Dissecting the response in response–effect compatibility

Voluntary actions are guided by sensory anticipations of body-related as well as environment-related action effects. Even though action effects in the environment typically resemble the action goal proper, anticipations of body-related effects can cause interference if they do not correspond to intended environment-related effects. The present study explored which specific response features cause such interference: the spatial location of the moving limb or its anatomical connection to the body causes such interference? Using a response–effect compatibility design with normal and crossed hand-key mappings, we show that environment-related effects are predominantly related to spatial rather than anatomical response features, ensuring that goal-directed behavior is flexible and efficient at the same time. Furthermore, results indicate that this mechanism applies to both, free- and forced-choice actions.     

Neural mechanisms of spatial stimulus–response compatibility: the effect of crossed-hand position

Previous psychological experiments have indicated the existence of a visual-proprioceptive interaction in spatial stimulus-response compatibility (SSRC) tasks, but there is little specific information on the neural basis of such interaction in humans. Using functional magnetic resonance imaging (fMRI), we compared the neural activity associated with two different aspects of spatial coding: the coding of the "internal" spatial position of motor-response effectors (i.e., the position of body parts) as obtained through proprioception, and the coding of "external" positions, i.e., the positions of visual stimuli. A 2 x 2 factorial design was used to investigate the spatial compatibility (incompatible versus compatible) between a visual stimulus and hand position (crossed versus uncrossed). The subjects were instructed to respond to stimuli presented to the right or left visual field with either the ipsilateral (compatible condition) or the contralateral hand (incompatible condition). The incompatible condition produced stronger activation in the bilateral superior parietal lobule, inferior parietal lobule, and bilateral superior frontal gyrus than the compatible condition. The crossed-hand condition produced stronger activation in the bilateral precentral gyrus, superior frontal gyrus, superior parietal lobule, and superior temporal gyrus than the uncrossed-hand condition. These results suggest that activity in the frontal-parietal regions is related to two functions: (1) representation of the visual stimulus-motor response spatial configuration in an SSRC task, and (2) integration between external visual and internal proprioceptive sensory information. The activation in the superior temporal gyrus was not affected by the visual stimulus-motor response spatial configuration in an SSRC task; rather, it was affected by the crossed-hand posture. Thus, it seems to be related to representing internal proprioceptive sensory information necessary to carry out motor actions.     

Exercise volume and intensity: a dose–response relationship with health benefits

Introduction

The health benefits of exercise are well established. However, the relationship between exercise volume and intensity and health benefits remains unclear, particularly the benefits of low-volume and intensity exercise.

Purpose

The primary purpose of this investigation was, therefore, to examine the dose–response relationship between exercise volume and intensity with derived health benefits including volumes and intensity of activity well below international recommendations.

Methods

Generally healthy, active participants (n = 72; age = 44 ± 13 years) were assigned randomly to control (n = 10) or one of five 13-week exercise programs: (1) 10-min brisk walking 1×/week (n = 10), (2) 10-min brisk walking 3×/week (n = 10), (3) 30-min brisk walking 3×/week (n = 18), (4) 60-min brisk walking 3×/week (n = 10), and (5) 30-min running 3×/week (n = 14), in addition to their regular physical activity. Health measures evaluated pre- and post-training including blood pressure, body composition, fasting lipids and glucose, and maximal aerobic power (VO₂max).

Results

Health improvements were observed among programs at least 30 min in duration, including body composition and VO₂max: 30-min walking 28.8–34.5 mL kg^?1 min^?1, 60-min walking 25.1–28.9 mL kg^?1 min^?1, and 30-min running 32.4–36.4 mL kg^?1 min^?1. The greater intensity running program also demonstrated improvements in triglycerides.

Conclusion

In healthy active individuals, a physical activity program of at least 30 min in duration for three sessions/per week is associated with consistent improvements in health status.     

