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Abstract Transesophageal echocardiography (TEE) has been the preferred imaging modality to help guide left atrial appendage closure. Newer technologies such as the Nuvision 4D Intracardiac echocardiography (ICE) catheter allow for real-time 3D imaging of cardiac anatomy. There are no direct comparison studies for procedural imaging between TEE and 4D ICE. To evaluate the performance and safety of left atrial appendage (LAA) closure procedures with the Watchman FLX and Amulet, guided by the Nuvision 4D ICE Catheter. This retrospective observational analysis was conducted on institutional LAAO National Cardiovascular Data Registry from January 2022 to March 2023. Patients had undergone LAA closure procedures with the Watchman FLX or Amulet device guided by TEE or a 4D ICE Catheter. The primary outcome evaluated was successful LAAO device placement. A total of 121 patients underwent LAAO device placement with 46 (38.0%) patients guided by 4D ICE during LAAO implantation. The 4D ICE group had a shorter procedural time compared with TEE guidance. Post procedural 45-day TEE post implant was also comparable for both groups with no patients in either group having incomplete closure of the left atrial appendage and peri-device leak > 5 mm. No device related complications (device related access, stroke, or pericardial effusion) occurred in either group at follow-up. There was no significant difference in device implant success or post procedural outcomes at 45 days in either the TEE or 4D ICE group. However, there was a noticeable improvement in procedural time with the 4D ICE catheter.

key Clinical Message Constrictive Pericarditis is a rare fibrotic conversion of the pericardium that results in non‐specific clinical symptoms such as hepatomegaly, ascites, pleural effusions, and lower extremity edema. A multi‐modal diagnostic approach with cardiac imaging tools, cardiac hemodynamic measurements, and tissue biopsy can be used to diagnose Constrictive Pericarditis. Abstract Constrictive Pericarditis is a rare complication resulting in the fibrotic conversion of the pericardium secondary to idiopathic, infective, post‐surgical, or post‐radiation etiologies. The rigid and restrictive nature of the pericardium can result in non‐specific symptoms of volume overload that can mimic liver cirrhosis or congestive heart failure. We present the case of a 73‐year‐old female with constrictive pericarditis who presented with vague symptoms of abdominal pain, abdominal bloating, and bilateral lower extremity edema. This case report highlights the clinical manifestation, invasive, and non‐invasive diagnostic work‐up, and management of constrictive pericarditis.

ABSTRACTImmunotherapy has revolutionized the treatment of cancers. Reinvigorating lymphocytes with checkpoint blockade has become a cornerstone of immunotherapy for multiple tumor types, but the treatment of glioblastoma has not yet shown clinical efficacy. A major hurdle to treat GBM with checkpoint blockade is the high degree of myeloid-mediated immunosuppression in brain tumors that limits CD8 T-cell activity. A potential strategy to improve anti-tumor efficacy against glioma is to use myeloid-modulating agents to target immunosuppressive cells, such as myeloid-derived suppressor cells (MDSCs) in the tumor microenvironment. We found that the co-inhibition of the chemokine receptors CCR2 and CCR5 in murine model of glioma improves the survival and synergizes robustly with anti-PD-1 therapy. Moreover, the treatment specifically reduced the infiltration of monocytic-MDSCs (M-MDSCs) into brain tumors and increased lymphocyte abundance and cytokine secretion by tumor-infiltrating CD8 T cells. The depletion of T-cell subsets and myeloid cells abrogated the effects of CCR2 and CCR5 blockade, indicating that while broad depletion of myeloid cells does not improve survival, specific reduction in the infiltration of immunosuppressive myeloid cells, such as M-MDSCs, can boost the anti-tumor immune response of lymphocytes. Our study highlights the potential of CCR2/CCR5 co-inhibition in reducing myeloid-mediated immunosuppression in GBM patients.

Antimicrobial resistance (AMR) is a global public health concern and needs to be monitored for control. In this study, synanthropic rodents trapped from humans and animal habitats in Puducherry, India, were screened as sentinels for bacterial pathogens of public health importance and antimicrobial resistance spillover. From the trapped rodents and shrews (n = 100) pathogens viz., Staphylococcus sp, E. coli and Salmonella sp were isolated from oropharyngeal and rectal swabs on Mannitol salt, Mac Conkey and Xylose lysine deoxycholate media respectively. The AMR genes in these isolates were screened by PCR. A total of 76, S. aureus and 19, Staphylococcus non aureus were isolated. E. coli was isolated in 89 samples and among the Salmonella sp (n = 59), 16, were S. enteritidis and 29, were S. typhimurium. A total of 46 MRSA isolates with mec A (n = 40) and mec C (n = 6) were detected. Also, 36.84% and 5.3% Staphylococcus non aureus isolates were tested to have mec A and mec C genes. AMR genes encoding ESBL [blaTEM in 21, blaSHV in 45 and blaCTX-M in 11] was tested positive in 77 E. coli isolates. Among, Salmonella isolates 44/45 were screened to have AMR genes [tet in 13, sul3 & sul4 in 20 and qnrA in 11]. Antibiotic sensitivity test confirmed the antimicrobial resistance. Isolation of pathogens of public health importance and demonstration of genetic elements conferring antimicrobial resistance in the synanthropic rodents confirms that they act as reservoirs and appropriate sentinels to monitor AMR spillover in the environment.

