Eureka: objective assessment of the empty pelvis syndrome to measure volumetric changes in pelvic dead space following pelvic exenteration.

BACKGROUND: Large tissue defects following pelvic exenteration (PE) fill with fluid and small bowel, leading to the empty pelvis syndrome (EPS). EPS causes a constellation of complications including pelvic sepsis and reduced quality of life. EPS remains poorly defined and cannot be objectively measured. Pathophysiology of EPS is multifactorial, with increased pelvic dead space potentially important. This study aims to describe methodology to objectively measure volumetric changes relating to EPS. METHODS: The true pelvis is defined by the pelvic inlet and outlet. Within the true pelvis there is physiological pelvic dead space (PDS) between the peritoneal reflection and the inlet. This dead space is increased following PE and is defined as the exenteration pelvic dead space (EPD). EPD may be reduced with pelvic filling and the volume of filling is defined as the pelvic filling volume (PFV). PDS, EPD, and PFV were measured intraoperatively using a bladder syringe, and Archimedes' water displacement principle. RESULTS: A patient undergoing total infralevator PE had a PDS of 50 ml. A rectus flap rendered the pelvic outlet watertight. EPD was then measured as 540 ml. Therefore there was a 10.8-fold increase in true pelvis dead space. An omentoplasty was placed into the EPD, displacing 130 ml; therefore, PFV as a percentage of EPD was 24.1%. CONCLUSIONS: This is the first reported quantitative assessment of pathophysiological volumetric changes of pelvic dead space; these measurements may correlate to severity of EPS. PDS, EPD, and PFV should be amendable to assessment based on perioperative cross-sectional imaging, allowing for potential prediction of EPS-related outcomes.

Adding to her woes: child bride's higher risk of hypertension at young adulthood.

BACKGROUND: Child marriage is associated with various adverse socio-economic and pregnancy outcomes. However, there remains a dearth of research on the long-term health implications of child marriage. As such, this study sought to expand upon the growing literature on child marriage, specifically examining the associations between child marriage and hypertension during young adult age. METHODS: We obtained data of 5369 women aged 20-34 from the Tajikistan Demographic and Health Survey 2017. Using multivariable logistic regression framework, we estimated the adjusted odds in favor of being hypertensive for women who were married before the age of 18. We also explored the presence of several stressors to understand the role of probable medication factors. RESULTS: We found that the odds of being hypertensive for young adult women married before the age of 18 were 1.6 (95% confidence interval: 1.1-2.4) times that of those who were not. Likelihood of having stressors, such as pregnancy loss or child death, marital control and spousal violence, was found higher among child brides compared to their peers. CONCLUSIONS: Findings suggest that child marriage may increase the risk of hypertension among young adult women. This work reinforces recommendations by the United Nations to the end child marriage.

COVID-19 SAFETY MEASURES AND THEIR EFFECTS ON GAMBLING HABITS: AN INVESTIGATIVE STUDY.

This study looked at the way COVID-19 was starting to affect gambling during first six weeks of emergency actions. The following factors were evaluated: the economic effect of COVID-19 on internet gambling, according to COVID-19, psychological issues, addiction to drugs, and risky gambling habits and intentions. Online survey with cross-sectional data of 2015 gamblers was conducted, with a subsample of 1048 people who gambled online (age 18 and older). Numerous metrics of correlation and probability ratio analyses were performed. The Issue of Gambling Intensity Index's extremely dangerous gamblers and those who have gambled online are more likely to engage in gambling online, according to the outcomes, even though there was an obvious transition toward physical gaming. The most predicted indicators for high-risk gamblers on the internet were moderate to severe depression and anxiety, reduced work weeks, convincing themselves to gamble by COVID-19, gambling under the effects of alcohol or cannabis, and dangerous gambling motivations related to psychological disorders, such as gambling to relieve anxiety and depressive disorders, chasing gambling damages, and trying to make money from gambling. This research has validated numerous risk connections associated with gambling risk, psychological issues, and substance use reported in previous studies on the worldwide recession and upcoming COVID-19-related investigations. In contrast to many other inquiries, the current research considers each component comprehensively. It offers more information on the risk factors associated with online gambling throughout the epidemic.

Single-step antibiotic-mediated synthesis of kanamycin-conjugated gold nanoparticles for broad-spectrum antibacterial applications.

