Metallic Impurities in Electrolysis: Catalytic Effect of Pb Traces in Reductive Amination and Acetone Reduction.

The electrochemical hydrogenation (e-hydrogenation) of unsaturated compounds like imines or carbonyls presents a benign reduction method. It enables direct use of electrons as reducing agent, water as proton source, while bypassing the need for elevated temperatures or pressures. In this contribution, we discuss the active species in electrocatalytic reductive amination with the transformation of acetone and methylamine as model reaction. Surprisingly, lead impurities in the ppm-range proved to possess a significant effect in e-hydrogenation. Accordingly, the influence of applied potential and cathode material in presence of 1 ppm Pb was investigated. Finally, we transferred the insights to the reduction of acetone manifesting comparable observations as for imine reduction. The results suggest that previous studies on electrochemical reduction in the presence of lead electrodes should be re-evaluated.

Impact of newborn screening for very-long-chain acyl-CoA dehydrogenase deficiency on genetic, enzymatic, and clinical outcomes.

Most infants with very-long-chain acyl-CoA dehydrogenase deficiency (VLCADD) identified by newborn screening (NBS) are asymptomatic at the time of diagnosis and remain asymptomatic. If this outcome is due to prompt diagnosis and initiation of therapy, or because of identification of individuals with biochemical abnormalities who will never develop symptoms, is unclear. Therefore, a 10-year longitudinal national cohort study of genetically confirmed VLCADD patients born before and after introduction of NBS was conducted. Main outcome measures were clinical outcome parameters, acyl-CoA dehydrogenase very long chain gene analysis, VLCAD activity, and overall capacity of long-chain fatty acid oxidation (LC-FAO flux) in lymphocytes and cultured skin fibroblasts. Median VLCAD activity in lymphocytes of 54 patients, 21 diagnosed pre-NBS and 33 by NBS was, respectively, 5.4% (95% confidence interval [CI]: 4.0-8.3) and 12.6% (95% CI: 10.7-17.7; P < 0.001) of the reference mean. The median LC-FAO flux was 33.2% (95% CI: 22.8-48.3) and 41% (95% CI: 40.8-68; P < 0.05) of the control mean, respectively. Clinical characteristics in 23 pre-NBS and 37 NBS patients revealed hypoglycemic events in 12 vs 2 patients, cardiomyopathy in 5 vs 4 patients and myopathy in 14 vs 3 patients. All patients with LC-FAO flux <10% developed symptoms. Of the patients with LC-FAO flux >10% 7 out of 12 diagnosed pre-NBS vs none by NBS experienced hypoglycemic events. NBS has a clear beneficial effect on the prevention of hypoglycemic events in patients with some residual enzyme activity, but does not prevent hypoglycemia nor cardiac complications in patients with very low residual enzyme activity. The effect of NBS on prevalence and prevention of myopathy-related complications remains unclear.

Closed Incision Negative Pressure Wound Therapy vs Conventional Dry Dressings After Primary Knee Arthroplasty: A Randomized Controlled Study.

BACKGROUND: The purpose of this study was to assess the effect of negative pressure wound therapy (NPWT) on quality of life (QoL), wound complications, and cost after primary knee arthroplasty. METHODS: A prospective analysis of 33 patients undergoing primary knee arthroplasty performed by 3 surgeons in one institution. The first 12 patients (3 bilateral and 9 unilateral) had conventional dry dressings (CDD) applied and cost of dressings was assessed. The other 21 patients all underwent bilateral knee arthroplasty and had either side randomized to receiving NPWT or CDD. Cost of dressings, wound complications, and QoL were compared. RESULTS: One patient had a reaction to the NPWT requiring readmission. Another had persistent wound drainage that required NPWT application. There were no wound issues in the remaining 31 patients. The average cost in the first 12 patients was Australian dollar $48.70 with an average of 1.5 changes on ward. In the 21 patients receiving both dressings, the average cost for CDD was less (Australian dollar $43.51 vs $396.02, P ≤ .011, effect size [ES] = 1.06). When comparing QoL factors, wound leakage (0.14 vs 0.39 P = .019, ES = 1.02), and wound protection (0.16 vs 0.33, P = .001, ES = 0.021) were better in the NPWT group. There was no other significant difference in QoL factors. The average number of changes on the ward was less for the NPWT group (1.19 vs 1.38, P = .317, ES = 1.02). CONCLUSION: We found no benefit in wound healing or cost with NPWT post knee arthroplasty. There was some benefit in NPWT QoL factors less wound leakage and better protection.

