Acquired TNFRSF14 mutations in follicular lymphoma are associated with worse prognosis

Clinical correlative studies have linked 1p36 deletions with worse prognosis in follicular lymphoma (FL). In this study, we sought to identify the critical gene(s) in this region that is responsible for conferring inferior prognosis. BAC array technology applied to 141 FL specimens detected a minimum region of deletion (MRD) of ～97 kb within 1p36.32 in 20% of these cases. Frequent single-nucleotide polymorphism-detected copy-neutral loss of heterozygosity was also found in this region. Analysis of promoter CpGs in the MRD did not reveal differential patterns of DNA methylation in samples that differed in 1p36 status. Exon sequencing of MRD genes identified somatic alterations in the TNFRSF14 gene in 3 of 11 selected cases with matching normal DNA. An expanded cohort consisting of 251 specimens identified 46 cases (18.3%) with nonsynonymous mutations affecting TNFRSF14. Overall survival (OS) and disease-specific survival (DSS) were associated with the presence of TNFRSF14 mutation in patients whose overall treatment included rituximab. We further showed that inferior OS and DSS were most pronounced in patients whose lymphomas contained both TNFRSF14 mutations and 1p36 deletions after adjustment for the International Prognostic Index [hazard ratios of 3.65 (95% confidence interval, 1.35-9.878, P=0.011) and 3.19 (95% confidence interval, 1.06-9.57, P=0.039), respectively]. Our findings identify TNFRSF14 as a candidate gene associated with a subset of FL, based on frequent occurrence of acquired mutations and their correlation with inferior clinical outcomes.     

Determinants of exclusive breastfeeding in a cohort of primiparous periurban peruvian mothers

The authors aimed to identify factors associated with exclusive breastfeeding (EBF) among 117 Peruvian mothers planning to breastfeed exclusively. Data were collected on days 0 and 3, and months 1, 3, and 6. Exclusive breastfeeding status was evaluated with a 24-hour recall of infant diet. Exclusive breastfeeding rates were 74%, 72%, and 35% at 1, 3, and 6 months, respectively. At 3 months, lower maternal education, greater breastfeeding frequency (day 3), greater breast pain (day 3), and depot medroxyprogesterone acetate use (3 months) were associated with EBF, after adjusting for EBF intentions. At 6 months, greater infant birth weight and mother-not employed were associated with EBF, after controlling for EBF intentions. More educated and working mothers, and infants with lower birth weight should be targeted in interventions to promote EBF in urban Peru. Research is also warranted to explore the factors linking depot medroxyprogesterone acetate use and breast pain with EBF duration.     

Continuous Glucose Monitoring Decreases Hypoglycemia Avoidance Behaviors,but Not Worry in Parents of Youth With New Onset Type 1 Diabetes

Background:Existing research shows that hypoglycemia fear (HF) is common in parents of children with established type 1 diabetes (T1D). We examined parental HF in the T1D recent-onset period and evaluated whether continuous glucose monitoring (CGM) adoption relates to improved outcomes of parental HF.Methods:In TACKLE-T1D, a prospective study of five- to nine-year olds with recent-onset T1D, parents completed the Hypoglycemia Fear Survey-Parents (HFS-P) at baseline (T1) and 6 (T2) and 12 (T3) months post-baseline. The HFS-P measures worry about hypoglycemia (HFS-Worry score) as well as hypoglycemia avoidance behaviors (HFS-Behavior score). We recorded CGM start dates for youth during the same time period through medical record review.Results:Between T1 and T2, 31 youth (32.3%) initiated CGM therapy, and between T2 and T3, an additional 17 youth (17.7%) began using CGM, leaving 48 youth who never initiated CGM therapy (50%) in the recent-onset period. Parents reported moderate HFS-Worry scores at T1 (32.9 ± 11.9), which increased between T1 and T2 (37.6 ± 11.4, P < .001) and plateaued between T2 and T3 (37.7 ± 12.4, P = .89). In contrast, parental HFS-Behavior scores decreased between T1 (33.1 ± 5.8) and T2 (32.2 ± 6.0, P = .005) and plateaued between T2 and T3 (32.2 ± 6.0, P = .95). Baseline HFS-Behavior and Worry scores were associated with increased adoption of CGM between T1-T2 and T2-T3, respectively. Parents of children initiating CGM therapy between T1 and T2 showed the largest decrease in HFS-Behavior (P = .03).Conclusions:Initiating CGM therapy within the first 12 months of T1D may help reduce parents’ use of hypoglycemia avoidance behaviors, but has little effect on parents’ hypoglycemia worry.     

