Nanoscale Three-Dimensional Imaging of Integrated Circuits Using a Scanning Electron Microscope and Transition-Edge Sensor Spectrometer.

X-ray nanotomography is a powerful tool for the characterization of nanoscale materials and structures, but it is difficult to implement due to the competing requirements of X-ray flux and spot size. Due to this constraint, state-of-the-art nanotomography is predominantly performed at large synchrotron facilities. We present a laboratory-scale nanotomography instrument that achieves nanoscale spatial resolution while addressing the limitations of conventional tomography tools. The instrument combines the electron beam of a scanning electron microscope (SEM) with the precise, broadband X-ray detection of a superconducting transition-edge sensor (TES) microcalorimeter. The electron beam generates a highly focused X-ray spot on a metal target held micrometers away from the sample of interest, while the TES spectrometer isolates target photons with a high signal-to-noise ratio. This combination of a focused X-ray spot, energy-resolved X-ray detection, and unique system geometry enables nanoscale, element-specific X-ray imaging in a compact footprint. The proof of concept for this approach to X-ray nanotomography is demonstrated by imaging 160 nm features in three dimensions in six layers of a Cu-SiO2 integrated circuit, and a path toward finer resolution and enhanced imaging capabilities is discussed.

Blood Flow Restricted Training and Time Trial Performance: A Cohort Study of World Class Rowers.

INTRODUCTION: This study aimed to explore the potential impact of incorporating blood-flow restriction (BFR) training within a training block characterized by minimal high-intensity work on 2000-m rowing ergometer time-trial (TT) performance in elite/world-class rowers. Physiological markers often associated with endurance performance (maximal aerobic capacity - VO2max, blood lactate thresholds and hemoglobin mass - Hbmass) were measured to determine whether changes are related to an improvement in performance. METHODS: Using a quasi-experimental, observational study design (no control group), 2000-m TT performance, VO2max, submaximal work rates eliciting blood lactate concentrations of ~2 and ~ 4 mmol·L-1, and Hbmass were measured before and after 4 weeks of non-competitive season training, which included BFR rowing. BFR training consisted of 11 sessions of 2x10 minutes of BFR rowing at a workload equating to blood lactate concentrations of ~2 mmol·L-1. Paired t-tests were used to compare pre/post values, and Pearson correlation was used to examine whether physiological changes were associated with changes to TT performance. RESULTS: TT performance improved in both female (1.09 ± 1.2%, ~4.6 ± 5.2 s; p < 0.01) and male (1.17 ± 0.48%, ~4.5 ± 1.9 s; p < 0.001) athletes. VO2max increased in female rowers only (p < 0.01), but both sexes had an increase in work rates eliciting blood lactate concentrations of 2 (female:184 ± 16 to 195 ± 15 W, p < 0.01; male:288 ± 23 to 317 ± 26 W, p = 0.04) and 4 mmol·L-1 (female:217 ± 13 to 227 ± 14 W, p = 0.02; male:339 ± 43 to 364 ± 39 W, p < 0.01). No changes in Hbmass (both sexes, p = 0.8) were observed. Improvements in TT performance were not related to physiological changes (all correlations p ≥ 0.2). CONCLUSIONS: After 4 weeks of training with BFR, the improvement in TT performance was greater than what is typical for this population. Physiological variables improved during this training block but did not explain improved TT performance.

Investigating the Relevance of Maximal Speed and Acceleration in Varsity-Level Female Ice Hockey Players.

