Serum levels of B-cell activating factor are associated with a reduced risk of chronic lymphocytic leukemia.

IMPACT: Immune dysregulation is thought to contribute to chronic lymphocytic leukemia (CLL) risk, but biological mechanisms are unclear. We discovered that increased serum levels of B-cell activating factor (BAFF), an important regulator of B-cell maturation, were associated with a decreased risk of CLL, even >10 years after blood draw. Our findings suggest that BAFF could be a useful biomarker to assess risk among individuals at high risk, such as those with monoclonal b-cell lymphocytosis.

Antinuclear Antibodies Are Associated with an Increased Risk of Diffuse Large B-Cell Lymphoma.

Immune dysregulation is thought to increase the risk of non-Hodgkin lymphoma (NHL), but the evidence varies by subtype. We evaluated whether antinuclear antibodies (ANA), double-stranded DNA antibodies (anti-dsDNA), and extractable nuclear antigen antibodies (anti-ENA) were associated with the risk of common NHL subtypes in a nested case-control study. The autoantibodies were tested in serum collected years prior to NHL diagnosis in 832 cases and 809 controls from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Logistic regression was used to determine odds ratios (ORs) and 95% confidence intervals (95% CI) for the association with NHL risk. No association was observed between ANA positivity and NHL risk overall (OR: 1.18, 95% CI: 0.88-1.58); however, ANA positivity was associated with an increased risk of diffuse large B-cell lymphoma (DLBCL) (OR: 1.83, 95% CI: 1.15-2.91), with 19.7% of cases and 12.2% of controls testing positive. The presence of either anti-ENA or anti-dsDNA was associated with an increased risk of NHL (OR: 2.93, 95% CI: 1.18-7.28), particularly DLBCL (OR: 3.51, 95% CI: 1.02-12.0) and marginal zone lymphoma (OR: 8.86, 95% CI: 1.26-62.0). Our study demonstrates that autoantibodies are associated with an elevated risk of DLBCL, providing support for autoimmunity as a risk factor.

Changes in lifestyles and depressive symptom among patients with chronic diseases during COVID-19 lockdown.

This study aims to investigate the impact of COVID-19 lockdown on lifestyle behaviors and depressive symptom among patients with NCDs (noncommunicable diseases). We incorporated a COVID-19 survey to the WELL China cohort, a prospective cohort study with the baseline survey conducted 8-16 months before the COVID-19 outbreak in Hangzhou, China. The COVID-19 survey was carried out to collect information on lifestyle and depressive symptom during lockdown. A total of 3327 participants were included in the COVID-19 survey, including 2098 (63.1%) reported having NCDs at baseline and 1457 (44%) without NCDs. The prevalence of current drinkers decreased from 42.9% before COVID-19 lockdown to 23.7% during lockdown, current smokers from 15.9 to 13.5%, and poor sleepers from 23.9 to 15.3%, while low physical activity increased from 13.4 to 25.2%, among participants with NCDs (P < 0.05 for all comparisons using McNemar's test). Participants with NCDs were more likely than those without to have depressive symptom (OR, 1.30; 95% CI 1.05-1.61), especially among those who need to refill their medication during the COVID-19 lockdown (OR, 1.52; 95% CI 1.15-2.02). Our findings provide insight into the development of targeted interventions to better prepare patients with NCDs and healthcare system to meet the challenge of future pandemic and lockdown.

Maladaptive myelination promotes generalized epilepsy progression.

Activity-dependent myelination can fine-tune neural network dynamics. Conversely, aberrant neuronal activity, as occurs in disorders of recurrent seizures (epilepsy), could promote maladaptive myelination, contributing to pathogenesis. In this study, we tested the hypothesis that activity-dependent myelination resulting from absence seizures, which manifest as frequent behavioral arrests with generalized electroencephalography (EEG) spike-wave discharges, promote thalamocortical network hypersynchrony and contribute to epilepsy progression. We found increased oligodendrogenesis and myelination specifically within the seizure network in two models of generalized epilepsy with absence seizures (Wag/Rij rats and Scn8a+/mut mice), evident only after epilepsy onset. Aberrant myelination was prevented by pharmacological seizure inhibition in Wag/Rij rats. Blocking activity-dependent myelination decreased seizure burden over time and reduced ictal synchrony as assessed by EEG coherence. These findings indicate that activity-dependent myelination driven by absence seizures contributes to epilepsy progression; maladaptive myelination may be pathogenic in some forms of epilepsy and other neurological diseases.

