Ventilatory efficiency during ramp exercise in relation to age and sex in a healthy Japanese population

BackgroundThe current understanding of ventilator efficiency variables during ramp exercise testing in the normal Japanese population is insufficient, and the responses of tidal volume (VT) and minute ventilation (V?E) to the ramp exercise test in the normal Japanese population are not known.MethodsA total of 529 healthy Japanese subjects aged 20–78 years underwent cardiopulmonary exercise testing using a cycle ergometer with ramp protocols. VT and V?E at rest, at anaerobic threshold, and at peak exercise were determined. The slope of V?E versus carbon dioxide (V?CO₂) (V?E vs. V?CO₂ slope), minimum V?E/V?CO₂, and oxygen uptake efficiency slope (OUES) were determined.ResultsFor males and females in their 20 s, peak VT (VTpeak) was 2192 ± 376 and 1509 ± 260 mL (p < 0.001), peak V?E (V?Epeak) was 80.6 ± 18.7 and 57.7 ± 13.9 L/min (sex differences p < 0.001), the V?E vs. V?CO₂ slope was 24.4 ± 3.2 and 25.7 ± 3.2 (p = 0.035), the minimum V?E/V?CO₂ was 24.2 ± 2.3 and 27.0 ± 2.8 (p < 0.001), and the OUES was 2452 ± 519 and 1991 ± 315 (p < 0.001), respectively. VTpeak and V?Epeak decreased with age and increased with weight and height. The V?E vs. V?CO₂ slope and minimum V?E/V?CO₂ increased with age, while conversely, the OUES decreased with age.ConclusionsWe have established the normal range of VT and V?E responses, the V?E vs. V?CO₂ slope, the minimum V?E/V?CO₂, and the OUES for a healthy Japanese population. Some of these parameters were influenced by weight, height, sex, and age. These results provide useful reference values for interpreting the results of cardiopulmonary exercise testing in cardiac patients.     

Prevalence of advanced liver fibrosis and steatosis in type-2 diabetics with normal transaminases: A prospective cohort study

BACKGROUND Nonalcoholic fatty liver disease(NAFLD)and type-2 diabetes mellitus(T2DM)have an intricate bidirectional relationship.Individuals with T2DM,not only have a higher prevalence of non-alcoholic steatosis,but also carry a higher risk of progression to nonalcoholic steatohepatitis.Experts still differ in their recommendations of screening for NAFLD among patients with T2DM.AIM To study the prevalence of NAFLD and advanced fibrosis among our patient population with T2DM.METHODS During the study period(November 2018 to January 2020),59 adult patients with T2DM and 26 non-diabetic control group individuals were recruited prospectively.Patients with known significant liver disease and alcohol use were excluded.Demographic data and lab parameters were recorded.Liver elastography was performed in all patients.RESULTS In the study group comprised of patients with T2DM and normal alanine aminotransferase levels(mean 17.8±7 U/L),81%had hepatic steatosis as diagnosed by elastography.Advanced hepatic fibrosis(stage F3 or F4)was present in 12%of patients with T2DM as compared to none in the control group.Patients with T2DM also had higher number of individuals with grade 3 steatosis[45.8%vs 11.5%,(P<0.00001)and metabolic syndrome(84.7%vs 11.5%,P<0.00001)].CONCLUSION A significant number of patients with T2DM,despite having normal transaminase levels,have NAFLD,grade 3 steatosis and advanced hepatic fibrosis as measured by liver elastography.     

Evidence of subjects sensitized to Leishmania infantum on the French Mediterranean coast: differences in gamma interferon production between this population and visceral leishmaniasis patients

The Marseilles region is an endemic area for visceral mediterranean leishmaniasis, but although the number of dog cases, the parasite's main host, is very high, only a few people develop the disease. We looked for sensitized healthy subjects among 25 healthy individuals living in this area by studying their in vitro lymphoproliferative response to Leishmania infantum antigens and gamma interferon synthesis. We found that 65% of tested subjects were sensitized against L. infantum. We compared their cell mediated immunity to that of 13 active Kala-Azar patients and 13 controls from non-endemic areas. In patients, results showed a specific cellular immuno-deficiency in the lymphocyte response to L. infantum antigens and a global deficiency of gamma interferon production. Interestingly, the healthy individuals from the endemic area who responded to L. infantum antigens were found to produce high gamma interferon levels after L. infantum antigen stimulation. After healing, the cell mediated-immunity of the 3 patients we followed up was similar to that of the sensitized tested healthy subjects, but the former were still producing antibodies at the time of study.     

