Miracle-dz/UniFAR-FTUs huggingface dataset:
Neural control of the lower urinary tract: Peripheral and spinal mechanisms

This review deals with individual components regulating the neural control of the urinary bladder. This article will focus on factors and processes involved in the two modes of operation of the bladder: storage and elimination. Topics included in this review include: (1) The urothelium and its roles in sensor and transducer functions including interactions with other cell types within the bladder wall (“sensory web”), (2) The location and properties of bladder afferents including factors involved in regulating afferent sensitization, (3) The neural control of the pelvic floor muscle and pharmacology of urethral and anal sphincters (focusing on monoamine pathways), (4) Efferent pathways to the urinary bladder, and (5) Abnormalities in bladder function including mechanisms underlying comorbid disorders associated with bladder pain syndrome and incontinence. Neurourol. Urodynam. 29: 128–139, 2010. © 2009 Wiley‐Liss, Inc.
Seguimiento clínico y ecocardiográfico de pacientes con miocardiopatía hipertrófica obstructiva tratados con ablación septal percutánea

Introduccion y objetivos La ablacion septal percutanea (ASP) es una opcion terapeutica para pacientes con miocardiopatia hipertrofica obstructiva (MCHO) con mala respuesta al tratamiento medico. El objetivo fue evaluar de forma prospectiva la evolucion clinica y ecocardiografica de los pacientes con MCHO tratados con ASP en nuestro centro. Metodos Se practicaron 35 ASP en 34 pacientes (79% varones) con MCHO sintomatica pese a que recibian un tratamiento medico optimizado. Se considero eficaz en 32 (reduccion del gradiente de presion en el tracto de salida del ventriculo izquierdo [GPTSVI] > 50%). Se realizo un seguimiento clinico y ecocardiografico, y se evaluaron la clase funcional (CF) y el GPTSVI. Resultados La edad media fue de 63 ± 12 anos. El seguimiento medio fue de 9 ± 3 meses. Inmediatamente despues de la ASP se redujo de manera significativa el GPTSVI (74,2 ± 25,3 a 26 ± 25 mmHg; p Conclusiones La ASP es una terapia eficaz en pacientes con MCHO sintomatica refractaria al tratamiento medico. Sin embargo, se asocia con un riesgo significativo de complicaciones, por lo que se reserva para pacientes seleccionados, especialmente para los de mayor edad o con alguna comorbilidad asociada.
Sedative use and incident cognitive decline among persons aged 75 years and older: a population-based longitudinal study

ABSTRACT Background: Acute exposure to sedative drugs may induce memory impairment, but there is mixed evidence that long-term sedative use may result in incident cognitive decline. The objective of this study was to investigate the use of sedative drugs and incident cognitive decline in a population-based sample of persons aged 75 years and older. Methods: The study sample comprised 781 participants in the Geriatric Multidisciplinary Strategy for the Good Care of the Elderly (GeMS) study in Kuopio, Finland. Data on health status, drug use, and sociodemographic factors were elicited during annual nurse interviews from 2004 to 2007. A linear mixed model was used to compare change in Mini-Mental State Examination (MMSE) scores (2005–2007) among users of sedative drugs in 2004 and 2005 (n = 139) to non-users of sedative drugs from 2004 to 2007 (n = 310). The model was adjusted for covariates including age, gender, education, depressive symptoms and antipsychotic use. Results: Unadjusted mean MMSE scores were 27.50 in 2005, 26.58 in 2006, and 25.95 in 2007 among users of sedative drugs. Unadjusted mean MMSE scores were 28.05 in 2005, 27.61 in 2006, and 27.09 in 2007 among non-users of sedative drugs. Adjusted mean MMSE scores were 0.31 points lower in 2005, 0.62 points lower in 2006, and 0.93 lower in 2007 among users compared to non-users of sedative drugs (P = 0.051). Conclusions: Sedatives were not associated with statistically significant cognitive decline. However, clinicians should maintain a judicious approach to prescribing sedative drugs given the risk of adverse drug events.
Re: "Exposure to maternal smoking during pregnancy as a risk factor for tobacco use in adult offspring".

