Background and Purpose: Cardiovascular disease (CVD) affects up to half of the patients with chronic obstructive pulmonary disease (COPD), which exerts deleterious impact on health outcomes and survivability. Vascular endothelial dysfunction marks the onset of cardiovascular disease. The present study examined the effect of a potent NADPH Oxidase (NOX) inhibitor and free-radical scavenger, apocynin, on COPD-related CVD. Experimental Approach: Male BALB/c mice were exposed to either room air (Sham) or cigarette smoke (CS) generated from 9 cigarettes per day, 5 days a week for up to 24 weeks with or without apocynin treatment (5 mg·kg-1·day-1, intraperitoneal injection). Key Results: Eight-weeks of apocynin treatment reduced airway neutrophil infiltration (by 42%) and completely preserved endothelial function and endothelial nitric oxide synthase (eNOS) activity against the oxidative insults of CS exposure. These preservative effects were maintained up until the 24-week time point. 24-week of apocynin treatment exhibited marked benefits on airway inflammation (reduced infiltration of macrophage, neutrophil and lymphocyte) and lung function decline (hyperinflation), and prevented airway collagen deposition by CS exposure. Conclusion and Implications: Limiting NOX activity may slow COPD progression and lower CVD risk, particularly when signs of oxidative stress become evident.

Since aluminum alloys have the low melting point and high thermal conductivity, friction stir weld (FSW)has been successfully used in the aerospace industry as an alternative to traditional welding methods. In the service of FSWed structures, the residual stress and external load would result in a secondary deformation and residual stress redistribution. Therefore, it is necessary to investigate the effect of residual stress on the FSWed fatigue responses. This paper studied the fatigue crack growth behavior of 2024-T3 and 7075-T6 homogeneous and dissimilar FSWed joints. The finite element model was built to calculate the fatigue crack growth rate of FSWed specimen, and the results were compared with the experiment results. It was demonstrated that residual stress significantly affected on the fatigue crack growth rate. Tensile residual stress promoted the crack growth, and it offset the decrease of fatigue crack growth rate by grain refinement. The numerical results also indicated that the longitudinal residual stress showed the greatest effect on the crack deflection. Under the same welding speed, the fatigue crack growth rate of 2024 increased with the increasing rotational speed. For the same rotational speed, the fatigue crack propagation rate of 7075 decreased with the increasing welding speed.

To prevent the problem of test chance in solid wood furniture joint strength testing and reduce the destructive test and test costs, the finite element method (FEM) and ABAQUS software were used to establish a cohesion model, which can predict the pull-out strength of L-shaped and T-shaped members using round tenon joints in the presence of adhesives. In addition, the effect of the diameter of the round tenon on the pull-out strength of the joints was investigated. The simulation results revealed that with the increase in the diameter, the pull-out strength of the double round tenon joint increased, indicating that the diameter of the round tenon is a key factor that affects the pull-out strength of joints. Furthermore, errors between the finite element analysis (FEA) results and the average test results of two members with different diameters were less than 15%, and the cloud diagrams of the structural stresses were consistent with the test results. Therefore, the established FEM is confirmed to be accurate and suitable for predicting the pull-out strength of designed round tenon joints in solid wood furniture. This paper provides new ideas and methods for the non-destructive testing of the structural-mechanical properties of solid wood furniture.

This is an extremely rare case of congenital lumbosacral junction kyphosis (CLSJK) in a 40-year-old woman due to S1-S2 hemivertebra. Performing surgery has helped to improve neurological disturbances but not completely after 1 year of follow-up.

Primary intramedullary spinal cord lymphoma (PISCL) is a rare cause of myelopathies. As PISCL is often underrecognized, delaying appropriate treatment, we sought to describe its presentation. We report two clinical cases of pediatric patients. The diagnosis of PISCL must be considered in a patient with symptoms of acute myelopathies.

