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Permeability is a key rock property important for scientific applications that require simulation of fluid flow. Although permeability is determined using core flooding experiments, recent advancements in micro-CT imaging and pore scale fluid flow simulations have made it possible to constrain permeability honoring pore scale rock structure. Previous studies have reported that complex association of pores and solid grains often results in preferential flow paths which influence the resulting velocity field and, hence, the upscaled permeability value. Additionally, the pore structure may change due to geochemical processes such as microbial growth, mineral precipitation and dissolution. This could result in a flow field which dynamically evolves spatially and temporally. It would require numerous experiments or full physics simulations to determine the resultant upscaled Darcy permeability for such dynamically changing systems. This study presents a graph theory-based approach to upscale permeability from pore-to-Darcy scale for changing pore structure. The method involves transforming a given micro-CT rock image to a graph network map followed by the identification of the least resistance path between the inlet and the outlet faces using Dijkstra's algorithm where resistance is quantified as a function of pore sizes. The least resistance path is equivalent to the path of lowest resistance within the domain. The method was tested on micro-CT images of the samples of Sherwood Sandstone, Ketton Limestone and Estaillades Limestone. The three micro-CT images were used to generate 30 synthetic scenarios for geochemically induced pore structure changes covering a range of pore and solid grain growth. The least resistance value obtained from Dijkstra's algorithm was observed to correlate with upscaled permeability value determined from full physics simulations, while improving computational efficiency by a factor of 250. This provides confidence in using graph theory method as a proxy for full physics simulations for determining effective permeability for samples with changing pore structure.

Pulsating heat pipe (PHP) is an implicit technique through a passive two-stage heat transfer system. This paper presents the experimentations on PHP contrived using copper with different inner tube diameters of 1, 1.5, 2, and 2.5 mm, respectively. The PHP is accused of acetone as a functional liquid with filling proportions varying from 50 to 90% of its volume with an increment of 10%. The effects of filling proportion and tube diameter on the thermal performance of PHP were investigated. The evaporator zone is electrically heated using a mica heater in the range of 20–80 W, and the condenser area is kept cool by the water circulation method. The results show that a 2 mm inner tube diameter performs best compared to other tube diameters, with a lower rate of thermal resistance of 0.49 K/W. Also, the performance of PHP is enhanced at a filling proportion of 60% for all the tube diameters. Further, CFD analysis was carried out for different filling ratios for a 2 mm diameter pipe at a constant heat input of 80 W, and it revealed that test outcomes were in line with CFD results. The deviation between the experimental and numerical studies was 10%. Considering the optimized parameters, i.e., tube diameter and filling ratio, the work was extended by adding SiO2 nanoparticles to the base fluid with 1–5 % mass concentration. The results showed a lower thermal resistance value of 0.3 W/K and a higher heat transfer coefficient of 828.64 W/m2 °K was obtained at 2% mass concentration of SiO2. Also, the proportional rise in heat transfer coefficient at 60 W is 11.46, 17, 14, 4.15, and 1.94% for 1, 2, 3, 4, and 5% mass concentration of SiO2 nanoparticles, respectively. Hence, the PHP operates better at a 2 mm diameter with a 60% filling ratio and 2% mass concentration of SiO2 nanoparticles.

A 65-year-old male was admitted for cardiogenic shock (ejection fraction: 15%) with severe aortic stenosis and regurgitation. He underwent emergency angiography and mechanical circulatory support. A multidisciplinary heart team discussed treatment options. Ultimately, he underwent successful emergency surgical aortic valve replacement with recovery on extracorporeal membrane oxygenation. (Level of Difficulty: Intermediate.)

Summary: Mutations of SHANK3 cause Phelan-McDermid syndrome (PMS), and these individuals can exhibit sensitivity to stress, resulting in behavioral deterioration. Here, we examine the interaction of stress with genotype using a mouse model with face validity to PMS. In Shank3ΔC/+ mice, swim stress produces an altered transcriptomic response in pyramidal neurons that impacts genes and pathways involved in synaptic function, signaling, and protein turnover. Homer1a, which is part of the Shank3-mGluR-N-methyl-D-aspartate (NMDA) receptor complex, is super-induced and is implicated in the stress response because stress-induced social deficits in Shank3ΔC/+ mice are mitigated in Shank3ΔC/+;Homer1a−/− mice. Several lines of evidence demonstrate that Shank3 expression is regulated by Homer1a in competition with crosslinking forms of Homer, and consistent with this model, Shank3 expression and function that are reduced in Shank3ΔC/+ mice are rescued in Shank3ΔC/+;Homer1a−/− mice. Studies highlight the interaction between stress and genetics and focus attention on activity-dependent changes that may contribute to pathogenesis.

