Acute Increase Research Articles

Acute flaccid paralysis on 11 years old child in Bali: a case report

Introduction: As medical professionals, we need to be aware of cases of acute flaccid paralysis, known as the current outbreak of polio infections in Indonesia. Polio is a highly contagious illness that primarily affects children under five. It can result in death (2-10% of those who were paralyzed) or lifelong paralysis (about 1 in 200 infections). The virus spreads from person to person mostly by the fecal-oral pathway. Contaminated foods and water are also less common routes of transmission. After the virus grows in the gut, it can enter the nerve system and paralyze people. Though it may vary from 4 to 35 days, the duration of incubation is typically 7 to 10 days. Approximately ninety percent of infected individuals either show no symptoms at all or have minor ones, hence the illness is typically not diagnosed. The purpose of this case report is to describe a case of acute flaccid paralysis and increase our awareness about the current polio outbreak. The Case: Eleven-year-old Korean child weighing 41 kg arrived to the clinic complaint of weakness in both limbs for the past five days. It happened throughout the day, particularly during the morning, and was felt abruptly. He also had instability when walking and trembling in both legs. He also experienced three episodes of watery diarrhea that day. In addition, he reported having puked twice in the two days before his clinic appointment. His calves had a motoric grade of 3 and a grade of 5 on his soles, indicating that his calves were weaker than his soles. It was discovered that the muscular tone was weak. No evidence of muscular atrophy was present. Positive tripod indication was seen. There were no abnormalities in sensibility. He was diagnosed with acute flaccid paralysis et causa suspected poliomyelitis dd Guillain Barre Syndrome dd hypokalemia paralysis et causa diarrhea and vomiting. Conclusion: Facing the polio outbreak in Indonesia, this case would serve as an example to raise awareness of acute flaccid paralysis cases, enabling early detection, differential diagnosis exclusion, and effective surveillance.

Ruthenium drug BOLD-100 regulates BRAFMT colorectal cancer cell apoptosis through AhR/ROS/ATR signaling axis modulation.

Patients with class I V600EBRAF-mutant (MT) colorectal cancer (CRC) have a poor prognosis and their response to combined anti-BRAF/EGFR inhibition remains limited. There is clearly an unmet need in further understanding the biology of V600EBRAFMT CRC. We have used differential gene expression of BRAFWT and MT CRC cells to identify pathways underpinning BRAFMT CRC. We tested a panel of molecularly/genetically subtyped CRC cells for their sensitivity to the Unfolded Protein Response (UPR) activator BOLD-100. To identify novel combination strategies for BOLD-100, we performed RNA sequencing and high-throughput drug screening. Pathway enrichment analysis identified that the UPR and DNA repair pathways were significantly enriched in BRAFMT CRC. We found that oncogenic BRAF plays a crucial role in mediating response to BOLD-100. Using a systems biology approach, we identified V600EBRAFMT-dependent activation of the replication stress response kinase ATR as a key mediator of resistance to BOLD-100. Further analysis identified acute increases in BRAFMT-dependent-reactive oxygen species (ROS) levels following treatment with BOLD-100 that was demonstrated to promote ATR/CHK1 activation and apoptosis. Furthermore, activation of ROS/ATR/CHK1 following BOLD-100 was found to be mediated through the AHR transcription factor and CYP1A1. Importantly, pharmacological blockade of this resistance pathway with ATR inhibitors synergistically increased BOLD-100-induced apoptosis and growth inhibition in BRAFMT models. These results unveil possible novel therapeutic opportunity for BRAFMT CRC. Implications: BOLD-100 induces BRAFMT-dependent replication stress, and targeted strategies against replication stress (eg. by using ATR inhibitors) in combination with BOLD-100 may serve as a potential novel therapeutic strategy for clinically aggressive BRAFMT CRC.

