Miracle-dz/UniFAR-FTUs huggingface dataset:
Clinical investigations of Toll-like receptor agonists

Background: Toll-like receptors (TLR) represent a family of surface molecules that function as primary sensors of the innate immune system to recognize microbial pathogens. Ligand binding to TLR results in activation of cellular signaling pathways that regulate expression of genes involved in inflammation and immunity. Objective: Use of synthetic TLR ligands (agonists) for treatment and prevention of infectious and neoplastic diseases. Methods: Review of literature about clinical investigations of agonists of TLR 4, 7, 8, and 9. Results/conclusions: Imiquimod was the first TLR agonist approved for treatment of anogenital warts, actinic keratosis and superficial basal cell carcinoma in humans. Several other agonists of TLRs 4, 7, 8 and 9 were also shown to be effective for treatment of infections and cancers and, furthermore, were used as adjuvants for vaccination. Based on safety and efficacy of the TLR agonists used to date, applications are likely to increase in the future.
COMPARACIÓN DE HISTOPATOLOGÍA, CULTIVO Y PCR EN EL DIAGNÓSTICO DE TUBERCULOSIS BOVINA Comparison of Histopathology, Culture and PCR for Diagnosis of Bovine Tuberculosis

In Mexico, diagnosis of the bovine tuberculosis, is conducted by using the tuberculine test, bacteriologic isolation and histopathological analysis. Considering that some diagnosis methods are not sufficiently reliable and specific to detect the presence of the casual agent of this disease, the use of the polymerase chain reaction (PCR) test was evaluated from tissues with lesion caused by possible Mycobacterium. PCR allowed to detect the presence of members of the complex Mycobacterium tuberculosis in 56% of the cases, compared with 29% obtained histopathological analysis and 22.0% with bacteriologic isolation. The sensibility of PCR compared with histopathological analysis was of 82% and compared with bacteriologic isolation was of 72%. The 45.6% of samples negative by histopathological analysis were positive by PCR. The PCR test is recommended to support the histopathologcial analysis with the advantage that PCR identified species from M. tuberculosis complex where M. bovis is included.
Adaptation, Specialization, and Coevolution within Phytobiomes

Growth patterns of individual plants and evolutionary trajectories of plant communities are intimately linked with and are critically affected by host-associated microbiomes. Research across systems has begun to shed light on how these phytobiomes are established and under laboratory and natural conditions, and have cultivated hope that a better understanding of the governing principles for host-microbe interactions can guide attempts to engineer microbiomes to boost agricultural yields. One important, yet relatively understudied, parameter in regards to phytobiome membership is the degree to which specialization and coevolution between plant species and microbial strains structures these communities. In this article, I provide an broad overview about current knowledge concerning mechanisms enabling adaptation and specialization of phytobiome communties to host plants as well as the potential for plants themselves to recruit and cultivate interactions with beneficial microbes. I further explore the possibility of host-beneficial microbe coevolution and suggest interactions that could promote the evolution of such close-knit partnerships. It is my hope that this overview will encourage future experiments that can begin to fill in this black box of ecological and evolutionary interactions across phytobiomes.
Reliability, validity, and responsiveness of the short form 36 (SF-36) health survey questionnaire in patients with Graves’ disease

Abstract Background: The SF-36 as a generic instrument has been used widely to evaluate health-related quality of life in both healthy subjects and groups of patients. However, no data can be found on its performance in patients with Graves’ disease. Hence, this study aimed to assess the reliability, validity, and responsiveness of the SF-36 in a Chinese population of patients with Graves’ disease. Methods: A total of 325 patients with Graves’ disease completed interviews that included the SF-36. Internal consistency was measured by Cronbach’s α and item-scale correlations. The validity of the SF-36 was studied by means of factor analysis and the association of this scale with sociodemographic and clinical variables. A standardized response mean was used to assess the responsiveness of the SF-36 to change. Results: Cronbach’s α coefficients surpassed the 0.70 criteria for seven subscales and 0.63 for the SF subscale indicating good internal consistency. The correlation coefficients between items and the remainder of the same subscale ranged from 0.51 to 0.96, which were all higher than with other subscales. A principal components factor analysis with varimax rotation identified eight factors. Hamilton Anxiety Rating Scale (HARS) scores correlated negatively to scores at the physical functioning, general health, social functioning, vitality, and role limitations due to emotional problems SF-36 subscales, while HARS scores correlated negatively only to scores on the mental health SF-36 subscale. No correlations were found between SF-36 scores and the levels of thyroid hormones. Responsiveness to improvements in health status was acceptable overall (standardized response means 0.33-0.88). Conclusion: The Chinese (mainland) version of the SF-36 is a suitable instrument that can be used in patients with Graves’ disease.
Direct CO(2) laser-based generation of holographic structures on the surface of glass.

