Ultrafast and high-throughput immunoassay assay to detect anti-SARS-CoV-2 IgG antibodies in dogs and cats.

The fact that SARS-CoV-2 has reportedly infected companion, livestock and wildlife animals may constitute a significant risk for virus reservoirs, ground for emerging variants and potential for novel reverse zoonosis. Hence, SARS-CoV-2 surveillance in animal species is crucial to prevent emerging variants which may spread to humans. The present study aimed to develop a simple, high-throughput and ultrafast magnetic bead immunoassay to detect anti-SARS-CoV-2 nucleocapsid and spike reactive IgG antibodies in dog and cat serum samples. The assays were validated using serum from eleven dogs and cats which had SARS-CoV-2 infections confirmed by real-time RT-PCR. The negative cohort consisted of pre-pandemic dog and cat samples. The assays performed at 73-82% sensitivity and 97.5-98% specificity for dogs and 71% sensitivity and 92-94% specificity for cats. The lower assay specificity for cats is explained by the fact that cat pre-pandemic sera showed high levels of cross-reactive with SARS-CoV-2 Nucleocapsid and Spike, supporting that these animals have been exposed to other coronavirus sharing structural similarities with SARS-CoV-2. These assays described in this work are now being used for SARS-CoV-2 surveillance and research purposes.

Recombinant proteins as promising antigens applied to the immunodiagnosis of Chagas disease: a scoping review.

Chagas disease (CD), caused by the protozoan Trypanosoma cruzi, is an important public health problem, occurring mainly in Latin America. The disease has a major social and economical effect, negatively impacting the life of the infected individuals, and bringing great costs to public health. An early and accurate diagnosis is essential for administration of early treatment. In addition, prognostic tests may aid disease management, decreasing hospitalization costs. However, the serological diagnostic scenario for CD still faces several challenges, making the development of new diagnostic kits a pressing matter. Facing this scenario, several researchers have expanded efforts in developing and testing new antigens, such as recombinant proteins and recombinant multiepitope proteins, with promising results. These recombinant antigens offer several advantages, such as improved sensitivity and specificity, in addition to facilitated scaling. Also, it has been possible to observe a rising number of studies using ELISA and point-of-care platforms, employing these antigens in the past few years. Among them, recombinant proteins were the most applied antigens, demonstrating great capacity to discriminate between positive and negative samples. Although fewer in number, recombinant multiepitope proteins also demonstrated an improved diagnostic performance. Indeed, a great number of studies employing these antigens showed sensitivity and specificity values above 90%, greatly impacting diagnostic accuracy. Nevertheless, despite the good results found, it is still possible to observe some bottlenecks in the development of new antigens, such as the scarcity of tests with sera from the acute phase and the variability of results in different geographic areas. In this sense, aiming to contribute to control and health programs, the continuous search for a more accurate serological diagnosis is essential, both for the acute and chronic phases of the disease.

Immunomodulatory Behavior of Tendon Magnetic Cell Sheets can be Modulated in Hypoxic Environments under Magnetic Stimulus.

Tissue environments play a crucial role in orchestrating cell behavior, guided by a complex interplay of various factors. Long lasting inflammatory signals compromise tendon homeostasis and promote tissue degeneration, while tissue oxygen levels affect local cells' responses with hypoxic environments influencing apoptosis, inflammatory mediators, and matrix production. Recent works have unveiled the therapeutic potential of pulsed electromagnetic field (PEMF) in modulating inflammatory signals expressed by human tendon cells (hTDCs), and in mitigating the hypoxia-induced effects on the regulation of inflammatory cytokines. Thus, we sought to investigate the role of hypoxic environments, namely, 1 and 2% oxygen tension, in the inflammatory profiles of magnetic cell sheets (magCSs) formed by magnetic nanoparticles internalized in contiguous hTDCs with intact cell-cell junctions and deposited matrix. We also aimed to explore the impact of PEMF over hypoxia-treated magCSs, including IL-1ß-primed-magCSs, with the objective of harnessing magnetic stimulation to guide abnormal inflammatory cell responses toward efficient treatments supporting tendon regenerative potential. Our findings revealed that low oxygen tensions amplified the expression of hypoxia-associated genes and of inflammatory markers in IL-1ß-primed-magCSs with an involvement of the NF-κB signaling pathway. Encouragingly, when PEMF was applied to IL-1ß-primed-magCSs under hypoxic conditions, it successfully modulated inflammatory cues by favoring IL-10 and IL-4, via the NF-κB pathway. These results signify the remarkable potential of PEMF in driving proregenerative strategies and opens up new approaches in tendon therapies, highlighting the transformative impact of immunomodulatory magnetic cell sheets.