Forskolin reverses the O-GlcNAcylation dependent decrease in GABAAR current amplitude at hippocampal synapses possibly at a neurosteroid site on GABAARs

GABAergic transmission is influenced by post-translational modifications, like phosphorylation, impacting channel conductance, allosteric modulator sensitivity, and membrane trafficking. O-GlcNAcylation is a post-translational modification involving the O-linked attachment of β-N-acetylglucosamine on serine/threonine residues. Previously we reported an acute increase in O-GlcNAcylation elicits a long-term depression of evoked GABAAR inhibitory postsynaptic currents (eIPSCs) onto hippocampal principal cells. Importantly, O-GlcNAcylation and phosphorylation can co-occur or compete for the same residue; whether they interact in modulating GABAergic IPSCs is unknown. We tested this by recording IPSCs from hippocampal principal cells and pharmacologically increased O-GlcNAcylation, before or after increasing serine phosphorylation using the adenylate cyclase activator, forskolin. Although forskolin had no significant effect on baseline eIPSC amplitude, we found that a prior increase in O-GlcNAcylation unmasks a forskolin-dependent increase in eIPSC amplitude, reversing the O-GlcNAc-induced eIPSC depression. Inhibition of adenylate cyclase or protein kinase A did not prevent the potentiating effect of forskolin, indicating serine phosphorylation is not the mechanism. Surprisingly, increasing O-GlcNAcylation also unmasked a potentiating effect of the neurosteroids 5α-pregnane-3α,21-diol-20-one (THDOC) and progesterone on eIPSC amplitude in about half of the recorded cells, mimicking forskolin. Our findings show that under conditions of heightened O-GlcNAcylation, the neurosteroid site on synaptic GABAARs is possibly accessible to agonists, permitting strengthening of synaptic inhibition.

Acute changes in kidney function and outcomes following an acute myocardial infarction: Insights from PARADISE-MI.

Pharmacologic blockade of neurohormonal pathways in patients with acute myocardial infarction (MI) can result in acute changes in biomarkers of kidney function. We evaluated the effect of sacubitril/valsartan versus ramipril on initial changes in serum creatinine and the association of these changes with longer-term outcomes among participants in PARADISE-MI. In this randomized, double-blind, active-controlled, event-driven trial, 5661 patients with an acute MI were assigned to receive sacubitril/valsartan or ramipril, with no run-in. The frequency of an initial pre-specified increase in serum creatinine (≥26.5 or ≥44 μmol/L) from baseline to week 1 was compared between arms. Multivariable Cox regression models were fit to examine the association of acute changes in serum creatinine with the primary cardiovascular composite outcome (cardiovascular death, first heart failure hospitalization, or outpatient heart failure), all-cause mortality, and longer-term changes in estimated glomerular filtration rate (eGFR). An initial increase in serum creatinine ≥26.5 μmol/L occurred in 155 of 2604 (6.0%) patients assigned to sacubitril/valsartan and 120 of 2603 (4.6%) patients assigned to ramipril (odds ratio [OR] 1.32; 95% confidence interval [CI] 1.03-1.68). The corresponding numbers for an increase ≥44 μmol/L were 57 (2.2%) and 42 (1.6%), respectively (OR 1.37; 95% CI 0.92-2.05). A higher odds of increased serum creatinine ≥26.5 and ≥44 μmol/L for sacubitril/valsartan versus ramipril appeared to be restricted to patients who had a greater decline in systolic blood pressure over the same period (p-interaction = 0.05 and 0.001, respectively). In multivariable analyses, neither an acute increase in serum creatinine ≥26.5 or ≥44 μmol/L was associated with a higher risk of cardiovascular outcomes, all-cause mortality, or differences in longer-term eGFR slope. Findings were similar across the randomized treatment arms (p-interaction >0.6 for all). Following acute MI, patients assigned to sacubitril/valsartan had a higher frequency of initial increases in serum creatinine at 1 week, compared with ramipril. In adjusted models, initial increases in serum creatinine with either treatment were not associated with adverse cardiovascular outcomes or changes in longer-term kidney function.

Anterior Chamber Air Bubble Dynamics With Decreases in Atmospheric Pressure.