Development of a closed-loop J–T cryoablation device with a long cooling area and multiple expansion parts

Cryoablation is a surgical procedure used to freeze defective cells by inserting a low temperature probe into a human body to destroy malignant tissues. Miniaturized Joule–Thomson (J–T) refrigerators are often used to minimize the volume of the cooling device and reduce the destruction zone of normal tissue. The cooling effects of the existing probes are not uniformly generated along the longitudinal direction of the probe, which makes their applications less effective in surgeries of incompetent great saphenous veins (GSVs), where the target cells are distributed over a broad range. Long uniform refrigeration is required across the entire area of the probe to apply the same cooling effects. In this paper, a closed-loop J–T cryoablation probe was designed and fabricated to provide uniform refrigeration over a large area, with multiple expansion parts. Using flow boiling heat transfer, uniform cooling of a 200 mm-long and 0.3 mm thickness piece of target tissue was possible and simulated in a gelatin solution. The developed probe produced a greater than 53 K min⁻¹ cooling rate and the cooling temperature was below 253 K to satisfy the required cell death conditions.     

Polymicrobial pneumococcal bacteraemia: a case–control study

European Journal of Clinical Microbiology & Infectious Diseases - Polymicrobial bacteraemia involving Streptococcus pneumoniae and other bacteria (e.g. Escherichia coli, Staphylococcus aureus,...     

Factors associated with influenza vaccination among adult cancer patients: a case–control study

Influenza vaccination is recommended for cancer patients; however, adherence is low. We aimed to identify predictive factors for vaccination among cancer patients. We conducted a case–control analysis of a patient cohort in the 2010–2011 influenza season. We included adult cancer patients with solid malignancies undergoing chemotherapy, and haematological patients with active disease. Patients who died between October and November 2010 (N = 43) were excluded from analysis. Cases received the 2011 seasonal influenza vaccine, and controls did not. Data were obtained from patients' records, and validated through personal interviews. We collected socio-demographic information, and data on the malignancy and co-morbidities and triggers for vaccination and non-vaccination. We performed bivariate and multivariable analyses, in which vaccination status was the dependent variable. Of 806 patients included in analysis, 387 (48%) were vaccinated. Variables associated with vaccination on bivariate analysis were older age, higher socio-economic status, lower crowding index, marital status (widowed > married > single), malignancy type (haematological > solid tumours) and time from diagnosis, low-risk malignancy, diabetes, past vaccination, country of birth (non-Russian origin), and physicians' recommendations. Predictive factors found to be independently associated with vaccination on multivariable analysis were past vaccinations, low-risk malignancy, and country of birth. In the analysis conducted among interviewees (N = 561), recommendations from the oncologist (OR 10.7, 95% CI 5.4–21.2) and from the primary-care physician (OR 3.35, 95% CI 2.05–5.49) were strong predictors for vaccination. We conclude that ‘habitual vaccinees’ continue influenza vaccinations when ill with cancer. Physicians' recommendations, especially the oncologist's, have a major influence on patients' compliance with influenza vaccination.     

Factors associated with local invasion in infective endocarditis: a nested case–control study

ObjectiveA substantial proportion of infective endocarditis (IE) cases are complicated by local invasion. The purpose of this study was to identify patient and disease characteristics associated with local invasion in surgically treated IE patients.MethodsThis was a nested case–control study. All episodes of IE for patients admitted to Cleveland Clinic from 1 January 2013 to 30 June 2016 were identified from the Cleveland Clinic IE Registry. Patients ≥18 years of age who underwent surgery for IE were included. Among these, cases were those with local invasion, controls were those without. Local invasion, defined as periannular extension, paravalvular abscess, intracardiac fistula or pseudoaneurysm, was ascertained from the surgical operative note. Associations of selected factors with local invasion were examined in a multivariable logistic regression model.ResultsAmong 511 patients who met inclusion criteria, 215 had local invasion. Mean age was 56 years; 369 were male. Overall 345 (68%) had aortic valve, 228 (45%) mitral valve, and 66 (13%) tricuspid or pulmonic valve involvement. Aortic valve involvement (OR 6.23, 95% CI 3.55–11.44), bioprosthetic valve (OR 3.88, 95% CI 2.36–6.44), significant paravalvular leak (OR 3.80, 95% CI 1.60–9.89), new atrioventricular nodal block (OR 3.77, 95% CI 1.87–7.90), infection with streptococci other than viridans group streptococci (OR 7.54, 95% CI 2.42–24.87) and presence of central nervous system emboli (OR 1.85, 95% CI 1.13–3.04) were associated with local invasion.DiscussionIntracardiac and microorganism factors, but not comorbid conditions, are associated with local invasion in IE.     