Background: Heart failure (HF) exacerbations often relate to poor self-care. Education programs improve outcomes, but are resource-intensive. We developed a video-based educational intervention and evaluated it in patients with HF. Methods: Congestive Heart Failure Outreach Program of Education was a pragmatic multicenter randomized trial. We included subjects with HF if they were hospitalized, seen in the emergency department (ED), or high-risk outpatients, and randomized them to intervention or control. Intervention included a 20-minute video, supplementary booklet, and 3 bimonthly newsletters focusing on salt and fluid restriction, daily weights, and medications. Subjects watched the video and were encouraged to review it at home, along with the booklet/newsletters. Control subjects received the booklet only. The primary outcome was the difference in cardiovascular hospitalizations or ED visits between groups at 6 months. Secondary outcomes included clinical events and in-hospital days. Results: We recruited 539 subjects from 22 centers in Canada and the United States. Baseline characteristics were similar in both groups: 64% were male and had a mean age of 66 (± 13) years, mean ejection fraction 31% (± 13.5), and 65% New York Heart Association Functional Classification III/IV. The primary outcome occurred in 57 subjects (21%) in the intervention group compared with 61 subjects (23%) in the control group (P = 0.66). There were no significant differences in prespecified secondary outcomes; however, death occurred in 18 subjects (7%) in the intervention group and 33 subjects (12%) in the control group (P = 0.03). Conclusion: Video education on self-care did not reduce hospitalizations or ED visits in patients with HF. Of note, mortality was lower in the intervention group. Résumé: Introduction: L’exacerbation de l’insuffisance cardiaque (IC) est souvent liée à une mauvaise prise en charge autonome des soins. Les programmes d’enseignement améliorent les résultats cliniques, mais exigent beaucoup de ressources. Nous avons conçu une intervention éducative par vidéo et l’avons évaluée auprès de patients atteints d’IC. Méthodes: Le Congestive Heart Failure Outreach Program of Education était une étude pragmatique multicentrique à répartition aléatoire. Nous avons sélectionné les sujets atteints d’IC s’ils étaient hospitalisés, vus au service des urgences (SU) ou patients en consultation externe exposés à un risque élevé, et les avons répartis de manière aléatoire au groupe d’intervention ou au groupe témoin. L’intervention a consisté en une vidéo de 20 minutes, un livret supplémentaire et 3 bulletins bimensuels portant sur la restriction du sel et des liquides, les mesures quotidiennes du poids et les médicaments. Après que les sujets eurent regardé la vidéo, nous les avons encouragés à la revoir à la maison, en plus de lire le livret et les bulletins. Les sujets témoins ont reçu seulement le livret. Le critère de jugement principal était la différence dans les hospitalisations en raison d’une maladie cardiovasculaire ou les visites au SU entre les groupes après 6 mois. Les critères de jugement secondaires étaient les événements cliniques et les jours d’hospitalisation. Résultats: Nous avons recruté 539 sujets de 22 centres au Canada et aux États-Unis. Les caractéristiques initiales étaient similaires dans les 2 groupes : 64 % étaient des hommes et avaient un âge moyen de 66 ans (± 13), une fraction d’éjection moyenne de 31 % (± 13,5), et 65 % avaient une classification fonctionnelle III/IV de la New York Heart Association. Le critère de jugement principal est survenu chez 57 sujets (21 %) dans le groupe d’intervention et chez 61 sujets (23 %) dans le groupe témoin (P = 0,66). Il n’y a eu aucune différence significative dans les critères secondaires prédéfinis. Toutefois, 18 sujets (7 %) du groupe d’intervention et 33 sujets (12 %) du groupe témoin sont morts (P = 0,03). Conclusion: L’enseignement sur les autosoins par vidéo n’a pas réduit les hospitalisations ou les visites au SU des patients atteints d’IC. Notamment, la mortalité a été plus faible dans le groupe d’intervention.

Summary: Mesenchymal stem cells (MSCs) reportedly exist in a vascular niche occupying the outer adventitial layer. However, these cells have not been well characterized in vivo in medium- and large-sized arteries in humans, and their potential pathological role is unknown. To address this, healthy and diseased arterial tissues were obtained as surplus surgical specimens and freshly processed. We identified that CD90 marks a rare adventitial population that co-expresses MSC markers including PDGFRα, CD44, CD73, and CD105. However, unlike CD90, these additional markers were widely expressed by other cells. Human adventitial CD90+ cells fulfilled standard MSC criteria, including plastic adherence, spindle morphology, passage ability, colony formation, and differentiation into adipocytes, osteoblasts, and chondrocytes. Phenotypic and transcriptomic profiling, as well as adoptive transfer experiments, revealed a potential role in vascular disease pathogenesis, with the transcriptomic disease signature of these cells being represented in an aortic regulatory gene network that is operative in atherosclerosis. : MSCs reportedly exist in a specific vascular niche, but these cells have not been well characterized in medium- and large-sized human arteries. To address this, surplus arterial tissues were obtained at surgery and freshly processed. We show that CD90 marks a human adventitial MSC population, with the CD90+ MSC transcriptomic signature being represented in an atherosclerotic regulatory gene network. Keywords: mesenchymal stem cell, adventitia, atherosclersis, cardiovascular

Summary: Compensation among paralogous transcription factors (TFs) confers genetic robustness of cellular processes, but how TFs dynamically respond to paralog depletion on a genome-wide scale in vivo remains incompletely understood. Using single and double conditional knockout of myocyte enhancer factor 2 (MEF2) family TFs in granule neurons of the mouse cerebellum, we find that MEF2A and MEF2D play functionally redundant roles in cerebellar-dependent motor learning. Although both TFs are highly expressed in granule neurons, transcriptomic analyses show MEF2D is the predominant genomic regulator of gene expression in vivo. Strikingly, genome-wide occupancy analyses reveal upon depletion of MEF2D, MEF2A occupancy robustly increases at a subset of sites normally bound to MEF2D. Importantly, sites experiencing compensatory MEF2A occupancy are concentrated within open chromatin and undergo functional compensation for genomic activation and gene expression. Finally, motor activity induces a switch from non-compensatory to compensatory MEF2-dependent gene regulation. These studies uncover genome-wide functional interdependency between paralogous TFs in the brain. : Majidi et al. study how transcription factors respond to paralog depletion by conditionally depleting MEF2A and MEF2D in mouse cerebellum. Depletion of MEF2D induces functionally compensatory genomic occupancy by MEF2A. Compensation occurs within accessible chromatin in a context-dependent manner. This study explores the interdependency between paralogous transcription factors. Keywords: MEF2, transcription factor, paralog, compensation, interdependency, gene expression, chromatin, chromatin accessibility, neuron, cerebellum, learning

The everolimus-eluting biovascular scaffold (BVS) does not contain any metal, therefore struts are not evident angiographically. Two adjacent platinum radio-opaque markers at each end facilitate precise location of stent ends. Here we report one case of anomalous left main stenting using BVS. The BVS got accidentally distorted in left main during the procedure, which was not visible on angiography but detected on OCT.

