Perfil epidemiológico de internações por doenças infecciosas e bacterianas em menores de 5 anos, de 2017 a 2021 / Perfil epidemiológico de las hospitalizaciones por enfermedades infecciosas y bacterianas más prevalentes en niños menores de 5 años, de 2017 a 2021 / Epidemiological profile of hospitalizations for the most prevalent infectious and bacterial diseases in children under 5 years, from2017 to 2021

Introdução:A internação representa um impacto considerável na vida de qualquer pessoa, podendo tomar proporções ainda maiores quando se trata de uma criança. A impossibilidade de realizar sua rotina, como brincar e ir à escola, faz com que a internação infantil assuma um contexto marcante.Dito isso, nota-se que grande parte dessas internações é evitável, sendo denominadasde Internações por Condições Sensíveis à Atenção Primária. Dessa forma, o atendimento ambulatorial de qualidade poderia resolver a maioria das enfermidades infantis, evitando esse desfecho.Objetivo:Elaborar um perfil epidemiológico de internações por doenças infecciosas e bacterianas mais prevalentes em menores de 5 anos, de 2017 a 2021, no Brasil. Metodologia:A pesquisa em questão se trata de um estudo ecológico de série temporal,elaborado através de informações coletadas por vias secundárias.Os dados foram coletados na plataforma DataSUS e no Sistema de Informação Hospitalar. Posteriormente, os dados foram processados e armazenados no aplicativo Microsoft Excel®, onde foram tratados e selecionados de acordo com sua relevância para a pesquisa. Resultados:Constata-se que a faixa etária situadaabaixo do primeiro ano de vidaapresenta um grau de hospitalização superior ao dascrianças que vãodo primeiro ao quarto ano completo.Quanto àfrequência relativa, depreende-se que diarreia e gastroenterite de origem infecciosa presumível apresentaram o maior índice de prevalência em relação às demais patologias, com o maior número chegando a 23,8% no ano de 2017 e o menor situando-se na faixa de 13,22% em 2020. Conclusões: Apesar do avanço na Atenção Primária à Saúde e da cobertura pré-natal, a assistência ainda é deficitária, sendo necessários mais investimentos na área e o fomento de políticas públicas que abranjam essa população (AU).

Introduction: Hospitalization represents a considerable impact on the life of any person, and can even take on even greater proportions when it comes to a child. The impossibility of realizing their routine, such as playing and going to school, means that hospitalization during childhood takes ona remarkable context. That said, it is noted that mostofthese hospitalizations are avoidable,and are called Ambulatory Care Sensitive Conditions. Thus, quality ambulatory care could solve most childhood illnesses, avoiding this outcome.Objective:To elaborate an epidemiological profile of hospitalizations for the most prevalent infectious and bacterial diseases in children under 5 years of age,from 2017 to 2021,in Brazil. Methodology: The research in question is an ecological study of time series, elaborated through information collected through secondary data sources. Data were collected from the DataSUS platform and the Hospital Information System. Subsequently, data were processed and stored in Microsoft Excel® application, where they were managedand selected according to their relevance to the research. Results:It is observed that the age group below the first year of life presents a higher degree of hospitalization thanthat of children ranging from the first to the fourth year. As for the relative frequency, it can be seen that diarrhea and gastroenteritis of presumable infectious origin had the highest prevalence rate compared to other pathologies, with the highest number reaching 23.8% in 2017 and the lowest being in the range of 13.22% in 2020. Conclusions: Despite the advances in Primary Health Care and prenatal coverage, assistance is still deficient, requiring more investments in the area and the promotion of public policies that cover this population (AU).

