Delay In Recovery Research Articles

Early Triassic (Griesbachian) Deposits of High-Energy Events at the Northwestern Upper Yangtze Region, China

Following the latest Permian mass extinction (LPME), the ocean experienced turbulent conditions due to elevated temperatures during the Griesbachian (Early Triassic). These adverse conditions resulted in a prolonged delay in biotic recovery. However, the current understanding of the sedimentological responses of the ocean at that time to these adverse conditions remains incomplete. The Griesbachian harsh ocean conditions led to the formation of abnormal carbonate rocks (known as anachronistic facies) all around the world. These facies were influenced by a combination of environmental conditions, biotic factors, and actualistic sedimentological processes (e.g., waves and currents, sedimentation). However, the role of actualistic sedimentological processes in forming anachronistic facies during the Griesbachian has been underemphasized in the existing studies. In this research, we examine calcirudite beds, such as flat-pebble conglomerates, from Member 1 of the Feixianguan Formation across multiple sections, including Shangsi, Yudongzi, Dagouli, and Jianfeng in the Upper Yangtze Region. Our analysis is grounded in field investigations, thin-section observations, and the study of triggering mechanisms and formation processes. We identified and described five calcirudite beds (S1–S5) in the Shangsi section, two beds (D1–D2) in the Dagouli section, one at Jianfeng (J1), and one (Y1) in the Yudongzi section. Bed S1 features matrix-supported flat pebbles with a normal grading, interpreted as the result of a debris flow mass-transport process. Beds S2, S3, D1, and J1 contain large mud rip-up clasts, ooids, and bioclasts, suggesting a potential link with tsunami backwash. Beds S4, D2, and Y1 display hummocky cross-stratification and ‘chrysanthemum-shaped’ flat pebbles, indicating storm influence. The presence of vermicular limestones in Bed S5 suggests harsh marine environmental conditions. Collectively, this evidence suggests that high-energy oceanic conditions, including tsunamis and frequent storms, potentially influenced Early Triassic biotic recovery.

Extreme events delay the detection of marine protected area effects: Implications for monitoring and management

The establishment of protected natural areas worldwide has surged in the last decade, with more protected area coverage expected in the future. In the case of marine protected areas (MPAs) that prohibit fishing, there are ongoing efforts to evaluate their effectiveness in conserving fish populations. Accurate assessments of MPA effects (namely, their ability to increase fish biomass within their boundaries) are crucial to support these evaluations. However, marine ecosystems are increasingly affected by extreme events including marine heatwaves, hypoxia, storms, and epizootic outbreaks. These events can disrupt population increases within MPAs, leading to delays in expected conservation outcomes and the misperception that protection may not be effective. However, it is currently unclear to what extent disturbances could bias MPA assessments and for how long. To address this gap, we used a population model based on a common nearshore fishery species from the USA west coast (blue rockfish, Sebastes mystinus) to evaluate the detectability of MPA effects when an acute disturbance occurs within the first decade of protection. We found that detecting MPA effects with high confidence can be delayed up to 10 years following an extreme disturbance. Furthermore, the before-after sampling design (as opposed to an inside-outside or before-after-control-impact, or BACI design) is most biased by a widespread disturbance event, especially with long (>5 years) and severe disturbances (>30 % population reduction). These findings indicate that extreme events can profoundly impact MPA assessments, causing delays in recovery and detectability. Our results provide a benchmark to calibrate monitoring and management evaluations accordingly.

