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Cell Reports May 2024The suprachiasmatic nucleus (SCN) encodes time of day through changes in daily firing; however, the molecular mechanisms by which the SCN times behavior are not fully...
The suprachiasmatic nucleus (SCN) encodes time of day through changes in daily firing; however, the molecular mechanisms by which the SCN times behavior are not fully understood. To identify factors that could encode day/night differences in activity, we combine patch-clamp recordings and single-cell sequencing of individual SCN neurons in mice. We identify PiT2, a phosphate transporter, as being upregulated in a population of VipNms SCN neurons at night. Although nocturnal and typically showing a peak of activity at lights off, mice lacking PiT2 (PiT2) do not reach the activity level seen in wild-type mice during the light/dark transition. PiT2 loss leads to increased SCN neuronal firing and broad changes in SCN protein phosphorylation. PiT2 mice display a deficit in seasonal entrainment when moving from a simulated short summer to longer winter nights. This suggests that PiT2 is responsible for timing activity and is a driver of SCN plasticity allowing seasonal entrainment.
Topics: Animals; Suprachiasmatic Nucleus; Mice; Neurons; Locomotion; Mice, Inbred C57BL; Vasoactive Intestinal Peptide; Male; Circadian Rhythm; Photoperiod; Mice, Knockout; Sodium-Phosphate Cotransporter Proteins, Type III; Phosphate Transport Proteins
PubMed: 38735047
DOI: 10.1016/j.celrep.2024.114220 -
Cell Reports May 2024Interneurons (INs), specifically those in disinhibitory circuits like somatostatin (SST) and vasoactive intestinal peptide (VIP)-INs, are strongly modulated by the...
Interneurons (INs), specifically those in disinhibitory circuits like somatostatin (SST) and vasoactive intestinal peptide (VIP)-INs, are strongly modulated by the behavioral context. Yet, the mechanisms by which these INs are recruited during active states and whether their activity is consistent across sensory cortices remain unclear. We now report that in mice, locomotor activity strongly recruits SST-INs in the primary somatosensory (S1) but not the visual (V1) cortex. This diverse engagement of SST-INs cannot be explained by differences in VIP-IN function but is absent in the presence of visual input, suggesting the involvement of feedforward sensory pathways. Accordingly, inactivating the somatosensory thalamus, but not decreasing VIP-IN activity, significantly reduces the modulation of SST-INs by locomotion. Model simulations suggest that the differences in SST-INs across behavioral states can be explained by varying ratios of VIP- and thalamus-driven activity. By integrating feedforward activity with neuromodulation, SST-INs are anticipated to be crucial for adapting sensory processing to behavioral states.
Topics: Animals; Interneurons; Somatostatin; Mice; Vasoactive Intestinal Peptide; Somatosensory Cortex; Male; Mice, Inbred C57BL; Locomotion; Behavior, Animal; Visual Cortex; Thalamus
PubMed: 38733587
DOI: 10.1016/j.celrep.2024.114197 -
Journal of Infection in Developing... Apr 2024Cytomegalovirus (CMV) infection has long been recognized as an important viral syndrome in the immunocompromised host. The disease is less well described in...
INTRODUCTION
Cytomegalovirus (CMV) infection has long been recognized as an important viral syndrome in the immunocompromised host. The disease is less well described in critically-ill patients. We evaluated the risk factors for the development of CMV infection in patients admitted to the intensive care unit (ICU). We also compared the outcomes of CMV infection in ICU patients to those of patients with hematological malignancies.
METHODOLOGY
This is a retrospective study composed of three arms: patients admitted to the ICU with infection (ICU + / CMV + arm), patients admitted to the ICU who did not develop CMV infection (ICU + / CMV- arm, and patients with hematological malignancies on the hematology ward without CMV infection (ICU - / CMV + arm).
RESULTS
Patients who were admitted to ICU for surgical causes had a decreased risk of CMV infection. On the other hand, receiving corticosteroids and vasoactive drugs was associated with an increased risk of CMV infection with adjusted odds ratios (aOR) of 2.4 and 25.3, respectively. Mortality was higher in ICU + / CMV + patients compared to ICU - / CMV + patients. In the ICU + /CMV + population, male sex and being on mechanical ventilation after CMV infection were independent predictors of mortality (aOR 4.6 and 5.0, respectively).