Unveiling the antitumor mechanism of 7α-acetoxy-6ß-hydroxyroyleanone from Plectranthus hadiensis in glioblastoma.

ETHNOPHARMACOLOGICAL RELEVANCE: Glioblastoma (GB) is the most aggressive and prevalent glioma within the central nervous system. Despite considerable efforts, GB continues to exhibit a dismal 5-year survival rate (∼6%). This is largely attributed to unfavorable prognosis and lack of viable treatment options. Therefore, novel therapies centered around plant-derived compounds emerge as a compelling avenue to enhance patient survival and well-being. The South African species, Plectranthus hadiensis Schweinf. (P. hadiensis), a member of the Lamiaceae family, has a history of use in traditional medicine for treating a range of diseases, including respiratory, digestive, and liver disorders. This species exhibits diverse biological activities, such as anti-inflammatory and antitumoral properties, likely attributed to its rich composition of naturally occurring diterpenes, like the abietane diterpene, 7α-acetoxy-6ß-hydroxyroyleanone (Roy). Roy has demonstrated promising antitumor effects in various cancer cell lines, making it a compelling candidate for further investigation into its mechanisms against GB. AIM OF THE STUDY: This study aims to investigate the antitumor activity and potential mechanism of Roy, a natural lead compound, in GB cells. MATERIAL AND METHODS: Roy was isolated from the acetonic extract of P. hadiensis and its antitumor mechanism was assessed in a panel of human GB cell lines (U87, A172, H4, U373, and U118) to mimic tumor heterogeneity. Briefly, the impact of Roy treatment on the metabolic activity of cells was evaluated by Alamar Blue® assay, while cell death, cell cycle regulation, mitochondrial membrane potential, and activated caspase-3 activity were evaluated by flow cytometry. Measurement of mRNA levels of target genes was performed by qPCR, while protein expression was assessed by Western blotting. Cell uptake and impact on mitochondrial morphology were evaluated by confocal microscopy. RESULTS: Roy induced G2/M cell cycle arrest, mitochondrial fragmentation, and apoptosis by inhibiting the expression of anti-apoptotic proteins and increasing the levels of activated caspase-3. The concentrations of Roy needed to achieve significant inhibitory outcomes were notably lower (6-9 fold) than those of temozolomide (TMZ), the standard first-line treatment, for achieving comparable effects. In addition, at low concentrations (16 µM), Roy affected the metabolic activity of tumor cells while having no significant impact on non-tumoral cells (microglia and astrocytes). CONCLUSION: Overall, Roy demonstrated a robust antitumor activity against GB cells offering a promising avenue for the development of novel chemotherapeutic approaches.

An Analysis of Drug-Related Problems in the Neurology Ward of a Tertiary Teaching Hospital: A Cross-Sectional Study.

Background and objective Drugs that act on the central nervous system have a high potential to cause drug-related problems (DRPs). A clinical pharmacist aided by collaborative efforts within an interdisciplinary healthcare team can prevent, detect, and resolve DRPs, thereby contributing to the promotion of medication safety and improving the quality of life of individuals under care. This study aimed to assess DRPs identified in the neurology ward of a tertiary hospital from February 2016 to November 2019. Methods This was a descriptive study with a cross-sectional and retrospective design involving secondary data collected from pharmaceutical care (PC) records. Student's t-tests, Pearson correlation coefficients, Poisson models, and logistic regression models were used to analyze the associations between age, number and type of medications, duration of hospitalization, and the occurrence of DRPs. Results A total of 130 patients were included in the study, and a total of 266 DRPs were detected, with 93 patients experiencing more than one DRP and 37 not presenting any DRPs. Necessity-related DRPs were the most prevalent (46.6%) type, followed by safety-related DRPs (28.6%). The prevalence of safety-related DRPs was higher in individuals older than 60 years (p<0.001). Conclusions Of note, 84.6% of the interventions suggested by pharmacists to resolve DRPs were accepted by the healthcare team. The high number of DRPs found underscores the importance of the clinical role of the pharmacist and interprofessional collaboration in the care of neurological patients, especially in the pharmaceutical follow-up of elderly individuals.

