Effects of resistance training on quality of life, fatigue, physical function, and muscular strength during chemotherapy treatment: a systematic review and meta-analysis.

PURPOSE: To systematically review and meta-analyse the efficacy of resistance training on quality of life (QOL), fatigue, physical function, and muscular strength in people diagnosed with cancer undergoing chemotherapy. METHODS: Electronic databases PubMed, Cochrane Central, CINAHL, SCOPUS and Web of Science were systematically searched for randomised controlled trials (RCTs) that compared the effects of resistance training to control on QOL, fatigue, physical function, and lower-body and upper-body muscular strength in adults undergoing chemotherapy. Standardised mean differences (SMDs) were pooled using a random effects model. Risk of bias was assess using the risk of bias tool for randomised trials (RoB 2). RESULTS: Seven RCTs encompassing 561 participants were included. The pooled results of seven RCTs showed that resistance training during chemotherapy significantly improved lower-body strength (n = 555, SMD 0.33, 95% CI 0.12 to 0.53, moderate-quality evidence, I2 = 23%) compared to control. There was no evidence for an effect of resistance training on QOL (n = 373, SMD 0.13, 95% CI -0.15 to 0.42, low-quality evidence, I2 = 0%), fatigue (n = 373, SMD -0.08, 95% CI -0.37 to 0.22, low-quality evidence, I2 = 20%), physical function (n = 198, SMD 0.61, 95% CI -0.73 to 1.95, very low-quality evidence, I2 = 83%), or upper-body strength (n = 413, SMD 0.37, 95% CI -0.07 to 0.80, very low-quality evidence, I2 = 69%). CONCLUSIONS: Resistance training may improve lower-body strength in patients undergoing chemotherapy treatment compared to control.

Feasibility of a novel exercise prehabilitation programme in patients scheduled for elective colorectal surgery: a feasibility randomised controlled trial.

BACKGROUND AND OBJECTIVES: To investigate the feasibility of delivering a functional exercise-based prehabilitation intervention and its effects on postoperative length of hospital stay, preoperative physical functioning and health-related quality of life in elective colorectal surgery. MATERIALS AND METHODS: In this randomised controlled feasibility trial, 22 elective colorectal surgery patients were randomly assigned to exercise prehabilitation (n = 11) or standard care (n = 11). Feasibility of delivering the intervention was assessed based on recruitment and compliance to the intervention. Impact on postoperative length of hospital stay and complications, preoperative physical functioning (timed up and go test, five times sit to stand, stair climb test, handgrip dynamometry and 6-min walk test) and health-related quality of life were also assessed. RESULTS: Over 42% of patients (84/198) screened were deemed ineligible for prehabilitation due to insufficient time existing prior to scheduled surgery. Of those who were eligible, approximately 18% consented to the trial. Median length of hospital stay was 8 [range 6-27] and 10 [range 5-12] days respectively for the standard care and prehabilitation groups. Patterns towards preoperative improvements for the timed up and go test, stair climb test and 6-min walk test were observed for all participants receiving prehabilitation but not standard care. CONCLUSIONS: Despite prehabilitation appearing to convey positive benefits on physical functioning, short surgical wait times and patient engagement represent major obstacles to implementing exercise prehabilitation programmes in colorectal cancer patients.

Test-Retest Reliability of a Commercial Linear Position Transducer (GymAware PowerTool) to Measure Velocity and Power in the Back Squat and Bench Press.

