An evaluation of the effects of localised skin cooling on microvascular, inflammatory, structural, and perceptual responses to sustained mechanical loading of the sacrum: A study protocol.

This study protocol aims to investigate how localised cooling influences the skin's microvascular, inflammatory, structural, and perceptual tolerance to sustained mechanical loading at the sacrum, evaluating factors such as morphology, physiology, and perceptual responses. The protocol will be tested on individuals of different age, sex, skin tone and clinical status, using a repeated-measure design with three participants cohorts: i) young healthy (n = 35); ii) older healthy (n = 35); iii) spinal cord injured (SCI, n = 35). Participants will complete three testing sessions during which their sacrum will be mechanically loaded (60 mmHg; 45 min) and unloaded (20 min) with a custom-built thermal probe, causing pressure-induced ischemia and post-occlusive reactive hyperaemia. Testing sessions will differ by the probe's temperature, which will be set to either 38°C (no cooling), 24°C (mild cooling), or 16°C (strong cooling). We will measure skin blood flow (via Laser Doppler Flowmetry; 40 Hz); pro- and anti-inflammatory biomarkers in skin sebum (Sebutape); structural skin properties (Optical Coherence Tomography); and ratings of thermal sensation, comfort, and acceptance (Likert Scales); throughout the loading and unloading phases. Changes in post-occlusive reactive hyperaemia will be considered as the primary outcome and data will be analysed for the independent and interactive effects of stimuli's temperature and of participant group on within- and between-subject mean differences (and 95% Confidence Intervals) in peak hyperaemia, by means of a 2-way mixed model ANOVA (or Friedman). Regression models will also be developed to assess the relationship between absolute cooling temperatures and peak hyperaemia. Secondary outcomes will be within- and between-subject mean changes in biomarkers' expression, skin structural and perceptual responses. This analysis will help identifying physiological and perceptual thresholds for the protective effects of cooling from mechanically induced damage underlying the development of pressure ulcers in individuals varying in age and clinical status.

Voluntary torque production is unaffected by changes in local thermal sensation during normothermia and hyperthermia.

NEW FINDINGS: What is the central question of this study? Hyperthermia reduces the human capacity to produce muscular force, which is associated with decreased neural drive: does mitigating a reduction in neural drive by altering localised thermal sensation help to preserve voluntary force output? What is the main finding and its importance? Altering thermal sensation by cooling and heating the head independent of core temperature did not change neural drive or benefit voluntary force production. Head cooling did slow the rate of rise in core temperature during heating, which may have practical applications in passive settings. ABSTRACT: This study investigated altered local head and neck thermal sensation on maximal and rapid torque production during voluntary contractions. Nine participants completed four visits in two environmental conditions: at rectal temperatures ∼39.5°C in hot (HOT; ∼50°C, ∼39% relative humidity) and ∼37°C in thermoneutral (NEU; ∼22°C, ∼46% relative humidity) conditions. Local thermal sensation was manipulated by heating in thermoneutral conditions and cooling in hot conditions. Evoked twitches and octets were delivered at rest. Maximum voluntary torque (MVT), normalised surface electromyography (EMG) and voluntary activation (VA) were assessed during brief maximal isometric voluntary contractions of the knee extensors. Rate of torque development (RTD) and EMG were measured during rapid voluntary contractions. MVT (P = 0.463) and RTD (P = 0.061) were similar between environmental conditions despite reduced VA (-6%; P = 0.047) and EMG at MVT (-31%; P = 0.019). EMG in the rapid voluntary contractions was also lower in HOT versus NEU during the initial 100 ms (-24%; P = 0.035) and 150 ms (-26%; P = 0.035). Evoked twitch (+70%; P < 0.001) and octet (+27%; P < 0.001) RTD during the initial 50 ms were greater in the HOT compared to NEU conditions, in addition to a faster relaxation rate of the muscle (-33%; P < 0.001). In conclusion, hyperthermia reduced neural drive without affecting voluntary torque, likely due to the compensatory effects of improved intrinsic contractile function and faster contraction and relaxation rates of the knee extensors. Changes in local thermal perception of the head and neck whilst hyperthermic or normothermic did not affect voluntary torque.

Heat acclimation reduces the effects of whole-body hyperthermia on knee-extensor relaxation rate, but does not affect voluntary torque production.

