Subjective Variables Research Articles

Unraveling the mystery of isocaloric endurance training - Influence of exercise modality, biological sex, and physical fitness

BackgroundA sedentary lifestyle with low energy expenditure (EE) is associated with chronic diseases and mortality. Barriers such as “lack of time” or “lack of motivation” are common reasons why physical exercise is neglected in the general population. To optimize EE in the time available, time-efficient but also enjoyable types of exercise are required. We therefore used an isocaloric approach to systematically investigate the effects of six different endurance exercise modalities on metabolic, mechanical, cardiorespiratory, and subjective variables in relation to biological sex and physical fitness. MethodsOut of 104, 92 healthy participants (21 recreationally trained and 18 trained females, 25 recreationally trained and 28 trained males) were subjected to physiological exercise testing to determine the exercise intensities for six exercise modalities, i.e., three different high-intensity interval training (HIIT) protocols (5 × 4 min, 15 × 1 min, 30 × 30 sec intervals), threshold (THR), speed endurance production (SEP), and low-intensity continuous endurance training (LIT). One of three HIIT sessions served as the reference for the subsequent isocaloric exercise modalities which were completed in randomized order. Metabolic and mechanical variables, i.e., EE during exercise, time to isocaloric EE (Tiso), relative and absolute fat contribution, post-exercise oxygen consumption (EPOC), mechanical energy, as well as cardiorespiratory and subjective variables, i.e., heart rate, oxygen uptake response, rating of perceived exertion, and enjoyment were assessed. Data were analyzed using a 6 × 2 × 2 repeated-measures ANOVA. ResultsAll three versions of HIIT and THR achieved the same EE during exercise for the same training duration. We found that LIT had a 1.6-fold (p < 0.001) and SEP a 1.3-fold (p < 0.001) longer Tiso compared to HIIT with no effects of biological sex (p = 0.42, pη2 = 0.01) or physical fitness (p = 0.09, pη2 = 0.04). There was a main effect of exercise modality on EPOC (p < 0.001, pη2 = 0.76) with highest values for HIIT 30 × 30 (p = 0.032) and lowest for LIT (p < 0.001). The highest relative and absolute amounts of fatty acids were measured during LIT (p < 0.001), and the lowest values were obtained during HIIT modalities. HIIT 30 × 30 was the most enjoyable version of HIIT (p = 0.007), while THR was the least enjoyable exercise modality (p = 0.008). ConclusionHIIT modalities are time-saving and enjoyable, regardless of sex and physical fitness. The results illustrate the relationship between exercise modality and metabolic, physiological, and subjective responses, and are thus of great interest to healthy individuals seeking time-saving and enjoyable exercise options.

Bilateral Idiopathic Carpal Tunnel Syndrome: Clinical-Functional Characterization and Efficacy of Two Combined Postoperative Physiotherapeutic Treatments.

To evaluate the efficacy of combined association instrument myofascial mobilization (IASTM) and stretching in patients with idiopathic bilateral carpal tunnel syndrome (CTS) operated on one hand and to analyze the response of the operated (OH) and non-operated (NH) hand according to the sequence of therapies. Research on these parameters has not yet been found in the literature. Randomized controlled crossover study with 43 participants using the objective and subjective outcome variables. Patients were randomly assigned to two groups: starting with stretching followed by IASTM and starting with IASTM followed by stretching. Then patients underwent surgery on the hand with more severe involvement and physical therapy rehabilitation was started 30 days after for a period of 4 weeks. After the 1-week interval the participants who started with stretching were referred to IASTM and vice versa, following the same previous patterns. The outpatient reassessments took place at 3 to 6 months. Crossover ANOVA and effect sizes were used as analysis methods. Time was the most significant outcome for all variables both during therapies and at 6-month follow-up. Regarding response to the combined therapies between OH and NH, there were differences for both OH and NH, with the greatest impact on NH for the palmar grip and VAS variables. The treatment sequences were significant for pain on the NH and mental SF-12, suggesting that starting with IASTM followed by stretching had a superior outcome for these outcomes. The combination of IASTM with stretching, used in the postoperative period of bilateral idiopathic CTS, proved to be supplementary, with significant results and large effect sizes for most of the outcomes assessed, both during the time of application of the therapies and in the 6-month follow-up for both hands, and may constitute a viable therapeutic alternative for this population.