To evaluate the effect of decreasing barometric pressure on intracameral bubble size and intraocular pressure (IOP) in eyes with varying air fills in the anterior chamber. A total of 36 human donor eyes received 30%, 50%, or 90% anterior chamber air fill. The eyes were subjected to decreases in atmospheric pressure down to 750 hPa, equal to 2400 m in altitude, and were repeatedly imaged using anterior segment OCT while IOP was measured continuously. Eyes with 30% air fill initially showed moderate increases in IOP yet rising to an average of 30.83 mm Hg at 850 hPa (mimicking 1400 m altitude) and 42.08 mm Hg at 750 hPa. Eyes with larger air bubbles showed more acute increases in IOP with increases to an average of 47.25 mm Hg in eyes with 50% air fill at 850 hPa and 63.33 mm Hg at 750 hPa. In eyes with 90% air fill in the anterior chamber, IOP readings with an average of 113.42 mm Hg were observed already at 850 hPa, at which point additional pressure reduction was not performed. While severe increases in IOP were observed with decreased atmospheric pressure in eyes with large air bubbles in the anterior chamber, small and moderately sized bubbles seem to allow for travel over modest changes in altitude.

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 XX(X): 000-000, 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, ps > 0.16) or relation recognition (rs < 0.28, ps > 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.

The inotropic and arrhythmogenic effects of acutely increased late INa are associated with elevated ROS but not oxidation of PKARIα.

Acute stimulation of the late sodium current (INaL) as pharmacologically induced by Anemonia toxin II (ATX-II) results in Na+-dependent Ca2+ overload and enhanced formation of reactive oxygen species (ROS). This is accompanied by an acute increase in the amplitude of the systolic Ca2+ transient. Ca2+ transient amplitude is determined by L-type Ca2+-mediated transsarcolemmal Ca2+ influx (ICa) into the cytosol and by systolic Ca2+ release from the sarcoplasmic reticulum (SR). Type-1 protein kinase A (PKARIα) becomes activated upon increased ROS and is capable of stimulating ICa, thereby sustaining the amplitude of the systolic Ca2+ transient upon oxidative stress. We aimed to investigate whether the increase of the systolic Ca2+ transient as acutely induced by INaL (by ATX-II) may involve stimulation of ICa through oxidized PKARIα. We used a transgenic mouse model in which PKARIα was made resistant to oxidative activation by homozygous knock-in replacement of redox-sensitive Cysteine 17 with Serine within the regulatory subunits of PKARIα (KI). ATX-II (at 1 nmol/L) was used to acutely enhance INaL in freshly isolated ventricular myocytes from KI and wild-type (WT) control mice. Epifluorescence and confocal imaging were used to assess intracellular Ca2+ handling and ROS formation. A ruptured-patch whole-cell voltage-clamp was used to measure INaL and ICa. The impact of acutely enhanced INaL on RIα dimer formation and PKA target structures was studied using Western blot analysis. ATX-II increased INaL to a similar extent in KI and WT cells, which was associated with significant cytosolic and mitochondrial ROS formation in both genotypes. Acutely activated Ca2+ handling in terms of increased Ca2+ transient amplitudes and elevated SR Ca2+ load was equally present in KI and WT cells. Likewise, cellular arrhythmias as approximated by non-triggered Ca2+ elevations during Ca2+ transient decay and by diastolic SR Ca2+-spark frequency occurred in a comparable manner in both genotypes. Most importantly and in contrast to our initial hypothesis, ATX-II did not alter the magnitude or inactivation kinetics of ICa in neither WT nor KI cells and did not result in PKARIα dimerization (i.e., oxidation) despite a clear prooxidant intracellular environment. The inotropic and arrhythmogenic effects of acutely increased INaL are associated with elevated ROS, but do not involve oxidation of PKARIα.

Dissimilar Changes in Serum Cortisol after Epileptic and Psychogenic Non-Epileptic Seizures: A Promising Biomarker in the Differential Diagnosis of Paroxysmal Events?

The hypothalamic-pituitary-adrenal axis is known to be involved in the pathogenesis of epilepsy and psychiatric disorders. Epileptic seizures (ESs) and psychogenic non-epileptic seizures (PNESs) are frequently differentially misdiagnosed. This study aimed to evaluate changes in serum cortisol and prolactin levels after ESs and PNESs as possible differential diagnostic biomarkers. Patients over 18 years with ESs (n = 29) and PNESs with motor manifestations (n = 45), captured on video-EEG monitoring, were included. Serum cortisol and prolactin levels as well as hemograms were assessed in blood samples taken at admission, during the first hour after the seizure, and after 6, 12, and 24 h. Cortisol and prolactine response were evident in the ES group (but not the PNES group) as an acute significant increase within the first hour after seizure. The occurrence of seizures in patients with ESs and PNESs demonstrated different circadian patterns. ROC analysis confirmed the accuracy of discrimination between paroxysmal events based on cortisol response: the AUC equals 0.865, with a prediction accuracy at the cutoff point of 376.5 nmol/L 0.811 (sensitivity 86.7%, specificity 72.4%). Thus, assessments of acute serum cortisol response to a paroxysmal event may be regarded as a simple, fast, and minimally invasive laboratory test contributing to differential diagnosis of ESs and PNESs.

