Commonalities and differences in injured patient experiences of accessing and receiving quality injury care: a qualitative study in three sub-Saharan African countries.

OBJECTIVES: To understand commonalities and differences in injured patient experiences of accessing and receiving quality injury care across three lower-income and middle-income countries. DESIGN: A qualitative interview study. The interviews were audiorecorded, transcribed and thematically analysed. SETTING: Urban and rural settings in Ghana, South Africa and Rwanda. PARTICIPANTS: 59 patients with musculoskeletal injuries. RESULTS: We found five common barriers and six common facilitators to injured patient experiences of accessing and receiving high-quality injury care. The barriers encompassed issues such as service and treatment availability, transportation challenges, apathetic care, individual financial scarcity and inadequate health insurance coverage, alongside low health literacy and information provision. Facilitators included effective information giving and informed consent practices, access to health insurance, improved health literacy, empathetic and responsive care, comprehensive multidisciplinary management and discharge planning, as well as both informal and formal transportation options including ambulance services. These barriers and facilitators were prevalent and shared across at least two countries but demonstrated intercountry and intracountry (between urbanity and rurality) variation in thematic frequency. CONCLUSION: There are universal factors influencing patient experiences of accessing and receiving care, independent of the context or healthcare system. It is important to recognise and understand these barriers and facilitators to inform policy decisions and develop transferable interventions aimed at enhancing the quality of injury care in sub-Saharan African nations.

Investigating a new approach for magnetic ionic liquids: Dispersive liquid-liquid microextraction coupled to pyrolysis gas-chromatography-mass spectrometry to determine flame retardants in sewage sludge samples.

This study addresses the analysis of emerging contaminants, often using chromatographic techniques coupled to mass spectrometry. However, sample preparation is often required prior to instrumental analysis, and dispersive liquid-liquid microextraction (DLLME) is a viable strategy in this context. DLLME stands out for its ability to reduce sample and solvent volumes. Notably, dispersive liquid-liquid microextraction using magnetic ionic liquids (MILs) has gained relevance due to the incorporation of paramagnetic components in the chemical structure, thereby eliminating the centrifugation step. A pyrolizer was selected in this work to introduce sample onto the GC column, since the MIL is extremely viscous and incompatible with direct introduction through an autosampler. This study is the first to report the use of a DLLME/MIL technique for sample introduction through a pyrolizer in gas chromatography coupled to mass spectrometry (GC-MS). This approach enables the MIL to be compatible with gas chromatography systems, resulting in optimized analytical and instrument performance. The analysis of polybrominated diphenyl ether flame retardants (PBDEs) was focused on the PBDE congeners 28, 47, 99, 100, and 153 in sewage sludge samples. The [P6,6,6,14+]2[MnCl42-] MIL was thoroughly characterized using UV-Vis, Fourier transform infrared spectroscopy (FTIR), and Raman spectroscopy, as well as thermal analysis. In the chromatographic method, a pyrolyzer was used in the sample introduction step (Py-GC-MS), and critical injection settings were optimized using multivariate approaches. Optimized conditions were achieved with a temperature of 220 °C, a pyrolysis time of 0.60 min, and an injection volume of 9.00 µL. DLLME optimization was performed through central compound planning (CCD), and optimized training conditions were achieved with 10.0 mg of MIL, 3.00 µL of acetonitrile (ACN) as dispersive solvent, extraction time of 60 s, and volume of a sample of 8.50 mL. Precision was observed to range from 0.11 % to 12.5 %, with limits of detection (LOD) of 44.4 µg L-1 for PBDE 28, 16.9 µg L-1 for PBDE 47 and PBDE 99, 33.0 µg L-1 for PBDE 100 and 375 µg L-1 for PBDE 153. PBDE 28 was identified and analyzed in the sludge sample at a concentration of 800 µg L-1. The use of MIL in dispersive liquid-liquid microextraction combined with pyrolysis gas chromatography-mass spectrometry enables identification and quantification of PBDEs in sewage sludge samples at concentrations down to the µg L-1 level.

Prevalence of orofacial pain in individuals with mild cognitive impairment or dementia: A systematic review and meta-analysis.

