Monocyte Regulation in Homeostasis and Malignancy.

Monocytes are progenitors to macrophages and a subclass of dendritic cells (monocyte-derived dendritic cells, MoDCs), but they also act as circulating sensors that respond to environmental changes and disease. Technological advances have defined the production of classical monocytes in the bone marrow through the identification of lineage-determining transcription factors (LDTFs) and have proposed alternative routes of differentiation. Monocytes released into the circulation can be recruited to tissues by specific chemoattractants where they respond to sequential niche-specific signals that determine their differentiation into terminal effector cells. New aspects of monocyte biology in the circulation are being revealed, exemplified by the influence of cancer on the systemic alteration of monocyte subset abundance and transcriptional profiles. These changes can act to enhance the metastatic spread of primary cancers and may offer therapeutic opportunities.

Interrater Reliability of the Scale for the Assessment and Rating of Ataxia, Berg Balance Scale, and Functional Independence Measure Motor Domain in Individuals With Hereditary Cerebellar Ataxia.

OBJECTIVE: To determine the interrater reliability of the Scale for the Assessment and Rating of Ataxia (SARA), Berg Balance Scale (BBS), and motor domain of the FIM (m-FIM) administered by physiotherapists in individuals with a hereditary cerebellar ataxia (HCA). DESIGN: Participants were assessed by 1 of 4 physiotherapists. Assessments were video-recorded and the remaining 3 physiotherapists scored the scales for each participant. Raters were blinded to each other's scores. SETTING: Assessments were administered at 3 clinical locations in separate states in Australia. PARTICIPANTS: Twenty-one individuals (mean age=47.63 years; SD=18.42; 13 male and 8 female) living in the community with an HCA were recruited (N=21). MAIN OUTCOME MEASURES: Total and single-item scores of the SARA, BBS, and m-FIM were examined. The m-FIM was conducted by interview. RESULTS: Intraclass coefficients (2,1) for the total scores of the m-FIM (0.92; 95% confidence interval [CI], 0.85-0.96), SARA (0.92; 95% CI, 0.86-0.96), and BBS (0.99; 95% CI, 0.98-0.99) indicated excellent interrater reliability. However, there was inconsistent agreement with the individual items, with SARA item 5 (right side) and item 7 (both sides) demonstrating poor interrater reliability and items 1 and 2 demonstrating excellent reliability. CONCLUSIONS: The m-FIM (by interview), SARA, and BBS have excellent interrater reliability for use when assessing individuals with an HCA. Physiotherapists could be considered for administration of the SARA in clinical trials. However, further work is required to improve the agreement of the single-item scores and to examine the other psychometric properties of these scales.

Improving chronic kidney disease detection and treatment in the United States: the chronic kidney disease cascade of care (C3) study protocol.

BACKGROUND: There are major gaps in the implementation of guideline-concordant care for persons with chronic kidney disease (CKD). The CKD Cascade of Care (C3) initiative seeks to improve CKD care by improving detection and treatment of CKD in primary care. METHODS: C3 is a multi-modal initiative deployed in three major academic medical centers within the Department of Veterans Affairs (VA) Health Care System: San Francisco VA, San Diego VA, and Houston VA. The main objective of the first phase of C3 described in this protocol is to establish the infrastructure for universal CKD detection among primary care patients at high-risk for CKD with a triple-marker screen comprising cystatin C, creatinine, and albuminuria. Across the three sites, a comprehensive educational intervention and the integration of primary care-based clinical champions will be employed with the goal of improving CKD detection and treatment. The San Francisco VA will also implement a practice-facilitation intervention leveraging telehealth and health informatics tools and capabilities for enhanced CKD detection. Parallel formative evaluation across the three sites will assess the feasibility and acceptability of integrating cystatin C as part of routine CKD detection in primary care practice. The effectiveness of the interventions will be assessed using a pre-post observational design for change in the proportion of patients tested annually for CKD. Secondary outcomes will assess change in the initiation of cardio-kidney protective therapies and in nephrology referrals of high-risk patients. DISCUSSION: The first phase of C3 is a multi-facility multi-modal initiative that aims to improve CKD care by implementing a triple-marker screen for enhanced CKD detection in primary care.

