Do bisphosphonates and RANKL inhibitors alter the progression of coronary artery calcification? A systematic review.

OBJECTIVES: To determine whether bisphosphonates and NF-κB ligand (RANKL) inhibitors delay coronary artery calcification (CAC). DESIGN: A systematic review was conducted. DATA SOURCES: MEDLINE, EMBASE and CENTRAL. ELIGIBILITY CRITERIA: Longitudinal studies investigating CAC progression in adults (>18 years) taking either a bisphosphonate or denosumab compared with those who did not. DATA EXTRACTION AND SYNTHESIS: Study and participant characteristics, and primary outcome ( ∆ CAC from baseline to follow-up) were extracted. The Risk Of Bias In Non-Randomised Studies-of Interventions (ROBINS-I) and Risk-of-Bias Tool for Randomised Trials (RoB2) tools were used to assess the risk of bias for observational and randomised controlled trials (RCTs), respectively. Outcome measures were reported. RESULTS: Four observational studies and one RCT (n=377) were included. Three studies solely reported the effect of bisphosphonates on ∆ CAC; one study (n=56) demonstrated a statistically significant CAC reduction in the intervention group (-372 mm3/year) compared with control (+159 mm3/year) (p<0.01). One study (n=14) demonstrated a difference in ∆ CAC between intervention (+880 mm3/year) versus control (+2220 mm3/year), however, no p value comparing groups was reported. One study (n=115) found no statistically significant difference between intervention and control.One study (n=42) exclusively investigated the effect of RANKL on ∆ CAC; there was a statistically significant reduction in CAC at 6-month follow-up between intervention (-133±124 modified Agatston unit (AU)) and control (+188±72 modified AU), p=0.03.One study (n=150) compared both bisphosphonates and denosumab to control and found no statistically significant difference between either intervention group and control over 24 months. Meta-analysis was not performed due to limited, heterogeneous studies. CONCLUSIONS: There is insufficient evidence supporting the correlation between bisphosphonate or RANKL inhibitor use and CAC progression. Further research is warranted.

Enhancing Guidewire Efficacy for Transradial Access: The EAGER Randomized Controlled Trial.

BACKGROUND: The 1.5 mm Baby J hydrophilic narrow J-tipped wire is a development of the standard 0.035" 3-mm J-tipped peripheral guidewire, designed to improve efficiency of transradial coronary procedures by safely navigating small caliber radial arteries to the aorta. There is currently a lack of evidence comparing the procedural success and safety of different peripheral guidewires used in transradial cardiac procedures. We compared the efficacy and safety of a narrow J-tipped hydrophilic 0.035" wire (intervention, Radifocus Baby J guidewire; TERUMO Co, Tokyo, Japan) versus a standard fixed-core 0.035" J wire (control). METHODS: Investigator-initiated, blinded, Australian, multicenter randomized trial in patients undergoing clinically indicated coronary angiography or percutaneous coronary intervention. Patients were randomized 1:1 to use either the control guidewire or the intervention guidewire. The primary end point (technical success) was defined as gaining aortic root access with the randomized guidewire. RESULTS: In all, 330 patients were randomized between October 2022 and June 2023 (median age was 69 years, 36% were female, and body mass index was 29 kg/m2). The primary end point was achieved more frequently in the intervention group (96% versus 84%; absolute risk reduction 12% [95% CI, 5.7-18.3]; P<0.001). Women assigned to the control wire experienced a higher failure rate compared with men (31% versus 8% in men; P<0.001). Fluoroscopy time was significantly lower in the Baby J group (median, 344 versus 491 seconds; P=0.024). The main mechanisms of failure using the control wire were radial artery spasm (15/26; 57%) and subclavian tortuosity (5/26; 19.2%). There were no differences in overall procedure times, major adverse cardiovascular events, or vascular complications between guidewires. CONCLUSIONS: A narrow 1.5 mm J-tipped hydrophilic guidewire resulted in greater technical success and reduced fluoroscopy time compared with the standard 3-mm J-tipped nonhydrophilic guidewire. The guidewire is safe and demonstrated key incremental benefits for the transradial approach, particularly in women. REGISTRATION: URL: https://www.anzctr.org.au/; Unique identifier: ACTRN12622001557729.

Cardiogenic shock without hypotension in acute severe primary mitral regurgitation: a case report.

