Gene expression profiling of diffuse large B-cell lymphoma (DLBCL) has revealed biologically and prognostically distinct subgroups: germinal center B-cell-like (GCB), activated B-celllike (ABC) and primary mediastinal (PM) DLBCL. The BCL6 gene is often translocated and/or mutated in DLBCL. Therefore, we examined the BCL6 molecular alterations in these DLBCL subgroups, and their impact on BCL6 expression and BCL6 target gene repression. BCL6 translocations at the major breakpoint region (MBR) were detected in 25 (18.8%) of 133 DLBCL cases, with a higher frequency in the PM (33%) and ABC (24%) subgroups than in the GCB (10%) subgroup. Translocations at the alternative breakpoint region (ABR) were detected in five (6.4%) of 78 DLBCL cases, with three cases in ABC and one case each in the GCB and the unclassifiable subgroups. The translocated cases involved IgH and non-IgH partners in about equal frequency and were not associated with different levels of BCL6 mRNA and protein expression. BCL6 mutations were detected in 61% of DLBCL cases, with a significantly higher frequency in the GCB and PM subgroups (470%) than in the ABC subgroup (44%). Exon-1 mutations were mostly observed in the GCB subgroup. The repression of known BCL6 target genes correlated with the level of BCL6 mRNA and protein expression in GCB and ABC subgroups but not with BCL6 translocation and intronic mutations. No clear inverse correlation between BCL6 expression and p53 expression was observed. Patients with higher BCL6 mRNA or protein expression had a significantly better overall survival. The biological role of BCL6 in translocated cases where repression of known target genes is not demonstrated is intriguing and warrants further investigation.

We observed differences in associations between diet and t(14;18)-defined subgroups of NHL. These findings should be interpreted cautiously because of the small sample.

Cell cycle regulation and DNA repair following damage are essential for maintaining genome integrity. DNA damage activates checkpoints in order to repair damaged DNA prior to exit to the next phase of cell cycle. Recently, we have shown the role of Ada3, a component of various histone acetyltransferase complexes, in cell cycle regulation, and loss of Ada3 results in mouse embryonic lethality. Here, we used adenovirus-Cre-mediated Ada3 deletion in Ada3fl/fl mouse embryonic fibroblasts (MEFs) to assess the role of Ada3 in DNA damage response following exposure to ionizing radiation (IR). We report that Ada3 depletion was associated with increased levels of phospho-ATM (pATM), γH2AX, phospho-53BP1 (p53BP1) and phospho-RAD51 (pRAD51) in untreated cells; however, radiation response was intact in Ada3−/− cells. Notably, Ada3−/− cells exhibited a significant delay in disappearance of DNA damage foci for several critical proteins involved in the DNA repair process. Significantly, loss of Ada3 led to enhanced chromosomal aberrations, such as chromosome breaks, fragments, deletions and translocations, which further increased upon DNA damage. Notably, the total numbers of aberrations were more clearly observed in S-phase, as compared with G₁ or G₂ phases of cell cycle with IR. Lastly, comparison of DNA damage in Ada3fl/fl and Ada3−/− cells confirmed higher residual DNA damage in Ada3−/− cells, underscoring a critical role of Ada3 in the DNA repair process. Taken together, these findings provide evidence for a novel role for Ada3 in maintenance of the DNA repair process and genomic stability.

