HIV matters when diagnosing TB in young children: an ancillary analysis in children enrolled in the INPUT stepped wedge cluster randomized study.

BACKGROUND: Children under age five years, particularly those living with HIV (CLHIV), are at risk for rapid progression of tuberculosis (TB). We aimed to describe TB clinical presentations, diagnostic pathways and treatment outcomes in CLHIV compared to children without HIV in Cameroon and Kenya. METHODS: This sub-analysis of a cluster-randomized trial evaluating the integration of pediatric TB services from May 2019 to March 2021 enrolled children age < 5 years with TB. We estimated the HIV infection rate with 95% confidence interval (CI). We compared TB clinical presentations, diagnostic pathways and treatment outcomes in CLHIV and children without HIV. Finally, we investigated whether HIV infection was associated with a shorter time to TB diagnosis (≤ 3 months from symptoms onset) after adjusting for covariates. Univariable and multivariable logistic regression analysis were performed with adjusted odds ratios (AORs) presented as measures of the association of covariates with HIV status and with shorter time to TB diagnosis. RESULTS: We enrolled 157 children with TB (mean age was 1.5 years) and 22/157 (14.0% [9.0-20.4%]) were co-infected with HIV. CLHIV were more likely to initially present with acute malnutrition (AOR 3.16 [1.14-8.71], p = 0.027). Most TB diagnoses (140/157, 89%) were made clinically with pulmonary TB being the most common presentation; however, there was weak evidence of more frequent bacteriologic confirmation of TB in CLHIV, 18% vs. 9% (p = 0.067), due to the contribution of lateral-flow urine lipoarabinomannan to the diagnosis. HIV positivity (AOR: 6.10 [1.32-28.17], p = 0.021) was independently associated with a shorter time to TB diagnosis as well as fatigue (AOR: 6.58 [2.28-18.96], p = 0.0005), and existence of a household contact diagnosed with TB (AOR: 5.60 [1.58-19.83], p = 0.0075), whereas older age (AOR: 0.35 [0.15-0.85], p = 0.020 for age 2-5 years), night sweats (AOR: 0.24 [0.10-0.60], p = 0.0022) and acute malnutrition (AOR: 0.36 [0.14-0.92], p = 0.034) were associated with a delayed diagnosis. The case fatality rate was 9% (2/22) in CLHIV and 4% (6/135) in children without HIV, p = 0.31. CONCLUSIONS: These results altogether advocate for better integration of TB services into all pediatric entry points with a special focus on nutrition services, and illustrate the importance of non-sputum-based TB diagnostics especially in CLHIV. TRIAL REGISTRATION: NCT03862261, first registration 05/03/2019.

Optical coherence tomography in diagnosis of inflammatory scalp disorders.

BACKGROUND: The common inflammatory scalp disorders share similar clinical manifestations, and patient work up require invasive, undesirable diagnostic procedures like biopsy to ensure correct diagnosis. Optical coherence tomography (OCT) is a non-invasive high-resolution imaging modality that has found a valuable tool to assist in the diagnose and evaluation of different skin diseases. OBJECTIVES: To describe the structural and vascular dynamic OCT (D-OCT) findings of inflammatory scalp disorders including scalp psoriasis, seborrhoeic dermatitis and contact dermatitis and to compare trichoscopy and OCT features. METHODS: Subjects with diagnosis of seborrhoeic dermatitis, psoriasis or contact dermatitis were enrolled in this study. OCT scans were taken on involved scalp, and the same scalp regions were evaluated by trichoscopy and compared with healthy scalp. RESULTS: A total of fourteen subjects (two healthy controls, four seborrhoeic dermatitis, five psoriasis and three contact dermatitis) participated. D-OCT imaging of vascular pattern in healthy scalp and the inflammatory scalp disorders were described. D-OCT images could enhance the clinician's ability to distinguish psoriasis from seborrhoeic dermatitis by objectively detect and assess red loop density. In scalp contact dermatitis, the vessels of the deep plexus were more dilated and fewer in number than those found in seborrhoeic dermatitis. CONCLUSION: Dynamic OCT provides information that more clearly elucidates changes at the level of the superficial and deep plexuses without invasively interfering with superficial structures. In the context of inflammatory scalp disorders, this is useful to discern disorders with overlapping symptoms and minimize the use of invasive biopsies to diagnose.