Introducción: La hospitalización representa un impacto considerable en la vida de cualquier persona, quepuede adquirir proporciones aún mayores cuando se trata de un niño. La imposibilidadde realizar su rutina, como jugar e ir al colegio, hace que la hospitalización infantiltengaun contexto notable. Dicho esto, cabe señalar que una gran parte de estas hospitalizaciones son evitables, denominándose Hospitalizaciones por Condiciones Sensibles a la Atención Ambulatoria. Así pues, una atención ambulatoria de calidad podría resolver la mayoría de las enfermedades infantiles, evitando este desenlace. Objetivo: Elaborar un perfil epidemiológico de las hospitalizaciones por enfermedades infecciosas y bacterianas más prevalentes en niños menores de 5 años, de 2017 a 2021, en Brasil. Metodología: La investigación en cuestión es un estudio ecológico de series temporales, elaborado a partir de información recogida por vías secundarias. Los datos se recogieron de la plataforma DataSUS y del Sistema de Información Hospitalaria. Posteriormente, los datos se procesaron y almacenaron en la aplicación Microsoft Excel®, donde se trataron y seleccionaron en función de su relevancia para la investigación. Resultados: Se observa que el grupo de edad inferior al primer año de vida presenta un mayor grado de hospitalización que los niños del primero al cuarto año completo. En cuanto a la frecuencia relativa, se puede inferirque la diarreay lagastroenteritis presumible origen infeccioso tuvieron la tasa de prevalencia más alta en relación con las demáspatologías, siendola cifra más alto el 23,8% en 2017 y lamás bajael rango del 13,22% en el 2020. Conclusiones: A pesar de los avances en la Atención Primariade Salud y en la cobertura prenatal, la asistencia aún es deficiente, por lo que se requieren mayoresinversiones en el área y la promoción de políticas públicas que cubran a esta población (AU).

Integrative systems biology reveals NKG2A-biased immune responses correlate with protection in infectious disease, autoimmune disease, and cancer.

Infection, autoimmunity, and cancer are principal human health challenges of the 21st century. Often regarded as distinct ends of the immunological spectrum, recent studies hint at potential overlap between these diseases. For example, inflammation can be pathogenic in infection and autoimmunity. T resident memory (TRM) cells can be beneficial in infection and cancer. However, these findings are limited by size and scope; exact immunological factors shared across diseases remain elusive. Here, we integrate large-scale deeply clinically and biologically phenotyped human cohorts of 526 patients with infection, 162 with lupus, and 11,180 with cancer. We identify an NKG2A+ immune bias as associative with protection against disease severity, mortality, and autoimmune/post-acute chronic disease. We reveal that NKG2A+ CD8+ T cells correlate with reduced inflammation and increased humoral immunity and that they resemble TRM cells. Our results suggest NKG2A+ biases as a cross-disease factor of protection, supporting suggestions of immunological overlap between infection, autoimmunity, and cancer.

Ophthalmic and immunopathological characterization of systemic infectious diseases in cats.

Ocular involvement in systemic diseases is frequent in cats; however, without concurrent clinical and ophthalmic examinations with gross and/or histologic analysis of the eye, these findings can be underdiagnosed. This article aims to provide gross, histologic, and immunohistochemical characteristics of ocular lesions from cats submitted to necropsy, focusing on those caused by systemic infectious agents. Cats that died due to a systemic infectious disease were selected based on necropsy diagnosis and presence of ocular lesions. Gross, histologic, and immunohistochemical findings were recorded. From April 2018 to September 2019, 849 eyes of 428 cats were evaluated. Histologic abnormalities were seen in 29% of cases, which were classified as inflammatory (41%), neoplastic (32%), degenerative (19%), and metabolic/vascular (8%). Macroscopic changes were present in one-third of eyes with histologic lesions. Of these, 40% were attributed to inflammatory or neoplastic diseases associated with infectious agents. The most important infectious agents causing ocular disease in this study were feline leukemia virus, feline infectious peritonitis virus, and Cryptococcus sp. The most common ocular abnormalities associated with infectious agents were uveitis (anterior, posterior, or panuveitis), optic neuritis, and meningitis of the optic nerve. Ocular lesions secondary to systemic infections in cats are frequent; however, these are not always diagnosed because gross lesions are less common than histologic lesions. Therefore, both gross and histologic evaluation of the eyes of cats is recommended, mainly for cases in which the clinical suspicion or necropsy diagnosis suggests that an infectious agent might be related to the cause of death.

