Physiological State Research Articles

Augmented Central Pain Processing Occurs after Osteoporotic Vertebral Compression Fractures and Is Associated with Residual Back Pain after Percutaneous Vertebroplasty.

A retrospective analysis. To investigate the occurrence of central sensitization (CS) in patients with osteoporotic vertebral compression fractures (OVCFs) and identify the association between CS and residual back pain (RBP). RBP is a vexing complication that affects 6.3%-17.0% of patients with OVCFs who underwent percutaneous vertebroplasty (PVP). Given the negative effect of RBP on patients' psychological and physiological statuses, efforts to preoperatively select patients who are at risk for RBP development have a high priority to offer additional treatment and minimize this complication. Preoperatively, all 160 patients with OVCFs underwent pressure-pain threshold (PPT), temporal summation (TS), conditioned pain modulation (CPM), and imaging assessments. Pain intensity and pain-related disability were evaluated before and after PVP. Preoperatively, patients with OVCFs had lower PPTs in both local pain and pain-free areas and lower CPM and higher TS in pain-free areas than healthy participants (p<0.05). Unlike patients with acute fractures, patients with subacute/chronic OVCFs showed higher TS with or without lower CPM in the pain-free area compared with healthy participants (p<0.05). Postoperatively, RBP occurred in 17 of 160 patients (10.6%). All preoperative covariates with significant differences between the RBP and non-RBP groups were subjected to multivariate logistic regression, showing that intravertebral vacuum cleft, posterior fascia edema, numeric rating pain scale scores for low back pain at rest, and TS were independently associated with RBP (p<0.05). Augmented central pain processing may occur in patients with OVCFs, even in the subacute stage, and this preexisting CS may be associated with RBP. Preoperative assessment of TS in pain-free areas may provide additional information for identifying patients who may be at risk of RBP development, which may be beneficial for preventing this complication.

Does Targeted Memory Reactivation during SWS and REM sleep have differential effects on mnemonic discrimination and generalization?

Targeted memory reactivation (TMR), or the presentation of learning-related cues during sleep, has been shown to benefit memory consolidation for specific memory traces when applied during non-rapid eye movement (NREM) sleep. Prior studies suggest that TMR during REM sleep may play a role in memory generalization processes, but evidence remains scarce. We tested the hypothesis that TMR exerts a differential effect on distinct mnemonic processes as a function of the sleep state (REM vs. NREM) in which TMR is delivered. Mnemonic discrimination and generalization of semantic categories were investigated using an adapted version of the Mnemonic Similarity Task, before and after sleep. Forty-eight participants encoded pictures from eight semantic categories, each associated with a sound. In the pre-sleep immediate test, they had to discriminate "old" (targets) from "similar" (lures) or "new" (foils) pictures. During sleep, half of the sounds were replayed in slow wave sleep (SWS) or REM sleep. Recognition, discrimination, and generalization memory indices were tested in the morning. These indices did not differ between SWS and REM TMR groups or reactivated and non-reactivated item categories. Additional results suggest a positive effect of TMR on performance for highly similar items mostly relying on mnemonic discrimination processes. During sleep, EEG activity after cue presentation increased in the delta-theta and sigma band in the SWS group, and in the beta band in the REM TMR group. These results do not support the hypothesis of a differential processing of novel memory traces when TMR is administered in distinctive physiological sleep states.

Carbon substrates promotes stress resistance and drug tolerance in clinical isolates of Candida tropicalis.

Candida tropicalis is a human pathogen and one of the most prevalent non-Candida albicans Candida (NCAC) species causing invasive infections. Azole antifungal resistance in C. tropicalis is also gradually increasing with the increasing incidence of infections. The pathogenic success of C. tropicalis depends on its effective response in the host microenvironment. To become a successful pathogen, cellular metabolism, and physiological status determine the ability of the pathogen to counter diverse stresses inside the host. However, to date, limited knowledge is available on the impact of carbon substrate metabolism on stress adaptation and azole resistance in C. tropicalis. In this study, we determined the impact of glucose, fructose, and sucrose as the sole carbon source on the fluconazole resistance and osmotic (NaCl), oxidative (H2O2) stress adaptation in C. tropicalis clinical isolates. We confirmed that the abundance of carbon substrates influences or increases drug resistance and osmotic and oxidative stress tolerance in C. tropicalis. Additionally, both azole-resistant and susceptible isolates showed similar stress adaptation phenotypes, confirming the equal efficiency of becoming successful pathogens irrespective of drug susceptibility profile. To the best of our knowledge, our study is the first on C. tropicalis to demonstrate the direct relation between carbon substrate metabolism and stress tolerance or drug resistance.