Preclinical studies have shown that peroxisome proliferator–activated receptor γ (PPAR-γ) ligands can exert antitumor effects against non–small cell lung cancer (NSCLC) and a variety of other cancers. In this study, we investigate the potential use of a PPAR-γ ligand, troglitazone (Tro), in combination with either of two chemotherapeutic agents, cisplatin (Cis) or paclitaxel (Pac), for the treatment of NSCLC. In vitro, treatment of NSCLC cell lines with Tro potentiated Cis- or Pac-induced growth inhibition. The potentiation of growth inhibition was observed only when Cis or Pac treatment was followed by Tro and not vice versa, demonstrating a sequence-specific effect. Median effect analysis revealed a synergistic interaction between Tro and Cis in the inhibition of NSCLC cell growth and confirmed the sequence-specific effect. We also found that Cis or Pac up-regulated the expression of PPAR-γ protein, accounting for the observed sequence-specific synergy. Similarly, experiments performed using a NSCLC xenograft model demonstrated enhanced effectiveness of combined treatment with Cis and PPAR-γ ligands, Tro or pioglitazone. Tumors from Cis-treated mice also demonstrated enhanced PPAR-γ expression. Together, our data demonstrate a novel sequence-specific synergy between PPAR-γ ligands and chemotherapeutic agents for lung cancer treatment.

In this study, we report novel and simple chemical syntheses of acyl dihydroxyacetone phosphate (DHAP) and 1-acyl glycero-3-phosphate [lysophosphatidic acid (LPA)], key intermediaries in the formation of glycerolipids containing ester and ether bonds. The synthesis of acyl DHAPs involved acylating the dimethyl ketal of DHAP by acid anhydride using 4-pyrrolidinopyridine as the catalyst, and the resulting product was deketalized by HClO4 in acetone to produce acyl DHAP. The acid anhydride was either added directly or generated in the reaction mixture from the corresponding fatty acid using dicyclohexylcarbodiimide as the condensing agent. Using these methods, a number of acyl DHAPs having short-, medium-, and long-chain saturated and unsaturated acyl groups were synthesized, with overall yields from 37% to 75%. The activities of these acyl DHAPs as substrates for guinea pig liver peroxisomal acyl DHAP:NADPH reductase and alkyl DHAP synthase were then determined. Next, starting from these acyl DHAPs, a variety of LPAs were synthesized by chemical reduction of the ketone group. Biological activities of these LPAs were determined by measuring their relative abilities to release intracellular Ca2+ via the LPA receptor. A combined chemical-enzymatic method is also described to prepare the natural LPA from the racemic mixture.

Activation of peroxisome proliferator-activated receptor-γ (PPAR-γ) results in inhibition of tumor growth in various types of cancers, but the mechanism(s) by which PPAR-γ induces growth arrest has not been completely defined. In a recent study, we demonstrated that treatment of A549 (human non small cell lung cancer cell line) tumor-bearing SCID mice with PPAR-γ ligands troglitazone (Tro) and pioglitazone significantly inhibits primary tumor growth. In this study, immunohistochemical analysis of Tro-treated and Pio-treated tumors with factor VIII antibody revealed a significant reduction in blood vessel density compared to tumors in control animals, suggesting inhibition of angiogenesis. Further analysis showed that treatment of A549 cells in vitro with Tro or transient transfection of A549 cells with constitutively active PPAR-γ (VP16-PPAR-γ) construct blocked the production of the angiogenic ELR +CXC chemokines IL-8 (CXCL8), ENA-78 (CXCL5), Gro-α (CXCL1). Similarly, an inhibitor of NF-ΚB activation (PDTC) also blocked CXCL8, CXCL5, CXCL1 production, consistent with their NF-ΚB-dependent regulation. Conditioned media from A549 cells induce human microvascular endothelial cell (HMVEC) chemotaxis. However, conditioned media from Tro-treated A549 cells induced significantly less HMVEC chemotaxis compared to untreated A549 cells. Furthermore, PPAR-γ activation inhibited NF-ΚB transcriptional activity, as assessed by TransAM reporter gene assay. Collectively, our data suggest that PPAR-γ ligands can inhibit tumor-associated angiogenesis by blocking the production of ELR+CXC chemokines, which is mediated through antagonizing NF-ΚB activation. These antiangiogenic effects likely contribute to the inhibition of primary tumor growth by PPAR-γ ligands.

Background: Accurate assessment of the probability of lung cancer (pCA) is critical in patients with pulmonary nodules (PNs) to help guide decision-making. We sought to validate a clinical-genomic classifier developed using whole-transcriptome sequencing of nasal epithelial cells from patients with a PN ≤ 30 mm who smoke or have previously smoked., Research Question: Can the pCA in individuals with a PN and a history of smoking be predicted by a classifier that uses clinical factors and genomic data from nasal epithelial cells obtained by cytologic brushing?, Study Design and Methods: Machine learning was used to train a classifier using genomic and clinical features on 1,120 patients with PNs labeled as benign or malignant established by a final diagnosis or a minimum of 12 months of radiographic surveillance. The classifier was designed to yield low-, intermediate-, and high-risk categories. The classifier was validated in an independent set of 312 patients, including 63 patients with a prior history of cancer (other than lung cancer), comparing the classifier prediction with the known clinical outcome., Results: In the primary validation set, sensitivity and specificity for low-risk classification were 96% and 42%, whereas sensitivity and specificity for high-risk classification was 58% and 90%, respectively. Sensitivity was similar across stages of non-small cell lung cancer, independent of subtype. Performance compared favorably with clinical-only risk models. Analysis of 63 patients with prior cancer showed similar performance as did subanalyses of patients with light vs heavy smoking burden and those eligible for lung cancer screening vs those who were not., Interpretation: The nasal classifier provides an accurate assessment of pCA in individuals with a PN ≤ 30 mm who smoke or have previously smoked. Classifier-guided decision-making could lead to fewer diagnostic procedures in patients without cancer and more timely treatment in patients with lung cancer., Competing Interests: Financial/Nonfinancial Disclosures The authors have reported to CHEST the following: J. H., J. D., M. J., W. A. B., and L. R. L. are employees of Veracyte, Inc, which developed the test; P. S. W. and G. C. K. are former employees. A. S. is an employee of Johnson & Johnson, Inc. M. M. W., C. R., D. J. F.-K., and C. R. L. have been the recipients of honoraria from Veracyte, Inc. None declared (K. M. R.-C., P. J. M.)., (Copyright © 2024. Published by Elsevier Inc.)

