COVID-19 related acute genital ulcer: a case report

Acute vulvar ulcer (Lipschütz's ulcer) is a rare lesion with local hyperimmunoreactivity triggered by infection, which is characterized by acute, painful, and necrotic ulcerations. This condition is usually found in non-sexually active adolescents, and it resolves spontaneously. We report a case of a 35-year-old woman who was diagnosed with COVID-19 who did not have severe symptoms, but had high levels of D-dimer for 9 days. The COVID-19 diagnosis was followed by the appearance of an acute, necrotic, extremely painful vulvar ulcer, although symptoms caused by COVID-19 had improved. We emphasize the importance of the differential diagnosis to exclude diseases such as Behçet's syndrome, Sexually Transmitted Infections, as well as the presence of viruses that generally trigger Lipschütz's ulcer, such as Epstein-Barr virus and cytomegalovirus. No treatment is usually necessary, however, in the present report due to the pain experienced by the patient, we successfully used oral prednisone.info:eu-repo/semantics/publishedVersio

Patients' perception regarding the influence of individual and social vulnerabilities on the adherence to tuberculosis treatment: a qualitative study

Background: Tuberculosis remains an important disease which mainly affects the majority of vulnerable individuals in society, who are subjected to poor living conditions and difficulties to access the services of public health. Under these circumstances, the present study aims to understand patients' perception in relation to the influence of individual and social vulnerabilities on the adherence to tuberculosis treatment. Methods: A qualitative descriptive cross sectional study was conducted in one large municipality at the state of Paraiba, Northeast of Brazil. The study subjects, who were residents of the study site, covered all tuberculosis cases diagnosed between March and June 2015. The sample was defined by the criteria of response saturation. All interviews were audio recorded, and data analysis was developed through the hermeneutic dialectic method and the theory of Generative Route Sense. The project was approved by the Research Ethics Committee of the University of Sao Paulo (USP). Results: A total of 13 individuals were interviewed and the responses were identified into two analytical categories: the difficulties they had and the enabling factors they could mention during their tuberculosis treatment. Patients brought up social exclusion as an obstacle to treatment adherence, which, along with stigmatization, weakened their link with family members and health professionals. Moreover, economic precariousness was a major hindrance to the maintenance of a proper diet and transportation access to health centers. However, social support and directly observed treatment helped to break down barriers of prejudice and to promote individual and family empowerment. Finally, patients also reported that their will to live and faith gave them the strength to continue with the treatment. Conclusions: According to patients in this study, social support and the strengthening of links with family members and health professionals may reduce social exclusion and other difficulties they face, thus encouraging them to the adhere to tuberculosis treatment.Univ Estadual Paraiba, Campina Grande, Paraiba, BrazilUniv Fed Rio Grande do Norte, Natal, RN, BrazilUniv Sao Paulo, Escola Enfermagem, Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Escola Paulista Enfermagem, Sao Paulo, BrazilFac Santa Maria, Cajazeiras, Paraiba, BrazilUniv Fed Sao Paulo, Escola Paulista Enfermagem, Sao Paulo, BrazilWeb of Scienc

Application of isothermal titration calorimetry in evaluation of protein–nanoparticle interactions

Nanoparticles (NPs) offer a number of advantages over small organic molecules for controlling protein behaviour inside the cell. Protein binding to the surface of NPs depends on their surface characteristics, composition and method of preparation (Mandal et al. in J Hazard Mater 248–249:238–245, 2013). It is important to understand the binding affinities, stoichiometries and thermodynamical parameters of NP–protein interactions in order to see which interaction will have toxic and hazardous consequences and thus to prevent it. On the other side, because proteins are on the brink of stability, they may experience interactions with some types of NPs that are strong enough to cause denaturation or significantly change their conformations with concomitant loss of their biological function. Structural changes in the protein may cause exposure of new antigenic sites, “cryptic” peptide epitopes, potentially triggering an immune response which can promote autoimmune disease (Treuel et al. in ACS Nano 8(1):503–513, 2014). Mechanistic details of protein structural changes at NP surface have still remained elusive. Understanding the formation and persistence of the protein corona is critical issue; however, there are no many analytical methods which could provide detailed information about the NP–protein interaction characteristics and about protein structural changes caused by interactions with nanoparticles. The article reviews recent studies in NP–protein interactions research and application of isothermal titration calorimetry (ITC) in this research. The study of protein structural changes upon adsorption on nanoparticle surface and application of ITC in these studies is emphasized. The data illustrate that ITC is a versatile tool for evaluation of interactions between NPs and proteins. When coupled with other analytical methods, it is important analytical tool for monitoring conformational changes in proteins

Synthetic Peptides Mimic gp75 from Paracoccidioides brasiliensis in the Diagnosis of Paracoccidioidomycosis

Paracoccidioidomycosis (PCM) is a systemic granulomatous disease, endemic in Latin America, caused by the thermal dimorphic fungus Paracoccidioides brasiliensis. Although some fungal antigens have already been characterized and used for serological diagnosis, cross-reactions have been frequently observed. Thus, the examination of fungal forms in clinical specimens or isolation of P. brasiliensis by culture is still the most frequent method for the diagnosis of this mycosis. In this study, a random peptide phage display library was used to select mimotopes of P. brasiliensis, which were employed as antigens in an indirect enzyme-linked immunosorbent assay. The protective monoclonal antibody against experimental PCM (anti-gp75) was used as molecular target to screen a phage display library. That approach led to a synthetic peptide named P2, which was synthesized and tested against PCM patients’ sera to check whether it was recognized. There was significant recognition of P2 by sera of untreated PCM patients when compared with normal human sera. Sera from treated PCM group, patients with other mycosis or co-infected with HIV had much lower recognition of P2 than untreated patient group. The test showed a sensitivity of 100 and 94.59% of specificity in relation to human sera control. These data indicate a potential use of P2 as diagnostic tool in PCM. Its application for serological diagnosis of PCM may contribute to the development and standardization of simpler, faster and highly reproducible immunodiagnostic tests at low cost