Nicotine from maternal smoking during pregnancy can cross the placental barrier, possibly resulting in fetal brain sensitization, as indicated by studies in which prenatal exposure to maternal smoking was associated with an increased risk of tobacco use among adolescent offspring. We investigated whether this association persists beyond adolescence by studying cigarette smoking and the use of snus (Swedish oral moist snuff) among 983 young adults from a prospective cohort study conducted in Stockholm, Sweden, between 2006 and 2010. Self-reported questionnaire datawere linkedwith datafromnationalpopulation-based registersfrom1983onward.Maternalsmokingduring pregnancy was consistently associated with snus use in offspring (e.g., for lifetime daily snus use, adjusted odds ratio = 2.04, 95% confidence interval: 1.32, 3.16; for use of >3 cans of snus per week vs. less, odds ratio = 3.85, 95% confidence interval: 1.57, 10.15). No association was apparent with offspring’ ss moking, age at onset of tobacco use, or changes in use between 2006 and 2010. These findings indicate that prenatal exposure to maternal smoking is associated with regular and heavy nicotine intake from smokeless tobacco rather than from smoking. This should befurtherexploredinepidemiologicstudiesthatsimultaneouslyaddresstherolesofgeneticsandsocialenvironments. cigarette smoking; prenatal exposure delayed effects; smoking; tobacco; tobacco, smokeless
Leptospirosis: a Public Health Hazard. Report of a Small Outbreak of Weil's Disease in Bathers.

About fifty years ago Weil 1 discovered an acute infectious disease with jaundice and fever to which his name was later applied. In 1914 Inada and Ido 2 proved the etiologic agent to be a spiral shaped micro-organism which Noguchi 3 shortly thereafter described in detail, naming it Leptospira icterohaemorrhagiae. Since the identification of this micro-organism there has gradually accumulated knowledge of other morphologically similar but serologically and immunologically different members of the same group of leptospiras. 4 They are distributed worldwide and are usually associted with rats and dogs. Many of them classed as Leptospira biflexa 5 are not pathogenic for man. In Europe at least three distinct pathogenic varieties are recognized: ( 1) Leptospira icterohaemorrhagiae of Weil's disease, (2) Leptospira canicola 6 of an infection in dogs transmissible to man and (3) Leptospira grippo-typhosa 7 of a syndrome known in different places as "summer influenza," "harvest fever," "mud fever,"
Inhalant and Prescription Medication Abuse among Adolescents: An Inexpensive, Accessible, and Misperceived Trend

Inhalant and prescription medication abuse, particularly among adolescents, are serious problems in our society. Several risk factors associated with inhalant and medication abuse among adolescents have been identified. As a result, adolescents may suffer multiple consequences in a range of developmental areas. The purpose of this article is to examine in-depth the prevalence, risk factors, and consequences associated with inhalant and prescription medication abuse among adolescents. Recommendations in the prevention and intervention of inhalant and prescription medication abuse are provided.
Relation between Hepatic and Plasma Concentrations of Vitamin A in Human Beings.

To recognize clinical and subclinical vitamin A deficiency the blood level of vitamin A, 1 visual tests for night blindness, 2 biomicroscopic changes in the cornea 3 and other means have been used. The results obtained and the conclusions drawn have varied. Some authors have concluded that vitamin A deficiency is common 4 ; others have considered it to be rare. 5 The liver is the main storage place for vitamin A. It contains about 95 per cent of the total amount of the vitamin in the body. 6 Therefore, it can serve as an index of the vitamin A status. Hence, it would seem that those tests for deficiency of the vitamin would be significant which parallel low or absent stores in the liver. The present study deals with the significance of the vitamin A level of the blood. The vitamin A concentration of human blood plasma was compared with the vitamin A content
Interferon Regulation Factor‐3 is a Critical Regulator of the Mature of Dendritic Cells from Mice

Interferon regulatory factor‐3 (IRF‐3) plays an important role in virus and double‐stranded RNA‐mediated induction of type I interferon and RANTES (regulated on activation normal T cell expressed and secreted), DNA damage signalling, tumour suppression and virus‐induced apoptosis. IRF‐3 had recently been shown to contribute to T‐cell activation in response to pathogens, which implicated an extensive immunological role for IRF‐3. Dendritic cells (DCs) played critical roles as professional APCs in the development of immune responses. However, it was unclear whether IRF‐3 had any effect on phenotype or function of DCs. In this study, it was shown that IRF‐3 acted as a promoter of DC maturation. The level of IRF‐3 expression was transiently upregulated and accumulated in the nucleus in TNF‐α‐induced immune maturation of mice DC cells. Knockdown of IRF‐3 by small interfering RNA in DC cells resulted in both phenotypic and functional immaturation, even without TNF‐α treatment. Overall, our data demonstrated for the first time that IRF‐3 was a critical regulator of mice DC maturation.
Pro‐IL‐16 is Associated with MHC Class II‐Mediated Negative Regulation of Mouse Resting B Cell Activation through MAP Kinases, NF‐κB and Skp2‐Dependent p27kip Regulation

