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Abstract Nature has developed numerous design motifs by arranging modest materials into complex architectures. The damage-tolerant, double-bouligand architecture found in the coelacanth fish scale is comprised of collagen fibrils helically arranged in a bilayer manner. Here, we exploit the toughening mechanisms of double-bouligand designs by engineering architected concrete using a large-scale two-component robotic additive manufacturing process. The process enables intricate fabrication of the architected concrete components at large-scale. The double-bouligand designs are benchmarked against bouligand and conventional rectilinear counterparts and monolithic casts. In contrast to cast concrete, double-bouligand design demonstrates a non-brittle response and a rising R-curve, due to a hypothesized bilayer crack shielding mechanism. In addition, interlocking behind and crack deflection ahead of the crack tip in bilayer double-bouligand architected concrete elicits a 63% increase in fracture toughness compared to cast counterparts.

Abstract Background Neoadjuvant chemotherapy (NAC) with radical cystectomy (RC) is the preferred first-line treatment for localized muscle-invasive bladder cancer (MIBC). In recent years, octogenarians have been undergoing RC uneventfully, but studies showed older adults receive NAC less often. We studied the utilization and effect of RC with or without NAC in octogenarians and compared survival outcomes between responders and non-responders. Methods In our retrospective study using the National Cancer Database (NCDB), we identified octogenarians with MIBC and urothelial histology who underwent RC with or without NAC between 2004 and 2018. The NAC cohort included patients who underwent RC with NAC, and the non-NAC cohort included those with or without adjuvant chemotherapy. The NAC cohort was subcategorized into responders and non-responders based on surgical pathology. Patients with comorbidity index > 1 were not included, thereby excluding patients with possible renal impairment. After propensity-matching, we compared the overall survival (OS) between NAC and non-NAC cohorts and responders and non-responders. Results 33924 patients underwent RC, and 3056 octogenarians met our selection. Among them, 396 received NAC, and 2660 did not receive NAC. Among those who received NAC, 112(28.3%) experienced downstaging, and 223(56.4%) exhibited upstaging or no change (p

Executing dermatosurgical procedures can be a challenging task in the pediatric population due to their hyperreactive and hypermobile behavioral responses to discomfort posed by these procedures. Thus, most of the dermatological procedures are to be performed in minimal or moderate (conscious) sedation. The objective of this review is to compare the different sedative drugs used in pediatric patients to achieve cooperation during a standard dermatological procedure. Other traditional methods of ensuring compliance by feeding and distracting the patient will be discussed briefly to help or add on to current knowledge in sedation of children during dermatosurgery. While sedatives can be effective in managing anxiety and pain in pediatric dermatosurgery, their use should be carefully considered given the potential adverse effects and risks involved in indiscriminate use and the decision to use sedatives should be individually tailored, considering factors such as the child’s age, medical history, and the nature of procedure being performed.

Abstract Whether the Main Himalayan Thrust can host a single surface-rupturing event in the Himalaya with a rupture length of > 700 km remains controversial. Previous paleoseismological studies in the Darjeeling-Sikkim Himalaya (DSH) suggested medieval surface-rupturing earthquakes, correlating them with the eleventh–thirteenth century events from Nepal and Bhutan and extending the coseismic rupture length > 700 km. Conversely, there is no rupture evidence of the 1714 Bhutan and 1934 Bihar–Nepal earthquakes in the DSH, resulting in a discrepancy in the rupture extent of the great earthquakes. Consequently, we conducted a paleoseismological investigation across a ~ 10 m-high fault scarp on the Himalayan Frontal Thrust at Chenga village, DSH, revealing a surface-faulting event during 1313–395 BCE. We suggest that the DSH is a 150 km-long independent segment bounded by a transverse ridge and fault and has a recurrence interval of ~ 949–1963 years, which is significantly larger than Nepal (~ 700–900 years) and Bhutan Himalaya (~ 339–761 years).

Abstract It has proved challenging to quantitatively relate the proteome to the transcriptome on a per-gene basis. Recent advances in data analytics have enabled a biologically meaningful modularization of the bacterial transcriptome. We thus investigate whether matched datasets of transcriptomes and proteomes from bacteria under diverse conditions can be modularized in the same way to reveal novel relationships between their compositions. We find that; (1) the modules of the proteome and the transcriptome are comprised of a similar list of gene products, (2) the modules in the proteome often represent combinations of modules from the transcriptome, (3) known transcriptional and post-translational regulation is reflected in differences between two sets of modules, allowing for knowledge-mapping when interpreting module functions, and (4) through statistical modeling, absolute proteome allocation can be inferred from the transcriptome alone. Quantitative and knowledge-based relationships can thus be found at the genome-scale between the proteome and transcriptome in bacteria.

Medicinal plants are considered as one of the main sources of biologically active molecules for various diseases, in addition to their traditional applications. Worldwide, interest on medicinal plants having nutritional value and used as food, is increasing day by day as these can prevent or delay the occurrence of chronic diseases. Further exploration of such plants require a thorough updated information on that plant species to ascertain what is known and what can be done. Medicago polymorpha, also known as Medicago denticulata is an annual dicotyledonous weed of family Fabaceae, which is found as a weed in agricultural lands, road sides and other disturbed areas. Herein, we have compiled the information related to traditional uses, chemical constituents, pharmacological activities and metal nanoparticles of M. polymorpha available in Scopus database, which will be a ready reference for the researchers working on this plant to further explore it. The plant contains a wide range of secondary metabolites and has been scientifically studied for its analgesic, antioxidant, hepatoprotective, antimicrobial, cytotoxic, anthelmintic, antiamnesic, antidiarrhoeal, antifungal, antidiabetic, and immunomodulatory activities.

This paper reviews the literature on zombie firms to provide a holistic view by delineating their formation, impact, widespread nature, prevention and policy implications. This paper uses a systematic literature review methodology, in which 76 papers published in journals ranked on the Australian Business Deans Council (ABDC) 2022 list were reviewed. The study period was from 2000 to 2022. Among the main findings, the widespread problems of zombie firms were evident. The authors found that consistent support, either in the form of government grants or a weak financial framework, was responsible for their formation. The suboptimal performance of factors of production, depressed job creation, low innovation and overall negative impact on economic activity are the consequences of zombification. This can be controlled by ensuring better bankruptcy codes, focused on government assistance, technology use and better due diligence by banks. This review serves as a reference point for future researchers as a cohesive and holistic study presenting a full picture of the problem, so that the proposed solutions are robust and tenable. This review is among the initial attempts to comprehensively study published work on zombie firms in terms of analyzing their region-specific nature, with an emphasis on definition, causes, impact and prevention.

Abstract Background When job demand exceeds job resources, burnout occurs. Burnout in healthcare workers extends beyond negatively affecting their functioning and physical and mental health; it also has been associated with poor medical outcomes for patients. Data-driven technology holds promise for the prediction of occupational burnout before it occurs. Early warning signs of burnout would facilitate preemptive institutional responses for preventing individual, organizational, and public health consequences of occupational burnout. This protocol describes the design and methodology for the decentralized Burnout PRedictiOn Using Wearable aNd ArtIficial IntelligEnce (BROWNIE) Study. This study aims to develop predictive models of occupational burnout and estimate burnout-associated costs using consumer-grade wearable smartwatches and systems-level data. Methods A total of 360 registered nurses (RNs) will be recruited in 3 cohorts. These cohorts will serve as training, testing, and validation datasets for developing predictive models. Subjects will consent to one year of participation, including the daily use of a commodity smartwatch that collects heart rate, step count, and sleep data. Subjects will also complete online baseline and quarterly surveys assessing psychological, workplace, and sociodemographic factors. Routine administrative systems-level data on nursing care outcomes will be abstracted weekly. Discussion The BROWNIE study was designed to be decentralized and asynchronous to minimize any additional burden on RNs and to ensure that night shift RNs would have equal accessibility to study resources and procedures. The protocol employs novel engagement strategies with participants to maintain compliance and reduce attrition to address the historical challenges of research using wearable devices. Trial Registration NCT05481138.

