Global benchmarks in primary robotic bariatric surgery redefine quality standards for Roux-en-Y gastric bypass and sleeve gastrectomy.

BACKGROUND: Whether the benefits of the robotic platform in bariatric surgery translate into superior surgical outcomes remains unclear. The aim of this retrospective study was to establish the 'best possible' outcomes for robotic bariatric surgery and compare them with the established laparoscopic benchmarks. METHODS: Benchmark cut-offs were established for consecutive primary robotic bariatric surgery patients of 17 centres across four continents (13 expert centres and 4 learning phase centres) using the 75th percentile of the median outcome values until 90 days after surgery. The benchmark patients had no previous laparotomy, diabetes, sleep apnoea, cardiopathy, renal insufficiency, inflammatory bowel disease, immunosuppression, history of thromboembolic events, BMI greater than 50 kg/m2, or age greater than 65 years. RESULTS: A total of 9097 patients were included, who were mainly female (75.5%) and who had a mean(s.d.) age of 44.7(11.5) years and a mean(s.d.) baseline BMI of 44.6(7.7) kg/m2. In expert centres, 13.74% of the 3020 patients who underwent primary robotic Roux-en-Y gastric bypass and 5.9% of the 4078 patients who underwent primary robotic sleeve gastrectomy presented with greater than or equal to one complication within 90 postoperative days. No patient died and 1.1% of patients had adverse events related to the robotic platform. When compared with laparoscopic benchmarks, robotic Roux-en-Y gastric bypass had lower benchmark cut-offs for hospital stay, postoperative bleeding, and marginal ulceration, but the duration of the operation was 42 min longer. For most surgical outcomes, robotic sleeve gastrectomy outperformed laparoscopic sleeve gastrectomy with a comparable duration of the operation. In robotic learning phase centres, outcomes were within the established benchmarks only for low-risk robotic Roux-en-Y gastric bypass. CONCLUSION: The newly established benchmarks suggest that robotic bariatric surgery may enhance surgical safety compared with laparoscopic bariatric surgery; however, the duration of the operation for robotic Roux-en-Y gastric bypass is longer.

Single anastomosis duodenal switch versus Roux-en-Y gastric bypass in patients with BMI ≥ 50 kg/m2: a multi-centered comparative analysis.

BACKGROUND: Roux-en-Y gastric bypass (RYGB) has consistently demonstrated excellent weight loss and comorbidity resolution. However, outcomes vary based on patient's BMI. Single anastomosis duodeno-ileostomy with sleeve (SADI-S) is a novel procedure with promising short-term results. The long-term outcomes of SADI-S in patients with BMI ≥ 50 kg/m2 are not well described. We aim to compare the safety and efficacy of SADI-S with RYGB in this patient population. METHODS: We performed a multicenter retrospective study of patients with a BMI ≥ 50 kg/m2 who underwent RYGB or SADI-S between 2008 and 2023. Patient demographics, peri- and post-operative characteristics were collected. Complication rates were reported at 6, 12, 24, and 60 months postoperatively. A multivariate linear regression was used to evaluate and compare weight loss outcomes between both procedures. RESULTS: A total of 968 patients (343 RYGB and 625 SADI-S; 68.3% female, age 42.9 ± 12.1 years; BMI 57.3 ± 6.7 kg/m2) with a mean follow-up of 3.6 ± 3.6 years were included. Patients who underwent RYGB were older, more likely to be female, and have a higher rate of sleep apnea (p < 0.001), hypertension (p = 0.015), dyslipidemia (p < 0.001), and type 2 diabetes (p = 0.016) at baseline. The rate of bariatric surgery-specific complications was lower after SADI-S compared to RYGB. We reported no bariatric surgery related deaths after 1 year following both procedures. SADI-S demonstrated statistically higher and sustained weight loss at each time interval compared to RYGB (p < 0.001) even after controlling for multiple confounders. Lastly, the rate of surgical non-responders was lower in the SADI-S cohort. CONCLUSIONS: In our cohort, SADI-S was associated with higher and sustained weight-loss results compared to RYGB. Comorbidity resolution was also higher after SADI-S. Both procedures demonstrate a similar safety profile. Further studies are required to validate the long-term safety of SADI-S compared to other bariatric procedures.

Creating your own line: reflections from early career scientists.

