Acute Increase Research Articles

Glucocorticoid receptors regulate central amygdala GABAergic synapses in Marchigian-Sardinian alcohol-preferring rats

Impairments in the function of the hypothalamic-pituitary-adrenal (HPA) axis and enhanced glucocorticoid receptor (GR) activity in the central amygdala (CeA) are critical mechanisms in the pathogenesis of alcohol use disorder (AUD). The GR antagonist mifepristone attenuates craving in AUD patients, alcohol consumption in AUD models, and decreases CeA γ-aminobutyric acid (GABA) transmission in alcohol-dependent rats. Previous studies suggest elevated GR activity in the CeA of male alcohol-preferring Marchigian-Sardinian (msP) rats, but its contribution to heightened CeA GABA transmission driving their characteristic post-dependent phenotype is largely unknown.We determined Nr3c1 (the gene encoding GR) gene transcription in the CeA in male and female msP and Wistar rats using in situ hybridization and studied acute effects of mifepristone (10 μM) and its interaction with ethanol (44 mM) on pharmacologically isolated spontaneous inhibitory postsynaptic currents (sIPSCs) and electrically evoked inhibitory postsynaptic potentials (eIPSPs) in the CeA using ex vivo slice electrophysiology.Female rats of both genotypes expressed more CeA GRs than males, suggesting a sexually dimorphic GR regulation of CeA activity. Mifepristone reduced sIPSC frequencies (GABA release) and eIPSP amplitudes in msP rats of both sexes, but not in their Wistar counterparts; however, it did not prevent acute ethanol-induced increase in CeA GABA transmission in male rats.In msP rats, GR regulates CeA GABAergic signaling under basal conditions, indicative of intrinsically active GR. Thus, enhanced GR function in the CeA represents a key mechanism contributing to maladaptive behaviors associated with AUD.

PHEOCHROMOCYTOMA AS A RARE CAUSE OF MYOCARDIAL INFARCTION

Objective: A 41-year-old man was admitted to the cardiac care unit with acute chest pain radiating to his left arm. For the previous 20 years, he had episodes of high blood pressure accompanied by shivering, sweating, anxiety, and headaches. Electrocardiography revealed ST elevation in the II, III, and aVF leads, as well as reciprocal ST depression in the I and aVL leads. Echocardiography showed hypokinesis of the mid inferior and basal inferior segments. Troponin level increased from 0.005 to 0.177 ng/ml. Aneurysms in the coronary arteries were discovered during an urgent coronary angiography. The patient was prescribed aspirin, angiotensin-converting enzyme inhibitor, and calcium channel blocker and discharged from the hospital. Design and method: Further testing included computed tomography (CT) of the aorta and coronary arteries. The aorta had no pathological findings, but the right coronary artery was dilated in the middle segment. A CT scan of the abdomen revealed a mass in the left adrenal gland, and later abdominal and retroperitoneal magnetic resonance imaging revealed a lipid-poor left adrenal mass. Biomarkers of adrenal gland function were evaluated and blood adrenalin (150 pg/ml normal range ‹125pg/ml) and noradrenalin (680pg/ml normal range ‹600pg/ml) levels were mildly elevated. The 24-hour urinary vanillylmandelic acid level was elevated (76,6umol vs. the normal range of 68umol). Cortisol and aldosterone levels in the blood were within normal ranges. Lateral transperitoneal adrenalectomy was eventually performed successfully. Results: Histological examination of the mass revealed a pheochromocytoma. The patient's blood pressure returned to normal after the left adrenalectomy, and episodes of sweating and anxiety accompanied by an acute increase in blood pressure disappeared. Conclusions: Pheochromocytoma is a rare neuroendocrine tumor that can cause life-threatening cardiovascular complications such as myocardial infarction and cardiac arrhythmias. Unfortunately, the clinical pattern of pheochromocytoma frequently remains without typical manifestations and needs detailed laboratory and radiological confirmation. This case emphasizes the importance of a comprehensive assessment of the patient with arterial hypertension, even in the presence of subclinical sympathetic overactivity.

Repetitive mild traumatic brain injury induces hippocampal neural immune signaling linked to astrocyte reactivity

