Design and optimization of an improved qPCR assay for the detection of Histoplasma capsulatum.

Background: This study aimed at improving a real-time polymerase-chain-reaction (qPCR) assay for the detection of Histoplasma capsulatum, a fungal pathogen that can cause severe respiratory infections in humans, in clinical and soil samples. Methods: Primer and probes were in-silico designed, in-silico and in-vitro evaluated including clinical biopsy materials and finally subjected to a real-world application with collected soil samples. Results: Applying the qPCR assay with liver and lung biopsies from 71 patients each, including 59 patients infected with human immunodeficiency virus (HIV), as well as with Sabouraud (SAB) agar culture as the diagnostic reference standard, diagnostic accuracy of the qPCR assay of 100% (5/5) sensitivity and 96% (63/66) specificity for liver samples and 100% (4/4) sensitivity and 94% (63/67) specificity for the lung samples was recorded. When applying the assay with soil samples from caves near of Presidente Figueiredo city, Amazonas, Brazil, one sample from the Maroaga cave was confirmed as positive. Conclusions: The improved qPCR assessed in this study was successful in detecting H. capsulatum with high efficiency and accuracy in in-vitro evaluation, including the identification of the target pathogen in both clinical and environmental samples.

Searching for new antifungals for the treatment of cryptococcosis.

There is a consensus that the antifungal repertoire for the treatment of cryptococcal infections is limited. Standard treatment involves the administration of an antifungal drug derived from natural sources (i.e., amphotericin B) and two other drugs developed synthetically (i.e., flucytosine and fluconazole). Despite treatment, the mortality rates associated with fungal cryptococcosis are high. Amphotericin B and flucytosine are toxic, require intravenous administration, and are usually unavailable in low-income countries because of their high cost. However, fluconazole is cost-effective, widely available, and harmless with regard to its side effects. However, fluconazole is a fungistatic agent that has contributed considerably to the increase in fungal resistance and frequent relapses in patients with cryptococcal meningitis. Therefore, there is an unquestionable need to identify new alternatives or adjuvants to conventional drugs for the treatment of cryptococcosis. A potential antifungal agent should be able to kill cryptococci and "bypass" the virulence mechanism of the yeast. Furthermore, it should have fungicidal action, low toxicity, high selectivity, easily penetrate the central nervous system, and widely available. In this review, we describe cryptococcosis, its conventional therapy, and failures arising from the use of drugs traditionally considered to be the reference standard. Additionally, we present the approaches used for the discovery of new drugs to counteract cryptococcosis, ranging from the conventional screening of natural products to the inclusion of structural modifications to optimize anticryptococcal activity, as well as drug repositioning and combined therapies.

Constrictive pericarditis heart failure in a patient with atrial fibrillation: A diagnostic challenge.

Constrictive pericarditis is an infrequent cause of heart failure. Diagnosis is challenging and requires a high level of suspicion. Subtle echocardiographic findings, as the pericardial bounce, could be the clue to diagnosis.

Magnetic Resonance Imaging in the Study of Cardiac Masses: A Case Series.

Cardiac masses are currently studied using multimodality imaging. For diagnosis, different imaging techniques that can provide complementary information are used. Cardiac magnetic resonance imaging (MRI) has become a fundamental tool for this type of pathology owing to its ability to provide tissue characterization, spatial accuracy, and the anatomic relationships of the different structures. This study presents a series of four clinical cases with an initial diagnosis of a cardiac mass. All cases were evaluated at a single center, and patients were aged 57 to 72 years. An etiological study was conducted on all patients using different imaging techniques, including MRI. This study describes the diagnostic and therapeutic procedures of the four cases, which included two intracardiac metastases and two benign tumors. Cardiac MRI was decisive in the diagnostic process, determining the clinical decision-making in all four cases. Cardiac MRI has emerged as a pivotal technique in the diagnosis of cardiac masses. It can provide a highly accurate histological diagnosis without the need for invasive techniques.