Orange, ST, Metcalfe, JW, Marshall, P, Vince, RV, Madden, LA, and Liefeith, A. Test-retest reliability of a commercial linear position transducer (GymAware PowerTool) to measure velocity and power in the back squat and bench press. J Strength Cond Res 34(3): 728-737, 2020-This study examined the test-retest reliability of the GymAware PowerTool (GYM) to measure velocity and power in the free-weight back squat and bench press. Twenty-nine academy rugby league players (age: 17.6 ± 1.0 years; body mass: 87.3 ± 20.8 kg) completed 2 test-retest sessions for the back squat followed by 2 test-retest sessions for the bench press. GYM measured mean velocity (MV), peak velocity (PV), mean power (MP), and peak power at 20, 40, 60, 80, and 90% of 1 repetition maximum (1RM). GYM showed good reliability (intraclass correlation coefficient [ICC] and standard error of measurement percentage, respectively) for the measurement of MV at loads of 40 (0.77, 3.9%), 60 (0.83, 4.8%), 80 (0.83, 5.8%), and 90% (0.79, 7.9%) of 1RM in the back squat. In the bench press, good reliability was evident for PV at 40 (0.82, 3.9%), 60 (0.81, 5.1%), and 80% (0.77, 8.4%) of 1RM, and for MV at 80 (0.78, 7.9%) and 90% (0.87, 9.9%) of 1RM. The measurement of MP showed good to excellent levels of reliability across all relative loads (ICC ≥0.75). In conclusion, GYM provides practitioners with reliable kinematic information in the back squat and bench press, at least with loads of 40-90% of 1RM. This suggests that strength and conditioning coaches can use the velocity data to regulate training load according to daily readiness and target specific components of the force-velocity curve. However, caution should be taken when measuring movement velocity at loads <40% of 1RM.

Effects of acute insulin-induced hypoglycaemia on endothelial microparticles in adults with and without type 2 diabetes.

AIMS: To assess whether endothelial microparticles (EMPs), novel surrogate markers of endothelial injury and dysfunction, are differentially produced in response to acute insulin-induced hypoglycaemia in adults with and without type 2 diabetes. MATERIALS AND METHODS: A prospective, parallel study was conducted in individuals with type 2 diabetes (n = 23) and controls (n = 22). Hypoglycaemia (<2.2 mmoL/L: <40 mg/dL) was achieved by intravenous infusion of soluble insulin. Blood samples were collected at baseline and at 0, 30, 60, 120, 240 minutes and 24 hours after hypoglycaemia and analysed for CD31+ (platelet endothelial cell adhesion molecule-1), CD54+ (intercellular adhesion molecule 1), CD62-E+ (E-selectin), CD105+ (endoglin), CD106+ (vascular cell adhesion molecule 1) and CD142+ (tissue factor) EMPs by flow cytometry. The peak elevations (% rise from 0 minutes after hypoglycaemia) in EMP within 240 minutes after insulin-induced hypoglycaemia were modelled using a regression model, with adjustment for relevant covariates. All EMPs were expressed as percentage from 0 minutes hypoglycaemia for each time point and total areas under the curve (AUC0min-24h ) were calculated. RESULTS: Following insulin-induced hypoglycaemia, levels of circulating EMPs were maximal at 240 minutes (P < 0.001) and returned to baseline values within 24 hours for both groups. The peak elevations (% rise from 0 minutes following hypoglycaemia) seen in CD31+ , CD54+ , CD62-E+ , CD105+ and CD142+ EMPs within 240 minutes were associated with diabetes status after adjustments for all relevant covariates. Individuals with type 2 diabetes showed increased CD31+ EMPs AUC0min-24h (P = 0.014) and CD105+ EMPs AUC0min-24h (P = 0.006) compared with controls, but there were no differences for CD54+ (P = 0.91), CD62-E+ (P = 0.14), CD106+ (P = 0.36) or CD142+ (P = 0.77) EMPs AUC0min-24h . CONCLUSIONS: The associations between peak elevations within 240 minutes after insulin-induced hypoglycaemia for CD31+ , CD54+ , CD62-E+ , CD105+ and CD142+ and diabetes status indicate that the assessment of a panel of EMPs within this timeframe would identify a hypoglycaemic event in this population. The greater overall responses over time (AUCs) for apoptosis-induced CD31+ and CD105+ EMPs suggest that hypoglycaemia exerts greater endothelial stress in type 2 diabetes.

Can sit-to-stand muscle power explain the ability to perform functional tasks in adults with severe obesity?