Background: Although low-dose CT (LDCT) scan imaging lung cancer screening (LCS) can reduce lung cancer mortality, it remains underused. Shared decision-making (SDM) is recommended to assess the balance of benefits and harms for each patient., Research Question: Do clinician-facing electronic health record (EHR) prompts and an EHR-integrated everyday SDM tool designed to support routine incorporation of SDM into primary care improve LDCT scan imaging ordering and completion?, Study Design and Methods: A preintervention and postintervention analysis was conducted in 30 primary care and four pulmonary clinics for visits with patients who met United States Preventive Services Task Force criteria for LCS. Propensity scores were used to adjust for covariates. Subgroup analyses were conducted based on the expected benefit from screening (high benefit vs intermediate benefit), pulmonologist involvement (ie, whether the patient was seen in a pulmonary clinic in addition to a primary care clinic), sex, and race and ethnicity., Results: In the 12-month preintervention phase among 1,090 eligible patients, 77 patients (7.1%) had LDCT scan imaging orders and 48 patients (4.4%) completed screenings. In the 9-month intervention phase among 1,026 eligible patients, 280 patients (27.3%) had LDCT scan imaging orders and 182 patients (17.7%) completed screenings. Adjusted ORs were 4.9 (95% CI, 3.4-6.9; P < .001) and 4.7 (95% CI, 3.1-7.1; P < .001) for LDCT imaging ordering and completion, respectively. Subgroup analyses showed increases in ordering and completion for all patient subgroups. In the intervention phase, the SDM tool was used by 23 of 102 ordering providers (22.5%) and for 69 of 274 patients (25.2%) for whom LDCT scan imaging was ordered and who needed SDM at the time of ordering., Interpretation: Clinician-facing EHR prompts and an EHR-integrated everyday SDM tool are promising approaches to improving LCS in the primary care setting. However, room for improvement remains. As such, further research is warranted., Trial Registry: ClinicalTrials.gov; No.: NCT04498052; URL: www., Clinicaltrials: gov., (Copyright © 2023 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background: We sought to compare outcomes for infants with tetralogy of Fallot with pulmonary atresia (TOF/PA) and confluent pulmonary arteries who underwent staged or primary complete surgical repair., Methods: This retrospective study included infants undergoing initial surgical intervention between 0 and 60 days of age with TOF/PA without aortopulmonary collaterals from 2009 to 2018 at 20 centers. The primary outcome was days alive and out of the hospital in the first year of life (DAOH365). Secondary outcomes were mortality at 1 year of age and a composite major complication outcome. Multivariable modeling with generalized estimating equations were used to compare outcomes between groups., Results: Of 221 subjects, 142 underwent staged repair and 79 underwent primary complete repair. There was no significant difference in median DAOH365 between the staged and primary repair groups (317 days [interquartile range, 278-336] vs 338 days [interquartile range, 314-348], respectively; adjusted P = .13). Nine staged repair patients (7%) died in the first year of life vs 5 primary repair patients (6%; adjusted odds ratio, 1.00; 95% CI, 0.25-3.95). At least 1 major complication occurred in 37% of patients who underwent staged repair vs 41% of patients who underwent primary complete repair (P = .75), largely driven by the need for unplanned cardiac reinterventions., Conclusions: For infants with TOF/PA with confluent pulmonary arteries, a surgical strategy of staged or primary complete repair resulted in statistically similar DAOH365, early mortality, and morbidity., (Published by Elsevier Inc.)

