Cytomegalovirus in Adenoma and Carcinoma Lesions: Detecting Mono-Infection and Co-Infection in Salivary Glands.

Salivary glands' neoplasms are hard to diagnose and present a complex etiology. However, several viruses have been detected in these neoplasms, such as HCMV, which can play a role in certain cancers through oncomodulation. The co-infections between HCMV with betaherpesviruses (HHV-6 and HHV-7) and polyomaviruses (JCV and BKV) has been investigated. The aim of the current study is to describe the frequency of HCMV and co-infections in patients presenting neoplastic and non-neoplastic lesions, including in the salivary gland. Multiplex quantitative polymerase chain reaction was used for betaherpesvirus and polyomavirus quantification purposes after DNA extraction. In total, 50.7% of the 67 analyzed samples were mucocele, 40.3% were adenoma pleomorphic, and 8.9% were mucoepidermoid carcinoma. Overall, 20.9% of samples presented triple-infections with HCMV/HHV-6/HHV-7, whereas 9.0% were co-infections with HCMV/HHV-6 and HCMV/HHV-7. The largest number of co-infections was detected in pleomorphic adenoma cases. All samples tested negative for polyomaviruses, such as BKV and JCV. It was possible to conclude that HCMV can be abundant in salivary gland lesions. A high viral load can be useful to help better understand the etiological role played by viruses in these lesions. A lack of JCV and BKV in the samples analyzed herein does not rule out the involvement of these viruses in one or more salivary gland lesion subtypes.

Anatomical Vascular Differences and Leishmania-Induced Vascular Morphological Changes Are Associated with a High Parasite Load in the Skin of Dogs Infected with Leishmania infantum.

Canine visceral leishmaniasis (CVL), caused by the protozoan Leishmania infantum, affects several organs, including the skin. Dogs are considered the major domestic reservoir animals for leishmaniasis, and through their highly parasitized skin, they can serve as a source of infection for sandfly vectors. Therefore, studies of the skin parasite-host relationship can contribute to the understanding of the infectious dissemination processes of parasites in the dermis and help to identify targets for diagnosis and treatment. Thus, the aim of this study was to evaluate the association of anatomical vascular differences and Leishmania-induced vascular morphological changes with clinical signs and parasite load by analyzing the ear and abdominal skin from dogs naturally infected with L. infantum. Paired samples of ear and abdominal skin from L. infantum-positive dogs (n = 26) were submitted for histological and immunohistochemistry analyses. The ear skin samples showed a more intense and more diffusely distributed granulomatous inflammatory reaction, a higher number and larger diameter of blood vessels, increased parasite load, higher expression of VEGF+ (vascular endothelial growth factor) and MAC 387+ (calprotectin) recently infiltrating cells, and more intense collagen disruption compared to the abdominal skin samples. Intracellular amastigotes were observed in blood vessels and inside endothelial cells and were diffusely distributed throughout the dermis in the ear skin samples. The NOS2/MAC387+ cell ratio was lower in the ear skin samples than in those of the abdomen, suggesting that in the ear dermis, the inflammatory infiltrate was less capable of producing NO and thereby control the parasite load. Together, these findings indicate how parasites and immune cells are distributed in the skin and suggest an important role for dermal vascularization in cellular influx and thereby in parasite dissemination through the skin of naturally infected dogs.

A 7-Month Multidisciplinary Healthy Lifestyle Intervention Effectively Improved Cardiometabolic Risk Profile of Firefighters.

OBJECTIVE: We investigated the effect of a 7-month healthy lifestyle intervention on cardiometabolic risk factors (CMRF) among male career military firefighters (FFs). METHODS: Forty-nine FFs participated in a 7-month workplace multiddisciplinary healthy lifestyle intervention designed to reduce CMRF through exercise, diet, and improved sleep. Medical assessments, accelerometry, and surveys at the beginning and end determined program effectiveness. RESULTS: At the end of the intervention period, there was a significant improvement in measures of body composition and blood glucose. The prevalence of hypertension also decreased significantly ( P < 0.01). The 57% of participants who fully adhered to the program had significantly greater improvements across multiple CMRF. Participants increased their physical activity and improved their diet following the intervention. CONCLUSIONS: This healthy lifestyle intervention was effective in changing behavior and lowering cardiometabolic risk among FFs.

