The importance of serological assays in diagnosing acute pulmonary histoplasmosis

Histoplasmosis is a systemic mycosis caused by inhalation of Histoplasma capsulatum microconidia. The disease does not normally affect immunocompetent individuals after a single, transient inhalation exposure. However, longer exposure may cause chronic or disseminated acute pulmonary infection. Herein, we report the case of a 24-year-old immunocompetent patient, who presented fever, cough and dyspnea for one month. The chest radiography revealed interstitial infiltrate and diffuse micronodules. The patient reported having had close and prolonged contact with bats. Diagnosis was confirmed by positive double immunodifusion and immunoblotting assays. She was treated with ketoconazole (400 mg) and there was complete resolution of the disease

Classical skyrmions in SU(N)/SO(N) cosets

We construct the skyrmion solutions appearing in the coset spaces SU(N)/SO(N) for N > 2 and compute their classical mass. For N = 3, the third homotopy group pi_3(SU(3)/SO(3)) = Z_4 implies the existence of two distinct solutions: the skyrmion of winding number two has spherical symmetry and is found to be the lightest non-trivial field configuration; the skyrmion and antiskyrmion of winding number plus and minus one are slightly heavier and of toroidal shape. For N >= 4, there is only one skyrmion since the third homotopy group is Z_2. It is found to have spherical symmetry and is significantly lighter than the N = 3 solutions.Comment: 14 pages, 3 figures; v2: discussion improve

Femtosecond control of electric currents at the interfaces of metallic ferromagnetic heterostructures

The idea to utilize not only the charge but also the spin of electrons in the operation of electronic devices has led to the development of spintronics, causing a revolution in how information is stored and processed. A novel advancement would be to develop ultrafast spintronics using femtosecond laser pulses. Employing terahertz (10$^{12}$ Hz) emission spectroscopy, we demonstrate optical generation of spin-polarized electric currents at the interfaces of metallic ferromagnetic heterostructures at the femtosecond timescale. The direction of the photocurrent is controlled by the helicity of the circularly polarized light. These results open up new opportunities for realizing spintronics in the unprecedented terahertz regime and provide new insights in all-optical control of magnetism.Comment: 3 figures and 2 tables in the main tex

Hypotrichosis with Juvenile Macular Dystrophy

Hypotrichosis with juvenile macular dystrophy is a rare autosomal recessive disease, characterized by hypotrichosis and progressive macular degeneration, leading to blindness in the first three decades of life. It is associated with mutations in the cadherin 3 gene, resulting in the abnormal expression of P-cadherin. We report a case of a 4-year-old female patient diagnosed with this genodermatosis.info:eu-repo/semantics/publishedVersio

The genome sequence of <i>Trypanosoma brucei gambiense</i>, causative agent of chronic Human African Trypanosomiasis

&lt;p&gt;&lt;b&gt;Background:&lt;/b&gt; &lt;i&gt;Trypanosoma brucei gambiense&lt;/i&gt; is the causative agent of chronic Human African Trypanosomiasis or sleeping sickness, a disease endemic across often poor and rural areas of Western and Central Africa. We have previously published the genome sequence of a &lt;i&gt;T. b. brucei&lt;/i&gt; isolate, and have now employed a comparative genomics approach to understand the scale of genomic variation between &lt;i&gt;T. b. gambiense&lt;/i&gt; and the reference genome. We sought to identify features that were uniquely associated with &lt;i&gt;T. b. gambiense&lt;/i&gt; and its ability to infect humans.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Methods and findings:&lt;/b&gt; An improved high-quality draft genome sequence for the group 1 &lt;i&gt;T. b. gambiense&lt;/i&gt; DAL 972 isolate was produced using a whole-genome shotgun strategy. Comparison with &lt;i&gt;T. b. brucei&lt;/i&gt; showed that sequence identity averages 99.2% in coding regions, and gene order is largely collinear. However, variation associated with segmental duplications and tandem gene arrays suggests some reduction of functional repertoire in &lt;i&gt;T. b. gambiense&lt;/i&gt; DAL 972. A comparison of the variant surface glycoproteins (VSG) in &lt;i&gt;T. b. brucei&lt;/i&gt; with all &lt;i&gt;T. b. gambiense&lt;/i&gt; sequence reads showed that the essential structural repertoire of VSG domains is conserved across &lt;i&gt;T. brucei&lt;/i&gt;.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Conclusions:&lt;/b&gt; This study provides the first estimate of intraspecific genomic variation within &lt;i&gt;T. brucei&lt;/i&gt;, and so has important consequences for future population genomics studies. We have shown that the &lt;i&gt;T. b. gambiense&lt;/i&gt; genome corresponds closely with the reference, which should therefore be an effective scaffold for any &lt;i&gt;T. brucei&lt;/i&gt; genome sequence data. As VSG repertoire is also well conserved, it may be feasible to describe the total diversity of variant antigens. While we describe several as yet uncharacterized gene families with predicted cell surface roles that were expanded in number in &lt;i&gt;T. b. brucei&lt;/i&gt;, no &lt;i&gt;T. b. gambiense&lt;/i&gt;-specific gene was identified outside of the subtelomeres that could explain the ability to infect humans.&lt;/p&gt