Non-invasive fluid biomarkers in the diagnosis of mild traumatic brain injury (mTBI): a systematic review

BackgroundDespite approximately 55.9 million annual mild traumatic brain injuries (mTBIs) worldwide, the accurate diagnosis of mTBI continues to challenge clinicians due to symptom ambiguity, reliance on subjective report and presentation...

Dual-feature Fusion Attention Network for Small Object Segmentation

Accurate segmentation of medical images is an important step during radiotherapy planning and clinical diagnosis. However, manually marking organ or lesion boundaries is tedious, time-consuming, and prone to error due to subjective variability of radiologist. Automatic segmentation remains a challenging task owing to the variation (in shape and size) across subjects. Moreover, existing convolutional neural networks based methods perform poorly in small medical objects segmentation due to class imbalance and boundary ambiguity. In this paper, we propose a dual feature fusion attention network (DFF-Net) to improve the segmentation accuracy of small objects. It mainly includes two core modules: the dual-branch feature fusion module (DFFM) and the reverse attention context module (RACM). We first extract multi-resolution features by multi-scale feature extractor, then construct DFFM to aggregate the global and local contextual information to achieve information complementarity among features, which provides sufficient guidance for accurate small objects segmentation. Moreover, to alleviate the degradation of segmentation accuracy caused by blurred medical image boundaries, we propose RACM to enhance the edge texture of features. Experimental results on datasets NPC, ACDC, and Polyp demonstrate that our proposed method has fewer parameters, faster inference, and lower model complexity, and achieves better accuracy than more state-of-the-art methods.

Multivariate patterns of disrupted sleep longitudinally predict affective vulnerability to psychosis in 22q11.2 Deletion Syndrome

22q11.2 deletion syndrome (22q11DS) contributes dramatically to increased genetic risk for psychopathology, and in particular schizophrenia. Sleep disorders, including obstructive sleep apnea (OSA), are also highly prevalent, making 22q11DS a unique model to explore their impact on psychosis vulnerability. Still, the contribution of sleep disturbances to psychosis vulnerability remains unclear. We characterized the sleep phenotype of 69 individuals with 22q11DS and 38 healthy controls with actigraphy and sleep questionnaires. Psychiatric symptoms were measured concomitantly with the baseline sleep assessment and at longitudinal follow-up, 3.58±0.85 years later. We used a novel multivariate partial-least-square-correlation (PLSC) approach to identify sleep patterns combining objective and subjective variables, which correlated with psychiatric symptoms. We dissected longitudinal pathways linking sleep disturbances to psychosis, using multi-layer-network-analysis. 22q11DS was characterized by a non-restorative sleep pattern, combining increased daytime fatigue despite longer sleep duration. Non-restorative sleep combined with OSA symptoms correlated with both emotional and psychotic symptoms. Moreover, a sleep pattern evocative of OSA predicted longitudinal worsening of positive and negative symptoms, by accentuating the effects of emotional dysregulation. These results suggest that sleep disturbances could significantly increase psychosis risk, along an affective pathway. If confirmed, this suggests that systematic screening of sleep quality could mitigate psychosis vulnerability in 22q11DS.