Searching for new antifungals for the treatment of cryptococcosis

ABSTRACT There is a consensus that the antifungal repertoire for the treatment of cryptococcal infections is limited. Standard treatment involves the administration of an antifungal drug derived from natural sources (i.e., amphotericin B) and two other drugs developed synthetically (i.e., flucytosine and fluconazole). Despite treatment, the mortality rates associated with fungal cryptococcosis are high. Amphotericin B and flucytosine are toxic, require intravenous administration, and are usually unavailable in low-income countries because of their high cost. However, fluconazole is cost-effective, widely available, and harmless with regard to its side effects. However, fluconazole is a fungistatic agent that has contributed considerably to the increase in fungal resistance and frequent relapses in patients with cryptococcal meningitis. Therefore, there is an unquestionable need to identify new alternatives or adjuvants to conventional drugs for the treatment of cryptococcosis. A potential antifungal agent should be able to kill cryptococci and "bypass" the virulence mechanism of the yeast. Furthermore, it should have fungicidal action, low toxicity, high selectivity, easily penetrate the central nervous system, and widely available. In this review, we describe cryptococcosis, its conventional therapy, and failures arising from the use of drugs traditionally considered to be the reference standard. Additionally, we present the approaches used for the discovery of new drugs to counteract cryptococcosis, ranging from the conventional screening of natural products to the inclusion of structural modifications to optimize anticryptococcal activity, as well as drug repositioning and combined therapies.

Stroke symptoms, risk factors awareness and personal decision making in Chile. A national survey.

BACKGROUND: Knowledge about stroke symptoms, correct decision in front of a stroke case and recognition of stroke risk factors are crucial to fight against stroke burden. We aimed to assess the stroke awareness among a sample of the Chilean population. METHODS: A closed-ended questions structured survey was applied in November 2019 using a computer-assisted telephone interviewing system. Probabilistic sample, random selection and stratification for region was used. Multivariate logistic regression model was used to estimate the association between participants' characteristics and responses. RESULTS: Of 706 participants, only 74.4% (95% CI 70.9-77.5) recognized at least one typical stroke symptom. Most (586, 82.4% 95% CI 75.2-89.7) chose to contact the emergency ambulance or directly go to the emergency department in case of a stroke symptom and recognized at least one risk factor (692, 97.9% CI 96.7-98.8). In multivariable analysis, sociodemographic characteristics associated to a worse recognition of at least one stroke symptom were being men (OR 0.67, 95% CI 0.47-0.96), being 55 years old or older (OR 0.59 95% CI 0.37-0.93) and from the lowest socioeconomic level (SES) (OR 0.33 95% CI 0.16-0.67). Female sex was associated with lower stroke risk factor knowledge (OR 0.64 95% IC 0.47-0.87). Participants who recognized at least one typical stroke symptom and would promptly seek care at an emergency department differed significantly between SES (p=0.001) and age groups (p=0.035). CONCLUSIONS: We found insufficient knowledge about stroke symptoms and best decisions making in the Chilean population. We describe gaps that can be targeted in future stroke awareness campaigns. There is a need to strengthen tailored stroke education particularly for underserved populations.

Stroke care and collaborative academic research in Latin America.

OBJECTIVE: A narrative overview of regional academic research collaborations to address the increasing burden and gaps in care for patients at risk of, and who suffer from, stroke in Latin America (LA). MATERIALS AND METHODS: A summary of experiences and knowledge of the local situation is presented. No systematic literature review was performed. RESULTS: The rapidly increasing burden of stroke poses immense challenges in LA, where prevention and manage-ment strategies are highly uneven and inadequate. Clinical research is increasing through various academic consortia and networks formed to overcome structural, funding and skill barriers. However, strengthening the ability to generate, analyze and interpret randomized evidence is central to further develop effective therapies and healthcare systems in LA. CONCLUSIONS: Regional networks foster the conduct of multicenter studies -particularly randomized controlled trials-, even in resource-poor regions. They also contribute to the external validity of international studies and strengthen systems of care, clinical skills, critical thinking, and international knowledge exchange.

