Human Subjects Research Articles

Development of Dual-Arm Human Companion Robots That Can Dance.

As gestures play an important role in human communication, there have been a number of service robots equipped with a pair of human-like arms for gesture-based human-robot interactions. However, the arms of most human companion robots are limited to slow and simple gestures due to the low maximum velocity of the arm actuators. In this work, we present the JF-2 robot, a mobile home service robot equipped with a pair of torque-controlled anthropomorphic arms. Thanks to the low inertia design of the arm, responsive Quasi-Direct Drive (QDD) actuators, and active compliant control of the joints, the robot can replicate fast human dance motions while being safe in the environment. In addition to the JF-2 robot, we also present the JF-mini robot, a scaled-down, low-cost version of the JF-2 robot mainly targeted for commercial use at kindergarten and childcare facilities. The suggested system is validated by performing three experiments, a safety test, teaching children how to dance along to the music, and bringing a requested item to a human subject.

P11.09.B STRUCTURAL REORGANIZATION IN MOTOR-ELOQUENT GLIOMA PATIENTS EXHIBITING MOTOR DEFICITS

Abstract BACKGROUND Recent advancements in navigated transcranial magnetic stimulation (nTMS) have significantly improved the localization of motor functions in human subjects. Although previous studies have demonstrated the occurrence of tumor-induced motor plasticity, the detailed mechanisms of motor function plasticity and reorganization in patients with tumors affecting motor-eloquent regions are not fully elucidated. Our study aims to investigate the functional plasticity of motor functions in patients with gliomas located within motor-eloquent regions, providing deeper insights into the mechanisms of functional plasticity. MATERIAL AND METHODS In this research, we studied 60 glioma patients with tumors located in the motor-eloquent region. These patients were categorized into two groups depending on whether they experienced motor impairments in the upper extremities. We utilized nTMS, including Motor Evoked Potentials (MEP), to outline the control regions of motor function in terms of area, localization, and Center of Gravity (CoG). These identified regions also acted as seeds for tracing the Corticospinal Tract (CST). RESULTS The study unveiled significant variations in cortical and subcortical motor function localizations between the groups. Patients with motor impairments exhibited a broader cortical distribution connected to motor functions and increased volumes of CST, reflecting compensatory adaptations with different fractional anisotropy (FA) values (FA 0.15, p=0.02; FA 0.10, p=0.04). The analysis of the CST also showed overlapping regions, particularly within the hand-knob areas, which is indicative of these areas acting as critical motor output pathways. Despite varying degrees of functional impairment, all patients maintained some degree of motor output capability. CONCLUSION These findings suggest that motor-eloquent gliomas induce significant cortical and subcortical reorganization of motor functions. A persistent network of CST fibers, crucial for preserving motor function, highlights a complex interplay between cortical adaptation and subcortical reorganization. This study underscores the resilience of motor pathways and their pivotal role in functional recovery and plasticity, emphasizing the clinical relevance of nTMS in the therapeutic planning and monitoring of patients with motor-eloquent gliomas.

Generative dynamical models for classification of rsfMRI data

ABSTRACT The growing availability of large-scale neuroimaging datasets and user-friendly machine learning tools has led to a recent surge in studies that use fMRI data to predict psychological or behavioral variables. Many such studies classify fMRI data on the basis of static features, but fewer try to leverage brain dynamics for classification. Here, we pilot a generative, dynamical approach for classifying resting-state fMRI (rsfMRI) data. By fitting separate hidden Markov models to the classes in our training data and assigning class labels to test data based on their likelihood under those models, we are able to take advantage of dynamical patterns in the data without confronting the statistical limitations of some other dynamical approaches. Moreover, we demonstrate that hidden Markov models are able to successfully perform within-subject classification on the MyConnectome dataset solely on the basis of transition probabilities among their hidden states. On the other hand, individual Human Connectome Project subjects cannot be identified on the basis of hidden state transition probabilities alone—although a vector autoregressive model does achieve high performance. These results demonstrate a dynamical classification approach for rsfMRI data that shows promising performance, particularly for within-subject classification, and has the potential to afford greater interpretability than other approaches.