MHC class II molecules, in addition to their essential role as antigen‐presenting molecules to CD4+ T cell receptor, have a signal‐transducing role related to B cell function. We identified pro‐IL‐16 as one of the proteins associated with MHC class II‐mediated signalling in an analysis of MHC class II‐associated molecules using immunoprecipitation and proteomics data obtained from the 38B9 resting B cell line, and investigated the role of pro‐IL‐16 in resting B cell activation. We found that pro‐IL‐16, rather than mature form of IL‐16, is present both in the cytoplasm and nucleus of resting B cells, and its expression is influenced by MHC class II‐mediated signalling. In addition, overexpression of pro‐IL‐16 impaired resting B cell proliferation and this inhibitory effect was mediated through regulating nuclear factor (NF)‐κB activation. Knock‐down of pro‐IL‐16 expression using siRNA decreased the level of cell‐cycle inhibitor p27kip and increased the level of Skp2. In addition, knock‐down of pro‐IL‐16 modulated mitogen‐activated protein kinase activation. Given that IL‐16 acts as an immunomodulator by impairing antigen‐induced T cell activation and its precursor, pro‐IL‐16, plays a role in regulating the cell cycle in T lymphocytes and T cell lymphoma, we concluded that pro‐IL‐16 is involved in resting B cell proliferation, similar to its function in T lymphocytes.
Inhibitors of BTK and ITK: State of the New Drugs for Cancer, Autoimmunity and Inflammatory Diseases

BTK and ITK are cytoplasmic tyrosine kinases of crucial importance for B and T cell development, with loss‐of‐function mutations causing X‐linked agammaglobulinemia and susceptibility to severe, frequently lethal, Epstein–Barr virus infection, respectively. Over the last few years, considerable efforts have been made in order to develop small‐molecule inhibitors for these kinases to treat lymphocyte malignancies, autoimmunity or allergy/hypersensitivity. The rationale is that even if complete lack of BTK or ITK during development causes severe immunodeficiency, inactivation after birth may result in a less severe phenotype. Moreover, therapy can be transient or only partially block the activity of BTK or ITK. Furthermore, a drug‐induced B cell deficiency is treatable by gamma globulin substitution therapy. The newly developed BTK inhibitor PCI‐32765, recently renamed Ibrutinib, has already entered several clinical trials for various forms of non‐Hodgkin lymphoma as well as for multiple myeloma. Experimental animal studies have demonstrated highly promising treatment effects also in autoimmunity. ITK inhibitors are still under the early developmental phase, but it can be expected that such drugs will also become very useful. In this study, we present BTK and ITK with their signalling pathways and review the development of the corresponding inhibitors.
Systematic Reviews and Meta-and Pooled Analyses Associations of Maternal Vitamin B 12 Concentration in Pregnancy With the Risks of Preterm Birth and Low Birth Weight : A Systematic Review and Meta-Analysis of Individual Participant Data

Tormod Rogne*, Myrte J. Tielemans, Mary Foong-Fong Chong, Chittaranjan S. Yajnik, Ghattu V. Krishnaveni, Lucilla Poston, Vincent W. V. Jaddoe, Eric A. P. Steegers, Suyog Joshi, Yap-Seng Chong, Keith M. Godfrey, Fabian Yap, Raquel Yahyaoui, Tinku Thomas, Gry Hay, Marije Hogeveen, Ahmet Demir, Ponnusamy Saravanan, Eva Skovlund, Marit P. Martinussen, Geir W. Jacobsen, Oscar H. Franco, Michael B. Bracken, and Kari R. Risnes
Quinoline‐3‐Carboxamides Modulate Primary T Cell‐Dependent B Cell Responses but do not Inhibit Functional Immunity

The effect of a quinoline‐3‐carboxamide on the T cell‐dependent B cell response was investigated in C57BL/6 mice after NP‐CGG immunization. The primary serum response to the hapten was slightly inhibited by treatment with a quinoline‐3‐carboxamide. This inhibition was paralleled by reduced numbers of germinal centre (GC) B cells and follicular T cells in the spleen up to 21 days after immunization. Also, both the number of GCs formed and their size were reduced by quinoline‐3‐carboxamide treatment. In contrast to the observation in the primary immune response, there was no inhibitory effect on the secondary immune response. These data could help to explain how quinoline‐3‐carboxamides can modulate immune function in autoimmune diseases without being immunosuppressive.
AIDS in Africa: Its Present and Future Impact