IMPROVEMENT OF CAPILLAROSCOPY METHOD FOR STUDYING HUMAN MICROCIRCULATION

The human circulatory system has historically captivated researchers in the field of medicine. Modern medicine, however, has moved beyond identifying a single crucial element, such as the heart or venous system, for maintaining blood flow. Instead, it emphasizes a more analytical approach, focusing on the interconnected functioning of all components within the system. The aim of this work is to analyze the existing methods of studying blood microcirculation and to improve the technology of capillaroscopy, technical means of raster microphotography to determine the physiological state and disorders of capillary circulation. To achieve this objective, we address the following tasks: analyzing existing non-invasive methods for studying the human vascular system; enhancing the optical capillaroscopy method through the utilization of modern high-resolution digital cameras, computer, and multimedia equipment, along with appropriate software for analyzing electronic images; developing a technological scheme and equipment design for digital microphotography of capillaries in the periungual region of the upper extremities; providing software solutions for registering and analyzing digital microphotographic images obtained through capillaroscopy; conducting experimental studies to explore the structure and properties of capillaries utilizing the developed technologies and equipment. Magnetic resonance imaging (MRI) enables the comprehensive evaluation of both anatomical and functional aspects of blood flow. Magnetic resonance angiography (MRA) capitalizes on the distinction between the signal emitted by moving tissue (blood) and that of surrounding stationary tissue, facilitating the acquisition of vascular images without the need for radiopaque contrast agents. Ultrasonography integrates Doppler and conventional ultrasound techniques, providing physicians with insights into blood vessel structure and blood flow dynamics. Traditional ultrasound employs sound waves that are imperceptible to the human ear and bounce off blood vessels, while Doppler ultrasound measures the velocity of sound wave reflection from moving elements. Ophthalmoscopy constitutes a fundamental component of standard ophthalmological examinations, serving as a pivotal tool for diagnosing eye conditions and evaluating the condition of blood vessels. Additionally, ophthalmoscopy aids in diagnosing autoimmune disorders. Capillaroscopy enables comprehensive assessments of both systemic and regional microcirculation disorders, facilitating the characterization of tissue metabolism. Dysfunction in capillary function contributes to circulatory impairments, leading to blood stasis, metabolic irregularities, and compromised immunity, thereby exacerbating existing conditions and predisposing individuals to new diseases. Optical computerized capillaroscopy offers a non-invasive means of visualizing, examining, and archiving capillary images, enabling clinicians to make informed assessments regarding blood microcirculation. Experimental validation of the optimized hardware and software capillaroscopy system was conducted using nail bed capillaries of a patient with type II diabetes mellitus undergoing insulin therapy for 10 years. This study underscores the importance of refining and enhancing optical capillaroscopy methodologies by leveraging high-resolution camera sensors and modern computational tools for image processing.

Wearable Sensors for Physiological Condition and Activity Monitoring

Rapid technological advancements have transformed the healthcare sector from traditional diagnosis and treatment to personalized health management. Biofluids such as teardrops, sweat, interstitial fluids, and exhaled breath condensate offer a rich source of metabolites that can be linked to the physiological status of an individual. More importantly, these biofluids contain biomarkers similar to those in the blood. Therefore, developing sensors for the noninvasive determination of biofluid‐based metabolites can overcome traditionally invasive and laborious blood‐test‐based diagnostics. In this context, wearable devices offer real‐time and continuous physiological conditions and activity monitoring. The first‐generation wearables included wristwatches capable of tracking heart rate variations, breathing rate, body temperature, stress responses, and sleeping patterns. However, wearable sensors that can accurately measure the metabolites are needed to achieve real‐time analysis of biomarkers. In this review, recent progresses in wearable sensors utilized to monitor metabolites in teardrops, breath condensate, sweat, and interstitial fluids are thoroughly analyzed. More importantly, how metabolites can be selectively detected, quantified, and monitored in real‐time is discussed. Furthermore, the review includes a discussion on the utility of, multifunctional sensors that combine metabolite sensing, human activity monitoring, and on‐demand drug delivery system for theranostic applications.