Titanium dioxide catalytic activity contributes to the process of free radical scavenging

TiO2 crystallochemical properties have been explored and correlated with the activity of this material in the scavenging of reactive oxygen and nitrogen species (ROS/RNS). It is well known that those highly reactive species are produced by inflammatory cells and neutralized by some oxides, such a titanium dioxide under light. Nevertheless, the mechanism of action of this ceramic material is yet to be fully understood. A set of reactions have been proposed that imply the presence of different valence states of titanium as the basis for the ROS/RNS scavenging, but in this work, we have demonstrated that those species are not always detected in TiO2-based materials, which are, in addition, active in depleting ROS/RNS. TiO2 powders with undetected Ti3+ have been obtained with a range of different properties—surface area, particle size, rutile–anatase ratio, and band gap values—by varying the powder processing conditions after synthesis through the sol precipitation route. The properties of the powders have been correlated with the scavenging activity of the materials toward two reactive species, DPPH· and peroxynitrite, always conducted under dark conditions. It was observed that despite the lack of Ti3+ states, TiO2 powders can still neutralize ROS/RNS. For the first time, this study explain how the catalytic activity of different TiO2 contribute to the free radical scavenging mechanism and the differences in scavenger activity shown by different TiO2 phases and mixtures.The authors thank Dr. Del Campo for his help with band gap measurements and Dr. GonzalezCalatayud for his helpful discussions. They acknowledge the European Project NERBIOS (NEST/STREP, FP6, 028473-2), the Conselho de Reitores das Universidades Portuguesas (Acções Integradas Luso-Espanholas, E-21/11), the Fundación General del CSIC, and La Obra Social LaCaixa for the financial support received (Proyectos Envejecimiento Cero, ref. 2001). M. Canillas acknowledges the JAE-CSIC Ph.D. fellowship received and B. Moreno acknowledges the Fondo Social Europeo and the JAEDoc program for their financial support

Integron gene cassettes harboring novel variants of D-alanine-D-alanine ligase confer high-level resistance to D-cycloserine

Antibiotic resistance poses an increasing threat to global health. To tackle this problem, the identification of principal reservoirs of antibiotic resistance genes (ARGs) plus an understanding of drivers for their evolutionary selection are important. During a PCR-based screen of ARGs associated with integrons in saliva-derived metagenomic DNA of healthy human volunteers, two novel variants of genes encoding a D-alanine-D-alanine ligase (ddl6 and ddl7) located within gene cassettes in the first position of a reverse integron were identified. Treponema denticola was identified as the likely host of the ddl cassettes. Both ddl6 and ddl7 conferred high level resistance to D-cycloserine when expressed in Escherichia coli with ddl7 conferring four-fold higher resistance to D-cycloserine compared to ddl6. A SNP was found to be responsible for this difference in resistance phenotype between the two ddl variants. Molecular dynamics simulations were used to explain the mechanism of this phenotypic change at the atomic scale. A hypothesis for the evolutionary selection of ddl containing integron gene cassettes is proposed, based on molecular docking of plant metabolites within the ATP and D-cycloserine binding pockets of Ddl

