Fluid dynamics of life: exploring the physiology and importance of water in the critical illness.

Water acknowledged as a vital component for life and the universal solvent, is crucial for diverse physiological processes in the human body. While essential for survival, the human body lacks the capacity to produce water, emphasizing the need for regular ingestion to maintain a homeostatic environment. The human body, predominantly composed of water, exhibits remarkable biochemical properties, playing a pivotal role in processes such as protein transport, thermoregulation, the cell cycle, and acid­base balance. This review delves into comprehending the molecular characteristics of water and its interactions within the human body. The article offers valuable insights into the intricate relationship between water and critical illness. Through a comprehensive exploration, it seeks to enhance our understanding of water's pivotal role in sustaining overall human health.

Trigeminal nerve stimulation: a current state-of-the-art review.

Nearly 5 decades ago, the effect of trigeminal nerve stimulation (TNS) on cerebral blood flow was observed for the first time. This implication directly led to further investigations and TNS' success as a therapeutic intervention. Possessing unique connections with key brain and brainstem regions, TNS has been observed to modulate cerebral vasodilation, brain metabolism, cerebral autoregulation, cerebral and systemic inflammation, and the autonomic nervous system. The unique range of effects make it a prime therapeutic modality and have led to its clinical usage in chronic conditions such as migraine, prolonged disorders of consciousness, and depression. This review aims to present a comprehensive overview of TNS research and its broader therapeutic potentialities. For the purpose of this review, PubMed and Google Scholar were searched from inception to August 28, 2023 to identify a total of 89 relevant studies, both clinical and pre-clinical. TNS harnesses the release of vasoactive neuropeptides, modulation of neurotransmission, and direct action upon the autonomic nervous system to generate a suite of powerful multitarget therapeutic effects. While TNS has been applied clinically to chronic pathological conditions, these powerful effects have recently shown great potential in a number of acute/traumatic pathologies. However, there are still key mechanistic and methodologic knowledge gaps to be solved to make TNS a viable therapeutic option in wider clinical settings. These include bimodal or paradoxical effects and mechanisms, questions regarding its safety in acute/traumatic conditions, the development of more selective stimulation methods to avoid potential maladaptive effects, and its connection to the diving reflex, a trigeminally-mediated protective endogenous reflex. The address of these questions could overcome the current limitations and allow TNS to be applied therapeutically to an innumerable number of pathologies, such that it now stands at the precipice of becoming a ground-breaking therapeutic modality.

Validación y reproducibilidad del cuestionario COPD-PS para la tamización de la EPOC: Bogotá, Colombia / Validation and reproducibility of the COPD-PS questionnaire for the screening of COPD: Bogotá, Colombia

Resumen Introducción: La enfermedad pulmonar obstructiva crónica es una afección con alta prevalencia a nivel mundial. Prevenible y tra table, pero con niveles de sub-diagnóstico muy altos. Es imperioso la utilización de herramientas de tamización; de fácil aplicación, interpretación y validadas en diferentes poblaciones, que ayudan no solo al clínico a la sospecha diagnostica, sino también al paciente a tomar conciencia sobre su enfermedad. Se busca validar el cuestionario COPD-Population Screener Questionnaire (COPD- PS) en una población colombiana. Materiales y métodos: Se realizó un estudio de cohorte prospectivo. Los participantes debían ser mayores de 40 años, tener una espirometría de buena calidad y haber realizado el cuestionario COPD-PS en dos oportunidades. La EPOC fue definida como un VEF1/ CVF < 0,7 y el antecedente de exposición a cigarrillo. Se realizó un análisis de reproducibilidad y validez. Resultado: De un total de 2199 sujetos potenciales, 1662 ingresaron al análisis final; la prevalencia de la EPOC en el estudio fue de 21,1%. Con el punto de corte de cuatro del cuestionario COPD-PS la sensibilidad fue del 77,2% y la especificidad de 46,3% con un área bajo la curva de características operativas del receptor de: 0,66(IC95%:0,63-0,69) (p < 0,01). Se obtuvo un coeficiente de correlación intraclase de 0,817(IC95%:0,79-0,84) y un coeficiente kappa de: 0,45(IC95%:0,31-0,59) (p < 0,01). Conclusión: El cuestionario COPD-PS es una herramienta con alta sensibilidad y buena reproducibilidad para la tamización de la EPOC, y podría ser una herramienta que oriente a la toma de espirometría en la búsqueda de sujetos no diagnosticados con esta patología.

