Tuberculosis - Reaping benefits from COVID-19 in Portugal

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The Cytotoxic T Lymphocyte Antigen-4+49A/G Single Nucleotide Polymorphism Association With Visceral Leishmaniasis

Background: Several lines of evidence approve that innate and adaptive immunity play key roles in the defense against visceral leishmaniasis (VL). The polymorphism within the cytotoxic T lymphocyte antigen 4 (CTLA-4) gene alters its expression. Objectives: The main aim of this study was to evaluate the polymorphism within the +49 position of the CTLA-4 gene of Iranian patients with VL in comparison with healthy controls. Materials and Methods: In this cross-sectional study, 88 patients with clinical presentations of VL, who were seropositive for Leishmania (group 1), 86 patients without clinical presentations but seropositive (group 2), and 115 healthy controls (group 3) were assessed with respect to the CTLA-4 +49A/G polymorphism, using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The anti-Leishmania antibody titration was evaluated using an immunofluorescence method. Results: Our results indicated that both CTLA-4 +49A/G polymorphisms were significantly associated with VL. Conclusions: According to the results, the polymorphisms within the +49 position of CTLA-4 can be associated with VL and may be considered as risk factors for the disease

Automatically generating streamlined constraint models with ESSENCE and CONJURE

Streamlined constraint reasoning is the addition of uninferred constraints to a constraint model to reduce the search space, while retaining at least one solution. Previously, effective streamlined models have been constructed by hand, requiring an expert to examine closely solutions to small instances of a problem class and identify regularities. We present a system that automatically generates many conjectured regularities for a given Essence specification of a problem class by examining the domains of decision variables present in the problem specification. These conjectures are evaluated independently and in conjunction with one another on a set of instances from the specified class via an automated modelling tool-chain comprising of Conjure, Savile Row and Minion. Once the system has identified effective conjectures they are used to generate streamlined models that allow instances of much larger scale to be solved. Our results demonstrate good models can be identified for problems in combinatorial design, Ramsey theory, graph theory and group theory - often resulting in order of magnitude speed-ups.Postprin

Heterogeneities in leishmania infantum infection : using skin parasite burdens to identify highly infectious dogs

Background: The relationships between heterogeneities in host infection and infectiousness (transmission to arthropod vectors) can provide important insights for disease management. Here, we quantify heterogeneities in Leishmania infantum parasite numbers in reservoir and non-reservoir host populations, and relate this to their infectiousness during natural infection. Tissue parasite number was evaluated as a potential surrogate marker of host transmission potential. Methods: Parasite numbers were measured by qPCR in bone marrow and ear skin biopsies of 82 dogs and 34 crab-eating foxes collected during a longitudinal study in Amazon Brazil, for which previous data was available on infectiousness (by xenodiagnosis) and severity of infection. Results: Parasite numbers were highly aggregated both between samples and between individuals. In dogs, total parasite abundance and relative numbers in ear skin compared to bone marrow increased with the duration and severity of infection. Infectiousness to the sandfly vector was associated with high parasite numbers; parasite number in skin was the best predictor of being infectious. Crab-eating foxes, which typically present asymptomatic infection and are non-infectious, had parasite numbers comparable to those of non-infectious dogs. Conclusions: Skin parasite number provides an indirect marker of infectiousness, and could allow targeted control particularly of highly infectious dogs

Transcription profiling reveals potential mechanisms of dysbiosis in the oral microbiome of rhesus macaques with chronic untreated SIV infection.

A majority of individuals infected with human immunodeficiency virus (HIV) have inadequate access to antiretroviral therapy and ultimately develop debilitating oral infections that often correlate with disease progression. Due to the impracticalities of conducting host-microbe systems-based studies in HIV infected patients, we have evaluated the potential of simian immunodeficiency virus (SIV) infected rhesus macaques to serve as a non-human primate model for oral manifestations of HIV disease. We present the first description of the rhesus macaque oral microbiota and show that a mixture of human commensal bacteria and "macaque versions" of human commensals colonize the tongue dorsum and dental plaque. Our findings indicate that SIV infection results in chronic activation of antiviral and inflammatory responses in the tongue mucosa that may collectively lead to repression of epithelial development and impact the microbiome. In addition, we show that dysbiosis of the lingual microbiome in SIV infection is characterized by outgrowth of Gemella morbillorum that may result from impaired macrophage function. Finally, we provide evidence that the increased capacity of opportunistic pathogens (e.g. E. coli) to colonize the microbiome is associated with reduced production of antimicrobial peptides

