Exposure to passive heat and cold stress differentially modulates cerebrovascular-CO2 responsiveness.

Heat and cold stress influence cerebral blood flow (CBF) regulatory factors (e.g., arterial CO2 partial pressure). However, it is unclear whether the CBF response to a CO2 stimulus (i.e., cerebrovascular-CO2 responsiveness) is maintained under different thermal conditions. This study aimed to compare cerebrovascular-CO2 responsiveness between normothermia, passive heat, and cold stress conditions. Sixteen participants (8 females; 25 ± 7 yr) completed two experimental sessions (randomized) comprising normothermic and either passive heat or cold stress conditions. Middle and posterior cerebral artery velocity (MCAv, PCAv) were measured during rest, hypercapnia (5% CO2 inhalation), and hypocapnia (voluntary hyperventilation to an end-tidal CO2 of 30 mmHg). The linear slope of the cerebral blood velocity (CBv) response to changing end-tidal CO2 was calculated to measure cerebrovascular-CO2 responsiveness, and cerebrovascular conductance (CVC) was used to examine responsiveness independent of blood pressure. CBv-CVC-CO2 responsiveness to hypocapnia was greater during heat stress compared with cold stress (MCA: +0.05 ± 0.08 cm/s/mmHg/mmHg, P = 0.04; PCA: +0.02 ± 0.02 cm/s/mmHg/mmHg, P = 0.002). CBv-CO2 responsiveness to hypercapnia decreased during heat stress (MCA: -0.67 ± 0.89 cm/s/mmHg, P = 0.02; PCA: -0.64 ± 0.62 cm/s/mmHg; P = 0.01) and increased during cold stress (MCA: +0.98 ± 1.33 cm/s/mmHg, P = 0.03; PCA: +1.00 ± 0.82 cm/s/mmHg; P = 0.01) compared with normothermia. However, CBv-CVC-CO2 responsiveness to hypercapnia was not different between thermal conditions (P > 0.08). Overall, passive heat, but not cold, stress challenges the maintenance of cerebral perfusion. A greater cerebrovascular responsiveness to hypocapnia during heat stress likely reduces an already impaired cerebrovascular reserve capacity and may contribute to adverse events (e.g., syncope).NEW & NOTEWORTHY This study demonstrates that thermoregulatory-driven perfusion pressure changes, from either cold or heat stress, impact cerebrovascular responsiveness to hypercapnia. Compared with cold stress, heat stress poses a greater challenge to the maintenance of cerebral perfusion during hypocapnia, challenging cerebrovascular reserve capacity while increasing cerebrovascular-CO2 responsiveness. This likely exacerbates cerebral hypoperfusion during heat stress since hyperthermia-induced hyperventilation results in hypocapnia. No regional differences in middle and posterior cerebral artery responsiveness were found with thermal stress.

Targeting workload to ameliorate risk of heat stress in industrial sugarcane workers.

OBJECTIVE: The aim of this study was to quantify the physiological workload of manual laborers in industrial sugarcane and assess the effect of receiving a rest, shade, and hydration intervention to reduce heat stress exposure risk. METHODS: In an observational study, physiological workload was evaluated for burned cane cutters (BCC), seed cutters (SC) and drip irrigation repair workers (DIRW) using heart rate (HR) recorded continuously (Polar®) across a work shift. Workers' percentage of maximal HR (%HRmax), time spent in different HR zones, and estimated core temperature (ECTemp) were calculated. The effect of increasing rest across two harvests was evaluated for BCC and SC. RESULTS: A total of 162 workers participated in this study [52 BCC (all male), 71 SC (13 female) and 39 DIRW (16 female)]. Average %HRmax across a work shift was similar between BCC and SC (BCC: 58%, SC: 59%), but lower in DIRW (51%). BCC and SC spent similar proportions of work shifts at hard/very hard intensities (BCC: 13%, SC: 15%), versus DIRW who worked mostly at light (46%) or light-moderate (39%) intensities. SC maximum ECTemp reached 38.2°C, BCC 38.1°C; while DIRW only reached 37.7°C. Females performed at a higher %HRmax than males across work shifts (SC 64% versus 58%; DIRW 55% versus 49%). An additional rest period was associated with a lower average %HRmax across a work shift in BCC. CONCLUSION: In this setting, BCC and SC both undertake very physiologically demanding work. Females maintained a higher workload than male co-workers. Regulated rest periods each hour, with water and shade access, appears to reduce physiological workload/strain.

Menstrual phase influences cerebrovascular responsiveness in females but may not affect sex differences.

