On the Determination of Elastic Properties of Single-Walled Boron Nitride Nanotubes by Numerical Simulation

The elastic properties of chiral and non-chiral single-walled boron nitride nanotubes in a wide range of their chiral indices and diameters were studied. With this aim, a three-dimensional finite element model was used to assess their rigidities and, subsequently, elastic moduli and Poisson’s ratio. An extensive study was performed to understand the impact of the input parameters on the results obtained by numerical simulation. For comparison, the elastic properties of single-walled boron nitride nanotubes are shown together with those obtained for single-walled carbon nanotubes.     

Reuniting overnutrition and undernutrition,macronutrients, and micronutrients

Over‐nutrition and its late consequences are a dominant theme in medicine today. In addition to the health hazards brought on by over‐nutrition, the medical community has recently accumulated a roster of health benefits with obesity, grouped under “obesity paradox.” Throughout the world and throughout history until the 20^th century, under‐nutrition was a dominant evolutionary force. Under‐nutrition brings with it a mix of benefits and detriments that are opposite to and continuous with those of over‐nutrition. This continuum yields J‐shaped or U‐shaped curves relating body mass index to mortality. The overweight have an elevated risk of dying in middle age of degenerative diseases while the underweight are at increased risk of premature death from infectious conditions. Micronutrient deficiencies, major concerns of nutritional science in the 20^th century, are being neglected. This “hidden hunger” is now surprisingly prevalent in all weight groups, even among the overweight. Because micronutrient replacement is safe, inexpensive, and predictably effective, it is now an exceptionally attractive target for therapy across the spectrum of weight and age. Nutrition‐related conditions worthy of special attention from caregivers include excess vitamin A, excess vitamin D, and deficiency of magnesium.     

Novel Mutations Including Deletions of the Entire OFD1 Gene in 30 Families with Type 1 Orofaciodigital Syndrome: A Study of the Extensive Clinical Variability

OFD1, now recognized as a ciliopathy, is characterized by malformations of the face, oral cavity and digits, and is transmitted as an X‐linked condition with lethality in males. Mutations in OFD1 also cause X‐linked Joubert syndrome (JBTS10) and Simpson–Golabi–Behmel syndrome type 2 (SGBS2). We have studied 55 sporadic and six familial cases of suspected OFD1. Comprehensive mutation analysis in OFD1 revealed mutations in 37 female patients from 30 families; 22 mutations have not been previously described including two heterozygous deletions spanning OFD1 and neighbouring genes. Analysis of clinical findings in patients with mutations revealed that oral features are the most reliable diagnostic criteria. A first, detailed evaluation of brain MRIs from seven patients with cognitive defects illustrated extensive variability with the complete brain phenotype consisting of complete agenesis of the corpus callosum, large single or multiple interhemispheric cysts, striking cortical infolding of gyri, ventriculomegaly, mild molar tooth malformation and moderate to severe cerebellar vermis hypoplasia. Although the OFD1 gene apparently escapes X‐inactivation, skewed inactivation was observed in seven of 14 patients. The direction of skewing did not correlate with disease severity, reinforcing the hypothesis that additional factors contribute to the extensive intrafamilial variability.     

Next-generation sequencing in X-linked intellectual disability

X-linked intellectual disability (XLID) is a genetically heterogeneous disorder with more than 100 genes known to date. Most genes are responsible for a small proportion of patients only, which has hitherto hampered the systematic screening of large patient cohorts. We performed targeted enrichment and next-generation sequencing of 107 XLID genes in a cohort of 150 male patients. Hundred patients had sporadic intellectual disability, and 50 patients had a family history suggestive of XLID. We also analysed a sporadic female patient with severe ID and epilepsy because she had strongly skewed X-inactivation. Target enrichment and high parallel sequencing allowed a diagnostic coverage of >10 reads for ~96% of all coding bases of the XLID genes at a mean coverage of 124 reads. We found 18 pathogenic variants in 13 XLID genes (AP1S2, ATRX, CUL4B, DLG3, IQSEC2, KDM5C, MED12, OPHN1, SLC9A6, SMC1A, UBE2A, UPF3B and ZDHHC9) among the 150 male patients. Thirteen pathogenic variants were present in the group of 50 familial patients (26%), and 5 pathogenic variants among the 100 sporadic patients (5%). Systematic gene dosage analysis for low coverage exons detected one pathogenic hemizygous deletion. An IQSEC2 nonsense variant was detected in the female ID patient, providing further evidence for a role of this gene in encephalopathy in females. Skewed X-inactivation was more frequently observed in mothers with pathogenic variants compared with those without known X-linked defects. The mutation rate in the cohort of sporadic patients corroborates previous estimates of 5–10% for X-chromosomal defects in male ID patients.     

Infrainguinal atherectomy: a retrospective review of a single-center experience

By decreasing plaque burden, atherectomy provides an alternative to angioplasty and stenting as a means of revascularizing patients with peripheral arterial disease. A new atherectomy device (SilverHawk) has recently been approved by the Food and Drug Administration, but the results with its use are unclear. We analyzed a series of consecutive patients undergoing atherectomy. We retrospectively reviewed the charts of 35 patients undergoing infrainguinal (IF) atherectomy in 38 limbs. The Trans-Atlantic Inter-Society Consensus (TASC) classification and Society of Vascular Surgery runoff scores were calculated. Time to event analysis was performed using Kaplan-Meier estimates. Risk factors affecting patency were analyzed with a multivariate Cox model. Mean patient age was 70 +/- 9.6 years. Indications for intervention were claudication (26%), rest pain (21%), and tissue loss (53%). Femoropopliteal (FP) atherectomy was performed in 68% and tibial atherectomy in 32%. For FP lesions, the TASC distribution was A, 42%; B, 23%; C, 4%; and D, 15%. The average lesion treatment length was 9.4 +/- 10.6 cm (range 1-40), and the runoff score was 5.1 +/- 3.5. For tibial lesions, the TASC distribution was A, 0%; B, 17%; C, 8%; and D, 75%. The average lesion treatment length was 9.2 +/- 6.0 cm (range 2-20), with a runoff score of 5.4 +/- 2.4. A total of 39% of patients had prior IF interventions. Adjunctive angioplasty of the atherectomized lesion was performed in 55% of cases, stenting in 0%, and adjunctive therapy for tandem lesions in 39%. The postoperative ankle-brachial index increased by 0.30 +/- 0.14 and toe pressures increased by 40 +/- 32.4 mm Hg. Mean follow-up was 10 +/- 8 months (range 0.3-23). During the studied period, seven patients required major limb amputation and five open surgical revascularization. Total primary and secondary patency rates were 66% and 70% at 1 year, respectively. Primary and secondary patency rates for FP atherectomy were 68% and 73% at 1 year, respectively. The limb salvage rate was 74% at 6 months. Patients with prior interventions in the atherectomized segment had an almost 10-fold decrease in primary patency. Atherectomy produces acceptable results, similar to those in reported series of conventional balloon angioplasty/stenting. Patients with prior IF interventions had a nearly 10-fold decrease in primary patency. A greater than sixfold decrease in patency rates was noted in patients who underwent simultaneous inflow or outflow procedures, but this finding did not reach statistical significance (p = 0.082). Future studies should focus on cost comparisons with other treatments such as angioplasty and stenting, and prospective randomized trials should be performed to compare these treatment alternatives.