Miracle-dz/UniFAR-FTUs huggingface dataset:
Cytomegalovirus-Specific T Cell Immunity Is Maintained in Immunosenescent Rhesus Macaques

Although CMV infection is largely benign in immunocompetent people, the specific T cell responses associated with control of this persistent virus are enormous and must be maintained for life. These responses may increase with advanced age and have been linked to an “immune risk profile” that is associated with poor immune responsiveness and increased mortality in aged individuals. Based on this association, it has been suggested that CMV-specific T cell responses might become dysfunctional with age and thereby contribute to the development of immune senescence by homeostatic disruption of other T cell populations, diminished control of CMV replication, and/or excess chronic inflammation. In this study, we use the rhesus macaque (RM) model of aging to ask whether the quantity and quality of CMV-specific T cell responses differ between healthy adult RMs and elderly RMs that manifest hallmarks of immune aging. We demonstrate that the size of the CD4+ and CD8+ CMV-specific T cell pools are similar in adult versus old RMs and show essentially identical phenotypic and functional characteristics, including a dominant effector memory phenotype, identical patterns of IFN-γ, TNF-α, and IL-2 production and cytotoxic degranulation, and comparable functional avidities of optimal epitope-specific CD8+ T cells. Most importantly, the response to and protection against an in vivo CMV challenge were identical in adult and aged RMs. These data indicate that CMV-specific T cell immunity is well maintained in old RMs and argue against a primary role for progressive dysfunction of these responses in the development of immune senescence.
Pooled nucleic acid testing to identify antiretroviral treatment failure during HIV infection in Seoul, South Korea

Abstract Background: There have been various efforts to identify less costly but still accurate methods for monitoring the response to HIV treatment. We evaluated a pooling method to determine if this could improve screening efficiency and reduce costs while maintaining accuracy in Seoul, South Korea. Methods: We conducted the first prospective study of pooled nucleic acid testing (NAT) using a 5 minipool + algorithm strategy versus individual viral load testing for patients receiving antiretroviral therapy (ART) between November 2011 and August 2012 at an urban hospital in Seoul, South Korea. The viral load assay used has a lower level of detection of 20 HIV RNA copies/ml, and the cost per assay is US$ 136. The 5 minipool +algorithm strategy was applied and 43 pooled samples were evaluated. The relative efficiency and accuracy of the pooled NAT were compared with those of individual testing. Results: Using the individual viral load assay, 15 of 215 (7%) plasma samples had more than 200 HIV RNA copies/ml. The pooled NAT using the 5 minipool + algorithm strategy was applied to 43 pooled samples; 111 tests were needed to test all samples when virologic failure was defined at HIV RNA ≥ 200 copies/ml. Therefore, 104 tests were saved over individual testing, with a relative efficiency of 0.48. When evaluating costs, a total of US$ 14,144 was saved for 215 individual samples during 10 months. The negative predictive value was 99.5% for all samples with HIV RNA ≥ 200 copies/ml. Conclusions: The pooled NAT with 5 minipool + algorithm strategy seems to be a very promising approach to effectively monitor patients receiving ART and to save resources.
Efficacy of a once-a-week screening programme to control extended-spectrum beta-lactamase-producing bacteria in a neonatal intensive care unit

Abstract Background: Extended-spectrum beta-lactamase (ESBL)-producing bacteria are an escalating problem threatening health. Devastating consequences can result in neonatal intensive care units (NICU) due to these bacteria. The aim of this study was to investigate the efficacy of once-a-week screening (July 2010 to September 2012) versus screening on demand (April 2008 to June 2010). Materials and methods: The investigation was an open retrospective descriptive study comparing 2 unpaired groups, the first exposed to screening on demand and the second to screening once a week. All other infection control measures were unchanged. Both groups were cared for in the NICU of Skåne University Hospital. Parameters compared were the proportion of cultured neonates, prevalence, time before detection, number of secondary cases, and clinical infections due to ESBL-producing bacteria. Results: The proportion of cultured neonates increased from 28% to 49% (p < 0.05) in period 2. The time from admission to detection was 8 days shorter in period 2 (p < 0.05). Secondary cases decreased from 44% to 9% (p < 0.05), and clinical infections from 4 to 0 cases (p < 0.05). During period 2, the prevalence of colonization was 1.77%. Conclusions: Once-a-week screening is a strategy to control the epidemiology of unwanted pathogens among newborn infants. It provides the opportunity for early intervention, thereby avoiding secondary cases and infections. Premature neonates in particular benefit from this approach. The prevalence of ESBL of 1.77% is low from an international perspective. ESBL appear to be introduced onto the ward by mothers colonized with ESBL.
Prevalencia de parásitos intestinales en niños de diferentes niveles de educación del distrito de San Marcos, Ancash, Perú.

