Acute Increase Research Articles

PTSD Increases Risk for Hypertension Development Through PVN Activation and Vascular Dysfunction in Sprague Dawley Rats.

This study investigates the impact of single prolonged stress (SPS), a model of post-traumatic stress disorder (PTSD), on cardiovascular responses, hypothalamic paraventricular nucleus (PVN) activity, and vascular function to elucidate the mechanisms linking traumatic stress to hypertension. Although SPS did not directly cause chronic hypertension in male Sprague Dawley (SD) rats, it induced acute but transient increases in blood pressure and heart rate and significantly altered the expression of hypertension-associated genes, such as vasopressin, angiotensin II type 1 receptor (AT1R), and FOSL1 in the PVN. Notably, mitochondrial reactive oxygen species (mtROS) were predominantly elevated in the pre-autonomic regions of the PVN, colocalizing with AT1R- and FOSL1-expressing cells, suggesting that oxidative stress may amplify sympathetic activation and stress responses. SPS also increased mRNA levels of pro-inflammatory cytokines (TNFα and IL1β) and inducible nitric oxide synthase (iNOS) in the aorta, and impaired vascular reactivity to vasoconstrictor and vasodilator stimuli, reflecting compromised vascular function. These findings suggest that SPS-sensitize neuroendocrine, autonomic, and vascular pathways create a state of cardiovascular vulnerability that could predispose individuals to hypertension when exposed to additional stressors. Understanding these mechanisms provides critical insights into the pathophysiology of stress-related cardiovascular disorders and underscores the need for targeted therapeutic interventions that address oxidative stress and modulate altered PVN pathways to mitigate the cardiovascular impact of PTSD and related conditions.

Vancomycin combined with piperacillin/tazobactam increases the risk of acute kidney injury compared with vancomycin plus other anti-pseudomonal beta-lactams: a systematic review and network meta-analysis.

To explore whether vancomycin plus piperacillin/tazobactam actually increases nephrotoxicity compared with other anti-pseudomonal beta-lactams (BLs). PubMed, Embase, Web of Science, Cochrane, CNKI, Wanfang and VIP were searched from inception to October 2023. The primary outcomes were acute kidney injury (AKI) as defined as acute increase in serum creatinine of 0.3 mg/dL or 50% and severe Stage 2-3 AKI. We included 70 studies (76 638 patients). Network meta-analysis indicated that vancomycin plus piperacillin/tazobactam was associated with significantly higher AKI risk than vancomycin plus cefepime (OR 2.55, 95% CI 2-3.28), vancomycin plus meropenem (OR 2.26, 95% CI 1.71-3.02) and vancomycin plus other uncommonly used BLs (OR 2.47, 95% CI 1.87-3.29). Also, vancomycin + piperacillin/tazobactam was associated with significantly higher Stage 2-3 AKI risk than vancomycin + cefepime (OR 2.22, 95% CI 1.34-3.62), vancomycin + meropenem (OR1.96, 95% CI 1.22-3.25) and vancomycin + uncommonly used BLs (OR 2.81, 95% CI 1.66-4.91). Vancomycin plus piperacillin/tazobactam did not result in a significant difference in the incidence of receiving dialysis treatment, mortality, length of stay and time to AKI. Subgroup analyses of studies conducting propensity score matching demonstrated vancomycin + piperacillin/tazobactam was associated with significantly higher AKI rates than vancomycin + cefepime (OR 2.19, 95% CI 1.38-3.47) and vancomycin + meropenem (OR 1.38, 95% CI. 1.18-1.60). Subgroup analysis of critically ill patients and children indicated that vancomycin + piperacillin/tazobactam was associated with significantly higher AKI rates. Vancomycin + piperacillin/tazobactam significantly increased the risk of AKI and severe Stage 2-3 AKI compared with vancomycin plus other BLs. More prospective studies are needed.

Abstract 4136700: Sodium-Potassium Pump: Newly O-GlcNAc Protein Offering Potential Benefits in Hemorrhagic Shock situation

