Vascular Control Research Articles

A synergic and compatible microbial-based consortium for biocontrol of Fusarium wilt of tomato

Bioconsortia, based on Chaetomium globosum (isolate CgCG-2), Pseudomonas putida (PpTS-1), Bacillus subtilis (BsS2BC-1), and Trichoderma harzianum (ThS17TH), were designed to develop eco-friendly alternatives for biocontrol of vascular wilt of tomato caused by Fusarium oxysporum f. sp. lycopersici (Fol). In vitro compatibilities of microbes in these consortia were assessed for growth, antagonism, and biocontrol-related gene expression. In these bioassays, the biocontrol isolates had positive interactions for the tested parameters. In pot experiments, seed and soil applications of culture suspensions of five different isolate mixtures were assessed, in comparisons with individual isolates, for efficacy in vascular wilt control after challenge inoculations with Fol under polyhouse conditions. Compared to experimental controls, the biocontrol isolate mixtures reduced vascular wilt incidence and promoted plant growth. PpTS-1 + CgCG-2 + ThS17TH was the most effective microbial consortium, giving 71% reduction of Fusarium wilt incidence compared to non-treated controls. This reduced incidence increased plant growth by 135%. Upregulation of genes encoding for allene oxide cyclase, pathogenesis-related proteins 3, and 5, and β-1,3-glucanase in tomato plants indicated that the reduction in vascular wilt by the consortia could be partly plant-mediated. This study provides new insights into the development of microbial-based consortia for the biocontrol of vascular wilt in tomato.

Knowledge and Practices of Dialysis Unit Staff Regarding the Care and Management of Vascular Access Infections

Background: Vascular access infections among dialysis patients are becoming the major concerns that contribute to a significant morbidity and mortality across the globe. Proper management and care must be planned according to the standard protocols for the prevention of these infections. Objective: The objective of the study was to assess the knowledge and practices of dialysis staff regarding vascular access infection control in tertiary care hospitals of Peshawar, Pakistan. Methodology: A cross-sectional study was conducted on dialysis staff including nurses and technicians (n=58). All hemodialysis staff (Nurses and Technician) was included in the study who were regularly working in dialysis unit and had at least 6 months of dialysis unit experience. Data was collected through a self-administered questionnaire and checklist with its proper validation. Data was analyzed through SPSS Version-20 for its proper presentation. Results: The finding of the study showed that around 44.94% of the questions were corrected by the nurses and technician on the knowledge assessment questionnaire while looking into their practices 28.5% of the correct practices were followed by them. Additionally it was found that private sector hospital nurses and technician scored more than public sector hospitals in knowledge and practices. Practical implication: It is one of the main responsibilities of the dialysis unit staff to have knowledge regarding vascular access infections. So based on their knowledge, they will maintain the aseptic protocol while practicing, which will ensure a low infection rate and prevent the patient from complications that will improve the patient's experience and reduce the length of stay. Conclusion: It is concluded from the research findings that nurses and technician knowledge and practices are not sufficient to prevent the vascular access infections; therefore they must be trained for the provision of best possible care among the dialysis patients. Keywords: Knowledge, Practice, Vascular Access, Infections, Dialysis, Nurse, Technicians

Endothelial-derived angiocrine factors as instructors of embryonic development.

Blood vessels are well-known to play roles in organ development and repair, primarily owing to their fundamental function in delivering oxygen and nutrients to tissues to promote their growth and homeostasis. Endothelial cells however are not merely passive conduits for carrying blood. There is now evidence that endothelial cells of the vasculature actively regulate tissue-specific development, morphogenesis and organ function, as well as playing roles in disease and cancer. Angiocrine factors are growth factors, cytokines, signaling molecules or other regulators produced directly from endothelial cells to instruct a diverse range of signaling outcomes in the cellular microenvironment, and are critical mediators of the vascular control of organ function. The roles of angiocrine signaling are only beginning to be uncovered in diverse fields such as homeostasis, regeneration, organogenesis, stem-cell maintenance, cell differentiation and tumour growth. While in some cases the specific angiocrine factor involved in these processes has been identified, in many cases the molecular identity of the angiocrine factor(s) remain to be discovered, even though the importance of angiocrine signaling has been implicated. In this review, we will specifically focus on roles for endothelial-derived angiocrine signaling in instructing tissue morphogenesis and organogenesis during embryonic and perinatal development.