Variability of Inflammatory Cell Counts on Bronchial Biopsies of Normal Subjects

Bronchial biopsies are currently used to study the pathophysiology of airway diseases, and comparisons are often made with biopsies from healthy volunteers. It is therefore important to evaluate the variability in each parameter analyzed in bronchial biopsies of healthy volunteers in order to be able to discriminate significant changes. We analyzed bronchial biopsies of 31 nonsmoking, nonatopic healthy subjects who volunteered as normal controls for studies on pathophysiology of asthma. Mean % epithelial desquamation was 23.7% of observed total epithelial length. No subepithelial fibrosis was observed. Inflammatory cell counts (/mm² connective tissue surface) were variable among subjects but not different between small (0.25 mm²) and large biopsies. Medians (range) of positive cells were for CD3: 20.5 (0–530.0), CD4: 6.2 (0–124.4), CD8: 1.8 (0–81.5), CD25: 0 (0–62.3), HLA-DR: 80.0 (3.5–524.2), EG1: 5.3 (0–180.6), EG2: 6.4 (0–48.8), AA1: 51.3 (0–286.4), CD45: 39.7 (0–448.5) and CD45ro: 28.6 (0–425.2). Subjects living in an urban area had significantly higher CD8-positive cell counts than those from suburban areas (p = 0.0001). The presence of an animal at home was associated with lower positive cell counts for CD4 (p = 0.02), CD45 (p = 0.02) and HLA-DR (p = 0.01). In conclusion, the variability in the number and expression of markers of activity of bronchial immune cells in normal subjects likely reflects variable host responses to environmental exposures and must be taken into account when compared to specimens obtained in subjects with airway diseases.     

新型冠状病毒影响下对药物Ⅰ期临床试验受试者管理的思考

2019年末至今新型冠状病毒肺炎疫情在全球蔓延,造成严重的经济冲击和社会影响,对药物临床试验的开展也带来诸多困难与挑战。基于药物I期临床试验受试人群和流程的特殊性,引发了对在新型冠状病毒肺炎疫情影响下药物I期临床试验受试者管理的一些思考。提出从受试者招募、筛选、入住的不同阶段,到受试者宣教、饮食管理及不良事件观察等多方面的应对策略,旨在探讨如何在疫情防控常态化情况下,更好地保护受试者安全与权益,加强临床试验的风险控制,确保试验的顺利完成。     

Electrophysiological responses to visuospatial regularity

Humans are quicker to detect reflectional than rotational or translational symmetry, despite the fact that these patterns are equally regular. We were interested in the neural correlates of these perceptual effects. Participants viewed random, reflection, rotation, and translation patterns while we recorded EEG from the scalp. Half the participants classified the pattern regularity overtly, the other half did not explicitly attend to pattern regularity but reported rare oddball trials, where two squares were embedded among the dots. The amplitude of a symmetry‐related ERP known as the sustained posterior negativity was most pronounced for reflection, then rotation and translation. We suggest that reflectional symmetry, despite its biological significance, may not be processed by unique visual mechanisms, but instead it could be a preferred stimulus for a more general regularity‐sensitive network in the extrastriate visual cortex.     

Comparison of video-recorded laryngeal movements during swallowing by normal young men with piezoelectric sensor and electromyographic signals

The movement of the larynx in five young men during the swallowing of a liquid was examined by simultaneously recording a video-movie, the trajectory of a piezoelectric sensor, and the surface electromyogram of the suprahyoid muscles (SH). The movies revealed swallowing was associated with four characteristic spatial points of laryngeal movement: (1) a slight movement in the superoposterior direction (1.9 ± 1.2 s; mean ± SD of the time elapsed after the command to swallow was issued); (2) the initiation of anterosuperior elevation (2.3 ± 1.3 s); (3) the turn at the highest position (3.2 ± 1.2 s); and (4) the return to the initial position (4.1 ± 1.4 s). The piezoelectric sensor and the SH electromyogram also detected characteristic temporal points that closely corresponded to the characteristic temporal points captured by the video. The advantages of using movies in swallowing research are discussed.     

Reliability of knee extensor neuromuscular structure and function and functional tests’ performance

IntroductionThe aim of this study was to evaluate the intra and inter-rater and inter-analyzer reliability of neuromuscular variables and functional tests.MethodsCross-sectional crossover design. Two independent raters and analyzers evaluated twenty-two healthy subjects. Knee-extensor strength was assessed from three maximal voluntary isometric contractions. Muscle activation was obtained from the vastus lateralis (VL), rectus femoris (RF), and vastus medialis (VM) muscles. VL and RF muscles’ architecture [fascicle length (FL), pennation angle (PA), muscle thickness (MT)] was obtained at rest by ultrasound. The time from five sit-to-stand (STS) trials, and the distance from the 6-min walk test (6MWT) were obtained. Intraclass correlation coefficient was determined and classified as strong (r = 0.75–1.00), moderate (r = 0.40–0.74), and weak (r < 0.40).ResultsStrong intra-rater reliability values were observed for strength (r = 0.97), muscle activation [VL (r = 0.91); RF (r = 0.92); VM (r = 0.80)], VL [FL (r = 0.90); PA (r = 0.94); MT (r = 0.99)] and RF [MT (r = 0.85)] muscle architecture, STS (r = 0.95), and 6MWT (r = 0.98). Inter-rater reliability also presented strong values for strength (r = 0.97), muscle activation [VL (r = 0.94); RF (r = 0.79); VM (r = 0.78)], muscle architecture VL [PA (r = 0.81) and MT (r = 0.88)] and RF [MT (r = 0.80)], STS (r = 0.93), and 6MWT (r = 0.98). A moderate correlation VL muscle architecture [FL (r = 0.69)]. Inter-analyzer muscle architecture reliability presented strong VL [FL (r = 0.77); PA (r = 0.76); MT (r = 0.91)] and RF [MT (r = 0.99)].ConclusionThe high intra and inter-rater and inter-analyzer reliability values for most variables is evidence that they can be used for clinical evaluation. Muscle architecture might need a longer training period by different raters and analyzers to increase reliability.