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Background: Vasodilation, autoregulation, and rising arterial pressure are three common concepts in cerebral compression, believed to improve cerebral blood flow to maintain the brain's nutrition. However, these concepts are unclear, unproven, and based on assumptions. This study aimed to correlate cerebral circulation with alterations of vital signs and to evaluate the above concepts based on physics and hemodynamics. Methods: Without new animal experiments, a large amount of data: recording of vital signs, long movies of cerebral circulation, and numerous photos of histological examination and microvessels obstruction in cerebral compression in cats was studied, and only partial and preliminary results were reported in 1970. The experiments were supported by an NIH grant for head injury, done before the 1985 Institutional Animal Care and Use Committee requirement. The advent of digital technology facilitated digitizing and stepwise correlating them and evaluating the validity of the above concepts. Results: As cerebral compression increased intracranial pressure (ICP), veins dilated, not arteries, and arterial microvessels obstructed, diminished, and stopped cerebral circulation. Simultaneously, vital signs deteriorated, and pupils became fixed and dilated. There was no evidence for what is believed as autoregulation. Conclusion: In cerebral compression, rising ICP obstructs cerebral arterial microvessels while simultaneously deteriorating vital signs. There is no evidence for dilatation of the arteries; only veins dilate, best-called venodilation. There is no evidence of autoregulation; what occurs is a cerebral compartmental syndrome. The terminal rise of arterial pressure is the hemodynamic result of cerebral circulation cessation, overloading the aorta. None of the concepts benefit the brain's nutrition. [ABSTRACT FROM AUTHOR]

RNA helicases are an evolutionary conserved class of nucleoside triphosphate dependent enzymes found in all kingdoms of life. Their cellular functions range from transcription regulation up to maintaining genomic stability and viral defence. As dysregulation of RNA helicases has been shown to be involved in several cancers and various diseases, RNA helicases are potential therapeutic targets. However, for selective targeting of a specific RNA helicase, it is crucial to develop a detailed understanding about its dynamics and regulation on a molecular and structural level. Deciphering unique features of specific RNA helicases is of fundamental importance not only for future drug development but also to deepen our understanding of RNA helicase regulation and function in cellular processes. In this review, we discuss recent insights into regulation mechanisms of RNA helicases and highlight models which demonstrate the interplay between helicase structure and their functions. [ABSTRACT FROM AUTHOR]

Abstract Background The aim of this study is to evaluate the impact of commonly administered sedatives (Propofol, Alfentanil, Fentanyl, and Midazolam) and vasopressor (Dobutamine, Ephedrine, Noradrenaline and Vasopressin) agents on cerebrovascular reactivity in moderate/severe TBI patients. Cerebrovascular reactivity, as a surrogate for cerebral autoregulation was assessed using the long pressure reactivity index (LPRx). We evaluated the data in two phases, first we assessed the minute-by-minute data relationships between different dosing amounts of continuous infusion agents and physiological variables using boxplots, multiple linear regression and ANOVA. Next, we assessed the relationship between continuous/bolus infusion agents and physiological variables, assessing pre-/post- dose of medication change in physiology using a Wilcoxon signed-ranked test. Finally, we evaluated sub-groups of data for each individual dose change per medication, focusing on key physiological thresholds and demographics. Results Of the 475 patients with an average stay of 10 days resulting in over 3000 days of recorded information 367 (77.3%) were male with a median Glasgow coma score of 7 (4–9). The results of this retrospective observational study confirmed that the infusion of most administered agents do not impact cerebrovascular reactivity, which is confirmed by the multiple linear regression components having p value > 0.05. Incremental dose changes or bolus doses in these medications in general do not lead to significant changes in cerebrovascular reactivity (confirm by Wilcoxon signed-ranked p value > 0.05 for nearly all assessed relationships). Within the sub-group analysis that separated the data based on LPRx pre-dose, a significance between pre-/post-drug change in LPRx was seen, however this may be more of a result from patient state than drug impact. Conclusions Overall, this study indicates that commonly administered agents with incremental dosing changes have no clinically significant influence on cerebrovascular reactivity in TBI (nor do they impair cerebrovascular reactivity). Though further investigation in a larger and more diverse TBI patient population is required.

Abstract Background The dysfunction of optic nerve head (ONH) hemodynamics has been suggested to be involved in the pathogenesis of normal-tension glaucoma (NTG). The aim of this study was to compare vasoreactivity in the ONH, nailfold, and facial skin in response to cold-water provocation in NTG patients and healthy controls. Methods We performed cold-water provocation in 14 eyes of 14 NTG patients and 15 eyes of 15 age-matched control subjects. Laser speckle flowgraphy-derived tissue-area mean blur rate (MT), skin blood flowmetry-derived pulse wave amplitude (PA), nailfold capillaroscopy-derived nailfold capillary diameter, and other clinical parameters were recorded at baseline and 4 and 6 min after the cold stimulus. We compared changes (as percentages) in these variables in the NTG and control subjects with a linear mixed-effects model and evaluated correlations between these changes with Spearman’s rank correlation coefficient. Results The interaction term between the NTG group (reference, control group) and the 4-min protocol step (reference, baseline) significantly affected the changes in MT, nailfold capillary diameter and PA (β = -9.51%, P = 0.017, β = -20.32%, P = 0.002; β = + 18.06%, P = 0.017, respectively). The change in MT was positively correlated with the change in nailfold capillary diameter, and negatively correlated with the change in PA (r = 0.39, P = 0.036; r = -0.40, P = 0.031, respectively). Conclusion NTG patients showed abnormal vasoconstriction in the ONH and nailfold and vasodilation in the facial skin in response to cold-water provocation.

