The Use of Flap Techniques to Preserve Limb Length in Patients with Transmetatarsal Amputations.

BACKGROUND: Chronic lower extremity wounds affect up to 13% of the US population. Transmetatarsal amputation (TMA) is frequently performed in patients with chronic forefoot wounds. TMA allows limb salvage and preserves functional gait, without need for prosthesis. Traditionally, when tension-free primary closure is not possible, a higher-level amputation is performed. This is the first series to evaluate the outcomes of local and free flap coverage of TMA stumps in patients with chronic foot wounds. METHODS: A retrospective cohort of patients who underwent TMA with flap coverage from 2015 through 2021 was reviewed. Primary outcomes included flap success, early postoperative complications, and long-term outcomes (limb salvage and ambulatory status). Patient-reported outcome measures using the Lower Extremity Functional Scale (LEFS) were also collected. RESULTS: Fifty patients underwent 51 flap reconstructions (26 local, 25 free flap) after TMA. Average age and body mass index were 58.5 years and 29.8 kg/m 2 , respectively. Comorbidities included diabetes [ n = 43 (86%)] and peripheral vascular disease [ n = 37 (74%)]. Flap success rate was 100%. At a mean follow-up of 24.8 months (range, 0.7 to 95.7 months), the limb salvage rate was 86.3% ( n = 44). Forty-four patients (88%) were ambulatory. The LEFS survey was completed by 24 surviving patients (54.5%). Mean LEFS score was 46.6 ± 13.9, correlating with 58.2% ± 17.4% of maximal function. CONCLUSIONS: Local and free flap reconstruction after TMA are viable methods of soft-tissue coverage for limb salvage. Applying plastic surgery flap techniques for TMA stump coverage allows for preservation of increased foot length and ambulation without a prosthesis. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Longitudinal analysis of anti-SARS-CoV-2 neutralizing antibody (NAb) titers in vaccinees using a novel giant magnetoresistive (GMR) assay.

The COVID-19 pandemic has highlighted the need to monitor important correlates of immunity on a population-wide level. To this end, we have developed a competitive assay to assess neutralizing antibody (NAb) titer on the giant magnetoresistive (GMR) biosensor platform. We compared the clinical performance of our biosensor with established techniques such as Ortho's VITROS Anti-SARS-CoV-2 IgG Quantitative Antibody test. Results obtained between the VITROS test and the GMR assay showed correlation (r = -0.93). We then validated the assay with patient plasma samples that had been tested using focus reduction neutralization testing (FRNT). The results obtained from our GMR assay exhibit a previously identified trend of increased NAb titers 2 weeks post-vaccination. We further evaluated NAb titers 6 months post-vaccination and observed waning neutralizing antibody titers over that time in vaccinated patients. In addition, we calibrated our assay to an arbitrary unit (IU/mL) using World Health Organization (WHO) reference plasma provided by the National Institute of Biological Standards and Control (NIBSC). Our biosensor provides highly specific and sensitive results in serum and plasma with analytical, clinical, and point-of-care (POC) applications due to quick turnaround times on samples and the cost-effectiveness of the platform.

Postoperative Respiratory Failure and Advanced Ventilator Settings.

Postoperative respiratory failure has a multifactorial etiology, of which atelectasis is the most common mechanism. Its injurious effects are magnified by surgical inflammation, high driving pressures, and postoperative pain. Chest physiotherapy and noninvasive ventilation are good options to prevent progression of respiratory failure. Acute respiratory disease syndrome is a late and severe finding, which is associated with high morbidity and mortality. If present, proning is a safe, effective, and underutilized therapy. Extracorporeal membrane oxygenation is an option only when traditional supportive measures have failed.

Aerial additive manufacturing with multiple autonomous robots.

