Antigenic and molecular evidence of Brucella sp.-associated epididymo-orchitis in frugivorous (Artibeus lituratus) and nectarivorous (Glossophaga soricina) bats in Brazil.

This study included 47 free-ranging bats from the State of Minas Gerais, Brazil. Six bats (12.8%) had genital inflammatory lesions, and two of them (one Artibeus lituratus and one Glossophaga soricina, a frugivorous and a nectarivorous, respectively) were diagnosed with Brucella sp. infection through PCR, and antigens in intralesional macrophages were detected using immunohistochemistry.

Czech dysplasia mimicking rheumatoid arthritis: Case series and literature review.

OBJECTIVE: This study reported a family with most members affected by Czech dysplasia. We examined the patients' clinical, laboratory, and imaging characteristics and evaluated their functional capacity using the Stanford Health Assessment Questionnaire-Disability Index. METHODS: The method used was case series description and literature review. RESULTS: This study showed that the pathogenic variant c.823C>T in the COL2A1 gene, which is a characteristic of Czech dysplasia, was found in 12 Brazilian individuals. Half of the patients in this family met the criteria for rheumatoid arthritis (RA) based on the 2010 American College of Rheumatology/European League Against Rheumatism classification criteria. Patients had arthritis in their hand joints, synovitis detected by ultrasound, and alterations in inflammatory tests. The Stanford Health Assessment Questionnaire-Disability Index assessment revealed that all patients exhibited moderate-to-severe functional disability. What distinguish Czech dysplasia from RA are an autosomal dominant inheritance pattern, platyspondyly, sensorineural hearing loss, and shortening of the metatarsal bones. CONCLUSIONS: It is important to consider Czech dysplasia as a potential differential diagnosis for RA. This autosomal dominant skeletal dysplasia is associated with normal height, short metatarsals, platyspondyly, hearing loss, enlarged epiphyses, and precocious osteoarthritis. Inflammatory findings such as arthritis, synovitis, and alteration of inflammatory markers may also be present in individuals with Czech dysplasia.

Paclitaxel-Loaded Lipid-Coated Magnetic Nanoparticles for Dual Chemo-Magnetic Hyperthermia Therapy of Melanoma.

Melanoma is the most aggressive and metastasis-prone form of skin cancer. Conventional therapies include chemotherapeutic agents, either as small molecules or carried by FDA-approved nanostructures. However, systemic toxicity and side effects still remain as major drawbacks. With the advancement of nanomedicine, new delivery strategies emerge at a regular pace, aiming to overcome these challenges. Stimulus-responsive drug delivery systems might considerably reduce systemic toxicity and side-effects by limiting drug release to the affected area. Herein, we report the development of paclitaxel-loaded lipid-coated manganese ferrite magnetic nanoparticles (PTX-LMNP) as magnetosomes synthetic analogs, envisaging the combined chemo-magnetic hyperthermia treatment of melanoma. PTX-LMNP physicochemical properties were verified, including their shape, size, crystallinity, FTIR spectrum, magnetization profile, and temperature profile under magnetic hyperthermia (MHT). Their diffusion in porcine ear skin (a model for human skin) was investigated after intradermal administration via fluorescence microscopy. Cumulative PTX release kinetics under different temperatures, either preceded or not by MHT, were assessed. Intrinsic cytotoxicity against B16F10 cells was determined via neutral red uptake assay after 48 h of incubation (long-term assay), as well as B16F10 cells viability after 1 h of incubation (short-term assay), followed by MHT. PTX-LMNP-mediated MHT triggers PTX release, allowing its thermal-modulated local delivery to diseased sites, within short timeframes. Moreover, half-maximal PTX inhibitory concentration (IC50) could be significantly reduced relatively to free PTX (142,500×) and Taxol® (340×). Therefore, the dual chemo-MHT therapy mediated by intratumorally injected PTX-LMNP stands out as a promising alternative to efficiently deliver PTX to melanoma cells, consequently reducing systemic side effects commonly associated with conventional chemotherapies.

Neurologic and cutaneous infection by Clostridium piliforme in a kitten with systemic Tyzzer disease.

