Miracle-dz/UniFAR-FTUs huggingface dataset:
Carcinoid Heart Disease

ABSTRACT Carcinoid heart disease is seen in 50% of patients with carcinoid syndrome and is the main cause of morbidity and mortality. The pathophysiology of carcinoid heart disease is still poorly understood; however, the disease is believed to be caused by chronic exposure to excessive circulating vasoactive substances produced by the neuroendocrine tumors. The advancement of cardiac imaging modalities, antitumor treatment, and cardiac surgery, has improved the prognosis of patients with carcinoid heart disease. Cardiac surgery is the most effective treatment in these patients and is recommended to be performed in an experienced center by a multidisciplinary team. Abbreviations: 5-HT: 5-hydroxytryptamine; CHD: carcinoid heart disease; TGF-β:transforming growth factor beta; ECM: extracellular matrix; 5-HIAA: 5-hydroxyindoleacetic acid; CgA: chromogranin A; NT-proBNP: B-type natriuretic peptide
Pore‐forming Staphylococcus aureus α‐toxin triggers epidermal growth factor receptor‐dependent proliferation

Staphylococcal α‐toxin is an archetypal killer protein that homo‐oligomerizes in target cells to create small transmembrane pores. The membrane‐perforating β‐barrel motif is a conserved attack element of cytolysins of Gram‐positive and Gram‐negative bacteria. Following the recognition that nucleated cells can survive membrane permeabilization, a profile of abundant transcripts was obtained in transiently perforated keratinocytes. Several immediate early genes were found to be upregulated, reminiscent of the cellular response to growth factors. Cell cycle analyses revealed doubling of S + G2/M phase cells 26 h post toxin treatment. Determination of cell counts uncovered that after an initial drop, numbers increased to exceed the controls after 2 days. A non‐lytic α‐toxin mutant remained without effect. The α‐toxin pore is too small to allow egress of cytosolic growth factors, and evidence was instead obtained for growth signalling via the epidermal growth factor receptor (EGFR). Inhibition of the EGFR or of EGFR‐proligand‐processing blocked the mitogenic effect of α‐toxin. Western blots with phospho‐specific antibodies revealed activation of the EGFR, and of the adapter protein Shc. Immediate early response and proliferation upon transient plasma membrane pore formation by bacterial toxins may represent a novel facet of the complex interaction between pathogen and host.
Gender differences in internet usage and task preferences

Although there has been much publicity about the Internet, empirical research focusing on it is still relatively sparse. Much of the existent research on the internet has been predicated upon data collected in Europe and America. To date, there is a dearth of published studies on the internet in the Asian context. This study examines gender differences in internet usage in Singapore, a small island of 650 square kilometres in south-east Asia. Data were collected on internet users via a questionnaire survey placed on the World Wide Web. 1370 usable responses were received, of which 89% were males and 11% were females. Gender differences in terms of the demographic profile of internet users, usage patterns, task preferences and factors affecting an enjoyable Internet experience are examined.
Antifertility activity of an indigenous plant preparation (ROC-101). II. Effect on the male reproductive system.

ROC-101 a plant preparation was administered orally to male and female rats and mice to determine its antifertility effects. The antifertility effects were considerably greater in the male than in the female. 50 and 100 g/kg diet of ROC-101 inhibited spermatogenesis in mice. Over a 3-week period of treatment with the 100 mg dose the number of primary and secondary spermatocytes diminished considerably. Testicular weights were reduced by 75% compared to controls in animals receiving ROC-101 for 4 weeks. The testes in this group exhibited only Sertoli cells type A spermatogonia and primary spermatocytes. There was no evidence of androgenic or antiandrogenic activity when ROC-101 was tested in castrated immature mice and rats. The action of ROC-101 appears to be similar to that of ORF-1616.
Effect of piperine on CYP2E1 enzyme activity of chlorzoxazone in healthy volunteers

