Effect of active recovery using individual maximum exercise capacity: a pilot study.

[Purpose] The intensity of active recovery (AR) for performance recovery is often determined using breath gas analyzers and other special equipment. However, such procedures are difficult to perform in the field or where facilities are inadequate. Although several AR methods using simple patient-derived information have been proposed, only a few have specifically addressed their immediate effects. The present study aimed to quantify the immediate effects of AR, which was determined using the maximum exercise capacity calculated using a physical fitness test without specialized devices. [Participants and Methods] Thirty-two healthy male participants were equally divided into AR and control groups. Each group performed squat jumps, followed by a recovery intervention of jogging at a set intensity in the AR group or rest in a seated position in the control group. Standing long jumps performed before and after the squat jumps as well as after the intervention were analyzed. [Results] The recovery rate for standing long jumps was significantly higher in the AR group than in the control group. [Conclusion] The results of this pilot study indicate that the implementation of AR based on maximum exercise capacity may enhance performance recovery and requires further validation in larger studies.

Mature human induced pluripotent stem cell-derived cardiomyocytes promote angiogenesis through alpha-B crystallin.

BACKGROUND: Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) can be used to treat heart diseases; however, the optimal maturity of hiPSC-CMs for effective regenerative medicine remains unclear. We aimed to investigate the benefits of long-term cultured mature hiPSC-CMs in injured rat hearts. METHODS: Cardiomyocytes were differentiated from hiPSCs via monolayer culturing, and the cells were harvested on day 28 or 56 (D28-CMs or D56-CMs, respectively) after differentiation. We transplanted D28-CMs or D56-CMs into the hearts of rat myocardial infarction models and examined cell retention and engraftment via in vivo bioluminescence imaging and histological analysis. We performed transcriptomic sequencing analysis to elucidate the genetic profiles before and after hiPSC-CM transplantation. RESULTS: Upregulated expression of mature sarcomere genes in vitro was observed in D56-CMs compared with D28-CMs. In vivo bioluminescence imaging studies revealed increased bioluminescence intensity of D56-CMs at 8 and 12 weeks post-transplantation. Histological and immunohistochemical analyses showed that D56-CMs promoted engraftment and maturation in the graft area at 12 weeks post-transplantation. Notably, D56-CMs consistently promoted microvessel formation in the graft area from 1 to 12 weeks post-transplantation. Transcriptomic sequencing analysis revealed that compared with the engrafted D28-CMs, the engrafted D56-CMs enriched genes related to blood vessel regulation at 12 weeks post-transplantation. As shown by transcriptomic and western blot analyses, the expression of a small heat shock protein, alpha-B crystallin (CRYAB), was significantly upregulated in D56-CMs compared with D28-CMs. Endothelial cell migration was inhibited by small interfering RNA-mediated knockdown of CRYAB when co-cultured with D56-CMs in vitro. Furthermore, CRYAB overexpression enhanced angiogenesis in the D28-CM grafts at 4 weeks post-transplantation. CONCLUSIONS: Long-term cultured mature hiPSC-CMs promoted engraftment, maturation and angiogenesis post-transplantation in infarcted rat hearts. CRYAB, which was highly expressed in D56-CMs, was identified as an angiogenic factor from mature hiPSC-CMs. This study revealed the benefits of long-term culture, which may enhance the therapeutic potential of hiPSC-CMs.

GRIA3 p.Met661Thr variant in a female with developmental epileptic encephalopathy.

The X-linked human glutamate receptor subunit 3 (GRIA3) gene (MIM *305915, Xq25) encodes ionotropic α amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA)-type glutamate receptor subunit 3, which mediates postsynaptic neurotransmission. Variants in this gene can cause a variety of neurological disorders, primarily reported in male patients. Here, we report a female patient with developmental and epileptic encephalopathy who carries the novel de novo GRIA3 variant NM_007325.5: c.1982T > C: p.Met661Thr.

Questionnaire survey on sleep habits of 3-year-old children in Asahikawa City: Comparison between 2005 and 2020.