Tyzzer disease (TD) is a highly fatal condition of animals caused by Clostridium piliforme and characterized pathologically by enteritis, hepatitis, myocarditis, and occasionally encephalitis. Cutaneous lesions have been reported only rarely in animals with TD, and infection of the nervous system has not been described in cats, to our knowledge. We describe here neurologic and cutaneous infection by C. piliforme in a shelter kitten with systemic manifestations of TD and coinfection with feline panleukopenia virus. Systemic lesions included necrotizing typhlocolitis, hepatitis, myocarditis, and myeloencephalitis. The cutaneous lesions consisted of intraepidermal pustular dermatitis and folliculitis, with necrosis of keratinocytes and ulceration. Clostridial bacilli were identified within the cytoplasm of keratinocytes by fluorescence in situ hybridization, and a PCR assay was positive for C. piliforme. C. piliforme can infect keratinocytes leading to cutaneous lesions in cats with the location suggesting direct contact with contaminated feces as a route of infection.

An Artificial Intelligence-as-a-Service Architecture for deep learning model embodiment on low-cost devices: A case study of COVID-19 diagnosis.

Coronavirus Disease-2019 (COVID-19) causes Severe Acute Respiratory Syndrome-Corona Virus-2 (SARS-CoV-2) and has opened several challenges for research concerning diagnosis and treatment. Chest X-rays and computed tomography (CT) scans are effective and fast alternatives to detect and assess the damage that COVID causes to the lungs at different stages of the disease. Although the CT scan is an accurate exam, the chest X-ray is still helpful due to the cheaper, faster, lower radiation exposure, and is available in low-incoming countries. Computer-aided diagnostic systems based on Artificial Intelligence (AI) and computer vision are an alternative to extract features from X-ray images, providing an accurate COVID-19 diagnosis. However, specialized and expensive computational resources come across as challenging. Also, it needs to be better understood how low-cost devices and smartphones can hold AI models to predict diseases timely. Even using deep learning to support image-based medical diagnosis, challenges still need to be addressed once the known techniques use centralized intelligence on high-performance servers, making it difficult to embed these models in low-cost devices. This paper sheds light on these questions by proposing the Artificial Intelligence as a Service Architecture (AIaaS), a hybrid AI support operation, both centralized and distributed, with the purpose of enabling the embedding of already-trained models on low-cost devices or smartphones. We demonstrated the suitability of our architecture through a case study of COVID-19 diagnosis using a low-cost device. Among the main findings of this paper, we point out the performance evaluation of low-cost devices to handle COVID-19 predicting tasks timely and accurately and the quantitative performance evaluation of CNN models embodiment on low-cost devices.

Prevalence of Platynosomum spp infection and its association with biliary lithiasis and secondary bacterial infections in free-ranging marmosets (Callithrix spp) of the Brazilian Atlantic Forest.

Platynosomosis is a parasitic disease caused by a trematode of the genus Platynosomum, a bile duct and gallbladder fluke that has been described in captive neotropical primates (New World primates; NWPs) and causes high morbidity and variable mortality. Although it is a major concern for ex-situ conservation of these animals, there are only a few studies of platynosomosis in free-ranging NWPs. Therefore, the aim of this study was to characterize platynosomosis in a free-ranging population of marmosets (Callithrix spp) from the Brazilian Atlantic Forest, focusing on the epidemiological and pathological aspects of the disease. A total of 1,001 marmosets were evaluated and on the basis of clinicoepidemiological data, histopathology, histochemistry and immunohistochemistry, we concluded that Platynosomum spp infection has a prevalence of 8.9% (confidence interval: 7.3-10.8%) in free-ranging marmosets, with a higher frequency in the Metropolitan Region of Rio de Janeiro. Infection was associated with fibrosing and proliferative cholangiohepatitis associated with biliary lithiasis (3.0% of cases) and secondary bacterial infections (14.6% of cases).

Profile of Gut Microbiota of Adults with Diabetes Mellitus Type 1: A Systematic Review.