Gender diversity training in Canadian paediatric postgraduate medical education: A needs assessment survey.

OBJECTIVES: Evaluate the current state of postgraduate medical education on gender diversity in Canadian paediatric residency programs, exploring both resident and program director perceptions. BACKGROUND: Primary care providers are seeing more gender diverse children and youth in their offices, along with an exponential growth in referrals to Canadian specialty clinics and potential for significant mental health comorbidities. Gender-affirming support and management have been shown to improve overall outcomes. There is no mandatory curriculum on gender diversity for Canadian paediatric residency programs. METHODS: Cross-sectional online surveys in English and French distributed to program directors (PDs) and paediatric residents in the 17 Canadian paediatric residency programs. Data were analyzed by descriptive statistics with 95% confidence intervals. RESULTS: Response rate was 88.2% from PDs and 24.5% from paediatric residents. Among PDs, 14.3% (95% confidence interval [CI]: 6.3, 22.3) reported a formal curriculum for gender diversity teaching. Sixty-four per cent (53.3, 75.2) of PDs estimated their residents received ≤ 2 hours teaching on gender diversity. Residents reported comfort levels ≤ 50% on specific topics. Among residents, 73.8% (67.9, 79.6) reported that mandatory time in a gender diversity clinic would be the most effective teaching tool while PDs favoured an online module (66.7% [58.2, 75.1]). Barriers to more teaching included lack of time in a busy curriculum. Over 90% of resident indicated that more teaching on gender diversity is required. CONCLUSIONS: Significant variability in education on gender diversity is seen amongst Canadian paediatric residency programs. Discussion regarding a formal paediatric curriculum on gender diversity is needed.

Space-time wiring specificity supports direction selectivity in the retina.

How does the mammalian retina detect motion? This classic problem in visual neuroscience has remained unsolved for 50 years. In search of clues, here we reconstruct Off-type starburst amacrine cells (SACs) and bipolar cells (BCs) in serial electron microscopic images with help from EyeWire, an online community of 'citizen neuroscientists'. On the basis of quantitative analyses of contact area and branch depth in the retina, we find evidence that one BC type prefers to wire with a SAC dendrite near the SAC soma, whereas another BC type prefers to wire far from the soma. The near type is known to lag the far type in time of visual response. A mathematical model shows how such 'space-time wiring specificity' could endow SAC dendrites with receptive fields that are oriented in space-time and therefore respond selectively to stimuli that move in the outward direction from the soma.

Variation in the prion protein gene (PRNP) sequence of wild deer in Great Britain and mainland Europe.

Susceptibility to prion diseases is largely determined by the sequence of the prion protein gene (PRNP), which encodes the prion protein (PrP). The recent emergence of chronic wasting disease (CWD) in Europe has highlighted the need to investigate PRNP gene diversity in European deer species, to better predict their susceptibility to CWD. Here we report a large genetic survey of six British deer species, including red (Cervus elaphus), sika (Cervus nippon), roe (Capreolus capreolus), fallow (Dama dama), muntjac (Muntiacus reevesii), and Chinese water deer (Hydropotes inermis), which establishes PRNP haplotype and genotype frequencies. Two smaller data sets from red deer in Norway and the Czech Republic are also included for comparison. Overall red deer show the most PRNP variation, with non-synonymous/coding polymorphisms at codons 98, 168, 226 and 247, which vary markedly in frequency between different regions. Polymorphisms P168S and I247L were only found in Scottish and Czech populations, respectively. T98A was found in all populations except Norway and the south of England. Significant regional differences in genotype frequencies were observed within both British and European red deer populations. Other deer species showed less variation, particularly roe and fallow deer, in which identical PRNP gene sequences were found in all individuals analysed. Based on comparison with PRNP sequences of North American cervids affected by CWD and limited experimental challenge data, these results suggest that a high proportion of wild deer in Great Britain may be susceptible to CWD.

Use of cyproheptadine to stimulate appetite and body weight gain: A systematic review.