280. FEASIBILITY OF ROBOTIC-ASSISTED SURGERY FOR BENIGN ESOPHAGEAL LESIONS: SINGLE-CENTER EXPERIENCE

Abstract Background Benign esophageal lesions are uncommon conditions compared to malignant cases. Thoracotomy is an extremely invasive procedure that can cause severe complications and delay recovery. Conventional VATS is limited in its approach to deep and narrow angles and difficult to manipulate due to abundance of vital structures that are always mobile in mediastinal area. Robotic-assisted surgery is a new challenge that aims to achieve minimally invasive procedures and improve postoperative outcomes for benign esophageal lesions. Methods We conducted a retrospective analysis of a single-center database from May 2012 to November 2022, including patients aged 20–75 years with diagnosed benign esophageal lesions such as esophageal leiomyoma and esophageal diverticulum who underwent robotic-assisted esophageal surgery using the Da Vinci Robotic surgery system. The operation was performed using either a transthoracic or transabdominal approach. Patient data, surgical procedures, interventions, and early outcomes (within 30 days post-operation) were collected and analyzed to assess postoperative variables. The study included 13 patients, and the primary outcome was the incidence of pulmonary complications during the hospital stay. Results The number of patients with each esophageal lesion was as follows: esophageal leiomyoma, 6 cases (46.1%); esophageal diverticulum, 3 cases (23.1%); and other benign lesions, 4 cases (30.8%). Robotics approaches were divided into 11 cases (84.6%) and 2 cases (15.4%) for transthoracic and transabdominal, respectively. The overall incidence of postoperative pulmonary complications was 5 cases (38.5%), with mild pulmonary infection occurred in 2 cases (15.4%). Other pulmonary complications occurred in the transthoracic approach due to patient characteristics related to underlying lung diseases, such as COPD and asthma. There was no evidence of 30 days mortality in our series. Conclusion Robotic-assisted surgery is feasible for benign esophageal surgery using both transthoracic and transabdominal approaches. Robotic devices can provide stabilization for both 3D camera views and instrument arms, particularly enhancing suturing ability. Robotic surgery is precise and maneuverable, with potential to perform intricate surgical procedures in tight angles and confined spaces such as the thoracic cavity and hiatal area. These factors can improve the overall operative outcome and enhance recovery due to minimally invasive access.

Outcomes Associated with Sodium-Glucose Cotransporter-2 Inhibitor Use in Acute Heart Failure Hospitalizations Complicated by AKI.

While sodium-glucose cotransporter-2 inhibitor (SGLT2i) use during acute heart failure (AHF) hospitalizations is associated with symptomatic improvement, reduction in re-hospitalizations, and mortality, these medications are often withheld during acute kidney injury (AKI) due to concerns about worsening glomerular filtration rate.We aimed to investigate the safety of SGLT2i exposure during AKI among patients hospitalized with AHF. We hypothesized that SGLT2i exposure would not worsen mortality but may prolong return of creatinine to baseline. This is a retrospective study of adults hospitalized across 5 Yale New Haven Health System hospitals between January 2020 and May 2022 with AHF complicated by KDIGO-defined AKI. Patients with stage 5 chronic kidney disease and those with potential contraindications to SGLT2i were excluded. We tested the association of SGLT2i use with kidney function recovery at 14 days and death at 30 days using time-varying, multivariable Cox-regression analyses. Of 3305 individuals hospitalized with AHF and AKI, 356 received SGLT2i following AKI diagnosis either as initiation or continuation. The rate of renal recovery was not significantly different among those exposed and unexposed to SGLT2i following AKI (adjusted HR 0.94, 95% CI 0.79-1.11, p=0.46). SGLT2i exposure was associated with lower risk of 30-day mortality (adjusted HR 0.45, 95% CI 0.23-0.87, p=0.02). Sensitivity analyses using an inverse probability weighted time-varying Cox regression analysis and using alternate definitions of AHF with different NT-proBNP cutoffs yielded similar results. Rates of renal recovery were similar between the exposed and unexposed cohorts regardless of the proximity of SGLT2i exposure to AKI diagnosis. In adults experiencing AHF-associated AKI, exposure to SGLT2i was associated with decreased mortality and no delay in renal recovery. Prospective studies are needed to elucidate the impact of SGLT2i exposure during AKI, particularly during heart failure hospitalizations.

Capillary Dynamics Regulate Post-Ischemic Muscle Damage and Regeneration in Experimental Hindlimb Ischemia.