A customized CO(2) laser micromachining system was used for the generation of phase holographic structures directly on the surface of fused silica (HPFS(®)7980 Corning) and Borofloat(®)33 (Schott AG) glass. This process used pulses of duration 10µs and nominal wavelength 10. 59µm. The pulse energy delivered to the glass workpiece was controlled by an acousto-optic modulator. The laser-generated structures were optically smooth and crack free. We demonstrated their use as diffractive optical elements (DOEs), which could be exploited as anti-counterfeiting markings embedded into valuable glass-made components and products.
A STUDY OF THE BENEFITS OF CANCER PATIENTS ENGAGING IN COMPLEMENTARY THERAPIES

Rudolph Cindy A______________ (Writer) (Last Name) (First Name) (Initial) A Study of the Benefits of Cancer Patients Engaging in Complementary Therapies (Title) M.S. Guidance and Counseling Dr. Ed Biggerstaff December 2002 52 (Graduate Major) (Research Advisor) (Month/Year) (No. of pages) American Psychological Association Style Manual, Fifth Edition_______ (Name of Style of Manual Used in this Study) The purpose of this study was to look at the benefits of cancer patients engaging in complementary therapies. Cancer affects a large number of people and their families every day. Different mortality rates and different treatment modalities exist for cancer patients based on the stage of their disease at the time of diagnosis and the kind of cancer that the patients are diagnosed with. Those patients and their families who are affected by cancer have many choices to make regarding treatment and self care. A literature review was conducted looking at the prevalence of cancer, common medical treatments that cancer patients endure, the psychological impacts of cancer, reasons for psychosocial interventions, and complementary therapies that cancer patients engage in.
Integrated Competence and the Maturing Doctor

practice to ensure patient confidence in health care (Caiman, 1996), but what is competence in relation to medical practice? Competence was ranked first of nine core values needed to guide the medical profession into the 21st century (British Medical Association Health Policy and Economic Research Unit, 1995). The term is used by the General Medical Council (CMC) (1993) in Tomorrow'sDoctors, the implementation of which
Cardiovascular risk and inhibition of cyclooxygenase: traditional nonsteroidal anti-inflammatory drugs and cyclooxygenase-2 inhibitors