OBJECTIVE: A systematic review identifying the use of cyproheptadine (CY) as an appetite stimulant was completed. METHOD: Studies of any design exploring the efficacy of CY as an appetite stimulant in all age groups and populations were included. Primary outcomes of studies included were weight gain, appetite stimulation, and/or caloric/nutritional intake increase. The review was completed in accordance with PRISMA standards. RESULTS: A total of 46 articles across 21 different treatment populations met criteria for the review, including 32 randomized controlled trials, 4 prospective cohort studies, 4 retrospective cohort studies, 4 case reports and 2 case series. Of these, 39 demonstrated that CY resulted in significant weight gain in the sample under study. Studies exploring the use of CY in those with malignant/progressive disease states, such as HIV and cancer, showed minimal to no benefit of the medication. Transient mild to moderate sedation was the most commonly reported side effect. Studies included were heterogeneous in terms of methods as well as study patient demographics, characteristics and concurrent medical conditions. Few studies provided objective measures of appetite change. DISCUSSION: CY appears to be a safe, generally well-tolerated medication that has utility in helping facilitate weight gain in patients drawn from a variety of underweight populations. Future prospective randomized controlled studies in low weight patients that include objective measures of appetite and intake are needed to better understand the mechanism by which CY augments weight gain.

UK news media representations of smoking, smoking policies and tobacco bans in prisons.

BACKGROUND: Prisoner smoking rates remain high, resulting in secondhand smoke exposures for prison staff and non-smoker prisoners. Several jurisdictions have introduced prison smoking bans with little evidence of resulting disorder. Successful implementation of such bans requires staff support. As news media representations of health and other issues shape public views and as prison smoking bans are being introduced in the UK, we conducted content analysis of UK news media to explore representations of smoking in prisons and smoke-free prisons. METHODS: We searched 64 national and local newspapers and 5 broadcast media published over 17 months during 2015-2016, and conducted thematic analysis of relevant coverage in 106 articles/broadcasts. RESULTS: Coverage was relatively infrequent and lacked in-depth engagement with the issues. It tended to reinforce a negative view of prisoners, avoid explicit concern for prisoner or prison staff health and largely ignore the health gains of smoke-free policies. Most coverage failed to discuss appropriate responses or support for cessation in the prison context, or factors associated with high prisoner smoking rates. Half the articles/broadcasts included coverage suggesting smoke-free prisons might lead to unrest or instability. CONCLUSIONS: Negative news media representations of prisoners and prison smoking bans may impact key stakeholders' views (eg, prison staff, policy-makers) on the introduction of smoke-free prison policies. Policy-makers' communications when engaging in discussion around smoke-free prison policies should draw on the generally smooth transitions to smoke-free prisons to date, and on evidence on health benefits of smoke-free environments and smoking cessation.

Adolescent pregnancy and eating disorders: a minireview and case report.

BACKGROUND: Despite the fact that eating disorders (EDs) during pregnancy and early child bearing can both individually increase risk to mother and child, there is a paucity of research exploring pregnancy in adolescence and concomitant EDs. CASE: We report the case of a 16-year-old female with atypical anorexia nervosa, who experiences a remission of her ED behavior during pregnancy, followed by a severe relapse in the post-partum period. CONCLUSION: In this case, pregnancy functioned as a motivator for remission in our patient with concomitant ED. Further research is needed to identify risks of EDs in adolescent pregnancy, to explore the trajectory of pre-existing EDs during pregnancy and to identify effective interventions for prolonging remission into the post-partum period.

Sodium bicarbonate ingestion and individual variability in time-to-peak pH.

