The surgical patient of yesterday, today, and tomorrow — a time-trend analysis based on a cohort of 8.7 million surgical patients

Background: Global healthcare delivery is challenged by the aging population and the increase in obesity and type 2 diabetes. The extent to which such trends affect the cohort of patients the authors surgically operate on remains to be elucidated. Comprising of 8.7 million surgical patients, the American College of Surgeons (ACS) National Surgical Quality Improvement Program (NSQIP) database can be analyzed to investigate the echo of general population dynamics and forecast future trends. Material and methods: The authors reviewed the ACS-NSQIP database (2008–2020) in its entirety, extracting patient age, BMI, and diabetes prevalence. Based on these data, the authors forecasted future trends up to 2030 using a drift model. Results: During the review period, median age increased by 3 years, and median BMI by 0.9 kg/m2. The proportion of patients with overweight, obesity class I, and class II rates increased. The prevalence of diabetes rose between 2008 (14.9%) and 2020 (15.3%). The authors forecast the median age in 2030 to reach 61.5 years and median BMI to climb to 29.8 kg/m2. Concerningly, in 2030, eight of ten surgical patients are projected to have a BMI above normal. Diabetes prevalence is projected to rise to 15.6% over the next decade. Conclusion: General population trends echo in the field of surgery, with the surgical cohort aging at an alarmingly rapid rate and increasingly suffering from obesity and diabetes. These trends show no sign of abating without dedicated efforts and call for urgent measures and fundamental re-structuring for improved future surgical care

Discovery and characterization of artifactual mutations in deep coverage targeted capture sequencing data due to oxidative DNA damage during sample preparation

As researchers begin probing deep coverage sequencing data for increasingly rare mutations and subclonal events, the fidelity of next generation sequencing (NGS) laboratory methods will become increasingly critical. Although error rates for sequencing and polymerase chain reaction (PCR) are well documented, the effects that DNA extraction and other library preparation steps could have on downstream sequence integrity have not been thoroughly evaluated. Here, we describe the discovery of novel C > A/G > T transversion artifacts found at low allelic fractions in targeted capture data. Characteristics such as sequencer read orientation and presence in both tumor and normal samples strongly indicated a non-biological mechanism. We identified the source as oxidation of DNA during acoustic shearing in samples containing reactive contaminants from the extraction process. We show generation of 8-oxoguanine (8-oxoG) lesions during DNA shearing, present analysis tools to detect oxidation in sequencing data and suggest methods to reduce DNA oxidation through the introduction of antioxidants. Further, informatics methods are presented to confidently filter these artifacts from sequencing data sets. Though only seen in a low percentage of reads in affected samples, such artifacts could have profoundly deleterious effects on the ability to confidently call rare mutations, and eliminating other possible sources of artifacts should become a priority for the research community.National Human Genome Research Institute (U.S.) (HG03067-05

Molecular insights into antibiotic resistance - how a binding protein traps albicidin

The worldwide emergence of antibiotic resistance poses a serious threat to human health. A molecular understanding of resistance strategies employed by bacteria is obligatory to generate less-susceptible antibiotics. Albicidin is a highly potent antibacterial compound synthesized by the plant-pathogenic bacterium Xanthomonas albilineans. The drug-binding protein AlbA confers albicidin resistance to Klebsiella oxytoca. Here we show that AlbA binds albicidin with low nanomolar affinity resulting in full inhibition of its antibacterial activity. We report on the crystal structure of the drug-binding domain of AlbA (AlbAS) in complex with albicidin. Both α-helical repeat domains of AlbAS are required to cooperatively clamp albicidin, which is unusual for drug-binding proteins of the MerR family. Structure-guided NMR binding studies employing synthetic albicidin derivatives give valuable information about ligand promiscuity of AlbAS. Our findings thus expand the general understanding of antibiotic resistance mechanisms and support current drug-design efforts directed at more effective albicidin analogs

Interface engineering of the photoelectrochemical performance of Ni-oxide-coated n-Si photoanodes by atomic-layer deposition of ultrathin films of cobalt oxide