Background: Cardiac arrest remains one of the leading causes of death. After successful resuscitation of patients in cardiac arrest, post-cardiac arrest syndrome develops, part of it being an impaired cerebral blood flow autoregulation. Monitoring cerebral blood flow autoregulation after cardiac arrest is important for optimizing patient care and prognosticating patients’ survival, yet remains a challenge. There are still gaps in clinical implications and everyday use. In this article, we present a systematic review of studies with different methods of monitoring cerebral blood flow autoregulation after non-traumatic cardiac arrest. Methods: A comprehensive literature search was performed from 1 June 2024 to 27 June 2024 by using multiple databases: PubMed, Web of Science, and the Cochrane Central Register of Controlled Trials. Inclusion criteria were studies with an included description of the measurement of cerebral blood flow autoregulation in adult patients after non-traumatic cardiac arrest. Results: A total of 16 studies met inclusion criteria. Our data show that the most used methods in the reviewed studies were near-infrared spectroscopy and transcranial Doppler. The most used mathematical methods for calculating cerebral autoregulation were cerebral oximetry index, tissue oxygenation reactivity index, and mean flow index. Conclusions: The use of various monitoring and mathematical methods for calculating cerebral blood flow autoregulation poses a challenge for standardization, validation, and daily use in clinical practice. In the future studies, focus should be considered on clinical validation and transitioning autoregulation monitoring techniques to everyday clinical practice, which could improve the survival outcomes of patients after cardiac arrest.

Pancreatic pseudocysts are collections of fluid localised within the pancreas or in the peripancreatic space, which can occur following acute pancreatitis or in patients with a history of acute pancreatitis and chronic pancreatitis. They are well-known complications of pancreatitis. The pathogenesis of pancreatitis depends on its etiology, where enzyme-rich fluid and products of autoregulation accumulate in acute pancreatitis, and cysts are formed due to obstructed ducts in chronic pancreatitis. The development of pancreatic pseudocysts is more commonly associated with chronic pancreatitis than acute pancreatitis. Unless ruptured, pancreatic pseudocysts are usually not hazardous. Diagnosis of pseudocysts has become easier with advanced diagnostic techniques such as ultrasound and Computed Tomography (CT) scans. Patients presenting with abdominal pain and elevated pancreatic enzymes should be suspected of having pseudocysts. Approximately one-third of these cases resolve spontaneously. In the past, surgery was the only management method, but recently, with newer techniques such as percutaneous drainage and endoscopic cyst enterostomy, management has become easier. Percutaneous drainage, performed under local anaesthesia, is a cost-effective procedure with very low complications. The recurrence rate is higher with single-needle treatment, so catheters are used to decrease recurrence. Drainage should be the first choice of management, but with advancing technology and endoscopic techniques, it may become more useful in the future with skilled practitioners. In this case report, we will examine the case of a 30-year-old male who presented with symptoms of pain in the epigastric region and was diagnosed with a pancreatic pseudocyst. This case demonstrates a rare presentation where the pseudocyst extends into the mediastinum and thorax.

Background: Despite the progress made in the study of subjective measures in resistance training, some questions remain unanswered. Here the authors investigated if ratings of perceived exertion (RPE) can predict task failure and bar velocity across exercises and loads as a primary outcome and whether a battery of subjective measures differ as a function of the lifted loads as a secondary outcome. Methods: In this preregistered study, 20 resistance-trained subjects (50% female) first completed a 1-repetition-maximum test of the barbell squat and bench press. In the second and third sessions, they completed 2 sets of squats followed by 2 sets of bench press to task failure, using 70% or 83% of 1-repetition maximum, while bar velocity was recorded. RPE scores were recorded after every repetition. In addition to RPE, rating of fatigue, affective valence, enjoyment, and load preferences were collected after set and session completion. Results: Across conditions, RPE was strongly correlated with reaching task failure (r =.86) and moderately correlated with bar velocity (r = −.58). The model indicates that an increase in 1 RPE unit is associated with an 11% shift toward task failure and a 4% reduction in bar velocity, with steeper slopes observed in the heavier condition. Negligible differences were observed between the load conditions in rating of fatigue, affective valence, enjoyment, and load preference. Conclusion: RPE scores, collected on a repetition-by-repetition basis, accurately reflected reaching task failure across loads and conditions. Hence, RPE can be used to prescribe repetition numbers during ongoing sets. The negligible differences between load conditions in rating of fatigue, affective valence, enjoyment, and load preference indicate that when sets are taken to task failure, loads can be selected based on individual preferences. [ABSTRACT FROM AUTHOR]

The heart has two intrinsic mechanisms to enhance contractile strength that compensate for increased mechanical load to help maintain cardiac output. When vascular resistance increases the ventricular chamber initially expands causing an immediate length-dependent increase of contraction force via the Frank-Starling mechanism. Additionally, the stress-dependent Anrep effect slowly increases contraction force that results in the recovery of the chamber volume towards its initial state. The Anrep effect poses a paradox: how can the cardiomyocyte maintain higher contractility even after the cell length has recovered its initial length? Here we propose a surface mechanosensor model that enables the cardiomyocyte to sense different mechanical stresses at the same mechanical strain. The cell-surface mechanosensor is coupled to a mechano-chemo-transduction feedback mechanism involving three elements: surface mechanosensor strain, intracellular Ca2+ transient, and cell strain. We show that in this simple yet general system, contractility autoregulation naturally emerges, enabling the cardiomyocyte to maintain contraction amplitude despite changes in a range of afterloads. These nontrivial model predictions have been experimentally confirmed. Hence, this model provides a new conceptual framework for understanding the contractility autoregulation in cardiomyocytes, which contributes to the heart's intrinsic adaptivity to mechanical load changes in health and diseases.

Calorie restriction (CR) typically promotes a reduction in body mass, which correlates with increased lifespan. We evaluated the overall changes in survival, body mass dynamics, and body composition following long-term graded CR (580 days/19 months) in male C57BL/6J mice. Control mice (0% restriction) were fed ad libitum in the dark phase only (12-hour ad libitum [12AL]). CR groups were restricted by 10%–40% of their baseline food intake (10CR, 20CR, 30CR, and 40CR). Body mass was recorded daily, and body composition was measured at 8 time points. At 728 days/24 months, all surviving mice were culled. A gradation in survival rate over the CR groups was found. The pattern of body mass loss differed over the graded CR groups. Whereas the lower CR groups rapidly resumed an energy balance with no significant loss of fat or fat-free mass, changes in the 30 and 40CR groups were attributed to higher fat-free mass loss and protection of fat mass. Day-to-day changes in body mass were less variable under CR than for the 12AL group. There was no indication that body mass was influenced by external factors. Partial autocorrelation analysis examined the relationship between daily changes in body masses. A negative correlation between mass on Day 0 and Day +1 declined with age in the 12AL but not the CR groups. A reduction in the correlation with age suggested body mass homeostasis is a marker of aging that declines at the end of life and is protected by CR. [ABSTRACT FROM AUTHOR]