BACKGROUND: This systematic review investigated the prevalence of orofacial pain in patients with mild cognitive impairment (MCI) or dementia. MATERIALS AND METHODS: The search was conducted in five databases (Medline (Ovid), Embase (Ovid), CINAHL, Scopus and LILACS), in three grey literature sources and in included articles' reference lists. Three independent reviewers performed study selection, quality appraisal and data extraction. The risk of bias was assessed with the National Institutes of Health tool. Prevalence was calculated using the random-effects model. Subgroup analysis and meta-regression were used to explore the heterogeneity of results. RESULTS: The database and grey literature search led to 12 246 results, from which nine studies were included; a further four were selected through citation searching. The total sample comprised 6115 patients with dementia and 84 with MCI. All studies had high risk of bias. The overall estimated pooled prevalence of orofacial pain among dementia participants was 19.0% (95% CI, 11.0%-27.0%; I2 , 97.1%, P < .001). Only one study included MCI participants, among which the prevalence of orofacial pain was 20.5%. Subgroup analysis demonstrated that the different sources of diagnosis might explain the heterogeneity. A higher prevalence of orofacial pain was observed in dementia participants aged over 80 years or living in nursing homes. Meta-regression analysis showed a nonlinear relationship between age and the prevalence of orofacial pain. CONCLUSIONS: The pooled data from the primary studies revealed that 2 out of 10 patients with dementia have orofacial pain. Further research is needed to clarify the magnitude in individuals with MCI.

Treating myofascial pain with dry needling: a systematic review for the best evidence-based practices in low back pain / Tratamento da dor miofascial com agulhamento a seco: uma revisão sistemática para as melhores práticas baseadas em evidências em lombalgia

Abstract Background Myofascial pain syndrome (MPS) is a common source of pain in primary care or pain clinics. There are many different ways to manage and treat MPS, such as physical exercise, trigger points massage, and dry needling. Objective The objective of this overview is to highlight and discuss the evidence-based treatment of myofascial pain by dry needling in patients with low back pain. Methods A systematic review was made based on meta-analysis (MA) and randomized controlled trials (RCTs) related to dry needling treatment for myofascial pain in patients with lumbar pain, published from 2000 to 2023. Results A total of 509 records were identified at first. Seventy were published before 2000, so they were excluded. From the remaining 439 studies, ninety-two were RCTs or MA, of which 86 additional studies were excluded for the following reasons: not related to dry needling treatment (n = 79), not published in English (n = 4), duplicated (n = 1), project protocol (n = 1), and not related to myofascial pain (n = 1). So, this review was based on 4 RCTs and two MA. These studies compared dry needling efficacy to other treatments, such as acupuncture, sham dry needling, laser therapy, physical therapy, local anesthetic injection, ischemic compression, and neuroscience education. Despite outcomes and follow-up period varied between them, they showed that dry needling can decrease post-intervention pain intensity and pain disability. Conclusion Dry needling is an effective procedure for the treatment of myofascial pain in patients with acute and chronic low back pain. Further high-quality studies are needed to clarify the long-term outcomes.

Resumo Antecedentes A síndrome dolorosa miofascial (SDM) é uma fonte comum de dor em centros primários de atenção à saúde ou nas clínicas de dor. Existem muitas formas diferentes de manejar e tratar a SDM, como o exercício físico, a massagem dos pontos de gatilho e o agulhamento a seco. Objetivo O objetivo desta revisão é destacar e discutir o tratamento baseado em evidências da dor miofascial por agulhamento a seco em doentes com dor lombar. Métodos Foi realizada uma revisão sistemática baseada em metanálises (MA) e ensaios clínicos randomizados (RCTs) relacionados ao tratamento da dor miofascial com agulhamento a seco em pacientes com dor lombar, publicados de 2000 a 2023. Resultados Foram identificados, inicialmente, um total de 509 registos. Setenta deles, publicados antes de 2000, foram excluídos. Dos 439 estudos restantes, 92 eram RCTs ou MA, dos quais 86 foram excluídos pelas seguintes razões: não relacionados a tratamento com agulhamento a seco (n = 79), não publicados em inglês (n = 4), duplicados (n = 1), protocolo de projeto (n = 1) e não relacionados com dor miofascial (n = 1). Assim, esta revisão baseou-se em quatro RCTs e duas MA. Esses estudos compararam a eficácia do agulhamento seco com outros tratamentos, tais como acupuntura, agulhamento a seco "sham", terapia com laser, fisioterapia, injeção de anestésico local, compressão isquêmica e educação em neurociências. Apesar de os resultados e o período de seguimento variarem entre os estudos, os estudos demonstram que o agulhamento a seco pode diminuir a intensidade da dor pós-intervenção e a incapacidade relacionada à dor. Conclusão O agulhamento a seco é um procedimento eficaz para o tratamento da dor miofascial em pacientes com dor lombar aguda e crônica. Mais estudos são necessários para esclarecer sua eficácia a longo prazo.