The changing landscape of academia can be difficult to navigate for anyone at any point throughout their career. One thing is certainly clear: effective mentorship is key to ensuring success, fueling scientific curiosity, and creating a sense of community. This article is a collection of personal reflections and stories, offering advice directed to aspiring and junior graduate trainees; it is written by Ph.D. students, postdoctoral researchers, early-stage assistant professors, and life-long educators. The objective of this article is to inform, empower, and inspire the next generation of physiologists.NEW & NOTEWORTHY This article is a collection of personal reflections and stories, offering advice directed to aspiring and junior graduate trainees that is written by Ph.D. students, postdoctoral researchers, early-stage assistant professors, and life-long educators. The objective of this article is to inform, empower, and inspire the next generation of physiologists.

Undergraduate students' perception of cardiorespiratory physiology during exercise: teleological vs. mechanistic thinking.

BACKGROUND: Physiology is widely recognized as a difficult course, which can potentially increase students' withdrawal and failures rates. Several factors are likely contributing to the difficulties in learning physiology, including inherent features of the discipline as well as aspects related to instructions and/or students' perception. With regards to the later, it is currently unknown how students of exercise physiology think and explain physiology in terms of its cause or consequence (i.e., teleological or mechanistic thinking). Therefore, the aims of the present study were to determine 1) whether undergraduate students' perception of cardiorespiratory physiology during exercise follows a predominant teleological or mechanistic thinking, and 2) whether prior enrollment in physiology courses can influence the predominance of teleological vs. mechanistic thinking. METHODS: The test instrument was an online questionnaire about exercise physiology consisting of nine incomplete sentences about exercise physiology where students had to choose between a teleological or a mechanistic complement. The questionnaire was administered to undergraduate students in the following areas: 1) Movement Sciences (n = 152), 2) Health-related (n = 81) and, 3) Health-unrelated programs (n = 64). Students in Movement Sciences and Health-related programs were also analyzed separately in the following categories: 1) students who previously undertook physiology courses, and 2) students who did not take physiology courses. RESULTS: Overall, all groups presented a percentage of teleological thinking above 58%, which is considerably high. Teleological thinking was significantly higher in health-unrelated programs than health-related and movement sciences programs (76 ± 16% vs. 58 ± 26% vs. 61 ± 25%; P < 0.01). Further, students with prior enrollment in physiology classes presented a significantly lower percentage of teleological thinking than students without physiology classes (59 ± 25% vs. 72 ± 22%, respectively; P < 0.01), but the overall teleological reasoning remained predominant. CONCLUSIONS: These results confirm the hypothesis that undergraduate students tend to present teleological as opposed to mechanistic thinking in exercise physiology. Furthermore, although undergraduate students with prior enrollment in physiology classes presented significantly lower teleological thinking, it remained highly predominant suggesting that teleological thinking is partially independent of the degree of familiarity with this discipline.

Acute hypoxia elicits lasting reductions in the sympathetic action potential transduction of arterial blood pressure in males.

Post-hypoxia sympathoexcitation does not elicit corresponding changes in vascular tone, suggesting diminished sympathetic signalling. Blunted sympathetic transduction following acute hypoxia, however, has not been confirmed and the effects of hypoxia on the sympathetic transduction of mean arterial pressure (MAP) as a function of action potential (AP) activity is unknown. We hypothesized that MAP changes would be blunted during acute hypoxia but restored in recovery and asynchronous APs would elicit smaller MAP changes than synchronous APs. Seven healthy males (age: 24 (3) years; BMI: 25 (3) kg/m2 ) underwent 20 min isocapnic hypoxia (PET O2 : 47 (2) mmHg) and 30 min recovery. Multi-unit microneurography (muscle sympathetic nerve activity; MSNA) and continuous wavelet transform with matched mother wavelet was used to detect sympathetic APs during baseline, hypoxia, early (first 7 min) and late (last 7 min) recovery. AP groups were classified as synchronous APs, asynchronous APs (occurring outside an MSNA burst) and no AP activity. Sympathetic transduction of MAP was quantified using signal-averaging, with ΔMAP tracked following AP group cardiac cycles. Following synchronous APs, ΔMAP was reduced in hypoxia (+1.8 (0.9) mmHg) and early recovery (+1.5 (0.7) mmHg) compared with baseline (+3.1 (2.2) mmHg). AP group-by-condition interactions show that at rest asynchronous APs attenuate MAP reductions compared with no AP activity (-0.4 (1.1) vs. -2.2 (1.2) mmHg, respectively), with no difference between AP groups in hypoxia, early or late recovery. Sympathetic transduction of MAP is blunted in hypoxia and early recovery. At rest, asynchronous sympathetic APs contribute to neural regulation of MAP by attenuating nadir pressure responses. KEY POINTS: Acute isocapnic hypoxia elicits lasting sympathoexcitation that does not correspond to parallel changes in vascular tone, suggesting blunted sympathetic transduction. Signal-averaging techniques track the magnitude and temporal cardiovascular responses following integrated muscle sympathetic nerve activity (MSNA) burst and non-burst cardiac cycles. However, this does not fully characterize the effects of sympathetic action potential (AP) activity on blood pressure control. We show that hypoxia blunts the sympathetic transduction of mean arterial pressure (MAP) following synchronous APs that form integrated MSNA bursts and that sympathetic transduction of MAP remains attenuated into early recovery. At rest, asynchronous APs attenuate the reduction in MAP compared with cardiac cycles following no AP activity, thus asynchronous sympathetic APs appear to contribute to the neural regulation of blood pressure. The results advance our understanding of sympathetic transduction of arterial pressure during and following exposure to acute isocapnic hypoxia in humans.