Optical coherence tomography for the investigation of frontal fibrosing alopecia.

BACKGROUND: Frontal fibrosing alopecia (FFA) is a cicatricial alopecia that affects the frontotemporal hairline, eyebrows and body hair. OCT is a non-invasive imaging technique useful in understanding skin architecture and vascularization. OBJECTIVE: To describe structural and vascular findings in FFA using OCT. METHODS: This was a case-control study conducted from the months of December 2016-February 2017. The study was IRB approved and conducted at the University of Miami Hospital outpatient dermatology hair and nail clinic in Miami, FL. Four patients with biopsy proven FFA, and three healthy age and sex-matched controls participated. OCT scans were taken on cicatricial alopecic band, inflammatory hairline, eyebrow, uninvolved scalp, facial papules, glabellar red dots and arm. The same body regions were evaluated in controls. RESULTS: Patients and controls were women aged 42-66. Results reveal epidermal thickness is increased in the inflammatory hairline (0.13 mm) and decreased in the alopecic band (0.08 mm) compared to controls (0.10 mm). Attenuation coefficient increased the inflammatory hairline and decreased in the alopecic band compared to controls. Vascular flow in the alopecic band is decreased compared to inflammatory scalp and controls in the superficial levels, but increased at deeper levels as compared to controls. Inflammatory tissue is consistently more vascular at all levels (P < 0.01). Vascular flows in each stage are significantly different than one another (P < 0.01). CONCLUSIONS: Increased vascular flow of the deep plexus in cicatricial stages can be a consequence of superficial tissue ischaemia or fibrosis. It is difficult to establish if the increased flow in the inflammatory stage is due to neovascularization as seen in other ischaemic diseases or is the result of the inflammatory response. OCT may be a useful non-invasive tool in imaging FFA. Not only can the technology assist in monitoring disease activity in a non-invasive manner, but it may elucidate new pathophysiologic findings.

Environmental Exposure of Children to Toxic Trace Elements (Hg, Cr, As) in an Urban Area of Yucatan, Mexico: Water, Blood, and Urine Levels.

Merida is the largest urban center in the Mexican State of Yucatan. Here domestic sewage is deposited in poorly built septic tanks and is not adequately treated. Because of contamination from such waste, water from the top 20 m of the aquifer is unsuitable for human consumption. Given this situation and because children are highly vulnerable to environmental pollution, including exposure to toxic trace elements, this study focused on evaluating the exposure of children to arsenic (As), chromium (Cr), and mercury (Hg) in water. It also evaluated the relationship between the levels of these elements in water and their concentrations in urine and blood. Among the 33 children monitored in the study, arsenic surpassed WHO limits for blood in 37% of the cases, which could result from the ingestion of poultry contaminated with organoarsenic compounds. In the case of WHO limits for Mercury, 65% of the water samples analyzed, 28% of urine samples, and 12% of blood samples exceeded them. Mercury exposure was correlated with biological sex, some lifestyle factors, and the zone in Merida in which children live. These data suggest that the levels of some toxic metals in children may be affected by water source, socioeconomic factors, and individual behavior.

Patients with a new variant of endemic pemphigus foliaceus have autoantibodies against arrector pili muscle, colocalizing with MYZAP, p0071, desmoplakins 1 and 2 and ARVCF.