PO-01-078 THE ACUTE PHYSIOLOGIC EFFECTS OF OSTEOPATHIC MANIPULATIVE TREATMENT IN PATIENTS WITH CARDIAC IMPLANTABLE ELECTRONIC DEVICES: A RANDOMIZED CONTROLLED TRIAL

Osteopathic manipulative treatment (OMT) is a procedure used to improve physiologic function and maintain homeostasis. OMT modulates the autonomic nervous system (ANS) and augments heart rate variability (HRV) in healthy subjects. The acute physiologic effects of OMT have been reported in patients with heart failure, but not in those with cardiac implantable electronic devices (CIEDs). To assess the short-term physiologic effects of OMT on heart rate, respiratory rate, arterial blood pressure, and HRV in patients with CIEDs. Cardiac patients with CIEDs at an osteopathic medical center were recruited into a randomized controlled trial (ClinicalTrials.gov ID: NCT0400474) and assigned to either OMT or light touch (control) groups. Short-term physiologic data was recorded pre and post intervention (including one minute HRV via photoplethysmography). HRV was calculated using root mean square of successive RR interval differences (RMSSD). Student’s t-test was used to compare groups; p < 0.05. 20 subjects were enrolled (10 OMT/10 control). Table 1 shows physiologic measurements prior to and post intervention. Changes in HR, RR, BP, and SpO2 were no different between groups before and after intervention; OMT HRV decreased by 12.39 + 34.05 ms, whereas control HRV increased by 19.94 + 18.54 ms (p=0.022). There was a significant decrease in HRV in the OMT group, but no difference in the remaining standard physiologic variables. The difference in HRV is opposite of what would be expected, and could be due to the effects of OMT on the ANS, altered cardiac response in this population, and possibly a decrease in ectopy. Further evaluation of CIED data (arrhythmias, HRV and activity level) may be helpful in determining the long-term effects of OMT on cardiac arrhythmia patients.

Electroneurophysiological responses to fabric-skin dynamic contact with different fabrics among different types of people

Electroneurophysiology has been more and more widely used to evaluate the tactile comfort of fabrics. In our previous study, it was found that three different types of subjects exist, namely extraordinary, ordinary, and non-sensitive people, corresponding to their electroneurophysiological responses to fabric-skin contact. In the current study, 19 subjects were recruited, including one extraordinary sensitive, eight ordinary sensitive and 10 non-sensitive subjects who were tested with a smooth cotton fabric and a rough polyester fabric in a fabric-skin dynamic contact experiment. Electromyography, electroencephalography, and electrocardiography signals of the human body, paired with subjective evaluation were carried out. The results show that the rough polyester fabric, compared with the smooth cotton fabric, tended to cause higher mean amplitude and larger waveform area of the myoelectric potential, reduced energy percentage of α wave, improved pneumogastric nerve activity and heart rate variability of the ordinary sensitive subjects, indicating more discomfort in fabric-skin dynamic contact. However, for the non-sensitive subjects, no consistent pattern could be observed in all of the above indicators. Therefore, the ordinary sensitive subjects are more suitable in clothing tactile comfort evaluation using electroneurophysiological measurements. In addition, it was found that ordinary sensitive subjects are predominantly females while non-sensitive subjects are most likely males.

Speech signal analysis as an aid to clinical diagnosis and assessment of mental health disorders

ObjectiveIn this study, we estimate speech features from different Verbal Fluency Tests (VFT) conditions to distinguish comorbid Bipolar Disorder (BD) in adults suffering from Attention Deficit Hyperactivity Disorder (ADHD) and to identify ADHD subtypes such as the inattentive (ADHD-I) from the combined one (ADHD-C). MethodsProsodic and spectral features in five conditions of VFTs were extracted and selected for the classification performed with machine learning methods. Specifically, a Support Vector Machine exploiting Recursive Features Elimination (SVM-RFE) has been trained with clinical scores and exploiting the within subject variability of speech features across VFT conditions. The final classification was optimized by combining the marginal classification outcomes obtained from the different VFTs using a voting scheme. ResultsOur results show that we successfully classify the ADHD+BD comorbidity and the ADHD subtypes according to clinician diagnosis. The results are discussed in the light of possible benefits of developing such approach within clinical research. ConclusionSignificant information is carried out by speech audio features acquired with VFTs, allowing to classify ADHD subtypes and comorbid patterns. This work clearly shows that the audio analysis of speech, along with properly designed speech tasks, is a candidate for the development of clinical decision support systems in psychiatry. SignificanceThis work represents a major contribution to the applications of speech analysis in ADHD subjects and could support clinicians by identifying objective biomarkers.