Endoscopic sleeve gastroplasty for treatment of class 1 and 2 obesity (MERIT): a prospective, multicentre, randomised trial.

BACKGROUND: Endoscopic sleeve gastroplasty (ESG) is an endolumenal, organ-sparing therapy for obesity, with wide global adoption. We aimed to explore the efficacy and safety of ESG with lifestyle modifications compared with lifestyle modifications alone. METHODS: We conducted a randomised clinical trial at nine US centres, enrolling individuals aged 21-65 years with class 1 or class 2 obesity and who agreed to comply with lifelong dietary restrictions. Participants were randomly assigned (1:1·5; with stratified permuted blocks) to ESG with lifestyle modifications (ESG group) or lifestyle modifications alone (control group), with potential retightening or crossover to ESG, respectively, at 52 weeks. Lifestyle modifications included a low-calorie diet and physical activity. Participants in the primary ESG group were followed up for 104 weeks. The primary endpoint at 52 weeks was the percentage of excess weight loss (EWL), with excess weight being that over the ideal weight for a BMI of 25 kg/m2. Secondary endpoints included change in metabolic comorbidities between the groups. We used multiple imputed intention-to-treat analyses with mixed-effects models. Our analyses were done on a per-protocol basis and a modified intention-to-treat basis. The safety population was defined as all participants who underwent ESG (both primary and crossover ESG) up to 52 weeks. FINDINGS: Between Dec 20, 2017, and June 14, 2019, 209 participants were randomly assigned to ESG (n=85) or to control (n=124). At 52 weeks, the primary endpoint of mean percentage of EWL was 49·2% (SD 32·0) for the ESG group and 3·2% (18·6) for the control group (p<0·0001). Mean percentage of total bodyweight loss was 13·6% (8·0) for the ESG group and 0·8% (5·0) for the control group (p<0·0001), and 59 (77%) of 77 participants in the ESG group reached 25% or more of EWL at 52 weeks compared with 13 (12%) of 110 in the control group (p<0·0001). At 52 weeks, 41 (80%) of 51 participants in the ESG group had an improvement in one or more metabolic comorbidities, whereas six (12%) worsened, compared with the control group in which 28 (45%) of 62 participants had similar improvement, whereas 31 (50%) worsened. At 104 weeks, 41 (68%) of 60 participants in the ESG group maintained 25% or more of EWL. ESG-related serious adverse events occurred in three (2%) of 131 participants, without mortality or need for intensive care or surgery. INTERPRETATION: ESG is a safe intervention that resulted in significant weight loss, maintained at 104 weeks, with important improvements in metabolic comorbidities. ESG should be considered as a synergistic weight loss intervention for patients with class 1 or class 2 obesity. This trial is registered with ClinicalTrials.gov, NCT03406975. FUNDING: Apollo Endosurgery, Mayo Clinic.

A single high-fat Western meal modulates vascular responsiveness to sympathetic activation at rest and during exercise in humans: a randomized controlled trial.