A 60-year-old gentleman who presented with features of end-organ hypoperfusion despite initial hypertension was promptly diagnosed with cardiogenic shock following evidence of hyperlactatemia on biochemistry and left ventricular global hypokinesis with severe mitral regurgitation on transthoracic echocardiogram. He responded well to dobutamine and later underwent definitive surgical mitral valve replacement.

An observational objective job analysis of role related tasks undertaken by Royal Navy sailors.

BACKGROUND: The current in-service Royal Naval Fitness Test has two elements to test the aerobic endurance and muscular strength of Service Personnel through generic field-based tests and a short job task simulation. However, in 2017 the Royal Navy (RN) identified a requirement to update their in-service fitness test to align with international best practice. OBJECTIVE: The purpose of this study was to conduct an Objective Job Task Analysis on critical, physically demanding tasks that could be undertaken by RN sailors during sea deployments. METHODS: Twenty-one training exercises were observed across a range of contexts; Type 23 Frigates, Type 45 Destroyers and at shore-based training facilities. A total of 203 RN personnel (age 27.8±7.1 years) were observed undertaking 36 job related tasks (e.g., 'firefighting', 'damage control', 'abandon ship' and 'casualty handling'). Tasks were evaluated by cardiovascular response, primary functional movements and contextual factors to aid a Military Judgement Panel in task list down-selection. RESULTS: 14 Criterion Tasks (e.g., 'firefighting', 'two-person magazine stowage' and 'casualty handling') were selected to progress to the next stage of the process. Five tasks were selected based on cardiovascular responses and a further nine tasks selected based on task ergonomics and other factors. CONCLUSION: This research has identified and quantified the most physically demanding, critical roles undertaken by RN sailors on sea deployments and will inform the development of the RN Physical Employment Standard.

Primary neurolymphomatosis diagnosed by spinal nerve root biopsy.

Primary neurolymphomatosis is the direct infiltration of lymphomatous neoplastic cells into nerve roots and/or peripheral nerves. A 67-year-old man had a 24-month history of progressive and severe left lower limb neuropathic pain, ipsilateral ankle dorsiflexion weakness and gait disturbance. Gadolinium-enhanced MRI showed thickening and enhancement of the cauda equina, L5, S1 and S2 nerve roots. 18Fluorodeoxyglucose positron emission tomography showed concordant hypermetabolism. L5 nerve root biopsy confirmed diffuse large B-cell lymphoma. One cycle of rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) chemotherapy resulted in remission, but this was not sustained. Primary neurolymphomatosis is rare and diagnostically challenging, and often the diagnosis is delayed. While biopsy is the gold standard for diagnosis, neuroimaging helps to characterise lesions and to determine the feasibility of biopsy.

A preliminary study of the thermal strain experienced by dive support boat personnel.

Anecdotal evidence indicated some British military dive support boat personnel suffer from uncomfortably cold hands and feet, which could impair their performance and be associated with reductions in core body temperature. This study collected preliminary data on thermal stress and cognitive performance of personnel taking part in a cold-weather training exercise. Six men were monitored during four boat transits in a range of climatic conditions (air temperature +1.2°C to -10.5°C, wind chill -4.5°C to 19.3°C). Core body temperature was measured with a radio pill and 12 skin sites (ISO 9886 plus hand, finger, foot and toe) with iButtons or thermistors. Self-reported thermal comfort and thermal sensation was also recorded. Reaction time and selective attention were measured pre- and post-transit. Participants' physical characteristics and personal clothing ensembles were recorded. No participant became hypothermic. Most participants' hand, foot and digit temperatures fell to below 15°C, indicating a risk of impaired dexterity, in addition to that arising from gloves. During the trial, hand and digit temperatures occasionally fell below 10°C. The limited data collected showed personal clothing choices could provide adequate thermal protection for these conditions and temperatures, and highlighted inter-individual variation and the need to allow for significant variation of day-to-day environmental conditions.

Does Collaboration between General Practitioners and Pharmacists Improve Risk Factors for Cardiovascular Disease and Diabetes? A Systematic Review and Meta-Analysis.

