Miracle-dz/UniFAR-FTUs huggingface dataset:
Short-Term Administration of Captopril and Nifedipine and Exercise-Induced Albuminuria in Normotensive Diabetic Patients With Early-Stage Nephropathy

Recent studies have demonstrated that short-term angiotensin converting enzyme (ACE) inhibition with captopril can reduce urinary albumin excretion rate (UAER) after exercise in normotensive diabetic patients with early-stage nephropathy. The aim of this study was to investigate whether this effect of ACE inhibition was due to a systemic hypotensive action or a specific action at the intrarenal level. Thus, we compared the acute effects of captopril and the Ca2+-channel blocker nifedipine on exercise-induced UAER in normotensive (blood pressure <165/95 mmHg) diabetic patients who were normoalbuminuric or microalbuminuric at rest (stage 2 or 3 of diabetic nephropathy). Twenty-five stage 2 diabetic nephropathy patients, 39 stage 3 diabetic nephropathy patients, and 12 nondiabetic subjects performed five submaximal cycloergometric exercises (90% of theoretical heart rate) on nonconsecutive days. The first two exercises were performed in basal conditions; the next three exercises were performed 24 h after administration of captopril (25 mg twice daily) or nifedipine AR (20 mg twice daily) or placebo (1 tablet twice daily) according to a randomized double-blind crossover trial. After placebo, blood pressure and UAER did not change at rest or 1 h after exercise. After captopril, blood pressure at rest and during exercise was similar to that observed after placebo. UAER at rest was not modified, whereas 1 h after exercise, it was significantly decreased both in stage 2 and stage 3 diabetic nephropathy patients (P < 0.001). After nifedipine, blood pressure decreased significantly at rest and during exercise in respect to placebo and captopril. UAER at rest did not change significantly. UAER 1 h after exercise was significantly decreased both in stage 2 and stage 3 diabetic nephropathy patients (P < 0.01 vs. placebo), but it was significantly higher than that observed after captopril (P < 0.01). Captopril is more effective than nifedipine in reducing exercise-induced UAER in normotensive diabetic patients even though it does not influence blood pressure response to exercise. The effects of captopril on UAER induced by exercise may be due to a specific action at the intrarenal level.
A cytochemical study of the adrenal cortex in hypo- and hyperthyroidism.

THE ADRENAL cortex enlarges in experimentally hyperthyroid animals and shrinks in animals made hypothyroid by thyroidectomy or by feeding antithyroid drugs such as thiouracil or thiourea (Marine, 1935; Leblond and Hoff, 1944; Baumann and Marine, 1945). It has not been ascertained whether these changes in the adrenal gland are caused by an altered reactivity of the cortex or whether they reflect modified rates of production of pituitary adrenotropin. Baumann and Marine state that the adrenal cortex “exercises an inhibitory control over the thyroid gland” and interpret the involution of the cortex after administration of thiouracil as an “attempt to compensate for loss of the thyroid secretion. ” There has been little support for their belief that the connection between these two glands is so direct. To us it seems more reasonable to interject the pituitary gland and its specific hormones into any suspected thyroid-adrenal inter-relationship.
Alcohol and pancreatitis mortality at the population level: experiences from 14 western countries.

AIMS To test if there is relationship between alcohol consumption and pancreatitis mortality at the population level. DATA AND METHODS Annual pancreatitis death rates for 1950-95 were converted into age-adjusted mortality rates per 100,000 inhabitants. Per capita alcohol consumption was measured by alcohol sales. The relationship was estimated with time-series analysis on data from 14 western countries. Several models were tested with different assumptions about risk function and lag structure. RESULTS According to the assumed most appropriate model, a positive relationship was found in each country, and statistical significance was reached in all countries except from Finland, Italy and Canada. The magnitude of the association was fairly consistent across countries, with the alcohol effect parameters ranging between 0.05 and 0.14. However, Sweden and Norway deviated from this pattern with estimates between 0.30 and 0.40. CONCLUSIONS Pancreatitis joins a wide range of causes of death where the mortality rate is influenced by per capita alcohol consumption, and more so in northern Europe. It is suggested that pancreatitis mortality is an important indicator of alcohol-related harm, not least because a large amount of morbidity is likely to be connected to the mortality rate.
Production of enterotoxins and toxic shock syndrome toxin by Staphylococcus aureus isolated from bovine mastitis in Brazil

