Transient Decrease Research Articles

Effects of Ornithine Aspartate and Empagliflozin on Memory Deficit Symptoms in Experimental Steatohepatitis

In this study, L-ornithine L-aspartate and empagliflozin were evaluated in terms of their potential effects on the hippocampus-dependent memory status in non-alcoholic steatohepatitis (NASH) in C57Bl/6 mice. NASH was found to be associated with an early transient decrease in the short-term recognition memory as well as a progressive reduction in the short-term spatial memory. L-ornithine L aspartate effectively prevented the impairment of recognition, rather than spatial, memory. At the same time, empagliflozin failed to improve the memory status of the animals.

Computational Simulation of Tumor-Induced Angiogenesis.

Cancer cells require higher oxygen levels and nutrition than normal cells. Cancer cells induce angiogenesis (the development of new blood vessels) from preexisting vessels. This biological process depends on the special, chemical, and physical properties of the microenvironment surrounding tumor tissues. The complexity of these properties hinders an understanding of their mechanisms. Various mathematical models have been developed to describe quantitative relationships related to angiogenesis. We developed a three-dimensional mathematical model that incorporates angiogenesis and tumor growth. We examined angiopoietin, which regulates the spouting and branching events in angiogenesis. The simulation successfully reproduced the transient decrease in new vessels during vascular network formation. This chapter describes the protocol used to perform the simulations.

Sleep Arousal-Related Ventricular Repolarization Lability Is Associated With Cardiovascular Mortality in Older Community-Dwelling Men

Sleep is fragmented by brief arousals, and excessive arousal burden has been linked to increased cardiovascular (CV) risk, but mechanisms are poorly understood. Do arousals trigger cardiac ventricular repolarization lability that may predispose people to long-term cardiovascular mortality? This study analyzed 407,541 arousals in the overnight polysomnograms of 2,558 older men in the Osteoporotic Fractures in Men sleep study. QT and RR intervals were measured beat-to-beat starting 15s prior to arousal onset until 15s past onset. Ventricular repolarization lability was quantified by using the QT variability index (QTVi). During 10.1 ± 2.5 years of follow-up, 1,000 men died of any cause, including 348 CV deaths. During arousals, QT and RR variability increased on average by 5 and 55ms, respectively, resulting in a paradoxical transient decrease in QTVi from 0.07 ± 1.68 to -1.00 ± 1.68. Multivariable Cox proportional hazards analysis adjusted for age, BMI, cardiovascular and respiratory risk factors, sleep-disordered breathing and arousal, diabetes, and Parkinson disease indicated that excessive QTVi during arousal was independently associated with all-cause and CV mortality (all-cause hazard ratio, 1.20 [95%CI, 1.04-1.38; P= .012]; CV hazard ratio, 1.29 [95%CI, 1.01 -1.65; P= .043]). Arousals affect ventricular repolarization. A disproportionate increase in QT variability during arousal is associated with an increased all-cause and CV mortality and may reflect ventricular repolarization maladaptation to the arousal stimulus. Whether arousal-related QTVi can be used for more tailored risk stratification warrants further study, including evaluating whether arousal suppression attenuates ventricular repolarization lability and reduces subsequent mortality. ClinicalTrials.gov; No.: NCT00070681; URL: www. gov.

Contribution of meniscus force to friction of multi-asperity sliding contact

Capillary adhesion contributes to friction of sliding multi-asperity contact in humid environment by increasing the solid-solid contact area; whereas the increased adhesion from capillary meniscus is hard to measure due to elastic recovery of contacting asperities. Here, we report the first direct measurement of increased interfacial adhesion from mesoscopic menisci in a macroscale multi-asperity contact comprising soft elastomer and glass surfaces with a diminishing water film. Results also found capillary adhesion and its contribution to a high transient friction coefficient decrease with increased interfacial roughness, which is consistent with prior literature hypotheses.