CONCLUSIONS
CMV infection in ICU patients is a potentially serious disease requiring close attention. The findings from our study help in identifying patients in the ICU at risk for CMV infection, thereby warranting frequent screening. Patients at high risk of death (male, on mechanical ventilation) should receive prompt treatment and intensive follow-up.
Topics: Humans; Cytomegalovirus Infections; Male; Retrospective Studies; Intensive Care Units; Female; Risk Factors; Middle Aged; Aged; Adult; Critical Illness
PubMed: 38728630
DOI: 10.3855/jidc.17853 -
ESC Heart Failure May 2024This study evaluated how well serial pulse pressure (PP) and PP adjusted by the vasoactive inotropic score (VIS) predicted venoarterial extracorporeal membrane...
AIMS
This study evaluated how well serial pulse pressure (PP) and PP adjusted by the vasoactive inotropic score (VIS) predicted venoarterial extracorporeal membrane oxygenation (VA-ECMO) weaning success and clinical outcomes in acute myocardial infarction complicated by cardiogenic shock (AMI-CS) patients.
METHODS AND RESULTS
A total of 213 patients with AMI-CS who received VA-ECMO between January 2010 and August 2021 were enrolled in the institutional ECMO registry. Serial PP and VIS were measured immediately, 12, 24, and 48 h after VA-ECMO insertion. PP adjusted by VIS was defined as PP/√VIS. The primary outcome was successful VA-ECMO weaning. Successful weaning from VA-ECMO was observed in 151 patients (70.9%). Immediately after VA-ECMO insertion, PP [successful vs. failed weaning, 26.0 (15.5-46.0) vs. 21.0 (12.5-33.0), P = 0.386] and PP/√VIS [11.1 (5.1-25.0) vs. 6.0 (3.1-14.2), P = 0.118] did not differ between the successful and failed weaning groups. Serial PP and PP adjusted by VIS at 12, 24, and 48 h after VA-ECMO insertion were significantly higher in patients with successful weaning than those with failed weaning [successful vs. failed weaning, 24.0 (4.0-38.0) vs. 12.5 (6.0-25.5), P = 0.007 for 12 h PP, and 10.1 (5.7-22.0) vs. 2.9 (1.7-5.9), P < 0.001 for 12 h PP/√VIS]. The 12 h PP/√VIS showed better discriminative function for successful weaning than 12 h PP alone [area under the curve (AUC) 0.80, 95% confidence interval (CI) 0.72-0.88, P < 0.001 vs. AUC 0.67, 95% CI 0.57-0.77, P = 0.002]. Patients with a low 12 h PP/√VIS (≤7) had higher rates of in-hospital mortality (44.4% vs. 19.8%, P < 0.001) and 6 month follow-up mortality (hazard ratio 2.41, 95% CI 1.49-3.90, P < 0.001) than those with a high 12 h PP/√VIS (>7).
CONCLUSIONS
PP adjusted by VIS taken 12 h following VA-ECMO initiation can predict weaning from VA-ECMO more successfully than PP alone, and its low value was associated with a higher risk of mortality in AMI-CS patients.
PubMed: 38724009
DOI: 10.1002/ehf2.14836 -
Annals of Cardiac Anaesthesia Jan 2024The aim of this study was to evaluate the prediction of vasoactive inotropic score (VIS) on early mortality and morbidity after coronary artery bypass grafting (CABG)...
INTRODUCTION
The aim of this study was to evaluate the prediction of vasoactive inotropic score (VIS) on early mortality and morbidity after coronary artery bypass grafting (CABG) and to determine the ideal time for score calculation.
MATERIALS AND METHODS
The study included patients who underwent isolated on-pump CABG surgery between November 2021 and November 2022. Pre, intra, and postoperative data were obtained by retrospective chart review. The final VIS value in the operating room (VISintra) and the highest VIS value in the first 24 hours in the intensive care unit (VISmax) were calculated. The patients were divided into two groups; Group 1 who developed early postoperative morbidity and mortality and Group 2 who did not. And the data were analyzed by groups.
RESULTS
A total of 221 patients with a mean age of 63.49 ± 9.96 years were evaluated and 73 (33%) were in Group 1. The cut-off value for VISintra was determined to be 6.20, VISmax was 6,05. VISintra and VISmax values were significantly higher in the poor outcome group. Multivariate analysis showed that only VISmax value was an independent variable on mortality-morbidity.
CONCLUSIONS
Our results imply that the vasoactive inotropic score is an easy and inexpensive score to calculate and can be used as a specific scoring system to predict poor early outcomes in CABG patients. According to statistical analyses, the most predictive time among VIS measurements was VISmax, the highest value calculated in the ICU in the first 24 hours postoperatively.
