Plantar Kinetics During Wheeled Knee Walker Use Compared to Different Assistive Walking Devices in Persons With Type 2 Diabetes Mellitus.

Background: Diabetic patients with foot ulcers are commonly prescribed assistive walking devices to unload the affected foot and promote tissue healing. However, the effect on shear loads to the contralateral foot is unknown. This study investigated the effect of a wheeled knee walker (WKW), compared to common devices, on compressive and shear plantar forces carried by the propulsive foot during walking in patients with type 2 diabetes mellitus. A secondary objective investigated plantar forces' correlations with body weight unloaded (BWU). Methods: Participants walked a maximum of 200 m per condition during normal walking or when using crutches, a standard walker, and a WKW in randomized order. Plantar forces were measured with force plates, and wireless force-sensitive pads measured BWU through the hands. The WKW was instrumented to measure BWU onto the seat and handlebars. Three-dimensional motion capture confirmed gait events. Results: The WKW produced the lowest vertical, braking, propulsive, and medial shear forces but the highest lateral shear force among all conditions. Using crutches or a walker had negligible medial and lateral shear (mean = -6.69 N and -7.80 N), with normal walking producing the highest medial shear. There was a poor relationship between BWU and assistive walking devices and shear force values. Conclusion: A WKW could be the preferred assistive device for unloading a diabetic foot ulcer. The magnitude of lateral force would need further investigation to determine ulceration risk, given patient susceptibility and neuropathy. Clinical Relevance: Understanding shear forces on the propulsive foot is important for minimizing contralateral limb tissue damage risk while treating an ulcer. Different assistive walking devices change walking patterns and affect shear forces on the plantar surface of the foot. Although the WKW minimizes several loading metrics, a clinical trial investigating assistive walking device compliance and wound healing in diabetic foot ulcer patients across devices is needed.

Impact of influenza vaccination history in the clinical course of older adults hospitalized with COVID-19.

BACKGROUND AND PURPOSE: Some studies have shown that influenza vaccination is associated with a lower risk of SARS-CoV-2 infection; in patients with COVID-19 infection, admission to intensive care is reduced, with less need for mechanical ventilation, shorter hospital stays, and reduced mortality. This study aimed to determine if a history of annual influenza vaccination impacts the clinical course of SARS-CoV-2 infection during hospitalization. METHODS: This was an observational, prospective, cohort study of patients older than 65 admitted to the COVID-19 unit from January to June 2021. The history of influenza vaccination over the last 5 years was assessed in each patient during hospitalization. We measured the length of hospital stay, the need for admission to the intensive care unit (ICU), the patient's oxygen requirements, complications during hospitalization, and outcome (medical discharge or death). Patients with a history of vaccination against SARS-CoV-2 were not included. RESULTS: We analyzed 125 patients, 50.4% (n=63) with history of influenza vaccination and 49.6% (n=62) without a history of influenza vaccination. In-hospital mortality was 44.8%, higher in the unvaccinated (54.8%) population (p=0.008). ICU admission was 27% higher in vaccinated (35%) patients (p=0.05). Patients without a history of influenza vaccination had a higher prevalence of cardiac (8% vs. 5%, p=0.04) and renal complications (29% vs. 13%, p=0.02). Patients with a history of vaccination had a greater need for invasive mechanical ventilation (25.4%, p=0.02). CONCLUSION: In this study, a history of influenza vaccination in older adults with SARS-CoV-2 infection was related to lower in-hospital mortality.

Intermediates in Mechanochemical Reactions.

Mechanochemical reactions offer methodological and environmental advantages for chemical synthesis, constantly attracting attention within the scientific community. Besides unmistakable sustainability advantages, the conditions under which mechanochemical reactions occur, namely solventless conditions, sometimes facilitate the isolation of otherwise labile or inaccessible products. Despite these advantages, limited knowledge exists regarding the mechanisms of these reactions and the types of intermediates involved. Nevertheless, in an expanding number of cases, ex situ and in situ monitoring techniques have allowed for the observation, characterization, and isolation of reaction intermediates in mechanochemical transformations. In this Minireview, we present a series of examples in which reactive intermediates have been detected in mechanochemical reactions spanning organic, organometallic, inorganic, and materials chemistry. Many of these intermediates were stabilized by non-covalent interactions, which played a pivotal role in guiding the chemical transformations. We believe that by uncovering and understanding such instances, the growing mechanochemistry community could find novel opportunities in catalysis and discover new mechanochemical reactions while achieving simplification in chemical reaction design.