A single high-fat Western meal transiently reduces endothelium-dependent vasodilation at rest, but the interaction with sympathetic vasoconstrictor activity during exercise remains unknown. Herein, we tested the hypothesis that a single high-fat Western meal would impair the ability of contracting skeletal muscle to offset vascular responsiveness to sympathetic activation during exercise, termed functional sympatholysis. In 18 (10 females/8 males) healthy young adults, forearm blood flow (Doppler ultrasound) and beat-to-beat arterial pressure (photoplethysmography) were measured during lower-body negative pressure (LBNP; -20 mmHg) applied at rest and simultaneously during low (15% maximum contraction) and moderate (30% maximum contraction)-intensity rhythmic handgrip exercise. The magnitude of sympatholysis was calculated as the difference of LBNP-induced changes in forearm vascular conductance (FVC) between handgrip and rest. Experiments were performed preprandial and 1 h, 2 h, and 3 h after a high- or low-fat meal. In the preprandial state, LBNP decreased resting FVC (Δ-54 ± 10%), and these responses were attenuated during low (Δ-17 ± 7%)- and moderate (Δ-8 ± 6%)-intensity handgrip exercise. Following a high-fat meal, LBNP induced attenuated decreases in resting FVC (3 h postprandial, Δ-47 ± 10%, P = 0.002 vs. preprandial) and blunted attenuation of FVC during low (3 h postprandial, Δ-23 ± 8%, P = 0.001 vs. preprandial)- and moderate (3 h postprandial, Δ-16 ± 6%, P < 0.001 vs. preprandial)-intensity handgrip exercise. The high-fat meal attenuated the magnitude of sympatholysis during low (preprandial, 38 ± 7 vs. 3 h postprandial, 23 ± 8%, P < 0.001)- and moderate (preprandial, 46 ± 11 vs. 3 h postprandial, 31 ± 10%, P < 0.001)-intensity handgrip exercise. The low-fat meal had no impact on these responses. In conclusion, a single high-fat Western meal modulates sympathetic vasoconstriction at rest and during low- and moderate-intensity handgrip exercise in young healthy adults.NEW & NOTEWORTHY We observed that a single high-fat Western meal, but not an isocaloric low-fat meal, attenuated the sympathetic vasoconstriction at rest and the ability of the active skeletal muscle to counteract the vascular responsiveness to sympathetic activation (i.e., functional sympatholysis) during low- and moderate-intensity rhythmic handgrip exercise in healthy young adults. Our findings highlight the potential deleterious vascular effect associated with the consumption of a Western diet.

Asymmetric dimethyl arginine in captive owl monkeys (Aotus sp).

Only four of 40 animals had measurable asymmetric dimethyl arginine (ADMA) levels. The young primate had the lowest value (53.4 ng/ml) when compared with the two adults (218.8 ± 9.3 ng/ml) and the elderly one (320.5 ng/ml). The ADMA levels in this study may relate to the echocardiographic abnormalities found, and possible hypertensive individuals.

Adiponectin levels in captive Owl Monkeys (Aotus sp.).

The mean serum value of adiponectin in captive Aotus sp. is 541.99 ng/mL ± 73.05. There is no influence of sex or age, but there is a moderate positive correlation between body weight and adiponectin levels in males.

Implementing novel modalities into an institutional enhanced recovery after bariatric surgery (ERABS) protocol.

INTRODUCTION: Enhanced recovery after bariatric surgery pathways are associated with improved postoperative outcomes. This study aims to assess efficacy and safety of three novel protocol contributions (transversus abdominis plane blocks, ketamine and fosaprepitant), as well as their impact on length of stay (LOS) and on postoperative complications. METHODS: Effectiveness and safety were retrospectively investigated in patients who underwent Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG) over a 6-year period in a single institution. Group 1 patients were not exposed to any of our suggested interventions, whereas Group 2 were exposed to all of three. RESULTS: Between January 2015 and August 2021, 1480 patients underwent primary SG (77.6%) or RYGB (22.4%); of those, 1132 (76.5%) and 348 (23.5%) were in Groups 1 and 2, respectively. Mean BMI and age were 45.87 versus 43.65 kg/m2 and 45.53 versus 44.99 years in groups 1 and 2, respectively. Suggested interventions were associated with lower operative times (84.79 ± 24.21 vs. 80.78 ± 32.8 min, p = 0.025). In Group 2, the mean LOS decreased in 0.18 day (1.79 ± 1.04 vs. 1.60 ± 0.90; p = 0.004). Overall complication rates were 8% and 8.6% for groups 1 and 2, respectively; readmission rates were 5.7% (64 pts) vs. 7.2% (25 pts), p > 0.05. Reoperations were less prevalent in Group 2 (1.5% vs. 1.1%; p = 0.79). CONCLUSION: Focus on optimized pain management, allied to a superior PONV control, may be relevant contributors for a lower LOS without negative impacts in complications rates.

Sleeve-Dor Fundoplication - An Innovative Surgical Technique to Avoid the Epidemic Long Term de Novo Gastroesophageal Reflux and Barrett´s Esophagus After Sleeve Gastrectomy for Obesity.