Additive manufacturing methods1-4 using static and mobile robots are being developed for both on-site construction5-8 and off-site prefabrication9,10. Here we introduce a method of additive manufacturing, referred to as aerial additive manufacturing (Aerial-AM), that utilizes a team of aerial robots inspired by natural builders11 such as wasps who use collective building methods12,13. We present a scalable multi-robot three-dimensional (3D) printing and path-planning framework that enables robot tasks and population size to be adapted to variations in print geometry throughout a building mission. The multi-robot manufacturing framework allows for autonomous three-dimensional printing under human supervision, real-time assessment of printed geometry and robot behavioural adaptation. To validate autonomous Aerial-AM based on the framework, we develop BuilDrones for depositing materials during flight and ScanDrones for measuring the print quality, and integrate a generic real-time model-predictive-control scheme with the Aerial-AM robots. In addition, we integrate a dynamically self-aligning delta manipulator with the BuilDrone to further improve the manufacturing accuracy to five millimetres for printing geometry with precise trajectory requirements, and develop four cementitious-polymeric composite mixtures suitable for continuous material deposition. We demonstrate proof-of-concept prints including a cylinder 2.05 metres high consisting of 72 layers of a rapid-curing insulation foam material and a cylinder 0.18 metres high consisting of 28 layers of structural pseudoplastic cementitious material, a light-trail virtual print of a dome-like geometry, and multi-robot simulations. Aerial-AM allows manufacturing in-flight and offers future possibilities for building in unbounded, at-height or hard-to-access locations.

The BlueScreen HC assay to predict the genotoxic potential of fragrance materials.

BlueScreen HC is a mammalian cell-based assay for measuring the genotoxicity and cytotoxicity of chemical compounds and mixtures. The BlueScreen HC assay has been utilized at the Research Institute for Fragrance Materials in a safety assessment program as a screening tool to prioritize fragrance materials for higher-tier testing, as supporting evidence when using a read-across approach, and as evidence to adjust the threshold of toxicological concern. Predictive values for the BlueScreen HC assay were evaluated based on the ability of the assay to predict the outcome of in vitro and in vivo mutagenicity and chromosomal damage genotoxicity assays. A set of 371 fragrance materials was assessed in the BlueScreen HC assay along with existing or newly generated in vitro and in vivo genotoxicity data. Based on a weight-of-evidence approach, the majority of materials in the data set were deemed negative and concluded not to have the potential to be genotoxic, while only a small proportion of materials were determined to show genotoxic effects in these assays. Analysis of the data set showed a combination of high positive agreement but low negative agreement between BlueScreen HC results, in vitro regulatory genotoxicity assays, and higher-tier test results. The BlueScreen HC assay did not generate any false negatives, thereby providing robustness when utilizing it as a high-throughput screening tool to evaluate the large inventory of fragrance materials. From the perspective of protecting public health, it is desirable to have no or minimal false negatives, as a false-negative result may incorrectly indicate the lack of a genotoxicity hazard. However, the assay did have a high percentage of false-positive results, resulting in poor positive predictivity of the in vitro genotoxicity test battery outcome. Overall, the assay generated 100% negative predictivity and 3.9% positive predictivity. In addition to the data set of 371 fragrance materials, 30 natural complex substances were evaluated for BlueScreen HC, Ames, and in vitro micronucleus assay, and a good correlation in all three assays was observed. Overall, while a positive result may have to be further investigated, these findings suggest that the BlueScreen HC assay can be a valuable screening tool to detect the genotoxic potential of fragrance materials and mixtures.

Uninterrupted CAG repeat drives striatum-selective transcriptionopathy and nuclear pathogenesis in human Huntingtin BAC mice.

In Huntington's disease (HD), the uninterrupted CAG repeat length, but not the polyglutamine length, predicts disease onset. However, the underlying pathobiology remains unclear. Here, we developed bacterial artificial chromosome (BAC) transgenic mice expressing human mutant huntingtin (mHTT) with uninterrupted, and somatically unstable, CAG repeats that exhibit progressive disease-related phenotypes. Unlike prior mHTT transgenic models with stable, CAA-interrupted, polyglutamine-encoding repeats, BAC-CAG mice show robust striatum-selective nuclear inclusions and transcriptional dysregulation resembling those in murine huntingtin knockin models and HD patients. Importantly, the striatal transcriptionopathy in HD models is significantly correlated with their uninterrupted CAG repeat length but not polyglutamine length. Finally, among the pathogenic entities originating from mHTT genomic transgenes and only present or enriched in the uninterrupted CAG repeat model, somatic CAG repeat instability and nuclear mHTT aggregation are best correlated with early-onset striatum-selective molecular pathogenesis and locomotor and sleep deficits, while repeat RNA-associated pathologies and repeat-associated non-AUG (RAN) translation may play less selective or late pathogenic roles, respectively.

