CpG-A and CpG-B oligonucleotides differentially enhance human peptide-specific primary and memory CD8+ T-cell responses in vitro

Two distinct types of CpG oligodeoxynucleotide (ODN) have been identified that differ in their capacity to stimulate antigen-presenting cells: CpG-A induces high amounts of interferon-alpha (IFN-alpha) and IFN-beta in plasmacytoid dendritic cells (PDCs), whereas CpG-B induces PDC maturation and is a potent activator of B cells but stimulates only small amounts of IFN-alpha and IFN-beta. Here we examined the ability of these CpG ODNs to enhance peptide-specific CD8+ T-cell responses in human peripheral blood mononuclear cells (PBMCs). The frequency of influenza matrix-specific "memory" CD8+ T cells was increased by both types of CpG ODN, whereas the frequency of Melan-A specific "naive" CD8+ T cells increased on stimulation with CpG-B but not with CpG-A. The presence of PDCs in PBMCs was required for this CpG ODN-mediated effect. The expanded cells were cytotoxic and produced IFN- on peptide restimulation. Soluble factors induced by CpG-A but not CpG-B increased the granzyme-B content and cytotoxicity of established CD8+ T-cell clones, each of which was IFN-alpha/-beta dependent. In conclusion, CpG-B seems to be superior for priming CD8+ T-cell responses, and CpG-A selectively enhances memory CD8+ T-cell responses and induces cytotoxicity. These results demonstrate distinct functional properties of CpG-A and CpG-B with regard to CD8 T cells.     

Biomaterial-based bone regeneration and soft tissue management of the individualized 3D-titanium mesh: An alternative concept to autologous transplantation and flap mobilization

Three-dimensional augmentation in severely atrophic bone and after cancer resection is a challenging clinical indication that is mostly solved using autologous bone transplantation. The development of the digital technique along with the additive manufacturing and three-dimensional (3D) printing opened new avenues for reconstructive oral and maxillofacial surgery. Therefore, patient-specific titanium mesh is a novel means of stabilizing the augmentation region using particulate bone substitute materials (BSMs) combined with autologous bone as a minimally invasive concept. However, dehiscence is a frequently reported complication in this field. Therefore, the aim of the present case series was to introduce a biomaterial-based regenerative concept in terms of exposed open healing to overcome the dehiscence related to 3D-titanium meshes. Additionally, this case series presents a novel protocol using a combination of xenogeneic BSMs with an autologous blood concentrate system (platelet-rich fibrin [PRF]) and collagen matrices without any autologous transplantation. Seven patients with alveolar ridge atrophy with different etiologies (cancer resection, severe atrophy after tooth loss, aplasia, trauma, implant infections) were treated using the open-healing concept. Therefore, after 3D augmentation using the described biomaterials, the flap margins were approximated, and the gap between the flap margins was bridged using a collagen matrix loaded with liquid PRF that was then covered by either a PTFE-based membrane or sterile latex. No periosteum splitting was performed at any time point. After a healing period of 4–8 months, all patients received dental implants as virtually planned. Bone biopsies were performed during dental insertion for histological evaluation. The augmentation area displayed a vital and well-vascularized newly formed bone that incorporated the BSM granules to build a hybrid bone. Additionally, open healing resulted in newly formed soft tissue without any signs of scar formation or fibrosis. The regenerated soft tissue was used to build a new flap during implant insertion and showed good functional and aesthetic results after implant insertion. The open-healing concept of the regeneration of the soft tissue along with bone tissue to regenerate a harmonic implantation bed is a minimally invasive intervention without periosteum splitting or large flap mobilization. However, further controlled clinical studies are needed to evaluate this concept in a larger patient cohort to outline the potential clinical benefit.     

Allosensitization in Heart Transplantation: An Overview

Transplant candidates might manifest circulating antibodies against human leukocyte antigens and nonhuman leukocyte antigens, a condition termed allosensitization. The presence of these antibodies decreases a given candidate's possible donor pool, thereby prolonging the time to transplantation. They are also associated with poorer posttransplant outcomes including increased morbidity and mortality. With the increasing use of ventricular assist devices as a bridge to transplantation, the prevalence of allosensitized transplant candidates has increased. This has implications for transplant programs in terms of donor-recipient matching and managing transplant-related complications, which are more common in this high risk cohort. Controversy exists as to the best approach in managing sensitized patients, before and after transplantation. Transplant centres have used various strategies to reduce antibody loads with mixed results being reported; moreover, it remains unclear as to whether attempts at desensitization translate into better posttransplant outcomes. As an alternative management approach, some centres participate in large organ sharing strategies and allocate organs based on the probability of finding a successful donor-recipient match. In this article, the immunological basis of allosensitization, its causes, implications, and therapeutic strategies to manage sensitized patients are reviewed. The literature in relation to desensitization therapies in heart transplant candidates is also reviewed.     

