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Platelet concentrate (PC) transfusion is administrated to reduce the hemostatic complications in patients with thrombocytopenia. Strength platelet against oxidative stress conditions lead to decrease in platelet storage lesion (PSL). This study was aimed to evaluate L-carnitine (LC) effects on platelet oxidative stress and platelet apoptosis during storage time. PC bags were randomly selected and each bag was divided into two equal parts. L-carnitine was added to test groups. Normal saline was added to control groups. Platelets count, mean platelet volume (MPV), pH, Platelet aggregation, nitric oxide metabolism (nitric/nitrate), total antioxidant capacity (TAC), malondealdehyde concentration (MDA), lactate dehydrogenase (LDH) enzyme activity, mitochondrial reactive oxygen species (ROS) and cytochrome C releasing were assayed by standard methods in 1, 3, 5 and 7 days of platelet storage. LDH enzyme activity was increased during storage but it had lower level in L-carnitine-treated platelets. LC treatment led to reduction in MDA concentration (3.35 ± 0.98 vs 5.3 ± 1.32, p = 0.003 and 6.52 ± 1.88 vs 5.67 ± 1.25, p = 0.005 for day 5 and day 7 respectively). Increased level of TAC was detected in LC-treated platelets in comparison to control (0.29 ± 0.06 vs 0.21 ± 0.05, p = 0.008 and 0.22 ± 0.03 vs 0.16 ± 0.03, p = 0.003 for day 5 and day 7 respectively). Interestingly, mitochondrial ROS and cytochrome C releasing was significantly lower in LC-treated versus control group during platelet storage. L-carnitine not only decreases mitochondrial ROS but also reduces cytochrome C releasing in PCs during storage. EI1 might be considered as safe additive to decrease PSL in the future.
Hydrogen/deuterium (H/D) exchange over a range of temperatures suggests a protein structural/mobility transition in the solid state below the system glass transition temperature (T
). The purpose of this study was to determine whether solid-state protein stability correlates with the difference between storage temperature and apparent T
where an abrupt change in mobility occurs, or alternatively, the extent of H/D exchange at a single temperature correlates directly to protein stability in lyophilized solids.
Solid-state H/D exchange was monitored by FTIR spectroscopy to study the extent of exchange and the apparent transition temperature in both pure recombinant human serum albumin (rHSA) and rHSA formulated with sucrose or trehalose. H/D exchange of freeze-dried formulations at 11% RH and temperatures from 30 to 80°C was monitored. Protein stability against aggregation at 40°C/11% RH for 6months was assessed by size exclusion chromatography (SEC).
Both sucrose and trehalose showed equivalent protection of protein secondary structure by FTIR. The rHSAsucrose formulation showed superior long-term stability at 40°C by SEC over the trehalose formulation, but the apparent T
determined from H/D exchange was much higher in the trehalose formulation. Instead, the extent of H/D exchange (X
) was lower in the sucrose formulation at the temperature of the stability studies (40°C) than found for the trehalose formulation, which was consistent with better stability in the sucrose formulation.
While apparent T
did not correlate with protein stability for rHSA, the extent of H/D exchange, X
, did.
While apparent Td did not correlate with protein stability for rHSA, the extent of H/D exchange, X∞, did.
We administered a questionnaire survey to assess the available clinical resources for the diagnosis and treatment of breast cancer and identify the issues faced by rural hospitals in the Tohoku region in Japan.
The term rural hospital was defined by the following three criteria the facility is a certified regional cancer center and hospital, no breast specialist is on staff, and ≥ 10 breast surgeries per year have been performed. Thirty-eight rural hospitals were eligible, and each was sent a self-administered questionnaire consisting of 26 questions by mail.
Responses were received from 29 of the 38 hospitals. Most of the hospitals had adequate facilities for diagnosis and treatment, but they needed specialists' support for ≥ 2days per month. Approximately half of the hospitals indicated that applying resources for diagnosis and treatment of breast cancer, especially during planning of treatment and management of advanced breast cancer patients, was a burden. Interestingly, the hospitals felt that beine issues in Tohoku..
In the present study, we evaluated if the presence of sexual abuse in the clinical history of patients with psychogenic non-epileptic seizures (PNES) is associated with a different psychopathological profile.
In a consecutive population of 63 PNES patients, we compared two demographically and clinically matched groups of patients with (no. 15) and without (no. 48) a history of sexual abuse using a comprehensive psychopathological assessment (Beck Depression Inventory, Hamilton Anxiety Rating Scale, Dissociative Experience Scale, Somatoform Dissociation Questionnaire, and Toronto Alexithymia Scale).
We found that the group of patients reporting sexual abuse is characterized by higher scores on Dissociative Experience Scale (p = 0.003) and Beck Depression Inventory (p = 0.001) with respect to the other group. No significant statistical differences in Hamilton Anxiety Rating Scale (p = 0.103), Toronto Alexithymia Scale (p = 0.137), and Somatoform Dissociation Questionnaire (p = 0.486) were captured. Moreover, we found that the negative effect on dissociate symptoms was also hampered by the increasing of seizure frequency.
This study reinforces the importance of traumatic screening in the clinical spectrum of PNES in order to implement and improve specific therapeutic strategies.