Hemorrhagic shock(HS) results from significant blood loss, leading to insufficient oxygen delivery, which causes metabolic changes and multi-organ dysfunction.The HS-related acute kidney injury developed by the patient are mainly due to alteration in Na/K ATPase.In previous O-GlcNAcylomic studies, we identified the Na/K ATPase as potentially O-GlcNAcylated.O-GlcNAcylation, a post-translational modification, plays a role in various cellular processes, such as cell survival and stress response.O-GlcNAcylation may have beneficial effect in shock situations. The objective of this study is to ascertain whether Na/K ATPase is O-GlcNAcylated and to elucidate its potential role during HS. Hemorrhagic shock was induced by an exsanguination of rats.They were then randomly treated or not with an O-GlcNAcase inhibitor, the NButGT(10mg/kg), to increase O-GlcNAc level.Blood pressure and heart rate were monitored throughout the experiment.Blood samples were collected for complete blood analysis, including biochemistry and gas measurements. kidneys were immediately frozen for histological and biochemical studies.To study the O-GlcNAcylation of Na/K ATPase an immunoprecipitation and Wheat Germ Agglutinin(WGA) based lectin affinity gel electrophoresis were used. HEK cells were treated with or without NButGT(100µM,6 hours) and/or ouabain(Na/K ATPase inhibitor) and a colorimetric kit was assessed to study O-GlcNAcylation impact on Na/K ATPase activity. O-GlcNAc levels increased by 2 folds in heart and kidney due to the NButGT treatment(p<0.05).Mean arterial pressure(MAP,p<0.01) and bicarbonate(p<0.01) are restored in treated group as kalemia(Sham:4.2 ± 0.1;HS:4.7±0.1;NButGT:4.3 ±0.1;mmol/L;p<0.05) and natremia(Sham:141.5±0.4;HS:139.8±0.5;NButGT:141.9 ±0.4; mmol/L;p<0.01).The study of the O-GlcNAcylation of the Na/K ATPase validated its O-GlcNAcylation.Histological analysis of the kidney showed that HS decreased Na/K ATPase expression, but treatment restored it(Sham:15.1±1.1;HS:10.3±0.6;NButGT:13.78±1.1;%area;p<0.05). An acute increase in O-GlcNAc levels through NButGT enhances Na/K ATPase activity. Increased O-GlcNAcylation during hemorrhagic shock restored MAP and reduced indicators of metabolic acidosis.Treatment with NButGT restored natremia and kalemia.This effect is linked to an increase in the expression and activity of Na/K ATPase.Our study is the first to confirm that Na/K ATPase is regulated by O-GlcNAcylation, particularly in terms of its localization and stability.

Response of the nephron arterial network and its interactions to acute hypertension: a simulation.

We simulated the dynamics of a group of 10 nephrons supplied from an arterial network and subjected to acute increases in blood pressure. Arterial lengths and topology were based on measurements of a vascular cast. The model builds on a previous version exercised at a single blood pressure with 2 additional features: pressure diuresis and the effect of blood pressure on efferent arteriolar vascular resistance. The new version simulates autoregulation, and reproduces tubule pressure oscillations. Individual nephron dynamics depended on mean arterial pressure and the axial pressure gradient required to cause blood flow through the arteries. Rhythmic blood withdrawal into afferent arterioles caused blood flow fluctuations in downstream vessels. Blood pressure dependent changes in nephron dynamics affected synchronization metrics. The combination of vascular pressure gradients and oscillations created a range of arterial pressures at the origins of the 10 afferent arterioles. Because arterial blood pressure in conscious animals has 1/f dynamics, we applied an arterial pressure pattern with such dynamics to the model. Amplitude of tubule pressure oscillations were affected by the 1/f blood pressure fluctuations, but the oscillation frequencies did not change. The pressure gradients required to deliver blood to all afferent arterioles impose a complexity that affects nephrons according to their locations in the network, but other interactions compensate to ensure the stability of the system. The sensitivity of nephron response to location on the network, and the constancy of the tubular oscillation frequency provide a spatial and time context.

Neuroinflammation, Stress-Related Suicidal Ideation, and Negative Mood in Depression

