Snake venom cysteine-rich secretory protein from Mojave rattlesnake venom (Css-CRiSP) induces acute inflammatory responses on different experimental models.

Snake venoms contain various molecules known for activating innate immunity and causing local effects associated with increased vascular permeability, such as vascular leakage and edema, common symptoms seen in snakebite envenomings. We have demonstrated that snake venom cysteine-rich secretory proteins (svCRiSPs) from North American pit vipers increase vascular permeability. This study aimed to explore the functional role of CRiSP isolated from Mojave rattlesnake (Crotalus scutulatus scutulatus) venom (Css-CRiSP) on the activation of inflammatory responses in different models. We measured the release of inflammatory mediators in cultured human dermal blood endothelial cells (HDBEC), lymphatic endothelial cells (HDLEC) and monocyte-derived macrophages (MDM) at 0.5, 1, 3, 6, and 24 h after treatment with Css-CRiSP (1 µM). We also determined the acute inflammatory response in BALB/c mice 30 min after intraperitoneal injection of the toxin (2 µg/mouse). Css-CRiSP induced the production of IL-8 and IL-6, but not TNF-α, in HDBEC and HDLEC in a time-dependent manner. In addition, Css-CRiSP significantly enhanced the production of IL-6, TNF-α, IL-8, and IL-1ß in MDM. Moreover, it caused a remarkable increase of chemotactic mediators in the exudates of experimental mice. Our results reveal that Css-CRiSPs can promote a sustained release of inflammatory mediators on cell lines and an acute activation of innate immunity in a murine model. These findings contribute to the growing body of evidence supporting the involvement of svCRiSPs in the augmentation of envenomation effects, specifically, the role of svCRiSPs in inducing vascular dysfunction, initiating early inflammatory responses, and facilitating the activation of leukocytes and releasing mediators. These findings will lead to a better understanding of the pathophysiology of envenoming by Mojave rattlesnakes, allowing the development of more efficient therapeutic strategies.

Fusariosis in Mexico: A 10-year retrospective series.

Fusarium species represent an opportunistic fungal pathogen. The data in Mexico about Fusarium infections in humans are scarce. Here, we present a retrospective series of patients with a confirmed diagnosis of fusariosis in eight different hospitals in Mexico from January 2010 to December 2019. The diagnosis of proven fusariosis was made according to the European Organization for Research and Treatment of Cancer and the Mycoses Study Group Education and Research Consortium (EORT/MSG) criteria. A total of 49 cases were identified in our series. Most patients had burn injuries (49%), and 37% had hematological malignancies. Most patients had fire injuries (40%), followed by electric injuries (8%), febrile neutropenia (10%), and pancytopenia (6%). Patients had skin and soft tissue involvement in 49%, followed by blood culture isolation and biopsies from different sites of the body (lung, sinuses, bone tissue, and eyes). Febrile neutropenia (10%) and fungemia (8%) were the most common clinical syndromes in immunosuppressed patients. Most patients received monotherapy (67%), where voriconazole was used in 30% of the cases, followed by conventional amphotericin B (16%), and lipidic formulations of amphotericin B in 10% (either liposomal amphotericin B or amphotericin B lipid complex). Combination therapy was used in 20% of the cases, and the most common combination therapy was triazole plus any lipidic formulation of amphotericin B (10%). Mortality related to Fusarium infection occurred in 22% of patients. Fusariosis is a serious threat. Burn injuries and hematologic malignancies represent the most common causes of infection in this small series from Mexico.

This study describes the epidemiological characteristics of patients with fusariosis from a multicenter cohort in Mexico. These findings provide information from this invasive fungal disease that threatens different countries in Latin America.

Proteomic Profiling of Extracellular Vesicles Isolated from Plasma and Peritoneal Exudate in Mice Induced by Crotalus scutulatus scutulatus Crude Venom and Its Purified Cysteine-Rich Secretory Protein (Css-CRiSP).