Introduction: Many foetal and maternal complications, such as polyhydramnios, macrosomia, birth injuries, and operative interference, are linked with Gestational Diabetes Mellitus (GDM). Among these, macrosomia is particularly significant, as it increases the risk of shoulder dystocia, brachial plexus injury, birth asphyxia, and maternal complications, including emergency Lower Segment Caesarean Section (LSCS), Postpartum Haemorrhage (PPH), and perineal trauma. Therefore, one of the most essential perinatal goals in GDM is to predict macrosomia by estimating birth weight, thereby preventing adverse maternal and foetal outcomes. Aim: To evaluate whether there is a correlation between the cross-sectional area of the Umbilical Cord (UCA) and the Neonatal Birth Weight (NBW) in pregnant women with GDM. Materials and Methods: A prospective cohort study was conducted in the Departments of Radiology and Obstetrics Bangalore Medical College, Bengaluru, Karnataka, India. A total of 100 pregnant women (50 with GDM and 50 without GDM) were recruited from July 2021 to July 2022. Ultrasound examination (USG) was performed on pregnant women after 36 weeks of gestation. The UCA was measured in a free-floating loop, and the NBW was measured using a digital scale. The correlation coefficient was calculated to determine the degree of correlation between UCA and NBW. Results: The mean age of the subjects was 26.5±3.9 years. The frequency of macrosomia was higher in the GDM group (8%) compared to the control group (4%). A strong positive correlation was observed between UCA and NBW in both diabetics (r=0.819) and control groups (r=0.736). Conclusion: A strong positive correlation exists between UCA and NBW in women with GDM. Therefore, it should be estimated during routine antenatal USG for the prediction of birth weight in such women.

Introduction: Intrathecal adjuvants can be added to extend the duration of analgesia. To achieve this, several adjuvants, such as the combination of dexmedetomidine with bupivacaine versus fentanyl with bupivacaine, have been used with local anaesthesia during lower limb surgeries. Aim: To compare the combination of dexmedetomidine versus fentanyl with bupivacaine administered intrathecally for the onset and duration of sensory and motor block, as well as their side-effects and the prolongation of postoperative analgesia in lower limb surgeries. Materials and Methods: A randomised clinical study was conducted on 120 American Society of Anaesthesiologists (ASA) grade I or II patients, aged between 18 and 65 years, who were admitted to the Department of Orthopaedics and General Surgery, Aarupadai Veedu Medical College and Hospital, Puducherry, India for lower limb surgeries under spinal anaesthesia. The patients were randomly assigned to two groups using a computer-generated technique. Group BD received 0.5% bupivacaine (2.5 mL)+10 mcg dexmedetomidine (0.5 mL), while Group BF received 0.5% bupivacaine (2.5 mL)+25 mcg fentanyl (0.5 mL). The onset and duration of sensory and motor blockade, haemodynamic parameters, sedation, and side-effects of the drugs were analysed. Statistical analysis was performed using Statistical Package for Social Sciences (SPSS) version 2.0 after collecting all the data. Results: There were no statistically significant differences in the subjects’ demographics or duration of surgery. However, the duration of sensory block and motor block was significantly prolonged in Group BD compared to Group BF, with values of 720±32 and 640±32, respectively. The mean Heart Rates (HR) differed significantly between of the two groups (p-value=0.03). There was no significant difference in sedation scores between the two groups. Group BD showed a higher incidence of bradycardia (n=35) and hypertension (n=32). Conclusion: The combination of dexmedetomidine with bupivacaine, when used intrathecally for lower limb surgeries, demonstrated superior effectiveness in terms of prolonging sensory and motor block duration and providing extended postoperative analgesia, compared to the combination of bupivacaine and fentanyl. However, it is important to note that patients receiving the dexmedetomidine-bupivacaine combination had a higher incidence of bradycardia and hypertension. Therefore, careful monitoring and management of haemodynamic parameters are necessary when using this combination.

Rural adolescents often overlook the significance of early career preparation, thus hampering their school-to-college transition. Regardless of overall growth, Karnataka, a state in India, confronts challenges in achieving a high transition rate, and a paucity of career maturity among rural youth exists. Recognizing a dire need to explore effective interventions for promoting career maturity, the study designed and demonstrated training among 76 Tenth-grade students from rural government schools. Qualitative questionnaires and focus group discussions elucidate the perceived impact of training on career maturity and identify the influence of career barriers and supports. Thematic and content analysis revealed an improved career outlook among participants by boosting career concern, curiosity, confidence, and control while alleviating career anxieties. Nevertheless, the findings uncovered persistent gender disparities. Exploration of models’ benefits and potential improvements informed the design of comprehensive training that facilitates early rural career development. The implications extend to policy, practice, and further research.

Nowadays, nanotechnology is extensively employed in the medical profession. In this study, we used the aqueous extract of the bark of Mitragyna parvifolia to synthesize silver nanoparticles (AgNPs) by microwave-assisted green synthesis. The synthesis of AgNPs was confirmed by visual color change to brown color and characteristic surface plasmon resonance peak at 432 nm. The hydrodynamic diameter of the AgNPs was 171.81 nm having a zeta potential of −24.14 mV; Fourier Transmission Infrared Spectroscopy confirmed the presence of different functional groups on the NP surface; Scanning Electron Microscope and High-Resolution Transmission Electron Microscopy indicated predominantly circular shape of nanoparticle; Selected Area Electron Diffraction and X-ray Diffraction analyses determined the crystalline structure of AgNPs. Energy-Dispersive X-ray indicated the elemental composition and formation of AgNPs. The AgNPs were screened at different concentrations for antioxidant activity, antimicrobial, and anticancer potential in breast cancer cells (MCF-7 and MDA-MB-231). The AgNPs exhibited remarkable antioxidant, antimicrobial, and anticancer activities. The sedative and antinociceptive activities were also tested on Swiss albino mice, which showed mild sedative and very potent antinociceptive activity. However, detailed mechanistic studies are warranted in the future for clinical application of the AgNPs as a biologically active agent as well as a carrier for drug delivery.

The Phyllanthus emblica L. highly medicinal value used for jaundice, anticancer, antioxidant, antiviral, antimicrobial etc., activities so for that current research explored the application of nanotechnology in developing anticancer strategies through the synthesis of silver nanoparticles (AgNPs) using natural extracts from leaves. Various characterization techniques were employed to assess the anticancer properties against the human MCF-7 Breast Cancer Cell Line. This study in UV‒visible spectroscopy AgNPs detected at 436 nm, FT-IR analysis indicated the presence of specific functional groups with high peak intensity at 3105 cm−1. In SEM measurements revealed synthesized AgNPs at 25.4 nm, TEM exposed perfectly round particles with a lattice spacing of 0.295 nm, and XRD analysis revealed reflections at (111), (200), (220), and (310) with corresponding 2θ values of 39.1°, 46.1°, 68.7°, and 79.2°, respectively, along with the observation of (311). EDX analysis confirmed the composite nature of quartz with AgNPs at a 50:50 ratio. Atomic force microscopy (AFM) images of AgNPs 30 nm in size. Furthermore, breast cancer one of the major disease, targeted application of our study focused anticancer activity against MCF-7 breast cancer cell line, observed that plant extract exhibits 92% cancer cell death at 500 µg/ml, showed potential anticancer activity against breast cancer cells. In flowcytometry cancer cells phase distribution was observed at AgNPs (100 to 200 µg/ml). Prolonged exposure to the extract led to cell death and arrested the apoptotic cell death cycle after 24 hours. Research has also evaluated the potential of nanoparticles to inhibit cancer progression, revealing promising prospects for enhancing anticancer therapies. During the treatment against cancer cells observed cell deaths, concluded that green, nanotechnology potential tool for modern world.

ABSTRACTIn the intricate tapestry of the exploration stage (14–25 years), students grapple with the challenges of self-discovery, career ambiguity, and the quest for purpose. Over the last few decades, a vast body of research evidence on the utility of ‘Social Cognitive Career Theory’ (SCCT) and ‘Career Maturity Inventory’ (CMI) in designing career interventions has emerged. This framework and instrument can potentially assist students in navigating the critical exploration stage. As espoused by Arksey and O’Malley, our scoping review outlines the utility of SCCT and CMI in designing early career intervention. In addition, we identify and document the facilitators and barriers to utilizing SCCT and CMI. It presents the nuanced application of the framework and the instrument in rural and urban settings. The findings affirm the robust utility of SCCT and CMI, thereby informing academicians and practitioners in designing and implementing effective early career interventions.