Introduction of an ultrathin (2 nm) film of cobalt oxide (CoO_x) onto n-Si photoanodes prior to sputter-deposition of a thick multifunctional NiO_x coating yields stable photoelectrodes with photocurrent-onset potentials of ~−240 mV relative to the equilibrium potential for O2(g) evolution and current densities of ~28 mA cm^(−2) at the equilibrium potential for water oxidation when in contact with 1.0 M KOH(aq) under 1 sun of simulated solar illumination. The photoelectrochemical performance of these electrodes was very close to the Shockley diode limit for moderately doped n-Si(100) photoelectrodes, and was comparable to that of typical protected Si photoanodes that contained np+ buried homojunctions

Racial Disparities in Surgical Outcomes after Mastectomy in 223,000 Female Breast Cancer Patients - A Retrospective Cohort Study

BACKGROUND: Breast cancer mortality and treatment differ across racial groups. It remains unclear whether such disparities are also reflected in perioperative outcomes of breast cancer patients undergoing mastectomy. STUDY DESIGN: We reviewed the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database (2008-2021) to identify female patients who underwent mastectomy for oncological purposes. The outcomes were stratified by five racial groups (white, Black/African American, Asian, American Indian/Alaska Native, and Native Hawaiian/Pacific Islander) and included 30-day mortality, reoperation, readmission, surgical and medical complications, and non-home discharge. RESULTS: The study population included 222,947 patients, 68% (n=151,522) of whom were white, 11% (n=23,987) Black/African American, 5% (n=11,217) Asian, 0.5% (n=1,198) American Indian/Alaska Native, and 0.5% (n=1,018) Native Hawaiian/Pacific Islander. While 136,690 (61%) patients underwent partial mastectomy, 54,490 (24%) and 31,767 (14%) women received simple and radical mastectomy, respectively. Overall, adverse events occurred in 17, 222 (7.7%) patients, the largest portion of which were surgical complications (n=7,246; 3.3%). Multivariable analysis revealed that being of Asian race was protective against perioperative complications (OR=0.71; P<0.001), whereas American Indian/Alaska Native women were most vulnerable to the complication occurrence (OR=1.41; P<0.001). Black/African American patients had a significantly lower risk of medical (OR=0.59; P<0.001) and surgical complications (OR=0.60; P<0.001) after partial and radical mastectomy, respectively, their likelihood of readmission (OR=1.14; P=0.045) following partial mastectomy was significantly increased. CONCLUSION: We identified American Indian/Alaska Native women as particularly vulnerable to complications following mastectomy. Asian patients experienced the lowest rate of complications in the perioperative period. Our analyses revealed comparable confounder-adjusted outcomes following partial and complete mastectomy between Black and white races. Our findings call for care equalization in the field of breast cancer surgery

Update on LIPID MAPS classification, nomenclature, and shorthand notation for MS-derived lipid structures

A comprehensive and standardized system to report lipid structures analyzed by mass spectrometry is essentialfor the communication and storage of lipidomics data. Herein, an update on both the LIPID MAPSclassification system and shorthand notation of lipid structures is presented for lipid categories Fatty Acyls(FA), Glycerolipids (GL), Glycerophospholipids (GP), Sphingolipids (SP), and Sterols (ST). With its majorchanges, i.e. annotation of ring double bond equivalents and number of oxygens, the updated shorthandnotation facilitates reporting of newly delineated oxygenated lipid species as well. For standardized reportingin lipidomics, the hierarchical architecture of shorthand notation reflects the diverse structural resolutionpowers provided by mass spectrometric assays. Moreover, shorthand notation is expanded beyond mammalianphyla to lipids from plant and yeast phyla. Finally, annotation of atoms is included for the use of stableisotope-labelled compounds in metabolic labelling experiments or as internal standards

The unexpected resurgence of Weyl geometry in late 20-th century physics

Weyl's original scale geometry of 1918 ("purely infinitesimal geometry") was withdrawn by its author from physical theorizing in the early 1920s. It had a comeback in the last third of the 20th century in different contexts: scalar tensor theories of gravity, foundations of gravity, foundations of quantum mechanics, elementary particle physics, and cosmology. It seems that Weyl geometry continues to offer an open research potential for the foundations of physics even after the turn to the new millennium.Comment: Completely rewritten conference paper 'Beyond Einstein', Mainz Sep 2008. Preprint ELHC (Epistemology of the LHC) 2017-02, 92 pages, 1 figur