Abstract 1. The purpose of the present study was to investigate the effect of piperine (PIP) on CYP2E1 enzyme activity and pharmacokinetics of chlorzoxazone (CHZ) in healthy volunteers. 2. An open-label, two period, sequential study was conducted in 12 healthy volunteers. A single dose of PIP 20 mg was administered daily for 10 days during treatment phase. A single dose of CHZ 250 mg was administered during control and after treatment phases under fasting conditions. The blood samples were collected at predetermined time intervals after CHZ dosing and analyzed by HPLC. 3. Treatment with PIP significantly enhanced maximum plasma concentration (Cmax) (3.14–4.96 μg/mL), area under the curve (AUC) (10.46–17.78 μg h/mL), half life (T1/2) (1.26–1.82 h) and significantly decreased elimination rate constant (Kel) (0.57–0.41 h − 1), apparent oral clearance (CL/F) (24.76–13.65 L/h) of CHZ when compared to control. In addition, treatment with PIP significantly decreased Cmax (0.22–0.15 μg/mL), AUC (0.94–0.68 μg h/mL), T1/2 (2.54–1.68 h) and significantly increased Kel (0.32–0.43 h − 1) of 6-hydroxychlorzoxazone (6-OHCHZ) as compared to control. Furthermore, treatment with PIP significantly decreased metabolite to parent (6-OHCHZ/CHZ) ratios of Cmax, AUC, T1/2 and significantly increased Kel ratio of 6-OHCHZ/CHZ, which indicate the decreased formation of CHZ to 6-OHCHZ. 4. The results suggest that altered pharmacokinetics of CHZ might be attributed to PIP mediated inhibition of CYP2E1 enzyme, which indicate significant pharmacokinetic interaction present between PIP and CHZ. The inhibition of CYP2E1 by PIP may represent a novel therapeutic benefit for minimizing ethanol induced CYP2E1 enzyme activity and results in reduced hepatotoxicity of ethanol.
Correction: Human Direct Actions May Alter Animal Welfare, a Study on Horses (Equus caballus)

The following paragraph in the Methods subsection "Horses' spine examination" should read as follows: "In order to ensure the repeatability of these findings, evaluation was double performed by a second licensed chiropractor, equally blind to results and unknown to horses, on 10 out of the 19 horses. Comparison of evaluations (localisation of vertebral sites affected) revealed a 94.28% ± 3.69% agreement, therefore confirming reliability of the evaluation. "
Buffalo Subclinical Mastitis Bacterial Pathogens in Iran

The aim of current study was to determine the bacterial causes of subclinical mastitis in buffaloes of Northwest Iran. 400 buffaloes were tested by California Mastitis Test (CMT) for detection of subclinical cases. 38 (9.5%) quarters were diagnosed as CMT positive. Sterile quarter based milk samples were collected from theses quarters and examined for bacterial pathogens. Total Bacterial Count (TBC) and culture were done as described by National Mastitis Council. Hind quarters were most affected (73%) (p<0.05). The most isolated pathogens were the Coagulase Negative Staphylococci (CNSs). Streptococcus spp. and Bacillus spp. were in the next position. Only 2 quarters were affected with Staphylococcus aureus. There were no significant differences between the prevalence of isolated bacteria from infected quarters. It is concluded major causes of buffalo’s subclinical mastitis are teat skin opportunistic bacteria.
Phase II trial of CHOP plus rituximab in patients with HIV-associated non-Hodgkin's lymphoma.