New insights from cross-correlation studies between solar activity indices and cosmic-ray flux during Forbush decrease events

Observed galactic cosmic ray intensity can be subjected to a transient decrease. These so-called Forbush decreases are driven by coronal mass ejection induced shockwaves in the heliosphere. By combining in situ measurements by space borne instruments with ground-based cosmic ray observations, we investigate the relationship between solar energetic particle flux, various solar activity indices, and intensity measurements of cosmic rays during such an event. We present cross-correlation study done using proton flux data from the SOHO/ERNE instrument, as well as data collected during some of the strongest Forbush decreases over the last two completed solar cycles by the network of neutron monitor detectors and different solar observatories. We have demonstrated connection between the shape of solar energetic particles fluence spectra and selected coronal mass ejection and Forbush decrease parameters, indicating that power exponents used to model these fluence spectra could be valuable new parameters in similar analysis of mentioned phenomena. They appear to be better predictor variables of Forbush decrease magnitude in interplanetary magnetic field than coronal mass ejection velocities.

Intraoperative hypotension during surgical treatment for Marfan syndrome scoliosis in children.

Purpose:To explore the occurrence and risk factors of intraoperative hypotension during children’s Marfan syndrome scoliosis surgery and summarize the associated hemodynamic features and handle measures.Methods:Twenty-two Marfan syndrome scoliosis patients who underwent spinal surgery at Beijing Children’s Hospital were retrospectively reviewed between January 2001 and January 2020. Intraoperative hypotension is defined as the minimum mean arterial pressure ≤ 60 mm Hg. The patients were divided into the hypotension group and the control group. Clinical, radiographic, and operative data were compared between the two groups. The risk factors, hemodynamic features, and handle measures for intraoperative hypotension in Marfan syndrome scoliosis surgery were analyzed and summarized.Results:Twenty-two patients were included in the study, with a mean age of 11.4 years at initial surgery. The follow-up period ranged from 24 to 152 months. Intraoperative hypotension occurred in 14 cases, with an incidence of 63.6%. The proportion of pulmonary dysfunction in the hypotension group was higher than in the control group (100.0% vs 50.0%, p < 0.05). The spinal flexibility was significantly lower in the hypotension group (28.3% ± 14.2% vs 46.5% ± 11.5%, p < 0.05). Fourteen patients with intraoperative hypotension had decreased intraoperative systolic blood pressure 21.0%–50.0% compared with baseline. One patient had a transient decrease in the muscle strength of the lower limbs. No complications were observed during the follow-up.Conclusion:The incidence of intraoperative hypotension in Marfan syndrome scoliosis children who underwent surgery was 63.6%. The risk factors included preoperative pulmonary dysfunction and poor spinal flexibility. Comprehensive preoperative evaluation and effective hemodynamic handling measures should be undertaken to prevent further complications in children with Marfan syndrome scoliosis.

Current knowledge about the processes of luteolysis and maternal recognition of pregnancy in camelids.

Camelids have many unique reproductive features that considerably differ from those of other domestic species. Females are induced ovulators with subsequent development of a corpus luteum (CL) with a short lifespan. Plasma progesterone concentration starts to increase on day 4, peaks on day 8-9 and, in non-pregnant animals, basal concentration is reached around day 10-11 post-induction of ovulation. Luteolytic pulses of prostaglandin F2α (PGF2α ) are firstly detected on day 7 or 8 (approximately on day 5-6 after ovulation), with maximal luteolytic peaks observed between days 9 and 11 post-mating, in coincidence with a high endometrial expression of cyclooxygenase 2, a limiting enzyme in prostaglandins synthesis. Unlike other species, oxytocin seems not to be involved in the luteolytic process in these species. The CL is the main source of progesterone secretion, and its function is required to support pregnancy. Despite constant research efforts, aspects of reproduction and maternal recognition of pregnancy in camelids remain not fully understood. A transient decrease and subsequent recovery in plasma progesterone concentration are observed after day 9 post-mating in pregnant animals in association with a pulsatile release of PGF2α and a transitory decrease in CL vascularization. Thus, embryo recognition should occur between days 8 and 12 post-mating. In camels, conceptus tissues exhibit aromatizing activity with the capacity to synthesize large amounts of oestradiol. Similarly, llama blastocysts secrete oestradiol-17β during the preimplantation stage, with a higher production during the elongation period. An increase in the endometrial expression of oestrogen receptor α is also observed on day 12 post-mating. All these evidences suggest that oestrogen could be the signal released by the embryo at the time of its recognition in camelids. Besides, nearly 98% of pregnancies are carried out in the left horn. A decrease in the endometrial expression of mucin 1 and 16 genes has been reported, suggesting that these changes are crucial for successful embryo implantation; however, no differences have been observed between horns. Thus, maternal recognition of pregnancy in camelids is a particularly complex process that must occur in a concise time to allow the rescue of the CL and embryo survival.