Internet of Things (IoT) in Healthcare

In this modern era, we have seen increased number of Heart disease Asthma, Diabetes and Mental health patients. So, in these conditions, IOT play a crucial role in this type of disease. Through the integration of sensors, software, and actuators for tracking and monitoring purposes into patients and their medications, smart healthcare plays a vital part in healthcare applications. Through the use of sensors, clinical care uses the Internet of Things to monitor patients' physiological status. Data is collected, evaluated, and sent remotely to processing centers so that appropriate actions can be taken. People's lifestyles are being significantly impacted by IOT devices. This growth is mostly being driven by interest in health and wellbeing. This approach has the potential to expedite the transformation of hospitals into smart ones and help physicians identify and recommend appropriate wearable IOT devices. This is not only for patients, it also useful for normal people to check own health status by using wearable IOT devices. The design and development of dependable and reasonably priced wireless sensing device based on the Node MCU microcontroller for the real-time collection of health vital signs including heart rate and body temperature. their engagement in healthcare benefit conveyance.

Metabolic profile and gene expression pattern of cytokines and antioxidants markers during different physiological stages in Barki ewes

BackgroundIn livestock, identifying the physiological and reproductive stages is valuable in guiding management decisions related to nutrition, veterinary procedures, and breeding programs. To achieve this goal, a cohort of Barki ewes in this research underwent observation across three pivotal physiological conditions: pre-pregnancy, late pregnancy, and early lactation. Blood samples were collected to investigate the changes in serum metabolic profile as well as gene expression pattern of cytokines and antioxidants markers during these stages.ResultsOur results showed that during late pregnancy, there was a significant (P < 0.05) increase in red blood cells (11.9 ± 0.5 1012/L), hemoglobin (10.8 ± 0.4 g/dl) and neutrophils count (7 ± 0.1 109/L) with significant decrease (P < 0.05) of total white blood cell count (9.1 ± 0.05 109/L). The packed cell volume (%) and monocyte count showed a significant (P < 0.05) decrease during both late pregnancy and early lactation stages. The serum concentrations of glucose, cholesterol, GSH, GPx, SOD and catalase displayed significant (P < 0.05) decrease during late pregnancy and early-lactation. Notably, during late pregnancy, there was a significant (P < 0.05) increase in the serum concentrations of albumin, globulin, urea, IGF-1, and malondialdehyde with significant decrease (P < 0.05) of total protein (4.9 ± 0.08 g/dl). Additionally, during early lactation, there was a significant (P < 0.05) increase in the serum levels of non-esterified fatty acids, triiodothyronine (T3), and thyroxin (T4). The gene expression profiles of cytokines (IL-4, IL-6, IL-8, and NFKB) were decreased in the ewes during late pregnancy compared to pre-pregnant and early lactation stages. In addition, the expression profile of antioxidant genes (SOD, CAT, GPX, and Nrf2) was significantly upsurged in the non-pregnant ewes compared to late pregnancy and early lactation ones.ConclusionsThe results concluded that different physiological status significantly affects the blood metabolic profile and gene expression pattern in Barki sheep. Our findings can be helpful in monitoring animal health and applying in breeding programs of Barki sheep under harsh environmental conditions.

Dissociative Symptoms and Interoceptive Integration.

Dissociative symptoms and disorders of dissociation are characterised by disturbances in the experience of the self and the surrounding world, manifesting as a breakdown in the normal integration of consciousness, memory, identity, emotion, and perception. This paper aims to provide insights into dissociative symptoms from the perspective of interoception, the sense of the body's internal physiological state, adopting a transdiagnostic framework.Dissociative symptoms are associated with a blunting of autonomic reactivity and a reduction in interoceptive precision. In addition to the central function of interoception in homeostasis, afferent visceral signals and their neural and mental representation have been shown to shape emotional feeling states, support memory encoding, and contribute to self-representation. Changes in interoceptive processing and disrupted integration of interoceptive signals into wider cognition may contribute to detachment from the body and the world, blunted emotional experience, and altered subjective recall, as experienced by individuals who suffer from dissociation.A better understanding of the role of altered interoceptive integration across the symptom areas of dissociation could thus provide insights into the neurophysiological mechanisms underlying dissociative disorders. As new therapeutic approaches targeting interoceptive processing emerge, recognising the significance of interoceptive mechanisms in dissociation holds potential implications for future treatment targets.