PURPOSE: To characterize and compare female ice hockey players' peak skating speed and acceleration ability during linear sprints and gameplay. We also sought to quantify the time spent at various speeds and the frequency of accelerations at different thresholds during games. METHODS: Seventeen varsity-level female ice hockey players (20 [1.4] y, 68.9 [4.9] kg, 167.6 [4.7] cm) participated in an on-ice practice session (performing 3 × 40-m linear sprints) and 4 regular-season games while being monitored using a local positioning system. Speed and acceleration were recorded from the sprint and within-game monitoring. Time on ice spent in relative skating speed zones and the frequency of accelerations at different intensities were recorded. RESULTS: Players' greatest peak speeds (29.5 [1.3] vs 28.3 [1.1] km/h) and accelerations (4.39 [0.48] vs 3.34 [0.36] m/s2) reached during gameplay were higher than those reached in linear sprinting (both P < .01). Peak in-game values were moderately predicted by linear sprint values for speed (r = .69, P < .01) but not for acceleration (r < .01, P = .95). Players spent little time at near-peak linear sprint speeds (≥80% [22.7 km/h], ∼3% time on ice; ≥90% [25.5 km/h], <1% of time on ice) during gameplay. However, 26% to 35% of accelerations recorded during the 4 games were ≥90% of linear sprint acceleration. CONCLUSIONS: Although skating speed may be advantageous in specific game situations, our results suggest that players spend little time at near-maximal speeds while accelerating frequently during games. This warrants further investigation of direction changes, skating transitions, repeated sprints, and other determinant variables potentially related to on-ice success and the implementation of training strategies to improve repeated acceleration or qualities beyond maximal skating speed.

Altered carbohydrate oxidation during exercise in overreached endurance athletes is applicable to training monitoring with continuous glucose monitors.

PURPOSE: The purpose of the study was to investigate whether carbohydrate utilization is altered during exercise in overreached endurance athletes and examine the utility of continuous glucose monitors (CGM) to detect overreaching status. METHODS: Eleven endurance athletes (M:8, F:3) completed a 5-week training block consisting of 1 week of reduced training (PRE), 3 weeks of high-intensity overload training (POST), and 1 week of recovery training (REC). Participants completed a Lamberts and Lambert Submaximal Cycling Test (LSCT) and 5 km time-trial at PRE, POST, and REC time points, 15 min following the ingestion of a 50 g glucose beverage with glucose recorded each minute via CGM. RESULTS: Performance in the 5 km time-trial was reduced at POST (∆-7 ± 10 W, p = 0.04, η p 2 = 0.35) and improved at REC (∆12 ± 9 W from PRE, p = 0.01, η p 2 = 0.66), with reductions in peak lactate (∆-3.0 ± 2.0 mmol/L, p = 0.001, η p 2 = 0.71), peak HR (∆-6 ± 3 bpm, p < 0.001, η p 2 = 0.86), and Hooper-Mackinnon well-being scores (∆10 ± 5 a.u., p < 0.001, η p 2 = 0.79), indicating athletes were functionally overreached. The respiratory exchange ratio was suppressed at POST relative to REC during the 60% (POST: 0.80 ± 0.05, REC: 0.87 ± 0.05, p < 0.001, η p 2 = 0.74), and 80% (POST: 0.93 ± 0.05, REC: 1.00 ± 0.05, p = 0.003, η p 2 = 0.68) of HR-matched submaximal stages of the LSCT. CGM glucose was reduced during HR-matched submaximal exercise in the LSCT at POST (p = 0.047, η p 2 = 0.36), but not the 5 km time-trial (p = 0.07, η p 2 = 0.28) in overreached athletes. CONCLUSION: This preliminary investigation demonstrates a reduction in CGM-derived glucose and carbohydrate oxidation during submaximal exercise in overreached athletes. The use of CGM during submaximal exercise following standardized nutrition could be employed as a monitoring tool to detect overreaching in endurance athletes.

Impact of Blood Flow Restriction Exercise on Central Hemodynamics and Fluid Regulating Hormones.