Risk of Hepatic Artery Complications After Liver Transplantation in Patients Who Received Pretransplant Transarterial Chemoembolization Therapy: A Single-Center Experience

Pretransplant transarterial chemoembolization (TACE) for patients with hepatocellular carcinoma (HCC) has been associated with an increased risk of hepatic artery thrombosis (HAT) after liver transplantation (LT). Innovative surgical LT and interventional vascular radiology TACE techniques may mitigate the risk of HAT. We sought to investigate the incidence of HAT after LT in patients who received pre-transplant TACE at our center. We performed a single-center retrospective review of all LT patients, >18 years of age, from October 1, 2012, to May 31, 2018. Outcomes were compared between patients who received pre-LT TACE and those who did not. Median follow-up was 26 months. Among the 162 LT recipients, 110 (67%) patients did not receive pre-LT TACE (Group I), while 52 (32%) received pre-LT TACE (Group II). The <30-day incidence rates of post-LT HAT were as follows: Group I=1.8% and Group II=1.9% (P=.9). Most hepatic arterial complications occurred >30 days after LT. Based on competing risks regression analysis, TACE was not associated with an increased risk of HAT. Patient or graft survivals were comparable between the 2 groups (P=.1 and .2, respectively). Our study shows a similar incidence of hepatic artery complications post-LT in patients who received TACE before LT compared with those who did not. In addition, we suggest that the surgical technique of early vascular control of the common hepatic artery during LT, in combination with a super-selective vascular intervention radiology approach, has clinical utility in reducing the risk of HAT in patients requiring pre-transplant TACE.

#3713 NEPHROLOGISTS’ AND PRIMARY CARE PHYSICIANS’ KNOWLEDGE ABOUT NOVEL TREATMENT OPTIONS FOR TYPE 2 DIABETES AND CKD AUGMENTED BY ONLINE MEDICAL EDUCATION

Abstract Background and Aims Diabetes is the number one cause of kidney failure and chronic kidney disease (CKD) associated with type 2 diabetes (T2D) increases the risk for cardiovascular events 2 to 3- fold thus highlighting the crucial need for early detection of CKD and comprehensive vascular risk control. Recently, novel treatment options with clear benefits for the prognosis of patients with T2D and CKD have emerged. The goal of this activity for primary care physicians (PCP) and nephrologists (NEPH) was to improve their understanding of the clinical benefits as well as safety considerations of selective non-steroidal mineralocorticoid antagonists (nsMRA) in the management of their patients with T2D and CKD. Method Two nephrology experts joined a 20-minute online video discussion with synchronized slides. Educational effect was assessed using a repeated-pair design with pre-/post-assessment. 3 multiple choice questions assessed knowledge, 1 question rated on a Likert-type scale assessed confidence. A paired samples t-test was conducted on overall average number of correct responses and for confidence rating, a McNemar's test was conducted at the question level (5% significance level). Cohen's d with correction for paired samples estimated the effect size of the education on number of correct responses. Data collection from 8/2/22 to 10/17/22. Results Conclusion Participation of PCP and NEPH in an online video expert discussion improved their understanding of the clinical benefits and safety aspects of selective nsMRA as well as their confidence in using such novel therapies for their patients with T2D and CKD in clinical practice.

#3204 CASE-BASED ONLINE MEDICAL EDUCATION ENHANCES PHYSICIANS’ KNOWLEDGE AND COMPETENCE IN THE MANAGEMENT OF PATIENTS WITH DIABETES WITH CARDIORENAL DISEASE