Contemporary Advances in Cardiac Remote Monitoring: A Comprehensive, Updated Mini-Review

Over the past decade, remote monitoring (RM) has become an increasingly popular way to improve healthcare and health outcomes. Modern cardiac implantable electronic devices (CIEDs) are capable of recording an increasing amount of data related to CIED function, arrhythmias, physiological status and hemodynamic parameters, providing in-depth and updated information on patient cardiovascular function. The extensive use of RM for patients with CIED allows for early diagnosis and rapid assessment of relevant issues, both clinical and technical, as well as replacing outpatient follow-up improving overall management without compromise safety. This approach is recommended by current guidelines for all eligible patients affected by different chronic cardiac conditions including either brady- and tachy-arrhythmias and heart failure. Beyond to clinical advantages, RM has demonstrated cost-effectiveness and is associated with elevated levels of patient satisfaction. Future perspectives include improving security, interoperability and diagnostic power as well as to engage patients with digital health technology. This review aims to update existing data concerning clinical outcomes in patients managed with RM in the wide spectrum of cardiac arrhythmias and Hear Failure (HF), disclosing also about safety, effectiveness, patient satisfaction and cost-saving.

Telomere length is longer following diapause in two solitary bee species

The mechanisms that underlie senescence are not well understood in insects. Telomeres are conserved repetitive sequences at chromosome ends that protect DNA during replication. In many vertebrates, telomeres shorten during cell division and in response to stress and are often used as a cellular marker of senescence. However, little is known about telomere dynamics across the lifespan in invertebrates. We measured telomere length in larvae, prepupae, pupae, and adults of two species of solitary bees, Osmia lignaria and Megachile rotundata. Contrary to our predictions, telomere length was longer in later developmental stages in both O. lignaria and M. rotundata. Longer telomeres occurred after emergence from diapause, which is a physiological state with increased tolerance to stress. In O. lignaria, telomeres were longer in adults when they emerged following diapause. In M. rotundata, telomeres were longer in the pupal stage and subsequent adult stage, which occurs after prepupal diapause. In both species, telomere length did not change during the 8 months of diapause. Telomere length did not differ by mass similarly across species or sex. We also did not see a difference in telomere length after adult O. lignaria were exposed to a nutritional stress, nor did length change during their adult lifespan. Taken together, these results suggest that telomere dynamics in solitary bees differ from what is commonly reported in vertebrates and suggest that insect diapause may influence telomere dynamics.

Increasing Eligibility to Transplant Through the Selective Cytopheretic Device: A Review of Case Reports Across Multiple Clinical Conditions.

A stable, minimum physiological health status is required for patients to qualify for transplant or artificial organ support eligibility to ensure the recipient has enough reserve to survive the perioperative transplant period. Herein, we present a novel strategy to stabilize and improve patient clinical status through extracorporeal immunomodulation of systemic hyperinflammation with impact on multiple organ systems to increase eligibility and feasibility for transplant/device implantation. This involves treatment with the selective cytopheretic device (SCD), a cell-directed extracorporeal therapy shown to adhere and immunomodulate activated neutrophils and monocytes toward resolution of systemic inflammation. In this overview, we describe a case series of successful transition of pediatric and adult patients with multiorgan failure to successful transplant/device implantation procedures by treatment with the SCD in the following clinical situations: pediatric hemophagocytic lymphohistiocytosis, and adult hepatorenal and cardiorenal syndromes. Application of the SCD in these cases may represent a novel paradigm in increasing clinical eligibility of patients to successful transplant outcomes.

Modulating Nonlinear Acoustic Response of Phospholipid-Coated Microbubbles with pH for Ultrasound Imaging.