This study examined the relationship between sit-to-stand (STS) power and physical function in adults with severe obesity. Thirty-eight adults (age: 44 ± 12 years; body mass index [BMI]: 45.2 ± 7.8 kg/m2) completed evaluations of STS power, strength and functional performance. STS power was measured with a wearable inertial sensor, strength was assessed with the isometric mid-thigh pull, and function was measured with the timed up-and-go (TUG), six-minute walk test (6MWT) and 30-s chair STS. Power and strength (normalised to body mass) entered regression models in addition to age, gender, BMI and physical activity (daily step count). Power displayed large univariate associations with TUG (r = 0.50) and 30-s chair STS (r = 0.67), and a moderate association with 6MWT (r = 0.49). Forward stepwise regression revealed that power independently contributed to TUG (ß = -0.40, p = 0.010), 30-s chair STS (ß = 0.67, p < 0.001) and 6MWT performance (ß = 0.27, p = 0.007). Power also appeared to be a superior determinant of function compared with strength. Power generated via the STS transfer largely underpins the ability to perform functional tasks in adults with severe obesity, although intervention studies are required to investigate a potentially causal relationship.

Short-Term Training and Detraining Effects of Supervised vs. Unsupervised Resistance Exercise in Aging Adults.

Orange, ST, Marshall, P, Madden, LA, and Vince, RV. Short-term training and detraining effects of supervised vs. unsupervised resistance exercise in aging adults. J Strength Cond Res 33(10): 2733-2742, 2019-This study compared the effects of a 4-week supervised (SUP) resistance training program and unsupervised (UNSUP) resistance training program followed by 12 weeks of detraining (DET). Thirty-six healthy aging adults (age: 53.6 ± 3.6 years; body mass index: 28.3 ± 5.1 kg·m) were randomly allocated to an SUP group (n = 17) or a UNSUP group (n = 19). Participants completed 3 training sessions per week using resistance bands and body weight movements. Measures of physical performance were administered at baseline, at the end of the training program, and after the DET period. Function was assessed with the 6-minute walk test (6MWT), timed up-and-go (TUG), 30-second chair sit-to-stand (STS), stair-climb test (SCT), 40-m fast-paced walk test (FPWT) and sit-and-reach test (SRT), whereas the isometric midthigh pull (IMTP) and hand grip test were used to measure muscle strength. After training, improvements in performance were found in the 6MWT, TUG, 30-second chair STS, SCT, FPWT, SRT, and IMTP (p ≤ 0.05), with no significant differences between groups (p > 0.05). In addition, most of the training-induced improvements remained significantly above baseline values after the DET period (p ≤ 0.05). No significant between-group differences were observed after training or DET (p > 0.05). Four weeks of either SUP or UNSUP resistance training is sufficient to substantially improve muscle strength and function in aging adults, and these gains are largely preserved after prescribed exercise cessation. Home-based resistance training seems to be a practical and effective alternative to traditional SUP programs that may help circumvent many barriers to physical activity in aging adults.

Validity and Reliability of a Wearable Inertial Sensor to Measure Velocity and Power in the Back Squat and Bench Press.