BACKGROUND: We identified a new variant of endemic pemphigus foliaceus in El Bagre, Colombia, South America, which we term El Bagre-EPF, and observed reactivity to arrector pili muscle (APM), thus we tested for autoimmunity to APM. METHODS: We took skin biopsies from 30 patients with El Bagre-EPF and 30 healthy controls (HCs) matched by age, sex and occupation, who were all from the endemic area, and tested these using direct immunofluorescence (DIF), confocal microscopy, immunohistochemistry and immunoblotting (IB). RESULTS: Of the 30 patients with El Bagre-EPF, 27 had autoantibodies to APM that colocalized with commercial antibodies to myocardium-enriched zonula occludens-1-associated protein (MYZAP), desmoplakin (DP)1 and DP2, plakophilin 4, and Armadillo repeat gene deleted in velo-cardio-facial syndrome (ARVCF) (P < 0.001, Fisher exact test). The positive staining also colocalized with Junctional Adhesion Molecule 1 (JAM-A), a control antibody for gap cell junctions. No HC samples were positive. In 27 of the 30 patients, serum that was APM-positive also displayed IB colocalization of their autoantibody molecular weights with the Progen antibodies (P < 0.001, Fisher exact test). CONCLUSIONS: Patients affected by El Bagre-EPF have autoantibodies to APM, colocalizing with the antibodies MYZAP, ARVCF, p0071, DP1 and DP2, suggesting that these molecules are El Bagre-EPF antigens. Further, all of these antigens represent components of cell junctions, indicating that the immune response is directed, at least partially, against cell junctions. The immune response in patients affected by El Bagre-EPF is polyclonal, and it includes B and T lymphocytes, mast cells, IgG, IgA, IgM, IgD, IgE, fibrinogen, albumin, complement/C1q, C3c and C4.

Water Consumption as Source of Arsenic, Chromium, and Mercury in Children Living in Rural Yucatan, Mexico: Blood and Urine Levels.

Studies investigating the correlation between metal content in water and metal levels in children are scarce worldwide, but especially in developing nations. Therefore, this study investigates the correlation between arsenic, chromium, and mercury concentrations in drinking and cooking water and in blood and urine samples collected from healthy and supposedly non-exposed children from a rural area in Yucatan, Mexico. Mercury in water shows concentrations above the recommended World Health Organization (WHO) value for drinking and cooking water. Also, 25% of the children show mercury in urine above the WHO recommended value. Multivariate analyses show a significant role for drinking and cooking water as a vector of exposure in children. Also, the factor analysis shows chronic exposure in the case of arsenic, as well as an ongoing detoxification process through urine in the case of mercury. Further studies should be done in order to determine other potential metal exposure pathways among children.

Assessing Antibody Strength: Comparison of MFI, C1q, and Titer Information.

The presence of donor-specific HLA antibodies before or after transplantation may have different implications based on the antibody strength. Yet, current approaches do not provide information regarding the true antibody strength as defined by antigen-antibody dissociation rate. To assess currently available methods, we compared between neat mean fluorescence intensity (MFI) values, C1q MFI values, ethylenediaminetetraacetic acid (EDTA)-treated samples, as well as titration studies and peak MFI values of over 7000 Luminex-based single-antigen HLA antibody data points. Our results indicate that neat MFI values do not always accurately depict antibody strength. We further showed that EDTA treatment (6%) does not always remove all inhibitory factors compared with C1q or titration studies. In this study of patients presenting with multiple antibody specificities, a prozone effect was observed in 71% of the cohort (usually not affecting all antibody specificities within a single serum sample, though). Similar to titration studies, the C1q assay was able to address the issue of potential inhibition; however, its limitation is its low sensitivity and inability to detect the presence of weak antibodies. Titration studies are the only method among the approaches used in this study to provide information suggesting antigen-antibody dissociation rates and are, therefore, likely to provide better indication of true antibody strength.

Organophosphorous pesticides research in Mexico: epidemiological and experimental approaches.