How Much Does Malaria Vector Control Quality Matter: The Epidemiological Impact of Holed Nets and Inadequate Indoor Residual Spraying

BACKGROUND: Insecticide treated nets (ITN) and indoor residual spraying (IRS) are the two pillars of malaria vector control in Africa, but both interventions are beset by quality and coverage concerns. Data from three control programs were used to investigate the impact of: 1) the physical deterioration of ITNs, and 2) inadequate IRS spray coverage, on their respective protective effectiveness. METHODS: Malaria indicator surveys were carried out in 2009 and 2010 in Bioko Island, mainland Equatorial Guinea and Malawi to monitor infection with P. falciparum in children, mosquito net use, net condition and spray status of houses. Nets were classified by their condition. The association between infection and quality and coverage of interventions was investigated. RESULTS: There was reduced odds of infection with P. falciparum in children sleeping under ITNs that were intact (Odds ratio (OR): 0.65, 95% CI: 0.55-0.77 and OR: 0.81, 95% CI: 0.56-1.18 in Equatorial Guinea and in Malawi respectively), but the protective effect became less with increasingly worse condition of the net. There was evidence for a linear trend in infection per category increase in deterioration of nets. In Equatorial Guinea IRS offered protection to those in sprayed and unsprayed houses alike when neighbourhood spray coverage was high (≥80%) compared to those living in areas of low IRS coverage (<20%), regardless of whether the house they lived in was sprayed or not (adjusted OR = 0.54, 95% CI 0.33-0.89). ITNs provided only personal protection, offering no protection to non users. Although similar effects were seen in Malawi, the evidence was much weaker than in Equatorial Guinea. CONCLUSIONS: Universal coverage strategies should consider policies for repair and replacement of holed nets and promote the care of nets by their owners. IRS programs should ensure high spray coverage since inadequate coverage gives little or no protection at all

Transcription of toll-like receptors 2, 3, 4 and 9, FoxP3 and Th17 cytokines in a susceptible experimental model of canine Leishmania infantum infection

Canine leishmaniosis (CanL) due to Leishmania infantum is a chronic zoonotic systemic disease resulting from complex interactions between protozoa and the canine immune system. Toll-like receptors (TLRs) are essential components of the innate immune system and facilitate the early detection of many infections. However, the role of TLRs in CanL remains unknown and information describing TLR transcription during infection is extremely scarce. The aim of this research project was to investigate the impact of L. infantum infection on canine TLR transcription using a susceptible model. The objectives of this study were to evaluate transcription of TLRs 2, 3, 4 and 9 by means of quantitative reverse transcription polymerase chain reaction (qRT-PCR) in skin, spleen, lymph node and liver in the presence or absence of experimental L. infantum infection in Beagle dogs. These findings were compared with clinical and serological data, parasite densities in infected tissues and transcription of IL-17, IL-22 and FoxP3 in different tissues in non-infected dogs (n = 10), and at six months (n = 24) and 15 months (n = 7) post infection. Results revealed significant down regulation of transcription with disease progression in lymph node samples for TLR3, TLR4, TLR9, IL-17, IL-22 and FoxP3. In spleen samples, significant down regulation of transcription was seen in TLR4 and IL-22 when both infected groups were compared with controls. In liver samples, down regulation of transcription was evident with disease progression for IL-22. In the skin, upregulation was seen only for TLR9 and FoxP3 in the early stages of infection. Subtle changes or down regulation in TLR transcription, Th17 cytokines and FoxP3 are indicative of the silent establishment of infection that Leishmania is renowned for. These observations provide new insights about TLR transcription, Th17 cytokines and Foxp3 in the liver, spleen, lymph node and skin in CanL and highlight possible markers of disease susceptibility in this model

Recombinant family 3 carbohydrate-binding module as a new additive for enhanced enzymatic saccharification of whole slurry from autohydrolyzed eucalyptus globulus wood

