Normal Activity Research Articles

Paediatric Activity Anomaly Detection using CNN-XGBoost for Early Intervention and Patient Safety

The development of a robust anomaly detection system capable of distinguishing between normal and abnormal activities in paediatric care settings is of paramount importance for early intervention and patient safety. This endeavor presents substantial challenges due to the unique characteristics of paediatric activities, making it necessary to employ a combination of Convolutional Neural Networks (CNNs) and XGBoost to effectively address these complexities. The initial step involves the assembly of a meticulously annotated dataset comprising video sequences encompassing a broad spectrum of paediatric activities, both normal and abnormal, with a strong emphasis on diversity and representativeness. This dataset is subjected to rigorous preprocessing to ensure consistency and quality. This research employs a Kalman filter as a pre-processing step. This filter helps to reduce noise and enhance the quality of the video data. By smoothing and stabilizing the trajectories of objects or subjects within the video frames, the Kalman filter provides a cleaner input for subsequent stages of the process. CNN employed for feature extraction from video frames, capturing both spatial and temporal cues. To account for the temporal dimension inherent in video data, by ensuring that the model can capture nuanced patterns in paediatric activities. The accuracy of the proposed method is 88%. The extracted features or sequences are input into an XGBoost classifier, designed as a binary classification task to differentiate between normal and abnormal activities. Robust model evaluation is conducted on validation and test datasets using appropriate performance metrics, with continuous feedback loops established with healthcare professionals and caregivers to fine-tune and optimize the model's performance.

Taste and its receptors in human physiology: A comprehensive look

AbstractIncreasing evidence shows that food has significance beyond traditional perception (providing nutrition and energy) in maintaining normal life activities. It is indicated that the sense of taste plays a crucial part in regulating human life activities. Taste is one of the basic physiological sensations in mammals, and it is the fundamental guarantee for them to perceive, select, and ingest nutrients in order to survive. With the advances in electrophysiology, molecular biology, and structural biology, studies on the intracellular and extracellular transduction mechanisms of taste have made great progress and gradually revealed the indispensable role of taste receptors in the regulation and maintenance of normal physiological activities. Up to now, how food regulates life activities through the taste pathway remains unclear. Thus, this review comprehensively and systematically summarizes the current study about the sense of taste, the function of taste receptors, the taste–structure relationship of gustatory molecules, the cross‐talking between distinctive tastes, and the role of the gut–organ axis in the realization of taste. Moreover, we also provide forward‐looking perspectives on taste research to afford a scientific basis for revealing the scientific connotation of taste receptors regulating body health.

Prevalence, severity and impacts of breathlessness in Indian adults: An exploratory, nationally representative, cross-sectional online survey.

There are no known estimates of the prevalence, severity and impacts from breathlessness in low- and middle-income countries. This study aimed to explore the prevalence, severity, self-attributed underlying conditions and impacts of breathlessness limiting exertion in community-dwelling adults in India. This exploratory, population-based online survey recruited a pre-planned sample of 3,000 adult respondents stratified by age, sex and rurality (quotas as per the 2011 Indian National Census). Measures included: demographics; breathlessness limiting exertion (modified Medical Research [mMRC] scale); health-related quality of life (EQ-5D-5L); and disability (World Health Organisation's Disability Assessment Schedule 2.0 12-item questionnaire [WHODAS-12]). Respondents (n = 3,046) had a mean age of 38 years (SD 15); 57% were male, 59% lived in rural areas and 33% had completed 12th grade. Breathlessness limiting exertion (mMRC ≥1) was reported by 44%, mostly attributed to poor nutrition (28%), lung conditions excluding tuberculosis (17%) or anaemia (13%). Compared to those without breathlessness, a higher proportion of people with breathlessness (mMRC ≥1) reported problems across all EQ-5D-5L dimensions. Most people reporting breathlessness (81%) indicated the symptom had adversely affected their normal activities. Disability scores (WHODAS-12 total and individual domains) increased as breathlessness worsened. To conclude, in India, conservative estimates indicate 626 million people live with breathlessness of whom 52 million people live with severe breathlessness. The symptom is associated with poorer health-related quality of life and marked disability, including reduced ability to perform daily activities.