Brain translocator protein 18k Da (TSPO) binding, a putative marker of neuroinflammatory processes (eg, gliosis), is associated with stress and elevated in depressed and suicidal populations. However, it is unclear whether neuroinflammation moderates the impact of daily life stress on suicidal ideation and negative affect, thereby increasing risk for suicidal behavior. To examine the association of TSPO binding in participants with depression with real-world daily experiences of acute stress-related suicidal ideation and negative affect, as well as history of suicidal behavior and clinician-rated suicidal ideation. Data for this cross-sectional study were collected from June 2019 through July 2023. Procedures were conducted at a hospital-based research center in New York, New York. Participants were recruited via clinical referrals, the Columbia University research subject web portal, and from responses to internet advertisements. Of 148 participants who signed informed consent for study protocols, 53 adults aged 18 to 60 years who met DSM-5 diagnostic criteria for current major depressive disorder completed procedures with approved data and were enrolled. Participants were free of schizophrenia spectrum disorders, active physical illness, cognitive impairment, and substance intoxication or withdrawal at the time of scan. All participants underwent positron emission tomography imaging of TSPO binding with 11C-ER176 and concurrent arterial blood sampling. A weighted average of 11C-ER176 total distribution volume (VT) was computed across 11 a priori brain regions and made up the primary outcome measure. Clinician-rated suicidal ideation was measured via the Beck Scale for Suicidal Ideation (BSS). A subset of participants (n = 21) completed 7 days of ecological momentary assessment (EMA), reporting daily on suicidal ideation, negative affect, and stressors. In the overall sample of 53 participants (mean [SD] age, 29.5 [9.8] years; 37 [69.8%] female and 16 [30.2%] male), 11C-ER176 VT was associated at trend levels with clinician-rated suicidal ideation severity (β, 0.19; 95% CI, -0.03 to 0.39; P = .09) and did not differ by suicide attempt history (n = 15; β, 0.18; 95% CI, -0.04 to 0.37; P = .11). Exploratory analyses indicated that presence of suicidal ideation (on BSS or EMA) was associated with higher 11C-ER176 VT (β, 0.21; 95% CI, 0.01 to 0.98; P = .045). In 21 participants who completed EMA, 11C-ER176 VT was associated with greater suicidal ideation and negative affect during EMA periods with stressors compared with nonstress periods (β, 0.12; SE, 0.06; 95% CI, 0.01 to 0.23; P = .03 and β, 0.19; SE, 0.06; 95% CI, 0.08 to 0.30; P < .001, respectively). TSPO binding in individuals with depression may be a marker of vulnerability to acute stress-related increases in suicidal ideation and negative affect. Continued study is needed to determine the causal direction of TSPO binding and stress-related suicidal ideation or negative affect and whether targeting neuroinflammation may improve resilience to life stress in patients with depression.

Cerebral Cortical Vasodilation via Nicotinic Receptors by Heated Tobacco Product Aerosol Extract in Rats

Introduction: Smoking increases the risk of lung cancer due to a number of components of smoke. The use of novel heated tobacco products (HTPs), alternative to conventional combustion cigarettes, has increased in recent years. However, the in vivo biological effects of HTPs are poorly understood. This study aimed to clarify the acute effects of injecting aerosol extract prepared from an HTP on regional cerebral blood flow (rCBF) in rat cortex by comparing them to the effects of injecting smoke extract prepared from conventional combustible cigarettes. Methods: In urethane anesthetized rats, rCBF was measured using laser speckle contrast imaging simultaneously with arterial pressure. Results: Both cigarette smoke extract and HTP aerosol extract, at a dose equivalent to 30 μg nicotine/kg, injected intravenously, increased cortical rCBF without changing arterial pressure. The magnitude and time course of the increased rCBF response to both extracts were similar throughout the cortical area, and the rCBF increases were all abolished by dihydro-β-erythroidine, an α4β2-preferring nicotinic acetylcholine receptor (nAChR) antagonist. Conclusion: In conclusion, our study demonstrated that the effect of injecting aerosol extract prepared from an HTP, an acute increase in cortical rCBF, is mediated via activation of α4β2-like neuronal nAChRs in the brain.

Basal forebrain activation improves working memory in senescent monkeys.

Brain aging contributes to cognitive decline and risk of dementia. Degeneration of the basal forebrain cholinergic system parallels these changes in aging, Alzheimer's dementia, Parkinson's dementia, and Lewy body dementia, and thus is a common element linked to executive function across the lifespan and in disease states. Here, we tested the potential of one-hour daily intermittent basal forebrain stimulation to improve cognition in senescent monkeys, and its mechanisms of action. Stimulation in five animals improved working memory duration in 8-12 weeks across all animals, with peak improvements observed in the first four weeks. In an ensuing three month period without stimulation, improvements were retained. With additional stimulation, performance remained above baseline throughout the 15 months of the study. Studies with a cholinesterase inhibitor produced inconsistent improvements in behavior. One of five animals improved significantly. Manipulating the stimulation pattern demonstrated selectivity for both stimulation and recovery period duration. Brain stimulation led to acute increases in cerebrospinal levels of tissue plasminogen activator, which is an activating element for two brain neurotrophins, Nerve Growth Factor (NGF) and Brain-Derived Growth Factor (BDNF). Stimulation also led to improved glucose utilization in stimulated hemispheres relative to contralateral. Glucose utilization also consistently declines with aging and some dementias. Together, these findings suggest that intermittent stimulation of the nucleus basalis of Meynert improves executive function and reverses some aspects of brain aging.

