HLA‐A SNPs and amino acid variants are associated with nasopharyngeal carcinoma in Malaysian Chinese

Nasopharyngeal carcinoma (NPC) arises from the mucosal epithelium of the nasopharynx and is constantly associated with Epstein–Barr virus type 1 (EBV‐1) infection. We carried out a genome‐wide association study (GWAS) of 575,247 autosomal SNPs in 184 NPC patients and 236 healthy controls of Malaysian Chinese ethnicity. Potential association signals were replicated in a separate cohort of 260 NPC patients and 245 healthy controls. We confirmed the association of HLA‐A to NPC with the strongest signal detected in rs3869062 (p = 1.73 × 10^?9). HLA‐A fine mapping revealed associations in the amino acid variants as well as its corresponding SNPs in the antigen peptide binding groove (p_{HLA‐A‐aa‐site‐99} = 3.79 × 10^?8, p_rs1136697 = 3.79 × 10^?8) and T‐cell receptor binding site (p_{HLA‐A‐aa‐site‐145} = 1.41 × 10^?4, p_rs1059520 = 1.41 × 10^?4) of the HLA‐A. We also detected strong association signals in the 5′‐UTR region with predicted active promoter states (p_rs41545520 = 7.91 × 10^?8). SNP rs41545520 is a potential binding site for repressor ATF3, with increased binding affinity for rs41545520‐G correlated with reduced HLA‐A expression. Multivariate logistic regression diminished the effects of HLA‐A amino acid variants and SNPs, indicating a correlation with the effects of HLA‐A*11:01, and to a lesser extent HLA‐A*02:07. We report the strong genetic influence of HLA‐A on NPC susceptibility in the Malaysian Chinese.     

Intraventricular CNS lesions: A pictorial essay

Intraventricular lesions of the central nervous system (CNS) can present a diagnostic challenge due to a range of differential diagnoses and radiological appearances. Both CT and MRI imaging findings, in combination with location and patient's age, can help limit the differentials. This pictorial essay presents the salient radiological features, location and demographics of the more common intraventricular lesions of the brain.     

Prevalence and risk factors of depression in the elderly nursing home residents in Singapore

Objectives: Depression is a common health problem in elderly nursing home (NH) residents and is often under-recognized and under-treated. This study aimed to determine the prevalence rates of depression and identify the risk factors associated with depression in the elderly NH population in Singapore.

Methods: A sample of 375 residents in six NHs in Singapore, aged 55 years and above, was assessed with the Structural Clinical Interview (SCID), based on the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) criteria. The association of demographic, functional and health-related characteristics with depression was examined using multivariate logistic regression analyses.

Results: Overall point prevalence for depression in the elderly NH residents was found to be 21.1% (95% confidence intervals (CI): 17.1%–25.6%). The prevalence rate for minor depression in the elderly NH residents was 14.4% (95% CI: 11.1%–18.5%) and 6.7% (95% CI: 4.5%–9.8%) for major depression. Significant risk factors that were found to be associated with depression were length of stay for more than 2 years, known history of depression, pain, and no or lack of social contact.

Conclusion: The prevalence rates for depression were high among NH residents in Singapore. More attention is needed to care for the psychosocial needs of elderly NH residents in Singapore.     

The optimal short version of the Zarit Burden Interview for dementia caregivers: diagnostic utility and externally validated cutoffs

Objectives: Using a sample of dementia caregivers, we compared the diagnostic utility of the various short versions of the Zarit Burden Interview (ZBI) with the original scale to identify the most optimal one. Next, we established externally validated cutoffs for the various ZBI versions using probable depression cases as a reference standard.

Methods: Caregivers (N = 394; 236 males; Age_mean = 56 years) were administered the ZBI and a self-report depression measure. Participants who exceeded the cutoff for the latter were identified as probable depression cases. For each of the ZBI versions, a receiver operating characteristic (ROC) curve was plotted against probable depression cases. The area under these ROC curves between the short versions and the original were then compared using a non-parametric approach.

Results: Compared to the original ZBI, the AUROC were similar for the 6-item, 7-item, and two 12-item versions, but significantly worse for the other short variants. The sensitivity and specificity of the cutoffs for all ZBI versions ranged from 77.3% to 85.2% and 60.1% to 79.8%, respectively.

Conclusions: The original ZBI had good utility in identifying probable depression in caregivers, while the 6-item variant can be a useful alternative when short versions are preferred.     

Physiological effects of anterior repositioning splint on temporomandibular joint disc displacement: a quantitative analysis

Anterior repositioning splints (ARS) are used primarily for the management of temporomandibular joint (TMJ) anterior disc displacement with reduction (ADDwR). However, the exact physiological effects of ARS are still unclear. This study investigated the short and long‐term effects of ARS on disc and condyle angles/positions by metric analysis. Twenty‐two subjects diagnosed with ADDwR were recruited. Maxillary full‐coverage ARS were fabricated, and MRI of TMJs was obtained before splint treatment, immediate post‐insertion and 6 months after splint treatment. Disc–condyle relationship was determined by disc–condyle angle measurement. Disc and condyle positions were described as X‐Y coordinates with the summit of glenoid fossa as the origin of the coordinates. Thirty‐two TMJs were classified as ADDwR and 12 were normal. Upon ARS insertion, all TMJs with ADDwR got normal disc–condyle relationships. The condyles moved significantly forward and downward, while the discs moved significantly backward and upward. MRI at 6 months after treatment (without ARS insertion) indicated that only 40·6% (13/32) of the joints were maintained in the normal disc–condyle relationship. The majority of condyles returned to their pre‐treatment positions, while the discs generally moved anteriorly again. The use of ARS resulted in forward and downward condyle movement, and a concurrent backward movement of the disc resulting in ideal spatial disc–condyle relationship. The stability of this relationship, however, could not be maintained in the majority of TMJs upon ARS removal. Findings explain the good short‐term clinical outcomes with ARS and their relatively lower efficacy in the long term.