BackgroundPeople living with multiple chronic conditions (MCCs) face substantial challenges in planning and coordinating increasingly complex care. Family caregivers provide important assistance for people with MCCs but lack sufficient support. Caregiver apps have the potential to help by enhancing care coordination and planning among the health care team, including patients, caregivers, and clinicians. ObjectiveWe aim to conduct a scoping review to assess the evidence on the development and use of caregiver apps that support care planning and coordination, as well as to identify key factors (ie, needs, barriers, and facilitators) related to their use and desired caregiver app functionalities. MethodsPapers intersecting 2 major domains, mobile health (mHealth) apps and caregivers, that were in English and published from 2015 to 2021 were included in the initial search from 6 databases and gray literature and ancestry searches. As per JBI (Joanna Briggs Institute) Scoping Review guidelines and PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews), 2 authors independently screened full texts with disagreements resolved by a third author. Working in pairs, the authors extracted data using a pilot-tested JBI extraction table and compared results for consensus. ResultsWe identified 34 papers representing 25 individual studies, including 18 (53%) pilot and feasibility studies, 13 (38%) qualitative studies, and 2 experimental or quasi-experimental studies. None of the identified studies assessed an intervention of a caregiver app for care planning and coordination for people with MCCs. We identified important caregiver needs in terms of information, support, and care coordination related to both caregiving and self-care. We compiled desired functionalities and features enabling apps to meet the care planning and care coordination needs of caregivers, in particular, the integration of caregiver roles into the electronic health record. ConclusionsCaregiver needs identified through this study can inform developers and researchers in the design and implementation of mHealth apps that integrate with the electronic health record to link caregivers, patients, and clinicians to support coordinated care for people with MCCs. In addition, this study highlights the need for more rigorous research on the use of mHealth apps to support caregivers in care planning and coordination.

Goal: Auto-injectors for self-administration of drugs are usually refrigerated. If not warmed up prior to the injection, ejection of the total drug volume is not guaranteed, as their spring and plunger mechanism cannot adjust for a change in viscosity of the drug. Here, we develop piezoelectric micro diaphragm pump that allows these modifications possible while investigating the effectiveness of this alternative dosing method. Methods: The dosing of highly viscous liquid of 25 mPa·s is made possible using application-specific micropump design. By comparing the analytical with experimental results, the practicality of the concept is verified. Results: Using a powerful piezoelectric stack actuator, the micropump achieves high fluid pressures of up to (368 ± 17) kPa. In order to assess the influence of viscosity, we characterize the fluidic performance of the designed micropump through 27G gauge needle for various water-glycerin mixtures. We find maximum flow rates of 2 mL/min for viscosities of up to 25 mPa·s. Conclusions: The developed micro diaphragm pump enables the development of smart auto-injectors with flow rate regulation to achieve drug delivery for high viscosity drugs through 27G needles.

Background The antitumor activity of natural killer (NK) cells can be enhanced by specific targeting with therapeutic antibodies that trigger antibody-dependent cell-mediated cytotoxicity (ADCC) or by genetic engineering to express chimeric antigen receptors (CARs). Despite antibody or CAR targeting, some tumors remain resistant towards NK cell attack. While the importance of ICAM-1/LFA-1 interaction for natural cytotoxicity of NK cells is known, its impact on ADCC induced by the ErbB2 (HER2)-specific antibody trastuzumab and ErbB2-CAR-mediated NK cell cytotoxicity against breast cancer cells has not been investigated.Methods Here we used NK-92 cells expressing high-affinity Fc receptor FcγRIIIa in combination with trastuzumab or ErbB2-CAR engineered NK-92 cells (NK-92/5.28.z) as well as primary human NK cells combined with trastuzumab or modified with the ErbB2-CAR and tested cytotoxicity against cancer cells varying in ICAM-1 expression or alternatively blocked LFA-1 on NK cells. Furthermore, we specifically stimulated Fc receptor, CAR and/or LFA-1 to study their crosstalk at the immunological synapse and their contribution to degranulation and intracellular signaling in antibody-targeted or CAR-targeted NK cells.Results Blockade of LFA-1 or absence of ICAM-1 significantly reduced cell killing and cytokine release during trastuzumab-mediated ADCC against ErbB2-positive breast cancer cells, but not so in CAR-targeted NK cells. Pretreatment with 5-aza-2'-deoxycytidine induced ICAM-1 upregulation and reversed NK cell resistance in ADCC. Trastuzumab alone did not sufficiently activate NK cells and required additional LFA-1 co-stimulation, while activation of the ErbB2-CAR in CAR-NK cells induced efficient degranulation independent of LFA-1. Total internal reflection fluorescence single molecule imaging revealed that CAR-NK cells formed an irregular immunological synapse with tumor cells that excluded ICAM-1, while trastuzumab formed typical peripheral supramolecular activation cluster (pSMAC) structures. Mechanistically, the absence of ICAM-1 did not affect cell–cell adhesion during ADCC, but rather resulted in decreased signaling via Pyk2 and ERK1/2, which was intrinsically provided by CAR-mediated targeting. Furthermore, while stimulation of the inhibitory NK cell checkpoint molecule NKG2A markedly reduced FcγRIIIa/LFA-1-mediated degranulation, retargeting by CAR was only marginally affected.Conclusions Downregulation of ICAM-1 on breast cancer cells is a critical escape mechanism from trastuzumab-triggered ADCC. In contrast, CAR-NK cells are able to overcome cancer cell resistance caused by ICAM-1 reduction, highlighting the potential of CAR-NK cells in cancer immunotherapy.