Treating myofascial pain with dry needling: a systematic review for the best evidence-based practices in low back pain.

BACKGROUND: Myofascial pain syndrome (MPS) is a common source of pain in primary care or pain clinics. There are many different ways to manage and treat MPS, such as physical exercise, trigger points massage, and dry needling. OBJECTIVE: The objective of this overview is to highlight and discuss the evidence-based treatment of myofascial pain by dry needling in patients with low back pain. METHODS: A systematic review was made based on meta-analysis (MA) and randomized controlled trials (RCTs) related to dry needling treatment for myofascial pain in patients with lumbar pain, published from 2000 to 2023. RESULTS: A total of 509 records were identified at first. Seventy were published before 2000, so they were excluded. From the remaining 439 studies, ninety-two were RCTs or MA, of which 86 additional studies were excluded for the following reasons: not related to dry needling treatment (n = 79), not published in English (n = 4), duplicated (n = 1), project protocol (n = 1), and not related to myofascial pain (n = 1). So, this review was based on 4 RCTs and two MA. These studies compared dry needling efficacy to other treatments, such as acupuncture, sham dry needling, laser therapy, physical therapy, local anesthetic injection, ischemic compression, and neuroscience education. Despite outcomes and follow-up period varied between them, they showed that dry needling can decrease post-intervention pain intensity and pain disability. CONCLUSION: Dry needling is an effective procedure for the treatment of myofascial pain in patients with acute and chronic low back pain. Further high-quality studies are needed to clarify the long-term outcomes.

ANTECEDENTES: A síndrome dolorosa miofascial (SDM) é uma fonte comum de dor em centros primários de atenção à saúde ou nas clínicas de dor. Existem muitas formas diferentes de manejar e tratar a SDM, como o exercício físico, a massagem dos pontos de gatilho e o agulhamento a seco. OBJETIVO: O objetivo desta revisão é destacar e discutir o tratamento baseado em evidências da dor miofascial por agulhamento a seco em doentes com dor lombar. MéTODOS: Foi realizada uma revisão sistemática baseada em metanálises (MA) e ensaios clínicos randomizados (RCTs) relacionados ao tratamento da dor miofascial com agulhamento a seco em pacientes com dor lombar, publicados de 2000 a 2023. RESULTADOS: Foram identificados, inicialmente, um total de 509 registos. Setenta deles, publicados antes de 2000, foram excluídos. Dos 439 estudos restantes, 92 eram RCTs ou MA, dos quais 86 foram excluídos pelas seguintes razões: não relacionados a tratamento com agulhamento a seco (n = 79), não publicados em inglês (n = 4), duplicados (n = 1), protocolo de projeto (n = 1) e não relacionados com dor miofascial (n = 1). Assim, esta revisão baseou-se em quatro RCTs e duas MA. Esses estudos compararam a eficácia do agulhamento seco com outros tratamentos, tais como acupuntura, agulhamento a seco "sham", terapia com laser, fisioterapia, injeção de anestésico local, compressão isquêmica e educação em neurociências. Apesar de os resultados e o período de seguimento variarem entre os estudos, os estudos demonstram que o agulhamento a seco pode diminuir a intensidade da dor pós-intervenção e a incapacidade relacionada à dor. CONCLUSãO: O agulhamento a seco é um procedimento eficaz para o tratamento da dor miofascial em pacientes com dor lombar aguda e crônica. Mais estudos são necessários para esclarecer sua eficácia a longo prazo.

Chronic Unilateral Headache Related to Scar Neuromas.