This study aimed to show the significance of capillary function in post-ischemic recovery from the perspective of physiological parameters, such as blood flow, hemoglobin oxygenation and tissue regeneration. Muscle-level microvascular alterations of blood flow and hemoglobin oxygenation, and post-ischemic myofiber and capillary responses were analyzed in aged, healthy C57Bl/6J mice (n = 48) and aged, hyperlipidemic LDLR-/-ApoB100/100 mice (n = 69) after the induction of acute hindlimb ischemia using contrast ultrasound, photoacoustic imaging and histological analyses, respectively. The capillary responses that led to successful post-ischemic muscle repair in C57Bl/6J mice included an early capillary dilation phase, preceding the return of arterial driving pressure, followed by an increase in capillary density that further supported satellite cell-induced muscle regeneration. Initial capillary enlargement was absent in the LDLR-/-ApoB100/100 mice with lifelong moderate hypercholesterolemia and led to an inability to recover arterial driving pressure, with a resulting increase in distal necrosis, chronic tissue damage and a delay in the overall recovery after ischemia. To conclude, this manuscript highlights, beyond arterial collateralization, the importance of the proper function of the capillary endothelium in post-ischemic recovery and displays how post-ischemic capillary dynamics associate beyond tissue blood flow to both hemoglobin oxygenation and tissue regeneration.

Assisted ambulation to improve health outcomes for older medical inpatients (AMBULATE): study protocol for a randomized controlled trial

BackgroundHospitalized older adults spend as much as 95% of their time in bed, which can result in adverse events and delay recovery while increasing costs. Observational studies have shown that general mobility interventions (e.g., ambulation) can mitigate adverse events and improve patients’ functional status. Mobility technicians (MTs) may address the need for patients to engage in mobility interventions without overburdening nurses. There is no data, however, on the effect of MT-assisted ambulation on adverse events or functional status, or on the cost tradeoffs if a MT were employed. The AMBULATE study aims to determine whether MT-assisted ambulation improves mobility status and decreases adverse events for older medical inpatients. It will also include analyses to identify the patients that benefit most from MT-assisted mobility and assess the cost-effectiveness of employing a MT.MethodsThe AMBULATE study is a multicenter, single-blind, parallel control design, individual-level randomized trial. It will include patients admitted to a medical service in five hospitals in two regions of the USA. Patients over age 65 with mild functional deficits will be randomized using a block randomization scheme. Those in the intervention group will ambulate with the MT up to three times daily, guided by the Johns Hopkins Mobility Goal Calculator. The intervention will conclude at hospital discharge, or after 10 days if the hospitalization is prolonged. The primary outcome is the Short Physical Performance Battery score at discharge. Secondary outcomes are discharge disposition, length of stay, hospital-acquired complications (falls, venous thromboembolism, pressure ulcers, and hospital-acquired pneumonia), and post-hospital functional status.DiscussionWhile functional decline in the hospital is multifactorial, ambulation is a modifiable factor for many patients. The AMBULATE study will be the largest randomized controlled trial to test the clinical effects of dedicating a single care team member to facilitating mobility for older hospitalized patients. It will also provide a useful estimation of cost implications to help hospital administrators assess the feasibility and utility of employing MTs.Trial registrationRegistered in the United States National Library of Medicine clinicaltrials.gov (# NCT05725928). February 13, 2023.

The opioid tramadol blocks the cardiac sodium channel Nav1.5 in HEK293 cells.

Opioids are associated with increased risk of sudden cardiac death. This may be due to their effects on the cardiac sodium channel (Nav1.5) current. In the present study, we aim to establish whether tramadol, fentanyl, or codeine affects Nav1.5 current. Using whole-cell patch-clamp methodology, we studied the effects of tramadol, fentanyl, and codeine on currents of human Nav1.5 channels stably expressed in HEK293 cells and on action potential (AP) properties of freshly isolated rabbit ventricular cardiomyocytes. In fully available Nav1.5 channels (holding potential -120 mV), tramadol exhibited inhibitory effects on Nav1.5 current in a concentration-dependent manner with an IC50 of 378.5 ± 33.2 µm. In addition, tramadol caused a hyperpolarizing shift of voltage-gated (in)activation and a delay in recovery from inactivation. These blocking effects occurred at lower concentrations in partially inactivated Nav1.5 channels: during partial fast inactivation (close-to-physiological holding potential -90 mV), IC50 of Nav1.5 block was 4.5 ± 1.1 μm, while it was 16 ± 4.8 μm during partial slow inactivation. The tramadol-induced changes on Nav1.5 properties were reflected by a reduction in AP upstroke velocity in a frequency-dependent manner. Fentanyl and codeine had no effect on Nav1.5 current, even when tested at lethal concentrations. Tramadol reduces Nav1.5 currents, in particular, at close-to-physiological membrane potentials. Fentanyl and codeine have no effects on Nav1.5 current.