Background: Combination intrapleural fibrinolytic and enzyme therapy (IET) has been established as a therapeutic option in pleural infection. Despite demonstrated efficacy, studies specifically designed and adequately powered to address complications are sparse. The safety profile, the effects of concurrent therapeutic anticoagulation, and the nature and extent of nonbleeding complications remain poorly defined., Research Question: What is the bleeding complication risk associated with IET use in pleural infection?, Study Design and Methods: This was a multicenter, retrospective observational study conducted in 24 centers across the United States and the United Kingdom. Protocolized data collection for 1,851 patients treated with at least one dose of combination IET for pleural infection between January 2012 and May 2019 was undertaken. The primary outcome was the overall incidence of pleural bleeding defined using pre hoc criteria., Results: Overall, pleural bleeding occurred in 76 of 1,833 patients (4.1%; 95% CI, 3.0%-5.0%). Using a half-dose regimen (tissue plasminogen activator, 5 mg) did not change this risk significantly (6/172 [3.5%]; P = .68). Therapeutic anticoagulation alongside IET was associated with increased bleeding rates (19/197 [9.6%]) compared with temporarily withholding anticoagulation before administration of IET (3/118 [2.6%]; P = .017). As well as systemic anticoagulation, increasing RAPID score, elevated serum urea, and platelets of < 100 × 10 9 /L were associated with a significant increase in bleeding risk. However, only RAPID score and use of systemic anticoagulation were independently predictive. Apart from pain, non-bleeding complications were rare., Interpretation: IET use in pleural infection confers a low overall bleeding risk. Increased rates of pleural bleeding are associated with concurrent use of anticoagulation but can be mitigated by withholding anticoagulation before IET. Concomitant administration of IET and therapeutic anticoagulation should be avoided. Parameters related to higher IET-related bleeding have been identified that may lead to altered risk thresholds for treatment., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objectives: We describe the use of a multipathogen platform, TaqMan array card (TAC) real-time polymerase chain reaction, for the detection of pathogens in patients hospitalized with severe respiratory illness (SRI)., Methods: Prospective hospital-based syndromic surveillance for acute and chronic SRI was carried out at two sentinel sites in South Africa between January and December 2017. We tested respiratory specimens for 21 respiratory pathogens and blood samples for nine bacteria using TAC. Pathogen detection was compared by age group and HIV status using the chi-square test., Results: During 2017, 956 patients of all ages were enrolled in the SRI surveillance, and of these, 637 (67%) patients were included in this study (637 blood, 487 naso- and oro-pharyngeal swabs, and 411 sputum specimens tested). At least one pathogen was detected in 83% (527/637) of patients. Common pathogens detected included Haemophilus influenzae (225/637; 35%), Streptococcus pneumoniae (224/637; 35%), rhinovirus (144/637; 23%), Staphylococcus aureus (129/637; 20%), Klebseilla pneumoniae (85/637; 13%), Mycobacterium tuberculosis (75/637; 12%), and respiratory syncytial virus (57/637; 9%). Multiple pathogens (≥2) were codetected in 57% (364/637) of patients., Conclusion: Although the use of a multi-pathogen platform improved pathogen yield, pathogen co-detections were common and would need clinical assessment for usefulness in individual-level treatment and management decisions., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Aim: To detect the prevalence of diabetic polyneuropathy (DPN) in children with type 1 diabetes (T1D) and to identify associated the risk factors., Methods: This cross-sectional study evaluated children aged between 2 and 16y with T1D for ≥2 y. Detailed neurological examination, neuropathy symptom score, and nerve conduction studies were done in all children to assess nerve dysfunction. Disease-related factors were evaluated for the prediction of neuropathy., Results: Sixty-six children (67% boys) were enrolled. The mean age at the time of diagnosis of T1D was 7.1 ± 2.6 years. The mean duration of diabetes was 4 ± 1.8 years. None of the patients had neuropathy on clinical examination or on the neuropathy symptom score. The prevalence of subclinical DPN was 18.2% (n = 12/66). The type of neuropathy was pure motor (n = 11, 91.6%) and mixed sensorimotor (n = 1, 8.3%). The common peroneal nerve was most commonly affected (n = 6, 50%), followed by the tibial (n = 4, 33.3%) nerve. The most common patterns of nerve involvement were mixed axonal and demyelination (n = 7, 58.3%), followed by axonal (n = 3, 25%) and demyelinating type (n = 2, 16.6%). Children with subclinical DPN had a significant reduction in velocity of tibial, common peroneal, median motor, and ulnar motor nerves; delayed latency in common peroneal, median motor, ulnar motor, and median sensory nerves compared to those without DPN (p value <0.05). A higher body mass index predicted the development of subclinical DPN (p value <0.05)., Conclusion: Nearly one-fifth of children with T1D have subclinical neuropathy as early as two years of the disease. A higher body mass index is significantly associated with DPN. Electrophysiological studies should be performed regularly to screen for nerve dysfunction and its progression., (Copyright © 2022 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.)

Objectives: Older nursing home residents make up the population at greatest risk of morbidity and mortality from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. No studies have examined the determinants of long-term antibody responses post vaccination in this group., Design: Longitudinal cohort study., Setting and Participants: Residents from 5 nursing homes assessed before vaccination, and 5 weeks and 6 months post vaccination, with the BNT162b2 messenger RNA SARS-CoV-2 vaccine., Methods: Comprehensive clinical assessment was performed, including assessment for comorbidity, frailty, and SARS-CoV-2 infection history. Serum nucleocapsid and anti-spike receptor binding domain (RBD) antibodies were analyzed at all timepoints. An in vitro angiotensin-converting enzyme (ACE2) receptor-spike RBD neutralization assay assessed serum neutralization capacity., Results: Of 86 participants (81.1 ± 10.8 years; 65% female), just under half (45.4%; 39 of 86) had evidence of previous SARS-CoV-2 infection. All participants demonstrated a significant antibody response to vaccination at 5 weeks and a significant decline in this response by 6 months. SARS-CoV-2 infection history was the strongest predictor of antibody titer (log-transformed) at both 5 weeks [β: 3.00; 95% confidence interval (CI): 2.32-3.70; P < .001] and 6 months (β: 3.59; 95% CI: 2.89-4.28; P < .001). Independent of SARS-CoV-2 infection history, both age in years (β: -0.05; 95% CI: -0.08 to -0.02; P < .001) and frailty (β: -0.22; 95% CI: -0.33 to -0.11; P < .001) were associated with a significantly lower antibody titer at 6 months. Anti-spike antibody titers at both 5 weeks and 6 months significantly correlated with in vitro neutralization capacity., Conclusions and Implications: In older nursing home residents, SARS-CoV-2 infection history was the strongest predictor of anti-spike antibody titers at 6 months, whereas age and frailty were independently associated with lower titers at 6 months. Antibody titers significantly correlated with in vitro neutralization capacity. Although older SARS-CoV-2 naïve nursing home residents may be particularly vulnerable to breakthrough SARS-CoV-2 infection, the relationship between antibody titers, SARS-CoV-2 infection, and clinical outcomes remains to be fully elucidated in this vulnerable population., (Copyright © 2021 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

The global COVID-19 pandemic has exposed the shortcomings of our health, social, and economic systems. While responding to the health crisis, governments are scrambling to understand and address the knock-on economic effects from market disruptions, and respond to other major disturbances (e.g. natural disasters). We conducted 61 key informant interviews with Indo-Fijian small-scale fisheries (SSF) actors (i.e. fishers, boat owners (that may or may not fish), crew members, and traders) in May 2020, two months after Fiji got its first case of COVID-19 and a month after Cyclone Harold hit the country. We examined how these SSF groups whose access to resources depends on their ability to navigate existing social relations of power, have lived through, experienced, and responded to the two stresses. We found the main impact of COVID-19 on SSF actors was the reduction in sales of fish (73.8 % of respondents) likely a result of reduction in local consumption and/or the loss of tourism markets. Loss of purchasing power meant almost a fifth of Indo-Fijian SSF actors interviewed (comprising 44.4 % of crew members, 16.4 % fishers, 11.5 % boat owners, 8.3 % traders) were unable to obtain sufficient food to meet their families' daily needs. Many of these SSF actors do not have access to social security or similar safety nets leaving them vulnerable to the current crisis as well as to other shocks and changes. Furthermore, social inequities and power relations surrounding access to fisheries resources and government aid contributed to their vulnerability to economic stresses from COVID-19 and a severe cyclone. An understanding of early impacts of COVID-19 on SSF through an intersectional lens can assist decision-makers to quickly mobilise assistance to help people who are most vulnerable, and avoid widening inequities among social groups., Competing Interests: The authors report no declarations of interest., (© 2021 The Author(s).)