Short-Term Effect of Stimulating the Pterygopalatine Ganglion Via Electroacupuncture on Choroidal Structure in Human Subjects.

Choroidal dysfunction is implicated in various ocular pathologies. The parasympathetic pterygopalatine ganglion (PPG) innervates orbital vessels supplying the choroid. While PPG stimulation has been shown to dilate cerebral blood flow, its effects on the choroid, particularly in human subjects, require further elucidation. This study aimed to investigate the short-term influence of PPG stimulation via electroacupuncture on choroidal structure. In this crossover study, 22 healthy adults received PPG electrical stimulation and sham stimulation for one session each on two separate days in a randomized order. Measurements including choroidal thickness (ChT), choroidal vascularity index (ChVI), central subfield thickness, axial length, anterior chamber depth, and lens thickness were recorded before and at intervals (0, 15, 30, 45, and 60minutes) postintervention. The ChT on the side receiving PPG stimulation demonstrated a sustained increase, peaking at 15minutes poststimulation (17.2µm, P < 0.001) and persisting for up to 60minutes. Conversely, the ChVI exhibited a more immediate response, with a peak increase immediately poststimulation (3.8%, P = 0.003), followed by a gradual return to baseline. ChT and ChVI in the contralateral eye showed a nonsignificant trend to decrease. Additionally, a notable reduction in ipsilateral axial length was observed at specific time points poststimulation. PPG activation via electroacupuncture elicited a short-term increase in ChT and ChVI in the ipsilateral eye compared to sham stimulation, with ChT increases trailing those of ChVI but displaying greater persistence. Electrical stimulation of the PPG can produce a short-term increase in ipsilateral ChT and ChVI.

Spectrum of delayed post-hypoxic leukoencephalopathy syndrome: A systematic review

BACKGROUND Delayed post hypoxic leukoencephalopathy syndrome (DPHLS), also known as Grinker’s myelinopathy, is a rare but significant neurological condition that manifests days to weeks after a hypoxic event. Characterized by delayed onset of neurological and cognitive deficits, DPHLS presents substantial diagnostic and therapeutic challenges. AIM To consolidate current knowledge on pathophysiology, clinical features, diagnostic approaches, and management strategies for DPHLS, providing a comprehensive overview and highlighting gaps for future research. METHODS Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyzes guidelines, we systematically searched PubMed, ScienceDirect and Hinari databases using terms related to delayed post-hypoxic leukoencephalopathy. Inclusion criteria were original research articles, case reports, and case series involving human subjects with detailed clinical, neuroimaging, or pathological data on DPHLS. Data were extracted on study characteristics, participant demographics, clinical features, neuroimaging findings, pathological findings, treatment, and outcomes. The quality assessment was performed using the Joanna Briggs Institute critical appraisal checklist. RESULTS A total of 73 cases were reviewed. Common comorbidities included schizoaffective disorder, bipolar disorder, hypertension, and substance use disorder. The primary causes of hypoxia were benzodiazepine overdose, opioid overdose, polysubstance overdose, and carbon monoxide (CO) poisoning. Symptoms frequently include decreased level of consciousness, psychomotor agitation, cognitive decline, parkinsonism, and encephalopathy. Neuroimaging commonly revealed diffuse T2 hyperintensities in cerebral white matter, sometimes involving the basal ganglia and the globus pallidus. Magnetic resonance spectroscopy often showed decreased N-acetylaspartate, elevated choline, choline-to-creatinine ratio, and normal or elevated lactate. Treatment is often supportive, including amantadine, an antioxidant cocktail, and steroids. Hyperbaric oxygen therapy may be beneficial in those with CO poisoning. Parkinsonism was often treated with levodopa. Most of the patients had substantial recovery over the course of months and many cases had some residual neurocognitive deficits. CONCLUSION DPHLS remains a complex and multifaceted condition with various etiologies and clinical manifestations. Early recognition and appropriate management are crucial to improving patient outcomes. Future research should focus on standardizing diagnostic criteria, using advanced imaging techniques, and exploring therapeutic interventions to improve understanding and treatment of DPHLS. Conducting prospective cohort studies and developing biomarkers for early diagnosis and monitoring will be essential to advance patient care.

