Alessandra Kimie Matsuno

The scorpion family Buthidae, renowned for its neurotoxin-rich venoms, dominates toxinology, while non-buthid venoms remain largely unexplored. Here, we present a comprehensive proteomic and biochemical characterization of the Amazonian chactid scorpion Brotheas amazonicus venom (BamazV), with emphasis on molecular complexity, proteolytic processing, and peptide diversity. Using an integrative venomics approach that combines molecular mass-based fractionation, reversed-phase chromatography, high-resolution mass spectrometry, N-terminal sequencing, and functional and immunological analyses, we reveal an unexpectedly complex venom profile enriched in high-molecular-weight components and extensively processed peptides, with more than 40 venom peptides sequenced by MS/MS and Edman degradation. The data provide evidence for non-canonical proteolytic events, including the generation of peptides from precursor regions not classically associated with mature venom components. In contrast to the venom of Tityus serrulatus, BamazV displays a “hydrolase-rich, neurotoxin-poor” profile, featuring a catalytically active Group III phospholipase A₂ (BamazPLA₂), a highly active hyaluronidase, metalloproteases, low-mass peptides, and potassium channel toxins. Our results suggest a hydrolytic prey-subjugation strategy, and limited cross-reactivity with commercial antivenom highlighted its distinct structural landscape. Overall, this study advances the understanding of venom evolution and proteolytic diversification in underexplored scorpion lineages, positioning B. amazonicus as a valuable model for investigating alternative venom strategies and identifying novel biotechnological scaffolds.

Scorpion envenomation is a leading cause of morbidity and mortality among accidents caused by venomous animals. Major clinical manifestations that precede death after scorpion envenomation include heart failure and pulmonary edema. Here, we demonstrate that cardiac dysfunction and fatal outcomes caused by lethal scorpion envenomation in mice are mediated by a neuro-immune interaction linking IL-1 receptor signaling, prostaglandin E_2, and acetylcholine release. IL-1R deficiency, the treatment with a high dose of dexamethasone or blockage of parasympathetic signaling using atropine or vagotomy, abolished heart failure and mortality of envenomed mice. Therefore, we propose the use of dexamethasone administration very early after envenomation, even before antiserum, to inhibit the production of inflammatory mediators and acetylcholine release, and to reduce the risk of death.

Objetivo: o transporte de crianças gravemente doentes envolve particularidades que aumentam o risco de complicações. O objetivo foi investigar o impacto de complicações registradas durante o transporte na mortalidade geral e na taxa de alta hospitalar.Método: estudo realizado em duas etapas. A primeira foi um estudo transversal, no qual, através de entrevista padronizada, dirigida ao médico que admitiu essas crianças, foram identificadas potenciais complicações ocorridas durante o transporte. Três médicos independentes auditaram esses dados. A segunda etapa foi uma coorte prospectiva onde os pacientes divididos em dois grupos (com e sem complicações no transporte) foram seguidos prospectivamente.Resultados: 143 crianças foram incluídas no estudo. Pelo menos uma complicação durante o transporte foi observada em 74 delas (52%). A complicação mais prevalente foi relacionada a falhas no monitoramento e nos dispositivos (42%). A ocorrência de complicações no transporte foi associada a maior mortalidade hospitalar (Hazard ratio - HR): 5,60; intervalo de confiança de 95% (IC95%): 1,26 - 26,65; p=0,013) e a menor taxa de alta hospitalar (HR: 0,48; IC95%: 0,31 - 0,74; p = 0,0007). Após regressão de Cox para ajuste de fatores de confusão, a presença de complicações permaneceu associada à mortalidade hospitalar (HR: 6,74; IC95%: 1,40 - 32,34); p = 0,017), porém deixou de se associar com a taxa de alta hospitalar (HR: 0,76; IC95%: 0,49 - 1,16; p=0,213).Conclusão: presença de complicações durante o transporte pediátrico foi frequente na região metropolitana de Ribeirão Preto, São Paulo, Brasil. A ocorrência de complicações foi um preditor independente de mortalidade hospitalar.

We aimed to assess the profile of respiratory viruses in young children hospitalized for acute lower respiratory tract infection (ALRI) and its association with disease severity, defined as need for pediatric intensive care unit (PICU) admission. Prospective observational cohort study. A tertiary-care university hospital in Brazil. Children younger than three years attending the pediatric emergency room with ALRI who were admitted to the hospital. None. Nasopharyngeal aspirates were collected from patients from June 1^st, 2008 to May 31^st, 2009within the first 48 hours of hospitalization. Nasopharyngeal aspirates were tested for 17humanrespiratory viruses by molecular and immunofluorescence based assays. Simple and multiple log-binomial regression models were constructed to assess associations of virus type with a need for PICU admission. Age, prematurity, the presence of an underlying disease and congenital heart disease were covariates. Nasopharyngeal aspirates were positive for at least one virus in 236 patients. Rhinoviruses were detected in 85.6% of samples, with a preponderance of rhinovirus C (RV-C) (61.9%). Respiratory syncytial virus was detected in 59.8% and human coronavirus (HCoV) in 11% of the samples. Co-detections of two to five viruses were found in 78% of the patients. The detection of HCoV alone (adjusted relative risk (RR) 2.18; 95% CI 1.15–4.15) or in co-infection with RV-C (adjusted RR 2.37; 95% CI 1.23–4.58) was independently associated with PICU admission. The detection of HCoV alone or in co-infection with RV-C was independently associated with PICU admission in young children hospitalized for ALRI.