AbstractBackgroundRepeated mild traumatic brain injuries (mTBIs) sustained within a “window of vulnerability” can lead to a cumulative severity of outcomes such as memory impairment, depression, and long‐term development of amyloid beta (Aβ) pathology and neurofibrillary tangles. We previously reported that acute increases in neural immune signaling within the MAPK pathway and expression of pro‐inflammatory cytokines were associated with low cerebral blood flow (CBF) and worse long‐term spatial learning and memory in a weight‐drop mouse model of repetitive mTBI. We hypothesized that an increasing number of injuries would lead to an increase in neural immune signaling, pathological markers, and glial activation in the hippocampus.MethodFemale 3xTg mice at 3‐4mo of age were subjected to 1x, 3x, or 5x weight‐drop closed head injuries (CHI) spaced once‐daily. Animals were sacrificed and brains harvested at 30min, 4h, 24h, or 1‐month after the final CHI (n = 7‐10/time point/injury group). 32 cytokines, 10 MAPK phospho‐proteins, Aβ42, Aβ40, phospho‐tau (pThr181), and total tau were measured by Luminex in hippocampal tissues. GFAP was measured by ELISA. CBF was non‐invasively measured immediately prior to sacrifice.ResultWe observed a steady increase in both total tau and phospho‐tau and a trend of increased GFAP in the hippocampus after repeated injuries. We then identified groups of cytokines and MAPK phospho‐proteins which co‐vary with either GFAP or phospho‐tau. GFAP‐associated cytokines showed a rapid acute increase after injury then a return to basal levels by 24h, while GFAP‐associated MAPK dynamics changed with repeated injury. Cytokines and MAPK phospho‐proteins showed a notably high degree of cross‐correlation 4h after repeated injury, when GFAP levels were at their highest. Multivariate analysis revealed that high levels of GFAP were associated with low CBF while increased phospho‐tau in the frontal cortex was associated with high CBF.ConclusionTogether, our data indicate an increase in hippocampal neural immune signaling and astrocyte reactivity after repetitive brain injury. Immune signaling changes may be causally linked to spatial learning and memory deficits after repetitive mTBI.

Causes of Death in Patients With Brain Metastases.

Advances in targeted therapies and wider application of stereotactic radiosurgery (SRS) have redefined outcomes of patients with brain metastases. Under modern treatment paradigms, there remains limited characterization of which aspects of disease drive demise and in what frequencies. This study aims to characterize the primary causes of terminal decline and evaluate differences in underlying intracranial tumor dynamics in patients with metastatic brain cancer. These fundamental details may help guide management, patient counseling, and research priorities. Using NYUMets-Brain-the largest, longitudinal, real-world, open data set of patients with brain metastases-patients treated at New York University Langone Health between 2012 and 2021 with SRS were evaluated. A review of electronic health records allowed for the determination of a primary cause of death in patients who died during the study period. Causes were classified in mutually exclusive, but collectively exhaustive, categories. Multilevel models evaluated for differences in dynamics of intracranial tumors, including changes in volume and number. Of 439 patients with end-of-life data, 73.1% died secondary to systemic disease, 10.3% died secondary to central nervous system (CNS) disease, and 16.6% died because of other causes. CNS deaths were driven by acute increases in intracranial pressure (11%), development of focal neurological deficits (18%), treatment-resistant seizures (11%), and global decline driven by increased intracranial tumor burden (60%). Rate of influx of new intracranial tumors was almost twice as high in patients who died compared with those who survived ( P < .001), but there was no difference in rates of volume change per intracranial tumor ( P = .95). Most patients with brain metastases die secondary to systemic disease progression. For patients who die because of neurological disease, tumor dynamics and cause of death mechanisms indicate that the primary driver of decline for many may be unchecked systemic disease with unrelenting spread of new tumors to the CNS rather than failure of local growth control.

Impact of Cigarette Smoking and Exercise on Arterial Stiffness: A Narrative Literature Review

PURPOSE: Smoking often causes acute and chronic cardiovascular disorders. Cigarette smoking increases oxidative stress, reduces nitric oxide bioavailability, and changes the extracellular matrix, impairing arterial stiffness. However, regular physical activity and smoking cessation significantly and rapidly reverse the detrimental effects. This narrative review summarizes the relevant research that describes the impacts of cigarette smoking on the cardiovascular system and demonstrates the therapeutic or preventative roles of exercise and smoking cessation in smoking-associated arterial stiffness.METHODS: We used scientific search engines, including PubMed, Web of Science, Google Scholar, and Wiley Online Library, to identify previous studies exploring the effects of smoking, exercise, and smoking cessation on arterial stiffness.RESULTS: We discussed the most important therapeutic and/or preventive roles of exercise and smoking cessation in decreasing arterial stiffness. Most studies have demonstrated that acute and chronic smoking increase arterial stiffness. Smoking and physical activity were negatively associated. However, this relationship was often attenuated or reversed during adult exercise interventions. In addition, smoking cessation reversed the effects of smoking on arterial stiffness.CONCLUSIONS: Smoking increases the risk of acute and chronic cardiovascular disease. Cigarette smoking deteriorates arterial stiffness by altering the vascular walls. However, regular exercise and smoking cessation can improve or prevent impaired arterial stiffness.

Blood tau-PT217 contributes to the anesthesia/surgery-induced delirium-like behavior in aged mice.

Blood phosphorylated tau at threonine 217 (tau-PT217) is a newly established biomarker for Alzheimer's disease and postoperative delirium in patients. However, the mechanisms and consequences of acute changes in blood tau-PT217 remain largely unknown. We investigated the effects of anesthesia/surgery on blood tau-PT217 in aged mice, and evaluated the associated changes in B cell populations, neuronal excitability in anterior cingulate cortex, and delirium-like behavior using positron emission tomography imaging, nanoneedle technology, flow cytometry, electrophysiology, and behavioral tests. Anesthesia/surgery induced acute increases in blood tau-PT217 via enhanced generation in the lungs and release from B cells. Tau-PT217 might cross the blood-brain barrier, increasing neuronal excitability and inducing delirium-like behavior. B cell transfer and WS635, a mitochondrial function enhancer, mitigated the anesthesia/surgery-induced changes. Acute increases in blood tau-PT217 may contribute to brain dysfunction and postoperative delirium. Targeting B cells or mitochondrial function may have therapeutic potential for preventing or treating these conditions.

