Miracle-dz/UniFAR-FTUs huggingface dataset:
Effects of Human Mesenchymal Stem Cells Transduced with Superoxide Dismutase on Imiquimod-Induced Psoriasis-Like Skin Inflammation in Mice.

AIMS The immunomodulatory and anti-inflammatory properties of mesenchymal stem cells (MSCs) have been proposed in several autoimmune diseases and successfully tested in animal models, but their contribution to psoriasis and underlying pathways remains elusive. Likewise, an increased or prolonged presence of reactive oxygen species and aberrant antioxidant systems in skin are known to contribute to the development of psoriasis and therefore effective antioxidant therapy is highly required. We explored the feasibility of using extracellular superoxide dismutase (SOD3)-transduced allogeneic MSCs as a novel therapeutic approach in a mouse model of imiquimod (IMQ)-induced psoriasis-like inflammation and investigated the poorly understood underlying mechanism. In addition, the chronicity and late-phase response of inflammation were evaluated during continued activation of antigen receptors by applying a booster dose of IMQ. RESULTS Subcutaneous injection of allogeneic SOD3-transduced MSCs significantly prevented psoriasis development in our IMQ-induced mouse model, likely through a suppression of proliferation and infiltration of various effector cells into skin with a concomitant modulated cytokine and chemokine expression and inhibition of signaling pathways such as toll-like receptor-7, nuclear factor-kappa B, p38 mitogen-activated kinase, and Janus kinase-signal transducer and activator of transcription, as well as adenosine receptor activation. INNOVATION AND CONCLUSION Our data offer a novel therapeutic approach to chronic inflammatory skin diseases such as psoriasis by leveraging immunomodulatory effects of MSCs as well as SOD3 expression.
A Case–control Study of Diphtheria in the High Incidence City of Hyderabad, India

Background: India accounts for approximately 72% of reported diphtheria cases globally, the majority of which occur in the state of Andhra Pradesh. The aim of this study is to better understand lack of knowledge on diphtheria vaccination and to determine factors associated with diphtheria and low knowledge and negative attitudes. Methods: We performed a 1:1 case–control study of hospitalized diphtheria cases in Hyderabad. Eligible case patients were 10 years of age or older, resided within the city of Hyderabad and were diagnosed with diphtheria per the case definition. Patients admitted to the hospital for nonrespiratory communicable diseases and residing in the same geographic region as that of cases were eligible for enrolment as controls Results: There were no statistical differences in disease outcome by gender, education, economic status and mean room per person sleeping in the house in case and control subjects. Not having heard of diphtheria (adjusted odds ratio: 3.56; 95% confidence intervals: 1.58–8.04] and not believing that vaccines can prevent people from getting diseases (adjusted odds ratio: 3.99; 95% confidence intervals: 1.18–13.45) remained significantly associated with diphtheria on multivariate analysis. Conclusion: To reduce the burden of diphtheria in India, further efforts to educate the public about diphtheria should be considered.
Evaluation of a new foam to increase skin hydration of the foot in type 2 diabetes: a pilot study

The aim of the present study was to evaluate the efficacy of a new product (Neuropad repair foam®) in promoting skin hydration of the foot in type 2 diabetes. Included in this study were 20 type 2 diabetic patients (10 men, mean age 61·40 ± 2·44 years). Patients applied Neuropad repair foam® on the plantar aspect of the right foot twice daily. No agent was applied on the left foot. Patients were examined at baseline, after 7 treatment days and after 14 treatment days. Evaluation of skin dryness was performed by means of the Multi Skin test Corneometer MC 900. In the right foot, skin capacitance was 26·55 ± 4·14 arbitrary units (a.u.) at baseline, 28·90 ± 4·53 a.u. after 7 days of treatment and 32·05 ± 4·54 a.u. after 14 days of treatment. There was a significant increase in skin capacitance from baseline to 7 days of treatment (P < 0·001), from baseline to 14 treatment days (P < 0·001), as well as from 7 to 14 days of treatment (P < 0·001). The same significant (P < 0·001) increases were observed both in men and in women. No changes were noted in the left foot. At baseline, there was no difference in skin capacitance between right and left foot (P = 0·186). However, skin capacitance was significantly higher on the right versus left foot, both after 7 days (P < 0·001) and after 14 days of treatment (P < 0·001). In conclusion, results with the new foam appear encouraging in ameliorating skin dryness in the diabetic foot and further investigation is warranted.
Monitoring prenatal alcohol exposure