Mechanistic Insight and Local Structure Evolution of NiPS3 upon Electrochemical Lithiation.

Transition metal phosphorus trisulfide materials have received considerable research interest since the 1980-1990s as they exhibit promising energy conversion and storage properties. However, the mechanistic insights into Li-ion storage in these materials are poorly understood to date. Here, we explore the lithiation of NiPS3 material by employing in situ pair-distribution function analysis, Monte Carlo molecular dynamics calculations, and a series of ex situ characterizations. Our findings elucidate complex ion insertion and storage dynamics around a layered polyanionic compound, which undergoes intercalation and conversion reactions in a sequential manner. This study of NiPS3 material exemplifies the Li-ion storage mechanism in transition metal phosphorus sulfide materials and provides insights into the challenges associated with achieving reliable, high-energy phosphorus trisulfide systems.

Photopatternable Porous Separators for Micro-Electrochemical Energy Storage Systems.

The miniaturization of electrochemical energy storage (EES) systems, one of the key challenges facing the rapid expansion of the Internet-of-Things, has been limited by poor performance of the various energy-storage components at the micrometer scale. Here, the development of a unique photopatternable porous separator that overcomes the electrolyte difficulties involving resistive losses at small dimensions is reported. The separator is based on modifying the chemistry of SU-8, an epoxy-derived photoresist, through the addition of a miscible ionic liquid. The ionic liquid serves as a templating agent, which is selectively removed by solution methods, leaving the SU-8 scaffold whose interconnected porosity provides ion transport from the confined liquid electrolyte. The photopatternable separator exhibits good electrochemical, chemical, thermal, and mechanical stability during the operation of electrochemical devices in both 2D and 3D formats. For the latter, the separator demonstrates the ability to form conformal coatings over 3D structures. The development of the photopatternable separator overcomes the electrolyte issues, which have limited progress in the field of micro-EES.

The POCUS Consult: How Point of Care Ultrasound Helps Guide Medical Decision Making.

Point of care ultrasound (POCUS) allows for rapid, real-time evaluation of cardiovascular and respiratory pathology. The advent of portable, handheld devices and increased recognition by accrediting bodies of the importance of POCUS in guiding clinical decision making has expanded its use across the hospital setting and within medical training programs. POCUS allows clinicians to begin immediate investigation into their differential diagnoses without waiting for a formal imaging study, enhancing the speed of clinical interpretation. In addition to its diagnostic utility, POCUS can also inform clinicians of patients' response to interventions when serial exams are obtained. This review examines the role of POCUS in the context of frequently encountered patients and highlights the key clinical questions that can be readily answered by POCUS.

Effects of Airspeed on the Respiratory Rate, Rectal Temperature, and Immunity Parameters of Dairy Calves Housed Individually in an Axial-Fan-Ventilated Barn.

At many modern dairy farms, calves raised in barns are kept in individual stalls separated by solid partitions, which act as barriers. Ventilation fans blowing air perpendicular to these stalls only provide the optimal airflow to the first few calves, while those further away receive a slower airflow. To ascertain whatever effects different airflow speeds may have on the health of animals kept in stalls located at increasing distances from ventilation fans, we divided a select group of 43 Holstein dairy calves into six subgroups based on age, and each subgroup was subjected to either a specified high-speed or low-speed airflow as follows: (1) Six 3-day-olds received high-speed airflow (D3-HA); (2) Six 3-day-olds received low-speed airflow (D3-LA); (3) Eight 19 (±3)-day-olds received high-speed airflow (D19-HA); (4) Eight 19 (± 3)-day-olds received low-speed airflow (D19-LA); (5) Eight 29 (±3)-day-olds received high-speed airflow (D29-HA); and (6) Seven 29 (±3)-day-olds received medium-speed airflow (D29-MA). These trials show that the rectal temperatures and respiratory rates of D19-LA (39.37 °C; 72.90 breaths/min) were significantly higher than those of D19-HA (39.14 °C; 61.57 breaths/min) (p ≤ 0.05), and those of D29-MA (39.40 °C; 75.52 breaths/min) were significantly higher than those of D29-HA (39.20 °C; 68.41 breaths/min) (p ≤ 0.05). At 33 (±3) days of age, those calves receiving high-speed airflow (p ≤ 0.05) registered significantly higher immunoglobulins A and M than calves receiving low-speed flow. Those calves subjected to a high-speed airflow also registered significantly lower tumor necrosis factor levels than those receiving low-speed flow (p ≤ 0.05). Among the 29 to 43-day-old calves, no significant differences in immunity parameters were found to exist between groups D29-HA and D29-MA. On the basis of these findings, we were able to conclude that in the warm season, when the calves were less than 0.5 months old, low-speed (0.17-0.18 m/s) airflows had no significant effect on calves; when the calves were 1 month old, low-speed airflow (0.20-0.21 m/s) may impair the immune functions; when the calves were 1 to 1.5 months old, the airflow velocity higher than 0.9 m/s can meet the needs of the calf without a negative impact on the calf.