Infectious Endocarditis Caused by Pseudomona aeruginosa on Bicuspid Aortic Valve.

We report the case of a 53-year-old man with psoriatic arthritis, suffering from a malignant and recidivant myoepithelioma in his right axilla and arm, and undergoing two surgeries, with the last one being performed a month prior to actual admission. After the last surgery, he was admitted to hospital with fever without a source. After physical examination, laboratory tests, blood cultures and transthoracic and transesophageal echocardiography, he was diagnosed with infectious endocarditis (IE) on a bicuspid aortic valve (BAV) caused by Pseudomona aeruginosa (PA). Antibiogram-guided antibiotic therapy with meropenem and tobramicin was initiated. However, in the presence of repetitive spleen infarctions and a large vegetation, 12 days after admission, a bioprosthesis aortic valve implantation was performed. The postsurgical evolution was favorable and prolonged antibiotic course with meropenem and tobramicin was completed. The pathological anatomy and the native valve cultured confirmed an IE caused by PA. Gram-negative non-HACEK IE cases are infrequent, accounting for 1.8% of the total IE cases. PA is the second most frequent bacillus in this group, causing endocarditis more prevalently when associated with healthcare procedures rather than injectable drug use. No prior case study has identified IE caused by PA related to a BAV in the last years.

A Preliminary Study on the Effect of the Instant Controlled Pressure Drop Technology (DIC) on Drying and Rehydration Kinetics of Maize Kernels (Zea mays L.).

Maize is one of the three worldwide cereal crops with the most outstanding production; however, its postharvest losses range from 2 to 40% due to inadequate harvesting, drying, and storage technologies. This study focuses on the Instant Controlled Pressure Drop technology (DIC) effect on maize kernels' drying and rehydration kinetics. In total, 19 different DIC treatments were carried out on maize kernels (~25% d.b.). The DIC parameters studied were steam pressure (0.1 to 0.4 MPa) and treatment time (10 to 90 s). After DIC treatment, drying kinetics were carried out by Convective Air Drying (CAD) at 50 °C and 0.4 ms-1 airflow. Rehydration kinetics and Water Holding Capacity (WHC) were evaluated at 20 °C. In comparison to CAD samples, DIC (0.4 MPa and 90 s) reduced the drying time from 180 min to ~108 min. Additionally, regarding the rehydration and WHC results, DIC achieved the same moisture content in only 3.5 min that controls achieved after 1 h of rehydration (0.40 g H2O/g dry matter). Moreover, DIC (0.4 MPa and nine cycles of 10 s) increased the WHC 2.3 times compared to the control. In this way, DIC could be a postharvest technology to improve maize kernels' drying operations and functional properties.

Practical Echocardiographic Approach of the Regurgitant Mitral Valve Assessment.

Mitral regurgitation is the second-most frequent valvular heart disease in Europe after degenerative aortic stenosis. It is associated with significant morbidity and mortality, and its prevalence is expected to increase with population aging. Echocardiography is the first diagnostic approach to assess its severity, constituting a challenging process in which a multimodality evaluation, integrating quantitative, semiquantitative and qualitative methods, as well as a detailed evaluation of the morphology and function of both left ventricle and atria is the key. In this review, we would like to provide a practical diagnosis approach on the mitral valve regurgitation mechanism, severity quantification, and planning of future therapeutic options.

Left atrial enlargement in competitive athletes and atrial electrophysiology.