Bolus tracking from pulsed x-ray projections: A feasibility study using a five-dimensional cardiac CT contrast dynamics model.

Cardiac computed tomography (CT) exams are some of the most complex CT exams due to the need to carefully time the scan when the heart chambers are near the peak contrast concentration. With current "bolus tracking" and "timing bolus" techniques, after contrast medium is injected, a target vessel or chamber is scanned periodically, and images are reconstructed to monitor the opacification. Both techniques have opportunities for improvement, such as reducing the contrast medium volume, the exam time, the number of manual steps, and improving the robustness of correctly timing the peak opacification. The objective of our study is to (1) develop a novel autonomous cardiac CT clinical workflow to track contrast bolus dynamics directly from pulsed x-ray projections, (2) develop a new five-dimensional virtual cardiac CT data generation tool with programmable cardiac profiles and bolus dynamics, and (3) demonstrate the feasibility of projection-domain prospective bolus tracking using a neural network trained and tested with the virtual data to find the contrast peak. In our proposed workflow, pulsed mode projections (PMPs) are acquired with a wide-open collimator under sparse view conditions (monitoring phase). Each time a new PMP is acquired, the neural network is used to estimate the contrast enhancement inside the target chambers. To train such a network, we introduce a new approach to generate clinically realistic virtual scan data based on a five-dimensional cardiac model, by synthesizing user-defined contrast bolus dynamics and patient electrocardiogram profiles. In this study, we investigated a scenario with one single PMP per rotation. To find the optimal PMP view angle, 20 angles were explored. For each angle, 300 virtual exams were generated from 115 human subject datasets and divided into training, validation, and testing groups. Twenty neural networks were trained and evaluated in total to find the optimal network. Finally, a simple bolus peak time estimation algorithm was developed and evaluated by comparing to the ground truth bolus peak time. To evaluate the accuracy of a bolus time-intensity curve estimated by the network, the cosine similarity between the estimation and the ground truth was computed. The cosine similarity was larger than 0.97 for all projection angles. A view angle corresponding to the x-ray tube at 30 degrees from vertical (left-anterior of subject) showed the lowest errors. The amplitude of the estimated bolus curves (in Hounsfield Units) was not always correctly predicted, but the shape was accurately predicted. This resulted in an RMSE of 1.23s for the left chambers and 0.78s for the right chambers in the contrast peak time estimation. In this study, we proposed an innovative real-time way to predict the contrast bolus peak in cardiac CT as well as an innovative approach to train a neural network using virtual but clinically realistic data. Our trained network successfully estimated the shape of the time-intensity curve for the target chambers, which led to accurate bolus peak time estimation. This technique could be used for autonomous diagnostic cardiac CT to trigger a diagnostic scan for optimal contrast enhancement.

Investigating the causal relationship between human blood metabolites and pulmonary hypertension: a two-sample Mendelian randomization study.

Several recent investigations have posited that distinct metabolites in the bloodstream may be correlated with the pathogenesis of Pulmonary Hypertension (PH). Nonetheless, the interrelationship between the pathogenesis of PH and metabolite fluctuations remains incompletely elucidated, and findings may differ across studies. In the extant research, data from 486 metabolite-and PH-related genetic variants in human subjects were procured based on Genome-Wide Association Studies (GWAS) and Finnish databases. Univariate Mendelian Randomization analyses were deployed to evaluate the causal relationships between them. The utilization of the randomized Inverse Variance weighted(IVW) method served as the primary analytic framework in this Mendelian Randomization (MR) study. Additionally, four alternative computational strategies, encompassing MR-Egger, were employed as auxiliary methods. A myriad of tests, including Cochran's Q Test, MR-Egger intercept test, MR-PRESSO, leave-one-out analysis, and linkage disequilibrium score were incorporated to assess the robustness of the study outcomes. Metabolite pathway analysis was also executed to identify potential metabolic pathways. After a series of validations and corrected for False discovery rate (FDR), we found a significant association between 1,5-anhydroglucitol (OR = 2.00, 95% CI: 1.39-2.89, P = 0.0002) and PH, and a significant association between pyridoxalate (OR = 0.59, 95% CI: 0.43-0.81, P = 0.0009) and 1-a achidonoylglycerophosphocholine (OR = 1.78, 95% CI: 1.22-2.58, P = 0.0026) had a suggested association with PH. In addition, the vitamin B6 metabolic pathway was also determined to be associated with PH. Conclusively, we isolated 1,5-anhydroglucitol, 1-arachidonoylglycerophosphocholine, and pyridoxate as causally implicated in PH, thereby proffering substantial theoretical substantiation for the formulation of future PH prevention and screening paradigms.