The epidemic of human immunodeficiency virus (HIV) infection has been particularly severe in sub-Saharan Africa, where over 6 million persons are currently estimated to be infected. This plague comes at a particularly inopportune time for the continent, as it is recovering from decades of severe social and economic problems. Despite the tragic accounts in the mass media of the acquired immunodeficiency syndrome (AIDS) epidemic as it affects households and communities, as well as available epidemiologic data and projections on the magnitude of the epidemic, until now no serious researchers have attempted a rigorous analysis of the true burden on these fragile societies. AIDS in Africa , by Tony Barnett and Piers Blaikie, attempts to partially meet this need by providing an overview of the social and economic consequences of AIDS in parts of Uganda, a country severely affected by the epidemic, and some generalizations about the African continent overall. The book
Interferon and Interferon‐Inducible Gene Activation in Patients with Type 1 Diabetes

Type 1 diabetes (T1D) is an autoimmune disease that is thought to be triggered by environmental factors in genetically susceptible individuals. Enteroviruses have been mentioned as the most probable induction component of the disease. Nevertheless, the literature is controversial regarding the association of T1D with viral infection and first‐line antiviral defence components, for example type I interferons (IFNs). Our aim was to test the hypothesis that an abnormality in IFN‐stimulated gene patterns may cause a failure in immunological tolerance and, thereby, initiate T1D as an autoimmune disorder. We studied material from 64 T1D and 36 control subjects, divided into two age groups: <10 years and ≥10 years old. Using a relative gene expression method, we observed a lower expression of interferon‐induced helicase 1 (IFIH1) and other type I IFN‐induced genes in the blood cells of T1D subjects, especially subjects under 10 years old, in spite of their higher IFN levels as measured by the pSTAT1‐inducing capacity of their sera. Likewise, freshly purified CpG‐stimulated cells from T1D patients showed significantly lower upregulation of IFN‐induced genes, that is IFIH1 and CXCL10, compared to cells from the control group. The identified dysregulation in the IFN‐α‐induced antiviral response in T1D patients, especially in early childhood, could be one of the factors affecting T1D development.
A NOVEL PROTEIN KINASE C INHIBITOR IN BOVINE SPERMATOZOA AND ITS EFFECTS ON THE DEVELOPMENT OF FERTILIZED OVA

We found a protein kinase C (PKC) inhibitor in bovine spermatozoa. The inhibitor was puriﬁed by Sephadex G-200 gel ﬁltration chromatography, isoelectric focusing and Mono Q chromatography. Inhibition of the PKC activity observed with 2 /lg of the purified inhibitor was comparable with that with 5 ,umol of chlorpromazine, a known potent inhibitor ofPKC. Molecular weight ofthis inhibitor was estimated to be about 63,000, and isoelectric point was pH 4.5. The inhibitor was inactivated when boiled, or digested with trypsin, whereas DNase and RNase were without effect, indicating that the inhibitor is a protein. The inhibitor is neither a protease nor a phosphatase. In fresh bovine spermatozoa, the PKC activity was almost undetectable probably because of the presence of the PKC inhibitor. When spermatozoa were incubated at pH 7.5 at 37°C for 12-16 h, more than half the activity of PKC inhibitor was lost, suggesting that the inhibitor was inactivated by proteolysis. When the purified inhibitor was microinjected into mouse fertilized ova, both the development of one-cell fertilized ova into two-cell stage ova, and two-cell late stage ova into four-cell stage ova were inhibited. In contrast, PKC microinjected into two-cell early stage ova promoted their development into the four-cell and eight-cell stages; two-cell early stage ova injected with saline remained in the same stage. The results suggest a regulatory role ofPKC and the PKC inhibitor in the development of fertilized ova.
Association between body mass index and cortical thickness: among elderly cognitively normal men and women