Widespread and irrational use of antibiotics results in the development of antibiotic-resistant bacteria. Thus, there is a need to develop novel antibacterial agents in order to replace conventional antibiotics and to increase the efficacy of already existing antibiotics by combining them with other materials. Herein, a single-step antibiotic-mediated synthesis of antibiotic-conjugated gold nanoparticles is reported. In this single-step method antibiotic Kanamycin, an aminoglycoside itself plays the role of reducing as well as capping agent by reducing gold salt into gold nanoparticles. The kanamycin-conjugated gold nanoparticles (Kan-AuNPs) were confirmed by UV-Visible spectroscopy and further physico-chemically characterized by various instrumental techniques. Synthesized Kan-AuNPs showed broad-spectrum antibacterial activity against Gram-positive Staphylococcus aureus as well as Gram-negative Escherichia coli bacterial strains. They are also found to be effective against Pseudomonas aeruginosa and pathogenic E. coli isolated from urinary tract infections (UTIs) patients, which are responsible to cause hospital-acquired infections like nosocomial, burn wound and UTIs. The minimum inhibitory concentration (MIC) of Kan-AuNPs is 50 µg ml-1 for S. aureus and E. coli, 125 µg ml-1 for P. aeruginosa and 100 µg ml-1 for E. coli isolated from UTIs patients. It is also evident that the MIC of Kan-AuNPs for antibacterial activity is lower as compared to antibiotic kanamycin alone for all bacterial strains. Hence, the one-step strategy of synthesis for Kan-AuNPs is a suitable strategy for fighting infectious bacterial strains in hospitals, healthcare and the pharmaceutical industry.

A multicenter prospective observational study on the use of type and screen method versus conventional type and crossmatch policy for pre-transfusion testing in the Indian population.

Despite knowing the benefits of the type and screen (TS) method in pre-transfusion testing (PTT), most transfusion centers in developing countries continue to be reluctant to adopt a TS strategy over the conventional type and antihuman globulin (AHG) crossmatch (TX) policy in their routine laboratory practice because of the cost of obtaining antibody screening reagents. To generate strong evidence, this multicenter, observational study was conducted in which we collected data prospectively over a 1-year period from six major blood centers in India. The primary objective of this study was to identify the discordance between TS and TX results. A secondary objective was to identify the allo-antibody specificity in patients with positive antibody detection tests. All patients with orders for red blood cell transfusion who met patient selection criteria were subjected to parallel testing by column agglutination technology (CAT) for both the antibody detection test (screen) using a commercial three-cell panel and for the AHG crossmatch. A total of 21,842 patients were tested. In 148 patients with incompatible crossmatches, samples from six patients gave negative results with the antibody detection test, whereas the antibody detection test was positive in samples from 118 patients among the 21,694 crossmatch-compatible cases. The TS approach achieved a positive percent agreement of 95.95 and was found to be significantly effective in preventing the transfusion of serologically incompatible blood. The risk associated with abbreviating the AHG crossmatch was found to be 0.009 percent. Most of the identified clinically significant alloantibodies were directed to Rh antigens (D>E>c>C>e), followed by anti-K and anti-M. This study has generated sufficient robust data for the Indian population by including patients from all major geographical areas of the country and concluded a satisfactory agreement level as well as non-inferiority to the current PTT policy. Therefore, TS policy can be implemented in developing countries with no compromise on blood safety, provided sufficient technical and infrastructural support are available.

Unconventional Transverse Transport above and below the Magnetic Transition Temperature in Weyl Semimetal EuCd_{2}As_{2}.

As exemplified by the growing interest in the quantum anomalous Hall effect, the research on topology as an organizing principle of quantum matter is greatly enriched from the interplay with magnetism. In this vein, we present a combined electrical and thermoelectrical transport study on the magnetic Weyl semimetal EuCd_{2}As_{2}. Unconventional contribution to the anomalous Hall and anomalous Nernst effects were observed both above and below the magnetic transition temperature of EuCd_{2}As_{2}, indicating the existence of significant Berry curvature. EuCd_{2}As_{2} represents a rare case in which this unconventional transverse transport emerges both above and below the magnetic transition temperature in the same material. The transport properties evolve with temperature and field in the antiferromagnetic phase in a different manner than in the paramagnetic phase, suggesting different mechanisms to their origin. Our results indicate EuCd_{2}As_{2} is a fertile playground for investigating the interplay between magnetism and topology, and potentially a plethora of topologically nontrivial phases rooted in this interplay.

Genome-wide integrated analysis of miRNA and mRNA expression profiles to identify differentially expressed miR-22-5p and miR-27b-5p in response to classical swine fever vaccine virus.

