C-Type LECTIN receptor-like kinase 1 and ACTIN DEPOLYMERIZING FACTOR 3 are key components of plasmodesmata callose modulation.

Plasmodesmata (PDs) are intercellular organelles carrying multiple membranous nanochannels that allow the trafficking of cellular signalling molecules. The channel regulation of PDs occurs dynamically and is required in various developmental and physiological processes. It is well known that callose is a critical component in regulating PD permeability or symplasmic connectivity, but the understanding of the signalling pathways and mechanisms of its regulation is limited. Here, we used the reverse genetic approach to investigate the role of C-type lectin receptor-like kinase 1 (CLRLK1) in the aspect of PD callose-modulated symplasmic continuity. Here, we found that loss-of-function mutations in CLRLK1 resulted in excessive PD callose deposits and reduced symplasmic continuity, resulting in an accelerated gravitropic response. The protein interactome study also found that CLRLK1 interacted with actin depolymerizing factor 3 (ADF3) in vitro and in plants. Moreover, mutations in ADF3 result in elevated PD callose deposits and faster gravitropic response. Our results indicate that CLRLK1 and ADF3 negatively regulate PD callose accumulation, contributing to fine-tuning symplasmic opening apertures. Overall, our studies identified two key components involved in the deposits of PD callose and provided new insights into how symplasmic connectivity is maintained by the control of PD callose homoeostasis.

Assisted reproductive techniques and subsequent risk of asthma and allergic rhinitis in offspring: a nationwide birth cohort study in South Korea.

OBJECTIVE: The relationship between assisted reproductive techniques (ART) and the risk of asthma and allergic rhinitis (AR) is controversial. Thus, we aimed to investigate the relationship between ART and the risk of asthma and AR in a nationwide, large-scale birth cohort. PATIENTS AND METHODS: This study utilized the National Health Insurance Service data in South Korea to conduct a nationwide, large-scale, population-based birth cohort. We included all infants born between 2017 and 2018. AR, asthma, food allergies, and atopic dermatitis were defined using the International Classification of Diseases tenth edition codes. Asthma was classified as allergic or non-allergic based on accompanying allergic diseases (AR, food allergy, or atopic dermatitis). Using 1:10 propensity score matching, we compared infants conceived through ART with those conceived naturally (non-ART). After matching, logistic regression was used to compare the hazard ratio for asthma and AR between the two groups. RESULTS: We included 543,178 infants [male infants, 280,194 (51.38%)]. After matching, 8,925 and 74,229 infants were selected for the ART and non-ART groups, respectively. The ART group showed a decreased risk of asthma in the offspring [adjusted hazard ratio (aHR), 0.45; 95% confidence interval (CI), 0.41-0.48]. Similarly, for AR, being conceived by ART was associated with a decreased risk of AR (aHR, 0.25; 95% CI, 0.12-0.37). ART offspring showed a decreased risk of asthma and AR in offspring compared to that observed in non-ART offspring. CONCLUSIONS: Our study offers important insights for clinicians, researchers, and parents regarding the health outcomes of ART-conceived infants and enhances our understanding of ART's impact on respiratory health.

Punctuated growth of InAs quantum dashes-in-a-well for enhanced 2-µm emission.

InAs quantum dashes (Qdash) engineered to emit near 2 µm are envisioned to be promising quantum emitters for next-generation technologies in sensing and communications. In this study, we explore the effect of punctuated growth (PG) on the structure and optical properties of InP-based InAs Qdashes emitting near the 2-µm wavelength. Morphological analysis revealed that PG led to an improvement in in-plane size uniformity and increases in average height and height distribution. A 2 × boost in photoluminescence intensity was observed, which we attribute to improved lateral dimensions and structural stabilization. PG encouraged formation of taller Qdashes while photoluminescence measurements revealed a blue-shift in the peak wavelength. We proposed that the blue-shift originates from the thinner quantum well cap and decreased distance between the Qdash and InAlGaAs barrier. This study on the punctuated growth of large InAs Qdashes is a step toward realizing bright, tunable, and broadband sources for 2-µm communications, spectroscopy, and sensing.

Surgery for maxillary oral squamous cell carcinoma: the effect of surgical resection margins and elective neck dissection on oncological outcomes.