The t(14;18) chromosomal translocation is the most common cytogenetic abnormality in non-Hodgkin lymphoma (NHL), occurring in 70-90% of follicular lymphomas (FL) and 30-50% of diffuse large B-cell lymphomas (DLBCL). Previous t(14;18)-NHL studies have not evaluated risk factors for NHL defined by both t(14;18) status and histology. In this population-based case-control study, t(14;18) status was determined in DLBCL cases using fluorescence in situ hybridization on paraffinembedded tumor sections. Polytomous logistic regression was used to evaluate the association between a wide variety of exposures and t(14;18)-positive (N 5 109) and -negative DLBCL (N 5 125) and FL (N 5 318), adjusting for sex, age, race, and study center. Taller height, more lifetime surgeries, and PCB180 exposure were associated with t(14;18)-positivity. Taller individuals (third tertile vs. first tertile) had elevated risks of t(14;18)-positive DLBCL (odds ratio [OR] 5 1.8, 95% confidence interval [CI] 1.1-3.0) and FL (OR 5 1.4, 95%CI 1.0-1.9) but not t(14;18)-negative DLBCL. Similar patterns were seen for individuals with more lifetime surgeries (131 vs. 0-12 surgeries; t(14;18)-positive DLBCL OR 5 1.4, 95%CI 0.7-2.7; FL OR 5 1.6, 95%CI 1.1-2.5) and individuals exposed to PCB180 greater than 20.8 ng/g (t(14;18)-positive DLBCL OR 5 1.3, 95%CI 0.6-2.9; FL OR 5 1.7, 95%CI 1.0-2.8). In contrast, termite treatment and high alpha-chlordane levels were associated with t(14;18)-negative DLBCL only, suggesting that these exposures do not act through t(14;18). Our findings suggest that putative associations between NHL and height, surgeries, and PCB180 may be t(14;18)-mediated and provide support for case-subtyping based on molecular and histologic subtypes. Future efforts should focus on pooling data to confirm and extend previous research on risk factors for t(14;18)-NHL subtypes.Non-Hodgkin lymphoma (NHL) comprises a group of closely related yet heterogeneous diseases. 1,2 Except for severe immunosuppression, the risk factors for most NHLs remain largely unknown. 3,4 Findings from epidemiologic studies have increasingly suggested that risk factors for NHL may differ by histologic subtype. [3][4][5] Two recent studies have suggested that characterizing NHLs by the presence of the t(14;18)(q32;q21) chromosomal translocations may also have etiologic relevance. 6-11 For example, a number of pesticides have been associated with t(14;18)-positive NHL but not t(14;18)-negative NHL in both studies. 6,9 One of the most common cytogenetic

Background The emergence of the COVID-19 pandemic has affected the lives of many people, including medical students. The present study explored internet addiction and changes in sleep patterns among medical students during the pandemic and assessed the relationship between them. Methods A cross-sectional study was carried out in seven countries, the Dominican Republic, Egypt, Guyana, India, Mexico, Pakistan, and Sudan, using a convenience sampling technique, an online survey comprising demographic details, information regarding COVID-19, the Pittsburgh Sleep Quality Index (PSQI), and the Internet Addiction Test (IAT). Results In total, 2749 participants completed the questionnaire. Of the total, 67.6% scored above 30 in the IAT, suggesting the presence of an Internet addiction, and 73.5% scored equal and above 5 in the PSQI, suggesting poor sleep quality. Internet addiction was found to be significant predictors of poor sleep quality, causing 13.2% of the variance in poor sleep quality. Participants who reported COVID-19 related symptoms had disturbed sleep and higher internet addiction levels when compared with those who did not. Participants who reported a diagnosis of COVID-19 reported poor sleep quality. Those living with a COVID-19 diagnosed patient reported higher internet addiction and worse sleep quality compared with those who did not have any COVID-19 patients in their surroundings. Conclusion The results of this study suggest that internet addiction and poor sleep quality are two issues that require addressing amongst medical students. Medical training institutions should do their best to minimize their negative impact, particularly during the current COVID-19 pandemic.

