Acceptance and Commitment Therapy plus usual care for improving quality of life in people with motor neuron disease (COMMEND): a multicentre, parallel, randomised controlled trial in the UK.

BACKGROUND: Motor neuron disease is a progressive, fatal neurodegenerative disease for which there is no cure. Acceptance and Commitment Therapy (ACT) is a psychological therapy incorporating acceptance, mindfulness, and behaviour change techniques. We aimed to evaluate the effectiveness of ACT plus usual care, compared with usual care alone, for improving quality of life in people with motor neuron disease. METHODS: We conducted a parallel, multicentre, two-arm randomised controlled trial in 16 UK motor neuron disease care centres or clinics. Eligible participants were aged 18 years or older with a diagnosis of definite or laboratory-supported probable, clinically probable, or possible familial or sporadic amyotrophic lateral sclerosis; progressive muscular atrophy; or primary lateral sclerosis; which met the World Federation of Neurology's El Escorial diagnostic criteria. Participants were randomly assigned (1:1) to receive up to eight sessions of ACT adapted for people with motor neuron disease plus usual care or usual care alone by a web-based system, stratified by site. Participants were followed up at 6 months and 9 months post-randomisation. Outcome assessors and trial statisticians were masked to treatment allocation. The primary outcome was quality of life using the McGill Quality of Life Questionnaire-Revised (MQOL-R) at 6 months post-randomisation. Primary analyses were multi-level modelling and modified intention to treat among participants with available data. This trial was pre-registered with the ISRCTN Registry (ISRCTN12655391). FINDINGS: Between Sept 18, 2019, and Aug 31, 2022, 435 people with motor neuron disease were approached for the study, of whom 206 (47%) were assessed for eligibility, and 191 were recruited. 97 (51%) participants were randomly assigned to ACT plus usual care and 94 (49%) were assigned to usual care alone. 80 (42%) of 191 participants were female and 111 (58%) were male, and the mean age was 63·1 years (SD 11·0). 155 (81%) participants had primary outcome data at 6 months post-randomisation. After controlling for baseline scores, age, sex, and therapist clustering, ACT plus usual care was superior to usual care alone for quality of life at 6 months (adjusted mean difference on the MQOL-R of 0·66 [95% CI 0·22-1·10]; d=0·46 [0·16-0·77]; p=0·0031). Moderate effect sizes were clinically meaningful. 75 adverse events were reported, 38 of which were serious, but no adverse events were deemed to be associated with the intervention. INTERPRETATION: ACT plus usual care is clinically effective for maintaining or improving quality of life in people with motor neuron disease. As further evidence emerges confirming these findings, health-care providers should consider how access to ACT, adapted for the specific needs of people with motor neuron disease, could be provided within motor neuron disease clinical services. FUNDING: National Institute for Health and Care Research Health Technology Assessment and Motor Neurone Disease Association.

PNGase H + variant from Rudaea cellulosilytica with improved deglycosylation efficiency for rapid analysis of eukaryotic N-glycans and hydrogen deuterium exchange mass spectrometry analysis of glycoproteins.

The analysis of glycoproteins and the comparison of protein N-glycosylation from different eukaryotic origins require unbiased and robust analytical workflows. The structural and functional analysis of vertebrate protein N-glycosylation currently depends extensively on bacterial peptide-N4-(N-acetyl-ß-glucosaminyl) asparagine amidases (PNGases), which are indispensable enzymatic tools in releasing asparagine-linked oligosaccharides (N-glycans) from glycoproteins. So far, only limited PNGase candidates are available for N-glycans analysis, and particularly the analysis of plant and invertebrate N-glycans is hampered by the lack of suitable PNGases. Furthermore, liquid chromatography-mass spectrometry (LC-MS) workflows, such as hydrogen deuterium exchange mass spectrometry (HDX-MS), require a highly efficient enzymatic release of N-glycans at low pH values to facilitate the comprehensive structural analysis of glycoproteins. Herein, we describe a previously unstudied superacidic bacterial N-glycanase (PNGase H+ ) originating from the soil bacterium Rudaea cellulosilytica (Rc), which has significantly improved enzymatic properties compared to previously described PNGase H+ variants. Active and soluble recombinant PNGase Rc was expressed at a higher protein level (3.8-fold) and with higher specific activity (~56% increase) compared to the currently used PNGase H+ variant from Dyella japonicum (Dj). Recombinant PNGase Rc was able to deglycosylate the glycoproteins horseradish peroxidase and bovine lactoferrin significantly faster than PNGase Dj (10 min vs. 6 h). The versatility of PNGase Rc was demonstrated by releasing N-glycans from a diverse array of samples such as peach fruit, king trumpet mushroom, mouse serum, and the soil nematode Caenorhabditis elegans. The presence of only two disulfide bonds shown in the AlphaFold protein model (so far all other superacidic PNGases possess more disulfide bonds) could be corroborated by intact mass- and peptide mapping analysis and provides a possible explanation for the improved recombinant expression yield of PNGase Rc.

Troponin interference with special regard to macrocomplex formation.

Biomarkers, such as troponin-T and troponin-I, are regarded as the gold standard laboratory parameter for diagnosing many cardiological diseases. These parameters have been approved for clinical use. Many cardiological guidelines recommend the analysis of troponins in the majority of cardiological disease diagnoses and to also gain prognostic information. Nonetheless, many medical circumstances could cause false troponin elevations. In this article, we focus on troponin artifacts, particularly macro-immune complex formation, as important interference factors. Therefore, we performed a literature search from 2006 to 06/2021.