Association between contact with a general practitioner and depressive symptoms during the COVID-19 pandemic and lockdown: a large community-based study in Hangzhou, China.

OBJECTIVES: To determine the association of general practitioner (GP) contact with depressive symptoms during the COVID-19 pandemic and lockdown in China. DESIGN: In April 2020, a follow-up survey was conducted on the basis of a baseline survey conducted between October 2018 and May 2019. SETTING: The survey was embedded in the Stanford Wellness Living Laboratory-China (WELL China) study, an ongoing prospective community-based cohort study during 2018-2019. PARTICIPANTS: The survey was conducted by telephone interview among 4144 adult urban residents participating in the WELL China study at baseline. We collected information on sociodemographic characteristics, depressive symptoms and GP contact during the lockdown period (February to March 2020). PRIMARY AND SECONDARY OUTCOME MEASURES: Depressive symptoms were measured using the WHO-Five Well-being Index, comprising five questionnaire items that briefly indicate psychological well-being. Logistic regression models were applied to assess the association between GP contact and depressive symptoms. RESULTS: In total, 3356 participants responded to the survey; 203 were excluded owing to missing data on depressive symptoms, leaving 3153 participants in the present study. During lockdown, 449 participants had GP contact. GP contact was significantly negatively associated with prevalent depressive symptoms (OR, 0.67; 95% CI 0.51 to 0.89; p<0.01) and incident depressive symptoms (OR 0.68; 95% CI 0.51 to 0.93; p<0.05). Stratified analysis showed a significant negative association between depressive symptoms and GP contact in individuals who were 45-64 years old (p<0.01), had a middle or high education (p<0.01) and had self-reported non-communicable diseases (p<0.05). CONCLUSIONS: Contact with GPs during the COVID-19 pandemic and lockdowns may have a negative association with depressive symptoms in community-dwelling populations. Given the possibility of further surges in COVID-19 infections, GPs' contact in the community should be enhanced.

Self-perception of speech changes in patients with Parkinson's disease following deep brain stimulation of the subthalamic nucleus.

Deep brain stimulation of the subthalamic nucleus (STN-DBS) improves the motor difficulties experienced by patients with Parkinson's disease (PD); however, the effects on speech are variable. In this study, patients rated their current post-surgery speech difficulties using the Voice Handicap Index (VHI) and used the same measure to retrospectively rate their pre-surgery speech. Scores pre- and post-surgery were also available on the UPDRS-III, and the patients' intelligibility was assessed by an independent listener. A control group of non-surgical patients with PD (medical group) also completed the VHI for comparison. VHI scores deteriorated equally in the two groups. However, the variability of the change scores in the surgical group was significantly greater than in the medical group. The correlation between the changes in the VHI and UPDRS scores for the surgical group was not significant. Correlations between the VHI scores and intelligibility were significant both before and after surgery, suggesting that patients accurately perceive their difficulties. The findings confirm the variability in the speech difficulties of patients following STN-DBS. The patients' ability to use the VHI offers a means of assessing the effects of their speech on their quality-of-life, and may be clinically useful post-STN-DBS.

Effects of contact location and voltage amplitude on speech and movement in bilateral subthalamic nucleus deep brain stimulation.

Subthalamic nucleus deep brain stimulation (STN-DBS) is particularly effective in improving limb symptoms in Parkinson's disease. However, speech shows a variable response. Contact site and amplitude of stimulation have been suggested as possible factors influencing speech. In this double blind study, we assessed 14 patients post bilateral STN-DBS, without medication. Six conditions were studied in random order as follows: stimulation inside the STN at low voltage (2 V) and at high voltage (4 V); above the STN at 2 V and at 4 V, at usual clinical parameters, and off-stimulation. The site of stimulation was defined on the postoperative stereotactic MRI data. Speech protocol consisted of the assessment of intelligibility of the dysarthric speech, maximum sustained phonation, and a 1-minute monologue. Movement was assessed using the UPDRS-III. Stimulation at 4 V significantly reduced the speech intelligibility (P = 0.004) independently from the site of stimulation. Stimulation at 4 V significantly improved the motor function. Stimulation inside the nucleus was significantly more effective than outside the nucleus (P = 0.0006). The significant improvement in movement coupled with significant deterioration in speech intelligibility when patients are stimulated inside the nucleus at high voltage indicates a critical role for electrical stimulation parameters in speech motor control.