Predictors of damage accrual and its impact on health-related quality of life of thrombotic antiphospholipid syndrome: Independent validation of the damage index for antiphospholipid syndrome (DIAPS).

OBJECTIVES: We aim to independently assess the validity of the damage index for antiphospholipid syndrome (DIAPS) in thrombotic antiphospholipid syndrome (APS) patients by exploring the prevalence and risk factors of organ damage and evaluating its impact on health-related quality of life (HR-QoL). METHODS: Cross-sectional study including all thrombotic APS patients (Sydney criteria) attending a Portuguese tertiary centre. Damage was assessed using the DIAPS, and HR-QoL using the 3- and 5-level EuroQol HR-QoL (EQ-D5-3L and 5L), and Visual Analogue Scale (VAS) applied via a phone questionnaire. Spearman's correlation between DIAPS and the HR-QoL scales was performed. Risk factors for damage accrual and HR-QoL impairment were explored using univariate and multivariate logistic regression. RESULTS: Among the 108 patients (female, 65.7%; white, 90.7%; primary APS, 75.9%; median disease duration, 6 years), damage (DIAPS≥1) developed in 48.2% of patients (mean ± SD DIAPS, 3.08 ± 1.83). DIAPS's neuropsychiatric domain was the most affected (24.2%), followed by the peripheral vascular domain (20.3%). No clinical, demographic nor laboratory parameters were significantly associated with damage. Regarding HR-QoL, pain/discomfort, anxiety/depression and usual activities domains were the most frequently impaired in both scales. DIAPS's domains correlated similarly with the EQ-5D-3L and 5L scales' individual domains. Female sex, medical disorders, secondary APS and type of presenting thrombosis (arterial) increased the risk of HR-QoL impairment. Total DIAPS was associated with higher odds of mobility, self-care and pain/discomfort impairment in both EQ-5D-3L and 5L scales but lost its independent risk in multivariable analysis. CONCLUSION: This external validation of DIAPS reinforces the ability of the score to correlate with HR-QoL while also highlighting risk factors for HR-QoL impairment other than damage accrual.

Brain damage serum biomarkers induced by COVID-19 in patients from northeast Brazil.

Neurological symptoms have been often reported in COVID-19 disease. In the present study, we evaluated brain damage associated with the increase of serum levels of neurological biomarkers S100B and neuron-specific enolase (NSE) induced by SARS-CoV-2 infection, in a population from Northeastern Brazil. Thirty-six healthy control (G1) individuals and 141 patients with confirmed COVID-19 were enrolled in this study. Positive-COVID-19 patients were divided into two groups according to the severity of illness by the National Institute of Health (NIH) criteria, 76 patients with mild symptoms for COVID-19 and (G2) and 65 with acute respiratory conditions requiring supplemental oxygenation via intensive care unit (ICU) admission (G3). A follow-up study was conducted with 23 patients from G2 14 (D14) and 21 (D21) days after the onset of symptoms. Serum levels of NSE and S100B were measured using the enzyme-linked immunoassay method (ELISA). Results revealed a significant positive association between G3 patients and S100B serum expression (p = 0.0403). The serum levels of NSE were also significantly enhanced in the G3 group compared to the control (p < 0.0001) and G2 group (p < 0.0001). In addition, clinical features such as symptoms and oxygenation status were not correlated with NSE or S100B serum expression. The follow-up study demonstrated a decrease over time (21 days) in NSE serum expression (p < 0.0001). These results suggest that brain damage is followed by acute virus exposure, with no long-term effects. Future work examining COVID-19 recovery will shed light on chronic neurological damage of SARS-CoV-2 infection.

Health equity related challenges and experiences during the rapid implementation of virtual care during COVID-19: a multiple case study.