Sustainable Fish Meal-Free Diets for Gilthead Sea Bream (Sparus aurata): Integrated Biomarker Response to Assess the Effects on Growth Performance, Lipid Metabolism, Antioxidant Defense and Immunological Status.

The growth of the aquaculture industry requires more sustainable and circular economy-driven aquafeed formulas. Thus, the goal of the present study was to assess in farmed gilthead sea bream (Sparus aurata L.) how different combinations of novel and conventional fish feed ingredients supported proper animal performance in terms of growth and physiological biomarkers of blood/liver/head kidney. A 77-day feeding trial was conducted with three experimental diets (PAP, with terrestrial processed animal protein from animal by-products; NOPAP, without processed animal protein from terrestrial animal by-products; MIX, a combination of alternative ingredients of PAP and NOPAP diets) and a commercial-type formulation (CTRL), and their effects on growth performance and markers of endocrine growth regulation, lipid metabolism, antioxidant defense and inflammatory condition were assessed at circulatory and tissue level (liver, head kidney). Growth performance was similar among all dietary treatments. However, fish fed the PAP diet displayed a lower feed conversion and protein efficiency, with intermediate values in MIX-fed fish. Such gradual variation in growth performance was supported by different biomarker signatures that delineated a lower risk of oxidation and inflammatory condition in NOPAP fish, in concurrence with an enhanced hepatic lipogenesis that did not represent a risk of lipoid liver degeneration.

Multidrug-Resistant Escherichia coli Accumulated by Freshwater Bivalves: An Underestimated Risk for Public Health?

As bioindicators, freshwater bivalves are crucial for the assessment of the contamination impact on different levels of biological integration. Escherichia coli is used as a bioindicator of water fecal contamination, representing a critical global concern, especially with the rise of multidrug-resistant (MDR) strains. Phylogenetic diversity, pathotypic characterization, and antibiotic resistance profiles of E. coli isolated from freshwater bivalves (Anodonta anatina) were assessed. Samples were collected from the Tua River in Northern Portugal, from two different sites, Chelas and Barcel, representing different degrees of contamination. Antimicrobial susceptibility testing was performed by the disk diffusion method, and characterizations of the phylogenetic groups and pathotypes were assessed by PCR-multiplex and real-time PCR-multiplex, respectively. Results showed that 60% of isolates were characterized as MDR, including resistance to carbapenems, considered the last resort against multidrug-resistant bacteria. Within this study, it was also possible to verify the antimicrobial resistance (AMR) profile differences between the two sampling sites, with bivalve isolates from the Chelas site showing a higher percentage of antibiotic resistance. Among the E. coli isolates, the highest prevalence (55%) was observed in group B1, followed by group D or E (15%), group A (10%), and group E or Clade I (10%). None of the isolates were classified as diarrheagenic E. coli (DEC). This work highlights the potential transmission of antimicrobial-resistant bacteria through bivalves in the food chain. The 'One Health' approach is crucial for combating antimicrobial resistance, namely in edible freshwater species, emphasizing active surveillance to protect human, animal, and environmental health against the spread of antibiotic-resistant bacteria in aquatic environments.

Treatment with lipoxin A4 improves influenza A infection outcome, induces macrophage reprogramming, anti-inflammatory and pro-resolutive responses.