BACKGROUND: Good sleep is essential for children's healthy growth. In 2005, we conducted a questionnaire survey on children's sleep habits and their background, targeting parents who attended health checkups for their 3-year-old children in Asahikawa City, Hokkaido. In 2020, we performed a secondary survey, including additional questions regarding media usage. We analyzed changes in children's sleep environment by comparing the results of both surveys. METHODS: Children from 500 families (n = 420; 219 males, 201 females; mean age, 3.6 years) who underwent 3.5-year-old health checkups (per the changed schedule in 2015) in Asahikawa City from July 2020 to November 2020 and their parents who had completely answered the questionnaire were included. RESULTS: The proportion of children who used childcare support system such as nursery schools or kindergarten increased from 30% in the previous survey to 95% in the present survey. The mean nocturnal sleep duration of children was 9.33 h in the present survey, 0.77 h shorter than that in the previous survey; similar to the previous survey results, it was significantly short (8.71 h) in children who went to bed after 10 PM. Moreover, it was significantly short in children who watched television for more than two hours or used media within two hours before going to bed or if parents used smartphones or watched motion pictures for >30 min/day. The rate of consulting pediatricians regarding sleep problems decreased from 3% to 2.4%. CONCLUSION: Parents' lifestyles greatly influenced children's sleep habits in 2020. Pediatricians should actively participate in managing children's sleep problems.

Anti-protease levels in cystic fibrosis are associated with lung function, recovery from pulmonary exacerbations and may be gender-related.

BACKGROUND AND OBJECTIVE: Neutrophil elastase (NE), is an important host defence against lung pathogens. Maintaining a homeostatic balance between proteases such as NE and anti-proteases such as secretory leukocyte protease inhibitor (SLPI), is important to prevent tissue damage. In the cystic fibrosis (CF) lung, elevated protease levels and impaired anti-protease defences contribute to tissue destruction. METHODS: We assessed lung function and sputum SLPI and NE levels from Pseudomonas aeruginosa infected and non-infected CF patients (median age 20 years at recruitment) during different phases of clinical disease. Healthy, never smokers served as healthy controls (HC). Sputum total cell counts (TCC) and colony forming units of P. aeruginosa were also determined in each sputum sample. RESULTS: Compared to HC, sputum SLPI was significantly reduced and NE increased in all CF subjects whether infected with P. aeruginosa or not, but the presence of P. aeruginosa worsened these parameters. Females with chronic P. aeruginosa infection had significantly lower sputum SLPI levels than males (p < 0.001). Higher sputum SLPI levels were associated with a significantly reduced rate of longitudinal decline in FEV1 % predicted (p < 0.05). Antibiotic treatment in P. aeruginosa-infected patients significantly decreased sputum TCC and increased SLPI levels, which positively correlated with improved lung function. CONCLUSION: Airway SLPI is deficient in CF, which appears more marked in P. aeruginosa-infected female patients. Importantly, a reduced anti-protease to protease ratio is associated with accelerated lung function decline. Treatment of an exacerbation is accompanied by partial recovery of anti-protease defences and significant improvement in lung function, an important clinical outcome.

Serum CC-Chemokine Ligand 2 Is Associated with Visceral Adiposity but Not Fibrosis in Patients with Non-Alcoholic Fatty Liver Disease.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is caused by ectopic fat accumulation in the liver as a consequence of metabolic perturbations associated with obesity, type 2 diabetes, dyslipidemia, and insulin resistance. People with NAFLD may develop metabolic and cardiovascular complications and/or liver-related complications, especially fibrosis and hepatocellular carcinoma, associated with high morbidity and mortality. Due to the high and increasing prevalence of NAFLD, there is an urgent need to identify people at risk of developing liver fibrosis and complications. CC-chemokine ligand 2 (CCL2) is chemokine that attracts inflammatory monocytes to stressed or injured tissues. Infiltrating inflammatory monocytes and CCL2 are strongly implicated in the pathogenesis of liver disease in animal models; however, evidence in patient cohorts is conflicting. METHODS: We investigated associations between circulating CCL2 and clinical parameters, including fibrosis assessed by liver stiffness measurement, in a cohort of 250 NAFLD patients. We also measured fatty acid binding protein 2 (FABP2), a putative biomarker of intestinal permeability in patients with liver disease, since pro-inflammatory gut-derived microbial products may induce inflammatory chemokines such as CCL2. RESULTS: Serum CCL2 levels were weakly associated with liver stiffness, but the association was no longer significant after accounting for age, diabetes, and BMI in a multivariable model. Consistent with this, girth and BMI were the strongest predictors of elevated circulating CCL2. Serum FABP2 was weakly, but significantly, correlated with CCL2, and negatively correlated with estimated glomerular filtration rate. CONCLUSION: Circulating CCL2 and FABP2 are associated with NAFLD comorbidities but not liver disease progression in patients with NAFLD.