BACKGROUND: Type 1 diabetes mellitus (T1DM) is a chronic disease of clinical importance, whose prevalence has increased in Brazil and worldwide. Among the possible factors involved in the genesis and control of the disease, the intestinal microbiota (IM) deserves to be highlighted, but studies that report differences between the IM of patients with T1DM and those who are healthy are still contradictory and scarce. OBJECTIVE: The objective of this paper was to evaluate the IM profile of T1DM and healthy patients, in order to verify possible differences and to evaluate the possibility of the influence of IM on glycemic control in T1DM. METHODS: Of the 2716 articles found, nine were included in this review, and all of which were randomized, observational, cross-sectional, cohort and case-control studies that characterized the composition of IM in adults with T1DM and healthy adults. RESULTS: Studies are very diverse, which makes it difficult to associate the IM profile with T1DM etiology and control, however it was found that there was a prevalence of the phylum Firmicutes in the IM of individuals with T1DM and that there was no significant difference in the relative abundance of Bacteroidetes in both populations. CONCLUSION: It was also possible to identify an inverse relationship of the genus Bifidobacterium and a positive relationship of the genera Bacteroidetes and Prevotella with the concentration ofglycated hemoglobin. More studies are needed to contemplate the characterization of IM in healthy and T1DM individuals.

Pathology and epidemiology of fatal toxoplasmosis in free-ranging marmosets (Callithrix spp.) from the Brazilian atlantic forest.

Toxoplasmosis is an important zoonotic disease that affects a wide range of warm-blooded host species. Neotropical primates (New World Primates; NWP) are highly susceptible, developing a lethal acute systemic disease. Toxoplasmosis in free-ranging NWP is poorly described, with only a few studies based on serosurveys. Herein we performed a retrospective study focusing on the epidemiology and pathology of toxoplasmosis among 1,001 free-ranging marmoset (Callithrix spp.) deaths from the Brazilian Atlantic Forest. This study included marmosets necropsied at the Instituto Municipal de Medicina Veterinária Jorge Vaitsman (IJV) from January 2017 to July 2019, which were found dead from all regions in the State of Rio de Janeiro. Histopathology, immunohistochemistry, and transmission electron microscopy were performed to better characterize toxoplasmosis in this free-ranging population. All samples were also tested for Yellow Fever Virus (YFV) RT-qPCR by the official diagnostic service. A total of 1,001 free-ranging marmosets were included in this study, with 16 (1.6%) cases of lethal Toxoplasma gondii infections identified both as individual cases and in outbreaks. Presence of infection was not associated with sex, age, geographical distribution, or year of death, and no co-infection with YFV was observed. The main pathological feature in these cases was random necrotizing hepatitis with detection of intralesional T. gondii zoites in all infected cases. Interstitial pneumonia rich in alveolar foamy macrophages and fibrin deposition, necrotizing myocarditis and necrotizing splenitis were also pathological features in affected marmosets. Therefore, toxoplasmosis was considered the cause of death in 1.6% of free-ranging marmosets in this retrospective series, including some cases associated with outbreaks. Necrotizing random hepatitis was a consistent pathological finding in affected cases and sampling of liver should be ensured from Callitrichid post mortem cases.

Mammaliicoccus (Staphylococcus) sciuri-induced suppurative meningoencephalitis and bacteremia in an infant western lowland gorilla (Gorilla gorilla gorilla).

Mammaliicoccus (Staphylococcus) sciuri has been rarely associated with infections and sepsis in humans. A 3-month-old male western lowland gorilla (Gorilla gorilla gorilla), born under human care, died after a traumatic event. Histologic, microbiologic, and molecular findings in postmortem demonstrated a suppurative meningoencephalitis and bacteremia associated with M. sciuri infection.

Effects of zoledronic acid therapy in fibrous dysplasia of bone: a single-center experience.

Objective: Fibrous dysplasia (FD) is a rare bone disorder that can involve any part of the skeleton, leading to bone pain, deformities, and fractures. Treatment with intravenous bisphosphonates has been used with variable results. Therefore, we aimed to evaluate the effects of zoledronic acid (ZA) therapy in patients with monostotic or polyostotic FD. Methods: The medical records of thirteen patients with FD evaluated between 2015 and 2020 were retrospectively analyzed. In the subgroup of patients treated with ZA (n = 7), data on pain relief, changes in bone turnover markers (BTMs), and adverse events following ZA infusions were retrieved. Moreover, radiological changes in response to treatment were recorded in patients who underwent radiological follow-up. Results: Of the patients, 5 (38%) presented with monostotic whereas 8 (62%) had polyostotic FD. Bone pain was a common finding (69%), and most patients (62%) exhibited elevated baseline BTMs. Partial or complete pain relief was reported in 6 of 7 patients treated with ZA. BTMs, especially C-telopeptide of type I collagen (CTX), significantly decreased after therapy (change rate: -61.8% [IQR -71, -60%]), and median CTX levels were significantly lower than at baseline (0.296 ng/mL [0.216, 0.298] vs. 0.742 ng/mL [0.549, 0.907], respectively; P = 0.04). No radiological improvement was observed in cases with radiological follow-up (n = 3). No serious adverse effects of ZA were reported. Conclusion: ZA treatment was well tolerated and provided beneficial effects in relieving bone pain and reducing BTMs, especially CTX. Our data reinforce the role of ZA in the treatment of FD-related bone pain.