Abstract Background and Aims Patients with type 2 diabetes (T2D) and chronic kidney disease (CKD) have a substantially impaired cardio-renal health prognosis and a reduced life expectancy highlighting the urgent need for early detection and comprehensive vascular risk control. The goal of this activity for primary care physicians (PCP) and diabetologists/endocrinologists (D/E) was to improve their understanding of and competence in managing patients with diabetes with cardiorenal disease in clinical practice. Method An interactive educational program including one detailed patient case challenges clinicians to apply most recent evidence-based guideline recommendations. Detailed scenarios prompt learners to determine the correct treatment and follow-up for the patient with expert commentaries providing in-depth advice at each stage and a conclusion at the end of the program. Educational effect was assessed using a repeated-pair design with pre-/post-assessment. 3 multiple choice questions assessed knowledge/competence, 1 question rated on a Likert-type scale assessed confidence. A paired samples t-test was conducted on overall average number of correct responses and for confidence rating, a McNemar's test was conducted at the question level (5% significance level). Cohen's d with correction for paired samples estimated the effect size of the education on number of correct responses. Data collection from 5/25/22 to 9/13/22. Results 74% of PCP (n = 74) improved their knowledge regarding the need for comprehensive vascular risk control in patients with T2D and CKD and their competence related to the practical implementation of the latest diabetes guidelines for the individualized management of these patients (p&amp;lt;.001; d = 0.56) • 56% of D/E (n = 32) advanced their knowledge regarding the need for comprehensive vascular risk control in patients with T2D and CKD (P&amp;lt;.01, d = 0.35) • 39% of PCP and 41% of D/E increased their confidence (p&amp;lt;.001 and p&amp;lt;.01 respectively) in proactively monitoring their patients with T2D for kidney disease Conclusion Participation of PCP and D/E in an interactive online case-based education program improved their understanding of the need for comprehensive vascular risk control and the competence of PCPs in managing patients with T2D and cardiorenal disease in clinical practice.

Vascular closure devices in living-donor nephrectomy: a much-needed systematic review and meta-analysis focusing on safety.

To assess the safety of vascular closure devices in living-donor nephrectomy (LDN), as staplers and non-transfixion techniques (polymer locking and metal clips) are the methods employed to secure the renal vessels during laparoscopic and robotic LDN, but the use of clips has come into question since the United States Food and Drug Administration and manufacturers issued a contraindication. A systematic review and meta-analysis were conducted to assess the safety of vascular closure devices (International Prospective Register of Systematic Reviews [PROSPERO] registration: CRD42022364349). The PubMed, Scopus, the Excerpta Medica dataBASE (EMBASE), and the Literatura Latino-Americana e do Caribe em Ciências da Saúde (LILACS) databases were searched in September 2022. For comparative and non-comparative studies, incidence estimates and odds ratios (ORs), respectively, for the main variables regarding safety of vascular closure devices were pooled by using random effects meta-analyses. Quality assessment of the included comparative studies was conducted using the Risk Of Bias In Non-randomised Studies of Interventions (ROBINS-I) tool. Of the 863 articles obtained, data were retrieved from 44 studies, which included 42 902 patients. In non-comparative studies, the pooled estimate rates for device failure, severe haemorrhage rate, conversion to open surgery, and mortality were similar for both clips and staplers. Regarding the meta-analyses for comparative studies (three studies), there were no significant differences between the two groups for the severe haemorrhage rate (OR 0.57, 95% confidence interval [CI] 0.18-1.75; P = 0.33), conversion to open surgery (OR 0.35, 95% CI 0.08-1.54; P = 0.16), or death rate (OR 3.64, 95% CI 0.47-28.45; P = 0.22). Based on weak evidence, device failure was lower in the polymer clip group (OR 0.41, 95% CI 0.23-0.75; P = 0.00). This study has confirmed that there is no evidence for the superiority of any vascular closure device in terms of safety in LDN. Standardised recommendations for vascular control in this context should be carefully designed and prospectively evaluated.

Comprehensive Cardiovascular and Renal Protection in Patients with Type 2 Diabetes.

Type 2 diabetes (T2DM) is one of the main public health care problems worldwide. It is associated with a marked increased risk of developing atherosclerotic vascular disease, heart failure, chronic kidney disease and death. It is essential to act during the early phases of the disease, through the intensification of lifestyle changes and the prescription of those drugs that have been shown to reduce these complications, with the aim not only of achieving an adequate metabolic control, but also a comprehensive vascular risk control. In this consensus document, developed by the different specialists that treat these patients (endocrinologists, primary care physicians, internists, nephrologists and cardiologists), a more appropriate approach in the management of patients with T2DM or its complications is provided. A particular focus is given to the global control of cardiovascular risk factors, the inclusion of weight within the therapeutic objectives, the education of patients, the deprescription of those drugs without cardiovascular benefit, and the inclusion of GLP-1 receptor agonists and SGLT2 inhibitors as cardiovascular protective drugs, at the same level as statins, acetylsalicylic acid, or renin angiotensin system inhibitors.