Validation and reproducibility of the COPD-PS questionnaire for the screening of COPD: Bogotá, Colombia

Abstract Introduction: Chronic obstructive pulmonary disease is a condition with high prevalence worldwide. It is preventable and treatable, but with very high levels of underdiagnosis. The use of screening tools is imperative. These tools are easily applied, interpreted, and validated in different populations and help not only the clinician to confirm the diagnostic suspicion, but also the patients to become aware of their disease. The objective is to validate the COPD-Population Screener Questionnaire (COPD-PS) in one Colombian population. Materials and Methods: A prospective cohort study was carried out. Participants had to be older than 40 years, show a good quality spirometry, and have completed the COPD-PS questionnaire twice. COPD was defined as FEV1/FVC < 0.7 and with a history of exposure to tobacco smoke. A reproducibility and validation analysis has been conducted. Result: Out of a total of 2.199 potential subjects, 1.662 entered the final analysis; the prevalence of COPD in the study was 21.1%. With the COPD-PS questionnaire cut-off point of four, the sensitivity was 77.2% and the specificity was 46.3%, with an area under the receiver operating characteristic curve of: 0.66 (95% CI: 0.63-0.69) (p<0.01). An intraclass correlation coefficient of 0.817 (95% CI: 0.79-0.84) and a kappa coefficient of: 0.45 (95% CI: 0.31-0.59) (p<0.01) were obtained. Conclusion: The COPD-PS questionnaire is a tool with high sensitivity and good reproducibility for the screening of COPD, and could suggest the use of a spirometry in subjects not diagnosed with this disease.

Increased levels of cortisol are associated with the severity of experimental visceral leishmaniasis in a Leishmania (L.) infantum-hamster model.

BACKGROUND: Several infectious diseases are associated with hypothalamic-pituitary-adrenal (HPA) axis disorders by elevating circulating glucocorticoids (GCs), which are known to have an immunosuppressive potential. We conducted this study in golden hamsters, a suitable model for human visceral leishmaniasis (VL), to investigate the relationship of Leishmania (L.) infantum infection on cortisol production and VL severity. METHODS: L. infantum-infected (n = 42) and uninfected hamsters (n = 30) were followed-up at 30, 120, and 180 days post-infection (dpi). Plasma cortisol was analyzed by radioimmunoassay and cytokines, inducible nitric oxide synthase (iNOS), and arginase by RT-qPCR. RESULTS: All hamsters showed splenomegaly at 180 dpi. Increased parasite burden was associated with higher arginase expression and lower iNOS induction. Cortisol levels were elevated in infected animals in all-time points evaluated. Except for monocytes, all other leucocytes showed a strong negative correlation with cortisol, while transaminases were positively correlated. Immunological markers as interleukin (IL)-6, IL-1ß, IL-10, and transforming growth-factor-ß (TGF-ß) were positively correlated to cortisol production, while interferon-γ (IFN-γ) presented a negative correlation. A network analysis showed cortisol as an important knot linking clinical status and immunological parameters. CONCLUSIONS: These results suggest that L. infantum increases the systemic levels of cortisol, which showed to be associated with hematological, biochemical, and immunological parameters associated to VL severity.

Avances y limitaciones en la investigación sobre factores sociales relativosa la Migración y Chagas / Advances and limitations in research about Migration and Chagas social factors

RESUMEN Este artículo presenta los resultados de una revisión bibliográfica sistemática en relación con las últimas investigaciones académicas sobre enfermedad de Chagas, población migrante y determinantes sociales. Por medio de un análisis de contenido categorial temático, los resultados dan cuenta de una predominante visión biomédica centrada en el control sanitario y en estrategias de educación hacia colectivos con la enfermedad de Chagas por sobre aquella que considera los determinantes sociales como factores que inciden en la transmisión de Chagas en migrantes. Desde una mirada interseccional, el artículo propone complejizar la forma de comprender el Chagas, aunando una perspectiva multidimensional y una aproximación transdisciplinar, que considere distintos ejes y factores de desigualdad que pueden incidir en las vivencias de las personas con Chagas, pero además que plantee críticamente los discursos y prácticas del ámbito de la salud.