Effects of zoledronic acid therapy in fibrous dysplasia of bone: a single-center experience

ABSTRACT Objective: Fibrous dysplasia (FD) is a rare bone disorder that can involve any part of the skeleton, leading to bone pain, deformities, and fractures. Treatment with intravenous bisphosphonates has been used with variable results. Therefore, we aimed to evaluate the effects of zoledronic acid (ZA) therapy in patients with monostotic or polyostotic FD. Subjects and methods: The medical records of thirteen patients with FD evaluated between 2015 and 2020 were retrospectively analyzed. In the subgroup of patients treated with ZA (n = 7), data on pain relief, changes in bone turnover markers (BTMs), and adverse events following ZA infusions were retrieved. Moreover, radiological changes in response to treatment were recorded in patients who underwent radiological follow-up. Results: Of the patients, 5 (38%) presented with monostotic whereas 8 (62%) had polyostotic FD. Bone pain was a common finding (69%), and most patients (62%) exhibited elevated baseline BTMs. Partial or complete pain relief was reported in 6 of 7 patients treated with ZA. BTMs, especially C-telopeptide of type I collagen (CTX), significantly decreased after therapy (change rate: −61.8% [IQR −71, −60%]), and median CTX levels were significantly lower than at baseline (0.296 ng/mL [0.216, 0.298] vs. 0.742 ng/mL [0.549, 0.907], respectively; P = 0.04). No radiological improvement was observed in cases with radiological follow-up (n = 3). No serious adverse effects of ZA were reported. Conclusion: ZA treatment was well tolerated and provided beneficial effects in relieving bone pain and reducing BTMs, especially CTX. Our data reinforce the role of ZA in the treatment of FD-related bone pain.

Cytotoxic activity in basal and tumoral cell lines of the C0K3N3 protein from the snake venom Crotalus durissus collilineatus, variety crotamine negative.

Snake venoms are natural sources of bioactive substances with therapeutic potential. In this work, we evaluated the cytotoxicity of the Crotalus durissus collilineatus, negative crotamine variety and the isolated fraction C0K3N3 in BALB C/3T3 and K562 cell lines. The results indicate that the C0K3N3 protein is more cytotoxic against the K562 tumor cell line than in the 3T3 baseline.

Non-thrombotic pulmonary embolism of brain, liver, or bone marrow tissues associated with traumatic injuries in free-ranging neotropical primates.

From 2016 to 2019, Southeastern Brazil faced an outbreak of yellow fever (YF) affecting both humans and New World primates (NWP). The outbreak was associated with a marked increase in traumatic lesions in NWP in the affected regions. Non-thrombotic pulmonary embolization (NTPE) can be a consequence of massive traumatic events, and it is rarely reported in human and veterinary medicine. Here, we describe NTPE of the brain, liver, and bone marrow in free-ranging NWP, highlighting the epidemiological aspects of these findings and the lesions associated with this condition, including data on traumatic injuries in wild NWP populations during the course of a recent YF outbreak. A total of 1078 NWP were necropsied from January 2017 to July 2019. Gross traumatic injuries were observed in 444 marmosets (44.3%), 10 howler monkeys (23.2%), 9 capuchins (31.0%), 1 titi-monkey (50.0%), and 1 golden lion tamarin (33.3%). NTPE was observed in 10 animals, including 9 marmosets (2.0%) and 1 howler monkey (10.0%). NTPE was identified in the lung and comprised hepatic tissue in 1 case, brain tissue in 1 case, and bone marrow tissue in 8 cases. Although uncommon, it is important to consider NTPE with pulmonary vascular occlusion during the critical care of traumatized NWP. In addition, this study highlights the importance of conservational strategies and environmental education focusing on One Health, not only to protect these free-ranging NWP populations but also to maintain the efficacy of epidemiological surveillance programs.