Peak Oxygen Consumption (V̇O 2peak ) Recovery Delay in a Pediatric Fontan Population.

The purpose of this study is to identify predictors and correlates of VO2RD in youth with Fontan. Cardiopulmonary exercise test data was used from a single center, cross-sectional study of children and adolescents (age, 8-21 yr) with Fontan physiology. The VO2RD was determined using time (s) to <90% of V̇O 2peak and categorized as "low" (≤10 s) or "high" (≥10 s). t Tests and χ 2 analysis were used to compare continuous and categorical variables, respectively. The analysis sample included 30 adolescents with Fontan physiology (age, 14.2 ± 2.4 yr; 67% male) with either right ventricular (RV) dominant (40%) or co/left ventricular (Co/LV) dominant (60%) systemic ventricular morphology. There were no differences in V̇O 2peak between the high and low VO2RD groups (high = 1.3 ± 0.4 L·min -1 ; low = 1.3 ± 0.3 L·min -1 ; P = 0.97). VO2RD in participants with RV dominance was significantly greater than in patients with Co/LV dominance (RV = 23.8 ± 15.8 s; Co/LV = 11.8 ± 16.1 s; P = 0.03). V̇O 2peak was not correlated with VO2RD when analyzed as high/low VO2RD groups. However, morphology of the systemic single ventricle (RV vs Co/LV) may be related to rate of recovery in V̇O 2 after a peak cardiopulmonary exercise test.

Drying intensity and acidity slow down microbial growth recovery after rewetting dry soils

Soil microbes perceive drying and rewetting (DRW) events as more or less harsh depending on the previous soil moisture history. If a DRW event is not perceived as harsh, microbial growth recovers rapidly after rewetting (referred to as ‘type 1’ response), while a harsh DRW will be followed by a delayed growth recovery (‘type 2’ response). Predicting these responses based on pedoclimatic factors is important because they can determine how carbon is partitioned between growth (soil C stabilization) and respiration (C loss to the atmosphere). To characterize the microbially perceived harshness between the two extreme types 1 and 2, and its pedoclimatic drivers, we described microbial growth with a single logistic function and respiration with a rescaled gamma distribution using ∼100 growth and respiration datasets. These functions captured microbial growth and respiration rates well during the recovery phase after rewetting. Therefore, the fitted parameters from these functions could help us to capture the continuum of microbial recovery between type 1 and 2 and characterize harshness levels. The product of growth parameters τ (delay time) and b (the slope of the growth curve at time τ) was an effective index that could capture and quantify perceived harshness because it allowed separating type 1 and 2 responses better than τ or b alone or than any other parameter describing the growth or respiration response. The drier the soil before rewetting and the lower the pH, the higher was the perceived harshness (τ×b), the longer the delay of growth recovery, and the larger the CO2 loss at rewetting. Overall, this study places soil microbial responses to DRW along a continuous gradient from fast to slow recovery, where the faster the recovery, the better adapted the microbial community is to the DRW event.

Adverse impact of delay of platelet recovery after autologous hematopoietic cell transplantation for aggressive non-Hodgkin lymphoma and multiple myeloma