Maxillary oral squamous cell carcinoma (OSCC) is uncommon. Surgical resection is challenging due to the anatomy, and the role of elective neck dissection (END) is not well-defined. A retrospective cohort study of patients with maxillary OSCC treated with primary surgery between 2007 and 2019 was conducted. Primary tumours of sinonasal origin with extension into the oral cavity were excluded. Survival analysis was performed using Kaplan-Meier and Cox proportional hazards models. Sixty-seven patients were included; mean follow-up was 55 months. On univariate analysis, clear (≥5 mm) margins were associated with higher disease-free (68% vs 36%, P = 0.019) and overall survival (75% vs 36%, P = 0.004) than close/involved (<5 mm) margins. In clinically node-negative patients, the risk of occult cervical metastasis in tumours with depth of invasion (DOI) ≥ 3 mm and T2-4 tumours was 22% and 25%, respectively. END in these groups was associated with a lower rate of loco-regional recurrence (DOI ≥3 mm subgroup: 5% vs 38%, P = 0.029; T2-4 subgroup: 6% vs 50%, P = 0.028) and longer time to recurrence (DOI ≥3 mm subgroup: 119 months vs 96 months, P = 0.042; T2-4 subgroup: 117 months vs 56 months, P = 0.031) than observation of the neck. On multivariate analysis, close/involved margins were associated with an increased risk of overall mortality (hazard ratio 3.4, 95% confidence interval 1.0-11.3, P = 0.043) and disease recurrence (hazard ratio 2.8, 95% confidence interval 1.1-7.1, P = 0.031). In maxillary OSCC, a ≥ 5 mm histological margin should remain the goal of ablative surgery. END should be considered in tumours with DOI ≥ 3 mm.

A combined exercise and cognitive training intervention induces fronto-cingulate cortical plasticity in first-episode psychosis patients.

OBJECTIVE: Schizophrenia (SZ) is characterized by neurobiological and associated cognitive and functional deficits, including pronounced cortical thinning, that lead to acute and long-term functional impairment. Research with older adults supports the role of non-pharmacological interventions, such as exercise (E) and cognitive training (CT), for cognitive impairments. This literature influenced the development of combined CT&E treatments for individuals with SZ. However, the impact of longer combined treatment duration (6 months) on neuroanatomy has yet to be explored in patients in the early course of the illness. The impact of adding exercise to cognitive training for key brain regions associated with higher-order cognition was examined here using magnetic resonance imaging (MRI) in first-episode psychosis (FEP) patients. METHODS: UCLA Aftercare Research Program patients with a recent first episode of schizophrenia were randomly assigned to either combined cognitive and exercise training (CT&E) (N = 20) or cognitive training alone (CT) (N = 17) intervention. Cortical thickness was measured longitudinally and analyzed for two regions of interest using FreeSurfer. RESULTS: Compared to patients in the CT group, those in the CT&E group demonstrated an increase in cortical thickness within the left anterior cingulate cortex over the six-month treatment period (ACC: F(1, 35) = 4.666, P < .04). Directional tendencies were similar in the left dorsolateral prefrontal cortex (DLPFC: F(1,35) = 4.132, P < .05). CONCLUSIONS: These findings suggest that exercise and cognitive training may synergistically increase fronto-cingulate cortical thickness to mitigate progressive neural atrophy in the early course of SZ. This combined intervention appears to be a valuable adjunct to standard pharmacologic treatment in FEP patients.

Analgesic effect of dexmedetomidine in colorectal cancer patients undergoing laparoscopic surgery.

OBJECTIVES: To evaluate the analgesic efficacy of intraoperative dexmedetomidine (DEX) for acute postoperative pain in colorectal cancer patients undergoing laparoscopic surgery. METHODS: We retrospectively analyzed data of 190 colorectal cancer patients who had undergone laparoscopic surgery between October 2020 and May 2021 at Samsung Medical Center, Seoul, Korea, with (n=74) or without intraoperative DEX (n=85) administration. The demographic, clinical, anesthetic, and postoperative data were compared. RESULTS: In total, 159 patients were enrolled. Demographic and clinical data were not different between the groups. The mean arterial pressure (p<0.001) and heart rate (p<0.001) were lower in the DEX group at the end of surgery and after extubation (p=0.003, p=0.001). The minimum alveolar concentration of sevoflurane was lower in the DEX group during surgery. At the post-anesthesia care unit (PACU) admission and discharge, pain scores (p<0.001, p=0.027) and fentanyl consumption (p<0.001) were significantly lower in the DEX group. On postoperative days 1-3, pain scores and opioid consumption were not different between the groups. The incidence of postoperative complications was not different between the groups. CONCLUSION: Continuous intraoperative DEX administration had an intraoperative analgesic effect as indicated by lower hemodynamic and fentanyl consumption. Furthermore, there was immediate postoperative analgesia as suspected by the lower pain scores and fentanyl dose during the PACU. However, pain scores and opioid consumption after the PACU remained unaffected.