Biocompatibility and Bone Regeneration by Shape Memory Polymer Scaffolds.

Biodegradable, shape memory polymer (SMP) scaffolds based on poly(ε-caprolactone) (PCL) offer unique advantages as a regenerative treatment strategy for critical-sized bone defects. In particular, a conformal fit may be achieved following exposure to warm saline, thereby improving osseointegration and regeneration. Advancing the clinical translation of these SMP scaffolds requires establishment of efficacy not only in non-loading models, but also load-bearing or load-sharing models. Thus, the present study evaluated the biocompatibility and bone regeneration potential of SMP scaffolds in a rabbit distal femoral condyle model. Two distinct SMP scaffold compositions were evaluated, a "PCL-only" scaffold formed from PCL-diacrylate (PCL-DA) and a semi-interpenetrating network (semi-IPN) formed from PCL-DA and poly(L-lactic acid) (PCL:PLLA). Semi-IPN PCL:PLLA scaffolds possess greater rigidity and faster rates of degradation versus PCL scaffolds. In vivo biocompatibility was assessed with a rat subcutaneous implantation model, whereas osseointegration was assessed with a 4 mm × 8 mm rabbit distal femoral condyle defect model. Both types of SMP scaffolds exhibited excellent biocompatibility marked by infiltration with fibrous tissue and a minimal inflammatory response. When implanted in the rabbit distal femur, both SMP scaffolds supported bone ingrowth. Collectively, these results demonstrate that the SMP scaffolds are biocompatible and integrate with adjacent host osseous tissues when implanted in vivo in a load-sharing environment. This study provides key proof-of-concept data necessary to proceed with large animal translational studies and clinical trials in human subjects.

Phase contrast MRI with minimized background phase errors.

Phase contrast MRI (PC-MRI) is used clinically to measure velocities in the body, but systematic background phase errors caused by magnetic field imperfections corrupt the velocity measurements with offsets that limit clinical utility. This work aims to minimize systematic background phase errors in PC-MRI, thereby maximizing the accuracy of velocity measurements. The MRI scanner's background phase errors from eddy currents and mechanical oscillations were modeled using the gradient impulse response function (GIRF). Gradient waveforms were then numerically optimized using the GIRF to create pulse sequences that minimize the background phase errors. The pulse sequences were tested in a static phantom where the predicted response could be compared directly to the measured background velocity. The optimized acquisitions were then tested in human subjects, where flow rates and background errors were compared to conventional PC-MRI. When using the GIRF-optimized gradient waveforms, the predicted background phase was within 0.6 [95% CI = -3.4, 5.4] mm/s of the measured background phase in a static phantom. Excellent agreement was seen for in vivo blood flow values (flow rate agreement = 0.96), and the background phase was reduced by 78.8 18.7%. This work shows that using a GIRF to model the effects of magnetic field imperfections combined with numerically optimized gradient waveforms enables PC-MRI waveforms to be designed to produce a minimal background phase in the most time-efficient manner. The methodology could be adapted for other MRI sequences where similar magnetic field errors affect measurements.