PURPOSE: This study investigated the effects of acute hyperthermia and heat acclimation (HA) on maximal and rapid voluntary torque production, and their neuromuscular determinants. METHODS: Ten participants completed 10 days of isothermic HA (50 °C, 50% rh) and had their knee-extensor neuromuscular function assessed in normothermic and hyperthermic conditions, pre-, after 5 and after 10 days of HA. Electrically evoked twitch and octet (300 Hz) contractions were delivered at rest. Maximum voluntary torque (MVT), surface electromyography (EMG) normalised to maximal M-wave, and voluntary activation (VA) were assessed during brief maximal isometric voluntary contractions. Rate of torque development (RTD) and normalised EMG were measured during rapid voluntary contractions. RESULTS: Acute hyperthermia reduced neural drive (EMG at MVT and during rapid voluntary contractions; P < 0.05), increased evoked torques (P < 0.05), and shortened contraction and relaxation rates (P < 0.05). HA lowered resting rectal temperature and heart rate after 10 days (P < 0.05), and increased sweating rate after 5 and 10 days (P < 0.05), no differences were observed between 5 and 10 days. The hyperthermia-induced reduction in twitch half-relaxation was attenuated after 5 and 10 days of HA, but there were no other effects on neuromuscular function either in normothermic or hyperthermic conditions. CONCLUSION: HA-induced favourable adaptations to the heat after 5 and 10 days of exposure, but there was no measurable benefit on voluntary neuromuscular function in normothermic or hyperthermic conditions. HA did reduce the hyperthermic-induced reduction in twitch half-relaxation time, which may benefit twitch force summation and thus help preserve voluntary torque in hot environmental conditions.

Progressive hyperthermia elicits distinct responses in maximum and rapid torque production.

OBJECTIVES: To investigate the effect of progressive whole-body hyperthermia on maximal, and rapid voluntary torque production, and their neuromuscular determinants. DESIGN: Repeated measures, randomised. METHODS: Nine participants performed sets of neuromuscular assessments in HOT conditions (∼50°C, ∼35% relative humidity) at rectal temperatures (Tre) of 37, 38.5 and 39.5°C and in CON conditions (∼22°C, ∼35% relative humidity) at a Tre of ∼37°C and pre-determined comparative time-points. Electrically evoked twitch (single impulse) and octet (8 impulses at 300Hz) responses were measured at rest. Maximum voluntary torque (MVT), surface electromyography (EMG) normalised to maximal M-wave, and voluntary activation (VA) were measured during 3-5s isometric maximal voluntary contractions. Rate of torque development (RTD) and normalised EMG were measured during rapid voluntary isometric contractions from rest. RESULTS: All neuromuscular variables were unaffected by time in CON. In HOT, MVT, normalised EMG at MVT and VA were lower at 39.5°C compared to 37°C (p<0.05). Early- (0-50ms) and middle- (50-100ms) phase voluntary RTD were unaffected by increased Tre (p>0.05), despite lower normalised EMG at Tre 39.5°C (p<0.05) in rapid contractions. In contrast, late-phase (100-150ms) voluntary RTD was lower at 38.5°C and 39.5°C compared to 37°C (p<0.05) in HOT. Evoked twitch and octet RTD increased with increased Tre (p<0.05). CONCLUSIONS: Hyperthermia reduced late-phase voluntary RTD, likely due to reduced neural drive and the reduction in MVT. In contrast, early- and middle-phase voluntary RTD were unaffected by hyperthermia, likely due to the conflicting effects of reduced neural drive but faster intrinsic contractile properties.

The effect of head and neck per-cooling on neuromuscular fatigue following exercise in the heat.

The effect of localised head and neck per-cooling on central and peripheral fatigue during high thermal strain was investigated. Fourteen participants cycled for 60 min at 50% peak oxygen uptake on 3 occasions: thermoneutral control (CON; 18 °C), hot (HOT; 35 °C), and HOT with head and neck cooling (HOTcooling). Maximal voluntary force (MVF) and central activation ratio (CAR) of the knee extensors were measured every 30 s during a sustained maximal voluntary contraction (MVC). Triplet peak force was measured following cycling, before and after the MVC. Rectal temperatures were higher in HOTcooling (39.2 ± 0.6 °C) and HOT (39.3 ± 0.5 °C) than CON (38.1 ± 0.3 °C; P < 0.05). Head and neck thermal sensation was similar in HOTcooling (4.2 ± 1.4) and CON (4.4 ± 0.9; P > 0.05) but lower than HOT (5.9 ± 1.5; P < 0.05). MVF and CAR were lower in HOT than CON throughout the MVC (P < 0.05). MVF and CAR were also lower in HOTcooling than CON at 5, 60, and 120 s, but similar at 30 and 90 s into the MVC (P > 0.05). Furthermore, they were greater in HOTcooling than HOT at 30 s, whilst triplet peak force was preserved in HOT after MVC. These results provide evidence that central fatigue following exercise in the heat is partially attenuated with head and neck cooling, which may be at the expense of greater peripheral fatigue. Novelty Central fatigue was greatest during hyperthermia. Head and neck cooling partially attenuated the greater central fatigue in the heat. Per-cooling led to more voluntary force production and more peripheral fatigue.

Impairment of Cycling Capacity in the Heat in Well-Trained Endurance Athletes After High-Intensity Short-Term Heat Acclimation.