Alcohol use during pregnancy is a leading, preventable cause of birth defects and developmental disabilities in the United States, with fetal alcohol syndrome (FAS) being one of the most severe outcomes. Current survey statistics find that approximately one in eight pregnant women (500,000 per year) report alcohol use, with approximately 80,000 reporting binge drinking. While annual rates have fluctuated, trends analysis finds that there has been no significant change in rates of prenatal alcohol exposure over the past 10‐year period. Development of effective programs to prevent FAS and to monitor the success of prevention efforts requires epidemiological data systems to inform these activities. This article describes alcohol use patterns among childbearing‐age women and data sources that can be used in monitoring this behavior. Published 2004 Wiley‐Liss, Inc.
Modeling early bactericidal activity in murine tuberculosis provides insights into the activity of isoniazid and pyrazinamide

Standard tuberculosis (TB) treatment includes an initial regimen containing drugs that are both rapidly bactericidal (isoniazid) and sterilizing (rifampin and pyrazinamide), and ethambutol to help prevent the emergence of drug resistance. Antagonism between isoniazid and pyrazinamide has been demonstrated in a TB treatment mouse model. Because isoniazid’s bactericidal activity is greatest during the initial two treatment days, we hypothesized that removing isoniazid after the second day would increase the effectiveness of the standard regimen. To test this hypothesis, we developed a mouse model to measure the early bactericidal activity (EBA) of drug regimens designed to analyze the essentiality of both isoniazid and pyrazinamide during the first 14 d of therapy. Our results clearly indicate that discontinuation of isoniazid after the second day of treatment increases the EBA of standard therapy in the mouse model, whereas omitting pyrazinamide during the first 14 d was detrimental. Substitution of moxifloxacin for isoniazid on day 3 did not increase the EBA compared with only removing isoniazid after day 2. Our data show that a mouse model can be used to analyze the EBA of TB drugs, and our findings support pursuing clinical trials to evaluate the possible benefit of removing isoniazid after the first 2 treatment days.
Cancer incidence and cause-specifi c mortality in male and female physicians: a cohort study in Estonia

Aims: To evaluate whether the presumed knowledge of physicians about healthier lifestyle decreases their risk of cancer and mortality, a retrospective cohort study of male and female physicians was conducted in Estonia. Methods: The cancer incidence and cause-specifi c mortality of 3,673 physicians (870 M, 2,803 F ) in Estonia was compared with the rates of the general population. Information on cancer cases and deaths in the cohort between 1983 and 1998 was obtained from the Estonian Cancer Registry and the mortality database of Estonia. Results: The standardized incidence ratio (SIR) for all cancers was 1.32 (95% confi dence interval (CI) 1.15-1.48) in women and 0.92 (95% CI 0.73-1.13) in men. Female physicians had an elevated risk for breast cancer (SIR 2.03, 95% CI 1.62-2.51) and myeloid leukaemia (SIR 3.69, 95% CI 1.35-8.02). Male physicians had an excess of skin melanoma (SIR 4.88, 95% CI 1.58-11.38). A large defi cit of lung cancer was observed (SIR 0.24, 95% CI 0.11-0.48). The very low all-cause mortality in the cohort (standardized mortality ratio 0.55, 95% CI 0.50-0.61) was mainly due to large defi cits in deaths from lung cancer, cardiovascular diseases and external causes. The suicide rate in the cohort was lower than in the general population. Conclusions: No health risks were observed in the cohort that could be linked to the occupational exposures of physicians. The pattern of cancer incidence and mortality seen in physicians in Estonia is similar to the pattern seen among professional classes in other countries.
Hepatic Secretion of Conjugated Drugs and Endogenous Substances