This study examined invasive cervical cancer (ICC) incidence trends in British Columbia (BC) by age and stage-at-diagnosis relative to World Health Organization ICC elimination targets (4 per 100,000 persons). Incident ICC cases (1971–2017) were obtained from the BC Cancer Registry. Annual age-standardized incidence rates (ASIRs) per 100,000 persons were generated using the direct method. ASIRs were examined among all ages 15+ years and eight age groups using Joinpoint Regression with the Canadian 2011 standard population. Standardized rate ratios (SRRs) compared stage II–IV (late) versus stage I (early) ASIRs by age (2010–2017). ICC ASIRs did not reach the elimination target. ASIRs declined from 18.88 to 7.08 per 100,000 persons (1971–2017). Stronger declines were observed among ages 45+ years, with the largest decline among ages 70–79 years (AAPC = −3.2%, 95% CI = −3.9% to −2.6%). Among ages 25–69 years, varying levels of attenuation in declining trends and stabilization were observed since the 1980s. SRRs indicated higher rates of late-stage ICC among ages 55+ years (SRR−55–69 years = 1.34, 95% CI = 1.08–1.71). Overall, ICC incidence declined in BC since 1971 but did not reach the elimination target. The pace of decline varied across age groups and increased with age. Continued efforts are needed to progress cervical cancer elimination among all age groups.

Given a graph G, a function of assigning distinct labels {1,2,...,|E(G)|} to E(G) such that w(a)≠w(b), ∀ a,b∈V(G) is an antimagic labeling of G where w(a) indicates the vertex sum obtained by summing up all the labels assigned to the edges incident on the vertex a. Let G, Hi, 1≤i≤m be connected graphs such that E(G)={e1,e2,...,em}. A new graph is constructed from G, Hi, 1≤i≤m by adding all possible edges between the end vertices of ei and V(Hi), i∈{1,2,...,m}. The resulting graph is called the generalized edge corona of G and (H1,H2,...,Hm) which is denoted as G⋄(H1,H2,...,Hm). We prove G ⋄ (H1,H2,...,Hm) is antimagic under certain conditions using an algorithmic approach where G has only one vertex of maximum degree three (excluding spider graphs containing uneven legs) and |V(Hi)|≥2, i∈{1,2,...,m}.

Acute brain injury (ABI) and neuroinflammation is reported in COVID-19 and acute respiratory distress syndrome (ARDS). It remains unclear if COVID-19 plays an independent role in development of ABI compared to those with non-COVID-19 ARDS. We aimed to evaluate if COVID-19 ARDS is associated with higher risk and specific patterns of ABI compared to non-COVID-19 ARDS. We conducted an age and sex matched case-control autopsy study at a tertiary academic center. Ten patients with COVID-19 ARDS were matched to 20 non-COVID-19 ARDS patients. Baseline demographics were comparable between the two groups including severity of ARDS (p = 0.3). The frequency of overall ABI (70 vs. 60%), infratentorial ABI (40 vs. 25%), ischemic infarct (40 vs. 25%), intracranial hemorrhage (30 vs. 35%), and hypoxic-ischemic brain injury (30 vs. 35%) was similar between COVID-19 and non-COVID-19 ARDS patients, respectively (p > 0.05). Intracapillary megakaryocytes were exclusively seen in 30% of COVID-19 patients. Overall, frequency and pattern of ABI in COVID-19 ARDS was comparable to non-COVID-19.

Promoters play a key role in influencing transcriptional regulation for fine-tuning the expression of genes. Heterologous promoter engineering has been a widely used concept to control the level of transcription in all model organisms. The strength of a promoter is mainly determined by its nucleotide composition. Many promoter libraries have been curated, but few have attempted to develop theoretical methods to predict the strength of promoters from their nucleotide sequence. Such theoretical methods are not only valuable in the design of promoters with specified strength but are also meaningful in understanding the mechanistic role of promoters in transcriptional regulation. In this study, we present a theoretical model to describe the relationship between promoter strength and nucleotide sequence in Saccharomyces cerevisiae. We infer from our analysis that the −49–10 sequence with respect to the Transcription Start Site represents the minimal region that can be used to predict promoter strength. https://qpromoters.com/ and a standalone tool https://github.com/DevangLiya/QPromoters to quickly quantify the strength of Saccharomyces cerevisiae promoters.

This work reports a straightforward and high-yielding synthesis of alkyl levulinates (ALs), a class of promising biofuel, renewable solvent, and chemical feedstock of renewable origin. ALs were prepared by the acid-catalyzed esterification of levulinic acid (LA) and by the alcoholysis of carbohydrate-derived chemical platforms, such as furfuryl alcohol (FAL) and α-angelica lactone (α-AGL). Phosphotungstic acid (PTA) was chosen as the solid acid catalyst for the transformation, which was heterogenized on humin-derived activated carbon (HAC) for superior recyclability. Using HAC as catalyst support expands the scope of valorizing humin, a complex furanic resin produced inevitably as a side product (often considered waste) during the acid-catalyzed hydrolysis/dehydration of sugars and polymeric carbohydrates. Under optimized conditions (150 °C, 7 h, 25 wt.% of 20%PTA/HAC-600 catalyst), ethyl levulinate (EL) was obtained in an 85% isolated yield starting from FAL. Using the general synthetic protocol, EL was isolated in 88% and 84% yields from LA and α-AGL, respectively. The 20%PTA/HAC-600 catalyst was successfully recovered from the reaction mixture and recycled for five cycles. A marginal loss in the yield of ALs was observed in consecutive catalytic cycles due to partial leaching of PTA from the HAC support.