Employing deep learning model to evaluate speech information in acoustic simulations of Cochlear implants

Acoustic vocoders play a key role in simulating the speech information available to cochlear implant (CI) users. Traditionally, the intelligibility of vocoder CI simulations is assessed through speech recognition experiments with normally-hearing subjects, a process that can be time-consuming, costly, and subject to individual variability. As an alternative approach, we utilized an advanced deep learning speech recognition model to investigate the intelligibility of CI simulations. We evaluated model’s performance on vocoder-processed words and sentences with varying vocoder parameters. The number of vocoder bands, frequency range, and envelope dynamic range were adjusted to simulate sound processing settings in CI devices. Additionally, we manipulated the low-cutoff frequency and intensity quantization of vocoder envelopes to simulate psychophysical temporal and intensity resolutions in CI patients. The results were evaluated within the context of the audio analysis performed in the model. Interestingly, the deep learning model, despite not being originally designed to mimic human speech processing, exhibited a human-like response to alterations in vocoder parameters, resembling existing human subject results. This approach offers significant time and cost savings compared to testing human subjects, and eliminates learning and fatigue effects during testing. Our findings demonstrate the potential of speech recognition models in facilitating auditory research.

Potentiation of Tumor Hallmarks by the Loss of GULO, a Vitamin C Biosynthesis Gene in Humans.

Vitamin C plays a significant role in various physiological functions. Humans depend on external sources of vitamin C due to the loss of the L-gulono-γ-lactone oxidase (GULO) gene that contributes to the synthesis of vitamin C. During the evolutionary loss of the GULO gene, physical, chemical, and biological factors were different from the present environmental settings. Besides the evolutionary genetic loss of the GULO gene, there is a gap in the insightful discussion on the potential implications of the non-functional GULO gene towards the predisposition of humans to cancer that faces hostile and carcinogenic environments. Various methods by which vitamin C modulates cellular processes related to cancer, including DNA repair, epigenetic changes, and redox balance, are discussed. Furthermore, we present experimental and clinical evidence indicating that vitamin C deficiency promotes tumor growth, metastasis, and therapy resistance, emphasizing its potential as a cancer phenotypic modulator. Therapeutic implications of restoring vitamin C levels in cancer treatment range from improving the efficacy of conventional medicines to exploiting metabolic vulnerabilities in tumors. The relevance of assessing vitamin C status in cancer patients and the basis for additional research into vitamin C supplementation as an adjuvant therapy is emphasized. This paper presents a comprehensive overview of the implications associated with the functional deficiency of the GULO gene in human subjects exhibiting diverse tumor hallmarks, encompassing ECM remodeling, hypoxia, epigenetic reprogramming, oxidative stress, and drug responsiveness.

Cochlear implants with dexamethasone-eluting electrode arrays reduce foreign body response in a murine model of cochlear implantation and human subjects.

The inflammatory foreign body response (FBR) following cochlear implantation (CI) can negatively impact CI outcomes, including increased electrode impedances. This study aims to investigate the long-term efficacy of dexamethasone eluting cochlear implant and locally delivered dexamethasone, a potent anti-inflammatory glucocorticoid on the intracochlear FBR and electrical impedance post-implantation in a murine model and human subjects. The left ears of CX3CR1 +/GFP Thy1 +/YFP (macrophage-neuron dual reporter) mice were implanted with dexamethasone-eluting cochlear implants (Dex-CI) or standard implant (Standard-CI) while the right ear served as unoperated control. Another group of dual reporter mice was implanted with a standard CI electrode array followed by injection of dexamethasone in the middle ear to mimic current clinical practice (Dex-local). Mouse implants were electrically stimulated with serial measurement of electrical impedance. Human subjects were implanted with either standard or Dex-CI followed by serial impedance measurements. Dex-CI reduced electrical impedance in the murine model and human subjects and inflammatory FBR in the murine model for an extended period. Dex-local in the murine model is ineffective for long-term reduction of FBR and electrode impedance. Our data suggest that dexamethasone eluting arrays are more effective than the current clinical practice of locally applied dexamethasone in reducing FBR and electrical impedance.

A Description of the Dental Health and Treatment of Ukraine Military at U.S. Army Clinics in Germany.