The differential expression of toll like receptors and RIG-1 correlates to the severity of infectious diseases.

The toll like receptors (TLRs) and RIG-1 are proteins involved in the initial reaction of the innate immune system to infectious diseases and, thus, can provide much information to the surgical pathologist in terms of the molecular dynamics of the infection. The TLRs (TLR1, 2, 3, 4, 7, 8) and RIG-1 distribution as determined by immunohistochemistry was examined in the following diseases: human papillomavirus (n = 30 including 15 squamous intraepithelial lesions (SIL), 5 cancers, and 10 controls); molluscum contagiosum (n = 8 including 4 controls), SARS-CoV2 (n = 52 including 20 mild, 5 fatal, and 27 controls) and reovirus infection as oncolytic therapy. Mild, regressing infection (molluscum contagiosum, mild SARS-CoV2 and low grade SIL) each showed the same pattern: marked up regulation of at least three of the TLRs/RIG-1 with decreased expression of none compared to the controls. Severe infection (fatal SARS-CoV2, and cervical cancer) each showed marked decrease expression in at least three of the TLRs/RIG-1. We recently documented an equivalent marked decrease expression of the TLRs/RIG-1 in the placenta in fatal in utero infections. The reoviral infected tissues showed an overall pattern of marked increase expression of TLRs/RIG-1, consistent with a strong anti-viral response. Thus, the in situ testing of infectious diseases by a panel of these early infectious disease recognition proteins may allow the surgical pathologist to predict the outcome of the disease which, in turn, may assist in the understanding of the role of the TLRs/RIG-1 in determining the fate of a given infectious process.

Breast imaging of infectious disease.

Infectious diseases of the breast can demonstrate a wide variety of clinical presentations and imaging appearances. Breast abscesses are often a complication of infectious mastitis of the breast. Puerperal mastitis is the most common cause of breast abscess, typically affecting postpartum females. Often diagnosed clinically, it is usually treated with antibiotics without need for imaging. Non-puerperal mastitis is relatively uncommon and typically subareolar in location. Patients can present with asymmetric breast thickening, a palpable lump, nipple discharge, or axillary adenopathy. These presentations can mimic malignancy. Herein, this pictorial review demonstrates imaging findings of common and uncommon infectious processes of the breast and clinically important mimickers of breast infection.

Endoplasmic reticulum stress mediates the myeloid-derived immune suppression associated with cancer and infectious disease.

Myeloid-derived suppressor cells (MDSCs), which are immature heterogeneous bone marrow cells, have been described as potent immune regulators in human and murine cancer models. The distribution of MDSCs varies across organs and is divided into three subpopulations: granulocytic MDSCs or polymorphonuclear MDSCs (G-MDSCs or PMN-MDSCs), monocytic MDSCs (M-MDSCs), as well as a recently identified early precursor MDSC (eMDSCs) in humans. Activated MDSCs induce the inactivation of NK cells, CD4+, and CD8+ T cells through a variety of mechanisms, thus promoting the formation of tumor immunosuppressive microenvironment. ER stress plays an important protecting role in the survival of MDSC, which aggravates the immunosuppression in tumors. In addition, ferroptosis can promote an anti-tumor immune response by reversing the immunosuppressive microenvironment. This review summarizes immune suppression by MDSCs with a focus on the role of endoplasmic reticulum stress-mediated immune suppression in cancer and infectious disease, in particular leprosy and tuberculosis.