ABSTRACT This article presents the results of a systematic bibliographic review in relation to the latest academic research on Chagas disease, the migrant population, and social determinants. By means of an analysis of thematic categorical content, the results reveal a predominant biomedical vision focused on health control and educational strategies for groups with Chagas disease over that which considers social determinants as factors that affect the Chagas transmission in migrants. From an intersectional perspective, the article proposes to make the way of understanding Chagas more complex, combining a multidimensional perspective and a transdisciplinary approach, which considers different axes and inequality factors that can influence the experiences of people with Chagas, but also critically considers discourses and practices in the field of health.

A Cytokine Network Balance Influences the Fate of Leishmania (Viannia) braziliensis Infection in a Cutaneous Leishmaniasis Hamster Model.

The golden hamster is a suitable model for studying cutaneous leishmaniasis (CL) due to Leishmania (Viannia) braziliensis. Immunopathological mechanisms are well established in the L. (L.) major-mouse model, in which IL-4 instructs a Th2 response towards progressive infection. In the present study, we evaluated the natural history of L. braziliensis infection from its first stages up to lesion establishment, with the aim of identifying immunological parameters associated with the disease outcome and parasitism fate. To this end, hamsters infected with 104, 105, or 106 promastigotes were monitored during the first hours (4h, 24h), early (15 days, 30 days) and late (50 days) post-infection (pi) phases. Cytokines, iNOS and arginase gene expression were quantified in the established lesions by reverse transcription-quantitative PCR. Compared to the 105 or 106 groups, 104 animals presented lower lesions sizes, less tissue damage, and lower IgG levels. Basal gene expression in normal skin was high for TGF-ß, and intermediary for TNF, IL-6, and IL-4. At 4hpi, no cytokine induction was observed in the 104 group, while an upregulation of IL-6, IL-10, and IL-4 was observed in the 106 group. At 15dpi, lesion appearance was accompanied by an increased expression of all assessed cytokines, markedly in the 105 and 106 groups. Upregulation of all investigated cytokines was observed in the late phase, although less expressive in the 104 group. IFN-γ was the depending variable influencing tissue damage, while IL-6 was associated to parasite load. The network correlating gene expression and clinical and laboratorial parameters indicated inoculum-independent associations at 15 and 30dpi. A strong positive network correlation was observed in the 104 group, but not in the 105 or 106 groups. In conclusion, IL-4, IL-6, IL-10, and TGF-ß are linked o L. braziliensis progression. However, a balanced cytokine network is the key for an immune response able to reduce the ongoing infection and reduce pathological damage.

Chagas and health promotion: dialogue inspired by the Curitiba Statement.

With the objective of providing an insightful analysis of Chagas disease in the world, the authors share their collective reflections about the current situation of this public health problem in: rural environments of Latin America; urban environments of endemic and non-endemic areas everywhere; and, at a global level. A perspective based on the 'Democracy and Health Promotion' axis allowed the development of an innovative update about Chagas disease as a model of a complex socio-environmental health problem, with a key set of elements that goes beyond biomedical aspects. The authors created a dialogue between the fundamental elements of the Curitiba Statement on Health Promotion and Equity and crucial aspects of a reflection on the reality of Chagas disease today that at the same time challenges the different actors involved. With that reference, the call to promote a 'critical analysis of viabilities and opportunities for action, considering the potentialities and barriers imposed by the complexity of social movements in the present context of recedes and the loss of rights' was emphasized repeatedly. Finally, on the occasion of the recent creation of the Technical Group on Information, Education and Communication to control Chagas disease, WHO Department of Control of Neglected Tropical Diseases, the authors share reflections to propose an inclusive and transformative approach of health promotion-what we hope is a new horizon for people affected, directly and indirectly, by Chagas disease.

Insulin Induces Relaxation and Decreases Hydrogen Peroxide-Induced Vasoconstriction in Human Placental Vascular Bed in a Mechanism Mediated by Calcium-Activated Potassium Channels and L-Arginine/Nitric Oxide Pathways.