Introduction: Mental health literacy (MHL) is an important mediator of mental health in the community. Recognition of schizophrenia by the presentation of a case vignette is often used to assess MHL. Various studies assessing MHL around the world have shown that the recognition of schizophrenia is low. This study was designed to use the case vignette method to assess the MHL in a sample of respondents in North India., Methodology: We translated a well-known case vignette of schizophrenia from english into hindi. A cross-sectional study design was followed. This case vignette was presented in the written format to 200 respondents in rural Punjab and Haryana. The case vignette was followed by questions regarding the identification and nature of the problem, what could be done about it and the familiarity of the respondent to the term 'schizophrenia'. The results were analysed through open coding., Results: Around 22% of the responses identified mental illness. The recognition of schizophrenia by name was only in one response. Most people attributed the condition of the protagonist in the case vignette to be due to stressful life situations. The respondents used the terms 'depression' and 'tension' as descriptors of mental illness. The correction of situations leading to stress and counselling by a psychiatrist was considered by most respondents to be useful. The familiarity with schizophrenia was 18%., Conclusions: MHL in our sample was low. Measures for improving the MHL in the community are needed. There may be a case for easier nomenclature with regards to MHL., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Pulmonary tuberculosis has varied patterns of clinical presentation. Here, we report a case of tuberculosis in a 44 year immunocompetent female patient who presented to us with multiple cysts in the lung parenchyma. The diagnosis was confirmed by the analysis of bronchoalveolar lavage fluid. She had secondary spontaneous pneumothorax and progressive respiratory failure despite anti-tubercular therapy. Acute or sub acute onset of multiple lung cysts is usually associated with pulmonary infection. Tuberculosis presenting as cystic lung disease is less common and atypical. High index of suspicion and early initiation of therapy is pivotal in management of such cases., Competing Interests: Conflicts of interest The authors have none to declare., (Copyright © 2019 Tuberculosis Association of India. Published by Elsevier B.V. All rights reserved.)

Objectives: Electrical cortical stimulation mapping (ECSM) is the current gold standard functional mapping technique; however, it is burdened by several limitations. Our objective in this study is to show that extended functional mapping modalities can (1) allow neurosurgeons to map and preserve eloquent regions that are inaccessible by the traditional ECSM technique and (2) factor into the operative decision-making process and surgical trajectory during resection of Rolandic brain tumors., Patients and Methods: A 55year old patient having a right Rolandic glioblastoma underwent subdural grid implantation followed by surgical resection. Multimodal functional mapping including electrical stimulation, high gamma power mapping, functional magnetic resonance imaging, and diffusion tensor imaging were performed to define the location of the patient's eloquent cortex and white matter tracts in relation to the tumor and determine the optimal surgical trajectory prior to resection., Results: The patient tolerated a safe surgical resection without any new postoperative deficits. ECSM mapping successfully delineated safe areas for resection as well as eloquent areas related to motor control and speech production. High gamma power analysis successfully mapped areas involved in arm reach. Functional MRI showed the regions related to finger tapping. DTI demonstrated the corticospinal tract and its relation to the hand motor cortex and the tumor., Conclusion: Adjunct mapping techniques used to supplement the data offered by ECSM can help advance the field of functional mapping and Rolandic surgery via broadening our accessibility to the human brain and providing a comprehensive map of eloquent grey and white matter structures and their relation to the tumor., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Introduction: Venous thromboembolism (VTE) is a major cause of morbidity and mortality in hospitalized patients with colon cancer. We assessed nationwide population-based trends in rates of hospitalization and mortality from VTE among patients with colon cancer to determine its impact., Methods: We queried the Nationwide Inpatient Sample (NIS) database entries from 2003 to 2011 to identify patients with colon cancer. Bivariate group comparisons between hospitalized patients with colon cancer with VTE to those without VTE were made. Multivariate logistic regression analysis was used to obtain adjusted odds ratios. The Cochrane-Armitage test for linear trend was used to assess occurrences of VTE and mortality rates among patients with colon cancer., Results: The total number patients with colon cancer was 1,502,743, of which 41,394 (2.75%) had VTE. The median age of the study population was 69 years; 51.5% were women. After adjusting for potential confounders, compared with those without VTE, patients with colon cancer with VTE had significantly higher inpatient mortality (6.26% vs. 5.52%, OR 1.15, P < .001) and greater disability at discharge (OR 1.38, P < .001), but were not associated with longer length of stay (LOS) or cost of hospitalization. From 2003 to 2011, despite an increase in hospitalization rate with VTE in patients with colon cancer, their mortality steadily declined., Conclusion: VTE in hospitalized patients with colon cancer is associated with a significantly higher inpatient mortality and greater disability, but not with longer LOS or cost of hospitalization. Furthermore, even though there has been a trend toward more frequent hospitalizations in this patient population, their mortality continues to decline., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Tuberculosis remains one of the 'Captains of the Men of Death' even today, particularly in the developing world. Its frequency is increased 14-fold in patients with chronic liver diseases (CLD) and liver cirrhosis, more so in those with decompensated disease, probably due to the cirrhosis-associated immune dysfunction syndrome, and case-fatality rates are high. The diagnosis of tuberculosis, particularly the interpretation of the Mantoux test, is also fraught with difficulties in CLD, especially after previous BCG vaccination. However, the greatest challenge in the patient with CLD or liver cirrhosis and tuberculosis is managing their therapy since the best first-line anti-tuberculosis drugs are hepatotoxic and baseline liver function is often deranged. Frequency of hepatotoxicity is increased in those with liver cirrhosis, chronic hepatitis B and chronic hepatitis C, possibly related to increased viral loads and may be decreased following antiviral therapy. If hepatotoxicity develops in those with liver cirrhosis, particularly decompensated cirrhosis, the risk of severe liver failure is markedly increased. Currently, there are no established guidelines for anti-tuberculosis therapy (ATT) in CLD and liver cirrhosis although the need for such guidelines is self-evident. It is proposed that ATT should include no more than 2 hepatotoxic drugs (RIF and INH) in patients with CLD or liver cirrhosis and stable liver function [Child-Turcotte-Pugh (CTP) ≤7], only a single hepatotoxic drug (RIF or INH) in those with advanced liver dysfunction (CTP 8-10) and no hepatotoxic drugs with very advanced liver dysfunction (CTP ≥11). A standard protocol should be followed for monitoring ATT-related hepatotoxicity and for stop rules and reintroduction rules in all these patients, on the lines proposed here. It is hoped that these proposals will introduce uniformity and result in streamlining the management of these difficult patients.