PURPOSE: The purpose of this study is to characterize both the efficacy of altered restriction pressures and consequences of optimized blood flow restriction (BFR) for altering the cardiovascular and fluid regulating response in humans. METHODS: This work comprised a series of related trials. Phase 1: during semi-recumbent cycling (5 min, 60 W) with BFR at 0%, 50%, 75%, 100%, and 125% of participants' lowest arterial occlusion pressure (LOP) echocardiographic images were collected alongside continuous heart rate (HR) and blood pressure (BP). In phase 2, 24 h fluid balance (intake-output) and fluid-regulating hormone responses were measured after a practical BFR exercise session (treadmill walking: 5·3 min, 1 min rest, 5 km·h -1 , 5% incline, 100% LOP). Phase 3 examined the magnitude and effect of blood volume distribution following BFR treadmill walking using a modified CO-rebreathe technique. RESULTS: Cardiac ejection fraction remained stable irrespective of cuff pressure and despite a reduction in end-diastolic volume (Δ of 11 ± 9 mL, P = 0.02). HR and BP were highest at 100% LOP (ΔHR = 18 ± 19 bpm, ΔSBP = 51 ± 30 mm Hg, ΔDBP = 33 ± 15 mm Hg, ΔRate Pressure Product = 76 ± 32 bpm·mm Hg·100 -1 ). BFR treadmill walking stimulated a greater release of fluid-regulating hormones than normal walking (Δrenin = BFR: 25.3 ± 24.2 vs CON: 9.1 ± 11.8 ng·L -1 ; Δcopeptin = BFR: 50.1 ± 97.9 vs. CON: 0.43 ± 0.8 pmol·L -1 ), but no difference in fluid retention was observed ( P = 0.2). Approximately 27% of total blood volume was confined to the legs during BFR, but the relative volume trapped in the legs was not related to fluid-regulating hormone release (renin r = -0.04, P = 0.9; copeptin r = 0.27, P = 0.3). CONCLUSIONS: BFR exercise elicits the largest cardiovascular effect using 100% LOP, with evidence of appreciable fluid regulating hormonal response during a typical BFR exercise session. The relative volume of blood sequestered in the limb does not appear to drive this response.

Exposure to air pollution as an environmental determinant of how Sjögren's disease is expressed at diagnosis.

OBJECTIVES: To analyse how the potential exposure to air pollutants can influence the key components at the time of diagnosis of Sjögren's phenotype (epidemiological profile, sicca symptoms, and systemic disease). METHODS: For the present study, the following variables were selected for harmonization and refinement: age, sex, country, fulfilment of 2002/2016 criteria items, dry eyes, dry mouth, and overall ESSDAI score. Air pollution indexes per country were defined according to the OECD (1990-2021), including emission data of nitrogen and sulphur oxides (NO/SO), particulate matter (PM2.5 and 1.0), carbon monoxide (CO) and volatile organic compounds (VOC) calculated per unit of GDP, Kg per 1000 USD. RESULTS: The results of the chi-square tests of independence for each air pollutant with the frequency of dry eyes at diagnosis showed that, except for one, all variables exhibited p-values <0.0001. The most pronounced disparities emerged in the dry eye prevalence among individuals inhabiting countries with the highest NO/SO exposure, a surge of 4.61 percentage points compared to other countries, followed by CO (3.59 points), non-methane (3.32 points), PM2.5 (3.30 points), and PM1.0 (1.60 points) exposures. Concerning dry mouth, individuals residing in countries with worse NO/SO exposures exhibited a heightened frequency of dry mouth by 2.05 percentage points (p<0.0001), followed by non-methane exposure (1.21 percentage points increase, p=0.007). Individuals inhabiting countries with the worst NO/SO, CO, and PM2.5 pollution levels had a higher mean global ESSDAI score than those in lower-risk nations (all p-values <0.0001). When systemic disease was stratified according to DAS into low, moderate, and high systemic activity levels, a heightened proportion of individuals manifesting moderate/severe systemic activity was observed in countries with worse exposures to NO/SO, CO, and PM2.5 pollutant levels. CONCLUSIONS: For the first time, we suggest that pollution levels could influence how SjD appears at diagnosis in a large international cohort of patients. The most notable relationships were found between symptoms (dryness and general body symptoms) and NO/SO, CO, and PM2.5 levels.

Influence of exposure to climate-related hazards in the phenotypic expression of primary Sjögren's syndrome.

