Nocardia ignorata, a new agent of human nocardiosis isolated from respiratory specimens in Europe and soil samples from Kuwait

Nocardia ignorata is a recently described species identified on the basis of a single isolate of unknown origin. Here we describe the epidemiological, phenotypic, and phylogenetic characteristics of this new species, based on five new clinical and soil isolates.     

A new method for monitoring the contamination of glycerol with diethylene glycol

A quartz crystal microbalance has been used to check the purity of glycerol. The experimental procedure involves no derivatization or other preliminary step except determination of water content. The protocol consists of the direct reading of the frequency of a quartz crystal with one face in contact with an aqueous solution of the glycerol to be tested. The method is inexpensive, simple, rapid, and highly sensitive; diethylene glycol contamination at the 3.61% level could be detected.     

Equity of access to health care for older adults in four major Latin American cities.

OBJECTIVES: To identify if older adults have equitable access to health services in four major Latin American cities and to determine if the inequities that are found follow the patterns of economic inequality in each of the four nations studied. METHODS: Data from persons age 60 and over in the cities of S?o Paulo, Brazil (n = 2,143); Santiago, Chile (n = 1,301); Mexico City, Mexico (n = 1,247); and Montevideo, Uruguay (n = 1,450) were collected through a collaboration led by the Pan American Health Organization. For our study, three process indicators of access (availability, accessibility, and acceptability) and one indicator of actual health services use (visit to a medical doctor in the past 12 months) were analyzed by wealth quintiles, health insurance type, education, health status, and demographic characteristics. RESULTS: Each of the four cities had a different level of access to care, and those levels of access were only weakly related to per capita national wealth. Given the relatively high level of wealth inequality in Brazil and the lower level in Uruguay, older persons in S?o Paulo had better-than-expected equity in access to care, while older persons in Montevideo had less equity than expected. Inequity in Mexico City was driven primarily by low levels of health insurance coverage. In Santiago, inequity followed socioeconomic status more than it did health insurance. CONCLUSIONS: In the four cities studied, health insurance and the operation of health systems mediate the link between economic inequality and inequitable access to health care. Therefore, special attention needs to be paid to equity of access in health services, independent of differences in economic inequality and national wealth.     

Regulation of matrix metalloproteinases 2 and 9 activities by peroxynitrites in term placentas from type 2 diabetic patients

Matrix metalloproteinases (MMPs) are proteolytic enzymes related to a proinflammatory environment in several diseases, including diabetes, which can be activated by reactive nitrogen species. This work aimed to determine MMP-2 and MMP-9 activities and nitration in term placentas from type 2 diabetic patients and verify the hypothesis that peroxynitrites are positive regulators of placental MMP-2 and MMP-9 activities. For this purpose, term placentas from healthy and type 2 diabetic patients were analyzed for MMP-2 and MMP-9 levels and activities, protein nitration, and nitration of MMP-2 and MMP-9. Villous explants were cultured in the presence of peroxynitrites for further evaluation of MMP-2 and MMP-9 activities. We found that MMP-2 and MMP-9 activities were increased in term placentas from diabetic patients. These changes were found even when MMP-2 protein concentrations were diminished and MMP-9 protein concentrations were not changed in the diabetic group. Increased protein nitration and specific nitration of MMP-2 and MMP-9 were found in term placentas from diabetic patients. Peroxynitrites were able to increase the activity of placental MMP-2 and MMP-9. Taken together, this study has shown for first time that peroxynitrites can nitrate and activate MMP-2 and MMP-9 in the placenta, a nitrative pathway possibly related to MMPs overactivity in the placentas from type 2 diabetic patients.     

New and emerging treatments for inflammatory itch

ObjectiveTo summarize recent therapeutic developments for chronic pruritus with a focus on allergic and type 2 inflammatory pathways.Data SourcesLiterature search of PubMed, industry websites, and review of the ClinicalTrials.gov database.Study SelectionsPeer-reviewed publications and public disclosures by industry relating to chronic pruritus pathophysiology and therapeutics.ResultsHistamine and immunoglobulin E remain primary targets for the treatment of itch in the setting of chronic urticaria. More recently, blockade of type 2 immune cell–associated cytokines, including interleukin (IL) 4, IL-13, and IL-31, and the epithelial cell–derived cytokines, specifically IL-33 and thymic stromal lymphopoietin, has and is revolutionizing the treatment of chronic pruritic dermatoses, such as atopic dermatitis and prurigo nodularis. Other novel targets include histamine receptor 4, Janus kinases, κ-opioid receptor, neurokinin 1 receptor, and phosphodiesterase 4.ConclusionAdvances in our understanding of the neuroimmunology of chronic pruritus have led to the identification of new therapeutic targets and the rapid development of cutting-edge clinical trials. Although incredible advances have already been made, chronic itch continues to be an area of great unmet need.     