BACKGROUND: Virtual care quickly became of crucial importance to health systems around the world during the COVID-19 pandemic. Despite the potential of virtual care to enhance access for some communities, the scale and pace at which services were virtualized did not leave many organizations with sufficient time and resources to ensure optimal and equitable delivery of care for everyone. The objective of this paper is to outline the experiences of health care organizations rapidly implementing virtual care during the first wave of the COVID-19 pandemic and examine whether and how health equity was considered. METHODS: We used an exploratory, multiple case study approach involving four health and social service organizations providing virtual care services to structurally marginalized communities in the province of Ontario, Canada. We conducted semi-structured qualitative interviews with providers, managers, and patients to understand the challenges experienced by organizations and the strategies put in place to support health equity during the rapid virtualization of care. Thirty-eight interviews were thematically analyzed using rapid analytic techniques. RESULTS: Organizations experienced challenges related to infrastructure availability, digital health literacy, culturally appropriate approaches, capacity for health equity, and virtual care suitability. Strategies to support health equity included the provision of blended models of care, creation of volunteer and staff support teams, participation in community engagement and outreach, and securement of infrastructure for clients. We put our findings into the context of an existing framework conceptualizing access to health care and expand on what this means for equitable access to virtual care for structurally marginalized communities. CONCLUSION: This paper highlights the need to pay greater attention to the role of health equity in virtual care delivery and situate that conversation around existing inequitable structures in the health care system that are perpetuated when delivering care virtually. An equitable and sustainable approach to virtual care delivery will require applying an intersectionality lens on the strategies and solutions needed to address existing inequities in the system.

Incidence and predictors of brain metastasis in colorectal cancer patients.

PURPOSE: Brain metastasis (BM) in colorectal cancer patients is rare and is associated with dismal outcomes. Our study aims to evaluate the incidence and predictors of BM in patients with colorectal cancer. METHODS: We performed a retrospective analysis (2010-2017) of patients with a primary diagnosis of colorectal cancer (CRC). Patients were stratified into two groups (BM vs. No-BM). Outcome measures were the incidence and predictors of BM. Multivariate logistic regression analysis was performed. RESULTS: A total of 230,806 patients were analyzed. A total of 0.30% (n = 691) of the patients were found to have BM. On multivariate logistics regression, bone (OR: 5.39 [3.36-8.65], p < 0.001), lung (OR: 3.75 [2.67-5.28], < 0.001), and distant node metastasis (OR: 32.75 [20.47-52.41], p < 0.001) were independent predictors of BM. CONCLUSION: Our study supports the low incidence of brain metastasis in patients with colorectal cancer. A unique set of characteristics is identified to confer an increased risk of brain metastases.

A Lateral Flow Test for Staphylococcus aureus in Nasal Mucus Using a New DNAzyme as the Recognition Element.

Detection of pathogenic bacteria in complex biological matrices remains a major challenge. Herein, we report the selection and optimization of a new DNAzyme for Staphylococcus aureus (SA) and the use of the DNAzyme to develop a simple lateral flow device (LFD) for detection of SA in nasal mucus. The DNAzyme was generated by in vitro selection using a crude extra/intracellular mixture derived from SA, which could be used directly for simple solution or paper-based fluorescence assays for SA. The DNAzyme was further modified to produce a DNA cleavage fragment that acted as a bridging element to bind DNA-modified gold nanoparticles to the test line of a LFD, producing a simple colorimetric dipstick test. The LFD was evaluated with nasal mucus samples spiked with SA, and demonstrated that SA detection was possible in minutes with minimal sample processing.

Does preoperative neoadjuvant chemotherapy impact short-term surgical outcomes in patients with locally advanced colon cancer?

BACKGROUND: Preoperative neoadjuvant chemotherapy (NAC) for colon cancer in advanced stages is associated with improved outcomes and tumor regression. The aim of our study was to identify outcomes in patients with colon cancer who received preoperative NAC. METHODS: A 4-year analysis of the American College of Surgeons-National Surgical Quality Improvement Program (ACS-NSQIP) was performed. We included patients with locally advanced colon cancer (non-metastatic T3, T4 with or without nodal involvement) who underwent colon cancer resection. Patients were stratified into two groups (NAC and No-NAC). Our outcome measures were anastomotic leaks, hospital length of stay (LOS), 30-day complications, 30-day mortality, and 30-day readmissions. We performed a multi-variable logistic regression analysis. RESULTS: We analyzed 90,055 patients of which 7694 (NAC: 7.8 % (n = 599) and No-NAC: 92.2% (n = 7095)) met the inclusion criteria and included in the analysis. Mean age was 67 ± 13 years, 51% were males, and 72% were whites. Patients in the NAC group were more likely to be younger (60 ± 12 years vs. 68 ± 13 years, p < 0.01) and males (62% vs. 50%, p < 0.01) compared to No-NAC. On regression analysis, preoperative NAC was independently associated with higher odds of anastomotic leak (OR 1.35 [1.05-1.97], p = 0.03) and 30-day readmission (OR 1.54 [1.24-2.05], p < 0.01) in reference to No-NAC. However, no association was found between NAC and 30-day complications and 30-day mortality. CONCLUSIONS: Preoperative NAC might be associated with adverse outcomes of anastomotic leaks and 30-day readmissions, however does not appear to impact 30-day complications nor 30-day mortality.