Objective- To assess the potential effect of Chorionic Villus Sampling (CVS) on placental perfusion by examining change in uterine artery pulsatility index (UtA-PI) between first and second trimesters of pregnancy. Design- It was a prospective observational study conducted between August 2017 to January 2019. Setting- Department of Obstetrics and Gynecology, Maulana Azad Medical College, New Delhi. Study Sample- Twenty-one singleton pregnancies where CVS was planned were included in the case group whereas forty-two low-risk singleton pregnancies with no invasive testing constituted the control group. Pregnancy resulting in miscarriage or, termination of pregnancy for affected fetus, or demise of fetus beyond 23 weeks or subsequent detection of anomaly or chromosomal defects were excluded. Methods- Dating scan along with first and second trimester UtA doppler study was done at 11-13+6 weeks and 22-24+6 weeks respectively using an ultrasound machine with 2-5 MHz trans-abdominal transducer. Main Outcome Measures- The primary outcome was to evaluate the change in UtA-PI between first and second trimesters of women undergoing CVS and comparing it with control group. Results- The difference between first and second trimester mean PI of case and control group were 0.71± 0.35 and 0.44± 0.45 respectively. This difference of fall in PI between the two groups was statistically significant (p= 0.010) with the change being higher in the CVS group. Conclusions- CVS does not cause undesirable effect on the UtA doppler. UtA doppler being a predictive marker of development of pre-eclampsia or FGR; this study affirms the safety of CVS in experienced hands.

Understanding the evolutionary consequences of anthropogenic change is imperative for estimating long-term species resilience. While contemporary genomic data can provide us with important insights into recent demographic histories, investigating past change using present genomic data alone has limitations. In comparison, temporal genomics studies, defined herein as those that incorporate time series genomic data, leverage museum collections and repeated field sampling to directly examine evolutionary change. As temporal genomics is applied to more systems, species, and questions, best practices can be helpful guides to make the most efficient use of limited resources. Here, we conduct a systematic literature review to synthesize the effects of temporal genomics methodology on our ability to detect evolutionary changes. We focus on studies investigating recent change within the past 200 years, highlighting evolutionary processes that have occurred during the past two centuries of accelerated anthropogenic pressure. We first identify the most frequently studied taxa, systems, questions, and drivers, before highlighting overlooked areas where further temporal genomic studies may be particularly enlightening. Then, we provide guidelines for future study and sample designs while identifying key considerations that may influence statistical and analytical power. Our aim is to provide recommendations to a broad array of researchers interested in using temporal genomics in their work.

Summary 1. Knowledge of the relationship between biodiversity and environmental factors provides insight into patterns of species richness and distribution in limnetic ecosystems. To this end, this study was conducted to test the effect of limnological characteristics of reservoirs on bird species richness and distribution along an age gradient of limnetic ecosystems in Tigray National Regional State. 2. To evaluate the relationship between limnological characteristics of reservoirs and patterns of bird species richness and distribution, six physicochemical variables, three morph-edaphic and biological variables were recorded for 35 reservoirs and analyzed by multivariate statistical techniques. Species richness data was subjected to a multiple regression analysis at limnological variables, biological variables and age of the reservoirs in order to investigate the most important explanatory factors influencing avian species richness and their distribution using Redundancy analysis (RDA). 3. 85 bird species from 54 genera, 25 families and 15 bird orders were recorded, with mean species richness 14.236.72 (mean  standard deviation) per reservoir. Five of these species are near threatened (NT) while other two species fall under critically endangered (CR) and vulnerable (VU) conservation status designations, respectively. Bird species richness was positively correlated with surface area of reservoirs. The RDA analysis identified two significant RDA axis and 34.4% of the variation in species richness is explained by environmental variation (R2adj = 0.34375; P < 0.001). Generally, water chemistry appears to play only a minor part in affecting bird species richness in reservoir in Tigray, Northern Ethiopia. However, chemical variables may be helpful to distinguish between used and unused sites for some species. 4. The result provides an important insight on the ecological relationship between waterbirds species richness and limnological characteristics of reservoirs. And plays a role towards strengthening our knowledge on aquatic bird ecology and natural history of African Eurasian Migratory waterbirds.

Unclassified hepatic hepatocellular adenoma in men is still a challenging entity regarding clinical manifestations, diagnosis, and treatment as in our case. It still need more investigations determining their characteristics, risk of complications and malignant transformation in order to improve their therapeutic care.