Resection of the Posterior Thigh Compartment and Modification of the Surgical Technique for Bulky Tumors

Objective: We present a 59-year-old male patient with a 6-month evolution lesion characterized by an increase in volume in the posterior region of the right thigh with expansive growth, pain of moderate intensity and limitation of gait. Clinical case: Magnetic resonance of the thigh that reports: "focal alteration within the thickness of the posterior superficial muscular plane, biceps femoris muscle short and long head, visible focal oval lesion, measuring approximately 10.44 cm × 7.3 cm with heterogeneous intensity, shows trabeculae, detritus and high intensity content". Drainage and biopsy report: malignant mesenchymal tumor. Tumor vascularization and suspected involvement of superficial branches in the deep femoral artery. With the improvement of the Malawer Sugarbaker surgical technique, the posterior septal tumor of the thigh was removed through a supine anteroposterior approach, vascular control, and cross surgical management of pathological anatomy. Adequate oncological resection with surgical result, evolution and satisfactory recovery. Conclusion: For large tumors that may or have been confirmed to have vascular involvement, modifying the classic technique of posterior thigh resection is a feasible and provable alternative method from a practical perspective, as it can better control tumor lesions during surgery. For large volume posterior chamber sarcoma with vascular involvement, it is recommended to adopt multidisciplinary management and utilize existing tools to personalize each clinical case.

Surgery of Colorectal Liver Metastases Involving the Inferior Vena Cava: A Systematic Review.

Combined hepatic and inferior vena cava (IVC) resection is the only potentially curative treatment for patients with colorectal liver metastases (CRLM) involving the IVC. Most of the existing data come from case reports or small case series. In this paper, a systematic review based on the PICO strategy was performed in accordance with the PRISMA statement. Papers from January 1980 to December 2022 were searched in Embase, PubMed, and the Cochrane Library databases. Articles considered for inclusion had to present data on simultaneous liver and IVC resection for CRLM and report surgical and/or oncological outcomes. From a total of 1175 articles retrieved, 29, including a total of 188 patients, met the inclusion criteria. The mean age was 58.3 ± 10.8 years. The most frequent techniques used were right hepatectomy ± caudate lobe for hepatic resections (37.8%), lateral clamping (44.8%) for vascular control, and primary closure (56.8%) for IVC repair. The thirty-day mortality reached 4.6%. Tumour relapse was reported in 65.8% of the cases. The median overall survival (OS) was 34 months (with a confidence interval of 30-40 months), and the 1-year, 3-year, and 5-year OS were 71.4%, 19.8%, and 7.1%, respectively. In the absence of prospective randomized studies, which are difficult to perform, IVC resection seems to be safe and feasible.

Placenta accreta spectrum with severe morbidity: fibrosis associated with cervical-trigonal invasion