Solid Molecular Phosphine Catalysts for Formic Acid Decomposition in the Biorefinery.

The co-production of formic acid during the conversion of cellulose to levulinic acid offers the possibility for on-site hydrogen production and reductive transformations. Phosphorus-based porous polymers loaded with Ru complexes exhibit high activity and selectivity in the base-free decomposition of formic acid to CO2 and H2 . A polymeric analogue of 1,2-bis(diphenylphosphino)ethane (DPPE) gave the best results in terms of performance and stability. Recycling tests revealed low levels of leaching and only a gradual decrease in the activity over seven runs. An applicability study revealed that these catalysts even facilitate selective removal of formic acid from crude product mixtures arising from the synthesis of levulinic acid.

Perspectives on deprescribing in older people with type 2 diabetes and/or cardiovascular conditions: challenges from healthcare provider, patient and caregiver perspective, and interventions to support a proactive approach.

INTRODUCTION: For people with type 2 diabetes and/or cardiovascular conditions, deprescribing of glucose-lowering, blood pressure-lowering and/or lipid-lowering medication is recommended when they age, and their health status deteriorates. So far, deprescribing rates of these so-called cardiometabolic medications are low. A review of challenges and interventions addressing these challenges in this population is pertinent. AREAS COVERED: We first provide an overview of relevant deprescribing recommendations. Next, we review challenges for healthcare providers (HCPs) to deprescribe cardiometabolic medication and provide insight in the patient and caregiver perspective on deprescribing. We summarize findings from research on implementing deprescribing of cardiometabolic medication and reflect on strategies to enhance deprescribing. We have used a combination of methods to search for relevant articles. EXPERT OPINION: There is a need for rigorous development and evaluation of intervention strategies aimed at proactive deprescribing of cardiometabolic medication. To address challenges at different levels, these should be multifaceted interventions. All stakeholders must become aware of the relevance of deintensifying medication in this population. Education and training for HCPs and patients should support patient-centered communication and shared decision-making. Development of procedures and tools to select eligible patients and conduct targeted medication reviews are important for implementation of deprescribing in routine care.

Origin of copper dissolution under electrocatalytic reduction conditions involving amines.

Cu dissolution has been identified as the dominant process that causes cathode degradation and losses even under cathodic conditions involving methylamine. Despite extensive experimental research, our fundamental and theoretical understanding of the atomic-scale mechanism for Cu dissolution under electrochemical conditions, eventually coupled with surface restructuring processes, is limited. Here, driven by the observation that the working Cu electrode is corroded using mixtures of acetone and methylamine even under reductive potential conditions (-0.75 V vs. RHE), we employed Grand Canonical density functional theory to understand this dynamic process under potential from a microscopic perspective. We show that amine ligands in solution directly chemisorb on the electrode, coordinate with the metal center, and drive the rearrangement of the copper surface by extracting Cu as adatoms in low coordination positions, where other amine ligands can coordinate and stabilize a surface copper-ligand complex, finally forming a detached Cu-amine cationic complex in solution, even under negative potential conditions. Calculations predict that dissolution would occur for a potential of -1.1 V vs. RHE or above. Our work provides a fundamental understanding of Cu dissolution facilitated by surface restructuring in amine solutions under electroreduction conditions, which is required for the rational design of durable Cu-based cathodes for electrochemical amination or other amine involving reduction processes.

Effects of a multicomponent communication training to involve older people in decisions to DEPRESCRIBE cardiometabolic medication in primary care (CO-DEPRESCRIBE): protocol for a cluster randomized controlled trial with embedded process and economic evaluation.