Postcraniotomy and posttraumatic headaches can result in scars generating local pain or referred pain following a neuropathic pattern. One hypothesis is that the pain can be caused and maintained by scar neuromas, developed after the nerve injury during the surgical process or trauma. This study reports two patients with chronic unilateral headaches: the first one with a posttraumatic scar in the parietal region and the other with a postsurgical scar in the mastoid region. In both patients, the headache was ipsilateral to the scar, suggesting primary headaches (trigeminal autonomic cephalalgia (TAC), as hemicrania continua and chronic cluster headache). Pharmacological treatment for these conditions failed. Instead, there was complete remission of the headache with anesthetic blockade of scar neuromas (demonstrated by clinical examination in both patients). An active search for traumatic or nontraumatic scars is recommended in all patients with refractory unilateral headaches, and anesthetic blocks for scar neuromas can be effective in treating this pain.

Hereditary thrombocytopenia with platelet sialic acid deficiency and mutations in the GNE genes.

BACKGROUND: The inherited macrothrombocytopenias are rare disorders and the underlying cause can be identified in many cases but in some, this can remain enigmatic. Platelet transfusions are often administered during hemorrhagic events. METHODS: A patient with previously unexplained inherited macrothrombocytopenia with a platelet count between 3-20 × 109 /L is described in which studies were performed using exome sequencing (ES) and platelet flow cytometry. RESULTS: Both the hemoglobin and white cell counts were normal. ES revealed two suspicious variants, one likely pathogenic and one a variant of uncertain significance, in the UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE) gene, and flow cytometry showed diminished expression of surface platelet sialic acid (about 5%) but normal red cell sialic acid. The Thrombopoietin (TPO) level was low, and the patient responded to TPO-mimetic treatment with an increase in the platelet count. CONCLUSION: Two variants in the GNE gene were able to be upgraded to pathogenic with apparently restricted expression to the megakaryocyte lineage. Platelet transfusion may be avoided in these patients with TPO-mimetic treatment.

Social Determinants of Seeking and Reaching Injury Care in South Africa: A Community-Based Qualitative Study.

Background: Timely access to quality injury care saves lives and prevents disabilities. The impact of social determinants of health on the high injury prevalence in South Africa is well documented, however, evidence of their role in accessing injury care is lacking. This study explored the social determinants of seeking and reaching injury care in South Africa. Methods: This was a qualitative study involving rural and urban patients, community members, and healthcare providers in Western Cape, South Africa. Data were obtained through semi-structured interviews and focus group discussions using an interview guide informed by the four-delays framework. Inductive and deductive approaches were used for thematic analysis. Results: A total of 20 individual interviews and 5 focus group discussions were conducted. There were 28 males (individual interviews: 13; focus groups: 15) and 22 females (individual interviews: 7; focus groups: 15), and their mean age was 41 (standard deviation ±15) years. Barriers to seeking and reaching injury care cut across five social determinants of health domains: healthcare access and quality; neighbourhood and environment; social and community context; education; and economic stability. The most prominent social determinants of seeking and reaching injury care were related to healthcare access and quality, including perceived poor healthcare quality, poor attitude of healthcare workers, long waiting time, and ambulance delays. However, there was a strong interconnection between these and neighbourhood and environmental determinants such as safety concerns, high crime rates, gangsterism, lack of public transportation, and social and community factors (presence/absence of social support and alcohol use). Barriers related to education and economic stability were less prevalent. Conclusion: We found a substantial role of neighbourhood, social, and community factors in seeking and reaching injury care. Therefore, efforts aimed at improving access to injury care and outcomes must go beyond addressing healthcare factors to include other social determinants and should involve collaborations with multiple sectors, including the community, the police, the transport department, and alcohol regulation agencies.

Equitable access to quality trauma systems in low-income and middle-income countries: assessing gaps and developing priorities in Ghana, Rwanda and South Africa.