Exploring Leishmania infantum cathepsin as a new molecular marker for phylogenetic relationships and visceral leishmaniasis diagnosis.

BACKGROUND: Leishmania infantum, the etiological agent of visceral leishmaniasis, is a neglected zoonosis that requires validation and standardization of satisfactory diagnostic methodologies. Thus, the aim of the present study was to evaluate the effectiveness of cathepsin L-like protease as a target for making molecular diagnoses and as a phylogenetic marker enabling to understand the intraspecies variations and evolutionary history of L. infantum in Brazil. METHODS: We used 44 isolates of L. infantum. The cathepsin L-like gene fragments were amplified, sequenced, manually aligned and analyzed using inference methods. The sequences generated were used to search and design oligonucleotide primers to be used in reactions specific to the target parasite. RESULTS: The cathepsin L-like gene did not show any intraspecies variability among the isolates analyzed. The pair of primers proposed amplified the target deoxyribonucleic acid (DNA) of L. infantum isolates and were effective for DNA amplification at concentrations of as low as 10- 11 ng/µl. The proposed marker did not present cross-reactions with other hemoparasites. When used for making the diagnosis in a panel of clinical samples from dogs, a positivity rate of 49.03% (102/208) was obtained, versus 14.42% (30/208) for a ribosomal internal transcribed spacer (ITS) marker. In samples from sandflies, the rate was 6.25% and from humans, 14.28%. CONCLUSIONS: The results described in this work allow us to infer that CatLeish-PCR is a sensitive and specific marker for use in diagnostic trials of L. infantum and in clinical and epidemiological surveys.

Emergent colectomy for colorectal cancer: A comparative analysis of open vs. minimally invasive approach.

INTRODUCTION: Emergent surgery for colorectal cancer (CRC) is associated with higher rates of morbidity and mortality and outcomes differ by surgical approach. METHODS: Our study compares short-term surgical outcomes of patients undergoing emergent colectomy for CRC using the open vs minimally invasive (MIS) approach. We performed a four-year review (2012-2015) of the ACS-NSQIP Colectomy dataset and included all adult patients with CRC who underwent emergent surgical intervention. Patients were stratified into groups based on surgical approach: Open and MIS (including laparoscopic and robotic). RESULTS: A total of 1855 (MIS: 279, Open: 1576) patients were included. Outcome measures were operative time, 30-day complications, 30-day readmission, and 30-day mortality. Multivariate Regression analysis was performed. Patients in the open group were more likely to be older (70y vs. 61y, p < 0.01), have higher ASA class, and were less likely to have received mechanical bowel preparation. On univariate analysis, patients in the MIS group had longer operative time (189 ± 41 min vs. 161 ± 69 min, p < 0.01). Patients in the open group had higher rates of mortality (6.7% vs. 3.8%, p < 0.01) and 30-day complications (28.1% vs. 16.7%, p < 0.01). On regression analysis, the open approach was independently associated with higher odds of 30-day mortality and 30-day complications. CONCLUSION: Given the lower overall mortality and complications, MIS colectomy may be a safer approach in the emergent treatment of patients with colorectal cancer.

Diversity of intestinal protozoa and clinical signs associated in wild-caught Phoneutria nigriventer kept in captivity for the anti-arachnid serum production.