Interactions and reactivity in crystalline intermediates of mechanochemical cyclorhodation reactions.

There is experimental evidence that solid mixtures of the rhodium dimer [Cp*RhCl2]2 and benzo[h] quinoline (BHQ) produce two different polymorphic molecular cocrystals called 4α and 4ß under ball milling conditions. The addition of NaOAc to the mixture leads to the formation of the rhodacycle [Cp*Rh-(BHQ)Cl], where the central Rh atom retains its tetracoordinate character. Isolate 4ß reacts with NaOAc leading to the same rhodacycle while isolate 4α does not under the same conditions. We show that the puzzling difference in reactivity between the two cocrystals can be traced back to fundamental aspects of the intermolecular interactions between the BHQ and [Cp*RhCl2]2 fragments in the crystalline environment. To support this view, we report a number of descriptors of the nature and strength of chemical bonds and intermolecular interactions in the extended solids and in a cluster model. We calculate formal quantum mechanical descriptors based on electronic structure, electron density, and binding and interaction energies including an energy decomposition analysis. Without exception, all descriptors point to 4ß being a transient structure higher in energy than 4α with larger local and global electrophilic and nucleophilic powers, a more favorable spatial and energetic distribution of the frontier orbitals, and a more fragile crystal structure.

Simultaneous recognition of dopamine and uric acid in real samples through highly sensitive new electrode fabricated using ZnO/carbon quantum dots: bio-imaging and theoretical studies.

Dopamine (DA) and uric acid (UA), which are vital components in human metabolism, cause several health problems if they are present in altered concentrations; thus, the determination of DA and UA is essential in real samples using selective sensors. In the present study, graphite carbon paste electrodes (CPE) were fabricated using ZnO/carbon quantum dots (ZnO/CQDs) and employed as electrochemical sensors for the detection of DA and UA. These electrodes were fully characterized via different analytical techniques (XRD, SEM, TEM, XPS, and EDS). The electrochemical responses from the modified electrodes were evaluated using cyclic voltammetry, square wave voltammetry, and electrochemical impedance spectroscopy. The results showed that the present electrode has exhibited high sensitivity towards DA, recognizing even at low concentrations (0.12 µM), and no inference was observed in the presence of UA. The ZnO/CQD electrode was applied for the simultaneous detection of co-existing DA and UA in real human urine samples and the peak potential separation between DA and UA was found to be greatly associated with the synergistic effect originated from ZnO and CQDs. The limit of detection (LOD) of the electrode was analyzed, and compared with other commercially available electrodes. Thus, the ZnO/CQD electrode was used to detect DA and UA in real samples, such as Saccharomyces cerevisiae cells.

Supramolecular intermediates in thermo-mechanochemical direct amidations.

We present a solvent-free thermo-mechanochemical approach for the direct coupling of carboxylic acids and amines, which avoids activators and additives. Detailed analysis of the reactions by ex situ and in situ monitoring methods led to the observation, isolation, and characterisation of multicomponent crystalline intermediates that precede the formation of amides. We applied our methodology for the quantitative synthesis of the active pharmaceutical ingredient moclobemide.

Hand loading, rates of perceived exertion, and usability during assisted walking in patients with type 2 diabetes mellitus.

BACKGROUND: Patients suffering from a diabetic foot ulcer often receive a non-weight bearing prescription of the affected limb to promote healing. Total unilalteral offloading of the affected foot necessitates walking aids that require loading at the hands during ambulation. Excessive loading at the hands can increase of the risk of crutch palsy. In addition, certain walking aids can also be more strenuous and less comfortable to use than others, resulting in lower prescription compliance. This study aimed to investigate hand loading, rates of perceived exertion, and usability of typically prescribed walking aids in patients with Type 2 Diabetes. METHODS: Twenty patients (12 F | 8 M, 61.0 ± 10.36 yrs., 90.54 ± 13.34 kg, 1.71 ± 0.08 m) walked as much as 200 m without assistance and with crutches, walkers, and a wheeled knee walker instrumented with flexible force-sensing pads on walking aid handles. Patients rated exertion using a Modified Borg Scale and completed a System Usability Scale questionnaire after each walking condition with or without walking aids. FINDINGS: Results show that using a wheeled knee walker required 94% less hand loading than crutches and walkers. Patients reported 45% lower exertion with the WKW compared to crutches and walkers, and scored the usability of the wheeled knee walker 106% higher than crutches and walkers. INTERPRETATION: The wheeled knee walker could be the preferred walking aid for total unilateral offloading because of the reduced loading demand at the hands, lower exertion during use, and greater usability compared to crutches and walkers.

