Intermediate hypocretin-1 cerebrospinal fluid levels and typical cataplexy: their significance in the diagnosis of narcolepsy type 1

Study ObjectivesThe diagnosis of narcolepsy type 1 (NT1) is based upon the presence of cataplexy and/or a cerebrospinal fluid (CSF) hypocretin-1/orexin-A level ≤ 110 pg/mL. We determined the clinical and diagnostic characteristics of patients with intermediate hypocretin-1 levels (111–200 pg/mL) and the diagnostic value of cataplexy characteristics in individuals with central disorders of hypersomnolence.MethodsRetrospective cross-sectional study of 355 people with known CSF hypocretin-1 levels who visited specialized Sleep-Wake Centers in the Netherlands. For n = 271, we had full data on cataplexy type (“typical” or “atypical” cataplexy).ResultsCompared to those with normal hypocretin-1 levels (>200 pg/mL), a higher percentage of individuals with intermediate hypocretin-1 levels had typical cataplexy (75% or 12/16 vs 9% or 8/88, p < .05), and/or met the diagnostic polysomnographic (PSG) and Multiple Sleep Latency Test (MSLT) criteria for narcolepsy (50 vs 6%, p < .001). Of those with typical cataplexy, 88% had low, 7% intermediate, and 5% normal hypocretin-1 levels (p < .001). Atypical cataplexy was also associated with hypocretin deficiency but to a lesser extent. A hypocretin-1 cutoff of 150 pg/mL best predicted the presence of typical cataplexy and/or positive PSG and MSLT findings.ConclusionIndividuals with intermediate hypocretin-1 levels or typical cataplexy more often have outcomes fitting the PSG and MSLT criteria for narcolepsy than those with normal levels or atypical cataplexy. In addition, typical cataplexy has a much stronger association with hypocretin-1 deficiency than atypical cataplexy. We suggest increasing the NT1 diagnostic hypocretin-1 cutoff and adding the presence of clearly defined typical cataplexy to the diagnostic criteria of NT1. Clinical trial information: This study is not registered in a clinical trial register, as it has a retrospective database design.     

2'-deoxyguanosine, 2'-deoxycytidine, and 2'-deoxyadenosine adducts resulting from the reaction of tetrahydrofuran with DNA bases

A recent study showed that tetrahydrofuran (THF), a widely used solvent, is carcinogenic in experimental animals. Despite its carcinogenic activity, there is a paucity of information regarding cellular toxicity, biomolecular damage, and genotoxicity induced by THF. We describe here the structural characterization of adducts produced by the reaction of oxidized THF with 2'-deoxyguanosine (dGuo-THF 1 and dGuo-THF 2), 2'-deoxyadenosine (dAdo-THF), and 2'-deoxycytidine (dCyd-THF). Adducts were isolated from in vitro reactions by reverse-phase HPLC and fully characterized on the basis of spectroscopic measurements. The stable derivatives obtained by the reduction of adducts with NaBH(4) (the case of dGuo-THF 1, dCyd-THF, and dAdo-THF) and the stable adduct dGuo-THF 2 were used as standards for optimization of chromatographic separations for adduct detection in DNA through HPLC/ESI/MS-MS. Using this methodology, we successfully detected the four adducts in calf thymus DNA reacted with oxidized THF. The present study also provides evidence that rat liver microsomal monooxigenases oxidize THF to the reactive electrophilic compounds that are able to damage the DNA molecule, as indicated by a significant increase in adduct dGuo-THF 1 level when NADPH was added to the THF/microsomes/dGuo incubation mixtures. Our data point to DNA-THF adducts as possible contributing factors to the toxicological effects of THF exposure.     

Coenzyme Q-10 treatment of patients with a 7445A--->G mitochondrial DNA mutation stops the progression of hearing loss

CONCLUSION: CoQ 10 may be helpful in delaying the progression of hearing loss in patients with the 7445A-->G mitochondrial mutation. Objective. To assess the effect of an antioxidant drug (Coenzyme Q-10) on the hearing level of patients with the mitochondrial DNA 7445A-->G mutation and associated sensorineural hearing loss (SNHL). Material and methods. We identified three patients with bilateral non-syndromic SNHL harboring the mitochondrial 7445A-->G mutation. Two patients had a family history of hearing loss with a strong matrilineal inheritance. The other patient did not have a family history of hearing loss. Two patients (1 with familial and 1 with sporadic SNHL) received treatment with 75 mg of Coenzyme Q-10 (CoQ10) twice a day for 1 year. The remaining patient with a familial form of hearing loss did not agree to take the treatment. Average bone conduction pure-tone thresholds for 0.5, 1, 2 and 4 kHz were obtained before and after diagnosis of mitochondrial hearing loss, and before and after treatment with CoQ10. Results. CoQ10-treated patients did not show any additional deterioration of their SNHL after 12 (familial case) and 13 months (sporadic case). The progression rate of SNHL was 6 dB/year in the 2 years prior to initiation of treatment in the familial case who received CoQ10 treatment. One year after being diagnosed with mitochondrial hearing loss, the patient who refused CoQ10 treatment exhibited an 11-dB deterioration of his hearing thresholds. There were no side-effects related to treatment with CoQ10.     