The present study was conducted to identify the differentially expressed miRNAs (DE miRNAs) in the peripheral blood mononuclear cells of crossbred pigs in response to CSF vaccination on 7 and 21 days of post vaccination as compared to unvaccinated control (0 dpv). Simultaneously, set of miRNA was predicted using mRNA seq data at same time point. The proportion of CD4-CD8+ and CD4+CD8+ increased after vaccination, and the mean percentage inhibition was 86.89% at 21 dpv. It was observed that 22 miRNAs were commonly expressed on both the time points. Out of predicted DE miRNAs, it was found that 40 and 35 DE miRNAs were common, obtained from miRNA seq analysis and predicted using mRNA seq data on 7 dpv versus 0 dpv and 21 dpv versus 0 dpv respectively. Two DE miRNAs, ssc-miR-22-5p and ssc-miR-27b-5p, were selected based on their log2 fold change and functions of their target genes in immune process/pathway of viral infections. The validations of DE miRNAs using qRT-PCR were in concordance with miRNA seq analysis. Two set of target genes, CD40 and SWAP70 (target gene of ssc-miR-22-5p) and TLR4 and Lyn (target gene of ssc-miR-27b-5p), were validated and were in concordance with results of RNA seq analysis at a particular time point (except TLR4). The first report of genome-wide identification of differentially expressed miRNA in response to live attenuated vaccine virus of classical swine fever revealed miR-22-5p and miR-27b-5p were differentially expressed at 7 dpv and 21 dpv.

Physics of suction cups.

We have developed a theory of air leakage at interfaces between two elastic solids with application to suction cups in contact with randomly rough surfaces. We present an equation for the airflow in narrow constrictions which interpolates between the diffusive and ballistic (Knudsen) air-flow limits. To test the theory, we performed experiments using two different suction cups, made from soft polyvinylchloride (PVC), in contact with sandblasted polymethylmethacrylate (PMMA) plates. We found that the measured time to detach (lifetime) of the suction cups was in good agreement with theory, except for surfaces with a root-mean-square (rms) roughness below ≈1 µm, where diffusion of plasticizer from the PVC to the PMMA surface caused blockage of critical constrictions. The suction cup volume, stiffness, and elastic modulus have a huge influence on the air leakage and hence the failure time of the cups. Based on our research we propose an improved biomimetic design of suction cups that could show improved failure times with varying degrees of roughness under dry and wet environments.

Rolling friction of elastomers: role of strain softening.

We study the temperature and velocity dependency of rolling friction. Steel and PMMA cylinders are rolled on sheets of nitrile butadiene rubber (NBR), with and without filler, and fluoroelastomer (FKM) with filler. Measurements of the rolling friction are performed for temperatures between -40 °C and 20 °C, and for velocities between 5 µm s-1 and 0.5 cm s-1. For the unfilled NBR, a smooth rolling friction master curve is obtained using the bulk viscoelastic frequency-temperature shift factor aT. For the filled rubber compounds, a small deviation from the bulk viscoelastic shift factor is observed at low temperatures. The experimental data are analyzed using an analytical theory of rolling friction. For the filled compounds, good agreement with theory is obtained when strain softening is included, which increases the rolling friction by a factor ∼2 for the filled FKM and ∼3 for the filled NBR compounds. For the unfilled NBR, the maximum of the rolling friction occurs at higher sliding speeds than predicted by the theory. We discuss the role of the adhesive (crack-opening) contribution to the rolling friction, and the role of frozen-in elastic deformations as the rubber is cooled down below the rubber glass transition temperature.

Accurate calculation of zero point energy from molecular dynamics simulations of liquids and their mixtures.

The two-phase thermodynamic (2PT) method is used to compute the zero point energy (ZPE) of several liquids and their mixtures. The 2PT method uses the density of states (DoS), which is computed from the velocity autocorrelation (VAC) function obtained from a short classical molecular dynamics trajectory. By partitioning the VAC and the DoS of a fluid into solid and gaslike components, quantum mechanical corrections to thermodynamical properties can be computed. The ZPE is obtained by combining the partition function of the quantum harmonic oscillator with the vibrational part of the solidlike DoS. The resulting ZPE is found to be in excellent agreement with both experimental and ab initio results. Solvent effects such as hydrogen bonding and polarization can be included by the utilization of ab initio density functional theory based molecular dynamics simulations. It is found that these effects significantly influence the DoS of water molecules. The obtained results demonstrate that the 2PT model is a powerful method for efficient ZPE calculations, in particular, to account for solvent effects and polarization.

Mercury and Organochlorines in the Terrestrial Environment of Schirmacher Hills, Antarctica.