The phylum Arthropoda comprises approximately 85% of all described animal species. The class Arachnida includes some invertebrates of great importance as they are either involved in the transmission of diseases or poses a risk of human envenomation. Spiders belonging to the genus Phoneutria sp., are the arachnids exhibiting medical importance. These animals were quarantined and maintained in captivity at the Biotério de Artrópodes of the Instituto Butantan, São Paulo, Brazil, for the production of the anti-arachnid serum. A total 509 feces samples from different Phoneutria nigriventer were analyzed, and 131 (25.73%) samples were found to be positive for flagellates and ciliates. All positive samples were subjected to DNA extraction and amplification of 18S gene. A total of 16 sequences were obtained and analyzed using BLAST. Sequences were identified as Colpoda steiini, one as Colpoda aspera, one to Colpoda sp., and one as "ciliated". Four identified as Parabodo caudatus, two as Urostipulosphaera sp., one as Helkesimastix sp., and one as a Euglena-like. The presence of clinical signs was observed in 16 spiders. The intestinal protozoa that affect armed spiders were identified for the first time as an initial step for understanding the parasitic diseases in these organisms.

Challenges and strategies for promoting health equity in virtual care: findings and policy directions from a scoping review of reviews.

OBJECTIVE: We sought to understand and synthesize review-level evidence on the challenges associated with accessibility of virtual care among underserved population groups and to identify strategies that can improve access to, uptake of, and engagement with virtual care for these populations. MATERIALS AND METHODS: A scoping review of reviews was conducted (protocol available at doi: 10.2196/22847). A total of 14 028 records were retrieved from MEDLINE, EMBASE, CINAHL, Scopus, and Epistemonikos databases. Data were abstracted, and challenges and strategies were identified and summarized for each underserved population group and across population groups. RESULTS: A total of 37 reviews were included. Commonly occurring challenges and strategies were grouped into 6 key thematic areas based on similarities across communities: (1) the person's orientation toward health-related needs, (2) the person's orientation toward health-related technology, (3) the person's digital literacy, (4) technology design, (5) health system structure and organization, and (6) social and structural determinants of access to technology-enabled care. We suggest 4 important directions for policy development: (1) investment in digital health literacy education and training, (2) inclusive digital health technology design, (3) incentivizing inclusive digital health care, and (4) investment in affordable and accessible infrastructure. DISCUSSION AND CONCLUSION: Challenges associated with accessibility of virtual care among underserved population groups can occur at the individual, technological, health system, and social/structural determinant levels. Although the policy approaches suggested by our review are likely to be difficult to achieve in a given policy context, they are essential to a more equitable future for virtual care.

Prevalence of Leishmania infantum in Dogs from Deforested Areas of the Amazon Biome.

Background and Objectives: Species of Leishmania genus are intracellular parasites responsible for severe zoonotic diseases worldwide, such as leishmaniasis. In Brazil, the most important species is Leishmania infantum. In the northern region, the state of Pará is notable, with a high number of cases reported in recent years. The second largest number of cases of human visceral leishmaniasis in the region in recent years has been reported in the city of Marabá (Pará state). We investigated the prevalence of L. infantum in domestic dogs from Marabá in Amazon region in Brazil. Materials and Methods: A total of 400 blood samples were tested using the dual-path platform chromatographic immunoassay (DPP® CVL-Bio-Manguinhos), and molecular diagnosis based in cathepsin L-like gene, which has better specificity and sensitivity than other similar tests. Results: The prevalence of L. infantum was 75.5% (302/400) in the serological test, and 59.25% (237/400) in molecular diagnosis, and 45.5% (182/400) in both tests. Interpretation and Conclusion: The results confirmed that the parasite L. infantum was prevalent in the dog population of the studied region and adoption of appropriate public policies are urgently needed.

Strongyloides stercoralis Gastric Ulcer: A Rare Cause of Upper Gastrointestinal Bleeding.