OBJECTIVES: To analyse how the key components at the time of diagnosis of the Sjögren's phenotype (epidemiological profile, sicca symptoms, and systemic disease) can be influenced by the potential exposure to climate-related natural hazards. METHODS: For the present study, the following variables were selected for harmonisation and refinement: age, sex, country, fulfilment of 2002/2016 criteria items, dry eyes, dry mouth, and overall ESSDAI score. Climate-related hazards per country were defined according to the OECD and included seven climate-related hazard types: extreme temperature, extreme precipitation, drought, wildfire, wind threats, river flooding, and coastal flooding. Climatic variables were defined as dichotomous variables according to whether each country is ranked among the ten countries with the most significant exposure. RESULTS: After applying data-cleaning techniques and excluding people from countries not included in the OECD climate rankings, the database study analysed 16,042 patients from 23 countries. The disease was diagnosed between 1 and 3 years earlier in people living in countries included among the top 10 worst exposed to extreme precipitation, wildfire, wind threats, river flooding, and coastal flooding. A lower frequency of dry eyes was observed in people living in countries exposed to wind threats, river flooding, and coastal flooding, with a level of statistical association being classified as strong (p<0.0001 for the three variables). The frequency of dry mouth was significantly lower in people living in countries exposed to river flooding (p<0.0001) and coastal flooding (p<0.0001). People living in countries included in the worse climate scenarios for extreme temperature (p<0.0001) and river flooding (p<0.0001) showed a higher mean ESSDAI score in comparison with people living in no-risk countries. In contrast, those living in countries exposed to worse climate scenarios for wind threats (p<0.0001) and coastal flooding (p<0.0001) showed a lower mean ESSDAI score in comparison with people living in no-risk countries. CONCLUSIONS: Local exposure to extreme climate-related hazards plays a role in modulating the presentation of Sjögren across countries concerning the age at which the disease is diagnosed, the frequency of dryness, and the degree of systemic activity.

Cardiovascular responses to combined mechanoreflex and metaboreflex activation in healthy adults: effects of sex and low- versus high-hormone phases in females.

Females generally have smaller blood pressure (BP) responses to isolated muscle mechanoreflex and metaboreflex activation compared with males, which may explain sex differences in BP responses to voluntary exercise. The mechanoreflex may be sensitized during exercise, but whether mechanoreflex-metaboreflex interactions differ by sex or variations in sex hormones remains unknown. Thirty-one young healthy subjects (females, n = 16) performed unilateral passive cycling (mechanoreflex), active cycling (40% peak Watts), postexercise circulatory occlusion (PECO; metaboreflex), and passive cycling combined with PECO (combined mechanoreflex and metaboreflex activation). Beat-to-beat BP, heart rate, inactive leg vascular conductance, and active leg muscle oxygenation were measured. Ten females underwent exploratory testing during low- and high-hormone phases of their self-reported menstrual cycle or oral contraceptive use. Systolic BP and heart rate responses did not differ between sexes during active cycling [Δ30 ± 9 vs. 29 ± 11 mmHg (males vs. females), P = 0.9; Δ33 ± 8 vs. 35 ± 6 beats/min, P = 0.4] or passive cycling with PECO (Δ26 ± 11 vs. 21 ± 10 mmHg, P = 0.3; Δ14 ± 7 vs. 18 ± 15 beats/min, P = 0.3). Passive cycling with PECO revealed additive, not synergistic, effects for systolic BP [males: Δ23 ± 14 vs. 26 ± 11 mmHg (sum of isolated passive cycling and PECO vs. combined activation); females: Δ26 ± 11 vs. 21 ± 12 mmHg, interaction P = 0.05]. Results were consistent in subset analyses with sex differences in active cycling BP (P > 0.1) and exploratory analyses of hormone phase (P > 0.4). Despite a lack of statistical equivalence, no differences in cardiovascular responses were found during combined mechanoreflex-metaboreflex activation between sexes or hormone levels. These results provide preliminary data regarding the involvement of muscle mechanoreflex-metaboreflex interactions in mediating sex differences in voluntary exercise BP responses.NEW & NOTEWORTHY The muscle mechanoreflex may be sensitized by metabolites during exercise. We show that cardiovascular responses to combined mechanoreflex (passive cycling) and metaboreflex (postexercise circulatory occlusion) activation are primarily additive and do not differ between males and females, or across variations in sex hormones in females. Our findings provide new insight into the contributions of muscle mechanoreflex-metaboreflex interactions as a cause for prior reports that females have smaller blood pressure responses to voluntary exercise.

Novel homozygous variants in PRORP expand the genotypic spectrum of combined oxidative phosphorylation deficiency 54.