This study determined variability in time-to-peak pH after consumption of 300 mg kg-1 of sodium bicarbonate. Seventeen participants (mean ± SD: age 21.38 ± 1.5 years; mass 75.8 ± 5.8 kg; height 176.8 ± 7.6 cm) reported to the laboratory where a resting capillary sample was taken. Then, 300 mg kg-1 of NaHCO3 in 450 ml of flavoured water was ingested. Participants rested for 90 min and repeated blood samples were procured at 10 min intervals for 60 min and then every 5 min until 90 min. Blood pH concentrations were measured. Results suggested that time-to-peak pH (64.41 ± 18.78 min) was variable with a range of 10-85 min and a coefficient of variation of 29.16%. A bimodal distribution occurred, at 65 and 75 min. In conclusion, athletes, when using NaHCO3 as an ergogenic aid, should determine their time-to-peak pH to best utilize the added buffering capacity this substance allows.

Gastrointestinal complications associated with anorexia nervosa: A systematic review.

OBJECTIVE: A systematic review identifying gastrointestinal (GI) complications attributable to anorexia nervosa (AN) was completed. METHOD: Studies of any design exploring the pathogenesis of complications and treatment strategies were included. The review was completed in accordance with PRISMA standards. RESULTS: A total of 123 articles were retained, including one randomized control trial. The majority of included studies were case reports and case series. Controlled studies demonstrated that patients with AN were more likely to have delays in gastric motility, gastric emptying and intestinal transit than comparator groups although results were not uniform across all studies. Published reports suggest that complications can occur at any segment of the GI tract. These issues may derive as a consequence of severe malnourishment, from eating disorder related symptoms such as self-induced purging or from the refeeding process itself. Multiple studies noted that patients with AN report high rates of GI symptoms although in the few cases where medical testing was undertaken, correlations between self-reported symptoms and measurable pathology were not demonstrated. DISCUSSION: GI complications may occur throughout the entire GI tract in patients with AN. It is recommended that clinicians use careful judgment when pursuing targeted investigation or introducing symptom specific treatments in response to GI complaints. Evidence suggests that most GI complications resolve with refeeding and cessation of ED symptoms.

The Effects of Novel Ingestion of Sodium Bicarbonate on Repeated Sprint Ability.

This work examined the influence of an acute dose of sodium bicarbonate (NaHCO3) on buffering capacity and performance during a repeated sprint ability (RSA) protocol. Eleven (mean ± SD: age 24.6 ± 6.1 years; mass 74.9 ± 5.7 kg; height 177.2 ± 6.7 cm) participated in the study, undertaking 4 test sessions. On the first visit to the laboratory, each participant ingested 300 mg · kg(-1) of NaHCO3 (in 450 ml of flavored water) and blood samples were obtained at regular intervals to determine the individual times peak pH and HCO3. In subsequent visits, participants ingested 300 mg · kg(-1) of NaHCO3, 270 mg · kg(-1) body mass (BM) of NaCI, or no drink followed by a RSA cycling protocol (10 × 6 seconds sprints with 60 seconds recovery), which commenced at each individuals predetermined ingestion peak pH response time. Blood samples were obtained before exercise and after the first, fifth, and 10th sprint to determine the blood pH, HCO3, and lactate (La) responses. Total work completed during the repeated sprint protocol was higher (p ≤ 0.05) in the NaHCO3 condition (69.8 ± 11.7 kJ) compared with both the control (59.6 ± 12.2 kJ) and placebo (63.0 ± 8.3 kJ) conditions. Peak power output was similar (p > 0.05) between the 3 conditions. Relative to the control and placebo conditions, NaHCO3 ingestion induced higher (p ≤ 0.05) blood pH and HCO3 concentrations before exercise and during the bouts, and higher lactate concentrations (p ≤ 0.05) after the final sprint. Results suggest that NaHCO3 improves the total amount of work completed during RSA through enhanced buffering capacity.

Leucine-enriched protein feeding does not impair exercise-induced free fatty acid availability and lipid oxidation: beneficial implications for training in carbohydrate-restricted states.