Malrotation: Management of Disorders of Gut Rotation for the General Surgeon.

In this article, we aim to provide the general surgeon with a clinical blueprint to navigate disorders of gut rotation. We emphasize that bilious emesis in a newborn is malrotation with volvulus until proven otherwise. Although an upper GI series can establish the diagnosis, surgical intervention should not be delayed until the child is ill-appearing. Following detorsion, the key steps are to broaden the mesentery, fully Kocherize the duodenum, and mobilize the cecum. If nonviable bowel is encountered, the principles of damage control can be applied to children. Every effort should be made to preserve bowel length.

An observational study of hydrodynamic impact on water mass transport due to tidal power generation.

The world's largest Sihwa Tidal Power Plant (TPP), located on the west coast of Korea, was built in 2011 for the purpose of improving water quality and producing renewable energy. After several years of actual operation, most of the original purpose was achieved, but unexpected coastal environmental changes such as tidal flat damage and sediment accumulation also occurred. In this study, in order to understand the causes of these environmental changes, field observations were conducted near TPP, and spatial and temporal variability of flow structure and water exchange process were investigated. Three-dimensional velocity data were collected along the closed line surrounding the outside of the TPP for 11 h during spring tide and analyzed according to two discharge phases: power generation phase (PGP) and drainage phase (DP). The results show that the depth-averaged maximum current velocity was more than three times greater at DP than at PGP. Jet-like flow during DP caused very high horizontal shear, whereas vertical shear was relatively weak, indicating that the horizontal and vertical flow structures were very different. The most notable result is that the mass transport patterns between PGP and DP are significantly different, i.e., during PGP, mass transport is dominated on the left side of the TPP, whereas during DP, it occurs at the front of the TPP. This means that there is a strong spatiotemporal asymmetry between the inflow from the downstream (outside of the TPP) during PGP and the outflow from the upstream (inside of the TPP) during DP. These asymmetric processes can have a significant impact on the material exchange and sediment transport near the TPP. Since observational studies on TPP are extremely rare, this study is expected to contribute to future TPP related research, such as numerical modeling.

Chrysosplenol-C Increases Contraction by Augmentation of Sarcoplasmic Reticulum Ca2+ Loading and Release via Protein Kinase C in Rat Ventricular Myocytes.

Naturally found chrysosplenol-C (4',5,6-trihydroxy-3,3',7-trimethoxyflavone) increases the contractility of cardiac myocytes independent of ß-adrenergic signaling. We investigated the cellular mechanism for chrysosplenol-C-induced positive inotropy. Global and local Ca2+ signals, L-type Ca2+ current (ICa), and contraction were measured from adult rat ventricular myocytes using two-dimensional confocal Ca2+ imaging, the whole-cell patch-clamp technique, and video-edge detection, respectively. Application of chrysosplenol-C reversibly increased Ca2+ transient magnitude with a maximal increase of ∼55% within 2- to 3-minute exposures (EC50 ≅ 21 µM). This chemical did not alter ICa and slightly increased diastolic Ca2+ level. The frequency and size of resting Ca2+ sparks were increased by chrysosplenol-C. Chrysosplenol-C significantly increased sarcoplasmic reticulum (SR) Ca2+ content but not fractional release. Pretreatment of protein kinase C (PKC) inhibitor but not Ca2+/calmodulin-dependent protein kinase II (CaMKII) inhibitor abolished the stimulatory effects of chrysosplenol-C on Ca2+ transients and Ca2+ sparks. Chrysosplenol-C-induced positive inotropy was removed by the inhibition of PKC but not CaMKII or phospholipase C. Western blotting assessment revealed that PKC-δ protein level in the membrane fractions significantly increase within 2 minutes after chrysosplenol-C exposure with a delayed (5-minute) increase in PKC-α levels in insoluble membrane. These results suggest that chrysosplenol-C enhances contractility via PKC (most likely PKC-δ)-dependent enhancement of SR Ca2+ releases in ventricular myocytes. SIGNIFICANCE STATEMENT: Study shows that chrysosplenol-C, a natural flavone showing a positive inotropic effect, increases SR Ca2+ releases on depolarizations and Ca2+ sparks with an increase of SR Ca2+ loading but not L-type Ca2+ current in ventricular myocytes. Chrysosplenol-C-induced enhancement in contraction is eliminated by PKC inhibition, and it is associated with redistributions of PKC to the membrane. These indicate that chrysosplenol-C enhances contraction via PKC-dependent augmentations of SR Ca2+ release and Ca2+ loading during action potentials.