Activatable microbubble contrast agents for contrast-enhanced ultrasound have a potential role for measuring physiologic and pathologic states in deep tissues, including tumor acidosis. In this study, we describe a novel observation of increased harmonic oscillation of phosphatidylcholine microbubbles (PC-MBs) in response to lower ambient pH using a clinical ultrasound scanner. MB echogenicity and nonlinear echoes were monitored at neutral and acidic pH using B-mode and Cadence contrast pulse sequencing (CPS), a harmonic imaging technique at 7.0 and 1.5 MHz. A 3-fold increase in harmonic signal intensity was observed when the pH of PC-MB suspensions was decreased from 7.4 to 5.5 to mimic normal and pathophysiological levels that can be encountered in vivo. This pH-mediated activation is tunable based on the chemical structure and length of phospholipids composing the MB shell. It is also reliant on the presence of phosphate groups, as the use of lipids without phosphate instead of phospholipids completely abrogated this phenomenon. The increased harmonic signal likely is the result of increased MB oscillation caused by a decrease of the interfacial tension induced at a lower pH, altering the lipid conformation. While relative signal changes are interpreted clinically as mostly related to blood flow, pH effects could be significant contributors, particularly when imaging tumors. While our observation can be used clinically, it requires further research to isolate the effect of pH from other variables. These findings could pave the way toward for the development of new smart ultrasound contrast agents that expand the clinical utility of contrast-enhanced ultrasound.

Nanozymes for the Therapeutic Treatment of Diabetic Foot Ulcers.

Diabetic foot ulcers (DFU) are chronic, refractory wounds caused by diabetic neuropathy, vascular disease, and bacterial infection, and have become one of the most serious and persistent complications of diabetes mellitus because of their high incidence and difficulty in healing. Its malignancy results from a complex microenvironment that includes a series of unfriendly physiological states secondary to hyperglycemia, such as recurrent infections, excessive oxidative stress, persistent inflammation, and ischemia and hypoxia. However, current common clinical treatments, such as antibiotic therapy, insulin therapy, surgical debridement, and conventional wound dressings all have drawbacks, and suboptimal outcomes exacerbate the financial and physical burdens of diabetic patients. Therefore, development of new, effective and affordable treatments for DFU represents a top priority to improve the quality of life of diabetic patients. In recent years, nanozymes-based diabetic wound therapy systems have been attracting extensive interest by integrating the unique advantages of nanomaterials and natural enzymes. Compared with natural enzymes, nanozymes possess more stable catalytic activity, lower production cost and greater maneuverability. Remarkably, many nanozymes possess multienzyme activities that can cascade multiple enzyme-catalyzed reactions simultaneously throughout the recovery process of DFU. Additionally, their favorable photothermal-acoustic properties can be exploited for further enhancement of the therapeutic effects. In this review we first describe the characteristic pathological microenvironment of DFU, then discuss the therapeutic mechanisms and applications of nanozymes in DFU healing, and finally, highlight the challenges and perspectives of nanozyme development for DFU treatment.

INVESTIGATION OF THE EFFICIENCY OF NON-STEROIDAL ANTI-INFLAMMATORY VETERINARY MEDICINAL PRODUCT IN THE COMPLEX TREATMENT OF DISEASES OF THE MUSCULOSKELETAL SYSTEM OF PIGS