BACKGROUND: Sleeve gastrectomy (SG) in current literature showed an increased risk of "de novo" gastroesophageal reflux disease (GERD) and increased risk for Barrett's esophagus in longer follow-up series, with a possibility of esophageal adenocarcinoma in this population. Adding primarily an anterior Dor Fundoplication to SG (Sleeve-Dor) may protect the patient for future and can potentially avoid these chronic complications for patients with obesity. METHODOLOGY: A standard SG is performed laparoscopically, and a small redundance of the fundus is maintained as a wrap, and this will be fixed to the right crura without dissection of the anatomy of the hiatus. The resulted anterior 180° Dor fundoplication is usually sufficient to relieve or to avoid reflux symptomatic. DISCUSSION: Based on our preliminary and literature experiences, the SG with anterior Dor fundoplication (Sleeve-Dor) procedure could provide favorable safety profile, satisfactory reflux control and good bariatric outcomes. The complication rate is lower compared to published for Nissen Sleeve or Sleeve-Rossetti technique, with no leaks or major complications recorded to date. Sleeve-Dor procedure may be a potential primary and standard surgery for morbidly obese patients, especially for patients with preoperative GERD symptoms without major findings at endoscopy.

Action potential amplitude and baroreflex resetting of action potential clusters mediate hypoxia-induced sympathetic long-term facilitation.

Baroreflex resetting permits sympathetic long-term facilitation (sLTF) following hypoxia; however, baroreflex control of action potential (AP) clusters and AP recruitment patterns facilitating sLTF is unknown. We hypothesized that baroreflex resetting of arterial pressure operating points (OPs) of AP clusters and recruitment of large-amplitude APs would mediate sLTF following hypoxia. Eight men (age: 24 (3) years; body mass index: 24 (3) kg/m2 ) underwent 20 min isocapnic hypoxia ( PETO2${P_{{\rm{ET}}{{\rm{O}}_{\rm{2}}}}}$ : 47 (2) mmHg) and 30 min recovery. Multi-unit microneurography (muscle sympathetic nerve activity; MSNA) and a continuous wavelet transform with matched mother wavelet was used to detect sympathetic APs during baseline, hypoxia, early (first 5 min), and late recovery (last 5 min). AP amplitude (normalized to largest baseline AP amplitude), percentage APs occurring outside a MSNA burst (percentage asynchronous APs), and proportion of APs firing in small (1-3), medium (4-6) and large (7-10) normalized cluster sizes was calculated. Normalized clusters were used to assess baroreflex OPs and sensitivity. Hypoxia increased total MSNA activity, which remained elevated during recovery (P < 0.0001). Baroreflex OPs were shifted rightward for all clusters in recovery, with no effect on slope. Compared to baseline, AP amplitude was elevated by 3 (2)% and 4 (2)% while asynchronous APs were reduced by 9 (5)% and 7 (6)% in early and late recovery, respectively. In early recovery, the proportion of APs firing in large clusters was increased compared to baseline. Hypoxia-induced sLTF is mediated by baroreflex resetting of AP clusters to higher OPs, reduced asynchronous AP firing, and increased contribution from large-amplitude APs. KEY POINTS: Acute isocapnic hypoxia resets the arterial baroreflex and permits long-lasting sympathoexcitation, termed sympathetic long-term facilitation. Our understanding of sympathetic long-term facilitation following hypoxia in humans is based on multiunit muscle sympathetic nerve activity and does not fully characterize the underlying baroreflex control of sympathetic neuronal subpopulations or their discharge/recruitment strategies. We show that sympathetic long-term facilitation is mediated by baroreflex resetting of sympathetic action potential clusters to higher arterial pressure operating points, a reduction in the percentage of action potentials firing asynchronously, and a shift toward larger amplitude action potential activity. The results advance our fundamental understanding of how the sympathetic nervous system mediates sympathetic long-term facilitation following exposure to acute isocapnic hypoxia in humans.

Assessing functional sympatholysis during rhythmic handgrip exercise using Doppler ultrasound and near-infrared spectroscopy: sex differences and test-retest reliability.