The achievement of patency of the microvascular anastomosis in free flap surgery is dependent on a number of factors, central to which is atraumatic handling of the vessel lumen, and intimal apposition. Initial laboratory studies demonstrating the superiority of the non-penetrating vascular closure staple (VCS - Anastoclip ®) were followed by our report in 1999 on a series of free flaps. There is still a paucity of data in the literature on the use of non-penetrating devices for microvascular anastomosis, and our review gives evidence to support the routine use of the VCS in microsurgical free flap surgery. We now report on its successful use over a thirteen year period in 819 free flap reconstructions. Our data indicates the VCS device to be as effective as sutured anastomoses in free tissue transfer surgery. There is also statistically significant data (Barnard's Exact Test) to demonstrate a higher vascular patency rate of the VCS device over sutured anastomoses when sub group analysis is performed. 'Take-back' revision rates were lower amongst flaps that employed VCS use. For arterial anastomoses, this equated to 3/654(0.05%) vs 4/170(2.4%) with hand-sewn anastomoses (p = 0.02). Similarly, for venous anastomoses the 'take-back' revision rate was 7/661(1.1%) vs 8/165(4.8%) with hand-sewn anastomoses (p = 0.003). Furthermore, the major advantage of the VCS is reduction in anastomosis time, from approximately 25 min per anastomosis for sutures to between five and 10 min for staples., (Copyright © 2011 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

Background: Malignant pleural effusions (MPEs) affect > 150,000 people each year in the United States. Current palliative options include pleurodesis and placement of an indwelling catheter, each with its own associated benefits. This study was conducted to determine the safety, efficacy, and feasibility of a rapid pleurodesis protocol by combining medical thoracoscopy with talc pleurodesis and simultaneous placement of a tunneled pleural catheter (TPC) in patients with symptomatic MPE., Methods: Patients with recurrent, symptomatic MPEs underwent medical thoracoscopy with placement of a TPC and talc poudrage. The TPC was drained per protocol until the output was < 150 mL/d on two consecutive drainage attempts and then removed. Patients were followed for up to 6 months., Results: Between October 2005 and September 2009, 30 patients underwent the procedure. The median duration of hospitalization following the procedure was 1.79 days. All patients showed an improvement in dyspnea and quality of life. Pleurodesis was successful in 92% of patients, and the TPC was removed at a median of 7.54 days. Complications included fever (two patients), the need for TPC replacement (one patient), and empyema (one patient)., Conclusion: Rapid pleurodesis can be achieved safely by combining medical thoracoscopy and talc poudrage with simultaneous TPC placement. Both hospital length of stay and duration of TPC use can be reduced significantly as compared with historical controls of either procedure alone. Future randomized trials are needed to confirm these results.

Celiac disease affects the proximal small intestine and is caused by a local immune response to dietary gluten. Celiac disease usually presents with chronic diarrhea; however, presentations with elevated hepatic transaminase levels in blood or with iron-deficiency anemia have been described. Celiac disease has been reported to be associated with autoimmune liver diseases. Hepatitis C virus (HCV) can also initiate autoimmune disease process. Therefore, HCV infection and celiac disease may occur together. Here, we describe 4 cases of celiac disease associated with chronic hepatitis C. This small case series indicates that chronic HCV infection and celiac disease are not causally associated.

Pulmonary alveolar proteinosis (PAP) is a disease characterized by the deposition of amorphous lipoproteinaceous material in the alveoli secondary to abnormal processing of surfactant by macrophages. Whole-lung lavage often is performed as the first line of treatment for this disease because it is a means to wash out the proteinaceous material from the alveoli and reestablish effective oxygenation and ventilation. Whole-lung lavage is a large-volume BAL that is performed mainly in the treatment of PAP. In brief, it involves the induction of general anesthesia followed by isolation of the two lungs with a double-lumen endotracheal tube and performance of single-lung ventilation while large-volume lavages are performed on the nonventilated lung. Warmed normal saline solution in 1-L aliquots (total volumes up to 20 L) is instilled into the lung, chest physiotherapy is performed, then the proteinaceous effluent is drained with the aid of postural positioning. The sequence of events is repeated until such time as the effluent, which is initially milky and opaque, becomes clear. This procedure results in significant clinical and radiographic improvement secondary to the washing out of the proteinaceous material from the alveoli. The whole-lung lavage video details all aspects of the procedure, including case selection, patient preparation and equipment, a step-by-step review of the procedure, and postoperative considerations.

