcoidosis is most secure when supported by a tissue biopsy exhibiting noncaseating epithelioid granulomas with absence of known granulomagenic agents in a patient with multi-organ disease. Clinicians must decide which site offers the best chance of achieving a diagnostic biopsy with the least patient risk and discomfort. METHODS 736 cases were enrolled in the NHLBI supported A Case Controlled Etiologic Study of Sarcoidosis (ACCESS) from November 1996 to June 1999. All cases required diagnostic organ biopsy (Bx) exhibiting non-caseating epithelioid granulomas without identifiable granulomagenic agent, within six months of recruitment. Positive Kveim-Siltzbach test was accepted in patients with Löfgren's syndrome. Bx sites were correlated with demographic data, chest radiographic stages, symptoms, pulmonary function and associated organ involvement. RESULTS Seven hundred and seventy-six diagnostic biopsies were performed. Five hundred and sixty-seven were intrathoracic, 198 extrathoracic. Eleven Kveim tests were positive. When cutaneous sarcoidosis or an enlarged extrathoracic lymph node was present, skin or lymph node Bx was the preferred procedure. Twenty-three different organs yielded diagnostic biopsies. CONCLUSIONS Biopsy diagnosis in sarcoidosis is almost always easily obtained. As shown by ACCESS, sarcoidosis offers a wide spectrum of diagnostic biopsy sites. The choice for biopsy is influenced by the presenting clinical constellation of organ involvement and the ease and safety of the biopsy procedure.
HEDIS Measures and Managed Care Enrollment

This article examines the relationship between 1996 health plan enrollment and both HEDIS-based plan performance ratings and individual HEDIS measures. Data were obtained from a large firm that collected, aggregated, and disseminated plan performance ratings to its employees. Plan market share regressions are estimated controlling for out-of-pocket price and model type in addition to the plan ratings and HEDIS measures. The results suggest that employees did not respond strongly to the provided ratings. There are several potential explanations for the lack of response, including difficulty understanding the ratings and never having seen them. In addition, employees may base their plan choices on information that is obtained from their own past experience, friends, family, and colleagues. The pattern of results suggests that such information is important. Counterintuitive signs most likely reflect an inverse correlation between some HEDIS ratings (or measures) and attributes employees observe informally.
The matrix attachment region-binding protein SATB1 participates in negative regulation of tissue-specific gene expression

The nuclear matrix has been implicated in several cellular processes, including DNA replication, transcription, and RNA processing. In particular, transcriptional regulation is believed to be accomplished by binding of chromatin loops to the nuclear matrix and by the concentration of specific transcription factors near these matrix attachment regions (MARs). A number of MAR-binding proteins have been identified, but few have been directly linked to tissue-specific transcription. Recently, we have identified two cellular protein complexes (NBP and UBP) that bind to a region of the mouse mammary tumor virus (MMTV) long terminal repeat (LTR) previously shown to contain at least two negative regulatory elements (NREs) termed the promoter-proximal and promoter-distal NREs. These NREs are absent from MMTV strains that cause T-cell lymphomas instead of mammary carcinomas. We show here that NBP binds to a 22-bp sequence containing an imperfect inverted repeat in the promoter-proximal NRE. Previous data showed that a mutation (p924) within the inverted repeat elevated basal transcription from the MMTV promoter and destabilized the binding of NBP, but not UBP, to the proximal NRE. By using conventional and affinity methods to purify NBP from rat thymic nuclear extracts, we obtained a single major protein of 115 kDa that was identified by protease digestion and partial sequencing analysis as the nuclear matrix-binding protein special AT-rich sequence-binding protein 1 (SATB1). Antibody ablation, distamycin inhibition of binding, renaturation and competition experiments, and tissue distribution data all confirmed that the NBP complex contained SATB1. Similar types of experiments were used to show that the UBP complex contained the homeodomain protein Cux/CDP that binds the MAR of the intronic heavy-chain immunoglobulin enhancer. By using the p924 mutation within the MMTV LTR upstream of the chloramphenicol acetyltransferase gene, we generated two strains of transgenic mice that had a dramatic elevation of reporter gene expression in lymphoid tissues compared with reporter gene expression in mice expressing wild-type LTR constructs. Thus, the 924 mutation in the SATB1-binding site dramatically elevated MMTV transcription in lymphoid tissues. These results and the ability of the proximal NRE in the MMTV LTR to bind to the nuclear matrix clearly demonstrate the role of MAR-binding proteins in tissue-specific gene regulation and in MMTV-induced oncogenesis.
[Women and health].

The author, active within a self help group in Neuchâtel, Switzerland, describes the reasons for the emergence, first in the U.S.A. , then in other countries, of the women's health movement and gives indications on the present situation in Switzerland. In the major cities groups exist or get presently organized. There is a great need for collegial information among women, for more time being dedicated to deal with physical, psychical and social aspects of health, and for fostering autonomy of the women in respect to their own body and care, including self examinations. Unfortunately, up to the present time, the medical profession has shown little interest in such endeavours, and plea is made for a more active participation on its part in the future.
Minimal residual disease monitoring in t(8;21) acute myeloid leukemia based on RUNX1‐RUNX1T1 fusion quantification on genomic DNA

Although acute myeloid leukemia (AML) with t(8;21) belongs to the favorable risk AML subset, relapse incidence may reach 30% in those patients. RUNX1‐RUNX1T1 fusion transcript is a well‐established marker for minimal residual disease (MRD) monitoring. In this study, we investigated the feasibility and performances of RUNX1‐RUNX1T1 DNA as MRD marker in AML with t(8;21). In 17/22 patients with t(8;21)‐positive AML treated in the French CBF‐2006 trial, breakpoints in RUNX1 and RUNX1T1 were identified using long‐range PCR followed by next‐generation sequencing. RUNX1‐RUNX1T1 DNA quantification was performed by real‐time quantitative PCR using patient‐specific primers and probe. MRD levels were evaluated in 71 follow‐up samples from 16 patients, with a median of four samples [range 2–7] per patient. RUNX1 breakpoints were located in intron 5 in all cases. RUNX1T1 breakpoints were located in intron 1b in 15 cases and in intron 1a in two cases. RUNX1‐RUNX1T1 MRD levels measured on DNA and RNA were strongly correlated (r = 0.8, P < 0.0001). Discordant MRD results were observed in 10/71 (14%) of the samples: in three samples from two patients who relapsed, RUNX1‐RUNX1T1 was detectable only on DNA, while RUNX1‐RUNX1T1 was detectable only on RNA in seven samples. MRD monitoring on genomic DNA is feasible, but with sensitivity variations depending on the patient breakpoint sequence and the qPCR assay efficiency. Although interpretation of the results is easier because it is closely related to the number of leukemic cells, this method greatly increases time, cost and complexity, which limits its interest in routine practice. Am. J. Hematol. 89:610–615, 2014. © 2014 Wiley Periodicals, Inc.