Thrombophilia in hemodialysis patients: Transfer to peritoneal dialysis is life saving

The majority of vascular access thrombosis episodes in hemodialysis patients are due to anatomic abnormalities. Thrombophilias are inherited, acquired or mixed disorders which also predispose to venous thromboembolism. They include protein C, protein S and antithrombin deficiencies, as well as gene mutations for prothrombin and factor V Leiden. The most important of the mixed cases is hyperhomocysteinemia, which includes both a genetic and an acquired substrate. We report two patients undergoing hemodialysis who suffered from multiple thrombotic events, the first due to factor V Leiden heterozygosity and the second because of hyperhomocysteinemia due to homozygosity for MTHFR C677T mutation. As no site for vascular access was left, transfer to peritoneal dialysis for both patients improved solute clearance and quality of life with no additional thrombotic events noted.     

Effect of Aryl Substituents and Fluorine Addition on the Optoelectronic Properties and Organic Solar Cell Performance of a High Efficiency Indacenodithienothiophene‐alt‐Quinoxaline π‐Conjugated Polymer

A series of donor‐acceptor (D‐A) π‐conjugated polymers, based on indacenodithienothiophene (IDTT) as an electron‐donating unit and quinoxaline as an electron‐deficient moiety, are synthesized via a Pd‐catalyzed Stille cross‐coupling polymerization. Molecular characteristics, photovoltaic parameters, and optoelectronic properties are examined through structural differences corresponding to thienyl versus phenyl side group substitutions on the IDTT and the non‐fluorinated versus the monofluoro quinoxaline derivatives. One of the most important outcome is that the power conversion efficiency (PCE) in the studied polymers is more device architecture dependent (conventional vs inverted) rather than chemical structure dependent. From single junction solar cells based on bulk heterojunction polymer:[6,6]‐phenyl‐C₇₁‐butyric acid methyl ester (PC₇₁BM) systems as the active layer, a maximum PCE of 5.33% has been achieved from the polymer containing the thienyl substituent on the IDTT and one fluorine atom on the quinoxaline. This demonstrates that finding the optimum molecular weight of ThIDTT‐QF or introducing the monofluoro‐quinoxaline in a regioregular motif in the polymer backbone significantly higher PCE can be expected versus the fully optimized high performance PhIDTT‐Q conjugated polymer.     

Parametric models for biomarkers based on flexible size distributions

Recent advances in social science surveys include collection of biological samples. Although biomarkers offer a large potential for social science and economic research, they impose a number of statistical challenges, often being distributed asymmetrically with heavy tails. Using data from the UK Household Panel Survey, we illustrate the comparative performance of a set of flexible parametric distributions, which allow for a wide range of skewness and kurtosis: the four‐parameter generalized beta of the second kind (GB2), the three‐parameter generalized gamma, and their three‐, two‐, or one‐parameter nested and limiting cases. Commonly used blood‐based biomarkers for inflammation, diabetes, cholesterol, and stress‐related hormones are modelled. Although some of the three‐parameter distributions nested within the GB2 outperform the latter for most of the biomarkers considered, the GB2 can be used as a guide for choosing among competing parametric distributions for biomarkers. Going “beyond the mean” to estimate tail probabilities, we find that GB2 performs fairly well with some disparities at the very high levels of glycated hemoglobin and fibrinogen. Commonly used linear models are shown to perform worse than almost all the flexible distributions.     

Fascia lata allograft bridging of a rotator cuff tear in a rabbit animal model

Purpose:

Despite advances in surgical treatment options, large rotator cuff (r-c) tears still represent a challenge for orthopedic surgeons. The purpose of this study was to evaluate the temporary and spatial histological incorporation of fascia lata allografts, used for bridging artificially created defects of the r-c.

Materials and Methods:

Seventy-two rabbits were divided into two groups and a supraspinatus tendinous defect was created. Half of the rabbit population underwent repair only, while in the other half, the defect was bridged utilizing fascia lata allograft. The animals were euthanized at 2, 4, and 6 weeks postoperative. Half of the specimens were evaluated histologically and the other half underwent mechanical testing.

Results:

There was an increased remodeling activity, fibroblastic in growth and strong presence of collagen fibers observed at 6 weeks on both groups. A gradually increasing mechanical strength was noticed by week 6 and increased toughness was also found at the same time period. There was no significant difference observed between the two groups regarding their histological and mechanical properties.

Conclusions:

In the difficult scenario of a large irreparable tear where the simple suture of the remaining r-c is impossible, allograft bridging, could be used with satisfactory results.

Clinical Relevance:

Treatment Study, Level 1.     

De novo missense variants in MEIS2 recapitulate the microdeletion phenotype of cardiac and palate abnormalities,developmental delay,intellectual disability and dysmorphic features

Gross deletions involving the MEIS2 gene have been described in a small number of patients with overlapping phenotypes of atrial or ventricular septal defects, cleft palate, and variable developmental delays and intellectual disability. Non‐specific dysmorphic features were noted in some patients, including broad forehead with high anterior hairline, arched eyebrows, thin or tented upper lip, and short philtrum. Recently, a patient with a de novo single amino acid deletion, c.998_1000delGAA (p.Arg333del), and a patient with a de novo nonsense variant, (c.611C>G, p.Ser204*), were reported with a similar, but apparently more severe phenotypes. Clinical whole exome sequencing (WES) performed at our clinical molecular diagnostic laboratory identified four additional patients with predicted damaging de novo MEIS2 missense variants. Our patients’ features closely resembled those previously reported in patients with gross deletions, but also included some less commonly reported features, such as autism spectrum disorder, hearing loss, and short stature, as well as features that may be unique to nucleotide‐level variants, such as hypotonia, failure to thrive, gastrointestinal, skeletal, limb, and skin abnormalities. All of the observed missense variants, Pro302Leu, Gln322Leu, Arg331Lys, and Val335Ala, are located in the functionally important MEIS2 homeodomain. Pro302Leu is found in the region between helix 1 and helix 2, while the other three are located in the DNA‐binding helix 3. To our knowledge, these are the first described de novo missense variants in MEIS2, expanding the known mutation spectrum of the newly recognized human disorder caused by aberrations in this gene.     

Clinical utility of level-of-evidence-1 disease forecast cancer biomarkers uPA and its inhibitor PAI-1

The prognostic and/or predictive value of the cancer biomarkers, urokinase-type plasminogen activator (uPA) and its inhibitor (plasminogen activator inhibitor [PAI]-1), determined by ELISA in tumor-tissue extracts, was demonstrated for several cancer types in numerous clinically relevant retrospective or prospective studies, including a multicenter breast cancer therapy trial (Chemo-N0). Consequently, for the first time ever for any cancer biomarker for breast cancer, uPA and PAI-1 have reached the highest level of evidence, level-of-evidence-1. At present, two other breast cancer therapy trials, NNBC-3 and Plan B, also incorporating uPA and PAI-1 as treatment-assignment tools are in effect. Furthermore, small synthetic molecules targeting uPA are currently in Phase II clinical trials in patients afflicted with advanced cancer of the ovary, breast or pancreas.