Age-dependent changes in circulating Tfh cells influence development of functional malaria antibodies in children.

T-follicular helper (Tfh) cells are key drivers of antibodies that protect from malaria. However, little is known regarding the host and parasite factors that influence Tfh and functional antibody development. Here, we use samples from a large cross-sectional study of children residing in an area of high malaria transmission in Uganda to characterize Tfh cells and functional antibodies to multiple parasites stages. We identify a dramatic re-distribution of the Tfh cell compartment with age that is independent of malaria exposure, with Th2-Tfh cells predominating in early childhood, while Th1-Tfh cell gradually increase to adult levels over the first decade of life. Functional antibody acquisition is age-dependent and hierarchical acquired based on parasite stage, with merozoite responses followed by sporozoite and gametocyte antibodies. Antibodies are boosted in children with current infection, and are higher in females. The children with the very highest antibody levels have increased Tfh cell activation and proliferation, consistent with a key role of Tfh cells in antibody development. Together, these data reveal a complex relationship between the circulating Tfh compartment, antibody development and protection from malaria.

Impact of body fat, body water content, and skeletal muscle mass index on peak salivary lactate levels after squat jump exercise in healthy non-athlete adult males.

BACKGROUND: In the rehabilitation and sports science fields, comprehensive assessment of the response to exercise is important for accurately prescribing exercise programs. Lactate is an important energy substrate that is frequently measured in clinical practice because it provides information on aerobic capacity. Salivary lactate, which can be measured non-invasively, has recently been focused on as an alternative to blood lactate. This study aimed to determine the combined effects of body fat, body water content, and skeletal muscle mass index on peak salivary lactate levels. METHODS: Thirty-seven non-athletic males performed a squat jump exercise. Their salivary lactate levels were measured before, immediately after, and every 5 min after the exercise using a simplified device. We also assessed body composition. A linear multiple regression analysis was performed with peak salivary lactate levels as the dependent variable and body fat ratio, body water content, and the skeletal muscle mass index as independent variables. RESULTS: The participants' body fat ratio (positive effect; p = 0.001) and body water content (negative effect; p = 0.035) significantly affected peak salivary lactate levels. Skeletal muscle mass index tended to positively influence salivary lactate levels (p = 0.099), albeit not significantly. The adjusted R-squared value of the model was 0.312 (p = 0.001). CONCLUSIONS: The combined effect of body fat, body water content, and skeletal muscle mass index on peak salivary lactate levels was 31.2%. Better nutritional guidance may be effective in promoting weight loss and increasing body water content to improve aerobic capacity in the rehabilitation setting.

Wisconsin syndrome with brain volume laterality: a case report and review of the literature.

BACKGROUND: Wisconsin syndrome is a congenital anomaly caused by a 3q interstitial deletion. It is associated with characteristic facies and developmental delays. Only 33 cases with a deletion estimated to be in the associated region 3q25 have been reported. CASE REPORT: We present the case of a 5-year-old Japanese girl with a 3q24q25.2 deletion. Her facial features corresponded to the Wisconsin syndrome phenotype, and she exhibited brain volume laterality, which has not been reported previously. CONCLUSION: The clinical features of our case may contribute to narrowing down the list of candidate genes of Wisconsin syndrome.

Maternal sleep disordered breathing assessed by Epworth Sleepiness Scale and abnormal feto-placental Dopplers.

