Proposal for a screening questionnaire for detecting habitual mouth breathing, based on a mouth-breathing habit score.

BACKGROUND: When mouth breathing becomes habitual, it can cause sleep disorders and abnormal maxillofacial growth, thus early detection of habitual mouth breathing is important. We created a questionnaire for early detection of habitual mouth breathing using a score based on a spectrum of factors found to be characteristic of mouth breathers. METHODS: First, a draft 50-question questionnaire was given to 101 random dental clinic patients, classified by dental professionals into habitual mouth breathers (n = 28) and nose breathers (n = 73). The 10 questions that significantly differentiated mouth and nose breathers (p < 0.05) were identified from this questionnaire. These questions, regarding nasal obstruction, open mouth at rest, awareness of mouth breathing, gum swelling and dental staining of the front teeth, bad breath, maxillary protrusion, nasal obstruction in childhood, bottle-feeding, and history of asthma, formed the basis for a second questionnaire. This second survey was completed by another 242 participants, separately classified into mouth breathing (n = 26), suspected mouth breathing (n = 40), and nose breathing groups (n = 176). RESULTS: Receiver operating characteristic curve analysis of the resulting mouth breathing habit scores, representing the responses to the 10-question survey, showed moderate checklist diagnosability. Sensitivity of cut-off values was 61.5% (specificity 92.0%) for the mouth-breathing group, and 77.5% (specificity 56.3%) for the suspected mouth-breathing group. Information was also obtained from visual assessment of maxillofacial characteristics. We found that the mouth-breathing and suspected mouth-breathing groups showed significantly high odds ratios for 7 items: discomfort while breathing and increased chin muscle tonus with lip closure, maxillary protrusion, tongue thrust, open mouth at rest, open bite, and childhood asthma. For 94.6% of the nose breathing group, ≥1 of these items applied. CONCLUSIONS: These findings were then used together to create a sample screening form. We believe that screening of this kind can facilitate more accurate diagnosis of habitual mouth breathing and contribute to its early detection.

A Phase I, Randomized, Controlled Clinical Study of CC-11050 in People Living With HIV With Suppressed Plasma Viremia on Antiretroviral Therapy (APHRODITE).

OBJECTIVE: Phosphodiesterase 4 inhibitors (PDE4i) are novel anti-inflammatory medications that have been approved for rheumatologic diseases and have been tested as host-directed therapy in tuberculosis. We examined the safety of CC-11050, a potent PDE4i in people living with HIV (PLWH) with suppressed HIV plasma viremia. We hypothesized that CC-11050 could be used to modulate HIV-related inflammation. METHOD: Thirty PLWH on antiretroviral therapy (ART) ≥ 1 year with suppressed HIV viremia were enrolled and randomized 2:1 to 12 weeks of CC-11050 200mg twice daily or placebo with follow-up at weeks 2, 4, 8, 12, and 16. Primary endpoint was safety. Secondary endpoints were the effect of CC-11050 on cytokines, monocyte, and T-cell activation and potential pharmacokinetic interaction between CC-11050 and Efavirenz (EFV). RESULTS: At baseline, median age was 49.5 years and CD4 count 459 cells/µL. Most frequent adverse events (grade 1 and 2 only) in CC-11050 group were headache, diarrhea, nausea, cough, nasal congestion, and restlessness. Over a 12-week period, the CC-11050 group had lower level of IL-8, adjusted for baseline level, group, and week (0.72-fold, P = .02), lower percentage of NK cells (0.87-fold, P = .02) and higher IL-6 level (1.48-fold, P = .03) compared to placebo (0.87-fold, P = .02). CC-11050 and EFV co-administration did not reveal any pharmacokinetic interaction. CONCLUSIONS: CC-11050 was well tolerated in PLWH, without affecting CD4 counts or plasma viremia, and led to a decrease in NK cells and plasma IL-8 level after 12-weeks of administration. Further study will be needed to elucidate the efficacy of CC-11050 as potential anti-inflammatory adjuvant strategy in HIV.

Aldosterone inhibits endothelial morphogenesis and angiogenesis through the downregulation of vascular endothelial growth factor receptor-2 expression subsequent to peroxisome proliferator-activated receptor gamma.

Angiogenesis plays a pivotal role in cardiovascular diseases such as ischemic heart disease, limb ischemia and heart failure, and has recently been shown to mediate various biological activities related to the pathogenesis of these diseases. In the present study, we evaluated the role of aldosterone in angiogenesis. Tube formation assay on Matrigel using human umbilical vein endothelial cells (HUVEC) revealed that aldosterone inhibited endothelial morphogenesis in a manner sensitive to eplerenone, a selective mineralocorticoid receptor antagonist. The anti-angiogenic effect of aldosterone was further confirmed by an in vivo angiogenesis assay using a Matrigel plug model in mice. Reverse transcription-mediated polymerase chain reaction and immunoblotting demonstrated that aldosterone downregulated the expression levels of vascular endothelial growth factor receptor-2 (VEGFR-2) and peroxisome proliferators-activated receptor gamma (PPAR gamma). VEGFR-2 expression was found to be enhanced in response to PPAR gamma activation by troglitazone, and attenuated by GW9662, a specific antagonist of PPAR gamma. In the tube formation assay, endothelial morphogenesis was stimulated by troglitazone, and inhibited by GW9662, indicating that PPAR gamma activation mediates positive regulation of angiogenesis through enhancement of VEGFR-2 expression. These data suggest that aldosterone inhibits angiogenesis through VEGFR-2 downregulation, subsequent to, at least in part, attenuation of PPAR gamma expression. The present findings provide a new insight into the possible therapeutic application of mineralocorticoid receptor blockade to various cardiovascular diseases.

A patient with wegener granulomatosis and intraventricular hemorrhage.

We report a case of intraventricular hemorrhage (IVH) in a 27-year-old man with Wegener granulomatosis (WG), successfully treated with corticosteroids and cyclophosphamide. Neurologic manifestations occur in 22%-54% of patients with WG, with cerebral vasculitis in less than 5%. Only 2 cases of IVH associated with WG have been reported at autopsy. This is the first reported case of in situ IVH associated with WG in a patient who survived. In patients with WG who present with neurologic manifestations, cerebral vasculitis with secondary intracranial hemorrhage should be considered, as these patients are often resistant to immunosuppressive therapies and may present with normal angiograms.