Topics: Humans; Retrospective Studies; Male; Female; Middle Aged; Postoperative Complications; Aged; Coronary Artery Bypass; Cardiac Surgical Procedures; Time Factors; Predictive Value of Tests; Morbidity
PubMed: 38722119
DOI: 10.4103/aca.aca_127_23 -
Annals of Cardiac Anaesthesia Jan 2024Ventricular septal rupture (VSR) is a rare but grave complication of acute myocardial infarction (AMI). It is a mechanical complication of myocardial infarction where...
BACKGROUND
Ventricular septal rupture (VSR) is a rare but grave complication of acute myocardial infarction (AMI). It is a mechanical complication of myocardial infarction where patients may present either in a compensated state or in cardiogenic shock. The aim of the study is to determine the in-hospital mortality. The study also aims to identify the predictors of outcomes (in-hospital mortality, vasoactive inotrope score (VIS), duration of ICU stay and mechanical ventilation in the postoperative period) and compare the clinical and surgical parameters between survivors and non-survivors.
METHODS
This is a retrospective study. The data of 90 patients was collected from the medical records and the data comprising of 13 patients who underwent VSR closure by single patch technique, or septal occluder, and those who expired before receiving the treatment, was excluded. The data of 77 patients diagnosed with post-AMI VSR and who underwent surgical closure of VSR by double patch technique was included in this study. Clinical findings and echocardiography parameters were recorded from the perioperative period. The statistical software used was SPSS version 27. The primary outcome was determining the in-hospital mortality. The secondary outcome was identifying the clinical parameters that are significantly more in the non-survivors, and the factors predicting the in-hopsital mortality and morbidity (increased duration of ICU stay, and of mechanical ventilation, postoperative requirement of high doses of vasopressors and inotropes). Subgroup analysis was done to identify the relation of various clinical parameters with the postoperative complications. The factors predicting the in-hospital mortality were illustrated by a forest plot.
RESULTS
The mean age of the patients was 60.35 (±9.9) years, 56 (72.7%) were males, and 21 (27.3%) were females. Requirement of mechanical ventilation preoperatively (OR 3.92 [CI 2.91-6.96]), cardiogenic shock at presentation (OR 4 [CI 2.33 - 6.85]), requirement of IABP (OR 2.05 [CI 1.38-3.94]), were predictors of mortality. The apical location of VSR had been favorable for survival. The EUROScore II at presentation correlated with the postoperative VIS (level of significance [LS] 0.0011, R 0.36. The in-hospital mortality in this study was 33.76%.
CONCLUSION
The in-hospital mortality of VSR is 33.76%. Cardiogenic shock at presentation, non-apical site of VSR, preoperative requirement of mechanical ventilation, high VIS preoperatively, perioperative utilization of IABP, prolonged CPB time, postoperative duration of mechanical ventilation, and high postoperative VIS were the factors associated with increased odds of in-hospital mortality.
Topics: Humans; Retrospective Studies; Male; Female; Ventricular Septal Rupture; Myocardial Infarction; Middle Aged; Hospital Mortality; Treatment Outcome; Aged; Length of Stay; Postoperative Complications; Respiration, Artificial
PubMed: 38722116
DOI: 10.4103/aca.aca_75_23 -
Acta Biochimica Polonica 2024Goal-directed fluid therapy, as a crucial component of accelerated rehabilitation after surgery, plays a significant role in expediting postoperative recovery and...
