Calcium-binding proteins: distribution and implication in mammalian placenta

During gestation, transport by the placenta is solely responsible for nutrient supply to the developing fetus. In this context, calcium (Ca²⁺) transport machinery of the placenta thus represents the primary tissue site for regulating fetal Ca²⁺ homeostasis. In humans, the transplacental movements of Ca²⁺ increase dramatically during the last trimester of gestation, when fetal skeletal mineralization is at its highest. However, little is known about the exact mechanism of transport. Evidence suggests that some developmentally expressed cytosolic Ca²⁺-binding proteins (CaBPs) have an important role in regulating or shuttling cytosolic Ca²⁺ since they are endowed with a high affinity for Ca²⁺ (∼10⁶ M ⁻¹). CaBPs belong to a large family of eukaryotic proteins containing a specific helix-loop-helix structure, referred to as the EF-hand motif, which counts more than 200 members. Several of these CaBPs were identified in the placenta: CaBP9k, CaBP28k, CaBP57k, oncomodulin, S-100P, S-100α, and S-100β. This review discusses the current views in this field to guide future investigations into the localization and functions of CaBPs during Ca²⁺ intracellular homeostasis in the placenta.     

Early epileptic seizures in ischaemic stroke treated by mechanical thrombectomy: influence of rt-PA

Journal of Neurology - The epileptogenicity of recombinant tissue-plasminogen activator (rt-PA) has been suggested, but seizures were not evaluated in randomised controlled trials. To evaluate...     

Genetic diversity of porcine sapoviruses, kobuviruses, and astroviruses in asymptomatic pigs: an emerging new sapovirus GIII genotype

Small, non-enveloped RNA viruses belonging to the genera Sapovirus, Kobuvirus, and Mamastrovirus are usually associated with gastroenteritis in humans and animals. These enteric pathogens are considered potential zoonotic agents. In this study, the prevalence and genetic diversity of sapoviruses (SaVs), kobuviruses (KoVs), and astroviruses (AstVs) in asymptomatic pigs were investigated using a PCR approach. KoV was found to be the most prevalent virus (87.3 %), followed by AstV (34.2 %) and SaV (10.2 %). Interestingly, the intra- and inter-cluster distances between porcine SaV capsid sequences revealed one strain (P38/11/CZ) that formed a new genotype within genogroup III of porcine SaVs, and it is tentatively called “P38/11-like” genotype. Moreover, this is the first report of porcine kobuvirus detection on Czech pig farms. The high prevalence rate of gastroenteritis-producing viruses in clinically healthy pigs represents a continuous source of infection of pigs, and possibly to humans.     

HHV-6 cell receptor CD46 expression on various cell subsets of six blood and graft sources: A prospective series

BackgroundCord Blood (CB) are increasingly used as an alternative stem cells source in adults for allogeneic Stem Cell Transplantation (allo-SCT). The risk of human herpesvirus (HHV-6) reactivation is significantly higher after CB transplant vs unrelated peripheral blood stem cells (PBSC) allo-SCT. Higher HHV-6 cell receptor CD46 expression on progenitor cells in CB may explain this difference.ObjectivesTo prospectively compare the HHV-6 cell receptor CD46 expression on various cell subsets of three freshly harvested blood sources on one hand and of three graft sources on the other hand.Study design52 samples were used for the purpose of this study. They were issued from peripheral blood (PB, n = 10), G-CSF mobilised PB (GCSF-PB, n = 10), cord blood (CB, n = 10), unmanipulated bone marrow (uBM, n = 5), leukapheresis product (LP, n = 10) and thawed CB graft (n = 7). CD46 expression was assessed by FACS analysis on total lymphocytes, monocytes, NK cells, T and B cells subsets, plasmacytoid (pDCs) dendritic cells and stem cells.ResultsAs all cell subsets were found CD46 positive, CD46 mean fluorescence intensity (MFI) was then considered for comparison between the three blood sources and the three graft sources. The most impressive result observed was that HHV-6 cell receptor CD46 expression was significantly reduced in almost all cell components of thawed CB graft compared to other graft sources.ConclusionsThis original study shows strong differences in term of quantitative CD46 expression between several blood and grafts samples. Our results suggest that other factors than the qualitative CD46 expression play a role in the higher HHV-6 reactivation observed after CB transplant in adults.     