Design Thinking and Innovation in the Informal Industries in Kenya

In the recent past there have been calls to have Kenyan products labeled ‘Made in Kenya’. By doing so, the proponents believe that products ‘Made in Kenya’ will flock the local stores and even find their way to the foreign markets, thereby making Kenya proud of itself as well as earning the much-needed foreign exchange. While ‘Made in Kenya’ labeled products would be a great step forward to Kenya’s economic wellbeing, showcase talents and skills of the youth and a boost to its image in the global market, the low technology predominantly used in Kenya and lack of design thinking, still remain the greatest impediment to innovation. Using low technology in manufacturing usually results in high production costs and lack of capacity to launch mass production in response to acute increase in market demands. For example, the informal manufacturing sector in Kenya commonly referred to as Jua Kali, is a collection of semi-organized, unregulated, smaller ventures that employ a large number of people and rely on low-level technologies. A significant amount of industrial output is devoted to meeting basic requirements, such as the provision of low-cost consumer goods and services. Wood and furniture, metal products, glass and pottery, clothes, and leather are all produced in this industry. The lack of design thinking and low-level technology used in the production process obviously results in more man-hour on each unit produced, yet this is rarely considered on the final price of the product. The prices to a large scale, are usually concerned with the cost of materials without considering other hidden costs. The drive is to make the products affordable to low-income consumers, in order to satisfy the traders’ basic needs. In a wider perspective, this study focused on the application of design thinking and its impact on innovations in the informal industries in Kenya. Specifically, the study sought to establish; the application of design thinking as a system of feasibility to increase innovation in the informal industries in Kenya, the application of design thinking as a system of desirability to increase innovation in the informal industries in Kenya and its impact on the innovation in the informal industries in Kenya, as well as the application of design thinking as a system of viability to increase innovation in the informal industries in Kenya. This study reviewed secondary sources and investigations others have previously conducted in relation to the title of the study. Conventional content analysis was used to analyze data. The process of analysis began with the development of the research questions, then the identification of the dataset, and thorough evaluation of the dataset. Our findings deepen the current understanding about policy innovation and technological intervention in the informal industries in Kenya. The findings could also benefit the Government of Kenya, Kenya Association of Manufacturers and Juakali Associations, in terms of policy formulation and enhancement of sector performance.

His bundle pacing and AV nodal ablation for non-controlled atrial arrhythmia: a technical challenge with major clinical benefits

Abstract Funding Acknowledgements Type of funding sources: None. Background His bundle pacing (HBP) is an appealing alternative to right ventricular pacing in patients referred for permanent ventricular pacing and AV nodal ablation (AVNA) as it preserves physiological ventricular activation. Only limited amount of data is available in the literature regarding HBP combined with AVNA. Purpose To provide further evidence on the feasibility and efficacy of this therapeutic approach in patients with uncontrolled atrial arrhythmia. Methods We prospectively included all patients who underwent AVNA after HBP in three different hospitals between 2017 and 2022. Results AVNA following HBP lead implantation was performed in 75 patients. A complete AV block was obtained in 58 patients (77%) whereas significant modulation of the AV node conduction (heart rate &amp;lt; 60bpm) was obtained in 12 (16%). AVNA failure was observed in 5 (7%). The recording of an atrial signal by the HBP lead was more frequently observed in patients with AVNA modulation/failure compared to patients with complete AV block (11/17 vs 5/58; p &amp;lt; 0.001). There was no lead dislodgment during the AVNA procedures. Acute HB capture threshold increase &amp;gt; 1V occurred in 11 patients (15%) with return to baseline value at day one in 9. NYHA class and LVEF significantly improved from baseline to last follow-up (3.0 ± 0.7 vs 1.6 ± 0.5, p &amp;lt; 0.001; 47 ± 14% vs 60 ± 9%; p &amp;lt; 0.0001, respectively), Conclusion AVNA combined with HBP for non-controlled atrial arrhythmia was feasible and clinically efficient. Implanting the HB lead on the ventricular aspect of the tricuspid annulus avoiding atrial signal recording can facilitate AVNA.

Acute kidney injury following percutaneous left atrial appendage occlusion: results from an international multicentre registry