INTRODUCTION AND OBJECTIVES: There are scarce data on left atrial (LA) enlargement and electrophysiological features in athletes. METHODS: Multicenter observational study in competitive athletes and controls. LA enlargement was defined as LA volume indexed to body surface area ≥ 34mL/m2. We analyzed its relationship with atrial electrocardiography parameters. RESULTS: We included 356 participants, 308 athletes (mean age: 36.4±11.6 years) and 48 controls (mean age: 49.3±16.1 years). Compared with controls, athletes had a higher mean LA volume index (29.8±8.6 vs 25.6±8.0mL/m2, P=.006) and a higher prevalence of LA enlargement (113 [36.7%] vs 5 [10.4%], P <.001), but there were no relevant differences in P-wave duration (106.3±12.5ms vs 108.2±7.7ms; P=.31), the prevalence of interatrial block (40 [13.0%] vs 4 [8.3%]; P=.36), or morphology-voltage-P-wave duration score (1.8±0.84 vs 1.5±0.8; P=.71). Competitive training was independently associated with LA enlargement (OR, 14.7; 95%CI, 4.7-44.0; P <.001) but not with P-wave duration (OR, 1.02; 95%CI, 0.99-1.04), IAB (OR, 1.4; 95%CI, 0.7-3.1), or with morphology-voltage-P-wave duration score (OR, 1.4; 95%CI, 0.9-2.2). CONCLUSIONS: LA enlargement is common in adult competitive athletes but is not accompanied by a significant modification in electrocardiographic parameters.

Ultrasound Assessment in Cardiogenic Shock Weaning: A Review of the State of the Art.

Cardiogenic shock (CS) is associated with a high in-hospital mortality despite the achieved advances in diagnosis and management. Invasive mechanical ventilation and circulatory support constitute the highest step in cardiogenic shock therapy. Once established, taking the decision of weaning from such support is challenging. Intensive care unit (ICU) bedside echocardiography provides noninvasive, immediate, and low-cost monitoring of hemodynamic parameters such as cardiac output, filling pressure, structural disease, congestion status, and device functioning. Supplemented by an ultrasound of the lung and diaphragm, it is able to provide valuable information about signs suggesting a weaning failure. The aim of this article was to review the state of the art taking into account current evidence and knowledge on ICU bedside ultrasound for the evaluation of weaning from mechanical ventilation and circulatory support in cardiogenic shock.

An Overview on Food Applications of the Instant Controlled Pressure-Drop Technology, an Innovative High Pressure-Short Time Process.

Food processing systematically aims at meeting the needs of consumers who are looking for total high quality and perfect food safety. As the various thermal and non-thermal food preservation technologies often affect the natural properties in terms of sensation, flavor, texture, etc., instant controlled pressure drop (DIC) has been conceived as a relevant, innovative process in this field. DIC uses high saturated steam pressure and short duration to provide a new way to expand biological matrices, improve drying, decontaminate, and extract biologically active compounds, among other attributes. Therefore, this review focuses on describing the applications of DIC technology on a wide range of products such as foods and by-products that have been processed both in the laboratory and on an industrial scale. The application of DIC has shown the possibility of a significant leap in quality improvement and cost reduction in the food industry. DIC reduces the drying time of fruits and vegetables, and improves the extraction of essential oils, vegetable oils, and antioxidant components. It also provides strong decontamination, eliminates vegetative microorganisms and spores, and reduces non-nutritional and allergenic components. Over the past 33 years, this technology has continued to expand its food applications and improve its characteristics on an industrial scale. But there are still many food unit operations that can be taken to the next level with DIC.

Role of Exercise Testing and Speckle Tracking Echocardiography in Paradoxical Severe Aortic Stenosis.

Introduction The clinical behavior and prognosis of patients with asymptomatic paradoxical low-gradient aortic stenosis (PLGAS) still remain controversial. Some authors consider PLGAS as an echocardiographically poorly quantified moderate AS (MAS). We aimed to investigate the clinical behavior of PLGAS by comparing it with that of asymptomatic high-gradient aortic stenosis (HG-AS) and MAS using transthoracic echocardiography (TTE) with speckle tracking imaging (STI) and cardiopulmonary exercise testing (CPET). The hypothesis of our study is, unlike that described by other authors, to demonstrate the existence of clinical and echocardiographic differences between PLGAS and MAS. Methods A cohort of 113 patients was included and categorized into three groups according to AS type: MAS (n=63), HG-AS (n=29), and PLGAS (n=21). Patients' clinical data were obtained. Patients underwent 2D TTE with STI and CPET. Results There were no significant differences in the clinical variables between the three AS groups. In the multivariate multinomial logistic regression analysis, with PLGAS being the reference category, the most powerful variable for establishing a difference with HG-AS was the left ventricular mass (LVM) indexed by body-surface area (odds ratio [OR]=1.04, confidence interval (CI)=1.01-1.06, p<0.05). The MAS group showed less abnormal CPET (OR=0.198, CI=0.06-0.69, p<0.05), and higher left ventricle global longitudinal strain rate (GLSR) (OR=0.003, CI=0.00-0.35, p<0.05) than the PLGAS group. Conclusions TTE with STI and CPET established the clear differences between patients with asymptomatic PLGAS and those with asymptomatic MAS, as well as the similarities between patients with PLGAS and those with HG-AS. Our data identify PLGAS as a completely different entity from MAS.