Abstract PO5-13-10: Determining tumor-driving cell signaling pathways in breast cancer: Support for targeted therapy selection

Abstract Introduction: Success of therapeutic interventions largely rely on the pathological and biological characteristics of the tumor and varies due to the heterogeneous nature of breast cancers. Signal transduction pathways play an important role and are often used as target for specific therapies like hormone treatment, PI3K inhibitors etc. Immunohistochemistry (IHC) is currently the first assessment to divide tumors for subtyping and treatment and, especially in more advanced disease, mutation analyses are often used. Both IHC and mutation analyses only analyze a specific part of a signal transduction pathway and do not correlate well with outcome. Therefore, there is a need for new approaches to look at signaling pathways in cancer. We have developed a methodology that measures and quantifies signal transduction pathways (STPs) activities to reveal potential tumor-driving STPs to identify new options for targeted therapy in breast cancer. Method: Using the mRNA-based OncoSIGNal pathway activity profiling qPCR test (InnoSIGN), STP activities of 7 pathways (AR, ER, PI3K, MAPK, HH, TGFβ and Notch) were measured and quantified on a scale from 0-100. By using a set of non-tumor epithelial breast tissue samples, a reference range for normal physiological pathway activity was defined. A threshold was set on the 95th percentile of this range. A pathway activity score above this threshold was considered to be high (activated). Using this methodology, 201 ER positive (based on IHC) and 64 triple negative FFPE breast tumor samples obtained from different study sites and commercial biobanks were analyzed, including samples from primary and metastatic lesions, to determine for each individual tumor its pathway activity profile and identify activated tumor-driving pathways. Results: In the 195 primary ER positive tumors, the ER pathway was found to be activated in 78% of the samples, even though all samples were strongly ER immunohistochemistry stain positive. In addition to ER pathway activation, occasionally other pathways were activated: PI3K in 37%, HH in 25%, MAPK in 19%, AR in 20%, TGFβ in 6%, and Notch in 1%, of these samples. Analysis of 27 metastatic samples of ER positive tumors revealed in only 63% an active ER pathway. Additionally, more frequently PI3K pathway was observed in 70% of the samples. Other frequencies of pathway activation were: AR in 7% and MAPK in 4%, No Notch and TGFβ activity was found in this cohort. In 76 of the 78 triple negative tumors (TNBC) the ER pathway was inactive as expected. Remarkably, 2 samples appeared to have an activated ER pathway. An activated MAPK pathway was found in 50%, PI3K in 49%, HH in 18%, AR in 14%, TGFβ in 5% and Notch in 3% of these TNBC tumors. Conclusion: Compared to ER positive primary tumors we observed in metastatic ER positive tumors less frequent activation of the ER and more frequent activation of the PI3K pathway, suggesting that the latter pathway is associated with a more aggressive tumor phenotype. The triple negative subtype is characterized predominantly by activation of the PI3K, MAPK, AR and/or HH pathways, which may create new options for personalized targeted therapy of this subtype. OncoSIGNal can be used to determine the tumor driving signaling pathways in breast cancer patients, guiding selection of personalized targeted therapies. Citation Format: Paul van de Wiel, Yvonne Wesseling-Rozendaal, Anke Pierik, Dianne van Strijp, Saskia Vermeer, Fatema Tashrifwala, Josette Hartnett, Robert Babkowski, Suzanne Rose. Determining tumor-driving cell signaling pathways in breast cancer: Support for targeted therapy selection [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-13-10.

An effective complex approach to the management of patients with chronic musculoskeletal low back pain and pains in other body sites

Low back pain (LBP) is a major public health problem globally. As life expectancy increases, the number of people with LBP will further increase in the coming decades. LBP is the leading cause of work productivity and activity impairment worldwide, therefore training of neurologists, primary care physicians, and general practitioners for timely and accurate diagnosis of LBP, as well as effective treatment of patients with LBP is an economically and socially significant challenge for medical practice. The clinical case describes the successful management of a female patient with LBP. It provides a modern, clear and effective approach to the diagnosis and treatment of musculoskeletal LBP. The typical comorbid disorders and factors that contribute to the pain syndrome chronicity are presented. The female patient was treated using a complex approach that included disease awareness conversations, kinesiotherapy, and pharmacotherapy in the form of a 10-day nonsteroidal anti-inflammatory drug (NSAID) course. Nimesil (nimesulide) with proven efficacy and safety in the treatment of musculoskeletal pain has become a drug of choice. It should be noted that nimesulide was prescribed to the patient from the first days of treatment concurrently with the beginning of a training course in kinesiology. The patient experienced a rapid pain relief while taking pharmacotherapy, which played an important role in supporting adherence to recommendations for increasing physical activity and taking training courses in kinesiology. The patient reported a significant decrease in pain on Day 10. After 1.5-month treatment, the pain regressed and she returned to her normal daily activities. The presented approach to therapy allows to provide LBP patients with a relatively fast pain relief, and the 6-month follow up period demonstrated sustainability of the therapeutic effect achieved.

Lower Third Leg Trauma Management Algorithm; Kasr Alainy Protocol.