Self-sufficient cytochromes P450 of the sub-family CYP116B have gained great attention in biotechnology due to their ability to catalyze challenging reactions towards a wide range of organic compounds without the need of a separate reductase partner. However, these P450s are often unstable in solution and their activity is limited to short reaction time. As the isolated heme domain of CYP116B5 has been shown to work as a peroxygenase with H2O2 without the need for expensive NAD(P)H, in this work protein engineering was used to generate a chimeric enzyme (CYP116B5-SOX), in which the native reductase domain is replaced by a monomeric sarcosine oxidase (MSOX) that is able to produce H2O2 with a controlled and continuous release in time. The full-length form enzyme (CYP116B5-fl) is expressed and characterized for the first time, allowing a detailed comparison to both the isolated heme domain (CYP116B5-hd) and CYP116B5-SOX. The catalytic activity of the three forms of the enzyme was studied using p-nitrophenol as substrate, and adding NADPH (CYP116B5-fl), H2O2 (CYP116B5-hd) and sarcosine (CYP116B5-SOX) as direct or indirect source of electrons. CYP116B5-SOX outperforms CYP116B5-fl by 10 folds and CYP116B5-hd by 3 folds, in terms of p-nitrocatechol produced per mg of enzyme per minute. CYP116B5-SOX represents an optimal model to exploit CYP116B5 and the same protein engineering approach could be used for P450s of the same class.

A document by Dragos Brezeanu. Click on the document to view its contents.

Variation among host-associated microbiomes is well documented across species, populations, and individuals. Understanding relationships between host-genetic and microbial variation is important for predicting coevolutionary dynamics between hosts and their microbiota and is also biomedically relevant to understanding why some humans are more susceptible to chronic disorders like Inflammatory Bowel Diseases (IBD). Unfortunately, the relative contributions of host genetics and the environment to microbiome variation have been difficult to study. Human research shows that genetic variation influences microbiome differences but confounding environmental effects cannot be controlled experimentally. Isogenic laboratory models can be used in controlled environments but often focus on large-effect mutations and do not recapitulate genetic variation observed in nature. Thus, although important factors impacting the microbiome have been identified, few studies have tested for the direct influence of natural host-genetic variation on microbiome differences within a controlled environment. To address this, we performed a common garden experiment using laboratory lines of genetically divergent populations of threespine stickleback fish - an outbred model organism commonly used for determining the genetic basis of complex traits in the context of natural genetic variation. Using germ-free derivation of divergent lines and hybrids between them in this experimental framework, we detected a clear, positive association between stickleback genetic dissimilarity and microbiome dissimilarity. With RAD-seq data we identified regions of the genome that contributed most significantly to this relationship. Importantly, we also highlight that heritable morphological traits like body size -when correlated with microbiome composition - need consideration in future host-associated microbiome studies.

The global urban population is expected to increase by 2.5 billion people over the next 30 years. Yet the doubling of urban landscapes in the last decades have already led to habitat loss and concomitant impacts to biodiversity. Nonetheless urban landscapes remain important for wildlife, and global syntheses have revealed that wealthy urban areas house more biodiversity, a ‘luxury effect’. We researched some of the mechanisms for the luxury effect for urban black-tailed deer, a species of increasing concern in urban landscapes across the northwestern Nearctic. We satellite collared twenty deer in an urban landscape in British Columbia, Canada, with high-resolution fix rates. We used generalized models in an information-theoretic framework to weigh evidence for competing hypotheses about the role of tree cover, productivity, public green spaces, and wealth in explaining deer selection. Wealth, manifesting as housing lot size, emerged as the dominant predictor of deer space-use, which is highly concentrated into very small home-ranges. Other landscape elements stemming from affluence, including golf courses and parklands, were also strongly selected by deer. We show post-colonization landscape conversion from dry semi-arid savannah to well-watered high-productivity landscapes is supporting deer, with ramifications for the rest of the biotic community. With urban landscapes becoming an increasingly important for biodiversity conservation, understanding these mechanisms can help to promote wildlife-human coexistence.