Objective Describe the clinical-surgical results of patients with PAS in the low-posterior cervical-trigonal space associated with fibrosis (PAS type 4) compared with PAS types in other locations (Types 1, upper bladder, 2 in upper parametrium) and in particular with PAS type 3, corresponding to dissectible cervical-trigonal invasion. The clinical-surgical results of using a standard hysterectomy were analyzed with a modified subtotal hysterectomy (MSTH) in patients with PAS type 4. Material and methods A descriptive, retrospective, multicenter study included 337 patients of PAS; thirty-two corresponding to PAS type 4, from three PAS reference hospitals, CEMIC, Buenos Aires, Argentina, Fundación Valle de Lili, Cali, Colombia, and Dr. Soetomo General Hospital, Surabaya, Indonesia, between January 2015 and December 2020. PAS was diagnosed by abdominal and transvaginal ultrasound and topographically characterized by ultrafast T2 weighted MRI. In persistent macroscopic hematuria after MSTH, the surgeon performs an intentional cystotomy and uses a square compression suture to achieve the hemostasis inside the bladder wall. According to a PAS topographical classification, the patients with low-vesical cervical involvement compared with PAS located in relation with the upper blader (type1), upper parametrium (type 2 upper), and also with PAS situated in the lower vesical-trigon space (type 3). PAS 3 and 4 are located in identical area, but in type 3, group A, the vesicouterine space was dissectible, and in type 4, group B, significant fibrosis made surgical dissection extremely challenging. Furthermore, group B was divided into patients treated with total hysterectomy (HT) and those treated with a modified subtotal hysterectomy (MSTH). The surgical requirements to perform an MSHT included the availability of proximal vascular control at the aortic level (internal manual aortic compression, aortic endovascular balloon, aortic loop, or aortic cross-clamping). Then surgeon performed an upper segmental hysterotomy, avoiding the abnormal placenta invasion area; after that, the fetus was delivered, and the umbilical cord was ligated. After uterine exteriorization, the surgeon applies a continuous circular suture with number 2 polyglactin 910, taking some portions of the myometrium -to avoid unintentional slipping- around the lower uterine segment and a 3–4 cm proximal to the abnormal adhesion of the placenta. After tightening hard the circular suture, the uterine segment was circumferentially cut, three centimeters proximal to the circular hemostatic sutures. Next, the surgery follows the upper steps of conventional hysterectomy without changes. Additionally, the histological presence of fibrosis was examined in all samples. Results Modified subtotal hysterectomy in patients with PAS type 4 (cervical-trigonal fibrosis) resulted in a significant clínico-surgical improvement over total hysterectomy. The median operative time and intraoperative bleeding were 140 min (IQR 90–-240) and 1895 mL (IQR 1300–2500) in patients undergoing modified subtotal hysterectomy, and 260 min (IQR 210–287) and 2900 mL (IQR 2150–5500) in patients treated with total hysterectomy, respectively. The complication rate was 20% for MSHT and 82.3% for patients with a total hysterectomy. Conclusions PAS in the cervical trigonal area associated with fibrosis implies a greater risk of complications due to uncontrollable bleeding and organ damage. MSTH is associated with lower morbidity and difficulties in PAS type 4. Prenatal or intrasurgical diagnosis is essential to plan surgical alternatives to improve the results.

Application of damage control tactics in combat injuries of limbs at the advanced stages of medical evacuation in modern war settings (literature review)

Relevance. Limb injuries occupy the first place in the structure of modern combat injuries and are one of the main reasons for the decline in fitness for military service and disability. In the conditions of conducting largescale hostilities, the role of the advanced stages of medical evacuation, where surgical care is provided according to the principles of damage control, increases. Features of the tactics of damage control in combat injuries of the extremities determine the need for special training of military surgeons.The objective is to consider the features and effectiveness of the provision of surgical care according to the principles of damage control in combat injuries of the extremities at the advanced stages of medical evacuation in armed conflicts of the last two decades (in the countries of the Middle East and Africa, Afghanistan, Ukraine).Methodology. A search was made for scientific articles in the PubMed database and the Scientific Electronic Library (eLIBRARY.ru), published from 2013 to 2023.Results and Discussion. Modern combat trauma of the extremities is characterized by a high frequency of vascular damage, extensive destruction of soft tissues and bones from the impact of damaging factors of explosive ammunition. Surgical interventions for combat injuries of the extremities (external fixation of bone fractures with rod devices, ligation or temporary vascular shunt of damaged vessels, fasciotomy, amputation) were the most frequent of all operations performed at the advanced stages of medical evacuation during modern military conflicts. The volume of surgical interventions corresponded to the first stage of orthopedics and vascular control of injuries and was determined by the severity of the condition of the wounded, the degree of ischemia and severity of limb injuries, and the medical and tactical situation.Conclusion. Assistance at the advanced stages of medical evacuation according to the principles of orthopedics and vascular damage control can significantly reduce the frequency of amputations and improve the functional results of treatment for combat injuries of the extremities.

Targeting immune cell trafficking and vascular endothelial cells in psoriasis.