Aborto infectocontagioso em éguas: uma revisão bibliográfica / Infectious-contagious abortion in mares: a literature review / Aborto infecto-contagioso en yeguas: una revisión de la literatura

O aborto infectocontagioso em éguas é um tema de grande relevância e interesse para os médicos veterinários e criadores de equinos. Além dos impactos econômicos decorrentes de perdas e redução das taxas reprodutivas, os surtos de abortos causados por doenças infectocontagiosas representam uma ameaça significativa para a saúde equina. Neste trabalho, realizamos uma revisão bibliográfica abrangente sobre as principais doenças que causam abortos infecciosos em éguas. Nosso objetivo é fornecer uma visão geral das patologias mais relevantes nesse contexto, abordando suas características clínicas, epidemiologia, diagnóstico e medidas de controle. Para isso, realizamos uma busca em bancos de dados renomados, como o PubMed e o Scopus, por artigos científicos relevantes publicados nos últimos dez anos. As informações selecionadas foram cuidadosamente analisadas, comparadas e sintetizadas, com o intuito de identificar as principais doenças e suas implicações na saúde reprodutiva das éguas. Esta revisão pretende auxiliar veterinários, pesquisadores e profissionais da área a compreenderem melhor essas doenças e desenvolverem estratégias eficazes de prevenção e controle.(AU)

El aborto infeccioso en yeguas es un tema de gran relevancia e interés para veterinarios y criadores de equinos. Además de las repercusiones económicas derivadas de las pérdidas y la reducción de las tasas reproductivas, los brotes de aborto causados por enfermedades infecciosas representan una importante amenaza para la salud equina. En este artículo, realizamos una revisión exhaustiva de la literatura sobre las principales enfermedades que causan abortos infecciosos en yeguas. Nuestro objetivo es ofrecer una visión general de las patologías más relevantes en este contexto, abordando sus características clínicas, epidemiología, diagnóstico y medidas de control. Para ello, buscamos en bases de datos de renombre como PubMed y Scopus artículos científicos relevantes publicados en los últimos diez años. La información seleccionada fue cuidadosamente analizada, comparada y sintetizada con el fin de identificar las principales enfermedades y sus implicaciones en la salud reproductiva de las yeguas. El objetivo de esta revisión es ayudar a veterinarios, investigadores y profesionales del sector a comprender mejor estas enfermedades y desarrollar estrategias eficaces de prevención y control.(AU)

Infectious abortion in mares is a topic of great relevance and interest for veterinarians and equine breeders. In addition to economic impacts from losses and reduced reproductive rates, abortion outbreaks caused by infectious diseases represent a significant threat to equine health. In this paper, we conduct a comprehensive literature review on the major diseases that cause infectious abortions in mares. Our goal is to provide an overview of the most relevant pathologies in this context, addressing their clinical features, epidemiology, diagnosis, and control measures. To this end, we searched renowned databases such as PubMed and Scopus for relevant scientific articles published in the last ten years. The selected information was carefully analyzed, compared and synthesized in order to identify the main diseases and their implications in the reproductive health of mares. This review aims to assist veterinarians, researchers, and professionals in the field to better understand these diseases and develop effective prevention and control strategies.(AU)

Biofilm in sino-nasal infectious diseases: the role nasal cytology in the diagnostic work up and therapeutic implications.

BACKGROUD: Biofilm formation has been recently recognised as one of the most important etiopathological mechanisms underlying chronic rhinosinusitis (CRS) and its recalcitrance. In this context, nasal cytology (NC) has become an integral part of diagnostic work up of patients suffering from sino-nasal diseases, since it is an easy-to-apply, reproducible and non-invasive diagnostic tool that allows to assess both the nasal inflammatory infiltrate and the presence of biofilms on nasal mucosal surface, further orienting the therapeutic choices in case of infectious diseases for eradicating infections and biofilms. Nevertheless, biofilms are typically resistant to common antibiotic treatments and may trigger or maintain chronic inflammation. Hence, the importance of correctly detecting the presence of biofilm and identifying new effective treatments. PURPOSE: The aim of this brief review is to better clarify the role of biofilm in the pathogenesis and recurrence of sino-nasal disorders and to highlight the role of nasal cytology (NC) in the rhino-allergologic diagnostic path and in the evaluation of the effectiveness of new treatments.