TO THE EDITOR: Recently Boue et al 1 published the results of a French phase II trial with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in 61 patients with HIVassociated non-Hodgkin’s lymphoma (HIV-NHL). They reported a complete remission rate of 77% and a 2-year survival of 75% without any increase of both toxic deaths and life-threatening infections. These results are similar to that of our pooled analysis of three international phase two studies using rituximab plus infusional cyclophosphamide, doxorucin and etoposide (R-CDE) 2 in 74 patients with HIV-NHL with a complete remission rate of 70% and a 2-year survival of 64%. However, a significant increase in hematologic toxicity and infections were found in the R-CDE study, in particular, grade 3 to 4 neutropenia in 78% of patients and infection in 31% of patients. These differences could be related to several factors. First, in the R-CDE study all patients were treated, while in the R-CHOP study only patients with good or intermediate prognosis (ie, no more than one of the following prognostic factors: CD4 cell count 100/dL, prior history of opportunistic infections, and Eastern Cooperative Oncology Group performance status 2) were enrolled. Second, due to the continuous infusion of R-CDE all patients used a central venous catheter, which is a risk factor for bacterial infections. Third, in the R-CDE study all antiretroviral drugs were allowed while in the R-CHOP study, the use of mielotoxic antiretroviral drugs, such as zidovudine or ritonavir, was avoided, leading to a low rate of grade 3 or 4 neutropenia (33% in R-CHOP v 78% in R-CDE). Last, the use of etoposide could have contributed to the increase of bone marrow toxicity. Overall, the results of the French study confirm the results of R-CDE with a high efficacy of the addition of rituximab to chemotherapy in the treatment of patients with HIV-NHL without any overall increase in severe toxicity. These results are in contrast with the previous US data published by Kaplan et al 3 where rituximab was associated to an unacceptable rate of treatment-related infectious deaths; although, the patient selection could be the reason for this toxicity. In conclusion, rituximab plus chemotherapy should be considered the standard treatment of patients with HIV-NHL. Randomized studies comparing rituximab plus CHOP versus rituximab plus infusional chemotherapy (CDE or etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin [EPOCH]) could be warranted in order to improve both response rate and overall survival.
Rapid HIV testing, pregnancy, antiretroviral prophylaxis and infant abandonment in St Petersburg

In St Petersburg, Russia, a rapid HIV-testing programme was implemented in April 2004 for high-risk women giving birth. Among 670 women without prenatal care who received rapid HIV testing, 6.4% (43) had positive results. Among HIV-positive mothers, receipt of intrapartum antiretroviral prophylaxis increased significantly compared to pre-programme levels (76 versus 41%). Additionally, infant abandonment increased significantly (50% versus 26%), and was 10 times greater in women with unintended versus intended pregnancies (73% versus 7%).
Accelerometer-determined physical activity and all-cause mortality in a national prospective cohort study of hypertensive adults

Objective: Research in the general population suggests an inverse association between physical activity and all-cause mortality. Less research on this topic has been conducted among hypertensive adults, but the limited studies also suggest an inverse association between physical activity and all-cause mortality among hypertensive adults. At this point, sex-specific differences are not well understood, and all of the physical activity–mortality studies among hypertensive adults have employed a self-report measure of physical activity. Therefore, the purpose of this study was to examine the sex-specific association between objectively measured physical activity and all-cause mortality among a national sample of hypertensive adults. Methods: Data from the 2003 to 2006 National Health and Nutrition Examination Survey, with follow-up through 2011, were employed. Hypertension status was defined using measured blood pressure and use of blood pressure-lowering medication. Physical activity was assessed via accelerometry. Results: After adjustments, for every 60-min increase in physical activity, hypertensive adults had a 19% (hazard rate = 0.81; 95% confidence interval: 0.72–0.91) reduced risk of all-cause mortality. There was also evidence of a dose–response relationship. Compared with those in the lowest tertile, those in the middle and upper tertiles had a 31 and 42% reduced all-cause mortality risk, respectively. There was no evidence of a sex-specific interaction effect. Conclusion: : Among hypertensive adults, objectively measured physical activity is associated with all-cause mortality risk in a dose–response manner.
Effect of drug transporter pharmacogenetics on cholestasis

Introduction: The liver is the central place for the metabolism of drugs and other xenobiotics. In the liver cell, oxidation and conjugation of compounds take place, and at the same time, bile formation helps in extrusion of these compounds via the biliary route. A large number of transporters are responsible for drug uptake into the liver cell and excretion into bile or efflux to the sinusoidal blood. Areas covered: Genetic variants of these transporters and their transactivators contribute to changes in drug handling and are also responsible for cholestatic syndromes of different severity. This review summarizes the current knowledge regarding the influence of these genetic changes. The review covers progressive hereditary cholestatic syndromes as well as recurrent or transient cholestatic syndromes such as drug-induced liver injury, intrahepatic cholestasis of pregnancy, and benign recurrent intrahepatic cholestasis. Expert opinion: Polymorphisms in transporter genes are frequent. For clinically relevant cholestatic syndromes, it often requires a combination of genetic variants or acquired triggers such as pregnancy or drug treatment. In combination with other pathogenetic aspects, genetic variants in drug transporters may contribute to our understanding of not only cholestatic diseases such as primary sclerosing cholangitis or primary biliary cirrhosis, but also the natural course of chronic liver disease in general.
Board of Regents of the University of Wisconsin System Parent-Child Quality Time : Does Birth Order Matter ?