INTRODUCTION: Influenza A is a virus from the Orthomixoviridae family responsible for high lethality rates and morbidity, despite clinically proven vaccination strategies and some anti-viral therapies. The eicosanoid Lipoxin A4 (LXA4) promotes the resolution of inflammation by decreasing cell recruitment and pro-inflammatory cytokines release, but also for inducing activation of apoptosis, efferocytosis, and macrophage reprogramming. OBJECTIVE: Here, we evaluated whether a synthetic lipoxin mimetic, designated AT-01-KG, would improve the course of influenza A infection in a murine model. METHOD: Mice were infected with influenza A/H1N1 and treated with AT-01-KG (1.7 µg/kg/day, i.p.) at day 3 post-infection. RESULTS: AT-01-KG attenuated mortality, reducing leukocyte infiltration and lung damage at day 5 and day 7 post-infection. AT-01-KG is a Formyl Peptide Receptor 2 (designated FPR2/3 in mice) agonist, and the protective responses were not observed in fpr2/3 -/- animals. In mice treated with LXA4 (50 µg/kg/day, i.p., days 3-6 post-infection), at day 7, macrophage reprogramming was observed, as seen by a decrease in classically activated macrophages and an increase in alternatively activated macrophages in the lungs. Furthermore, the number of apoptotic cells and cells undergoing efferocytosis was increased in the lavage of treated mice. Treatment also modulated the adaptive immune response, increasing the number of T helper 2 cells (Th2) and regulatory T (Tregs) cells in the lungs of the treated mice. CONCLUSION: Therefore, treatment with a lipoxin A4 analog was beneficial in a model of influenza A infection in mice. The drug decreased inflammation and promoted resolution and beneficial immune responses, suggesting it may be useful in patients with severe influenza.

Treatment with lipoxin A 4 improves influenza A infection outcome through macrophage reprogramming, anti-inflammatory and pro-resolutive responses.

Objective and design: Here, we evaluated whether a synthetic lipoxin mimetic, designated AT-01-KG, would improve the course of influenza A infection in a murine model. Treatment: Mice were infected with influenza A/H1N1 and treated with AT-01-KG (1.7 mg/kg/day, i.p.) at day 3 post-infection. Methods: Mortality rate was assessed up to day 21 and inflammatory parameters were assessed at days 5 and 7. Results: AT-01-KG attenuated mortality, reducing leukocyte infiltration and lung damage at day 5 and day 7 post-infection. AT-01-KG is a Formyl Peptide Receptor 2 (designated FPR2/3 in mice) agonist, and the protective responses were not observed in FPR2/3 -/- animals. In mice treated with LXA4 (50mg/kg/day, i.p., days 3-6 post-infection), at day 7, macrophage reprogramming was observed, as seen by a decrease in classically activated macrophages and an increase in alternatively activated macrophages in the lungs. Furthermore, the number of apoptotic cells and cells undergoing efferocytosis was increased in the lavage of treated mice. Treatment also modulated the adaptive immune response, increasing the number of anti-inflammatory T cells (Th2) and regulatory T (Tregs) cells in the lungs of the treated mice. Conclusions: Therefore, treatment with a lipoxin A4 analog was beneficial in a model of influenza A infection in mice. The drug decreased inflammation and promoted resolution and beneficial immune responses, suggesting it may be useful in patients with severe influenza.

Antibiotic resistance: Assessing knowledge and misconceptions among Portuguese students and science teachers.

Antimicrobial resistance poses one of the most significant medical challenges for humanity. The current burden is overwhelming and is projected to escalate rapidly, with predictions for 2050 indicating 10 million deaths per year due to antibiotic-resistant microorganisms. Enhancing public awareness and education on this topic is crucial in efforts to mitigate this issue. In our study, we translated an existing questionnaire on antimicrobial resistance into Portuguese, validated it, and applied it between December 2020 and March 2021 to a group of Portuguese students (n = 112) and science teachers (n = 95). A majority of the students surveyed (65.1%) incorrectly believed that antibiotics could treat colds/flus. As anticipated, the teachers outperformed the students in the questionnaire. However, difficulties with this topic were evident in both groups. Most notably, the misconception that the human body becomes resistant to antibiotics was prevalent among most participants (77.0% of students and 68.4% of teachers). Consistent with previous studies in other populations and geographic locations, our research reveals a worrying lack of knowledge about antimicrobial resistance among Portuguese students and science teachers. Consequently, it is deemed urgent to implement effective measures to raise awareness and educate on this topic.

A Mini-Review of Diagnostic Methods for the Antigen and Antibody Detection of Rocky Mountain and Brazilian Spotted Fever.