AC-ASPECTS, ACh-ASPECTS, and H-ASPECTS: new imaging scales to assess territorial and total cerebral hemispheric ischemic injury.

The extent of ischemic injury in acute stroke is assessed in clinical practice using the Acute Stroke Prognosis Early CT Score (ASPECTS) rating system. However, current ASPECTS semi-quantitative topographic scales assess only the middle cerebral artery (MCA) (original ASPECTS) and posterior cerebral (PC-ASPECTS) territories. For treatment decision-making in patients with anterior cerebral artery (ACA) occlusions and internal carotid artery (ICA) occlusions with large ischemic cores, measures of all hemispheric regions are desirable. In this cohort study, anatomic rating systems were developed for the anterior cerebral (AC-ASPECTS, 3 points) and anterior choroidal artery (ACh-ASPECTS, 1 point) territories. In addition, a total supratentorial hemisphere (H-ASPECTS, 16 points) score was calculated as the sum of the MCA ASPECTS (10 regions), supratentorial PC-ASPECTS (2 regions), AC-ASPECTS (3 regions), and ACh-ASPECTS (1 region). Three raters applied these scales to initial and 24 h CT and MR images in consecutive patients with ischemic stroke (IS) due to ICA, M1-MCA, and ACA occlusions. Imaging ratings were obtained for 96 scans in 50 consecutive patients with age 74.8 (±14.0), 60% female, NIHSS 15.5 (9.25-20), and occlusion locations ICA 34%; M1-MCA 58%; and ACA 8%. Treatments included endovascular thrombectomy +/- thrombolysis in 72%, thrombolysis alone in 8%, and hemicraniectomy in 4%. Among experienced clinicians, inter-rater reliability for AC-, ACh-, and H-ASPECTS scores was substantial (kappa values 0.61-0.80). AC-ASPECTS abnormality was present in 14% of patients, and ACh-ASPECTS abnormality in 2%. Among patients with ACA and ICA occlusions, H-ASPECTS scores compared with original ASPECTS scores were more strongly associated with disability level at discharge, ambulatory status at discharge, discharge destination, and combined inpatient mortality and hospice discharge. AC-ASPECTS, ACh-ASPECTS, and H-ASPECTS expand the scope of acute IS imaging scores and increase correlation with functional outcomes. This additional information may enhance prognostication and decision-making, including endovascular thrombectomy and hemicraniectomy.

Neurosurgical Management of Traumatic Brain Injury

The neurosurgical management of traumatic brain injury (TBI) plays a critical role in ensuring acute survival and mitigating secondary brain damage, which significantly impacts patients' quality of life. TBI is defined as an external force impacting the skull, leading to brain injuries and subsequent functional impairments. It is a leading cause of mortality and morbidity, particularly among young individuals. The initial clinical examination is crucial, with external signs like scalp injuries, hematomas, nasal fluid leakage, skull deformities, and neurological deficits providing important clues to injury patterns. Pupil examination is particularly critical, as mydriasis coupled with reduced consciousness may indicate an acute life-threatening increase in intracranial pressure (ICP), necessitating immediate neurosurgical intervention. TBI assessment often utilizes the Glasgow Coma Scale (GCS), classifying injuries as mild (GCS 13-15), moderate (GCS 9-12), or severe (GCS <9). Even mild TBI can lead to long-term complications. TBI should be viewed as a disease process rather than a singular event. Primary brain damage results from shearing forces on the parenchyma, manifesting as contusions, hematomas, or diffuse axonal injury. Secondary brain damage is driven by mechanisms such as inflammation and spreading depolarizations. Treatment aims not only to secure immediate survival but also to reduce secondary injuries, with ICP management being crucial. Neurosurgical interventions are guided by cranial pathologies, with options including ICP monitoring, burr hole trepanation, craniotomy. In severe TBI cases with refractory ICP elevation, decompressive craniectomy may be performed as a last resort, significantly reducing mortality but often resulting in high morbidity and vegetative states, necessitating careful consideration of indications.