Cerebral blood flow (CBF) autoregulation (AR) can be monitored using invasive modalities, such as intracranial pressure (ICP) and arterial blood pressure (ABP) to calculate the CBF AR index (PRx). Monitoring PRx can reduce the extent of secondary brain damage in patients. Rheoencephalography (REG) is an FDA-approved non-invasive method to measure CBF. REGx, a CBF AR index, is calculated from REG and arm bioimpedance pulse waves. Our goal was to test REG for neuromonitoring. 28 measurement sessions were performed on 13 neurocritical care patients. REG/arm bioimpedance waveforms were recorded on a laptop using a bioimpedance amplifier and custom-built software. The same program was used for offline data processing. Case #1: The patient's mean REGx increased from − 0.08 on the first day to 0.44 on the second day, indicating worsening intracranial compliance (ICC) (P < 0.0001, CI 0.46–0.58). Glasgow Coma Scale (GCS) was 5 on both days. Case #2: REGx decreased from 0.32 on the first recording to 0.07 on the last (P = 0.0003, CI − 0.38 to − 0.12). GCS was 7 and 14, respectively. Case #3: Within a 36-minute recording, REGx decreased from 0.56 to − 0.37 (P < 0.0001, 95%, CI − 1.10 to − 0.76). Central venous pressure changed from 14 to 9 mmHg. REG pulse wave morphology changed from poor ICC to good ICC morphology. Bioimpedance recording made it possible to quantify the active/passive status of CBF AR, indicate the worsening of ICC, and present it in real time. REGx can be a suitable, non-invasive alternative to PRx for use in head-injured patients. [ABSTRACT FROM AUTHOR]

• Dynamic cerebral autoregulation in postpartum individuals with and without preeclampsia showed a faster, but less effective response to changes in blood pressure, compared with healthy non-pregnant female volunteers. Changes in dynamic cerebral autoregulation (DCA) may contribute to postpartum maternal cerebrovascular complications after preeclampsia. We hypothesized that DCA is impaired in the first week postpartum after diagnosis of preeclampsia with severe features (PSF), compared with normotensive postpartum individuals and healthy non-pregnant female volunteers. We measured DCA within seven days after delivery in individuals with and without PSF, using transcranial Doppler and continuous arterial blood pressure monitoring with finger plethysmography. Historical data from 28 healthy female non-pregnant volunteers, collected using the same methods, were used for comparison. We used generalized harmonic wavelets to estimate autoregulation parameters (phase shift and gain) in very low frequency and low frequency bands, with lower phase shift and higher gain indicating impaired DCA function. We compared DCA parameters between the three groups using the Kruskal Wallis test. A total of 69 postpartum participants contributed data, of whom 49 had preeclampsia with severe features. Median phase shifts in both postpartum groups were higher compared with historical controls across all frequency ranges (p = 0.001), indicating faster autoregulatory response. Gain was higher in both postpartum groups than in historical controls across all frequency ranges (p = 0.04), indicating impaired dampening effect. We found that postpartum individuals, regardless of preeclampsia diagnosis, had higher phase shifts and higher gain than healthy non-pregnant/postpartum female volunteers. Our results suggest hyperdynamic DCA with impaired dampening effect in the first week postpartum, regardless of preeclampsia diagnosis. [ABSTRACT FROM AUTHOR]

Abstract Background Although vasopressor and sedative agents are commonly used within the intensive care unit to mediate systemic and cerebral physiology, the full impact such agents have on cerebrovascular reactivity remains unclear. Using a prospectively maintained database of high-resolution critical care and physiology, the time-series relationship between vasopressor/sedative administration, and cerebrovascular reactivity was interrogated. Cerebrovascular reactivity was assessed through intracranial pressure and near infrared spectroscopy measures. Using these derived measures, the relationship between hourly dose of medication and hourly index values could be evaluated. The individual medication dose change and their corresponding physiological response was compared. Given the high number of doses of propofol and norepinephrine, a latent profile analysis was used to identify any underlying demographic or variable relationships. Finally, using time-series methodologies of Granger causality and vector impulse response functions, the relationships between the cerebrovascular reactivity derived variables were compared. Results From this retrospective observational study of 103 TBI patients, the evaluation between the changes in vasopressor or sedative agent dosing and the previously described cerebral physiologies was completed. The assessment of the physiology pre/post infusion agent change resulted in similar overall values (Wilcoxon signed-ranked p value > 0.05). Time series methodologies demonstrated that the basic physiological relationships were identical before and after an infusion agent was changed (Granger causality demonstrated the same directional impact in over 95% of the moments, with response function being graphically identical). Conclusions This study suggests that overall, there was a limited association between the changes in vasopressor or sedative agent dosing and the previously described cerebral physiologies including that of cerebrovascular reactivity. Thus, current regimens of administered sedative and vasopressor agents appear to have little to no impact on cerebrovascular reactivity in TBI.

Background and Objectives: Impedance plethysmography and Doppler ultrasound, in most cases, are considered as independent methods for analyzing hemodynamics. This work shows the presence of similarities in the shape of pulse waves recorded by the two indicated methods at rest and during exercise tests. The dynamics of the volume and velocity of blood flow in the radial artery was studied at rest, during an occlusive test and a test with a deep breath. Materials and Methods: The method of impedance rheography was used to determine the dynamics of the blood volume in the artery, and the method of ultrasound dopplerography was used to determine the linear velocity of arterial blood flow. The equation that considers the irregular distribution of erythrocytes velocity in the cross-section of a blood vessel has been obtained for a correct quantitative description of the dynamics of the volumetric blood flow velocity. Results: It has been determined that both the deep breath test and the occlusive test lead to vasodilation of the radial artery. In this case, the test with deep breath causes the appearance of an additional peak in the diastole which agrees in time with the negative (retrograde) diastolic peak of the blood flow velocity. Comparative analysis of the integrated velocity and volume waves demonstrates phase matching and a linear dependence of the shape of these waves at rest which are disrupted during the deep breath test. Conclusions: The proposed equation for calculating volumetric blood flow enables one to study the processes of autoregulation of blood flow in vessels by controlling the balance of changes in blood volume and velocity by the methods of impedance rheography and ultrasound dopplerography and can potentially form the basis for the development of appropriate methods of functional diagnostics.