Natural killer (NK) cells are attractive effectors for adoptive immunotherapy of cancer. Results from first-in-human studies using chimeric antigen receptor (CAR)-engineered primary NK cells and NK-92 cells are encouraging in terms of efficacy and safety. In order to further improve treatment strategies and to test the efficacy of CAR-NK cells in a personalized manner, preclinical screening assays using patient-derived tumor samples are needed. Zebrafish (Danio rerio) embryos and larvae represent an attractive xenograft model to study growth and dissemination of patient-derived tumor cells because of their superb live cell imaging properties. Injection into the organism’s circulation allows investigation of metastasis, cancer cell-to-immune cell-interactions and studies of the tumor cell response to anti-cancer drugs. Here, we established a zebrafish larval xenograft model to test the efficacy of CAR-NK cells against metastatic breast cancer in vivo by injecting metastatic breast cancer cells followed by CAR-NK cell injection into the Duct of Cuvier (DoC). We validated the functionality of the system with two different CAR-NK cell lines specific for PD-L1 and ErbB2 (PD-L1.CAR NK-92 and ErbB2.CAR NK-92 cells) against the PD-L1-expressing MDA-MB-231 and ErbB2-expressing MDA-MB-453 breast cancer cell lines. Injected cancer cells were viable and populated peripheral regions of the larvae, including the caudal hematopoietic tissue (CHT), simulating homing of cancer cells to blood forming sites. CAR-NK cells injected 2.5 hours later migrated to the CHT and rapidly eliminated individual cancer cells throughout the organism. Unmodified NK-92 also demonstrated minor in vivo cytotoxicity. Confocal live-cell imaging demonstrated intravascular migration and real-time interaction of CAR-NK cells with MDA-MB-231 cells, explaining the rapid and effective in vivo cytotoxicity. Thus, our data suggest that zebrafish larvae can be used for rapid and cost-effective in vivo assessment of CAR-NK cell potency and to predict patient response to therapy.

Introduction: The risk of developing oral diseases is higher among individuals with disabilities compared to those who do not have any form of impairment or disability. Dental caries and periodontal diseases are the two most prevalent diseases among the individuals with disabilities worldwide and dental treatment is considered as the greatest unattended health need and oral diseases can have varying impacts on well-being and life quality of people. Aim: To assess the impact of oral health on the Oral Health Related Quality of Life (OHRQoL) of patients with intellectual disabilities in Chennai, India. Materials and Methods: The present cross-sectional school-based study which was conducted in the Department of Public Health Dentistry, Tagore Dental College and Hospital, Chennai,Tamil Nadu, India, from August 2021 to September 2021. Study was conducted among the parents of 12-25-year-old intellectually disabled individuals studying in special schools in Chennai, India. The estimated sample size was 122 with 95% of power and effect size of 0.3. OHRQoL of the participants with intellectual disabilities was assessed using the short-form versions of the Parental-Caregivers Perceptions Questionnaire (P-CPQ) and impact of Oral health on the family life of participants with intellectual disabilities using Family Impact Scale (FIS). Clinical examination of oral health status was assessed using self-designed proforma based on the World Health Organisation (WHO) basic oral health survey 2013. Data was analysed using Statistical Package for the Social Sciences (SPSS) software version 24.0. Results: The number of participants between 12-18 years was 111 (91%) and 19-25 years was 11 (9%) and 68 (55.7%) were males and 54 (44.3%) were females. The results showed that most of the parents 83 (68.03%) were concerned about their child’s bad breath with regard to P-CPQ and with regard to the FIS highest mean was recorded for child needs more attention from them (2.93±0.89) and sleep disturbances (2.80±0.49) among parents. Most (n=52, 42.6%) of them had decayed teeth compared to filled (n=14, 11.5%) and missing teeth (n=17, 13.9%). Majority (n=83, 68.1%) of the participant had fair oral hygiene. There was a positive correlation of oral symptoms and social well-being with the dentition status, Oral Hygiene Index-Simplified (OHI-S) and gingival index. Conclusion: A positive correlation was recorded between the oral symptoms of P-CPQ with the oral health status of the study population with stronger correlation recorded for oral hygiene. With regard to functional limitation there was a negative correlation with gingival index and for emotional well-being there was a negative correlation with dentition status and gingival index.

Introduction Falls are an important public health issue with consequences that include injuries, quality of life reduction and high healthcare costs. Studies show that falls prevention strategies are effective in reducing falls rate among community-dwelling older adults. However, the evaluation for effectiveness was usually done in a controlled setting with homogeneous population, and thus may not be generalisable to a wider population. This study aims to evaluate the impact of community falls prevention programmes with group-based strength and balance exercises, on falls risk and health outcomes for older adults with falls risk in Singapore.Methods and analysis This is a pragmatic closed cohort stepped-wedge cluster randomised trial design study, which involves sequential crossover of clusters from the waitlist control condition to the intervention condition, with the sequence of crossover randomly determined. The intervention will be sequentially rolled out to 12 clusters (a minimum of 5 participants/cluster), over 6 time periods with 8-week intervals in Central and North regions of Singapore. The primary analysis will be conducted under the intention-to-treat principle. A general linear mixed model or generalised estimating equation analysis appropriate for a multilevel longitudinal study incorporating an appropriate error distribution and link function will be used. Markov model will be developed to estimate the incremental cost per quality-adjusted life years and incremental cost per fall prevented from the implementation of falls prevention strategies from a societal perspective. Conditional on there being clinically relevant differences in short-term outcomes, we will implement simulation modelling to project the long-term divergence in trajectories for outcomes and costs using the Markov model.Ethics and dissemination Ethics approval has been obtained. Results will be disseminated in publications and other relevant platforms.Trial registration number NCT04788251.