By-products resulting from lignocellulosics pretreatment affect the digestibility of resulting whole slurries, but this can be minimized by additives supplementation. In this work, a family 3 carbohydrate-binding module (CBM3), recombinantly produced from Escherichia coli, was used as additive in the enzymatic hydrolysis of the whole slurry from autohydrolyzed Eucalyptus globulus wood (EGW). At the higher dosage used (30 mg/gsolids), CBM3 led to an increase in glucose yield from 75 to 89%. A similar result was obtained for bovine serum albumin (BSA) (11% increase), which has a well-documented additive effect. CBM3 had no effect on the non-productive binding of enzymes, since it could not bind to EGW lignin, while it rapidly bound to cellulose, as shown by fluorescence microscopy. CBM3 is a valid additive for enhanced lignocellulosic saccharification and a valuable alternative to costly additives (e.g. polyethylene glycol) as it can be affordably produced from heterologous bacterium, thus contributing to more cost-efficient biomass valorization bioprocesses.This work was developed under the strategic funding of UID/BIO/04469/2013 unit, COMPETE 2020 (POCI-01-0145-FEDER-006684) and BioTecNorte operation (NORTE-01-0145-FEDER-000004) funded by the European Regional Development Fund under the scope of Norte2020—Programa Operacional Regional do Norte. The research leading to the reported results has received funding from Fundação para a Ciência e a Tecnologia (FCT) through the project MultiBiorefinery (POCI-01–0145-FEDER-016403) and through grants to C. Oliveira (SFRH/BPD/110640/2015) and D. Gomes (SFRH/BD/88623/2012).info:eu-repo/semantics/publishedVersio

Pheochromocytoma presenting with arterial and intracardiac thrombus in a 47-year-old woman: a case report

<p>Abstract</p> <p>Introduction</p> <p>Pheochromocytoma is a rare cause of hypertension but it could have severe consequences if not recognized and treated appropriately. The association of pheochromocytoma and thrombosis is even rarer but significantly increases management complexity, morbidity and mortality. To the best of our knowledge, this is the first report of a patient with pheochromocytoma presenting with left axillary arterial and intracardiac thrombus.</p> <p>Case presentation</p> <p>A 47-year-old Caucasian woman with a past medical history of hypertension presented for medical attention with left arm numbness. Doppler ultrasound showed an obstructing thrombus in her left axillary artery. She had symptom resolution after stent placement in her left axillary artery. A subsequent echocardiogram demonstrated a large intracardiac mass and abdominal computed tomography revealed a 7 cm mass between her spleen and left kidney. Labile blood pressure was noted during admission and she had very high levels of plasma and 24-hour urine catecholamines and metanephrines tests. A (123)I- metaiodobenzylguanidine scan showed intense uptake in the left abdominal mass. After adequate alpha blockage with phenoxybenzamine, laparoscopic tumor resection was performed without complications. She had normal metanephrines and complete symptom resolution afterwards. The intracardiac mass also disappeared with anticoagulation. All other endocrine laboratory abnormalities returned to normal after surgery.</p> <p>Conclusion</p> <p>Arterial and ventricular thrombosis occurring in patients with pheochromocytoma is rare. A multi-disciplinary approach is necessary in caring for this type of patient. Catecholamines likely contributed to the development of thrombosis in our patient. Early recognition of pheochromocytoma is the key to improving outcome.</p

A Critical Review of Biomarkers Used for Monitoring Human Exposure to Lead: Advantages, Limitations, and Future Needs

Lead concentration in whole blood (BPb) is the primary biomarker used to monitor exposure to this metallic element. The U.S. Centers for Disease Control and Prevention and the World Health Organization define a BPb of 10 μg/dL (0.48 μmol/L) as the threshold of concern in young children. However, recent studies have reported the possibility of adverse health effects, including intellectual impairment in young children, at BPb levels < 10 μg/dL, suggesting that there is no safe level of exposure. It appears impossible to differentiate between low-level chronic Pb exposure and a high-level short Pb exposure based on a single BPb measurement; therefore, serial BPb measurements offer a better estimation of possible health outcomes. The difficulty in assessing the exact nature of Pb exposure is dependent not so much on problems with current analytical methodologies, but rather on the complex toxicokinetics of Pb within various body compartments (i.e., cycling of Pb between bone, blood, and soft tissues). If we are to differentiate more effectively between Pb stored in the body for years and Pb from recent exposure, information on other biomarkers of exposure may be needed. None of the current biomarkers of internal Pb dose have yet been accepted by the scientific community as a reliable substitute for a BPb measurement. This review focuses on the limitations of biomarkers of Pb exposure and the need to improve the accuracy of their measurement. We present here only the traditional analytical protocols in current use, and we attempt to assess the influence of confounding variables on BPb levels. Finally, we discuss the interpretation of BPb data with respect to both external and endogenous Pb exposure, past or recent exposure, as well as the significance of Pb determinations in human specimens including hair, nails, saliva, bone, blood (plasma, whole blood), urine, feces, and exfoliated teeth