Abstract BackgroundArtificial intelligence (AI) chatbots have the potential to assist individuals with chronic health conditions by providing tailored information, monitoring symptoms, and offering mental health support. Despite their potential benefits, research on public attitudes toward health care chatbots is still limited. To effectively support individuals with long-term health conditions like long COVID (or post–COVID-19 condition), it is crucial to understand their perspectives and preferences regarding the use of AI chatbots. ObjectiveThis study has two main objectives: (1) provide insights into AI chatbot acceptance among people with chronic health conditions, particularly adults older than 55 years and (2) explore the perceptions of using AI chatbots for health self-management and long COVID support. MethodsA web-based survey study was conducted between January and March 2023, specifically targeting individuals with diabetes and other chronic conditions. This particular population was chosen due to their potential awareness and ability to self-manage their condition. The survey aimed to capture data at multiple intervals, taking into consideration the public launch of ChatGPT, which could have potentially impacted public opinions during the project timeline. The survey received 1310 clicks and garnered 900 responses, resulting in a total of 888 usable data points. ResultsAlthough past experience with chatbots (PP ConclusionsAI hesitancy is not uniform across all health domains and user groups. Despite persistent AI hesitancy, there are promising opportunities for chatbots to offer support for chronic conditions in areas of lifestyle enhancement and mental well-being, potentially through voice-based user interfaces.

Abstract Stroke is not only associated with muscle weakness, but also associated with reduced muscle fatigue resistance and reduced desaturation during exercise that may be caused by a reduced oxidative capacity and/or microvasculature. Therefore, the objective of the present study was to determine the effects of stroke on muscle mass, fiber size and shape, capillarization and oxidative capacity of the rat m. extensor carpi radialis (ECR) and m. flexor carpi ulnaris (FCU) after a photothrombotic stroke in the forelimb region of the primary sensorimotor cortex. The main observation of the present study was that 4 weeks after induction of stroke there were no significant changes in muscle fiber size and shape. Although there was no significant capillary rarefaction, there was some evidence for remodeling of the capillary bed as reflected by a reduced heterogeneity of capillary spacing (p = 0.006) that may result in improved muscle oxygenation. In the ECR, but not in the FCU, this was accompanied by reduction in muscle fiber oxidative capacity as reflected by reduced optical density of sections stained for succinate dehydrogenase (p = 0.013). The reduced oxidative capacity and absence of significant capillary rarefaction resulted in a capillary to fiber ratio per unit of oxidative capacity that was higher after stroke in the ECR (p = 0.01), but not in the FCU. This suggests that at least during the early stages, stroke is not necessarily accompanied by muscle fiber atrophy, and that stroke‐induced reductions in oxidative capacity resulting in relative excess of capillarization are muscle specific.

ABSTRACT Fast growth phenotypes are achieved through optimal transcriptomic allocation, in which cells must balance tradeoffs in resource allocation between diverse functions. One such balance between stress readiness and unbridled growth in E. coli has been termed the fear versus greed (f/g) tradeoff. Two specific RNA polymerase (RNAP) mutations observed in adaptation to fast growth have been previously shown to affect the f/g tradeoff, suggesting that genetic adaptations may be primed to control f/g resource allocation. Here, we conduct a greatly expanded study of the genetic control of the f/g tradeoff across diverse conditions. We introduced 12 RNA polymerase (RNAP) mutations commonly acquired during adaptive laboratory evolution (ALE) and obtained expression profiles of each. We found that these single RNAP mutation strains resulted in large shifts in the f/g tradeoff primarily in the RpoS regulon and ribosomal genes, likely through modifying RNAP-DNA interactions. Two of these mutations additionally caused condition-specific transcriptional adaptations. While this tradeoff was previously characterized by the RpoS regulon and ribosomal expression, we find that the GAD regulon plays an important role in stress readiness and ppGpp in translation activity, expanding the scope of the tradeoff. A phylogenetic analysis found the greed-related genes of the tradeoff present in numerous bacterial species. The results suggest that the f/g tradeoff represents a general principle of transcriptome allocation in bacteria where small genetic changes can result in large phenotypic adaptations to growth conditions.IMPORTANCETo increase growth, E. coli must raise ribosomal content at the expense of non-growth functions. Previous studies have linked RNAP mutations to this transcriptional shift and increased growth but were focused on only two mutations found in the protein’s central region. RNAP mutations, however, commonly occur over a large structural range. To explore RNAP mutations’ impact, we have introduced 12 RNAP mutations found in laboratory evolution experiments and obtained expression profiles of each. The mutations nearly universally increased growth rates by adjusting said tradeoff away from non-growth functions. In addition to this shift, a few caused condition-specific adaptations. We explored the prevalence of this tradeoff across phylogeny and found it to be a widespread and conserved trend among bacteria.

BackgroundThe occupational burnout epidemic is a growing issue, and in the United States, up to 60% of medical students, residents, physicians, and registered nurses experience symptoms. Wearable technologies may provide an opportunity to predict the onset of burnout and other forms of distress using physiological markers. ObjectiveThis study aims to identify physiological biomarkers of burnout, and establish what gaps are currently present in the use of wearable technologies for burnout prediction among health care professionals (HCPs). MethodsA comprehensive search of several databases was performed on June 7, 2022. No date limits were set for the search. The databases were Ovid: MEDLINE(R), Embase, Healthstar, APA PsycInfo, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Web of Science Core Collection via Clarivate Analytics, Scopus via Elsevier, EBSCOhost: Academic Search Premier, CINAHL with Full Text, and Business Source Premier. Studies observing anxiety, burnout, stress, and depression using a wearable device worn by an HCP were included, with HCP defined as medical students, residents, physicians, and nurses. Bias was assessed using the Newcastle Ottawa Quality Assessment Form for Cohort Studies. ResultsThe initial search yielded 505 papers, from which 10 (1.95%) studies were included in this review. The majority (n=9) used wrist-worn biosensors and described observational cohort studies (n=8), with a low risk of bias. While no physiological measures were reliably associated with burnout or anxiety, step count and time in bed were associated with depressive symptoms, and heart rate and heart rate variability were associated with acute stress. Studies were limited with long-term observations (eg, ≥12 months) and large sample sizes, with limited integration of wearable data with system-level information (eg, acuity) to predict burnout. Reporting standards were also insufficient, particularly in device adherence and sampling frequency used for physiological measurements. ConclusionsWith wearables offering promise for digital health assessments of human functioning, it is possible to see wearables as a frontier for predicting burnout. Future digital health studies exploring the utility of wearable technologies for burnout prediction should address the limitations of data standardization and strategies to improve adherence and inclusivity in study participation.

Background & Aims: Metabolomic and lipidomic analyses provide an opportunity for novel biological insights. Cholangiocarcinoma (CCA) remains a highly lethal cancer with limited response to systemic, targeted, and immunotherapeutic approaches. Using a global metabolomics and lipidomics platform, this study aimed to discover and characterize metabolomic variations and associated pathway derangements in patients with CCA. Methods: Leveraging a biospecimen collection, including samples from patients with digestive diseases and normal controls, global serum metabolomic and lipidomic profiling was performed on 213 patients with CCA and 98 healthy controls. The CCA cohort of patients included representation of intrahepatic, perihilar, and distal CCA tumours. Metabolome-wide association studies utilizing multivariable linear regression were used to perform case–control comparisons, followed by pathway enrichment analysis, CCA subtype analysis, and disease stage analysis. The impact of biliary obstruction was evaluated by repeating analyses in subsets of patients only with normal bilirubin levels. Results: Of the 420 metabolites that discriminated patients with CCA from controls, decreased abundance of cysteine-glutathione disulfide was most closely associated with CCA. Additional conjugated bile acid species were found in increased abundance even in the absence of clinically relevant biliary obstruction denoted by elevated serum bilirubin levels. Pathway enrichment analysis also revealed alterations in caffeine metabolism and mitochondrial redox-associated pathways in the serum of patients with CCA. Conclusions: The presented metabolomic and lipidomic profiling demonstrated multiple alterations in the serum of patients with CCA. These exploratory data highlight novel metabolic pathways in CCA and support future work in therapeutic targeting of these pathways and the development of a precision biomarker panel for diagnosis. Impact and implications: Cholangiocarcinoma (CCA) is a highly lethal hepatobiliary cancer with limited treatment response, highlighting the need for a better understanding of the disease biology. Using a global metabolomics and lipidomics platform, we characterized distinct changes in the serum of 213 patients with CCA compared with healthy controls. The results of this study elucidate novel metabolic pathways in CCA. These findings benefit stakeholders in both the clinical and research realms by providing a foundation for improved disease diagnostics and identifying novel targets for therapeutic design.