BACKGROUND: Deprescribing of medication for cardiovascular risk factors and diabetes has been incorporated in clinical guidelines but proves to be difficult to implement in primary care. Training of healthcare providers is needed to enhance deprescribing in eligible patients. This study will examine the effects of a blended training program aimed at initiating and conducting constructive deprescribing consultations with patients. METHODS: A cluster-randomized trial will be conducted in which local pharmacy-general practice teams in the Netherlands will be randomized to conducting clinical medication reviews with patients as usual (control) or after receiving the CO-DEPRESCRIBE training program (intervention). People of 75 years and older using specific cardiometabolic medication (diabetes drugs, antihypertensives, statins) and eligible for a medication review will be included. The CO-DEPRESCRIBE intervention is based on previous work and applies models for patient-centered communication and shared decision making. It consists of 5 training modules with supportive tools. The primary outcome is the percentage of patients with at least 1 cardiometabolic medication deintensified. Secondary outcomes include patient involvement in decision making, healthcare provider communication skills, health/medication-related outcomes, attitudes towards deprescribing, medication regimen complexity and health-related quality of life. Additional safety and cost parameters will be collected. It is estimated that 167 patients per study arm are needed in the final intention-to-treat analysis using a mixed effects model. Taking loss to follow-up into account, 40 teams are asked to recruit 10 patients each. A baseline and 6-months follow-up assessment, a process evaluation, and a cost-effectiveness analysis will be conducted. DISCUSSION: The hypothesis is that the training program will lead to more proactive and patient-centered deprescribing of cardiometabolic medication. By a comprehensive evaluation, an increase in knowledge needed for sustainable implementation of deprescribing in primary care is expected. TRIAL REGISTRATION: The study is registered at ClinicalTrials.gov (identifier: NCT05507177).

Results of a cosmetovigilance survey in The Netherlands.

BACKGROUND: Cosmetic products contribute considerably to the incidence of contact dermatitis. In response to a resolution of the Council of Europe, the National Institute for Public Health and the Environment (RIVM) in The Netherlands set up a pilot project to report undesirable effects attributed to cosmetic products. OBJECTIVES: To provide an overview of undesirable effects attributed to cosmetic products and to identify the ingredients involved. The information could contribute to the assessment of whether current EU legislation on cosmetics provides adequate protection. PATIENTS/METHODS: General practitioners, dermatologists and consumers in The Netherlands completed questionnaires on reported undesirable effects of cosmetics. Dermatologists also carried out patch tests and, where necessary, tests with specific batch ingredients of the associated cosmetic product. A website and a public awareness campaign were launched to encourage consumers to report undesirable effects. RESULTS: Between July 2009 and May 2011, the RIVM received more than 1600 reports. Severe undesirable effects were claimed in 1-4% of the cases. The most frequently reported cosmetic products were make-up and moisturisers, and the most frequently identified allergens were isothiazolinones and fragrance ingredients. Three patients tested positive for co-polymers/cross-polymers. CONCLUSIONS: Further investigations are recommended on the prevalence of isothiazolinone-induced allergic contact dermatitis and the allergenic potential of co-polymers/cross-polymers.

Notes on the Melitaea ornata Christoph, 1893, complex in the Levant (Lepidoptera: Nymphalidae) including new synonymy and observations on lectotype designations for Melitaea phoebe dorae Graves, 1925.

Two independent designations for a lectotype of Melitaea phoebe dorae Graves, 1925, are discussed and resolved. Errors of labelling in presentation of some Melitaea taxa in recent literature are identified. Synonymy of the name klili Benyamini, 2021, with M. telona Fruhstorfer, 1908, is confirmed; the name tzinensis Benyamini, 2023 syn nov., is discussed and placed in synonymy with M. telona Fruhstorfer, 1908.

Investigations into the Melitaea ornata species complex in the Levant: M. telona and the newly erected species Melitaea klili Benyamini, 2021 (Lepidoptera: Nymphalidae).

Melitaea klili Benyamini, 2021 was recently described from Israel as a species closely related to M. telona Fruhstorfer, 1908, but different in phenology, ecological preferences and with an allopatric distribution. Here, based on comparative examinations of mitochondrial DNA-barcodes, male genitalia and larval behaviour under laboratory conditions, we synonymize M. klili with M. telona. The COI barcodes of M. klili were found to be identical to those of M. telona. Analysis of 658 bp fragment of the mitochondrial gene COI demonstrated that the minimum uncorrected p-distance between M. ornata and M. telona was 1.98%. This value is remarkably less than the 3% threshold traditionally accepted as a species boundary in DNA barcoding studies. The morphological differences between these taxa are minimal. In fact, M. ornata and M. telona represent two phylogenetic lineages, the taxonomic status of which (separate species or subspecies of the same species) is intermediate and debatable.