Soft tissue defects in the lower third of the leg present significant challenges for surgeons. Despite various options available for soft tissue coverage, selecting the most suitable option is limited by potential complications. In response to this challenge, some surgeons have sought to develop algorithms to guide decision-making in the management of lower leg trauma. This prospective observational cross-sectional study included 53 patients with traumatic injuries to the lower third leg and ankle regions. Each patient underwent a management plan based on our proposed algorithm, which incorporated the utilization of negative pressure wound therapy and dermal substitutes. Outcomes were assessed in terms of the ability to achieve complete coverage, complication rates, duration of hospital stay, and return to normal daily activity. The proposed algorithm proved to be comprehensive and easily applicable, achieving complete coverage in 98.1% of cases. The mean duration for definitive coverage was 21.89 ± 12.84 days, and the majority of cases (81.1%) returned to normal daily activity within a mean duration of 60.69 ± 56.7 days. The use of dermal substitutes resulted in achieving coverage in wounds with exposed structures, with favorable outcomes in cases with a mean size of 11.39 ± 10.05 cm². Our algorithm provides a safe and effective approach to manage traumatic defects of the lower third leg and ankle, considering the patient's general condition and the complexity of the wound. Proper utilization of dermal substitutes and negative pressure wound therapy is emphasized in the algorithm.

Associations between Illicit ADHD Medication Use and Aspects of Mental Distress Among College Students

The illicit use of Attention-Deficit Hyperactivity Disorder (ADHD) medication has become a prevalent issue on college campuses. Illicit ADHD medications are used without a medical prescription. The concern is that these medications are psychostimulants that may alter brain chemistry and affect the quality of brain maturity in individuals who do not need them medically, which potentially can affect mental health. An alarmingly high percent of reported illicit ADHD medication users are college aged students between the age of 18 and 22 years. Little is known about the effect of illicit ADHD medication use on mental well-being among college students. Thus, the purpose of the study was to assess the impact of illicit ADHD medication use on different aspects of mental distress among college students. The study collected 702 responses from undergraduate students at several US colleges and included self-reported data on illicit Adderall use, age and symptoms of mental distress. The anonymous survey was created in Google Forms. Mental distress was evaluated through The Kessler Psychological Distress Scale (K10). The data were analyzed in SPSS, Version 28.0, using Pearson’s Correlation Coeffcient. Of the 72.5% of the participants who reported using ADHD medication without a prescription, 71.4% reported academic reasons as their motivation for use. There is a positive correlation between feelings of worthlessness and illicit ADHD medication use (p<0.05). Age was negatively correlated with feelings nervous (p<0.01) and restless or fidgety (p<0.01). Additionally, a negative correlation was found between age and being able to do only half or less of what you would normally have been able to do (p<0.01). On the other hand, illicit ADHD medication use was negatively correlated with feeling that everything was an effort (p<0.05), as well feeling unable to work or carry out normal activities (p<0.01). Our results suggest that students who use ADHD medication illicitly are more likely to experience symptoms of mental distress. Interestingly, our findings propose that the younger the age of use, the higher the risk of mental distress. We received no support or financial grants. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

AGPAT3 deficiency impairs adipocyte differentiation and leads to a lean phenotype in mice

Acylglycerophosphate acyltransferases (AGPATs) catalyze the de novo formation of phosphatidic acid to synthesize glycerophospholipids and triglycerides. AGPATs demonstrate unique physiological roles despite a similar biochemical function. AGPAT3 is highly expressed in the testis, kidney, and liver, with intermediate expression in adipose tissue. Loss of Agpat3 is associated with reproductive abnormalities and visual dysfunction. However, the role of AGPAT3 in adipose tissue and whole-body metabolism has not been investigated. We found that male Agpat3-KO mice exhibited reduced body weights with decreased white and brown adipose tissue mass. Such changes were less pronounced in the female Agpat3-KO mice. Agpat3-KO mice have reduced plasma insulin growth factor 1 (IGF1) and insulin levels and diminished circulating lipid metabolites. They manifested intact glucose homeostasis and insulin sensitivity despite a lean phenotype. Agpat3-KO mice maintained an energy balance with normal food intake, energy expenditure, and physical activity, except for increased water intake. Their adaptive thermogenesis was also normal despite reduced brown adipose mass and triglyceride content. Mechanistically, Agpat3 was elevated during mouse and human adipogenesis and enriched in adipocytes. Agpat3-knockdown 3T3-L1 cells and Agpat3-deficient mouse embryonic fibroblasts (MEFs) have impaired adipogenesis in vitro. Interestingly, pioglitazone treatment rescued the adipogenic deficiency in Agpat3 deficient cells. We conclude that AGPAT3 regulates adipogenesis and adipose development. It is possible that adipogenic impairment in Agpat3 deficient cells potentially leads to reduced adipose mass. Findings from this work support the unique role of AGPAT3 in adipose tissue. This work was supported by the National Institute of Diabetes and Digestive and Kidney Diseases [1R56 DK135657] and the National Heart, Lung and Blood Institute [2R01HL132182-01] to W.C. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Limited preoperative forward flexion does not impact outcomes between anatomic or reverse shoulder arthroplasty for primary glenohumeral arthritis

