Milestone Achievement and Neurodevelopment of Rural Amazonian Toddlers (12 to 24 Months) with Different Methylmercury and Ethylmercury Exposure

Neurological outcomes (Gesell development schedules [GDS]), age of walking, and age of talking were studied in 299 toddlers (12 to 24 mo) in relation to environmental (fish consumption and tin mining) exposure. Exposure to fish methylmercury (MeHg) consumption and iatrogenic ethylmercury (EtHg) in Thimerosal-containing vaccines (TCV) was quantified in toddlers from two rural villages (n?=?91, Itapuã; n?=?218, Bom Futuro) respectively populated by fishers and cassiterite miners. Median total hair Hg (HHg) concentrations of infants from Itapuã (3.5 μg/g) were significantly higher than those of infants from Bom Futuro (2.2 μg/g). Median EtHg exposure from TCV was also significantly higher in toddlers from Itapuã (137.5 μg) than in those from Bom Futuro (112.5 μg). There were no significant differences between groups for any of the Gesell schedules; however, there were proportionally more compromised toddlers (GDS < 70) in Itapuã than Bom Futuro. Median age of talking was not statistically different but median age of walking was significantly higher in Bom Futuro. In toddlers from both villages, of fishers and miners, HHg concentrations were significantly correlated with family fish consumption. A logistic regression model was applied to all infants after classification into two groups: above or below the median Gesell schedules. Overall, there was no distinctive pattern of neurodevelopment associated with either HHg or EtHg exposure; however, nutritional status was significantly associated with GDS. In conclusion, milestone achievement was delayed in toddlers from tin-ore mining communities. Despite significantly higher exposure to both forms of organic Hg (MeHg from maternal fish consumption, and EtHg from TCV) in toddlers from the fishing village, significant differences were seen only among the proportions of most severely affected toddlers (GDS < 70).     

An Alternative Approach to Selecting Patients for High‐risk Screening with Breast MRI

Current guidelines for adding breast MRI to annual screening mammography are based entirely upon stratification of risk, with a heavy focus on lifetime calculations. This approach is fraught with difficulty due to the reliance on mathematical models that vary widely in their calculations, the inherent age discrimination of using lifetime risks rather than short‐term incidence, and the failure to incorporate mammographic density, the latter being an independent risk as well as the greatest predictor of mammographic failure. By utilizing a system of patient selection similar to what was used in the American College of Radiology Imaging Network (ACRIN) 6666 trial for multi‐modality imaging, 33 women without a prior diagnosis of breast cancer were found to harbor mammographically occult carcinoma through MRI screening. These 33 patients represent a 2% yield, closely approximating the yields seen in prospective MRI screening trials of women at very high risk of breast cancer. Using the “~20–25%” minimum established by the American Cancer Society and later the National Comprehensive Cancer Network, the Gail model would have prompted the use of MRI in only 9 of 33 (27.3%) patients, the Claus model 1 of 33 (3%), and the Tyrer–Cuzick model 12 of 33 (36.4%). Using all three models and opting for the highest calculated risk, then including BRCA‐positivity, still would have identified only 16 of 33 (48.5%) patients with occult breast cancer discovered by MRI. Only one patient was BRCA‐positive, and none had lobular carcinoma in situ, while 6 of 33 patients (18.2%) had atypical ductal hyperplasia (ADH). Measures are proposed to refine patient selection for MRI screening through the use of short‐term or categorical risks, mammographic density, while maintaining cost‐effectiveness through longer MRI screening intervals.     

Impact of donor-specific antibodies on long-term graft survival with pediatric liver transplantation

BACKGROUNDIn a previous paper, we reported a high prevalence of donor-specific antibody (DSA) in pediatric patients with chronic rejection and expressed the need for confirmation of these findings in a larger cohort.AIMTo clarify the importance of DSAs on long-term graft survival in a larger cohort of pediatric patients.METHODSWe performed a retrospective analysis of 123 pediatric liver transplantation (LT) recipients who participated in yearly follow-ups including Luminex testing for DSA at our center. The cohort was split into two groups according to the DSA status (DSA-positive n = 54, DSA-negative n = 69). Groups were compared with regard to liver function, biopsy findings, graft survival, need for re-LT and immunosuppressive medication.RESULTSDSA-positive pediatric patients showed a higher prevalence of chronic rejection (P = 0.01), fibrosis (P < 0.001) and re-transplantation (P = 0.018) than DSA-negative patients. Class II DSAs particularly influenced graft survival. Alleles DQ2, DQ7, DQ8 and DQ9 might serve as indicators for the risk of chronic rejection and/or allograft fibrosis. Mean fluorescence intensity levels and DSA number did not impact graft survival. Previous episodes of chronic rejection might lead to DSA development.CONCLUSIONDSA prevalence significantly affected long-term liver allograft performance and liver allograft survival in our cohort of pediatric LT. Screening for class II DSAs in combination with assessment of protocol liver biopsies for chronic antibody-mediated rejection improved early identification of patients at risk of graft loss.     