Biallelic hypomorphic variants in PRORP have been recently described as causing the autosomal recessive disorder combined oxidative phosphorylation deficiency type 54 (COXPD54). COXPD54 encompasses a phenotypic spectrum of sensorineural hearing loss and ovarian insufficiency (Perrault syndrome) to leukodystrophy. Here, we report three additional families with homozygous missense PRORP variants with pleiotropic phenotypes. Each missense variant altered a highly conserved residue within the metallonuclease domain. In vitro mitochondrial tRNA processing assays with recombinant TRMT10C, SDR5C1 and PRORP indicated two COXPD54-associated PRORP variants, c.1159A>G (p.Thr387Ala) and c.1241C>T (p.Ala414Val), decreased pre-tRNAIle cleavage, consistent with both variants impacting tRNA processing. No significant decrease in tRNA processing was observed with PRORP c.1093T>C (p.Tyr365His), which was identified in an individual with leukodystrophy. These data provide independent evidence that PRORP variants are associated with COXPD54 and that the assessment of 5' leader mitochondrial tRNA processing is a valuable assay for the functional analysis and clinical interpretation of novel PRORP variants.

Clinical and molecular characterization of novel FARS2 variants causing neonatal mitochondrial disease.

FARS2 encodes the mitochondrial phenylalanyl-tRNA synthetase (mtPheRS), which is essential for charging mitochondrial (mt-) tRNAPhe with phenylalanine for use in intramitochondrial translation. Many biallelic, pathogenic FARS2 variants have been described previously, which are mostly associated with two distinct clinical phenotypes; an early onset epileptic mitochondrial encephalomyopathy or a later onset spastic paraplegia. In this study, we report on a patient who presented at 3 weeks of age with tachypnoea and poor feeding, which progressed to severe metabolic decompensation with lactic acidosis and seizure activity followed by death at 9 weeks of age. Rapid trio whole exome sequencing identified compound heterozygous FARS2 variants including a pathogenic exon 2 deletion on one allele and a rare missense variant (c.593G > T, p.(Arg198Leu)) on the other allele, necessitating further work to aid variant classification. Assessment of patient fibroblasts demonstrated severely decreased steady-state levels of mtPheRS, but no obvious defect in any components of the oxidative phosphorylation system. To investigate the potential pathogenicity of the missense variant, we determined its high-resolution crystal structure, demonstrating a local structural destabilization in the catalytic domain. Moreover, the R198L mutation reduced the thermal stability and impaired the enzymatic activity of mtPheRS due to a lower binding affinity for tRNAPhe and a slower turnover rate. Together these data confirm the pathogenicity of this FARS2 variant in causing early-onset mitochondrial epilepsy.

Feasibility evaluation of two novel systems for the automated preparation and extended storage of DMSO cryopreserved platelets.

BACKGROUND: Manufacturing methods for dimethyl sulfoxide (DMSO)-cryopreserved platelets (CPPs) are manual and labor intensive. Thawing and prepare-for-transfusion steps are in an open system that requires transfusion within 4 h. A fill-and-finish system (CUE) can automate the manufacturing process. A newly configured bag system allows freezing, thawing, and use of resuspension solutions while maintaining the functionally closed system, and extending the post-thaw shelf life beyond 4 h. Our objective is to evaluate the feasibility of the CUE system and the functionally closed bag system. STUDY DESIGN AND METHODS: DMSO was volumetrically added to double-dose apheresis platelets, concentrated, and delivered to a 50- or 500-mL ethylene-vinyl acetate (EVA) bag by the CUE (n = 12). The functionally closed bag system contained 25 mL platelet additive solution 3 (PAS-3) in a 50-mL EVA bag. Control CPP (n = 2) were manually prepared. PAS-3 and CPP were thawed together. CPP were stored up to 98 h (20-24°C) and tested using a standard assay panel. RESULTS: CUE prepared CPP met the design targets: volume, platelet content, and DMSO concentration. CUE CPP P-selectin was high. CD42b, phosphatidylserine (PS) expression, and live cell percentage were favorable compared to controls and favorably maintained over storage. The thrombin generation potency was slightly reduced compared to controls. The 50 mL EVA bag maintained pH for up to 30 h, and the 500 mL EVA bag beyond 76 h. DISCUSSION: The CUE system presents a technically feasible method to prepare CPP. A functionally closed bag system with resuspension solution was successful and can extend the post-thaw storage time of CPP.

Implementation of a Gastrografin Order Set for Small Bowel Obstruction Across a Health System: A Cohort Study.