BackgroundAnatomic total shoulder arthroplasty (TSA) remains the treatment of choice for primary glenohumeral osteoarthritis with an intact rotator cuff (PGHOA). However, reverse total shoulder arthroplasty (RSA) has gained popularity as a primary procedure in selected patients who may be at risk for postoperative rotator cuff dysfunction or glenoid loosening. The purpose of this study was to compare short-term outcomes between TSA and RSA in patients with PGHOA and limited preoperative forward flexion (FF). MethodsA retrospective review was performed on a multi-institutional registry of patients to identify patients aged less than 80 years undergoing TSA or RSA for PGHOA with preoperative FF ≤ 90°. Forty-five TSAs were identified and matched by age and sex to 45 patients undergoing RSA. A subset of 22 TSAs and 24 RSAs with severely limited preoperative FF of ≤ 70° was also analyzed. Range of motion including FF, external rotation and internal rotation, strength, and patient-reported outcomes including visual analog scale pain score, Western Ontario Osteoarthritis of the Shoulder index score, Veterans RAND 12 mental score, American Shoulder and Elbow Surgeons score, and Constant-Murley score were evaluated at a minimum of 2 years postoperative. ResultsNo significant differences were observed in postoperative FF, external rotation, or strength measurements between groups. The limited FF TSA group achieved significantly improved internal rotation compared to the RSA group (L2 vs. L4, P < .002). No significant differences were observed between TSA and RSA in American Shoulder and Elbow Surgeons, visual analog scale, Constant, or Single Assessment Numeric Evaluation scores (P > .05) for both the overall comparison and subset of patients with FF of ≤ 70°. However, patients in the RSA cohort showed a significantly higher return to normal sporting activities than the TSA group. ConclusionPatients aged less than 80 years with PGHOA and limited preoperative FF achieve similar postoperative range of motion and patient-reported outcomes whether treated with TSA or RSA. Therefore, limited preoperative FF does not appear to be a major determinant of outcomes for PGHOA.

Effects of the use of face masks on the vital signs and headache of healthy healthcare workers during the COVID-19 pandemic: A hospital-based cross-sectional study

The study aimed to assess the impact of wearing protective facial masks (PFMs) on various health parameters of hospital staff amidst the COVID-19 pandemic. The aim of this study was to investigate the effects of wearing a face mask on blood oxygen saturation, heart rate, headache, fatigue, and shortness of breath in hospital staff during routine work shifts and COVID-19. In this study, participants from various clinical, administrative, and hospital cleaning professions who had at least one month of work experience were enrolled and their oxygen saturation (SpO2), heart rate (HR), and headache were measured during routine shifts with normal daily activities. The fatigue severity scale (FSS) and the modified Borg dyspnea scale were used to assess the participants. The significance level was set at 0.05. SpO2 and HR were lower at the end of the work shift than at the beginning (93.96 ± 1.57 vs. 95.03 ± 1.7 and 82.1 ± 11.83 vs. 83.93 ± 12.31, respectively). According to the result of the Borg scale, 59.2 % of the participants did not feel short of breath and 34.3 % had “mild-moderate” shortness of breath. The total FSS (21.46 ± 2.31) showed that the participants did not fall into the “fatigued” category. The Kruskal-Wallis test showed no significant difference in Borg score, FSS, HR, and SpO2 participants with different mask types (P > 0.05). The result of the Kruskal-Wallis test also showed no significant difference in Borg score between the occupational groups (P = 0.073). The results showed that the frequency of pre-existing headaches had increased in 18.2 % of the respondents. The findings indicated that wearing PFMs did not have a notable impact on oxygen levels and heart rate during the regular tasks of hospital staff. However, the use of PFMs led to the development of new headaches associated with PFMs or worsened existing headaches.

Mobilenet, inception ResNet and GoogleNet for epilepsy detection using spectrogram images

Epilepsy is considered the most common cerebral disorder, around 1% of the worldwide population suffer from it. Recently, detection of epilepsy has attracted more and more attention. It has become a hastily increasing problem that can worsen their conditions which necessitate a specific and crucial attention where the symptoms can be an impaired awareness or motor symptoms. Besides that, the difficult process of manual inspection of electroencephalography electroencephalogram (EEG). This paper proposes using transfer learning models to detect both normal and epileptic brain activity and auto-classify signals from the brain. The models considered for this study are GoogleNet, MobileNet, and inception residual neural network inception ResNet. These models were associated with seven different classifiers such as discriminant. These classifiers were tested, analyzed and compared with each other. The efficiency of models is comparatively evaluated through result using multiple metrics. We therefore attained an accuracy of 96.53%, a precision of 97.18%, a false positive rate of 2.78% and an F1-score of 96.50%. Finally, comparison of the suggested approach with existing research shows that the performance of epilepsy classification has been markedly enhanced.