Objetivo: Investigar la prevalencia de parasitosis intestinal en estudiantes del Distrito de San Marcos, en el departamento de Ancash, Peru. Material y metodos: Se analizaron en total 1303 muestras de heces de ninos de nivel inicial, primario y secundario, mediante examen directo. Resultados: Se encontro uno o mas parasitos intestinales en 65,0% de los estudiantes. De las 845 muestras positivas para parasitos, se encontro un parasito en 82,0% dos en18,0% predominando los protozoarios sobre los helmintos. Los enteroparasitos patogenos encontrados segun su frecuencia fueron: Giardia lamblia 23,7%, Ascaris lumbricoides 16,9% e Hymenolepis nana 9,6%. La frecuencia del enteroparasito no patogeno Entamoeba coli fue 31,8%. Conclusiones: Existe un alto indice de parasitismo en la poblacion rural de la sierra de Ancash, lo que estaria en relacion con las deficientes condiciones de saneamiento ambiental en esta zona, por lo que es necesario que en los colegios de la zona, se de educacion sobre higiene personal y ademas, mejorar las condiciones de saneamiento.
Anti-inflammatory, analgesic and antioxidant properties of Bursera morelensis bark from San Rafael, Coxcatlán, Puebla (México): Implications for cutaneous wound healing

Bursera morelensis Ramirez bark is used by people of San Rafael, Coxcatlan, in Puebla State, Mexico, as a traditional remedy to heal skin wounds. In the present study, we evaluated anti-inflammatory, analgesic and antioxidant activities of the methanolic extract (MP) obtained from the bark. Our results demonstrated that MP of B. morelensispossesses anti-inflammatory activity by inhibition of paw edema induced by carrageenan in rats. The dose of 50 mg/kg was comparable with indomethacin used as reference standard. The extract (50 mg/kg) also diminished 28.01% of the number of neutrophils migrating into the peritoneal cavity. At the same dose, an analgesic activity of the extract was observed by inhibition of acetic acid induced writhing response in mice. The extract also showed a strong capacity of DPPH radical scavenging with an EC50 of 3.05 µg/mL that was comparable with quercetin (EC50 = 4.45 µg/mL). The biological activities of the extract are attributed to its mixture of phenolic compounds (50.5%), particularly phenilpropanoids and flavonoids. The anti-inflammatory, analgesic and antioxidant properties shown by the extract favor the wound healing, thus controlling the inflammatory process without inhibiting it. This study supports the traditional use of B. morelensis bark for the treatment of acute skin wounds. Key words: Bursera morelensis, anti-inflammatory, analgesic, antioxidant, wound healing, phenolic compounds
Adenosinergic Regulation of the Expansion and Immunosuppressive Activity of CD11b+Gr1+ Cells

Extracellular adenosine and purine nucleotides are elevated in many pathological situations associated with the expansion of CD11b+Gr1+ myeloid-derived suppressor cells (MDSCs). Therefore, we tested whether adenosinergic pathways play a role in MDSC expansion and functions. We found that A2B adenosine receptors on hematopoietic cells play an important role in accumulation of intratumoral CD11b+Gr1high cells in a mouse Lewis lung carcinoma model in vivo and demonstrated that these receptors promote preferential expansion of the granulocytic CD11b+Gr1high subset of MDSCs in vitro. Flow cytometry analysis of MDSCs generated from mouse hematopoietic progenitor cells revealed that the CD11b+Gr-1high subset had the highest levels of CD73 (ecto-5′-nucleotidase) expression (Δmean fluorescence intensity [MFI] of 118.5 ± 16.8), followed by CD11b+Gr-1int (ΔMFI of 57.9 ± 6.8) and CD11b+Gr-1−/low (ΔMFI of 12.4 ± 1.0) subsets. Even lower levels of CD73 expression were found on Lewis lung carcinoma tumor cells (ΔMFI of 3.2 ± 0.2). The high levels of CD73 expression in granulocytic CD11b+Gr-1high cells correlated with high levels of ecto-5′-nucleotidase enzymatic activity. We further demonstrated that the ability of granulocytic MDSCs to suppress CD3/CD28-induced T cell proliferation was significantly facilitated in the presence of the ecto-5′-nucleotidase substrate 5′-AMP. We propose that generation of adenosine by CD73 expressed at high levels on granulocytic MDSCs may promote their expansion and facilitate their immunosuppressive activity.
Information Technology and Quantitative Management ( ITQM 2015 ) The Decision Model for the Internet Services in the Context of Development