Energy pile groups for thermal energy storage in unsaturated soils

• Energy pile groups provide superior thermal energy storage performance over boreholes. • Both energy pile geometry and number of internal heat exchangers are important. • Lower thermal conductivity of unsaturated soils leads to higher heat retention. • Transient decreases in degree of saturation were observed over several years. • Heat transfer in unsaturated soil can be enhanced in some cases via vapor diffusion. A coupled heat transfer and water flow model implemented in COMSOL and validated against measurements from a tank scale test was applied to investigate the application of energy pile groups for thermal energy storage in unsaturated soil layers. The novel focus of the investigation was understanding the long-term thermo-hydraulic response of the unsaturated soil within the energy pile group during heat injection at high temperature up to 90 °C and associated impacts on the heat storage performance. Unsaturated soil layers are advantageous for thermal energy storage due to enhanced convective heat transfer during injection associated with vapor diffusion and favorable insulation properties during storage associated with lower thermal conductivity of soils surrounding a heat storage system. Evolutions in temperature and degree of saturation in soil layers having different hydraulic properties and water table depths were simulated during five years of operating a group of five energy piles with inlet fluid temperatures of 90 °C during heat injection and 30 °C during heat extraction. Transient fluctuations in the degree of saturation were observed in all soil layers simulated, but a permanent decrease was only observed for a soil layer having a greater air entry suction after several cycles of heating and cooling. While the heat storage in energy pile groups in unsaturated soil layers was always between that of dry and saturated soils with no groundwater flow, the soil hydraulic properties and water table depth were found to control both the rate of heat transfer and the total heat stored. When comparing the performance of energy pile groups with a group of borehole heat exchangers commonly used in heat storage applications, the energy piles were approximately 1.2 times more effective in extracting heat with a faster response confirming their suitability for heat storage.

EFFECTS OF 2-METHYL-2-THIAZOLINE ON CIRCULATORY DYNAMICS AND INTESTINAL VASCULAR SYSTEM IN RABBITS WITH ENDOTOXIC SHOCK.

ABSTRACTWe hypothesized that circulatory and jejunal mucosal blood flow would improve after 2-methyl-2thiazoline (2MT) administration in endotoxic shock. This study aimed to evaluate changes in systemic circulation and in superior mesenteric venous (SMV) blood flow and jejunal mucosal tissue blood flow of the intestinal vascular system over time after administration of 2MT in rabbits with endotoxic shock. We created four groups (n = 6 each): control group, LPS (1 mg/kg) group, 2MT (80 mg/kg) group, and LPS-2MT group. As indicators of circulation, we measured MAP, heart rate, cardiac index, lactic acid level, SMV blood flow, and jejunal mucosal tissue blood flow every 30 min from 0 to 240 min. The drop in MAP observed in the LPS group was suppressed by 2MT administration. Superior mesenteric venous blood flow dropped temporarily with LPS administration but then rose thereafter. After administration of 2MT to the LPS group, SMV blood flow began to rise earlier than that in the LPS group and did not decline below that of the control group thereafter. In the LPS group, jejunal mucosal tissue blood flow transiently decreased and then increased but at a lower level than that in the control group. However, in the LPS-2MT group, although a transient decrease in jejunal mucosal tissue blood flow was observed, its flow then improved to the level of the control group. An interaction between 2MT and LPS was observed for jejunal mucosal tissue blood flow from 90 to 180 min and at 240 min (P < 0.05). We showed that 2MT maintained MAP and improved SMV blood flow and jejunal mucosal tissue blood flow. In a rabbit model of endotoxic shock, 2MT had a positive effect on MAP and jejunal mucosal tissue blood flow.