Systolic Function in the Fontan Circulation is Exercise, but not Preload, Recruitable

BackgroundFontan circulatory failure with impaired systolic function is well documented; however, its mechanisms are not fully understood. We aimed to explore the myocardial functional reserve in adolescent patients with Fontan circulation in response to exercise or acute preload increase. MethodsOur study comprised 32 patients (median age: 16.7 years, range: 15.4–17.9 years, 12 females) with Fontan circulation. Echocardiographic imaging was performed during exercise using a recumbent cycle ergometer and during heart catheterization with a rapid infusion of 0.9% saline infusion at 5 mL/kg body weight. We measured myocardial peak longitudinal strain (LS) in a 4-chamber view during specific time intervals before, during, and after the exercise (LSstress) and volume load (LScath). During catheterization, central venous pressure (CVP) and ventricular end-diastolic pressures (VEDP) were simultaneously recorded. A control group of 16 healthy individuals participated in the exercise test. ResultsThe mean LSstress was less negative for patients than for controls (P≤0.001 at all stages); however, it significantly improved from -18.4±5.5% at baseline to -22.0±6.5% (P=0.004) at maximal loading. LSstress at maximal loading did not correlate with changes in heart rate. During catheterization, the mean LScath was -19.6±6.0% at baseline and did not improve significantly at 1.00–2.00 min and at 4.00–6.00 min after saline infusion. In more than half of the patients, LScath worsened or improved with less than -2% after the saline infusion. Worsening in LScath correlated with CVP and VEDP in all conditions (P≤0.017). There was no difference in LSstress or LScath between the morphological right ventricle and the morphological left ventricle. ConclusionPatients with Fontan circulation demonstrate systolic myocardial functional reserve that can be recruited with exercise stress but not with an acute increase in preload.

Acute Effects of High-Intensity Resistance Exercise on Recognition of Relational Memory, Lactate, and Serum and Plasma Brain-Derived Neurotrophic Factor.

Baumgartner, NW, Belbis, MD, Kargl, C, Holmes, MJ, Gavin, TP, Hirai, DM, and Kao, S-C. Acute effects of high-intensity resistance exercise on recognition of relational memory, lactate, and serum and plasma brain-derived neurotrophic factor. J Strength Cond Res 38(11): 1867-1878, 2024-Acute aerobic exercise improves memory, but this phenomenon is understudied in response to resistance exercise (RE) despite evidence that RE-induced increases in lactate and brain-derived neurotrophic factor (BDNF) play mechanistic roles in memory performance. To determine the acute effect of RE on lactate, BDNF, and their associations with object and relational memory, blood lactate, and serum and plasma BDNF were taken from 36 adults (average age 23.64 ± 3.89 years; 18 woman) before and immediately after 42 minutes of high-intensity RE and a rest condition on counterbalanced days. Subjects then immediately studied a series of paired objects and completed object and relational recognition tasks. Results revealed a condition by trial interaction, previously studied objects were remembered less accurately following RE ( d = 0.66) but recognition occurred faster ( d = 0.28), indicating a speed-accuracy tradeoff following RE. There was no effect of either intervention on relational recognition performance. Lactate ( d = 3.68) and serum BDNF ( d = 0.74) increased following RE, whereas there was no time-related change in lactate and serum BDNF following rest. However, changes in lactate and BDNF did not predict any measures of object ( rs < 0.25, p s > 0.16) or relation recognition ( rs < 0.28, p s > 0.13). Collectively, these findings suggest that acute high-intensity RE selectively improves the processing speed of recognizing objects at the cost of less accurate recognition of previously studied objects. Furthermore, changes in object and relational memory performance are unlikely driven by acute increases in lactate or BDNF following high-intensity RE.

Redox Imbalance and Cardiovascular Pathogenesis: Exploring the Therapeutic Potential of Phytochemicals

Abstract: The intriguing role of the oxidation system in cardiovascular disease lies in its contribution to chronic and acute increases in intracellular reactive oxygen species (ROS), driving the progression of cardiovascular diseases (CVDs). ROS, produced as by-products of oxidative physiological and metabolic events, act as mediators in various signaling pathways contributing to cardiovascular pathology. The delicate equilibrium between the production of free radicals and antioxidant defense shifts in favor of the former, resulting in redox imbalance and extensive cellular damage. Among CVDs, coronary artery disease (CAD) remains as the leading cause of death globally. Understanding the significance of oxidative damage in the dysfunction of endothelial cells, atherosclerosis, and other pathogenic events and pathways is crucial for preventing and managing CVD. Consequently, it is imperative to comprehend the mechanism/s underlying the pathogenic alterations of CVD due to oxidative damage to develop effective prevention strategies. Many studies have reported bioactive phytochemical/s as potential therapies against CVDs, modulating ROS generation, controlling the CVD-related inflammatory mediators and protecting the vascular system. Therefore, this review provides an update for understanding how the phytoconstituents exhibit preventive roles in oxidative stress-related CVD, thus improving the quality of life of people. This study conducted a thorough literature search on CVD, oxidative imbalance, and phytoconstituents. The search was performed using multiple search engines and the main keywords, and only English publications until June 2023 were included. However, there is a need for more research and clinical trials to fully elucidate the efficacy and safety of these phytochemicals for managing the disease.