The effects of sympathetic activity on vasoconstriction are dampened in active skeletal muscle during exercise, a phenomenon termed functional sympatholysis. Limited work has examined the influence of sex on the magnitude of sympatholysis or the test-retest reliability of measurements. In 16 women and 15 men, forearm blood flow (FBF; Doppler ultrasound), muscle oxygenation (near-infrared spectroscopy, NIRS), and beat-to-beat mean arterial pressure (MAP; photoplethysmography) were measured during lower-body negative pressure (LBNP; -20 mmHg) at rest and simultaneously during rhythmic handgrip exercise (30% maximum contraction). Measures were taken twice within the same visit (separated by 15 min) and repeated on a second visit. Forearm vascular conductance (FVC) was calculated as FBF/MAP. The magnitude of sympatholysis was calculated as the difference of LBNP-induced changes between handgrip and rest. LBNP decreased FBF (Δ-45 ± 15%), FVC (Δ-45 ± 16%), and muscle oxygenation (Δ-14 ± 11%); however, these responses were attenuated when LBNP was applied during rhythmic handgrip exercise (Δ-7 ± 9%, Δ-9 ± 10%, and Δ-6 ± 9%, respectively). The magnitude of sympatholysis was not different between men and women (FBF: 40 ± 16% vs. 35 ± 9%, P = 0.37; FVC: 38 ± 16% vs. 35 ± 11%, P = 0.53; muscle oxygenation: 5 ± 9% vs. 11 ± 10%, P = 0.11). Furthermore, sympatholysis measurements demonstrated good to excellent intraday (intraclass-correlation coefficients; ICC ≥ 0.85) and interday (ICC ≥ 0.72) test-retest reliability (all P ≤ 0.01) in both sexes. The coefficients of variation were larger with NIRS (68-91%) than with Doppler ultrasound (16%-22%) assessments of functional sympatholysis. Collectively, these findings demonstrate that assessments of functional sympatholysis are not impacted by biological sex and that Doppler ultrasound-derived measures of sympatholysis have better within-subject reliability than NIRS-derived measures in young healthy adults.

Sympathetic transduction of blood pressure during graded lower body negative pressure in young healthy adults.

Sympathetic transduction of blood pressure (BP) is correlated negatively with resting muscle sympathetic nerve activity (MSNA) in cross-sectional data, but the acute effects of increasing MSNA are unclear. Sixteen (4 female) healthy adults (26 ± 3 years) underwent continuous measurement of heart rate, BP, and MSNA at rest and during graded lower body negative pressure (LBNP) at -10, -20, and -30 mmHg. Sympathetic transduction of BP was quantified in the time (signal averaging) and frequency (MSNA-BP gain) domains. The proportions of MSNA bursts firing within each tertile of BP were calculated. As expected, LBNP increased MSNA burst frequency (P < 0.01) and burst amplitude (P < 0.02), although the proportions of MSNA bursts firing across each BP tertile remained stable (all P > 0.44). The MSNA-diastolic BP low-frequency transfer function gain (P = 0.25) was unchanged during LBNP; the spectral coherence was increased (P = 0.03). Signal-averaged sympathetic transduction of diastolic BP was unchanged (from 2.1 ± 1.0 at rest to 2.4 ± 1.5, 2.2 ± 1.3, and 2.3 ± 1.4 mmHg; P = 0.43) during LBNP, but diastolic BP responses following nonburst cardiac cycles progressively decreased (from -0.8 ± 0.4 at rest to -1.0 ± 0.6, -1.2 ± 0.6, and -1.6 ± 0.9 mmHg; P < 0.01). As a result, the difference between MSNA burst and nonburst diastolic BP responses was increased (from 2.9 ± 1.4 at rest to 3.4 ± 1.9, 3.4 ± 1.9, and 3.9 ± 2.1 mmHg; P < 0.01). In conclusion, acute increases in MSNA using LBNP did not alter traditional signal-averaged or frequency-domain measures of sympathetic transduction of BP or the proportion of MSNA bursts firing at different BP levels. The factors that determine changes in the firing of MSNA bursts relative to oscillations in BP require further investigation.

Potentiation of GABAergic synaptic transmission by diazepam acutely increases resting beat-to-beat blood pressure variability in young adults.