Conjugate export pumps of the multidrug resistance protein (MRP) family mediate the ATP-dependent secretion of anionic conjugates across the canalicular and the basolateral hepatocyte membrane into bile and sinusoidal blood, respectively. Xenobiotic and endogenous lipophilic substances may be conjugated with glutathione, glucuronate, sulfate, or other negatively charged groups and thus become substrates for export pumps of the MRP family. The apical isoform, MRP2 (gene symbol ABCC2), has been localized to the apical membrane of several polarized epithelia and particularly to the canalicular membrane of hepatocytes. Absence of functionally active MRP2 glycoprotein from this membrane domain prevents the secretion of many anionic conjugates into bile. Prototypic endogenous substrates of high affinity for recombinant human MRP2 include bisglucuronosyl bilirubin, monoglucuronosyl bilirubin, and the glutathione S-conjugate leukotriene C4. Several mutations in the human MRP2 gene have been identified that lead to the absence of MRP2 from the canalicular membrane and to the conjugated hyperbilirubinemia of Dubin-Johnson syndrome. MRP2-mediated conjugate export represents a decisive final step in the detoxification of drugs, toxins, and endogenous substances. The basolateral isoform, MRP3 (gene symbol ABCC3), is upregulated in MRP2 deficiency and in extrahepatic cholestasis. MRP3 mediates the ATP-dependent transport of anionic conjugates, particularly of glucuronides and sulfoconjugates, across the basolateral hepatocyte membrane into sinusoidal blood. The inverse regulation of MRP3 and MRP2 expression under many conditions is consistent with their distinct localization and with a compensatory role of MRP3 in the hepatic secretion of anionic conjugates during impaired transport into bile.
Usefulness of N-acetylcysteine or ascorbic acid versus placebo to prevent contrast-induced acute kidney injury in patients undergoing elective cardiac catheterization: a single-center, prospective, randomized, double-blind, placebo-controlled trial.

BACKGROUND Contrast-induced acute kidney injury (CI-AKI) is a serious complication of procedures requiring contrast media associated with rising costs, prolonged hospitalization, and increased mortality. The aim of this study was to assess whether prophylactic administration of standard dosages of intravenous N-acetylcysteine or ascorbic acid reduce the incidence of CI-AKI in patients with chronic renal insufficiency undergoing elective cardiac catheterization. METHODS In a single-center, prospective, randomized, double-blind, placebo-controlled trial, the preventive effects of N-acetylcysteine and ascorbic acid were evaluated in 520 patients with chronically impaired renal function (serum creatinine ≥1.3 mg/dL) undergoing elective cardiac catheterization. The study drugs (600 mg N-acetylcysteine, 500 mg ascorbic acid, placebo) were administered intravenously twice (at 24 hours and 1 hour before the procedure). Serum creatinine, estimated glomerular filtration rate (eGFR) and serum urea were assessed at baseline and at 24 hours and 72 hours after contrast media exposure. CI-AKI was defined as a postangiographical increase in serum creatinine ≥0.5 mg/dL. Results. The incidence of CI-AKI was 27.6% in the N-acetylcysteine group (P=.20 vs placebo group) and in 24.5% in the ascorbic acid group (P=.11 vs placebo group). CI-AKI occurred in 32.1% of the placebo group. CONCLUSIONS Standard doses of N-acetylcysteine and ascorbic acid did not prevent CI-AKI in patients at high risk undergoing cardiac catheterization with non-ionic, low-osmolality contrast agent.
Multifaceted Mechanisms of HIV-1 Entry Inhibition by Human α-Defensin*♦

Background: Human neutrophil peptide 1 (HNP-1) inhibits HIV-1 infection by a poorly defined mechanism. Results: Effects of HNP-1 on individual steps of virus-cell fusion were examined. Conclusion: HNP-1 interferes with all major steps of HIV-1 entry, from CD4/coreceptor binding to virus uptake and refolding of Env glycoprotein. Significance: The ability of HNP-1 to block HIV-1 uptake suggests a novel universal mechanism for antiviral activity. The human neutrophil peptide 1 (HNP-1) is known to block the human immunodeficiency virus type 1 (HIV-1) infection, but the mechanism of inhibition is poorly understood. We examined the effect of HNP-1 on HIV-1 entry and fusion and found that, surprisingly, this α-defensin inhibited multiple steps of virus entry, including: (i) Env binding to CD4 and coreceptors; (ii) refolding of Env into the final 6-helix bundle structure; and (iii) productive HIV-1 uptake but not internalization of endocytic markers. Despite its lectin-like properties, HNP-1 could bind to Env, CD4, and other host proteins in a glycan- and serum-independent manner, whereas the fusion inhibitory activity was greatly attenuated in the presence of human or bovine serum. This demonstrates that binding of α-defensin to molecules involved in HIV-1 fusion is necessary but not sufficient for blocking the virus entry. We therefore propose that oligomeric forms of defensin, which may be disrupted by serum, contribute to the anti-HIV-1 activity perhaps through cross-linking virus and/or host glycoproteins. This notion is supported by the ability of HNP-1 to reduce the mobile fraction of CD4 and coreceptors in the plasma membrane and to precipitate a core subdomain of Env in solution. The ability of HNP-1 to block HIV-1 uptake without interfering with constitutive endocytosis suggests a novel mechanism for broad activity against this and other viruses that enter cells through endocytic pathways.
Effect of a Home Exercise Program Based on Tai Chi in Patients with End-Stage Renal Disease

