Nonacid reflux episodes reaching the pharynx are important factors associated with cough

BACKGROUND: Gastroesophageal reflux is implicated in the pathogenesis of asthma and chronic cough. To date most studies have focused on acid reflux measured by pH below the upper esophageal sphincter (UES). The aim of this study was to assess the relationship between cough and reflux through the UES into the pharynx. METHODS: Thirty-seven patients with asthma (19) and chronic cough (18) were recruited from the respiratory clinic. Reflux was monitored using a combined multichannel intraluminal impedance and pH probe by detecting (1) bolus reflux episodes within the esophagus and in the pharynx and (2) acidic reflux episodes within the esophagus and in the pharynx. All acid suppressive therapy was stopped for at least 7 days before the study. Demonstration of cough being linked to reflux was achieved using the symptom association probability (SAP). This was calculated using a 2-minute association window between symptoms and bolus entry into the esophagus. SAP was considered positive if >95%. RESULTS: A positive SAP for cough was noted in 7/26 patients reporting symptoms on the day of monitoring. Compared with SAP-negative patients, SAP-positive patients had both a greater number [median (interquartile range), 5(2 to 8) vs. 2(0 to 4), P<0.05] and a higher proportion of reflux episodes crossing the UES into the pharynx [25%(14% to 28%) vs. 7% (2% to 14%), P<0.02]. There was no difference in the number of reflux episodes or acid exposure time in the distal esophagus between SAP-positive and SAP-negative patients. Only 1% to 2% of episodes were detected by the pharyngeal pH sensor. CONCLUSIONS: Impedance detected pharyngeal reflux episodes are important factors in symptom production in cough patients.

The special Sm core structure of the U7 snRNP: far-reaching significance of a small nuclear ribonucleoprotein

The polypeptide composition of the U7 small nuclear ribonucleoprotein (snRNP) involved in histone messenger RNA (mRNA) 3' end formation has recently been elucidated. In contrast to spliceosomal snRNPs, which contain a ring-shaped assembly of seven so-called Sm proteins, in the U7 snRNP the Sm proteins D1 and D2 are replaced by U7-specific Sm-like proteins, Lsm10 and Lsm11. This polypeptide composition and the unusual structure of Lsm11, which plays a role in histone RNA processing, represent new themes in the biology of Sm/Lsm proteins. Moreover this structure has important consequences for snRNP assembly that is mediated by two complexes containing the PRMT5 methyltransferase and the SMN (survival of motor neurons) protein, respectively. Finally, the ability to alter this polypeptide composition by a small mutation in U7 snRNA forms the basis for using modified U7 snRNA derivatives to alter specific pre-mRNA splicing events, thereby opening up a new way for antisense gene therapy.

The HIV care cascade in Switzerland: reaching the UNAIDS/WHO targets for patients diagnosed with HIV.

OBJECTIVES To describe the HIV care cascade for Switzerland in the year 2012. DESIGN/METHODS Six levels were defined: (i) HIV-infected, (ii) HIV-diagnosed, (iii) linked to care, (iv) retained in care, (v) on antiretroviral treatment (ART), and (vi) with suppressed viral load (VL). We used data from the Swiss HIV Cohort Study (SHCS) complemented by a nationwide survey among SHCS physicians to estimate the number of HIV-patients not registered in the cohort. We also used Swiss ART sales data to estimate the number of patients treated outside the SHCS network. Based on the number of patients retained in care, we inferred the estimates for levels (i) to (iii) from previously published data. RESULTS We estimate that (i) 15,200 HIV-infected individuals lived in Switzerland in 2012 (margins of uncertainty, 13,400-19,300). Of those, (ii) 12,300 (81%) were diagnosed, (iii) 12,200 (80%) linked, and (iv) 11,900 (79%) retained in care. Broadly based on SHCS network data, (v) 10,800 (71%) patients were receiving ART, and (vi) 10,400 (68%) had suppressed (<200 copies/ml) VLs. The vast majority (95%) of patients retained in care were followed within the SHCS network, with 76% registered in the cohort. CONCLUSIONS Our estimate for HIV-infected individuals in Switzerland is substantially lower than previously reported, halving previous national HIV prevalence estimates to 0.2%. In Switzerland in 2012, 91% of patients in care were receiving ART, and 96% of patients on ART had suppressed VL, meeting recent UNAIDS/WHO targets.