A frequent chromosomal translocation in mature B-cell non-Hodgkin lymphoma affects band 3q27 and results in deregulation of the B-cell lymphoma 6 (BCL6) gene. Two breakpoint clusters have been described thus far, the major breakpoint region (MBR) and an alternative breakpoint region (ABR) that is located 245 - 285 kb 5' to BCL6. Translocation at the MBR predominates in diffuse large B-cell lymphoma, whereas translocation at the ABR is reported to be frequently associated with grade 3B follicular lymphoma. However, translocation at the ABR has not been studied in a large series of follicular lymphomas, particularly t(14;18)-negative follicular lymphomas. Therefore, we studied BLC6 rearrangements at the MBR and ABR by using break-apart fluorescence in situ hybridization (FISH) probes in 142 cases of follicular lymphomas, including 63 t(14;18)-negative and 79 t(14;18)-positive cases. Conventional cytogenetic (karyotype) analysis was also performed in 58 of the 63 t(14;18)-negative cases. BCL6 rearrangement was found in 26% of t(14;18)-negative and 19% of t(14;18)-positive follicular lymphoma. t(14;18)-negative cases showed a high frequency of rearrangement at the ABR (12%) with an ABR:MBR ratio of 0.86, compared to only 5% with an ABR:MBR ratio of 0.36 in the t(14;18)-positive cases. BCL6 rearrangements were found in all grades of follicular lymphoma but were most frequent in grade 3 t(14;18)-negative follicular lymphoma (60%). FISH analysis had a higher sensitivity for detecting BCL6 rearrangements than conventional cytogenetics. In conclusion, BCL6 rearrangements occur at a similar frequency in t(14;18)-negative follicular lymphoma and diffuse large B-cell lymphoma. However, t(14;18)-negative follicular lymphoma appears to have a higher frequency of rearrangement at the ABR compared with t(14;18)-positive follicular lymphoma and diffuse large B-cell lymphoma. Therefore, it is important to perform FISH analysis with ABR to determine possible involvement of BCL6 rearrangement in follicular lymphoma, especially in t(14;18)-negative cases.

Introduction: Adult idiopathic intracranial hypertension (IIH) is often linked to obesity, however, causes of IIH in children are not well understood. This project identifies potential risk factors and features of pediatric IIH. Methods: This study consisted of a retrospective chart review of patients ages 5–17 years who were seen at a tertiary care children’s hospital and diagnosed with IIH. Diagnostic criteria included the presence of papilledema, normal neurological exam, normal neuroimaging, normal cerebrospinal fluid composition, and an opening pressure of a lumbar puncture >28 mmHg. Results: Of the 26 cases of IIH, 19 met all diagnostic criteria for this study, while seven patients were probable IIH, as they lacked papilledema. Intracranial pressure ranged from 28 to 66 mmHg, with a mean of 40.23 mmHg (±10.74). Overall, 50.0% (95% CI: 29.9–70.1%) of IIH patients were obese, with patients 12 years of age and younger exhibiting an overall obesity rate of 30.7% and patients 13 years of age and older having an obesity rate of 69.2%. The overall allergy rate in this IIH patient population was 46.2% (95% CI: 26.6–66.6%). Conclusion: Obesity appears to have no association with IIH in younger cases, but it is a more common feature in older children. An autoimmune component may play a role in pediatric IIH, given the high rate of atopy observed in this pediatric IIH patient cohort. Because a diagnosis of IIH can have an absence of optic nerve edema, taking a detailed history and performing a thorough examination are keys to diagnosing IIH in the pediatric population.

PurposeChild abuse is a leading cause of death in infants, which is often associated with abusive head trauma (AHT). The purpose of this retrospective analysis was to identify ocular and systemic findings in confirmed cases of AHT and compare them to a group of non-abusive head trauma (NAHT) patients.Patients and methodsA retrospective chart review of 165 patients with accidental and non-accidental trauma admitted between 2013 and 2015 to Children’s Hospital and Medical Center in Omaha, NE, USA, was performed. Diagnosis of AHT was made after the analysis of ocular and systemic findings by various subspecialists. The NAHT group consisted of accidental trauma, abusive trauma without significant apparent head involvement on initial evaluation and unconfirmed AHT cases.ResultsOf the 165 presenting cases, 30 patients were diagnosed with AHT and 127 were diagnosed with NAHT. Ocular findings in AHT patients were significant for retinal hemorrhages (63%) and vitreous hemorrhages (37%), while NAHT patients had no ocular findings (p<0.001). Neuroimaging revealed subdural hemorrhages (SDHs) in 29 out of 30 AHT patients (97%) and in 27 out of 127 NAHT patients (21%). Seizures were present in 43% of AHT patients (n=13) and only in 8% of NAHT patients (n=10).ConclusionAHT has statistically significant findings of retinal and vitreous hemorrhages. The absence of diffuse retinal hemorrhages, however, does not preclude the AHT diagnosis as more than one-third of AHT patients lacked retinal hemorrhages. SDHs, loss of consciousness and history of seizures also have high correlation with a diagnosis of AHT.