Injuries in low-income and middle-income countries are prevalent and their number is expected to increase. Death and disability after injury can be reduced if people reach healthcare facilities in a timely manner. Knowledge of barriers to access to quality injury care is necessary to intervene to improve outcomes. We combined a four-delay framework with WHO Building Blocks and Institution of Medicine Quality Outcomes Frameworks to describe barriers to trauma care in three countries in sub-Saharan Africa: Ghana, South Africa and Rwanda. We used a parallel convergent mixed-methods research design, integrating the results to enable a holistic analysis of the barriers to access to quality injury care. Data were collected using surveys of patient experiences of injury care, interviews and focus group discussions with patients and community leaders, and a survey of policy-makers and healthcare leaders on the governance context for injury care. We identified 121 barriers across all three countries. Of these, 31 (25.6%) were shared across countries. More than half (18/31, 58%) were predominantly related to delay 3 ('Delays to receiving quality care'). The majority of the barriers were captured using just one of the multiple methods, emphasising the need to use multiple methods to identify all barriers. Given there are many barriers to access to quality care for people who have been injured in Rwanda, Ghana and South Africa, but few of these are shared across countries, solutions to overcome these barriers may also be contextually dependent. This suggests the need for rigorous assessments of contexts using multiple data collection methods before developing interventions to improve access to quality care.

The Role of Dimorphism Regulating Histidine Kinase (Drk1) in the Pathogenic Fungus Paracoccidioides brasiliensis Cell Wall.

Dimorphic fungi of the Paracoccidioides genus are the causative agents of paracoccidioidomycosis (PCM), an endemic disease in Latin America with a high incidence in Brazil. This pathogen presents as infective mycelium at 25 °C in the soil, reverting to its pathogenic form when inhaled by the mammalian host (37 °C). Among these dimorphic fungal species, dimorphism regulating histidine kinase (Drk1) plays an essential role in the morphological transition. These kinases are present in bacteria and fungi but absent in mammalian cells and are important virulence and cellular survival regulators. Hence, the purpose of this study was to investigate the role of PbDrk1 in the cell wall modulation of P. brasiliensis. We observed that PbDrk1 participates in fungal resistance to different cell wall-disturbing agents by reducing viability after treatment with iDrk1. To verify the role of PbDRK1 in cell wall morphogenesis, qPCR results showed that samples previously exposed to iDrk1 presented higher expression levels of several genes related to cell wall modulation. One of them was FKS1, a ß-glucan synthase that showed a 3.6-fold increase. Furthermore, confocal microscopy analysis and flow cytometry showed higher ß-glucan exposure on the cell surface of P. brasiliensis after incubation with iDrk1. Accordingly, through phagocytosis assays, a significantly higher phagocytic index was observed in yeasts treated with iDrk1 than the control group, demonstrating the role of PbDrk1 in cell wall modulation, which then becomes a relevant target to be investigated. In parallel, the immune response profile showed increased levels of proinflammatory cytokines. Finally, our data strongly suggest that PbDrk1 modulates cell wall component expression, among which we can identify ß-glucan. Understanding this signalling pathway may be of great value for identifying targets of antifungal molecular activity since HKs are not present in mammals.

Extracellular Vesicles From Sporothrix brasiliensis Yeast Cells Increases Fungicidal Activity in Macrophages.

Sporotrichosis is a subcutaneous mycosis and is distributed throughout the world, although most cases belong to endemic regions with a warmer climate such as tropical and subtropical areas. The infection occurs mainly by traumatic inoculation of propagules. Similarly, to other organisms, Sporothrix brasiliensis display many biological features that aid in its ability to infect the host, such as extracellular vesicles, bilayered biological structures that provides communication between host cells and between fungi cells themselves. Recently, research on Sporothrix complex have been focused on finding new molecules and components with potential for therapeutic approaches. Here, we study the relationship among EVs and the host's macrophages as well as their role during infection to assess whether these vesicles are helping the fungi or inducing a protective effect on mice during the infection. We found that after cocultivation with different concentrations of purified yeasts EVs from Sb, J774 macrophages displayed an increased fungicidal activity (Phagocytic Index) resulting in lower colony-forming units the more EVs were added, without jeopardizing the viability of the macrophages. Interleukins IL-6, IL-10, and IL-12 were measured during the infection period, showing elevated levels of IL-12 and IL-6 in a dose-dependent manner, but no significant change for IL-10. We also assessed the expression of important molecules in the immune response, such as MHC class II and the immunoglobulin CD86. Both these molecules were overexpressed in Sb yeasts infected mice. Our results indicate that EVs play a protective role during Sporothrix brasiliensis infections.

