Genetic testing for inherited eye conditions in over 6,000 individuals through the eyeGENE network

Genetic testing in a multisite clinical trial network for inherited eye conditions is described in this retrospective review of data collected through eyeGENE®, the National Ophthalmic Disease Genotyping and Phenotyping Network. Participants in eyeGENE were enrolled through a network of clinical providers throughout the United States and Canada. Blood samples and clinical data were collected to establish a phenotype:genotype database, biorepository, and patient registry. Data and samples are available for research use, and participants are provided results of clinical genetic testing. eyeGENE utilized a unique, distributed clinical trial design to enroll 6,403 participants from 5,385 families diagnosed with over 30 different inherited eye conditions. The most common diagnoses given for participants were retinitis pigmentosa (RP), Stargardt disease, and choroideremia. Pathogenic variants were most frequently reported in ABCA4 (37%), USH2A (7%), RPGR (6%), CHM (5%), and PRPH2 (3%). Among the 5,552 participants with genetic testing, at least one pathogenic or likely pathogenic variant was observed in 3,448 participants (62.1%), and variants of uncertain significance in 1,712 participants (30.8%). Ten genes represent 68% of all pathogenic and likely pathogenic variants in eyeGENE. Cross‐referencing current gene therapy clinical trials, over a thousand participants may be eligible, based on pathogenic variants in genes targeted by those therapies. This article is the first summary of genetic testing from thousands of participants tested through eyeGENE, including reports from 5,552 individuals. eyeGENE provides a launching point for inherited eye research, connects researchers with potential future study participants, and provides a valuable resource to the vision community.     

Tuberculosis Microepidemics among Dispersed Migrants,Birmingham, UK, 2004–2013

To determine if local transmission was responsible for rising tuberculosis incidence in a recently dispersed migrant community in Birmingham, UK, during 2004–2013, we conducted enhanced epidemiologic investigation of molecular clusters. This technique identified exact locations of social mixing and chains of apparent recent transmission, which can be helpful for directing resources.     

Variation in the Timing and Frequency of Sucking and Swallowing over an Entire Feeding Session in the Infant Pig Sus scrofa

Feeding is a rhythmic behavior that consists of several component cycle types. How the timing of these cycles changes over a complete feeding sequence is not well known. To test the hypothesis that cycle frequency/duration changes as a function of time spent feeding, we examined complete feeding sequences in six infant pigs, using EMG of mylohyoid and thyrohyoid as cycle markers. We measured the instantaneous frequency of sucking and of swallowing cycles in 19 sequences. Each sequence contained three qualitatively distinctive phases of sucking frequency. Phase 1 started with cycles at a very high frequency and quickly dropped to a more constant level with low variation, which characterized phase 2. Phase 3 had a steady level of frequency but was interspersed with a number of high- or low-frequency cycles. Each phase differed from the others in patterns of within-phase variation and among-phase variation. Phase 2 had the least variation, and phase 3 had the largest range of frequencies. The number of sucks per swallow also differed among phases. These patterns, which characterize normative feeding, could indicate a physiologic basis in satiation. In human infant clinical studies, where data collection is often limited, these results indicated the utility of collecting data in different phases. Finally, these results can be used as a template or pattern with which to assess clinically compromised infants.     

Whole liver versus split liver versus living donor in the adult recipient: an analysis of outcomes by graft type

BACKGROUND: We studied patient and graft survival rates in adult liver transplant recipients, analyzing outcomes based on donor source (deceased donor [DD] vs. living donor [LD]) and graft type (whole liver vs. partial liver). METHODS: A retrospective database analysis of all adult liver transpants performed at our center over a 7-year period of time. RESULTS: Between 1999 and 2005, 384 liver transplants were performed in adult recipients, either as a whole liver from a deceased donor (DD-WL, n=284), split liver from a DD (DD-SL, n=31), or a partial transplant from a living donor (LD, n=69). DD-SL transplants were performed with a full right or left lobe graft, while LD transplants used the right lobe. Demographic differences in the three groups were most noticeable for lower model for end-stage liver disease scores in LD recipients (P<0.001) and younger donor age in DD-SL recipients (P<0.001). Superior graft survival results were seen in LD recipients versus either DD-WL recipients or DD-SL recipients (P=0.02 and P=0.05, respectively). Multivariate analysis showed hepatitis C (HR=1.53, P=0.05) and hepatocellular carcinoma (HR=1.74, P=0.03) to be significant risk factors for patient survival. Hepatitis C (HR=1.61, P=0.03) and donor age more than 50 (HR=1.64, P=0.04) were significant risk factors for graft survival. However, neither graft type nor donor source were significant independent risk factors for patient or graft survival. CONCLUSIONS: Our data suggests that the status of the recipient is probably a more important determinant of outcome than graft type or donor source.     