Background aimsThe prognostic impact of platelet recovery after autologous hematopoietic cell transplantation (AHCT) on clinical outcomes remains to be elucidated. We aimed to clarify the impact of platelet recovery on clinical outcomes, risk factors of delayed platelet recovery and the necessary dose of CD34+ cells for prompt platelet recovery in each patient. MethodsUsing a nationwide Japanese registry database, we retrospectively analyzed clinical outcomes of 5222 patients with aggressive non-Hodgkin lymphoma (NHL) or multiple myeloma (MM). ResultsAt a landmark of 28 days after AHCT, a delay of platelet recovery was observed in 1102 patients (21.1%). Prompt platelet recovery was significantly associated with superior overall survival (hazard ratio [HR] 0.32, P < 0.001), progression-free survival (HR 0.48, P < 0.001) and decreased risks of disease progression (HR 0.66, P < 0.001) and non-relapse/non-progression mortality (HR 0.19, P < 0.001). The adverse impacts of a delay of platelet recovery seemed to be more apparent in NHL. In addition to the dose of CD34+ cells/kg, disease status, performance status and the hematopoietic cell transplant-specific comorbidity index in both diseases were associated with platelet recovery. We then stratified the patients into three risk groups according to these factors. For the purpose of achieving 70% platelet recovery by 28 days in NHL, the low-, intermediate- and high-risk groups needed more than 2.0, 3.0 and 4.0 × 106 CD34+ cells/kg, respectively. In MM, the low-risk group needed approximately 1.5 × 106 CD34+ cells/kg, whereas the intermediate- and high-risk groups required 2.0 and 2.5 × 106 CD34+ cells/kg to achieve about 80% platelet recovery by 28 days. ConclusionsA delay of platelet recovery after AHCT was associated with inferior survival outcomes.

Decellularized Graft for Repairing Severe Peripheral Nerve Injuries in Sheep.

Peripheral nerve injuries resulting in a nerve defect require surgical repair. The gold standard of autograft (AG) has several limitations, and therefore, new alternatives must be developed. The main objective of this study was to assess nerve regeneration through a long gap nerve injury (50 mm) in the peroneal nerve of sheep with a decellularized nerve allograft (DCA). A 5-cm long nerve gap was made in the peroneal nerve of sheep and repaired using an AG or using a DCA. Functional tests were performed once a month and electrophysiology and echography evaluations at 6.5 and 9 months postsurgery. Nerve grafts were harvested at 9 months for immunohistochemical and morphological analyses. The decellularization protocol completely eliminated the cells while preserving the extracellular matrix of the nerve. No significant differences were observed in functional tests of locomotion and pain response. Reinnervation of the tibialis anterior muscles occurred in all animals, with some delay in the DCA group compared with the AG group. Histology showed a preserved fascicular structure in both AG and DCA; however, the number of axons distal to the nerve graft was higher in AG than in DCA. The decellularized graft assayed supported effective axonal regeneration when used to repair a 5-cm long gap in the sheep. As expected, a delay in functional recovery was observed compared with the AG because of the lack of Schwann cells.

Therapy of acute respiratory viral infections in adults in outpatient clinical practice: new opportunities for the prevention of bacterial complications (Results of the observational program RAPORT)

The frequency of routine prescription of systemic antibacterial drugs in outpatient practice is still unreasonably high despite the desire to reduce them. Under the auspices of the Alliance of Clinical Chemotherapists and Microbiologists, the observational program RAPORT was conducted to assess the therapeutic potential (including bacterial complications preventing) of Raphamin in routine clinical practice in adults with acute respiratory viral infection (ARVI). The program included 14,033 patients aged 1897 years with ARVI who received an investigational drug (ID) as monotherapy (93%) or in combination with basic therapy (7%). The frequency of prophylactic prescribing antibacterial drugs was 0.6%. It was shown that fever duration was 2.311.38 days, and the duration of the disease 3.61.52 days. In 99.4% of patients, ID allowed to avoid the development of bacterial complications and prescription of antibacterial drugs. ID showed a stable therapeutic effect in patients who started treatment late, as well as in patients with a moderate course of ARVI, there was no delay in recovery. The results obtained a broad prospect for the use of ID in order to minimize the number of bacterial complications and the frequency of use of antibiotics in ARVI, which may reduce rate of resistance of topical pathogens in the future.