The effect of abdominal functional electrical stimulation on blood pressure in people with high level spinal cord injury.

Single centre training study. To investigate, in a group of people with spinal cord injury (SCI), the effect of transcutaneous functional electrical stimulation of the abdominal muscles (abdominal FES) during cough training on blood pressure (BP), and how it is affected by injury characteristics and alters over time. Laboratory and community. Sixteen participants with SCI (C4-T5) underwent 25 of abdominal FES cough training (5 sets of 10 stimulated coughs) over 6 weeks as part of a previously published study on the effect of abdominal FES training on cough. Systolic BP (SBP), diastolic BP (DBP) and calculated mean arterial pressure (MAP) were measured at the completion of each set. Abdominal FES coughing resulted in an average ~30% acute increase in BP from initial resting BP across all sessions in almost all participants (p < 0.001). However, the increase in BP during abdominal FES coughs from rest reduced over the 25 sessions of training by ~35% for SBP, MAP and DBP (p = 0.024, p = 0.013 and p = 0.042, respectively). There was no meaningful change in resting BP over time (p = 0.935, p = 0.705 and p = 0.988, respectively). Overall, increases in BP during abdominal FES coughs were greatest for those with chronic injuries and cervical injuries. Transcutaneous abdominal FES during cough training acutely increases BP. However, the magnitude of the increase is reduced after 25 sessions of training. Abdominal FES may offer a solution to combat orthostatic hypotension, but its effectiveness may diminish over time.

The effect of intravenous hydromorphone alone or in combination with midazolam or dexmedetomidine on intraocular pressure in dogs

ObjectiveTo evaluate the effect of intravenous (IV) hydromorphone alone or in combination with midazolam or dexmedetomidine on intraocular pressure (IOP) in dogs. Study designProspective, randomized, blinded, crossover study. AnimalsA group of seven healthy, ophthalmologically normal, adult Beagle dogs. MethodsA total of four IV drug combinations were evaluated: hydromorphone 0.1 mg kg–1 (H); hydromorphone 0.1 mg kg–1 and dexmedetomidine 0.001 mg kg–1 (HD); hydromorphone 0.1 mg kg–1 and midazolam 0.2 mg kg–1 (HM2); and hydromorphone 0.1 mg kg–1 and midazolam 0.4 mg kg–1 (HM4). Treatment order was randomized, with a 2 week washout period between treatments. IOP and sedation scores were obtained before (T0) and 3, 30, 60, 240 and 480 minutes after drug injection. To account for repeated measurements for each dog across treatments and time points, mixed models were used to compare IOP at T0 by eye and to describe changes from T0 in IOP (averaged across eyes) and sedation scores. ResultsIn treatment H, IOP increased significantly from baseline levels [predicted mean increase of 5.5 mmHg [95% confidence interval (CI): 3.7–7.3] at T3 (p < 0.001) and 2.7 mmHg (95% CI: 0.9–4.5) at T30 (p = 0.005)]. In treatment HD, mean IOP increased from baseline by 2.3 mmHg (95% CI: 0.5–4.1) at T30 (p = 0.014). In treatment HM2, mean IOP increased by 2.5 mmHg (95% CI: 0.2–4.9) at T30 (p = 0.035). In treatment HM4, IOP did not change significantly from baseline at any time point. Sedation scores over time did not differ significantly between treatments. Conclusions and clinical relevanceInjection of IV hydromorphone alone (0.1 mg kg–1) caused a transient increase in IOP and might not be appropriate if an acute increase in IOP is undesirable. Addition of dexmedetomidine or midazolam to hydromorphone, at the doses studied, appears to attenuate this increase in IOP.

Hyperoxia does not improve the acute upper thermal tolerance of a tropical marine fish (Lutjanus apodus).

Fish can experience hyperoxia in shallow environments due to photosynthetic activity and this has been suggested to provide them with a metabolic refuge during acute warming. However, this hypothesis has never been tested on a tropical marine species. Thus, we fitted 29°C-acclimated wild schoolmaster snapper (Lutjanus apodus; a species known to experience diel hyperoxia in mangrove creeks and coastal waters) with Transonic® flow probes and exposed them to an acute increase in temperature (at 1°Ch-1) in respirometers under normoxia and hyperoxia (150% air saturation), until their critical thermal maximum (CTmax). The CTmax of both groups was ∼39°C, and no differences in maximum cardiac function were recorded as the fish were warmed. However, temperature-induced factorial aerobic scope was significantly greater in fish tested under hyperoxia. These data suggest that hyperoxia will not protect coastal tropical fish species during marine heat waves, despite its effects on metabolic scope/capacity.