Identification of an ex vivo inhibitor of the schizophrenia biomarker Ndel1 by high throughput screening.

Ndel1 oligopeptidase activity shows promise as a potential biomarker for diagnosing schizophrenia (SCZ) and monitoring early-stage pharmacotherapy. Ndel1 plays a pivotal role in critical aspects of brain development, such as neurite outgrowth, neuronal migration, and embryonic brain formation, making it particularly relevant to neurodevelopmental disorders like SCZ. Currently, the most specific inhibitor for Ndel1 is the polyclonal anti-Ndel1 antibody (NOAb), known for its high specificity and efficient anti-catalytic activity. NOAb has been vital in measuring Ndel1 activity in humans and animal models, enabling the prediction of pharmacological responses to antipsychotics in studies with patients and animals. To advance our understanding of in vivo Ndel1 function and develop drugs for mental disorders, identifying small chemical compounds capable of specifically inhibiting Ndel1 oligopeptidase is crucial, including within living cells. Due to challenges in obtaining Ndel1's three-dimensional structure and its promiscuous substrate recognition, we conducted a high-throughput screening (HTS) of 2,400 small molecules. Nine compounds with IC50-values ranging from 7 to 56 µM were identified as potent Ndel1 inhibitors. Notably, one compound showed similar efficacy to NOAb and inhibited Ndel1 within living cells, although its in vivo use may pose toxicity concerns. Despite this, all identified compounds hold promise as candidates for further refinement through rational drug design, aiming to enhance their inhibitory efficacy, specificity, stability, and biodistribution. Our ultimate goal is to develop druggable Ndel1 inhibitors that can improve the treatment and support the diagnosis of psychiatric disorders like SCZ.

Lectin-based carbohydrate profile of megakaryocytes in murine fetal liver during development.

Hematopoiesis is the process by which blood cells are generated. During embryonic development, these cells migrate through different organs until they reach the bone marrow, their definitive place in adulthood. Around E10.5, the fetal liver starts budding from the gut, where first hematopoietic cells arrive and expand. Hematopoietic cell migration occurs through cytokine stimulation, receptor expression, and glycosylation patterns on the cell surface. In addition, carbohydrates can modulate different cell activation states. For this reason, we aimed to characterize and quantify fetal megakaryocytic cells in mouse fetal liver according to their glycan residues at different gestational ages through lectins. Mouse fetuses between E11.5 and E18.5 were formalin-fixed and, paraffin-embedded, for immunofluorescence analysis using confocal microscopy. The results showed that the following sugar residues were expressed in proliferating and differentiating megakaryocytes in the fetal liver at different gestational ages: α-mannose, α-glucose, galactose, GlcNAc, and two types of complex oligosaccharides. Megakaryocytes also showed three proliferation waves during liver development at E12.5, E14.5, and E18.5. Additionally, the lectins that exhibited high and specific pattern intensities at liver capsules and vessels were shown to be a less time-consuming and robust alternative alternative to conventional antibodies for displaying liver structures such as capsules and vessels, as well as for megakaryocyte differentiation in the fetal liver.

Capture ELISA for KPC Detection in Gram-Negative Bacilli: Development and Standardisation.

The detection of KPC-type carbapenemases is necessary for guiding appropriate antibiotic therapy and the implementation of antimicrobial stewardship and infection control measures. Currently, few tests are capable of differentiating carbapenemase types, restricting the lab reports to their presence or not. The aim of this work was to raise antibodies and develop an ELISA test to detect KPC-2 and its D179 mutants. The ELISA-KPC test was designed using rabbit and mouse polyclonal antibodies. Four different protocols were tested to select the bacterial inoculum with the highest sensitivity and specificity rates. The standardisation procedure was performed using 109 previously characterised clinical isolates, showing 100% of sensitivity and 89% of specificity. The ELISA-KPC detected all isolates producing carbapenemases, including KPC variants displaying the ESBL phenotype such as KPC-33 and -66.