The Role of Crystalline Intermediates in Mechanochemical Cyclorhodation Reactions Elucidated by in-Situ X-ray Powder Diffraction and Computation.

The occurrence of crystalline intermediates in mechanochemical reactions might be more widespread than previously assumed. For example, a recent study involving the acetate-assisted C-H activation of N-Heterocycles with [Cp*RhCl2 ]2 by ball milling revealed the formation of transient cocrystals between the reagents prior to the C-H activation step. However, such crystalline intermediates were only observed through stepwise intervallic ex-situ analysis, and their exact role in the C-H activation process remained unclear. In this study, we monitored the formation of discrete, stoichiometric cocrystals between benzo[h]quinoline and [Cp*RhCl2 ]2 by ball milling using in-situ synchrotron X-ray powder diffraction. This continuous analysis revealed an initial cocrystal that transformed into a second crystalline form. Computational studies showed that differences in noncovalent interactions made the [Cp*RhCl2 ]2 unit in the later-appearing cocrystal more reactive towards NaOAc. This demonstrated the advantage of cocrystal formation before the acetate-assisted metalation-deprotonation step, and how the net cooperative action of weak interactions between the reagents in mechanochemical experiments can lead to stable supramolecular assemblies, which can enhance substrate activation under ball-milling conditions. This could explain the superiority of some mechanochemical reactions, such as acetate-assisted C-H activation, compared to their solution-based counterparts.

Microstructure, Phase Evolution, and Chemical Behavior of CrCuFeNiTiAlx High Entropy Alloys Processed by Mechanical Alloying.

High entropy alloys (HEAs) of the type CrCuFeNiTi-Alx were processed through mechanical alloying. The aluminum concentration was varied in the alloy, to determine its effect on the HEAs' microstructure, phase formation, and chemical behavior. X-ray diffraction studies performed on the pressureless sintered samples revealed the presence of structures composed of face centered cubic (FCC) and body centered cubic (BCC) solid-solution phases. Since the valences of the elements that form the alloy are different, a nearly stoichiometric compound was obtained, increasing the final entropy of the alloy. The aluminum was partly responsible for this situation, which also favored transforming part of the FCC phase into BCC phase on the sintered bodies. X-ray diffraction also indicated the formation of different compounds with the alloy's metals. Bulk samples exhibited microstructures with different phases. The presence of these phases and the results of the chemical analyses revealed the formation of alloying elements that, in turn, formed a solid solution and, consequently, had a high entropy. From the corrosion tests, it could be concluded that the samples with a lower aluminum content were the most resistant to corrosion.

Muscle activation and rating of perceived exertion of typically developing children during DRY and aquatic treadmill walking.

Aquatic treadmill gait training is a poorly understood rehabilitation method that alters bodyweight support, increases lower limb resistance, and assists with postural stability. This training could be an attractive tool for clinical populations with balance control issues or limited weight-bearing prescriptions for the lower limb. As a first step, the purpose of this study was to quantify differences in mean muscle activity of the tibialis anterior, rectus femoris, medial gastrocnemius, and semitendinosus, and perceived exertion (RPE) in typically developing children (7:8 M:F, age = 11.3 ± 4.1 years, 1.46 ± 0.18 m, and 44.2 ± 16.8 kg) during dry and aquatic treadmill walking at 75 %, 100 %, and 125 % self-selected speed. We hypothesized that the greatest mean muscle activity, normalized to percent maximum voluntary contraction and averaged across all strides, would be observed during 125 % dry treadmill walking and that aquatic treadmill walking would produce lower RPE. Overall, aquatic treadmill walking reduced mean medial gastrocnemius activity by 50.2 % (padj < 0.001), increased mean rectus femoris activity at least 32.8 % (padj < 0.006), and produced 78.0 % (padj = 0.007) greater RPE compared to dry treadmill walking. This study provides normative pediatric data for future aquatic treadmill walking studies in clinical populations to help inform gait rehabilitation protocols.

Runs of homocigosity and its association with productive traits in Mexican Holstein cattle.