Reassessment of the status of some European and Asian Melitaea taxa described as subspecies of Melitaea phoebe ([Denis amp; Schiffermller], 1775), with designations of lectotypes where appropriate (Lepidoptera: Nymphalidae).

Morphological characters of value in distinguishing Melitaea phoebe from M. ornata are exemplified from photographs of specimens from sympatric and partially synchronic populations in the Russian Federation and Slovenia. Type material of a number of subspecies classified as M. phoebe have been examined and confirmed as being subspecies of M. phoebe or as subspecies of either M. ornata or M. telona. Larval and adult morphology of M. telona is very similar to those of M. ornata, making morphological separation difficult. Distribution of M. telona forms a major criterion for separation. Lectotypes are designated for amanica Rebel, 1917 and dorae Graves, 1925. The name enoch Higgins, 1941 is recognised as a distinct species and the names abbas Gross Ebert, 1975 and zagrosi Tth Varga, 2011 synonymised with Melitaea enoch.

[Neonatal screening in Europe revisited: An ISNS-perspective on the current state and developments since 2010]. / Dépistage néonatal en Europe - Évolution au cours de la dernière décennie et analyse de la situation actuelle par la Société internationale de dépistage néonatal.

Neonatal screening (NBS) was initiated in Europe during the 1960s with the screening for phenylketonuria. The panel of screened disorders ("conditions") then gradually expanded, with a boost in the late 1990's with the introduction of tandem mass spectrometry (MS/MS), making it possible to screen for 40-50 conditions in one blood spot. The most recent additions to screening programmes (screening for cystic fibrosis, severe combined immunodeficiency and spinal muscular atrophy) were assisted by or realised through the introduction of molecular genetics techniques. For this survey we collected data from 51 European countries. We report on the developments between 2010 and 2020, and highlight the achievements made during this period. We also identify areas where further progress can be made, mainly by exchanging knowledge and learning from experiences in neighbouring countries. Between 2010 and 2020, most NBS programmes in geographical Europe have matured considerably, both in terms of methodology (modernised) and with regards to the panel of conditions screened (expanded). These developments indicate that more collaboration in Europe through European organisations is gaining momentum. Only by working together can we accomplish the timely detection of newborn infants potentially suffering from one of the many rare diseases and take appropriate actions.

TITLE: Dépistage néonatal en Europe - Évolution au cours de la dernière décennie et analyse de la situation actuelle par la Société internationale de dépistage néonatal. ABSTRACT: Le dépistage néonatal a débuté en Europe dans les années 1960 avec celui de la phénylcétonurie. Le nombre de maladies dépistées a, par la suite, augmenté progressivement, de manière plus marquée à la fin des années 1990 avec l'arrivée de la spectrométrie de masse en tandem (MS/MS) qui a permis le dépistage de 40 à 50 maladies sur une seule goutte de sang séché. Les ajouts les plus récents à cette liste de maladies (mucoviscidose, déficits immunitaires combinés sévères et atrophie musculaire spinale) ont été rendus possibles grâce à la génétique moléculaire. À partir des informations provenant de 51 pays d'Europe, nous décrivons dans cette revue l'évolution du dépistage entre 2010 et 2020, ainsi que les progrès réalisés pendant cette période, tout en soulignant les aspects qui méritent d'être améliorés. Des progrès pourront en effet être accomplis grâce aux échanges d'informations et, pour certains pays, en tirant profit de l'expérience acquise dans des pays voisins. La plupart des programmes de dépistage mis en place dans l'Europe « géographique ¼ au cours de cette période ont gagné en maturité en termes méthodologiques (modernisation des techniques) et en termes quantitatifs (augmentation du nombre des maladies dépistées). Ces développements nous montrent que la collaboration entre les différentes organisations s'accélère en Europe. Ce n'est qu'en travaillant ensemble que nous pourrons identifier en temps opportun les nouveau-nés atteints d'une des nombreuses maladies rares détectables et prendre les mesures qui s'imposent.