Non-persistent pesticides, such as organophosphorous (OP) insecticides have been extensively used in Mexico, and becoming a public health problem. This review presents data of OP use and related toxicity from epidemiological and experimental studies conducted in Mexico. Studies in agricultural workers from several regions of the country reported moderate to severe cholinergic symptoms, including decreased acetylcholinesterase (AChE) activity (the main acute OP toxic effect that causes an over accumulation of the neurotransmitter acetylcholine), revealing the potential risk of intoxication of Mexican farmers. OP exposure in occupational settings has been associated with decreased semen quality, sperm DNA damage and as endocrine disrupter, particularly in agricultural workers. Alterations in female reproductive function have also been observed, as well as adverse effects on embryo development by prenatal exposure in agricultural communities. This illustrates that OP exposure represents a risk for reproduction and offspring well-being in Mexico. The genotoxic effects of this group of pesticides in somatic and sperm cells are also documented. Lastly, we present data about gene-environmental interactions regarding OP metabolizing enzymes, such as paraoxonase-1 (PON1) and its role in modulating their toxicity, particularly on semen quality and sperm DNA integrity. In summary, readers will see the important health problems associated with OP exposure in Mexican populations, thereby the need of capacitation programs to communicate farmers the proper handling of agrochemicals to prevent their toxic effects and of more well designed human studies to support data of the current situation of workers and communities dedicated to agriculture activities.

Impact of myoglobin oxygenation state prior to frozen storage on color stability of thawed beef steaks through retail display.

Consumers consider beef color to be an indicator of freshness and therefore it is a major factor when purchasing beef. The ideal conditions for maintaining color throughout retail display following frozen storage have yet to be well established. Therefore, the objective of this study was to determine the effects of myoglobin oxygenation levels (especially high oxygenation) during freezing on color stability of thawed steaks during retail display (RD) and to determine the impact that frozen storage duration, aging, and packaging films have on meat color after thawing under RD conditions. USDA Choice strip loins (n = 36) were aged for 4 or 20 d. Steaks were randomly assigned to a myoglobin oxygenation level [deoxymyoglobin (DeOxy; packaged within 3 min), oxygenation (Oxy; oxygenated in air for 30 min), or high oxygenation (HiOxy; packaged for 24 h in 80% O2)]. Steaks were then vacuum packaged in oxygen permeable or impermeable film and immediately frozen (-10 °C). Following either 0, 2, 4, or 6 months of frozen storage at -5 °C, steaks were removed from the packaging and immediately placed under simulated RD conditions for 7 d. During RD, instrumental color and subjective color were measured every day after the initial 24 h thaw period. Steaks were analyzed for instrumental color (L*, a*, b*), a*:b* ratio, percentage oxymyoglobin, metmyoglobin, and deoxymyoglobin, delta E, redness ratio, subjective discoloration, and lipid oxidation. For all days of RD, steaks that were frozen for 0 months had higher a* values (greater redness) than steaks frozen for 6 months which typically had the lowest a* values (P < .0001). HiOxy steaks frozen for 6 months had the lowest amounts of percentage oxymyoglobin than all other frozen storage periods and myoglobin oxygenation levels on days 4-7 of RD (P < .05). The HiOxy steaks frozen for 4 and 6 months had higher percentage metmyoglobin than DeOxy and Oxy, regardless of packaging (P < .05). Delta E, discoloration, and lipid oxidation were greatest for HiOxy steaks compared to Oxy and DeOxy (P < .05). Extended storage brought about detrimental color effects for all differing levels of myoglobin oxygenation. The HiOxy steaks through the first few days of RD and frozen for under 6 months provided had bright cherry red color, similar to that of DeOxy and Oxy. However, with extended frozen storage and RD, HiOxy steaks had worse color characteristics (more discoloration) than the other myoglobin oxygenation levels.

Consistency of Multi-Month Antiretroviral Therapy Dispensing and Association with Viral Load Coverage among Pediatric Clients Living with HIV in Mozambique

With the increase in uptake of multi-month antiretroviral therapy dispensing (MMD) for children, little is known about consistency of MMD receipt over time and its association with virological outcomes. This analysis aims to assess the uptake of 3-month MMD among children, consistent receipt of MMD after uptake, and clinical outcomes following transition to MMD in 16 health facilities in Gaza and Inhambane Provinces. This is a secondary analysis involving children <15 years living with HIV with clinical visits during the period from September 2019 to August 2020. Of 4383 children, 82% ever received MMD (at least one pickup of a 3-month MMD supply) during the study period but only 40% received it consistently (defined as MMD at every visit during the study period). Consistent MMD was most common among older children and children without indications of clinical instability. Overall viral load (VL) coverage was 40% (733/1851). Consistent MMD was significantly associated with lower odds of having a VL (0.78, 95% CI: 0.64-0.95). In conclusion, while receipt of a multi-month supply was common particularly during the early days of the COVID-19 pandemic, only a minority of children received consistent MMD; however, there is a need to ensure children with fewer visits still receive timely VL monitoring.