Sífilis mimetizando lúpus eritematoso sistêmico: um relato de caso / Syphilis mimicking systemic lupus erythematosus: a case report / Sífilis que simula lupus eritematoso sistémico: informe de un caso

O Lúpus Eritematoso Sistêmico (LES) é uma patologia crônica, de origem autoimune e inflamatória. As diversas manifestações clínicas existentes em pacientes acometidos pelo LES, sejam elas sistêmicas ou órgãos-alvo, possibilitam variados diagnósticos diferenciais. Dentre as manifestações clínicas que possibilitam estes diagnósticos está o acometimento cutâneo, com vasta variabilidade de apresentação. Da mesma forma, a sífilis também possui apresentação cutânea, tornando possível o diferencial de diagnóstico com outras patologias, inclusive o próprio LES. O presente estudo tem como objetivo relatar um caso de sífilis mimetizando lúpus eritematoso sistêmico, descrever o quadro clínico apresentado pelo paciente, bem como as ferramentas utilizadas para diagnóstico, e a posterior abordagem terapêutica. O caso relatado refere-se a um paciente de 29 anos, do sexo masculino, procedente de Campos Novos (SC), que apresentou um quadro clínico e laboratorial de lúpus-like induzido por uma infecção aguda de sífilis. A resolução completa de critérios inflamatórios de LES ocorreu após tratamento correto da doença infecciosa, com total melhora clínica e sorológica.

Systemic lupus erythematosus (SLE) is a chronic autoimmune inflammatory disease. The various clinical manifestations in SLE patients, both systemic and in target organs, allow for various differential diagnoses. Among the clinical manifestations that aid in diagnosis are the cutaneous injuries, which have a wide range of presentations. Syphilis also has cutaneous manifestations, which aid in the differential diagnosis from other pathologies, including SLE. The present study aims to report a case of syphilis mimicking SLE, describe the clinical condition presented by the patient, the tools used for diagnosis, and the therapeutic approach. The case reported refers to a 29- year-old male patient from Campos Novos (SC), who showed a clinical and laboratory lupus-like condition induced by an acute syphilis infection. The full resolution of SLE inflammatory criteria occurred following appropriate treatment for the infectious disease, with complete clinical and serological improvement.

El lupus eritematoso sistémico (LES) es una enfermedad inflamatoria autoinmune crónica. Las diversas manifestaciones clínicas de los pacientes con LES, tanto sistémicas como en órganos diana, permiten realizar varios diagnósticos diferenciales. Entre las manifestaciones clínicas que ayudan al diagnóstico se encuentran las lesiones cutáneas, que tienen una amplia gama de presentaciones. La sífilis también tiene manifestaciones cutáneas, que ayudan al diagnóstico diferencial con otras patologías, incluido el LES. El presente estudio tiene como objetivo comunicar un caso de sífilis que simula un LES, describir el cuadro clínico presentado por la paciente, las herramientas utilizadas para el diagnóstico y el abordaje terapéutico. El caso relatado se refiere a un paciente masculino de 29 años, natural de Campos Novos (SC), que presentó un cuadro clínico y de laboratorio semejante al lupus, inducido por una infección aguda por sífilis. La resolución completa de los criterios inflamatorios del LES ocurrió tras el tratamiento adecuado de la enfermedad infecciosa, con mejoría clínica y serológica completa.

Early IFN-ß administration protects cigarette smoke exposed mice against lethal influenza virus infection without increasing lung inflammation.