Given that the enhanced oxidative adaptations observed when training in carbohydrate (CHO)-restricted states is potentially regulated through free fatty acid (FFA)-mediated signalling and that leucine-rich protein elevates muscle protein synthesis, the present study aimed to test the hypothesis that leucine-enriched protein feeding enhances circulating leucine concentration but does not impair FFA availability or whole body lipid oxidation during exercise. Nine males cycled for 2 h at 70% VO2peak when fasted (PLACEBO) or having consumed a whey protein solution (WHEY) or a leucine-enriched whey protein gel (GEL), administered as 22 g 1 h pre-exercise, 11 g/h during and 22 g 30 min post-exercise. Total leucine administration was 14.4 g and 6.3 in GEL and WHEY, respectively. Mean plasma leucine concentrations were elevated in GEL (P = 0.001) compared with WHEY and PLACEBO (375 ± 100, 272 ± 51, 146 ± 14 µmol L(-1), respectively). No differences (P = 0.153) in plasma FFA (WHEY 0.53 ± 0.30, GEL 0.45 ± 0.25, PLACEBO 0.65 ± 0.30, mmol L(-1)) or whole body lipid oxidation during exercise (WHEY 0.37 ± 0.26, GEL 0.36 ± 0.24, PLACEBO 0.34 ± 0.24 g/min) were apparent between trials, despite elevated (P = 0.001) insulin in WHEY and GEL compared with PLACEBO (38 ± 16, 35 ± 16, 22 ± 11 pmol L(-1), respectively). We conclude that leucine-enriched protein feeding does not impair FFA availability or whole body lipid oxidation during exercise, thus having practical applications for athletes who deliberately train in CHO-restricted states to promote skeletal muscle adaptations.

Exploring avoidant/restrictive food intake disorder in eating disordered patients: a descriptive study.

OBJECTIVE: To assess and compare clinical characteristics of patients with avoidant/restrictive food intake disorder (ARFID) to those with anorexia nervosa (AN). METHOD: A retrospective review of adolescent eating disorder (ED) patients assessed between 2000 and 2011 that qualified for a diagnosis of ARFID was completed. A matched AN sample was used to compare characteristics between groups. RESULTS: Two hundred and five patients met inclusion criteria and were reviewed in detail. Of these, 34 (5%) patients met criteria for ARFID. A matched sample of 36 patients with AN was used to draw comparisons. Patients with ARFID were younger than those with AN, more likely to present before age 12, and more likely to be male. Patients in both groups presented at low weights. Common eating-specific behaviors and symptoms in the ARFID group included food avoidance, loss of appetite, abdominal pain, and fear of vomiting. Rates of comorbid psychiatric diagnoses and medical morbidity were high in both groups. Almost 80% of AN patients and one-third of ARFID patients required hospital admission as a result of medical instability. Symptom profiles in 4/34 ARFID patients resulted in eventual reclassification to AN. DISCUSSION: This study supports the notion that a small percentage of adolescent patients presenting with restrictive eating disorders meet criteria for ARFID. Patients are younger than average, more likely to be male compared to adolescent AN samples, and have high rates of psychiatric and medical morbidity. The study also suggests that a proportion of patients evolve into AN as treatment progresses.

Application and comparison of point-of-care devices for field evaluation of underlying health status of Guatemalan sugarcane workers.

With chronic disease prevalence on the rise globally, surveillance and monitoring are critical to improving health outcomes. Point-of-care (POC) testing can facilitate epidemiological research and enhance surveillance systems in limited resource settings, but previous research has identified bias between POC devices and laboratory testing. We compared the performance of two POC blood analyzers, the iSTAT handheld (Abbott, Princeton, NJ, USA) and the StatSensor Creatinine (Nova Biomedical, Waltham, MA, USA) to concurrent blood samples analyzed at a local laboratory that were collected from 89 agricultural workers in Guatemala. We measured creatinine and other measures of underlying health status with the POC and the lab blood samples. Pearson correlation coefficients, Bland-Altman plots, no intercept linear regression models and two-sample t-tests were used to evaluate the agreement between the POC and lab values collected across three study days and to assess differences by study day in a field setting. On average there was no observed difference between the iSTAT and lab creatinine measurements (p = 0.91), regardless of study day. Using lab creatinine as the gold standard, iSTAT creatinine results were more accurate compared to the Statsensor, which showed some bias, especially at higher values. The iSTAT had good agreement with the lab for sodium and blood urea nitrogen (BUN), but showed differences for potassium, anion gap, bicarbonate (TCO2), glucose, and hematocrit. In this tropical field setting, the research team devised a protocol to prevent the devices from overheating. In limited resource settings, POC devices carry advantages compared to traditional lab analyses, providing timely results to patients, researchers, and healthcare systems to better evaluate chronic health conditions. Technical challenges due to use of POC devices in high heat and humidity environments can be addressed using a standard protocol for transporting and operating the devices.