Survivability Mapping Strategy for Virtual Wireless Sensor Networks for Link Failures in the Internet of Things

In the case of virtual wireless sensor networks, a link-failure-oriented survivable virtual sensor network mapping algorithm (F-SVNE) is proposed to address the issue of link failure in the underlying wireless sensor network. First, the algorithm utilizes the fast routing strategy and creates a backup route set based on a multi-path selection algorithm to reduce the delay in fault recovery caused by path selection. Second, the survivable virtual sensor network mapping algorithm is adopted based on the routing set. Finally, in the mapping stage, the efficiency and reliability of the algorithm are comprehensively considered, and the path with the largest survival probability is selected from the backup route set of the faulty link to remap the virtual link affected by the link failure. Empirical results demonstrate that the F-SVNE algorithm can efficaciously lessen the failure recovery delay, and improve the long-term average revenue–cost ratio and average failure recovery rate.

Anti-vascular endothelial growth factors in combination with vitrectomy for complications of proliferative diabetic retinopathy.

Anti-vascular endothelial growth factors in combination with vitrectomy for complications of proliferative diabetic retinopathy.

What is needed to make a simple density-dependent response population model consistent with data for eastern North Pacific gray whales?

Census estimates indicate that the eastern North Pacific gray whale population showed an increase rate of some 3.2% per annum from 1968-1988. Further, historic records suggest that the population was ‘commercially extinct’ at the end of the 19th century. The standard HITTER-FITTER population model trajectories which pass through the 1987-88 census estimate of some 21,113, and utilise the customary historic commercial catch series, are inconsistent with both of these features; in particular, they generally show a decrease over the 1968-1988 period. The quantitative extent of various possible adjustment factors that would be needed to resolve these inconsistencies is examined. Depensation effects alone cannot account for the inconsistencies, while a model used to incorporate an additional response delay in recovery from exploitation produces unrealistic population oscillations. Other adjustment factors can, however, produce a 1968-1988 annual population increase rate of 2% or more, and all also correspond to a depletion of the population in 1900 to less than 25% of its size at the onset of commercial whaling in 1846. These are: an increase in the carrying capacity from 1846-1988 of at least 2.5 times; an underestimation of the historic commercial catch from 1846-1900 of at least 60%; or annual aboriginal catch levels prior to the commercial fishery at least three times those estimated by the 1990 Special Meeting of the Scientific Committee (IWC, 1993). These limits weaken if the adjustment factors are considered in combination rather than separately. The results appear insensitive to values assumed for the biological parameters of the population model (natural mortality, age at first parturition, age at recruitment and MSY level). However, they are sensitive to assumptions concerning data inputs, viz the accuracy of the 1987-88 census estimate used, and a 2:1 female:male ratio assumed for the commercial catches for which this information is not available. All trajectories which reflect a 1968-88 annual increase rate of 2% or more correspond to MSYR values (in terms of a 5+ exploitable population) of at least 4%. Fits of the population model to the series of gray whale census estimates are mis-specified, unless either or both of the historic commercial and aboriginal catches have been substantially underestimated (or carrying capacity has increased). The precision of these fits, conditional on fixed levels for such underestimation, is quite high, with coefficients of variation of about 10% for historic population sizes and about 20% for MSYR. There are indications that even if allowance was made for the uncertainty about these levels of underestimation, MSYR would remain relatively robustly estimated to be some 5% (or about 4% if expressed in terms of uniform selectivity on the 1+ population).

The effectiveness of non-pharmacological sleep interventions for improving inpatient sleep in hospital: A systematic review and meta-analysis

BackgroundSleep disturbance is common in hospital. The hospital environment can have a negative impact on sleep quality, through factors such as noise, light, temperature, and nursing care disruptions. Poor sleep can lead to delays in recovery, wound healing, and increase risk of post-operative infection. MethodsWe conducted a systematic review evaluating the effectiveness of non-pharmacological sleep interventions for improving inpatient sleep. The primary outcome was sleep quality, the secondary outcome was length of hospital stay, the harm outcome was adverse events. MEDLINE, Embase, CINAHL, PsycINFO and the Cochrane Library were searched from inception to 17th February 2022. Meta-analysis was conducted using a fixed effects model, with narrative synthesis for studies with no useable data. Risk of bias was assessed with the Cochrane tool. Results76 studies identified with 5375 people randomised comparing 85 interventions. Interventions focused on physical sleep aids (n = 26), relaxation (n = 25), manual therapy (n = 12), music (n = 9), psychological therapy (n = 5), light therapy (n = 3), sleep protocols (n = 2), milk and honey (n = 1), exercise (n = 1), and nursing care (n = 1). In meta-analysis, medium to large improvements in sleep quality were noted for sleep aids, relaxation, music, and manual therapies. Results were generally consistent in studies at lower risk of bias. Length of hospital stay and adverse events were reported for some studies, with benefit in some trials but this was not consistent across all interventions. ConclusionsPhysical sleep aids, relaxation, manual therapy and music interventions have a strong evidence base for improving inpatient sleep quality. Research is needed to evaluate how to optimise interventions into routine care.