A comparative analysis of conduction system pacing and biventricular pacing in patients undergoing atrioventricular node ablation: a systematic review and meta-analysis

Abstract Background Atrioventricular node ablation (AVNA) with concomitant permanent pacemaker implantation is a well-established management strategy for patients with atrial fibrillation demonstrating refractory and uncontrolled ventricular rates. Conduction system pacing (CSP) utilising His bundle pacing (HBP) or left bundle branch area pacing (LBBAP), has emerged as an alternative to conventional pacing (CP) (including right ventricular pacing (RVP) and biventricular pacing (BVP). The aims and objectives of this systematic review and meta-analysis is to provide a comprehensive summary and synthesis of clinical outcomes in the literature for CSP in comparison to BVP when facilitated with AVNA. Methods This study protocol was registered in the PROSPERO registry and the review was conducted as per the PRISMA guidelines. MEDLINE, EMBASE and Cochrane Library were searched for relevant studies from inception till January 11th, 2024. Results were synthesised using a random effects meta-analysis. Risk of bias (ROB) assessment was carried out with the RoB 2 and ROBINS-I tool. Results From a total of 259 references identified, 122 full texts were assessed and 5 studies (1 randomised control trial, 2 prospective observational studies, and 2 retrospective observational studies) were included in the review. A total of 738 patients (HBP-294 and LBBAP-444) received CSP and BVP implantation with AVNA, respectively. All devices were implanted successfully with a cumulative total of 4 patients in the HBP population demonstrating acute threshold hold increase following AVN. There was no loss of capture on follow-up in either treatment groups. HBP resulted in a narrower QRSd with a reduction of -35.3 ms (95% confidence interval [CI] -63.8 to -6.78; P&amp;lt;0.05; I2=96.6%) vs BVP. For left ventricular ejection fraction (LVEF), a weighted mean increase of 3.50% (95% CI -0.55%-7.54%; P=0.02, I2=65.8%) was observed following HBP implantation in comparison to BVP (Figure 1). Furthermore, LBBAP also demonstrated a weighted mean increase in LVEF of 6.02% (95%CI -4.05%-16.1%; P&amp;lt;0.05; I2=90.7%) in comparison to BVP. The mean NYHA score was reduced by -0.54 (95% CI -1.07 to -0.02; P=0.05, I2=65.5%) after HBP implantation when compared to BVP. There was a cumulative total of 45 and 65 events of heart failure associated hospitalisation in the HBP and BVP, respectively (OR 0.69; 95% CI 0.19-1.18; P=0.99, I2 =0.00). Conclusion To our knowledge, this is the first methodologically robust systematic review and meta-analysis evaluating the outcomes of CSP with AVNA. Overall, both CSP modalities demonstrated feasibility and application as an effective CRT alternative to facilitate AVNA along with a narrower QRSd ,improved LVEF and trend of better clinical outcomes. While these preliminary findings are promising, further RCTs will be necessary to establish the long-term efficacy and safety of this approach.

Glucocorticoid and glycemic responses to immune challenge in a viviparous snake afflicted with an emerging mycosis.

Disease may be both a cause and consequence of stress, and physiological responses to infectious disease may involve stress coping mechanisms that have important fitness consequences. For example, glucocorticoid and glycemic responses may affect host fitness by altering resource allocation and use in hosts, and these responses may be affected by competing stressors. To better understand the factors that affect host responses to infection, we challenged the immune system of field acclimatized pygmy rattlesnakes, Sistrurus miliarius, with a sterile antigen, lipopolysaccharide (LPS), and measured the glucocorticoid and glycemic response in healthy non-reproductive snakes, snakes afflicted with an emerging mycosis (ophidiomycosis), and pregnant snakes. We hypothesized that LPS challenge would result in a glucocorticoid and glycemic response typical of the vertebrate acute phase response (APR), and therefore predicted that LPS challenge would result in an acute increase in plasma corticosterone (CORT) and a decline in plasma glucose in all individuals. Additionally, we hypothesized that the APR would be attenuated in individuals simultaneously coping with additional challenges to homeostasis (i.e., disease or reproduction). As predicted, immune challenge elicited an acute increase in plasma CORT and a decrease in plasma glucose. Snakes coping with ophidiomycosis and pregnant snakes were able to mount a robust glucocorticoid and hypoglycemic response to LPS challenge, which was contrary to our hypothesis. Our findings clarify directions of causality linking infection, glucocorticoids, and glucose, and emphasize the importance of future research examining the fitness consequences of interactions between stress and disease in wildlife threatened by emerging pathogens.