The objective of this study was to describe the runs of homozygosity (ROH) detected in the Mexican Holstein population and to associate them with milk, fat and protein yields, and conformation final score. After imputation and genomic quality control, 4,227 genotyped animals with 100,806 SNPs markers each were used. ROH with a minimum length of 1 Mb and a minimum of 10 SNPs were included in the analysis. One heterozygous SNP marker and five missing genotypes per ROH were allowed. A total of 425,098 ROH were found in the studied population (71.83 ± 10.73 ROH per animal), with an average length and coverage of 4.80 ± 0.77 Mb, and 276.89 Mb, respectively. The average chromosome length covered by ROH was 10.40 ± 3.70 Mb. ROH between 1 and 2 Mb were the most frequent in the population (51.33%) while those between 14 and 16 Mb were the least frequent (1.20%). Long chromosomes showed a larger number of ROH. Chromosomes 10 and 20, had a greater percentage of their length covered by ROH because they presented a largest number of long ROH (>8 Mb). From the total ROH, 17 were detected in 1,847 animals and distributed among different chromosomes, and were associated with milk, fat and protein yield and percentage, and conformation final score. Of the ROH with effects on production traits, the majority were found with a length between 1 and 4 Mb. These results show evidence of genomic regions preserved by genetic selection and associated with the improvement of the productivity and functionality of dairy cattle.

Alterations to plantar loading and ankle range of motion of the contralateral foot during assisted walking in patients with Type 2 Diabetes Mellitus.

AIMS: Patients with diabetic foot ulcers are instructed to be non-weight bearing on the affected limb to promote healing. Therefore, the aim of this study was to investigate the effect of different assistive devices on whole foot plantar loading, peak forefoot force, ankle range of motion, and locomotion speed during gait in patients with Type 2 Diabetes Mellitus. METHODS: Participants walked normally, with crutches, a walker, and a wheeled knee walker (WKW) in randomized order. Force sensitive insoles and 3D motion capture were used to record plantar normal force and ankle kinematics. Force sensitive pads were wrapped around handles of the crutches and walker to measure bodyweight offloaded onto the assistive device. An instrumented WKW was used to measure bodyweight offloaded onto the handlebars and knee cushion. RESULTS: Locomotion with the WKW produced the lowest whole foot plantar loading and peak forefoot force in the propulsive limb, while also producing the greatest ankle range of motion and locomotion speed amongst assistive devices. CONCLUSIONS: This pre-clinical study found that the WKW could be the preferred assistive device for total unilateral offloading of diabetic foot ulcers as it reduced propulsive limb whole foot and forefoot plantar loading while retaining ankle range of motion and locomotion speed.

Polymer and small molecule mechanochemistry: closer than ever.

The formation and scission of chemical bonds facilitated by mechanical force (mechanochemistry) can be accomplished through various experimental strategies. Among them, ultrasonication of polymeric matrices and ball milling of reaction partners have become the two leading approaches to carry out polymer and small molecule mechanochemistry, respectively. Often, the methodological differences between these practical strategies seem to have created two seemingly distinct lines of thought within the field of mechanochemistry. However, in this Perspective article, the reader will encounter a series of studies in which some aspects believed to be inherently related to either polymer or small molecule mechanochemistry sometimes overlap, evidencing the connection between both approaches.

Nanostructured silicate catalysts for environmentally benign Strecker-type reactions: status quo and quo vadis.

Chemical processes are usually catalytic transformations. The use of catalytic reagents can reduce the reaction temperature, decrease reagent-based waste, and enhance the selectivity of a reaction potentially avoiding unwanted side reactions leading to green technology. Chemical processes are also frequently based on multicomponent reactions (MCRs) that possess evident improvements over multistep processes. Both MCRs and catalysis tools are the most valuable principles of green chemistry. Among diverse MCRs, the three-component Strecker reaction (S-3-CR) is a particular transformation conducive to the formation of valuable bifunctional building blocks (α-amino nitriles) in organic synthesis, medicinal chemistry, drug research, and organic materials science. To be a practical synthetic tool, the S-3-CR must be achieved using alternative energy input systems, safe reaction media, and effective catalysts. These latter reagents are now deeply associated with nanoscience and nanocatalysis. Continuously developed, nanostructured silicate catalysts symbolize green pathways in our quest to attain sustainability. Studying and developing nanocatalyzed S-3-CR condensations as an important model will be suitable for achieving the current green mission. This critical review aims to highlight the advances in the development of nanostructured catalysts for technologically important Strecker-type reactions and to analyze this progress from the viewpoint of green and sustainable chemistry.

Cocrystal Formation Precedes the Mechanochemically Acetate-Assisted C-H Activation with [Cp*RhCl2 ]2.

