Miracle-dz/UniFAR-FTUs huggingface dataset:
Nutritional and Pharmacological Strategies to Regulate Microglial Polarization in Cognitive Aging and Alzheimer’s Disease

The study of microglia, the immune cells of the brain, has experienced a renaissance after the discovery of microglia polarization. In fact, the concept that activated microglia can shift into the M1 pro-inflammatory or M2 neuroprotective phenotypes, depending on brain microenvironment, has completely changed the understanding of microglia in brain aging and neurodegenerative diseases. Microglia polarization is particularly important in aging since an increased inflammatory status of body compartments, including the brain, has been reported in elderly people. In addition, inflammatory markers, mainly derived from activated microglia, are widely present in neurodegenerative diseases. Microglial inflammatory dysfunction, also linked to microglial senescence, has been extensively demonstrated and associated with cognitive impairment in neuropathological conditions related to aging. In fact, microglia polarization is known to influence cognitive function and has therefore become a main player in neurodegenerative diseases leading to dementia. As the life span of human beings increases, so does the prevalence of cognitive dysfunction. Thus, therapeutic strategies aimed to modify microglia polarization are currently being developed. Pharmacological approaches able to shift microglia from M1 pro-inflammatory to M2 neuroprotective phenotype are actually being studied, by acting on many different molecular targets, such as glycogen synthase kinase-3 (GSK3) β, AMP-activated protein kinase (AMPK), histone deacetylases (HDACs), etc. Furthermore, nutritional approaches can also modify microglia polarization and, consequently, impact cognitive function. Several bioactive compounds normally present in foods, such as polyphenols, can have anti-inflammatory effects on microglia. Both pharmacological and nutritional approaches seem to be promising, but still need further development. Here we review recent data on these approaches and propose that their combination could have a synergistic effect to counteract cognitive aging impairment and Alzheimer’s disease (AD) through immunomodulation of microglia polarization, i.e., by driving the shift of activated microglia from the pro-inflammatory M1 to the neuroprotective M2 phenotype.
Increased Expression of Hsp40 Chaperones, Transcriptional Factors, and Ribosomal Protein Rpp0 Can Cure Yeast Prions*

The Sup35 (eRF3) translation termination factor of Saccharomyces cerevisiae can undergo a prion-like conformational conversion, thus resulting in the [PSI +] nonsense-suppressor determinant.In vivo this process depends critically on the chaperone Hsp104, whose lack or overexpression can cure [PSI +]. The use of artificial prion [PSI + PS] based on a hybrid Sup35PS with prion domain from the yeast Pichia methanolicaallowed us to uncover three more chaperones, Ssb1, Ssa1, and Ydj1, whose overexpression can cure prion determinants. Here, we used the [PSI + PS] to search a multicopy yeast genomic library for novel factors able to cure prions. It was found that overexpression of the Hsp40 family chaperones Sis1 and Ynl077w, chaperone Sti1, transcriptional factors Sfl1 and Ssn8, and acidic ribosomal protein Rpp0 can interfere with propagation and manifestation of [PSI + PS] in a prion strain-specific manner. Some of these factors also affected the manifestation and propagation of conventional [PSI +]. Excess of Sfl1, Ssn8, and Rpp0 influenced at least one of the tested chaperone-specific promoters,SSA4, HSP104, and model promoters, with either the heat shock or stress response elements. Thus, the induction of chaperone expression by these proteins could explain their prion-curing effects.
Reduced Vital Capacity in Insulin-Dependent Diabetes

Spirometry was performed on 88 children with insulindependent diabetes mellitus (IDDM) and 216 healthy controls living in Sheffield. Children with IDDM had significantly lower percentage predicted forced vital capacity (FVC) than did control children or reference norms. There was no evidence that the reduced FVC was confined to a subgroup of children, and there was no correlation with duration of IDDM or glycemic control. A longitudinal study of 27 children with IDDM did not show progressive deterioration in percentage predicted FVC with age. These findings suggest that a tendency toward reduced lung volumes exists in IDDM and may not be a direct result of the metabolic disturbances in the disease.
Impact du méthylmercure sur le potentiel de migration, le statut énergétique et les mécanismes de détoxication chez la civelle d’anguille européenne (Anguilla anguilla) : Etudes in situ et expérimentale