Predictors of survival and technical success of bronchoscopic interventions in malignant airway obstruction

Background: Malignant airway obstruction (MAO) leads to quality of life impairment and increased mortality. Interventional bronchoscopy allows airway patency restoring, leading to a better survival. We investigated predictors of survival and successful bronchoscopic intervention among MAO patients. Methods: This observational prospective study enrolled 100 patients who were newly diagnosed with MAO. Survival was estimated with Kaplan-Meier method and curves compared by log-rank test. Multivariate analyses were performed using Cox proportional hazard models. Univariate and multivariate logistic regression were used for odds ratio calculation. Results: A proportion of 73% of the patients were male with a median age was 62.5 years (range, 21–88 years). Lung cancer was the most common primary malignancy (74%). The majority had single (61%), endoluminal (62%) lesions and were classified as grade III in Myer Cotton scale (57%). The most used techniques comprised mechanical debulking (n=81) and laser therapy (n=68). Twenty-two airway stents were placed. While eleven patients were considered untreatable, technical success was achieved in 78%. Haemorrhage was the most common acute complication (16%). No deaths occurred as a result of the procedure. Median global survival was 8 months. Adjusting for age and Eastern Cooperative Oncology Group Performance Status (ECOG), extrinsic compression or mixed airway obstructions [hazard ratio (HR) =2.075; P=0.012], successful bronchoscopic intervention (HR =0.468; P=0.025) and initiation of cancer treatment (HR =0.373; P=0.006) were independent predictors of survival. The absence of distal airway patency on thoracic CT was independently associated with failure of the intervention [odds ratio (OR) =0.013; P<0.001]. Conclusions: Interventional bronchoscopy has proven to be an efficient and safe strategy to manage MAO patients. The patients who benefit the most in terms of survival are those with purely endoluminal lesions, in whom technical success was achieved and those whose cancer-specific treatment was initiated. Distal airway patency on thoracic CT predicts the technical success of bronchoscopic intervention

Mixed medullary-papillary thyroid carcinoma with mixed lymph node metastases: A case report

Mixed medullary-follicular-derived carcinoma is a very rare event. It is extremely important to make the correct diagnosis, due to prognostic and treatment implications. A genetic study of these patients is advisable to exclude the presence of MEN 2.We would like to acknowledge all the endocrinologists, surgeons, geneticists, radiologists, and pathologists of IPO-Porto

Regulation of immunity during visceral Leishmania infection

Unicellular eukaryotes of the genus Leishmania are collectively responsible for a heterogeneous group of diseases known as leishmaniasis. The visceral form of leishmaniasis, caused by L. donovani or L. infantum, is a devastating condition, claiming 20,000 to 40,000 lives annually, with particular incidence in some of the poorest regions of the world. Immunity to Leishmania depends on the development of protective type I immune responses capable of activating infected phagocytes to kill intracellular amastigotes. However, despite the induction of protective responses, disease progresses due to a multitude of factors that impede an optimal response. These include the action of suppressive cytokines, exhaustion of specific T cells, loss of lymphoid tissue architecture and a defective humoral response. We will review how these responses are orchestrated during the course of infection, including both early and chronic stages, focusing on the spleen and the liver, which are the main target organs of visceral Leishmania in the host. A comprehensive understanding of the immune events that occur during visceral Leishmania infection is crucial for the implementation of immunotherapeutic approaches that complement the current anti-Leishmania chemotherapy and the development of effective vaccines to prevent disease.The research leading to these results has received funding from the European Community’s Seventh Framework Programme under grant agreement No.602773 (Project KINDRED). VR is supported by a post-doctoral fellowship granted by the KINDReD consortium. RS thanks the Foundation for Science and Technology (FCT) for an Investigator Grant (IF/00021/2014). This work was supported by grants to JE from ANR (LEISH-APO, France), Partenariat Hubert Curien (PHC) (program Volubilis, MA/11/262). JE acknowledges the support of the Canada Research Chair Program