Strongyloidiasis is an infection caused by Strongyloides stercoralis. Gastrointestinal manifestations typically include duodenitis, chronic enterocolitis, and malabsorption, while gastric involvement is very rare. In this case report, the -authors present a case of upper gastrointestinal bleeding caused by a gastric ulcer with a challenging etiological diagnosis. In Portugal, there have been reports in the past century of autochthonous cases of S. stercoralis infection suggesting endemic zones, but with the current sanitation infrastructure strongyloidiasis is thought to be rare. A 56-year-old Caucasian male smoker with a history of significant weight loss presented to the emergency department with hema-temesis and abdominal pain. Upper endoscopy revealed a giant gastric ulcer with a macroscopic appearance suggestive of malignancy. Further investigation with CT scan highlighted gastric wall thickness and a spiculated lung lesion in the upper right lobe without lymph node involvement or metastatic disease. Bronchoscopy with bronchial brushing was performed. Histological examination identified squamous cell carcinoma of the lung and the patient was referred to Oncological Pneumology. Gastric ulcer biopsies ruled out malignancy and identified fragments of nematodes with inflammatory infiltrates and fibrinogranulocytic exudate, suggestive of S. stercoralis. Accordingly, the diagnosis of strongyloidiasis was made and further confirmed with molecular methods and serology. The giant gastric ulcer was affirmed to be caused by S. stercoralis infection and the patient was treated with ivermectin with improvement of epigastric pain. On reevaluation 6 weeks later the patient was asymptomatic, had gained weight, parasitological stool examinations were negative, and upper endoscopy showed complete ulcer healing. Further tests were done targeting risk factors for strongyloidiasis, and in addition to the presence of malignancy, other underlying causes for immunosuppression were ruled out. In this case report strongyloidiasis was manifested by gastric involvement with upper gastrointestinal bleeding in a patient who was subsequently diagnosed with squamous cell carcinoma of the lung.

A estrongiloidíase é uma infecção causada por Strongyloides stercoralis. As manifestações gastrointestinais tipicamente incluem duodenite, enterocolite crónica e má absorção, sendo o envolvimento gástrico muito raro. Neste caso clínico, os autores apresentam um caso de hemorragia digestiva alta causada por uma úlcera gástrica com um diagnóstico etiológico desafiante. Em Portugal no século passado existiram casos autóctones de infecção a S. stercoralis sugerindo zonas endémicas, mas com a actual infraestrutura de saneamento a estrongiloidíase é rara. Homem de 56 anos de idade, caucasiano, fumador, com história de perda ponderal significativa, admitido no Serviço de Urgência por hematemeses e dor abdominal. A endoscopia digestiva alta realizada revelou uma úlcera gástrica gigante com aparência macroscópica sugestiva de malignidade. A investigação subsequente com tomografia computadorizada (TC) destacou a presença de espessamento gástrico e uma lesão pulmonar espiculada no lobo superior direito, sem envolvimento ganglionar ou doença metastática. Foi realizada broncofibroscopia com escovado brônquico tendo o exame histológico identificado carcinoma pavimento celular do pulmão, pelo que o doente foi referenciado para a Pneumologia Oncológica. As biópsias da úlcera gástrica descartaram malignidade e identificaram fragmentos de nemátodes com infiltrados inflamatórios e exsudado fibrino-granulocítico, sugestivo de Strongyloides stercoralis. Consequentemente, foi feito o diagnóstico de estrongiloidíase, confirmado com métodos moleculares e sorologia. Admitiu-se que a úlcera gástrica gigante terá sido causada pela infecção por Strongyloides stercoralis e o doente foi tratado com ivermectina com melhoria da dor epigástrica. Em reavaliação, seis semanas depois, o doente estava assintomático, com ganho ponderal, os exames parasitológicos das fezes estavam negativos e a endoscopia digestiva alta mostrou cicatrização completa da úlcera. Foram realizados exames adicionais para investigação de factores de risco para estrongiloidíase, tendo sido excluídas outras causas de imunossupressão subjacente para além da presença de malignidade. Neste caso clínico, a estrongiloidíase manifestou-se por envolvimento gástrico com hemorragia digestiva alta num doente que foi posteriormente diagnosticado com carcinoma pavimento celular do pulmão.

Large-vessel vasculitis induced by pegfilgrastim.