Removal of osseointegrated dental implants: a systematic review of explantation techniques

Objectives

This systematic review aims to evaluate current literature regarding available techniques for removal of osseointegrated implants in terms of explantation’s success, complications, and bone loss.

Material and methods

Two reviewers conducted a systematic literature search through electronic databases (PubMed and EMBASE), complimented by manual and grey literature searches. Successful explantation was defined as the primary outcome. Complications and availability of residual bone for immediate implantation were defined as secondary outcomes.

Results

Eighteen articles, comprising 372 implants and 241 patients, were included. Five techniques were identified: reverse torque, trephines, burs, piezosurgery, and laser-assisted explantation. Peri-implantitis was the most common reason for explantation, followed by crestal bone loss, fracture, and malpositioning. The reverse torque was the most frequently reported technique (284 implants) with 87.7% success rate. Burs were used for explantation of 49 implants with a 100% success rate, while trephines were utilized for removal of 35 implants with 94% success. Piezosurgery (11 implants) and Er.Cr:YSGG laser (1 implant) showed 100% success. One study reported perforation of the sinus floor following trephine explantation, while another reported fracture of 3 implants following reverse torque application. Further analysis was hindered by the quality of the available studies and their lack of data.

Conclusions

Reverse torque seems the most conservative, and in the authors’ opinion, should be the first choice for explantation despite its inferior success rate. Additional studies with randomized controlled designs and larger sample sizes are required.

Clinical relevance

Dental implants have become the leading choice to replace missing teeth with gradually increasing numbers of complications and failures. An effective, conservative, and economic explantation technique is necessary to allow a successive implant placement.

     

Laboratory Biosafety: Benchmarking public health pain management practices during school immunizations

BackgroundPain and fear during immunizations can affect children and their future behaviour toward immunization. These negative experiences can be amplified when children receive vaccines as part of school-based immunization programs, where parental or tutor supports are missing. In 2015, HELPinKIDS&ADULTS, a Canadian network of experts, published a clinical practice guideline (CPG) on the management of pain and fear during immunization. This guideline has been endorsed by international, national and provincial organizations. However, the level of integration and implementation of the CPG into local and community immunization programs such as school-based immunization clinics is unclear.MethodsAn investigation whether public health units in Ontario integrated and implemented the pain and fear interventions recommended by the CPG into school-based immunization policies and practices was concluded.ResultsThe study shows that the majority of public health units do have pain and fear policies and procedures in place, but interventions are not integrated in a consistent and formal manner, leading to suboptimal uptake of interventions during immunizations at school.ConclusionFor pain interventions to be applied with sufficient fidelity and in enough individuals to have a meaningful effect, organizational leaders need to create directives and procedures that support implementation in a systematic and accountable manner.     

Active chi-like sequences are present in the ITS1 region of polyembryonic adult Collyriclum faba trematodes encysted in pairs