Boosting arousal and cognitive performance through alternating posture: Insights from a multi-method laboratory study.

This study investigated the role of arousal and effort costs in the cognitive benefits of alternating between sitting and standing postures using a sit-stand desk, while measuring executive functions, self-reports, physiology, and neural activity in a 2-h laboratory session aimed to induce mental fatigue. Two sessions were conducted with a one-week gap, during which participants alternated between sitting and standing postures each 20-min block in one session and remained seated in the other. In each block, inhibition, switching, and updating were assessed. We examined effects of time-on-task, acute (local) effects of standing versus sitting posture, and cumulative (global) effects of a standing posture that generalize to the subsequent block in which participants sit. Results (N = 43) confirmed that time-on-task increased mental fatigue and decreased arousal. Standing (versus sitting) led to acute increases in arousal levels, including self-reports, alpha oscillations, and cardiac responses. Standing also decreased physiological and perceived effort costs. Standing enhanced processing speed in the flanker task, attributable to shortened nondecision time and speeded evidence accumulation processes. No significant effects were observed on higher-level executive functions. Alternating postures also increased heart rate variability cumulatively over time. Exploratory mediation analyses indicated that the positive impact of acute posture on enhanced drift rate was mediated by self-reported arousal, whereas decreased nondecision time was mediated by reductions in alpha power. In conclusion, alternating between sitting and standing postures can enhance arousal, decrease effort costs, and improve specific cognitive and physiological outcomes.

Climate-Driven Increases in Source Water Natural Organic Matter: Implications for the Sustainability of Drinking Water Treatment.

This study presents an updated analysis spanning over two decades (1999-2023) of climate, water quality, and operational data from two drinking water facilities in Atlantic Canada that previously experienced gradual increases in the natural organic matter (NOM) concentration and brownification. The goal was to assess the impact of recent extreme weather events on acute NOM concentration increases and drinking water treatment processes. In 2023, a dry spring combined with a warm and wet summer caused NOM in the water supplies to increase by >67% (as measured by color). To mitigate increased NOM concentration, the alum dose nearly doubled in 2023 compared to that in 2022. Disinfection byproducts were elevated following the event but remained within the compliance levels. From 1999 to 2023, the two plants responded to gradual climate change impacts and brownification, with alum dose increases of between 4.1 and 8.3 times. Equivalent CO2 emissions were estimated for alum usage, which increased by 3 to 7-fold in 2023 compared to when the plants were commissioned decades prior. The plants were not only adversely impacted by climate change but also contributed to the global CO2 burden. Thus, a paradigm shift toward sustainable alternatives for NOM removal is required in the water sector, and climate change adaptation and mitigation principles are urgently needed.

Enhancing recovery and reducing readmissions: The impact of remote monitoring on acute postoperative care in outpatient total joint arthroplasty

IntroductionOutpatient total joint arthroplasty (TJA) is gaining popularity in the United States. With a shift towards value-based healthcare and bundled payment models, the importance of safe discharge after TJA is pertinent in reducing readmissions and subsequent cost of care. However, many acute issues or complications may not occur until after discharge which can result in emergency department visits and readmission. Our study aims to characterize the effect of remote monitoring devices on acute postoperative recovery in TJA discharged within 24 h. We hypothesized there would be a decreased readmission rate in the remote home monitoring cohort. MethodsThis prospective cohort compared 50 outpatient TJAs (primary total hip and total knee replacements) defined as discharged within 24 h with a remote home monitoring device to 50 outpatient TJAs who did not receive remote monitoring. Demographics, hospital length of stay, American Society of Anesthesiology scores, and Charlson Comorbidity Index were compared with no significant difference observed between cohorts (p > 0.05). Patients’ vital signs were transmitted to a virtual response center for up to 48 h after discharge. An on-call medical team reviewed the transmissions and if prompted, would contact the patient to troubleshoot and triage. Primary outcome was 30-day hospital readmissions rates, while 30-day ED visits and patient satisfaction scores for the remote home monitoring were measured as secondary outcomes. ResultsWithin the remote monitoring cohort there was a 20 % incidence (10 patients) of abnormal vitals captured and 2 patients visited the ED, however there were no readmissions attributed to this group. Readmission rates and ED visits in the control non-monitored group were significantly higher at 12 % (p = 0.03), secondary to syncope, uncontrolled postoperative pain, cellulitis, hip dislocations, and postoperative fever. Of the patients who received remote monitoring, 14 % had trouble connecting the device to their smartphone, 44 % felt home monitoring helped in their care while recovering at home, 52 % made them feel safer, and 70 % would recommend this program. ConclusionsRemote home monitoring with a virtual response team after outpatient TJA is a feasible way to mitigate readmissions in the acute postoperative period and increase patient satisfaction. Efforts to minimize costs should not be implemented at the expense of patients’ health outcomes with a goal to find an appropriate balance between both agendas. Level of evidenceTherapeutic Level III.