Granulocyte colony-stimulating factor (G-CSF) is increasingly being used to prevent febrile neutropenia associated with chemotherapy. Large-vessel vasculitis (LVV) has been recognized as a rare side effect of G-CSF treatment. We report a case of G-CSF associated LVV in a patient with breast cancer. While clear pathogenic mechanisms remain unknown, G-CSF may cause vasculitis due to inflammatory cytokines production. This adverse reaction should be recognized in patients with suggestive symptoms following the administration of pegfilgrastim. A 56-year-old woman with luminal B breast cancer who had undergone surgery and adjuvant chemotherapy, initially with paclitaxel, was started on a doxorubicin plus cyclophosphamide protocol, followed by supportive use of long-acting G-CSF pegfilgrastim. Following the administration of pegfilgrastim, the patient developed intermittent fever and was given empiric antibiotics in the outpatient setting with no improvement. There were no signs of cancer progression, and the contrast-enhanced CT scan highlighted wall thickening of the aortic arch and the proximal segment of the subclavian artery, which was not present in previous imaging studies. The patient was diagnosed with LVV, and a differential diagnosis was performed to rule out paraneoplastic setting, immune-mediated diseases, infection or other drug-induced vasculitis. Treatment with steroids was initiated and tapered with significant improvement and resolution of the radiological signs of aortitis.

Molecular Diagnosis and Prevalence of Trypanosoma vivax (Trypanosomatida: Trypanosomatidae) in Buffaloes and Ectoparasites in the Brazilian Amazon Region.

Trypanosoma vivax Ziemann is a parasite that affects both wild and domestic ungulates and is transmitted mechanically via tabanids and other blood-sucking insects in the Americas. A total of 621 blood samples from water buffaloes (Bubalus bubalis (Linnaeus) (Artiodactyla: Bovidae), and 184 ectoparasite samples (Amblyomma cajennense (Fabricius) sensu stricto and Rhipicephalus (Boophilus) microplus (Canestrini) (Acari: Ixodidae), and Haematopinus tuberculatus (Burmeister) (Phthiraptera: Haematopinidae)) were obtained from 60 farms in the State of Pará, Brazilian Amazon. Twelve buffalo blood samples (1.89%) and 11 ectoparasites (6%) were positive for T. vivax based on the cathepsin L-like gene. All sequences were 99% similar to T. vivax from northeastern Brazil (EU753788) in amplified PCR assays on each of the hosts tested.

A Case of Brucellosis with Possible Ileal Involvement.

INTRODUCTION: Brucellosis is a zoonotic disease that can involve different organs and tissues. Fever, fatigue, lymphadenopathy, hepatosplenomegaly, cytopenia, and arthritis are the usual modes of presentation. Gastrointestinal manifestations of human brucellosis are common but documented ileal involvement is extremely rare. CASE DESCRIPTION: A 68-year-old female presented with a history of 10 days of intense temporal migraine, photophobia, and phonophobia with partial response to paracetamol. The patient referred night sweats, anorexia, and colicky abdominal pain after her meals for the past 4 months followed by diarrhea. She denied nausea, vomiting, hypersensitivity of the scalp, blurry vision, melena, or rectal bleeding. She denied travelling or contact with animals. Physical examination revealed fever (38.3°C) and splenomegaly. Laboratory workup revealed Hb 7.8 g/dL, leukopenia (3.47 × 109/L), C-reactive protein 5.94 mg/dL, and erythrocyte sedimentation rate 23 mm/h. Abdominal ultrasound showed hepatic steatosis and mild homogeneous splenomegaly. Chest radiography was normal. Lumbar puncture; transcranial, carotid, and temporal arteries Doppler, and head computed tomography (CT) did not show any significant changes. Abdominal CT showed diffuse thickening of the ileum and some mildly swollen locoregional lymph nodes. Fecal calprotectin was not elevated. Blood cultures and serologies were positive for Brucella (positive Rose-Bengal test, ELISA IgM-positive, IgG-negative anti-brucella antibody serology and positive Huddleson reaction - titer 1:320). The patient was started on rifampicin 600 mg/day and doxycycline 100 mg q. 12 h for 10 weeks with good clinical and analytical response. Upper and lower gastrointestinal endoscopy were normal, although the last was done already under antibiotic treatment. DISCUSSION: Although gastrointestinal manifestations of brucellosis are quite common, ileitis is thought to be extremely rare. In countries where brucellosis is endemic, doctors must consider this diagnosis when faced with patients with systemic symptoms and diarrhea or abdominal pain. Early recognition of brucellosis and institution of appropriate therapy usually leads to a good recovery without complications.