During influenza A virus (IAV) infection, it is unclear whether type I interferons (IFNs) have defensive antiviral effects or contribute to immunopathology in smokers. We treated nonsmoking (NS) and cigarette smoke (CS)-exposed mice intranasally with early (prophylactic) or late (therapeutic) IFN-ß. We compared the mortality and innate immune responses of the treated mice following challenge with IAV. In NS mice, both early and late IFN-ß administration decreased the survival rate in mice infected with IAV, with late IFN-ß administration having the greatest effect on survival. In contrast, in CS-exposed mice, early IFN-ß administration significantly increased survival during IAV infection while late IFN-ß administration did not alter mortality. With regards to inflammation, in NS mice, IFN-ß administration, especially late administration, significantly increased IAV-induced inflammation and lung injury. Early IFN-ß administration to CS-exposed mice did not increase IAV-induced inflammation and lung injury as occurred in NS mice. Our results demonstrate, although IFN-ß administration worsens the susceptibility of NS mice to influenza infection with increased immunopathology, early IFN-ß administration to CS-exposed mice, which have suppression of the intrinsic IFN response, improved outcomes during influenza infection.

Characterization of Keterah orthonairovirus and evaluation of therapeutic candidates against Keterah orthonairovirus infectious disease.

The species Keterah orthonairovirus is a member of the genus Orthonairovirus. Few studies have focused on this species, and there remains no treatment for Issyk-Kul fever, an infectious disease caused by a Keterah orthonairovirus. This study was performed to characterize this species using two viruses, Issyk-Kul virus (ISKV) and Soft tick bunyavirus (STBV), in cell culture and type I interferon receptor knockout (IFNAR-/-) mice and to evaluate the efficacy of serum transfusion using a mouse model of ISKV infection. The two viruses replicated in many kinds of mammal- and tick-derived cell lines but showed few different characteristics in tropism and antigenicity against anti-viral sera in cell culture. Neither virus caused clinical signs in wild-type mice, but both caused lethal infection in IFNAR-/- mice. ISKV caused more acute death than STBV in IFNAR-/- mice. In both viral infections in IFNAR-/- mice, macroscopic abnormalities were prominent in the liver. Similar levels of viral genome between ISKV- and STBV-infected IFNAR-/- mice were observed in blood, liver, lymphoid tissues and adrenal gland at moribund stages. Hematologic abnormalities in IFNAR-/- mice infected with these viruses, including leukopenia and thrombocytopenia, and biochemical abnormalities indicating liver damage were prominent. In addition, blood levels of many kinds of cytokines and chemokines such as granulocyte colony-stimulating factor, interleukin-6, tumor necrosis factor-α, interferon gamma-induced protein 10 and monocyte chemoattractant protein-1 were elevated. ISKV-immunized serum transfusion after infection delayed the time to death of IFNAR-/- mice. Thus, the present study showed that the species Keterah orthonairovirus could proliferate in most mammal-derived cell lines and cause severe liver lesions and death in IFNAR-/- mice and that serum transfusion might be effective in treatment against Issyk-Kul fever.

PANoptosis: A New Insight Into Oral Infectious Diseases.

The oral microbiome, one of the most complex and intensive microbial ecosystems in the human body, comprises bacteria, archaea, fungi, protozoa, and viruses. Dysbiosis of the oral microbiome is the initiating factor that leads to oral infectious diseases. Infection is a sophisticated biological process involving interplay between the pathogen and the host, which often leads to activation of programmed cell death. Studies suggest that pyroptosis, apoptosis, and necroptosis are involved in multiple oral infectious diseases. Further understanding of crosstalk between cell death pathways has led to pyroptosis, apoptosis, and necroptosis being integrated into a single term: PANoptosis. PANoptosis is a multifaceted agent of the immune response that has important pathophysiological relevance to infectious diseases, autoimmunity, and cancer. As such, it plays an important role in innate immune cells that detect and eliminate intracellular pathogens. In addition to the classical model of influenza virus-infected and Yersinia-infected macrophages, other studies have expanded the scope of PANoptosis to include other microorganisms, as well as potential roles in cell types other than macrophages. In this review, we will summarize the pathophysiological mechanisms underlying inflammation and tissue destruction caused by oral pathogens. We present an overview of different pathogens that may induce activation of PANoptosis, along with the functional consequences of PANoptosis in the context of oral infectious diseases. To advance our understanding of immunology, we also explore the strategies used by microbes that enable immune evasion and replication within host cells. Improved understanding of the interplay between the host and pathogen through PANoptosis will direct development of therapeutic strategies that target oral infectious diseases.