Urothelial Piezo1 channels do not alter voiding or afferent nerve sensitivity in the mouse

The mechanosensitive piezo ion channels, Piezo1 and Piezo2, are expressed in tissues of the lower urinary tract, including the urothelium and sensory nerves. Interest in a role of piezo mechanosensitive ion channels in mediating sensory physiology in the lower urinary tract has been highlighted by the recent reports of putative voiding dysfunction in mice lacking Piezo2 channels in the lower extremities and sensory nerves (Marshall et al 2020) and Piezo1/2 in urothelium (Dalghi et al 2022). To investigate the potential role of urothelial Piezo1 channels in mediating normal function in the lower urinary tract, we generated a mouse line in which the Piezo1 gene can be conditionally knocked out in the urothelium (Piezo1UPKcKO mice). We examined spontaneous voiding behavior in male and female Piezo1UPKcKO and control mice during the light and dark phases of the day/night cycle. There were no gender differences in voiding parameters in our study (p=0.659, 3-way ANOVA), thus we did not isolate gender as a variable for further analysis. Piezo1UPKcKO mice (n=9) voided 6 ± 1 times per 24 hours, while the control mice (n=11) voided 7 ± 1 times per 24 hours (p = 0.7281). A clear nocturnal voiding pattern was observed with both Piezo1UPKcKO and control mice exhibiting more frequent voids during the dark cycle, but there were no differences in the number of voids, intermicturition intervals, or void volumes in any cycle between Piezo1UPKcKO and control mice. These results indicate that spontaneous voiding behavior remains fully intact in both male and female Piezo1UPKcKO mice during the light and dark phases of the day/night cycle. Furthermore, in an ex vivo bladder model where we measure afferent nerve output from the bladder during filling cycles, sensory nerve activity in the Piezo1UPKcKO mice was similar to that in bladders from control animals. The maximum frequency of afferent nerve activity during bladder filling reached 295 ± 28 Hz in control mice (n=6) and 336 ± 34 Hz in Piezo1UPKcKO mice (n=6; p = 0.368). Functional Piezo1 activity could be demonstrated in bladders from both Piezo1UPKcKO and control mice, as the pharmacological activator for Piezo1 channels, Yoda1 (5 μM) increased maximum afferent nerve activity during bladder filling by 60 ± 15 Hz in control mice (P = 0.0029) and 33 ± 15 Hz in Piezo1UPKcKO mice (P = 0.0567). In Ca2+ imaging experiments, we found that Yoda1 induced an increase in Ca2+ signaling events in urothelial tissue from control mice. Thus, it appears that urothelial cells express functional Piezo1 ion channels, but activity of these channels is not required for maintaining normal sensory nerve activity and voiding behavior. This work was supported by a grant from the National Institute of Diabetes and Digestive and Kidney Diseases (R01DK125543). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Telomerase Reverse Transcriptase Prevents Doxorubicin-induced Microvascular Endothelial Dysfunction

Introduction &amp; Objective: Doxorubicin (Dox) is a frequently used chemotherapeutic known to induce cardiovascular (CV) complications by impairing microvascular- and cardiac function. We previously submitted an abstract showing that Dox-induced microvascular dysfunction preceded Dox-induced cardiac dysfunction and thus microvascular dysfunction might contribute to the damage of the heart itself.&gt;Microvascular function specifically relies upon the adequate release of the vasodilator nitric oxide (NO). Our previous work showed that Telomerase Reverse Transcriptase (TERT), the catalytic subunit of telomerase, is necessary for physiological release of NO to mediate vasodilation. NO suppresses reactive oxygen species (ROS) levels. While Dox correlates with increased ROS production and suppressed TERT activity, attenuated TERT activity may explain the elevated levels of ROS after Dox exposure. The objective of this study was to determine whether TERT transcriptional activation is suffcient to protect against Dox-induced microvascular endothelial- and cardiac dysfunction. We utilized cycloastragenol (CAG) as transcriptional activator. Hypothesis: We hypothesized that TERT transcriptional activation is suffcient to prevent or attenuate Dox-induced endothelial dysfunction. Methods: WT or TERT loss-of-function rats on a Sprague Dawley background were assigned to untreated control-, CAG-, Dox and CAG+Dox groups. Animals were ~14 weeks of age to start the six-week protocol. Dox and CAG+Dox animals received one weekly IP Dox-injection (3x 4mg/kg*BW). CAG administer via diet with 50-60mg of CAG/day*BW. Microvascular function was assessed six-weeks after the first dose of Dox via videomicroscopy. Vasodilator responses to flow (flow-mediated dilation; FMD) and mediators of dilation (NO, H2O2) via fluorescent probes were evaluated. Cardiac function was evaluated using echocardiography. Human microvessels were treated either with 100nM Dox or 1μM CAG or a combination of both. Results: Dox treatment resulted in reduction in FMD in both WT and TERT mutant animals. Smooth-muscle dependent vasodilation was not impaired indicating endothelial impairment. CAG prevented Dox-induced endothelial dysfunction in WT but not TERT mutant rats. AGS499 another activator of TERT showed similar results suggestion a TERT mediated phenotype. Dox-treated WT animals exhibited an increase in H2O2 but not NO production. This phenotype was opposite in CAG+Dox WT animals. TERT mutant animals showed an increase in H2O2 but not NO production even without Dox. To assess which vasodilator mediates dilation to flow, we used L-NAME and PEG-Catalase to block NO- and H2O2, respectively. In CAG+Dox WT animals, L-NAME blocked the vasodilatory response to flow, while PEG-Cat blocked the vasodilatory response non-significantly. Similarly, we observed this protective effect of TERT in the human microcirculation. Human adipose microvessels treated over-night with Dox showed no vasodilatory response to flow while CAG+Dox treated vessels dilated normally similar to untreated control vessels. Smooth muscle function was not affected in neither group. Conclusion: We show evidence that TERT prevents Dox-induced endothelial dysfunction in an in vivo model and using human tissue. We highlight the specificity to TERT by a) using a genetic model lacking normal TERT activity and b) showing similar results using two different compounds which have been shown to activate TERT/promote TERT transcriptional activation. Ultimately, the present data shows that CAG is a potential therapeutic to counteract the detrimental effects of Dox treatment in the CV system via TERT signaling. RO1 HL133029-01. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Clinical and Electrophysiological Outcomes of Left Bundle Area Pacing Compared to Biventricular Pacing: An Updated Meta-analysis.