Estrogen receptor α is not a candidate gene for metabolic syndrome in Caucasian elderly subjects

Objective

Variants of estrogen receptor α (ERα) have been associated with obesity, dyslipidemia, diabetes and blood pressure. The Middle East registers some of the highest rate of metabolic syndrome worldwide. The aim of this study is to investigate the relationship between metabolic syndrome, a clustered combination of these metabolic factors, and polymorphisms PvuII and XbaI of ERα in Lebanese Caucasian elderly overweight subjects.

Material/Methods

250 Caucasian Lebanese unrelated elderly men and women, median age 71 years, were studied. ERα intronic polymorphisms variants, PvuII and XbaI diplotypes and genotypes, were examined. Associations with metabolic syndrome, defined by the American Heart Association/National Heart, Lung, and Blood Institute (AHA/NHLBI), and its components, namely high density lipoprotein (HDL), fasting glucose levels, blood pressure, and waist circumference were evaluated in regression models.

Results

ER α diplotypes and genotypes distributions were similar between participants with and without metabolic syndrome, in the overall group of subjects, and by gender. No consistent associations between the diplotypes and genotypes tested and metabolic syndrome, or its components, could be detected.

Conclusions

Genetic variants in ERα were not associated with metabolic syndrome or its components, in a group of 250 Lebanese Caucasian elderly participants, a group with a high prevalence of metabolic syndrome.     

Major nutrient compositions and functional properties of sorghum flour at 0–3 days of grain germination

Germination is of importance to improving nutritional attributes of cereal grains for human consumption. The effect of germination time on major nutrient compositions and functional properties of sorghum flour was investigated in this study. Grains of Butanua, a new Sudanese sorghum cultivar, were germinated for 0,?1,?2, and 3 days to analyze their chemical and functional properties. The contents of starch, protein, oil, foaming stability, bulk density, and least gelation concentration of sorghum flour decreased, whereas oil absorption capacity, foaming capacity, and emulsion capacity and stability enhanced with an increase in germination time. Improved functional properties of sorghum flour by germination of the grains not only make it useful and suitable for various food processing formulations, but also improve the food product quality. This new finding will beneficially help develop innovative technologies, design new types of functional foods, and promote both sorghum production and relevant food processing industry in the future.     

Biallelic loss of function variants in SYT2 cause a treatable congenital onset presynaptic myasthenic syndrome

Synaptotagmins are integral synaptic vesicle membrane proteins that function as calcium sensors and regulate neurotransmitter release at the presynaptic nerve terminal. Synaptotagmin‐2 (SYT2), is the major isoform expressed at the neuromuscular junction. Recently, dominant missense variants in SYT2 have been reported as a rare cause of distal motor neuropathy and myasthenic syndrome, manifesting with stable or slowly progressive distal weakness of variable severity along with presynaptic NMJ impairment. These variants are thought to have a dominant‐negative effect on synaptic vesicle exocytosis, although the precise pathomechanism remains to be elucidated. Here we report seven patients of five families, with biallelic loss of function variants in SYT2, clinically manifesting with a remarkably consistent phenotype of severe congenital onset hypotonia and weakness, with variable degrees of respiratory involvement. Electrodiagnostic findings were consistent with a presynaptic congenital myasthenic syndrome (CMS) in some. Treatment with an acetylcholinesterase inhibitor pursued in three patients showed clinical improvement with increased strength and function. This series further establishes SYT2 as a CMS‐disease gene and expands its clinical and genetic spectrum to include recessive loss‐of‐function variants, manifesting as a severe congenital onset presynaptic CMS with potential treatment implications.     