Europeenne, (Anguilla anguilla) a conduit a une diminution du nombre d’anguille jaune dans les bassins versants. En 2007, le reglement (CE) instaure que 60% des civelles pechees (<12 cm de long) doivent etre dedies a des operations de repeuplement. Cependant, pour migrer et coloniser un nouvel environnement, les civelles doivent avoir une bonne condition energetique. Or, les civelles ne s’alimentent pas ou peu durant leur migration estuarienne et la vitesse d’utilisation de leurs reserves depend de divers facteurs (temperature, contaminants etc.). Dans l’estuaire de l’Adour, differents travaux ont mis en evidence de fortes concentrations en methylmercure (MeHg) dans les sediments et une bioaccumulation de ce compose chez l’anguille jaune. L’exposition au MeHg entraine la mise en place de processus de detoxication qui pourraient etre couteux en energie ce qui, chez des organismes jeunant comme les civelles, conduirait a une perte de poids pouvant affecter leurs capacites de migration. Pour etudier l’impact du methylmercure sur le potentiel de migration des civelles, nous avons tout d’abord (1) effectuer un etat des lieux des concentrations en MeHg des civelles de l’estuaire de l’Adour, (2) evaluer l’effet du MeHg sur deux synchroniseurs de la migration estuarienne: le signal crepusculaire et l’alternance des marees chez les civelles grâce a l’utilisation de traceurs isotopiques et (3) etudier dans le milieu naturel (Adour) le comportement de migration, les taux de contamination au mercure et les mecanismes de detoxication des civelles. Nos resultats montrent des fluctuations temporelles et saisonnieres de la concentration en MeHg des civelles prelevees en entree et en milieu de l’estuaire. Par ailleurs, l’exposition au MeHg, en milieu controle, a augmente l'activite des civelles mais pas leur comportement de migration. Cependant, suite a la contamination, la structure mitochondriale et le metabolisme ont ete modifies suggerant un plus fort stress oxydant et une activation des defenses antioxydantes notamment des civelles ayant un faible potentiel de migration (non migrantes). En complement, l’etude en milieu naturel a mis en evidence une plus forte demande energetique pour les civelles non migrantes entrainant une augmentation du fonctionnement des mitochondries et pouvant conduire a un plus fort stress oxydant.
Hypoxia augments MHC class I antigen presentation via facilitation of ERO1‐α‐mediated oxidative folding in murine tumor cells

To establish an effective cancer immunotherapy, it is crucial that cancer cells present a cancer‐specific antigen in a hypoxic area, a hallmark of the tumor microenvironment. Here, we show the impact of hypoxia on MHC class I antigen presentation in vitro and in vivo in murine tumors. Activation of antigen‐specific CTLs by tumor cells that had been pre‐incubated under a condition of hypoxia was enhanced compared with that by tumor cells pre‐incubated under a condition of normoxia. Cell surface expression of MHC class I‐peptide complex on the tumor cells was increased under a condition of hypoxia, thereby leading to higher susceptibility to specific CTLs. We show that the hypoxia‐inducible ER‐resident oxidase ERO1‐α plays an important role in the hypoxia‐induced augmentation of MHC class I‐peptide complex expression. ERO1‐α facilitated oxidative folding of MHC class I heavy chains, thereby resulting in the augmentation of cell surface expression of MHC class I‐peptide complex under hypoxic conditions. These results suggest that since the expression of MHC class I‐peptide complex is augmented in a hypoxic tumor microenvironment, strategies for inhibiting the function of regulatory T cells and myeloid‐derived suppressor cells and/or immunotherapy with immune checkpoint inhibitors are promising for improving cancer immunotherapy.
Dynamic Changes in the Follicular Transcriptome and Promoter DNA Methylation Pattern of Steroidogenic Genes in Chicken Follicles throughout the Ovulation Cycle