Rocky Mountain or Brazilian spotted fever, caused by Rickettsia rickettsii, is a fulminant, seasonal, and neglected disease that occurs in focal points of North America and South America. Its rapid detection is essential for the better prognosis and survival rate of infected individuals. However, disease diagnosis still faces challenges as the accuracy of many of the available laboratory tests fluctuates. This review aimed to analyze methods for antibody or antigen detection, their gaps, and their evolution over time. A search was conducted to find all studies in the Pubmed database that described the antibody or antigen detection of R. rickettsii infections. Initially, a total of 403 articles were screened. Of these articles, only 17 fulfilled the pre-established inclusion criteria and were selected. Among the different methods applied, the IFA technique was the one most frequently found in the studies. However, it presented varied results such as a low specificity when using the indirect method. Other techniques, such as ELISA and immunohistochemistry, were also found, although in smaller numbers and with their own limitations. Although some studies showed promising results, there is a pressing need to find new techniques to develop a rapid and effective diagnosis of R. rickettssi infection.

Clinical and uterine cervix characteristics of women with Mycoplasma and Ureaplasma in genital discharge.

OBJECTIVE: The objective of this study was to assess the clinical and uterine cervix characteristics of patients displaying vaginal discharge with positive results for Mycoplasma sp. and/or Ureaplasma spp. METHODS: An analytical cross-sectional study involving women aged 18-45 years was conducted. Microbiological assessments included Ureaplasma and Mycoplasma cultures, as well as human papillomavirus hybrid capture using ecto and endocervix swabs. All tests were two-tailed, and significance was set at p<0.05. RESULTS: Among 324 women, Ureaplasma prevalence was 17.9%, and Mycoplasma prevalence was 3.1%. The Ureaplasma-positive group exhibited a higher frequency of urinary tract infections (39.1 vs. 19%, p=0.002) and human papillomavirus (39.7 vs. 12.8%, p≤0.001) compared with controls. The Mycoplasma-positive group showed a higher frequency of non-contraceptive use compared with controls (66.2 vs. 30.0%, p=0.036). Abnormal colposcopic findings were more prevalent in the Mycoplasma/Ureaplasma-positive group than in controls (positive: 65% vs. control: 35%, p=0.001). Pap smear findings did not differ between the groups. CONCLUSION: Ureaplasma spp. was associated with urinary tract infections and human papillomavirus, while the presence of Mycoplasma sp. was linked to reduced contraceptive use. When analyzing both pathogens together, a higher frequency of abnormal colposcopic findings was observed, with no difference in cytological findings in the positive group.

Endobronchial Ulceration: A Different Manifestation of Antineutrophil Cytoplasmic Antibodies (ANCA)-Associated Vasculitis.

Vasculitis with pulmonary involvement is often associated with antineutrophil cytoplasmic antibody (ANCA). We describe a case involving a 66-year-old male patient diagnosed with granulomatosis with polyangiitis (GPA). Following the onset of hemoptysis, bronchoscopy revealed endobronchial ulcers correlated with GPA. Bronchial biopsies and bronchoalveolar lavage identified Staphylococcus aureus (S. aureus), which is associated with GPA relapses. The patient began immunosuppression to induce remission, and Avacopan was subsequently introduced for the treatment of GPA and microscopic polyangiitis (MPA).

Mechanical stimulation-induced purinome priming fosters osteogenic differentiation and osteointegration of mesenchymal stem cells from the bone marrow of post-menopausal women.