The article presents the results of clinical trials of a non-steroidal anti-inflammatory veterinary drug when administered to fattening piglets with clinical signs of musculoskeletal diseases. For the treatment of the diseases, piglets of the experimental (I) and control (II) groups received an antimicrobial drug based on the tetracycline antibiotic. The animals of the experimental group were additionally administered orally with drinking water the test non-steroidal anti-inflammatory drug based on acetylsalicylic, ascorbic and citric acids, in the recommended dosage by the manufacturer. Blood for laboratory tests was selected from piglets before and after the use of drugs. Studies of hematological and biochemical parameters were conducted according to generally accepted methods. The therapeutic efficiecy of the drug and its effect on the morphofunctional state of the body was evaluated by comparing the statistically processed data obtained before and after treatment, as well as in comparison with the indicators of animals of the control group. The analysis of hematological parameters of piglets during the experiment showed a decrease in the number of leukocytes in the animal’s blood after the use of drugs. The normalization of the leukogram was also noted by reducing the relative number of rod-nuclear neutrophils. In particular, this indicator decreased by 17.4% in group I piglets, and by 12% in group II piglets. It is noted that the clinical response to therapy was faster and more pronounced in animals, which used a non-steroidal anti-inflammatory drug in combination with an antimicrobial drug than in piglets, which were treated only by antibiotic. According to the results of biochemical studies, it was found that the content of urea in the serum of animals of both groups before the use of drugs exceeded more than 3 times the upper limit of physiological values for a given age group of piglets. After therapy with the drugs a significant decrease in the urea content in the blood serum of groups 1 and 2 animals was noted by 3.42 and 2.98 times, respectively. It is established that the activity of marker enzymes of the liver physiological state (ALT, AST) in the serum of group I piglets after complex treatment with the studied drugs was slightly reduced and was within the physiological values. In the serum of group II animals, which were treated only with antimicrobial drug, ALT activity increased by 12,0 %, and AST – by 38,6 %, compared to the initial data, and exceeded the limit of physiological values. An increase in the content of iron by 37.4 % in the blood of group I piglets, compared to the period before drug administration, was noted. No adverse reactions and negative phenomena were detected during the use of the test drug, and the drug was well tolerated. According to the clinical condition of the experimental group animals and the results of laboratory tests it was established that the use of non-steroidal anti-inflammatory drugs based on acetylsalicylic, ascorbic and citric acids simultaneously with antimicrobial therapy led to a faster improvement in the state of the musculoskeletal system. Observation during the month of the piglet’s clinical conditions confirmed the safety of the drug in the recommended dosage and method of administration in the combined treatment of inflammatory processes of the musculoskeletal system.

THORACIC SEGMENTAL SPINAL ANAESTHESIA IN UPPER ABDOMINAL SURGERIES AND SIMPLE MASTECTOMY-A CASE SERIES

Objective: To observe safety and efficacy of Segmental thoracic spinal anesthesia (STSA) in upper abdominal and breast surgeries. Methods: 14 cases were selected, out of which 6 laparoscopic cholecystectomy (LC), 4 open cholecystectomy (OC), 3 emergency exploratory laparotomy and 1 simple mastectomy. Under full aseptic precaution, segmental thoracic spinal anesthesia was administered through midline approach in T8-9 space for upper abdominal surgeries and T5-6 space in a simple mastectomy. Using 25G Quincke spinal needle 1.5 ml [7.5 mg] of 0.5% Isobaric Levobupivacaine mixed with 0.4 ml (20µg) Fentanyl was given in abdominal surgeries and 1.2 ml [6 mg] of 0.5% Isobaric Levobupivacaine mixed with 0.4 ml (20µg) Fentanyl in simple mastectomy. Results: Age group of patients ranged from 25 to 65 y, Male: Female ratio of 4:10, Body Mass Index (BMI) range of 22 to 24.9 with physiological status of ASA I to ASA III. Hemodynamically, hypotension was observed in every patient after 5-10 min of STSA well managed with fluid and vasopressors with no bradycardia. Average width of sensory block was T3 to L1-2 in upper abdominal surgeries and T1 to T8 in a simple mastectomy. Motor block was Modified Bromage Scale (MBS) of 0 to 1 during and postoperatively. Regarding analgesia, Visual Analogue Scale (VAS) score was 0 intraoperatively and 0-1 postoperatively. Sedation score was 2 both intraoperatively and postoperatively with no significant complications and good patient and surgeon satisfaction. Conclusion: Segmental thoracic spinal anaesthesia is a safe and effective procedure with good patient and surgeon satisfaction.