Accident prevention activity and accident experience in the Republic of Korea military.

INTRODUCTION: According to data released by the Korea National Statistical Office, the number of accidents has been decreasing since 2012. However, a considerable number of deaths related to safety accidents (23-46 deaths) are still reported annually. This study aimed to observe the correlation between accident prevention activities in the Republic of Korea (ROK) military and the incidence of safety accidents. METHODS: The study used data from the 2014-2015 Military Health Survey and included 13 618 responses (Army: 8414 (61.8%); Navy/Marine: 2262 (16.6%); Air Force: 2942 (21.6%)) from the ROK military personnel. Accident experiences and thoughts on accident prevention activities were self-reported. Multiple logistic regression analysis was used to examine the validity of accident prevention activity and accident experience. RESULTS: Of the 13 618 military personnel who responded, 12.0% reported experiencing safety accidents in the military and 1020 (7.5%) felt that accident prevention activities in the military were insufficient. On logistic regression analysis, we found a significant difference (insufficiency OR=1.56, CI 1.31 to 1.86). In particular, military personnel who belong to the Army and Navy were more likely to think that accident prevention activities were insufficient. In addition, military personnel who experienced falls/slips, crash, and laceration/puncture wound/amputation/penetrating wound accidents were more likely to think accident prevention activities were insufficient. CONCLUSIONS: Our study found that accident prevention activities in the military and accident experiences were related. It is necessary for the ROK Ministry of Defense, Army, Navy and Air Force headquarters to re-evaluate their accident prevention systems.

Hong Kong Geriatrics Society and Hong Kong Urological Association consensus on personalised management of male lower urinary tract symptoms in the era of multiple co-morbidities and polypharmacy.

Lower urinary tract symptoms (LUTS) are common complaints of adult men. Benign prostatic hyperplasia (BPH) represents the most common underlying cause. As the incidence of BPH increases with age, and pharmacological treatment is a major part of the disease's management, the majority of patients with LUTS are managed by primary care practitioners. There are circumstances in which specialist care by urologists or geriatricians is required, such as failure of medical treatment, adverse effects from medical treatment, or complications from BPH. Referral choices can be confusing to patients and even practitioners in different specialties under such circumstances. There is currently no local consensus about the diagnosis, medical management, or referral mechanism of patients with BPH. A workgroup was formed by members of The Hong Kong Geriatrics Society (HKGS) and the Hong Kong Urological Association (HKUA) to review evidence for the diagnosis and medical treatment of LUTS. A consensus was reached by HKGS and HKUA on an algorithm for the flow of male LUTS care and the use of uroselective alpha blockers, antimuscarinics, beta-3 adrenoceptor agonists, and 5α-reductase inhibitors in the primary care setting. This consensus by HKGS and HKUA provides a new management paradigm of male LUTS.

Associations between earplug use and hearing loss in ROK military personnel.