Interleukin (IL)-1β is a potential target for treatment of several inflammatory diseases, including envenomation by the scorpion Tityus serrulatus. In this context, bioactive lipids such as prostaglandin (PG)E₂ and leukotriene (LT)B₄ modulate the production of IL-1β by innate immune cells. Pattern recognition receptors (PRRs) that perceive T. serrulatus venom (TsV), and orchestrate LTB₄, PGE₂, and cyclic adenosine monophosphate (cAMP) production to regulate IL-1β release are unknown. Furthermore, molecular mechanisms driving human cell responses to TsV remain uncharacterized. Here, we identified that both CD14 and CD36 control the synthesis of bioactive lipids, inflammatory cytokines, and mortality mediated by TsV. CD14 induces PGE₂/cAMP/IL-1β release and inflammation. By contrast, CD36 shunts eicosanoid metabolism toward production of LTB₄, which represses the PGE₂/cAMP/IL-1β axis and mortality. Of importance, the molecular mechanisms observed in mice strongly correlate with those of human cell responses to TsV. Overall, this study provides major insights into molecular mechanisms connecting CD14 and CD36 with differential eicosanoid metabolism and inflammation mediated by IL-1β.

Zika virus (ZIKV) is a mosquito-borne flavivirus, which has been related to severe neurological complications in neonates. However, many clinical aspects of the infection remain unclear, especially in pediatric patients. In this case report we describe the uncommon presentation of ZIKV infection in a pediatric patient with acute gastrointestinal involvement hospitalized in a Brazilian Emergency Unit. Dengue hemorrhagic fever was initially suspected, however, the molecular result for Dengue was negative. Molecular testing for other arboviruses (ZIKV and Chikungunya), revealed positive for ZIKV RNA result in both blood and saliva. The ZIKV load in saliva (6.947 copies/mL) was higher than the vetected ZIKV RNA in plasma (1.945 copies/mL). Additionally, the performed abdominal ultrasound revealed mesenteric lymphadenitis without abdominal retention of fluids. The presentation of this case demonstrates that ZIKV can be involved in a broader range of clinical conditions than currently assumed, including pediatric emergencies, especially in regions with extensive ZIKV outbreaks.

Background: Respiratory syncytial virus (RSV) is associated with severe lower respiratory tract infection (LRTI), especially in preterm infants. Other viruses, co-detected with RSV, may play a role in the severity of respiratory outcomes. Methods: This prospective epidemiologic study of severe LRTI incidence among children born ≤35 weeks gestational age at 3 sites in Brazil (2008–2010) followed a birth cohort for 1 year post-enrollment. Nasal washes from subjects with LRTI were tested for respiratory viruses using polymerase chain reaction. The primary outcome was the incidence of severe LRTI requiring hospitalization associated with RSV infection. Secondary outcomes included identification of viruses associated with LRTI, alone or coinfections, and risk factors associated with severe LRTI. Results: Among 303 subjects, 176 (58.1%) experienced LRTI. Among these subjects, 162 had samples tested using polymerase chain reaction; 27.8% (45/162) experienced severe LRTI. More subjects with severe LRTI were infected with RSV (30/45, 66.7%) than with other viruses. RSV was present in 33.1% (143/432) of LRTI events tested, 57.3% (82/143) were coinfections. RSV was the virus most frequently associated with severe LRTIs (34/56 events, 60.7%); 50% (17/34 events) single and 50% coinfections. Significantly longer hospital stays were associated with LRTI events involving RSV coinfections compared with RSV single infections (P = 0.012). Infants with severe LRTIs had significantly lower mean RSV-IgG levels at study entry compared with those with nonsevere or no LRTIs (P < 0.05). Conclusions: This study confirms the association of RSV alone or as a coinfection with severe LRTI and reinforces the importance of providing adequate prophylaxis for susceptible infants.

The diagnosis of ventilator-associated pneumonia (VAP) is a challenge, particularly after cardiac surgery. The use of biological markers of infection has been suggested to improve the accuracy of VAP diagnosis. We aimed to evaluate the usefulness of soluble triggering receptor expressed on myeloid cells (sTREM)-1 in the diagnosis of VAP following cardiac surgery.

Princípios de Prescrição Médica Hospitalar Para Estudantes de Medicina