Background and aims: Sex differences in the rate and occurrence of cerebrovascular diseases (e.g., stroke) indicate a role for female sex hormones (i.e., oestrogen and progesterone) in cerebrovascular function and regulation. However, it remains unclear how cerebrovascular function differs between the sexes, and between distinct phases of the menstrual cycle. This study aimed to compare cerebrovascular-CO2 responsiveness in 1) females during the early follicular (EF), ovulatory (O) and mid-luteal (ML) phases of their menstrual cycle; and 2) males compared to females during phases of lower oestrogen (EF) and higher oestrogen (O). Methods: Eleven females (25 ± 5 years) complete experimental sessions in the EF (n = 11), O (n = 9) and ML (n = 11) phases of the menstrual cycle. Nine males (22 ± 3 years) completed two experimental sessions, approximately 2 weeks apart for comparison to females. Middle and posterior cerebral artery velocity (MCAv, PCAv) was measured at rest, during two stages of hypercapnia (2% and 5% CO2 inhalation) and hypocapnia (voluntary hyperventilation to an end-tidal CO2 of 30 and 24 mmHg). The linear slope of the cerebral blood velocity response to changes in end-tidal CO2 was calculated to measure cerebrovascular-CO2 responsiveness.. Results: In females, MCAv-CO2 responsiveness to hypocapnia was lower during EF (-.78 ± .45 cm/s/mmHg) when compared to the O phase (-1.17 ± .52 cm/s/mmHg; p < .05) and the ML phase (-1.30 ± .82; p < .05). MCAv-CO2 responsiveness to hypercapnia and hypo-to-hypercapnia, and PCAv-CO2 responsiveness across the CO2 range were similar between menstrual phases (p ≥ .20). MCAv-CO2 responsiveness to hypo-to hypercapnia was greater in females compared to males (3.12 ± .91 cm/s/mmHg vs. 2.31 ± .46 cm/s/mmHg; p = .03), irrespective of menstrual phase (EF or O). Conclusion: Females during O and ML phases have an enhanced vasoconstrictive capacity of the MCA compared to the EF phase. Additionally, biological sex differences can influence cerebrovascular-CO2 responsiveness, dependent on the insonated vessel.

A Systematic Review and Meta-Analysis Examining Whether Changing Ovarian Sex Steroid Hormone Levels Influence Cerebrovascular Function.

Sex differences in cerebrovascular disease rates indicate a possible role for ovarian sex steroid hormones in cerebrovascular function. To synthesise and identify knowledge gaps, a systematic review and meta-analysis was conducted to assess how ovarian sex steroid hormone changes across the lifespan affect cerebrovascular function in women. Three databases (EMBASE, MEDLINE and Web of Science) were systematically searched for studies on adult cerebrovascular function and ovarian sex steroid hormones. Forty-five studies met pre-defined inclusion criteria. Studied hormone groups included hormone replacement therapy (HRT; n = 17), pregnancy (n = 12), menstrual cycle (n = 7), menopause (n = 5), oral contraception (n = 2), and ovarian hyperstimulation (n = 2). Outcome measures included pulsatility index (PI), cerebral blood flow/velocity (CBF), resistance index (RI), cerebral autoregulation, and cerebrovascular reactivity. Meta-analysis was carried out on HRT studies. PI significantly decreased [-0.05, 95% CI: (-0.10, -0.01); p = 0.01] in post-menopausal women undergoing HRT compared to post-menopausal women who were not, though there was considerable heterogeneity (I 2 = 96.8%). No effects of HRT were seen in CBF (p = 0.24) or RI (p = 0.77). This review indicates that HRT improves PI in post-menopausal women. However, there remains insufficient evidence to determine how changing ovarian sex steroid hormone levels affects cerebrovascular function in women during other hormonal phases (e.g., pregnancy, oral contraception).

Corrigendum: Cerebral Hemodynamic and Neurotrophic Factor Responses Are Dependent on the Type of Exercise.

[This corrects the article DOI: 10.3389/fphys.2020.609935.].

Cerebral Hemodynamic and Neurotrophic Factor Responses Are Dependent on the Type of Exercise.