Since the start of the Russo-Ukrainian war, most reports have focused on trauma and combat conditions. Trauma care is essential; however, disease and nonbattle injuries (DNBIs) also burden armies and reduce combat effectiveness. Dental emergencies (DEs) account for a substantial portion of DNBI, but there is limited information on Ukrainian military dental readiness. In September 2023, investigators were informed that Ukrainian military personnel were treated for DEs at 2 dental clinics in Germany. The investigators requested deidentified data from the Corporate Dental System (CDS), which is a repository for dental treatment records utilized by the U.S. Army. The data request captured DE treatment performed for Ukrainian military personnel in Germany from January 1, 2023, to September 20, 2023. The CDS report on DE encounters included the following: Gender, age, procedure codes, and provider narratives. This study was approved by the U.S. Army Institute of Surgical Research Institutional Review Board as research not involving human subjects and provided Log Number H-24-030nh. The CDS report captured 408 Ukrainian military DE encounters. A total of 360 Ukrainian military personnel were treated for DE during the 9-month reporting period in 2023. Oral surgery was the most common DE treatment category and accounted for 55.8% (N = 201) of DE procedures. Restorative dentistry procedures accounted for 18.1% of DE procedures. Of the 27 multiple category treatments, 25 had oral surgery procedures as one of the treatments. Restorative dentistry procedures were performed in 19 of the multiple category cases. The DEs in the Ukrainian military cohort suggest that chronic, untreated dental disease has progressed without routine care for years. The assertion that caries has progressed to a nonrestorable condition is supported by the distribution that 63% of all DE visits included oral surgery treatment. Based on the distribution of dental treatment, US dental officers must be proficient in oral surgery and prosthodontic care.

Multi-branch deep learning neural network prediction model for the development of angular biosensors based on sEMG.

Human gait motion intention recognition is very important for the lower extremity exoskeleton robot to accurately synchronize and respond to the user's natural motion. And motion intention recognition is generally performed through sEMG. Deep learning neural networks perform well in dealing with high-dimensional data and nonlinear relationships such as sEMG, but different deep learning neural networks have their own advantages in dealing with different types of data. Therefore, a multi-branch deep learning neural network, which enables different neural networks to process different feature items, could achieve more accurate and efficient motion intention recognition. The purpose of this study is to 1) Establish a multi-branch deep learning neural network model to achieve accurate gait recognition and effective estimation of joint angles. 2) Quantify the performance of the multi-branch deep learning neural network model in gait recognition and joint angle prediction using sEMG. This study involved the collection of sEMG and plantar pressure data during walking in human subjects. Firstly, the collected signals are filtered and denoised to ensure the quality and reliability of the data. Calculate the time domain features and the frequency domain features to capture the key information of gait. Then, using the sensitivity difference of different structural neural networks to different feature data, a multi-branch deep learning neural network model is developed, in which the extracted features are used as the input of the model. The output of the model includes gait cycle and joint angle, so as to realize the accurate recognition of human gait and the effective estimation of joint angle. The results show that the proposed method has high accuracy in identifying human gait and estimating joint angles. The multi-branch neural network model successfully integrates time-domain and frequency-domain features and provides reliable prediction of gait cycle and joint angle. The highest accuracy of gait recognition is 95.42%, the lowest is 90.11%, and the average is 92.16%. The average error of joint angle estimation is 3.19. This study designed a human walking gait recognition and joint angle prediction model to achieve accurate human lower limb motion intention recognition.The model can be integrated into the sEMG sensor to design a angular biosensors, which can predict the human joint angle in real time.

