Occupational exposure to coal and risk of multiple health outcomes: A case report

Occupational cutaneous squamous‐cell carcinoma has an increased incidence, but rarely suspected. When located in an uncovered skin area, it is closely linked to polycyclic aromatic hydrocarbons exposure. However, single pulmonary anthracosis nodule is rarely described in the literature. The association of both diseases due to the same exposure remains uncommon.     

Aldosterone, mineralocorticoid receptor, and heart failure

Several large clinical studies have demonstrated the important benefit of mineralocorticoid receptor (MR) antagonists in patients with heart failure, left ventricular dysfunction after myocardial infarction, hypertension or diabetic nephropathy. Aldosterone adjusts the hydro-mineral balance in the body, and thus participates decisively to the control of blood pressure. This traditional view of the action of aldosterone restricted to sodium reabsorption in epithelial tissues must be revisited. Clinical and experimental studies indicated that chronic activation of the MR in target tissues induces structural and functional changes in the heart, kidneys and blood vessels. These deleterious effects include cardiac and renal fibrosis, inflammation and vascular remodeling. It is important to underscore that these effects are due to elevated MR activation that is inadequate for the body salt requirements.Aldosterone is generally considered as the main ligand of MR. However, this is a matter of debate especially in heart. Complexity arises from the glucocorticoids with circulating concentrations much higher than those of aldosterone, and the fact that the MR has a high affinity for 11β-hydroxyglucocorticoids. Nevertheless, the beneficial effects of MR inhibition in patients with heart failure emphasize the importance of this receptor in cardiovascular tissue. Diverse experimental models and strains of transgenic mice have allowed to dissect the effects of aldosterone and the MR in the heart. Taken together experimental and clinical data clearly highlight the deleterious cardiovascular effects of MR stimulation.     

Rational and design of SATRACD study: detecting subclinical anthracycline therapy related cardiac dysfunction in low income country

BackgroundAnthracycline therapy-related cardiac dysfunction (ATRCD) is the most notorious adverse side-effect of chemotherapy. It has become a significant cardiovascular health concern for long-term cancer survivors. With the emerging concept of subclinical ATRCD and newer diagnostictools (Speckle Tracking Echocardiography (STE) and biomarkers), detecting anthracycline cardiac toxicity at an early stage has become an important step to prevent severe cardiac dysfunction and improve the cardiovascular outcome in cancer survivors. Despite the increasing population at risk in sub-Saharan Africa (SSA), there is no contemporary data in Uganda to address the burden, pathogenesis and risk factors of subclinical ATRCD. This big gap in knowledge has led to a lack of local guidelines for monitoring and management of ATRCD.MethodsSATRACD (Detecting Subclinical Anthracycline Therapy Related Cardiac Dysfunction In Low Income Country) study is an observational prospective cohort study. Three hundred and fifty-three anthracycline naïve cancer patients will be recruited at baseline. Patients are followed up on completion of anthracycline-based chemotherapy and at 6 months after completion of anthracycline therapy. Data on demographics, cancer profile and clinical presentation will be collected at baseline. Comprehensive cardiac assessment will be performed at each visit, including electrocardiogram, conventional echocardiography, STE, cardiac and oxidative stress markers. We will be able to determine the incidence of subclinical and clinical ATRCD at 6 months after completion of anthracycline therapy, determine whether hypertension is a major risk factor for ATRCD, evaluate the role of conventional echocardiography parameters, and biomarkers for detecting subclinical ATRCD.ConclusionThis SATRACD study will provide contemporary data on Ugandan cancer patients who have subclinical and clinical ATRCD, help in the development of local strategies to prevent and manage ATRCD, and improve cardiovascular outcome for Ugandan cancer survivors.     

Lupus hepatitis

We report the case of 42 year-old man who presents an acute polyarthritis associated with systemic manifestation and immunologic disorders related to systemic lupus erythematosus. Hepatic tests show cholostase and cytolysis. Hepatic involvement is linked with systemic lupus erythematosus after exclusion of hepatotoxic drugs, viral hepatitis and absence of anti mitochondrial and anti muscle antibodies. Lupus hepatitis seems to be correlated with autoantibodies to ribosomal P protein. Its treatment remains to be defined.     