Objective: To assess whether inter-professional, bidirectional collaboration between general practitioners (GPs) and pharmacists has an impact on improving cardiovascular risk outcomes among patients in the primary care setting. It also aimed to understand the different types of collaborative care models used. Study design: Systematic review and Hartung-Knapp-Sidik-Jonkman random effects meta-analyses of randomised control trials (RCTs) in inter-professional bidirectional collaboration between GP and pharmacists assessing a change of patient cardiovascular risk in the primary care setting. Data sources: MEDLINE, EMBASE, Cochrane, CINAHL and International Pharmaceutical Abstracts, scanned reference lists of relevant studies, hand searched key journals and key papers until August 2021. Data synthesis: Twenty-eight RCTs were identified. Collaboration was associated with significant reductions in systolic and diastolic blood pressure (23 studies, 5,620 participants) of -6.42 mmHg (95% confidence interval (95%CI) -7.99 to -4.84) and -2.33 mmHg (95%CI -3.76 to -0.91), respectively. Changes in other cardiovascular risk factors included total cholesterol (6 studies, 1,917 participants) -0.26 mmol/L (95%CI -0.49 to -0.03); low-density lipoprotein (8 studies, 1,817 participants) -0.16 mmol/L (95%CI -0.63 to 0.32); high-density lipoprotein (7 studies, 1,525 participants) 0.02 mmol/L (95%CI -0.02 to 0.07). Reduction in haemoglobin A1c (HbA1C) (10 studies, 2,025 participants), body mass index (8 studies, 1,708 participants) and smoking cessation (1 study, 132 participants) was observed with GP-pharmacist collaboration. Meta-analysis was not conducted for these changes. Various models of collaborative care included verbal communication (via phone calls or face to face), and written communication (emails, letters). We found that co-location was associated with positive changes in cardiovascular risk factors. Conclusion: Although it is clear that collaborative care is ideal compared to usual care, greater details in the description of the collaborative model of care in studies is required for a core comprehensive evaluation of the different models of collaboration.

The associations between women who are immigrants, refugees, or asylum seekers, access to universal healthcare, and the timely uptake of antenatal care: A systematic review.

BACKGROUND: The World Health Organization (WHO) recommends that antenatal care (ANC) commence before 12 weeks' gestation to reduce the risk of obstetric and perinatal complications. Immigrants, refugees, and asylum seekers are at higher risk for late or non-initiation of ANC, and exclusion from universal healthcare (UHC) may be a contributing factor. AIMS: The aims were to synthesise evidence regarding uptake of ANC and to examine if this is associated with inadequate access to UHC and to evaluate the link between ANC and the risk of pregnancy outcomes in the immigrant, refugee and asylum seeker population. METHODS: The review was performed according to meta-analysis of observational studies in epidemiology (MOOSE) guidelines. Five databases were systematically searched. Abstracts were screened against inclusion criteria, and eligible papers underwent data extraction by two independent reviewers per paper. The ROBINS-I tool was used to assess risk of bias. RESULTS: Twelve studies were included in the final review. All studies reported that ANC was delayed for women who were classified as immigrants, refugees, and asylum seekers as per the WHO recommendations, and this was statistically significant compared to controls in 11 of 12 studies (P < 0.05). Findings regarding ANC uptake and pregnancy complications were too heterogeneous to conclusively report an association. CONCLUSION: Immigrants, refugees and asylum seekers who are excluded from UHC present significantly later to ANC than receiving-country-born women with full access to UHC. The link between delayed ANC due to inadequate UHC access and pregnancy complications remains unclear due to the heterogeneous nature of the studies.

Do bisphosphonates and RANKL inhibitors alter the progression of coronary artery calcification? A systematic review and meta-analysis protocol.

INTRODUCTION: Whether bisphosphonates and RANKL inhibitors play a novel role in delaying cardiovascular calcification is unknown. Their action on regulatory enzymes in the mevalonic acid pathway, which is implicated in both bone and lipid metabolism, may be a novel therapeutic target to manage coronary artery disease (CAD). Such therapies may particularly be relevant in those for whom traditional cardiovascular therapies are no longer sufficient to control disease progression. METHODS AND ANALYSIS: We will perform a systematic review which aims to synthesise evidence regarding whether use of bisphosphonates or use of the RANKL inhibitor denosumab delays coronary artery calcium (CAC) progression. Eligible studies will include longitudinal studies investigating CAC progression in patients aged >18 years taking either a bisphosphonate or denosumab compared with those who do not. Embase, MEDLINE and Cochrane will be searched using prespecified search terms. Studies will be screened by title and abstract independently and then in full to determine suitability for inclusion in the review. Extracted data will include that relating to study and participant characteristics. The primary outcome will be the CAC score. Secondary outcomes will include aortic and carotid artery calcification. Meta-analysis will be performed if sufficient data are available. ETHICS AND DISSEMINATION: This study does not require ethics as it is a systematic review of the literature. The results of the review described within this protocol will be distributed via presentations at relevant conferences and publication within a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: The systematic review pertaining to this protocol is registered with PROSPERO (Registration ID: CRD42022312377).