Placebo effect on gait: a way to reduce the dual-task cost in older adults

The ability to perform two tasks simultaneously is essential for daily activities. In older adults, this ability is markedly reduced, as evidenced by the dual-task cost on gait. Preliminary evidences indicate that the dual-task cost can be influenced by different types of manipulations. Here, we explored the effectiveness of a new approach to reduce the dual-task cost, based on the placebo effect, a psychobiological phenomenon whereby a positive outcome follows the administration of an inert device thought to be effective. Thirty-five healthy older adults were asked to walk on a sensorized carpet (single-task condition) and to walk while counting backward (dual-task condition) in two sessions (pre-test and post-test). A placebo group, randomly selected, underwent sham transcranial direct current stimulation over the supraorbital areas between sessions, along with information about its positive effects on concentration and attention. A control group did not receive any intervention between sessions. The dual-task cost was significantly reduced in the placebo group at the post-test session compared to the pre-test for several gait parameters (Cohen's d > 1.43). At the post-test session, the dual-task cost was also lower in the placebo group than in the control group (d > 0.73). Cognitive (number of subtractions and number of errors) and subjective (perceived mental fatigability) variables remained stable across sessions. The reduced dual-task cost in the placebo group could indicate the ability to re-establish the allocation of attentional resources between tasks. These findings could contribute to the development of cognitive strategies that leverage positive expectations to boost motor control in older adults.

SUBJECTIVE FACTORS AFFECTING THE CELLULAR YIELD OF PROGENITOR CELLS IN BONE MARROW ASPIRATION CONCENTRATE OF ILIAC CREST: A RETROSPECTIVE ANALYSIS OF 63 PATIENTS

We aim to analyze the role of patient-related factors on the yield of progenitor cells in the bone marrow aspiration concentrate (BMAC).We performed a retrospective analysis of patients who underwent autologous iliac crest-based BMAC therapy between Jan 2021–and June 2021. Patient-related factors such as age, sex, and comorbidities and procedure variables such as aspirate volume were analyzed. The yield of the bone marrow aspiration concentrate was assessed with MNC count and CFU assay from the aspirates.63 patients with a mean age of 51.33±17.98 years were included in the study. There were 31 males and 32 females in the study population with a mean volume of 67.16±17.312 ml being aspirated from the iliac crest for the preparation of BMAC. The final aspirate had a mean MNC count of 20.16±15.73×10^6 cells which yielded a mean of 11±12 CFUs. We noted significant negative correlation between age and MNC count (r=minus;0.671, p&lt;0.001) and CFUs (r=minus;0.688, p&lt;0.001). We did not find the sex to have any significant role in MNC (p=0.082) count or CFUs formed (p=0.348). The presence of comorbidity significantly reduced the MNC count (p=0.003) and CFUs formed (p=0.005). The aspiration volume significantly negatively correlated with MNC count (r=minus;0.731, p&lt;0.001) and CFUs (r=minus;0.618, p&lt;0.001).The MNC count and CFUs formed from the BMAC depend on the patient-specific subjective variables such as age, and comorbid conditions present in them. Sex and volume of aspiration do not alter the MNC count or the CFUs formed from BMAC.

Exploring Objective and Subjective Correlates with the Vitality of Agro-Industrial Complex Companies in Korea

Empirical studies on agro-industrial complexes are few. Facing the issue of their sustainability, the vitality of the complex is analyzed in South Korean settings through structural equation modeling of the survey data of 600 companies. Unlike the existing literature on regional economics, the survey evaluates objective characteristics at the local, complex, and company levels while incorporating psychometrics, subjective qualities of the local environment, the complex itself, infrastructure, networking, and supportive policy. Among the objective characteristics, significant variables in the employment and sales models turn out to be consistent and mainly at the company level. Among the subjective variables, employment size and sales are associated with the qualities of infrastructure and supportive policy. Specifically, potential employees will be attracted by accessible transportation systems to neighboring major cities rather than convenience facilities within the complex. Sales may be improved by providing direct support for the marketing of each company compared to indirect support regarding agro-industrial complexes, infrastructure, and networking.