Impact of transient decrease in mixed venous oxygen saturation on prognosis in off-pump coronary artery bypass surgery: a retrospective cohort study.

The prognostic consequences of transient hemodynamic deterioration due to cardiac displacement, which is most severe during left circumflex artery (LCX) grafting in off-pump coronary artery bypass surgery (OPCAB) are unknown. This study aimed to investigate the association between mixed venous oxygen saturation (SvO2) < 60% during LCX grafting and the occurrence of composite of morbidity endpoints. Data of patients who underwent elective OPCAB between January 2010 and December 2019 were reviewed. Logistic regression analysis was performed to detect risk factors for the composite of morbidity endpoints, defined as 30-day or in-hospital mortality, postoperative myocardial infarction, prolonged mechanical ventilation > 24 h, cerebrovascular accident, and acute kidney injury. Among 1,071 patients, the composite of morbidity endpoints occurred in 303 (28%) patients. SvO2 < 60% during LCX grafting was significantly associated with the composite of morbidity (OR: 2.72, 95% CI [1.60, 4.61], P < 0.001) along with advanced age, chronic kidney disease, ratio of early mitral inflow velocity to mitral annular early diastolic velocity, and EuroSCORE II. Other major hemodynamic variables including the cardiac index were not associated with the outcome. Additional regression analysis revealed pre-operative anemia as a predictor of SvO2 < 60% during LCX grafting (OR: 2.09, 95% CI [1.33, 3.29], P = 0.001). A decrease in SvO2 < 60%, albeit confined to the period of cardiac displacement, was associated with a 2.7-fold increased risk of detrimental outcomes after OPCAB, implying the prognostic importance of this transient deterioration in oxygen supply-demand balance.

Transient decrease in sound tolerance levels following hearing deprivation in normal-hearing subjects

ObjectiveTo determine the circadian influence on sound sensitivity produced by temporal hearing deprivation in healthy normal human subjects. DesignParticipants underwent bilateral earplugging before completion of anthropometry, the author's developed questionnaire, the Hamilton Anxiety and Depression Inventory, pure tone audiometry (PTA), stapedial reflex thresholds (SRT), distortion products otoacoustic emissions input/output (DPOAE-I/O), and uncomfortable loudness levels (ULLs). Afterward, the participants were randomly divided into group A, starting at 8:00 a.m. and finishing at 8:00 p.m., and group B, starting at 4:00 p.m. and ending at 4:00 a.m. Serum cortisol levels and audiological test results were obtained at the beginning and end of the session and 24-h free urinary cortisol levels were measured. Study sampleThirty healthy volunteers. ResultsPTA was 2.68 and 3.33 dB HL in groups A and B, respectively, with no statistical difference between them. ULLs were significantly lower in group A compared to group B, with an average of 8.1 dB SPL in group A and 3.3 dB SPL in group B (p < 0.0001). A SRT shift was observed in group A, with no difference in group B, and a night shift in DPOAE-I/O in group B. ConclusionsReduced loudness tolerance is demonstrated during daytime hearing deprivation in contrast to nighttime; this may be due to increased central gain in the awake cortex.

Takotsubo Cardiomyopathy After Cocaine Intoxication.