Increased vascular permeability is a frequent outcome of viperid snakebite envenomation, leading to local and systemic complications. We reported that snake venom cysteine-rich secretory proteins (svCRiSPs) from North American pit vipers increase vascular permeability both in vitro and in vivo. They also induce acute activation of several adhesion and signaling molecules that may play a critical role in the pathophysiology of snakebites. Extracellular vesicles (EVs) have gained interest for their diverse functions in intercellular communication, regulating cellular processes, blood-endothelium interactions, vascular permeability, and immune modulation. They also hold potential as valuable biomarkers for diagnosing, predicting, and monitoring therapeutic responses in different diseases. This study aimed to identify proteins in peritoneal exudate and plasma EVs isolated from BALB/c mice following a 30 min post-injection of Crotalus scutulatus scutulatus venom and its purified CRiSP (Css-CRiSP). EVs were isolated from these biofluids using the EVtrap method. Proteomic analysis of exudate- and plasma-derived EVs was performed using LC-MS/MS. We observed significant upregulation or downregulation of proteins involved in cell adhesion, cytoskeleton rearrangement, signal transduction, immune responses, and vesicle-mediated transports. These findings suggest that svCRiSPs play a crucial role in the acute effects of venom and contribute to the local and systemic toxicity of snakebites.

El regreso a clases presenciales de educación física ante la COVID-19 en México / The return to face-to-face physical education classes against COVID-19 in Mexico / O retorno às aulas presenciais de educação física antes do COVID-19 no México

La presente investigación tuvo como objetivo conocer el nivel de cumplimiento de las medidas académicas y de salud, limpieza e higiene que se implementaron en la sesión de educación física en el regreso a clases presenciales en México. Para ello, se siguió un diseño cuantitativo no experimental de corte transversal, a través de la cual se recogió información por medio de una escala tipo Likert. Los resultados indican que el 55% de los profesores de educación física están de acuerdo en que las medidas académicas establecidas, les facilitó lograr la recuperación y reforzamiento de los aprendizajes de sus alumnos, así mismo, el 81,2% afirma que se están llevando a cabo medidas preventivas de contagio y mitigación de la COVID-19 en las actividades escolares. Se concluye que las medidas propuestas por las autoridades educativas para el regreso a clases presenciales son aceptables, sin embargo, se identifican limitantes en lo que se refiere al abasto de materiales de sanitización y limpieza entregados por las autoridades educativas.

This research was conducted in order to determine the level of compliance to the health, cleanliness, and hygiene measures implemented during physical education sessions when returning to school in Mexico. For this purpose, a non-experimental cross-sectional quantitative design was followed, through which information was collected by means of a Likert-type scale. The results indicate that 55% of the physical education teachers agree that the measures established helped them to recover and reinforce what their students learnt. Likewise, 81,2% assert that they are now carrying out preventive measures for the contagion and mitigation of COVID-19 during school activities. It is concluded that the measures proposed by the educational authorities for the return to school are acceptable. However, there are some limitations identified in terms of the supply of sanitizing and cleaning materials provided by the educational authorities.

O objetivo desta pesquisa foi determinar o nível de cumprimento das medidas acadêmicas e de saúde, limpeza e higiene que foram implementadas na sessão de educação física ao retornar às aulas presenciais no México. Para isso, seguiu-se um delineamento quantitativo transversal não experimental, por meio do qual as informações foram coletadas por meio de uma escala do tipo Likert. Os resultados indicam que 55% dos professores de educação física concordam que as medidas acadêmicas estabelecidas facilitam a recuperação e o reforço da aprendizagem de seus alunos, da mesma forma, 81,2% afirmam que estão realizando medidas preventivas de contágio e mitigação de COVID-19 nas atividades escolares. Conclui-se que as medidas propostas pelas autoridades educacionais para o retorno às aulas presenciais são aceitáveis, porém, são identificadas limitações quanto ao fornecimento de materiais de higienização e limpeza entregues pelas autoridades educacionais.

Evaluation of Signaling Pathways Profiling in Human Dermal Endothelial Cells Treated by Snake Venom Cysteine-Rich Secretory Proteins (svCRiSPs) from North American Snakes Using Reverse Phase Protein Array (RPPA).