The role of a potential biomarker in patients with migraine: review and new insights.

Introduction: The search for an ideal biomarker for migraine has persisted for a long time. There is plentiful evidence of potential biomarkers for migraine found in cerebrospinal fluid, blood, and saliva.Areas covered: Herein, the authors highlight and discuss the most promising candidates in the literature. An electronic search was performed for studies published between 2010 and 2020 in MEDLINE, PubMed, and EMBASE, related to potential biomarkers in migraine patients, found in cerebrospinal fluid, saliva, and serum, focusing on biomarkers that can be related to treatment and clinical outcomes.Expert opinion: An ideal biomarker, or a panel of biomarkers, could revolutionize the way we address and propose treatments for this disease. Once severe presentations and phenotypes have been identified using a reliable biomarker, patients could be treated at earlier disease stages with more specific medications. The most important biomarkers with the most significant levels of evidence comprised calcitonin gene-related peptide (CGRP), glutamate, nerve growth factor, some inflammatory (CRP, TNF-α, interleukins) and oxidative stress markers. CGRP was associated with episodic, chronic migraine and response to treatment. Pituitary adenylate cyclase-activating polypeptide is an emerging neuropeptide involved in migraine diagnostics and severity. New genetic and epigenetic biomarkers will be candidates for future research.

Can Allodynia Predict Headache Related to Personal Protective Equipment for the Prevention of COVID-19?

In this complex context of coronavirus disease 2019 (COVID-19), headache medicine has been completely affected by this new reality, with new types of headaches directly or indirectly related to COVID-19 being detected. Personal protective equipment (PPE) was recommended for workers in many professions that did not previously require wearing masks leading to new headaches, or the exacerbation of past headaches, especially among health workers. A 57-year-old female working in a secondary care hospital had a history of migraine twice/month without aura and allodynia symptom checklist (ASC12) scored as 7 before COVID-19 outbreak. She began to work with PPE (surgical masks, face shield and surgical cap) and migraines became daily (bifrontal, pulsatile, with photophobia, nausea, vomiting and of severe intensity, visual analog scale: 7), starting after 1 h of wearing protective equipment and lasted for at least 6 h during the day. There was no adequate response to treatment. The headache frequency retuned to twice/month after the patient stayed home 45 days due to another condition. It is hypothesized here that people with allodynia symptoms when exposed to PPE are more susceptible to the development of new headaches or to the worsening of existing primary headaches. The relationship between previous allodynia determined with the ASC12 questionnaire and new headaches, or past primary headaches that have become worse during the COVID-19 pandemic in workers using PPE, should be better investigated in order to clarify this hypothesis. Cutaneous allodynia could be related with the sensitivity to PPE and headache progression.

Toxic effects in Aphanomyces brasiliensis and zebrafish embryos caused by oomyceticides.

In fish farming, high losses occur during egg incubation and larviculture due to diseases caused by oomycetes. This study aimed to identify the oomycete species that occurs in zebrafish Danio rerio eggs and to evaluate the oomyceticidal effect of copper sulfate, bronopol and methylene blue on the mycelial growth of this organism, as well as to determine the lethal and sublethal toxicity of these compounds in embryos of D. rerio. The isolates were cultivated in yeast-starch medium to determine the concentration necessary to inhibit mycelial growth by 50% (IC50) and 100% (minimum oomyceticidal concentration) after a 96 h exposure to these compounds. In addition, tests with D. rerio eggs were conducted to determine the lethal concentrations for 50% of the organisms (96h-LC50), and the concentrations that inhibited 17% of the eggs hatching (96h-IC17) after 96 h. The organism responsible for the mortality of D. rerio eggs was classified by classical and molecular methods as Aphanomyces brasiliensis, representing the first report of this pathogen in zebrafish eggs. IC50 values could be determined for both bronopol and copper sulfate, whereas methylene blue had low effectiveness against the oomycete. Copper showed high toxicity to D. rerio eggs at low concentrations, while methylene blue and bronopol toxicity was low and similar to each other. The use of bronopol at a concentration of 4.8 mg l-1 for the treatment of zebrafish eggs allows controlling the pathology without causing deleterious effects to the treated organisms.