Reproductive effort affects cellular response in the mantle of Nodipecten subnodosus scallops exposed to acute hyperthermia

In marine ecosystems, temperature regulates the energy metabolism of animals. In the last decades, the temperature increase was related to mass mortality events of marine ectotherms, particularly during high-energy investment for reproduction. In scallops, the mantle has been poorly investigated while this tissue covers more than 40 % of the body mass, contributing to the perception of surrounding environmental stimuli. Our aim was to assess the cellular and molecular responses linked to energy metabolism in the mantle of adult N. subnodosus facing acute hyperthermia during reproductive effort. Scallops collected in spring (late gametogenesis) and summer (ripe gonads) were exposed to a control temperature (22 °C) or acute hyperthermia (30 °C) for 24 h. In spring, increased arginine kinase (AK) activity together with increased pyruvate kinase/citrate synthase ratio (PK/CS) suggested an enhanced carbohydrate, pyruvate, and arginine metabolism to maintain the adenylate energy charge (AEC) in the mantle of scallops coping with acute thermal increase. In summer, animals decreased their AEC (5 %) and arginine phosphate pool (40 %) and increased their anaerobic metabolism as shown by enhanced activities of lactate dehydrogenase (LDH) and octopine dehydrogenase (ODH), respectively. The abundance of twenty proteins involved in energy metabolism (isocitrate dehydrogenase, ATP synthase subunit β), protein protection (cognate heat shock protein 70), and cytoskeleton (actins and tubulins) were affected only by season. These results underlie the role of the mantle of N. subnodosus in the seasonal responses of this tissue to thermal fluctuations during reproductive effort with possible implications for the physiological performance of scallops under heat waves in wild or harvest conditions.

Residential Water Consumption Patterns: A Theoretical Review

The global water crisis and acute increase in water demand have increased stress on water resources in urban areas, particularly in water-scarce regions like Egypt. Many current strategies of sustainable water demand management show low effectiveness due to a lack of understanding of how water is used in households, and a failure to consider the environmental and urban diversity that shapes water consumption patterns in Egypt. This understanding requires knowing how water is consumed for micro-components of water use (i.e., end-uses such as bathing, cooking, and toilet use). This research aims to develop a conceptual/theoretical framework for probable worldwide water consumption patterns and their shaping factors, to be used as an auxiliary tool in future data collection and analysis in Egypt, which is an essential step to contextualize water consumption patterns and develop more sustainable water demand management strategies. The study reviews and analyzes water end-use data from 39 major cities in developed and developing countries to identify trends and critical factors in household water consumption. It documents six different major trends in household water consumption patterns with main water activities: cooking, bathing, washing machines, faucets, and toilet use. It also identifies and categorizes the patterns-shaping factors into five main groups: socioeconomic characteristics, physical, spatial, climatic conditions, and political restrictions. Moreover, significant correlations emerge between pattern elements and shaping forces such as income and washing machine usage, the presence/absence of children/elders and use of basin, and dietary culture and cooking consumption. Given the research findings, household consumption patterns in Egyptian cities are expected to be high in kitchens, showers, and toilets, and average in laundry and faucets. The study underscores the importance of considering factors such as socio-economic characteristics, water policies, spatial influences, water supply efficiency, and consumer health in forthcoming investigations, as these are believed to substantially influence household water consumption in Egypt.

A Rare Case of Acute Promyelocytic Leukemia with Concomitant PML-RARA Fusion and TP53 Loss/ider(17)(q10)t(15;17) Showing Complete Clinical and Molecular response: A Case Report

Abstract Introduction/Objective To report a case with rare cytogenetic abnormality: a patient with newly diagnosed acute promyelocytic leukemia (APL) with cytogenetic findings of t(15;17)(q24;q21), trisomy 8 and ider(17)(q10)t(15;17)-TP53 loss. The presence of isochromosome 17q may indicate the possibility of an unfavorable outcome. However, the case showed complete clinical and molecular response. Methods/Case Report A case of a 53-year-old female with history of ITP post-splenectomy presented with persistent hematuria, easy bruising, and worsening fatigue. She had mild microcytic anemia, moderate thrombocytopenia, 3% promyelocytes, and 14% blasts on differential CBC count. With increased PT, PTT, LDH, Uric acid and decreased fibrinogen level, APL was clinically suspected. The patient was initiated on all-trans retinoic acid (ATRA), allopurinol, and IV fluids. Bone marrow (BM) biopsy confirmed the diagnosis with unusual cytogenetic findings. The patient underwent induction and consolidation therapies (4 weeks each) with ATRA plus Arsenic Trioxide (ATO) and followed- up with a series of marrow biopsies, cytogenetic and molecular studies. Results (if a Case Study enter NA) The patient demonstrated complete clinical, histological, and molecular response. She tolerated the treatment without major side effects, showing improvement in CBC counts, coagulation profile and tumor lysis labs. Initial BM exam revealed hypercellularity with infiltrating sheets of atypical hypergranular promyelocytes (~80%) and minimal residual left trilineage hematopoiesis. Flow cytometry revealed a CD34 negative, CD117 variable abnormal promyelocyte population (~67% of total events). FISH was positive for PML/RARA translocation (15; 17) and TP53 loss. Karyotype showed 46,XX,der(15)t(15;17)(q24;q21),ider(17)(q10)t(15;17)[12]/47,idem,+8[9]. By the end of treatment, BM biopsy was normocellular with trilineage hematopoiesis and no definitive evidence of acute leukemia or increase in blasts. The Karyotype was normal. Quantitative PCR for PML-RARA was negative, indicating complete molecular remission. Conclusion In this unique case of APL with unusual cytogenetic abnormalities the literature demonstrates controversial data. The patient achieved complete clinical and molecular remission following standard treatment. This may indicate the limited prognostic significance of these additional cytogenetic abnormalities in this case.