The role of the vasculature in inflammatory skin disorders is an exciting area of investigation. Vascular endothelial cells (ECs) play instrumental roles in maintaining the vascular barrier and control of blood flow. Furthermore, ECs contribute to a variety of immune responses, such as targeting immune cells to specific areas of vascular damage, infection, or foreign material. However, mechanisms through which ECs participate in immune-mediated responses remain to be fully explored. In this issue of the JCI, Li, Shao, et al. report on vascular endothelial glycocalyx destruction and the mechanisms through which EC dysfunction contributes to the well-characterized immune-mediated features of psoriasis, a chronic inflammatory skin disease. Here, we discuss the implications of these findings and highlight some risks and benefits of existing therapies designed to target immune cell trafficking in a variety of inflammatory conditions.

Vascular traffic control of neutrophil recruitment to the liver by microbiota-endothelium crosstalk

During bloodstream infections, neutrophils home to the liver as part of an intravascular immune response to eradicate blood-borne pathogens, but the mechanisms regulating this crucial response are unknown. Using invivo imaging of neutrophil trafficking in germ-free and gnotobiotic mice, we demonstrate that the intestinal microbiota guides neutrophil homing to the liver in response to infection mediated by the microbial metabolite D-lactate. Commensal-derived D-lactate augments neutrophil adhesion in the liver independent of granulopoiesis in bone marrow or neutrophil maturation and activation in blood. Instead, gut-to-liver D-lactate signaling primes liver endothelial cells to upregulate adhesion molecule expression in response to infection and promote neutrophil adherence. Targeted correction of microbiota D-lactate production in a model of antibiotic-induced dysbiosis restores neutrophil homing to the liver and reduces bacteremia in a model of Staphylococcus aureus infection. These findings reveal long-distance traffic control of neutrophil recruitment to the liver by microbiota-endothelium crosstalk.

Effect of obesity on the vascular response to sympathetic activation during hypoxia in female participants

Background: Activation of the sympathetic nervous system causes vasoconstriction and an acute reduction in peripheral blood flow. However, during hypoxia, sympathetically-mediated vasoconstriction is attenuated in young females without obesity. Given sustained increases in sympathetic activity associated with obesity may create a greater propensity to vasoconstrict in response to sympathetic activation, we sought to examine the effect of obesity on the vascular response to sympathetic activation during hypoxia. We hypothesized sympathetically-mediated vasoconstriction during hypoxia would be greater in premenopausal female adults with obesity when compared to females without obesity. Methods: Blood pressure (BP, finger photoplethysmography) and forearm blood flow (FBF, venous occlusion plethysmography) were assessed in premenopausal female adults with obesity (n=5, 25±3 yrs, 37±1 kg/m2, 48±1% body fat) and without obesity [n=19, 23±1 yrs, 23±1 kg/m2, (33±2% body fat, n=8)]. Data were combined from two cohorts (IRB #2022525, 2011312) to test present hypotheses. Participants completed two trials consisting of a 2-min cold pressor test (CPT) during baseline normoxia (98±1% SpO2) and following 3-5 min of steady-state hypoxia (0.10±0.01 FiO2, 82±1% SpO2). FBF was normalized for BP (forearm vascular conductance, FVC) and a change in FVC during the last 1-min of CPT was calculated (ΔFVC). The main effect of group (obese, non-obese), condition (normoxia, hypoxia) and the interaction of group and condition were compared using a two-way repeated measures ANOVA. Results: In female participants without obesity, ΔFVC during normoxia was attenuated during hypoxia (-0.57±0.19 vs +0.36±0.34 mL/dL/100mmHg/min; p=0.009). Conversely, in female participants with obesity, ΔFVC during normoxia did not differ from the response during hypoxia (-0.31±0.46 vs -0.87±0.34 mL/dL/100mmHg/min; p=0.382). Group differences in ΔFVC were not observed during normoxia (p=0.657), but were present during hypoxia (p=0.039). Conclusion: Sympathetically-mediated vasoconstriction is attenuated during steady-state hypoxia in premenopausal females without obesity, whereas this response is not observed in female adults with obesity. These preliminary data advance our understanding of the impact of obesity on hypoxic vascular control in premenopausal female participants and have implications for conditions in which hypoxia and sympathetic activation are observed ( e.g., sleep apnea, heart failure, COVID-19). NIH HL130339 (JKL), NIH HL153523 (JKL), AHA 909014 (DWJ) This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Hydration as a modulator of renal vascular control during physical work in the heat