Biosafety of Non-Surface Modified Carbon Nanocapsules as a Potential Alternative to Carbon Nanotubes for Drug Delivery Purposes

BACKGROUND: Carbon nanotubes (CNTs) have found wide success in circuitry, photovoltaics, and other applications. In contrast, several hurdles exist in using CNTs towards applications in drug delivery. Raw, non-modified CNTs are widely known for their toxicity. As such, many have attempted to reduce CNT toxicity for intravenous drug delivery purposes by post-process surface modification. Alternatively, a novel sphere-like carbon nanocapsule (CNC) developed by the arc-discharge method holds similar electric and thermal conductivities, as well as high strength. This study investigated the systemic toxicity and biocompatibility of different non-surface modified carbon nanomaterials in mice, including multi-walled carbon nanotubes (MWCNTs), single-walled carbon nanotubes (SWCNTs), carbon nanocapsules (CNCs), and C ₆₀ fullerene (C ₆₀). The retention of the nanomaterials and systemic effects after intravenous injections were studied. METHODOLOGY AND PRINCIPAL FINDINGS: MWCNTs, SWCNTs, CNCs, and C ₆₀ were injected intravenously into FVB mice and then sacrificed for tissue section examination. Inflammatory cytokine levels were evaluated with ELISA. Mice receiving injection of MWCNTs or SWCNTs at 50 µg/g b.w. died while C ₆₀ injected group survived at a 50% rate. Surprisingly, mortality rate of mice injected with CNCs was only at 10%. Tissue sections revealed that most carbon nanomaterials retained in the lung. Furthermore, serum and lung-tissue cytokine levels did not reveal any inflammatory response compared to those in mice receiving normal saline injection. CONCLUSION: Carbon nanocapsules are more biocompatible than other carbon nanomaterials and are more suitable for intravenous drug delivery. These results indicate potential biomedical use of non-surface modified carbon allotrope. Additionally, functionalization of the carbon nanocapsules could further enhance dispersion and biocompatibility for intravenous injection

Incorporation of DPP6a and DPP6K Variants in Ternary Kv4 Channel Complex Reconstitutes Properties of A-type K Current in Rat Cerebellar Granule Cells

Dipeptidyl peptidase-like protein 6 (DPP6) proteins co-assemble with Kv4 channel α-subunits and Kv channel-interacting proteins (KChIPs) to form channel protein complexes underlying neuronal somatodendritic A-type potassium current (ISA). DPP6 proteins are expressed as N-terminal variants (DPP6a, DPP6K, DPP6S, DPP6L) that result from alternative mRNA initiation and exhibit overlapping expression patterns. Here, we study the role DPP6 variants play in shaping the functional properties of ISA found in cerebellar granule (CG) cells using quantitative RT-PCR and voltage-clamp recordings of whole-cell currents from reconstituted channel complexes and native ISA channels. Differential expression of DPP6 variants was detected in rat CG cells, with DPP6K (41±3%)>DPP6a (33±3%)>>DPP6S (18±2%)>DPP6L (8±3%). To better understand how DPP6 variants shape native neuronal ISA, we focused on studying interactions between the two dominant variants, DPP6K and DPP6a. Although previous studies did not identify unique functional effects of DPP6K, we find that the unique N-terminus of DPP6K modulates the effects of KChIP proteins, slowing recovery and producing a negative shift in the steady-state inactivation curve. By contrast, DPP6a uses its distinct N-terminus to directly confer rapid N-type inactivation independently of KChIP3a. When DPP6a and DPP6K are co-expressed in ratios similar to those found in CG cells, their distinct effects compete in modulating channel function. The more rapid inactivation from DPP6a dominates during strong depolarization; however, DPP6K produces a negative shift in the steady-state inactivation curve and introduces a slow phase of recovery from inactivation. A direct comparison to the native CG cell ISA shows that these mixed effects are present in the native channels. Our results support the hypothesis that the precise expression and co-assembly of different auxiliary subunit variants are important factors in shaping the ISA functional properties in specific neuronal populations

A Genome-Wide Linkage Scan for Distinct Subsets of Schizophrenia Characterized by Age at Onset and Neurocognitive Deficits

As schizophrenia is genetically and phenotypically heterogeneous, targeting genetically informative phenotypes may help identify greater linkage signals. The aim of the study is to evaluate the genetic linkage evidence for schizophrenia in subsets of families with earlier age at onset or greater neurocognitive deficits.Patients with schizophrenia (n  =  1,207) and their first-degree relatives (n  =  1,035) from 557 families with schizophrenia were recruited from six data collection field research centers throughout Taiwan. Subjects completed a face-to-face semi-structured interview, the Continuous Performance Test (CPT), the Wisconsin Card Sorting Test, and were genotyped with 386 microsatellite markers across the genome.A maximum nonparametric logarithm of odds (LOD) score of 4.17 at 2q22.1 was found in 295 families ranked by increasing age at onset, which had significant increases in the maximum LOD score compared with those obtained in initial linkage analyses using all available families. Based on this subset, a further subsetting by false alarm rate on the undegraded and degraded CPT obtained further increase in the nested subset-based LOD on 2q22.1, with a score of 7.36 in 228 families and 7.71 in 243 families, respectively.We found possible evidence of linkage on chromosome 2q22.1 in families of schizophrenia patients with more CPT false alarm rates nested within the families with younger age at onset. These results highlight the importance of incorporating genetically informative phenotypes in unraveling the complex genetics of schizophrenia