BACKGROUND: Mechanical stimulation (MS) significantly increases the release of adenine and uracil nucleotides from bone marrow-derived mesenchymal stem cells (BM-MSCs) undergoing osteogenic differentiation. Released nucleotides acting via ionotropic P2X7 and metabotropic P2Y6 purinoceptors sensitive to ATP and UDP, respectively, control the osteogenic commitment of BM-MSCs and, thus, bone growth and remodelling. Yet, this mechanism is impaired in post-menopausal (Pm)-derived BM-MSCs, mostly because NTPDase3 overexpression decreases the extracellular accumulation of nucleotides below the levels required to activate plasma membrane-bound P2 purinoceptors. This prompted us to investigate whether in vitro MS of BM-MSCs from Pm women could rehabilitate their osteogenic commitment and whether xenotransplantation of MS purinome-primed Pm cells promote repair of critical bone defects in an in vivo animal model. METHODS: BM-MSCs were harvested from the neck of femora of Pm women (70 ± 3 years old) undergoing total hip replacement. The cells grew, for 35 days, in an osteogenic-inducing medium either submitted (SS) or not (CTR) to MS (90 r.p.m. for 30 min) twice a week. Increases in alkaline phosphatase activity and in the amount of osteogenic transcription factors, osterix and osteopontin, denoted osteogenic cells differentiation, while bone nodules formation was ascertain by the alizarin red-staining assay. The luciferin-luciferase bioluminescence assay was used to quantify extracellular ATP. The kinetics of the extracellular ATP (100 µM) and UDP (100 µM) catabolism was assessed by HPLC. The density of P2Y6 and P2X7 purinoceptors in the cells was assessed by immunofluorescence confocal microscopy. MS-stimulated BM-MSCs from Pm women were xenotransplanted into critical bone defects drilled in the great trochanter of femora of one-year female Wistar rats; bone repair was assessed by histological analysis 10 days after xenotransplantation. RESULTS: MS-stimulated Pm BM-MSCs in culture (i) release 1.6-fold higher ATP amounts, (ii) overexpress P2X7 and P2Y6 purinoceptors, (iii) exhibit higher alkaline phosphatase activity and overexpress the osteogenic transcription factors, osterix and osteopontin, and (iv) form larger bone nodules, than CTR cells. Selective blockage of P2X7 and P2Y6 purinoceptors with A438079 (3 µM) and MRS 2578 (0.1 µM), respectively, prevented the osteogenic commitment of cultured Pm BM-MSCs. Xenotransplanted MS purinome-primed Pm BM-MSCs accelerated the repair of critical bone defects in the in vivo rat model. CONCLUSIONS: Data suggest that in vitro MS restores the purinergic cell-to-cell communication fostering the osteogenic differentiation and osteointegration of BM-MSCs from Pm women, a strategy that may be used in bone regeneration and repair tactics.

Influence of Aldehyde Dehydrogenase Inhibition on Stemness of Endometrial Cancer Stem Cells.

Endometrial cancer is one of the most common gynaecological malignancies. Although often diagnosed at an early stage, there is a subset of patients with recurrent and metastatic disease for whom current treatments are not effective. Cancer stem cells (CSCs) play a pivotal role in triggering tumorigenesis, disease progression, recurrence, and metastasis, as high aldehyde dehydrogenase (ALDH) activity is associated with invasiveness and chemotherapy resistance. Therefore, this study aimed to evaluate the effects of ALDH inhibition in endometrial CSCs. ECC-1 and RL95-2 cells were submitted to a sphere-forming protocol to obtain endometrial CSCs. ALDH inhibition was evaluated through ALDH activity and expression, sphere-forming capacity, self-renewal, projection area, and CD133, CD44, CD24, and P53 expression. A mass spectrometry-based proteomic study was performed to determine the proteomic profile of endometrial cancer cells upon N,N-diethylaminobenzaldehyde (DEAB). DEAB reduced ALDH activity and expression, along with a significant decrease in sphere-forming capacity and projection area, with increased CD133 expression. Additionally, DEAB modulated P53 expression. Endometrial cancer cells display a distinct proteomic profile upon DEAB, sharing 75 up-regulated and 30 down-regulated proteins. In conclusion, DEAB inhibits ALDH activity and expression, influencing endometrial CSC phenotype. Furthermore, ALDH18A1, SdhA, and UBAP2L should be explored as novel molecular targets for endometrial cancer.

Global Distribution of Canine Visceral Leishmaniasis and the Role of the Dog in the Epidemiology of the Disease.