OBJECTIVE: Excessive daytime sleepiness is a frequently described phenomenon in pregnant women. The Epworth Sleepiness Scale (ESS) is a self reported standardized method of assessing sleep propensity and has been used extensively within pregnant populations. An elevated score is associated with sleep disordered breathing, as well as adverse obstetric and neonatal outcomes which may be indicative of a degree of placental dysfunction. Thus the aim of this study was to prospectively assess women using the Epworth questionnaire in conjunction with an ultrasound in both the second and third trimesters to determine if there was a difference in ESS scores across gestation and if a mid or late gestation assessment was correlated with Doppler ultrasound measures of fetal well-being. MATERIALS AND METHODS: Participants were prospectively recruited from a tertiary obstetric hospital and completed both an Epworth questionnaire and ultrasound examination in the second and third trimesters. RESULTS: A total of 302 women took part in this cohort study. There was a statistically significant (p = .02) increase in ESS score across gestation. There was however no correlation identified in either the second or third trimester between ESS score and umbilical artery pulsatility index, middle cerebral artery pulsatility index, cerebroplacental ratio, umbilical venous flow, uterine artery pulsatility index or estimated fetal weight. A higher birth weight is associated with a higher ESS score in the second trimester but not in the third trimester (p = .03). CONCLUSIONS: Maternal sleep disordered breathing assessed by the ESS score is only correlated with increased birth weight but not with fetal Doppler parameters in low risk pregnancies.

The impact of a modified carbohydrate formula, and its constituents, on glycaemic control and inflammatory markers: A nested mechanistic sub-study.

BACKGROUND: Hyperglycaemia occurs frequently in the critically ill. Dietary intake of advanced glycation end-products (AGEs), specifically Nε-(carboxymethyl)lysine (CML), may exacerbate hyperglycaemia through perturbation of insulin sensitivity. The present study aimed to determine whether the use of nutritional formulae, with varying AGE loads, affects the amount of insulin administered and inflammation. METHODS: Exclusively tube fed patients (n = 35) were randomised to receive Nutrison Protein Plus Multifibre®, Diason® or Glucerna Select®. Insulin administration was standardised according to protocol based on blood glucose (<10 mmol L-1 ). Samples were obtained at randomisation and 48 h later. AGEs in nutritional formula, plasma and urine were measured using mass spectrometry. Plasma inflammatory markers were measured using an enzyme-linked immunosorbent assay and multiplex bead-based assays. RESULTS: AGE concentrations of CML in nutritional formulae were greatest with delivery of Nutrison Protein Plus® (mean [SD]; 6335 pmol mol-1 [2436]) compared to Diason® (4836 pmol mol-1 [1849]) and Glucerna Select® (4493 pmol mol-1 [1829 pmol mol-1 ]) despite patients receiving similar amounts of energy (median [interquartile range]; 12 MJ [8.2-13.7 MJ], 11.5 MJ [8.3-14.5 MJ], 11.5 MJ [8.3-14.5 MJ]). More insulin was administered with Nutrison Protein Plus® (2.47 units h-1 [95% confidence interval (CI) = 1.57-3.37 units h-1 ]) compared to Diason® (1.06 units h-1 [95% CI = 0.24-1.89 units h-1 ]) or Glucerna Select® (1.11 units h-1 [95% CI = 0.25-1.97 units h-1 ]; p = 0.04). Blood glucose concentrations were similar. There were associations between greater insulin administration and reductions in circulating interleukin-6 (r = -0.46, p < 0.01), tumour necrosis factor-α (r = -0.44, p < 0.05), high sensitivity C-reactive protein (r = -0.42, p < 0.05) and soluble receptor for advanced glycation end-products (r = -0.45, p < 0.01) concentrations. CONCLUSIONS: The administration of greater AGE load in nutritional formula potentially increases the amount of insulin required to maintain blood glucose within a normal range during critical illness. There was an inverse relationship between exogenous insulin and plasma inflammatory markers.

The splicing effect of variants at branchpoint elements in cancer genes.

PURPOSE: Branchpoint elements are required for intron removal, and variants at these elements can result in aberrant splicing. We aimed to assess the value of branchpoint annotations generated from recent large-scale studies to select branchpoint-abrogating variants, using hereditary cancer genes as model. METHODS: We identified branchpoint elements in 119 genes associated with hereditary cancer from 3 genome-wide experimentally-inferred and 2 predicted branchpoint data sets. We then identified variants that occur within branchpoint elements from public databases. We compared conservation, unique variant observations, and population frequencies at different nucleotides within branchpoint motifs. Finally, selected minigene assays were performed to assess the splicing effect of variants at branchpoint elements within mismatch repair genes. RESULTS: There was poor overlap between predicted and experimentally-inferred branchpoints. Our analysis of cancer genes suggested that variants at -2 nucleotide, -1 nucleotide, and branchpoint positions in experimentally-inferred canonical motifs are more likely to be clinically relevant. Minigene assay data showed the -2 nucleotide to be more important to branchpoint motif integrity but also showed fluidity in branchpoint usage. CONCLUSION: Data from cancer gene analysis suggest that there are few high-risk alleles that severely impact function via branchpoint abrogation. Results of this study inform a general scheme to prioritize branchpoint motif variants for further study.