Cysteine-Rich Secretory Proteins (CRiSPs) are typically found in many snake venoms; however, the role that these toxins play in the pathophysiology of snakebites is still unclear. Herein, we compared the effects of snake venom CRiSPs (svCRiSPs) from the most medically important species of North American snakes on endothelial cell permeability and vascular permeability. We used reverse phase protein array (RPPA) to identify key signaling molecules on human dermal lymphatic (HDLECs) and blood (HDBECs) endothelial cells treated with svCRiSPs. The results showed that Css-CRiSP isolated from Crotalus scutulatus scutulatus and App-CRiSP from Agkistrodon piscivorus piscivorus are the most potent causes of increase vascular and endothelial permeability in comparison with other svCRiSPs used in this study. We examined the protein expression levels and their activated phosphorylation states in HDLECs and HDBECs induced by App-CRiSP and Css-CRiSP using RPPA. Interestingly, both App-CRiSP and Css-CRiSP induced caveolin-1 expression in HDBECs. We also found that stimulating HDBECs with Css-CRiSP and App-CRiSP significantly induced the phosphorylation of mTOR and Src, respectively. In HDLECs, Css-CRiSP significantly downregulated the expression of N-Cadherin and phospholipase C-gamma, while App-CRiSP significantly enhanced Akt and JNK phosphorylation. These results suggest that the increased endothelial permeability in HDLECs and HDBECs by Css-CRiSP and App-CRiSP may occur through different pathways.

Examination of the Efficacy and Cross-Reactivity of a Novel Polyclonal Antibody Targeting the Disintegrin Domain in SVMPs to Neutralize Snake Venom.

Snake envenomation can result in hemorrhage, local necrosis, swelling, and if not treated properly can lead to adverse systemic effects such as coagulopathy, nephrotoxicity, neurotoxicity, and cardiotoxicity, which can result in death. As such, snake venom metalloproteinases (SVMPs) and disintegrins are two toxic components that contribute to hemorrhage and interfere with the hemostatic system. Administration of a commercial antivenom is the common antidote to treat snake envenomation, but the high-cost, lack of efficacy, side effects, and limited availability, necessitates the development of new strategies and approaches for therapeutic treatments. Herein, we describe the neutralization ability of anti-disintegrin polyclonal antibody on the activities of isolated disintegrins, P-II/P-III SVMPs, and crude venoms. Our results show disintegrin activity on platelet aggregation in whole blood and the migration of the SK-Mel-28 cells that can be neutralized with anti-disintegrin polyclonal antibody. We characterized a SVMP and found that anti-disintegrin was also able to inhibit its activity in an in vitro proteolytic assay. Moreover, we found that anti-disintegrin could neutralize the proteolytic and hemorrhagic activities from crude Crotalus atrox venom. Our results suggest that anti-disintegrin polyclonal antibodies have the potential for a targeted approach to neutralize SVMPs in the treatment of snakebite envenomations.

Radiotherapy induced cavernomas in adult cancer patients.

Cerebral Cavernomas (CC) are vascular malformations located in the Central Nervous System (CNS) characterized by endothelium-lined vascular channels without parenchyma between them, whose main risk is hemorrhage. The aim of this study is to report adult cancer patients that developed CC after radiotherapy (RT) to the CNS during oncological surveillance.

Manifestaciones bucales de la sífilis / Oral symptoms of syphilis

La sífilis, enfermedad que por largo tiempo ha constituido un problema médico-social, presenta manifestaciones bucales, y son éstos hallazgos clínicos los que en algunas ocasiones permiten el diagnóstico de la enfermedad. En el presente trabajo se revisan las generalidades, bacteriología, tratamiento y etapas de la enfermedad, junto con presentar 2 casos clínicos de pacientes que presentan lesiones orales

Consideracions acerca de la atención odontológica en el senescente / Odontological care of the elderly patient

When planning an odontological treatment for an advanced age patient, a series of disorders that occur with ageing must be considered, both systemic as well as local. The aged person's stomatological system has its own characterístics, and for this reason odontological specialties must be adapted to them when making a treatment