The molecular mechanisms associated with follicle maturation and ovulation are not well defined in avian species. In this study, we used RNA-seq to study the gene expression profiles of the chicken follicles from different developmental stages (pre-hierarchical, pre-ovulatory and post-ovulatory). Transcriptomic analysis revealed a total of 1,277 and 2,310 genes were differentially expressed when follicles progressed through the pre-hierarchical to hierarchical and pre-ovulatory to post-ovulatory transitions, respectively. The differentially expressed genes (DEG) were involved in signaling pathways such as adherens junction, apoptosis and steroid biosynthesis. We further investigated the transcriptional regulation of follicular steroidogenesis by examining the follicle-specific methylation profiles of Star (steroidogenic acute regulatory protein), Cyp11a1 (cytochrome P450, family 11, subfamily a, polypeptide 1) and Hsd3b (hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerase 1), genes encoding the key enzymes for progesterone synthesis. The varied patterns of DNA methylation in proximal promoters of Star and Cyp11a1but not Hsd3b in different follicles could play a major role in controlling gene expression as well as follicular steroidogenic activity. Finally, the promoter-reporter analysis suggests that TGF-β could be involved in the regulation of Hsd3b expression during ovulation. Together, current data not only provide novel insights into the molecular mechanisms of follicular physiology in chicken follicles, but also present the first evidence of epigenetic regulation of ovarian steroidogenesis in avian species.
Characteristics of Acute Nongonococcal Urethritis in Men Differ by Sexual Preference

ABSTRACT Nongonococcal urethritis (NGU) is a common clinical syndrome, but no etiological agent is identified in a significant proportion of cases. Whether the spectrum of pathogens differs between heterosexual men (MSW) and men who have sex with men (MSM) is largely unstudied but of considerable clinical relevance. A retrospective review was done using the electronic medical record database of Melbourne Sexual Health Centre, Australia. Cases were first presentations of symptomatic acute NGU with ≥5 polymorphonuclear leukocytes (PMNL)/high-powered field (HPF) on urethral Gram stain between January 2006 and December 2011. First-stream urine was tested for Chlamydia trachomatis and Mycoplasma genitalium by PCR. Demographic, laboratory, and behavioral characteristics of cases were examined by univariate and multivariable analyses. Of 1,295 first presentations of acute NGU, 401 (32%; 95% confidence interval [CI] of 29 to 34%) had C. trachomatis and 134 (11%; 95% CI of 9 to 13%) had M. genitalium detected. MSM with acute NGU were less likely to have C. trachomatis (adjusted odds ratio [AOR] = 0.4; 95% CI of 0.3 to 0.6) or M. genitalium (AOR = 0.5; 95% CI of 0.3 to 0.8) and more likely to have idiopathic NGU (AOR = 2.4; 95% CI of 1.8 to 3.3), to report 100% condom use for anal/vaginal sex (AOR = 3.6; 95% CI of 2.7 to 5.0), or to have engaged in sexual activities other than anal/vaginal sex (AOR = 8.0; 95% CI of 3.6 to 17.8). Even when C. trachomatis or M. genitalium was detected, MSM were more likely than MSW to report consistent condom use (OR = 4.7; 95% CI of 2.6 to 8.3). MSM with acute NGU are less likely to have the established bacterial sexually transmitted infections (STIs) and more likely to report protected anal sex or sexual activity other than anal sex prior to symptom onset than MSW. These data suggest that the etiologic spectrum of pathogens differs between MSM and MSW in acute NGU and that relatively low-risk practices are capable of inducing acute NGU.
Growth hormone treatment, final height, insulin-like growth factors, ghrelin, and adiponectin in four siblings with Seckel syndrome

Abstract Objective: To report on the effect of growth hormone (GH) treatment on final height (FH) and to describe the insulin-like growth factor (IGF) system, ghrelin, and adiponectin (ADPN) in children with Seckel syndrome. Subjects and results: Four severely growth-retarded Iraqi siblings (two girls and two boys) with Seckel syndrome were referred at ages 16.5, 14.4, 12.4, and 10.4 years. They were born at term, but their growth was retarded and birth weight ranged between 1 and 1.5 kg. The children were healthy and had a normal response to GH provocative test. Long-term GH treatment of the youngest brother and sister increased the FH by 7.2 and 3.4 cm, respectively, compared with their older brother and sister. At FH, body mass index standard deviation scores (BMISDS) ranged from –3.0 to –3.9. Serum levels of immunoreactive IGF-1, bioactive IGF-1, and IGF-binding protein 3 were all within normal to high range before GH treatment and increased after GH treatment. Fasting plasma ghrelin remained severely reduced. Despite low BMISDS, plasma ADPN was moderately reduced and showed an almost complete absence of the low-molecular-weight subform. Conclusion: This is the first report on the effect of GH treatment on FH in children with Seckel syndrome. GH may have increased FH. In addition to growth defects and reduced BMISDS, patients with Seckel syndrome are characterized by low fasting ghrelin levels, low total ADPN, and near deficiency of the low-molecular-weight ADPN subform. The possible significance of the hormonal changes requires further investigations.
Introduction to functional programming