We report the levels of mercury (Hg) and nine organochlorine pesticides [OCPs: α-hexachlorocyclohexane (HCH), ß-HCH, γ-HCH, δ-HCH, α-Endosulfan, ß-Endosulfan, Endosulfan sulfate, p,p'-dichlorodiphenyldichloroethylene (DDE) and p,p'-dichlorodiphenyldichloroethane (DDD)] in the terrestrial environment (moss and soil) and water (OCPs only) of Schirmacher Hills, Antarctica. This area has never been studied for mercury and not for OCPs since 1988. Mercury levels in moss, 66 ± 37 ng/g dry weight (dw), are comparable to other Antarctic locations. Levels of α-HCH, below detection to 4.48 ng/g dw, and p,p'-DDE, below detection to 31 ng/g dw, in mosses are lower or marginally higher than other Antarctic locations. No other OCPs were detected in moss. None of the OCPs were detected in soil. This suggests that Schirmacher Hills may be considered as a background site with respect to mercury and analyzed OCPs, despite the operation of two old research stations (Maitri, est. 1989, and Novolazarevskaya, est. 1961) in the region.

Genome-wide association studies of placebo and duloxetine response in major depressive disorder.

We investigated variants associated with treatment response in depressed patients treated with either the antidepressant duloxetine or placebo using a genome-wide approach. Our sample (N=391) included individuals aged 18-75 years, diagnosed with major depressive disorder and treated with either duloxetine or placebo for up to 8 weeks. We conducted genome-wide associations for treatment response as operationalized by percentage change in Montgomery-Åsberg Depression Rating Scale score from baseline, as well as mixed models analyses across five time points. In the placebo-treated subsample (N=205), we observed a genome-wide association with rs76767803 (ß=0.69, P=1.25 × 10-8) upstream of STAC1. STAC1 rs76767803 was also associated with response using mixed model analysis (χ2=3.95; P=0.001). In the duloxetine-treated subsample (N=186), we observed suggestive associations with ZNF385D (rs4261893; ß=-0.46, P=1.55 × 10-5), NCAM1 (rs2303377; ß=0.45, P=1.76 × 10-5) and MLL5 (rs117986340; ß=0.91, P=3.04 × 10-5). Our findings suggest that a variant upstream of STAC1 is associated with placebo response, which might have implications for treatment optimization, clinical trial design and drug development.

Efficient syntheses and anti-cancer activity of xenortides A-D including ent/epi-stereoisomers.

A one-pot, two-step, total synthesis of naturally occurring xenortides A, B, C and D, (Xens A-D) isolated from the bacterium Xenorhabdus nematophila, and an entire complementary set of stereoisomers, has been achieved. Compounds were synthesized utilizing an isocyanide-based Ugi 4-CR followed by facile N-Boc deprotection. The reaction sequence took advantage of the chiral pool of N-Boc protected amino acids (l-Leu/Val and d-Leu/Val) with aryl isocyanides, phenyl acetaldehyde and methylamine giving the desired Xens A-D (A and B >98% ee) and all subsequent stereoisomers in reasonable yields upon deprotection followed by separation of diastereomers. Also, detailed mechanistic insights for diastereoselectivity of (-)-Xen A, as a model in the Ugi 4-CR, has been described. Moreover, for the first time, this focused library was screened for cytotoxicity against a panel of epithelial cancer cell lines as well as normal cell lines with an MTT proliferation assay. The structure-activity relationship (SAR) study demonstrated that tryptamides Xen B and D were more active than phenylethylamides Xen A and C. Furthermore, (-)-Xen B (IC50 = 19-25 µM) and ent-(+)-Xen D (IC50 = 21-26 µM) gave the highest cytotoxicity and they were also found to be non-toxic toward normal cells. Importantly, the SAR results indicate that the stereochemistry at C8 and C11 in (-)-Xen B and ent-(+)-Xen D play a critical role in cytotoxic activity.

Rubber friction: The contribution from the area of real contact.

There are two contributions to the friction force when a rubber block is sliding on a hard and rough substrate surface, namely, a contribution Fad = τf A from the area of real contact A and a viscoelastic contribution Fvisc from the pulsating forces exerted by the substrate asperities on the rubber block. Here we present experimental results obtained at different sliding speeds and temperatures, and we show that the temperature dependency of the shear stress τf, for temperatures above the rubber glass transition temperature Tg, is weaker than that of the bulk viscoelastic modulus. The physical origin of τf for T > Tg is discussed, and we propose that its temperature dependency is determined by the rubber molecule segment mobility at the sliding interface, which is higher than in the bulk because of increased free-volume effect due to the short-wavelength surface roughness. This is consistent with the often observed reduction in the glass transition temperature in nanometer-thick surface layers of glassy polymers. For temperatures T < Tg, the shear stress τf is nearly velocity independent and of similar magnitude as observed for glassy polymers such as PMMA or polyethylene. In this case, the rubber undergoes plastic deformations in the asperity contact regions and the contact area is determined by the rubber penetration hardness. For this case, we propose that the frictional shear stress is due to slip at the interface between the rubber and a transfer film adsorbed on the concrete surface.

