Discovery and preclinical evaluation of anti-miR-17 oligonucleotide RGLS4326 for the treatment of polycystic kidney disease.

Autosomal dominant polycystic kidney disease (ADPKD), caused by mutations in either PKD1 or PKD2 genes, is one of the most common human monogenetic disorders and the leading genetic cause of end-stage renal disease. Unfortunately, treatment options for ADPKD are limited. Here we report the discovery and characterization of RGLS4326, a first-in-class, short oligonucleotide inhibitor of microRNA-17 (miR-17), as a potential treatment for ADPKD.

Assessment of cumulative health risk in the World Trade Center general responder cohort.

Background: Multiple comorbidities have been reported among rescue/recovery workers responding to the 9/11/2001 WTC disaster. In this study, we developed an index that quantifies the cumulative physiological burden of comorbidities and predicts life expectancy in this cohort.

Methods: A machine learning approach (gradient boosting) was used to model the relationship between mortality and several clinical parameters (laboratory test results, blood pressure, pulmonary function measures).

The association between body mass index and gastroesophageal reflux disease in the World Trade Center Health Program General Responder Cohort.

Background: There is increasing concern about the obesity epidemic in the United States. Obesity is a potential risk factor for a number of chronic diseases, including gastroesophageal reflux disease (GERD). This analysis examined whether body mass index (BMI) was associated with physician-diagnosed GERD in World Trade Center (WTC) general responders.

Sex differences in asthma and gastroesophageal reflux disease incidence among the World Trade Center Health Program General Responder Cohort.

Background: Asthma and gastroesophageal reflux disease (GERD) are two common conditions among the responders to the WTC attacks. This study examined whether the cumulative incidence rates of asthma and GERD differed by sex among 24,022 and 23,557 WTC responders, respectively.

Methods: Cox proportional hazards regression was used to examine the sex difference in the rate of onset of physician-diagnosed asthma or GERD, from 9/12/2001 through 12/31/2015.

Posttraumatic stress symptoms and smoking among World Trade Center disaster responders: A longitudinal investigation.

Purpose: The current longitudinal study examined posttraumatic stress disorder (PTSD) symptom severity in relation to smoking abstinence and reduction over time among responders to the World Trade Center (WTC) disaster.

Method: Participants were 763 police and 1881 non-traditional (e.g.

Posttraumatic stress disorder and the risk of respiratory problems in World Trade Center responders: longitudinal test of a pathway.

Objective: Posttraumatic stress disorder (PTSD) is associated with high medical morbidity, but the nature of this association remains unclear. Among responders to the World Trade Center (WTC) disaster, PTSD is highly comorbid with lower respiratory symptoms (LRS), which cannot be explained by exposure alone. We sought to examine this association longitudinally to establish the direction of the effects and evaluate potential pathways to comorbidity.

World Trade Center disaster and sensitization to subsequent life stress: A longitudinal study of disaster responders.

Purpose: The current study examined the role of World Trade Center (WTC) disaster exposure (hours spent working on the site, dust cloud exposure, and losing friend/loved one) in exacerbating the effects of post-disaster life stress on posttraumatic stress disorder (PTSD) symptoms and overall functioning among WTC responders.

Method: Participants were 18,896 responders (8466 police officers and 10,430 non-traditional responders) participating in the WTC Health Program who completed an initial examination between July, 2002 and April, 2010 and were reassessed an average of two years later.

Results: Among police responders, there was a significant interaction, such that the effect of post-disaster life stress on later PTSD symptoms and overall functioning was stronger among police responders who had greater WTC disaster exposure (β's=.

Post-disaster stressful life events and WTC-related posttraumatic stress, depressive symptoms, and overall functioning among responders to the World Trade Center disaster.

Background: The current study examined contributions of post-disaster stressful life events in relation to the maintenance of WTC-related posttraumatic stress, depressive symptoms, and overall functioning among rescue, recovery, and clean-up workers who responded to the September 11, 2001 World Trade Center (WTC) terrorist attacks.

Methods: Participants were 18,896 WTC responders, including 8466 police officers and 10,430 non-traditional responders (85.8% male; 86.

Cancer incidence in world trade center rescue and recovery workers, 2001-2008.

Background: World Trade Center (WTC) rescue and recovery workers were exposed to a complex mix of pollutants and carcinogens.

Objective: The purpose of this investigation was to evaluate cancer incidence in responders during the first 7 years after 11 September 2001.

Methods: Cancers among 20,984 consented participants in the WTC Health Program were identified through linkage to state tumor registries in New York, New Jersey, Connecticut, and Pennsylvania.

Persistence of multiple illnesses in World Trade Center rescue and recovery workers: a cohort study.

Background: More than 50,000 people participated in the rescue and recovery work that followed the Sept 11, 2001 (9/11) attacks on the World Trade Center (WTC). Multiple health problems in these workers were reported in the early years after the disaster. We report incidence and prevalence rates of physical and mental health disorders during the 9 years since the attacks, examine their associations with occupational exposures, and quantify physical and mental health comorbidities.

Development of methods to monitor ionization modification from dosing vehicles and phospholipids in study samples.

Two approaches to monitor the matrix effect on ionization in study samples were described. One approach is the addition of multiple reaction monitoring transitions to the bioanalytical methods to monitor the presence of known ionization modification-causing components of the matrix, for example, m/z 184→125 (or m/z 184→184) and m/z 133→89 may be used for phospholipids and polyethylene oxide containing surfactants, respectively. This approach requires no additional equipment and can be readily adapted for most method.

The effect of one versus two nights of in-laboratory continuous positive airway pressure titration on continuous positive airway pressure compliance.

Objective: To investigate continuous positive airway pressure (CPAP) compliance after one versus two nights of CPAP titration.

Method: A chart review and a telephone questionnaire interview were conducted in 110 sleep apnea patients who received one or two nights of CPAP titration. Of these patients, 78 followed through with phone interview.