Influence of Patient and Clinician Gender on Emergency Department HEART Scores: A Secondary Analysis of a Prospective Observational Trial

Clinical decision aids can decrease health care disparities. However, many clinical decision aids contain subjective variables that may introduce clinician bias. The HEART score is a clinical decision aid that estimates emergency department (ED) patients' cardiac risk. We sought to explore patient and clinician gender's influence on HEART scores. In this secondary analysis of a prospective observational trial, we examined a convenience sample of adult ED patients at one institution presenting with acute coronary syndrome symptoms. We compared ED clinician-generated HEART scores with researcher-generated HEART scores blinded to patient gender. The primary outcome was agreement between clinician and researcher HEART scores by patient gender overall and stratified by clinician gender. Analyses used difference-in-difference (DiD) for continuous score and prevalence-adjusted, bias-adjusted Kappa (PABAK) for binary (low versus moderate/high risk) score comparison. All 336 clinician-patient pairs from the original study were included. In total, 47% (158/336) of patients were women, and 52% (174/336) were treated by a woman clinician. The DiD between clinician and researcher HEART scores among men versus women patients was 0.24 (95% CI-0.01 to 0.48). Compared with researchers, men clinicians assigned a higher score to men versus women patients (DiD 0.51 [95% CI 0.16 to 0.87]), whereas women clinicians did not (DiD 0.00 [95% CI-0.33 to 0.33]). Agreement was the highest among women clinicians (PABAK 0.72; 95% CI 0.61 to 0.81) and lowest among men clinicians assessing men patients (PABAK 0.47; 95% CI 0.29 to 0.66). Patient and clinician gender may influence HEART scores. Researchers should strive to understand these influences in developing and implementing this and other clinical decision aids.

SupportPrim—a computerized clinical decision support system for stratified care for patients with musculoskeletal pain complaints in general practice: study protocol for a randomized controlled trial

BackgroundMusculoskeletal disorders represented 149 million years lived with disability world-wide in 2019 and are the main cause of years lived with disability worldwide. Current treatment recommendations are based on “one-size fits all” principle, which does not take into account the large degree of biopsychosocial heterogeneity in this group of patients. To compensate for this, we developed a stratified care computerized clinical decision support system for general practice based on patient biopsychosocial phenotypes; furthermore, we added personalized treatment recommendations based on specific patient factors to the system. In this study protocol, we describe the randomized controlled trial for evaluating the effectiveness of computerized clinical decision support system for stratified care for patients with common musculoskeletal pain complaints in general practice. The aim of this study is to test the effect of a computerized clinical decision support system for stratified care in general practice on subjective patient outcome variables compared to current care.MethodsWe will perform a cluster-randomized controlled trial with 44 general practitioners including 748 patients seeking their general practitioner due to pain in the neck, back, shoulder, hip, knee, or multisite. The intervention group will use the computerized clinical decision support system, while the control group will provide current care for their patients. The primary outcomes assessed at 3 months are global perceived effect and clinically important improvement in function measured by the Patient-Specific Function Scale (PSFS), while secondary outcomes include change in pain intensity measured by the Numeric Rating Scale (0–10), health-related quality of life (EQ-5D), general musculoskeletal health (MSK-HQ), number of treatments, use of painkillers, sick-leave grading and duration, referral to secondary care, and use of imaging.DiscussionThe use of biopsychosocial profile to stratify patients and implement it in a computerized clinical decision support system for general practitioners is a novel method of providing decision support for this patient group. The study aim to recruit patients from May 2022 to March 2023, and the first results from the study will be available late 2023.Trial registrationThe trial is registered in ISRCTN 11th of May 2022: 14,067,965.

Cardiopulmonary exercise testing to indicate increased ventilatory variability in subjects with dysfunctional breathing.