Rationale and design of the rigorous atrial analysis in advanced interatrial block (ARABIA) prospective study.

BACKGROUND: Advanced interatrial block (IAB) is present in 10% of subjects ≥75 years and is associated with the risk of clinical events. METHODS AND RESULTS: Prospective multicenter study that will include subjects ≥75 years without exclusion criteria (indication for anticoagulation, cardiac devices, severe valve disease, systolic dysfunction, moderate or severe cognitive impairment, poor echocardiographic window, non-sinus rhythm or partial IAB, stroke, and life expectancy <2 years). A total of 356 subjects, 178 patients with advanced IAB (exposed) and 178 matched individuals with normal P-wave (non-exposed) will be included. Electrocardiogram and advanced transthoracic echocardiography will be performed. Two substudies will include magnetic resonance imaging: cardiac (86 subjects, 43 exposed, and 43 non-exposed) and brain (86 subjects, 43 exposed, and 43 non-exposed). The follow-up will be 2 years. Our main objective is to determine the association of advanced IAB, P-wave duration, and atrial imaging parameters (I] atrial global longitudinal strain, II] maximal left atrial volume index, III] left atrial ejection fraction, IV] left atrial fibrosis - % total left atrial area V] inter- and intra-atrial asynchrony/dyssynchrony) with clinical events (atrial fibrillation, stroke, cognitive impairment, and mortality). The secondary objective is to assess the association of the P-wave duration with atrial imaging parameters and of both with cerebral microemboli in magnetic resonance imaging. CONCLUSION: Our study will provide data regarding the association of advanced IAB, P-wave duration, and atrial imaging parameters with clinical events. We will also assess the association P-wave duration-atrial imaging parameters-cerebral microemboli.

Impact of COVID-19 Pandemic on Stroke Severity and Mortality in the South-East of Santiago, Chile.

Background and purpose; Chile has been one of the most affected countries by the COVID-19 pandemic, with one of the highest case rates per population. This has affected the epidemiological behaviour of various pathologies. We analyze the impact of the pandemic on the number of admissions due to stroke, its severity and mortality in Santiago, Chile. METHODS: a multicenter observational study based on the records of the 3 hospitals of the South East health service in Santiago, Chile. We recorded the number of patients admitted for ischemic stroke between 01 January 2020 and 30 June 2020. We grouped the cases into two periods, pre-pandemic and pandemic, according to the setting of the state of emergency in Chile. RESULTS: 431 patients were admitted with ischemic stroke during the study period. There was a non-significant decrease in weekly admissions (17 vs 15 patients per week). No differences were observed in the proportion of patients with medical treatment (p = 0.810), IVT (p = 0.638), EVT (p = 0.503) or IVT + EVT (p = 0.501). There was a statistically significant increase in the NIHSS on admission (7.23 vs 8.78, p = 0.009) and mortality (5.2% vs 12.4%, p = 0.012). In a multivariate analysis the NIHSS on admission was associated with the increased mortality (RR 1.11, CI 1.04-1.19, p = 0.003). CONCLUSION: We found an increase in the severity of ischemic stroke on admission and in-hospital mortality during the pandemic period. The main factor to increase in-hospital mortality was the NIHSS on admission.