Species- and organ-specificity of secretory proteins derived from human prostate and seminal vesicles

Polyclonal antibodies against semenogelin (SG) isolated from human seminal vesicle secretion and acid phosphatase (PAP), β‐microseminoprotein (β‐MSP), and Prostate‐Specific Antigen (PSA) derived from human prostatic fluid, as well as a monoclonal antibody against β‐MSP were used for immunocytochemical detection of the respective antigens in different organs from different species. SG immunoreactivity was detected in the epithelium of the pubertal and adult human and in monkey seminal vesicle, ampulla of the vas deferens, and ejaculatory duct. PAP, β‐MSP, and PSA immunoreactivities were detected in the pubertal and adult human prostate and the cranial and caudal monkey prostate. With the exception of a weak PSA immunoreactivity in the proximal portions of the ejaculatory duct, none of the latter antisera reacted with seminal vesicle, ampullary, and ejaculatory duct epithelium. Among the non‐primate species studied (dog, bull, rat, guinea pig) only the canine prostatic epithelium displayed a definite immunoreactivity with the PAP antibody and a moderate reaction with the PSA antibody. No immunoreaction was seen in bull and rat seminal vesicle and canine ampulla of the vas deferens with the SG antibody. The same was true for the (ventral) prostate of rat, bull, and dog for β‐MSP. The epithelium of the rat dorsal prostate showed a slight cross‐reactivity with the monoclonal antibody against β‐MSP and one polyclonal antibody against PSA. The findings indicate a rather strict species‐dependent expression of human seminal proteins which show some similarities in primates, but only marginal relationship to species with different physiology of seminal fluid

SOD3 Reduces Inflammatory Cell Migration by Regulating Adhesion Molecule and Cytokine Expression

Inflammatory cell migration characteristic of ischemic damages has a dual role providing the tissue with factors needed for tissue injury recovery simultaneously causing deleterious development depending on the quality and the quantity of infiltrated cells. Extracellular superoxide dismutase (SOD3) has been shown to have an anti-inflammatory role in ischemic injuries where it increases the recovery process by activating mitogen signal transduction and increasing cell proliferation. However, SOD3 derived effects on inflammatory cytokine and adhesion molecule expression, which would explain reduced inflammation in vascular lesions, has not been properly characterized. In the present work the effect of SOD3 on the inflammatory cell extravasation was studied in vivo in rat hind limb ischemia and mouse peritonitis models by identifying the migrated cells and analyzing SOD3-derived response on inflammatory cytokine and adhesion molecule expression. SOD3 overexpression significantly reduced TNFα, IL1α, IL6, MIP2, and MCP-1 cytokine and VCAM, ICAM, P-selectin, and E-selectin adhesion molecule expressions in injured tissues. Consequently the mononuclear cell, especially CD68+ monocyte and CD3+ T cell infiltration were significantly decreased whereas granulocyte migration was less affected. According to our data SOD3 has a selective anti-inflammatory role in ischemic damages preventing the migration of reactive oxygen producing monocyte/macrophages, which in excessive amounts could potentially further intensify the tissue injuries therefore suggesting potential for SOD3 in treatment of inflammatory disorders

Understanding Soft Errors in Uncore Components

The effects of soft errors in processor cores have been widely studied. However, little has been published about soft errors in uncore components, such as memory subsystem and I/O controllers, of a System-on-a-Chip (SoC). In this work, we study how soft errors in uncore components affect system-level behaviors. We have created a new mixed-mode simulation platform that combines simulators at two different levels of abstraction, and achieves 20,000x speedup over RTL-only simulation. Using this platform, we present the first study of the system-level impact of soft errors inside various uncore components of a large-scale, multi-core SoC using the industrial-grade, open-source OpenSPARC T2 SoC design. Our results show that soft errors in uncore components can significantly impact system-level reliability. We also demonstrate that uncore soft errors can create major challenges for traditional system-level checkpoint recovery techniques. To overcome such recovery challenges, we present a new replay recovery technique for uncore components belonging to the memory subsystem. For the L2 cache controller and the DRAM controller components of OpenSPARC T2, our new technique reduces the probability that an application run fails to produce correct results due to soft errors by more than 100x with 3.32% and 6.09% chip-level area and power impact, respectively.Comment: to be published in Proceedings of the 52nd Annual Design Automation Conferenc