This study assessed the accuracy of a smartphone telematics algorithm that classifies car trips as driver or non-driver. Participants’ trips were measured for 4 weeks by Way to Drive, a research telematics application that uses the same data algorithms as leading auto-insurance companies. At the end of each week, participants completed a survey prompting them to review trips within the app and report time and nature of any misclassified trips. Overall accuracy of driver vs. non-driver classification was high (96.5 %, SD = 5.1 %). Sensitivity, the percentage of actual driver trips classified as such, was also high (97.5 %, SD = 4.6 %). Specificity, the percentage of non-driver trips classified as such, was slightly lower and more variable (91.2 %, SD = 14.8 %). The algorithm’s accuracy was generally robust to a variety of phone characteristics, vehicle features, and driving habits.

Background: Military recruits and athletes have high occurrence of stress fractures, with very high incidence among military recruits. Symptomatic stress fractures can be disabling in some people. This study aims at identifying pattern and distribution of such fractures in Nepal Police trainee and assess the risk factors and demographics that may help to develop the local guidelines. Methods: This study analysed 65 police trainees who presented to the orthopaedic Out Patient Department at Nepal Police and Province Police Hospital diagnosed as a case of stress fracture from 29 December, 2020 to 29 December, 2021. Ethical approval was obtained and different variables analysed were age, sex, Body Mass Index, location of fracture, duration of pain, method of treatment, time to heal the fracture and time to pain free mobilisation of patient. Results: There were 65 trainees with 86 sites of fracture at different bones with 50.8% (33) of male population. The majority of fracture was located at tibia (58.1%) followed by pubic rami (33.7%) with potentially debilitating fracture neck of femur seen in 4.6% subjects. Mean duration of pain was 20.7±14.2 days with mean time for pain free mobilisation 42.2±17.7 days after presentation. 96.5% of those recovered with conservative treatment (activity restriction or cast). Conclusions: The location of stress fracture depends upon the type of training or activities. Modification of activities in early phase of training with early visit for medical care in case of trainees with increasing pain may decrease morbidities and complications requiring operative treatment. Keywords: Nepal Police; stress fracture; trainees.

Summary: Electrical stimulation (ESTIM) has shown to be an effective symptomatic treatment to treat pain associated with peripheral nerve damage. However, the neuroprotective mechanism of ESTIM on peripheral neuropathies is still unknown. In this study, we identified that ESTIM has the ability to enhance mitochondrial trafficking as a neuroprotective mechanism against chemotherapy-induced peripheral neuropathies (CIPNs). CIPN is a debilitating and painful sequalae of anti-cancer chemotherapy treatment which results in degeneration of peripheral nerves. Mitochondrial dynamics were analyzed within axons in response to two different antineoplastic mechanisms by chemotherapy drug treatments paclitaxel and oxaliplatin in vitro. Mitochondrial trafficking response to chemotherapy drug treatment was observed to decrease in conjunction with degeneration of distal axons. Using low-frequency ESTIM, we observed enhanced mitochondrial trafficking to be a neuroprotective mechanism against CIPN. This study confirms ESTIM enhances regeneration of peripheral nerves by increased mitochondrial trafficking.

Concrete additive manufacturing (AM) is an emerging technology that enables the fabrication of complex and efficient geometries with intricate features. Here, the mechanical performance of bio-inspired sinusoidally architected concrete is investigated in comparison to monolithic, cast counterparts. A robotic additive manufacturing process was utilized to fabricate sinusoidal architectures in three orientations (denoted X, Y, and Z) and two rectilinear architectures and compared to conventionally cast specimens of equivalent geometries. Single-edge bend and single-edge-notched bend experiments were performed to test the strength and fracture toughness, respectively. Unlike rectilinear architectures, the X and Z-Sinusoidal architected concrete elicited a flexural strength and fracture toughness statistically equivalent to cast counterparts, whereas the Y-Sinusoidal architecture exhibited a 71 % increase in flexural strength as compared to the cast counterparts. Finite element simulations were carried out to evaluate the effect of sinusoidal frequency and amplitude on stress distribution through the test specimens. In addition, a theoretical analysis of stress concentration was conducted to understand the role of sinusoidal perturbation from surface to core. The sinusoidal architectures were observed to produce stress concentrations and non-uniform stress profiles (depending on two design variables, i.e., amplitude, A, and wavelength, λ), which led to outperforming rectilinear additively manufactured and cast counterparts.

Converting biowaste into a functional product is put to the test by the growing amount of biowaste in the world and the environmental problems it causes. In this research study, we synthesized, characterized, and evaluated bluish-green luminescent carbon nanodots (CNDs) from cow dung and expired tomato sauces via a hydrothermal synthesis method at 160 °C for 8 h. The carbon nanodots were fabricated without additional passivating agents and exhibited good physicochemical and optical properties. The intrinsic properties of carbon nanodots were characterized using various spectral techniques. First, we evaluated the cytotoxic potential of carbon nanodots against A-375 human melanoma cell lines. This study revealed that carbon nanodots exhibited potent cytotoxicity and significantly inhibited the proliferation of A-375 cells in a dose-dependent manner. Next, we demonstrated these carbon nanodot's free radical scavenging potential by employing 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay. The bluish-green fluorescent carbon nanodots fabricated using a green synthesis approach have broad potential for biological applications.

Abstract After a period of unprecedented progress against malaria in the 2000s, halving the global disease burden by 2015, gains overall in sub-Saharan Africa have slowed and even reversed in some places, beginning well before the COVID-19 pandemic. The highly effective drugs, treated nets, and diagnostics that fueled the initial progress all face some threats to their effectiveness, and global funding to maintain and increase their use over the long term is not guaranteed. Malaria vaccines are among the most promising new interventions that could accelerate the elimination of malaria. Vaccines are still in early stages of rollout in children, the age group (along with pregnant women) that has been the focus of malaria strategies for a century. At the same time, over the past decade, a case has been made, based largely on evidence from verbal autopsies in at least a few high-transmission areas, that the malaria death rate among adults has been greatly underestimated. Could vaccinating adults help to bring down the adult malaria mortality rate, contribute to reduced transmission, or both? A randomized trial of a malaria vaccine is proposed in Sierra Leone, a highly endemic setting, to shed light on this proposition.

Cerebrovascular disease (CeVD) is a leading cause of death and disability worldwide. Early detection of behavioral and physiologic changes associated with CeVD may be critical to improving patient outcomes. The growing prevalence of remote monitoring tools, from wearable devices to smartphone applications, which facilitate in situ observation of patients, holds promise for more timely recognition and possible prevention of stroke. The goal of this review was to examine and establish categories of innovation with digital sensors that monitor physiologic and behavioral variables in situ to augment the current CeVD screening and diagnostic processes. Guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist, a search strategy spanning multiple databases from January 2012 to September 30, 2022, was implemented, aggregating 729 articles, of which 51 (7.0%) met the inclusion criteria. The articles were divided into 2 categories on the basis of their focus: physiologic and behavioral. Physiologic articles were sorted into 1 of the following 6 subcategories according to the signal(s) monitored: motor function, heart rhythm, heart rate, kinematic analysis, physical activity, and blood pressure. Behavioral articles were sorted into the following 3 subcategories: mood, cognitive function, and fatigue. Most studies used a wearable accelerometer, photoplethysmography-enabled smartwatch, or smartphone-based sensors. This scoping review identified disparate methods and conclusions associated with the use of digital sensors for in situ physiologic and behavioral monitoring of patients with CeVD. Although most articles evaluated pilot validation and feasibility trials, the lack of randomized controlled trials was identified as a critical gap specific to this evolving research area.