Intracellular Ca-carbonate biomineralization is widespread in cyanobacteria

Cyanobacteria have played a significant role in the formation of past and modern carbonate deposits at the surface of the Earth using a biomineralization process that has been almost systematically considered induced and extracellular. Recently, a deep-branching cyanobacterial species, Candidatus Gloeomargarita lithophora, was reported to form intracellular amorphous Ca-rich carbonates. However, the significance and diversity of the cyanobacteria in which intracellular biomineralization occurs remain unknown. Here, we searched for intracellular Ca-carbonate inclusions in 68 cyanobacterial strains distributed throughout the phylogenetic tree of cyanobacteria. We discovered that diverse unicellular cyanobacterial taxa form intracellular amorphous Ca-carbonates with at least two different distribution patterns, suggesting the existence of at least two distinct mechanisms of biomineralization: (i) one with Ca-carbonate inclusions scattered within the cell cytoplasm such as in Ca. G. lithophora, and (ii) another one observed in strains belonging to the Thermosynechococcus elongatus BP-1 lineage, in which Ca-carbonate inclusions lie at the cell poles. This pattern seems to be linked with the nucleation of the inclusions at the septum of the cells, showing an intricate and original connection between cell division and biomineralization. These findings indicate that intracellular Ca-carbonate biomineralization by cyanobacteria has been overlooked by past studies and open new perspectives on the mechanisms and the evolutionary history of intra- and extracellular Ca-carbonate biomineralization by cyanobacteria.Cyanobacteria are a phylogenetically and ecologically diverse phylum of Gram-negative bacteria that have impacted the global cycle of carbon on the Earth for billions of years and induced the oxygenation of the atmosphere (1–3). By performing oxygenic photosynthesis—a unique capability that appeared only once in evolution—in this particular group of bacteria, cyanobacteria have contributed significantly to the primary production on the past and present Earth (4). Moreover, cyanobacteria have received great attention from geologists as major players in the formation of carbonate sedimentary deposits such as stromatolites (5, 6), the oldest ones formed by cyanobacteria possibly as old as 2.98 billion years (Ga) (7). Fossils of Ca-carbonate–encrusted cyanobacterial cells (calcimicrobes) have been looked for extensively. The temporal distribution of calcimicrobes in the geological record dating back as far as the early Proterozoic (∼2.5–2.3 Ga) (8) has been interpreted as the result of paleoenvironmental and/or evolutionary changes (9, 10). Despite the importance of carbonate biomineralization by cyanobacteria in the formation of calcimicrobes and sedimentary deposits, the involved mechanisms are still poorly understood (11, 12). Some authors have proposed that cyanobacterial calcification might be promoted by CO₂-concentrating mechanisms (CCMs) that possibly developed in the late Proterozoic to accommodate photosynthetic carbon limitation under low CO₂ fugacity (10). This model states that bicarbonates are actively imported into the cells, transformed to CO₂ within carboxysomes for fixation by ribulose-1,5-bisphosphate carboxylase/oxygenase. The resulting alkalinity is transferred outside the cells, which raises the external pH and thus induces CaCO₃ precipitation (13). Other authors have stressed the importance of cell-surface properties of some cyanobacteria for the nucleation of CaCO₃ minerals and did not observe notable effects of photosynthesis on CaCO₃ precipitation (14). In any case, precipitation of CaCO₃ by cyanobacteria has been invariably considered a noncontrolled and extracellular process.This paradigm has been questioned recently by the discovery of a new deep-branching cyanobacterial species, Candidatus Gloeomargarita lithophora, enriched from the hyperalkaline Lake Alchichica (Mexico) and forming amorphous carbonates intracellularly (15). However, many studies characterized the ultrastructure of cyanobacteria (16, 17) and explored their impact on calcification (11, 18, 19), but none of them reported the presence of intracellular carbonates. Here, we investigated whether intracellular carbonate biomineralization is restricted to one particular species and/or specific environmental condition or whether it exists in other diverse cyanobacteria; this is essential to assess the evolution of intracellular carbonate biomineralization and its significance at geological timescales. For this purpose, we screened 68 cyanobacterial strains scattered throughout the phylogenetic tree of cyanobacteria (Fig. 1) to search for intracellular carbonates.Open in a separate windowFig. 1.Bayesian phylogenetic tree of 16S rRNA gene sequences of the cyanobacterial strains observed by electron microscopy. Strains forming intracellular Ca-carbonates are shown in color (green for those with Ca-carbonate inclusions at the cell poles and red for those with inclusions scattered in the cytoplasm). The tree is based on 1,292 conserved sites; numbers at branches are posterior probabilities (only those >0.75 are shown).     