Learning to identify near-threshold luminance-defined and contrast-defined letters in observers with amblyopia

We assessed whether or not the sensitivity for identifying luminance-defined and contrast-defined letters improved with training in a group of amblyopic observers who have passed the critical period of development. In Experiment 1, we tracked the contrast threshold for identifying luminance-defined letters with training in a group of 11 amblyopic observers. Following training, six observers showed a reduction in thresholds, averaging 20%, for identifying luminance-defined letters. This improvement transferred extremely well to the untrained task of identifying contrast-defined letters (average improvement = 38%) but did not transfer to an acuity measurement. Seven of the 11 observers were subsequently trained on identifying contrast-defined letters in Experiment 2. Following training, five of these seven observers demonstrated a further improvement, averaging 17%, for identifying contrast-defined letters. This improvement did not transfer to the untrained task of identifying luminance-defined letters. Our findings are consistent with predictions based on the locus of learning for first- and second-order stimuli according to the filter-rectifier-filter model for second-order visual processing.     

Spectral-domain optical coherence tomography features of acute syphilitic posterior placoid chorioretinitis: the role of autoimmune response in pathogenesis

Purpose

Syphilis is an infectious disease that can cause a wide variety of ocular signs. One of the rarest manifestations of ocular syphilis is acute syphilitic posterior placoid chorioretinitis (ASPPC). We report on the spectral-domain optical coherence tomography (SD-OCT) features of a case diagnosed with unilateral ASPPC.

Methods

A 64-year-old man presented with a sudden loss of visual acuity (VA) in the right eye. His only clinical sign was a large, geographic, yellow-white lesion centered on the right fovea. Our patient was studied with SD-OCT on presentation and during follow-up, as well as with fluorescein and indocyanine green angiography, electrophysiological study, and serologic and autoimmune screening.

Results

Laboratory workup revealed positive serology for active syphilis and elevated anti-beta2 glycoprotein I antibodies. SD-OCT showed a marked distortion of both the choroidal and outer retinal architecture. After treatment, best-corrected VA improved to 20/25. Pattern electroretinography displayed a severe reduction of P50 amplitude, which improved in late follow-up. Six months after presentation, VA was 20/25 and anti-beta2 glycoprotein I antibodies returned to normal levels.

Conclusions

Our findings are compatible with immunologically mediated temporary physiological impairment of the neuroretina, since the changes seen by SD-OCT could not have normalized if they were due to anatomical injury. The results of our study provide clues to understanding the pathogenesis of this disease and allow us to define a characteristic temporal sequence of events in ASPPC.Key Words: Syphilis, Placoid, Chorioretinitis, Spectral-domain optical coherence tomography, Beta2 glycoprotein     

Observational assessment of family functioning in families with children who have type 1 diabetes mellitus

OBJECTIVE: Children with type 1 diabetes mellitus have a complex treatment regimen that includes insulin therapy and dietary requirements (e.g., matching insulin and carbohydrate intake). Previous research has shown that parents of children with type 1 diabetes mellitus report significant mealtime challenges and higher parenting stress compared to parents of healthy controls. The objective of the current study was to compare family functioning in children with type 1 diabetes mellitus (ages 2-8) to a matched, healthy control sample. Sixty-six families (33 diabetes; 33 controls) participated in a home visit at which their evening meal was videotaped. Tapes were then coded using the McMaster Interaction Coding System to objectively assess family functioning. RESULTS: Results indicated that families in the diabetes group demonstrated significantly poorer family functioning in a majority of areas (communication, affect management, family roles, overall functioning) compared to the healthy control sample. Additionally, families with lower socioeconomic status and families of male children evidenced poorer overall family functioning for both groups. CONCLUSIONS: Results also suggest that family-focused interventions for young children with type 1 diabetes should include components targeting family functioning in the areas of communication, affect management, and family roles.