Studies with neuronal cells: From basic studies of mechanisms of neurotoxicity to the prediction of chemical toxicity.

Neurotoxicology considers that chemicals perturb neurological functions by interfering with the structure or function of neural pathways, circuits and systems. Using in vitro methods for neurotoxicity studies should include evaluation of specific targets for the functionalism of the nervous system and general cellular targets. In this review we present the neuronal characteristics of primary cultures of cortical neurons and of cerebellar granule cells and their use in neurotoxicity studies. Primary cultures of cortical neurons are constituted by around 40% of GABAergic neurons, whereas primary cultures of cerebellar granule cells are mainly constituted by glutamatergic neurons. Both cultures express functional GABAA and ionotropic glutamate receptors. We present neurotoxicity studies performed in these cell cultures, where specific neural targets related to GABA and glutamate neurotransmission are evaluated. The effects of convulsant polychlorocycloalkane pesticides on the GABAA, glycine and NMDA receptors points to the GABAA receptor as the neural target that accounts for their in vivo acute toxicity, whereas NMDA disturbance might be relevant for long-term toxicity. Several compounds from a list of reference compounds, whose severe human poisoning result in convulsions, inhibited the GABAA receptor. We also present cell proteomic studies showing that the neurotoxic contaminant methylmercury affect mitochondrial proteins. We conclude that the in vitro assays that have been developed can be useful for their inclusion in an in vitro test battery to predict human toxicity.

Team approach to manage difficult-to-treat TB cases: Experiences in Europe and beyond.

As recommended by the World Health Organization (WHO), optimal management of MDR-TB cases can be ensured by a multi-speciality consultation body known as 'TB Consilium'. This body usually includes different medical specialities, competences and perspectives (e.g., clinical expertise both for adults and children; surgical, radiological and public health expertise; psychological background and nursing experience, among others), thus lowering the risk of making mistakes - or managing the patients inappropriately, in order to improve their clinical outcomes. At present, several high MDR-TB burden countries in the different WHO regions (and beyond) have introduced TB Consilium-like bodies at the national or subnational level to reach consensus on the best treatment approach for their patients affected by TB. In addition, in countries/settings where a formal system of consultation does not exist, specialized staff from MDR-TB reference centres or international organizations usually spend a considerable amount of their working time responding to phone or e-mail clinical queries on how to manage M/XDR-TB cases. The aim of this manuscript is to describe the different experiences with the TB Consilia both at the international level (European Respiratory Society - ERS/WHO TB Consilium) and in some of the countries where this experience operates successfully in Europe and beyond. The Consilium experiences are described around the following topics: (1) history, aims and focus; (2) management and funding; (3) technical functioning and structure; (4) results achieved. In addition a comparative analysis of the TB Consilia in the different countries has been performed.

Impacto en la salud mental de los profesionales sanitarios que prestan asistencia a pacientes durante el brote del Covid-19 / Impact on the mental wellbeing of health professionals who provide care to patients during the Covid-19 outbreak

Las principales repercusiones de pandemias anteriores en el personal sanitario son los problemas de salud mental. Sin embargo, existe poca evidencia disponible relacionada a cómo el COVID-19 está afectando la salud mental en el personal sanitario. El objetivo de esta revisión de literatura fue analizar el impacto que ha tenido la pandemia en la salud mental de los profesionales de salud. Se realizó una revisión de literatura narrativa utilizando las bases de datos de Proquest y PubMed, 11 artículos fueron seleccionados de acuerdo al cumplimiento de los criterios definidos. Los trastornos mentales más frecuentes en el personal sanitario que trabaja directamente en la atención de pacientes Covid-19 son: el estrés, depresión, ansiedad y la angustia, insomnio, hiperactividad y baja calidad de vida, afectan también al personal sanitario. Estos trastornos mentales son provocados por diversos factores como el exceso de carga laboral, miedo a infectarse e infectar a sus familias, falta de medios de protección personal y temor de ser discriminados entre otros. La pandemia del COVID-19 afecta negativamente la salud mental de los profesionales de salud que trabajan directamente en la atención de pacientes, así también como la calidad de vida, por lo que es fundamental tomar acciones para proteger a los funcionarios de salud.