The Internet Services in the Context of Development (ISCD) model is structured in four levels of hierarchy based on the Analytical Hierarchy Processes (AHP) theory. The model provides a formal approach of establishing the relative importance of Internet services in the context of fostering national development. This paper presents the fundamental concepts of the model. Pairwise Comparisons (PCs) technique the cornerstone of the AHP theory is used as the baseline technique for measuring the intensity of preference between the Internet traffic classes (therein their respective services they deliver to end users) in the process of formulating the judgment matrix. The ISCD model is modelled to process data obtained from a group of individual decision makers that are independent from each other. Hence decision makers are weighted in the process of aggregating their priority vectors and the normalized weighted geometric mean method (NWGMM) is used to compute the group’s priority vector, which is the final output of the model. © 2015 The Authors. Published by Elsevier B.V. Selection and/or peer-review under responsibility of the organizers of ITQM 2015
FLUOCINOLONE ACETONIDE 0·2% CREAM—A CO‐OPERATIVE CLINICAL TRIAL *

SUMMARY. The response to a 0·2% fluocinolone acetonide cream is reported in 192 patients with a variety of skin conditions. Results were particularly successful in chronic discoid lupus erythematosus, necrobiosis lipoidica, lichen planus and granuloma annulare. Some cases of pustular psoriasis of the palms and of keloids responded well. Occasional benefit occurred in mycosis fungoides and in pemphigus erythematosus but in general the results in these last 2 conditions were disappointing. No serious adverse effects were seen in this series.
Relevance of the MEK/ERK Signaling Pathway in the Metabolism of Activated Macrophages: A Metabolomic Approach

The activation of immune cells in response to a pathogen involves a succession of signaling events leading to gene and protein expression, which requires metabolic changes to match the energy demands. The metabolic profile associated with the MAPK cascade (ERK1/2, p38, and JNK) in macrophages was studied, and the effect of its inhibition on the specific metabolic pattern of LPS stimulation was characterized. A [1,2-[13C]2]glucose tracer-based metabolomic approach was used to examine the metabolic flux distribution in these cells after MEK/ERK inhibition. Bioinformatic tools were used to analyze changes in mass isotopomer distribution and changes in glucose and glutamine consumption and lactate production in basal and LPS-stimulated conditions in the presence and absence of the selective inhibitor of the MEK/ERK cascade, PD325901. Results showed that PD325901-mediated ERK1/2 inhibition significantly decreased glucose consumption and lactate production but did not affect glutamine consumption. These changes were accompanied by a decrease in the glycolytic flux, consistent with the observed decrease in fructose-2,6-bisphosphate concentration. The oxidative and nonoxidative pentose phosphate pathways and the ratio between them also decreased. However, tricarboxylic acid cycle flux did not change significantly. LPS activation led to the opposite responses, although all of these were suppressed by PD325901. However, LPS also induced a small decrease in pentose phosphate pathway fluxes and an increase in glutamine consumption that were not affected by PD325901. We concluded that inhibition of the MEK/ERK cascade interferes with central metabolism, and this cross-talk between signal transduction and metabolism also occurs in the presence of LPS.
Pathologic Predictors of Tumor Response to Preoperative Chemotherapy in Locally Advanced Breast Carcinoma