The production of toxic shock syndrome toxin 1 (TSST‐1) and enterotoxins (SE) A, B, C and D by bovine mastitis isolates of Staphylococcus aureus was evaluated by immunodiffusion using the Optimum‐Sensitivity Plate method. S. aureus strains were isolated from bovine mastitis in 23 dairy herds in the state of Minas Gerais, Brazil, during 1994–9. Of 127 isolates, 83 (65·04%) produced one or several toxins, and among them production of SE was found in 54 (43·0%) isolates, of which 1138 (29·09%) secreted enterotoxin identified as type D. TSST‐1 was found in 5829 (45·723·0%) isolates.
Enteroviruses in sludge: multiyear experience with four wastewater treatment plants

We describe our experience with the isolation of viruses from four treatment plants located in different geographic areas. Over a period of 3 years, 297 enteroviruses were isolated from 307 sludge samples. The highest frequency of viral isolation (92%), including multiple isolates from single samples, was obtained from a treatment plant serving the smallest population. Excluding the polioviruses, 22 different enterovirus serotypes were isolated. The methods used to isolate the viruses were relatively simple and included an elution procedure in which beef extract was used and a disinfection step. No concentration procedure was used. Of three cell culture systems used, the RD line of human rhabdomyosarcoma cells was by far the most useful for the isolation of echoviruses; BGM and HeLa cells were particularly useful for the isolation of group B coxsackieviruses. A seasonal effect on viral isolation rates from sludge was observed.
Expression of eukaryotic‐like protein in the microbiome of sponges

Eukaryotic‐like proteins (ELPs) are classes of proteins that are found in prokaryotes, but have a likely evolutionary origin in eukaryotes. ELPs have been postulated to mediate host–microbiome interactions. Recent work has discovered that prokaryotic symbionts of sponges contain abundant and diverse genes for ELPs, which could modulate interactions with their filter‐feeding and phagocytic host. However, the extent to which these ELP genes are actually used and expressed by the symbionts is poorly understood. Here, we use metatranscriptomics to investigate ELP expression in the microbiomes of three different sponges (Cymbastella concentrica, Scopalina sp. and Tedania anhelens). We developed a workflow with optimized rRNA removal and in silico subtraction of host sequences to obtain a reliable symbiont metatranscriptome. This showed that between 1.3% and 2.3% of all symbiont transcripts contain genes for ELPs. Two classes of ELPs (cadherin and tetratricopeptide repeats) were abundantly expressed in the C. concentrica and Scopalina sp. microbiomes, while ankyrin repeat ELPs were predominant in the T. anhelens metatranscriptome. Comparison with transcripts that do not encode ELPs indicated a constitutive expression of ELPs across a range of bacterial and archaeal symbionts. Expressed ELPs also contained domains involved in protein secretion and/or were co‐expressed with proteins involved in extracellular transport. This suggests these ELPs are likely exported, which could allow for direct interaction with the sponge. Our study shows that ELP genes in sponge symbionts represent actively expressed functions that could mediate molecular interaction between symbiosis partners.
RIG‐I activation inhibits HIV replication in macrophages

The RIG‐I signaling pathway is critical in the activation of the type I IFN‐dependent antiviral innate‐immune response. We thus examined whether RIG‐I activation can inhibit HIV replication in macrophages. We showed that the stimulation of monocyte‐derived macrophages with 5′ppp‐dsRNA, a synthetic ligand for RIG‐I, induced the expression of RIG‐I, IFN‐α/β, and several IRFs, key regulators of the IFN signaling pathway. In addition, RIG‐I activation induced the expression of multiple intracellular HIV‐restriction factors, including ISGs, several members of the APOBEC3 family, tetherin and CC chemokines, the ligands for HIV entry coreceptor (CCR5). The inductions of these factors were associated with the inhibition of HIV replication in macrophages stimulated by 5′ppp‐dsRNA. These observations highlight the importance of RIG‐I signaling in macrophage innate immunity against HIV, which can be beneficial for the treatment of HIV disease, where intracellular immune defense is compromised by the virus.
Dynamin‐Actin Cross Talk Contributes to Phagosome Formation and Closure