BACKGROUND The development of non-selective nonsteroidal anti-inflammatory drugs (tNSAIDs) and, more recently, of selective inhibitors of the cycloooxygenase-2 isoform (COXIBs), has contributed greatly towards the effective management of patients with arthritis and pain complaints. Although COXIBs have demonstrated an improved gastrointestinal tolerability compared with tNSAIDs, the cardiovascular effects of the two drugs types are much controversial. By blocking prostacyclin formation but leaving platelet-derived thromboxane A2 generation unopposed, the potential gastrointestinal benefit of COXIBs may come at cost of increased thrombotic risk. AIM OF THE STUDY This review aims at analysing the cardiovascular effects of the tNSAIDs and COXIBs. METHOD This review addresses the controversy of effects of COXIBs and tNSAIDs in 4 segments. It begins with a discussion about pathophysiological effects of cyclooxygenase inhibition on cardiovascular system. This is followed by a systematic review and meta-analysis of a control, randomized, double blind study and population-based matched case-control study to compare the risk of serious cardiovascular events with tNSAIDs and COXIBs. Then it answers to key questions with the aim to assist the clinicians for a systematic approach to evaluate the risk-benefit-ratio of NSAIDs in the clinical practice. Finally we analyse the open questions associated with the use of NSAIDs and the cardiovascular events. RESULTS The use of rofecoxib demonstrated an increase in adverse cardiovascular events. This toxic effect is not dose-related. The relationship between celecoxib and cardiovascular risk is less clear. The results of different clinical trials are conflicting: some didn’t demonstrate increase in cardiovascular toxicity but the APC study and recently a metanalysis reported a significant incidence of adverse cardiovascular events. Also valdecoxib and parecoxib appear to have increased risk for cardiovascular toxicity. Eterocoxib is still the object of three ongoing clinical trials. The TARGET study demonstrated for lumiracoxib a low increase in cardiovascular events compared with ibuprofen and naproxen. Also the use of ibuprofen (800 mg t.i.d.), diclofenac (75 mg b.i.d.) and indomethacin is reported to cause adverse cardiovascular events. The use of naprosen shows a better profile regarding cardiovascular toxicity. tNSAIDSs can worse clinical condition of patients affected by chronic cardiac failure and rofecoxib but not celecoxib can disclose clinical cardiac failure. A politherapy with both tNSAIDs and rofecoxib demonstrated an increase of blood arterial pressure and peripheral oedema. CONCLUSIONS This review confirms the findings from randomized trials, meta-analysis and observational studies regarding the risk of cardiovascular events with rofecoxib, valdecoxib e parecoxib, whereas the evidence for other COXIBs is not so clear. Also in the class of tNSAID some drugs (diclofenac and ibuprofen) can have an increased cardiovascular toxicity.
Mycotic Aneurysm of the Femoral Profunda Artery in Active Infectious Endocarditis—A Case Report

This case report describes a twenty-seven-year-old male who pre sented with a mycotic aneurysm of the right femoral profunda artery (FPA) appearing in the course of ac tive infectious endocarditis (Staphy loccus aureus). The aneurysm, 6 x 4 cm at the origin of the FPA, exerted growing pressure on the superficial femoral artery, causing its complete compression by the end of the third week following onset of symptoms. After resection of the mycotic aneu rysm and use of an interpolated re versed saphenous vein graft, the patient recovered uneventfully and was found in good condition on a five-year follow-up.
Testing two models describing how methylome-wide studies in blood are informative for psychiatric conditions.

AIM As the primary relevant tissue (brain) for psychiatric disorders is commonly not available, we aimed to investigate whether blood can be used as a proxy in methylation studies on the basis of two models. In the 'signature' model methylation-disease associations occur because a disease-causing factor affected methylation in the blood. In the 'mirror-site' model the methylation status in the blood is correlated with the corresponding disease-causing site in the brain. MATERIALS, METHODS & RESULTS: Methyl-binding domain enrichment and next-generation sequencing of the blood, cortex and hippocampus from four haloperidol-treated and ten untreated C57BL/6 mice revealed high levels of correlation in methylation across tissues. Despite the treatment inducing a large number of methylation changes, this correlation remains high. CONCLUSION Our results show that, consistent with the signature model, factors that affect brain processes (i.e., haloperidol) leave biomarker signatures in the blood and, consistent with the mirror-site model, the methylation status of many sites in the blood mirror those in the brain.
The value and role of the interview in the student admissions process: a review

Despite the widespread popularity of the admissions interview, its use is controversial. This review considers the strengths and weaknesses of the interview in medical, dental and allied health professions student admissions. The important issues regarding its subjectivity, reliability and validity are covered, with particular attention being given to the effects on these factors of the amount of preparation and type of interview format used. Also reviewed are studies which have investigated the effectiveness of the interview as an admissions tool in terms of its ability to predict students' academic and clinical performance.
Prenatal exposure to mixtures of xenoestrogens and genome-wide DNA methylation in human placenta.