Reimmunization of children immunized at 18 months of age with Haemophilus influenzae type b vaccine

We studied the response to reimmunization at 36 months of age with Haemophilus influenzae type b (Hib) polyribosylribitol phosphate (PRP) capsular polysaccharide vaccine. Children enrolled in the study had previously received PRP or PRP plus diphtheria and tetanus toxoids with pertussis vaccine at 18 months of age. A control group of children, who received a first dose at 36 months of age, was also studied. Ninety-five percent of children receiving a second dose of vaccine had a postimmunization anti-capsular antibody level of greater than or equal to 1 microgram/mL. In comparison, 70% of 36-month-old children who received their first dose of PRP had a postimmunization level greater than or equal to 1 microgram/mL (P = 0.09). The geometric mean titer at 37 months of age was 8.64 micrograms/mL in children who had received two doses of PRP vaccine, compared with 2.19 micrograms/mL in the group who received only one dose of PRP at 36 months of age (P = 0.04). We conclude that infants immunized at 17 to 19 months of age with PRP had an excellent immunologic response to reimmunization at 36 months of age.     

Consumption of vegetables and fruits and risk of subtypes of head–neck cancer in the Netherlands Cohort Study

There is limited prospective data on the relationship between consumption of vegetables and fruits and the risk of head–neck cancer (HNC) subtypes [i.e., oral cavity cancer (OCC), oro‐/hypopharyngeal cancer (OHPC) and laryngeal cancer (LC)]. Therefore, we investigated these associations within the Netherlands Cohort Study, in which 120,852 participants completed a 150‐item food frequency questionnaire at baseline in 1986. After 20.3 years of follow‐up, 415 cases of HNC (131 OCC, 88 OHPC, three oral cavity/pharynx unspecified or overlapping and 193 LC) and 3,898 subcohort members were available for case–cohort analysis using Cox proportional hazards models. Total vegetable and fruit consumption was inversely associated with risk of HNC overall [multivariable‐adjusted rate ratios for highest vs. lowest quartile: 0.61, 95% confidence interval (CI) 0.44–0.85, p trend 0.002] and all HNC subtypes, with the strongest associations for OCC. Total vegetable intake and total fruit intake were also associated with a decreased risk of HNC overall and HNC subtypes. No significant interaction was found between vegetable and fruit intake and alcohol consumption or cigarette smoking. In conclusion, in this large‐scale cohort study, consumption of vegetables and fruits was associated with a decreased risk of HNC overall and all subtypes. Consumption of vegetables and fruits (or of specific groups of them) may protect against HNC and its subtypes.     

Factors Contributing to Delay in Driving Licensure Among U.S. High School Students and Young Adults

PurposeMore teens delay in driving licensure (DDL). It is conceivable they miss Graduated Driver Licensing (GDL) safety benefits. We assessed prevalence, disparities, and factors associated with DDL among emerging adults.MethodsData used were from all seven waves (W1–7) of the NEXT Generation Health Study (W1 in 10th grade [2009–2010]). The outcome variable was DDL (long-DDL [delayed >2 years], intermediate-DDL [delayed 1–2 years] versus no-DDL), defined as participants receiving driver licensure ≥1 year after initial eligibility. Independent variables included sex, urbanicity, race/ethnicity, family structure, parental education, family affluence, parental monitoring knowledge, parent perceived importance of alcohol nonuse, and social media use. Logistic regressions were conducted.ResultsOf 2,525 participants eligible for licensure, 887 (38.9%) reported intermediate-DDL and 1,078 (30.1%) long-DDL. Latinos (adjusted odds ratio [AOR] = 2.5 vs. whites) and those with lower affluence (AOR = 2.5 vs. high) had higher odds of intermediate-DDL. Latinos (AOR = 4.5 vs. whites), blacks (AOR = 2.3 vs. whites), those with single parent (AOR = 1.7 vs. both biological parents), whose parents’ education was high school or less (AOR = 3.7 vs. bachelor+) and some college (AOR = 2.0 vs. bachelor+) levels, and those with lower affluence (AOR = 4.4 vs. high) had higher odds of long-DDL. Higher mother’s monitoring knowledge (AOR = .6) was associated with lower odds of long-DDL, but not intermediate-DDL.ConclusionsSome teens that DDL “age out” of protections afforded to them by GDL driver restrictions. Minority race/ethnicity, socioeconomic status, urbanicity, and parenting factors contribute to DDL. Further study of these factors and their individual/collective contributions to DDL is needed to understand potential unintended consequences of GDL, particularly in more vulnerable youth.     

Moving beyond “the Down Low”: A critical analysis of terminology guiding HIV prevention efforts for African American men who have secretive sex with men

HIV continues to affect African American populations in the United States at disproportionate levels. Recent reports have described potentially high-risk behaviors of African American men who identify as heterosexual but who engage in secretive sex with other men. These men have been referred to as being “on the Down Low,” and this terminology has been used to label subgroups of African American men and explain sexual risks for HIV infection in the African American community. In this paper, we argue that an uncritical use of this terminology for guiding public health and HIV prevention strategies can be problematic and counterproductive because it (a) stigmatizes and exoticizes secretive same-sex sexuality as a unique issue among African American men, and (b) ignores the social conditions under which HIV transmission occurs. We explore some historical roots contributing to current perspectives on African American men's sexuality, describe the use of the term “on the Down Low” and its application to same-sex behavior among African American men, and explain how this term can both clarify and potentially ambiguate efforts to address HIV risk among African American men. Recommendations for research and HIV prevention strategies are also provided.