Historically, studies have examined how local habitat, resources and species interactions influence community structure in stream ecosystems. Increasingly, though, attention has turned to understanding how regional factors (e.g. dispersal) interact with local conditions to influence communities. Often dispersal of organisms occurs in spatially constrained habitats, which can drastically influence community assembly. Dendritic networks are an example, and have a branching spatial configuration with some branches of the system more connected to others, making dispersal easier, while other locations are more isolated. As interest in multi-scale community assembly mechanisms has increased, less work has focused on the relationship between community assembly and ecosystem processes. Here, we sought to understand how consumer-resource interactions unfold in river networks. We predicted that stream network location would mediate detritivore (shredder) richness and abundance, and in turn would be associated with a shift in decomposition of organic matter (leaf litter). To examine this, we manipulated leaf litter species in isolated (headwaters) and connected (mainstem) stream reaches. We found that shredder richness and abundance were influenced by both leaf litter quality and network location. Headwater environments supported a stronger consumer-resource relationship, and shredder communities were further richer and more abundant. This was not the case in mainstem locations. In these relatively harsher environments, we offer that shredders did not appear to be actively feeding on the resources, but rather utilizing leaf litter more for habitat. Our results suggest river network position has important implications for how ecosystem function changes across spatially constrained environments.

Protein-protein and protein-peptide interactions (PPIs and PPepI) belong to a similar category of interactions yet seemingly subtle differences exist among them. To characterize differences between protein-protein (PPI) and protein-peptide interactions (PPepI), we have focussed on two important class of residues- hotspot and anchor residues. Using implicit solvation-based free-energy calculations, a very large-scale alanine scanning has been performed on benchmarking dataset, consisting of over 5500 interface residues. The differences in the two categories are more pronounced, if the hotspot data is divided into three distinct types, namely - weak hotspots (having binding free energy loss upon Ala mutation, ΔΔG, 2-10 kcal/mol), moderate hotspots (ΔΔG, 10-20 kcal/mol) and strong hotspots (ΔΔG ≥ 20 kcal/mol). The analysis suggests that for PPI, weak hotspots are predominantly populated by polar and hydrophobic residues. The distribution shifts towards charged and polar residues for moderate hotspot and charged residues (principally Arg) are overwhelmingly present in the strong hotspot. In contrast, in the PPepI dataset, the distribution shifts from predominantly hydrophobic and polar (in the weak type) to almost similar preference for polar, hydrophobic and charged residues (in moderate type) and finally the charged residue (Arg) and Trp are mostly occupied in the strong type. In anchor residue class of both categories, the preferred residues are Arg, Tyr and Leu, possesing bulky side chaing and which also strike a delicate balance between side chain flexibility and rigidity. The present knowledge should aid in effective design of biologics, when augmentation or disruption of PPI are substituted with the peptide-based mimics.

Nucleoside diphosphate kinase (NDK) protein of Porphyromonas gingivalis (P. gingivalis) plays an important role in immune evasion and apoptosis inhibition of host cells. It has the potential to cause cancer, however, its structure has not yet been determined. Here we established a 3D structure of P.gingivalis NDK protein using an in-silico approach and performed the structural analysis of the model protein. 3D structure of NDK was predicted through homology modelling using modeller. Structural domains predicted for the model belongs to the NDK family. Structural homology was further confirmed by functional annotation of the model which includes ATP binding and nucleotide diphosphate kinase function, indicating that it is an NDK protein. Structural alignment of the putative model shows the alpha-beta folds are structurally conserved among NDK from prokaryotes and eukaryotes. The structure-based phylogenetic analysis depicts a significant evolutionary relationship of the modeled protein with the NDK of prokaryotes. Furthermore, the MD simulation approach stabilized the model structure and provides a thermo-stable protein structure that can be used as a therapeutic target for further studies.

Formulas to calculate multivector exponentials in a basis-free representation and orthonormal basis are presented for an arbitrary Clifford geometric algebra , . The formulas are based on the analysis of roots of characteristic polynomial of a multivector. Elaborate examples how to use the formulas in practice are presented. The results are generalised to arbitrary functions of multivector and may be useful in the quantum circuits or in the problems of analysis of evolution of the entangled quantum states.