BACKGROUND In utero exposure to xenostrogens may modify the epigenome. We explored the association of prenatal exposure to mixtures of xenoestrogens and genome-wide placental DNA methylation. MATERIALS & METHODS Sex-specific associations between methylation changes in placental DNA by doubling the concentration of TEXB-alpha exposure were evaluated by robust multiple linear regression. Two CpG sites were selected for validation and replication in additional male born placentas. RESULTS No significant associations were found, although the top significant CpGs in boys were located in the LRPAP1, HAGH, PPARGC1B, KCNQ1 and KCNQ1DN genes, previously associated to birth weight, Type 2 diabetes, obesity or steroid hormone signaling. Neither technical validation nor biological replication of the results was found in boys for LRPAP and PPARGC1B. CONCLUSION Some suggestive genes were differentially methylated in boys in relation to prenatal xenoestrogen exposure, but our initial findings could not be validated or replicated.
Modelando la Varianza de la Forma: Morfometría Geométrica Aplicaciones en Biología Evolutiva

La comparacion de caracteres anatomicos entre organismos ha sido un elemento central de la biologia comparada. Historicamente, la clasificacion taxonomica y la comprension de la diversidad biologica se han basado en descripciones morfologicas. En base a una revolucion matematica cuantitativa, el estudio de la morfologia ha tenido un importante enfasis gracias al desarrollo del analisis de la forma mediante la combinacion de metodos estadisticos multivariados y nuevas maneras de visualizacion. El objetivo de la presente revision es dar una vision actualizada sobre los avances del estudio de la morfometria geometrica (MG) en biologia evolutiva, asi como introducir a tematicas en fuerte desarrollo (e.g. estabilidad del desarrollo, integracion y modularidad morfologicas, entre otras). Se espera proporcionar una vision amplia del uso de la MG en biologia evolutiva, destacando la necesidad de aumentar el esfuerzo de investigacion en esta disciplina, junto con llamar la atencion acerca de la utilidad de la MG como una herramienta efectiva, precisa, amigable y barata para cuantificar y estudiar la variacion morfologica.
Macrophages, atherosclerosis and the potential of netrin-1 as a novel target for future therapeutic intervention.

Atherosclerosis is a chronic inflammatory disease that is distinguished by the persistence of cholesterol-laden macrophages in plaques of the arterial wall[1]. Based on observational studies that extend into the era of modern atherosclerosis research (which dates to the introduction in the early 90's of mouse models of the disease), the prevailing view has been that the recruitment of monocytes into atherosclerotic plaques is an unproductive exercise, in which these cells are fated to become macrophage foam cells that persist in this site, establishing chronic inflammation, until eventually dying by either necrosis or apoptosis. Unlike in other tissues, macrophages that accumulate in plaques appear to have a diminished capacity to migrate[2–5], and go from being chemotactic to chemostatic, thereby contributing to a failure to resolve the inflammatory process in arteries set in motion by the retention of atherogenic lipoproteins. Moreover, the impaired efferocytotic ability of these macrophages prevents the clearance of their dying compatriots[6], further contributing to the pro-inflammatory milieu of the plaque and ultimately resulting in the formation of a necrotic core. In such unstable plaques, inflammasome-activating cholesterol crystals[7] and pro-thrombotic tissue factor accumulate in this graveyard of dead macrophages, further adding to the mayhem.
Prevalência de Streptococcus suis sorotipo 2: discussão da literatura brasileira Prevalence of Streptococcus suis serotype 2: discussion of the Brazilian literature

Streptococcus suis is considered worldwide as one of the pathogens of biggest health and economic impact in the swine industry. Among the serotypes described as zoonotic, serotype 2 is the most frequently isolated from diseased animals and humans in most countries. The study of the epidemiology of infections in Brazil is important and may help in the development of effective control measures. The aim of this study was to conduct a critical review of Brazilian literature, with support of the world literature, addressing the diagnosis of the agent and its prevalence in clinically ill animals and healthy carriers, especially regarding to the prevalence of the serotype 2 in the country.
Inhibition by Spinal μ- and δ-Opioid Agonists of Afferent-Evoked Substance P Release