Abstract Objective Noninvasive ventilation (NIV) has become an increasingly accepted mode of treatment for acute respiratory failure. Concept of NIV has revolutionized the treatment of acute respiratory failure in terms of the spectrum of diseases that can be successfully managed, the locations of its application, and achievable goals. The study was aimed at analyzing various aspects of NIV failure. Material and methods In this prospective observational study, all patients who underwent NIV therapy for acute respiratory failure from September 2019 to June 2020 were recruited. The clinical, radiological, laboratory and other relevant data from patients satisfying inclusion criteria were collected and analyzed using appropriate statistical tools. Results Out of the 96 NIV applications, 19 (19.8%) failed NIV application in the form of intubation in 12 and in-hospital mortality in 8 (8.3% of the total group). A total of 73.7% (14/19) had an early failure, and 26.3% (5/19) had late failure. The median length of hospital stay was significantly higher in NIV failure group compared to NIV success group (p 0.05). NIV failure and in-hospital mortality were found to be higher in patients with pneumonia and ILD group, respectively (p 77 mm Hg measured 1–2 h after NIV initiation, hyponatremia, and prior NIV failure history were identified as the independent predictors of NIV failure. Using NIV as a treatment modality in respiratory failure secondary to pneumonia has more chances of failure (p

Abstract Background Two chief hurdles in most cancer treatments are chemoresistance and tumor recurrence, especially counting hepatocellular carcinoma (HCC). Most conformist chemotherapy fails to completely cure HCC patients because of its susceptibility to develop multidrug resistance (MDR) through factors such as hypoxia, cancer stem cells, and drug efflux mechanism cancer stem cells (CSC) which are significant factors involved in chemoresistance. It has been exposed that targeting liver cancer stem cells and chemotherapeutic drugs have a better selected, overall survival rate for hepatocellular carcinoma patients. Aim This study aims to investigate the effectiveness of targeting stem cells for liver cancer using a therapy that targets EpCAM in combination with chemotherapy and how this approach can enhance the treatment outcomes in hepatocellular carcinoma, the most prevalent kind of liver cancer. Results The outcome was studied by flow cytometry, Western blot, RT-PCR, and cytotoxicity assays. EpCAM gene silenced and XAV939-treated cells showed decreased expression of CD133, a liver cancer stem cell (LCSC) marker in flow cytometry analysis, and reduced expression of ABCG2 gene, which is a reliable marker for chemoresistance in RT-PCR and western blot analysis; it was also unable to form colonies in colony forming assay. Similarly, in the spheroid formation assay, EpCAM gene silenced cells and XAV939-treated cells in combinations with cisplatin treatment were powerless to appear spheroid, whereas cisplatin alone-treated cells showed spheroids. In the cytotoxicity assay, cisplatin alone and combined with EpCAM silenced and XAV939-treated cells showed more lactate dehydrogenase (LDH) release than EpCAM silenced arm XAV939 treated components. Conclusion These findings confirm our hypothesis that conventional chemotherapy kills cancer cells but not cancer stem cells. We believe EpCAM-targeted therapy enhances chemosensitivity and decreases relapsed chances. This approach might be the best option for a better prognosis for hepatocellular carcinoma patients.

BackgroundTo describe outcomes of high-risk patients with coronavirus disease 2019 (COVID-19) treated with sotrovimab, other monoclonal antibodies (mAbs), or antivirals, and patients who did not receive early COVID-19 treatment. We also evaluate the comparative effectiveness of sotrovimab versus no treatment in preventing severe clinical outcomes.MethodsThis observational retrospective cohort study analyzed Mayo Clinic electronic health records. Non-hospitalized adult patients diagnosed with COVID-19 from May 26, 2021 and April 23, 2022 and at high risk of COVID-19 progression were eligible. The primary outcome was 29-day all-cause hospitalization and/or death. Outcomes were described for patients treated with sotrovimab, other mAbs, or antivirals, and eligible but untreated patients, and compared between sotrovimab-treated and propensity score (PS)-matched untreated cohorts.ResultsWe included 35,485 patients (sotrovimab, 1369; other mAbs, 6488; antivirals, 133; high-risk untreated, 27,495). A low proportion of patients treated with sotrovimab (n = 33/1369, 2.4%), other mAbs (n = 147/6488, 2.3%), or antivirals (n = 2/133, 1.5%) experienced all-cause hospitalization or death. Among high-risk untreated patients, the percentage of all-cause hospitalization or death was 3.3% (n = 910/27,495). In the PS-matched analysis, 2.5% (n = 21/854) of sotrovimab-treated patients experienced all-cause hospitalization and/or death versus 2.8% (n = 48/1708) of untreated patients (difference, -0.4%; p = 0.66). Significantly fewer sotrovimab-treated patients required intensive care unit admission (0.5% vs 1.8%; difference, -1.3%; p = 0.002) or respiratory support (3.5% vs 8.7%; difference, -5.2%; p < 0.001).ConclusionsThere was no significant difference in the proportion of sotrovimab-treated and PS-matched untreated patients experiencing 29-day all-cause hospitalization or mortality, although significantly fewer sotrovimab-treated patients required intensive care unit admission or respiratory support.

India's growing population and extensive unscientific structures put the country at risk of suffering major casualties during earthquakes. To make buildings more earthquake-resistant, and develop safe and durable structures for future, we need seismic sustainability. For this purpose, Cities should adopt ‘seismic microzonation’, which includes Site response analysis (SRA). In this paper, SRA for eight places in Varanasi (India) was performed using the equivalent linear technique subjected to four significantly different strong motions (Bhuj, Uttarkashi, Chamba, and Kobe motion). Geotechnical data from various government and private entities have been gathered for this purpose. Analysis has been conducted using equivalent linear approach in DEEPSOIL software. The results of the study have been formulated in terms of surface time histories, response spectra, Fourier spectra and PGA along the depth. These findings may be applied to dynamic analysis and structural design, as well as the preparation of advanced dynamic lab tests. Furthermore, sites in Varanasi have been found to considerably enhance ground motion, thus a site-specific design approach must be implemented for important constructions.

BackgroundDiabetes is a worldwide chronic condition causing morbidity and mortality, with a growing economic burden on health care systems. Complications from poorly controlled diabetes are associated with increased socioeconomic costs and reduced quality of life. Smartphones have become an influential platform, providing feasible tools such as health apps to deliver tailored support to enhance the ability of patients with diabetes for self-management. Gro Health is a National Health Service division X–certified digital health tool used to deliver educational and monitoring support to facilitate the development of skills and practices for maintaining good health. ObjectiveThis study aims to assess self-reported outcomes of the Gro Health app among users with diabetes and prediabetes and identify the factors that determine engagement with the digital health tool. MethodsThis was a service evaluation of self-reported data collected prospectively by the developers of the Gro Health app. The EQ-5D questionnaire is a standardized tool used to measure health status for clinical and economic appraisal. Gro Health users completed the EQ-5D at baseline and 6 months after using the app. Users provided informed consent for the use of their anonymized data for research purposes. EQ-5D index scores and visual analogue scale (VAS) scores were calculated at baseline and 6 months for individuals with prediabetes and type 2 diabetes. Descriptive statistics and multiple-regression models were used to assess changes in the outcome measures and determine factors that affected engagement with the digital tool. ResultsA total of 84% (1767/2114) of Gro Health participants completed EQ-5D at baseline and 6 months. EQ-5D index scores are average values that reflect people’s preferences about their health state (1=full health and 0=moribund). There was a significant and clinically meaningful increase in mean EQ-5D index scores among app users between baseline (0.746, SD 0.23) and follow-up (0.792, SD 0.22; P

IMPORTANCE:. Meropenem dosing is typically guided by creatinine-based estimated glomerular filtration rate (eGFR), but creatinine is a suboptimal GFR marker in the critically ill. OBJECTIVES:. This study aimed to develop and qualify a population pharmacokinetic model for meropenem in critically ill adults and to determine which eGFR equation based on creatinine, cystatin C, or both biomarkers best improves model performance. DESIGN, SETTING, AND PARTICIPANTS:. This single-center study evaluated adults hospitalized in an ICU who received IV meropenem from 2018 to 2022. Patients were excluded if they had acute kidney injury, were on kidney replacement therapy, or were treated with extracorporeal membrane oxygenation. Two cohorts were used for population pharmacokinetic modeling: a richly sampled development cohort (n = 19) and an opportunistically sampled qualification cohort (n = 32). MAIN OUTCOMES AND MEASURES:. A nonlinear mixed-effects model was developed using parametric methods to estimate meropenem serum concentrations. RESULTS:. The best-fit structural model in the richly sampled development cohort was a two-compartment model with first-order elimination. The final model included time-dependent weight normalized to a 70-kg adult as a covariate for volume of distribution (Vd) and time-dependent eGFR for clearance. Among the eGFR equations evaluated, eGFR based on creatinine and cystatin C expressed in mL/min best-predicted meropenem clearance. The mean (se) Vd in the final model was 18.2 (3.5) liters and clearance was 11.5 (1.3) L/hr. Using the development cohort as the Bayesian prior, the opportunistically sampled cohort demonstrated good accuracy and low bias. CONCLUSIONS AND RELEVANCE:. Contemporary eGFR equations that use both creatinine and cystatin C improved meropenem population pharmacokinetic model performance compared with creatinine-only or cystatin C-only eGFR equations in adult critically ill patients.

