Chromothripsis in lipoblastoma: second reported case with complex PLAG1 rearrangement.

Lipoblastomas (LPBs) are rare benign neoplasms derived from embryonal adipose that occur predominantly in childhood. LPBs typically present with numeric or structural rearrangements of chromosome 8, the majority of which involve the pleomorphic adenoma gene 1 (PLAG1) proto-oncogene on chromosome 8q12. Here, we report on a LPB case on which showed evidence of chromothripsis. This is the second reported case of chromothripsis in LPB.

Merkel cell carcinoma presenting as a malignant pleural effusion post-COVID-19 hospitalization: A case report and literature review.

Merkel cell carcinoma (MCC) is a rare, highly aggressive neuroendocrine carcinoma of the skin, associated with immunosuppression, UV light exposure, and the Merkel cell polyomavirus (MCPyV). Cases of metastatic MCC diagnosed in body fluid cytology are extremely rare; only five cases have been reported previously in the English literature. We present a case of a 65-year-old male with acute respiratory failure and an enlarged right pleural effusion. He had two hospitalizations for COVID-19 pneumonia 2 months prior, for which he received steroid treatment and tocilizumab. Emergent thoracentesis was done, with pleural fluid sent for cytologic evaluation. Both the Papanicolaou stained ThinPrep slide and cell block demonstrated clusters of predominantly small to medium sized blue round cells with hyperchromatic nuclei, scant cytoplasm and fine chromatin, in a background of rare mesothelial cells, macrophages and numerous lymphocytes. Tumor cells were positive for CD56, chromogranin, synaptophysin, SAT2B, MCPyV, and CK20 in perinuclear dot like pattern, while negative for TTF-1 and CD45 immunostains. Ki67 proliferative index was approximately 40%. The patient had a history of MCC of the right ulnar forearm 4 years before the current presentation, which was unknown to us at the time of cytologic evaluation. To the best of our knowledge, this is the sixth case of metastatic MCC diagnosed by fluid cytology and the first reported in a patient receiving immunosuppressive treatment for COVID-19. Further reporting of such cases may increase awareness, especially when prior history is not readily available, such as in our case.

Geographic variation in the growth status of indigenous school children and youth in Mexico.

OBJECTIVE: To analyze variation in the growth status of indigenous children and youth attending bilingual schools, escuelas albergues, for the indigenous population in México. MATERIALS AND METHODS: The children and youth attended escuelas albergues in 1,009 localities in 21 Mexican states in 2012. Heights and weights of 31,448 boys and 27,306 girls 6-18 years of age were measured by trained staff at each school; the BMI was calculated. The students were divided into five geographic regions for analysis: North, Central, South-Gulf, South-Pacific, and South-Southeast. Growth status was compared to United States reference percentiles (P). RESULTS: Mean heights of children and youth from the five regions varied between P10 and P5 of the reference until about 13 years (girls) and 14 years (boys); subsequently, heights were ≤P5. Mean weights in both sexes were at P25 of the reference between 6 and 12 years, and then varied between P25 and P10 in boys and were ≥P25 in girls. Given the elevated weights relative to heights compared to the reference, mean BMIs of indigenous boys and girls were at or above the reference medians. Children and youth in the North and Central regions were, on average, taller than those in the South-Pacific and South-Southeast regions, while heights of those in the South-Gulf region were generally intermediate. In contrast, mean weights and BMIs differed negligibly among the regions. CONCLUSIONS: The geographic gradient in heights of indigenous children and youth was consistent with a north-to-south pattern noted among indigenous adults in studies spanning 1898 through 2013. Variation in height among children and youth likely reflected ethnic-specific and geographic variation interacting with economic and nutritional factors.

Biomonitoring of Metals, Polybrominated Diphenyl Ethers, Polychlorinated Biphenyls, and Persistent Pesticides in Vietnamese Female Electronic Waste Recyclers.

OBJECTIVE: Electronic waste is increasing. It is frequently recycled in developing countries. This is the first study to report metals, polybrominated diphenyl-ethers (PBDEs), polychlorinated biphenyls (PCBs), 2,2-bis(4-chlorophenyl)-1,1,1-trichloroethane (p,p'-DDT), and p,p'-DDE concentrations in female e-waste workers. METHODS: Female Vietnamese recyclers and non-recyclers were studied. Metals and halogenated organics were measured in blood and urine, and compared with levels in women in the US National Health and Nutrition Examination Survey (NHANES). RESULTS: Recyclers had higher serum PBDE than nonrecyclers. PCB-138/158 and PCB-153 were higher in 18 to less than 38-year-old nonrecyclers. Median urinary arsenic in both cohorts was six to seven-fold higher than NHANES. Median lead in blood and urine was 40% to 60% higher in recyclers than nonrecyclers. Lead in nonrecyclers was four to six-fold higher than NHANES. Both cohorts had higher arsenic and mercury than NHANES. CONCLUSION: Occupational exposure to PBDEs and lead occurred in recyclers. Environmental exposure to arsenic, lead, and mercury occurred in both cohorts. Occupational and environmental remediation are recommended.

MicroRNA group disorganization in aging.

Among non-coding RNAs, microRNAs may be one of the best known subgroups, due to their unique function of negatively controlling gene expression, by either degrading target messages or binding to their 3'-untranslated region to inhibit translation. Thus gene expression can be repressed through post-transcriptional regulation, implemented as a 'dimmer switch', in contrast to the all-or-none mode of suppression. Work from our laboratory and others shows that during aging, dysregulated expression of microRNAs generally occurs in groups, suggesting that their actions may be functionally coordinated as a 'pack' by common transcriptional regulators; the accumulation of these 'pack' disorganizations may be the underlying culprit contributing to the pathoetiology of many age-dependent disease states. The fact that many microRNAs are coordinated in their expression, due to either the close proximity of their genomic locations or sharing the same transcriptional regulation, suggests that future strategies for correcting age-dependent microRNA disorganization may need to involve a system biology, rather than a reductionist, approach. Therefore, understanding age-dependent changes of microRNA expression in 'packs' may open an entirely new frontier, i.e. how particular groups of non-coding RNAs, functioning together, contribute to mechanisms regulating aging and longevity.

LRRK2 modulates vulnerability to mitochondrial dysfunction in Caenorhabditis elegans.

Mutations in leucine-rich repeat kinase 2 (LRRK2) cause autosomal-dominant familial Parkinson's disease. We generated lines of Caenorhabditis elegans expressing neuronally directed human LRRK2. Expressing human LRRK2 increased nematode survival in response to rotenone or paraquat, which are agents that cause mitochondrial dysfunction. Protection by G2019S, R1441C, or kinase-dead LRRK2 was less than protection by wild-type LRRK2. Knockdown of lrk-1, the endogenous ortholog of LRRK2 in C. elegans, reduced survival associated with mitochondrial dysfunction. C. elegans expressing LRRK2 showed rapid loss of dopaminergic markers (DAT::GFP fluorescence and dopamine levels) beginning in early adulthood. Loss of dopaminergic markers was greater for the G2019S LRRK2 line than for the wild-type line. Rotenone treatment induced a larger loss of dopamine markers in C. elegans expressing G2019S LRRK2 than in C. elegans expressing wild-type LRRK2; however, loss of dopaminergic markers in the G2019S LRRK2 nematode lines was not statistically different from that in the control line. These data suggest that LRRK2 plays an important role in modulating the response to mitochondrial inhibition and raises the possibility that mutations in LRRK2 selectively enhance the vulnerability of dopaminergic neurons to a stressor associated with Parkinson's disease.