Abstract: Tumor response to preoperative chemotherapy varies from complete to partial to none. To evaluate pathologic predictors of tumor response to preoperative chemotherapy, we reviewed 287 cases of locally advanced breast carcinoma treated with chemotherapy prior to definitive surgery. The patients ranged in age from 18 to 79 years (mean, 48 years). There were 77 (26.8%) patients with stage II disease, 194 (67.6%) with stage III disease, and 16 (5.6%) with stage IV disease. Following the initial diagnosis of invasive carcinoma (by fine‐needle aspirate or cutting needle biopsy), the patients received three to four cycles of both doxorubicin‐based and cyclophosphamide‐based regimens followed by mastectomy or lumpectomy with axillary dissection. The pathologic parameters that were evaluated included stage, clinical tumor size, and tumor nuclear grade (NG). The latter was performed on fine‐needle aspirates using Black's nuclear grading system wherein NG1 was considered well differentiated; NG2, moderately differentiated; and NG3, poorly differentiated. Based on pathologic examination of the resected specimens, tumor responses were categorized into complete response, partial response, no response, or progressive disease. The overall response rate was 71% (12% complete and 59% partial responses). In univariate analyses, tumor size and nuclear grade were significantly related to pathologic tumor response to chemotherapy (p = 0.04 and p = 0.0003, respectively), while disease stage was not (p = 0.17). In multivariate analyses, size remained significant even when NG was present in the equation (p = 0.013). Similarly, when size was included, NG remained significant (p = 0.002). NG3 tumors showed better response than NG2 or NG1 tumors did. While 19.3% of NG3 tumors showed complete response, none of the NG1 tumors completely responded to chemotherapy. Initial tumor size was inversely proportional to degree of tumor response. Our findings indicate that tumor clinical size and nuclear grade are important independent predictors of response to preoperative chemotherapy and that poorly differentiated tumors and small tumors showed the most response.
Perception of Fatigue Among Surgeons During Night Shifts

It is well known that sleep deprivation induces fatigue and that fatigue induces impaired cognition. Studies have demonstrated that long work hours, restricted sleep, time pressure and high demands may cause impaired performance in physicians. Some studies have shown through laparoscopic simulation that surgeons, when deprived of sleep, take longer to perform the procedure, make more unnecessary movements with their instruments and significantly more mistakes. Surgeons with an opportunity for sleep of less than 6 hours on the previous on-call night shift had an 83% increase in risk of postoperative complications when working the following day.
High incidence of independent second malignancies after non-muscle-invasive bladder cancer

Abstract Objective. The incidence of urogenital tumours is constantly increasing as a result of over-proportional ageing of the population in industrialized nations. Follow-up of non-muscle-invasive bladder cancer (NMIBC) primarily relies on the detection of either relapse or progression and does not include screening for second malignancies. This study investigated the incidence of independent non-urothelial second malignancies and associated risk factors in patients with NMIBC. Material and methods. The charts of 380 consecutive patients (297 men and 83 women) with newly diagnosed NMIBC over a 16-year period at a Swiss hospital were analysed retrospectively. Age, stage of bladder tumour, smoking status, and occurrence of second and third malignancies were registered. Observed incidences of independent non-urothelial malignancies were compared with age- and gender-specific rates based on data from the National Institute for Cancer Epidemiology and Registration by calculating standardized incidence ratios (SIRs). Results. Mean age at first NMIBC diagnosis was 69.9 years. Histological stage of the NMIBC was pTa in 241 patients (63.4%), pT1 in 102 (26.8%)and pTis in 37 (9.7%). During follow-up, 62 independent non-urothelial second or third malignancies were observed in 48 men (16.2%) and 10 women (12.0%). In male patients, prostate and lung cancer (SIR 4.3 and 5.7, respectively) were more frequent than expected in the general population, as were lung and uterine cancer in women. Conclusions. Follow-up in patients with NMIBC should pay special attention to independent non-urothelial malignancies. Investigations for non-urological malignant disease, especially for lung cancer, should form part of the standard follow-up in NMIBC patients.
Vitamin D Inhibits Monocyte/Macrophage Proinflammatory Cytokine Production by Targeting MAPK Phosphatase-1