IntroductionCocaine is a highly addictive substance that stimulates the sympathetic nervous system and cardiovascular system. A multitude of adverse cardiovascular events are associated with cocaine use including arrhythmia, congestive heart failure, coronary artery spasm and myocarditis.Case ReportWe present a rare case of Takotsubo cardiomyopathy after recent use of cocaine in a female without any other identifiable risk factor.DiscussionTakotsubo cardiomyopathy (TCM) is a reversible cause of cardiomyopathy characterized by transient decrease in ejection fraction. Cocaine is a sympathomimetic that causes catecholamine surge and a variety of cardiovascular abnormalities. The association of cocaine use with Takotsubo cardiomyopathy is a rare occurrence, however the prognosis is generally good if diagnosis is made promptly.ConclusionPhysician vigilance is required to diagnose this rare cause of cardiomyopathy and reduce morbidity and mortality.LEARNING POINTSThis case highlights the need to investigate the use of cocaine in patients with cardiovascular disease because it may influence the disease diagnosis and management strategies.Left heart catheterization is imperative for diagnosis, and cessation of cocaine is the primary goal of post discharge therapy.This case shows that TCM should be suspected in a patient with a history of cocaine use.

Effect Of Age And Range Of Motion On Knee Extensor Muscle Torque-Velocity And Fatigue Characteristics

While it is well accepted that muscle fatigue (transient decrease in peak torque) is task-specific, little information exists regarding the influence of joint range of motion (ROM) on fatigue. Further, given the age-related changes in the torque-velocity (T-V) relationship, it is reasonable to expect that ROM may influence fatigue differently in young and older muscle. PURPOSE: To determine the effect of knee joint ROM on knee extensor muscle torque-velocity and fatigue characteristics in young and older adults. METHODS: After providing written informed consent, 7 young (29 ± 5 yr, 5F) and 5 older (70 ± 4, 4F) adults had each leg randomly assigned to a 35 or 75 deg ROM condition. Using dynamometry (Biodex S4, Biodex, Shirley NY), T-V characteristics (peak torque at 60, 120, 150, 180, 240, and 300 deg∙s-1, in random order) were measured in 1 leg and fatigue (% initial peak torque) during 120 maximal contractions (once every 2 s at 120 deg∙s-1) was measured in the other. The protocols were switched at a second visit, such that each leg ultimately completed both protocols at either 35 or 75 deg ROM. All torque data were normalized to thigh lean mass (kg), determined using dual x-ray absorptiometry (Lunar iDXA, General Electric, Chicago IL). Statistics: rmANOVA, mean ± SD. RESULTS:The T-V relationship did not differ by ROM in young (p = 0.10). In contrast, the older adults did not attain 300 deg∙s-1over 35 deg and torques were lower for 35 than 75 between 60 - 240 deg∙s-1 (p = 0.04). Fatigue was greater during 75 deg ROM (young: to 46 ± 14% initial, older: to 28 ± 18%) than 35 deg ROM (young: to 71 ± 13% initial, older: to 66 ± 8%; ROM effect p < 0.001), with no effect of age or age x ROM interaction (p ≥ 0.12). CONCLUSION: Overall, the T-V data showed that young, but not older, adults were able to attain peak torque within 35 deg. Presumably, age-related slowing of contraction velocity contributed to this deficit. Greater fatigue in both groups during contractions at 75 deg ROM, likely due to the greater duty cycle and total work in this task, indicates that ROM is an important factor in the task specificity of fatigue. The apparent lack of an effect of age on the ROM-related difference in fatigue at a moderate velocity suggests that differences in the T-V relationship were not exacerbated by fatigue in the older group. Additional work is needed to confirm this result.

