Flexible bronchoscopic management of benign tracheal stenosis: long term follow-up of 115 patients

<p>Abstract</p> <p>Background</p> <p>Management of benign tracheal stenosis (BTS) varies with the type and extent of the disease and influenced by the patient's age and general health status, hence we sought to investigate the long-term outcome of patients with BTS that underwent minimally invasive bronchoscopic treatment.</p> <p>Methods</p> <p>Patients with symptomatic BTS were treated with flexible bronchoscopy therapeutic modalities that included the following: balloon dilatation, laser photo-resection, self-expanding metal stent placement, and High-dose rate endobronchial brachytherapy used in cases of refractory stent-related granulation tissue formation.</p> <p>Results</p> <p>A total of 115 patients with BTS and various cardiac and respiratory co-morbidities with a mean age of 61 (range 40-88) were treated between January 2001 and January 2009. The underlining etiologies for BTS were post - endotracheal intubation (N = 76) post-tracheostomy (N = 30), Wegener's granulomatosis (N = 2), sarcoidosis (N = 2), amyloidosis (N = 2) and idiopathic BTS (N = 3). The modalities used were: balloon dilatation and laser treatment (N = 98). Stent was placed in 33 patients of whom 28 also underwent brachytherapy. Complications were minor and mostly included granulation tissue formation. The overall success rate was 87%. Over a median follow-up of 51 months (range 10-100 months), 30 patients (26%) died, mostly due to exacerbation of their underlying conditions.</p> <p>Conclusions</p> <p>BTS in elderly patients with co-morbidities can be safely and effectively treated by flexible bronchoscopic treatment modalities. The use of HDR brachytherapy to treat granulation tissue formation following successful airway restoration is promising.</p

Characterization of greater middle eastern genetic variation for enhanced disease gene discovery

The Greater Middle East (GME) has been a central hub of human migration and population admixture. The tradition of consanguinity, variably practiced in the Persian Gulf region, North Africa, and Central Asia1-3, has resulted in an elevated burden of recessive disease4. Here we generated a whole-exome GME variome from 1,111 unrelated subjects. We detected substantial diversity and admixture in continental and subregional populations, corresponding to several ancient founder populations with little evidence of bottlenecks. Measured consanguinity rates were an order of magnitude above those in other sampled populations, and the GME population exhibited an increased burden of runs of homozygosity (ROHs) but showed no evidence for reduced burden of deleterious variation due to classically theorized ‘genetic purging’. Applying this database to unsolved recessive conditions in the GME population reduced the number of potential disease-causing variants by four- to sevenfold. These results show variegated genetic architecture in GME populations and support future human genetic discoveries in Mendelian and population genetics

EVs’ Integration Impact on the Reliability of Saudi Arabia’s Power System

This paper investigates the effect of involving electric vehicles (EVs) in the load profile on the generation system. The impact was studied from a reliability perspective on Saudi Arabia’s total generation system capacity as one source supplying the expected load for the year 2030. The EV load profile was then added. The outcomes were examined considering the gradual penetration percentage to the total load. The reliability indices measured are the loss of load probability (LOLP) and the expected energy not supplied (EENS). The results show that the estimated generation system of Saudi Vision 2030 will not withstand the estimated number of EVs without negatively impacting reliability. Similarly, the reliability assessment was conducted for the central region considering EVs in Riyadh City to verify Saudi Vision 2030. The results show that EV integration will greatly affect the electrical network’s reliability. Furthermore, a sensitivity analysis was conducted for Saudi Arabia and the central region to assess the generation system better. The study shows that investing in the generation infrastructure is essential to handle EV growth for the upcoming years. The work introduced in this paper will also help decision-makers make appropriate planning decisions in the future

The Combination of Radiation with PARP Inhibition Enhances Senescence and Sensitivity to the Senolytic, Navitoclax, in Triple Negative Breast Tumor Cells

Despite significant advances in the treatment of triple-negative breast cancer, this disease continues to pose a clinical challenge, with many patients ultimately suffering from relapse. Tumor cells that recover after entering into a state of senescence after chemotherapy or radiation have been shown to develop a more aggressive phenotype, and to contribute to disease recurrence. By combining the PARP inhibitor (PARPi), talazoparib, with radiation, senescence was enhanced in 4T1 and MDA-MB-231 triple-negative breast cancer cell lines (based on SA-β-gal upregulation, increased expression of CDKN1A and the senescence-associated secretory phenotype (SASP) marker, IL6). Subsequent treatment of the radiation- and talazoparib-induced senescent 4T1 and MDA-MB231 cells with navitoclax (ABT-263) resulted in significant apoptotic cell death. In immunocompetent tumor-bearing mice, navitoclax exerted a modest growth inhibitory effect when used alone, but dramatically interfered with the recovery of 4T1-derived tumors induced into senescence with ionizing radiation and talazoparib. These findings support the potential utility of a senolytic strategy in combination with the radiotherapy/PARPi combination to mitigate the risk of disease recurrence in triple-negative breast cancer

In search of triallelism in Bardet-Biedl syndrome

Genomics, epigenetics, population genetics and bioinformatic

In search of triallelism in Bardet–Biedl syndrome

Bardet–Biedl syndrome (BBS) is a model disease for ciliopathy in humans. The remarkable genetic heterogeneity that characterizes this disease is consistent with accumulating data on the interaction between the proteins encoded by the 14 BBS genes identified to date. Previous reports suggested that such interaction may also extend to instances of oligogenic inheritance in the form of triallelism which defies the long held view of BBS as an autosomal recessive disease. In order to investigate the magnitude of triallelism in BBS, we conducted a comprehensive analysis of all 14 BBS genes as well as the CCDC28B-modifier gene in a cohort of 29 BBS families, most of which are multiplex. Two in trans mutations in a BBS gene were identified in each of these families for a total of 20 mutations including 12 that are novel. In no instance did we observe two mutations in unaffected members of a given family, or observe the presence of a third allele that convincingly acted as a modifier of penetrance and supported the triallelic model of BBS. In addition to presenting a comprehensive genotype/phenotype overview of a large set of BBS mutations, including the occurrence of nonsyndromic retinitis pigmentosa in a family with a novel BBS9 mutation, our study argues in favor of straightforward autosomal recessive BBS in most cases