Kidney Cadmium Concentrations in an Urban Sri Lankan Population: an Autopsy Study.

Contamination and bioaccumulation of toxic heavy metals in our geo-environment is a growing public health concern. Human biomonitoring is an essential step in assessing the population risk of chronic exposure to environmental contaminants. Whole kidneys collected from a cohort of 92 deceased individuals undergoing forensic autopsies in Colombo, Sri Lanka, were analysed for cadmium (Cd) bioaccumulation using ICP-MS. Mean age of the population was 55.4 ± 15.4 years. Mean and median renal Cd concentrations of the total population were 4.38 and 2.60 µg g-1 w/w, respectively, which were below estimated toxic ranges. Males accumulated higher levels of Cd than females (p = 0.377). Cd concentrations were higher in the < 60 age group than the > 60 age group (p = 0.92), while the highest levels were reported in 51-60 age group. However, no significant correlation was found between renal Cd concentration and age (Æ®b = - 0.005, p = 0.94). Individuals who smoked, chewed betel or consumed alcohol were found to have elevated renal Cd concentrations in comparison to those who did not use these substances. This is the largest autopsy study on renal Cd bioaccumulation in Sri Lanka, and the findings do not indicate a high exposure risk to environmental Cd contamination at present.

Increased Intensity Of PCR Testing Reduced COVID-19 Transmission Within Countries During The First Pandemic Wave.

Experts agree that reverse transcription-polymerase chain reaction (PCR) testing is critical in controlling coronavirus disease 2019 (COVID-19), but decision makers disagree on how much testing is optimal. Controlling for interventions and ecological factors, we used linear regression to quantify testing's impact on COVID-19's average reproduction number, which represents transmissibility, in 173 countries and territories (which account for 99 percent of the world's COVID-19 cases) during March-June 2020. Among interventions, PCR testing had the greatest influence: a tenfold increase in the ratio of tests to new cases reported reduced the average reproduction number by 9 percent across a range of testing levels. Our results imply that mobility reductions (for example, shelter-in-place orders) were less effective in developing countries than in developed countries. Our results help explain how some nations achieved near-elimination of COVID-19 and the failure of lockdowns to slow COVID-19 in others. Our findings suggest that the testing benchmarks used by the World Health Organization and other entities are insufficient for COVID-19 control. Increased testing and isolation may represent the most effective, least costly alternative in terms of money, economic growth, and human life for controlling COVID-19.

EBV-associated primary CNS lymphoma occurring after immunosuppression is a distinct immunobiological entity.

Primary central nervous system lymphoma (PCNSL) is confined to the brain, eyes, and cerebrospinal fluid without evidence of systemic spread. Rarely, PCNSL occurs in the context of immunosuppression (eg, posttransplant lymphoproliferative disorders or HIV [AIDS-related PCNSL]). These cases are poorly characterized, have dismal outcome, and are typically Epstein-Barr virus (EBV)-associated (ie, tissue-positive). We used targeted sequencing and digital multiplex gene expression to compare the genetic landscape and tumor microenvironment (TME) of 91 PCNSL tissues all with diffuse large B-cell lymphoma histology. Forty-seven were EBV tissue-negative: 45 EBV- HIV- PCNSL and 2 EBV- HIV+ PCNSL; and 44 were EBV tissue-positive: 23 EBV+ HIV+ PCNSL and 21 EBV+ HIV- PCNSL. As with prior studies, EBV- HIV- PCNSL had frequent MYD88, CD79B, and PIM1 mutations, and enrichment for the activated B-cell (ABC) cell-of-origin subtype. In contrast, these mutations were absent in all EBV tissue-positive cases and ABC frequency was low. Furthermore, copy number loss in HLA class I/II and antigen-presenting/processing genes were rarely observed, indicating retained antigen presentation. To counter this, EBV+ HIV- PCNSL had a tolerogenic TME with elevated macrophage and immune-checkpoint gene expression, whereas AIDS-related PCNSL had low CD4 gene counts. EBV-associated PCNSL in the immunosuppressed is immunobiologically distinct from EBV- HIV- PCNSL, and, despite expressing an immunogenic virus, retains the ability to present EBV antigens. Results provide a framework for targeted treatment.