Acute Effects Of Different Exercise Modes On Salivary Iga And Plasma Cortisol Secretory Responses

Salivary Immunoglobulin A (IgA) prevent bacterial attachment to the mucosal surfaces. High-intensity or long-term exercise causes a transient decrease in oral immune function through decreased salivary IgA secretion, and this response is associated with exercise-induced stress, such as cortisol. However, it is unclear whether differences in exercise modes affect salivary IgA and plasma cortisol secretory responses. PURPOSE:The purpose of this study was to examine whether differences in exercise modes affect salivary IgA and plasma cortisol secretory responses to a single bout of exercise. METHODS:Seven healthy young males with no exercise habits participated in the study. Subjects randomly performed two conditions: moderate-intensity continuous exercise (MICE) for 20 min cycle exercise at a work rate equivalent to 70% VO2max, and high-intensity interval exercise (HIIE, same total exercising volume to MICE) for 20 min cycle exercise, consisting of five 2 min bouts at 90% VO2max with 2 min active recovery at 50% VO2max. Saliva and blood samples were collected before, immediately after, 30 min after each exercise condition. The salivary IgA secretion rate was calculated from salivary IgA concentration and saliva volume per minute. RESULTS:In MICE, change in salivary IgA secretion rate at immediately after and 30 min after exercise was significantly lower than that before exercise (P < 0.05), but did not change in HIIE. In addition, the amount of change (area under the curve) in salivary IgA secretion rate in MICE was lower than that in HIIE (P < 0.05). Plasma cortisol concentration did not change in both MICE and HIIE. However, there was a significant negative correlation between salivary IgA secretion rate and plasma cortisol concentration in MICE (r = -0.544, P < 0.05). CONCLUSIONS:These results suggest that the salivary IgA secretory response may differ with different exercise modes. In MICE, the reduced salivary IgA secretory response may be associated with the increase in systemic cortisol concentration. Supported by Grants-in-Aid for Scientific Research (#19 K22828, M. Iemitsu)

Brain region-specific microglial and astrocytic activation in response to systemic lipopolysaccharides exposure.

Microglia cells are the macrophage population within the central nervous system, which acts as the first line of the immune defense. These cells present a high level of heterogeneity among different brain regions regarding morphology, cell density, transcriptomes, and expression of different inflammatory mediators. This region-specific heterogeneity may lead to different neuroinflammatory responses, influencing the regional involvement in several neurodegenerative diseases. In this study, we aimed to evaluate microglial response in 16 brain regions. We compared different aspects of the microglial response, such as the extension of their morphological changes, sensitivity, and ability to convert an acute inflammatory response to a chronic one. Then, we investigated the synaptic alterations followed by acute and chronic inflammation in substantia nigra. Moreover, we estimated the effect of partial ablation of fractalkine CX3C receptor 1 (CX3CR1) on microglial response. In the end, we briefly investigated astrocytic heterogeneity and activation. To evaluate microglial response in different brain regions and under the same stimulus, we induced a systemic inflammatory reaction through a single intraperitoneal (i.p.) injection of lipopolysaccharides (LPS). We performed our study using C57BL6 and CX3CR1+/GFP mice to investigate microglial response in different regions and the impact of CX3CR1 partial ablation. We conducted a topographic study quantifying microglia alterations in 16 brain regions through immunohistochemical examination and computational image analysis. Assessing Iba1-immunopositive profiles and the density of the microglia cells, we have observed significant differences in region-specific responses of microglia populations in all parameters considered. Our results underline the peculiar microglial inflammation in the substantia nigra pars reticulata (SNpr). Here and in concomitance with the acute inflammatory response, we observed a transient decrease of dopaminergic dendrites and an alteration of the striato-nigral projections. Additionally, we found a significant decrease in microglia response and the absence of chronic inflammation in CX3CR1+/GFP mice compared to the wild-type ones, suggesting the CX3C axis as a possible pharmacological target against neuroinflammation induced by an increase of systemic tumor necrosis factor-alpha (TNFα) or/and LPS. Finally, we investigated astrocytic heterogeneity in this model. We observed different distribution and morphology of GFAP-positive astrocytes, a heterogeneous response under inflammatory conditions, and a decrease in their activation in CX3CR1 partially ablated mice compared with C57BL6 mice. Altogether, our data confirm that microglia and astrocytes heterogeneity lead to a region-specific inflammatory response in presence of a systemic TNFα or/and LPS treatment.

Decrease in Bone Formation and Bone Resorption during Intravenous Methylprednisolone Pulse Therapy in Patients with Graves' Orbitopathy.