BACKGROUND: The use of Gastrografin (GG) in the management of adhesive small bowel obstruction (SBO) has been shown to decrease the length of stay and operative intervention. METHODS: This retrospective cohort study examined patients with an SBO diagnosis prior to implementation (PRE, January 2017-January 2019) and following implementation (POST, January 2019-May 2021) of a GG challenge order set made available across 9 hospitals within a health care system. Primary outcomes were utilization of the order set across facilities and over time. Secondary outcomes included time to surgery for operative patients, rate of surgery, nonoperative length of stay, and 30-day readmission. Standard descriptive, univariate, and multivariable regression analyses were performed. RESULTS: PRE cohort had 1746 patients and POST had 1889. The utilization of GG increased from 14% to 49.5% following implementation. Significant variability existed within the hospital system with utilization at each individual hospital from 11.5% to 60%. There was an increase in surgical intervention (13.9% vs 16.4%, P = .04) and decrease in nonoperative LOS (65.6 vs 59.9 hours, P < .001) following implementation. For POST patients, multivariable linear regression showed significant reduction in nonoperative length of stay (-23.1 hours, P < .001) but no significant difference in time to surgery (-19.6 hours, P = .08). DISCUSSION: The availability of a standardized order set for SBO can result in increased Gastrografin administration across hospital settings. The implementation of a Gastrografin order set was associated with decreased length of stay in nonoperative patients.

Outcomes of patients undergoing single-level arthroplasty versus anterior lumbar interbody fusion.

BACKGROUND: Compared to vertebral body fusion, artificial discs are thought to lessen the risks of adjacent segment disease and the need for additional surgery by maintaining spinal mobility as they mimic the intervertebral disc structure. No studies have compared the rates of postoperative complications and the requirement for secondary surgery at adjacent segments among patients who have undergone anterior lumbar interbody fusions (ALIF) versus those undergoing lumbar arthroplasty. METHODS: An all-payer claims database identified 11,367 individuals who underwent single-level ALIF and lumbar arthroplasty for degenerative disc disease (DDD) between January 2010 and October 2020. Rates of complications following surgery, the need for additional lumbar surgeries, length of stay (LOS), and postoperative opioid utilization were assessed in matched cohorts based on logistic regression models. Kaplan-Meyer plots were created to model the probability of additional surgery. RESULTS: Following 1:1 exact matching, 846 records of patients who had undergone ALIF or lumbar arthroplasty were analyzed. All-cause readmission within 30-30 days following surgery was significantly higher in patients undergoing ALIF versus arthroplasty (2.6% vs. 0.71%, p = 0.02). LOS was significantly lower among the patients who had undergone ALIF (1.043 ± 0.21 vs. 2.17 ± 1.7, p < .001). CONCLUSIONS: ALIF and lumbar arthroplasty procedures are equally safe and effective in treating DDD. Our findings do not support that single-level fusions may biomechanically necessitate revisional surgeries.

A tabletop X-ray tomography instrument for nanometer-scale imaging: reconstructions.

We show three-dimensional reconstructions of a region of an integrated circuit from a 130 nm copper process. The reconstructions employ x-ray computed tomography, measured with a new and innovative high-magnification x-ray microscope. The instrument uses a focused electron beam to generate x-rays in a 100 nm spot and energy-resolving x-ray detectors that minimize backgrounds and hold promise for the identification of materials within the sample. The x-ray generation target, a layer of platinum, is fabricated on the circuit wafer itself. A region of interest is imaged from a limited range of angles and without physically removing the region from the larger circuit. The reconstruction is consistent with the circuit's design file.

Occurrence of quantifiable and semi-quantifiable poly- and perfluoroalkyl substances in united states wastewater treatment plants.