This study examined acute cerebral hemodynamic and circulating neurotrophic factor responses to moderate intensity continuous exercise (MICT), guideline-based high intensity interval exercise (HIIT), and sprint interval exercise (SIT). We hypothesized that the pattern of middle cerebral artery velocity (MCAv) response would differ between interval and continuous exercise, with SIT inducing the smallest increase from rest, while increases in neurotrophic factors would be intensity-dependent. In a randomized crossover design, 24 healthy adults (nine females) performed three exercise protocols: (i) MICT (30 min), (ii) HIIT (4 × 4 min at 85% HRmax), and (iii) SIT (4 × 30 s supramaximal). MCAv significantly increased from rest across MICT (Δ13.1 ± 8.5 cm⋅s-1, p < 0.001) and all bouts of HIIT (Δ15.2 ± 9.8 cm⋅s-1, p < 0.001), but only for the initial bout of SIT (Δ17.3 ± 11.6 cm⋅s-1, p < 0.001). Immediately following each interval bout, MCAv increased (i.e., rebounded) for the SIT (9-14% above rest, p ≤ 0.04), but not HIIT protocol. SIT alone induced significant elevations from rest to end-exercise in vascular endothelial growth factor (VEGF; Δ28 ± 36%, p = 0.017) and brain-derived neurotrophic factor (BDNF, Δ149% ± 162%, p < 0.001) and there were greater increases in lactate than in either other protocol (>5-fold greater in SIT, p < 0.001), alongside a small significant reduction at the end of active recovery in insulin-like growth factor 1 (IGF-1, Δ22 ± 21%, p = 0.002). In conclusion, while the nature of the response may differ, both guideline-based and sprint-based interval exercise have the potential to induce significant changes in factors linked to improved cerebrovascular and brain health.

Effects of Shared Decision Making on Opioid Prescribing After Hysterectomy.

OBJECTIVE: To evaluate the effects of shared decision making using a simple decision aid for opioid prescribing after hysterectomy. METHODS: We conducted a prospective quality initiative study including all patients undergoing hysterectomy for benign, nonobstetric indications between March 1, 2018, and July 31, 2018, at our academic institution. Using a visual decision aid, patients received uniform education regarding postoperative pain management. They were then educated on the department's guidelines regarding the maximum number of tablets recommended per prescription and the mean number of opioid tablets used by a similar cohort of patients in a previously published study at our institution. Patients were then asked to choose their desired number of tablets to receive on discharge. Structured telephone interviews were conducted 14 days after surgery. The primary outcome was total opioids prescribed before compared with after implementation of the decision aid. Secondary outcomes included opioid consumption, patient satisfaction, and refill requests after intervention implementation. RESULTS: Of 170 eligible patients, 159 (93.5%) used the decision aid (one patient who used the decision aid was subsequently excluded from the analysis owing to significant perioperative complications), including 110 (69.6%) laparoscopic, 40 (25.3%) vaginal, and eight (5.3%) abdominal hysterectomies. Telephone surveys were completed for 89.2% (n=141) of participants. Student's t-test showed that patients who participated in the decision aid (post-decision aid cohort) were discharged with significantly fewer oral morphine equivalents than patients who underwent hysterectomy before implementation of the decision aid (pre-decision aid cohort) (92±35 vs 160±81, P<.01), with no significant change in the number of requested refills (9.5% [n=15] vs 5.7% [n=14], P=.15). In the post-decision aid cohort, 76.6% of patients (n=121) chose fewer tablets than the guideline-allotted maximum. Approximately 76% of patients (n=102) reported having leftover tablets. CONCLUSION: This quality improvement initiative illustrates that a simple decision aid can result in a significant decrease in opioid prescribing without compromising patient satisfaction or postoperative pain management.

Opioid Prescribing Patterns, Patient Use, and Postoperative Pain After Hysterectomy for Benign Indications.