Power flow solution of the system with a full-power converter may get lost during low-voltage ride-through （LVRT）. Therefore， the change law of grid equivalent parameters and power flow characteristics during the fault is analyzed， and the law of influence of different system variables on the existence of power flow solution is analyzed qualitatively by numerical calculation considering the control characteristics of the converter. Based on the variation law of the grid equivalent parameters and the real-time calculation of the determinant of the Jacobi matrix of power flow， an active current amplitude limiting and autoregulation method is proposed that only requires the non-fault grid equivalent parameters and the measured voltage at the grid-connected point. The simulation results show that the proposed method can ensure the existence of the power flow solution during LVRT and is conducive to the safe and stable operation of the power system.

Ce varia 2022 rassemble six articles évoquant la formation à distance, l’autorégulation des apprentissages ainsi que les interactions et dynamiques de coopération ou de collaboration dans les groupes. Il comporte deux articles de recherche, deux articles de praticiens, un article de discussion et une note de lecture. Les recherches et réflexions menées des deux côtés de l’Atlantique et partagées dans ce numéro peuvent constituer des sources d’inspiration pour les chercheurs aussi bien que les praticiens. En effet, ces différents textes font ressortir l’importance des interactions et de la régulation des échanges au sein des collectifs, que ces derniers soient composés d’élèves de primaire et d’enseignants, aussi bien que d’étudiants en formation à distance ou de chercheurs et praticiens réunis pour réaliser un projet

The purpose of this investigation was to determine the validity and reliability of the Humac360 linear position transducer (LPT) as compared to Tendo Weightlifting Analyzer. Seventeen recreationally active men and women completed three visits. Visit one included maximal strength assessments via one-repetition maximum (1RM) for the barbell back squat. On visits two and three, participants completed two sets of three repetitions at 30-, 50-, 60-, and 70% 1RM. Mean Concentric Velocity (MCV), Peak Velocity (PV), Displacement (D), and Duration (T) were collected. Repetition data agreement was assessed with Intraclass Correlation Coefficients (ICCs) and were categorized as poor (0.90). Significance was accepted at an alpha (p) value < 0.05. Repetition-to-repetition comparisons between devices demonstrate varying degrees of agreement, with significant differences between devices across all intensities and all measurements (p < 0.001). Inter-set reliability was excellent for MCV, PV, D, and T with the exceptions of MCV and PV at 70% 1RM (ICC2,k = 0.548 and 0.816). Inter-session reliability data demonstrated reduced agreeableness in an intensity-dependent manner, with ICCs decreasing and SEMs increasing with increases in intensity. The Humac360 LPT does not appear to be valid when compared to the criterion reference, though we contend it maintains construct validity. Coaches may use the Humac360 LPT as a tool to monitor fatigue, and the associated changes in trainee movement velocity on an inter-set and inter-session basis.

Background: The aim of this study is to evaluate the impact of commonly administered sedatives (Propofol, Alfentanil, Fentanyl, and Midazolam) and vasopressor (Dobutamine, Ephedrine, Noradrenaline and Vasopressin) agents on cerebrovascular reactivity in moderate/severe TBI patients. Cerebrovascular reactivity, as a surrogate for cerebral autoregulation was assessed using the long pressure reactivity index (LPRx). We evaluated the data in two phases, first we assessed the minute-by-minute data relationships between different dosing amounts of continuous infusion agents and physiological variables using boxplots, multiple linear regression and ANOVA. Next, we assessed the relationship between continuous/bolus infusion agents and physiological variables, assessing pre-/post- dose of medication change in physiology using a Wilcoxon signed-ranked test. Finally, we evaluated sub-groups of data for each individual dose change per medication, focusing on key physiological thresholds and demographics. Results: Of the 475 patients with an average stay of 10 days resulting in over 3000 days of recorded information 367 (77.3%) were male with a median Glasgow coma score of 7 (4–9). The results of this retrospective observational study confirmed that the infusion of most administered agents do not impact cerebrovascular reactivity, which is confirmed by the multiple linear regression components having p value > 0.05. Incremental dose changes or bolus doses in these medications in general do not lead to significant changes in cerebrovascular reactivity (confirm by Wilcoxon signed-ranked p value > 0.05 for nearly all assessed relationships). Within the sub-group analysis that separated the data based on LPRx pre-dose, a significance between pre-/post-drug change in LPRx was seen, however this may be more of a result from patient state than drug impact. Conclusions: Overall, this study indicates that commonly administered agents with incremental dosing changes have no clinically significant influence on cerebrovascular reactivity in TBI (nor do they impair cerebrovascular reactivity). Though further investigation in a larger and more diverse TBI patient population is required. [ABSTRACT FROM AUTHOR]

Masters-level weightlifters diagnosed with cancer can return to training as a part of a successful treatment plan. Many older adults at higher risk for cancer participate in masters weightlifting meets worldwide. Resuming activities enjoyed before diagnosis is part of a return to normalcy for these athletes. This article recommends using autoregulation integrated with periodization principles to account for changes in the body due to surgery, side effects from masters cancer treatments, and age-related declines that affect masters athletes. Surgery, chemotherapy, and radiation therapy require adjusting workouts from prediagnosis levels to insure a safe and successful recovery while athletes experience side effects from treatments. Autoregulation is recommended to help strength and conditioning specialists assist in daily exercise prescriptions for patients with cancer who experience good and bad days during months of treatment cycles. Resistance training is an evidence-based practice for a successful recovery, and existing literature provides a basis for recommendations found in this article to support program development for masters weightlifters returning to advanced resistance training. [ABSTRACT FROM AUTHOR]