Orange, ST, Metcalfe, JW, Liefeith, A, Marshall, P, Madden, LA, Fewster, CR, and Vince, RV. Validity and reliability of a wearable inertial sensor to measure velocity and power in the back squat and bench press. J Strength Cond Res 33(9): 2398-2408, 2019-This study examined the validity and reliability of a wearable inertial sensor to measure velocity and power in the free-weight back squat and bench press. Twenty-nine youth rugby league players (18 ± 1 years) completed 2 test-retest sessions for the back squat followed by 2 test-retest sessions for the bench press. Repetitions were performed at 20, 40, 60, 80, and 90% of 1 repetition maximum (1RM) with mean velocity, peak velocity, mean power (MP), and peak power (PP) simultaneously measured using an inertial sensor (PUSH) and a linear position transducer (GymAware PowerTool). The PUSH demonstrated good validity (Pearson's product-moment correlation coefficient [r]) and reliability (intraclass correlation coefficient [ICC]) only for measurements of MP (r = 0.91; ICC = 0.83) and PP (r = 0.90; ICC = 0.80) at 20% of 1RM in the back squat. However, it may be more appropriate for athletes to jump off the ground with this load to optimize power output. Further research should therefore evaluate the usability of inertial sensors in the jump squat exercise. In the bench press, good validity and reliability were evident only for the measurement of MP at 40% of 1RM (r = 0.89; ICC = 0.83). The PUSH was unable to provide a valid and reliable estimate of any other criterion variable in either exercise. Practitioners must be cognizant of the measurement error when using inertial sensor technology to quantify velocity and power during resistance training, particularly with loads other than 20% of 1RM in the back squat and 40% of 1RM in the bench press.

Cancer bioimprinting and cell shape recognition for diagnosis and targeted treatment.

Cancer incidence and mortality have both increased in the last decade and are predicted to continue to rise. Diagnosis and treatment of cancers are often hampered by the inability to specifically target neoplastic cells. Bioimprinting is a promising new approach to overcome shortfalls in cancer targeting. Highly specific recognition cavities can be made into polymer matrices to mimic lock-and-key actions seen in in vivo biological systems. Early studies concentrated on molecules and were inhibited by template size complexity. Surface imprinting allows the capture of increasingly complex motifs from polypeptides to single cell organisms and mammalian cells. Highly specific cell shape recognition can also be achieved by cell interaction with imprints that can be made into polymer matrices to mimic biological systems at a molecular level. Bioimprinting has also been used to achieve nanometre scale resolution imaging of cancer cells. Studies of bioimprint-based drug delivery on cancer cells have been recently trialled in vitro and show that this approach can potentially improve existing chemotherapeutic approaches. This review focuses on the possible applications of bioimprinting with particular regards to cancer understanding, diagnosis and therapy. Cell imprints, incorporated into biosensors can allow the limits of detection to be improved or negate the need for extensive patient sample processing. Similar cell imprinting platforms can be used for nanoscale imaging of cancer morphology, as well as to investigate topographical signalling of cancer cells in vitro. Lastly, bioimprints also have applications as selective drug delivery vehicles to tumours with the potential to decrease chemotherapy-related side effects.

Implications of a pre-exercise alkalosis-mediated attenuation of HSP72 on its response to a subsequent bout of exercise.

The aim of this study was to investigate if a pre-exercise alkalosis-mediated attenuation of HSP72 had any effect on the response of the same stress protein after a subsequent exercise. Seven physically active males [25.0 ± 6.5 years, 182.1 ± 6.0 cm, 74.0 ± 8.3 kg, peak aerobic power (PPO) 316 ± 46 W] performed a repeated sprint exercise (EXB1) following a dose of 0.3 g kg(-1) body mass of sodium bicarbonate (BICARB), or a placebo of 0.045 g kg(-1) body mass of sodium chloride (PLAC). Participants then completed a 90-min intermittent cycling protocol (EXB2). Monocyte expressed HSP72 was significantly attenuated after EXB1 in BICARB compared to PLAC, however, there was no difference in the HSP72 response to the subsequent EXB2 between conditions. Furthermore there was no difference between conditions for measures of oxidative stress (protein carbonyl and HSP32). These findings confirm the sensitivity of the HSP72 response to exercise-induced changes in acid-base status in vivo, but suggest that the attenuated response has little effect upon subsequent stress in the same day.

Duramycin-induced calcium release in cancer cells.