Objective Previous reports have documented the benefits of exercise on the well-being of renal patients. However, fewer than 50% of our end-stage renal disease (ESRD) patients engage in regular exercise. To promote exercise, we implemented a home-based exercise program. The aim of the program was to reduce barriers to exercise by helping patients to exercise at their convenience and without the need to travel. The effect of the program was evaluated 3 months after implementation. Patients and Methods Each study participant received a videotape that demonstrated 30 minutes of low-capacity aerobic exercise. Participants were advised to exercise by following the demonstration on the videotape. Encouragement was given over the telephone. Self-reports on practice were recorded in a log book that was also provided. The effect of the program was evaluated by comparing outcomes data before, and 3 months after, implementation of the program. Outcomes assessment included functional mobility (timed “Up & Go” test), muscle flexibility (“Sit & Reach” test), physical capacity (“Six-Minute Walk”), and quality of life [Kidney Disease Quality of Life Short Form (KDQOL-SF)]. Results The program began with 72 participants. Over time, 39 dropped out. The remaining 33 participants included 11 men and 22 women with a mean age of 52.8 ± 9.8 years. They exercised 3 – 7 times weekly. Significant improvements were observed in the timed “Up & Go” (p = 0.003) and “Sit & Reach” (p < 0.001) tests. Improvements in the “Six-Minute Walk” (p = 0.130) and in KDQOL-SF scores for emotional well-being (p = 0.456), pain (p = 0.100), burden of kidney disease (p = 0.061), and general health (p = 0.085) were statistically insignificant. Conclusions Physically, patients with ESRD benefit from home-based low-capacity aerobic exercise. A home-based program provides an alternative to outdoor and group exercise. In view of a high drop-out rate, intensive promotion and encouragement should be considered to achieve a positive outcome.
Caspase-3 Regulates Catalytic Activity and Scaffolding Functions of the Protein Tyrosine Phosphatase PEST, a Novel Modulator of the Apoptotic Response

ABSTRACT The protein tyrosine phosphatase PEST (PTP-PEST) is involved in the regulation of the actin cytoskeleton. Despite the emerging functions attributed to both PTPs and the actin cytoskeleton in apoptosis, the involvement of PTP-PEST in apoptotic cell death remains to be established. Using several cell-based assays, we showed that PTP-PEST participates in the regulation of apoptosis. As apoptosis progressed, a pool of PTP-PEST localized to the edge of retracting lamellipodia. Expression of PTP-PEST also sensitized cells to receptor-mediated apoptosis. Concertedly, specific degradation of PTP-PEST was observed during apoptosis. Pharmacological inhibitors, immunodepletion experiments, and in vitro cleavage assays identified caspase-3 as the primary regulator of PTP-PEST processing during apoptosis. Caspase-3 specifically cleaved PTP-PEST at the 549DSPD motif and generated fragments, some of which displayed increased catalytic activity. Moreover, caspase-3 regulated PTP-PEST interactions with paxillin, leupaxin, Shc, and PSTPIP. PTP-PEST acted as a scaffolding molecule connecting PSTPIP to additional partners: paxillin, Shc, Csk, and activation of caspase-3 correlated with the modulation of the PTP-PEST adaptor function. In addition, cleavage of PTP-PEST facilitated cellular detachment during apoptosis. Together, our data demonstrate that PTP-PEST actively contributes to the cellular apoptotic response and reveal the importance of caspases as regulators of PTPs in apoptosis.
B‐Cell Chronic Lymphocytic Leukemia, a Clonal Disease of B Lymphocytes with Receptors that Vary in Specificity for (Auto)antigens