Dermatofibrosarcoma protuberans (DFSP) is a relatively rare neoplasm affecting the skin. It is an infiltrative tumour of intermediate malignancy, with a limited potential for metastasis but a high rate of recurrence. The incidence in children is even less frequent, although a proportion of those identified in adulthood may reflect a delay in diagnosis of childhood DFSP. We report the experience of DFSP seen at The Children's Hospital at Westmead (Sydney, Australia). Three children aged 5, 10 and 11 years of age underwent surgical excision of their lesions. Recurrence was evident in one child whose initial histopathology was not definitive for DFSP, and whose initial surgery had not involved wide local excision. All three children were male, and all had lesions affecting their trunk. One child whose lesion was thought to have been evident since birth may have represented congenital DFSP.

Objective: To assess the prevalence and characteristics of airway involvement in relapsing polychondritis (RP)., Methods: Retrospective chart review and data analysis of RP patients seen in the Rheumatology Clinic and the Complex Airway Center at Beth Israel Deaconess Medical Center from January 2004 through February 2008., Results: RP was diagnosed in 145 patients. Thirty-one patients had airway involvement, a prevalence of 21%. Twenty-two patients were women (70%), and they were between 11 and 61 years of age (median age, 42 years) at the time of first symptoms. Airway symptoms were the first manifestation of disease in 17 patients (54%). Dyspnea was the most common symptom in 20 patients (64%), followed by cough, stridor, and hoarseness. Airway problems included the following: subglottic stenosis (n = 8; 26%); focal and diffuse malacia (n = 15; 48%); and focal stenosis in different areas of the bronchial tree in the rest of the patients. Twelve patients (40%) required and underwent intervention including balloon dilatation, stent placement, tracheotomy, or a combination of the above with good success. The majority of patients experienced improvement in airway symptoms after intervention. One patient died during the follow-up period from the progression of airway disease. The rest of the patients continue to undergo periodic evaluation and intervention., Conclusion: In this largest cohort described in the English language literature, we found symptomatic airway involvement in RP to be common and at times severe. The nature of airway problems is diverse, with tracheomalacia being the most common. Airway intervention is frequently required and in experienced hands results in symptom improvement.

We prospectively analyzed the results of extracorporeal membrane oxygenation (ECMO) done in our Pediatric Cardiac Unit from January to December 2007. We present a series of nine patients who required ECMO after open heart surgery for congenital heart disease (CHD). The overall survival rate of these patients was 77.8%. The survival rate was 100% in patients who were electively put on ECMO after intracardiac repair for tetralogy of fallot, 50% in patients who were put on ECMO following the arterial switch operation and 50% in patients who were put on ECMO after VSD closure. Our results seem to suggest that patients placed on ECMO electively rather than after a cardiac arrest posts congenital cardiac surgeries have a better outcome.

Thermal ablation using argon plasma coagulation (APC) is a commonly used modality in the bronchoscopic management of central airway obstruction and hemoptysis. In experienced hands, APC is considered to be a relatively safe tool. Reported complications associated with APC use are rare and include hemorrhage, airway perforation, or airway fires. Systemic gas embolism has been reported with APC during laparoscopic hepatic surgeries, and we have reported one case of systemic gas embolism with cardiovascular collapse in the past. We now report the first case series of systemic, life-threatening gas embolism occurring as a complication of bronchoscopic application of APC.

The role of noninvasive ventilation (NIV) in the management of acute respiratory distress syndrome (ARDS) is controversial. The aim of this study was to assess the effect of NIV on the rate of endotracheal intubation and intensive care unit (ICU) mortality in patients with ARDS. We searched the MEDLINE database for relevant studies published from 1980 to September 2005, and included studies if (a) the design was a randomized controlled trial; (b) patients had ARDS irrespective of the underlying etiology; (c) the interventions compared NIV and medical therapy with medical therapy alone; and (d) outcomes included need for endotracheal intubation and/or ICU survival. The addition of NIV to standard care in the setting of ARDS did not reduce the rate of endotracheal intubation (absolute risk reduction (RR) 13.5%, 95% confidence interval (CI) -5.2% to 31.3%), and had no effect on ICU survival (absolute RR 4.8%, 95% CI -12.8% to 22.1%). However, the trial results were significantly heterogeneous. Thus, current evidence suggests that patients with ARDS are unlikely to have any significant benefits on outcome when NIV is added to standard therapy. However, this analysis is limited by the presence of significant heterogeneity; hence large randomized controlled trials are required to settle this issue.

Study Objective: s: To analyze the perception of sexual content (PSC) of tobacco advertisements and its potential impact on the process of smoking in adolescents., Design, Participants, and Setting: A questionnaire was administered to 1,186 adolescents at the National Institute of Respiratory Diseases in Mexico City to determine the PSC. In addition, age, gender, susceptibility, receptivity, parental smoking and education, anxiety, depressive symptoms, school category, and grade were determined., Interventions and Measurements: The images of two advertisements were projected in color onto a screen. One of the images had unquestionable sexual content. The impact of the images was evaluated at the same time in the questionnaire., Results: Forty-one percent of participants were nonsmokers (25% nonsusceptible and 16% susceptible), whereas 59% were smokers (47% experimenters and 12% established). Sixty-six percent were receptive to promotions of the tobacco companies. Seventy-two percent perceived sexual contents in the advertisements. A logistic regression model showed that receptivity (odds ratio [OR], 2.1; 95% confidence interval [CI], 1.3 to 3.4), minimal PSC (OR, 2.6; 95% CI, 1.7 to 4.0), and high PSC (OR, 4.4; 95% CI, 2.4 to 8.0) were significantly associated with the status of smokers, whether experimenters or established. The strongest association was found with established smokers. Further analysis showed that male gender was significantly associated with high levels of PSC., Conclusions: These results show that a high percentage of adolescents perceived sexual content in the tobacco advertisement, which, independent of the subject's receptivity, plays a role in the process of smoking, especially in male adolescents.