OBJECTIVE: To quantify physician prescribing patterns and patient opioid use in the 2 weeks after hysterectomy at an academic institution and to determine whether patient factors predict postsurgical opioid use and pain recovery. METHODS: We conducted a prospective quality initiative study by recruiting all English-speaking patients undergoing hysterectomy for benign, nonobstetric indications at a university hospital between August 2015 and December 2015, excluding those with major medical morbidities or substance abuse. Before hysterectomy, patients completed the Fibromyalgia Survey, a validated measure of centralized pain. After hysterectomy, opioid use (converted to oral morphine equivalents) and pain scores (0-10 numeric rating scale) were collected by a daily diary and a structured telephone interview 14 days after surgery. Primary outcomes were total opioid prescribed and consumed in the 2 weeks after hysterectomy. Secondary outcomes included daily opioid use and daily pain severity for 14 days after hysterectomy. RESULTS: Of 103 eligible patients, 102 (99%) agreed to participate, including 44 (43.1%) laparoscopic, 42 (41.2%) vaginal, and 16 (15.7%) abdominal hysterectomies. Telephone surveys were completed on 89 (87%) participants; diaries were returned from 60 (59%) participants. Diary nonresponders had different baseline characteristics than nonresponders. Median amount of opioid prescribed was 200 oral morphine equivalents (interquartile range 150-250). Patients reported using approximately half of the opioids prescribed with a median excess of 110 morphine equivalents (interquartile range 40-150). The best fit model of total opioid consumption identified preoperative Fibromyalgia Survey Score, overall body pain, preoperative opioid use, prior endometriosis, abdominal hysterectomy (compared with laparoscopic), and uterine weight as significant predictors. Highest tertile of Fibromyalgia Survey Score was associated with greater daily opioid consumption (13.9 [95% CI 3.0-24.8] greater oral morphine equivalents at baseline, P=.02). CONCLUSION: Gynecologists at a large academic medical center prescribe twice the amount of opioids than the average patient uses after hysterectomy. A personalized approach to prescribing opioids for postoperative pain should be considered.

Risk Factors and Outcomes for Conversion to Laparotomy of Laparoscopic Hysterectomy in Benign Gynecology.

OBJECTIVE: To estimate the incidence and factors for conversion to laparotomy in women scheduled for laparoscopic hysterectomy for benign gynecologic indications and to examine the effect of conversion on patient outcomes. METHODS: A retrospective cohort study of a Michigan multicenter prospective database was abstracted from January 1, 2013, through July 2, 2014. Participants were collected from an all-payer quality and safety database maintained by the Michigan Surgical Quality Collaborative. Women with a preoperative indication of cancer or obstetric indications were excluded. A logistic regression model was used to calculate odds of conversion using patient preoperative and intraoperative attributes. RESULTS: During the study period, 6,992 women underwent an attempted laparoscopic hysterectomy with 3.93% (n=275) converted to laparotomy. After adjusting for socioeconomic differences, hysterectomy indication, and intraoperative factors, there were decreased odds of conversion to laparotomy with use of robotic-assisted laparoscopy compared with traditional laparoscopy (adjusted odds ratio [OR] 0.14, 95% confidence interval [CI] 0.07-0.25) with a predicted risk of conversion of 0.8% compared with 5.4% (P<.001). High-volume surgeons were less likely to convert to laparotomy compared with low- and medium-volume surgeons (adjusted OR 0.66, 95% CI 0.47-0.92) with a predicted risk of conversion of 1.4% compared with 2.25% (P=.015). Conversion was associated with moderate or severe adhesive disease and increasing specimen weight. Conversion was associated with increased rates of surgical site infection, blood transfusion, severe sepsis, and reoperation. CONCLUSION: This analysis demonstrates that conversion to laparotomy is associated with increased odds of postoperative morbidity, and robotic assistance and surgeon volume are strongly associated with decreased odds of conversion.

A Favorability Score for Vaginal Hysterectomy in a Statewide Collaborative.

STUDY OBJECTIVE: Because it is associated with fewer complications and more rapid recovery, the vaginal approach is preferred for benign hysterectomy. Patient characteristics that traditionally favor a vaginal approach include adequate vaginal access, small uterine size, and low suspicion for extrauterine disease. However, the low proportion of hysterectomies performed vaginally in the United States suggests that these data are not routinely applied in clinical practice. We sought to analyze the association of parity, prior pelvic surgery, and uterine weight with the use of the vaginal, laparoscopic, robotic, and abdominal approaches to hysterectomy. DESIGN: A retrospective cohort study (Canadian Task Force classification II-2). SETTING: The Michigan Surgical Quality Collaborative is a statewide organization of 52 academic and community hospitals in Michigan funded by Blue Cross and Blue Shield of Michigan/Blue Care Network, including patients from all insurance payers. PATIENTS: Five thousand six hundred eight women undergoing hysterectomy for benign gynecologic conditions from January 1, 2013, through December 8, 2013, and included in the Michigan Surgical Quality Collaborative. INTERVENTIONS: To assess potential for vaginal hysterectomy, a favorability score of 0, 1, 2, or 3 was calculated by summing 1 point each for parity ≥1, no prior pelvic surgery, and uterine weight <250 g. Frequencies of surgical approaches to hysterectomy were compared using chi-square tests across favorability scores. MEASUREMENTS AND MAIN RESULTS: The use of robotic hysterectomy was most frequent (41.9%, n = 2349/5608) followed by abdominal (19.7%, n = 1103/5608), laparoscopic (14.4%, n = 809/5608), vaginal (13.5%, n = 758/5608), and laparoscopic-assisted vaginal (10.5%, n = 589/5608) hysterectomy. With favorability scores of 0, 1, 2, and 3, vaginal hysterectomy was performed in 0.6% (n = 1/167), 5% (n = 66/1324), 13.7% (n = 415/3036), and 25.5% (n = 276/1081) of cases and abdominal hysterectomy in 41.9% (n = 70/167), 30.8% (n = 408/1324), 17.5% (n = 531/3036), and 8.7% (n = 94/1081), respectively. There was little variation in the rates of laparoscopic hysterectomy (13.3%-16.8%, p = .429) and robotic hysterectomy (39.5%-42.4%, p = .518) across favorability scores. CONCLUSION: In a population of women undergoing hysterectomy in the state of Michigan, the use of vaginal and abdominal hysterectomy varied with respect to parity, prior pelvic surgery, and uterine weight, but there was little variation in the use of laparoscopic and robotic approaches. The favorability score could potentially be used as a quality improvement tool to evaluate practice patterns with respect to the use of various surgical approaches to hysterectomy.