Resting beat-to-beat blood pressure variability is a powerful predictor of cardiovascular events and end-organ damage. However, its underlying mechanisms remain unknown. Herein, we tested the hypothesis that a potentiation of GABAergic synaptic transmission by diazepam would acutely increase resting beat-to-beat blood pressure variability. In 40 (17 females) young, normotensive subjects, resting beat-to-beat blood pressure (finger photoplethysmography) was continuously measured for 5-10 min, 60 min after the oral administration of either diazepam (10 mg) or placebo. The experiments were conducted in a randomized, double-blinded, and placebo-controlled design. Stroke volume was estimated from the blood pressure waveform (ModelFlow) permitting the calculation of cardiac output and total peripheral resistance. Direct recordings of muscle sympathetic nerve activity (MSNA, microneurography) were obtained in a subset of subjects (n = 13), and spontaneous cardiac and sympathetic baroreflex sensitivity were calculated. Compared with placebo, diazepam significantly increased the standard deviation of systolic blood pressure (4.7 ± 1.4 vs. 5.7 ± 1.5 mmHg, P = 0.001), diastolic blood pressure (3.8 ± 1.2 vs. 4.5 ± 1.2 mmHg, P = 0.007), and mean blood pressure (3.8 ± 1.1 vs. 4.5 ± 1.1 mmHg, P = 0.002), as well as cardiac output (469 ± 149 vs. 626 ± 259 mL/min, P < 0.001) and total peripheral resistance (1.0 ± 0.3 vs. 1.4 ± 0.6 mmHg/L/min, P < 0.001). Similar results were found using different indices of variability. Furthermore, diazepam reduced MSNA (placebo: 22 ± 6 vs. diazepam: 18 ± 8 bursts/min, P = 0.025) without affecting the arterial baroreflex control of heart rate (placebo: 18.6 ± 6.7 vs. diazepam: 18.8 ± 7.0 ms/mmHg, P = 0.87) and MSNA (placebo: -3.6 ± 1.2 vs. diazepam: -3.4 ± 1.5 bursts/100 Hb/mmHg, P = 0.55). Importantly, these findings were not impacted by biological sex. We conclude that GABAA receptors modulate resting beat-to-beat blood pressure variability in young adults.

Lipid profile, apolipoproteins A-1 and B in owl monkeys (Aotus infulatus) in captivity.

BACKGROUND: Owl monkeys (Aotus infulatus) are frequently affected by heart diseases and, as in humans, dyslipidemia is one of the predisposing factors for adverse cardiovascular events. In view of this, the study of the lipid profile and plasma apolipoproteins can contribute to the clinical management of this neotropical primate species. METHODS: Lipid profile as well as A-1 and B apolipoprotein values were analyzed in 60 owl monkeys, studying their relationship with body biometry and the presence of cardiac alterations. RESULTS: Animals suspected of having heart disease did not show significant differences (p < .05) in terms of biometry or in relation to lipid profile and apolipoproteins A-1 and B values; however, higher values of LDL and ApoB and ApoB/ApoA-1 were observed in this group. CONCLUSIONS: This study is the first to describe the lipid profile and apolipoprotein values in owl monkeys, and further work will be needed to better elucidate the worthiness of LDL, ApoB, and the ApoB/ApoA-1 ratio in this primate species.

The exercise pressor reflex: An update.

The exercise pressor reflex is a feedback mechanism engaged upon stimulation of mechano- and metabosensitive skeletal muscle afferents. Activation of these afferents elicits a reflex increase in heart rate, blood pressure, and ventilation in an intensity-dependent manner. Consequently, the exercise pressor reflex has been postulated to be one of the principal mediators of the cardiorespiratory responses to exercise. In this updated review, we will discuss classical and recent advancements in our understating of the exercise pressor reflex function in both human and animal models. Particular attention will be paid to the afferent mechanisms and pathways involved during its activation, its effects on different target organs, its potential role in the abnormal cardiovascular response to exercise in diseased states, and the impact of age and biological sex on these responses. Finally, we will highlight some unanswered questions in the literature that may inspire future investigations in the field.

A ligand motif enables differential vascular targeting of endothelial junctions between brain and retina.

Endothelial heterogeneity has important implications in health and disease. Molecular markers selectively expressed in the vasculature of different organs and tissues are currently being explored in targeted therapies with promising results in preclinical and clinical studies. Noteworthy is the role that combinatorial approaches such as phage display have had in identifying such markers by using phage as nanoparticles and surrogates for billions of different peptides, screening noninvasively the vascular lumen for binding sites. Here, we show that a new peptide motif that emerged from such combinatorial screening of the vasculature binds selectively to blood vessels in the brain in vivo but not to vessels in other organs. Peptides containing a conserved motif in which amino acids Phenylalanine-Arginine-Tryptophan (FRW) predominate could be visualized by transmission electron microscopy bound to the junctions between endothelial cells in all areas of the brain, including the optic nerve, but not in other barrier-containing tissues, such as intestines and testis. Remarkably, peptides containing the motif do not bind to vessels in the retina, implying an important molecular difference between these two vascular barriers. Furthermore, the peptide allows for in vivo imaging, demonstrating that new tools for studying and imaging the brain are likely to emerge from this motif.