The impact on obstetric and perinatal outcomes in term infants following the introduction of a colour-coded, hierarchical cardiotocography classification system: A retrospective non-inferiority study.

BACKGROUND: Queensland introduced a colour-coded cardiotocograph (CTG) classification system (green, blue, yellow and red) to complement the Royal Australian and New Zealand College of Obstetricians and Gynaecologists prose-based classification system of 'low, unlikely, maybe or likely' fetal compromise. AIMS: The aim of the study was to determine the clinical impact of the introduction of the colour-coded CTG classification system compared to the prose-based system. We hypothesised there would be no change in the rate of operative delivery for intrapartum fetal compromise (OD-IFC). MATERIALS AND METHODS: This retrospective non-inferiority study from November 2014 to May 2018 used routinely collected data from the Mater Mother's Hospital. Non-insured women with a singleton, non-anomalous, cephalic fetus at term, attempting a vaginal birth with continuous intrapartum CTG were included. The primary outcome was OD-IFC. Secondary outcomes included various obstetric and perinatal outcomes. Non-inferiority analysis was performed with a pre-specified non-inferiority margin of 2% risk difference. RESULTS: Eleven thousand seven hundred and twenty-seven participants were included. The OD-IFC rate was similar across the study groups (prose-based 15.1% vs colour-coded 15.3%, adjusted odds ratio (aOR) 1.02, 95% CI 0.93-1.13) with the adjusted risk difference of 0.29% (95% CI -0.98 to 1.56), which did not exceed the inferiority margin. There were more spontaneous (aOR 1.11, 95% CI 1.04-1.19) and fewer instrumental (aOR 0.87, 95% CI 0.80-0.95) vaginal births in the colour-coded cohort. There were no differences in neonatal outcomes. CONCLUSIONS: Reassuringly, the colour-coded CTG classification system was non-inferior to the prose-based system, did not influence OD-IFC but was associated with more spontaneous vaginal deliveries.

Risk of metastatic disease using [18F]PSMA-1007 PET/CT for primary prostate cancer staging.

BACKGROUND: Accurate prostate cancer imaging is critical for patient management. Multiple studies have demonstrated superior diagnostic accuracy of [68Ga]-PSMA-11 PET/CT over conventional imaging for disease detection, with validated clinical and biochemical predictors of disease detection. More recently [18F]PSMA-1007 offers theoretical imaging advantages, but there is limited evidence of clinical and biochemical predictors of scan findings in the staging population. This study investigates the association of clinical variables with imaging characteristics among patients who underwent [18F]PSMA-1007 PET/CT for primary staging of men with histopathologically confirmed prostate carcinoma. A retrospective review of 194 consecutive patients imaged between May 2019 to May 2020 was performed. Association between imaging variables (presence and distribution of metastatic disease, primary tumour SUVmax) and clinical variables (EAU risk criteria) were assessed using descriptive statistics, logistic regression model and ROC analysis. RESULTS: The median age, PSA level and ISUP grade were 70 years, 10 ng/mL and ISUP grade 3, respectively. There were 36.6% of patients with intermediate-risk and 60.8% of patients with high-risk disease. ISUP grade was associated with the presence of metastasis overall (p = 0.008) as well as regional nodal (p = 0.003), non-regional nodal (p = 0.041) and bone (p = 0.006) metastases. PSA level was associated with metastatic disease overall (p = 0.001), regional (p = 0.001) and non-regional nodal metastases (p = 0.004), but not with bone metastases (p = 0.087). There were too few visceral metastases for meaningful analysis. SUVmax of the primary prostatic tumour was associated with ISUP grade (p = 0.004), PSA level (p < 0.001) and AJCC stage (p = 0.034). PSA > 20 ng/mL and ISUP grade > 3 had a specificity of 85% (95% CI 78-91%) and 60% (95% CI 50-68%) and a sensitivity of 36% (95% CI 25-49%) and 62% (95% CI 49-74%), respectively, for detection of metastatic disease. CONCLUSION: Metastatic disease according to [18F]PSMA-1007 PET/CT was associated with ISUP grade and PSA level. This is the largest study using [18F]PSMA-1007 PET/CT to confirm a positive correlation of PSA level, ISUP grade and stage with primary prostate tumour SUVmax.