Accuracy of 68Ga-PSMA PET/CT for lymph node and bone primary staging in prostate cancer.

PURPOSE: The aim of this study is to assess the accuracy of the 68Ga-PSMA PET/CT for lymph nodes and bones in the primary stage of prostate cancer. METHODS: A total of 126 patients who were submitted to 68Ga-PSMA PET/CT from January 2016 to February 2019 for prostate cancer staging, detection of clinically significant lesions or active surveillance were included in this study. All studies were read by 2 experienced physicians (a nuclear physician and a radiologist). The reports were made in consensus and used by one of the authors to classify the exam in positive or negative. We evaluated presence of abnormal uptake in the prostate, lymph nodes, and bone. The reference standards were histopathological confirmation, confirmatory imaging exams and/or clinical follow-up showing lesion(s) regression after specific treatment, or typical osseous metastatic lesions and highly increased PSA levels. RESULTS: Measurement of diagnostic performance indicated a sensitivity, specificity and accuracy of 75%, 96.3%, and 90.8%, respectively, for lymph node involvement, and 90.9%, 50%, and 76.5%, respectively for metastatic bone lesions. CONCLUSION: This study showed high specificity and accuracy of 68Ga-PSMA PET/CT for lymph node and bone involvement in prostate cancer staging.

ACUTE NECROTIZING AND EOSINOPHILIC MYOCARDITIS IN A CHIMPANZEE (PAN TROGLODYTES).

Cardiac disease is of importance in captive chimpanzee (Pan troglodytes) health. Here we report an eosinophilic and necrotizing myocarditis in a 17-y-old chimpanzee with no previous history of cardiac disease that progressed to death within 48 h. Toxic and infectious causes were ruled out. The chimpanzee had eosinophilia at different occasions in previous years. The animal had a severe, diffuse, and acute monophasic necrotizing myocarditis, with a moderate lymphoplasmacytic infiltrate that was rich in eosinophils. Ante- and postmortem investigations are compatible with an unusual eosinophilic myocarditis with clinical evolution and morphology comparable with human eosinophilic myocarditis secondary to hypereosinophilic syndrome.

Dexmedetomidine reduces postoperative cognitive and behavioral dysfunction in adults submitted to general anesthesia for non-cardiac surgery: meta-analysis of randomized clinical trials.

INTRODUCTION AND OBJECTIVES: Dexmedetomidine (DEX) has been associated with a decrease in postoperative cognitive and behavioral dysfunction in patients submitted to general anesthesia, whether inhalation or total intravenous anesthesia. Consequently, the DEX effects on postoperative agitation and delirium in patients submitted to general anesthesia for non-cardiac surgery have been investigated. METHOD: A systematic review and meta-analysis of randomized and double-blind clinical trials (RCTs) was undertaken assessing adults submitted to elective procedures under general anesthesia receiving DEX or placebo. The search included articles published in English in the Pubmed and Web of Science databases using keywords such as dexmedetomidine, delirium, and agitation. Duplicate publications, studies involving cardiac surgery or using active control (other than saline solution) were included. A random effects model was adopted using the DerSimonian-Laird method and estimate of Odds Ratio (OR) for dichotomous variables, and weighted mean difference for continuous variables, with their respective 95% Confidence Intervals (95% CI). RESULTS: Of the 484 articles identified, 15 were selected comprising 2,183 patients (1,079 and 1,104 patients in the DEX and control group, respectively). The administration of DEX was considered a protective factor for postoperative cognitive and behavioral dysfunction (OR=0.36; 95% CI 0.23-0.57 and p<0.001), regardless of the anesthesia technique used. CONCLUSION: Dexmedetomidine administration reduced by at least 43% the likelihood of postoperative cognitive and behavioral dysfunction in adult patients submitted to general anesthesia for non-cardiac surgery.