Strain-dependent host transcriptional responses to toxoplasma infection are largely conserved in mammalian and avian hosts

Toxoplasma gondii has a remarkable ability to infect an enormous variety of mammalian and avian species. Given this, it is surprising that three strains (Types I/II/III) account for the majority of isolates from Europe/North America. The selective pressures that have driven the emergence of these particular strains, however, remain enigmatic. We hypothesized that strain selection might be partially driven by adaptation of strains for mammalian versus avian hosts. To test this, we examine in vitro, strain-dependent host responses in fibroblasts of a representative avian host, the chicken (Gallus gallus). Using gene expression profiling of infected chicken embryonic fibroblasts and pathway analysis to assess host response, we show here that chicken cells respond with distinct transcriptional profiles upon infection with Type II versus III strains that are reminiscent of profiles observed in mammalian cells. To identify the parasite drivers of these differences, chicken fibroblasts were infected with individual F1 progeny of a Type II x III cross and host gene expression was assessed for each by microarray. QTL mapping of transcriptional differences suggested, and deletion strains confirmed, that, as in mammalian cells, the polymorphic rhoptry kinase ROP16 is the major driver of strain-specific responses. We originally hypothesized that comparing avian versus mammalian host response might reveal an inversion in parasite strain-dependent phenotypes; specifically, for polymorphic effectors like ROP16, we hypothesized that the allele with most activity in mammalian cells might be less active in avian cells. Instead, we found that activity of ROP16 alleles appears to be conserved across host species; moreover, additional parasite loci that were previously mapped for strain-specific effects on mammalian response showed similar strain-specific effects in chicken cells. These results indicate that if different hosts select for different parasite genotypes, the selection operates downstream of the signaling occurring during the beginning of the host's immune response. © 2011 Ong et al

Macaques vaccinated with live-attenuated SIV control replication of heterologous virus

An effective AIDS vaccine will need to protect against globally diverse isolates of HIV. To address this issue in macaques, we administered a live-attenuated simian immunodeficiency virus (SIV) vaccine and challenged with a highly pathogenic heterologous isolate. Vaccinees reduced viral replication by ∼2 logs between weeks 2–32 (P ≤ 0.049) postchallenge. Remarkably, vaccinees expressing MHC-I (MHC class I) alleles previously associated with viral control completely suppressed acute phase replication of the challenge virus, implicating CD8+ T cells in this control. Furthermore, transient depletion of peripheral CD8+ lymphocytes in four vaccinees during the chronic phase resulted in an increase in virus replication. In two of these animals, the recrudescent virus population contained only the vaccine strain and not the challenge virus. Alarmingly, however, we found evidence of recombinant viruses emerging in some of the vaccinated animals. This finding argues strongly against an attenuated virus vaccine as a solution to the AIDS epidemic. On a more positive note, our results suggest that MHC-I–restricted CD8+ T cells contribute to the protection induced by the live-attenuated SIV vaccine and demonstrate that vaccine-induced CD8+ T cell responses can control replication of heterologous challenge viruses

Protein-coding variants implicate novel genes related to lipid homeostasis contributing to body-fat distribution.

Body-fat distribution is a risk factor for adverse cardiovascular health consequences. We analyzed the association of body-fat distribution, assessed by waist-to-hip ratio adjusted for body mass index, with 228,985 predicted coding and splice site variants available on exome arrays in up to 344,369 individuals from five major ancestries (discovery) and 132,177 European-ancestry individuals (validation). We identified 15 common (minor allele frequency, MAF ≥5%) and nine low-frequency or rare (MAF &lt;5%) coding novel variants. Pathway/gene set enrichment analyses identified lipid particle, adiponectin, abnormal white adipose tissue physiology and bone development and morphology as important contributors to fat distribution, while cross-trait associations highlight cardiometabolic traits. In functional follow-up analyses, specifically in Drosophila RNAi-knockdowns, we observed a significant increase in the total body triglyceride levels for two genes (DNAH10 and PLXND1). We implicate novel genes in fat distribution, stressing the importance of interrogating low-frequency and protein-coding variants