PURPOSE: To investigate the effects of short-term, high-intensity interval-training (HIIT) heat acclimation (HA). METHODS: Male cyclists/triathletes were assigned into either an HA (n = 13) or a comparison (COMP, n = 10) group. HA completed 3 cycling heat stress tests (HSTs) to exhaustion (60% Wmax; HST1, pre-HA; HST2, post-HA; HST3, 7 d post-HA). HA consisted of 30-min bouts of HIIT cycling (6 min at 50% Wmax, then 12 × 1-min 100%-Wmax bouts with 1-min rests between bouts) on 5 consecutive days. COMP completed HST1 and HST2 only. HST and HA trials were conducted in 35°C/50% relative humidity. Cycling capacity and physiological and perceptual data were recorded. RESULTS: Cycling capacity was impaired after HIIT HA (77.2 [34.2] min vs 56.2 [24.4] min, P = .03) and did not return to baseline after 7 d of no HA (59.2 [37.4] min). Capacity in HST1 and HST2 was similar in COMP (43.5 [8.3] min vs 46.8 [15.7] min, P = .54). HIIT HA lowered resting rectal (37.0°C [0.3°C] vs 36.8°C [0.2°C], P = .05) and body temperature (36.0°C [0.3°C] vs 35.8°C [0.3°C], P = .03) in HST2 compared with HST1 and lowered mean skin temperature (35.4°C [0.5°C] vs 35.1°C [0.3°C], P = .02) and perceived strain on day 5 compared with day 1 of HA. All other data were unaffected. CONCLUSIONS: Cycling capacity was impaired in the heat after 5 d of consecutive HIIT HA despite some heat adaptation. Based on data, this approach is not recommended for athletes preparing to compete in the heat; however, it is possible that it may be beneficial if a state of overreaching is avoided.

Assessment of Minimum Inhibitory Concentrations of Telavancin by Revised Broth Microdilution Method in Phase 3 Hospital-Acquired Pneumonia/Ventilator-Associated Pneumonia Clinical Isolates.

INTRODUCTION: The broth microdilution method (BMD) for testing telavancin minimum inhibitory concentrations (MICs) was revised (rBMD) in 2014 to improve the accuracy, precision, and reproducibility of the testing method. The aim of this study was to determine the effect of the revised method on telavancin MIC values for Staphylococcus aureus (S. aureus) clinical isolates obtained from hospital-acquired pneumonia (HAP) patients. METHODS: Isolates from patients who participated in the phase 3 Assessment of Telavancin for Treatment of HAP Studies were retested using the rBMD method. RESULTS: Retesting of 647 isolates produced a range of telavancin MIC values from 0.015 µg/mL to 0.12 µg/mL with MIC50/90 values of 0.06/0.06 µg/mL for the total pool of samples. For methicillin-resistant S. aureus (MRSA), MIC50/90 values were 0.06/0.12 µg/mL. These values are up to 4-fold lower than MIC50/90 values obtained using the original method. These results were used in part to justify lowering the telavancin breakpoints. All tested isolates remained susceptible to telavancin at the revised susceptibility breakpoint of ≤0.12 µg/mL. Overall, the clinical cure rate for microbiologically evaluable telavancin-treated patients was 78% for S. aureus, 76% for patients with MRSA, and 79% for patients with isolates with reduced susceptibility to vancomycin (MIC ≥1 µg/mL). CONCLUSION: Results from the rBMD method support the in vitro potency of telavancin against S. aureus. TRIAL REGISTRATION: ATTAIN (NCT00107952 and NCT00124020). FUNDING: Theravance Biopharma Antibiotics, Inc.

John B. Murphy: unique among American surgeons.

John B. Murphy (1857-1916), one of the most outstanding and controversial surgeons of his age, was a product of the strong clinical programs that developed in Chicago in the late 19th century. Heavily influenced by Christian Fenger, surgeon and surgical pathologist, he went to Europe for training under Theodore Billroth and others. He applied results of his dog lab experiments to human problems while maintaining a large private practice. He is best known for his teaching clinics, for his groundbreaking work with a button for intestinal anastomosis, and for encouraging early operation in appendicitis. Though often in trouble with his fellow surgeons who accused him of stealing patients, especially in the Haymarket affair and when Theodore Roosevelt was shot, he nevertheless made many contributions to the care of surgical patients and development of academic surgery.

Charles R. Drew: surgeon, scientist, and educator.

The first African-American Surgeon to achieve extensive training in medical research in the modern era was Dr. Charles Drew (1904-1950) who completed a doctoral degree in medical sciences at Columbia University in 1940. He became the director of the American Red Cross Blood Bank program during World War II and received many accolades for his work with plasma. This historical vignette reviews the details of his life as a scientist and surgical educator while fighting the overpowering racism which black professionals were subjected to during that time. The controversial aspects and facts of his premature death in an automobile accident in the South are explored as well.