ABSTRACT The bacterial lifestyle is plastic, requiring transcriptional, translational, and metabolic tailoring for survival. These dynamic cellular processes are energy intensive; therefore, flexible energetics is requisite for adaptive plasticity. An intricate network of complementary and supplementary pathways exists in bacterial energy metabolism. There are two main entry points for electrons in the aerobic electron transport system, NADH dehydrogenase (NDH) and succinate dehydrogenase (SDH), receiving electrons from NADH and succinate, respectively. Aerobic bacterial phyla have a non-proton-pumping NADH dehydrogenase, which is often the primary dehydrogenase under aerobiosis. Here, we report adaptive changes supporting growth restoration in an Escherichia coli strain lacking the primary dehydrogenase. Growth optimization is achieved by reducing the activity of succinate dehydrogenase, and thus we demonstrate a physiological discord between proton-pumping NADH dehydrogenase and succinate dehydrogenase in supporting growth. Beyond the fundamental understanding of the bioenergetic network, identifying this compensatory feature provides impetus to rational antimicrobial combinations for targeting the non-proton-pumping dehydrogenase. IMPORTANCE Energy generation pathways are a potential avenue for the development of novel antibiotics. However, bacteria possess remarkable resilience due to the compensatory pathways, which presents a challenge in this direction. NADH, the primary reducing equivalent, can transfer electrons to two distinct types of NADH dehydrogenases. Type I NADH dehydrogenase is an enzyme complex comprising multiple subunits and can generate proton motive force (PMF). Type II NADH dehydrogenase does not pump protons but plays a crucial role in maintaining the turnover of NAD+. To study the adaptive rewiring of energy metabolism, we evolved an Escherichia coli mutant lacking type II NADH dehydrogenase. We discovered that by modifying the flux through the tricarboxylic acid (TCA) cycle, E. coli could mitigate the growth impairment observed in the absence of type II NADH dehydrogenase. This research provides valuable insights into the intricate mechanisms employed by bacteria to compensate for disruptions in energy metabolism.

BackgroundThe expanding population of older adults with obesity is a public health challenge, in part, because of the increased risk of fractures despite normal or high bone mineral density. Potential factors predisposing to fractures in this group include sarcopenia associated with obesity and impaired bone quality. We aimed to determine the contribution of sarcopenic obesity (SO) indices to bone strength as assessed by microfinite element analysis (μFEA) of high-resolution peripheral quantitative computed tomography (HR-pQCT).MethodsOne-hundred eighty-nine older (age ≥ 65 years) adults with obesity (BMI ≥ 30 kg/m2) participated in lifestyle intervention trials at our medical center. All underwent baseline measurements of bone strength (failure load and stiffness) using μFEA from HR-pQCT of the distal radius and tibia. In addition, SO indices [appendicular lean mass/weight (ALM/W) and percent body fat (FM%)] by dual-energy X-ray absorptiometry and handgrip strength (HGS) by dynamometry were assessed. SO was diagnosed and staged based on the 2022 ESPEN and EASO expert consensus statement.ResultsBoth ALM/W and HGS were positively correlated explaining 28% to 36% of the variance in failure load and stiffness at the distal radius and tibia (all p < 0.001). In contrast, FM% was negatively correlated explaining 22% to 31% of the variance in failure load and stiffness at the distal radius and tibia (all p < 0.001). The associations of SO indices with failure load and stiffness remained significant after controlling for age, sex, race/ethnicity, diabetes, and 25-OH vitamin D (ALM/W: R2 = 0.301 to 0.448, HGS: R2 = 0.346 to 0.472, FM%: R2 = 0.299 to 0.432) (p < 0.001 to 0.011). SO was diagnosed in 75/189 (40%) participants with 66/75 (88%) having functional or metabolic complications (stage II). Participants with SO had lower failure load and stiffness at the distal radius than participants with no SO (both p < 0.05).ConclusionThese findings demonstrate that lower muscle mass and strength and higher fat mass may impair bone quality. Therefore, interventions that focus on preserving muscle mass and strength while reducing fat mass may be important to decrease fracture risk when older adults with obesity undertake lifestyle intervention therapy.

Aims: The metabolic equivalent of task (MET) score examines patient performance in relation to energy expenditure before and after knee arthroplasty. This study assesses its use in a knee arthroplasty population in comparison with the widely used Oxford Knee Score (OKS) and EuroQol five-dimension index (EQ-5D), which are reported to be limited by ceiling effects. Methods: A total of 116 patients with OKS, EQ-5D, and MET scores before, and at least six months following, unilateral primary knee arthroplasty were identified from a database. Procedures were performed by a single surgeon between 2014 and 2019 consecutively. Scores were analyzed for normality, skewness, kurtosis, and the presence of ceiling/floor effects. Concurrent validity between the MET score, OKS, and EQ-5D was assessed using Spearman’s rank. Results: Postoperatively the OKS and EQ-5D demonstrated negative skews in distribution, with high kurtosis at six months and one year. The OKS demonstrated a ceiling effect at one year (15.7%) postoperatively. The EQ-5D demonstrated a ceiling effect at six months (30.2%) and one year (39.8%) postoperatively. The MET score did not demonstrate a skewed distribution or ceiling effect either at six months or one year postoperatively. Weak-moderate correlations were noted between the MET score and conventional scores at six months and one year postoperatively. Conclusion: In contrast to the OKS and EQ-5D, the MET score was normally distributed postoperatively with no ceiling effect. It is worth consideration as an arthroplasty outcome measure, particularly for patients with high expectations. Cite this article: Bone Jt Open 2023;4(3):129–137.

Dengue virus (DENV) is spread mostly by biting by the infected female mosquitoes of the species Aedes aegypti, that are commonly found in tropical and subtropical zones of globe. Some studies have shown that nearly fifty percent of the globe are susceptible to DENV. Most infections by DENV are asymptomatic. Clinical infections vary from mild fever to serious diseases including hemorrhagic fever and shock syndrome. The main objective of this study was to estimate DENV infection by rapid diagnostic (RDTs) kit methods in a tertiary care setting. This retrospective study was done at Crimson Hospital, Butwal, Nepal from June to November 2019. Serum samples of all dengue fever suspected patients were tested for DENV antigen as Dengue nonstructural protein 1(NS1) and DENV specific antibodies as IgM and IgG by using World Health Organization Good Manufacturing Practices (GMP) certified rapid solid phase immunochromatographic method. All laboratory test results were tabulated by using MS-Excel and analyzed by statistical package for the Social Sciences software version 20. Out of 821 samples tested, 518 were positive, including 322 (62.16%) reactive for dengue NS1 Protein, 121 (23.35%) for IgM, 62 (11.96%) for IgG and 13 (2.50%) were positive for both IgG and IgM antibodies. Our study showed high prevalence of dengue infection during monsoon to post-monsoon and the infection rate was higher in males (71.72%) than in females (53.36%). According to our findings, DENV infection is prevalent in Butwal, Nepal. Early diagnosis, better case management, faster public health response and effective health policy towards the control of mosquito vectors may reduce the dengue burden and must be implemented in Nepal.

Abstract Background Emotional behavior problems (EBP) are the most common and persistent mental health issues in early childhood. Early intervention programs are crucial in helping children with EBP. Parent–child interaction therapy (PCIT) is an evidence-based therapy designed to address personal difficulties of parent–child dyads as well as reduce externalizing behaviors. In clinical practice, parents consistently struggle to provide accurate characterizations of EBP symptoms (number, timing of tantrums, precipitating events) even from the week before in their young children. The main aim of the study is to evaluate feasibility of the use of smartwatches in children aged 3–7 years with EBP. Methods This randomized double-blind controlled study aims to recruit a total of 100 participants, consisting of 50 children aged 3–7 years with an EBP measure rated above the clinically significant range (T-score ≥ 60) (Eyberg Child Behavior Inventory-ECBI; Eyberg & Pincus, 1999) and their parents who are at least 18 years old. Participants are randomly assigned to the artificial intelligence-PCIT group (AI-PCIT) or the PCIT-sham biometric group. Outcome parameters include weekly ECBI and Pediatric Sleep Questionnaire (PSQ) as well as Child Behavior Checklist (CBCL) obtained weeks 1, 6, and 12 of the study. Two smartphone applications (Garmin connect and mEMA) and a wearable Garmin smartwatch are used collect the data to monitor step count, sleep, heart rate, and activity intensity. In the AI-PCIT group, the mEMA application will allow for the ecological momentary assessment (EMA) and will send behavioral alerts to the parent. Discussion Real-time predictive technologies to engage patients rely on daily commitment on behalf of the participant and recurrent frequent smartphone notifications. Ecological momentary assessment (EMA) provides a way to digitally phenotype in-the-moment behavior and functioning of the parent–child dyad. One of the study’s goals is to determine if AI-PCIT outcomes are superior in comparison with standard PCIT. Overall, we believe that the PISTACHIo study will also be able to determine tolerability of smartwatches in children aged 3–7 with EBP and could participate in a fundamental shift from the traditional way of assessing and treating EBP to a more individualized treatment plan based on real-time information about the child’s behavior. Trial registration The ongoing clinical trial study protocol conforms to the international Consolidated Standards of Reporting Trials (CONSORT) guidelines and is registered in clinicaltrials.gov (ID: NCT05077722), an international clinical trial registry.