INTRODUCTION: The easiest way to prevent noise-induced hearing loss (NIHL) is to wear earplugs. The Republic of Korea (ROK) Ministry of National Defense (MND) is supplying earplugs to prevent NIHL, but many patients still suffer from this. We speculated that earplugs would have a high NIHL rate, depending on the rate of use of earplugs, regardless of the rate of supply. Therefore, we conducted this study to investigate the relationship between the use of earplugs and hearing loss by ROK military personnel. METHODS: The study used data from the Military Health Survey conducted in 2014-2015, which included 13 470 questionnaires completed by ROK military personnel. Hearing loss and earplug use were self-reported. Logistic regression analysis was used to assess associations between earplug use and hearing loss. RESULTS: The study sample included 13 470 ROK military personnel (response rate of 71.2%) (Army, 8330 (61.8%); Navy/Marines, 2236 (16.6%); and Air Force, 2904 (21.6%)). Overall, 18.8% of Korean military personnel reported that they always wore earplugs, and 2.8% reported hearing loss. In logistic regression analysis, there were significant differences in the rates of hearing loss associated with wearing earplugs sometimes (OR=1.48, 95% CI 1.07 to 2.05) and never wearing earplugs (OR=1.53, 95% CI 1.12 to 2.10). In subgroup analysis, in Air Force, non-combat branch, forward area and long-term military service personnel increased hearing loss was associated with not wearing earplugs. CONCLUSION: Our study confirmed that within the ROK military, there is an association between hearing loss and lack of earplug use. In the ROK MND, Army, Navy/Marines and Air Force headquarters must provide guidelines for the use of earplugs during field training to protect military personnel's hearings and, if necessary, need to be regulated or institutionalised.

Dynamic trend or static variable: Shock Index Pediatric-Adjusted (SIPA) in warzone trauma.

BACKGROUND: Civilian studies suggest that trending Shock-Index Pediatric Adjusted(SIPA) values can prove useful in the prediction of trauma outcomes. The purpose of this study was to evaluate the relationship between trends in SIPA and outcomes in pediatric warzone trauma. METHODS: Retrospective review of the Department of Defense Trauma Registry from 2008 to 2015, including all patients age ≤17years. SIPA was calculated both pre-hospital and upon arrival, then classified as "normal" or "abnormal" based upon previously validated thresholds. Patients were stratified into groups based on the trend of their SIPA (1-normal to normal, 2-normal to abnormal, 3-abnormal to normal, 4-abnormal to abnormal). Key outcomes including ICU admission, severe injury, mechanical ventilation, and mortality were then compared between groups. RESULTS: 669 patients were included, mean ISS 12 ± 10. The most common mechanism of injury was blast (46.5%). Overall, 43% were stratified into Group 1, 13.9% into Group 2, 14.8% into Group 3, and 28.0% into Group 4. Those patients with a persistently abnormal SIPA (Group 4) had significantly increased incidence of severe injury, ICU admission, need for mechanical ventilation, and mortality. CONCLUSION: Trends in SIPA may be used to predict trauma outcomes for children injured in warzones, with persistently abnormal values associated with worse outcomes overall.

Pediatric adjusted reverse shock index multiplied by Glasgow Coma Scale as a prospective predictor for mortality in pediatric trauma.

INTRODUCTION: Shock index and its pediatric adjusted derivative (pediatric age-adjusted shock index [SIPA]) have demonstrated utility as prospective predictors of mortality in adult and pediatric trauma populations. Although basic vital signs provide promise as triage tools, factors such as neurologic status on arrival have profound implications for trauma-related outcomes. Recently, the reverse shock index multiplied by Glasgow Coma Scale (GCS) score (rSIG) has been validated in adult trauma as a tool combining early markers of physiology and neurologic function to predict mortality. This study sought to compare the performance characteristics of rSIG against SIPA as a prospective predictor of mortality in pediatric war zone injuries. METHODS: Retrospective review of the Department of Defense Trauma Registry, 2008 to 2016, was performed for all patients younger than 18 years with documented vital signs and GCS on initial arrival to the trauma bay. Optimal age-specific cutoff values were derived for rSIG via the Youden index using receiver operating characteristic analyses. Multivariate logistic regression was performed to validate accuracy in predicting early mortality. RESULTS: A total of 2,007 pediatric patients with a median age range of 7 to 12 years, 79% male, average Injury Severity Score of 11.9, and 62.5% sustaining a penetrating injury were included in the analysis. The overall mortality was 7.1%. A total of 874 (43.5%) and 685 patients (34.1%) had elevated SIPA and pediatric rSIG scores, respectively. After adjusting for demographics, mechanism of injury, initial vital signs, and presenting laboratory values, rSIG (odds ratio, 4.054; p = 0.01) was found to be superior to SIPA (odds ratio, 2.742; p < 0.01) as an independent predictor of early mortality. CONCLUSION: Reverse shock index multiplied by GCS score more accurately identifies pediatric patients at highest risk of death when compared with SIPA alone, following war zone injuries. These findings may help further refine early risk assessments for patient management and resource allocation in constrained settings. Further validation is necessary to determine applicability to the civilian population. LEVEL OF EVIDENCE: Prognostic study, level IV.