Potential of an anti-bevacizumab idiotype scFv DNA-based immunization to elicit VEGF-binding antibody response.

Anti-idiotype antibodies have been considered for vaccination approaches against different diseases, including cancers. Based on that, we previously described an anti-bevacizumab idiotype monoclonal antibody, 10.D7, that revealed detectable antitumor effects on a vascular endothelial growth factor (VEGF)-dependent tumor model. Herein, we evaluated the possible applicability of a single-chain variable fragment (scFv) for the 10.D7 antibody in a gene immunization strategy. After checking that mammalian cells transfected to express the 10.D7 scFv are recognized by bevacizumab, it was explored the ability of our scFv construction, in a gene-based scheme, to elicit an immune response containing VEGF-binding antibodies. The results provide evidence that the designed 10.D7 scFv construct maintains the anti-bevacizumab idiotype features and has potential to activate an immune response recognizing VEGF.

Capture ELISA for KPC detection in gram-negative bacilli: development and standardisation

The detection of KPC-type carbapenemases is necessary for guiding appropriate antibiotic therapy and the implementation of antimicrobial stewardship and infection control measures. Currently, few tests are capable of differentiating carbapenemase types, restricting the lab reports to their presence or not. The aim of this work was to raise antibodies and develop an ELISA test to detect KPC-2 and its D179 mutants. The ELISA-KPC test was designed using rabbit and mouse polyclonal antibodies. Four different protocols were tested to select the bacterial inoculum with the highest sensitivity and specificity rates. The standardisation procedure was performed using 109 previously characterised clinical isolates, showing 100% of sensitivity and 89% of specificity. The ELISA-KPC detected all isolates producing carbapenemases, including KPC variants displaying the ESBL phenotype such as KPC-33 and -66.

Digital psychosocial intervention for depression among older adults in socioeconomically deprived areas in Brazil (PRODIGITAL-D): protocol for an individually randomised controlled trial.

BACKGROUND: Depression in older adults is a challenge for health systems in most low- and middle-income countries (LMICs). Digital strategies for the management of this condition have been emerging worldwide, but the effectiveness of most of them is still unclear, especially among older adults. Thus, we aim to assess the effectiveness and cost-effectiveness of a digital psychosocial intervention to treat depression among older adults living in socioeconomically deprived areas in Guarulhos, Brazil. METHODS: We will conduct a two-arm individually randomised controlled trial with 1:1 allocation ratio. Five hundred older adults aged 60 years or over with depressive symptomatology (9-item Patient Health Questionnaire score, PHQ-9 ≥ 10) and registered with one of the primary care clinics will be recruited to participate in this study. A 6-week digital psychosocial programme, named Viva Vida, will be delivered via WhatsApp to participants allocated to the intervention arm. The Viva Vida will send psychoeducational and behavioural activation audio and visual messages 4 days a week for 6 weeks. The control arm will only receive a single message with general information about depression. The primary outcome will be the proportion of depression recovery (PHQ-9 < 10) assessed at 3 months. The cost-effectiveness of the intervention will be assessed at 5 months. A detailed process evaluation will be used to explore context and important implementation outcomes. DISCUSSION: This programme was based on the PROACTIVE intervention and designed to be delivered without face-to-face contact. If effective, it could be a simple treatment option, appropriate not only when social distancing is required, but it could also be included as a regular public health programme to initiate depression treatment, particularly in LMICs where resources allocated to mental health are scarce. TRIAL REGISTRATION: Registro Brasileiro de Ensaios Clínicos (ReBEC), RBR-4c94dtn. Registered on 22 October 2021 (submitted on 03 August 2021).

