Overview of prospects for inflammation pathways in autism spectrum disorders

Autism spectrum disorders (ASD) represent a heterogeneous group of neurodevelopmental disorders which are both severe and frequent. Understanding its pathophysiology could lead to identifying promising new markers and treatments. For years, a growing number of studies have pointed to an important involvement of the immuno-inflammatory system in ASD. Extensive reviews have already addressed this topic. Yet, this field of investigations is not well known to practitioners even those working with ASD patients. Our main objective is to provide an introduction to these new insights through a mini review of the literature. A first field of antenatal studies connects fetal features and maternal infections to ASD by means of the participation of maternal immune activation (MIA) associated with the production of a particular pro inflammatory cytokinic profile with IL-1, IL-6 and TNF and IL-17. Maternal autoantibodies and other immune-related disorders can also lead to impairment of fetal neurodevelopment. Other postnatal studies have shown the correlation between ASD and autoantibodies and between ASD and inflammatory environment through impaired interleukin levels (IL-6 being the most extensively investigated). Disruption of intestinal microbiota appears to be a possible pathogenic mechanism of ASD. The growing paths opened recently between immunology and psychiatry appear to be promising in the understanding of ASD. It could eventually participate in the development of diagnostic markers and help the emergence of new personalized therapeutics suitable for these patients.     

Cervicovaginal shedding of hepatitis C viral RNA is associated with the presence of menstrual or other blood in cervicovaginal fluids

BackgroundThe role of sexual activity in hepatitis C virus (HCV) transmission remains controversial. Studies to date have not explored the relationship between HCV shedding in cervicovaginal fluids and the presence of menstrual or other blood.ObjectivesSince cross-sectional studies may underestimate the prevalence of viral shedding, we performed a 56-day longitudinal study of cervical HCV shedding.Study designWomen self-collected cervicovaginal swabs for 56 consecutive days, while keeping a diary of menses and genital symptoms. Swabs were tested for HCV RNA and cellular DNA by quantitative PCR, and hemoglobin by spectrophotometry.ResultsSixteen women contributed a total of 701 cervicovaginal swabs (mean collection period 48 days, range 18–56). Detection of HCV RNA was associated with detection of hemoglobin. Premenopausal women were more likely than post-menopausal women to have HCV RNA detected in cervicovaginal fluids. For premenopausal women, detection of HCV RNA was more likely during menstruation (OR = 56.4) or when hemoglobin was detected in cervicovaginal fluids, even if menstruation was not occurring (OR = 35.4). No woman post-hysterectomy had HCV RNA detected in cervicovaginal fluids on any day, regardless of whether hemoglobin was detected.ConclusionsOur findings are consistent with a low likelihood of sexual transmission of HCV. The results suggest that shedding of HCV RNA in the female genital tract is associated with the presence of blood, and requires the presence of a cervix. Clinicians should consider advising premenopausal women who are concerned about transmitting infection that infectivity may increase during menstruation.     

Acquired Antibodies to αIIbβ3 in Glanzmann Thrombasthenia: From Transfusion and Pregnancy to Bone Marrow Transplants and Beyond

Patients with the inherited bleeding disorder Glanzmann thrombasthenia (GT) possess platelets that lack αIIbβ3 integrin and fail to aggregate, and have moderate to severe mucocutaneous bleeding. Many become refractory to platelet transfusions due to the formation of isoantibodies to αIIbβ3 with the rapid elimination of donor platelets and/or a block of function. Epitope characterization has shown isoantibodies to be polyclonal and to recognize different epitopes on the integrin with β3 a major site and αvβ3 on endothelial and vascular cells a newly recognized target. Pregnancy in GT can also lead to isoantibody formation when fetal cells with β3 integrins pass into the circulation of a mother lacking them; a consequence is neonatal thrombocytopenia and a high risk of mortality. Antibody removal prior to donor transfusions can provide transient relief, but all evidence points to recombinant FVIIa as the first choice for GT patients either to stop bleeding or as prophylaxis. Promoting thrombin generation by rFVIIa favors GT platelet interaction with fibrin, and the risk of deep vein thrombosis also associated with prolonged immobilization and catheter use requires surveillance. Although having a high risk, allogeneic bone marrow transplantation associated with different stem cell sources and conditioning regimens has proved successful in many cases of severe GT with antibodies, and often, the associated conditioning and immunosuppressive therapy leads to loss of isoantibody production. Animal models of gene therapy for GT show promising results, but isoantibody production can be stimulated and CRISPR/Cas9 technology has yet to be applied. Up-to-date consensus protocols for dealing with isoantibodies in GT are urgently required, and networks providing patient care should be expanded.     

Preoperative and postoperative assessment of temporal and masseter muscle size with magnetic resonance imaging in patients undergoing unilateral temporomandibular joint surgery