Acute exercise activates the AHR in peripheral blood mononuclear cells in an intensity-dependent manner.

The kynurenine pathway (KP) of tryptophan degradation generates several metabolites such as kynurenine (KYN) or kynurenic acid (KA) that serve as endogenous ligands of the aryl hydrocarbon receptor (AHR). Due to its distinct biological roles particularly modulating the immune system, the AHR is a current therapeutic target across different inflammation-related diseases. Here, we show an acute exercise-induced increase in AHR ligand availability on a systemic level and a kynurenine pathway activation in peripheral blood mononuclear cells (PBMCs). Concurrently, the AHR is activated in PBMCs following acute exercise. Exercise effects on both, kynurenic acid and AHR activation in PBMCs were greater in response to high-intensity interval exercise (HIIE) (50 min, six 3-min intervals at 90% V̇o2peak, and 3-min intervals at 50% V̇o2peak in between) compared with workload-matched moderate-intensity continuous exercise (MICE) (50 min). In conclusion, these data indicate a novel mechanistic link in how exercise modulates the immune system through the kynurenine pathway-AHR axis, potentially underlying exercise-induced benefits in various chronic diseases.NEW & NOTEWORTHY The findings of this study show that acute endurance exercise activates a receptor that has been described to integrate metabolic signals into the immune system. We uncover a potential mechanistic link on how exercise modulates the immune system through the kynurenine pathway-AHR axis, potentially underlying exercise-induced benefits in various chronic diseases and of relevance for other cell types.

Testosterone and Erythrocyte Lifespan.

Endogenous and exogenous androgens increase circulating erythrocytes and hemoglobin but their effects on erythrocyte lifespan is not known. To investigate androgen effects on immature and mature erythrocyte lifespan in humans and mice using novel non-radioactive minimally invasive methods. Human erythrocyte lifespan was estimated using alveolar carbon monoxide concentration and blood hemoglobin in Levitt's formula in hypogonadal or transgender men before and up to 18 weeks after commencing testosterone (T) treatment. Erythrocyte lifespan was estimated in androgen receptor (AR) knockout and wild-type mice after T or dihydrotestosterone (DHT) treatment of intact females or orchidectomized males using in vivo biotin labelling of erythrocyte surface epitopes for reticulocytes (Ter119+CD71+) and two markers of erythrocytes (CD45-, Ter119+CD71-) monitoring their blood disappearance rate by flow cytometry. Before treatment, hypogonadal and transgender men had marked reduction in erythrocyte lifespan compared with controls. T treatment increased erythrocyte lifespan at 6 weeks but returned to pre-treatment levels at 18 weeks while serum T and blood hemoglobin were increased by T treatment remaining elevated at 18-weeks. In mice T and DHT treatment had higher erythrocyte (but not reticulocyte) lifespan but neither orchidectomy nor AR inactivation significantly influenced erythrocyte or reticulocyte lifespan. We conclude that hypogonadal men have reduced erythrocyte lifespan and acute androgen-induced increase in circulating erythrocyte lifespan may contribute to the well-known erythropoietic effects of androgens, but longer-term effects require further investigation to determine how much they contribute to androgen-induced increases in circulating hemoglobin.