Molecular insights into the development of hepatic metastases in colorectal cancer: a metastasis prediction study.

OBJECTIVE: Colorectal cancer is presently the third most commonly diagnosed cancer in the United States. In this study, we identified molecular differences between hepatic and non-hepatic metastases in colorectal cancer and evaluated their prognostic significance. MATERIALS AND METHODS: We downloaded primary data from the NCBI Gene Expression Omnibus (GSE6988, GSE62321, GSE50760, and GSE28722). To identify the molecular differences, we used the Significance Analysis of Microarray method. We selected nine prognostic genes (SYTL2, PTPLAD1, CDS1, RNF138, PIGR, WDR78, MYO7B, TSPAN3, and ATP5F1) with hepatic metastasis prediction score in colorectal cancer (hereafter referred to as LASSO Score). We confirmed the prognostic significance of the LASSO Score by using Kaplan-Meier survival analysis, multivariate analysis, the time-dependent area under the curve (AUC) of Uno's C-index, and the AUC of the receiver operating characteristic curve at 1-5 years. RESULTS: Survival analysis revealed that a high LASSO Score is associated with a poor prognosis in colorectal cancer patients with hepatic metastases (p = 0). Analysis of C-indices and AUC values from the receiver operating characteristic curve further supported this prediction by the LASSO Score. Multivariate analysis confirmed the prognostic significance of the LASSO Score (p = 1.13e-06). CONCLUSIONS: This study reveals the biological mechanisms underlying hepatic metastases in colorectal cancer and will help in developing targeted therapies for colorectal cancer.

Focused Changes in Opioid Prescribing Yield Far-reaching Benefits Through Culture Change and Attention to Opioid Minimization.

OBJECTIVE: Standardization of prescriptions after specific procedures (laparoscopic appendectomy, cholecystectomy, inguinal/umbilical hernia repair) significantly reduces opioid prescriptions for these targeted procedures. We sought to determine the impact of increased attention to responsible opioid prescribing in the absence of protocolization. DESIGN: Prescription practices of Laparoscopic Sleeve Gastrectomies and Roux-en-y Gastric Bypasses at a tertiary medical center (October 1, 2016-September 30, 2018) were retrospectively reviewed. Patients were grouped into whether surgical intervention took place before or after institution of an unrelated opioid protocol in November 2017. Patients with chronic opioid use or extended hospital stay (>4 days) were excluded. Discharge prescriptions, oral morphine equivalents (OME), and need for repeat prescriptions were compared. SETTING: This study was set at Madigan Army Medical Center in Tacoma, Washington. PARTICIPANTS: All general surgery residents engaged in clinical duties at our institution during the dates of the study were included. RESULTS: Study population included 187 patients, with 91 patients undergoing surgery prior to the protocol and 88 post-protocol. Preprotocol patients were provided an average of 413 OME (SD 103) and 5.5% required repeat opioid prescriptions within 3 months of surgery. The most common opioid prescription was 300 mL of oxycodone elixir (450 OME, 88%). Postprotocol, opioid prescriptions fell 61% to an average of 161 OME (SD 71, p < 0.001). Repeat opioid requirements remained statistically unchanged (8.0%, p = 0.562). The most common opioid prescription postprotocol included 20 oxycodone tablets (150 OME, 76%). CONCLUSIONS: Opioid reduction efforts reap benefits beyond those procedures specifically targeted. Focus on responsible opioid prescribing through standardization, even when limited to certain procedures, may result in a hospital culture change with global opioid prescription reduction.

Administration of recombinant human placental growth factor decreases blood pressure in obese hypertensive pregnant rats.