Relationship between skeletal muscle mass and blood lactate level reduction after short squat jumps in healthy adult non-athletes.

[Purpose] Blood lactate reduction helps in understanding muscle recovery. Although light exercise and stretching are known interventions to reduce its concentration, the impact of skeletal muscle mass on blood lactate clearance is unknown. This study aimed to determine the relationships between blood lactate reduction and skeletal muscle mass following exercise. [Participants and Methods] Healthy non-athletic males performed squat jumps for 1 minute and 30 seconds. Blood lactate level was measured before and immediately after the exercise and then every 2 minutes for a period of 20 minutes. The decrease in blood lactate level was estimated as the difference between the minimum and maximum values. The rate of decrease was calculated by dividing the decrease in blood lactate level by time. Blood lactate level was measured using Lactate ProTM 2, while skeletal muscle mass was assessed using InBody 430. [Results] There was a significant positive correlation between skeletal muscle mass, the amount of blood lactate level reduction, and the rate of reduction of blood lactate level. [Conclusion] Our results demonstrated that greater skeletal muscle mass enabled a greater decrease in blood lactate level, suggesting that skeletal muscle mass may be involved in the reduction of blood lactate level after a squat jump. Interventions to increase skeletal muscle mass may promote more efficient lactate metabolism and muscle fatigue recovery.

Germline ERBB3 mutation in familial non-small-cell lung carcinoma: expanding ErbB's role in oncogenesis.

Lung cancer is the commonest cause of cancer deaths worldwide. Although strongly associated with smoking, predisposition to lung cancer is also heritable, with multiple common risk variants identified. Rarely, dominantly inherited non-small-cell lung cancer (NSCLC) has been reported due to somatic mutations in EGFR/ErbB1 and ERBB2. Germline exome sequencing was performed in a multi-generation family with autosomal dominant NSCLC, including an affected child. Tumour samples were also sequenced. Full-length wild-type (wtErbB3) and mutant ERBB3 (mutErbB3) constructs were transfected into HeLa cells. Protein expression, stability, and subcellular localization were assessed, and cellular proliferation, pAkt/Akt and pERK levels determined. A novel germline variant in ERBB3 (c.1946 T > G: p.Iso649Arg), coding for receptor tyrosine-protein kinase erbB-3 (ErbB3), was identified, with appropriate segregation. There was no loss-of-heterozygosity in tumour samples. Both wtErbB3 and mutErbB3 were stably expressed. MutErbB3-transfected cells demonstrated an increased ratio of the 80 kDa form (which enhances proliferation) compared with the full-length (180 kDa) form. MutErbB3 and wtErbB3 had similar punctate cytoplasmic localization pre- and post-epidermal growth factor stimulation; however, epidermal growth factor receptor (EGFR) levels decreased faster post-stimulation in mutErbB3-transfected cells, suggesting more rapid processing of the mutErbB3/EGFR heterodimer. Cellular proliferation was increased in mutErbB3-transfected cells compared with wtErbB3 transfection. MutErbB3-transfected cells also showed decreased pAkt/tAkt ratios and increased pERK/tERK 30 min post-stimulation compared with wtErbB3 transfection, demonstrating altered signalling pathway activation. Cumulatively, these results support this mutation as tumorogenic. This is the first reported family with a germline ERBB3 mutation causing heritable NSCLC, furthering understanding of the ErbB family pathway in oncogenesis.

Convergent validity of a simplified device and relationship between blood lactate and salivary lactate after a vertical squat jump in healthy non-athletes.