Automatic and imperative motor activations in stimulus–response compatibility: magnetoencephalographic analysis of upper and lower limbs

The stimulus–response (S–R) compatibility effect refers to the difference in performance due to the spatial S–R relationship in choice reaction time. We investigated the mechanism of neural activities in S–R compatibility at the level of the primary motor cortices for upper and lower limbs responses using magnetoencephalography (MEG). In the S–R compatible task, subjects were required to respond on the same side of the stimulus light using either an upper or lower limb. In the incompatible task, subjects were required to respond in the reverse manner. Premotor times of upper and lower limbs were faster for the compatible response than for the incompatible response. The neuromagnetic brain activities related to response execution were estimated using a multi-dipole model. Stimulus-locked MEG indicated that the current moments of motor dipoles for both effectors occurred bilaterally and reached the first peak at a constant delay irrespective of whether the task was compatible or incompatible. This indicates that the neural activation of the primary motor cortex is automatically synchronized with the stimulus onset. Response-locked MEG showed that the peak current moment of the motor dipole contralateral to the response was stronger for the compatible task than for the incompatible one regardless of whether the responses were made using the upper or lower limbs. The MEG results suggest that automatic motor activation facilitates imperative motor activation for a compatible response, whereas it is not sufficient to prime imperative motor activation for an incompatible response.     

Establishing a quantitative framework for regulatory interpretation of genetic toxicity dose–response data: Margin of exposure case study of 48 compounds with both in vivo mutagenicity and carcinogenicity dose–response data

Quantitative relationships between carcinogenic potency and mutagenic potency have been previously examined using a benchmark dose (BMD)-based approach. We extended those analyses by using human exposure data for 48 compounds to calculate carcinogenicity-derived and genotoxicity-derived margin of exposure values (MOEs) that can be used to prioritize substances for risk management. MOEs for 16 of the 48 compounds were below 10,000, and consequently highlighted for regulatory concern. Of these, 15 were highlighted using genotoxicity-derived (micronucleus [MN] dose–response data) MOEs. A total of 13 compounds were highlighted using carcinogenicity-derived MOEs; 12 compounds were overlapping. MOEs were also calculated using transgenic rodent (TGR) mutagenicity data. For 10 of the 12 compounds examined using TGR data, the results similarly revealed that mutagenicity-derived MOEs yield regulatory decisions that correspond with those based on carcinogenicity-derived MOEs. The effect of benchmark response (BMR) on MOE determination was also examined. Reinterpretation of the analyses using a BMR of 50% indicated that four out of 15 compounds prioritized using MN-derived MOEs based on a default BMR of 5% would have been missed. The results indicate that regulatory decisions based on in vivo genotoxicity dose–response data would be consistent with those based on carcinogenicity dose–response data; in some cases, genotoxicity-based decisions would be more conservative. Going forward, and in the absence of carcinogenicity data, in vivo genotoxicity assays (MN and TGR) can be used to effectively prioritize substances for regulatory action. Routine use of the MOE approach necessitates the availability of reliable human exposure estimates, and consensus regarding appropriate BMRs for genotoxicity endpoints.     

Splenectomy correlates with increased risk of pulmonary tuberculosis: a case–control study in Taiwan

This study investigated whether there was an association between splenectomy and pulmonary tuberculosis. This was a case–control study using the database of the Taiwan National Health Insurance Programme. We identified 18 960 patients (aged 20 years or older) with newly diagnosed pulmonary tuberculosis as the case group and 73 988 participants without pulmonary tuberculosis as the control group from 1998 to 2011. Both groups were matched for sex, age (per 5 years) and index year of pulmonary tuberculosis diagnosis. The risk of pulmonary tuberculosis associated with splenectomy and other co-morbidities was estimated. After controlling for confounders, multivariable logistic regression analysis showed that the odds of pulmonary tuberculosis were 1.91 in patients with splenectomy (95% CI 1.06–3.44), compared with the participants without splenectomy. Chronic obstructive pulmonary diseases (OR 3.07, 95% CI 2.94–3.21), pneumoconiosis (OR 2.20, 95% CI 1.90–2.56), chronic kidney diseases (OR 1.49, 95% CI 1.33–1.67), diabetes mellitus (OR 1.57, 95% CI 1.50–1.64) and chronic liver diseases (OR 1.31, 95% CI 1.25–1.37) were associated with an increased risk of pulmonary tuberculosis. The sub-analysis demonstrated that the odds of pulmonary tuberculosis were 4.81 (95% CI 2.31–10.0) for patients co-morbid with splenectomy and any of the above diseases. Splenectomy is associated with a 1.9-fold increased risk of pulmonary tuberculosis in Taiwan. There is a synergistic effect between splenectomy and other co-morbidities on the risk of pulmonary tuberculosis.     