Occupational heat stress increases the risk of developing kidney injury (KI), which is due to the development of hyperthermia and/or hypohydration. It is speculated that this KI is caused by a relative mismatch in oxygen supply (i.e., reductions in renal perfusion) and demand (due to increased sodium reabsorption) in the renal tubules. That said, the modulatory role of hydration on renal vascular control during physical work in the heat is largely unknown. Recent observations indicate that ad lib drinking largely prevents hypohydration during simulated occupational heat stress. Thus, we tested the hypothesis that, compared to ad libitum drinking, fluid restriction induces a pro-vasoconstrictor state in the renal vasculature during physical work in the heat.On two occasions, six healthy adults (1 woman) completed 2 h of exercise in a wet bulb globe temperature of 30±0°C, conditions that are commonly experienced by U.S. outdoor workers. Exercise consisted of completing eight circuits involving treadmill walking (10 min) and rowing (5 min) at a workload eliciting an oxygen uptake of 1.2 L/min, the work intensity observed during agriculture work. In the drinking trial (Drink), subjects were provided 237 mL of sport drink every 15 min and drank ad libitum, which is compliant with workplace hydration recommendations. In the fluid restriction trial (NoDrink), no fluid was provided. Rectal temperature and body mass loss were recorded in each trial. Blood pressure and right renal segmental blood velocity (BV, Doppler ultrasound) was measured before, and following 60 and 120 min of exercise. Before and following exercise, a cold pressor test (CPT) was used to assess the renal vasoconstrictor response to sympathetic activation by immersing the subject’s foot in an agitated ice slurry for 2 min. Blood pressure and segmental BV were measured during each minute of the CPT. Segmental artery vascular resistance (VR) was calculated as mean arterial pressure divided by segmental BV. Data presented as mean ± SD.Average rectal temperature was not different between Drink (37.8±0.4°C) and NoDrink (37.9±0.4°C, p=0.517). Body mass loss was greater in NoDrink (3.1±0.7%) vs. Drink (1.8±0.8%, p=0.014). Segmental BV did not change differently between trials (interaction: p=0.651). Segmental VR did not differ between trials before (Drink: 2.7±0.6, NoDrink: 2.5±0.6 mmHg/cm/s) or after 60 (Drink: 2.8±0.7, NoDrink: 2.6±0.6 mmHg/cm/s) and 90 (Drink: 2.5±0.3, NoDrink: 2.3±0.8 mmHg/cm/s) min of exercise (interaction: p=0.988). Peak increases in segmental VR during the CPT did not differ between trials before (Drink: 0.5 ± 0.7, NoDrink: 0.9 ± 0.6 mmHg/cm/s) or after (Drink: 0.4 ± 0.7, NoDrink: 0.4 ± 0.6 mmHg/cm/s) exercise (interaction: p=0.405).These findings preliminarily indicate that fluid replacement does not modify renal vascular control during physical work in the heat. NCT: NCT05458843. Supported by: R01OH011528 This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Parvalbumin interneuron activity drives fast inhibition-induced vasoconstriction followed by slow substance P-mediated vasodilation

The role of parvalbumin (PV) interneurons in vascular control is poorly understood. Here, we investigated the hemodynamic responses elicited by optogenetic stimulation of PV interneurons using electrophysiology, functional magnetic resonance imaging (fMRI), wide-field optical imaging (OIS), and pharmacological applications. As a control, forepaw stimulation was used. Stimulation of PV interneurons in the somatosensory cortex evoked a biphasic fMRI response in the photostimulation site and negative fMRI signals in projection regions. Activation of PV neurons engaged two separable neurovascular mechanisms in the stimulation site. First, an early vasoconstrictive response caused by the PV-driven inhibition is sensitive to the brain state affected by anesthesia or wakefulness. Second, a later ultraslow vasodilation lasting a minute is closely dependent on the sum of interneuron multiunit activities, but is not due to increased metabolism, neural or vascular rebound, or increased glial activity. The ultraslow response is mediated by neuropeptide substance P (SP) released from PV neurons under anesthesia, but disappears during wakefulness, suggesting that SP signaling is important for vascular regulation during sleep. Our findings provide a comprehensive perspective about the role of PV neurons in controlling the vascular response.