Duramycin, through binding with phosphatidylethanolamine (PE), has shown potential to be an effective antitumour agent. However, its mode of action in relation to tumour cells is not fully understood. PE expression on the surface of a panel of cancer cell lines was analysed using duramycin and subsequent antibody labelling, and then analysed by flow cytometry. Cell viability was also assessed by flow cytometry using annexin V and propidium iodide. Calcium ion (Ca) release by tumour cells in response to duramycin was determined by spectrofluorometry following incubation with Fluo-3, AM. Confocal microscopy was performed on the cancer cell line AsPC-1 to assess real-time cell response to duramycin treatment. Duramycin could detect cell surface PE expression on all 15 cancer cell lines screened, which was shown to be duramycin concentration dependent. However, higher concentrations induced necrotic cell death. Duramycin induced calcium ion (Ca) release from the cancer cell lines also in a concentration-dependent and time-dependent manner. Confocal microscopy showed an influx of propidium iodide into the cells over time and induced morphological changes. Duramycin induces Ca release from cancer cell lines in a time-dependent and concentration-dependent manner.

Enhanced anticancer effect of lysozyme-functionalized metformin-loaded shellac nanoparticles on a 3D cell model: role of the nanoparticle and payload concentrations.

Here we used a 3D human hepatic tumour cell culture model to assess the in vitro efficacy of "active" metformin-loaded nanoparticles (NPs) as anticancer therapeutics. The metformin nanocarrier design was repurposed from previous studies targeting bacterial and fungal biofilms with antimicrobials loaded in protease-coated nanoparticles. These active nanocarriers were constructed with shellac cores loaded with metformin as the anticancer agent and featured a surface coating of the cationic protease lysozyme. The lysozyme's role as a nanocarrier surface coating is to partially digest the extracellular matrix (ECM) of the 3D tumour cell culture which increases its porosity and the nanocarrier penetration. Hep-G2 hepatic 3D clusteroids were formed using a water-in-water (w/w) Pickering emulsion based on an aqueous two-phase system (ATPS). Our specific metformin nano-formulation, comprising 0.25 wt% lysozyme-coated, 0.4 wt% metformin-loaded, 0.2 wt% shellac NPs sterically stabilized with 0.25 wt% Poloxamer 407, demonstrated significantly enhanced anticancer efficiency on 3D hepatic tumour cell clusteroids. We examined the role of the lysozyme surface functionality of the metformin nanocarriers in their ability to kill both 2D and 3D hepatic tumour cell cultures. The anticancer efficiency at high metformin payloads was compared with that at a high concentration of nanocarriers with a lower metformin payload. It was discovered that the high metformin payload NPs were more efficient than the lower metformin payload NPs with a higher nanocarrier concentration. This study introduces a reliable in vitro model for potential targeting of solid tumours with smart nano-therapeutics, presenting a viable alternative to animal testing for evaluating anticancer nanotechnologies.

Brain and Lung Biomarker Responses to Hyperoxic Hypobaric Decompression.

INTRODUCTION: Biomarker responses to intensive decompression indicate systemic proinflammatory responses and possible neurological stress. To further investigate responses, 12 additional brain and lung biomarkers were assayed.METHODS: A total of 15 healthy men (20 to 50 yr) undertook consecutive same-day ascents to 25,000 ft (7620 m), following denitrogenation, breathing 100% oxygen. Venous blood was sampled at baseline (T0), after the second ascent (T8), and next morning (T24). Soluble protein markers of brain and lung insult were analyzed by enzyme-linked immunosorbent assay with plasma microparticles quantified using flow cytometry.RESULTS: Levels of monocyte chemoattractant protein-1 and high mobility group box protein 1 were elevated at T8, by 36% and 16%, respectively, before returning to baseline. Levels of soluble receptor for advanced glycation end products fell by 8%, recovering by T24. Brain-derived neurotrophic factor rose by 80% over baseline at T24. Monocyte microparticle levels rose by factors of 3.7 at T8 and 2.7 at T24 due to early and late responses in different subjects. Other biomarkers were unaffected or not detected consistently.DISCUSSION: The elevated biomarkers at T8 suggest a neuroinflammatory response, with later elevation of brain-derived neurotrophic factor at T24 indicating an ongoing neurotrophic response and incomplete recovery. A substantial increase at T8 in the ratio of high mobility group box protein 1 to soluble receptor for advanced glycation end products suggests this axis may mediate the systemic inflammatory response to decompression. The mechanism of neuroinflammation is unclear but elevation of monocyte microparticles and monocyte chemoattractant protein-1 imply a key role for activated monocytes and/or macrophages.Connolly DM, Madden LA, Edwards VC, Lee VM. Brain and lung biomarker responses to hyperoxic hypobaric decompression. Aerosp Med Hum Perform. 2024; 95(9):667-674.