Goal-directed fluid therapy, as a crucial component of accelerated rehabilitation after surgery, plays a significant role in expediting postoperative recovery and enhancing the prognosis of major surgical procedures. In line with this, the present study aimed to investigate the impact of target-oriented fluid therapy on volume management during ERAS protocols specifically for gastrointestinal surgery. Patients undergoing gastrointestinal surgery at our hospital between October 2019 and May 2021 were selected as the sample population for this research. 41 cases of gastrointestinal surgery patients were collected from our hospital over 3 recent years. Compared with T1, MAP levels were significantly increased from T2 to T5; cardiac output (CO) was significantly decreased from T2 to T3, and significantly increased from T4 to T5; and SV level was significantly increased from T3 to T5. Compared with T2, HR and cardiac index (CI) were significantly elevated at T1 and at T3-T5. Compared with T3, SVV was significantly decreased at T1, T2, T4, and T5; CO and stroke volume (SV) levels were increased significantly at T4 and T5. In this study, pressor drugs were taken for 23 days, PACU residence time was 40.22 ± 12.79 min, time to get out of bed was 12.41 ± 3.97 h, exhaust and defecation time was 18.11 ± 7.52 h, and length of postoperative hospital stay was 4.47 ± 1.98 days. The average HAMA score was 9.11 ± 2.37, CRP levels were 10.54 ± 3.38 mg/L, adrenaline levels were 132.87 ± 8.97 ng/L, and cortisol levels were 119.72 ± 4.08 ng/L. Prealbumin levels were 141.98 ± 10.99 mg/L at 3 d after surgery, and 164.17 ± 15.84 mg/L on the day of discharge. Lymphocyte count was 1.22 ± 0.18 (10/L) at 3 d after surgery, and 1.47 ± 0.17 (10/L) on the day of discharge. Serum albumin levels were 30.51 ± 2.28 (g/L) at 3 d after surgery, and 33.52 ± 2.07 (g/L) on the day of discharge. Goal-directed fluid therapy (GDFT) under the concept of Enhanced Recovery After Surgery (ERAS) is helpful in volume management during radical resection of colorectal tumors, with good postoperative recovery. Attention should be paid to the influence of pneumoperitoneum and intraoperative posture on GDFT parameters.
Topics: Humans; Fluid Therapy; Male; Female; Middle Aged; Digestive System Surgical Procedures; Aged; Enhanced Recovery After Surgery; Stroke Volume; Length of Stay; Cardiac Output; Adult
PubMed: 38721303
DOI: 10.3389/abp.2024.12377 -
BMJ Open May 2024SARS-CoV-2 mainly infects respiratory endothelial cells, which is facilitated through its spike protein binding to heparan sulphate. Calcium dobesilate (CaD) is a...
Study protocol for assessment of the efficacy of calcium dobesilate versus placebo on SARS-CoV-2 viral load in outpatients with COVID-19 (CADOVID study): a randomised, placebo-controlled, double-blind, monocentric phase II trial.
INTRODUCTION
SARS-CoV-2 mainly infects respiratory endothelial cells, which is facilitated through its spike protein binding to heparan sulphate. Calcium dobesilate (CaD) is a well-established, widely available vasoactive and angioprotective drug interacting with heparan sulphate, with the potential to interfere with the uptake of SARS-CoV-2 by epithelial cells. The CADOVID trial aims to evaluate the efficacy and safety of CaD in reducing the SARS-CoV-2 viral load in non-hospitalised adult patients diagnosed with COVID-19, confirmed by a positive SARS-CoV-2 PCR, including its efficacy to reduce the impact of persistent COVID-19 symptoms.
METHODS AND ANALYSIS
This is a randomised, placebo-controlled, double-blind, monocentric phase II trial. Enrolment began in July 2022. A total of 74 adult patients will be randomly allocated to the CaD arm or the placebo group with a 1:1 ratio, respectively. Participants in the intervention arm will receive two capsules of CaD 500 mg two times per day and the placebo arm will receive two matching capsules of mannitol 312.5 mg two times per day, with a treatment period of 7 days for both arms, followed by a 77-day observational period without treatment administration. Participants will be asked to complete secured online questionnaires using their personal smartphone or other electronic device. These include a COVID-19 questionnaire (assessing symptoms, temperature measurement, reporting of concomitant medication and adverse events), a COVID-19 persistent symptoms' questionnaire and the Short Form 12-Item (SF-12) survey. SARS-CoV-2 PCR testing will be performed on nasopharyngeal swabs collected on days 1, 4, 8 and 21. The primary endpoint is the reduction from baseline of SARS-CoV-2 viral load determined by RT-PCR at day 4.
ETHICS AND DISSEMINATION
This trial has received approval by the Geneva Regional Research Ethics Committee (2022-00613) and Swissmedic (701339). Dissemination of results will be through presentations at scientific conferences and publication in scientific journals.
TRIAL REGISTRATION NUMBER
NCT05305508; Clinicaltrials.gov; Swiss National Clinical Portal Registry (SNCTP 000004938).
Topics: Adult; Female; Humans; Male; Middle Aged; Calcium Dobesilate; Clinical Trials, Phase II as Topic; COVID-19; COVID-19 Drug Treatment; Double-Blind Method; Outpatients; Randomized Controlled Trials as Topic; SARS-CoV-2; Treatment Outcome; Viral Load
PubMed: 38719313
DOI: 10.1136/bmjopen-2023-079574 -
Journal of Pharmacological and... 2024The principle of proportionality of the systolic area of the central aortic pressure to stroke volume (SV) has been long known. The aim of the present work was to...