It is estimated that 1 billion people around the world are vitamin D deficient. Vitamin D deficiency has been linked to various inflammatory diseases. However, the mechanism by which vitamin D reduces inflammation remains poorly understood. In this study, we investigated the inhibitory effects of physiologic levels of vitamin D on LPS-stimulated inflammatory response in human blood monocytes and explored potential mechanisms of vitamin D action. We observed that two forms of the vitamin D, 1,25(OH)2D3, and 25(OH)D3, dose dependently inhibited LPS-induced p38 phosphorylation at physiologic concentrations, IL-6 and TNF-α production by human monocytes. Upon vitamin D treatment, the expression of MAPK phosphatase-1 (MKP-1) was significantly upregulated in human monocytes and murine bone marrow-derived macrophages (BMM). Increased binding of the vitamin D receptor and increased histone H4 acetylation at the identified vitamin D response element of the murine and human MKP-1 promoters were demonstrated. Moreover, in BMM from MKP1−/− mice, the inhibition of LPS-induced p38 phosphorylation by vitamin D was completely abolished. Vitamin D inhibition of LPS-induced IL-6 and TNF-α production by BMM from MKP-1−/− mice was significantly reduced as compared with wild-type mice. In conclusion, this study identified the upregulation of MKP-1 by vitamin D as a novel pathway by which vitamin D inhibits LPS-induced p38 activation and cytokine production in monocytes/macrophages.
A Unique Role for ITK in Survival of Invariant NKT Cells Associated with the p53-Dependent Pathway in Mice

Invariant NKT (iNKT) cells play important roles in the immune response. ITK and TXK/RLK are Tec family kinases that are expressed in iNKT cells; the expression level of ITK is ∼7-fold higher than that of TXK. Itk−/− mice have reduced iNKT cell frequency and numbers, with defects in development and cytokine secretion that are exacerbated in Itk/Txk double-knockout mice. In contrast, there is no iNKT cell defect in Txk−/− mice. To determine whether ITK and TXK play distinct roles in iNKT cell development and function, we examined mice that overexpress TXK in T cells at levels similar to Itk. Overexpression of TXK rescues the maturation and cytokine secretion of Itk−/− iNKT cells, as well as altered expression of transcription factors T-bet, eomesodermin, and PLZF. In contrast, the increased apoptosis observed in Itk−/− splenic iNKT cells is not affected by TXK overexpression, likely due to the lack of effect on the elevated expression of p53 regulated proapoptotic pathways Fas, Bax, and Bad in those cells. Supporting this idea, p53−/− and Bax−/− mice have increased splenic iNKT cells. Our results suggest that TXK plays an overlapping role with ITK in iNKT cell development and function but that ITK also has a unique function in the survival of iNKT cells, likely via a p53-dependent pathway.
Inflammatory Spleen Monocytes Can Upregulate CD11c Expression Without Converting into Dendritic Cells

Monocytes can differentiate into various cell types with unique specializations depending on their environment. Under certain inflammatory conditions, monocytes upregulate expression of the dendritic cell marker CD11c together with MHC and costimulatory molecules. These phenotypic changes indicate monocyte differentiation into a specialized subset of dendritic cells (DCs), often referred to as monocyte-derived DCs or inflammatory DCs (iDCs), considered important mediators of immune responses under inflammatory conditions triggered by infection or vaccination. To characterize the relative contribution of cDCs and iDCs under conditions that induce strong immunity to coadministered Ags, we analyzed the behavior of spleen monocytes in response to anti-CD40 treatment. We found that under sterile inflammation in mice triggered by CD40 ligation, spleen monocytes can rapidly and uniformly exhibit signs of activation, including a surface phenotype typically associated with their conversion into DCs. These inflammatory monocytes remain closely related to their monocytic lineage, preserving expression of CD115, scavenging function, tissue distribution and poor capacity for Ag presentation characteristic of their monocyte precursors. In addition, 3–4 d after delivery of the inflammatory stimuli, these cells reverted to a monocyte-associated phenotype typical of the steady state. These findings indicate that, in response to anti-CD40 treatment, spleen monocytes are activated and express certain DC surface markers without acquiring functional characteristics associated with DCs.
The Dutch Musculoskeletal Questionnaire (DMQ)

The Dutch Musculoskeletal Questionnaire (DMQ) is the subject of the 5th chapter of the Handbook of human factors and ergonomics methods. The DMQ allows ergonomists and occupational health professionals to measure work-related musculoskeletal risk factors and symptoms in worker populations in a quick yet standardized way. There are a standard version, a short version and an extended version. The questionnaire includes the following sections: background variables, tasks, musculoskeletal workload, work pace and psychosocial working conditions, health, lifestyle, perceived bottlenecks and ideas for improvements. This chapter gives background information (including an internetlink to download the DMQ), information about application and procedure.