Left bundle branch area pacing (LBBAP) is a novel pacing strategy that uses the conduction system distal to the left bundle branch block level for direct activation of the left bundle and right ventricular myocardium. Our meta-analysis compared the structural, electrophysiological, clinical, and procedural outcomes of LBBAP and biventricular pacing (BVP). The meta-analysis included two randomized controlled trials and showed significant reductions in the left ventricular (LV) systolic and diastolic volumes with LBBAP compared to BVP, together with statistically significant reductions in the QRS duration, New York Heart Association (NYHA) functional class, and heart failure (HF) hospitalizations. The fluoroscopic time was also significantly shorter in the LBBAP group. However, no significant change in the LV ejection fraction was noted. Procedural complications were slightly higher in the LBBAP group, albeit not to a statistically significant degree. Our findings suggest that LBBAP may be a superior alternative to standard BVP in improving the structural, electrophysiological, and clinical components of cardiomyopathy, including the NYHA class and HF hospitalizations. LBBAP is a more physiological pacing strategy that results in normal ventricular activation and may be a viable alternative to BVP for cardiac synchronization therapy.

Tibial Bone Co-Morbidities Following Volumetric Muscle Loss Injury and Physical Inactivity

Volumetric muscle loss (VML) injuries are a traumatic loss of muscle, limiting regenerative potential and resulting in chronic loss of function. In isolation the bone adjacent to the VML injury is often overlooked, but known association between the tissues are important to long-term health and function. Recent work suggests decrements in both bones and muscles of VML-injured limbs, as well as a distinct relationship between VML and bone health. The clinically injured VML population is expected to undergo considerable periods of physical inactivity or a long-term sedentary lifestyle, and thus decreased loading, after VML. Our objective was to investigate the concomitant impact of VML on the adjacent bone, with and without the restriction of physical activity (reduced ~50% of daily ambulation). We hypothesized that with restriction of physical activity, the tibia adjacent to the VML would have functional impairments greater than those with normal physical activity (daily ambulation &gt;1km). Adult male C57BI/6J mice (n=41) underwent unilateral VML to the posterior hindlimb compartment or served as uninjured age-matched controls, then were randomized to standard or restricted activity cages for 8-wks. Terminally (age 20-wks), mice underwent in vivo muscle function testing. Adjacent tibia were assessed for strength, mid‐diaphysis cortical geometry, and intrinsic material properties, and the metaphyseal trabecular bone structure was evaluated by microcomputed tomography and three‐point bending. A subset of tibias was saved for histologic staining (H&amp;E, TRAP). Data were evaluated by two-way ANOVA. There were no absolute or normalized functional muscle deficits following 8-wks of inactivity. That said, there were significant VML-functional deficits (~42% of uninjured) that are not exacerbated by inactivity (p&lt;0.001). Cortical geometric changes in the bone were primarily a result of physical inactivity, with thickness and cross-sectional moment of inertia both diminished independent of injury (p≤0.018). However, there were no differences in cortical bone volume, diameter, or cross-sectional area (p≥0.056). Trabecular bone mineral density was lower in all VML-injured tibias compared to uninjured (p=0.003). While there was no difference across groups for trabecular spacing (p&gt;0.397), there was a reduction in bone mineral density across all VML-injured, compared to uninjured tibias (p=0.003). The functional capacity of the tibia to resist fracture (i.e., ultimate load during 3‐point bending) was ~21% lower with inactivity (p=0.018), while there was only a trend for VML injury to impact resistance to fracture. Stiffness was calculated during the onset to ultimate load and ~15% less in the VML injured and inactivity VML tibias (p=0.016). Tibia of VML injured and inactive groups appear to have greater lipid accumulation compared to uninjured tibias. While discordant with muscle function, physical activity restriction with and without VML injury impairs adjacent tibia. Inactivity alone had the greatest impact on the cortical bone properties, while VML with and without physical inactivity impacted trabecular tibia properties. This study demonstrates the impact of VML with and without physical inactivity on the tibia, furthering the complexity of traumatic injury on the musculoskeletal system. W81XWH‐20‐10885 (JAC &amp; SMG); S10OD025177. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Response mechanisms of resistance in L-form bacteria to different target antibiotics: Implications from oxidative stress to metabolism