The hepatic extramedullary hematopoiesis during experimental murine Schistosomiasis mansoni.

Many years ago, our research group has demonstrated extramedullary hematopoiesis in the peripheral zone of murine hepatic schistosomal granulomas. In the present study, we revisit this phenomenon using new technical and conceptual approaches. Therefore, newborn mice were percutaneously infected by Schistosoma mansoni cercariae and euthanized between 35- and 60-days post infection. Liver samples were submitted to histopathology and immunohistochemical analyses. Cells under mitosis and/or expressing Ki67 demonstrated the proliferation of hematopoietic cells both around the parasite's eggs trapped in the liver and around hepatic vessels. After 50 days post infection, proliferating cells at different levels on differentiation were located preferentially in the peripheral zone of the granulomas, around the vessels and inside the sinusoids. The presence of acidic and sulfated glycoconjugates, reticular fibers and the absence of fibronectin characterized the microenvironment for attraction and maintenance of hematopoiesis. Some neutrophils secreted MMP9 from the earliest points of infection, indicating degradation of the extracellular matrix in regions of histolysis and a possible chemoattraction of hematopoietic stem cells to the liver. Fall-3+ cells and Sca-1+ cells indicated that early hematopoietic progenitors could be mobilized to the liver. Groups of vWF+ megakaryocytes suggest chemoattraction of these cells and/or migration, proliferation, and differentiation of very immature progenitors to this organ. The increase of blood vessels and extramedullary hematopoiesis in this environment, where markers of immature hematopoietic and endothelial cells have been identified, points to the possibility of the presence of progenitors for endothelial and hematopoietic cells in the liver during the infection. There is also the possibility of concomitant migration of more differentiated hematopoietic progenitors, that proliferate and differentiate in the liver, and the occurrence of angiogenesis caused by inflammation or release of ovular antigens that stimulate the activation and proliferation of endothelial cells. Altogether, these data increase knowledge about a murine model that is of interest for investigating the pathology of the schistosomiasis and also the dynamics of hematopoiesis.

Oral Trypanosoma cruzi Acute Infection in Mice Targets Primary Lymphoid Organs and Triggers Extramedullary Hematopoiesis.

During the acute phase of Chagas disease, Trypanosoma cruzi circulation through the bloodstream leads to high tissue parasitism in the host. In primary lymphoid organs, progenitor cell reduction paralleled transient immunosuppression. Herein we showed that acute oral infection in mice promotes diffuse parasitism in bone marrow cells at 14 and 21 days post-infection (dpi), with perivascular regions, intravascular regions, and regions near the bone being target sites of parasite replication. Phenotypic analysis of hematopoietic differentiation in the bone marrow of infected mice showed that the cell number in the tissue is decreased (lineage-negative and lineage-positive cells). Interestingly, analysis of hematopoietic branching points showed that hematopoietic stem and progenitor cells (HSPCs) were significantly increased at 14 dpi. In addition, the pool of progenitors with stem plasticity (HSC-MPP3), as well as multipotent progenitors (MPPs) such as MPP4, also showed this pattern of increase. In contrast, subsequent progenitors that arise from MPPs, such as common lymphoid progenitors (CLPs), lymphoid-primed MPPs (LMPPs), and myeloid progenitors, were not enhanced; conversely, all presented numeric decline. Annexin V staining revealed that cell death increase in the initial hematopoietic branching point probably is not linked to CLPs and that myeloid progenitors decreased at 14 and 21 dpi. In parallel, our investigation provided clues that myeloid progenitor decrease could be associated with an atypical expression of Sca-1 in this population leading to a remarkable increase on LSK-like cells at 14 dpi within the HSPC compartment. Finally, these results led us to investigate HSPC presence in the spleen as a phenomenon triggered during emergency hematopoiesis due to mobilization or expansion of these cells in extramedullary sites. Splenocyte analysis showed a progressive increase in HSPCs between 14 and 21 dpi. Altogether, our study shows that the bone marrow is a target tissue in T. cruzi orally infected mice, leading to a hematopoietic disturbance with LSK-like cell bias accounting on HSPCs possibly affecting myeloid progenitor numbers. The LMPP and CLP reduction converges with defective thymocyte development. Lastly, it is tempting to speculate that the extramedullary hematopoiesis seen in the spleen is a mechanism involved in the hematological maintenance reported during the acute phase of oral T. cruzi infection.