Abstract Funding Acknowledgements Type of funding sources: None. Background Acute kidney injury (AKI) is a serious complication after invasive cardiac procedures and has been associated with a higher incidence of periprocedural complications and increased mortality. Data on the occurrence of AKI associated with left atrial appendage occlusion (LAAO) are very limited. Purpose To report the incidence, predictors, and clinical implications of AKI following percutaneous LAAO. Methods This multicenter registry included 2124 patients with successful Watchman implantation. AKI was defined according to the AKI Network criteria as an increase in serum creatinine of ≥0.3 mg/dL or of ≥50% over the course of 48 hours post-procedure. Patients meeting this definition were further categorized in three stages: stage 1, increase in serum creatinine ≥ 0.3 mg/dl (≥ 26.4 μmol/l) or of 1.5 to 2 times compared to baseline; stage 2, increase in serum creatinine of 2 to 3 times compared to baseline; stage 3, increase in serum creatinine of &amp;gt; 3 times compared to baseline or serum creatinine ≥ 4.0 mg/dl [≥ 354 μmol/l] with an acute increase of at least 0.5 mg/dl [44 μmol/l]. Results Post-procedural AKI was documented in 68 (5.5%) of 1234 patients with creatinine determination between 24 and 48 hours post-LAAO. Among them, 63 (92.6%) patients had AKI stage 1, 4 (5.9%) had AKI stage 2, and 1 (1.5%) had AKI stage 3. AKI was associated with higher CHA2DS2-VASc (5.3 ± 1.4 vs. 4.8 ± 1.4; p=0.001) and HAS-BLED (3.8 ± 0.9 vs. 3.5 ± 1.0; p=0.01) scores at baseline, as well as a higher prevalence of diabetes mellitus (p=0.04) and CHF (p&amp;lt;0.001). At multivariate analysis (Table 1), independent predictors of AKI were CKD stage 4/5 (OR: 1.998; 95% CI: 1.018 – 3.923; p=0.04), and CHF (OR: 2.286; 95% CI: 1.328 – 3.934; p=0.01). The average follow-up was 13 ± 7 months. The annualized rates of cardiovascular mortality were 5.5% in AKI and 1.0% in non-AKI patients (p=0.01). The annualized rates of overall mortality were 15.1% in AKI and 3.4% in non-AKI patients (p&amp;lt;0.001). Conclusion AKI was an infrequent complication following percutaneous LAAO and a powerful predictor of cardiovascular and overall mortality during follow-up.

Does High-Intensity Exercise Cause Acute Liver Injury in Patients with Fontan Circulation? A Prospective Pilot Study.

The Fontan procedure results in chronic hepatic congestion and Fontan-associated liver disease (FALD) characterized by progressive liver fibrosis and cirrhosis. Exercise is recommended in this population, but may accelerate the progression of FALD from abrupt elevations in central venous pressure. The aim of this study was to assess if acute liver injury occurs after high-intensity exercise in patients with Fontan physiology. Ten patients were enrolled. Nine had normal systolic ventricular function and one had an ejection fraction < 40%. During cardiopulmonary exercise testing, patients had near-infrared spectroscopy (NIRS) to measure oxygen saturation of multiple organs, including the liver, and underwent pre- and post-exercise testing with liver elastography, laboratory markers, and cytokines to assess liver injury. The hepatic and renal NIRS showed a statistically significant decrease in oxygenation during exercise, and the hepatic NIRS had the slowest recovery compared to renal, cerebral, and peripheral muscle NIRS. A clinically significant increase in shear wave velocity occurred after exercise testing only in the one patient with systolic dysfunction. There was a statistically significant, albeit trivial, increase in ALT and GGT after exercise. Fibrogenic cytokines traditionally associated with FALD did not increase significantly in our cohort; however, pro-inflammatory cytokines that predispose to fibrogenesis did significantly rise during exercise. Although patients with Fontan circulation demonstrated a significant reduction in hepatic tissue oxygenation based on NIRS saturations during exercise, there was no clinical evidence of acute increase in liver congestion or acute liver injury following high-intensity exercise.

Beneficial or detrimental activity of regulatory T cells, indoleamine 2,3-dioxygenase, and heme oxygenase-1 in the lungs is influenced by the level of virulence of Mycobacterium tuberculosis strain infection.

Tuberculosis (TB) caused by the complex Mycobacterium tuberculosis (Mtb) is the main cause of death by a single bacterial agent. Last year, TB was the second leading infectious killer after SARS-CoV-2. Nevertheless, many biological and immunological aspects of TB are not completely elucidated, such as the complex process of immunoregulation mediated by regulatory T cells (Treg cells) and the enzymes indoleamine 2,3-dioxygenase (IDO) and heme oxygenase 1 (HO-1). In this study, the contribution of these immunoregulatory factors was compared in mice infected with Mtb strains with different levels of virulence. First Balb/c mice were infected by intratracheal route, with a high dose of mild virulence reference strain H37Rv or with a highly virulent clinical isolate (strain 5186). In the lungs of infected mice, the kinetics of Treg cells during the infection were determined by cytofluorometry and the expression of IDO and HO-1 by RT-PCR and immunohistochemistry. Then, the contribution of immune-regulation mediated by Treg cells, IDO and HO-1, was evaluated by treating infected animals with specific cytotoxic monoclonal antibodies for Treg cells depletion anti-CD25 (PC61 clone) or by blocking IDO and HO-1 activity using specific inhibitors (1-methyl-D,L-tryptophan or zinc protoporphyrin-IX, respectively). Mice infected with the mild virulent strain showed a progressive increment of Treg cells, showing this highest number at the beginning of the late phase of the infection (28 days), the same trend was observed in the expression of both enzymes being macrophages the cells that showed the highest immunostaining. Animals infected with the highly virulent strain showed lower survival (34 days) and higher amounts of Treg cells, as well as higher expression of IDO and HO-1 one week before. In comparison with non-treated animals, mice infected with strain H37Rv with depletion of Treg cells or treated with the enzymes blockers during late infection showed a significant decrease of bacilli loads, higher expression of IFN-g and lower IL-4 but with a similar extension of inflammatory lung consolidation determined by automated morphometry. In contrast, the depletion of Treg cells in infected mice with the highly virulent strain 5186 produced diffuse alveolar damage that was similar to severe acute viral pneumonia, lesser survival and increase of bacillary loads, while blocking of both IDO and HO-1 produced high bacillary loads and extensive pneumonia with necrosis. Thus, it seems that Treg cells, IDO and HO-1 activities are detrimental during late pulmonary TB induced by mild virulence Mtb, probably because these factors decrease immune protection mediated by the Th1 response. In contrast, Treg cells, IDO and HO-1 are beneficial when the infection is produced by a highly virulent strain, by regulation of excessive inflammation that produced alveolar damage, pulmonary necrosis, acute respiratory insufficiency, and rapid death.