The differentiation state of the Schwann cell progenitor drives phenotypic variation between two contagious cancers.

Contagious cancers are a rare pathogenic phenomenon in which cancer cells gain the ability to spread between genetically distinct hosts. Nine examples have been identified across marine bivalves, dogs and Tasmanian devils, but the Tasmanian devil is the only mammalian species known to have given rise to two distinct lineages of contagious cancer, termed Devil Facial Tumour 1 (DFT1) and 2 (DFT2). Remarkably, DFT1 and DFT2 arose independently from the same cell type, a Schwann cell, and while their ultra-structural features are highly similar they exhibit variation in their mutational signatures and infection dynamics. As such, DFT1 and DFT2 provide a unique framework for investigating how a common progenitor cell can give rise to distinct contagious cancers. Using a proteomics approach, we show that DFT1 and DFT2 are derived from Schwann cells in different differentiation states, with DFT2 carrying a molecular signature of a less well differentiated Schwann cell. Under inflammatory signals DFT1 and DFT2 have different gene expression profiles, most notably involving Schwann cell markers of differentiation, reflecting the influence of their distinct origins. Further, DFT2 cells express immune cell markers typically expressed during nerve repair, consistent with an ability to manipulate their extracellular environment, facilitating the cell's ability to transmit between individuals. The emergence of two contagious cancers in the Tasmanian devil suggests that the inherent plasticity of Schwann cells confers a vulnerability to the formation of contagious cancers.

The Role of Extracellular Vesicles from Human Macrophages on Host-Pathogen Interaction.

The nano-sized membrane enclosed extracellular vesicles (EVs) released by virtually all cell types play an essential role in intercellular communication via delivering bio-molecules, such as nucleic acids, proteins, lipids, and other molecules to recipient cells. By mediating an active and steady-state cell-to-cell communication, EVs contribute to regulating and preserving cellular homeostasis. On the other hand, EVs can also spread pathogen-derived molecules during infections, subverting the host immune responses during infections and thus worsening pathophysiological processes. In recent years, the biological functioning of EVs has become a widespread research field in basic and clinical branches of medical sciences due to their potential role in therapeutic applications for several diseases. This review aims to summarize the main recent findings regarding the implication of EVs shed by human macrophages (MΦ-EVs) and how they can modulate the host immune response to control or increase the damage caused by infectious agents. We will also present the methods used to describe MΦ-EVs, as well as the potential of these EVs as disease diagnostic tools for some human pathogens. We believe that an in-depth understanding of the host-pathogen interactions mediated by MΦ-EVs may trigger the development of innovative therapeutic strategies against infectious diseases.

The RHO Family GTPases: Mechanisms of Regulation and Signaling.

Much progress has been made toward deciphering RHO GTPase functions, and many studies have convincingly demonstrated that altered signal transduction through RHO GTPases is a recurring theme in the progression of human malignancies. It seems that 20 canonical RHO GTPases are likely regulated by three GDIs, 85 GEFs, and 66 GAPs, and eventually interact with >70 downstream effectors. A recurring theme is the challenge in understanding the molecular determinants of the specificity of these four classes of interacting proteins that, irrespective of their functions, bind to common sites on the surface of RHO GTPases. Identified and structurally verified hotspots as functional determinants specific to RHO GTPase regulation by GDIs, GEFs, and GAPs as well as signaling through effectors are presented, and challenges and future perspectives are discussed.

Arginine-dependent immune responses.