Host cholesterol influences the activity of sterol biosynthesis inhibitors in Leishmania amazonensis.

A significant percentage of exogenous cholesterol was found in promastigotes and amastigotes of all studied species of Leishmania, suggesting a biological role for this molecule. Previous studies have shown that promastigotes of Leishmania uptake more low-density lipoprotein (LDL) particles under pharmacological pressure and are more susceptible to ergosterol inhibition in the absence of exogenous sources of cholesterol. This work shows that the host's LDL is available to intracellular amastigotes and that the absence of exogenous cholesterol enhances the potency of sterol biosynthesis inhibitors in infected macrophages. A complete understanding of cholesterol transport to the parasitophorous vacuole can guide the development of a new drug class to be used in combination with sterol biosynthesis inhibitors for the treatment of leishmaniases.

Carcinoma basocelular de couro cabeludo x alopecia frontal fibrosante: desafio diagnóstico e terapêutico / Basal cell carcinoma of the scalp x frontal fibrosing alopecia: diagnostic and therapeutic challenge

O carcinoma basocelular é considerado a neoplasia mais comum do mundo, tem como principal fator de risco a radiação ultravioleta, pode aparecer em todo o corpo incluindo couro cabeludo. A alopecia frontal fibrosante é uma alopecia cicatricial primária, variante do líquen planopilar. A associação entre as duas patologias não tem relato prévio na literatura. Neste caso apresenta-se paciente feminina, pós-menopausa, atendida por queixa de queda de cabelo, com diagnóstico histopatológico de alopecia frontal fibrosante e carcinoma basocelular de couro cabeludo. A distinção das margens tumorais para exérese completa da neoplasia é complexa apenas pela dermatoscopia e exame físico, devido á presença de áreas de atrofia em comum. Então se optou pela cirurgia micrográfica de Mohs para delimitação histopatológica de margens.

BCC is considered the most common neoplasia in the world, it can appear throughout the body including the scalp. Frontal fibrosing alopecia is a primary scarring alopecia, variant of lichen planopilaris. The association between the two pathologies has not been previously reported in the literature. In this case it is presented a brazilian female patient complaining of hair loss, with histopathological diagnosis of AFF and scalp BCC. The distinction of tumor margins for neoplastic excision is complex only by dermoscopy and physical examination, due to areas of common atrophy. So Mohs micrographic surgery was chosen for histopathological delimitation of margins.

A comparative analysis of metaheuristics applied to adaptive curriculum sequencing.

The effective adoption of online learning depends on user satisfaction as distance education approaches suffer from a lack of commitment that may lead to failures and dropouts. The adaptive learning literature argues that an alternative to achieve student satisfaction is to treat them individually, delivering the educational content in a personalized manner. In addition, the sequencing of this content-called Adaptive Curriculum Sequencing (ACS)-is important to avoid cognitive overload and disorientation. The search for an optimal sequence from ever-growing databases is an NP-Hard combinatorial optimization problem. Although some approaches have been proposed, it is challenging to assess their contributions due to the lack of benchmark data available. This paper presents a procedure to create synthetic dataset to evaluate ACS approaches and, as a concept proof, analyzes metaheuristics usually used in ACS approaches: Genetic Algorithm, Particle Swarm Optimization (PSO) and Prey-Predator Algorithm using student's learning goals and their extrinsic and intrinsic information. We also propose an approach based on Differential Evolution (DE). The computational experiments include synthetic datasets with a varied amount of learning materials and real-world datasets for comparison. The results show that DE performed better than the other methods when less than 500 learning materials are used while PSO performed better for larger problems.