Prognostic significance of laboratory parameters in assessment the severity of the course and outcome of coronavirus disease (COVID-19)

The objective – to evaluate the dynamics and prognostic value of inflammatory markers and other laboratory parameters in the blood of patientswith COVID-19 and to assess the severity of the course and mortality in this disease. Materials and Methods. The clinical and laboratory data of 819 patients with COVID-19 treated in a hospital were retrospectively analyzed. In 700 (85.5 %) patients, the disease occurred in a moderate form, these patients were recovered. Patients with severe course (n = 119) were treated in the intensive care unit, of which 47 (39.5 %) patients had a favorable outcome and 72 (60.5 %) patients died. All patients underwent clinical, biochemical (including IL-6) and coagulological studies at admission and in dynamics. The concentration of IL-1ß, IL-8, IL-10, tumor necrosis factor TNF-α were additionally measured in patients with severe COVID-19. Results. Initially, patients with severe disease, compared with moderate, had higher levels of C-reactive protein (p &lt; 0.001), LDH (p = 0,007), D-dimers (p = 0.028), fibrinogen (p = 0.014), the number of white blood cells (p = 0.018), as well as lower levels of albumin (p &lt; 0.001). In the group of patients with fatal outcome, higher levels of LDH (p = 0.008), creatinine (p = 0.009), urea (p &lt; 0.001), troponin (p = 0.024), D-dimers (p = 0.002), fibrinogen (p = 0.009), the relative content of immature leukocytes (p = 0.004), neutrophil to lymphocyte ratio (p = 0.022) were found than in survivors. On the 7th day of hospitalization, an acute increase in ferritin, urea, D-dimers, LDH, interleukins was noted in the group of deceased patients. Using the observer’s operating curves method, predictors of an unfavorable outcome in COVID-19 were determined: IL-10 above 9.46 pg/ml (area under the ROC curve AUC = 0.902), urea above 6.6 mmol/L (AUC = 0.815), TNF-α above 12.6 pg/ml (AUC = 0.799), C-reactive protein above 59.6 mg/L (AUC = 0.714), LDH above 348 U/L (AUC = 0.702), neutrophil to lymphocyte ratio above 4.94 (AUC = 0.700), IL-6 above 62.2 pg/ml (AUC = 0.686), ferritin above 772 μg/L (AUC = 0.654). Conclusions. Baseline levels of LDH, D-dimers, and fibrinogen have a discriminatory ability to determine both the severity and the outcome of COVID-19. The severity of the inflammatory response upon admission correlates with the severity of the disease, but has no prognostic value. At the time of admission, patients with an unfavorable outcome already have initial manifestations of organ dysfunction (assessed by creatinine, urea, and troponin levels). On the 7th day of hospitalization, the relationship of values and the outcome appears in ferritin and interleukin 6. The presence of a strong correlation between the levels of interleukins IL-6, IL-8, IL-10, TNF-α makes it possible to measure any of them.

An acute increase in Left Atrial volume and left ventricular filling pressure during Adenosine administered myocardial hyperaemia: CMR First-Pass Perfusion Study

ObjectiveTo investigate whether left atrial (LA) volume and left ventricular filling pressure (LVFP) assessed by cardiovascular magnetic resonance (CMR) change during adenosine delivered myocardial hyperaemia as part of a first-pass stress perfusion study.Methods and resultsWe enrolled 33 patients who had stress CMR. These patients had a baseline four-chamber cine and stress four-chamber cine, which was done at peak myocardial hyperaemic state after administering adenosine. The left and right atria were segmented in the end ventricular diastolic and systolic phases. Short-axis cine stack was segmented for ventricular functional assessment. At peak hyperaemic state, left atrial end ventricular systolic volume just before mitral valve opening increased significantly from baseline in all (91 ± 35ml vs. 81 ± 33ml, P = 0.0002), in males only (99 ± 35ml vs. 88 ± 33ml, P = 0.002) and females only (70 ± 26ml vs. 62 ± 22ml, P = 0.02). The right atrial end ventricular systolic volume increased less significantly from baseline (68 ± 21ml vs. 63 ± 20ml, P = 0.0448). CMR-derived LVFP (equivalent to pulmonary capillary wedge pressure) increased significantly at the peak hyperaemic state in all (15.1 ± 2.9mmHg vs. 14.4 ± 2.8mmHg, P = 0.0002), females only (12.9 ± 2.1mmHg vs. 12.3 ± 1.9mmHg, P = 0.029) and males only (15.9 ± 2.8mmHg vs. 15.2 ± 2.7mmHg, P = 0.002) cohorts.ConclusionLeft atrial volume assessment by CMR can measure acute and dynamic changes in preloading conditions on the left ventricle. During adenosine administered first-pass perfusion CMR, left atrial volume and LVFP rise significantly.