Charge generation in low-polarity solvents: poly(ionic liquid)-functionalized particles.

We present a straightforward strategy for the synthesis of highly charged poly(ionic liquid)-functionalized particles in low-polarity solvents. A series of cationic liquid monomers consisting of a tetraalkyl ammonium cation and a fluorinated tetrakis[phenyl] borate anion linked, via a C3-alkyl chain, to a methacrylate unit were synthesized. The addition of this ionic monomer to a conventional dispersion polymerization of methyl methacrylate and methacrylic acid at 80 °C in a mixed dodecane/hexane solvent yielded spherical, highly monodisperse particles with mean diameters of between ~50 and 2500 nm with high electrophoretic mobility and stability in nonpolar solvents such as dodecane. The surface potential in dodecane could be adjusted in the range from 0 to 180 ± 9 mV by altering the ratio of ionic monomer to methacrylate monomers. The particles open up new opportunities for the electrostatic assembly of nanoparticles and organized structures in nonpolar environments.

A systematic review and meta-analysis of the role of radiology in the diagnosis of occult inguinal hernia.

BACKGROUND: Inguinal hernias are a common cause of groin pain. Most hernias are detectable by clinical examination and many patients proceed to hernia repair on the basis of history and examination findings alone. However, a significant proportion of patients with symptoms suggestive of groin hernia are found to have a normal clinical examination. Several radiological techniques have been developed to solve the dilemma posed by occult inguinal hernias. No systematic review or meta-analysis has addressed this common clinical problem. METHODS: A systematic review and meta-analysis were undertaken of relevant articles in Medline, Embase, and the Cochrane database. Studies were assessed using the QUADAS tool. Statistical analysis was undertaken. RESULTS: We have shown in this meta-analysis that ultrasound has a sensitivity of 86% and a specificity of 77% in occult inguinal hernias. Computed tomography has a sensitivity of 80% and a specificity of 65%. Herniography has a sensitivity of 91% and a specificity of 83%. CONCLUSIONS: Based on this systematic review, herniography should be considered as the initial investigation for occult inguinal hernia where available. In centers where this is not available, ultrasound of the groin should be used with good clinical judgment. When there is still diagnostic uncertainty, further investigation with magnetic resonance imaging should be considered to exclude alternative pathology.

Meta-analysis of sonography in the diagnosis of inguinal hernias.

Groin hernias are common conditions, and there is a need for accurate imaging when the clinical diagnosis is not clear. A meta-analysis was undertaken to investigate the diagnostic accuracy of sonography in the diagnosis of inguinal hernias. After review of literature searches, 9 original articles were included. Data were pooled and statistically analyzed. In the studies included, sensitivity ranged from 92.7% to 100%; specificity ranged from 22.2% to 100%; the positive predictive value ranged from 83.3 to 100%; and the negative predictive value ranged from 40 to 100%. Sonography has overall sensitivity of 96.6 %, specificity of 84.8%, and a positive predictive value of 92.6%. In cases of diagnostic uncertainty, sonography offers value as an initial imaging modality. It has advantages over other radiologic methods, as it is inexpensive and has minimal complications. When the clinical diagnosis of an inguinal hernia is uncertain, sonographic findings should be interpreted in conjunction with clinical judgment, as its diagnostic accuracy is reduced in the absence of any clinically palpable hernia.

Effectiveness of the perioperative encounter in promoting regular exercise and physical activity: a systematic review and meta-analysis.