Prevalencia de cardiopatías congénitas diagnosticadas o tratadas por cateterismo cardíaco en pediatría / Prevalence of congenital heart disease diagnosed or treated by cardiac catheterism in pediatrics

Resumen Objetivo: Determinar las cardiopatías congénitas más diagnosticadas a través de cateterismo cardíaco en una población pediátrica de la costa norte colombiana durante el período de 2007 a 2016. Materiales y métodos: Estudio descriptivo, retrospectivo y multicéntrico, cuya población corresponde al total de pacientes de 0 a 18 años en quienes se realizó cateterismo cardíaco diagnóstico o terapéutico, o ambos, en diferentes ciudades de la costa norte colombiana en el período de 2007 a 2016. Para la tabulación de la información se utilizó el programa Epi Info 7.0. La muestra se integró con 4,245 pacientes. Resultados: El género predominante fue el femenino (53.5%), con una media de edad de 3.9 ± 4.9 años y una mayor prevalencia de 1 a 11 meses de vida (40.6%). Conclusiones: La comunicación interventricular fue la cardiopatía congénita más diagnosticada mediante cateterismo cardíaco (29.2%), seguida por el conducto arterioso persistente (23.1%), comunicación interauricular (11.7%), tetralogía de Fallot (6.8%), estenosis pulmonar (6.7%), transposición de grandes vasos (3.5%), atresia pulmonar con comunicación interventricular (2.5%), canal AV total (2.4%), doble salida ventricular derecha (2.4%), coartación de aorta (1%), insuficiencia mitral (0.98%), atresia tricuspídea (0.96%), atresia pulmonar sin comunicación interventricular (0.73%), doble salida ventricular derecha (0.5%) y otras malformaciones (4.2%).

Abstract Objective: To determine the most frequent congenital heart diseases diagnosed by cardiac catheterization in the pediatric population of the north coast of Colombia, during the period 2007 to 2016. Materials and methods: Descriptive, retrospective and multicentric study; the population corresponds to the total number of patients between 0 and 18 years of age in which diagnostic and therapeutic cardiac catheterization was performed in different cities of the Colombian north coast in the period 2007 to 2016. Epi Info 7.0 software was used for tabulation of information. Total sample was conformed of 4.245 patients. Results: The sex mostly involved was the female with 53.5%, a mean age of 3.9 ± 4.9 years, with a higher prevalence between 1 and 11 months of life with 40.6%. Conclusions: The ventricular septal defect was the most frequent congenital heart disease diagnosed by cardiac catheterization with 29.2%, followed in frequency by the persistent conducto with 23.1%, the atrial septal defect 11.7%, tetralogy of Fallot with 6.8%, pulmonary stenosis with 6.7%, transposition of large vessels 3.5%, pulmonary atresia with ventricular septal defect 2.5%, total AV channel 2.4%, double right ventricular outlet 2.4%, coarctation of aorta on 1 %, mitral insufficiency 0.98%, tricuspid atresia 0.96%, pulmonary atresia without ventricular septal defect 0.73%, double right ventricular outlet 0.5% and other malformations 4.2%.

Extracellular Vesicles from Sporothrix Yeast Cells.

Sporotrichosis is an emerging deep mycosis and a public health concern in Brazil. This mycosis is caused by the traumatic inoculation of several species of Sporothrix from nature. However, when cats transmit the disease to humans as zoonotic transmission, severe extracutaneous manifestations are observed. Therefore, effective control of the disease requires the engagement of host receptors by pathogen-derived molecules to stimulate the immune response. In this context, extracellular vesicles from Sporothrix sp contribute to intracellular communication with host cells. In addition, however, extracellular vesicles may contribute to the spread of this fungus via delivering molecules such as proteins, nucleic acids, and lipids. Thus, understanding mechanisms behind extracellular vesicles related to Sporothrix may provide us with a way to understand and identify its capacity to manipulate the host immune system and spread the infection.