Background: The dysfunction of optic nerve head (ONH) hemodynamics has been suggested to be involved in the pathogenesis of normal-tension glaucoma (NTG). The aim of this study was to compare vasoreactivity in the ONH, nailfold, and facial skin in response to cold-water provocation in NTG patients and healthy controls. Methods: We performed cold-water provocation in 14 eyes of 14 NTG patients and 15 eyes of 15 age-matched control subjects. Laser speckle flowgraphy-derived tissue-area mean blur rate (MT), skin blood flowmetry-derived pulse wave amplitude (PA), nailfold capillaroscopy-derived nailfold capillary diameter, and other clinical parameters were recorded at baseline and 4 and 6 min after the cold stimulus. We compared changes (as percentages) in these variables in the NTG and control subjects with a linear mixed-effects model and evaluated correlations between these changes with Spearman's rank correlation coefficient. Results: The interaction term between the NTG group (reference, control group) and the 4-min protocol step (reference, baseline) significantly affected the changes in MT, nailfold capillary diameter and PA (β = -9.51%, P = 0.017, β = -20.32%, P = 0.002; β = + 18.06%, P = 0.017, respectively). The change in MT was positively correlated with the change in nailfold capillary diameter, and negatively correlated with the change in PA (r = 0.39, P = 0.036; r = -0.40, P = 0.031, respectively). Conclusion: NTG patients showed abnormal vasoconstriction in the ONH and nailfold and vasodilation in the facial skin in response to cold-water provocation. [ABSTRACT FROM AUTHOR]

Patients with Moyamoya Angiopathy (MMA) display structurally altered vessels with decreased cerebral autoregulatory capacity, so aggressive lowering of systemic hypertension may aggravate ischemic symptoms, whereas uncontrolled hypertension may promote hemorrhage. This study provides an in-depth analysis of the role of hypertension in adult MMA patients including long-term analysis of clinical and radiological development. In this single-center retrospective analysis of 137 adult MMA patients with 206 surgically treated hemispheres angiographic images, clinical/operative data were reviewed and scored. Univariate Cox-regression analysis was performed to evaluate hypertension as a predictor for negative angiographic and clinical outcomes following revascularization surgery. A total of 50% of patients were being treated for hypertension prior to the first surgery. Patients with and without hypertension did not differ in terms of age, gender, diagnosis, symptom onset or disease severity (Berlin and Suzuki Grades). Although hypertension did not statistically significantly affect postoperative collaterals, moyamoya vessels or STA-MCA bypass patency, patients with hypertension showed higher rates of bypass patency and better bypass filling compared to those without hypertension. No significant differences in adverse events were found in patients with and without systemic hypertension and the presence of systemic hypertension was not found to predict negative clinical or radiological outcomes. In conclusion, the rate of systemic hypertension in MMA patients appears to be higher than the general population; however, this is not associated with an increased risk of postoperative complications or negative angiographic development following revascularization procedures. Systemic hypertension may also positively influence the rate of bypass patency and filling following revascularization procedures. [ABSTRACT FROM AUTHOR]

Simple Summary: In insects, sex determination is generated using intricate and variegate biological processes that may be effectively described as variations on a common theme. In the model system Drosophila melanogaster, genetic and biochemical studies have shown that the female-specific Transformer (TRA) and the non-sex-specific Transformer2 (TRA2) are RNA-binding proteins that physically interact to promote female differentiation by female-specific alternative splicing of downstream genes. This tra gene responds and transduces different primary sex-determining signals, and its master function is widely conserved in Diptera, Coleoptera, and Hymenoptera. Here, combining yeast two-hybrid and computational methodologies, we demonstrate that the TRA and TRA2 orthologs of the agricultural pest Ceratitis capitata physically interact through a molecular mechanism that could be evolutionarily conserved in other species. These technical approaches can be helpful to verify or to identify other proteins interacting with TRA and TRA2, for example, those promoting male sex determination in this and other species, as well as to design new compounds that could induce masculinization of XX individuals in applications of the Sterile Insect Technique. In the model system for genetics, Drosophila melanogaster, sexual differentiation and male courtship behavior are controlled by sex-specific splicing of doublesex (dsx) and fruitless (fru). In vitro and in vivo studies showed that female-specific Transformer (TRA) and the non-sex-specific Transformer 2 (TRA2) splicing factors interact, forming a complex promoting dsx and fru female-specific splicing. TRA/TRA2 complex binds to 13 nt long sequence repeats in their pre-mRNAs. In the Mediterranean fruitfly Ceratitis capitata (Medfly), a major agricultural pest, which shares with Drosophila a ~120 million years old ancestor, Cctra and Cctra2 genes seem to promote female-specific splicing of Ccdsx and Ccfru, which contain conserved TRA/TRA2 binding repeats. Unlike Drosophila tra, Cctra autoregulates its female-specific splicing through these putative regulatory repeats. Here, a yeast two-hybrid assay shows that CcTRA interacts with CcTRA2, despite its high amino acid divergence compared to Drosophila TRA. Interestingly, CcTRA2 interacts with itself, as also observed for Drosophila TRA2. We also generated a three-dimensional model of the complex formed by CcTRA and CcTRA2 using predictive approaches based on Artificial Intelligence. This structure also identified an evolutionary and highly conserved putative TRA2 recognition motif in the TRA sequence. The Y2H approach, combined with powerful predictive tools of three-dimensional protein structures, could use helpful also in this and other insect species to understand the potential links between different upstream proteins acting as primary sex-determining signals and the conserved TRA and TRA2 transducers. [ABSTRACT FROM AUTHOR]

Two novel treatments for diabetic kidney disease have emerged after decades with little progression. Both agents were developed for improved glycemic control in patients with type-2 diabetes. However, large clinical trials showed renoprotective effects beyond their ability to lower plasma glucose levels, body weight, and blood pressure. How this renal protection occurs is unknown. We will discuss their physiological effects, with special focus on the renal effects. We discuss how these drugs affect the function of the diabetic and nondiabetic kidneys to elucidate mechanisms by which the renoprotection could arise. Diabetic kidney disease affects the glomerular capillaries, which are usually protected by the renal autoregulatory mechanisms, the myogenic response, and the tubuloglomerular feedback mechanism. Animal models with reduced renal autoregulatory capacity develop chronic kidney disease. Despite different cellular targets, both drugs are suspected to affect renal hemodynamics through changes in the renal autoregulatory mechanisms. The glucagon-like peptide-1 receptor agonists (GLP-1RAs) exert a direct vasodilatory effect on the afferent arteriole (AA) positioned just before the glomerulus. Paradoxically, this effect is expected to increase glomerular capillary pressure, causing glomerular injury. In contrast, the sodium-glucose transporter-2 inhibitors (SGLT2i) are believed to activate the tubuloglomerular feedback mechanism to elicit vasoconstriction of the afferent arteriole. Because of their opposing effects on the renal afferent arterioles, it appears unlikely that their renoprotective effects can be explained by common effects of renal hemodynamics, but both drugs appear to add protection to the kidney beyond what can be obtained with classical treatment targeted at lowering blood glucose levels and blood pressure. [ABSTRACT FROM AUTHOR]