In recent years, there has been a marked shift in focus towards sustainable and renewable energy solutions, particularly in the context of developing nations. This article explores the immense potential of hybrid renewable energy (RE) systems for ushering in a transformative change in electrifying remote and rural areas within these countries. The importance of such endeavours becomes paramount as a multitude of nations globally seek strategies to diminish carbon footprints. Renewable energy systems, combining sources such as solar, wind, hydro, and biomass, emerge as crucial assets in this drive, especially when considering regions that remain largely isolated from major electrical grids. The growing emphasis on research in this domain, coupled with favourable policies, signifies a promising trajectory for RE in developing nations. Such hybrid models, by capitalising on the diverse spectrum of renewable resources at hand, are on the brink of initiating a revolution in rural electrification strategies. This review accentuates the urgency and significance of rapidly integrating these avant-garde systems, setting the stage for a future that is not only environmentally conscious but also ensures broader and more equitable access to energy.

Thrombin is a key enzyme involved in the development and progression of many cardiovascular diseases. Direct thrombin inhibitors (DTIs), with their minimum off-target effects and immediacy of action, have greatly improved the treatment of these diseases. However, the risk of bleeding, pharmacokinetic issues, and thrombotic complications remain major concerns. In an effort to increase the effectiveness of the DTI discovery pipeline, we developed a two-stage machine learning pipeline to identify and rank peptide sequences based on their effective thrombin inhibitory potential. The positive dataset for our model consisted of thrombin inhibitor peptides and their binding affinities (KI) curated from published literature, and the negative dataset consisted of peptides with no known thrombin inhibitory or related activity. The first stage of the model identified thrombin inhibitory sequences with Matthew’s Correlation Coefficient (MCC) of 83.6%. The second stage of the model, which covers an eight-order of magnitude range in KI values, predicted the binding affinity of new sequences with a log room mean square error (RMSE) of 1.114. These models also revealed physicochemical and structural characteristics that are hidden but unique to thrombin inhibitor peptides. Using the model, we classified more than 10 million peptides from diverse sources and identified unique short peptide sequences (KI. Based on the binding energies of the interaction of the peptide with thrombin, we identified a promising set of putative DTI candidates. The prediction pipeline is available on a web server.

Autologous blood transfusion is defined as the collection of blood from the patient, either preoperatively or intraoperatively, and its transfusion back to the same patient as and when required. We report a case of a 23-year-old pregnant female, G3P1L1A1, presenting with severe Rh alloimmunization, along with a baby requiring intrauterine transfusion for fetal anemia, planned for elective cesarean section and autologous blood transfusion.

Background In this study, we aimed to investigate the prevalence, timing, risk factors, and outcomes of acute respiratory distress syndrome (ARDS) in patients with aneurysmal subarachnoid hemorrhage (aSAH). Methods PubMed and four other databases were searched for randomized controlled trials (RCTs) and observational studies of patients 18 years or older through October 20, 2021. Study quality was assessed, using the Cochrane Risk of Bias tool for RCTs and the Newcastle-Ottawa scale for cohort and case-control studies. High-grade aSAH was defined as a Hunt-Hess grade ≥3 and/or a modified Fisher score ≥3. A good neurological outcome was defined as a Glasgow outcome scale score ≥4. Random-effects meta-analyses were conducted to estimate the pooled outcome prevalence and 95% confidence interval (CI). Results Eleven observational studies (n=6,107) met the inclusion criteria. Overall, 15% of the patients (95% CI, 10.5–20.0; I2=97.8%) developed ARDS after aSAH, with a mean time of 3 days (95% CI, 1.9–3.7; I2=54%). Overall survival at discharge was 80% (95% CI, 75–86; I2=96%), and 67% of aSAH patients (95% CI, 54.9–78.9; I2=94%) had a good neurological outcome at any time. The aSAH cohort without ARDS had a higher rate of survival than those with ARDS (79% vs. 49%, P=0.028). Male sex, patients with a high-grade aSAH, patients who developed pneumonia, and systemic inflammatory response syndrome during hospital admission were at a higher risk of developing ARDS. Conclusion In this meta-analysis, approximately one in six patients developed ARDS after aSAH, with a mean time of 3 days from the initial presentation, and ARDS was associated with increased mortality.

Lead (Pb2+), a ubiquitously present heavy metal toxin, has various detrimental effects on memory and cognition. However, the molecular processes affected by Pb2+ causing structural and functional anomalies are still unclear. To explore this, we employed behavioral and proteomic approaches using rat pups exposed to lead acetate through maternal lactation from postnatal day 0 (P0) until weaning. Behavioral results from three-month-old rats clearly emphasized the early life Pb2+ exposure induced impairments in spatial cognition. Further, proteomic analysis of synaptosomal fractions revealed differential alteration of 289 proteins, which shows functional significance in elucidating Pb2+ induced physiological changes. Focusing on the association of Small Ubiquitin-like MOdifier (SUMO), a post-translational modification, with Pb2+ induced cognitive abnormalities, we identified 45 key SUMO target proteins. The significant downregulation of SUMO target proteins such as metabotropic glutamate receptor 3 (GRM3), glutamate receptor isoforms 2 and 3 (GRIA 2 and GRIA3) and flotilin-1 (FLOT1) indicates SUMOylation at the synapses could contribute to and drive Pb2+ induced physiological imbalance. These findings identify SUMOylation as a vital protein modifier with potential roles in hippocampal memory consolidation and regulation of cognition. Data availbility: The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifier PXD034212&#34.