The role of dimorphism regulating histidine kinase (Drk1) in the pathogenic fungus Paracoccidioides brasiliensis cell wall

Dimorphic fungi of the Paracoccidioides genus are the causative agents of paracoccidioidomycosis (PCM), an endemic disease in Latin America with a high incidence in Brazil. This pathogen presents as infective mycelium at 25 °C in the soil, reverting to its pathogenic form when inhaled by the mammalian host (37 °C). Among these dimorphic fungal species, dimorphism regulating histidine kinase (Drk1) plays an essential role in the morphological transition. These kinases are present in bacteria and fungi but absent in mammalian cells and are important virulence and cellular survival regulators. Hence, the purpose of this study was to investigate the role of PbDrk1 in the cell wall modulation of P. brasiliensis. We observed that PbDrk1 participates in fungal resistance to different cell wall-disturbing agents by reducing viability after treatment with iDrk1. To verify the role of PbDRK1 in cell wall morphogenesis, qPCR results showed that samples previously exposed to iDrk1 presented higher expression levels of several genes related to cell wall modulation. One of them was FKS1, a β-glucan synthase that showed a 3.6-fold increase. Furthermore, confocal microscopy analysis and flow cytometry showed higher β-glucan exposure on the cell surface of P. brasiliensis after incubation with iDrk1. Accordingly, through phagocytosis assays, a significantly higher phagocytic index was observed in yeasts treated with iDrk1 than the control group, demonstrating the role of PbDrk1 in cell wall modulation, which then becomes a relevant target to be investigated. In parallel, the immune response profile showed increased levels of proinflammatory cytokines. Finally, our data strongly suggest that PbDrk1 modulates cell wall component expression, among which we can identify β-glucan. Understanding this signalling pathway may be of great value for identifying targets of antifungal molecular activity since HKs are not present in mammals.

Fonsecaeapedrosoi Conidia and Hyphae Activate Neutrophils Distinctly: Requirement of TLR-2 and TLR-4 in Neutrophil Effector Functions.

Chromoblastomycosis is a chronic and progressive subcutaneous mycosis caused mainly by the fungus Fonsecaea pedrosoi. The infection is characterized by erythematous papules and histological sections demonstrating an external layer of fibrous tissue and an internal layer of thick granulomatous inflammatory tissue containing mainly macrophages and neutrophils. Several groups are studying the roles of the innate and adaptive immune systems in F. pedrosoi infection; however, few studies have focused on the role of neutrophils in this infection. In the current study, we verify the importance of murine neutrophils in the killing of F. pedrosoi conidia and hyphae. We demonstrate that phagocytosis and reactive oxygen species during infection with conidia are TLR-2- and TLR-4-dependent and are essential for conidial killing. Meanwhile, hyphal killing occurs by NET formation in a TLR-2-, TLR-4-, and ROS-independent manner. In vivo experiments show that TLR-2 and TLR-4 are also important in chromoblastomycosis infection. TLR-2KO and TLR-4KO animals had lower levels of CCL3 and CXCL1 chemokines and impaired neutrophil migration to the infected site. These animals also had higher fungal loads during infection with F. pedrosoi conidia, confirming that TLR-2 and TLR-4 are essential receptors for F. pedrosoi recognition and immune system activation. Therefore, this study demonstrates for the first time that neutrophil activation during F. pedrosoi is conidial or hyphal-specific with TLR-2 and TLR-4 being essential during conidial infection but unnecessary for hyphal killing by neutrophils.

Intracellular PRRs Activation in Targeting the Immune Response Against Fungal Infections.

The immune response against fungal infections is complex and exhibits several factors involving innate elements that participate in the interaction with the fungus. The innate immune system developed pattern recognition receptors that recognize different pathogen-associated molecular patterns present both on the surface of the fungi cell wall and on their genetic material. These receptors have the function of activating the innate immune response and regulating a subsequent adaptive immune response. Among pattern recognition receptors, the family of Toll-like receptors and C-type lectin receptors are the best described and characterized, they act directly in the recognition of pathogen-associated molecular patterns expressed on the wall of the fungus and consequently in directing the immune response. In recent years, the role of intracellular pattern recognition receptors (TLR3, TLR7, TLR8, and TLR9) has become increasingly important in the pathophysiology of some mycoses, as paracoccidioidomycosis, cryptococcosis, aspergillosis, and candidiasis. The recognition of nucleic acids performed by these receptors can be essential for the control of some fungal infections, as they can be harmful to others. Therefore, this review focuses on highlighting the role played by intracellular pattern recognition receptors both in controlling the infection and in the host's susceptibility against the main fungi of medical relevance.