Cord Blood Proteomic Profiles, Birth Weight, and Early Life Growth Trajectories

The cord blood proteome, a repository of proteins derived from both mother and fetus, might offer valuable insights into the physiological and pathological state of the fetus. However, its association with birth weight and growth trajectories early in life remains unexplored. To identify cord blood proteins associated with birth weight and the birth weight ratio (BWR) and to evaluate the associations of these cord blood proteins with early growth trajectories. This cohort study included 288 mother-child pairs from the ongoing prospective Environmental Influence on Early Aging birth cohort study. Newborns were recruited from East-Limburg Hospital in Genk, Belgium, between February 2010 and November 2017 and followed up until ages 4 to 6 years. Data were analyzed from February 2022 to September 2023. The outcome of interest was the associations of 368 inflammatory-related cord blood proteins with birth weight or BWR and with early life growth trajectories (ie, rapid growth at age 12 months and weight, body mass index [BMI] z score, waist circumference, and overweight at age 4-6 years) using multiple linear regression models. The BWR was calculated by dividing the birth weight by the median birth weight of the population-specific reference growth curve, considering parity, sex, and gestational age. Results are presented as estimates or odds ratios (ORs) for each doubling in proteins. The sample included 288 infants (125 [43.4%] male; mean [SD] gestation age, 277.2 [11.6] days). The mean (SD) age of the child at the follow-up examination was 4.6 (0.4) years old. After multiple testing correction, there were significant associations of birth weight and BWR with 7 proteins: 2 positive associations: afamin (birth weight: coefficient, 341.16 [95% CI, 192.76 to 489.50]) and secreted frizzled-related protein 4 (SFRP4; birth weight: coefficient, 242.60 [95% CI, 142.77 to 342.43]; BWR: coefficient, 0.07 [95% CI, 0.04 to 0.10]) and 5 negative associations: cadherin EGF LAG 7-pass G-type receptor 2 (CELSR2; birth weight: coefficient, -237.52 [95% CI, -343.15 to -131.89]), ephrin type-A receptor 4 (EPHA4; birth weight: coefficient, -342.78 [95% CI, -463.10 to -222.47]; BWR: coefficient, -0.11 [95% CI, -0.14 to -0.07]), SLIT and NTRK-like protein 1 (SLITRK1; birth weight: coefficient, -366.32 [95% CI, -476.66 to -255.97]; BWR: coefficient, -0.11 [95% CI, -0.15 to -0.08]), transcobalamin-1 (TCN1; birth weight: coefficient, -208.75 [95% CI, -305.23 to -112.26]), and unc-5 netrin receptor D (UNC5D; birth weight: coefficient, -209.27 [95% CI, -295.14 to -123.40]; BWR: coefficient, -0.07 [95% CI, -0.09 to -0.04]). Further evaluation showed that 2 proteins were still associated with rapid growth at age 12 months (afamin: OR, 0.32 [95% CI, 0.11-0.88]; TCN1: OR, 2.44 [95% CI, 1.26-4.80]). At age 4 to 6 years, CELSR2, EPHA4, SLITRK1, and UNC5D were negatively associated with weight (coefficients, -1.33 to -0.68 kg) and body mass index z score (coefficients, -0.41 to -0.23), and EPHA4, SLITRK1, and UNC5D were negatively associated with waist circumference (coefficients, -1.98 to -0.87 cm). At ages 4 to 6 years, afamin (OR, 0.19 [95% CI, 0.05-0.70]) and SLITRK1 (OR, 0.32 [95% CI, 0.10-0.99]) were associated with lower odds for overweight. This cohort study found 7 cord blood proteins associated with birth weight and growth trajectories early in life. Overall, these findings suggest that stressors that could affect the cord blood proteome during pregnancy might have long-lasting associations with weight and body anthropometrics.

Transcriptomic analysis-guided assessment of precision-cut tumor slices (PCTS) as an ex-vivo tool in cancer research

With cancer immunotherapy and precision medicine dynamically evolving, there is greater need for pre-clinical models that can better replicate the intact tumor and its complex tumor microenvironment (TME). Precision-cut tumor slices (PCTS) have recently emerged as an ex vivo human tumor model, offering the opportunity to study individual patient responses to targeted therapies, including immunotherapies. However, little is known about the physiologic status of PCTS and how culture conditions alter gene expression. In this study, we generated PCTS from head and neck cancers (HNC) and mesothelioma tumors (Meso) and undertook transcriptomic analyses to understand the changes that occur in the timeframe between PCTS generation and up to 72 h (hrs) in culture. Our findings showed major changes occurring during the first 24 h culture period of PCTS, involving genes related to wound healing, extracellular matrix, hypoxia, and IFNγ-dependent pathways in both tumor types, as well as tumor-specific changes. Collectively, our data provides an insight into PCTS physiology, which should be taken into consideration when designing PCTS studies, especially in the context of immunology and immunotherapy.