Abstract Background/Objective: Non-clinical aspects of life, such as social, environmental, behavioral, psychological, and economic factors, what we call the sociome, play significant roles in shaping patient health and health outcomes. This paper introduces the Sociome Data Commons (SDC), a new research platform that enables large-scale data analysis for investigating such factors. Methods: This platform focuses on “hyper-local” data, i.e., at the neighborhood or point level, a geospatial scale of data not adequately considered in existing tools and projects. We enumerate key insights gained regarding data quality standards, data governance, and organizational structure for long-term project sustainability. A pilot use case investigating sociome factors associated with asthma exacerbations in children residing on the South Side of Chicago used machine learning and six SDC datasets. Results: The pilot use case reveals one dominant spatial cluster for asthma exacerbations and important roles of housing conditions and cost, proximity to Superfund pollution sites, urban flooding, violent crime, lack of insurance, and a poverty index. Conclusion: The SDC has been purposefully designed to support and encourage extension of the platform into new data sets as well as the continued development, refinement, and adoption of standards for dataset quality, dataset inclusion, metadata annotation, and data access/governance. The asthma pilot has served as the first driver use case and demonstrates promise for future investigation into the sociome and clinical outcomes. Additional projects will be selected, in part for their ability to exercise and grow the capacity of the SDC to meet its ambitious goals.

Improvements in bioengineering methodology and tools have allowed for significant progress in the development of therapeutics and diagnostics in medicine, as well as progress in many other diverse industries, such as materials manufacturing, food and agriculture, and consumer goods. Glioblastomas present significant challenges to adequate treatment, in part due to their immune-evasive and manipulative nature. Rational-design bioengineering using novel scaffolds, biomaterials, and inspiration across disciplines can push the boundaries in treatment development to create effective therapeutics for glioblastomas. In this review, we will discuss bioengineering strategies currently applied across diseases and disciplines to inspire creative development for GBM immunotherapies.

The concomitant hydrolysis and dehydration of biomass-derived cellulose and hemicellulose to furfural (FUR) and 5-(hydroxymethyl)furfural (HMF) under acid catalysis allows a dramatic reduction in the oxygen content of the parent sugar molecules with a 100% carbon economy. However, most applications of FUR or HMF necessitate synthetic modifications. Catalytic hydrogenation and hydrogenolysis have been recognized as efficient strategies for the selective deoxygenation and energy densification of biomass-derived furfurals generating water as the sole byproduct. Efficient and eco-friendly catalysts have been developed for the selective hydrogenation of furfurals affording renewable furanic compounds such as 2-methylfuran, 2,5-dimethylfuran and 2-methyltetrahydrofuran with potential applications as biofuel, solvent and chemical feedstock. Hydrogen gas or hydrogen donor molecules, required for the above processes, can also be renewably obtained from biomass using catalytic processes, enabling a circular economy. In this review, the recent developments in the energy densification of furfurals to furanic compounds of commercial significance are elaborated, emphasizing the role of catalyst and the reaction parameters employed. Critical discussion on sourcing hydrogen gas required for the processes, using hydrogen donor solvents, catalyst design and the potential markets of furanic intermediates have been made. Critical evaluations of the accomplishments and challenges in this field are also provided.

Abstract Background The concept of periodontal regeneration has been revolutionised since the introduction of growth factors and bioactive bone substitutes which ensures optimal regeneration of the diseased periodontium. The aim of the present study was to evaluate the efficacy of Amniotic membrane + Biphasic Calcium phosphate as compared to Collagen membrane + Biphasic Calcium phosphate for the management of periodontal intrabony defects. Methods 50 systemically healthy patients with localised moderate to severe periodontitis, sites which had a Probing Pocket Depth (PPD) ≥ 6 mm and an intrabony component of ≥ 3 mm as detected on Intra oral periapical radiographs (IOPAR) and bone sounding were recruited based on specific inclusion and exclusion criteria. They were randomly allocated by computer generated tables to Collagen membrane + Biphasic Calcium phosphate and Amniotic membrane + Biphasic Calcium phosphate groups. The amount of bone fill and changes in Probing Pocket Depth, Clinical Attachment Level were measured at baseline and six months. Results The results of the present study showed a mean reduction in the PPD of 2.89 ± 0.69 mm in the Collagen membrane + Biphasic Calcium phosphate group and 2.95 ± 0.57 mm in the Amniotic membrane + Biphasic Calcium phosphate group and CAL gain of 2.60 ± 1.43 mm in Collagen membrane + Biphasic Calcium phosphate group 3.18 ± 1.13 mm in the Amniotic membrane + Biphasic Calcium phosphate group at 6 months follow-up with no statistical significance between the groups. In terms of Defect resolution, 98.62 ± 6.51 % was achieved in Collagen membrane + Biphasic Calcium phosphate group and 98.25 ± 7.21 % in Amniotic membrane + Biphasic Calcium phosphate group. Conclusions Within the limitations of the present study, it can be concluded that AM can be used as a barrier membrane, in conjunction with Biphasic calcium phosphate, and provides comparable results to Collagen membrane with Biphasic calcium phosphate when used in the management of periodontal intrabony defects.