From the Publisher: This is a thorough introduction to the fundamental concepts of functional programming. The book clearly expounds the construction of functional programming as a process of mathematical calculation, but restricts itself to the mathematics relevant to actual program construction. It covers simple and abstract datatypes, numbers, lists, examples, trees, and efficiency. It includes a simple, yet coherent treatment of the Haskell class; a calculus of time complexity; and new coverage of monadic input-output.
Etude de l’établissement des réservoirs VIH lors de la primo-infection et de l’impact des traitements antirétroviraux très précoces sur ces réservoirs

La primo-infection est un moment critique de l’etablissement du reservoir justifiant de l’initiation d’un traitement precoce. Nous avons initie un essai randomise evaluant l’impact de deux ans d’un traitement antiretroviral intense (essai ANRS147 OPTIPRIM, tritherapie versus pentatherapie) sur le reservoir et avons initie des etudes physiopathologiques au cours de cet essai. Nous montrons ainsi la faible diversite genetique des virus en primo-infection dans les compartiments sanguins et rectaux. Le reservoir s’etablit des le premier mois de l’infection par diffusion d’un cluster viral homogene au sein des lymphocytaires T CD4 naifs (TN) et memoires centrales (TCM), transitionnelles (TTM), effectrices (TEM) quiescents. Il en resulte une perturbation de l’homeostasie lymphocytaire associee a une faible contribution au reservoir des cellules peu differenciees a longue demi-vie, TN et TCM. Par ailleurs nous montrons que la majorite des patients au moment de leur primo-infection n’ont pas la capacite de developper des reponses T CD8 a meme de supprimer la replication virale comme chez les patients HIV Controllers. Apres deux ans de traitement, nous observons que la diversite virale n’a pas evolue, par contre la taille du reservoir est fortement reduite. Les anomalies de l’homeostasie lymphocytaire T CD4 persistent, par contre le traitement tres precoce a permis de proteger les TN et TCM. Il n’y a pas de benefice additionnel d’une pentatherapie mais nous avons valide le concept qu’un traitement precoce permet d’induire un controle virologique au long cours apres arret de traitement. Nos resultats indiquent qu’un traitement plus long que deux ans permettrait de renforcer la diminution du reservoir. Ces resultats seront a prendre en compte pour l’elaboration de futurs essais en primo-infection visant a reduire le reservoir pour une remission au long cours.
Adherence and Decision Aids

Background. Patient adherence to medication or lifestyle interventions is a serious concern. Interventions to improve adherence exist, but their effects are usually small. Several authors suggested that decision aids may positively affect adherence. Objective. This presentation examines the role of decision aids in adherence research through development of a model and a narrative review. Methods and Results. I: A model was developed to organize pathways relating decision aids and adherence. There is clinical evidence for these pathways, suggesting that decision aids may potentially improve adherence. The model is helpful when considering measures to study decision aids and adherence. II: A narrative review of decision aids and adherence was done. A systematic search resulted in 11 randomized studies. Two studies, both in the hypertension management domain, were positive. Shortcomings were identified regarding the range of adherence measures, the sample size, and the study design. It is argued that outcomes for the option “nonadherent” behavior should be described explicitly in the decision aid to inform patients about the costs and benefits of nonadherent behavior. Conclusions. A relation between decision aids and adherence is plausible in view of the psychological and medical literature. A systematic search showed that experimental evidence relating decision aids and adherence is inconclusive. Rigorous trials on this topic are worthwhile. Such trials should employ adequate sample sizes, multiple adherence measures, and a control arm delivering usual care. The decision aid should describe the option “being nonadherent” and its outcomes.
Ornamental indoor plants in hospital rooms enhanced health outcomes of patients recovering from surgery.