Phagocytosis is a mechanism used by macrophages to internalize and eliminate microorganisms or cellular debris. It relies on profound rearrangements of the actin cytoskeleton that is the driving force allowing plasma membrane extension around the particle. The closure step of phagocytosis, however, remains poorly defined. We used a dedicated experimental setup with Total Internal Reflection Fluorescence Microscopy (TIRFM) to monitor phagosome formation and closure in three dimensions in living cells. We show that dynamin‐2, which mediates the scission of endocytic vesicles, was recruited early and concomitantly with actin during phagosome formation. Dynamin‐2 accumulated at the site of phagosome closure in living macrophages. Inhibition of its activity with dominant negative mutants or drugs demonstrated that dynamin‐2 is implicated in actin dynamics and pseudopod extension. Depolymerization of actin led to impaired dynamin‐2 recruitment or activity. Finally, we show that dynamin‐2 plays a critical role in the effective scission of the phagosome from the plasma membrane. Thus, we establish that a cross talk between actin and dynamin takes place for phagosome formation and closure before dynamin functions for scission.
Dominant Species and Diversity: Linking Relative Abundance to Controls of Species Establishment

Ecological theories make divergent predictions about whether extant species inhibit or promote the establishment of new species and which aspects of community composition determine these interactions; diversity, individual dominant species, and neutral interactions have all been argued to be most important. We experimentally tested these predictions by removing plant biomass (0%, 7%, 100%) from boreal forest understory communities. The 7% removals were restricted to the numerically dominant species, the second most dominant species, or many low‐abundance species, thereby separating the effects of species composition from those of biomass. We tested the effects of all removal treatments on seedling establishment. Competitive effects were driven by one dominant species and were inconsistent with resource complementarity, neutral, or competition‐colonization models. Facilitative effects were apparent only following removal of all vegetation, of which the most dominant species comprised more than 80%. Our results indicate that numerically dominant species in a community can influence the establishment of new species more than species diversity, but the direction of interaction can shift from facilitative to competitive as community density increases.
NK Cells Can Trigger Allograft Vasculopathy: The Role of Hybrid Resistance in Solid Organ Allografts1

Progressive arterial stenosis (cardiac allograft vasculopathy (CAV)) is a leading cause of long-term failure of organ transplants. CAV remains intractable, in part because its mechanisms are insufficiently understood. A central proposition is that MHC-driven alloimmune processes play a necessary role in CAV, as shown by the absolute requirement for histoincompatibility between donor and recipient for its production. Two immunological pathways have been implicated involving reactivity to donor MHC Ags by either T or B cells. In this study, we use a novel system of semiallogeneic cardiac transplants between parental donors and F1 hybrid recipients to provide evidence that NK cells, members of the innate immune system, also contribute to the generation of CAV in mice. This finding marks the first demonstration that the hybrid resistance phenomenon occurs in solid organ allografts. Extension of these experiments to recipients deficient in T cells demonstrates that this third pathway of CAV, the NK cell-triggered pathway, involves the recruitment of T cells not responsive to donor alloantigens. Finally, transplants performed with donors or recipients deficient in IFN-γ revealed that recipient-derived IFN-γ is necessary for CAV formation in parental to F1 transplants, suggesting a possible effector mechanism by which NK cells can promote CAV. Together, these results define a previously unknown pathway toward CAV and assign a novel role to NK cells in organ allograft rejection.
Periimplant soft tissue barrier at experimental one-piece mini-implants with different surface topography in humans: A light-microscopic overview and histometric analysis.

BACKGROUND Following connection to the oral cavity, osseointegrated dental implants and surrounding tissues are exposed to microbiologic and biomechanical challenges. The establishment of a firm functional periimplant soft tissue barrier (PSTB) is considered to be important to protect the implant's interface from invasion of bacteria. The current knowledge on the histologic architecture of the PSTB is mainly based on animal experiments. PURPOSE The aim of this study was to histologically characterize the PSTB formed in humans around experimental one-piece mini-implants with different surface topography. MATERIALS AND METHODS Five patients received a total of 12 experimental titanium, one-piece mini-implants with an oxidized (n = 4), an acid-etched (n = 4), or a machined (n = 4) surface distal to therapeutic implants. Following transmucosal healing of 8 weeks and at abutment connection of the regular implants, the mini-implants were harvested with a layer of surrounding hard and soft tissue. The specimens were fixed and processed for histologic sectioning according to standard procedures. The most central bucco-oral section cut in the long axis was used for morphologic analyses of the PSTB. The vertical soft tissue morphology was quantified using histometric measurements. RESULTS The overall height of the soft tissue, that is, the biologic width, was around 4 to 4.5 mm and consisted of an epithelial and a supracrestal connective tissue barrier. The junctional epithelium established the attachment to the implant surface, whereas the collagen fibers and fibroblasts of the connective tissue seal were oriented parallel to the implant. The epithelial attachment was shorter at the oxidized and acid-etched surfaces compared with the machined surfaces. Accordingly, the oxidized and acid-etched mini-implants exhibited a longer zone of connective tissue seal. CONCLUSION The periimplant soft tissue formed at the experimental one-piece mini-implants in humans was of a character similar to that described in animal studies. The oxidized and acid-etched implants revealed less epithelial downgrowth and longer connective tissue seal than machined implants.
Vectored Gag and Env but Not Tat Show Efficacy against Simian-Human Immunodeficiency Virus 89.6P Challenge in Mamu-A*01-Negative Rhesus Monkeys