Purpose: Different organs have different autoregulatory capacities for blood pressure changes and/or circulatory volume changes. This study assessed the autoregulation of the stomach, liver, kidney and skeletal muscle, under baseline, hypovolemic, and post-fluid-resuscitation conditions using near-infrared spectroscopy (NIRS). Methods: Ten pigs (bodyweight 24.5 ± 0.5 kg) were anesthetized with 2.5% isoflurane and administered 0.5, 1, 2 and 5 µg kg− 1 min− 1 of phenylephrine at 10-min intervals, followed by similar stepwise infusion of sodium nitroprusside (SNP) to induce a wide range of mean arterial pressures (MAPs). A 600-ml bleed was induced to create the hypovolemic condition, and only phenylephrine was re-administered. Hydroxyethyl starch (600 ml) was infused to create the post-fluid-resuscitation condition, and phenylephrine and SNP were re-administered. Average relationships between mean arterial pressure (MAP) and each tissue oxygenation index (TOI) were assessed, and the individual relationships were evaluated based on the correlation coefficients between MAP and TOI during each vasoactive drug infusion. Results: Based on the evaluation using each TOI as a substitute of blood flow, the kidney autoregulation was robust, similar to muscle, but had a prominent lower limit. The stomach had weaker autoregulation than the kidney and muscle. The liver had no autoregulation. The kidney TOI showed 2-fold greater changes in response to volume condition changes than the stomach and liver TOIs. Conclusion: In our NIRS-based assessment of autoregulatory capacity, the liver oxygenation is highly blood pressure dependent, and the kidney is highly susceptible and the skeletal muscle is highly tolerable to low blood pressure and volume loss. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a global healthcare crisis. The TgF344-AD rat is an AD model exhibiting age-dependent AD pathological hallmarks. We confirmed that AD rats developed cognitive deficits at 6 months without alteration of any other major biophysical parameters. We longitudinally characterized cerebral hemodynamics in AD rats at 3, 4, 6, and 14 months. The myogenic responses of the cerebral arteries and arterioles were impaired at 4 months of age in the AD rats. Consistent with the ex vivo results, the AD rat exhibited poor autoregulation of surface and deep cortical cerebral blood flow 2 months preceding cognitive decline. The dysfunction of cerebral hemodynamics in AD is exacerbated with age associated with reduced cerebral perfusion. Further, abolished cell contractility contributes to cerebral hemodynamics imbalance in AD. This may be attributed to enhanced ROS production, reduced mitochondrial respiration and ATP production, and disrupted actin cytoskeleton in cerebral vascular contractile cells. [ABSTRACT FROM AUTHOR]

Cardiopulmonary bypass (CPB) has revolutionized cardiac surgery but poses challenges such as hemodynamic instability and adverse clinical outcomes. Achieving optimal perfusion during CPB ensures adequate oxygen delivery to vital organs. Although mean arterial pressure is a key determinant of perfusion pressure, clear guidelines for optimal perfusion have yet to be established. Autoregulation, the organ's ability to maintain consistent blood flow, plays a vital role in perfusion. Individual variability in autoregulation responses and intraoperative factors necessitate an individualized approach to determining the autoregulation range. Continuous assessment of autoregulation during surgery allows for personalized perfusion targets, optimizing organ perfusion. Exploring techniques like multimodal intravenous anesthesia guided by electroencephalogram can enhance perfusion maintenance within the auto-regulatory range. By adopting an individualized approach to perfusion targets on CPB, we can improve outcomes and enhance patient care. [ABSTRACT FROM AUTHOR]

Background: Although vasopressor and sedative agents are commonly used within the intensive care unit to mediate systemic and cerebral physiology, the full impact such agents have on cerebrovascular reactivity remains unclear. Using a prospectively maintained database of high-resolution critical care and physiology, the time-series relationship between vasopressor/sedative administration, and cerebrovascular reactivity was interrogated. Cerebrovascular reactivity was assessed through intracranial pressure and near infrared spectroscopy measures. Using these derived measures, the relationship between hourly dose of medication and hourly index values could be evaluated. The individual medication dose change and their corresponding physiological response was compared. Given the high number of doses of propofol and norepinephrine, a latent profile analysis was used to identify any underlying demographic or variable relationships. Finally, using time-series methodologies of Granger causality and vector impulse response functions, the relationships between the cerebrovascular reactivity derived variables were compared. Results: From this retrospective observational study of 103 TBI patients, the evaluation between the changes in vasopressor or sedative agent dosing and the previously described cerebral physiologies was completed. The assessment of the physiology pre/post infusion agent change resulted in similar overall values (Wilcoxon signed-ranked p value > 0.05). Time series methodologies demonstrated that the basic physiological relationships were identical before and after an infusion agent was changed (Granger causality demonstrated the same directional impact in over 95% of the moments, with response function being graphically identical). Conclusions: This study suggests that overall, there was a limited association between the changes in vasopressor or sedative agent dosing and the previously described cerebral physiologies including that of cerebrovascular reactivity. Thus, current regimens of administered sedative and vasopressor agents appear to have little to no impact on cerebrovascular reactivity in TBI. [ABSTRACT FROM AUTHOR]

Some genes can promote or repress their own expressions, which is called autoregulation. Although gene regulation is a central topic in biology, autoregulation is much less studied. In general, it is extremely difficult to determine the existence of autoregulation with direct biochemical approaches. Nevertheless, some papers have observed that certain types of autoregulations are linked to noise levels in gene expression. We generalize these results by two propositions on discrete-state continuous-time Markov chains. These two propositions form a simple but robust method to infer the existence of autoregulation from gene expression data. This method only needs to compare the mean and variance of the gene expression level. Compared to other methods for inferring autoregulation, our method only requires non-interventional one-time data, and does not need to estimate parameters. Besides, our method has few restrictions on the model. We apply this method to four groups of experimental data and find some genes that might have autoregulation. Some inferred autoregulations have been verified by experiments or other theoretical works. [ABSTRACT FROM AUTHOR]