Perioperative care for drug abusers in the opioid crisis era

Background: Narcotic abuse and addiction have recently emerged as significant global issues. The consumption of dependence-inducing substances has become increasingly prevalent among younger generations in numerous countries, exacerbating the problem. Until 2015, South Korea had been relatively narcotic-free; however, this is no longer true. Consequently, encountering narcotic abusers in clinical settings, including operating rooms, is becoming more common. It is crucial to be prepared for these phenomena.Current Concepts: Research on managing narcotic abusers during the perioperative period remains insufficient. In 2023, the American Society of Regional Anesthesiologists and Pain Medicine published guidelines for the perioperative management of cannabinoid users. The decision to discontinue or continue medical cannabinoids before surgery remains uncertain. When managing patients with short- or long-term exposure to cannabinoids, anesthetic requirements tend to decrease in cases of acute intoxication and increase among long-term users. Therefore, the duration from the last use should be considered when adjusting the anesthetic dose.Discussion and Conclusion: Punishment is not a viable solution in a reality where narcotic abuse is increasingly common. Preventing addiction in individuals and supporting addicts’ treatment and rehabilitation is essential. There is an urgent need for interest and research focused on narcotic abuse.

Effects of active and sham tDCS on the soleus H-reflex during standing

Weak transcranial direct current stimulation (tDCS) is known to affect corticospinal excitability and enhance motor skill acquisition, whereas its effects on spinal reflexes in actively contracting muscles are yet to be established. Thus, in this study, we examined the acute effects of Active and Sham tDCS on the soleus H-reflex during standing. In fourteen adults without known neurological conditions, the soleus H-reflex was repeatedly elicited at just above M-wave threshold throughout 30 min of Active (N = 7) or Sham (N = 7) 2-mA tDCS over the primary motor cortex in standing. The maximum H-reflex (Hmax) and M-wave (Mmax) were also measured before and immediately after 30 min of tDCS. The soleus H-reflex amplitudes became significantly larger (by 6%) ≈1 min into Active or Sham tDCS and gradually returned toward the pre-tDCS values, on average, within 15 min. With Active tDCS, the amplitude reduction from the initial increase appeared to occur more swiftly than with Sham tDCS. An acute temporary increase in the soleus H-reflex amplitude within the first minute of Active and Sham tDCS found in this study indicates a previously unreported effect of tDCS on the H-reflex excitability. The present study suggests that neurophysiological characterization of Sham tDCS effects is just as important as investigating Active tDCS effects in understanding and defining acute effects of tDCS on the excitability of spinal reflex pathways.

Maternal elevated inflammation impairs placental fatty acids β-oxidation in women with gestational diabetes mellitus.

An adverse proinflammatory milieu contributes to abnormal cellular energy metabolism response. Gestational diabetes mellitus (GDM) is closely related to an altered maternal inflammatory status. However, its role on lipid metabolism regulation in human placenta has not yet been assessed. The aim of this study was to examine the impact of maternal circulating inflammatory mediators ([TNF]-α, [IL]-6, and Leptin) on placental fatty acid metabolism in GDM pregnancies. Fasting maternal blood and placental tissues were collected at term deliveries from 37 pregnant women (17 control and 20 GDM). Molecular approach techniques as radiolabeled lipid tracers, ELISAs, immunohistochemistry and multianalyte immunoassay quantitative analysis, were used to quantify serum inflammatory factors' levels, to measure lipid metabolic parameters in placental villous samples (mitochondrial fatty acid oxidation [FAO] rate and lipid content [Triglycerides]), and to analyze their possible relationships. The effect of potential candidate cytokines on fatty acid metabolism in ex vivo placental explants culture following C-section a term was also examined. Maternal serum IL-6, TNF-α and leptin levels were significantly increased in GDM patients compared with control pregnant women (9,9±4,5 vs. 3,00±1,7; 4,5±2,8 vs. 2,1±1,3; and 10026,7±5628,8 vs. 5360,2±2499,9 pg/ml, respectively). Placental FAO capacity was significantly diminished (~30%; p<0.01), whereas triglyceride levels were three-fold higher (p<0.01) in full-term GDM placentas. Uniquely the maternal IL-6 levels showed an inverse and positive correlation with the ability to oxidize fatty acids and triglyceride amount in placenta, respectively (r= -0,602, p=0.005; r= 0,707, p=0.001). Additionally, an inverse correlation between placental FAO and triglycerides was also found (r=-0.683; p=0.001). Interestingly, we ex vivo demonstrated by using placental explant cultures that a prolonged exposure with IL-6 (10 ng/mL) resulted in a decline in the fatty acid oxidation rate (~25%; p=0.001), along to acute increase (2-fold times) in triglycerides accumulation (p=0.001), and in lipid neutral and lipid droplets deposits. Enhanced maternal proinflammatory cytokines levels (essentially IL-6) is closely associated with an altered placental fatty acid metabolism in pregnancies with GDM, which may interfere with adequate delivery of maternal fat across the placenta to the fetus.