Analysis of Dental-related Emergency Department Utilization in Michigan

Objective: Emergency departments (ED) are critical to the United States healthcare system. However, they are known to be inefficient environments to deliver definitive care including management of dental emergencies. ED’s may also serve as an inadvertent, but important, stop gap for individuals who lack dental coverage. The nation’s healthcare system continues to struggle with inadequate resources to provide dental care for vulnerable patients who disproportionately suffer from dental-related conditions. Method: This study is an analysis on dental-related ED utilization in the state of Michigan. The authors collaborated with the Michigan Health &amp; Hospital Association who provided data from the Michigan Inpatient and Outpatient Database for dental-related hospital emergency department (ED) visits in Michigan hospitals during 2018-2019. University of Michigan Medical School’s committee on human subjects’ research reviewed the protocol and provided IRB exemption (HUM00192629). Results: State funded Medicaid (33%) and federally funded Medicare (33%) were the most common payer types for patients with dental-related conditions who reported to Michigan ED’s from 2018 to 2019. Charges per ED encounter was the highest for Medicare, $2,900-$3,200, and lowest for other payers, $1,300-$1,500. Charges for ED-inpatient per encounter were the highest for Medicare ($22,000-$24,000). The age range for which patients most frequently presented to the emergency department (ED) was 25-64. However, expenses per encounter for patients 65 and older were roughly two to three times higher than for patients in other age ranges. Conclusion: The study revealed a disproportionately higher percentage of patients who identified as Black presented to Michigan emergency departments (30%) with a dental-related emergency.

Investigating the Hepatic Response to Orlistat and White Tea in Rats on a High-Fat Diet.

High-fat diets have detrimental health impacts that increase the likelihood of developing obesity and metabolic syndrome. This study aimed to examine the potential antioxidant and anti-inflammatory effects of orlistat and white tea in rats fed a high-fat diet. Thirty-two rats were randomized into four groups: control (standard diet), HFD (high-fat diet), HFD+Orlistat (high-fat diet+orlistat), and HFD+WT (high-fat diet+white tea extract). A significant increase in malondialdehyde (MDA) levels and a decrease in total thiol (TT) levels were detected in the HFD group (p < 0.001). On the other hand, a decrease in the MDA level (p < 0.001) and an increase in the TT level were observed in the orlistat and white tea groups compared with those in the HFD group (p < 0.001). Histopathological examinations revealed that, compared with the HFD alone, orlistat and white tea reduced fat accumulation, prevented degenerative changes in hepatocytes, and decreased the histopathological damage score (p = 0.001). Immunohistochemical examinations of nuclear factor-kappa B (NF-kB/p65) revealed that compared with the HFD, orlistat and white tea reduced immunopositivity (p = 0.001). White tea decreases lipid peroxidation and oxidative stress. Both white tea and orlistat decreased fat formation and inflammation in the liver and regulated inflammation by reducing Nf-kB positivity. Nevertheless, further research is needed to assess their impact on human subjects.

A systematic review of unique methods for measuring discount rates

AbstractDiscount rates play a pivotal role in various fields, capturing the trade-off between present and future, influencing predictions of unhealthy behaviors. Despite substantial variations in discount rates across studies, methods, and individuals, our goal was to systematically overview diverse methods for measuring discount rates. We conducted a comprehensive literature review across multiple databases, targeting English studies introducing and utilizing discounting measurement methods in human subjects. Two authors screened titles and abstracts, with full text review split between them. Extracted data encompassed bibliographic details, theoretical aspects (e.g., discount function), and operational features (e.g., elicitation procedure). After deduplication, 4976, 218, and 83 records underwent title and abstract screening, full text screening, and inclusion, respectively. A total of 86 unique methods were identified. Predominantly, methods were devised for money (75%) and health (22%) discounting. Network analysis on citations indicated limited cross-disciplinary overlap. Only about one fourth, one third, and one third of methods possessed theoretically desirable traits: i) allowance for negative discount rates, ii) application of multiple discount functions, and iii) correction for non-linear utility of outcomes. Diverse discounting measurement methods exist, showcasing varied theoretical and operational characteristics. These differences may stem from the isolation of development in fields like psychology, experimental economics, and health economics. Our systematic review aids readers in choosing methods aligned with their priorities when measuring discount rates.

The role of institutional ethics committees in Austria : Report of the Commission on Ethics and Scientific Integrity of the Karl Landsteiner University of Health Sciences 2018-2023.