HIGHLIGHTS Short-term incubation with insulin increases the L-arginine transport in HUVECs.Short-term incubation with insulin increases the NO synthesis in HUVECs.Insulin induces relaxation in human placental vascular bed.Insulin attenuates the constriction induced by hydrogen peroxide in human placenta.The relaxation induced by insulin is dependent on BKCa channels activity in human placenta. Insulin induces relaxation in umbilical veins, increasing the expression of human amino acid transporter 1 (hCAT-1) and nitric oxide synthesis (NO) in human umbilical vein endothelial cells (HUVECs). Short-term effects of insulin on vasculature have been reported in healthy subjects and cell cultures; however, its mechanisms remain unknown. The aim of this study was to characterize the effect of acute incubation with insulin on the regulation of vascular tone of placental vasculature. HUVECs and chorionic vein rings were isolated from normal pregnancies. The effect of insulin on NO synthesis, L-arginine transport, and hCAT-1 abundance was measured in HUVECs. Isometric tension induced by U46619 (thromboxane A2 analog) or hydrogen peroxide (H2O2) were measured in vessels previously incubated 30 min with insulin and/or the following pharmacological inhibitors: tetraethylammonium (KCa channels), iberiotoxin (BKCa channels), genistein (tyrosine kinases), and wortmannin (phosphatidylinositol 3-kinase). Insulin increases L-arginine transport and NO synthesis in HUVECs. In the placenta, this hormone caused relaxation of the chorionic vein, and reduced perfusion pressure in placental cotyledons. In vessels pre-incubated with insulin, the constriction evoked by H2O2 and U46619 was attenuated and the effect on H2O2-induced constriction was blocked with tetraethylammonium and iberiotoxin, but not with genistein, or wortmannin. Insulin rapidly dilates the placental vasculature through a mechanism involving activity of BKCa channels and L-arginine/NO pathway in endothelial cells. This phenomenon is related to quick increases of hCAT-1 abundance and higher capacity of endothelial cells to take up L-arginine and generate NO.

Development of real-time PCR assays for evaluation of immune response and parasite load in golden hamster (Mesocricetus auratus) infected by Leishmania (Viannia) braziliensis.

BACKGROUND: Cutaneous leishmaniasis (CL) is a neglected disease with a broad spectrum of clinical manifestations, ranging from small cutaneous nodules to severe mucosal tissue destruction. Leishmania (Viannia) braziliensis is the main species attributed to CL in the Americas. However, studies of experimental infection are limited in the murine model due to the self-resolutive pattern of the disease. Previously, our group demonstrated that the hamster model reproduces many of the clinical and histopathological features observed in humans. Herein, we standardized a RT-qPCR gene expression assay to evaluate a panel of immunological markers and a qPCR assay in order to quantify with high sensitivity and reproducibility the parasite load in skin lesions. METHODS: Hamsters were intradermally infected in the footpad with 10(5) promastigotes of L. (V.) braziliensis and 110 days post-infection skin lesions and popliteal lymph nodes were removed for RNA and DNA extraction, both from the same tissue fragment. Gene expression of IFN-É£, IL-10, TGF-ß TNF, IL-4, IL-6, iNOS and arginase were measured using non-infected animal tissue as a calibrator. Parasite load was quantified from DNA extracted from lesions by qPCR targeting Leishmania kDNA and normalized by hamster GAPDH, using a SYBR Green-based absolute quantification methodology. RESULTS: A relative quantification RT-qPCR assay was standardized for the evaluation of mRNA levels from skin and lymph node samples of golden hamsters, with PCR efficiencies ranging from 92.3 to 116.4 %. In uninfected animals, higher basal mRNA levels in lymph nodes were observed for IFN-É£, TGF-ß, TNF and IL-4 (111.4 ± 92.2; 5.6 ± 1.2; 5.3 ± 1.7; and 60.3 ± 26.8, respectively) in comparison to skin. In golden hamsters infected with L. (V.) braziliensis, an increase in the expression of all immunological markers evaluated was observed, ranging from 2.7 ± 0.2 for TGF-ß to 1018.5 ± 809.0 for iNOS in skin lesions, and 2.4 ± 1.6 for TGF-ß to 600.2 ± 666.4 for iNOS in popliteal lymph nodes. Interestingly, significantly higher levels of IFN-É£, TNF and IL-10 mRNA were observed in skin in comparison to lymph nodes, while a lower significant level of arginase mRNA was observed in skin. In parallel, parasite loads were quantified by qPCR from the skin lesions of infected animals, ranging from 27.0 to 6647.0, with a median of 553.4 (416.7-1504.0) parasites/mg skin equivalents, whereas lesion size varied from 0.3 to 3.1 mm. Despite the tendency of larger lesions to present higher parasite load, the correlation observed was not statistically significant. CONCLUSIONS: In this study, we describe for the first time a sensitive, reproducible and cheaper molecular assay to quantify from the same tissue fragment the gene expression of immunological markers and the parasite load in skin lesions, observing a mixed profile of immune response in the hamster model infected by L. (V.) braziliensis.