'I'm a failure again, I can't do it': Attitudes towards, and experiences of, exercise participation in adults with class III obesity.

OBJECTIVES: Living within a larger body brings unique challenges to exercise participation, which are poorly understood. This qualitative study explored the attitudes towards, and experiences of, exercise participation in adults with class III obesity. DESIGN: Individual semi-structured qualitative interviews. METHODS: We recruited 30 adults with class III obesity (body mass index: 45.8 ± 8.6 kg/m2) from a specialist multidisciplinary weight management service. Participants took part in semi-structured interviews while participating in a 6-month home-based aerobic and resistance exercise intervention. Open-ended questions were used flexibly to explore their views and experiences of exercise, encompassing barriers, motives and perceived benefits. Transcripts were analysed using reflexive thematic analysis. RESULTS: Three themes were developed: (1) a web of barriers; (2) tailored exercise facilitates positive experiences; and (3) a desire to live a normal life. People with class III obesity perceived that they were unable to do exercise; a view that was attributed to perceived judgement, low physical function, pain during everyday activities and failed weight loss attempts. These complex physical and psychosocial barriers to exercise were described as contributing to exercise avoidance. High value was placed on tailored exercise that accommodates the unique needs of moving in a larger body. A desire to carry out everyday tasks underpinned motivations for exercise. CONCLUSIONS: Our findings suggest that multi-component obesity interventions should move away from generic exercise prescriptions designed to maximize energy expenditure, and instead move towards addressing the unique physical and psychosocial needs of people who have class III obesity with tailored person-centred and weight-neutral exercise prescriptions.

Photothermal colloid antibodies for shape-selective recognition and killing of microorganisms.

We have developed a class of selective antimicrobial agents based on the recognition of the shape and size of the bacterial cells. These agents are anisotropic colloid particles fabricated as negative replicas of the target cells which involve templating of the cells with shells of inert material followed by their fragmentation. The cell shape recognition by such shell fragments is due to the increased area of surface contact between the cells and their matching shell fragments which resembles antibody-antigen interaction. We produced such "colloid antibodies" with photothermal mechanism for shape-selective killing of matching cells. This was achieved by the subsequent deposition of (i) gold nanoparticles (AuNPs) and (ii) silica shell over yeast cells, which were chosen as model pathogens. We demonstrated that fragments of these composite AuNP/silica shells act as "colloid antibodies" and can bind to yeast cells of the same shape and size and deliver AuNPs directly onto their surface. We showed that after laser irradiation, the localized heating around the AuNPs kills the microbial cells of matching shape. We confirmed the cell shape-specific killing by photothermal colloid antibodies in a mixture of two bacterial cultures of different cell shape and size. This approach opens a number of avenues for building powerful selective biocides based on combinations of colloid antibodies and cell-killing strategies which can be applied in new antibacterial therapies.

The influence of exogenous carbohydrate provision and pre-exercise alkalosis on the heat shock protein response to prolonged interval cycling.