Functional activity and connectivity signatures of ketamine and lamotrigine during negative emotional processing: a double-blind randomized controlled fMRI study

Ketamine is a highly effective antidepressant (AD) that targets the glutamatergic system and exerts profound effects on brain circuits during negative emotional processing. Interestingly, the effects of ketamine on brain measures are sensitive to modulation by pretreatment with lamotrigine, which inhibits glutamate release. Examining the antagonistic effects of ketamine and lamotrigine on glutamate transmission holds promise to identify effects of ketamine that are mediated through changes in the glutamatergic system. Investigating this modulation in relation to both the acute and sustained effects of ketamine on functional activity and connectivity during negative emotional processing should therefore provide novel insights. 75 healthy subjects were investigated in a double-blind, single-dose, randomized, placebo-controlled, parallel-group study with three treatment conditions (ketamine, lamotrigine pre-treatment, placebo). Participants completed an emotional face viewing task during ketamine infusion and 24 h later. Acute ketamine administration decreased hippocampal and Default Mode Network (DMN) activity and increased fronto-limbic coupling during negative emotional processing. Furthermore, while lamotrigine abolished the ketamine-induced increase in functional connectivity, it had no acute effect on activity. Sustained (24 h later) effects of ketamine were only found for functional activity, with a significant reduction in the posterior DMN. This effect was blocked by pretreatment with lamotrigine. Our results suggest that both the acute increases in fronto-limbic coupling and the delayed decrease in posterior DMN activity, but not the attenuated limbic and DMN recruitment after ketamine, are mediated by altered glutamatergic transmission.

HYPERTENSIVE CRISES: HYPERTENSIVE EMERGENCY AND CRISIS MANAGEMENT DURING ANESTHESIA

Introduction: hypertensive crisis is characterized by an acute and massive increase in blood pressure. Hypertensive crises encompass several clinical situations with different severity and prognosis, including hypertensive urgency and hypertensive emergency. The difference between the latter depends on whether the situation is life-threatening for the affected individual. Objective: to detail current information related to hypertensive crises, especially hypertensive emergency, definition, differentiation, etiology, epidemiology, pathophysiology, histology, clinical history, physical examination, management, differential diagnosis, prognosis and complications. Methodology: a total of 28 articles were analyzed in this review, including review and original articles, as well as clinical cases, of which 15 bibliographies were used because the other articles were not relevant to this study. The sources of information were PubMed, Google Scholar and Cochrane; the terms used to search for information in Spanish, Portuguese and English were: hypertensive crises, hypertensive emergencies, hypertensive emergencies, arterial hypertension. Results: approximately 1-2% of adults with hypertension suffer hypertensive crises. Multiple case series show that short-term treatment of hypertensive emergencies has good results; however, long-term results are unknown. The main drawback is that follow-up of individuals is lost and the medication regimen is frequently modified. Untreated hypertensive emergencies have very high morbidity and mortality and if the patient does not receive adequate education about the severity of hypertension, this trend is likely to continue. Conclusions: given the high prevalence of hypertension, it is crucial that health care professionals are able to differentiate between hypertensive emergencies and hypertensive emergencies to provide appropriate and timely treatment. Rapid blood pressure reduction is critical in the treatment of hypertensive emergencies. The choice of medications should consider both efficacy and safety to avoid further complications. A detailed clinical evaluation can help identify the underlying cause and guide treatment, highlighting the importance of an individualized approach. Lack of timely treatment can lead to severe consequences, emphasizing the need for proper management in critical situations. Constant training in the management of hypertensive emergencies is essential to reduce the morbidity and mortality associated with this condition.The management of hypertension during anesthesia is critical, as its prompt detection and control are fundamental to prevent serious complications. Despite the lack of specific criteria to suspend surgery in hypertensive patients, it is essential to evaluate each case individually, prioritizing target organ damage over blood pressure levels. KEY WORDS: crisis, emergency, urgency, hypertension.