mPed: a computer program for converting pedigree data to a format used by the PMx-software for conservation genetic analysis

There is a growing need for conservation genetic management of animal populations when individual relatedness data (pedigrees) are available. Such data can be used to monitor rates of inbreeding and loss of genetic diversity. Traditionally, pedigree analysis for conservation management has focused on zoo populations of threatened wild animals; available software has been developed in that context. Population Management x (PMx) is a free software for estimating genetic parameters including inbreeding, kinship, founder allele contribution and survival. PMx is an accessory program to the zoo studbook platform Single Population Analysis and Records Keeping System (SPARKS) and is not easily applied outside this platform, but such use is of interest for various domestic breeds or wild populations. We developed a converter program (mPed) for making pedigrees of any studbook format fitting the input requirements of PMx. mPed can be downloaded free at www.popgen.su.se/mped.php.     

Alzheimer’s disease and type 2 diabetes: the association study of polymorphisms in tumor necrosis factor-alpha and apolipoprotein E genes

Type 2 diabetes (T2D) and Alzheimer??s disease (AD) are two progressive disorders with high prevalence worldwide. Polymorphisms in tumor necrosis factor-alpha (TNF-??) and apolipoprotein E (ApoE) genes might be associated with both T2D and AD, representing possible genetic markers for the development of the AD in subjects with T2D. The aim was to determine ApoE and G-308A TNF-?? gene polymorphisms in unrelated Croatian Caucasians: 207 patients with sporadic AD, 196 T2D patients and 456 healthy controls. Patients with AD had higher frequency of ApoE4 allele compared to T2D patients and controls. The significant association, observed between ApoE2 allele and T2D, disappeared after the data were adjusted for age and sex. The genotype or allele frequencies of G-308A TNF-?? gene polymorphism were similar among the patients with AD, T2D and healthy controls. In conclusion, these results do not support the hypothesis that the A allele of G-308A TNF-?? gene polymorphism is associated either with AD or T2D. Our data confirm the association between the ApoE4 allele and AD, and point out the E2 allele of ApoE gene as the possible risk factor for T2D.     

Ultrasound-guided autologous myoblast injections into the extrinsic urethral sphincter: tissue engineering for the treatment of stress urinary incontinence

Introduction and hypothesis

Limitations of the existing treatment methods for stress urinary incontinence (SUI) have encouraged investigation of new therapeutic approaches in the field of regenerative medicine. Enabled by tissue engineering technology safety, feasibility and efficacy of ultrasound-guided intrasphincteric autologous myoblast implantation to treat SUI presented in the accompanying video were assessed in a pilot study of 38 women.

Methods

Following upper arm muscle biopsy, autologous myoblast suspension was injected into the extrinsic urethral sphincter under transurethral ultrasound visualization. Functional electrical stimulation (FES) was used postoperatively to possibly enhance cell integration. Objective and subjective parameters were compared at 6 weeks, 3 months, and 6 months postoperatively.

Results

The tissue harvest, laboratory tissue processing, and myoblast implantation were successful in all 38 patients. No serious adverse events were reported through the course of the study. Objective and subjective measurements collected at baseline were significantly improved at 6 weeks postoperatively. Additional improvement or a plateau was observed at 3 and 6 months postoperatively, not being negatively influenced by discontinuation of FES. Of the patients, 23.7 % considered their SUI cured, and 52.6 % reported improvement at 6 months; 95 % would recommend this treatment to others.

Conclusions

Intrasphincteric ultrasound-guided autologous myoblast injection for SUI is feasible. This simple to perform and well-tolerated minimally invasive procedure safely produced promising initial results.     

Absence of donor CD40 protects renal allograft epithelium and preserves renal function

Blocking the CD40‐CD154 pathway prevents allograft rejection and induces donor‐specific tolerance in various experimental models. However, the translation to clinical studies has been hampered by unexpected thromboembolic complications of CD154‐blocking antibodies. Thus, blocking CD40 instead is now considered as an alternative strategy. Here, we evaluated the role of donor CD40 in allospecific T‐cell responses in vitro and in an in vivo model for renal transplantation. Fully MHC‐mismatched allografts from CD40‐deficient donors displayed better renal function than wild type. These functional data correlated with a lower level of apoptosis in renal tubular epithelial cells and higher expression of PD‐L1, which is most probably because of a reduced Th17 response in recipients of a CD40‐deficient donor. This hypothesis was supported in vitro, where donor CD40 expression was important for the induction of direct allospecific T‐cell responses. Especially the induction of Th17 cells was critically dependent on donor CD40. IL‐17A in conjunction with interferon‐γ in turn rendered renal tubular epithelial cells to a more costimulatory state by upregulating CD40 and downregulating PD‐L1 expression. In conclusion, CD40 blockade not only reduces the allospecific T‐cell responses, but might also lead to protection of tubular epithelium from apoptosis and thereby preserve kidney allograft function.     

Enhanced thrombin generation in women with a history of oral contraception-related venous thrombosis

Introduction

In women who suffer venous thrombosis (VT) during oral contraceptive (OC) use, a transient risk factor (OC) is removed during the acute event, while most co-existing forms of thrombophilia persist and presumably continue to maintain hypercoagulability. The aim of this study was to establish if hypercoagulability persists long after OC-related VT and if it could be attributed to thrombophilia.

Materials and Methods

60 women (age 33.0 ± 8.5 years) were investigated 5 – 64 (median 33) months after OC-related VT (patients) and compared to 63 apparently healthy women (controls). All women were tested for thrombophilia, activated partial thromboplastin time (APTT), fibrinogen, D-dimer, P-selectin and C-reactive protein. Thrombin generation was measured by Technothrombin® TGA assay. Overall haemostasis potential (OHP) assay with overall coagulation potential (OCP) and overall fibrinolytic potential (OFP) as supplementary parameters were measured by repeated fibrin formation and degradation registration.

Results

In patients increased endogenous thrombin potential (4205 ± 440 nM x min vs 4015 ± 421 nM x min, p = 0.017), increased OCP (22.6 ± 4.6 Abs-sum vs 20.8 ± 4.1 Abs-sum, p = 0.025), shorter APTT (30.9 ± 3.8 s vs 33.4 ± 3.6 s, p < 0.001) and lower antithrombin activity (99, 93-105% vs 104, 100-109%, p < 0.05) were observed. Thrombophilia was observed in 22/60 (36%) patients and in 5/63 (7.9%, p < 0.001) controls. The only significant difference between thrombophilic and non-thrombophilic patients was higher soluble P-selectin in the former subgroup (22, 20-33 μg/L vs 17, 12-22 μg/L, p = 0.012).

Conclusions

In women with a history of OC-related VT persistent hypercoagulability was observed, which, however was not augmented by the presence of thrombophilia.     

The role of linguistic context in deriving word meanings in individuals with Down Syndrome

Deriving the meaning of unknown words from context and its relationship to text comprehension was investigated in 24 individuals with Down syndrome and in 24 typically developing children matched for the Peabody Picture Vocabulary Test (PPVT) score.The study consisted of three phases. Unknown words were identified during the first phase (PPVT). Those words were presented embedded in brief linguistic contexts during the second phase. Recognition (maintenance) of word meanings was verified in the third and final phase. Both groups of participants recognized the meanings of a noteworthy number of words in contexts and a high percentage of these was maintained when they were presented at a later date without the support of context. Over and above group differences and basic linguistic skills, text comprehension seems to predict the ability to use context. Context provides the semantic information necessary to extract word meaning by activating relevant world knowledge.