Dysfunctional breathing (DB) is a common, but largely underappreciated, cause of chronic dyspnea. Under visual inspection, most subjects with DB present with larger sequential changes in ventilation (V̇E) and breathing pattern (tidal volume (VT) and breathing frequency (f)) before and/or during incremental cardiopulmonary exercise testing (CPET). Currently, however, there are no objective criteria to indicate increased ventilatory variability in these subjects. 20 chronically dyspneic subjects with DB and 10 age- and sex-matched controls performed CPET on a cycle ergometer. Cut-offs to indicate increased V̇E, VT, f, and f/VT ratio variability (Δ= highest-lowest 20 s arithmetic mean) over the last resting minute (rest ), the 2sd min of unloaded exercise (unload ), and the 3rd min of loaded exercise (load ) were established by ROC curve analyses. Subjects with DB presented with increased V̇E, higher ventilatory variability, higher dyspnea burden, and lower exercise capacity compared to controls (p<0.05). ΔV̇Eload (> 4.1 L/min), Δfrest (> 5 breaths/min; bpm), Δfunload (> 4 bpm), Δfload (> 5 bpm), Δf/VTrest (> 4.9 bpm/L), and Δf/VTload (> 1.3 bpm/L) differentiated DB from a normal pattern (areas under the curve ranging from 0.729 to 0.845). High Δf, in particular, was associated with DB across all CPET phases. This study provides objective criteria to indicate increased ventilatory variability during incremental CPET in dyspneic subjects with DB. Large variability in breathing frequency seems particularly useful in this context, a finding that should be prospectively confirmed in larger studies. This article is protected by copyright. All rights reserved.

Abstract 5388: A unified computational pathology method to quantify HER2 expression from raw IHC and IF images in breast cancer

Abstract Background: The development of automated quantitative methods to measure biomarker expression such as HER2 aims at reducing the subjective variability of pathologist-performed biomarker assessment of immunohistochemically (IHC) stained tissue slides. As an example, the deep learning-based Quantitative Continuous Scoring (QCS) algorithm [1] enables the objective measurement of biomarker expression based on the detection of individual tumor cells in the tumor regions and - for each cell, on the instance segmentation of its nucleus, cytoplasm, and membrane compartments. Methods: In order to extend the QCS image analysis to similarly analyze tissue slides stained with immunofluorescence (IF), we re-trained the fully supervised deep-learning models, adjusted the normalization of images on tissue controls to account for variability between different staining batches, and finally used the normalized signal in IF instead of the Optical Density (OD) signal in IHC as a 8-bit grayscale image on which the biomarker expression is estimated. We performed QCS on HER2 IF images (HER2 clone 29D8 [CST], imaged with Vectra [Akoya] in parallel with HER2 IHC clone 4B5 [Roche Tissue Diagnostics]) performed on 26 primary and metastatic breast cancer samples representing the full range of HER2 expression, from null to highly overexpressed. Results: Our analysis demonstrated that the QCS-based scoring on IHC-HER2 images correlates with the QCS-based scoring on IF-HER2 images. We observed a Pearson correlation of R=0.92 between the median membrane OD in IHC and the median normalized membrane signal in IF. Defining a positive cell as having an estimated membrane expression higher than a given so-called positivity threshold, we found a median Pearson correlation of R=0.85 between the percentage of positive cells detected in IHC and the percentage of positive cells detected in IF for increasing values of positivity thresholds. Correlation of the QCS median normalized membrane signal in IF was R=0.91 with mRNA (ERBB2 transcript levels [Nano String]) and R=0.88 with IHC-based H-scores, against R=0.83 and R=0.87 respectively for the QCS median membrane OD signal in IHC. Conclusion: We describe the extension of a computational pathology-based approach for biomarker quantification in IHC to IF stained tissue slides. The consistency of the image analysis method translates into the consistency of the measurements in the two imaging methods. The use of IF could enable the improved quantification of expression, co-localization and spatial distribution of multiple proteins on the tissue sample.

A Learned Map for Places and Concepts in the Human Medial Temporal Lobe.