This study reports an innovative approach for producing nanoplastics (NP) from various types of domestic waste plastics without the use of chemicals. The plastic materials used included water bottles, styrofoam plates, milk bottles, centrifuge tubes, to-go food boxes, and plastic bags, comprising polyethylene terephthalate (PET), polystyrene (PS), polypropylene (PP), high-density polyethylene (HDPE), and Poly (Ethylene-co-Methacrylic Acid) (PEMA). The chemical composition of these plastics was confirmed using Raman and FTIR spectroscopy, and they were found to have irregular shapes. The resulting NP particles ranged from 50 to 400 nm in size and demonstrated relative stability when suspended in water. To assess their impact, the study investigated the effects of these NP particulates on cell viability and the expression of genes involved in inflammation and oxidative stress using a macrophage cell line. The findings revealed that all types of NP reduced cell viability in a concentration-dependent manner. Notably, PS, HDPE, and PP induced significant reductions in cell viability at lower concentrations, compared to PEMA and PET. Moreover, exposure to NP led to differential alterations in the expression of inflammatory genes in the macrophage cell line. Overall, this study presents a viable method for producing NP from waste materials that closely resemble real-world NP. Furthermore, the toxicity studies demonstrated distinct cellular responses based on the composition of the NP, shedding light on the potential environmental and health impacts of these particles.

Background: Arts and Humanities (A/H) training is a powerful strategy to help medical students develop key competencies which align with the CanMEDS roles that Canadian physicians are expected to embody. Students with backgrounds in A/H may enter medical school with the skills and dispositions that A/H training provides. This paper explores the varied experiences of medical students with prior A/H backgrounds, with an emphasis on how they navigate relationships with their student cohorts and participate in undergraduate medical training environments. Methods: Descriptive qualitative research methodology was used to conduct and analyze semi-structured interviews exploring the perspectives of Canadian medical students with either a A/H degree or training in A/H (n = 13). Domains such as identity, integration of interests, and challenges in maintaining A/H interests during medical training were explored. Results: Participants described their A/H identity as intertwined with their identity as medical trainees and described their sense of interconnection between the disciplines. Challenges included imposter syndrome and difficulties in relating with peers from science backgrounds. Participants described returning to their A/H interests as a tool for wellness amidst medical training. Conclusions: Medical students with a background in A/H training describe this background as offering both affordances and challenges for their sense of identity, belonging, and wellness. These students offer an untapped resource: they come with dispositions of value to medicine, and they perceive a positive, hidden A/H curriculum that supports their maintenance of these dispositions during training. Understanding more about these hidden treasures could help foster the development of well-rounded and humanistic physicians in the entire medical class.

Dairy is an economically significant industry that caters to the huge demand for food products in people's lives. To remain profitable, farmers need to manage their farms and the health of the dairy cows in their herds. There are, however, many risks to cow health that can lead to significant challenges to dairy farm management and have the potential to lead to significant losses. Such risks include cow udder infections (i.e., mastitis) and cow lameness. As automation and data recording become more common in the agricultural sector, dairy farms are generating increasing amounts of data. Recently, these data are being used to generate insights into farm and cow health, where the objective is to help farmers manage the health and welfare of dairy cows and reduce losses from cow health issues. Despite the level of data generation on dairy farms, this information is often difficult to access due to a lack of a single, central organization to collect data from individual farms. The prospect of such an organization, however, raises questions about data ownership, with some farmers reluctant to share their farm data for privacy reasons. In this study, we describe a new data mesh architecture designed for the dairy industry that focuses on facilitating access to data from farms in a decentralized fashion. This has the benefit of keeping the ownership of data with dairy farmers while bringing data together by providing a common and uniform set of protocols. Furthermore, this architecture will allow secure access to the data by research groups and product development groups, who can plug in new projects and applications built across the data. No similar framework currently exists in the dairy industry, and such a data mesh can help industry stakeholders by bringing the dairy farms of a country together in a decentralized fashion. This not only helps farmers, dairy researchers, and product builders but also facilitates an overview of all dairy farms which can help governments to decide on regulations to improve the dairy industry at a national level.

Summary: Relationships between the genome, transcriptome, and metabolome underlie all evolved phenotypes. However, it has proved difficult to elucidate these relationships because of the high number of variables measured. A recently developed data analytic method for characterizing the transcriptome can simplify interpretation by grouping genes into independently modulated sets (iModulons). Here, we demonstrate how iModulons reveal deep understanding of the effects of causal mutations and metabolic rewiring. We use adaptive laboratory evolution to generate E. coli strains that tolerate high levels of the redox cycling compound paraquat, which produces reactive oxygen species (ROS). We combine resequencing, iModulons, and metabolic models to elucidate six interacting stress-tolerance mechanisms: (1) modification of transport, (2) activation of ROS stress responses, (3) use of ROS-sensitive iron regulation, (4) motility, (5) broad transcriptional reallocation toward growth, and (6) metabolic rewiring to decrease NADH production. This work thus demonstrates the power of iModulon knowledge mapping for evolution analysis.

Background: This study assessed the potential cost-effectiveness of high (80–100%) vs low (21–35%) fraction of inspired oxygen (FiO2) at preventing surgical site infections (SSIs) after abdominal surgery in Nigeria, India, and South Africa. Methods: Decision-analytic models were constructed using best available evidence sourced from unbundled data of an ongoing pilot trial assessing the effectiveness of high FiO2, published literature, and a cost survey in Nigeria, India, and South Africa. Effectiveness was measured as percentage of SSIs at 30 days after surgery, a healthcare perspective was adopted, and costs were reported in US dollars ($). Results: High FiO2 may be cost-effective (cheaper and effective). In Nigeria, the average cost for high FiO2 was $216 compared with $222 for low FiO2 leading to a −$6 (95% confidence interval [CI]: −$13 to −$1) difference in costs. In India, the average cost for high FiO2 was $184 compared with $195 for low FiO2 leading to a −$11 (95% CI: −$15 to −$6) difference in costs. In South Africa, the average cost for high FiO2 was $1164 compared with $1257 for low FiO2 leading to a −$93 (95% CI: −$132 to −$65) difference in costs. The high FiO2 arm had few SSIs, 7.33% compared with 8.38% for low FiO2, leading to a −1.05 (95% CI: −1.14 to −0.90) percentage point reduction in SSIs. Conclusion: High FiO2 could be cost-effective at preventing SSIs in the three countries but further data from large clinical trials are required to confirm this.