SOD3 Decreases Ischemic Injury Derived Apoptosis through Phosphorylation of Erk1/2, Akt, and FoxO3a

Extracellular superoxide dismutase (SOD3), which dismutates superoxide anion to hydrogen peroxide, has been shown to reduce the free radical stress derived apoptosis in tissue injuries. Since both superoxide anion and hydrogen peroxide have a marked impact on signal transduction pathways and could potentially explain a number of apoptosis and survival -related phenomena in different pathological conditions, we clarified the impact of SOD3 on Akt and Erk1/2 cell survival pathways in rat hind limb injury model. Based on our data, the hind limb ischemic rats treated with virally delivered sod3 have milder injury and less apoptosis than control animals that could be due to parallel activation of pro-proliferative and anti-apoptotic Erk1/2 and Akt pathways. The common downstream factor of both signaling pathways, the apoptosis related forkhead box protein O3a (FoxO3a), was phosphorylated and translocated to the cytoplasm in sod3 treated tissues and cell line. Additionally, we obtained increased mRNA production of elk-1, ets-1, and microRNA 21 (miR-21), whereas synthesis of bim mRNA was decreased in sod3 overexpressing tissues. We further showed that overexpression of sod3 modulated redox related gene expression by downregulating nox2 and inos when compared to injured control animals. The study shows the complexity of SOD3-derived effects on tissue injury recovery that are not limited to the reduction of superoxide anion caused cellular stress but highlights the impact of SOD3 related signal transduction on tissue functions and suggests an important role for SOD3 in attenuating cell stress effects in different pathological conditions

Cognitive function after cardiac arrest and temperature management; rationale and description of a sub-study in the Target Temperature Management trial

Background: Mild to moderate cognitive impairment is common amongst long-term survivors of cardiac arrest. In the Target Temperature Management trial (TTM-trial) comatose survivors were randomized to 33 degrees C or 36 degrees C temperature control for 24 hours after cardiac arrest and the effects on survival and neurological outcome assessed. This protocol describes a sub-study of the TTM-trial investigating cognitive dysfunction and its consequences for patients' and relatives' daily life. Methods/Design: Sub-study sites in five European countries included surviving TTM patients 180 days after cardiac arrest. In addition to the instruments for neurological function used in the main trial, sub-study patients were specifically tested for difficulties with memory (Rivermead Behavioural Memory Test), attention (Symbol Digit Modalities Test) and executive function (Frontal Assessment Battery). Cognitive impairments will be related to the patients' degree of participation in society (Mayo-Portland Adaptability Inventory-4), health related quality of life (Short Form Questionnaire-36v2 (c)), and the caregivers' situation (Zarit Burden Interview (c)). The two intervention groups (33 degrees C and 36 degrees C) will be compared with a group of myocardial infarction controls. Discussion: This large international sub-study of a randomized controlled trial will focus on mild to moderate cognitive impairment and its consequences for cardiac arrest survivors and their caregivers. By using an additional battery of tests we may be able to detect more subtle differences in cognitive function between the two intervention groups than identified in the main study. The results of the study could be used to develop a relevant screening model for cognitive dysfunction after cardiac arrest

Automated lesion detection of breast cancer in [18F] FDG PET/CT using a novel AI-Based workflow

UNLABELLED: Applications based on artificial intelligence (AI) and deep learning (DL) are rapidly being developed to assist in the detection and characterization of lesions on medical images. In this study, we developed and examined an image-processing workflow that incorporates both traditional image processing with AI technology and utilizes a standards-based approach for disease identification and quantitation to segment and classify tissue within a whole-body [ METHODS: One hundred thirty baseline PET/CT studies from two multi-institutional preoperative clinical trials in early-stage breast cancer were semi-automatically segmented using techniques based on PERCIST v1.0 thresholds and the individual segmentations classified as to tissue type by an experienced nuclear medicine physician. These classifications were then used to train a convolutional neural network (CNN) to automatically accomplish the same tasks. RESULTS: Our CNN-based workflow demonstrated Sensitivity at detecting disease (either primary lesion or lymphadenopathy) of 0.96 (95% CI [0.9, 1.0], 99% CI [0.87,1.00]), Specificity of 1.00 (95% CI [1.0,1.0], 99% CI [1.0,1.0]), DICE score of 0.94 (95% CI [0.89, 0.99], 99% CI [0.86, 1.00]), and Jaccard score of 0.89 (95% CI [0.80, 0.98], 99% CI [0.74, 1.00]). CONCLUSION: This pilot work has demonstrated the ability of AI-based workflow using DL-CNNs to specifically identify breast cancer tissue as determined by