Should COVID-19 be branded to viral thrombotic fever?

Coronaviruses can cause a diverse array of clinical manifestations, from fever with symptoms of the common cold to highly lethal severe acute respiratory syndrome (SARS) and middle east respiratory syndrome (MERS). SARS-CoV-2, the coronavirus discovered in Hubei province, China, at the end of 2019, became known worldwide for causing coronavirus disease 2019 (COVID-19). Over one year's time period, the scientific community has produced a large bulk of knowledge about this disease and countless reports about its immune-pathological aspects. This knowledge, including data obtained in postmortem studies, points unequivocally to a hypercoagulability state. However, the name COVID-19 tells us very little about the true meaning of the disease. Our proposal is more comprehensive; it intends to frame COVID-19 in more clinical terminology, making an analogy to viral haemorrhagic fever (VHF). Thus, we found irrefutable evidence in the current literature that COVID-19 is the first viral disease that can be branded as a viral thrombotic fever. This manuscript points out that SARS-CoV-2 goes far beyond pneumonia or SARS. COVID-19 infections promote remarkable interactions among the endothelium, coagulation, and immune response, building up a background capable of promoting a "thrombotic storm," much more than a "cytokine storm." The importance of a viral protease called main protease (Mpro) is highlighted as a critical component for its replication in the host cell. A deeper analysis of this protease and its importance on the coagulation system is also discussed for the first time, mainly because of its similarity with the thrombin and factor Xa molecules, as recently pointed out by structural comparison crystallographic structures.

Amentoflavone as an Ally in the Treatment of Cutaneous Leishmaniasis: Analysis of Its Antioxidant/Prooxidant Mechanisms.

Treatment of leishmaniasis is a challenging subject. Although available, chemotherapy is limited, presenting toxicity and adverse effects. New drugs with antileishmanial activity are being investigated, such as antiparasitic compounds derived from plants. In this work, we investigated the antileishmanial activity of the biflavonoid amentoflavone on the protozoan Leishmania amazonensis. Although the antileishmanial activity of amentoflavone has already been reported in vitro, the mechanisms involved in the parasite death, as well as its action in vivo, remain unknown. Amentoflavone demonstrated activity on intracellular amastigotes in macrophages obtained from BALB/c mice (IC50 2.3 ± 0.93 µM). No cytotoxicity was observed and the selectivity index was estimated as greater than 10. Using BALB/c mice infected with L. amazonensis we verified the effect of an intralesional treatment with amentoflavone (0.05 mg/kg/dose, in a total of 5 doses every 4 days). Parasite quantification demonstrated that amentoflavone reduced the parasite load in treated footpads (46.3% reduction by limiting dilution assay and 56.5% reduction by Real Time Polymerase Chain Reaction). Amentoflavone decreased the nitric oxide production in peritoneal macrophages obtained from treated animals. The treatment also increased the expression of ferritin and decreased iNOS expression at the site of infection. Furthemore, it increased the production of ROS in peritoneal macrophages infected in vitro. The increase of ROS in vitro, associated with the reduction of NO and iNOS expression in vivo, points to the antioxidant/prooxidant potential of amentoflavone, which may play an important role in the balance between inflammatory and anti-inflammatory patterns at the infection site. Taken together these results suggest that amentoflavone has the potential to be used in the treatment of cutaneous leishmaniasis, working as an ally in the control and development of the lesion.

Recovery of Synthetic Zika Virus Based on Rio-U1 Isolate Using a Genetically Stable Two Plasmid System and cDNA Amplification.