The main repercussions of previous pandemics on health workers are mental health problems. However, there is little evidence available related to how COVID-19 is affecting mental wellbeing in healthcare personnel. This literature review's objective was to analyze the impact that the pandemic has had on the mental wellbeing of health professionals. A narrative literature review was carried out using the Proquest and PubMed databases; 11 articles were selected according to the defined criteria' fulfillment. The most frequent mental disorders in health personnel who work directly in the care of Covid-19 patients are: stress, depression, anxiety and anguish, insomnia, hyperactivity, and low quality of life, which also affect health personnel. These mental disorders are caused by various factors such as excessive workload, fear of becoming infected and infecting their families, lack of means of personal protection, and fear of being discriminated against, among others. The COVID-19 pandemic negatively affects the mental wellbeing of health professionals who work directly in patient care and the quality of life, so it is essential to take action to protect health workers.

Diagnostic utility of handheld ultrasonography as an extension of the physical examination of patients with heart failure. / Utilidad diagnóstica de la ecografía de bolsillo en la insuficiencia cardiaca.

BACKGROUND AND OBJECTIVES: Conventional echocardiography is the technique of choice for assessing left ventricular function and the presence of structural heart disease in patients with heart failure. The aim of this study was to assess the diagnostic performance of handheld ultrasonography performed by a medical internist on patients with a clinical diagnosis of heart failure. PATIENTS AND METHODS: Cross-sectional observational study of 212 patients diagnosed with heart failure in a hospital center. A medical internist with basic training in echocardiography performed an examination using handheld ultrasonography and semiquantitatively assessed several variables. The patients' left ventricular systolic function was assessed, along with the cavity dimensions, significant valvular heart disease, pericardial effusion and the diameter of the inferior vena cava. RESULTS: The examination using handheld ultrasonography was conducted in less than 6minutes. The agreement between the diagnoses of the medical internist and the expert echocardiographist was very good (k>0.81) for the diameter, hypertrophy and left ventricular systolic function, valvular regurgitation, pericardial effusion and diameter of the inferior vena cava. CONCLUSIONS: Handheld echocardiography performed by a medical internist, as an extension of the physical examination of patients with heart failure, is a valid and safe test that helps increase the diagnostic performance.

Comparison of interlaboratory survey date in terms of receiver operating characteristic (ROC) indices.

Receiver Operating Characteristic (ROC) analysis in the field of visual imaging has hitherto dealt with the performance of imaging modalities, system displays, or individual readers. This study combines previously established interlaboratory survey techniques with ROC concepts to evaluate selected indices of group discrimination and of group decision criteria in a quantitative and comparative manner. One hundred forty-two subscribers to the College of American Pathologists Phantom-Imaging Series performed a series of visual detection tasks on a fabricated radioactive phantom image. Results suggest that group performance may be legitimately assessed by ROC analysis if the variables of system modality, image display, and cases are controlled, and the number of trials is sufficiently large. The latter condition may be fully satisfied through interlaboratory survey techniques that utilize currently existing peer groups.

Scintigraphic detection of segmental bile-duct obstruction.

In a patient with acute obstructive jaundice, cholescintigraphy with technetium-99m-labeled iminodiacetic acid (HIDA) showed uniformly reduced uptake in the left lobe of the liver. Endoscopic retrograde cholangiopancreatography (ERCP) demonstrated cholelithiasis and obstruction of the distal hepatic duct. Surgery, and later a T-tube cholangiogram, confirmed the presence of numerous stones in the left intrahepatic and common hepatic ducts. The liver was free of tumor. Intrahepatic segmental ductal obstruction may produce a spectrum of patterns on hepatobiliary imaging ranging from reduced uptake to intrahepatic pooling.