In vitro and integrated in vivo strategies to reduce animal use in genotoxicity testing.

Scientific, financial, and ethical drivers have led to unprecedented interest in implementing human-relevant, mechanistic in vitro and in silico testing approaches. Further, as non-animal approaches are being developed and validated, researchers are interested in strategies that can immediately reduce the use of animals in toxicology testing. Here, we aim to outline a testing strategy for assessing genotoxicity beginning with standard in vitro methods, such as the bacterial reverse mutation test and the in vitro micronucleus test, followed by a second tier of in vitro assays including those using advanced 3D tissue models. Where regulatory agencies require in vivo testing, one demonstrated strategy is to combine genotoxicity studies traditionally conducted separately into a single test or to integrate genotoxicity studies into other toxicity studies. Standard setting organisations and regulatory agencies have encouraged such strategies, and examples of their use can be found in the scientific literature. Employing approaches outlined here will reduce animal use as well as study time and costs.

Carbon Nanotube Exposure Triggers a Cerebral Peptidomic Response: Barrier Compromise, Neuroinflammation, and a Hyperexcited State.

The unique physicochemical properties of carbon nanomaterials and their ever-growing utilization generate a serious concern for occupational risk. Pulmonary exposure to these nanoparticles induces local and systemic inflammation, cardiovascular dysfunction, and even cognitive deficits. Although multiple routes of extrapulmonary toxicity have been proposed, the mechanism for and manner of neurologic effects remain minimally understood. Here, we examine the cerebral spinal fluid (CSF)-derived peptidomic fraction as a reflection of neuropathological alterations induced by pulmonary carbon nanomaterial exposure. Male C57BL/6 mice were exposed to 10 or 40 µg of multiwalled carbon nanotubes (MWCNT) by oropharyngeal aspiration. Serum and CSFs were collected 4 h post exposure. An enriched peptide fraction of both biofluids was analyzed using ion mobility-enabled data-independent mass spectrometry for label-free quantification. MWCNT exposure induced a prominent peptidomic response in the blood and CSF; however, correlation between fluids was limited. Instead, we determined that a MWCNT-induced peptidomic shift occurred specific to the CSF with 292 significant responses found that were not in serum. Identified MWCNT-responsive peptides depicted a mechanism involving aberrant fibrinolysis (fibrinopeptide A), blood-brain barrier permeation (homeobox protein A4), neuroinflammation (transmembrane protein 131L) with reactivity by astrocytes and microglia, and a pro-degradative (signal transducing adapter molecule, phosphoglycerate kinase), antiplastic (AF4/FMR2 family member 1, vacuolar protein sorting-associated protein 18) state with the excitation-inhibition balance shifted to a hyperexcited (microtubule-associated protein 1B) phenotype. Overall, the significant pathologic changes observed were consistent with early neurodegenerative disease and were diagnostically reflected in the CSF peptidome.

The incidence of breast health issues and the efficacy of a sports bra fit and issue service in British Army recruits.

Increasing retention of female recruits throughout Basic Training (BT) is a key priority for the British Army. The aims of this study were two-fold; (i) quantify breast health issues and sports bra usage within female British Army recruits, and (ii) assess the influence of professionally fitted sports bras on breast health and bra fit issues across 13 weeks of BT. A survey was completed by 246 female recruits that identified the incidence of breast health issues during BT. Subsequently, 33 female recruits were provided with professionally fitted sports bras during Week-1 of BT. Recruits completed a survey in Week-1 (Pre) and Week-13 (Post). There was a high incidence of bra issues during BT, which did not reduce following the implementation of professionally fitted sports bras. The authors recommend further research into the specific functional requirements of breast support relative to the demands of BT and the needs of the female recruit. Practitioner Summary: The British Army have a duty of care to ensure female recruits are equipped sufficiently for the demands of training. Despite the implementation of a sports bra fitting and issue service bra fit issues remained high. Further research into the specific functional requirements of breast support during training is recommended. Abbreviations: BT: Basic Training; ATR(W): Army Training Regiment Winchester; ATC(P): Army Training Centre Pirbright; BMI: Body Mass Index; NRS: Numeric Rating Scale; FET: Fisher's Exact Test.