Vitamins C and E Associated With Cryotherapy in the Recovery of the Inflammatory Response After Resistance Exercise: A Randomized Clinical Trial.

ABSTRACT: de Brito, E, Teixeira, AdO, Righi, NC, Paulitcth, FdS, da Silva, AMV, and Signori, LU. Vitamins C and E associated with cryotherapy in the recovery of the inflammatory response after resistance exercise: A randomized clinical trial. J Strength Cond Res 36(1): 135-141, 2022-The objective of this research was to compare the effects of cryotherapy associated with vitamins (C and E) on the recovery of the inflammatory response from the resistance exercise (RE) session of untrained volunteers. Fourteen subjects (26.2 ± 5 years old, 25.8 ± 3 kg·m-2) underwent 4 sessions of RE with different forms of recovery. The RE consisted of 4 sets of 10 maximal repetitions for each exercise (extensor bench, squat, and leg press). The recoveries were randomized and comprised the passive (control), with vitamins C (1 g) and E (800 UI) supplementation 40 minutes before exercise, with cryotherapy (immersion in water 15° C for 10 minutes), and the association (vitamins and cryotherapy). Hemogram, inflammatory markers (C-reactive protein and creatine kinase [CK]), and parameters of oxidative stress (lipid peroxidation [LPO] and antioxidant capacity against radical peroxyl) were evaluated before (baseline) and after (0, 30, and 120 minutes) the RE sessions. Muscle pain (primary outcome) was evaluated 24 hours after exercise. C-reactive protein (p = 0.010) and LPO (p < 0.001) increased (120 minutes) only in passive recovery. Recovery with cryotherapy (30 minutes), with vitamins and the association (0 and 30 minutes) delayed increases in CK (p < 0.001). Antioxidant capacity against radical peroxyl increased (30 minutes) only in recovery with the association (p < 0.011). The pain decreased in the recoveries with cryotherapy and association (p < 0.001). The association of vitamins (C and E) with cryotherapy attenuated the inflammatory response and pain, favoring recovery after an acute RE session.

Muscle sympathetic single-unit responses during rhythmic handgrip exercise and isocapnic hypoxia in males: the role of sympathoexcitation magnitude.

A small proportion of postganglionic muscle sympathetic single units can be inhibited during sympathoexcitatory stressors in humans. However, whether these responses are dependent on the specific stressor or the level of sympathoexcitation remains unclear. We hypothesize that, when matched by sympathoexcitatory magnitude, different stressors can evoke similar proportions of inhibited single units. Multiunit and single-unit muscle sympathetic nerve activity (MSNA) were recorded in seven healthy young males at baseline and during 1) rhythmic handgrip exercise (40% of maximum voluntary contraction) and 2) acute isocapnic hypoxia (partial pressure of end-tidal O2 47 ± 3 mmHg). Single units were classified as activated, nonresponsive, or inhibited if the spike frequency was above, within, or below the baseline variability, respectively. By design, rhythmic handgrip and isocapnic hypoxia similarly increased multiunit total MSNA [Δ273 ± 208 vs. Δ254 ± 193 arbitrary units (AU), P = 0.84] and single-unit spike frequency (Δ8 ± 10 vs. Δ12 ± 13 spikes/min, P = 0.12). Among 19 identified single units, the proportions of activated (47% vs. 68%), nonresponsive (32% vs. 16%), and inhibited (21% vs. 16%) single units were not different between rhythmic handgrip and isocapnic hypoxia (P = 0.42). However, only 9 (47%) single units behaved with concordant response patterns across both stressors (7 activated, 1 nonresponsive, and 1 inhibited during both stressors). During the 1-min epoch with the highest increase in total MSNA during hypoxia (Δ595 ± 282 AU, P < 0.01) only one single unit was inhibited. These findings suggest that the proportions of muscle sympathetic single units inhibited during stress are associated with the level of sympathoexcitation and not the stressor per se in healthy young males.NEW & NOTEWORTHY Subpopulations of muscle sympathetic single units can be inhibited during mild sympathoexcitatory stress. We demonstrate that rhythmic handgrip exercise and isocapnic hypoxia, when matched by multiunit sympathoexcitation, induce similar proportions of single-unit inhibition, highlighting that heterogeneous single-unit response patterns are related to the level of sympathoexcitation independent of the stressor type. Interestingly, only 47% of single units behaved with concordant response patterns between stressors, suggesting the potential for functional specificity within the postganglionic neuronal pool.