This work reports the experimentally studied mechanochemical formation of rhodacycles by ball milling pyridine- and quinoline-derived substrates and [Cp*RhCl2 ]2 in the presence of NaOAc. Ex-situ analysis of the mechanochemical reactions using powder X-ray diffraction (PXRD), solid-state UV-vis spectroscopy and ATR-FTIR spectroscopy revealed the formation of unexpected cocrystals between the substrates and the rhodium dimer prior to the C-H activation step. This sequence of events differs from the generally accepted steps in solution in which cleavage of [Cp*RhCl2 ]2 is initiated by acetate ions. Additionally, the mechanochemical approach enabled the synthesis of the six-membered rhodacycle [Cp*Rh(2-benzilpyridine)Cl], a metal complex repeatedly reported as inaccessible in solution. Altogether, the results of this investigation clarify some of the fundamental aspects of mechanochemical cyclometallations.

Multi-faceted reactivity of N-fluorobenzenesulfonimide (NFSI) under mechanochemical conditions: fluorination, fluorodemethylation, sulfonylation, and amidation reactions.

In the search for versatile reagents compatible with mechanochemical techniques, in this work we studied the reactivity of N-fluorobenzenesulfonimide (NFSI) by ball milling. We corroborated that, by mechanochemistry, NFSI can engage in a variety of reactions such as fluorinations, fluorodemethylations, sulfonylations, and amidations. In comparison to the protocols reported in solution, the mechanochemical reactions were accomplished in the absence of solvents, in short reaction times, and in yields comparable to or higher than their solvent-based counterparts.

Mechanistic Insights on the Mechanosynthesis of Phenytoin, a WHO Essential Medicine.

In recent years, mechanochemistry has enriched the toolbox of synthetic chemists, enabling faster and more sustainable access to new materials and existing products, including active pharmaceutical ingredients (APIs). However, molecular-level understanding of most mechanochemical reactions remains limited, delaying the implementation of mechanochemistry in industrial applications. Herein, we have applied in situ monitoring by Raman spectroscopy to the mechanosynthesis of phenytoin, a World Health Organization (WHO) Essential Medicine, enabling the observation, isolation, and characterization of key molecular-migration intermediates involved in the single-step transformation of benzil, urea, and KOH into phenytoin. This work contributes to the elucidation of a reaction mechanism that has been subjected to a number of interpretations over time and paints a clear picture of how mechanosynthesis can be applied and optimized for the preparation of added-value molecules.

The optics of the human eye at 8.6 µm resolution.

Ocular optics is normally estimated based on up to 2,600 measurement points within the pupil of the eye, which implies a lateral resolution of approximately 175 µm for a 9 mm pupil diameter. This is because information below this resolution is not thought to be relevant or even possible to obtain with current measurement systems. In this work, we characterize the in vivo ocular optics of the human eye with a lateral resolution of 8.6 µm, which implies roughly 1 million measurement points for a pupil diameter of 9 mm. The results suggest that the normal human eye presents a series of hitherto unknown optical patterns with amplitudes between 200 and 300 nm and is made up of a series of in-phase peaks and valleys. If the results are analysed at only high lateral frequencies, the human eye is also found to contain a whole range of new information. This discovery could have a great impact on the way we understand some fundamental mechanisms of human vision and could be of outstanding utility in certain fields of ophthalmology.

Statistical Evaluation of the Material-Source Effects on the DSR Rheological Properties of Plant-Mix Extracted Asphalt-Binders.

The work presented in this paper was carried out to statistically evaluate and quantify the material-source effect on the asphalt-binder's rheological properties using Analysis of Variance (ANOVA) and Tukey's Honestly Significant Difference (Tukey´s HSD) test. The study focused on the Asphalt-Binders' high-temperature rheological properties, namely, the G*, δ, G*/Sin(δ) and G*/(1 - (1/Tan(δ)Sin(δ))) parameters, measured using the Dynamic Shear Rheometer (DSR) device. The DSR data analyzed in the study were extracted from the Texas flexible pavements and overlays database, namely, the Texas Data Storage System (DSS), covering two Asphalt-Binders (ABs), performance grade (PG) 64-22 and PG 76-22 plant-mix extracted ABs that were treated as rolling thin film oven (RTFO) residue, and sourced from 14 different suppliers. The study findings substantiate that material-source has an effect on the high-temperature rheological properties of ABs. Additionally, it was also concluded that in as much as performance superiority and costs are crucial issues in deciding the AB source/provider, consistency and quality aspects cannot be disregarded. Therefore, material-source effects should be inclusively evaluated from both performance (rheological properties) and quality (consistence) standpoints as well as cost considerations when choosing a supplier. In general, the study contributes to the state-of-the-art enrichment on aspects of material-source effects on RTFO residue ABs' high-temperature rheological properties, consistency, variability, and data quality.