This study reinforces the importance of traumatic screening in the clinical spectrum of PNES in order to implement and improve specific therapeutic strategies.
To investigate the diagnostic performance of absolute myocardial blood flow (MBF), MBF
, and visual analysis of dynamic CT myocardial perfusion imaging (CT-MPI) for the detection of hemodynamically significant coronary stenosis.
Consecutive patients with chest pain and intermediate-to-high pre-test probability of obstructive coronary artery disease were prospectively enrolled. All patients were referred for dynamic CT-MPI and fractional flow reserve (FFR) measurements within 4weeks. Absolute MBF, MBF
(mean MBF of stenosis-subtended territories versus that of reference territories), and visually identified perfusion defect were tested for the diagnostic performance with reference to FFR.
Sixty-two patients with 95 target vessels were included for final analysis. The mean radiation dose for dynamic CT-MPI was 3.0 (2.2-4.0) mSv. #link# The mean lesion-based absolute MBF value was significantly lower in ischemic segments than that in non-ischemic segments (78.0 (65.0-86.0) mL/min/100mL vs. 133.0 (117.5-163.8) m = 0.413), which were larger than that of visual analysis (AUC = 0.802, both p < 0.01). link2 • The vessel-based sensitivity, specificity, and diagnostic accuracy were 84.3%, 97.7%, and 90.5% for absolute MBF and 96.1%, 93.2%, and 94.7% for MBF
.
• The mean MBF and MBFratio were significantly lower in ischemic segments than those in non-ischemic segments. • Absolute MBF and MBFratio had similar AUCs for the detection of hemodynamically significant lesions (AUC = 0.942 vs. 0.956, p = 0.413), which were larger than that of visual analysis (AUC = 0.802, both p less then 0.01). • The vessel-based sensitivity, specificity, and diagnostic accuracy were 84.3%, 97.7%, and 90.5% for absolute MBF and 96.1%, 93.2%, and 94.7% for MBFratio.Selenium represents an essential trace nutrient that is necessary for biological functions. Deficiencies can induce disease, but excess can induce toxicity. Selenium deficiency is a major concern in underdeveloped countries, while also posing as a toxic pollutant in waterways surrounding landfills, agricultural areas, and fossil fuel production sites. We examined the microbiome of selenomethionine (SeMet) fed American alligators (Alligator mississippiensis) at the beginning and end of a 7-week exposure experiment. Alligators were randomly divided into three groups control and 1000 or 2000 ppm SeMet. DNA from before exposure (oral and cloaca swabs) and post-exposure (oral, cloaca, small & large intestines) sampling were extracted and amplified for bacterial 16 s rRNA. While treatment did not seem to have much effect, we observed a predominance of Fusobacteriaceae and Porpyromonodaceae across all tissue types. Cetobacterium and Clostridium are the most abundant genera as potential indicators of the aquatic and carrion feeding lifestyle of alligators.
The objective of this study was to investigate stress levels among women undergoing elective oocyte cryopreservation by comparing their self-reported quality of life measures with women undergoing in vitro fertilization during the fertility treatment cycle.
Patients undergoing oocyte retrieval at a single institution were offered a voluntary, anonymous, and written questionnaire. The survey was adapted and validated from the Fertility Quality of Life tool to assess self-reported fertility treatment-related problems and was tested for construct validity and reliability. Based on exploratory factor analyses, three subscales were created as follows fertility treatment-related stress, tolerability, and environment. Relationships between patient characteristics and fertility treatment-related measures were examined with Fisher's exact test, ANOVA, and multivariate regression with significance p < 0.05.
A total of 461 patients (331 IVF, 130 egg freeze) were included in the analysis. Medically indicated egg developing stress reduction strategies for all women undergoing egg freezing.
Temelimab (formerly called GNbAC1) is an immunoglobulin (Ig)G4 monoclonal antibody that targets the human endogenous retroviral envelope protein HERV-W-Env, shown to be associated with the pathogenesis of certain autoimmune disorders such as multiple sclerosis (MS) and type 1 diabetes mellitus (T1D). By neutralizing HERV-W-Env, temelimab could act as a disease-modifying therapy for these disorders. It is currently in clinical development for MS and T1D.
The safety information on temelimab (including potential infusion-related reactions, malignancies, pregnancies and antidrug antibodies) collected during three phase I and four phase II clinical trials was reviewed and is summarized in this article.
In the entire development program, 54 healthy volunteers received single doses of temelimab in three phase I studies, and 334 MS or T1D patients received temelimab for a total estimated exposure of 465 patient-years in four phase II trials. No differences were observed between numbers of treatment-emergent adverse events (TEAEs) or serious adverse events (SAEs) between treatment groups (including placebo), and the number of SAEs was limited. link3 Furthermore, no differences were observed in laboratory evaluations, vital signs, electrocardiogram (ECG), or physical examinations between treatment groups. Rare potential infusion-related reactions were reported. Temelimab treatment was not associated with an increased risk of infections or infestations.
These results suggest that treatment with temelimab was not associated with any particular type of AE. Overall, temelimab was safe and very well tolerated over the tested dose range after repeated monthly administrations.
These results suggest that treatment with temelimab was not associated with any particular type of AE. Overall, temelimab was safe and very well tolerated over the tested dose range after repeated monthly administrations.