A chemical structure-based approach for estimating the added levels of flavourings to foods for the purpose of assessing consumer intake.

Intake assessment and hazard profile of chemical substances are the two critical inputs in a safety assessment. Human intake assessment presents challenges that stem either from the absence of data or from numerous sources of variability and uncertainty, which have led regulators to adopt conservative approaches that inevitably overestimate intake. Refinements of intake assessments produce more realistic estimates and help prioritise areas of concern and better direct investment of resources. However, use levels (ULs), which represent the usual added amount of flavourings to food products, are the starting point for refined intake assessments, are data-intensive, and data availability is often a limitation. The work presented here was undertaken to investigate the use level patterns of substances used as flavourings in foods and to develop a systematic tool for data extrapolation based on chemical structure. The available dataset consists of use levels reported through eight industry surveys and hence are representative of industry uses rather than regulatory limits, which are higher by design and not realistic. A systematic statistical analysis was undertaken to determine whether the industry-reported UL data can be used to estimate use levels of flavouring substances belonging to the same chemical group for which such data are not available. Predictive modelling approaches were explored to evaluate relationships in the data and utilised additional variables relevant to technological considerations, such as volatility losses upon heat treatment, and Tanimoto index-based pair-wise structural similarity scores to determine whether more granular similarity information can reduce the within-group variability. The analyses indicated that the use levels of flavouring substances can reasonably be estimated based on the available data using chemical group classifications stratified by food category. Source of uncertainty and limitations are discussed.

Cardiopulmonary Resuscitation in Intensive Care Unit Patients With Coronavirus Disease 2019.

Cardiopulmonary resuscitation (CPR) in patients with severe acute respiratory syndrome coronavirus-2-associated disease (coronavirus disease 2019) poses a unique challenge to health- care providers due to the risk of viral aerosolization and disease transmission. This has caused some centers to modify existing CPR procedures, limit the duration of CPR, or consider avoiding CPR altogether. In this review, the authors propose a procedure for CPR in the intensive care unit that minimizes the number of personnel in the immediate vicinity of the patient and conserves the use of scarce personal protective equipment. Highlighting the low likelihood of successful resuscitation in high-risk patients may prompt patients to decline CPR. The authors recommend the preemptive placement of central venous lines in high-risk patients with intravenous tubing extensions that allow for medication delivery from outside the patients' rooms. During CPR, this practice can be used to deliver critical medications without delay. The use of a mechanical compression system for CPR further reduces the risk of infectious exposure to health- care providers. Extracorporeal membrane oxygenation should be reserved for patients with few comorbidities and a single failing organ system. Reliable teleconferencing tools are essential to facilitate communication between providers inside and outside the patients' rooms. General principles regarding the ethics and peri-resuscitative management of coronavirus 2019 patients also are discussed.

Steric Impediment of Ion Migration Contributes to Improved Operational Stability of Perovskite Solar Cells.

The operational instability of perovskite solar cells (PSCs) is known to mainly originate from the migration of ionic species (or charged defects) under a potential gradient. Compositional engineering of the "A" site cation of the ABX3 perovskite structure has been shown to be an effective route to improve the stability of PSCs. Here, the effect of size-mismatch-induced lattice distortions on the ion migration energetics and operational stability of PSCs is investigated. It is observed that the size mismatch of the mixed "A" site composition films and devices leads to a steric effect to impede the migration pathways of ions to increase the activation energy of ion migration, which is demonstrated through multiple theoretical and experimental evidence. Consequently, the mixed composition devices exhibit significantly improved thermal stability under continuous heating at 85 °C and operational stability under continuous 1 sun illumination, with an extrapolated lifetime of 2011 h, compared to the 222 h of the reference device.