Sympathetic and blood pressure reactivity in young adults with major depressive disorder

BackgroundSympathetic and blood pressure (BP) hyper-reactivity to stress may contribute to increased cardiovascular disease (CVD) risk in adults with major depressive disorder (MDD); however, whether this is evident in young adults with MDD without comorbid disease remains unclear. We hypothesized that acute stress-induced increases in muscle sympathetic nerve activity (MSNA) and BP would be exaggerated in young adults with MDD compared to healthy non-depressed young adults (HA) and that, in adults with MDD, greater symptom severity would be positively related to MSNA and BP reactivity. MethodsIn 28 HA (17 female) and 39 young adults with MDD of mild-to-moderate severity (unmedicated; 31 female), MSNA (microneurography) and beat-to-beat BP (finger photoplethysmography) were measured at rest and during the cold pressor test (CPT) and Stroop color word test (SCWT). ResultsThere were no group differences in resting MSNA (p = 0.24). Neither MSNA nor BP reactivity to either the CPT [MSNA: ∆24 ± 10 HA vs. ∆21 ± 11 bursts/min MDD, p = 0.67; mean arterial pressure (MAP): ∆22 ± 7 HA vs. ∆21 ± 10 mmHg MDD, p = 0.46)] or the SCWT (MSNA: ∆-4 ± 6 HA vs. ∆-5 ± 8 bursts/min MDD, p = 0.99; MAP: ∆7 ± 8 HA vs ∆9 ± 5 mmHg MDD; p = 0.82) were different between groups. In adults with MDD, symptom severity predicted MAP reactivity to the CPT (β = 0.78, SE = 0.26, p = 0.006), but not MSNA (p = 0.42). LimitationsThe mild-to-moderate symptom severity reflects only part of the MDD spectrum. ConclusionsNeither sympathetic nor BP stress reactivity are exaggerated in young adults with MDD; however, greater symptom severity may amplify BP reactivity to stress, thereby increasing CVD risk.

General and anxiety-linked influences of acute serotonin reuptake inhibition on neural responses associated with attended visceral sensation

Ordinary sensations from inside the body are important causes and consequences of our affective states and behaviour, yet the roles of neurotransmitters in interoceptive processing have been unclear. With a within-subjects design, this experiment tested the impacts of acute increases of endogenous extracellular serotonin on the neural processing of attended internal sensations and the links of these effects to anxiety using a selective serotonin reuptake inhibitor (SSRI) (20 mg citalopram) and a placebo. Twenty-one healthy volunteers (fourteen female, mean age 23.9) completed the Visceral Interoceptive Attention (VIA) task while undergoing functional magnetic resonance imaging (fMRI) with each treatment. The VIA task required focused attention on the heart, stomach, or visual sensation. The relative neural interoceptive responses to heart sensation [heart minus visual attention] (heart-IR) and stomach sensation [stomach minus visual attention] (stomach-IR) were compared between treatments. Visual attention subtraction controlled for the general effects of citalopram on sensory processing. Citalopram was associated with lower interoceptive processing in viscerosensory (the stomach-IR of bilateral posterior insular cortex) and integrative/affective (the stomach-IR and heart-IR of bilateral amygdala) components of interoceptive neural pathways. In anterior insular cortex, citalopram reductions of heart-IR depended on anxiety levels, removing a previously known association between anxiety and the region’s response to attended heart sensation observed with placebo. Preliminary post hoc analysis indicated that citalopram effects on the stomach-IR of the amygdalae corresponded to acute anxiety changes. This direct evidence of general and anxiety-linked serotonergic influence on neural interoceptive processes advances our understanding of interoception, its regulation, and anxiety.

Complementary use of conduction system pacing techniques for the “pace and ablate” strategy in permanent atrial fibrillation - a case report