Using data from the American Time Use Survey, I find that a first-born child receives 20-30 more minutes of quality time each day with his or her parent than a second-born child of the same age from a similar family. The birth-order difference results from parents giving roughly equal time to each child at any point in time while the amount of parent-child quality time decreases as children get older. These results provide a plausible explanation for recent research showing a very significant effect of birth order on child outcomes.
Undifferentiated carcinoma of the gallbladder. A clinicopathologic, histochemical, and immunohistochemical study of 21 patients with a poor prognosis

Among 284 cases of carcinoma of the gallbladder, 21 were identified as undifferentiated carcinoma (UC), with little glandular or other specific epithelial differentiation. These tumors were classified into three histologic types according to the components: (1) small cell type (eight cases); (2) pleomorphic cell type (eight cases); and (3) spindle cell or pseudosarcomatous type (five cases). Histochemical and immunohistochemical study by the immunoperoxidase technique revealed that most of the tumors (13/21) contained mucosubstances, and that all examples of the UC were immunoreactive for epithelial membrane antigen (EMA), keratin, and carcinoembryonic antigen (CEA), thereby indicating the epithelial nature of the neoplastic cells. Vimentin immunoreactivity was found in nine tumors. In 19, the tumor contained various neoplastic endocrine cells, including somatostatin‐immunoreactive (14/19), gastrinimmunoreactive (14/19), human chorionic gonadotropin (HCG)‐immunoreactive (9/19), pancreatic polypeptide‐immunoreactive (4/19), and serotonin‐immunoreactive cells (4/19). The prognosis of patients with UC of the gallbladder was poorer than that of patients with differentiated adenocarcinoma.
Lopinavir Protein Binding In Vivo Through the 12-Hour Dosing Interval

Most protease inhibitors available for the treatment of human immunodeficiency virus (HIV) infection are highly bound to plasma proteins, mainly &agr;-1 acid glycoprotein. Therapeutic drug monitoring (TDM) of total protease inhibitor (PI) concentrations has been increasing in the past few years; however, the pharmacological activity of the PIs is dependent on unbound drug entering cells harboring HIV. There is little information available on unbound drug concentrations of these drugs in vivo. The aim of the study was to measure unbound plasma concentrations of lopinavir (LPV) and to relate them to the total plasma concentrations to establish the unbound percentage in vivo during a full dosage interval. A pharmacokinetic study was performed in HIV-infected subjects (n = 23; median CD4 cell count = 290 × 106 cells · L−1; viral load < 50 copies · mL−1) treated with a LPV/ritonavir (RTV)-containing regimen. Ultrafiltration was used to separate unbound LPV in all plasma samples (n = 115). Equilibrium dialysis was also used to compare with ultrafiltration measurements in 10/23 patients at baseline and 2 hours after drug intake. Total and unbound LPV concentrations were measured by a fully validated method using high-performance liquid chromatography–mass spectometry (HPLC-MS/MS). Based on a comparison of AUCunbound/AUCtotal, the mean (± SD) unbound percentage of LPV from all the samples studied (n = 115) was 0.92% (± 0.22) when measured with ultrafiltration and 1.32% (± 0.44) when equilibrium dialysis was used (n = 20), showing a higher drug recovery (P = 0.048). The unbound percentage of LPV was found to be significantly higher after 2 h than at baseline (P < 0.05 with both methods), suggesting a concentration-dependent binding of LPV that has not been observed in vitro. However, the clinical significance of such phenomena is still unclear.
The collapsing variant of focal segmental glomerulosclerosis in children

The collapsing variant of focal segmental glomerulosclerosis (FSGS) is a renal injury that may be idiopathic or associated with various factors; it is characterized by glomerular collapse, which leads to steroid-resistant nephrotic syndrome (NS) and progressive chronic renal failure. FSGS has not been well studied in children, in which most of the cases are idiopathic. We report six cases of the collapsing variant of FSGS in HIV-negative children who were resistant to immunosuppressive treatment. Three of the children died.
Effect of age of growing turkeys on digesta viscosity and nutrient digestibility of maize, wheat, barley and oats fed as such or with enzyme supplementation