Both quantifiable and semi-quantifiable poly- and perfluoroalkyl substances (PFAS) were evaluated in the influent, effluent, and biosolids of 38 wastewater treatment plants. PFAS were detected in all streams at all facilities. For the means of the sums of detected, quantifiable PFAS concentrations were 98 ± 28 ng/L, 80 ± 24 ng/L, and 160,000 ± 46,000 ng/kg (dry weight basis) in the influent, effluent, and biosolids (respectively). In the aqueous influent and effluent streams this quantifiable PFAS mass was typically associated with perfluoroalkyl acids (PFAAs). In contrast, quantifiable PFAS in the biosolids were primarily polyfluoroalkyl substances that potentially serve as precursors to the more recalcitrant PFAAs. Results of the total oxidizable precursor (TOP) assay on select influent and effluent samples showed that semi-quantified (or, unidentified) precursors accounted for a substantial portion (21 to 88%) of the fluorine mass compared to that associated with quantified PFAS, and that this fluorine precursor mass was not appreciably transformed to perfluoroalkyl acids within the WWTPs, as influent and effluent precursor concentrations via the TOP assay were statistically identical. Evaluation of semi-quantified PFAS, consistent with results of the TOP assay, showed the presence of several classes of precursors in the influent, effluent, and biosolids; perfluorophosphonic acids (PFPAs) and fluorotelomer phosphate diesters (di-PAPs) occurred in 100 and 92% of biosolid samples, respectively. Analysis of mass flows showed that, for both quantified (on a fluorine mass basis) and semi-quantified PFAS, the majority of PFAS exited WWTPs through the aqueous effluent compared to the biosolids stream. Overall, these results highlight the importance of semi-quantified PFAS precursors in WWTPs, and the need to further understand the impacts of their ultimate fate in the environment.

Investigation of oxidative phosphorylation activity and complex composition in mitochondrial disease.

A multidisciplinary approach to the laboratory diagnosis of mitochondrial disease has long been applied, with crucial information provided by deep clinical phenotyping, blood investigations, and biomarker screening as well as histopathological and biochemical testing of biopsy material to support molecular genetic screening. In an era of second and third generation sequencing technologies, traditional diagnostic algorithms for mitochondrial disease have been replaced by gene agnostic, genomic strategies including whole-exome sequencing (WES) and whole-genome sequencing (WGS), increasingly supported by other 'omics technologies (Alston et al., 2021). Whether a primary testing strategy, or one used to validate and interpret candidate genetic variants, the availability of a range of tests aimed at determining mitochondrial function (i.e., the assessment of individual respiratory chain enzyme activities in a tissue biopsy or cellular respiration in a patient cell line) remains an important part of the diagnostic armory. In this chapter, we summarize several disciplines used in the laboratory investigation of suspected mitochondrial disease, including the histopathological and biochemical assessment of mitochondrial function, as well as protein-based techniques to assess the steady-state levels of oxidative phosphorylation (OXPHOS) subunits and assembly of OXPHOS complexes via traditional (immunoblotting) and cutting-edge (quantitative proteomic) approaches.

Impact of COVID-19 on volume of elective and nonelective ventral hernia repair.

BACKGROUND: The significant decrease in elective surgery during the COVID-19 pandemic prompted fears that there would be an increase in emergency or urgent operations for certain disease states. The impact of COVID-19 on ventral hernia repair is unknown. This study aimed to compare volumes of elective and nonelective ventral hernia repairs performed pre-COVID-19 with those performed during the COVID-19 pandemic. METHODS: An analysis of a prospective database from 8 hospitals capturing patient admissions with the International Classification of Diseases, Tenth Revision Procedure Coding System for ventral hernia repair from January 2017 through June 2021 were included. During, COVID-19 was defined as on or after March 2020. RESULTS: Comparing 3,558 ventral hernia repairs pre-COVID-19 with 1,228 during COVID-19, there was a significant decrease in the mean number of elective ventral hernia repairs per month during COVID-19 (pre-COVID-19: 61 ± 5 vs during COVID-19 19: 39 ± 11; P < .001), and this persisted after excluding the initial 3-month COVID-19 surge (61 ± 5 vs 42 ± 9; P < .001). There were fewer nonelective cases during the initial 3-month COVID-19 surge (32 ± 9 vs 24 ± 4; P = .031), but, excluding the initial surge, there was no difference in nonelective volume (32 ± 9 vs 33 ± 8; P = .560). During COVID-19, patients had lower rates of congestive heart failure (elective: 9.0% vs 6.6%; P = .0047; nonelective: 17.7% vs 11.6%; P < .001) and chronic obstructive pulmonary disease (elective: 13.7% vs 10.2%; P = .017; nonelective: 17.9% vs 12.0%; P < .001) and underwent fewer component separations (10.2% vs 6.4%; P ≤ .001). Intensive care unit admissions decreased for elective ventral hernia repairs (7.7% vs 5.0%; P = .016). Length of stay, cost, and readmission were similar between groups. CONCLUSION: Elective ventral hernia repair volume decreased during COVID-19 whereas nonelective ventral hernia repairs transiently decreased before returning to baseline. During COVID-19, patients appeared to be lower risk and less complex. The possible impact of the more complex patients delaying surgery is yet to be seen.