Background: Treatment with glucocorticoids (GCs) is associated with side effects. In contrast to the well-known negative impact on bone tissue exerted by oral GCs, few data are available regarding intravenous GCs. We investigated the influence of intravenous methylprednisolone (IVMP) on bone turnover markers (BTM): amino-terminal propeptide of type I procollagen (P1NP) and the C-terminal telopeptide of type I collagen (CTX), and on calcium metabolism parameters: 1,25-dihydroxyvitamin D (1,25(OH)2D), 25-hydroxyvitamin D (25(OH)D), calcium (Ca), phosphate (P), and intact parathormone (iPTH). Methods: In a prospective study, 23 consecutive subjects with Graves’ orbitopathy were included and treated with IVMP according to the European Group on Graves’ Orbitopathy recommendations. We evaluated effects on BTM occurring during the first 7 days after 0.5 g IVMP, and after the therapy with 12 IVMP pulses with a cumulative dose of 4.5 g. Results: We observed prompt but transient decrease of P1NP (p < 0.001) and the reduction of CTX (p = 0.02) after the first IVMP pulse. Following the full course of IVMP therapy, both P1NP and CTX were found decreased (p < 0.05 and p < 0.01, respectively). Conclusions: A single pulse of 0.5 g IVMP already decreases bone formation and resorption; however, this change is transient. The full therapy is associated with suppression of bone turnover.

Modeling early changes associated with cartilage trauma using human-cell-laden hydrogel cartilage models

BackgroundTraumatic impacts to the articular joint surface are known to lead to cartilage degeneration, as in post-traumatic osteoarthritis (PTOA). Limited progress in the development of disease-modifying OA drugs (DMOADs) may be due to insufficient mechanistic understanding of human disease onset/progression and insufficient in vitro models for disease and therapeutic modeling. In this study, biomimetic hydrogels laden with adult human mesenchymal stromal cells (MSC) are used to examine the effects of traumatic impacts as a model of PTOA. We hypothesize that MSC-based, engineered cartilage models will respond to traumatic impacts in a manner congruent with early PTOA pathogenesis observed in animal models.MethodsEngineered cartilage constructs were fabricated by encapsulating adult human bone marrow-derived mesenchymal stem cells in a photocross-linkable, biomimetic hydrogel of 15% methacrylated gelatin and promoting chondrogenic differentiation for 28 days in a defined medium and TGF-β3. Constructs were subjected to traumatic impacts with different strains or 10 ng/ml IL-1β, as a common comparative method of modeling OA. Cell viability and metabolism, elastic modulus, gene expression, matrix protein production and activation of catabolic enzymes were assessed.ResultsCell viability staining showed that traumatic impacts of 30% strain caused an appropriate level of cell death in engineered cartilage constructs. Gene expression and histo/immunohistochemical analyses revealed an acute decrease in anabolic activities, such as COL2 and ACAN expression, and a rapid increase in catabolic enzyme expression, e.g., MMP13, and inflammatory modulators, e.g., COX2. Safranin O staining and GAG assays together revealed a transient decrease in matrix production 24 h after trauma that recovered within 7 days. The decrease in elastic modulus of engineered cartilage constructs was coincident with GAG loss and mediated by the encapsulated cells. The acute and transient changes observed after traumatic impacts contrasted with progressive changes observed using continual IL-1β treatment.ConclusionsTraumatic impacts delivered to engineered cartilage constructs induced PTOA-like changes in the encapsulated cells. While IL-1b may be appropriate in modeling OA pathogenesis, the results of this study indicate it may not be appropriate in understanding the etiology of PTOA. The development of a more physiological in vitro PTOA model may contribute to the more rapid development of DMOADs.

Local anatomy, stimulation site, and time alter directional deep brain stimulation impedances.