Collyriclum faba (Plagiochiida: Collyriclidae) adults occur in pairs within subcutaneous cysts. Here, we tested the extensive C. faba infrapopulation for five DNA loci known to display variability among Central European C. faba individuals. The infrapopulation tested shared 100 % similarity in four of the five mitochondrial and nuclear DNA loci tested. Contrariwise, the internal transcribed spacer 1 (ITS1) loci in all but one individual differed from each other. We found only 0.0–1.5 base substitutions per 1,000 sites within the cysts, while we found 0.7–9.0 substitutions between the cysts of the single host and 3.0–9.0 substitutions when comparing C. faba individuals isolated from different host individuals. We observed the most of the ITS1 variability within 48 bp repetitive sequences featured by the chi-like sequence 5′-GCTTGTCTGCC-3′ at their beginning. Similarly to the extensive C. faba infrapopulation examined, we determined the presence of highly variable number of repetitive sequences within the ITS1 locus of C. faba isolated from multiple host species and from various geographic locations. While similar variability was observed earlier in mutually unrelated specimens of several Schistosomatidae and Microphallidae species, here, we for the first time document it among multiple individuals of a single infracommunity possessing single mitochondrial haplotype. Lower ITS1 evolutionary divergence rates observed between individuals within the cysts when compared to those between the cysts suggest that the recombination occurs at multiple stages of the life cycle. We propose DNA recombination involving chi-like sequences to serve as a general feature shared by multiple families of digenetic trematodes to increase genetic diversity of their polyembryonic populations infecting their definitive hosts.     

Increased myofilament Ca2+ sensitivity and diastolic dysfunction as early consequences of Mybpc3 mutation in heterozygous knock-in mice

Hypertrophic cardiomyopathy (HCM) is frequently caused by mutations in MYBPC3 encoding cardiac myosin-binding protein C (cMyBP-C). The mechanisms leading from gene mutations to the HCM phenotype remain incompletely understood, partially because current mouse models of HCM do not faithfully reflect the human situation and early hypertrophy confounds the interpretation of functional alterations. The goal of this study was to evaluate whether myofilament Ca(2+) sensitization and diastolic dysfunction are associated or precede the development of left ventricular hypertrophy (LVH) in HCM. We evaluated the function of skinned and intact cardiac myocytes, as well as the intact heart in a recently developed Mybpc3-targeted knock-in mouse model carrying a point mutation frequently associated with HCM. Compared to wild-type, 10-week old homozygous knock-in mice exhibited i) higher myofilament Ca(2+) sensitivity in skinned ventricular trabeculae, ii) lower diastolic sarcomere length, and faster Ca(2+) transient decay in intact myocytes, and iii) LVH, reduced fractional shortening, lower E/A and E'/A', and higher E/E' ratios by echocardiography and Doppler analysis, suggesting systolic and diastolic dysfunction. In contrast, heterozygous knock-in mice, which mimic the human HCM situation, did not exhibit LVH or systolic dysfunction, but exhibited higher myofilament Ca(2+) sensitivity, faster Ca(2+) transient decay, and diastolic dysfunction. These data demonstrate that myofilament Ca(2+) sensitization and diastolic dysfunction are early phenotypic consequences of Mybpc3 mutations independent of LVH. The accelerated Ca(2+) transients point to compensatory mechanisms directed towards normalization of relaxation. We propose that HCM is a model for diastolic heart failure and this mouse model could be valuable in studying mechanisms and treatment modalities.     

Interactions between glucocorticoids and warfarin in chronic inflammatory (autoimmune) diseases

Glucocorticosteroids are still very important part of the treatment of chronic inflammatory disorders. Their use is often accompanied by unpleasant adverse effects, problems associated with withdrawal during their long-term use and interactions with concomitantly administered drugs. One of the important interactions that may often occur in clinical practice is interaction with warfarin. Despite the fact that as glucocorticosteroids so warfarin are used for many years and seem to be completely known, their co-administration is still accompanied by uncertainties. The interaction may have pharmacodynamic or pharmacokinetic character and both types result in increased risk of bleeding. The pharmacodynamic interaction can be expected to increase a risk of gastrointestinal bleeding to which a gastrotoxicity of glucocorticosteroids contributes. A pharmacokinetic interaction is considered to influence a hepatic metabolism of warfarin and to increase its availability. The exact mechanism is still not fully understood. Manifestations of both types of interactions are taken up with a delay. Co-administration requires increased attention and close monitoring of international normalized ratio. At higher doses of glucocorticosteroids proton pump inhibitors are also effective in prevention of gastrotoxicity.