OBJECTIVES: To examine cerebrovascular pressure reactivity index (PRx) in a large cohort of children with severe traumatic brain injury (sTBI) in association with physiologic variables and outcome. DESIGN: Retrospective observational cohort study. SETTING: Red Cross War Memorial Children's Hospital in Cape Town, South Africa. PATIENTS: Pediatric (≤ 14 yr old) sTBI patients with intracranial pressure (ICP) monitoring (postresuscitation Glasgow Coma Score [Glasgow Coma Scale (GCS)] of ≤ 8). MEASUREMENTS AND MAIN RESULTS: Data were analyzed from ICM+ files sampled at 100Hz. PRx (a mathematical indicator of pressure reactivity) was calculated as a moving correlation coefficient between ICP and mean arterial pressure (MAP) as previously described. Associations between PRx, age, GCS, ICP, MAP, and cerebral perfusion pressure (CPP) were examined with summary measures and correlation analysis using high-frequency data. Associations between PRx and mortality/outcome were examined with multivariable logistic regression analysis and the prognostic ability of PRx with receiver operating characteristic (ROCs) curves. The dataset included over 1.7 million minutes (28,634 hr) of MAP and ICP data in 196 children. The series mortality was 10.7% (21/196), and unfavorable outcome 29.6% (58/196). PRx had a moderate positive correlation with ICP (r = 0.44; p < 0.001), a moderate negative correlation with CPP (r = -0.43; p < 0.001), and a weak negative correlation with MAP (r = –0.21; p = 0.004). PRx was consistently higher in patients with poor outcome and had a strong, independent association with mortality (ROC area under the curve = 0.91). A PRx threshold of 0.25 showed the best predictive ability for mortality. CONCLUSIONS: This is the largest cohort of children with PRx analysis of cerebrovascular reactivity to date. PRx had a strong association with outcome that was independent of ICP, CPP, GCS, and age. The data suggest that impaired autoregulation is an independent factor associated with poor outcome and may be useful in directing clinical care. [ABSTRACT FROM AUTHOR]

Introduction: Acute traumatic spinal cord injury is routinely managed by surgical decompression and instrumentation of the spine. Guidelines also suggest elevating mean arterial pressure to 85mmHg to mitigate secondary injury. However, the evidence for these recommendations remains very limited. There is now considerable interest in measuring spinal cord perfusion pressure by monitoring mean arterial pressure and intraspinal pressure. Here, we present our first institutional experience of using a strain gauge pressure transducer monitor to measure intraspinal pressure and subsequent derivation of spinal cord perfusion pressure. Case presentation: The patient presented to medical attention after a fall off of scaffolding. A trauma assessment was completed at a local emergency room. He did not have any motor strength or sensation to the lower extremities. A computed tomography (CT) scan of the thoracolumbar spine confirmed a T12 burst fracture with retropulsion of bone fragments into the spinal canal. He was taken to surgery for urgent decompression of the spinal cord and instrumentation of the spine. A subdural strain gauge pressure monitor was placed at the site of injury through a small dural incision. Mean arterial pressure and intraspinal pressure were then monitored for 5days after surgery. Spinal cord perfusion pressure was derived. The procedure was performed without complication and the patient underwent rehabilitation for 3months where he regained some motor and sensory function in his lower extremities. Conclusion: The first North American attempt at insertion of a strain gauge pressure monitor into the subdural space at the site of injury following acute traumatic spinal cord injury was performed successfully and without complication. Spinal cord perfusion pressure was derived successfully using this physiological monitoring. Further research efforts to validate this technique are required. [ABSTRACT FROM AUTHOR]

Histones, which make up nucleosomes, undergo various post-translational modifications, such as acetylation, methylation, phosphorylation, and ubiquitylation. In particular, histone methylation serves different cellular functions depending on the location of the amino acid residue undergoing modification, and is tightly regulated by the antagonistic action of histone methyltransferases and demethylases. The SUV39H family of histone methyltransferases (HMTases) are evolutionarily conserved from fission yeast to humans and play an important role in the formation of higher-order chromatin structures called heterochromatin. The SUV39H family HMTases catalyzes the methylation of histone H3 lysine 9 (H3K9), and this modification serves as a binding site for heterochromatin protein 1 (HP1) to form a higher-order chromatin structure. While the regulatory mechanism of this family of enzymes has been extensively studied in various model organisms, Clr4, a fission yeast homologue, has made an important contribution. In this review, we focus on the regulatory mechanisms of the SUV39H family of proteins, in particular, the molecular mechanisms revealed by the studies of the fission yeast Clr4, and discuss their generality in comparison to other HMTases. [ABSTRACT FROM AUTHOR]

²The purpose of this investigation was to determine if average concentric velocity (ACV) of a single repetition at 70% of one-repetition maximum (1RM), ACV of the first repetition of a set to failure at 70% of 1RM, or the velocity loss during the set could predict the number of repetitions performed in the back squat. Fifty-six resistance-trained individuals participated in the study (male = 41, age = 23 ± 3 yrs, 1RM = 162.0 ± 40.0 kg; female = 15, age = 21 ± 2 yrs, 1RM = 81.5 ± 12.5 kg). After 1RM testing, participants performed single repetition sets with 70% of 1RM and a set to failure with 70% of 1RM. ACV was recorded on all repetitions. Regression model comparisons were performed, and Akaike Information Criteria (AIC) and Standard Error of the Estimate (SEE) were calculated to determine the best model. Neither single repetition ACV at 70% of 1RM (R² = 0.004, p = 0.637) nor velocity loss (R² = 0.011, p = 0.445) were predictive of total repetitions performed in the set to failure. The simple quadratic model using the first repetition of the set to failure (Y = β0 + β1XACVFirst + β2X2ACVFirst + ε) was identified as the best and most parsimonious model (R2 = 0.259, F = 9.247, p < 0.001) due to the lowest AIC value (311.086). A SEE of 2.21 repetitions was identified with this model. This average error of ~2 repetitions warrants only cautious utilization of this method to predict total repetitions an individual can perform in a set, with additional autoregulatory or individualization strategies being necessary to finalize the training prescription. [ABSTRACT FROM AUTHOR]