In 2016, the world experienced the unprecedented Zika epidemic. The ZIKV emerged as a major human pathogen due to its association with the impairment of perinatal development and Guillain-Barré syndrome. The occurrence of these severe cases of Zika points to the significance of studies for understanding the molecular determinants of flavivirus pathogenesis. Reverse genetics is a powerful method for studying the replication and determinants of pathogenesis, virulence, and viral attenuation of flaviviruses, facilitating the design of vaccines and therapeutics. However, the main hurdle in the development of infectious clones is the instability of full-length cDNA in Escherichia coli. Here, we described the development of a genetically stable and efficient infectious clone based on the ZIKV Rio-U1 isolated in the 2016 epidemic in Brazil. The employed strategy consisted of cloning the viral cDNA genome into two stable plasmid subclones and obtaining a high-quality cDNA template with increment in DNA mass for in vitro transcription by PCR amplification. The strategy for developing a ZIKV infectious cDNA clone designed in this study was successful, yielding a replicative and efficient clone-derived virus with high similarities with its parental virus, Rio-U1, by comparison of the proliferation capacity in mammal and insect cells. The infection of AG129 immunocompromised mice caused identical mortality rates, with similar disease progression and morbidity in the animals infected with the parental and the cDNA-derived virus. Histopathological analyses of mouse brains infected with the parental and the cDNA-derived viruses revealed a similar pathogenesis degree. We observed meningoencephalitis, cellular pyknosis, and neutrophilic invasion adjacent to the choroid plexus and perivascular cuffs with the presence of neutrophils. The developed infectious clone will be a tool for genetic and functional studies in vitro and in vivo to understand viral infection and pathogenesis better.

Generation and functional characterization of a single-chain variable fragment (scFv) of the anti-FGF2 3F12E7 monoclonal antibody.

Single-chain variable fragments (scFvs) are small-sized artificial constructs composed of the immunoglobulin heavy and light chain variable regions connected by a peptide linker. We have previously described an anti-fibroblast growth factor 2 (FGF2) immunoglobulin G (IgG) monoclonal antibody (mAb), named 3F12E7, with notable antitumor potential revealed by preclinical assays. FGF2 is a known angiogenesis-associated molecule implicated in tumor progression. In this report, we describe a recombinant scFv format for the 3F12E7 mAb. The results demonstrate that the generated 3F12E7 scFv, although prone to aggregation, comprises an active anti-FGF2 product that contains monomers and small oligomers. Functionally, the 3F12E7 scFv preparations specifically recognize FGF2 and inhibit tumor growth similar to the corresponding full-length IgG counterpart in an experimental model. In silico molecular analysis provided insights into the aggregation propensity and the antigen-recognition by scFv units. Antigen-binding determinants were predicted outside the most aggregation-prone hotspots. Overall, our experimental and prediction dataset describes an scFv scaffold for the 3F12E7 mAb and also provides insights to further engineer non-aggregated anti-FGF2 scFv-based tools for therapeutic and research purposes.

Carcinoma basocelular na vulva: um relato de caso de neoplasia cutânea em área especial / Basal cell carcinoma of the vulva: a case report of cutaneous neoplasia in a special area

O carcinoma basocelular (CBC) é o câncer de pele mais comum.¹ Entre os fatores de risco para seu desenvolvimento estão a exposição a radiações ionizantes e não ionizantes, alguns produtos químicos e cicatrizes prévias.² Porém, o fator mais importante é a exposição à radiação ultravioleta, o que explica a maior incidência dessa neoplasia em áreas fotoexpostas. O CBC em áreas não expostas é incomum. O objetivo deste relato é descrever um caso de CBC recorrente na vulva, demonstrar a importância do exame dermatológico em áreas incomuns e relatar a aplicação da cirurgia micrográfica de Mohs.

Basal cell carcinoma (BCC) is the most common skin cancer¹. Among the risk factors for its development are exposure to ionizing and non-ionizing radiation, some chemicals, and previous scars.² However, the most important factor is exposure to ultraviolet radiation, which explains the higher incidence of this neoplasm in photo-exposed areas.¹ BCC in unexposed areas is uncommon. The purpose of this report is to describe a case of recurrent BCC in the vulva, to demonstrate the importance of dermatological examination in unusual areas, and to report the application of Mohs micrographic surgery