Background: Emergency departments (EDs) are complex, sociotechnical, high-paced, safety-critical work systems that have been disproportionately affected by the COVID-19 pandemic. Despite training, consistent compliance with recommended PPE use during COVID-19 pandemic has been challenging. Healthcare workers (HCWs) have had adapt to overcome these challenges to ensure their own safety and patient safety. We sought to identify barriers in the work system that impede the recommended COVID-19 PPE use in EDs. Methods: We conducted semistructured, in-depth interviews over ZoomTM from August 2020–May 2021 with 45 HCWs from the ED (ie, physicians, nurses, ancillary support staff, etc) affiliated with a large, tertiary-care, academic medical center. These audio-recorded interviews were transcribed and analyzed using a hybrid (inductive and deductive) qualitative coding approach in NVivo software. The deductive portion was guided by the SEIPS work system model, a well-known human-factors conceptual framework. Results: We identified multiple work-system factors in the ED that impede compliance with the recommended COVID-19 PPE use. In addition, ED HCWs have reported making a variety of adaptations or developing strategies to overcome these barriers. Some of these adaptations were made to the PPE physically (eg, trimming portions of PPE), and others were related to the tasks and/or processes associated with PPE, such as filming their own training video demonstrating PPE donning and doffing techniques, and environment services staff checking a patient’s status with nurses prior to entering the patient’s room when there was no COVID-19 signage on the door. Conclusions: Consistent compliance with COVID-19 PPE use in ED clinical practice is challenging and can be negatively affected by a variety of work system factors. Resilience strategies developed by HCWs can provide critical information with regards to HCW needs and potential directions for innovation. Future efforts should focus on not only changing individual HCW behavior through training but also on improving the PPE and ED work system design.

Background: The effectiveness of PPE in preventing self-contamination of healthcare workers (HCWs) and transmission of pathogens (airborne and contact) in the emergency department (ED) is highly dependent on consistent, appropriate use of and other interactions (eg, storing, cleaning, etc) with the PPE. Pre–COVID-19 studies focused primarily on individual HCW contributions to incorrect or suboptimal PPE use. We conducted an analysis of ED video recordings using a human-factors engineering framework (ie, The Systems Engineering Initiative for Patient Safety, SEIPS), to identify work-system–level contributions to inappropriate PPE usage by HCWs while they provide care in their actual clinical care environment. Methods: In total, 47 video sessions (each ~15 minute) were recorded between June 2020 and May 2021 using a GoPro camera in an 8-bed pod area, designated for persons under investigation (PUI) and confirmed COVID-19–positive patients, in an ED of a large, tertiary-care, academic medical center. These recordings captured a ‘landscape view’: 2 video cameras were set up to capture the entire ED pod area and HCWs as they provided care. A team with hemorrhagic fever expertise, infection prevention and control expertise, and ED expertise reviewed each video together and extracted data using a semistructured form. Results: Guided by the 5 components of the SEIPS work system model, (ie, task, physical environment, person, organization, tools and technology), multiple work system failure points influencing HCWs appropriate use of PPE were identified. For example, under the task component, HCWs were observed not doffing and donning in recommended sequence. Also, inconsistencies with COVID-19 status signage on a patient’s door and ambiguous labelling of work areas designated as clean (donning) and dirty (doffing) sites acted as a barrier to appropriate PPE use under the physical environment section. Conclusions: Human factors–based analysis of video recordings of actual ED work identified a variety of work system factors that impede appropriate or correct use of PPE by HCWs. Future efforts to improve appropriate PPE use should focus on eliminating or mitigating the effects of these work system factors.

No portion of this manuscript has previously been presented. Meningiomas, the most common primary intracranial tumors, are histologically categorized by the World Health Organization (WHO) grading system. While higher WHO grade is generally associated with poor clinical outcomes, a significant subset of grade I tumors recur or progress, indicating a need for more reliable models of meningioma behavior. Several groups have developed risk scores based on molecular or immunologic characteristics. These classification schemes show promise, with several models preliminarily demonstrating similar or superior accuracy to WHO grading. Improved understanding of immune system recognition and targeting of meningioma subtypes is necessary to advance the predictive power, as well as develop new therapies. Here, we characterize meningioma molecular drivers, predictive of recurrence and progression, and describe specific aspects of the immune response to meningiomas while highlighting critical questions and ongoing research. Relevant manuscripts of interest were identified using a systematic approach and synthesized into this focused review. Finally, we summarize the ongoing and completed clinical trials for immunotherapy in meningiomas and offer perspective on future directions.

Background: Communication plays a vital role in breaking down barriers between the patient and dental health professional, thereby strengthening treatment alliance. The proliferation of modes, speed of communication and reflexivity of knowledge have implications for health promotion. Aim: To evaluate the effect of social media-based oral health promotion programme in improving oral health among 18-20-year-old college students in Chennai city. Material and Methods: The interventional study consisted of college students between 18-20 years in Chennai city. A total of 140 participants with an allocation ratio of 1:1 were randomly assigned to the intervention and control group. Oral health education was provided to all the students using various oral health education aids. Status of participants for WhatsApp addiction, oral health Knowledge, Attitude and Practice (KAP) and oral health status (Simplified Oral Hygiene Index [OHI-S] and Modified Gingival Index [MGI]) were assessed. The intervention was given to the interventional group through WhatsApp using pictures, videos and text messages at first, second and third months. Follow up examinations were carried out for both the groups at the first, third and sixth month. Independent sample t-test to compare the mean values and Chi-Square to compare proportions between groups were used. Results: Statistically significant difference was seen in OHI-S [Mean- 2.52 (T0) to 0.77 (T3) P 0.001] and MGI [Mean- 1.58 (T0) to 0.58 (T3) P 0.001] scores among the intervention group. The percentage change in the KAP score from baseline to sixth month was comparatively higher among the intervention group. Conclusions: The intervention given through the WhatsApp application significantly improved the oral health status and KAP among its users.