Background: Community-acquired pneumonia is a differential diagnosis of acute exacerbation of chronic obstructive pulmonary disease (COPD); further both have similar pathogenic spectra. Both the American Thoracic Society and the European Respiratory Society follow similar empirical antibiotic choices for the two conditions. However, there are some differences in the bacterial spectra between the two conditions, particularly when the severity of the disease differs. In the present study, we want to study the differences in the clinical features, bacteriological spectra, and antibiotic susceptibilities in patients with community-acquired pneumonia versus patients with COPD exacerbation and provide a scientific basis for antibiotic selection. Aims: 1. To analyze the differences in the pathogenic spectra and antibiotic sensitivity profile between COPD exacerbation and community acquired pneumonia. 2. To study the differences in the clinical features and outcomes of the two conditions. Subjects and Methods: The study was a prospective observational study conducted from November 2019 to May 2020 in Bangalore Medical College and Research Institute on 30 patients diagnosed with acute exacerbation of COPD and 30 patients diagnosed with community acquired pneumonia. Detailed history, physical examination, and standard laboratory tests were taken on admission. The presence of new consolidation on chest radiograph was recorded. Sputum specimens collected by expectoration and tracheal suctioning or bronchoalveolar lavage were analyzed by Gram staining and microscopy and also by culture. The isolates were also tested for antibiotic sensitivity. The severity of Chronic obstructive pulmonary disease (COPD) exacerbation was assessed by the DECAF score and the severity of the CAP group was assessed by the Pneumonia Severity Index. The differences between the two groups were analyzed. The progression of the disease and the outcomes were observed. Results: Out of 30 (100%) participants in each group, both pneumonia and COPD participants had higher percentage of male participants; 24 (80%) and 26 (86.7%) participants, respectively. The COPD-exacerbation group was significantly older than the community-acquired pneumonia group (63.20 ± 11.82 vs. 43.73 ± 16.58). Klebsiella pneumoniae, Pseudomonas, Streptococcus pneumoniae, and Escherichia Coli were the most commonly isolated species in COPD subjects, whereas S. pneumoniae, Staphylococcus aureus, Haemophilus influenzae, and other organisms were more commonly isolated from pneumonia participants. The drug-resistance rates of S. pneumoniae to penicillin, macrolide and quinolone antibiotics commonly used empirically to treat community acquired pneumonia was 52.6%, 79% and 79% respectively. The sensitivity of Pseudomonas to Carbapenems was 50% and to fluoroquinolones was 16.7% while all the strains were found to be resistant to Aminoglycosides, Penicillin, Cephalosporins, and Macrolides. Conclusions: In our study, we found that K. pneumoniae was the most common pathogen in patients with an exacerbation of COPD while S. pneumoniae was the most common pathogen in patients with community acquired pneumonia. In our study the organisms responsible for community acquired pneumonia were largely resistant to penicillins, macrolides, and tetracyclines, which are the antibiotics of choice for empirical treatment. Similarly, in patients with exacerbation of COPD, the organisms isolated had a far greater degree of resistance to the above-mentioned antibiotics than that seen in our patients with pneumonia. We conclude that antibiotic regimens should be culture driven rather than empirical to be effective while also countering drug resistance.

Background: According to the Global Burden of Disease 2018, chronic obstructive pulmonary disease (COPD) is the third leading cause of death worldwide, and in India, COPD is the second leading cause of death among noncommunicable diseases. Among India's 1.31 billion people, about 6% of children and 2% of adults have bronchial asthma. Infective exacerbations of both COPD and Bronchial asthma are common. However, there are some differences in the bacterial spectra between the two conditions, and profiling the bacteria responsible for the exacerbations will help in choosing appropriate antibiotics and also to combat the issue of drug resistance. Aims: (1) To analyze the bacteriological profile of patients with infective exacerbation of COPD and bronchial asthma. (2) To study the outcomes among these patients. Subjects and Methods: The study was a prospective observational study conducted from November 2019 to May 2020 in Bangalore Medical College and Research Institute on 50 patients diagnosed with acute exacerbation of COPD and 50 patients diagnosed with an exacerbation of bronchial asthma. Detailed history, physical examination, and standard laboratory tests were done on admission. Sputum samples were collected from the patients and analyzed by Gram staining and microscopy and also by culture. The differences between the two groups were analyzed. The progression of the disease and the outcomes were observed. Results: 100 patients were included in our study, 50 each in COPD and bronchial asthma. The study was conducted in hospitals attached to BMCRI. Bacteriological profile was assessed by sputum culture and antibiotic sensitivity in the COPD and asthma groups, respectively. In our study, in the COPD group, majority (80%) of patients were males, the mean age was 64.34 ± 9.876, and 80% were smokers with 20% having exposure to biomass. The most common growth in COPD exacerbation was Streptococcus pneumoniae (18%) followed by Haemophilus influenzae and Klebsiella pneumoniae. Mortality in COPD exacerbation was 12%. In the asthma group, female preponderance was seen (54%), mean age was 40.64 ± 13.11. Majority of patients were cases of childhood asthma. Growth was seen in 32% of exacerbations and the most common organism was Streptococcus pneumoniae. Mortality was 4% and importantly due to comorbidities. Conclusions: Bacterial exacerbations are more common in COPD, while it is not so in bronchial asthma. Viral exacerbations and atypical bacterial exacerbations are more common and asthma associated with pneumonia is the cause for culture growth. Mortality is considerably low in the asthma group compared to COPD exacerbations.

Genistein (GEN), a natural isoflavone possesses a wide range of pharmacological properties and nutraceutical applications. GEN has been studied for its anticancer activity against different types of cancers, but its use in clinical practice is limited due to its low water solubility, rapid metabolism and excretion, lack of cancer cell targeting and poor bioavailability. In the present study, we investigated folate receptor-targeted and PEGylated poly(lactide-co-glycolide) nanoparticles (PLGA-PEG-FA NPs) containing GEN for targeted delivery to ovarian cancer cells. PLGA-PEG and PLGA-PEG-FA polymer conjugates were synthesized and characterized. Nano-precipitation method was employed for the fabrication of NPs of PLGA, PLGA-PEG and PLGA-PEG-FA containing GEN. GEN containing PLGA-PEG and PLGA-PEG-FA NPs prepared were small (104.17 ± 1.61 and 125.41 ± 3.11 nm, respectively) and exhibited sustained release of GEN for around six days. Folate-decorated PLGA-PEG NPs showed increased cellular uptake in comparison to non-targeted PLGA-PEG NPs. The GEN containing PLGA-PEG-FA NPs showed superior anticancer activity than non-targeted PLGA and PLGA-PEG NPs in folate receptor-overexpressing ovarian cancer cell line, SKOV-3. The IC50 of GEN, GEN encapsulated NPs of PLGA, PLGA-PEG and PLGA-PEG-FA were 51.48, 26.70, 23.43 and 11.98 µg/ml, respectively. Folate-targeted PLGA nanoparticles could be developed for potential target-specific delivery of GEN in the treatment of ovarian cancer.

Abstract Background Respiratory distress syndrome (RDS) is a potentially fatal condition of neonate occurring due to alveolar surfactant deficiency causing inefficient gaseous exchange and leading to hampered respiratory function. Purpose of our study is to investigate the role of Doppler indices in antenatal prediction of clinical Respiratory Distress Syndrome (RDS) in late preterm and early term foetuses using Main pulmonary artery (MPA) Doppler indices. The current study was conducted on 342 pregnant women between 34 and 39 weeks of gestational age, who came for routine third trimester ultrasound examination. The standard foetal biometric parameters, gestational age and estimated foetal weight were first obtained. The MPA Doppler indices like pulsatility index (PI), resistivity index (RI), peak systolic velocity (PSV), systolic/diastolic ratio and acceleration time/ejection time (At/Et) were recorded and correlated with the postnatal development of RDS. Results Of the 342 foetuses, neonatal RDS was diagnosed in 47 foetuses. Foetuses diagnosed with RDS had statistically higher PI and RI values, whereas At/Et ratio and PSV were lower. At/Et ratio, PI and RI, PSV showed significant correlation with gestational age and the most statistically significant correlation was found with At/Et ratio. A cut-off value of 0.2865 (sensitivity 89.45%, specificity 94.79%) and 0.3155 (sensitivity 93.22%, specificity 96.78%) correlated strongly with development of RDS in late preterm foetuses and early term infants. Conclusion Foetal MPA indices like PSV, RI, PI and especially Foetal At/Et ratio is a promising non-invasive tool which helps in identifying foetuses at risk and may be very useful to plan delivery in complicated pregnancies and also for better post-natal care of the neonate.

Advanced technologies for muscle tracking provide easy access to identify and track muscle activity, often for the purposes of therapeutic interventions. The necessity of muscle trackers arises from the acute and chronic sources that disrupt neuromuscular control, resulting in an impaired ability to perform daily activities without assistance. In the context of human–machine interfaces, muscle trackers can serve as the “sensory” component, providing real‐time information to machines, such as exoskeletons and prosthetics, that can act upon such information for therapeutic and functional aid. Recently developed devices for muscle tracking rely on combinations of sensor modalities and algorithms to extract information from biosignals track muscle activity, or even extrapolate kinematic information, including gestures. However, a number of obstacles remain to be overcome to further facilitate the practical implementation of muscle‐tracking technologies, the most notable being real‐time analysis of biosignal data and extracting kinematic information from complex movements. This review attempts to cover the mechanisms behind various sensor modalities and algorithms commonly used for muscle tracking, as well as establish the current state of applications within the field. Given its multidisciplinary nature and ability to free users from rehabilitation constraints, the field of muscle tracking holds significant promise for future study.