A novel biallelic frameshift variant in C2orf69 causing developmental regression,seizures, microcephaly,autistic features,and hypertonia

Combined oxidative phosphorylation deficiency type 53 (COXPD53) is an autosomal recessive neurodevelopmental disorder (NDD) caused by homozygous variants in the gene C2orf69. Here, we report a novel frameshift variant c.187_191dupGCCGA, p.D64Efs*56 identified in an individual with clinical presentation of COXPD53 with developmental regression and autistic features. The variant c.187_191dupGCCGA, p.D64Efs*56 represents the most N-terminal part of C2orf69. Notable clinical features of COXPD53of the proband include developmental delay, developmental regression, seizures, microcephaly, and hypertonia. Structural brain defects of cerebral atrophy, cerebellar atrophy, hypomyelination, and thin corpus callosum were also observed. While we observe strong phenotypic overlap among affected individuals with C2orf69 variants, developmental regression and autistic features have not been previously described in individuals with COXPD53. Together, this case expands the genetic and clinical phenotypic spectrum of C2orf69-associated COXPD53.     

Efficacy of an eConsult service to cure hepatitis C in primary care

In 2016, an eConsult service was developed within a safety net health system to expand access to hepatitis C (HCV) treatment in the primary care setting. The eConsult system provides individualized treatment recommendations from specially trained primary care pharmacists and primary care physicians to primary care providers with less experience in the rapidly changing treatment of HCV. Since its launch, this service has had a large impact in expanding care to a largely homeless and low-income urban population within our health system. We now aim to evaluate its efficacy in curing HCV. In this retrospective cohort study, we describe rates of sustained virologic response 12 weeks after treatment completion (SVR12) for those who received primary care-based HCV treatment through the eConsult system with those who were treated in primary care independent of an eConsult from 2017 to 2019. We found there was no significant difference in the proportion of patients who achieved SVR12 between the two groups. Overall, >90% of patients who received treatment achieved SVR12. Approximately 40% of patients treated for HCV received an eConsult, suggesting utility of the eConsult in expanding access and coordinating treatment for patients within our network.     

Comparative analysis of different methods used for molecular characterization of Burkholderia cepacia complex isolated from noncystic fibrosis conditions

PurposeBurkholderia is a Gram-negative opportunistic bacterium capable of causing severe nosocomial infections. The aim of this study was to characterize Burkholderia cepacia complex and to compare different molecular methods used in its characterization.MethodsIn this study, 45 isolates of Burkholderia cepacia complex (Bcc) isolated from clinical cases were subjected to RAPD (Random amplified polymorphic DNA), recA-RFLP (Restriction fragment length polymorphism), 16SrDNA-RFLP, whole-cell protein analysis, recA DNA sequencing and biofilm assay.ResultsOf the 45 isolates tested, 97.7% were sensitive to ceftazidime, 82.2% were sensitive to Cotrimoxazole, 73.3% were sensitive to meropenem, 55.5% were sensitive to minocycline and 42.2% were sensitive to levofloxacin. Majority of the isolates harbored all the tested virulence genes except bpeA and cblA. The RAPD generated 11 groups (R1-R11), recA-RFLP 10 groups (A1-A10), 16SrRNA-RFLP 5 groups (S1–S5) and SDS-PAGE (Sodium Dodecyl Sulphate-Polyacrylamide gel electrophoresis) whole cell protein analysis revealed 12 groups (C1–C12). recA sequencing revealed that most of the isolates belonging to the genomovar III Burkholderia cenocepacia. Though all the methods are found to be efficient in differentiating Burkholderia spp., recA-RFLP was highly discriminatory at 96% similarity value. The study also identified a new strain Burkholderia pseudomultivorans for the first time in the country. Further, recA sequencing could identify the strains to species level. Majority of the multidrug-resistant strains also showed moderate to strong biofilm-forming ability, which further contributes to the virulence characteristics of the pathogens.ConclusionsThe study highlights the importance of combination of molecular methods to characterize Burkholderia cepacia complex. Molecular typing of these human pathogens yields important information for the clinicians in order to initiate the most appropriate therapy in the case of severe infections and to implement preventive measures for the effective control of transmission of Burkholderia spp.     