Piezo1 regulates expression of BK and TRPV4 channels in mouse cortical collecting duct (CCD)

Within the CCD, an acute increase in tubular fluid flow rate (TFFR) leads to an immediate high amplitude increase in [Ca 2+ ] i , due to release of IP3-sensitive internal Ca 2+ stores coupled to extracellular Ca 2+ entry at the basolateral membrane in both principal (PC) and intercalated (IC) cells therein (Liu et al., 2003, 2005, 2007). This is followed by a decay in [Ca 2+ ] i to a sustained plateau elevation due, at least in part, to luminal Ca 2+ entry through TRPV4 (Berrout et al., 2012). This flow-induced increase in [Ca 2+ ] i is necessary for BK channel-mediated flow induced K + secretion (FIKS) in the microperfused mammalian CCD. We generated a mouse with IC-specific targeted deletion of the mechanosensitive Ca 2+ permeable channel, Piezo1, which is expressed on the basolateral membranes of PCs and ICs in the mouse CCD (Dalghi et al., 2019). Microperfused CCDs isolated from these IC-PIEZO1-KO mice fed a high K (HK, 5% K + ) diet and subject to an increase in TFFR did not exhibit either a peak or plateau elevation in [Ca 2+ ] i in response to flow, and FIKS was eliminated. The absence of FIKS and the plateau elevation in [Ca 2+ ] during sustained flow in the CCDs of KO mice led us to examine whether BK and TRPV4 channel expression was impacted by deletion of PIEZO1.Indirect immunofluorescence (IF) staining was performed to examine expression and localization of the BK and TRPV4 channels in PCs and ICs of IC-PIEZO1-KO mice. Whole cell and apical + subapical fluorescence intensities in cryosections were analyzed using LAS X software from a total of 3 male and 3 female control mice and 3 male and 3 female IC-PIEZO1-KO mice fed HK diet x 10d.IF analysis showed reduced whole cell BKα expression in ICs of both male (p≤0.05) and female (p≤0.01) IC-PIEZO1-KO mice. We also saw reduced BKα expression in PCs from female but not male KOs. In addition, ICs in female but not male KO mice had reduced whole cell TRPV4 expression vs. controls (p≤0.01). Also, whole cell expression of TRPV4 in PCs from female KO mice was reduced vs. female controls (p≤0.01). The ratio of apical-to-whole cell expression of BKα was similar in PCs and ICs of KO and control mice. Male, but not female, KO mice had modestly reduced apical TRPV4 expression in PCs vs. controls (p≤0.01). Piezo1 plays a role in the regulation of BK and TRPV4 channel expression in CCDs. In addition, sex differences exist in whole cell expression of these channels in response to IC-selective deletion of PIEZO1. R01 DK038470 (TK, LMS); R01 DK129285 (TK, LMS); P30 DK079307 (TK) This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Peripapillary Retinoschisis in a Patient with Severe Primary Open Angle Glaucoma

Peripapillary retinoschisis is a rare finding that may be associated with the progression of primary open angle glaucoma (POAG). Potential pathophysiological mechanisms have been proposed to explain this association, such as acute and chronic increase in intraocular pressure, vitreopapillary traction, and Müller cell dysfunction from optic nerve head deformation. OCT imaging has revealed hyper-reflective strut-like pillars within the schisis cavity described as “bridging structures.” While peripapillary retinoschisis may spontaneously resolve, other strategies may include lowering intraocular pressure, intraocular injections, or pars plana vitrectomy.present a patient with peripapillary retinoschisis incidentally found during a workup for primary open angle glaucoma.

Sympathetic and blood pressure reactivity to acute stress in young adults with major depressive disorder: the influence of depressive symptomatology