The aim of this study was to assess any change between the preoperative and postoperative sizes of temporal and masseter muscles with magnetic resonance imaging (MRI) in patients undergoing unilateral temporomandibular joint surgery.This study was designed and implemented retrospectively. For clinical evaluation, a visual analog scale (VAS) and maximum mouth opening (MMO) were used. In order to make a preoperative diagnosis and perform a 6-month control, muscle size was measured in millimeters (mm) on T1 axial sections in MRI. Statistical analyses were performed using the SPSS 23.0 software package. Numeric variables were compared between two dependent groups using the Wilcoxon signed rank test. Statistical significance was set at p < 0.05.Twelve patients who underwent unilateral discectomy plus dermis-fat grafting, with classical preauricular inverse L incision, were included in the study, and data for eleven female patients were evaluated. The difference in size between the operated and non-operated sides was found to be statistically insignificant at the preoperative stage for both masseter muscle (operated side m^M: 13.264 ± 1.822 mm; non-operated side m^M: 13.264 ± 2.315 mm; p^M = 0.929) and temporal muscle (operated side m^T: 20.345 ± 2.609 mm; non-operated side m^T: 20.582 ± 2.366 mm; p^T = 0.594). There was a significant size reduction in the masseter muscle on the operated side in the postoperative period (preop m^M: 13.264 ± 1.822 mm; postop m^M: 12.036 ± 1.728 mm; p^M = 0.018). Although there was also a size reduction in the operated side of the temporal muscle in the postoperative period, that difference did not reach statistical significance (preop m^T: 20.345 ± 2.609 mm; postop m^T: 19.445 ± 1.603 mm; p^T = 0.182). On the non-operated side, there were no significant postoperative changes in the sizes of either the masseter muscle (preop m^M: 13.264 ± 2.315 mm; postop m^M: 12.682 ± 2.059 mm; p^M = 0.248) or the temporal muscle (preop m^T: 20.582 ± 2.366; postop m^T: 19.891 ± 3.487 mm; p^T = 0.625).Considering the study findings as a whole, a size reduction was observed in the operated side of the masseter muscle after TMJ surgery. The etiology of this change may be surgical trauma to the temporal and masseter muscles, skeletal alteration resulting from condylar change secondary to discectomy, and patients restraining themselves from application of maximum bite force as a result of a self-protection mechanism due to postoperative pain.     

A randomized clinical trial on the efficacy of a patient-adapted autonomous exercise regime for patients with head and neck cancer

Patients undergoing surgical therapy of head and neck malignancies are known to exhibit a high number of comorbidities and frequently present a high nosocomial morbidity. Physiotherapy (PT) improves the clinical course of patients after extensive surgery. The aim of this study was to establish and then compare an additional individualized autonomous exercise plan with standard physiotherapy. 69 consecutive patients undergoing surgical treatment of head and neck cancer were randomized into two groups. The control group received standard clinical physiotherapy, the intervention group an additional autonomous exercise plan, adapted to the patient's performance profile. The patients randomized to the intervention group showed significantly fewer signs of fatigue (5.5 ± 3.5 vs. 3.7 ± 2.7, p = 0.048) and fewer digestive problems (4.7 ± 3.3 vs. 2.3 ± 2.7; p = 0.009) compared with the patients of the control group. In addition, a significantly shorter hospital stay was observed (17.7 ± 6.3 vs. 13.4 ± 3.4 days, p = 0.005), which was positively influenced by the early start of the exercises (r = 0.623, p = 0.001) and frequent practice (r = 0.432, p = 0.031). Patients with head and neck cancer therapy can benefit from an autonomous, individualized exercise plan. In coordination with the physiotherapists, mobilization should be as early and intensive as possible.     

Usefulness of hematopoietic progenitor cell monitoring to predict autologous peripheral blood stem cell harvest timing: A single-center retrospective study

IntroductionIn autologous peripheral blood stem cell harvest (APBSCH), CD34-positive cells have been measured to assess the numbers of hematopoietic stem cells, but measurement requires specialized equipment. Recently, there was a report that peripheral blood hematopoietic progenitor cells (HPCs) are useful indicators of the presence of hematopoietic stem cells. We examined the usefulness of HPC monitoring to predict APBSCH timing.MethodsWe retrospectively analyzed the relationship between HPC and collected CD34-positive cells in 84 consecutive patients who underwent APBSCH.ResultsAccording to the receiver operating characteristics curve for the collection of ≥2 × 106 CD34-positive cells/kg, the HPC cut-off value on the day before collection was 21/μL, while that on the day of collection was 41/μL. No significant factors were found in the univariate analysis except for the HPC count on the day before collection (p < 0.001) and the day of collection (p < 0.001). According to the multivariate analysis, the HPC count on the day before collection (p < 0.001) and the day of collection (p < 0.001) were also factors that strongly influenced the quantity of CD34-positive cells collected.ConclusionOur results suggest that the HPC count on not only the day of collection but also the day before collection is a good indicator for appropriate APBSCH timing.     

The epigenetically active small chemical N-methyl pyrrolidone (NMP) prevents estrogen depletion induced osteoporosis

Currently, there are several treatments for osteoporosis however; they all display some sort of limitation and/or side effects making the need for new treatments imperative. We have previously demonstrated that NMP is a bioactive drug which enhances bone regeneration in vivo and acts as an enhancer of bone morphogenetic protein (BMP) in vitro. NMP also inhibits osteoclast differentiation and attenuates bone resorption.In the present study, we tested NMP as a bromodomain inhibitor and for osteoporosis prevention on ovariectomized (OVX) induced rats while treated systemically with NMP. Female Sprague–Dawley rats were ovariectomized and weekly NMP treatment was administrated 1 week after surgery for 15 weeks. Bone parameters and related serum biomarkers were analyzed. 15 weeks of NMP treatment decreased ovariectomy-induced gained weight in average by 43% and improved bone mineral density (BMD) and bone volume over total volume (BV/TV) in rat femur on average by 25% and 41% respectively. Moreover, mineral apposition rate and bone biomarkers of bone turnover in the treatment group were at similar levels with those of the Sham group.Due to the function of NMP as a low affinity bromodomain inhibitor and its mechanism of action involving osteoblasts/osteoclasts balance and inhibitory effect on inflammatory cytokines, NMP is a promising therapeutic compound for the prevention of osteoporosis.