Risk factors for candidaemia in hospitalized patients with liver cirrhosis: a multicentre case–control–control study

ObjectivesThe aim of this study was to evaluate the risk factors for candidaemia in patients with liver cirrhosis.MethodsThis was a case–control–control (1:2:2) study performed in four Italian tertiary centres from 2006 to 2015. Cases were patients with liver cirrhosis developing candidaemia. For every case of candidaemia we enrolled two additional patients undergoing blood cultures for suspected infection yielding isolation of a bacterial pathogen (control A) and two additional patients undergoing blood cultures for suspected infection yielding negative results (control B). Patients were matched according to age, sex and model for end stage liver disease at hospital admission.ResultsDuring the study period 90 cases, 180 controls A and 180 controls B were included. At multivariate analysis assessed by means of multinomial conditional regression models, factors independently associated with candidaemia were previous (<30 days) acute-on-chronic liver failure (relative risk ratio (RRR) 2.22 (95% confidence interval (CI) 1.09–4.54), p = 0.046), previous(<30 days) gastrointestinal endoscopy (RRR 2.38 (95% CI 1.19–4.78) p = 0.014), previous(<30 days) antibiotic treatment for at least 7 days (RRR 2.74 (95% CI 1.00–7.48), p = 0.049), presence of central venous catheter (RRR 2.77 (95% CI 1.26–6.09, p = 0.011), total parenteral nutrition (RRR 3.90 (95% CI 1.62–9.40), p = 0.002) at infection onset and length of in-hospital stay >15 days (RRR 4.63 (95% CI 2.11–10.18), p <0.001] Conversely, rifaximin treatment was associated with lower rate of candidaemia (RRR 0.38 (95% CI 0.19–0.77), p = 0.007). Multivariable analysis for 30-day mortality showed that patients with isolation of Candida spp. from blood cultures had worse outcome when compared with controls even though the difference did not reach a statistical significance (hazard ratio 1.64 (95% 0.97–2.75) p = 0.06).ConclusionsWe identified previous antibiotic use, gastrointestinal endoscopy or acute-on-chronic liver failure and presence of central venous catheter especially for parenteral nutrition as independent factors associated with candidaemia. Surprisingly, chronic rifaximin use was a protective factor.     

Senescent endothelial progenitor cells from dogs with pulmonary arterial hypertension: a before–after self-controlled study

Previous studies have underlined the importance of endothelial dysfunction and microvascular occlusion in the pathogenesis of pulmonary artery hypertension (PAH). Since the endothelial progenitor cells (EPCs) are involved in maintaining endothelial homeostasis, we observed the change of peripheral EPCs in canines before and after PAH onset. PAH was induced by intra-pulmonary artery injection of dehydromonocrotaline (DHMC) in nine beagles. Before and 48 h and 6 weeks after DHMC injection, 40 ml peripheral blood was obtained from the femoral vein. Circulating EPCs were identified as CD133 + KDR + cells and numerated by fluorescence-activated cell sorter; the EPCs functional capacity was determined by in vitro tubule-forming assay. The senescence of EPCs was determined by β-galactosidase staining. At each time point, 2 ml blood from femoral artery was obtained for arterial oxygen pressure (PaO₂). Forty-eight  hours after DHMC injection, treated beagles suffered from hypoxemia; however, both the number and the tubule-forming capacity of EPCs were transiently raised. Six weeks later, PAH was confirmed by obviously high mean pulmonary arterial pressure (20.2 ± 1.64 vs. 11.3 ± 2.0 mmHg, p < 0.05) and low PaO₂ (69.30 ± 9.15 vs. 95.94 ± 1.43 mmHg, p < 0.01) in beagles after DHMC treatment, and their EPCs exhibited a predominant decrease in either the number (206.1 ± 26.8 vs. 632.8 ± 42.8 cells/ml blood, p < 0.01) or the tubule-forming capacity (21.1 ± 2.8 vs. 11.2 ± 2.8 tubules/×200 field, p < 0.01). Additionally, senescence-associated β-galactosidase-positive EPCs were significantly increased. Our data suggested that, after the acute stage of DHMC injury to pulmonary vessels, the EPCs from PAH beagles suffered from exhaustion and senescence.     