Visceral leishmaniasis is a disease caused by protozoa of the species Leishmania (Leishmania) infantum (syn = Leishmania chagasi) and Leishmania (Leishmania) donovani, which are transmitted by hematophagous insects of the genera Lutzomyia and Phlebotomus. The domestic dog (Canis familiaris) is considered the main urban reservoir of the parasite due to the high parasite load on its skin, serving as a source of infection for sandfly vectors and, consequently, perpetuating the disease in the urban environment. Some factors are considered important in the perpetuation and spread of canine visceral leishmaniasis (CVL) in urban areas, such as stray dogs, with their errant behavior, and houses that have backyards with trees, shade, and organic materials, creating an attractive environment for sandfly vectors. CVL is found in approximately 50 countries, with the number of infected dogs reaching millions. However, due to the difficulty of controlling and diagnosing the disease, the number of infected animals could be even greater. In the four continents endemic for CVL, there are reports of disease expansion in endemic countries such as Brazil, Italy, Morocco, and Tunisia, as well as in areas where CVL is not endemic, for example, Uruguay. Socio-environmental factors, such as migration, drought, deforestation, and global warming, have been pointed out as reasons for the expansion into areas where it had been absent. Thus, the objective of this review is to address (i) the distribution of CVL in endemic areas, (ii) the role of the dog in the visceral leishmaniasis epidemiology and the factors that influence dog infection and the spread of the disease, and (iii) the challenges faced in the control of CVL.

Advancements in Biomarkers and Molecular Targets in Hematological Neoplasias.

Hematological neoplasias are among the most common cancers worldwide, and the number of new cases has been on the rise since 1990, reaching 1 [...].

Genetic profile of Brazilian patients with LAMA2-related dystrophies.

LAMA2-related dystrophies (LAMA2-RD) constitute a rare neuromuscular disorder with a broad spectrum of phenotypic severity. Our understanding of the genotype-phenotype correlations in this condition remains incomplete, and reliable clinical data for clinical trial readiness is limited. In this retrospective study, we reviewed the genetic data and medical records of 114 LAMA2-RD patients enrolled at seven research centers in Brazil. We identified 58 different pathogenic variants, including 21 novel ones. Six variants were more prevalent and were present in 81.5% of the patients. Notably, the c.1255del, c.2049_2050del, c.3976 C>T, c.5234+1G>A, and c.4739dup variants were found in patients unable to walk and without cortical malformation. In contrast, the c.2461A>C variant was present in patients who could walk unassisted. Among ambulatory patients, missense variants were more prevalent (p < 0.0001). Although no specific hotspot regions existed in the LAMA2, 51% of point mutations were in the LN domain, and 88% of the missense variants were found within this domain. Functional analysis was performed in one intronic variant (c.4960-17C>A) and revealed an out-of-frame transcript, indicating that the variant creates a cryptic splicing site (AG). Our study has shed light on crucial phenotype-genotype correlations and provided valuable insights, particularly regarding the Latin American population.

Psychosocial Factors Associated With Vulvodynia.

OBJECTIVES: We set out to identify the psychosocial factors associated with vulvodynia and the effects on sexuality, mental health, and quality of life. MATERIALS AND METHODS: PubMed, LILACS, Embase, CINAHL, Web of Science, Scopus, and PsycINFO were searched in August 2023. Two authors selected and extracted the data independently. The risk of bias was assessed using the Newcastle-Ottawa Scale for Observational Studies. To rank the strength of evidence, the Grading of Recommendations Assessment, Development and Evaluation Working Group (GRADE) approach was utilized. RESULTS: A total of 3,182 articles were identified. Twenty-two observational studies (8 cohorts and 14 case-controls) met the eligibility criteria and were included, comprising 2,624 patients. Vulvodynia has been associated with psychological factors (anxiety and depression) and social factors (childhood exposure to physical and sexual abuse, posttraumatic stress, and domestic abuse). Concerning sexual function, the most frequent outcomes were dyspareunia and sexual dysfunction. Only one study assessed quality of life, which showed that women with chronic vulvar pain had greater difficulty performing physical activities and experienced negative moods and feelings. The assessment of the risk of bias showed that the average quality of studies was good to excellent. However, the studies failed to select the nonexposed cohort or control group to describe the results, and often, the study population was rather small, which made it impossible to carry out a meta-analysis. CONCLUSIONS: The certainty of evidence for the associations between anxiety and depression, vulvodynia, and sexual functioning suggests that combating these factors could improve overall quality of life in vulvodynia patients.