Abstract Introduction The feasibility of the conduction system pacing combined with atrioventricular node ablation was demonstrated in patients with atrial fibrillation in whom rate control can’t be achieved with medication and heart failure. Clinical case We present a case of an 82-year-old man with a personal history of permanent atrial fibrillation, admitted with symptoms of heart failure. The resting electrocardiogram showed a very fast ventricular response, and the echocardiography showed a depressed left ventricular function, raising the suspicion of a tachycardia-mediated cardiomyopathy. Since the patient was on maximum doses of atrioventricular nodal-blocking drugs, we opted for a physiological pacing and atrioventricular node ablation strategy. First, the His bundle capture was achieved at low pacing thresholds, and ablation of the atrioventricular node was attempted. Unfortunately, after several failed attempts, an acute increase in the His bundle capture threshold was noted, suggesting inadvertent tissue ablation beneath the pacing lead. In this scenario, we removed the lead from the His bundle area and achieved optimal left bundle branch area pacing. With the lead in this position, atrioventricular node ablation was performed during the first attempt. At the six-month follow-up, there was no recovery of atrioventricular node conduction. Device interrogation revealed stable pacing and sensing parameters, and there was a significant improvement in clinical status and left ventricular function. Conclusions Mastering both His bundle pacing and left bundle branch area pacing offers the potential to overcome intraprocedural challenges, giving alternative strategies to achieve physiological pacing. These approaches can be used interchangeably based on the evolving dynamics of the procedure and the patient’s specific needs.

Is Workload Associated With Oblique Injuries in Professional Baseball Players?

Oblique strains have become a common injury among professional baseball players. The influence of player workload on oblique strains remains unknown. To determine whether workload is a risk factor for oblique strains in professional baseball players. We hypothesized that fewer days of rest, more innings pitched/fielded per game, and more batters faced/plate appearances per game would significantly increase a player's risk of sustaining an oblique strain. Case-control study; Level of evidence, 3. All professional baseball players who sustained an oblique strain between 2011 and 2017 were identified using the Major League Baseball Health and Injury Tracking System. A separate dataset of player usage-days of rest per game, innings pitched or fielded per game, and batters faced or plate appearances per game-was used to determine the workload. We compared these usage variables between player games ≤2, ≤6, ≤12, and >12 weeks before a documented oblique strain with player games from a control group of players with no oblique strains. In a paired analysis, we compared acute (player games ≤2, ≤6, and ≤12 weeks preinjury) versus chronic (player games >12 weeks preinjury) workloads. There were 311 oblique strains in pitchers and 392 oblique strains in position players during the study period. In pitchers, more innings pitched and more batters faced were associated with a subsequent oblique strain (P < .001 for all). In position players, fewer days of rest, more innings fielded, and more plate appearances were associated with a subsequent oblique strain (P < .001 for all). Pitchers who pitched ≥7 innings per game had a 2.4-fold (95% CI, 1.4-4.9) increased risk of subsequent oblique strain compared with those who pitched 1 inning per game. The percentage of position players with a subsequent oblique strain increased by 2.1-fold (95% CI, 1.3-3.5) with >4 plate appearances compared with 1 plate appearance per game. Our analysis demonstrated that workload was associated with an increased risk of sustaining an oblique injury in professional baseball players. High workload over time was more predictive of oblique strains compared to acute increases over chronic baseline workload.

Out of the Closet, but Not Out of the Woods: The Longitudinal Associations Between Identity Disclosure, Discrimination, and Nonsuicidal Self-Injury Among Sexual Minoritized Young Adults.

Sexual minoritized individuals engage in non-suicidal self-injury (NSSI) at higher rates than their heterosexual peers. Disclosing one's sexual minoritized identity can put one at risk for experiencing discrimination, which is linked to greater engagement in NSSI. However, discrimination has yet to be tested as a mechanism linking sexual identity disclosure to NSSI. Understanding how sexual identity disclosure impacts NSSI has the potential to inform interventions to reduce sexual orientation disparities in NSSI. To address this gap, the current study examined sexual orientation-based discrimination as a mediator of the longitudinal association between sexual identity disclosure and NSSI among 792 sexual minoritized young adults. Higher levels of disclosure at baseline were associated with greater likelihood of NSSI at two-month follow-up via greater discrimination at one-month follow-up, even after controlling for baseline levels of depression and demographic characteristics. The indirect effect became non-significant after controlling for previous levels of discrimination and NSSI. Findings provide partial support for the hypothesis that identity disclosure may precede exposure to discrimination and, in turn, engagement in NSSI. However, identity disclosure does not appear to predict acute increases in discrimination. Future research is encouraged to examine these prospective associations with longer intervals between assessments, as the indirect effect of identity disclosure on NSSI via discrimination may continue to accumulate over time. Findings highlight the need to reduce discrimination following sexual identity disclosure through the implementation of equitable and affirmative practices in school, healthcare, and other settings to improve the well-being of sexual minoritized young adults.