[Purpose] The aims of this study were 1) to examine the convergent validity between Lactate pro 2 and a standard JCA-BM 8000 automatic analyzer using salivary lactate and 2) to investigate the relationship between blood and salivary lactate levels after a vertical squat jump. [Participants and Methods] Healthy non-athletes participated in this observational study. The participants performed a vertical squat jump for 1 min 30 s. Blood and salivary lactate levels were measured before and after exercise using Lactate Pro 2. [Results] The intraclass correlation coefficient between Lactate Pro 2 and the JCA-BM 8000 automatic analyzer was 0.773, which can be considered as substantial convergent validity. However, in some samples, the salivary lactate level was out of the measurable range, and numerical values could not be obtained. The cross-correlation function between the blood and salivary lactate levels was 0.535 at lag 0 and 0.750 at lag 1, which indicated a 5-min lag between the salivary and blood lactate values. [Conclusion] Salivary lactate levels can be easily measured using Lactate Pro 2, although its sensitivity needs to be resolved. Further research is required for salivary lactate level, which can be collected non-invasively, to be used as an alternative parameter to blood lactate level.

Factors associated with low levels of patient satisfaction following peripheral nerve block.

Peripheral nerve blocks can provide surgical anaesthesia as well as excellent postoperative analgesia. When questioned postoperatively, however, some patients report low levels of satisfaction with their nerve block experience. At our hospital, patients undergoing regional anaesthesia have their patient characteristics, block characteristics and postoperative feedback routinely recorded in a block registry. We analysed data from 979 consecutive patients undergoing peripheral nerve block for orthopaedic surgery to identify factors associated with low levels of patient satisfaction. The primary outcome was patient satisfaction with their peripheral nerve block (scale 1-5: 4-5 is 'satisfied', 1-3 is 'not satisfied'). Eighty-nine percent (871/979) of patients reported being 'satisfied' with their block. Factors negatively associated with patient satisfaction were rebound pain (adjusted odds ratio (aOR) 0.19, 95% confidence interval (CI) 0.04 to 0.85 for moderate rebound pain; aOR 0.11, 95% CI 0.03 to 0.48 for severe rebound pain), discomfort during the block (aOR 0.37, 95% CI 0.16 to 0.82 for moderate discomfort; aOR 0.19, 95% CI 0.05 to 0.76 for severe discomfort) and pain in the post-anaesthesia care unit (aOR 0.30, 95% CI 0.17 to 0.55 for pain ≥8/10). Only 24% (26/108) of patients who reported being 'not satisfied' stated that they would be unwilling to undergo a hypothetical future nerve block. Rebound pain of at least moderate intensity, procedural discomfort of at least moderate intensity and severe pain in the post-anaesthesia care unit are all negatively associated with patient satisfaction. Of these factors, rebound pain occurs most frequently, being present in 52% (403/777) of our respondents.

Serum matrix metalloproteinase 7 (MMP7) is a biomarker of fibrosis in patients with non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) affects 25% of the adult population globally. Since liver fibrosis is the most important predictor of liver-related complications in patients with NAFLD, identification of patients with advanced fibrosis among at-risk individuals is an important issue in clinical practice. Transient elastography is the best evaluated non-invasive method used in referral centres to assess liver fibrosis, however serum-based tests, such as the Enhanced Liver Fibrosis (ELF) score, have a practical advantage as first-line tests due to their wider availability and lower cost. We previously identified matrix metalloproteinase 7 (MMP7) as a serum biomarker of histological advanced fibrosis in a mixed-etiology patient cohort. In this study we aimed to determine the association between MMP7 and fibrosis, assessed by transient elastography, in patients with NAFLD. Serum MMP7 levels were measured in a cohort of 228 patients with NAFLD. Associations between MMP7, liver stiffness measurement (LSM), ELF score and clinical parameters were determined using logistic regression modelling. Serum MMP7 was associated with clinically significant fibrosis (LSM ≥ 8.2), independent of age, gender, BMI and diabetes. The addition of MMP7 significantly improved the diagnostic performance of the ELF test, particularly in patients over the age of 60. Combinations of serum biomarkers have the potential to improve the sensitivity and specificity of detection of advanced fibrosis in at-risk patients with NAFLD. We have demonstrated that serum MMP7 is independently associated with clinically significant fibrosis and improves the diagnostic performance of currently available tests in older patients.