Music and low-frequency vibrations for the treatment of chronic musculoskeletal pain in elderly: A pilot study.

BACKGROUND: Transcutaneous vagal nerve stimulation has analgesic potential and might be elicited by abdominally administered low-frequency vibrations. The objective was to study the safety and effect of a combination of music and abdominally administered low-frequency vibrations on pain intensity in elderly patients with chronic musculoskeletal pain. METHODS: This trial was an international multicenter, randomized controlled pilot study. Patients at age ≥ 65 years with musculoskeletal pain for ≥ 3 months and a daily pain score ≥ 4 out of 10 were recruited at three centers. They were randomized to receive either a combination of music and low-frequency (20-100 Hz) vibrations administered to the abdomen, or a combination with the same music but with higher frequency (200-300 Hz) vibrations administered to the abdomen. Low-frequency vibrations were expected to result in pain reduction measured with a numeric pain rating scale (NRS). Patients in both groups received eight treatments of the music combined with the vibrations in three weeks. Primary outcomes were safety (Serious Adverse Events) and pain intensity measured at baseline, after the last treatment and at six weeks follow-up. Multilevel linear model analyses were performed to study group and time effects. RESULTS: A total of 45 patients were analyzed according to intention-to-treat principle. After 344 treatments, 1 Adverse Event was found related to the intervention, while 13 Adverse Events were possibly related. A multilevel linear model showed that the interaction effect of group by time did not predict pain intensity (F[1, 45.93] = 0.002, p = 0.97) when comparing pain intensity at baseline, after the last treatment and at follow-up. CONCLUSIONS: The combination of music and abdominally administered vibrations was found to be safe and well tolerated by the elderly patients. However, over time, neither the low-frequency treatment group nor the high-frequency treatment group provided clinically meaningful pain relief. There is no evidence that the low-frequency treatment elicited vagal nerve stimulation. TRIAL REGISTRATION: The trial was prospectively registered in the Netherlands Trial Register (NTR: NL7606) on 21-03-2019.

Mg(OH)2 -Facilitated Liquid-Phase Conversion of Lactic Acid into 1,2-Propanediol over Cu: An Experimental and Theoretical Study.

Mg(OH)2 is found to exhibit superior performance in the liquid-phase conversion of lactic acid (LA) into 1,2-propanediol over Cu. A conversion of 90 % with a selectivity of 98 % is achieved at 513 K and 5 MPa H2 . Mg(LA)2 could be identified as a crucial intermediate in this reaction, as it undergoes faster conversion than the combination of LA and Mg(OH2 ) and regeneration of Mg(OH)2 through the conversion of Mg(LA)2 as a substrate. DFT calculations reveal that the energetic span of the reaction decreases from 46.6 kcal mol-1 catalyzed with no cation to 43.6 kcal mol-1 with [Mg(OH)]+ , confirming the facilitating effect of Mg(OH)2 .

Flexion deformity and laxity as a function of knee position at the time of tensioning of rigid anatomic hamstring ACL grafts.

BACKGROUND: Anatomic ACL grafts routinely display the anisometric length-tension behaviour seen in the native ligament with maximum length in full knee extension. Recent improvements in hamstring graft preparation and fixation have improved graft rigidity to the point where total graft lengthening after implantation may be less than 1 mm. Despite this it remains common practice to fix these grafts in a knee flexed position. METHODS: Nineteen participants underwent all-inside ACL reconstruction with optimally preconditioned 4 strand semitendinosus grafts using bi-cortical adjustable suspensory loop fixation. Using a computer navigation system, baseline measures of anisometricity, extension range, and tibial rotation were made. The graft was tensioned and provisionally fixed with the knee flexed 5° beyond its anisometric point and extension range recorded. The graft was then definitively fixed with the knee fully extended and extension range and tibial rotation recorded again. Anterior laxity measurements were made pre-operatively and postoperatively using a manual arthrometer and compared to those from the contralateral limb. RESULTS: Fixing the graft with the knee flexed produced a mean FD of 10.9° (p < 0.0001) and fixing in extension restored full extension (p = 0.661). Fixing in extension restored anterior laxity at 30° (p = 0.224) and at 90° (p = 0.668). There were very strong correlations between post-operative and control extension range (r = 0.931, p < 0.0001) and anterior laxity and 30° (r = 0.830, p < 0.0001) measures. Constraint of tibial internal rotation increased by 2.9° during the pivot-shift (p < 0.001) and increased with pivot shift grade (r = 0.474, p = 0.040). CONCLUSION: Fixing rigid anatomic hamstring grafts in a knee flexed position routinely produces a flexion deformity. Tensioning and fixing grafts with the knee fully extended restores full extension and anterior laxity at 30° and 90°. Rotational constraint is significantly improved and correlates with the pivot-shift grade. CLINICAL RELEVANCE: Rigid anatomic grafts should be tensioned and fixed with the knee fully extended.