Effect of ß1 /ß2 -adrenoceptor blockade on ß3 -adrenoceptor activity in the rat cremaster muscle artery.

BACKGROUND AND PURPOSE: The physiological role of vascular ß3 -adrenoceptors is not fully understood. Recent evidence suggests cardiac ß3 -adrenoceptors are functionally effective after down-regulation of ß1 /ß2 -adrenoceptors. The functional interaction between the ß3 -adrenoceptor and other ß-adrenoceptor subtypes in rat striated muscle arteries was investigated. EXPERIMENTAL APPROACH: Studies were performed in cremaster muscle arteries isolated from male Sprague-Dawley rats. ß-adrenoceptor expression was assessed through RT-PCR and immunofluorescence. Functional effects of ß3 -adrenoceptor agonists and antagonists and other ß-adrenoceptor ligands were measured using pressure myography. KEY RESULTS: All three ß-adrenoceptor subtypes were present in the endothelium of the cremaster muscle artery. The ß3 -adrenoceptor agonists mirabegron and CL 316,243 had no effect on the diameter of pressurized (70 mmHg) cremaster muscle arterioles with myogenic tone, while the ß3 -adrenoceptor agonist SR 58611A and the nonselective ß-adrenoceptor agonist isoprenaline caused concentration-dependent dilation. In the presence of ß1/2 -adrenoceptor antagonists nadolol (10 µM), atenolol (1 µM) and ICI 118,551 (0.1 µM) both mirabegron and CL 316,243 were effective in causing vasodilation and the potency of SR 58611A was enhanced, while responses to isoprenaline were inhibited. The ß3 -adrenoceptor antagonist L 748,337 (1 µM) inhibited vasodilation caused by ß3 -adrenoceptor agonists (in the presence of ß1/2 -adrenoceptor blockade), but L 748,337 had no effect on isoprenaline-induced vasodilation. CONCLUSION AND IMPLICATIONS: All three ß-adrenoceptor subtypes were present in the endothelium of the rat cremaster muscle artery, but ß3 -adrenoceptor mediated vasodilation was only evident after blockade of ß1/2 -adrenoceptors. This suggests constitutive ß1/2 -adrenoceptor activity inhibits ß3 -adrenoceptor function in the endothelium of skeletal muscle resistance arteries.

No Differences Between Beetroot Juice and Placebo on Competitive 5-km Running Performance: A Double-Blind, Placebo-Controlled Trial.

The authors examine the effect of an acute dose of beetroot juice on endurance running performance in "real-world" competitive settings. In total, 70 recreational runners (mean ± SD: age = 33.3 ± 12.3 years, training history = 11.9 ± 8.1 years, and hours per week training = 5.9 ± 3.5) completed a quasi-randomized, double-blind, placebo-controlled study of 5-km competitive time trials. Participants performed four trials separated by 1 week in the order of prebaseline, two experimental, and one postbaseline. Experimental trials consisted of the administration of 70-ml nitrate-rich beetroot juice (containing ∼4.1 mmol of nitrate, Beet It Sport®) or nitrate-depleted placebo (containing ∼0.04 mmol of nitrate, Beet It Sport®) 2.5 hr prior to time trials. Time to complete 5 km was recorded for each trial. No differences were shown between pre- and postbaseline (p = .128, coefficient variation = 2.66%). The average of these two trials is therefore used as baseline. Compared with baseline, participants ran faster with beetroot juice (mean differences = 22.2 ± 5.0 s, p < .001, d = 0.08) and placebo (22.9 ± 4.5 s, p < .001, d = 0.09). No differences in times were shown between beetroot juice and placebo (0.8 ± 5.7 s, p < .875, d = 0.00). These results indicate that an acute dose of beetroot juice does not improve competitive 5-km time-trial performance in recreational runners compared with placebo.