Noise-induced hearing loss,nationality, and blood pressure

Noise exposure has been associated with increased catecholamine production and blood pressure elevation in laboratory studies and in human volunteers. Epidemiologic studies have given conflicting results. In order to determine whether noise-induced hearing loss predicts a rise in blood pressure, we reviewed occupational medicine records in an occupational health center serving three companies where noise exposure is commonly found. Height, weight, blood pressure, and screening audiometry are obtained as par of routine occupational health screening, and the results of the screening visit are abstracted from written clinical records. The results of pure tone screening audiometry are reported in nonstandardized fashion (Normal, WNL, NAD, for example, for normal). We reviewed records from 1990 and 1991 inclusive. One investigator, blind to blood pressure status, assigned each record to “no hearing loss,” “not codable,” or “hearing loss assumed to be due to noise” on the basis of the written audiometry report. Hearing loss due to causes other than noise was considered not codable. No attempt was made to quantify severity of hearing loss. Two hundred and sixteen charts were excluded as “not codable,” 1,535 were classified as having no hearing loss, and 610 had some degree of hearing loss, most probably due to noise exposure. To adjust for confounding covariates, multiple regression analysis was used and indicated that hearing status improves the regression model for predicting diastolic blood pressure (p = 0.04), following age, nationality, body mass index (BMI), and month of testing, although the effect is small. Stratification by age and BMI revealed increased diastolic pressure in the group with hearing loss under age 45, regardless of obesity. Only age and BMI significantly improved the regression model for systolic blood pressure for the group as a whole. However, when large national groupings were evaluated independently, noise-induced hearing loss was associated with higher systolic and diastolic readings among Asians (n = 539) and Sub-Saharan Africans (n = 75), with correlation coefficients ranging from 0.18 to 0.32. Noise-induced hearing loss failed to improve the blood pressure regression model for Europeans/North Americans (n = 150), Arabs (n = 1020), or North Africans (n = 352). In this study, hearing loss attributed to industrial noise exposure appears to be associated with elevated resting blood pressure only within certain ethnic groups.     

Nested case-control study of occupational chemical exposures and prostate cancer in aerospace and radiation workers

BACKGROUND: To date, little is known about the potential contributions of occupational exposure to chemicals to the etiology of prostate cancer. Previous studies examining associations suffered from limitations including the reliance on mortality data and inadequate exposure assessment. METHODS: We conducted a nested case-control study of 362 cases and 1,805 matched controls to examine the association between occupational chemical exposures and prostate cancer incidence. Workers were employed between 1950 and 1992 at a nuclear energy and rocket engine-testing facility in Southern California. We obtained cancer-incidence data from the California Cancer Registry and seven other state cancer registries. Data from company records were used to construct a job exposure matrix (JEM) for occupational exposures to hydrazine, trichloroethylene (TCE), polycyclic aromatic hydrocarbons (PAHs), benzene and mineral oil. Associations between chemical exposures and prostate cancer incidence were assessed in conditional logistic regression models. RESULTS: With adjustment for occupational confounders, including socioeconomic status, occupational physical activity, and exposure to the other chemicals evaluated, the odds ratio for low/moderate TCE exposure was 1.3; 95%CI = 0.8 to 2.1, and for high TCE exposure was 2.1; 95%CI = 1.2 to 3.9. Furthermore, we noted a positive trend between increasing levels of TCE exposure and prostate cancer (P-value for trend = 0.02). CONCLUSION: Our results suggest that high levels of TCE exposure are associated with prostate cancer among workers in our study population.     

Ranibizumab as an adjunct to laser for macular edema secondary to branch retinal vein occlusion

Purpose:

To compare the safety, efficacy, and dosing regimen of intravitreal ranibizumab as an adjunct to laser therapy for the treatment of macular edema secondary to branch retinal vein occlusion (BRVO).

Materials and Methods:

Thirty eyes of 30 patients of BRVO of at least 6 weeks duration were randomized into three groups: Group 1 received grid laser treatment alone, Group 2 received a single dose of intravitreal injection of ranibizumab (0.5 mg / 0.05 ml) followed by grid laser treatment on 7^th day following injection, while Group 3 received three loading doses of intravitreal ranibizumab at monthly interval (i.e. 0, 1, & 2 months) + standard laser treatment 7 days after the 1^st injection. Outcome measure noted at 6 months follow-up were the improvement in best-corrected visual acuity (BCVA) and central macular thickness (CMT).

Results:

At 6 months follow-up, there was an average gain of 12 letters (P=0.05), 17.5 letters (P=0.05) and 19 letters (P=0.05) in groups 1, 2, and 3, respectively, with the decrease in CMT being 208.7 μm (P=0.05), 312.9 μm (P= 0.05) and 326.8 μm (P=0.05), respectively, in these groups. Gain in BCVA of more than 3 lines was noted in 1/10 patients in Group 1(10%) as compared to 3/10 (30%) and 4/10 (40%) patients in groups 2 and 3, respectively.

Conclusion:

The gain in BCVA and reduction in CMT were better with combination therapy (single- and triple- dose regimen) compared to grid laser alone. Single dose of intravitreal ranibizumab with grid laser seems to be an effective therapy.