An evidence-based systematic review of Aloe vera by the natural standard research collaboration

An evidence-based systematic review including written and statistical analysis of scientific literature, expert opinion, folkloric precedent, history, pharmacology, kinetics/dynamics, interactions, adverse effects, toxicology, and dosing.     

Unilateral Superior Laryngeal Nerve Lesion in an Animal Model of Dysphagia and Its Effect on Sucking and Swallowing

We tested two hypotheses relating to the sensory deficit that follows a unilateral superior laryngeal nerve (SLN) lesion in an infant animal model. We hypothesized that it would result in (1) a higher incidence of aspiration and (2) temporal changes in sucking and swallowing. We ligated the right-side SLN in six 2–3-week-old female pigs. Using videofluoroscopy, we recorded swallows in the same pre- and post-lesion infant pigs. We analyzed the incidence of aspiration and the duration and latency of suck and swallow cycles. After unilateral SLN lesioning, the incidence of silent aspiration during swallowing increased from 0.7 to 41.5 %. The durations of the suck containing the swallow, the suck immediately following the swallow, and the swallow itself were significantly longer in the post-lesion swallows, although the suck prior to the swallow was not different. The interval between the start of the suck containing a swallow and the subsequent epiglottal movement was longer in the post-lesion swallows. The number of sucks between swallows was significantly greater in post-lesion swallows compared to pre-lesion swallows. Unilateral SLN lesion increased the incidence of aspiration and changed the temporal relationships between sucking and swallowing. The longer transit time and the temporal coordinative dysfunction between suck and swallow cycles may contribute to aspiration. These results suggest that swallow dysfunction and silent aspiration are common and potentially overlooked sequelae of unilateral SLN injury. This validated animal model of aspiration has the potential for further dysphagia studies.     

Vitamin D insufficiency in myeloproliferative neoplasms and myelodysplastic syndromes: clinical correlates and prognostic studies

Vitamin D insufficiency is commonly observed in the general population; observational studies have suggested an association with increased risk of cancer development. We examined the clinical and prognostic relevance of low plasma levels of 25-hydroxyvitamin D (25[OH]D) in myeloproliferative neoplasms (MPN) and myelodysplastic syndromes (MDS). A total of 409 patients were studied: 247 (60%) with primary myelofibrosis (PMF), 74 (18%) with de novo MDS, 63 (15%) with polycythemia vera (PV), and 25 (6%) with essential thrombocythemia (ET). Plasma 25(OH)D levels were measured by liquid chromatography-tandem mass spectrometry; a level lower than 25 ng/mL indicated vitamin D insufficiency and a level lower than 10 ng/mL indicated severe deficiency. The proportion of patients with 25(OH)D insufficiency was significantly greater in PMF (48%) and PV (43%) when compared with ET (28%) and MDS (28%) (P = 0.01). Severe 25(OH)D deficiency was significantly more frequent in ET (12%) and PMF (9%), compared with PV (3%) and MDS (1%) (P = 0.05). There were no significant correlations between 25(OH)D insufficiency, or severe deficiency, and a variety of clinical or laboratory variables in PMF, MDS, or PV. Furthermore, Vitamin D insufficiency did not influence either overall or leukemia-free survival in PMF, MDS, or PV (P > 0.05). We conclude that while hypovitaminosis D is relatively common in MPN and MDS, its clinical relevance for prognosis is limited.