Sex Differences in Training Loads during British Army Basic Training.

PURPOSE: To compare training loads between men and women during 14 wk of British Army standard entry basic training. METHODS: Thirty-one male (mean ± SD: age, 21 ± 4 yr; height, 1.78 ± 0.08 m; mass, 77.1 ± 10.5 kg) and 28 female (age, 22 ± 4 yr; height, 1.65 ± 0.05 m; mass, 63.9 ± 8.9 kg) British Army recruits had external (distance) and internal (HR, training impulse [TRIMP], RPE) training loads measured during weeks 1, 2, 6, 12, and 13 of basic training. Total energy expenditure was measured during weeks 1 to 2 and weeks 12 to 13. RESULTS: Daily distance was higher for men than women (13,508 ± 666 vs 11,866 ± 491 m, respectively, P < 0.001). Average daily HR (29% ± 3% vs 30% ± 3% HR reserve) and RPE (4 ± 1 vs 4 ± 1) were not different between men and women, respectively (P ≥ 0.495). Daily TRIMP was higher for women than men (492 ± 130 vs 261 ± 145 au, respectively, P < 0.001). Total energy expenditure was higher for men than women during weeks 1 to 2 (4020 ± 620 vs 2847 ± 323 kcal·d, respectively) and weeks 12 to 13 (4253 ± 556 kcal·d vs 3390 ± 344 kcal·d, respectively) (P < 0.001). Daily RPE, HR, and TRIMP were related to daily distance (R = 0.18-0.57, P ≤ 0.037), and daily RPE was related to daily TRIMP and HR (R = 0.37-0.77, P ≤ 0.001). CONCLUSIONS: Sex differences in training loads could contribute to the greater injury risk for women during basic training. Daily RPE appears a practical option for measuring internal training load during military training.

Estimates of Tibial Shock Magnitude in Men and Women at the Start and End of a Military Drill Training Program.

INTRODUCTION: Foot drill is a key component of military training and is characterized by frequent heel stamping, likely resulting in high tibial shock magnitudes. Higher tibial shock during running has previously been associated with risk of lower limb stress fractures, which are prevalent among military populations. Quantification of tibial shock during drill training is, therefore, warranted. This study aimed to provide estimates of tibial shock during military drill in British Army Basic training. The study also aimed to compare values between men and women, and to identify any differences between the first and final sessions of training. MATERIALS AND METHODS: Tibial accelerometers were secured on the right medial, distal shank of 10 British Army recruits (n = 5 men; n = 5 women) throughout a scheduled drill training session in week 1 and week 12 of basic military training. Peak positive accelerations, the average magnitude above given thresholds, and the rate at which each threshold was exceeded were quantified. RESULTS: Mean (SD) peak positive acceleration was 20.8 (2.2) g across all sessions, which is considerably higher than values typically observed during high impact physical activity. Magnitudes of tibial shock were higher in men than women, and higher in week 12 compared with week 1 of training. CONCLUSIONS: This study provides the first estimates of tibial shock magnitude during military drill training in the field. The high values suggest that military drill is a demanding activity and this should be considered when developing and evaluating military training programs. Further exploration is required to understand the response of the lower limb to military drill training and the etiology of these responses in the development of lower limb stress fractures.

Sex differences in neuromuscular fatigability in response to load carriage in the field in British Army recruits.

OBJECTIVES: Women are resistant to neuromuscular fatigue compared to men in response to a range of exercise tasks. The sex differences in the neuromuscular responses to load carriage have yet to be investigated. DESIGN: Prospective cohort study. METHODS: Twenty-three male and 19 female British Army recruits completed a 9.7km loaded march within 90min, with the weight carried dependent on military trade (16±2kg for men and 15±1kg for women). Isometric maximal voluntary contraction (MVC) force of the knee extensors and vertical jump (VJ) height were examined pre- and post-loaded march to examine neuromuscular fatigue. Heart rate (HR) was recorded throughout and ratings of perceived exertion (RPE) was recorded following the march. RESULTS: HR was higher for women (173±9bmin-1, 83±6% heart rate reserve) than men (158±8bmin-1, 72±6% heart rate reserve) (p≤0.001). RPE following the march was also higher for women than men (6±2 vs 4±2, respectively, p<0.001). The loss in MVC force was greater for men than women (-12±9% vs -9±13%, respectively, p=0.031), however VJ height was impaired to a similar extent (-5±11% vs -5±6%, respectively, p=0.582). CONCLUSIONS: The greater physiological stress during load carriage for women compared to men did not translate to a greater severity of knee extensor muscle fatigue, with women demonstrating fatigue resistance.