The effects of age of growing turkeys and β-glucanase-xylanase activity-containing feed enzyme supplementation on digestibility and feeding value of pelleted maize, wheat, barley and oats were investigated in growing turkeys using excreta collection and ileal sampling by slaughter. Excreta were collected and turkeys were slaughtered at 4, 8 and 12 weeks of age. Viscosity of jejuno-duodenal digesta, caecal volatile fatty acid concentration, ileal crude protein digestibility, total tract fat digestibility and AMEN were assayed using titanium dioxide as an indigestible marker. The highest viscosities were observed in barley and wheat. Viscosity of wheat, barley and oats digesta decreased while caecal volatile fatty acid concentration, fat digestibility and AMEN increased with age. Ileal crude protein digestibility was highest in wheat and lowest in barley. Ileal crude protein digestibility significantly declined with age in most feeding treatments. Enzyme reduced digesta viscosity most efficiently in wheat and barley and improved ileal crude protein digestibility, total tract fat digestibility and AMEN in wheat, barley and oats, but interactions occurred, the effect of enzyme on viscosity being the most remarkable for wheat and barley and for the young birds.
Optimal interval screening and surveillance of abdominal aortic aneurysms.

OBJECTIVES to determine safe and optimal intervals of rescreening and surveillance for AAA. METHODS hospital-based mass screening of 6339 65-73-year-old men from 1994-98. 76.4% attended. One hundred and ninety-one (4%) had AAA53 cm. Twenty-four (0.5%) were initially >5 cm and referred for surgery, while the rest were offered annual control scans to check for expansion. Later, all 348 (7.5%) men who 3 to 5 years ago had an ectatic aorta (infrarenal aortic diameter of 25-29 mm or distal/renal aortic diameter ratio >1.2) were offered rescreening. Of these, 62 (18%) died before rescanning, while 248 of the survivors attended rescreening (87%). Furthermore, a random sample of 380 of those with non-ectatic aortas were offered rescreening. Of these, 49 (13%) died before rescreening (p=0.06), while 275 (83%) of the survivors attended re-screening. RESULTS none of the controls had developed AAA. Of those who initially had an 25-29 mm aorta, 29% had developed AAA (size range 30-48 mm) with expansion rates varying from 1.0 to 4.7 mm/year. Only 3.5% with a ratio >1.2 developed AAA (size range: 30-34 mm) with expansion rates from 1.3 to 2.4 mm/year. During the fourth year of surveillance some AAA initially sized below 3.5 cm expanded to above 5 cm, while some sized 3.5-3.9 cm did so during the second year, >4 cm did so during the first year of surveillance. CONCLUSION rescreening for AAA can be restricted to initially ectatic aortas sized 25-29 mm at 5-year intervals. Surveillance of small AAA can be restricted to 1-4 year intervals.
Increased DNA Vaccine Delivery and Immunogenicity by Electroporation In Vivo

DNA vaccines have been demonstrated to be potent in small animals but are less effective in primates. One limiting factor may be inefficient uptake of DNA by cells in situ. In this study, we evaluated whether cellular uptake of DNA was a significant barrier to efficient transfection in vivo and subsequent induction of immune responses. For this purpose, we used the technique of electroporation to facilitate DNA delivery in vivo. This technology was shown to substantially increase delivery of DNA to cells, resulting in increased expression and elevated immune responses. The potency of a weakly immunogenic hepatitis B surface Ag DNA vaccine was increased in mice, as seen by a more rapid onset and higher magnitude of anti-hepatitis B Abs. In addition, the immunogenicity of a potent HIV gag DNA vaccine was increased in mice, as seen by higher Ab titers, a substantial reduction in the dose of DNA required to induce an Ab response, and an increase in CD8+ T cell responses. Finally, Ab responses were enhanced by electroporation against both components of a combination HIV gag and env DNA vaccine in guinea pigs and rabbits. Therefore, cellular uptake of DNA is a significant barrier to transfection in vivo, and electroporation appears able to overcome this barrier.