288 Propranolol Use in Adult Burn Patients: Results from a Multi-center Safety and Efficacy Trial

Abstract Introduction The hypermetabolic response induced by a large burn is associated with increased cardiac work, total body wasting, and impaired physical function, leading to delays in psychosocial recovery and reintegration into society, and persistence of chronic conditions. Modulation of this response could reduce long-term burn morbidity. Catecholamines drive burn-induced hypermetabolism, therefore clinicians have employed the non-selective beta-adrenergic receptor blocker propranolol to reduce cardiac stress and the hypermetabolic response. Here, in a masked, placebo-controlled study, we investigated the safety and efficacy of the administration of propranolol to adult burn patients during the acute hospitalization period. Methods Adults with large burns (n=157, mean 38 ± 15% TBSA) were enrolled at 13 participating centers. Subjects were randomized to receive placebo (n=75) or propranolol (n=82) with data collected for 72 and 79 subjects, respectively. Propranolol administration was initiated with an oral dose of 0.2 mg/kg dose and adjusted to decrease mean heart rate by 20%. The primary endpoint was effect on cardiac rate pressure product (CRPP), while the secondary endpoints included infections and survival. Adverse events were also tracked. Assessments were conducted between the time of consent and discharge, with a long-term follow-up visit occurring approximately 5 months post-burn on average. Results CRPP was significantly reduced with propranolol during the acute hospitalization period (p&amp;lt; 0.0001, Fig 1). The initial dose of propranolol adequately reduced heart rate in most patients. Infections were not different between cohorts. Cardiac complications (atrial arrhythmias, ventricular arrhythmias, cardiac arrest) occurred at similar rates for each group, as did additional complications (abdominal compartment syndrome, deep vein thromboses, pneumothorax, pulmonary embolus). Mortality was similar for both the placebo and propranolol cohorts. Post-discharge heart rates and blood pressures were similar in both groups at approximately 5 months following injury. Conclusions This study demonstrates that the short-term administration of propranolol to adults with large burns decreases CRPP without increasing complications, infections, or mortality. Furthermore, a safe dosing strategy was identified. This strategy may be effective for reducing acute cardiac stress and hypermetabolism. Future studies should focus on the effects of propranolol administration for longer periods, determining the effects on additional endpoints like the hypermetabolic response, pathologic scarring, long-term cardiac dysfunction, whether smaller burns benefit from the administration of propranolol.

Did the unemployment benefits extension between 2009–2013 deter entrepreneurship in the US? Some evidence and a model of unemployment benefits and entrepreneurship

The 2007–2008 financial crisis severely dampened the American entrepreneurial sector, and the rate of business formation remained low until 2014. This study empirically assesses whether the extensions of unemployment benefits (EUB) contributed to the delay in recovery in entrepreneurship. We then introduce a general equilibrium occupational choice model of unemployment benefits and entrepreneurship and use sharp discontinuity and variations across states in the maximum duration of benefits at the end of 2013 to identify the negative impact of EUB on startups. Eliminating the EUB increased entrepreneurship by 1.4–1.78 percentage points in 2014. Regarding the model, moderate increases in unemployment benefits primarily affect entrepreneurship through the extensive margin by deterring low-ability and necessity entrepreneurs while having little impact on decisions for high-ability agents; however, overly generous unemployment benefits can negatively impact entrepreneurship, the labor market and the overall economy.