Relação entre função motora e cognitiva na paralisia cerebral hemiplégica / Relationship between motor and cognitive function in hemiplegic cerebral palsy

Introdução: Crianças com paralisia cerebral hemiplégica (PCH) exibem dificuldades funcionais na utilização do membro superior hemiparético, repercutindo negativamente no desempenho em realizar atividades de vida diária. Atualmente, os déficits motores nessa população são acompanhados por distúrbios sensoriais, dificuldades na aprendizagem, alterações de comportamento e comunicação e défices cognitivos gerais. Objetivo: Investigar a possível associação entre os déficits motores e cognitivos de crianças com PCH, verificando ainda a influência da lateralidade da hemiplegia. Métodos: Participaram do estudo 30 crianças com PCH (idade média = 10,48 ± 2,46 anos). Os participantes foram submetidos aos seguintes testes: Assisting Hand Assessment (AHA), Matrizes Progressivas Coloridas de Raven, o Subteste cubos do Wechsler Intelligence Scale for Children fourth Edition - WISC IV e a fluência verbal semântica de animais. Resultados: Os grupos foram homogêneos em relação ao sexo e idade (p > 0.05). Os grupos não diferiram em relação ao nível de desempenho motor, memória de trabalho, inteligência e fluência verbal (p > 0,05). O desempenho motor correlacionou com todas as variáveis cognitivas. Conclusão: Em crianças com PCH o desempenho motor correlacionou fortemente com funções cognitivas. Além disso, a lateralidade da lesão cerebral não influenciou o desempenho em tarefas motoras e cognitivas. (AU)

Introduction: Children with hemiplegic cerebral palsy (HCP) exhibit functional difficulties in using the hemiparetic upper limb, negatively impacting their performance in carrying out activities of daily living. Currently, motor deficits in this population are accompanied by sensory disorders, learning difficulties, changes in behavior and communication and general cognitive deficits. Objective: To investigate the possible association between motor and cognitive deficits in children with PCH, also verifying the influence of laterality in hemiplegia. Methods: Thirty children with PCH participated in the study (mean age = 10.48 ± 2.46 years). Participants were subjected to the following tests: Assisting Hand Assessment (AHA), Raven's Colorful Progressive Matrices, the Wechsler Intelligence Scale for Children fourth Edition - WISC IV Subtest and the semantic verbal fluency of animals. Results: The groups were homogeneous in relation to sex and age (p > 0.05). The groups did not differ in relation to the level of motor performance, working memory, intelligence and verbal fluency (p> 0.05). Motor performance correlated with all cognitive variables. Conclusion: In children with PCH, motor performance correlated strongly with cognitive functions. In addition, the laterality of the brain injury did not influence performance in motor and cognitive tasks. (AU)

Sorting pain out of salience: assessment of pain facial expressions in the human fetus.

INTRODUCTION: The question of whether the human fetus experiences pain has received substantial attention in recent times. With the advent of high-definition 4-dimensional ultrasound (4D-US), it is possible to record fetal body and facial expressions. OBJECTIVE: To determine whether human fetuses demonstrate discriminative acute behavioral responses to nociceptive input. METHODS: This cross-sectional study included 5 fetuses with diaphragmatic hernia with indication of intrauterine surgery (fetoscopic endoluminal tracheal occlusion) and 8 healthy fetuses, who were scanned with 4D-US in 1 of 3 conditions: (1) acute pain group: Fetuses undergoing intrauterine surgery were assessed in the preoperative period during the anesthetic injection into the thigh; (2) control group at rest: Facial expressions at rest were recorded during scheduled ultrasound examinations; and (3) control group acoustic startle: Fetal facial expressions were recorded during acoustic stimulus (500-4000 Hz; 60-115 dB). RESULTS: Raters blinded to the fetuses' groups scored 65 pictures of fetal facial expressions based on the presence of 12 items (facial movements). Analyses of redundancy and usefulness excluded 5 items for being of low discrimination capacity (P>0.2). The final version of the pain assessment tool consisted of a total of 7 items: brow lowering/eyes squeezed shut/deepening of the nasolabial furrow/open lips/horizontal mouth stretch/vertical mouth stretch/neck deflection. Odd ratios for a facial expression to be detected in acute pain compared with control conditions ranged from 11 (neck deflection) to 1,400 (horizontal mouth stretch). Using the seven-item final tool, we showed that 5 is the cutoff value discriminating pain from nonpainful startle and rest. CONCLUSIONS: This study inaugurates the possibility to study pain responses during the intrauterine life, which may have implications for the postoperative management of pain after intrauterine surgical interventions.