Langerhans cells protect from allergic contact dermatitis in mice by tolerizing CD8(+) T cells and activating Foxp3(+) regulatory T cells

Allergic contact dermatitis is the most frequent occupational disease in industrialized countries. It is caused by CD8(+) T cell-mediated contact hypersensitivity (CHS) reactions triggered at the site of contact by a variety of chemicals, also known as weak haptens, present in fragrances, dyes, metals, preservatives, and drugs. Despite the myriad of potentially allergenic substances that can penetrate the skin, sensitization is relatively rare and immune tolerance to the substance is often induced by as yet poorly understood mechanisms. Here we show, using the innocuous chemical 2,4-dinitrothiocyanobenzene (DNTB), that cutaneous immune tolerance in mice critically depends on epidermal Langerhans cells (LCs), which capture DNTB and migrate to lymph nodes for direct presentation to CD8(+) T cells. Depletion and adoptive transfer experiments revealed that LCs conferred protection from development of CHS by a mechanism involving both anergy and deletion of allergen-specific CD8(+) T cells and activation of a population of T cells identified as ICOS(+)CD4(+)Foxp3(+) Tregs. Our findings highlight the critical role of LCs in tolerance induction in mice to the prototype innocuous hapten DNTB and suggest that strategies targeting LCs might be valuable for prevention of cutaneous allergy.     

Renal transplantation in the elderly: a survey

For ten years, an increase in the number of elderly patients on renal transplant waiting lists has occured. In an attempt to close the widening gap between supply and demand and because the demand for kidneys for younger patients already surpasses the supply, transplant physicians nowadays accept organs from older donors that might have been deemed inappropriate in the past. Programs of age matching between donors and recipients and of dual-kidneys transplantation have emerged. The initial results of these programs are encouraging with excellent patient and graft survival at one and three years.     

Acute leukoencephalitis in infant treated by high-dose corticosteroid. A case report

The authors report a case of acute post infectious leukoencephalitis observed in a tow-years and a half children admitted to our hospital for fiver with suddent condition deterioration, obnibulation, coma and paralysis of the 6th and 7th cranial nerve. Cerebrospinal fluid study showed lymphocytosis with negative culture. Head magnetic resonance imaging demonstrated diffuse high signals over the white matter on T2 weighted images so the diagnosis was confirmed. High dose corticosteroid therapy was effective.     

AT1 blockade abolishes left ventricular hypertrophy in heterozygous cMyBP‐C null mice: role of FHL1

This research investigated the impact of angiotensin AT1 receptor (Agtr1) blockade on left ventricular (LV) hypertrophy in a mouse model of human hypertrophic cardiomyopathy (HCM), which carries one functional allele of Mybpc3 gene coding cardiac myosin‐binding protein C (cMyBP‐C). Five‐month‐old heterozygous cMyBP‐C knockout (Het‐KO) and wild‐type mice were treated with irbesartan (50 mg/kg/day) or vehicle for 8 weeks. Arterial blood pressure was measured by tail cuff plethysmography. LV dimension and function were accessed by echocardiography. Myocardial gene expression was evaluated using RT‐qPCR. Compared with wild‐type littermates, Het‐KO mice had greater LV/body weight ratio (4.0 ± 0.1 vs. 3.3 ± 0.1 mg/g, P < 0.001), thicker interventricular septal wall (0.70 ± 0.02 vs. 0.65 ± 0.01 mm, P < 0.02), lower Mybpc3 mRNA level (?43%, P < 0.02), higher four‐and‐a‐half LIM domains 1 (Fhl1, +110%, P < 0.01), and angiotensin‐converting enzyme 1 (Ace1, +67%, P < 0.05), but unchanged Agtr1 mRNA levels in the septum. Treatment with irbesartan had no effect in wild‐type mice but abolished septum‐predominant LV hypertrophy and Fhl1 upregulation without changes in Ace1 but with an increased Agtr1 (+42%) in Het‐KO mice. Thus, septum‐predominant LV hypertrophy in Het‐KO mice is combined with higher Fhl1 expression, which can be abolished by AT1 receptor blockade, indicating a role of the renin‐angiotensin system and Fhl1 in cMyBP‐C‐related HCM.