Cryopreservation of Allogeneic Hematopoietic Cell Products During COVID-19 Pandemic: Graft Characterization and Engraftment Outcomes

The COVID-19 pandemic triggered the deployment of unfamiliar measures to safeguard successful allogeneic hematopoietic cell transplantation (allo-HCT). Among these measures, cryopreservation offered logistical benefits that could outlast the pandemic, including graft availability and timely clinical service. The purpose of this study was to evaluate graft quality and hematopoietic reconstitution in patients transplanted with cryopreserved allogeneic stem cell products during the COVID-19 pandemic. We evaluated 44 patients who underwent allo-HCT using cryopreserved grafts consisting of hematopoietic progenitor cells (HPC) apheresis (A) and bone marrow (BM) products at Mount Sinai Hospital. Comparative analyses of 37 grafts infused fresh during the one-year period preceding the pandemic were performed. Assessment of cellular therapy products included total nucleated cell and CD34+ cell enumeration, viability, and post-thaw recovery. The primary clinical endpoint was the evaluation of engraftment (absolute neutrophil count [ANC] and platelet count) and donor chimerism (presence of CD33+ and CD3+ donor cells) at day +30 and +100 post-transplant. Adverse events related to cell infusion were also analyzed. Patient characteristics were comparable between the fresh and cryopreserved groups with 2 exceptions in the HPC-A cohort: the number of patients in the cryopreserved group that received haploidentical grafts was 6 times that in the fresh group, and the number of patients in the fresh group with a Karnofsky performance score >90 was double that in the cryopreserved group. The quality of HPC-A and HPC-BM products was not affected by cryopreservation, and all grafts met the release criteria for infusion. The pandemic did not affect the time between collection and cryopreservation (median, 24 hours) and time in storage (median, 15 days). Median time to ANC recovery was significantly delayed in recipients of cryopreserved HPC-A (15 vs 11 days, P=.0121), and there was a trend toward delayed platelet engraftment (24 vs 19 days, P=.0712). The delay in ANC and platelet recovery was not observed when only matched graft recipients were compared. Cryopreservation did not affect the ability of HPC-BM grafts to engraft and reconstitute hematopoiesis, and there was no difference in the rates of ANC and platelet recovery. Achievement of donor CD3/CD33 chimerism was not affected by cryopreservation of either HPC-A or HPC-BM products. Graft failure was observed in only 1 case, a recipient of cryopreserved HPC-BM. Three recipients of cryopreserved HPC-A grafts died before ANC engraftment from infectious complications. Remarkably, 22% of our studied population had myelofibrosis, and almost half received cryopreserved HPC-A grafts with no graft failure observed. Finally, patients receiving cryopreserved grafts were at a higher risk of infusion-related adverse events than those receiving fresh grafts. Cryopreservation of allogeneic grafts results in adequate product quality with minimal impact on short-term clinical outcomes, except for an increased risk of infusion-related adverse events. Cryopreservation is a safe option in terms of graft quality and hematopoietic reconstitution with logistical benefits, but additional data are needed to determine long-term outcomes and assess whether this is a suitable strategy for at-risk patients.

A non-canonical role of ATG8 in Golgi recovery from heat stress in plants.

Above-optimal growth temperatures, usually referred to as heat stress (HS), pose a challenge to organisms' survival as they interfere with essential physiological functions and disrupt cellular organization. Previous studies have elucidated the complex transcriptional regulatory networks involved in plant HS responses, but the mechanisms of organellar remodelling and homeostasis during plant HS adaptations remain elusive. Here we report a non-canonical function of ATG8 in regulating the restoration of plant Golgi damaged by HS. Short-term acute HS causes vacuolation of the Golgi apparatus and translocation of ATG8 to the dilated Golgi membrane. The inactivation of the ATG conjugation system, but not of the upstream autophagic initiators, abolishes the targeting of ATG8 to the swollen Golgi, causing a delay in Golgi recovery after HS. Using TurboID-based proximity labelling, we identified CLATHRIN LIGHT CHAIN 2 (CLC2) as an interacting partner of ATG8 via the AIM-LDS interface. CLC2 is recruited to the cisternal membrane by ATG8 to facilitate Golgi reassembly. Collectively, our study reveals a hitherto unanticipated process of Golgi stack recovery from HS in plant cells and uncovers a previously unknown mechanism of organelle resilience involving ATG8.