Distinct lines of research in both humans and animals point to a specific role of the hippocampus in both spatial and episodic memory function. The discovery of concept cells in the hippocampus and surrounding medial temporal lobe (MTL) regions suggests that the MTL maps physical and semantic spaces with a similar neural architecture. Here, we studied the emergence of such maps using MTL microwire recordings from 20 patients (9 female, 11 male) navigating a virtual environment featuring salient landmarks with established semantic meaning. We present several key findings. The array of local field potentials in the MTL contains sufficient information for above-chance decoding of subjects' instantaneous location in the environment. Closer examination revealed that as subjects gain experience with the environment the field potentials come to represent both the subjects' locations in virtual space and in high-dimensional semantic space. Similarly, we observe a learning effect on temporal sequence coding. Over time, field potentials come to represent future locations, even after controlling for spatial proximity. This predictive coding of future states, more so than the strength of spatial representations per se, is linked to variability in subjects' navigation performance. Our results thus support the conceptualization of the MTL as a memory space, representing both spatial- and nonspatial information to plan future actions and predict their outcomes.SIGNIFICANCE STATEMENT Using rare microwire recordings, we studied the representation of spatial, semantic, and temporal information in the human MTL. Our findings demonstrate that subjects acquire a cognitive map that simultaneously represents the spatial and semantic relations between landmarks. We further show that the same learned representation is used to predict future states, implicating MTL cell assemblies as the building blocks of prospective memory functions.

Pharmaceutical Micropellets: A Multi-particulate Drug Delivery System

Abstract: The major target of Pharmaceutical Sciences is to design a successful and suitable dosage forms for effective therapy, considering individual patient needs and compliance. Development of new technology or development of new dosage form using the existing technology is growing in importance and attracting increased interest, as they are specifically effective at a comparably low dose. Pellets falling in the size range of 1-1000μm are of great interest in the pharmaceutical industry for a variety of reasons which are not only offer flexibility in dosage form design and development, but are also utilized to improve the safety and efficacy of bioactive agents. The most important factor responsible for the proliferation of pelletized products is the popularity of controlled release technology in the delivery of drugs. Moreover, controlled release pellets are less susceptible to dose dumping than the reservoir-type single unit formulations. In case of oral products these pellets solve difficult taste-masking problems, disperse freely in the gastro intestinal tract, invariably maximize drug absorption, reduce peak plasma fluctuations and minimize potential side effects without appreciably lowering drug bioavailability, and also reduce variations in gastric emptying rate and overall transit time, thus, intra and inter subject variability of plasma profiles, which are common with single unit regimens, are minimized.

Accurate demarcation of a biased nucleus from H&E-stained follicular lymphoma tissues samples

ABSTRACT In recent days, automated demarcation of biased nuclei of follicular lymphoma has become a standard framework in the pipeline of quantitative histopathology. It has received substantial consideration due to subjective variability between different oncologists. This difference can occasionally result in erroneous conclusions, distinct prognostic reports, and inconsistent treatment. This paper provides additional input to an oncologist to ease the prognosis process. This approach defines a local criterion fitting function in neighbourhood of each point based on image intensity. An assumption is pixel intensity will remain constant next to the point. Integration of these local neighbourhood centres leads us to define the global criterion of image segmentation. Segmentation accuracy is evaluated using region-based measures and the optimal segmentation accuracy of 98.6% is achieved using the DICE coefficient. By using locally formulated energy, execution time is also reduced in comparison to the contour algorithm. This technique is independent of the initialization.