PDX1-MODY: A rare missense mutation as a cause of monogenic diabetes

Maturity-Onset Diabetes of the Young type 4 is a rare form of diabetes mellitus, caused by mutations in the PDX1 gene. However, only a few mutations in this gene have been associated as a cause of monogenic diabetes up to date. It makes difficult to create a clinical manifestation profile of this disease and, consequently, to improve the therapeutic management for these patients. Here we report a normal weight woman, diagnosed with diabetes mellitus at 27 years old, during her first pregnancy. At the time of the recruitment, she was 40 years old and had a body mass index of 23.9 kg/m², glycated hemoglobin level of 9.6%, and fasting plasma glucose (FPG) of 254 mg/dL. She presented no diabetic complications and she was being treated with insulin. She reported a family history of diabetes mellitus characteristic of an autosomal dominant mode of inheritance. Molecular analysis of the PDX1 gene revealed the missense variant c.532G > A (p.(Glu178Lys)) segregating from the patient to her son, reported as diabetic. It was absent in her healthy daughter. The c.532G > A seems to be a rare variant, absent in human variants databases, and among 86 normoglycemic controls. Eight in silico algorithms classified this variant as probably pathogenic. Additionally, analysis of the evolutionary conservation showed the glutamic acid in the position 178 of PDX-1 protein as conserved among several species. Our findings reinforce the importance of screening rare MODY genes among families with suspicion of monogenic diabetes to help better understand the clinical manifestations of this disease.     

Bioprosthetic Valve Thrombosis and Obstruction Secondary to COVID-19

Patients with COVID-19 may present a hypercoagulable state, with an important impact on morbidity and mortality. Because of this situation pulmonary embolism is a frequent complication during the course of infection. We present the case of a patient recently discharged, after admission with confirmed COVID-19, who developed a pulmonary embolism and thrombosis of a biological mitral valve prosthesis, producing valve obstruction and stenosis. After 15 days of anticoagulant treatment, resolution of the thrombus and normalisation of prosthetic valve function was observed. This case supports current recommendations of administering full-dose anticoagulation therapy to COVID-19 patients with biological heart valve prosthesis, even after the acute phase of infection.     

Deformación miocárdica de la aurícula izquierda en pacientes con lupus eritematoso sistémico

BackgroundIn patients with systemic lupus erythematosus (SLE), left ventricle diastolic dysfunction (LVDD) may be the only manifestation of cardiac involvement in anticipation of systolic dysfunction. It has been seen that myocardial deformation of the left atrium (LA), through the LA global longitudinal strain (LAGLS), may be useful in assessing diastolic function.ObjectiveTo evaluate LA function through myocardial deformation in patients with LES, and compare the LA strain in patients with active, inactive and controls.MethodsFifty patients with SLE were included and compared with 50 healthy controls paired by age and gender. Myocardial deformation was measured by transthoracic echocardiogram, to investigate the LAGLS, the strain of the three phases of the LA cycle and the strain rate. The differences between groups were compared in univariate analysis.ResultsLAGLS in SLE patients was less than in the controls (41.6% vs. 50.5%; p = .02), and in the 3 phases of the LA cycle. There were no differences in the LA strain rate in both groups (SLE 2.5 s^?1 vs. controls 2.75 s^?1; p = .1). It was also found that the LAGLS was lesser in active patients than controls and inactive.ConclusionsSLE patients have lower myocardial deformation of the LA, which is expressed as a lower diastolic function correlating with early subclinical myocardial damage.     

Long‐term oral administration of melatonin improves spatial learning and memory and protects against cholinergic degeneration in middle‐aged Ts65Dn mice,a model of Down syndrome

Ts65Dn mice (TS), the most commonly used model of Down syndrome (DS), exhibit phenotypic characteristics of this condition. Both TS mice and DS individuals present cognitive disturbances, age‐related cholinergic degeneration, and increased brain expression of β‐amyloid precursor protein (AβPP). These neurodegenerative processes may contribute to the progressive cognitive decline observed in DS. Melatonin is a pineal indoleamine that has been reported to reduce neurodegenerative processes and improve cognitive deficits in various animal models. In this study, we evaluated the potentially beneficial effects of long‐term melatonin treatment on the cognitive deficits, cholinergic degeneration, and enhanced AβPP and β‐amyloid levels of TS mice. Melatonin was administered for 5 months to 5‐ to 6‐month‐old TS and control (CO) mice. Melatonin treatment improved spatial learning and memory and increased the number of choline acetyltransferase (ChAT)‐positive cells in the medial septum of both TS and CO mice. However, melatonin treatment did not significantly reduce AβPP or β‐amyloid levels in the cortex or the hippocampus of TS mice. Melatonin administration did reduce anxiety in TS mice without inducing sensorimotor alterations, indicating that prolonged treatment with this indoleamine is devoid of noncognitive behavioral side effects (e.g., motor coordination, sensorimotor abilities, or spontaneous activity). Our results suggest that melatonin administration might improve the cognitive abilities of both TS and CO mice, at least partially, by reducing the age‐related degeneration of basal forebrain cholinergic neurons. Thus, chronic melatonin supplementation may be an effective treatment for delaying the age‐related progression of cognitive deterioration found in DS.