5‐Aminolevulinic acid synthase (ALAS) is a pyridoxal 5′‐phosphate (PLP)‐dependent enzyme that catalyzes the first and rate‐limiting step of heme biosynthesis in α‐proteobacteria and several non‐plant eukaryotes. All ALAS homologs contain a highly conserved catalytic core, but eukaryotes also have a unique C‐terminal extension that plays a role in enzyme regulation. Several mutations in this region are implicated in multiple blood disorders in humans. In Saccharomyces cerevisiae ALAS (Hem1), the C‐terminal extension wraps around the homodimer core to contact conserved ALAS motifs proximal to the opposite active site. To determine the importance of these Hem1 C‐terminal interactions, we determined the crystal structure of S. cerevisiae Hem1 lacking the terminal 14 amino acids (Hem1 ΔCT). With truncation of the C‐terminal extension, we show structurally and biochemically that multiple catalytic motifs become flexible, including an antiparallel β‐sheet important to Fold‐Type I PLP‐dependent enzymes. The changes in protein conformation result in an altered cofactor microenvironment, decreased enzyme activity and catalytic efficiency, and ablation of subunit cooperativity. These findings suggest that the eukaryotic ALAS C‐terminus has a homolog‐specific role in mediating heme biosynthesis, indicating a mechanism for autoregulation that can be exploited to allosterically modulate heme biosynthesis in different organisms. PDB Code(s): 8EIM; [ABSTRACT FROM AUTHOR]

Training with blood flow restriction (BFR) has been shown to be a useful technique to improve muscle hypertrophy, muscle strength and a host of other physiological benefits in both healthy and clinical populations using low intensities [20%-30% 1- repetition maximum (1RM) or <50% maximum oxygen uptake (VO2max)]. However, as BFR training is gaining popularity in both practice and research, there is a lack of awareness for potentially important design characteristics and features associated with BFR cuff application that may impact the acute and longitudinal responses to training as well as the safety profile of BFR exercise. While cuff width and cuff material have been somewhat addressed in the literature, other cuff design and features have received less attention. This manuscript highlights additional cuff design and features and hypothesizes on their potential to impact the response and safety profile of BFR. Features including the presence of autoregulation during exercise, the type of bladder system used, the shape of the cuff, the set pressure versus the interface pressure, and the bladder length will be addressed as these variables have the potential to alter the responses to BFR training. As more devices enter the marketplace for consumer purchase, investigations specifically looking at their impact is warranted. We propose numerous avenues for future research to help shape the practice of BFR that may ultimately enhance efficacy and safety using a variety of BFR technologies. [ABSTRACT FROM AUTHOR]

Main conclusion: Lysin motif (LysM)-receptor-like kinase (RLK) and leucine-rich repeat (LRR)-RLK mediated signaling play important roles in the development and regulation of root nodule symbiosis in legumes. The availability of water and nutrients in the soil is a major limiting factor affecting crop productivity. Plants of the Leguminosae family form a symbiotic association with nitrogen-fixing Gram-negative soil bacteria, rhizobia for nitrogen fixation. This symbiotic relationship between legumes and rhizobia depends on the signal exchange between them. Plant receptor-like kinases (RLKs) containing lysin motif (LysM) and/or leucine-rich repeat (LRR) play an important role in the perception of chemical signals from rhizobia for initiation and establishment of root nodule symbiosis (RNS) that results in nitrogen fixation. This review highlights the diverse aspects of LysM-RLK and LRR receptors including their specificity, functions, interacting partners, regulation, and associated signaling in RNS. The activation of LysM-RLKs and LRR-RLKs is important for ensuring the successful interaction between legume roots and rhizobia. The intracellular regions of the receptors enable additional layers of signaling that help in the transduction of signals intracellularly. Additionally, symbiosis receptor-like kinase (SYMRK) containing the LRR motif acts as a co-receptor with Nod factors receptors (LysM-RLK). Cleavage of the malectin-like domain from the SYMRK ectodomain is a mechanism for controlling SYMRK stability. Overall, this review has discussed different aspects of legume receptors that are critical to the perception of signals from rhizobia and their subsequent role in creating the mutualistic relationship necessary for nitrogen fixation. Additionally, it has been discussed how crucial it is to extrapolate the knowledge gained from model legumes to crop legumes such as chickpea and common bean to better understand the mechanism underlying nodule formation in crop legumes. Future directions have also been proposed in this regard. [ABSTRACT FROM AUTHOR]

IntroductionAcute traumatic spinal cord injury is routinely managed by surgical decompression and instrumentation of the spine. Guidelines also suggest elevating mean arterial pressure to 85 mmHg to mitigate secondary injury. However, the evidence for these recommendations remains very limited. There is now considerable interest in measuring spinal cord perfusion pressure by monitoring mean arterial pressure and intraspinal pressure. Here, we present our first institutional experience of using a strain gauge pressure transducer monitor to measure intraspinal pressure and subsequent derivation of spinal cord perfusion pressure.Case presentationThe patient presented to medical attention after a fall off of scaffolding. A trauma assessment was completed at a local emergency room. He did not have any motor strength or sensation to the lower extremities. A computed tomography (CT) scan of the thoracolumbar spine confirmed a T12 burst fracture with retropulsion of bone fragments into the spinal canal. He was taken to surgery for urgent decompression of the spinal cord and instrumentation of the spine. A subdural strain gauge pressure monitor was placed at the site of injury through a small dural incision. Mean arterial pressure and intraspinal pressure were then monitored for 5 days after surgery. Spinal cord perfusion pressure was derived. The procedure was performed without complication and the patient underwent rehabilitation for 3 months where he regained some motor and sensory function in his lower extremities.ConclusionThe first North American attempt at insertion of a strain gauge pressure monitor into the subdural space at the site of injury following acute traumatic spinal cord injury was performed successfully and without complication. Spinal cord perfusion pressure was derived successfully using this physiological monitoring. Further research efforts to validate this technique are required.

Training with blood flow restriction (BFR) has been shown to be a useful technique to improve muscle hypertrophy, muscle strength and a host of other physiological benefits in both healthy and clinical populations using low intensities [20%–30% 1-repetition maximum (1RM) or