Opioid μ- and δ-receptors are present on the central terminals of primary afferents, where they are thought to inhibit neurotransmitter release. This mechanism may mediate analgesia produced by spinal opiates; however, when they used neurokinin 1 receptor (NK1R) internalization as an indicator of substance P release, Trafton et al. (1999) noted that this evoked internalization was altered only modestly by morphine delivered intrathecally at spinal cord segment S1-S2. We reexamined this issue by studying the effect of opiates on NK1R internalization in spinal cord slices and in vivo. In slices, NK1R internalization evoked by dorsal root stimulation at C-fiber intensity was abolished by the μ agonist [d-Ala2, N-Me-Phe4, Gly-ol5]-enkephalin (DAMGO) (1 μm) and decreased by the δ agonist [d-Phe2,5]-enkephalin (DPDPE) (1 μm). In vivo, hindpaw compression induced NK1R internalization in ipsilateral laminas I-II. This evoked internalization was significantly reduced by morphine (60 nmol), DAMGO (1 nmol), and DPDPE (100 nmol), but not by the κ agonist trans-(1S,2S)-3,4-dichloro-N-mathyl-N-[2-(1-pyrrolidinyl)cyclohexyl]-benzeneacetamide hydrochloride (200 nmol), delivered at spinal cord segment L2 using intrathecal catheters. These doses of the μ and δ agonists were equi-analgesic as measured by a thermal escape test. Lower doses neither produced analgesia nor inhibited NK1R internalization. In contrast, morphine delivered by percutaneous injections at S1-S2 had only a modest effect on thermal escape, even at higher doses. Morphine decreased NK1R internalization after systemic delivery, but at a dose greater than that necessary to produce equivalent analgesia. All effects were reversed by naloxone. These results indicate that lumbar opiates inhibit noxious stimuli-induced neurotransmitter release from primary afferents at doses that are confirmed behaviorally as analgesic.
The potential of aerobic exercise training in mitigating cardiovascular side effects of cancer therapy.

Office of Health Promotion Research, University of Vermont, Burlington, VT 05401, USA Department of Internal Medicine, University of Vermont, Burlington, VT 05446, USA Vermont Center on Behavior Health & Vermont Cancer Center, Burlington, VT 05401, USA *Author for correspondence: susan.lakoski@uvm.edu
Managing incidental findings in population based biobank research

With the introduction of whole genome sequencing in medical research, the debate on how to handle incidental findings is becoming omnipresent. Much of the literature on the topic so far, seems to defend the researcher’s duty to inform, the participant’s right to know combined with a thorough informed consent in order to protect and secure high ethical standards in research. In this paper, we argue that this ethical response to incidental findings and whole genome sequencing is appropriate in a clinical context, in what we call therapeutic research. However, we further argue, that it is rather inappropriate in basic research, like the research going on in public health oriented population based biobanks. Our argument is based on two premises: First, in population based biobank research the duties and rights involved are radically different from a clinical based setting. Second, to introduce the ethical framework from the clinical setting into population based basic research, is not only wrong, but it may lead to unethical consequences. A Norwegian population based biobank and the research-ethical debate in Norway on the regulation of whole genome sequencing is used as an illustrative case to demonstrate the pitfalls when approaching the debate on incidental findings in population based biobank research.
Doença celíaca e infertilidade feminina: associação freqüentemente negligenciada

OBJETIVO: Verificar a existencia de associacao entre subfertilidade ou infertilidade e concomitante presenca de doenca celiaca nas mulheres atendidas em ambulatorio de hospital geral especializado em reproducao humana. METODOS: O delineamento do estudo foi do tipo caso-controle. Os casos foram constituidos por um grupo de 200 mulheres com queixa de dificuldade para engravidar, e um grupo controle formado por 400 mulheres atendidas no mesmo ambulatorio com queixas variadas, mas sem problemas de fertilidade. Ambos os grupos de pacientes foram submetidos a pesquisa de anticorpos antiendomisio pelo metodo de imunofluorescencia indireta. Nos casos positivos, o diagnostico foi confirmado por biopsia duodenal endoscopica e exame histopatologico. RESULTADOS: Os testes antiendomisio no grupo com dificuldade para engravidar resultaram positivos em tres pacientes (1,5%). O diagnostico de doenca celiaca foi confirmado por subsequente exame histopatologico da mucosa duodenal. Todas as pacientes pertencentes ao grupo controle apresentaram testes sorologicos negativos. CONCLUSOES: O fato de terem sido encontrados casos de doenca celiaca somente entre mulheres com queixas de dificuldade para engravidar parece um dado relevante e sugestivo de ser a doenca celiaca mais comum entre mulheres inferteis; porem, ha necessidade de novos estudos com tamanho de amostra maior para confirmacao definitiva dessa provavel associacao.