Diagnostic accuracy of transbronchial lung cryobiopsy for interstitial lung disease diagnosis (COLDICE): a prospective, comparative study.

BACKGROUND: Transbronchial lung cryobiopsy (TBLC) is a novel technique for sampling lung tissue for interstitial lung disease diagnosis. The aim of this study was to establish the diagnostic accuracy of TBLC compared with surgical lung biopsy (SLB), in the context of increasing use of TBLC in clinical practice as a less invasive biopsy technique. METHODS: COLDICE was a prospective, multicentre, diagnostic accuracy study investigating diagnostic agreement between TBLC and SLB, across nine Australian tertiary hospitals. Patients with interstitial lung disease aged between 18 and 80 years were eligible for inclusion if they required histopathological evaluation to aid diagnosis, after detailed baseline evaluation. After screening at a centralised multidisciplinary discussion (MDD), patients with interstitial lung disease referred for lung biopsy underwent sequential TBLC and SLB under one anaesthetic. Each tissue sample was assigned a number between 1 and 130, allocated in a computer-generated random sequence. Encoded biopsy samples were then analysed by masked pathologists. At subsequent MDD, de-identified cases were discussed twice with either TBLC or SLB along with clinical and radiological data, in random non-consecutive order. Co-primary endpoints were agreement of histopathological features in TBLC and SLB for patterns of definite or probable usual interstitial pneumonia, indeterminate for usual interstitial pneumonia, and alternative diagnosis; and for agreement of consensus clinical diagnosis using TBLC and SLB at MDD. Concordance and κ values were calculated for each primary endpoint. This study is registered with the Australian New Zealand Clinical Trials Registry, ACTRN12615000718549. FINDINGS: Between March 15, 2016, and April 15, 2019, we enrolled 65 patients (31 [48%] men, 34 [52%] women; mean age 66·1 years [SD 9·3]; forced vital capacity 83·7% [SD 14·2]; diffusing capacity for carbon monoxide 63·4% [SD 12·8]). TBLC (7·1 mm, SD 1·9) and SLB (46·5 mm, 14·9) samples were each taken from two separate ipsilateral lobes. Histopathological agreement between TBLC and SLB was 70·8% (weighted κ 0·70, 95% CI 0·55-0·86); diagnostic agreement at MDD was 76·9% (κ 0·62, 0·47-0·78). For TBLC with high or definite diagnostic confidence at MDD (39 [60%] of 65 cases), 37 (95%) were concordant with SLB diagnoses. In the 26 (40%) of 65 cases with low-confidence or unclassifiable TBLC diagnoses, SLB reclassified six (23%) to alternative high-confidence or definite MDD diagnoses. Mild-moderate airway bleeding occurred in 14 (22%) patients due to TBLC. The 90-day mortality was 2% (one of 65 patients), following acute exacerbation of idiopathic pulmonary fibrosis. INTERPRETATION: High levels of agreement between TBLC and SLB for both histopathological interpretation and MDD diagnoses were shown. The TBLC MDD diagnoses made with high confidence were particularly reliable, showing excellent concordance with SLB MDD diagnoses. These data support the clinical utility of TBLC in interstitial lung disease diagnostic algorithms. Further studies investigating the safety profile of TBLC are needed. FUNDING: University of Sydney, Hunter Medical Research Institute, Erbe Elektromedizin, Medtronic, Cook Medical, Rymed, Karl-Storz, Zeiss, and Olympus.