ABSTRACT Background: There is increasing evidence of a relationship between underweight or obesity and dementia risk. Several studies have investigated the relationship between body weight and brain atrophy, a pathological change preceding dementia, but their results are inconsistent. Therefore, we aimed to evaluate the relationship between body mass index (BMI) and cortical atrophy among cognitively normal participants. Methods: We recruited cognitively normal participants (n = 1,111) who underwent medical checkups and detailed neurologic screening, including magnetic resonance imaging (MRI) in the health screening visits between September 2008 and December 2011. The main outcome was cortical thickness measured using MRI. The number of subjects with five BMI groups in men/women was 9/9, 148/258, 185/128, 149/111, and 64/50 in underweight, normal, overweight, mild obesity, and moderate to severe obesity, respectively. Linear and non-linear relationships between BMI and cortical thickness were examined using multiple linear regression analysis and generalized additive models after adjustment for potential confounders. Results: Among men, underweight participants showed significant cortical thinning in the frontal and temporal regions compared to normal weight participants, while overweight and mildly obese participants had greater cortical thicknesses in the frontal region and the frontal, temporal, and occipital regions, respectively. However, cortical thickness in each brain region was not significantly different in normal weight and moderate to severe obesity groups. Among women, the association between BMI and cortical thickness was not statistically significant. Conclusions: Our findings suggested that underweight might be an important risk factor for pathological changes in the brain, while overweight or mild obesity may be inversely associated with cortical atrophy in cognitively normal elderly males.
Porphyromonas gingivalis B cell Antigen Epitope Vaccine, pIRES‐ragB'‐mGITRL, Promoted RagB‐Specific Antibody Production and Tfh Cells Expansion

The outer membrane protein RagB is one of the major virulence factors of Porphyromonas gingivalis (P. gingivalis). To prevent periodontitis and associated systemic diseases induced by P. gingivalis, we built B cell antigen epitope vaccine characterized by pIRES‐ragB'‐mGITRL to induce a protective immune responses. The B cell antigen epitope and scrambled peptide of ragB were predicted, cloned into pIRES and constructed pIRES‐ragB', pIRES‐scrambled epitopes and pIRES‐ragB'‐mGITRL. pIRES‐ragB'‐mGITRL was transfected into COS‐7 cells. Subsequently, the 6‐week‐old female BALB/c mice were challenged by P. gingivalis following three time immunization by pIRES, pIRES‐ragB', pIRES‐scrambled epitopes and pIRES‐ragB'‐mGITRL. The levels of RagB‐specific antibody in the serum and Tfh cells in the spleen were measured by ELISA and flow cytometry, respectively. And higher levels of RagB‐specific IgG were produced in the immunized mice with pIRES‐ragB'‐mGITRL. Additionally, the number of Tfh cells was also expanded and lesions were diminished in pIRES‐ragB'‐mGITRL mice comparing with control groups. Our results clearly demonstrated that P. gingivalis B cell antigen epitope vaccine, pIRES‐ragB'‐mGITRL, could induce protective immune responses. Furthermore, our data also indicated that pIRES‐ragB'‐mGITRL was a potential therapeutic vaccine against P. gingivalis.
Transferrinrezeptoren in Plattenepithelkarzinomen aus dem Kopf-Hals-Bereich*

Für den Transport von Eisen im Kbrper spielt das Protein Transferrin eine wichtige Rolle. Dieses Transportprotein wird uber einen spezifischen Transferrinrezepror (TR) der Zelimembran in die Zelle eingeschleusr. Beobachrungen Ober einen gesteigerten Nachweis dieses Rezeprors in starker proliferierenden Geweben veranIaren uns zu prüfen, ob der Grad der Anwesenheit des TRs nicht als Indikaror für mehr oder weniger proliferierende Gewebeanreile in Tumoren zu verwenden ist. Proben von 60 Plarrenepirhelkarainornen des Kopfund Halsbereiches unrersuchren wir immunhisrochemisch auf die Anwesenheit von TR, ihre Konzentrarion und Verreilung. In alien Tumoren war eine Expression von Rezeptoren nachzuweisen, und zwar mit einem relariv homogenen Verteilungsmuster bei germgen intraund inrerrumoralen Unrerschieden. Die proliferative Aktivitàt der Tumoren, die mittels des monoklonalen Antikorpers Ki67 bestimmt wurde, korrelierte zwar mit einer aligemeinen Steigerung der Expression des TRs, ohne aber das klare Verteilungsmusrer des IC 67 zu zeigen. Die mehr diffuse Verteilung des Transferrinrezeptors heR nur eine semiquantitative Auswertung zu. Sic ist offenbar nicht rein proliferarionsassoziiert und damit als Marker zur Bestimmung proliferariver Akriviraten ungeeigner. Transferrin Receptors in Squamous Cell Carcinomas in the Head and Neck Region