Evaluation of VEGF-A and CCL2 in dogs with brachycephalic obstructive airway syndrome or canine idiopathic pulmonary fibrosis and in normocephalic dogs

Peer reviewe

A measurement of the differential cross section for the two-body photodisintegration of 3He at theta_LAB = 90deg using tagged photons in the energy range 14 -- 31 MeV

The two-body photodisintegration of 3He has been investigated using tagged photons with energies from 14 -- 31 MeV at MAX-lab in Lund, Sweden. The two-body breakup channel was unambiguously identified by the (nonsimultaneous) detection of both protons and deuterons. This approach was made feasible by the over-determined kinematic situation afforded by the tagged-photon technique. Proton- and deuteron-energy spectra were measured using four silicon surface-barrier detector telescopes located at a laboratory angle of 90deg with respect to the incident photon-beam direction. Average statistical and systematic uncertainties of 5.7% and 6.6% in the differential cross section were obtained for 11 photon-energy bins with an average width of 1.2 MeV. The results are compared to previous experimental data measured at comparable photon energies as well as to the results of two recent Faddeev calculations which employ realistic potential models and take into account three-nucleon forces and final-state interactions. Both the accuracy and precision of the present data are improved over the previous measurements. The data are in good agreement with most of the previous results, and favor the inclusion of three-nucleon forces in the calculations.Comment: 12 pages, 13 figures; further Referee comments addresse

Total colonic aganglionosis : multicentre study of surgical treatment and patient-reported outcomes up to adulthood

Background: Surgery for total colonic aganglionosis (TCA) is designed to preserve continence and achieve satisfactory quality of life. This study evaluated a comprehensive group of clinical and social outcomes. Methods: An international multicentre study from eight Nordic hospitals involving examination of case records and a patient-reported questionnaire survey of all patients born with TCA between 1987 and 2006 was undertaken. Results: Of a total of 116 patients, five (4 center dot 3 per cent) had died and 102 were traced. Over a median follow-up of 12 (range 0 center dot 3-33) years, bowel continuity was established in 75 (73 center dot 5 per cent) at a median age of 11 (0 center dot 5-156) months. Mucosectomy with a short muscular cuff and straight ileoanal anastomosis (SIAA) (29 patients) or with aJpouch (JIAA) (26) were the most common reconstructions (55 of 72, 76 per cent). Major early postoperative complications requiring surgical intervention were observed in four (6 per cent) of the 72 patients. In 57 children aged over 4 years, long-term functional bowel symptoms after reconstruction included difficulties in holding back defaecation in 22 (39 per cent), more than one faecal accident per week in nine (16 per cent), increased frequency of defaecation in 51 (89 per cent), and social restrictions due to bowel symptoms in 35 (61 per cent). Enterocolitis occurred in 35 (47 per cent) of 72 patients. Supplementary enteral and/or parenteral nutrition was required by 51 (55 per cent) of 93 patients at any time during follow-up. Of 56 responders aged 2-20 years, true low BMI for age was found in 20 (36 per cent) and 13 (23 per cent) were short for age. Conclusion: Reconstruction for TCA was associated with persistent bowel symptoms, and enterocolitis remained common. Multidisciplinary follow-up, including continuity of care in adulthood, might improve care standards in patients with TCA.Peer reviewe

Brain injury after cardiac arrest

Publisher Copyright: © 2021 Elsevier LtdAs more people are surviving cardiac arrest, focus needs to shift towards improving neurological outcomes and quality of life in survivors. Brain injury after resuscitation, a common sequela following cardiac arrest, ranges in severity from mild impairment to devastating brain injury and brainstem death. Effective strategies to minimise brain injury after resuscitation include early intervention with cardiopulmonary resuscitation and defibrillation, restoration of normal physiology, and targeted temperature management. It is important to identify people who might have a poor outcome, to enable informed choices about continuation or withdrawal of life-sustaining treatments. Multimodal prediction guidelines seek to avoid premature withdrawal in those who might survive with a good neurological outcome, or prolonging treatment that might result in survival with severe disability. Approximately one in three admitted to intensive care will survive, many of whom will need intensive, tailored rehabilitation after discharge to have the best outcomes.Peer reviewe