Que no tengan miedo de nosotros:el Chagas según los propios protagonistas / Não tenham medo de nós: a doença de Chagas segundo os protagonistas / Do not be afraid of us: Chagas disease as explained by people affected by it

El artículo da cuenta de un estudio internacional realizado entre octubre de 2011 y enero de 2012, como fundamento para el diseño y elaboración de un material audiovisual (spot) con el objeto de sensibilizar y visibilizar la problemática del Chagas. La investigación, de carácter cualitativo, recogió los datos de 38 encuestas, respondidas por personas afectadas y especialistas en la temática. La información para cada grupo se ordenó según aspectos que las personas asociaban con la palabra Chagas, y dificultades, retos, desafíos y logros vinculados. Para cada punto se presenta un análisis de las respuestas, relatos y anécdotas relacionadas. Las conclusiones refuerzan la necesidad de conocer y dar a conocer las dificultades que viven las personas afectadas por el Chagas, considerando que se trata de una realidad que tiene diversas manifestaciones dependiendo del contexto...

O artigo apresenta um estudo internacional realizado entre outubro de 2011 e janeiro de 2012, no qual se baseou o desenho e elaboração de um vídeo (spot) que tinha como objetivo a sensibilização e promoção da visibilidade da problemática vinculada à doença de Chagas. A pesquisa, de caráter qualitativo, analisou a informação recolhida por meio de 38 questionários respondidos por pessoas afetadas e especialistas sobre a doença. A informação, para cada um dos dois grupos, foi classificada de acordo com os aspectos que as pessoas associavam com a palavra Chagas, e as dificuldades, adversidades, desafios e conquistas vinculadas com a doença. Para cada um dos referidos aspectos, apresenta-se uma análise das respostas, relatos e anedotas. As conclusões reforçam a necessidade de se conhecer e divulgar as dificuldades vividas pelas pessoas afetadas pela doença de Chagas, tendo em mente que se trata de uma realidade que se manifesta de forma diversa dependendo do contexto...

This paper presents an international study that was conducted between October 2011 and January 2012, in which a video (spot) to boost awareness and raise the profile of Chagas disease issues was designed and developed. This study was of qualitative nature and analyzed information that was gathered from 38 questionnaires that had been answered by individuals affected by the disease and by specialists on this disease. The information from each group was classified according to factors that they associated with the word Chagas, along with the difficulties, adversities, challenges, objectives and achievements relating to the disease. The responses, reports and anecdotes relating to each of these factors were analyzed. The conclusions emphasize the need to know and make known the difficulties that people affected by Chagas disease experience, bearing in mind that the realities are manifested differently depending on the context...

Intranasal vaccination with leishmanial antigens protects golden hamsters (Mesocricetus auratus) against Leishmania (Viannia) Braziliensis infection.

BACKGROUND: Previous results have shown that oral and intranasal administration of particulate Leishmania (Leishmania) amazonensis antigens (LaAg) partially protects mice against L. amazonensis infection. However, vaccination studies on species of the subgenus Viannia, the main causative agent of cutaneous and mucosal leishmaniasis in the Americas, have been hampered by the lack of easy-to-handle bio-models that accurately mimic the human disease. Recently, we demonstrated that the golden hamster is an appropriate model for studying the immunopathogenesis of cutaneous leishmaniasis caused by L. (Viannia) braziliensis. Using the golden hamster model, our current study investigated whether the protective effect of intranasal immunisation with LaAg can be extended to L. braziliensis infection. METHODOLOGY/PRINCIPAL FINDINGS: Golden hamsters vaccinated with either two intranasal (IN) doses of LaAg (10 µg) or two intramuscular doses of LaAg (20 µg) were challenged 2 weeks post-vaccination with L. braziliensis. The results showed that IN immunisation with LaAg significantly reduced lesion growth and parasitic load as well as serum IgG and IgG2 levels. At the experimental endpoint on day 114 post-infection, IN-immunised hamsters that were considered protected expressed IFN-γ and IL10 mRNA levels that returned to uninfected skin levels. In contrast to the nasal route, intramuscular (IM) immunisation failed to provide protection. CONCLUSIONS/SIGNIFICANCE: These results demonstrate for the first time that the nasal route of immunisation can induce cross protection against L. braziliensis infection.