New paradigms in the diagnosis and management of endometriosis.

PURPOSE OF REVIEW: Endometriosis is a common gynecologic condition estimated to affect 10-15% of reproductive-aged women, 30% of women with subfertility, and 80% of women with chronic pelvic pain. Although mainstays of diagnosis and treatment are still commonly applied, there have been various advances in the modalities of diagnosis and management of this complex condition. This article provides an updated review of novel findings regarding the diagnosis and management of this challenging disease. RECENT FINDINGS: Despite an abundance of studies on noninvasive diagnostic markers for endometriosis, there is no single imaging study, biomarker or panel of biomarkers that has been validated for clinical diagnosis. New technologies, such as use of indocyanine green and fluorescence, which visualize neovascularization often associated with endometriosis may improve diagnostic detection of endometriosis at the time surgery, but have not been demonstrated to improve pain outcomes after surgery. Hormone suppression remains the mainstay therapy prior to and following surgery. Although most methods demonstrate similar efficacy in reducing endometriosis-associated pain, newer pharmacologic agents that may prove advantageous include oral gonadotropin receptor antagonists, selective progesterone receptor modulators, and angiogenesis inhibitors. SUMMARY: Although there have been some advances in the study of noninvasive imaging and biomarkers, more investigation into effective modalities are being conducted and are needed.

Laparoscopic-assisted vaginal hysterectomy in a patient with placenta percreta.

Placenta percreta is a problem encountered with increasing frequency due to the rising rate of cesarean delivery. Conservative management of this condition is associated with decreased perioperative morbidity. When hysterectomy is necessary, a laparoscopic approach can provide additional benefits. We present the case of a woman with placenta percreta with bladder invasion who was undergoing conservative management and then required delayed hysterectomy. Laparoscopic-assisted vaginal hysterectomy was successfully performed. We review the techniques used to ensure a good outcome and the advantages of a minimally invasive approach to hysterectomy in this patient with placenta percreta.

Ability of honeybee, Apis mellifera, to detect and discriminate odors of varieties of canola (Brassica rapa and Brassica napus) and snapdragon flowers (Antirrhinum majus).

Honeybees (Apis mellifera) use odors to identify and discriminate among flowers during foraging. This series of experiments examined the ability of bees to detect and discriminate among the floral odors of different varieties of two species of canola (Brassica rapa and Brassica napus) and also among three varieties of snapdragons (Antirhinnum majus). Individual worker honeybees were trained using a proboscis extension assay. The ability of bees to distinguish a floral odor from an air stimulus during training increased as the number of flowers used during training increased. Bees conditioned to the odor of one variety of flower were asked to discriminate it from the odors of other flowers in two different training assays. Bees were unable to discriminate among flowers at the level of variety in a randomized presentation of a reinforced floral odor and an unreinforced floral odor. In the second type of assay, bees were trained with one floral variety for 40 trials without reinforcement and then tested with the same variety or with other varieties and species. If a bee had been trained with a variety of canola, it was unable to differentiate the odor of one canola flower from the odor of other canola flowers, but it could differentiate canola from the odor of a snapdragon flower. Bees trained with the odor of snapdragon flowers readily differentiated the odor of one variety of a snapdragon from the odor of other varieties of snapdragons and also canola flowers. Our study suggests that both intensity and odor quality affect the ability of honeybees to differentiate among floral perfumes.