Background: Low levels of physical activity (PA) are associated with poorer health outcomes. The perioperative encounter (extending from initial contact in primary care to beyond discharge from hospital) is potentially a good time to intervene, but data regarding the effectiveness of interventions are scarce. To address this, we systematically reviewed existing literature to evaluate the effectiveness of interventions applied perioperatively to facilitate PA in the medium to long-term (at least six months after the intervention). Methods: In this systematic review and meta-analysis, we searched Central Register of Controlled Trials (CENTRAL, Cochrane Library), MEDLINE, CINAHL, Embase, PsycInfo, and SPORTDiscus from database inception to October 22nd 2020, with an updated search done on August 4th 2022. We searched clinical trials registers, and conducted forward- and backward-citation searches. We included randomised controlled trials and quasi-randomised trials comparing PA interventions with usual care, or another PA intervention, in adults who were scheduled for, or had recently undergone, surgery. We included trials which reported our primary outcomes: amount of PA or whether participants were engaged in PA at least six months after the intervention. A random effects meta-analysis was used to pool data across studies as risk ratios (RR), or standardised mean differences (SMDs), which we interpreted using Cohen. We used the Cochrane risk of bias tool and used GRADE to assess the certainty of the evidence. This study is registered with PROSPERO, CRD42019139008. Findings: We found 57 trials including 8548 adults and compared 71 interventions facilitating PA. Most interventions were started postoperatively and included multiple components. Compared with usual care, interventions may slightly increase the number of minutes of PA per day or week (SMD 0.17, 95% CI 0.09-0.26; 14 studies, 2172 participants; I2 = 0%), and people's engagement in PA at the study's end (RR 1.19, 95% CI 0.96-1.47; 9 studies, 882 participants; I2 = 25%); this was moderate-certainty evidence. Some studies compared two different types of interventions but it was often not feasible to combine data in analysis. The effect estimates generally indicated little difference between intervention designs and we judged all the evidence for these comparisons to be very low certainty. Thirty-six studies (63%) had low risk of selection bias for sequence generation, 27 studies (47%) had low risk of bias for allocation concealment, and 56 studies (98%) had a high risk of performance bias. For detection bias for PA outcomes, we judged 30 studies (53%) that used subjective measurement tools to have a high risk of detection bias. Interpretation: Interventions delivered in the perioperative setting, aimed at enhancing PA in the medium to long-term, may have overall benefit. However, because of imprecision in some of the findings, we could not rule out the possibility of no change in PA. Funding: National Institute for Health Research Health Services and Delivery Research programme (NIHR127879).

Amino acids 1811-1960 of myosin heavy chain 9 is involved in murine gammaherpesvirus 68 infection.

Myosin heavy chain 9 (MYH9) has been identified as a crucial factor in gammaherpesvirus infection. Murine gammaherpesvirus 68 (MHV-68) was used as an appropriate viral model for investigating gammaherpesviruses in vivo and developing antiviral treatments. However, the roles of MYH9 in MHV-68 infection have not been documented. In the study, the relationship between the expression of MYH9 and MHV-68 infection and MYH9 as the antiviral target were analyzed. The results revealed that MYH9 was enriched on the cell surface and co-localized with MHV-68 upon viral infection. Knocking down MYH9 with siRNA or using the specific inhibitor of MYH9 activity, Blebbistatin, resulted in the decreasing of MHV-68 infection. Furthermore, polyclonal antibodies against MYH9 reduced infection by approximately 74% at a dose of 100 µg/ml. The study determined that MYH9 contributes to MHV-68 infection by interacting with viral glycoprotein 150 (gp150) in the BHK-21 cell membrane. The specific region of MYH9, amino acids 1811-1960 (C-150), was identified as the key domain involved in the interaction with MHV-68 gp150 and was found to inhibit MHV-68 infection. Moreover, C-150 was also shown to decrease HSV-1 infection in Vero cells by approximately 73%. Both C-150 and Blebbistatin were found to inhibit MHV-68 replication and reduce histopathological lesions in vivo in C57BL/6J mice. Taken together, these findings suggested that MYH9 is crucial for MHV-68 infection through its interaction with viral gp150 and that C-150 may be a promising antiviral target for inhibiting MHV-68 infection in vitro and in vivo.