Análise molecular da resposta imune no modelo hamster dourado e avaliação da eficácia da vacina LACK DNA por via intranasal contra infecção por Leishmania (Viannia) braziliensis / Molecular analysis of the immune response in the golden hamster model and evaluating the effectiveness of LACK DNA vaccine intranasally against infection by Leishmania (V. ) braziliensis

Estudos anteriores no modelo murino demonstraram a possibilidade deindução de proteção através da imunização por via mucosa, tanto com antígenosbrutos (lisado total de promastigotas de Leishmania amazonensis - LaAg) comoatravés de vacina de DNA (DNA plasmideal com o gene que codifica a proteínaLACK - LACK DNA), contra a leishmaniose cutânea (LC) causada por L.amazonensis, e a leishmaniose visceral causada por L. infantum. No entanto,estudos de vacinação contra as espécies do subgênero Viannia, principaisresponsáveis pela LC nas Américas, são dificultados devido à falta de modelosexperimentais de fácil manuseio que reproduzam a doença humana. Recentementefoi demonstrado pelo nosso grupo que o hamster dourado é um modelo adequadopara o estudo da imunopatogênese da leishmaniose cutânea causada por L. (V.)braziliensis e que o antígeno LaAg administrado por via intranasal induziu proteçãocontra a infecção por L. (V.) braziliensis no modelo. Entretanto, as abordagensimunológicas e moleculares para os estudos no modelo hamster são limitadas pelapouca disponibilidade de insumos comerciais disponíveis. Nesse trabalho,padronizamos um ensaio por RT-qPCR para avaliação de marcadores molecularesem pele de hamsters infectados por L. braziliensis, pela expressão gênica de IFN-gama,TGF-beta, TNF, IL-10, IL-4, IL-6, iNOS e arginase, e investigamos o efeito protetor daimunização intranasal com a vacina gênica LACK DNA, administrada em protocolosprime-boost homólogo (50mig/dose) e heterólogo (LACK DNA-50mig / LaAg-10mig) nainfecção por L. braziliensis...

Previous studies in murine models demonstrated the possibility to induceprotection by mucosal immunization with crude antigens (total lysate of Leishmaniaamazonensis promastigotes - LaAg) as well as through DNA vaccine (plasmid DNAwith the gene encoding LACK protein - LACK DNA) against cutaneous leishmaniasis(CL) caused by L. amazonensis and visceral leishmaniasis caused by L. infantum.However, vaccination studies against Viannia subgenus (the main cause for CL inAmericas) are hampered due to the lack of experimental models which are easilyexecuted to mimic this disease as it occurs in humans. Recently, it was demonstratedby our group that the golden hamster is an appropriate model to studyimmunopathological aspects of cutaneous leishmaniasis caused by L. (V.)braziliensis. Furthermore, it was also demonstrated that LaAg antigen administeredintranasally induces protection against L. (V.) braziliensis infection in the model.However, immunological and molecular approaches for studies in hamster modelsare limited by the low availability of commercial products. In this study, westandardized an assay by RT-qPCR for assessment of molecular markers in the skinof hamsters infected by L. braziliensis, through the relative gene expressionquantification of IFN-gama, TGF-beta, TNF, IL-10, IL-4, IL-6, iNOS and arginase, and theprotective effect of intranasal immunization with LACK DNA vaccine (administered inhomologous prime-boost protocol 50 mcg/dose) and heterologous prime-boost(LACK DNA 50 mcg in first dose/LaAg-10mg in second dose), against L. braziliensisinfection. The results demonstrated that immunization with LACK DNA homologousprime boost did not induce protection against L. braziliensis infection in hamstermodel since there was no significant difference in lesion size, in parasite load, andIgG and IgG 2 anti-Leishmania levels on day 110 after infection, compared with thecontrol groups (PBS and DNA)...