The aim of this study was to observe the intracellular heat shock protein 72 (HSP72) and heme oxygenase-1 (HSP32) response to prolonged interval cycling following the ingestion of carbohydrates (CHO) and sodium bicarbonate (NaHCO(3)). Six recreationally active males (mean ± SD; age 23.2 ± 2.9 years, height 179.5 ± 5.5 cm, body mass 76.5 ± 6.8 kg, and peak power output 315 ± 36 W) volunteered to complete a 90 min interval cycling exercise on four occasions. The trials were completed in a random and blinded manner following ingestion of either: placebo and an artificial sweetener (P-P), NaHCO(3) and sweetener (B-P), placebo and CHO (P-CHO), and NaHCO(3) and CHO (B-CHO). Both HSP72 and HSP32 were significantly increased in monocytes and lymphocytes from 45 min post-exercise (p ≤ 0.039), with strong relationships between both cell types (HSP72, r = 0.83; HSP32, r = 0.89). Exogenous CHO had no influence on either HSP72 or HSP32, but the ingestion of NaHCO(3) significantly attenuated HSP32 in monocytes and lymphocytes (p ≤ 0.042). In conclusion, the intracellular stress protein response to 90 min interval exercise is closely related in monocytes and lymphocytes, and HSP32 appears to be attenuated with a pre-exercise alkalosis.

The physiological stress response to high-intensity sprint exercise following the ingestion of sodium bicarbonate.

The purpose of this study was to investigate the effects of pre-exercise alkalosis on the physiological stress response to high-intensity exercise. Seven physically active males (age 22 ± 3 years, height 1.82 ± 0.06 m, mass 81.3 ± 8.4 kg and peak power output 300 ± 22 W) performed a repeated sprint cycle exercise following a dose of 0.3 g kg(-1) body mass of sodium bicarbonate (NaHCO(3)) (BICARB), or a placebo of 0.045 g kg(-1) body mass of sodium chloride (PLAC). Monocyte-expressed heat shock protein 72 (HSP72) and plasma thiobarbituric acid reactive substances (TBARS) were significantly attenuated in BICARB compared to PLAC (p = 0.04 and p = 0.039, respectively), however total anti-oxidant capacity, the ratio of oxidised to total glutathione, cortisol, interleukin 6 and interleukin 8 were not significantly induced by the exercise. In conclusion, monocyte-expressed HSP72 is significantly increased following high-intensity anaerobic exercise, and its attenuation following such exercise with the ingestion of NaHCO(3) is unlikely to be due to a decreased oxidative stress.

Immobilised-enzyme microreactors for the identification and synthesis of conjugated drug metabolites.

The study of naturally circulating drug metabolites has been a focus of interest, since these metabolites may have different therapeutic and toxicological effects compared to the parent drug. The synthesis of metabolites outside of the human body is vital in order to conduct studies into the pharmacological activities of drugs and bioactive compounds. Current synthesis methods require significant purification and separation efforts or do not provide sufficient quantities for use in pharmacology experiments. Thus, there is a need for simple methods yielding high conversions whilst bypassing the requirement for a separation. Here we have developed and optimised flow chemistry methods in glass microfluidic reactors utilising surface-immobilised enzymes for sulfonation (SULT1a1) and glucuronidation (UGT1a1). Conversion occurs in flow, the precursor and co-factor are pumped through the device, react with the immobilised enzymes and the product is then simply collected at the outlet with no separation from a complex biological matrix required. Conversion only occurred when both the correct co-factor and enzyme were present within the microfluidic system. Yields of 0.97 ± 0.26 µg were obtained from the conversion of resorufin into resorufin sulfate over 2 h with the SULT1a1 enzyme and 0.47 µg of resorufin glucuronide over 4 h for UGT1a1. This was demonstrated to be significantly more than static test tube reactions at 0.22 µg (SULT1a1) and 0.19 µg (UGT1a1) over 4 h. With scaling out and parallelising, useable quantities of hundreds of micrograms for use in pharmacology studies can be synthesised simply.

Digital Health Solutions for Weight Loss and Obesity: A Narrative Review.