The existing cocrystal preparation of CL-20 is difficult to form large-scale production. And new ligands and processes are needed to change the current situation. Molecular dynamics simulation was performed on CL-20/DNDA7(3.5-dinitro-3.5-diazaheptane) and CL-20/HMX cells. Radial function analysis, Hirshfeld surface comparison analysis, and growth simulation analysis were performed on the simulation results. The results show that: Decreasing the temperature is beneficial to increase the strength of the hydrogen bond of CL-20/DNDA7 cocrystal, especially at 203K; The maximum initiation N-N bond length is smaller than that of CL-20 crystal and CL-20/HMX cocrystal; The hydrogen bond interaction of CL-20/HMX cocrystal is lower than that of CL-20/DNDA5 and CL-20/DNDA7 cocrystal. Decreasing the temperature is beneficial to cocrystal formation. The sensitivity of CL-20/DNDA7 is lower than that of CL-20 and CL-20/HMX cocrystal. CL-20 is more likely to form hydrogen bonds with linear nitroamine explosives than CL-20/HMX. Keywords: cocrystal; Molecular dynamics simulation; hydrogen bond interaction; sensitivity

We present a rare case of anagrelide-induced pericardial effusion that is presented with tamponade physiology in a patient with essential thrombocythemia. After cautiously weighing the risks and benefits of further invasive interventions following an unsuccessful pericardiocentesis, the decision was to stop anagrelide while managing the pericardial effusion medically.

Background  Indocyanine green (ICG) fluoresces in the near infra-red (NIR) spectrum. It is widely used in adult oncological surgery for identification of tumor margins and lymph node sampling. However, its use in the pediatric population is limited. This is the first study in children to assess its feasibility in minimally invasive surgery (MIS) for oncological disease Methods  This was an open label, prospective, single centre, feasibility study recruiting consecutive patients eligible for MIS tumor resection. ICG was injected intravenously at induction of anaesthesia and/or intra-parenchymally for patients having tumor nephrectomy. Patient demographics, intraoperative appearances, nodal fluorescence, post-operative histopathology, and surgeon Likert ratings were collected. Results Seventeen patients conformed to the inclusion criteria. Five had a Wilms tumor, 4 had lung metastases and 8 had other tumors (neuroblastoma, inflammatory myofibroblastic tumor, ganglioneuroma, phaeochromocytoma, adrenal tumor). For those having lymph node sampling, a median of 8(3-9) nodes were sampled. Lung metastases were easily identifiable, and all had negative margins. Tumors containing viable disease fluoresced and were completely resected, whilst benign and heavily treated tumors were afluorescent. There were no adverse events relating to ICG. Conclusion  Based on this small sample, injection of ICG during induction of anaesthesia is safe and effective in showing tumor margins in patients who have had little or no neoadjuvant chemotherapy as well as in metastectomy in Wilms and osteosarcoma. Its use in renal tumor resection results in adequate nodal sampling. Further studies are needed to confirm these preliminary results.

Miliary tuberculosis (MTB) is a rare, disseminated, and active form of tuberculosis caused by Mycobacterium tuberculosis bacilli. It is mostly seen in immune-compromised patients but is sometimes reported in immune-competent hosts. We reported a 40-year-old immune-competent patient who presented with pyrexia of unknown origin.

We are hopeful that CTFR modulation does have a positive impact of bone health, but we have concerns about this study design being used to support the hypothesis.

December 12, 2022To the Editors of the Journal of Cardiovascular Electrophysiology:Please find the editorial for manuscript ID JCE-22-0730.R2 attached.Thank you,Steven Zweibel MDTitle: What We Don’t Know Might Harm Our Patients: AF Detection Utilizing a Single Chamber ICDShort Title: Atrial Arrhythmia Detection in Single Chamber ICD PatientsSteven L. Zweibel MD, FACC, FHRS

A rational multiscale method is proposed for selecting an economical and sustainable solvent for the direct hydration of cyclohexene. At the molecular scale, liquid-liquid phase equilibrium was estimated using group contribution methods to rapidly screen the potential solvent candidates from a range of organics using a novel evaluation index. At the reactor scale, these candidates were experimentally investigated to pick out the solvents that could significantly improve the conversion, without introducing side reactions and deactivating the catalyst. At the process scale, the total annual cost and CO2 emission were calculated to evaluate the eco-efficiency. Using this new multiscale method, acetophenone was selected as an eco-efficient solvent from over 100 organics, resulting in the reduction of TAC by 7.8% and CO2 emission by 16.9% in the production process. Also, acetophenone led to the increase of cyclohexanol yield from 12.3% to 27.6% without the occurrence of side reactions or catalyst deactivation.