Advances in enhanced sampling along adaptive paths of collective variables.

Study of complex activated molecular transitions by molecular dynamics (MD) simulation can be a daunting task, especially when little knowledge is available on the reaction coordinate describing the mechanism of the process. Here, we assess the path-metadynamics enhanced sampling approach in combination with force field and ab initio [density functional theory (DFT)] MD simulations of conformational and chemical transitions that require three or more collective variables (CVs) to describe the processes. We show that the method efficiently localizes the average transition path of each process and simultaneously obtains the free energy profile along the path. The new multiple-walker implementation greatly speeds-up the calculation, with an almost trivial scaling of the number of parallel replicas. Increasing the dimensionality by expanding the set of CVs leads to a less than linear increase in the computational cost, as shown by applying the method to a conformational change in increasingly longer polyproline peptides. Combined with DFT-MD to model acid (de-)protonation in explicit water solvent, the transition path and associated free energy profile were obtained in less than 100 ps of simulation. A final application to hydrogen fuel production catalyzed by a hydrogenase enzyme showcases the unique mechanistic insight and chemical understanding that can be obtained from the average transition path.

Adhesion between rubber and glass in dry and lubricated condition.

We study the adhesion between differently processed glass and filled bromobutyl rubber in dry conditions, in water, and in silicone oil. The boundary line between contact and non-contact in adhesion experiments can be considered as a mode I crack, and we show that viscoelastic energy dissipation, close to the opening (or closing) crack tip and surface roughness, strongly affects the work of adhesion. We observe strong adhesion hysteresis and, in contrast to the Johnson-Kendall-Roberts theory prediction for elastic solids, this results in a pull-off force (and work of adhesion) which depends on the loading force and contact time. In particular, for the system immersed in water and silicone oil, we register very weak adhesive bonding. For glass ball with baked-on silicone oil, the pull-off force is nearly independent of the contact time, but this is not observed for the unprocessed glass surface.

RNA Seq analysis for transcriptome profiling in response to classical swine fever vaccination in indigenous and crossbred pigs.

In present investigation, differential expression of transcriptome after classical swine fever (CSF) vaccination has been explored at the cellular level in crossbred and indigenous (desi) piglets. RNA Sequencing by Expectation-Maximization (RSEM) package was used to quantify gene expression from RNA Sequencing data, and differentially expressed genes (DEGs) were identified using EBSeq, DESeq2, and edgeR softwares. After analysis, 5222, 6037, and 6210 common DEGs were identified in indigenous post-vaccinated verses pre-vaccinated, crossbred post-vaccinated verses pre-vaccinated, and post-vaccinated crossbred verses indigenous pigs, respectively. Functional annotation of these DEGs showed enrichment of antigen processing-cross presentation, B cell receptor signaling, T cell receptor signaling, NF-κB signaling, and TNF signaling pathways. The interaction network among the immune genes included more number of genes with greater connectivity in vaccinated crossbred than the indigenous piglets. Higher expression of IRF3, IL1ß, TAP1, CSK, SLA2, SLADM, and NF-kB in crossbred piglets in comparison to indigenous explains the better humoral response observed in crossbred piglets. Here, we predicted that the processed CSFV antigen through the T cell receptor signaling cascade triggers the B cell receptor-signaling pathway to finally activate MAPK kinase and NF-κB signaling pathways in B cell. This activation results in expression of genes/transcription factors that lead to B cell ontogeny, auto immunity and immune response through antibody production. Further, immunologically important genes were validated by qRT-PCR.

Role of Preload in Adhesion of Rough Surfaces.

Adhesion between glass and bromobutyl and polydimethylsiloxane elastomers is investigated. We show that viscoelastic energy dissipation close to the opening (or closing) crack tip, and surface roughness, strongly affect the work of adhesion. We observe strong adhesion hysteresis and we show, in contrast to the Johnson-Kendall-Roberts theory prediction for elastic solids, that this results in a pull-off force, and effective work of adhesion to be dependent on the maximum loading force.