INTRODUÇÃO: A brucelose é uma zoonose que pode envolver diferentes órgãos e tecidos. A apresentação habitual consiste em febre, cansaço, linfadenopatias, hepatoesplenomegalia, citopenias ou artrite. As manifestações gastrointestinais de brucelose humana são comuns, mas a documentação do envolvimento ileal é extremamente rara. DESCRIÇÃO DO CASO: Doente de 68 anos, sexo feminino, apresentouse com quadro com dez dias de evolução de cefaleia temporal intensa, fotofobia e sonofobia, com resposta parcial a terapêutica com paracetamol. A doente referia sudorese noturna, anorexia e dor abdominal tipo cólica após as refeições durante os últimos quatro meses seguida de diarreia. Negava náuseas, vómitos, hipersensibilidade do escalpe, visão turva, melenas ou retorragia. Negava viagens ou contacto com animais. Ao exame objetivo destacavase febre (38,3 ° C) e esplenomegalia. Os estudos laboratoriais revelaram Hb 7,8 g/dL, leucopenia (3,109 × 47/L), proteína C-reativa 5,94 mg/dL, velocidade de sedimentação 23 mm/h. A ecografia abdominal mostrou ligeiro aumento do fígado (estatose) e esplenomegalia ligeira e homogénea. Radiografia de tórax normal. Punção lombar; Doppler transcraniano, carotídeo e das artérias temporais e tomografia computorizada (CT) craniana sem alterações significativas. A CT abdominal mostrou espessamento difuso do íleon e algumas pequenas adenopatias locorregionais. As hemoculturas e serologias foram positivas para Brucela (Rosa Bengala positivo, serologia anti-Brucela ELISA IgM-positivo, IgG-negativo; reação de Huddleson positiva - título 1: 320). Foi iniciada terapêutica com rifampicina 600 mg/dia e doxiciclina 100 mg de 12 em 12 h durante 10 semanas com boa resposta clínica e laboratorial. Endoscopia digestiva alta e baixa sem alterações, apesar de a última ter sido realizada já sob terapêutica antibiótica. DISCUSSÃO: Embora as manifestações gastrointestinais de brucelose sejam comuns, pensase que a ileíte seja extremamente rara. Em países onde a brucelose é endémica, os médicos devem considerar esta hipótese diagnóstica quando na presença de sintomas sistémicos e diarreia ou dor abdominal. O reconhecimento precoce da brucelose e a instituição de terapêutica adequada levam geralmente a uma boa recuperação sem complicações.

Canine Visceral Leishmaniasis in São Paulo, Brazil, the Most Populous City of South America: Isolation, Molecular Diagnosis, and Phylogenetic Inferences.

Background and Objectives: Canine visceral leishmaniasis affects dogs, the main urban reservoirs, which favor the transmission and expansion of this zoonotic disease in areas with high anthropization process and human density. We investigated the occurence of Leishmania infatum based in molecular diagnosis, and phylogenetic analysis of isolates obtained from dogs in metropolitan region of São Paulo. Methods: A total of 201 dogs were tested by parasitological and molecular diagnosis. Phylogenetic analysis based sequences from SSUrDNA and gGAPDH genes were performed. Results: The parasitological diagnosis revealed 5% (10/201) of positivity, and the sequences obtained from seven isolates were clustered with L. infantum in phylogentic analysis based on SSUrDNA and gGAPDH genes. A total of 24.9% (50/201) of dogs were positive in molecular diagnosis based on cathepsin L-like marker. Interpretation and Conclusion: According to this study, it is necessary to implement a surveillance policy of visceral leishmaniasis, intensifying the actions of diagnosis, prevention, and control of this zoonosis.

Quantum dots functionalized with 3-mercaptophenylboronic acids as novel nanoplatforms to evaluate sialic acid content on cell membranes.