Cardiovascular magnetic resonance of cardiac tumors and masses

Cardiac masses diagnosis and treatment are a true challenge, although they are infrequently encountered in clinical practice. They encompass a broad set of lesions that include neoplastic (primary and secondary), non-neoplastic masses and pseudomasses. The clinical presentation of cardiac tumors is highly variable and depends on several factors such as size, location, relation with other structures and mobility. The presumptive diagnosis is made based on a preliminary non-invasive diagnostic work-up due to technical difficulties and risks associated with biopsy, which is still the diagnostic gold standard. The findings should always be interpreted in the clinical context to avoid misdiagnosis, particularly in specific conditions (e.g., infective endocarditis or thrombi). The modern multi-modality imaging techniques has a key role not only for the initial assessment and differential diagnosis but also for management and surveillance of the cardiac masses. Cardiovascular magnetic resonance (CMR) allows an optimal non-invasive localization of the lesion, providing multiplanar information on its relation to surrounding structures. Moreover, with the additional feature of tissue characterization, CMR can be highly effective to distinguish pseudomasses from masses, as well as benign from malignant lesions, with further differential diagnosis of the latter. Although histopathological assessment is important to make a definitive diagnosis, CMR plays a key role in the diagnosis of suspected cardiac masses with a great impact on patient management. This literature review aims to provide a comprehensive overview of cardiac masses, from clinical and imaging protocol to pathological findings.     

Expression of the human MUC1 mucin cDNA in a hamster pancreatic tumor cell line HP-1.

A full length cDNA for the human mucin gene, MUC1, under the control of human beta actin promoter, was transfected into a carcinogen induced hamster pancreatic ductal tumor cell line, HP-1. Transfectants were selected by resistance to geneticin. Integration of the foreign human MUC1 cDNA occurred at multiple sites in the genome of HP-1. Northern blot analysis showed MUC1 expression in cells transfected with MUC1 cDNA placed in the correct orientation, but not in control cells (HP-1 cells transfected with vector alone, or with the MUC1 cDNA placed in the antisense orientation). Western blot analysis using monoclonal antibody HMFG-2, which is reactive with the MUC1 protein, showed results consistent with the Northern blot data. Positive immunoperoxidase staining using HMFG-2 was seen in HP-1 cells transfected with MUC1 cDNA but not with untransfected or HP-1 control cells. The integration of human MUC1 mucin gene in HP-1 cells caused no significant change in the growth rate of HP-1 cells in vitro, but resulted in an enhanced growth rate for xenografts of MUC1 transfected HP-1 cells grown in nude mice.     

Regulation of phosphatidylinositol turnover in brain synaptoneurosomes: stimulatory effects of agents that enhance influx of sodium ions.

Norepinephrine and carbamoylcholine stimulate accumulation of [3H]inositol phosphates from [3H]inositol-labeled guinea pig cerebral cortical synaptoneurosomes through interaction with alpha 1-adrenergic and muscarinic receptors, respectively. In addition to such agonist, a variety of natural products that affect voltage-dependent sodium channels can markedly stimulate accumulation of [3H]inositol phosphates. These include alkaloids that activate sodium channels, such as batrachotoxin, veratridine, and aconitine; peptide toxins that alter activation or slow inactivation of sodium channels, such as various scorpion toxins from Leiurus, Centruroides, and Tityus species; and agents that cause repetitive firing of sodium channel-dependent action potentials, such as pyrethroids and pumiliotoxin B. Ouabain, and agent that will increase accumulation of internal sodium by inhibition of Na+, K+-ATPase, also stimulates formation of [3H]inositol phosphates, as does monensin, a sodium ionophore. Tetrodotoxin and saxitoxin, specific blockers of voltage-dependent sodium channels, prevent or reduce the stimulatory effects of sodium channel agents and ouabain on phosphatidylinositol turnover, while having lesser or no effect, respectively, on receptor-mediated or monensin-mediated stimulation. Removal of extracellular sodium ions markedly reduces stimulatory effects of sodium channel agents, while removal of extracellular calcium ions with EGTA blocks both receptor-mediated and sodium channel agent-mediated phosphatidylinositol turnover. The results provide evidence for a hitherto unsuspected messenger role for sodium ions in excitable tissue, whereby neuronal activity and the resultant influx of sodium will cause activation of phospholipase systems involved in hydrolysis of phosphatidylinositols, thereby generating two second messengers, the inositol phosphates, which mobilize calcium from internal stores, and the diacylglycerols, which activate protein kinase C.     

Multimodality imaging in COVID-19 patients: A key role from diagnosis to prognosis

The integrated clinical, laboratory and ultrasound approach is essential for the diagnosis, evaluation and monitoring of the patient's therapy in coronavirus disease 2019 pneumonia. The ideal imaging approach in this context is not yet well defined. Chest X-ray is characterized by low sensitivity in identifying earlier lung changes. The "bedside" pulmonary ultrasound has an undeniable series of advantages in the patient at high infectious risk and can provide incremental data in the respiratory intensive care for the serial control of the individual patient as well as for the home delivery of the stabilized subjects. Pulmonary computed tomography shows high sensitivity but should not be routinely performed in all patients, because in the first 48 h it can be absolutely negative and in the late phase the imaging findings may not change the therapeutic approach. Echocardiography should be limited to patients with hemodynamic instability to assess ventricular function and pulmonary pressures.