Reduction in False-Positive Aspergillus Serum Galactomannan Enzyme Immunoassay Results Associated with Use of Piperacillin-Tazobactam in the United States

Piperacillin-tazobactam (PTZ) is known to cause false-positive results in the Platelia Aspergillus enzyme-linked immunoassay (EIA), due to contamination with galactomannan (GM). We tested 32 lots of PTZ and 27 serum specimens from patients receiving PTZ. GM was not detected in the lots of PTZ; one serum specimen (3.7%) was positive. PTZ formulations commonly used in the United States today appear to be a rare cause for false-positive GM results.     

CD138 mRNA expression from peripheral blood of patients with follicular and diffuse large B cell lymphoma: relation to disease progression and treatment response

Syndecans are among those transmembrane PGs which act via their heparan sulphate chains as receptors for different matrix elements (e.g. collagen I–III, fibronectin, thrombospondin, tenascin) and co-receptors for growth factors (e.g. bFGF, aFGF, GM-CSF, IL-3, IFNg). We hypothesized that there is a positive relationship between the expression of syndecan-1 (CD138) and treatment response in non-Hodgkin’s lymphoma. To identify the expression of syndecan-1 (CD138) in cases of non-Hodgkin’s lymphoma and to correlate its expression with treatment response and disease stage, this study was carried out as a cross-sectional study and included 30 patients with non-Hodgkin’s lymphomas attending Suez Canal University Hospital; diagnosis of patients was made by routine histological and immunohistochemical examination. CD138 mRNA expression was assessed by TaqMan technique using real-time PCR method. There was increased expression of CD138 mRNA in patients with follicular lymphoma than in patients with diffuse large B cell lymphoma (6.25 versus 3.46, respectively) (p?≤?0.05). Syndecan-1 (CD138) mRNA expression from peripheral blood may be a useful marker for follicular lymphoma and can be used as a marker of treatment response in patients with follicular and diffuse large B cell lymphoma.     

Systematic review of viscoelastic testing (TEG/ROTEM) in obstetrics and recommendations from the women's SSC of the ISTH

Thromboelastography (TEG) and rotational thromboelastometry (ROTEM) are point‐of‐care viscoelastic devices that use whole blood samples to assess coagulation and fibrinolysis. These devices have been studied extensively in cardiac surgery, but there is limited robust evidence supporting its use in obstetrics. The hesitancy toward its routine use in obstetrics may be due to the current lack of randomized controlled trials and large observational studies. The study aims to systematically review studies that investigated TEG/ROTEM use in pregnancy or peripartum, and to provide recommendations for future studies to fill current research gaps. We performed a systematic review of studies on viscoelastic testing in obstetrics. Included studies were original research, used TEG or ROTEM during pregnancy or peripartum, and published in English. Ninety‐three studies, spanning 31 years from 1989 to 2020 and with a total of 32,817 participants, were included. Sixty‐two (66.7%) of the studies used TEG and 31 (33.3%) used ROTEM. To date, there are a total of two randomized controlled trials on TEG/ROTEM use in obstetrics. ROTEM may be used to guide transfusion therapy for postpartum hemorrhage. TEG and ROTEM can detect the hypercoagulable changes associated with pregnancy. Variability between study protocols and results suggests the need for future large prospective high‐quality studies with standardized protocols to investigate the utility of TEG/ROTEM in assessing risk for thrombosis and hemorrhage as well as in guiding prophylaxis and treatment in obstetric patients. This review identifies the gaps and provides concrete recommendations for future studies to fill those gaps.     

Guidance on the diagnosis and management of platelet‐type von Willebrand disease: A communication from the Platelet Physiology Subcommittee of the ISTH

Platelet‐type von Willebrand disease (PT‐VWD) is a rare autosomal dominant platelet bleeding disorder, with 55 patients reported worldwide so far, probably frequently misdiagnosed. Currently, there are no clear guidelines for the diagnosis and management of PT‐VWD and this may contribute to misdiagnosis and thus to inappropriate treatment of these patients. This report provides expert opinion‐based consensus recommendations for the standardized diagnostic and management approach to PT‐VWD. Tests essential in the diagnostic workup are platelet count and size, ristocetin‐induced platelet agglutination with mixing studies, and sequencing of platelet GP1BA gene. Platelet transfusions and von Willebrand factor‐rich concentrates (if VWF is low) are the most effective treatments. This consensus may help to avoid misdiagnosis and guide appropriate management of patients with this disease.