The principle of proportionality of the systolic area of the central aortic pressure to stroke volume (SV) has been long known. The aim of the present work was to evaluate an in silico solution derived from this principle for modelling SV (iSV model) in cardiovascular safety pharmacology studies by telemetry. Blood pressure was measured in the abdominal aorta in accordance with standard practice. Central aortic pressure was modelled from the abdominal aortic pressure waveform using the N-point moving average (NPMA) method for beat-to-beat estimation of SV. First, the iSV was compared to the SV measured by ultrasonic flowmetry in the ascending aorta (uSV) after various pharmacological challenges in beagle dogs anaesthetised with etomidate/fentanyl. The iSV showed minimal bias (0.2 mL i.e. 2%) and excellent agreement with uSV. Then, previous telemetry studies including reference vasoactive and inotropic compounds were retrospectively reanalysed to model drug effects on stroke volume (iSV), cardiac output (iCO) and systemic vascular resistance (iSVR). Among them, the examples of nicardipine and isoprenaline highlight risks of erroneous or biased estimation of drug effects from the abdominal aortic pressure due to pulse pressure amplification. Furthermore, the examples of verapamil, quinidine and moxifloxacin show that iSV, iCO and iSVR are earlier biomarkers than blood pressure itself for predicting drug effect on blood pressure. This in silico modelling approach included in vivo telemetry safety pharmacology studies can be considered as a New Approach Methodology (NAM) that provides valuable additional information and contribute to improving non-clinical translational research to the clinic.
Topics: Animals; Dogs; Stroke Volume; Computer Simulation; Vascular Resistance; Telemetry; Cardiac Output; Blood Pressure; Male
PubMed: 38719163
DOI: 10.1016/j.vascn.2024.107512 -
BMC Anesthesiology May 2024Dynamic fluctuations of arterial blood pressure known as blood pressure variability (BPV) may have short and long-term undesirable consequences. During surgical... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Dynamic fluctuations of arterial blood pressure known as blood pressure variability (BPV) may have short and long-term undesirable consequences. During surgical procedures blood pressure is usually measured in equal intervals allowing to assess its intraoperative variability, which significance for peri and post-operative period is still under debate. Lidocaine has positive cardiovascular effects, which may go beyond its antiarrhythmic activity. The aim of the study was to verify whether the use of intravenous lidocaine may affect intraoperative BPV in patients undergoing major vascular procedures.
METHODS
We performed a post-hoc analysis of the data collected during the previous randomized clinical trial by Gajniak et al. In the original study patients undergoing elective abdominal aorta and/or iliac arteries open surgery were randomized into two groups to receive intravenous infusion of 1% lidocaine or placebo at the same infusion rate based on ideal body weight, in concomitance with general anesthesia. We analyzed systolic (SBP), diastolic (DBP) and mean arterial blood (MAP) pressure recorded in 5-minute intervals (from the first measurement before induction of general anaesthesia until the last after emergence from anaesthesia). Blood pressure variability was then calculated for SBP and MAP, and expressed as: standard deviation (SD), coefficient of variation (CV), average real variability (ARV) and coefficient of hemodynamic stability (C10%), and compared between both groups.
RESULTS
All calculated indexes were comparable between groups. In the lidocaine and placebo groups systolic blood pressure SD, CV, AVR and C10% were 20.17 vs. 19.28, 16.40 vs. 15.64, 14.74 vs. 14.08 and 0.45 vs. 0.45 respectively. No differences were observed regarding type of surgery, operating and anaesthetic time, administration of vasoactive agents and intravenous fluids, including blood products.
CONCLUSION
In high-risk vascular surgery performed under general anesthesia, lidocaine infusion had no effect on arterial blood pressure variability.
TRIAL REGISTRATION
ClinicalTrials.gov; NCT04691726 post-hoc analysis; date of registration 31/12/2020.
Topics: Humans; Lidocaine; Male; Female; Blood Pressure; Aged; Anesthetics, Local; Vascular Surgical Procedures; Middle Aged; Double-Blind Method; Infusions, Intravenous; Anesthesia, General; Monitoring, Intraoperative
PubMed: 38714924
DOI: 10.1186/s12871-024-02550-5