Dietary choline and betaine intake, cardio-metabolic risk factors and prevalence of metabolic syndrome among overweight and obese adults

BackgroundCholine is an important metabolite involved in phospholipids synthesis, including serum lipids, and is the immediate precursor of betaine. There are numerous studies with inconsistent results that evaluated the association between dietary choline intakes with cardiovascular risk factors. In addition, the association between dietary betaine and choline intakes with cardio-metabolic risk factors is not well studied. In the current study, our aim was to evaluate dietary choline and betaine intakes in the usual diet of obese individuals and to assess its association with serum lipids, blood pressure and glycemic markers among obese individuals.MethodsWe recruited a total number of 359 obese people aged between 20 and 50 years in the present study. A semi-quantitative food frequency questionnaire (FFQ) was used for dietary assessment; dietary choline and betaine intakes were calculated using the United States Department of Agriculture (USDA) database. National cholesterol education program adult treatment panel (NCEP-ATP)-III criteria was used metabolic syndrome (MetS) definition. Enzymatic methods were used to assess biochemical variables. Body composition was measured with the bioelectrical impedance analysis (BIA) method.ResultsHigher body mass index (BMI), waist to hip ratio (WHR), fat-free mass (FFM) and basal metabolic rate (BMR) were observed in higher tertiles of dietary choline intake (P < 0.01). There was no significant difference in terms of biochemical parameters among different tertiles of dietary choline intake, while systolic blood pressure (SBP) and diastolic blood pressure (DBP) were reduced in higher betaine tertiles (P < 0.05). For total dietary choline and betaine intakes, there was a reduction in DBP and low density lipoprotein (LDL) concentrations (P < 0.05). Also, a non-significant reduction in serum total cholesterol (TC), triglyceride (TG) and MetS prevalence was observed in higher tertiles of dietary choline and betaine intakes. After classification of the study population according to MetS status, there was no significant difference in biochemical variables in subjects with MetS (P > 0.05), while in the non-MetS group, SBP, DBP, TG and insulin levels reduced in higher tertiles of dietary betaine and choline (P > 0.05).ConclusionAccording to our findings, higher dietary intakes of choline and betaine were associated with lower levels of blood pressure and LDL concentrations among obese individuals. Further studies are warranted to confirm the results of the current study.

Pathway-Based Polygenic Risk Scores for Schizophrenia and Associations With Reported Psychotic-like Experiences and Neuroimaging Phenotypes in the UK Biobank

BackgroundSchizophrenia is a heritable psychiatric disorder with a polygenic architecture. Genome-wide association studies have reported that an increasing number of risk-associated variants and polygenic risk scores (PRSs) explain 17% of the variance in the disorder. Substantial heterogeneity exists in the effect of these variants, and aggregating them based on biologically relevant functions may provide mechanistic insight into the disorder. MethodsUsing the largest schizophrenia genome-wide association study conducted to date, we associated PRSs based on 5 gene sets previously found to contribute to schizophrenia pathophysiology—postsynaptic density of excitatory synapses, postsynaptic membrane, dendritic spine, axon, and histone H3-K4 methylation—along with respective whole-genome PRSs, with neuroimaging (n > 29,000) and reported psychotic-like experiences (n > 119,000) variables in healthy UK Biobank subjects. ResultsSeveral variables were significantly associated with the axon gene-set (psychotic-like communications, parahippocampal gyrus volume, fractional anisotropy thalamic radiations, and fractional anisotropy posterior thalamic radiations (β range −0.016 to 0.0916, false discovery rate–corrected p [pFDR] ≤ .05), postsynaptic density gene-set (psychotic-like experiences distress, global surface area, and cingulate lobe surface area [β range −0.014 to 0.0588, pFDR ≤ .05]), and histone gene set (entorhinal surface area: β = −0.016, pFDR = .035). From these, whole-genome PRSs were significantly associated with psychotic-like communications (β = 0.2218, pFDR = 1.34 × 10−7), distress (β = 0.1943, pFDR = 7.28 × 10−16), and fractional anisotropy thalamic radiations (β = −0.0143, pFDR = .036). Permutation analysis revealed that these associations were not due to chance. ConclusionsOur results indicate that genetic variation in 3 gene sets relevant to schizophrenia may confer risk for the disorder through effects on previously implicated neuroimaging variables. Because associations were stronger overall for whole-genome PRSs, findings here highlight that selection of biologically relevant variants is not yet sufficient to address the heterogeneity of the disorder.