Effects of prefrontal cortex damage on emotion understanding: EEG and behavioural evidence.

Humans are highly social beings that interact with each other on a daily basis. In these complex interactions, we get along by being able to identify others' actions and infer their intentions, thoughts and feelings. One of the major theories accounting for this critical ability assumes that the understanding of social signals is based on a primordial tendency to simulate observed actions by activating a mirror neuron system. If mirror neuron regions are important for action and emotion recognition, damage to regions in this network should lead to deficits in these domains. In the current behavioural and EEG study, we focused on the lateral prefrontal cortex including dorsal and ventral prefrontal cortex and utilized a series of task paradigms, each measuring a different aspect of recognizing others' actions or emotions from body cues. We examined 17 patients with lesions including (n = 8) or not including (n = 9) the inferior frontal gyrus, a core mirror neuron system region, and compared their performance to matched healthy control subjects (n = 18), in behavioural tasks and in an EEG observation-execution task measuring mu suppression. Our results provide support for the role of the lateral prefrontal cortex in understanding others' emotions, by showing that even unilateral lesions result in deficits in both accuracy and reaction time in tasks involving the recognition of others' emotions. In tasks involving the recognition of actions, patients showed a general increase in reaction time, but not a reduction in accuracy. Deficits in emotion recognition can be seen by either direct damage to the inferior frontal gyrus, or via damage to dorsal lateral prefrontal cortex regions, resulting in deteriorated performance and less EEG mu suppression over sensorimotor cortex.

Serum-borne bioactivity caused by pulmonary multiwalled carbon nanotubes induces neuroinflammation via blood-brain barrier impairment.

Pulmonary exposure to multiwalled carbon nanotubes (MWCNTs) causes indirect systemic inflammation through unknown pathways. MWCNTs translocate only minimally from the lungs into the systemic circulation, suggesting that extrapulmonary toxicity may be caused indirectly by lung-derived factors entering the circulation. To assess a role for MWCNT-induced circulating factors in driving neuroinflammatory outcomes, mice were acutely exposed to MWCNTs (10 or 40 µg/mouse) via oropharyngeal aspiration. At 4 h after MWCNT exposure, broad disruption of the blood-brain barrier (BBB) was observed across the capillary bed with the small molecule fluorescein, concomitant with reactive astrocytosis. However, pronounced BBB permeation was noted, with frank albumin leakage around larger vessels (>10 µm), overlain by a dose-dependent astroglial scar-like formation and recruitment of phagocytic microglia. As affirmed by elevated inflammatory marker transcription, MWCNT-induced BBB disruption and neuroinflammation were abrogated by pretreatment with the rho kinase inhibitor fasudil. Serum from MWCNT-exposed mice induced expression of adhesion molecules in primary murine cerebrovascular endothelial cells and, in a wound-healing in vitro assay, impaired cell motility and cytokinesis. Serum thrombospondin-1 level was significantly increased after MWCNT exposure, and mice lacking the endogenous receptor CD36 were protected from the neuroinflammatory and BBB permeability effects of MWCNTs. In conclusion, acute pulmonary exposure to MWCNTs causes neuroinflammatory responses that are dependent on the disruption of BBB integrity.

dFatp regulates nutrient distribution and long-term physiology in Drosophila.

Nutrient allocation and usage plays an important part in regulating the onset and progression of age-related functional declines. Here, we describe a heterozygous mutation in Drosophila (dFatp) that alters nutrient distribution and multiple aspects of physiology. dFatp mutants have increased lifespan and stress resistance, altered feeding behavior and fat storage, and increased mobility. Concurrently, mutants experience impairment of cardiac function. We show that endurance exercise reverses increased lipid storage in the myocardium and the deleterious cardiac function conferred by dFatp mutation. These findings establish a novel conserved genetic target for regulating lifespan and physiology in aging animals. These findings also highlight the importance of varying exercise conditions in assessing aging functions of model organisms.