Research involving human subjects or identifiable human material and data must be assessed by an ethics committee. The Karl Landsteiner University of Health Sciences has established a Commission on Ethics and Scientific Integrity to evaluate medical research conducted by its faculty and students and at its affiliated hospitals.All projects submitted to the Commission on Ethics and Scientific Integrity between 2018 and 2023 were analyzed regarding their major characteristics, the duration of the evaluation process, and votes issued.A total of 520 applications were electronically submitted during the observation period. Most of the studies were retrospective data analyses in the field of oncology, psychology and surgery. Most studies included less than 100 volunteers. Of the applications 50% received afinal vote within 5months, during which several revision rounds took place. Overall, about 77% of votes issued during the observation period were positive and 2% were rejections. In 11% files were closed due to withdrawal. In 11% final votes were pending at the end of the observation period due to requests for revisions.Our results emphasize the importance of institutional ethics committees using the example of the Commission on Ethics and Scientific Integrity at the Karl Landsteiner University. Such committees fill agap in evaluating research not covered by Austrian legal regulations. Continuous development of standards, operating procedures, and national and international collaborations are required to assess and minimize risks to trial subjects and to provide asafe and productive environment for research in human medicine and related fields.

Serum uric acid: an independent risk factor for cardiovascular disease in Pakistani Punjabi patients

BackgroundIt is well-known that serum uric acid (SUA) can increase the risk of hypertension, diabetes, obesity and dyslipidemia. However, its independent association with the risk of cardiovascular diseases (CVD) is controversial particularly in different populations. Hence, this study was aimed to assess an independent association of SUA with CVD risk in a Punjabi Pakistani cohort.MethodsThis is a retrospective observational study in which 502 human subjects having CVD, hypertension and/or diabetes were grouped based on SUA levels as normouricemia (n = 266) and hyperuricemia (n = 236). Role of SUA was assessed in increasing the risk of CVD independent of other key confounding factors (i.e. age, gender, dyslipidemia, hypertension, diabetes, dietary and life-style habits). All clinical and biochemical data were analyzed in SPSS (ver. 20).ResultsSubjects aged 55 ± 13 years were of both genders (males: 52%). SUA levels were significantly different among clinical subtypes of CVD [i.e. acute coronary syndrome (ACS), myocardial infarction (MI) and heart failure (HF)]. Spearman correlation showed a significantly positive association between CVD and SUA (rho = 0.149, p < 0.001). Multivariate logistic regression of SUA quartiles showed that hyperuricemia is associated with CVD [3rd quartile: OR: 1.78 (CI: 1.28–2.48), p = 0.001 and 4th quartile: OR: 2.37 (CI: 1.72–3.27), p < 0.001]. Moreover, this association remained significant even after adjusting for confounding factors.ConclusionThis study showed that SUA is positively associated with CVD, thus it can act as an independent risk factor for CVD.

Partnering for Progress: Lessons Learned From Mental Health Assessment for Youth Living With HIV in India Through Community-Based Participatory Research

Youth living with HIV (YLHIV) face diverse mental health challenges necessitating interventions informed by their lived experiences. Failure to do so can perpetuate a self-reinforcing cycle of misaligned and ineffective support, further exacerbating existing vulnerabilities. This study directly addresses this gap by using a community-based participatory research (CBPR) approach to empower YLHIV in India to address their mental health challenges. YLHIV actively participated in adapting and implementing a culturally responsive mental health screening program. The study, incorporating CBPR principles at every step aimed to identify practical methods for integrating YLHIV voices in research, and showcase the value of YLHIV participation in co-creating and implementing impactful interventions. Six youth investigators aged 18-24, born with HIV and residing in southern Indian states underwent certification in human subjects’ protection and training in mental health screening and survey administration techniques. They actively shaped the research process by culturally adapting standardized mental health screening tools (PHQ-9, GAD-7) through iterative discussions with experts, drawing on their own perspectives. Following field assessments of the mental health screening tools among their peers, they documented their reflections in surveys and written essays. Youth investigators’ involvement improved the research process by optimizing tools, combating stigma, and facilitating reliable data collection. Beyond data collection, the youth investigators’ participation significantly boosted their own knowledge, self-confidence, and research skills. This study serves as an illustrative model of CBPR in mental health research among YLHIV, highlighting the importance of interactive training, continuous feedback mechanisms, and respectful youth engagement in fostering impactful research that can inform tailored sustainable interventions.