Aging, Immunity, and COVID-19: How Age Influences the Host Immune Response to Coronavirus Infections?

The novel coronavirus severe acute respiratory syndrome coronavirus 2 causing the Coronavirus disease (COVID-19) pandemic has ravaged the world with over 72 million total cases and over 1.6 million deaths worldwide as of early December 2020. An overwhelming preponderance of cases and deaths is observed within the elderly population, and especially in those with pre-existing conditions and comorbidities. Aging causes numerous biological changes in the immune system, which are linked to age-related illnesses and susceptibility to infectious diseases. Age-related changes influence the host immune response and therefore not only weaken the ability to fight respiratory infections but also to mount effective responses to vaccines. Immunosenescence and inflamm-aging are considered key features of the aging immune system wherein accumulation of senescent immune cells contribute to its decline and simultaneously increased inflammatory phenotypes cause immune dysfunction. Age-related quantitative and qualitative changes in the immune system affect cells and soluble mediators of both the innate and adaptive immune responses within lymphoid and non-lymphoid peripheral tissues. These changes determine not only the susceptibility to infections, but also disease progression and clinical outcomes thereafter. Furthermore, the response to therapeutics and the immune response to vaccines are influenced by age-related changes within the immune system. Therefore, better understanding of the pathophysiology of aging and the immune response will not only help understand age-related diseases but also guide targeted management strategies for deadly infectious diseases like COVID-19.

Impact of conditioning regimen on peripheral blood hematopoietic cell transplant.

AIM: To investigate infused hematopoietic cell doses and their interaction with conditioning regimen intensity +/- total body irradiation (TBI) on outcomes after peripheral blood hematopoietic cell transplant (PBHCT). METHODS: Our retrospective cohort included 247 patients receiving a first, T-replete, human leukocyte antigen-matched allogeneic PBHCT and treated between 2001 and 2012. Correlations were calculated using the Pearson product-moment correlation coefficient. Overall survival and progression free survival curves were generated using the Kaplan-Meier method and compared using the log-rank test. RESULTS: Neutrophil engraftment was significantly faster after reduced intensity TBI based conditioning [reduced intensity conditioning (RIC) + TBI] and > 4 × 106 CD34+ cells/kg infused. A higher total nucleated cell dose led to a higher incidence of grade II-IV acute graft-versus-host disease in the myeloablative + TBI regimen group (P = 0.03), but no significant difference in grade III-IV graft-versus-host disease. A higher total nucleated cell dose was also associated with increased incidence of moderate/severe chronic graft-versus-host disease, regardless of conditioning regimen. Overall and progression-free survival were significantly better in patients with a RIC + TBI regimen and total nucleated cell dose > 8 × 108/kg (3 years, overall survival: 70% vs 38%, P = 0.02, 3 years, progression free survival: 64% vs 38%, P = 0.02). CONCLUSION: TBI and conditioning intensity may alter the relationship between infused cell doses and outcomes after PBHCT. Immune cell subsets may predict improved survival after unmanipulated PBHCT.

Electrochemical and Spectroscopic Analysis of the Ionogel-Electrode Interface.

Ionogels, pseudo-solid-state electrolytes consisting of an ionic liquid electrolyte confined in a mesoporous inorganic matrix, have attracted interest recently due to their high ionic conductivity and physicochemical stability. These traits, coupled with their inherent solution processability, make them a viable solid electrolyte for solid-state battery systems. Despite the promising properties of ionogels, there have been very few investigations of the electrode-ionogel interface. In the present study, X-ray photoelectron spectroscopy, Raman spectroscopy, and electrochemical measurements were utilized to probe the surface reactions occurring at the electrode-ionogel interface for several electrode materials. Our results indicate that the sol acidity initiates breakdown of the organic constituents of the sol and reduction of the transition metals present in the electrode materials. This chemical attack forms an organic surface layer and affects the electrode composition, both of which can impede Li+ access. By modifying the silica sol-gel reaction via a two-step acid-base catalysis, these interfacial reactions can be avoided. Results are shown for a LiCoO2 electrode in which a high Li-ion capacity and stable cycling were achieved.