A mechanosensitive vascular niche for Drosophila hematopoiesis

Hematopoietic stem and progenitor cells maintain blood cell homeostasis by integrating various cues provided by specialized microenvironments or niches. Biomechanical forces are emerging as key regulators of hematopoiesis. Here, we report that mechanical stimuli provided by blood flow in the vascular niche control Drosophila hematopoiesis. In vascular niche cells, the mechanosensitive channel Piezo transduces mechanical forces through intracellular calcium upregulation, leading to Notch activation and repression of FGF ligand transcription, known to regulate hematopoietic progenitor maintenance. Our results provide insight into how the vascular niche integrates mechanical stimuli to regulate hematopoiesis.

The Influence of Resection Size and Pringle Maneuver on Operating Time and Intraoperative Bleeding in Patients with Colorectal Metastases in the Liver

BACKGROUND: The extent of the resection, whether clamped or non-clamping resection is factor that influences the operating time and intraoperative bleeding, the development of modern techniques for vascular control and resection, and determine of lesser blood loss, morbidity, and mortality. AIM: The aim of this study was to determine the experience of General and Hepatobiliary Surgery Clinic at Aleksandrovska Hospital Sofia, Republic of Bulgaria in the treatment of patients with colorectal metastases in the liver and to compare literature reports on the influence of the extent of resection and Pringle maneuver (IPM) on operating time and perioperative bleeding. MATERIALS AND METHODS: This retrospective study covers the time period from January 01, 2006, until December 31, 2015. A total of 239 patients were included, from which: 179 patients were treated with radical surgery, 5 with palliative intervention, and 55 were subjected on operability exploration. RESULTS: The use of the IPM for vascular control insignificantly influenced the prolonged operative time, while intraoperative blood loss was significantly lower in patients with Pringle &lt;15 min. There was no association between IPM and resection type, while intraoperative blood loss and operating time were significantly greater in patients with major resection. CONCLUSION: Resection size is directly proportional to operating time and perioperative blood loss, but it does not significantly influence perioperative morbidity. The IPM does not influence operating time, while blood loss is significantly lower in the group of patients with Pringle &lt;15 min.

Assessment of a novel biliary-specific near-infrared fluorescent dye (BL-760) for intraoperative detection of bile ducts and biliary leaks during hepatectomy in a preclinical swine model.

Postoperative bile leakage is a common complication of hepatobiliary surgery and frequently requires procedural intervention. Bile-label 760 (BL-760), a novel near-infrared dye, has emerged as a promising tool for identifying biliary structures and leakage, owing to its rapid excretion and strong bile specificity. This study aimed to assess the intraoperative detection of biliary leakage using intravenously administered BL-760 compared with intravenous (IV) and intraductal (ID) indocyanine green (ICG). Laparotomy and segmental hepatectomy with vascular control were performed on two 25-30 kg pigs. ID ICG, IV ICG, and IV BL-760 were administered separately, followed by an examination of the liver parenchyma, cut liver edge, and extrahepatic bile ducts for areas of leakage. The duration of intra- and extrahepatic fluorescence detection was assessed, and the target-to-background (TBR) of the bile ducts to the liver parenchyma was quantitatively measured. In Animal 1, after intraoperative BL-760 injection, three areas of leaking bile were identified within 5 min on the cut liver edge with a TBR of 2.5-3.8 that was not apparent to the naked eye. In contrast, after IV ICG administration, the background parenchymal signal and bleeding obscured the areas of bile leakage. A second dose of BL-760 demonstrated the utility of repeated injections, confirming two of the three previously visualized areas of bile leakage and revealing one previously unseen leak. In Animal 2, neither ID ICG nor IV BL-760 injections showed obvious areas of bile leakage. However, fluorescence signals were observed within the superficial intrahepatic bile ducts after both injections. BL-760 enables the rapid intraoperative visualization of small biliary structures and leaks, with the benefits of fast excretion, repeatable intravenous administration, and high-fluorescence TBR in the liver parenchyma. Potential applications include the identification of bile flow in the portal plate, biliary leak or duct injury, and postoperative monitoring of drain output. A thorough assessment of the intraoperative biliary anatomy could limit the need for postoperative drain placement, a possible contributor to severe complications and postoperative bile leak.