A growing body of evidence indicates that, over the course of evolution of the immune system, arginine has been selected as a node for the regulation of immune responses. An appropriate supply of arginine has long been associated with the improvement of immune responses. In addition to being a building block for protein synthesis, arginine serves as a substrate for distinct metabolic pathways that profoundly affect immune cell biology; especially macrophage, dendritic cell and T cell immunobiology. Arginine availability, synthesis, and catabolism are highly interrelated aspects of immune responses and their fine-tuning can dictate divergent pro-inflammatory or anti-inflammatory immune outcomes. Here, we review the organismal pathways of arginine metabolism in humans and rodents, as essential modulators of the availability of this semi-essential amino acid for immune cells. We subsequently review well-established and novel findings on the functional impact of arginine biosynthetic and catabolic pathways on the main immune cell lineages. Finally, as arginine has emerged as a molecule impacting on a plethora of immune functions, we integrate key notions on how the disruption or perversion of arginine metabolism is implicated in pathologies ranging from infectious diseases to autoimmunity and cancer.

RETROSPECTIVE REVIEW OF HISTOLOGIC FINDINGS IN CAPTIVE GILA MONSTERS (HELODERMA SUSPECTUM) AND BEADED LIZARDS (HELODERMA HORRIDUM).

A retrospective study was performed by reviewing all Heloderma spp. submissions to Northwest ZooPath from 1996 to 2019. Necropsy and biopsy specimens from 106 captive Gila monsters (Heloderma suspectum) and 49 captive beaded lizards (Heloderma horridum) were reviewed. Inflammatory diseases were the most frequently diagnosed condition in Heloderma spp., and were diagnosed in 72% of all animals examined, including 76% of Gila monsters and 63% of beaded lizards. The most common cause of inflammation was bacterial infection, which was present in 52% of all Heloderma spp. with inflammation. Enterocolitis was common in Gila monsters (20%) and beaded lizards (14%), but the underlying causes were different for each species. Cryptosporidium spp. was the most common cause of enterocolitis in Gila monsters (36%) but was not identified in beaded lizards. Amoebiasis was a common cause of enterocolitis in Gila monsters (27%) and was the most common cause of enterocolitis in beaded lizards (57%). Deposition diseases were diagnosed in 34% of all Heloderma spp. The most frequently diagnosed deposition disease in beaded lizards was urolithiasis-nephrolithiasis (12%). This disease was not diagnosed in Gila monsters. Deposition diseases that were common in Gila monsters and beaded lizards included hepatic lipidosis and renal gout. Neoplasia was diagnosed in 17% of all Heloderma spp., including 17% of Gila monsters and 18% of beaded lizards. The most common neoplasm of Heloderma spp. was renal adenocarcinoma, which was equally common in Gila monsters and beaded lizards. Less common diagnoses included degenerative diseases, trauma, nutritional disease, nonneoplastic proliferative disease, nondegenerative cardiovascular disease, and congenital malformation.

Managing adult patients with infectious diseases in emergency departments: international ID-IRI study.

We aimed to explore factors for optimizing antimicrobial treatment in emergency departments. A single-day point prevalence survey was conducted on January 18, 2020, in 53 referral/tertiary hospitals in 22 countries. 1957 (17%) of 11557 patients presenting to EDs had infections. The mean qSOFA score was 0.37 ± 0.74. Sepsis (qSOFA ≥ 2) was recorded in 218 (11.1%) patients. The mean qSOFA score was significantly higher in low-middle (1.48 ± 0.963) compared to upper-middle (0.17 ± 0.482) and high-income (0.36 ± 0.714) countries (P < 0.001). Eight (3.7%) patients with sepsis were treated as outpatients. The most common diagnoses were upper-respiratory (n = 877, 43.3%), lower-respiratory (n = 316, 16.1%), and lower-urinary (n = 201, 10.3%) infections. 1085 (55.4%) patients received antibiotics. The most-commonly used antibiotics were beta-lactam (BL) and BL inhibitors (n = 307, 15.7%), third-generation cephalosporins (n = 251, 12.8%), and quinolones (n = 204, 10.5%). Irrational antibiotic use and inappropriate hospitalization decisions seemed possible. Patients were more septic in countries with limited resources. Hence, a better organizational scheme is required.