ABSTRACT Simian-human immunodeficiency virus (SHIV) challenge studies in rhesus macaques were conducted to evaluate the efficacy of adenovirus-based vaccines in the context of different major histocompatibility complex class I genetic backgrounds and different vaccine compositions. Mamu-A*01 allele-negative rhesus monkeys were immunized with one of the following vaccine constructs: (i) replication-defective recombinant adenovirus type 5 (Ad5) expressing human immunodeficiency virus type 1 (HIV-1) Tat (Ad5/HIVTat); (ii) Ad5 vector expressing simian immunodeficiency virus (SIV) Gag (Ad5/SIVGag); (iii) Ad5 vector expressing the truncated HIV-1jrfl Env, gp140 (Ad5/gp140_jrfl); (iv) Ad5 vector expressing the SHIV-89.6P gp140 (Ad5/gp140_89.6P); or (v) the combination of Ad5/SIVGag and Ad5/gp140_jrfl. Following intravenous challenge with SHIV-89.6P, only those cohorts that received vaccines expressing Gag or Env exhibited an attenuation of the acute viremia and associated CD4-cell lymphopenia. While no prechallenge neutralizing antibody titers were detectable in either Ad5/gp140-vaccinated group, an accelerated neutralizing antibody response was observed in the Ad5/gp140_89.6P-vaccinated group upon viral challenge. The set-point viral loads in the Ad5/SIVGag- and Ad5/gp140_jrfl-vaccinated groups were associated with the overall strength of the induced cellular immune responses. To examine the contribution of Mamu-A*01 allele in vaccine efficacy against SHIV-89.6P challenge, Mamu-A*01-positive monkeys were immunized with Ad5/SIVGag. Vaccine-mediated protection was significantly more pronounced in the Mamu-A*01-positive monkeys than in Mamu-A*01-negative monkeys, suggesting the strong contributions of T-cell epitopes restricted by the Mamu-A*01 molecule. The implications of these results in the development of an HIV-1 vaccine will be discussed.
Activation and Regulation of Platelet-Activating Factor Receptor: Role of Gi and Gq in Receptor-Mediated Chemotactic, Cytotoxic, and Cross-Regulatory Signals1

Platelet-activating factor (1-O-alkyl-2-acetyl-sn-glycerolphosphocholine; PAF) induces leukocyte accumulation and activation at sites of inflammation via the activation of a specific cell surface receptor (PAFR). PAFR couples to both pertussis toxin-sensitive and pertussis toxin-insensitive G proteins to activate leukocytes. To define the role(s) of Gi and Gq in PAF-induced leukocyte responses, two G-protein-linked receptors were generated by fusing Gαi3 (PAFR-Gαi3) or Gαq (PAFR-Gαq) at the C terminus of PAFR. Rat basophilic leukemia cell line (RBL-2H3) stably expressing wild-type PAFR, PAFR-Gαi3, or PAFR-Gαq was generated and characterized. All receptor variants bound PAF with similar affinities to mediate G-protein activation, intracellular Ca2+ mobilization, phosphoinositide (PI) hydrolysis, and secretion of β-hexosaminidase. PAFR-Gαi3 and PAFR-Gαq mediated greater GTPase activity in isolated membranes than PAFR but lower PI hydrolysis and secretion in whole cells. PAFR and PAFR-Gαi3, but not PAFR-Gαq, mediated chemotaxis to PAF. All three receptors underwent phosphorylation and desensitization upon exposure to PAF but only PAFR translocated βarrestin to the cell membrane and internalized. In RBL-2H3 cells coexpressing the PAFRs along with CXCR1, IL-8 (CXCL8) cross-desensitized Ca2+ mobilization to PAF by all the receptors but only PAFR-Gαi3 activation cross-inhibited the response of CXCR1 to CXCL8. Altogether, the data indicate that Gi exclusively mediates chemotactic and cross-regulatory signals of the PAFR, but both Gi and Gq activate PI hydrolysis and exocytosis by this receptor. Because chemotaxis and cross-desensitization are exclusively mediated by Gi, the data suggest that differential activation of both Gi and Gq by PAFR likely mediate specific as well as redundant signaling pathways.
Biomimetic transformations of parthenolide.