Periodontal infections and community-acquired pneumonia: a case–control study

The aim of this study was to evaluate if the presence of periodontal infections (PI) is associated with community-acquired pneumonia (CAP) in a group of patients admitted to a hospital. A total of 140 patients were enrolled in this case–control study, with 70 patients having CAP (case group) and the other 70 patients diagnosed with other systemic diseases (control group). A periodontal examination was carried out to assess pocket probing depth (PPD), clinical attachment loss (CAL), bleeding on probing (BOP), and presence of bacterial plaque (BP). CAL and BOP showed higher scores in the case group over the control group. They were, respectively, 3.16?±?2.43 mm and 0.33?±?0.24 % for the case group, and 1.99?±?2.23 mm and 0.25?±?0.24 % for the control group (p?<?0.05). High scores for BP were observed in both groups (case: 97.1 %; control: 98.6 %, p?=?1.0000). Chronic periodontitis (CP) was more frequent in patients with CAP (case: 61.4 %; control: 41.4 %). The presence of moderate or severe CP increased the risk for CAP [odds ratio (OR)?=?4.4, 95 % confidence interval (CI)?=?1.4–13.8], even when adjusted for age, ethnicity, gender, and smoking. Moderate and severe chronic periodontitis were associated with CAP in this study.     

Subjectivity in chromosome band–level estimation: a multicenter study

PurposeChromosome band level is the primary quality indicator for G-banded metaphase chromosome analysis. Although current professional guidelines address the minimum necessary band level for constitutional studies, there is no study documenting the comparative performance of different band-level estimation methods.MethodsThis study compared 5 band-level estimation methods (Stallard, Vancouver, Welborn, United Kingdom External Quality Assurance Scheme, and Ford) in a multicenter study in which 82 readers from 7 different clinical cytogenetics laboratories evaluated the same 10 karyotypes (5 from amniotic fluid and 5 from peripheral blood) by each method.ResultsThere was a 94% correlation between the five band-level estimation methods. The Welborn method yielded significantly lower scores for amniotic fluid karyotypes (P < 0.01) but not for peripheral blood karyotypes (P = 0.75). The distribution of scores obtained from different readers suggests a high level of subjectivity in chromosome band–level assessment. The variation in band-level estimation did not correlate with reader experience or study center, except for readers from one laboratory, for which the distribution of scores was significantly lower (P < 0.01).ConclusionThe results from this study suggest that the consistent use of one method is more important than the actual method employed for monitoring karyotype quality.Genet Med16 2, 170–175.     

Chilblains during lockdown are associated with household exposure to SARS-CoV-2: a multicentre case–control study

ObjectivesDuring the COVID-19 pandemic, numerous cases of chilblains have been reported. However, in most cases, RT-PCR or serology did not confirm SARS-CoV-2 infection. Hypotheses have been raised about an interferon-mediated immunological response to SARS-CoV-2, leading to effective clearance of the SARS-CoV-2 without the involvement of humoral immunity. Our objective was to explore the association between chilblains and exposure to SARS-CoV-2.MethodsIn this multicentre case–control study, cases were the 102 individuals referred to five referral hospitals for chilblains occurring during the first lockdown (March to May 2020). Controls were recruited from healthy volunteers' files held by the same hospitals. All members of their households were included, resulting in 77 case households (262 individuals) and 74 control households (230 individuals). Household exposure to SARS-CoV-2 during the first lockdown was categorized as high, intermediate or low, using a pre-established algorithm based on individual data on symptoms, high-risk contacts, activities outside the home and RT-PCR testing. Participants were offered a SARS-CoV-2 serological test.ResultsAfter adjustment for age, the association between chilblains and viral exposure was estimated at OR 3.3, 95% CI (1.4–7.3) for an intermediate household exposure, and 6.9 (2.5–19.5) for a high household exposure to SARS-CoV-2. Out of 57 case households tested, six (11%) had positive serology for SARS-CoV-2, whereas all control households tested (n = 50) were seronegative (p = 0.03). The effect of potential misclassification on exposure has been assessed in a bias analysis.DiscussionThis case–control study demonstrates the association between chilblains occurring during the lockdown and household exposure to SARS-CoV-2.