African American Patients Experience Worse Outcomes than Hispanic Patients Following Bariatric Surgery: an Analysis Using the MBSAQIP Data Registry.

BACKGROUND: Obesity rates in Hispanics and African Americans (AAs) are higher than in Caucasians in the USA, yet the rate of metabolic and bariatric surgery (MBS) for weight loss remains lower for both Hispanics and AAs. METHODS: Patient demographics and outcomes of adult AA and Hispanic patients undergoing sleeve gastrectomy (SG) or Roux-en-Y gastric bypass (RYGB) procedures were analyzed using the MBSAQIP dataset [2015-2018] using unmatched and propensity-matched data. RESULTS: In total, 173,157 patients were included, of whom 98,185 were AA [56.7%] [21,163-RYGB; 77,022-SG] and 74,972 were Hispanic [43.3%] [20,282-RYGB; 54,690-SG]). Preoperatively, the AA cohort was older, had more females, and higher BMIs with higher rates of all tracked obesity-related medical conditions except for diabetes, venous stasis, and prior foregut surgery. Intra- and postoperatively, AAs were more likely to experience major complications including unplanned ICU admission, 30-day readmission/reintervention, and mortality. After propensity matching, the differences in ED visits, treatment for dehydration, 30-day readmission, 30-day intervention, and pulmonary embolism remained for both SG and RYGB cohorts. Progressive renal insufficiency and ventilator use lost statistical significance in both cohorts. Conversely, 30-day reoperation, postoperative ventilator requirement, unplanned intubation, unplanned ICU admission, and mortality lost significance in the RYGB cohort, but not SG patients. CONCLUSION: Outcomes for AA patients were worse than for Hispanic patients, even after propensity matching. After matching, differences in major complications and mortality lost significance for RYGB, but not SG. These data suggest that outcomes for RYGB may be driven by the presence and severity of pre-existing patient-related factors.

Impact of COVID-19 on common non-elective general surgery diagnoses.

BACKGROUND: During the COVID-19 pandemic, public health and hospital policies were enacted to decrease virus transmission and increase hospital capacity. Our aim was to understand the association between COVID-19 positivity rates and patient presentation with EGS diagnoses during the COVID pandemic compared to historical controls. METHODS: In this cohort study, we identified patients ≥ 18 years who presented to an urgent care, freestanding ED, or acute care hospital in a regional health system with selected EGS diagnoses during the pandemic (March 17, 2020 to February 17, 2021) and compared them to a pre-pandemic cohort (March 17, 2019 to February 17, 2020). Outcomes of interest were number of EGS-related visits per month, length of stay (LOS), 30-day mortality and 30-day readmission. RESULTS: There were 7908 patients in the pre-pandemic and 6771 in the pandemic cohort. The most common diagnoses in both were diverticulitis (29.6%), small bowel obstruction (28.8%), and appendicitis (20.8%). The lowest relative volume of EGS patients was seen in the first two months of the pandemic period (29% and 40% decrease). A higher percentage of patients were managed at a freestanding ED (9.6% vs. 8.1%) and patients who were admitted were more likely to be managed at a smaller hospital during the pandemic. Rates of surgical intervention were not different. There was no difference in use of ICU, ventilator requirement, or LOS. Higher 30-day readmission and lower 30-day mortality were seen in the pandemic cohort. CONCLUSIONS: In the setting of the COVID pandemic, there was a decrease in visits with EGS diagnoses. The increase in visits managed at freestanding ED may reflect resources dedicated to supporting outpatient non-operative management and lack of bed availability during COVID surges. There was no evidence of a rebound in EGS case volume or substantial increase in severity of disease after a surge declined.