Abstract: B‐Cell chronic lymphocytic leukemia (B‐CLL) is an incurable disease that is relatively common among aging Caucasians. Patients with this leukemia can be divided into prognostic categories using clinical staging parameters, as well as molecular features [presence or absence of IgVH mutations in rearranged VHDJH segments that code for the leukemic B cell's receptor for antigen (BCR)]. In addition, the deduced amino acid structure of the BCRs from patients that fall into different prognostic categories is shared, to varying degrees, within these groups. In this paper, the molecular features of the genes that code for the BCRs of B‐CLL patients are reviewed, and these are comapred to antibodies of known specificity. These comparisons suggest that the BCRs of many cases resemble autoantibodies, and in some cases, antibodies to microbial antigens. Antigen‐binding analyses confirm these impressions, and also indicate that polyreactivity appears to distinguish cases with worse clinical outcomes differ from those with better outcomes. The persistence of autoreactivity and polyreactivity is somewhat surprising, because IgV DNA sequence analyses suggest that many of the B cells that become leukemic have undergone one form or another of receptor editing. Thus, B‐CLL appears to be a disease of B‐cell clones that have undergone various types of receptor reconfiguration and yet retain inappropriate antigen‐binding properties.
Hepatic steatosis in morbidly obese patients undergoing gastric bypass surgery: assessment with open-system 1H-MR spectroscopy.

OBJECTIVE The purpose of this study was to assess, with histopathologic control, the use of open-system 1-T (1)H MR spectroscopy for the evaluation of hepatic steatosis in morbidly obese patients undergoing gastric bypass surgery. SUBJECTS AND METHODS Patients underwent (1)H MR spectroscopy (MRS) for the assessment of steatosis before and 3 months after surgery. Liver biopsy was performed during surgery. Hepatic steatosis was expressed as the ratio of fat peak area to cumulative water and fat peak areas. Histopathologic percentage of steatosis was graded as none (0-5%), mild (5-33%), moderate (33-66%), or severe (> 66%). The accuracy of (1)H-MRS and Spearman correlation coefficient were calculated. Differences between groups were assessed with the Wilcoxon signed rank and Mann-Whitney tests. RESULTS The study included 38 patients (median age, 45.5 years; median body mass index, 47.7). Before surgery, median steatosis measured with (1)H-MRS was 5.8%. The accuracy of (1)H-MRS was 89% (32/36), and the (1)H-MRS findings correlated with the histopathologic assessment of steatosis (r = 0.85, p < 0.001). With (1)H-MRS, no steatosis was discriminated from mild steatosis (p = 0.011), mild was discriminated from moderate steatosis (p < 0.001), and moderate was discriminated from severe steatosis (p = 0.021). Three months after surgery, steatosis had decreased to 3.1% (p < 0.001). The prevalence of hepatic steatosis measured with (1)H-MRS decreased from 53% to 32%. CONCLUSION In the care of morbidly obese patients undergoing assessment of hepatic steatosis and changes in steatosis after gastric bypass surgery, (1)H-MRS with an open 1-T MRI system is feasible. Measurements of hepatic fat with (1)H-MRS are accurate and correlate with clinical and histopathologic results.
The Effectiveness of External Information Channels in Facilitating Innovation Within Software Development Groups

This study of forty-nine software development groups investigated the effectiveness of ten information channels, linking the software groups to potential information resources about new developments in software methodologies, as a means of facilitating software group innovativeness. While the findings suggest that software group innovativeness can be improved by providing appropriate external information channels, this relationship is contingent on a software groups internal environment. The channels most commonly provided by those organizations participating in the study tended to be those least effective in promoting innovation.
LSO PET/CT Pico performance improvements with ultra Hi-Rez option

Factors which may improve image quality in PET systems include spatial resolution and scatter fraction. By reducing the energy window, the size of the crystal elements and thickness, the spatial resolution and scatter fraction can be improved. The LSO PET/CT Pico system, which consists of an 8times8 crystal array per detector block, operates on an energy window of 400 to 650 keV. The new LSO PET/CT Hi-Rez system includes a 13times13 crystal array per detector block, a decrease of 20% in crystal thickness and a narrower energy window of 425 to 650 keV. Improvements in spatial resolution and in scatter fraction are therefore expected. Although a reduction in sensitivity may result, the image quality of the system should not be affected. In order to evaluate the overall performance of the new system, tests from the NEMA NU 2-2001 protocol were conducted on LSO PET/CT Pico and Hi-Rez systems, and their results were compared. The Hi-Rez system presented an improvement in spatial resolution of 27% at 1cm and 28% at 10 cm. The scatter fraction on the Pico and Hi-Rez systems indicate average values of 41% and 34% respectively, equivalent to a decrease of 17% for the Hi-Rez system. The sensitivity of the Hi-Rez system diminished by 22% and changes of less than 4% were observed for the peak NEC rate. The improvements in spatial resolution and scatter fraction obtained in our measurements may create significant advances in the physician's ability to detect small lesions in PET/CT images