Personal exercise programmes have long been used and prescribed for weight loss and the improvement of quality of life in obese patients. While individualised programmes are usually the preferred option, they can be more costly and challenging to deliver in person. A move to digital programmes with a wider reach has commenced, and demand has increased due to the SARS-CoV-2 pandemic. In this review, we evaluate the current status of digital exercise programme delivery and its evolution over the past decade, with a focus on personalisation. We used specific keywords to search for articles that met our predetermined inclusion and exclusion criteria in order to provide valuable evidence and insights for future research. We identified 55 studies in total in four key areas of focus, from the more recent development of apps and personal digital assistants to web-based programmes and text or phone call interventions. In summary, we observed that apps may be useful for a low-intensity approach and can improve adherence to programmes through self-monitoring, but they are not always developed in an evidence-based manner. Engagement and adherence are important determinants of weight loss and subsequent weight maintenance. Generally, professional support is required to achieve weight loss goals.

Early Human Pathophysiological Responses to Exertional Hypobaric Decompression Stress.

INTRODUCTION: Consistent blood biomarkers of hypobaric (altitude) decompression stress remain elusive. Recent laboratory investigation of decompression sickness risk at 25,000 ft (7620 m) enabled evaluation of early pathophysiological responses to exertional decompression stress.METHODS: In this study, 15 healthy men, aged 20-50 yr, undertook 2 consecutive (same-day) ascents to 25,000 ft (7620 m) for 60 and 90 min, breathing 100% oxygen, each following 1 h of prior denitrogenation. Venous blood was sampled at baseline (T0), immediately after the second ascent (T8), and next morning (T24). Analyses encompassed whole blood hematology, endothelial microparticles, and soluble markers of cytokine response, endothelial function, inflammation, coagulopathy, oxidative stress, and brain insult, plus cortisol and creatine kinase.RESULTS: Acute hematological effects on neutrophils (mean 72% increase), eosinophils (40% decrease), monocytes (37% increase), and platelets (7% increase) normalized by T24. Consistent elevation (mean five-fold) of the cytokine interleukin-6 (IL-6) at T8 was proinflammatory and associated with venous gas emboli (microbubble) load. Levels of C-reactive protein and complement peptide C5a were persistently elevated at T24, the former by 100% over baseline. Additionally, glial fibrillary acidic protein, a sensitive marker of traumatic brain injury, increased by a mean 10% at T24.CONCLUSIONS: This complex composite environmental stress, comprising the triad of hyperoxia, decompression, and moderate exertion at altitude, provoked pathophysiological changes consistent with an IL-6 cytokine-mediated inflammatory response. Multiple persistent biomarker disturbances at T24 imply incomplete recovery the day after exposure. The elevation of glial fibrillary acidic protein similarly implies incomplete resolution following recent neurological insult.Connolly DM, Madden LA, Edwards VC, D'Oyly TJ, Harridge SDR, Smith TG, Lee VM. Early human pathophysiological responses to exertional hypobaric decompression stress. Aerosp Med Hum Perform. 2023; 94(10):738-749.

Increased inducible heat shock protein 72 expression associated with PBMC isolated from patients with haematological tumours.

BACKGROUND: Heat shock protein 72 (Hsp72) is a highly inducible stress protein and molecular chaperone. Cancers have been shown to be associated with increased Hsp72 expression within the tumour itself and this may lead to resistance to apoptosis. METHODS: Peripheral blood mononuclear cells (PBMC) were isolated from patients diagnosed with chronic lymphocytic leukaemia (CLL) (n = 27) and chronic myelomonocytic leukaemia (CMML) (n = 16) and Hsp72 expression was characterized on both the cell surface and intracellularly by flow cytometry. To allow for comparison PBMC from breast cancer patients (n = 25) and healthy volunteers (n = 19) were included. RESULTS: Both lymphocytes and monocytes from CLL and CMML patients showed high levels of total Hsp72 expression (4-6 fold increase) in comparison to breast cancer and healthy subjects. The majority of Hsp72 in these tumours was determined to be cell-surface expressed (64-93% of cell total Hsp72). CONCLUSIONS: A correlation was observed between lymphocyte and monocyte total Hsp72 expression (p < 0.001) suggesting a common stress response pathway may exist in these blood cells and there are stress conditions present within the circulation. Hsp72 expression was not found to be related to white blood cell count.