Due to the specific action on bacterial cell wall, β-lactam antibiotics have gained widespread usage as they exhibit a high degree of specificity in targeting bacteria, but causing minimal toxicity to host cells. Under antibiotic pressure, bacteria may opt to shed their cell walls and transform into L-form state as a means to evade the antibiotic effects. In this study, we explored and identified diverse optimal conditions for both Gram-negative bacteria (E. coli DH5α (CTX)) and Gram-positive bacteria (B. subtilis ATCC6633), which were induced to L-form bacteria using lysozyme (0.5 ppm) and meropenem (64 ppm). Notably, when bacteria transformed into L-form state, both bacterial strains showed varying degrees of increased resistance to antibiotics polymyxin E, meropenem, rifampicin, and tetracycline. E. coli DH5α (CTX) exhibited the most significant enhancement in resistance to tetracycline, with a 128-fold increase, while B. subtilis ATCC6633 showed a 32-fold increase in resistance to tetracycline and polymyxin E. Furthermore, L-form bacteria maintained their normal metabolic activity, combined with enhanced oxidative stress, served as an adaptive strategy promoting the sustained survival of L-form bacteria. This study provided a theoretical basis for comprehending antibiotic resistance mechanisms, developing innovative treatment strategies, and confronting global antibiotic resistance challenges.

Approaching Electroencephalographic Pathological Spikes in Terms of Solitons

A delicate balance between dissipative and nonlinear forces allows traveling waves termed solitons to preserve their shape and energy for long distances without steepening and flattening out. Solitons are so widespread that they can generate both destructive waves on oceans’ surfaces and noise-free message propagation in silica optic fibers. They are naturally observed or artificially produced in countless physical systems at very different coarse-grained scales, from solar winds to Bose–Einstein condensates. We hypothesize that some of the electric oscillations detectable by scalp electroencephalography (EEG) could be assessed in terms of solitons. A nervous spike must fulfill strict mathematical and physical requirements to be termed a soliton. They include the proper physical parameters like wave height, horizontal distance and unchanging shape; the appropriate nonlinear wave equations’ solutions and the correct superposition between sinusoidal and non-sinusoidal waves. After a thorough analytical comparison with the EEG traces available in the literature, we argue that solitons bear striking similarities with the electric activity recorded from medical conditions like epilepsies and encephalopathies. Emerging from the noisy background of the normal electric activity, high-amplitude, low-frequency EEG soliton-like pathological waves with relatively uniform morphology and duration can be observed, characterized by repeated, stereotyped patterns propagating on the hemispheric surface of the brain over relatively large distances. Apart from the implications for the study of cognitive activities in the healthy brain, the theoretical possibility to treat pathological brain oscillations in terms of solitons has powerful operational implications, suggesting new therapeutical options to counteract their detrimental effects.

Access to and quality of elective care: a prospective cohort study using hernia surgery as a tracer condition in 83 countries