An investigation of BF3-mediated rearrangements of parthenolide [1] provided micheliolide [5] as a major product. Minor reaction products included 10 (14)-dehydro-5 alpha-hydroxy-trans-guaianolide [2], 9,10-dehydro-5 alpha-hydroxy-trans-guaianolide [3], the xanthanolide 2-desoxy-6-epi-parthemollin [4], 1,2-dehydro-4 alpha-hydroxyguaianolide [6], 11,13-dehydrocompressanolide [7], and bicyclo[6.2. 0]dec-10(14)-en-12,6-olide [8]. Their mechanisms of formation were interpreted as rearrangements involving carbocation intermediates.
First Detection of G 12 Rotaviruses in Newborns with Neonatal Rotavirus Infection at All India Institute of Medical Sciences , New Delhi , India

First Detection of G12 Rotaviruses in Newborns with Neonatal Rotavirus Infection at All India Institute of Medical Sciences, New Delhi, India Pratima Ray,* S. Sharma, R. K. Agarwal, K. Longmei, J. R. Gentsch, V. K. Paul, R. I. Glass, and M. K. Bhan Center for Diarrheal Disease Research and Neonatal Unit, Department of Pediatrics, All India Institute of Medical Sciences, New Delhi 110029, India; Gastroenteritis and Respiratory Viruses Laboratory Branch, Centers for Disease Control and Prevention, Atlanta, Georgia; and Fogarty International Center, National Institutes of Health, Bethesda, Maryland
Subclinical Atherosclerosis in Patients With Inflammatory Bowel Diseases: A Systematic Review and Meta-Analysis

We evaluated the differences in major markers of cardiovascular (CV) risk between inflammatory bowel diseases (IBDs) and controls by a systematic review and a meta-analysis. We searched PubMed, EMBASE, and Cochrane databases for literature comparing CV risk markers in IBDs and controls. The overall mean carotid intima–media thickness (CIMT), flow-mediated dilation (FMD%), and carotid–femoral pulse wave velocity (cfPWV) difference between patients with IBDs and control groups were calculated. Twenty-eight studies were included in the meta-analysis, including 16 studies with data on CIMT, 7 studies reporting FMD%, and 9 studies on cfPWV. Compared to controls, patients with IBDs showed significantly higher CIMT (standardized mean difference [SMD]: 0.534 mm; 95% confidence interval [CI], 0.230 to 0.838; P = .001), significantly lower FMD% (SMD, −0.721%; 95% CI, −1.020 to −0.421; P < .0001), and significantly increased cfPWV (SMD, 0.849; 95% CI, 0.589 to 1.110; P < .0001). When analyzing subgroups with ulcerative colitis and Crohn disease (CD), all results were still significant except CIMT in CD. Our findings support the current evidence for an elevated CV burden in patients with IBD and support the clinical utility of markers of subclinical atherosclerosis in the management of these patients.
Publication bias in obesity treatment trials?

OBJECTIVE The present investigation examined the extent of publication bias (namely the tendency to publish significant findings and file away non-significant findings) within the obesity treatment literature. DESIGN Quantitative literature synthesis of four published meta-analyses from the obesity treatment literature. Interventions in these studies included pharmacological, educational, child, and couples treatments. METHODS To assess publication bias, several regression procedures (for example weighted least-squares, random-effects multi-level modeling, and robust regression methods) were used to regress effect sizes onto their standard errors, or proxies thereof, within each of the four meta-analysis. A significant positive beta weight in these analyses signified publication bias. RESULTS There was evidence for publication bias within two of the four published meta-analyses, such that reviews of published studies were likely to overestimate clinical efficacy. The lack of evidence for publication bias within the two other meta-analyses might have been due to insufficient statistical power rather than the absence of selection bias. CONCLUSIONS As in other disciplines, publication bias appears to exist in the obesity treatment literature. Suggestions are offered for managing publication bias once identified or reducing its likelihood in the first place.