Major depressive disorder (MDD) is episodic in nature, highly recurrent, and associated with increased cardiovascular disease (CVD) risk. Sympathetic overactivation in response to acute stress may contribute to MDD-CVD comorbidity. However, few studies have investigated acute sympathetic stress reactivity in young adults with MDD or considered the potential influence of depressive symptom severity on these responses. We hypothesized that 1) acute stress-induced increases in muscle sympathetic nerve activity (MSNA) and blood pressure (BP) would be greater in young adults with MDD (unmedicated) compared to healthy non-depressed adults (HA) and 2) the magnitude of responsiveness would be graded in relation to symptom severity. Twenty-nine HA (22±5 yrs; 17 female) and 40 adults with MDD having mild-to-moderately severe depressive symptoms (23±6 yrs; 32 female) participated. Adults with MDD were also subclassified as having either low (l-MDD, n=25) or high symptom severity (h-MDD, n=15). MSNA (microneurography) and beat-to-beat BP (photoplethysmography) were measured at rest and during the cold pressor test (CPT) and the Stroop color word test (SCWT). There were no group differences in either resting MSNA (17±9 HA vs. 14±6 bursts/min MDD, p=0.39) or mean arterial pressure (MAP; 86±6 HA vs. 84±5 mmHg MDD, p=0.25). The CPT elicited increases in MSNA and MAP (both p&lt;0.01), but the magnitude was not different between groups (MSNA: Δ24±12 HA vs. Δ19±9 bursts/min MDD, p=0.22; MAP: Δ24±8 HA vs. Δ23±9 mmHg MDD, p=0.45). The SCWT also elicited increases in MAP (p&lt;0.01) that were not different between groups (Δ10±7 HA vs Δ10±6 mmHg MDD; p=0.76). Surprisingly, the SCWT failed to cause increases in MSNA (p&gt;0.05), which also did not differ between groups (Δ-2±7 HA vs. Δ-2±8 bursts/min MDD, p=0.92). When further classifying adults with MDD into symptom severity subgroups, there likewise were no differences in MSNA reactivity to either acute stressor (both p&gt;0.05). Interestingly, adults with h-MDD exhibited greater increases in MAP than adults with l-MDD during the CPT (Δ28±9 h-MDD vs. Δ20±8 mmHg l-MDD, p&lt;0.01) but not during the SCWT (Δ9±4 h-MDD vs. Δ11±7 mmHg l-MDD, p=0.63). Contrary to our hypothesis, these data demonstrate that neither acute stress-induced sympathetic activation nor the ensuing increase in BP are exaggerated in young adults with MDD. However, the severity of active depressive symptomatology may influence BP reactivity to generalized stress stimuli, thereby influencing CVD risk profiles. NIH R21MH123928 and R00 HL133414 This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Difference in functional constituents of myocardial passive compliance renders BalbC/J mice sensitive to pulmonary edema compared to C57BL6/J mice

Study objective: We have found different survival rates in response to a 4-day angiotensin II (AngII) and high salt diet - treatment in two mouse strains, BalbC/J and C57BL6/J. The mortality is increased in BalbC/J mice alongside increased lung weight but the reason is unknown. Hypothesis: We hypothesize the increased mortality is due to differences in myocardial compliance. Methodology: Male mice were treated with AngII by osmotic mini-pump infusion and fed a high salt-diet (3%) for 4 days. At the end of the treatment the lungs were weighed. Left ventricle (LV) passive compliance was assessed by Langendorff, and collagen and non-collagen functional fractions using demembranated trabecular strips. A commercial assay was used to determine total collagen of the myocardium. All procedures were approved by the local ethics committee. Comparisons were carried out using unpaired t-test. All intervals reflect standard error of the mean. Data: Lung weights of animals before treatment were similar in BalbC/J (148 ± 8.8 mg (n=5)) and C57BL6/J (155 ± 12 mg (n=5)) mice (p&gt;0.05). After treatment they were higher in BalbC/J (255 ± 24 mg (n=7)) than C57BL6/J (166 ± 5.1 mg (n=6)) (p&lt;0.01). LV passive strain was higher in BalbC/J (62.4 ± 11.9 mN/mm2 (n=9)) than C57BL6/J (28.2 ± 2.3 mN/mm2 (n=7)) (p&lt;0.05), at 36 μl LV inflation past 5 mmHg end-diastolic pressure. In demembranated trabeculae, passive stiffness was higher in BalbC/J (38.7 ± 5.5 mN/mm2 (n=6)) than C57BL6/J (22.5 ± 2.0 mN/mm2 (n=6)) (p&lt;0.05) at baseline, as measured by passive tension at 15 % stretch from sarcomere length 2.0 μm. This was derived from the non-collagen fraction which was higher in BalbC (23.4 ± 2.8 mN/mm2 (n=6)) than C57BL6/J (12.4 ± 1.3 mN/mm2 (n=6)) (p&lt;0.01), unlike the collagen fraction that was the same (BalbC/J 15.3 ± 3.8 mN/mm2 (n=6), C57BL6/J 10.1 ± 1.5 mN/mm2 (n=6) (p&gt;0.05)). There was no difference in myocardial collagen content (BalbC/J 0.20 ± 0.01 μg/μl (n=7), C57BL6/J 0.18 ± 0.01 μg/μl (n=9) (p&gt;0.05)). Summary of results: Gross organ evaluation by Langendorff indicates higher myocardial stiffness in BalbC/J than C57BL6/. This renders the heart susceptible to backward failure. This is supported by findings in demembranated tissue bundles. The origin of this appears to lie in the non-collagen fraction of passive stiffness, as indicated by functional and biochemical assays. Conclusion: An acute lung weight increase indicates pulmonary edema. The most common reason for this is backwards failure of the LV. Our investigations into myocardial function suggest that BalbC/J mice has a propensity for this due to lower compliance secondary to increased non-collagen fraction, compared to C57BL6/J. This is likely caused by titin-derived stiffness. Therapies to modulate titin-derived stiffness may be useful to avoid backward failure. These findings also represent important knowledge for the research community modeling human heart disease on the backbone of two common mouse strains. The study was funded with grants from the Swedish Society of Medical Research and Åke Wiberg Foundation to HI, Swedish Heart-Lung Foundation to MH, and from Uppsala University Hospital to HI and MH. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.