Timely and safe elective health care facilitates return to normal activities for patients and prevents emergency admissions. Surgery is a cornerstone of elective care and relies on complex pathways. This study aimed to take a whole-system approach to evaluating access to and quality of elective health care globally, using inguinal hernia as a tracer condition. This was a prospective, international, cohort study conducted between Jan 30 and May 21, 2023, in which any hospital performing inguinal hernia repairs was eligible to take part. Consecutive patients of any age undergoing primary inguinal hernia repair were included. A measurement set mapped to the attributes of WHO's Health System Building Blocks was defined to evaluate access (emergency surgery rates, bowel resection rates, and waiting times) and quality (mesh use, day-case rates, and postoperative complications). These were compared across World Bank income groups (high-income, upper-middle-income, lower-middle-income, and low-income countries), adjusted for hospital and country. Factors associated with postoperative complications were explored with a three-level multilevel logistic regression model. 18 058 patients from 640 hospitals in 83 countries were included, of whom 1287 (7·1%) underwent emergency surgery. Emergency surgery rates increased from high-income to low-income countries (6·8%, 9·7%, 11·4%, 14·2%), accompanied by an increase in bowel resection rates (1·2%, 1·4%, 2·3%, 4·2%). Overall waiting times for elective surgery were similar around the world (median 8·0 months from symptoms to surgery), largely because of delays between symptom onset and diagnosis rather than waiting for treatment. In 14 768 elective operations in adults, mesh use decreased from high-income to low-income countries (97·6%, 94·3%, 80·6%, 61·0%). In patients eligible for day-case surgery (n=12 658), day-case rates were low and variable (50·0%, 38·0%, 42·1%, 44·5%). Complications occurred in 2415 (13·4%) of 18 018 patients and were more common after emergency surgery (adjusted odds ratio 2·06, 95% CI 1·72-2·46) and bowel resection (1·85, 1·31-2·63), and less common after day-case surgery (0·39, 0·34-0·44). This study demonstrates that elective health care is essential to preventing over-reliance on emergency systems. We identified actionable targets for system strengthening: clear referral pathways and increasing mesh repair in lower-income settings, and boosting day-case surgery in all income settings. These measures might strengthen non-surgical pathways too, reducing the burden on society and health services. NIHR Global Health Research Unit on Global Surgery and Portuguese Hernia and Abdominal Wall Society (Sociedade Portuguesa de Hernia e Parede Abdominal).

Comparative study of open onlay mesh repair versus laparoscopic intraperitoneal dual mesh repair for ventral hernia

Background: Ventral abdominal wall hernia surgery is a common procedure in the armamentarium of surgeons. The most common forms of these surgical procedures in adults are the repair of incisional hernias and surgery for paraumbilical hernias. Aims and Objectives: Open onlay mesh repair versus laparoscopic intraperitoneal dual mesh repair (intraperitoneal onlay mesh[IPOM]) for ventral hernia compared to the duration of surgery, post-operative pain, postoperative complications, post-operative hospital stay, return to normal activity, recurrence, and cosmesis. Materials and Methods: The prospective non-randomized study was done in the Maharani Laxmi Bai Medical College, Jhansi, between January 2021 and June 2022 including 100 patients was applied for treatment of ventral hernia repair. Fifty patients were subjected to Group A (open onlay mesh repair) and 50 patients were subjected to Group B (laparoscopic intraperitoneal dual mesh repair). Results: The mean surgery durations were significantly lower in laparoscopic repair when compared to open repair (P&lt;0.001). Themean post-operative stay in the hospital was shorter for the laparoscopic group than for the open hernia group (10.28±2.100 vs. 8.02±1.378 days; P≤0.001). Return to activity or normal daily work is significantly lower in the laparoscopic group as compared to open repair of hernia (5.12±0.659 vs. 2.94±0.550 days; P&lt;0.001). There were fewer post-operative complications with laparoscopy. Conclusion: Laparoscopic intraperitoneal dual mesh repair (IPOM) for ventral hernia in our experience was safe and resulted in fewer complications, shorter hospital stays, and better cosmesis results. Hence, it should be considered the better choice for ventral hernia repair.

Effect of nano-silver coated catheter combined with comprehensive care on postoperative infection and rehabilitation in patients after coronary artery bypass grafting (CABG)

Coronary artery bypass grafting (CABG) is an effective treatment method for coronary atherosclerosis, aiming to improve patients’ quality of life and facilitate their return to normal activities after surgery. This study examines the effects of comprehensive nursing intervention and application of nano-silver coated catheter on postoperative infection and rehabilitation among patients who have undergone coronary artery bypass grafting. The study included 72 patients, randomly assigned into an intervention group and a control group, with 36 patients in each. The control group received standard care, while the intervention group received comprehensive care along with postoperative application of nano-silver coated catheter. The study compared various factors, including the Hamilton Anxiety Scale (HAMA) score, quality of life score, postoperative recovery, postoperative infection, satisfaction, and adverse reactions between the two groups. The intervention group exhibited better scores in HAMD, HAMA, PSQI and quality of survival score when compared to the control group. Moreover, the intervention group experienced an earlier time to first bowel movement and first defecation after surgery. The intervention group also demonstrated lower rates of urinary protein detection, pathogen detection, and serum inflammatory factor levels compared to the control group. Additionally, the overall incidence of complications in the control group was higher at 27.8% compared to 8.3% in the intervention group. Furthermore, the satisfaction level in the intervention group was significantly higher at 97.2%, in contrast to 83.3% in the control group. Overall, comprehensive care combined with the postoperative application of a nano-silver coated catheter can effectively address patients’ emotional needs and accelerate recovery. It also reduces the incidence of infection, ultimately enhancing the quality of life and satisfaction levels among patients. This study provides a good nursing plan for the postoperative recovery of CABG patients, which is conducive to promoting the speed of postoperative recovery and improving the quality of life of patients.