OBJECTIVES: Although epidemiological studies have shown that obesity is associated with increased incidence of hypertension during pregnancy, the mechanisms linking these two comorbidities are not as well studied. Previous investigations detected lower levels of the anti-hypertensive and pregnancy-related factor, placental growth factor (PlGF), in obese hypertensive pregnancies. Therefore, we examined whether obese hypertensive pregnant rats have reduced PlGF and whether increasing its levels by administering recombinant human (rh)PlGF reduces their blood pressure. METHODS: We utilized a genetic model of obesity characterized to be heavier, hypertensive and fertile, namely rats having heterozygous deficiency of the melanocortin-4 receptor (MC4R-def). RESULTS: MC4R-def obese rats had lower circulating levels of PlGF than wild-type lean controls at gestational day 19. Also, assessment of the PlGF receptor, Flt-1, in the vasculature showed that its levels were reduced in aorta and kidney glomeruli but increased in small mesenteric arteries. Chronic intraperitoneal administration of rhPlGF from gestational day 13-19 significantly increased circulating PlGF levels in both obese and lean rats, but reduced blood pressure only in the obese pregnant group. The rhPlGF treatment did not alter maternal body and fat masses or circulating levels of the adipokines, leptin and adiponectin. In addition, this treatment did not impact average foetal weights but increased placental weights regardless of obese or lean pregnancy. CONCLUSION: PlGF is reduced in MC4R-def obese hypertensive pregnant rats, which is similar to findings in obese hypertensive pregnant women, while increasing its levels with exogenous rhPlGF reduces their blood pressure.

Validation of a novel partial resuscitative endovascular balloon occlusion of the aorta device in a swine hemorrhagic shock model: Fine tuning flow to optimize bleeding control and reperfusion injury.

OBJECTIVES: Partial restoration of aortic flow during resuscitative endovascular balloon occlusion of the aorta (REBOA) is advocated by some to mitigate distal ischemia. Our laboratory has validated the mechanics and optimal partial REBOA (pREBOA) flow rates using a prototype device. We hypothesize that pREBOA will increase survival when compared with full REBOA (fREBOA) in prolonged nonoperative management of hemorrhagic shock. METHODS: Twenty swine underwent placement of aortic flow probes, zone 1 REBOA placement, and 20% blood volume hemorrhage. They were randomized to either solid organ or abdominal vascular injury. The pREBOA arm (10 swine) underwent full inflation for 10 minutes and then deflation to a flow rate of 0.5 L/min for 2 hours. The fREBOA arm (10 swine) underwent full inflation for 60 minutes, followed by deflation/resuscitation. The primary outcome is survival, and secondary outcomes are serologic/pathologic signs of ischemia-reperfusion injury and quantity of hemorrhage. RESULTS: Two of 10 swine survived in the fREBOA group (2/5 solid organ injury; 0/5 abdominal vascular injury), whereas 7 of 10 swine survived in the pREBOA group (3/5 solid organ injury, 4/5 abdominal vascular injury). Survival was increased (p = 0.03) and hemorrhage was higher in the pREBOA group (solid organ injury, 1.36 ± 0.25 kg vs. 0.70 ± 0.33 kg, p = 0.007; 0.86 ± 0.22 kg vs. 0.71 ± 0.28 kg, not significant). Serum evidence of ischemia was greater with fREBOA, but this was not significant (e.g., lactate, 16.91 ± 3.87 mg/dL vs. 12.96 ± 2.48 mg/dL at 120 minutes, not significant). Swine treated with pREBOA that survived demonstrated trends toward lower alanine aminotransferase, lower potassium, and higher calcium. The potassium was significantly lower in survivors at 60 minutes and 90 minutes time points (5.97 ± 0.60 vs. 7.53 ± 0.90, p = 0.011; 6.67 ± 0.66 vs. 8.15 ± 0.78, p = 0.029). Calcium was significantly higher at 30 minutes, 60 minutes, and 90 minutes (8.56 ± 0.66 vs. 7.50 ± 0.40, p = 0.034; 8.63 ± 0.62 vs. 7.15 ± 0.49, p = 0.019; 8.96 ± 0.64 vs. 7.00, p = 0.028). CONCLUSION: Prolonged pREBOA at a moderate distal flow rate provided adequate hemorrhage control, improved survival, and had evidence of decreased ischemic injury versus fREBOA. Prophylactic aggressive calcium supplementation may have utility before and during the reperfusion phase.