Prefrontal Correlates of Passengers’ Mental Activity Based on fNIRS for High-Level Automated Vehicles

AbstractWith the spread adoption of artificial intelligence, the great challenges confronted by the intelligent safety concern-safety of the intended functionality has become the biggest roadblock to the mass production of high-level automated vehicles, notably arising from perception algorithm deficiencies. This paper focuses a cut-in scenario, dividing this scenario into low-risk and high-risk segments predicated on the kinetic energy field, and the mental activities of passengers on prefrontal cortex, are analyzed within these delineated segments. Two experiments are then conducted, leveraging driving simulators and real-world vehicles, respectively. Experiment results indicate that high risk may result in the passengers’ mental activity on prefrontal cortex change. This revelation posits a potential avenue for augmenting the intended functionality of automated vehicle by using passengers’ physiological state.

Validation of a bupropion, dextromethorphan, and omeprazole cocktail for simultaneous phenotyping of cytochrome P450 2B11, 2D15, and 3A12 activities in dogs.

Develop a cytochrome P450 (CYP) phenotyping cocktail for dogs using specific substrates for hepatic P450 enzymes CYP2B11, CYP2D15, and CYP3A12 and determine whether alternative sampling methods (saliva and urine) or single time point samples could be used instead of multiple blood sampling. 12 healthy client-owned dogs (8 females and 4 males) from February 2019 to May 2019. In a randomized crossover study, dogs received oral administration of the probe drug bupropion (75 mg), dextromethorphan (30 mg), or omeprazole (40 mg) alone or as a 3-drug combination (Program in Individualized Medicine [PrIMe] cocktail) to evaluate simultaneous phenotyping of CYP2B11, CYP2D15, and CYP3A12. Pharmacokinetic profiles for the probe drugs and metabolites were determined using plasma, saliva, and urine. Dogs received probe drugs alone or combined. Pharmacokinetic profiles up to 6 hours postdose for the probe drugs and metabolites were determined using plasma, saliva, and urine. The PrIMe cocktail was well tolerated. There was no statistically significant interaction between the probe drugs when administered together. Single time point plasma metabolic ratios at 4 hours postdose for all probe drugs strongly correlated with the corresponding area under the plasma concentration-versus-time curve (AUC) ratios. Saliva AUC metabolic ratios for CYP3A12 and CYP2D15 and 6-hour urine for CYP2B11 and CYP2D15 were correlated with plasma AUC ratios. The PrIMe cocktail can be used for simultaneous CYP phenotyping using plasma 4-hour single time point sample metabolic ratios. Saliva and urine sampling are suitable for specific CYPs. The PrIMe cocktail has potential as a useful tool in dogs to detect clinically important CYP-mediated drug-drug interactions, identify novel pharmacogenes, determine the drug-metabolizing phenotype of individual dogs, aid in individualized dose selection, and evaluate the effects of various physiological states on drug metabolism.

Technology-enhanced mindfulness-based collaborative social reasoning to improve adolescents' social-emotional competencies.

This study reports the preliminary efficacy of an innovative school-based, technology-enhanced social-emotional learning program called "mindfulness-based collaborative social reasoning" (MBCSR) for middle school students. MBCSR was developed by an interdisciplinary team of educational psychologists, mindfulness researchers, computer scientists, and health experts. We integrated the strengths of contemplative approaches, collaborative small group discussions, learning technology, and multidimensional assessments of students' social-emotional outcomes. Using a quasi-experimental design, the study was implemented in four sixth-grade English language arts classrooms (2 experimental and 2 business-as-usual control; N = 74) in a public middle school in the Midwest of the United States. It was co-implemented by researchers and teachers, with sessions occurring for 45 minutes, once per week, for 8 weeks. The MBCSR group showed greater self-efficacy for using Upa-yoga and mindful breathing to regulate their emotions and behaviors ( = .13), and lower externalizing ( = .07) and bullying behaviors ( = .09) at the posttest compared to the control group, after controlling for baseline differences. Students in the experimental group overall showed positive and relaxed emotional and physiological states during the sessions. There were no significant differences between the two groups in mindfulness, emotional regulation, and social skills. This program sets an example for integrating social-emotional learning and academic learning into students' daily content instruction.