BACKGROUND Clinical trials have not been reported concerning the health benefits of viewing indoor plants on stress and recovery of surgical patients within a hospital setting. Using various medical and psychologic measurements, this study performed a randomized clinical trial with surgical patients to evaluate whether plants in hospital rooms have therapeutic influences. METHODS Ninety (90) patients recovering from a hemorrhoidectomy were randomly assigned to either control or plant rooms. With half the patients, live plants were placed in their rooms during postoperative recovery periods. Data collected for each patient included length of hospitalization, analgesics used for postoperative pain control, vital signs, ratings of pain intensity, pain distress, anxiety and fatigue, the State-Trait Anxiety Inventory Form Y-1, the Environmental Assessment Scale, and the Patient's Room Satisfaction Questionnaire. RESULTS Viewing plants during the recovery period had a positive influence linking directly to health outcomes of surgical patients. Patients in hospital rooms with plants and flowers had significantly more positive physiologic responses evidenced by lower systolic blood pressure, and lower ratings of pain, anxiety, and fatigue than patients in the control room. Patients with plants also felt more positively about their rooms and evaluated them with higher satisfaction when compared with patients in similar rooms without plants. Based on patients' comments, plants brightened up the room environment, reduced stress, and also conveyed positive impressions of hospital employees caring for patients. CONCLUSIONS Findings of this study confirmed the therapeutic value of plants in the hospital environment as a noninvasive, inexpensive, and effective complementary medicine for surgical patients. Health care professionals and hospital administrators need to consider the use of plants and flowers to enhance healing environments for patients.
Clinical Significance of the Soleal Vein and Related Drainage Veins, in Calf Vein Thrombosis in Autopsy Cases with Massive Pulmonary Thromboembolism.

OBJECTIVE To clarify the histopathological characteristics of deep vein thrombosis (DVT) resulting in lethal pulmonary thromboembolism (PE). SUBJECTS AND METHODS We investigated 100 autopsy cases of PE from limb DVT. The distribution and chronology of DVT in each deep venous segment were examined. Venous segments were classified into three groups: iliofemoral vein, popliteal vein and calf vein (CV). The CV was subdivided into two subgroups, drainage veins of the soleal vein (SV) and non drainage veins of SV. RESULTS Eighty-nine patients had bilateral limb DVTs. CV was involved in all limbs with DVT with isolated calf DVTs were seen in 47% of patients. Fresh and organized thrombi were detected in 84% of patients. SV showed the highest incidence of DVTs in eight venous segments. The incidence of DVT gradually decreased according to the drainage route of the central SV. Proximal tips of fresh thrombi were mainly located in the popliteal vein and tibioperoneal trunk, occurring in these locations in 63% of limbs. CONCLUSIONS SV is considered to be the primary site of DVT; the DVT then propagated to proximal veins through the drainage veins. Lethal thromboemboli would occur at proximal veins as a result of proximal propagation from calf DVTs.
A Retrospective Study on Transmission of Adult T Cell Leukemia Virus by Blood Transfusion: Seroconversion in Recipients

Possible transmission of adult T cell leukemia virus (ATLV) by blood transfusion was studied retrospectively. Of 41 recipients of whole blood or blood components containing cells from donors having antibodies to antigen that is associated with ATLV (anti‐ATLA), 26 (63.4%) produced anti‐ATLA. However, no anti‐ATLA was detected in all 14 recipients of fresh‐frozen plasma prepared from anti‐ATLA‐positive donors. None of 252 recipients of blood with cell components from anti‐ATLA‐negative donors produced anti‐ATLA. The development of anti‐ATLA in the recipients may correspond to antibody production after establishment of primary infection with ATLV that is associated with cells in blood from anti‐ATLA‐positive donors who are ATLV carriers.
Effect of Meteorological Parameters on Fine and Coarse Particulate Matter Mass Concentration in a Coal-Mining Area in Zonguldak, Turkey

Abstract In this work, the effect of meteorological parameters and local topography on mass concentrations of fine (PM2.5) and coarse (PM2.5–10) particles and their seasonal behavior was investigated. A total of 236 pairs of samplers were collected using an Anderson Dichotomous sampler between December 2004 and October 2005. The average mass concentrations of PM2.5, PM2.5–10, and particulate matter less than 10 μm in aerodynamic diameter (PM10) were found to be 29.38, 23.85, and 53.23 μ/m3, respectively. The concentrations of PM2.5 and PM10 were found to be higher in heating seasons (December to May) than in summer The increase of relative humidity, cloudiness, and lower temperature was found to be highly related to the increase of particulate matter (PM) episodic events. During non-rainy days, the episodic events for PM2.5 and PM10 were increased by 30 and 10.7%, respectively. This is a result of the extensive use of fuel during winter for heating purposes and also because of stagnant air masses formed because of low temperature and low wind speed over the study area.