Sialic acids (SAs) modulate essential physiological and pathological conditions, including cell-cell communication, immune response, neurological disorders, and cancer. Besides, SAs confer negative charges to cell membranes, also contributing to hemorheology. Phenylboronic acids, called as mimetic lectins, have been highlighted to study SA profiles. The association of these interesting molecules with the optical properties of quantum dots (QDs) can provide a deeper/complementary understanding of mechanisms involving SAs. Herein, we explored the thiol affinity to the QD surface to develop a simple, fast and direct attachment procedure to functionalize these nanocrystals with 3-mercaptophenylboronic acids (MPBAs). The functionalization was confirmed by fluorescence correlation spectroscopy and inductively coupled plasma spectrometry. The conjugate specificity/efficiency was proved in experiments using red blood cells (RBCs). A labeling >90% was found for RBCs incubated with conjugates, which reduced to 17% after neuraminidase pretreatment. Moreover, QDs-MPBA conjugates were applied in a comparative study using acute (KG-1) and chronic (K562) myelogenous leukemia cell lines. Results indicated that KG-1 membranes have a greater level of SA, with 100% of cells labeled and a median of fluorescence intensity of ca. 2.5-fold higher when compared to K562 (94%). Therefore, this novel QDs-MPBA conjugate can be considered a promising nanoplatform to evaluate SA contents in a variety of biological systems.

Evaluating internalization and recycling of folate receptors in breast cancer cells using quantum dots.

Folic acid (FA) regulates metabolic activities essential to the human body. FA receptor (FR) overexpression has been reported for many cancers, but there are still few or conflicting data about FRs in breast cancer cells. Quantum dots (QDs) have arisen as tools to elucidate aspects on FRs, due to their unique physicochemical properties. Herein, QDs conjugated to FA were explored to study the internalization and recycling of FRs in breast cancer cells, using HeLa as an out-group control. QDs were covalently conjugated to FA under different conditions. The best conjugate was applied to study FRs in HeLa, MCF7, MDA-MB231, and T47D cells applying confocal microscopy and flow cytometry analyses. The conjugation efficiency and specificity were evaluated, respectively, using fluorescence correlation spectroscopy (FCS) and saturation assays. FCS confirmed the effectiveness of the conjugation. HeLa and T47D had/internalized a higher amount of FRs (95% and 90% of labeling, respectively) than MDA-MB231 cells (68%). MCF7 cells seem to have very low functional FRs (3%). Saturation assays proved the specificity of QD-FA conjugates and suggested that FR recycling rate is low in the majority of cells studied, except for T47D. QD-FA conjugates were successfully developed. Therapies targeting FRs may be more effective for HeLa, T47D, and MDA-MB231.

Changes to trimethylamine-N-oxide and its precursors in nascent metabolic syndrome.

Background Metabolic syndrome (MetS), a cardio-metabolic cluster afflicting 35% of American adults, increases cardiovascular disease (CVD) and type-2 diabetes (T2DM) risk. Increased levels of trimethylamine N-oxide (TMAO), a metabolite derived from choline and L-carnitine, correlates with CVD and T2DM. However, the precise role of TMAO and its precursors in MetS remains unclear. We tested the hypothesis that choline, L-carnitine and TMAO in MetS patients without CVD or T2DM would be altered and correlate with inflammatory markers. Materials and methods This was an exploratory study of 30 patients with nascent MetS (without CVD or T2DM) and 20 matched controls. MetS was defined by the Adult Treatment Panel III criteria. TMAO and its precursors were evaluated from each patient's frozen early morning urine samples and quantified using liquid chromatography/mass spectrometry (LC-MS). These amines were correlated with a detailed repertoire of biomarkers of inflammation and adipokines. Results L-carnitine was significantly increased (p = 0.0002) compared to controls. There was a trend for a significant increase in TMAO levels (p = 0.08). Choline was not significantly altered in MetS. L-carnitine correlated significantly with soluble tumor necrosis factor 1 (sTNFR1) and leptin, and inversely to adiponectin. TMAO correlated with IL-6, endotoxin and chemerin. Neither choline, nor L-carnitine significantly correlated with TMAO. Conclusion L-carnitine is directly correlated with markers of inflammation in nascent MetS. Cellular L-carnitine could be a biomediator or marker of inflammation in the pathogenesis of MetS, and the sequelae of CVD and T2DM.