Directional deep brain stimulation (DBS) contacts provide greater spatial flexibility for therapy than traditional ring-shaped electrodes, but little is known about longitudinal changes of impedance and orientation. We measured monopolar and bipolar impedance of DBS contacts in 31 patients who underwent unilateral subthalamic nucleus deep brain stimulation as part of a randomized study (SUNDIAL, NCT03353688). At different follow-up visits, patients were assigned new stimulation configurations and impedance was measured. Additionally, we measured the orientation of the directional lead during surgery, immediately after surgery, and 1 year later. Here we contrast impedances in directional versus ring contacts with respect to local anatomy, active stimulation contact(s), and over time. Directional contacts display larger impedances than ring contacts. Impedances generally increase slightly over the first year of therapy, save for a transient decrease immediately post-surgery under general anesthesia during pulse generator placement. Local impedances decrease at active stimulation sites, and contacts in closest proximity to internal capsule display higher impedances than other anatomic sites. DBS leads rotate slightly in the immediate postoperative period (typically less than the angle of a single contact) but otherwise remain stable over the following year. These data provide useful information for setting clinical stimulation parameters over time.

Cysteinyl Maresins Reprogram Macrophages to Protect Mice from Streptococcus pneumoniae after Influenza A Virus Infection.

ABSTRACTInfluenza A virus (IAV) infections are a leading cause of mortality worldwide. Excess mortality during IAV epidemics and pandemics is attributable to secondary bacterial infections, particularly pneumonia caused by Streptococcus pneumoniae. Resident alveolar macrophages (rAMs) are early responders to respiratory infections that coordinate initial host defense responses. Maresin conjugates in tissue regeneration (MCTRs) are recently elucidated cysteinyl maresins that are produced by and act on macrophages. Roles for MCTRs in responses to respiratory infections remain to be determined. Here, IAV infection led to transient decreases in rAM numbers. Repopulated lung macrophages displayed transcriptional alterations 21 days post-IAV with prolonged susceptibility to secondary pneumococcal infection. Administration of a mix of MCTR1 to 3 or MCTR3 alone post-IAV decreased lung inflammation and bacterial load 48 and 72 h after secondary pneumococcal infection. MCTR-exposed rAMs had increased migration and phagocytosis of Streptococcus pneumoniae, reduced secretion of CXCL1, and a reversion toward baseline levels of several IAV-induced pneumonia susceptibility genes. Together, MCTRs counter regulated post-IAV changes in rAMs to promote a rapid return of bacteria host defense.

The Evaluation of the Obstetric Outcomes in Re-Pregnancy after Recovery from Peripartum Cardiomyopathy

The exceptional form of pregnancy specific idiopathic congestive heart failure is known as peripartum cardiomyopathy. Its onset is highly observed during the last month of pregnancies. Objective: To evaluate the cardiac outcomes in the subsequent pregnancies of patients having history of the cardiomyopathy. Methods: It is a retrospective cohort study conducted at Gynae unit Timergara Teaching hospital Dir Lower KPK for the duration of one year from March 2021 to March 2022. The seventy six patients that had history of peripartum cardiomyopathy with re-pregnancy were selected for the study. The participants were aware of the study and written consent was signed by them. The echocardiography examination of each patients were reviewed. The demographic data maternal and neonatal outcomes data of index was recorded. The SPSS software was used for the statistical analysis of the data. Results: Data of seventy six patients that had history of peripartum cardiomyopathy with re-pregnancy were evaluated. The average age of mother at the time of delivery was 26 years. There were 30 patients that reported about mood disorders and they were already taking medications during the pregnancy. 15 patients reported about migraine headache. There were only small number of patients that had prior diagnosis of cardiovascular diseases. The chronic hypertension was observed in 3 patients and 4 patients had Wolf-Parkinson-White syndrome. Conclusions: In this study the effect of re-pregnancy on cardiac outcomes were studied among patients who had a history of peripartum cardiomyopathy. Patients having peripartum cardiomyopathy history and recover LV function are at risk for a transient minor decrease in LV ejection fraction during future pregnancies. The promising obstetric and neonatal outcomes were observed.