Here, the authors use a molecular epidemiological approach to investigate the frequency and intensity of clustering of HIV with different set-point viral loads and find that frequently transmitted strains in genetic transmission clusters have significantly higher viral loads than nonclustered viruses.

Context: Motivation serves to be an integral part of health promotion to children at the learning phase of their life. Aim: Evaluation of the effectiveness of musical toothbrush over regular toothbrush in the debris and gingival bleeding scores among children. Settings and Design: This was a single-blinded parallel, randomized controlled trial conducted among 6–10-year-old schoolchildren in Chennai. Methods: One hundred participants with allocation ratio of 1:1 were assigned to musical and regular toothbrush group by simple randomization. After baseline evaluation (T0) of Debris Index-Simplified (DI-S) and Gingival Bleeding Index (GBI), outcome variables were assessed for a period of 3 months (T1, T2, and T3). Statistical Analysis Used: Friedman test and Mann–Whitney statistical test were used to compare the outcome variables within and across the two groups. Results: Thirty-two boys and 68 girls (mean age: 8.53 years) participated in the study. Statistically significant difference was seen in DI-S score among musical toothbrush group (mean: 0.50 [T3] and GBI score: 8.18% [T3]) when compared to regular toothbrush group (mean: 1.59 [T3] and GBI score: 23.54 [T3]) at the end of the 3rd month. Conclusion: Although both the musical and regular toothbrushes effectively reduced the DI-S and GBI scores, former showed effective change among children when compared to the latter.

Background: The last few decades have witnessed the growth of diabetes mellitus which is affecting all sections of the society. Complications of diabetes and its management present a still further challenge to health care providers. Methods: A hospital-based cross-sectional study was conducted at Pondicherry Institute of Medical Sciences, India, to find out the treatment and follow-up of patients with diabetes mellitus and also to estimate ocular manifestations among the study subjects. Results: Regular treatment was found among 80% while regular follow-up was seen in 55.7% of the diabetic patients. Two-thirds of the patients were on oral hypoglycemic agents only. 18.6% of the patients tested their blood glucose levels once a month. Visit to an ophthalmologist was made in the last 12 months by 32.9% of them. Ocular manifestations were present in both vegetarians 80% and non-vegetarians 76% respectively. Diabetics practicing sedentary lifestyle had more ocular manifestations 87% as compared to 62.5% in those who did not exercise. Ocular manifestation was also higher among those with elevated blood glucose levels 74.4% in comparison to 61.3% among those with normal blood glucose levels. Conclusion: This study highlights the importance of regular treatment and follow-up by patients with diabetes in relation to development of ocular manifestations. Exercise in diabetes is a key factor in delaying complications such as retinopathy.

The automated transport of cells can enable far-reaching cell culture research. However, to date, such automated transport has been achieved with large pump systems that often come with long fluidic connections and a large power consumption. Improvement is possible with space- and energy-efficient piezoelectric micro diaphragm pumps, though a precondition for a successful use is to enable transport with little to no mechanical stress on the cell suspension. This study evaluates the impact of the microfluidic transport of cells with the piezoelectric micro diaphragm pump developed by our group. It includes the investigation of different actuation signals. Therewith, we aim to achieve optimal fluidic performance while maximizing the cell viability. The investigation of fluidic properties proves a similar performance with a hybrid actuation signal that is a rectangular waveform with sinusoidal flanks, compared to the fluidically optimal rectangular actuation. The comparison of the cell transport with three actuation signals, sinusoidal, rectangular, and hybrid actuation shows that the hybrid actuation causes less damage than the rectangular actuation. With a 5% reduction of the cell viability it causes similar strain to the transport with sinusoidal actuation. Piezoelectric micro diaphragm pumps with the fluidically efficient hybrid signal actuation are therefore an interesting option for integrable microfluidic workflows.

Abstract Background The current low access to virological testing to confirm chronic viraemic HCV infection in low- and middle-income countries (LMIC) is limiting the rollout of hepatitis C (HCV) care. Existing tests are complex, costly and require sophisticated laboratory infrastructure. Diagnostic manufacturers need guidance on the optimal characteristics a virological test needs to have to ensure the greatest impact on HCV diagnosis and treatment in LMIC. Our objective was to develop a target product profile (TPP) for diagnosis of HCV viraemia using a global stakeholder consensus-based approach. Methods Based on the standardised process established to develop consensus-based TPPs, we followed five key steps. (i) Identifying key potential global stakeholders for consultation and input into the TPP development process. (ii) Informal priority-setting exercise with key experts to identify the needs that should be the highest priority for the TPP development; (iii) Defining the key TPP domains (scope, performance and operational characteristics and price). (iv) Delphi-like process with larger group of key stakeholder to facilitate feedback on the key TPP criteria and consensus building based on pre-defined consensus criteria. (v) A final consensus-gathering meeting for discussions around disputed criteria. A complementary values and preferences survey helped to assess trade-offs between different key characteristics. Results The following key attributes for the TPP for a test to confirm HCV viraemic infection were identified: The scope defined is for both HCV detection as well as confirmation of cure. The timeline of development for tests envisioned in the TPP is 5 years. The test should be developed for use by health-care workers or laboratory technicians with limited training in countries with a medium to high prevalence of HCV (1.5–3.5% and >3.5%) and in high-risk populations in low prevalence settings (