Soluble platelet endothelial cell adhesion molecule 1 (sPECAM-1) improves diagnostic accuracy of D-Dimer in patients with suspected deep vein thrombosis (DVT).

D-Dimer has a high sensitivity but a low specificity for the diagnosis of deep vein thrombosis (DVT) which limits its implementation as a general screening parameter. There is a demand for additional biomarkers to improve its diagnostic accuracy. Soluble platelet endothelial cell adhesion molecule 1 (sPECAM-1) is generated at the site of venous thrombosis, thus, represents a promising biomarker. Patients with clinically suspected DVT (N = 159) were prospectively recruited and underwent manual compression ultrasonography (CCUS) to confirm or exclude DVT. The diagnostic value of D-Dimer, sPECAM-1 and the combination of both was assessed. sPECAM-1 levels were significantly higher in patients with DVT (N = 44) compared to patients without DVT (N = 115) (85.9 [76.1/98.0] ng/mL versus 68.0 [50.1/86.0] ng/mL; p < 0.001) with a diagnostic sensitivity of 100% and a specificity of 28.7% at the cut point > 50.2 ng/mL. sPECAM-1 improved the diagnostic accuracy of D-Dimer: the combination of both biomarkers yielded a ROC-AUC of 0.925 compared to 0.905 for D-Dimer alone and 0.721 for sPECAM-1 alone with a reduction of false-positive D-Dimer cases 72- > 43 (Δ = - 31.9%). The discrimination mainly occurred in a subgroup of patients characterized by an inflammatory background (defined by c-reactive protein level > 1 mg/mL). sPECAM-1 represents a novel diagnostic biomarker for venous thrombosis. It does not qualify as a diagnostic biomarker alone but improves the diagnostic accuracy of D-Dimer in patients with suspected DVT.

Ten caveats of learning analytics in health professions education: A consumer's perspective.

A group of 22 medical educators from different European countries, gathered in a meeting in Utrecht in July 2019, discussed the topic of learning analytics (LA) in an open conversation and addressed its definition, its purposes and potential risks for learners and teachers. LA was seen as a significant advance with important potential to improve education, but the group felt that potential drawbacks of using LA may yet be under-exposed in the literature. After transcription and interpretation of the discussion's conclusions, a document was drafted and fed back to the group in two rounds to arrive at a series of 10 caveats educators should be aware of when developing and using LA, including too much standardized learning, with undue consequences of over-efficiency and pressure on learners and teachers, and a decrease of the variety of 'valid' learning resources. Learning analytics may misalign with eventual clinical performance and can run the risk of privacy breaches and inescapability of documented failures. These consequences may not happen, but the authors, on behalf of the full group of educators, felt it worth to signal these caveats from a consumers' perspective.

Monocenter Investigation Micra® MRI study (MIMICRY): feasibility study of the magnetic resonance imaging compatibility of a leadless pacemaker system.

AIMS: As in vivo real-life data are still scarce, we conducted a study to assess the safety and feasibility of cardiac magnetic resonance imaging (MRI) in patients with a leadless pacemaker system. METHODS AND RESULTS: In this prospective non-randomized interventional trial, we enrolled 15 patients with an MRI conditional Micra® leadless pacemaker system to undergo either a 1.5 T or 3.0 T cardiac MRI scan. Clinical adverse events as well as device parameters such as pacing threshold, sensing, impedance, and battery life were assessed at baseline as well as 1 and 3 months after the scan. Device parameter changes between different time points were tested for statistical significance and compared with pre-set cut-off values. Fourteen patients underwent the cardiac MRI scan according to the protocol as well as the scheduled follow-up visits. One participant was excluded from analysis, as the MRI scan was not possible because of severe claustrophobia. Other clinical events did not occur during the scan and the follow-up period. Device parameters stayed stable and changes during the observational period were statistically not significant (changes vs. baseline: pacing threshold: 0.01 ± 0.05 V, P = 0.308, 0.01 ± 0.07 V, P = 0.419, sensing: -0.15 ± 1.11 mV, P = 0.658, -0.19 ± 1.17 mV, P = 0.800, impedance: -7.86 ± 30.7 Ohm, P = 0.447, -7.86 ± 25.77 Ohm, P = 0.183, at 1 and 3 months follow-up, respectively). Parameter changes were not statistically different between patients who underwent imaging at 1.5 T (n = 7) or 3.0 T (n = 7). CONCLUSION: In our set of patients with a Micra® leadless pacemaker, cardiac magnetic resonance imaging at either 1.5 T or 3.0 T proved feasible and safe with no relevant changes in device parameters within 3 months of follow-up.

Sympathetic Response and Outcomes Following Renal Denervation in Patients With Chronic Heart Failure: 12-Month Outcomes From the Symplicity HF Feasibility Study.

BACKGROUND: Heart failure (HF) is associated with chronic sympathetic activation. Renal denervation (RDN) aims to reduce sympathetic activity by ablating the renal sympathetic nerves. We investigated the effect of RDN in patients with chronic HF and concurrent renal dysfunction in a prospective, multicenter, single-arm feasibility study. METHODS AND RESULTS: Thirty-nine patients with chronic systolic HF (left ventricular ejection fraction [LVEF] <40%, New York Heart Association class II-III,) and renal impairment (estimated glomerular filtration rate [eGFR; assessed with the use of the Modification of Diet in Renal Disease equation] < 75 mL • min-1 • 1.73 m-2) on stable medical therapy were enrolled. Mean age was 65 ± 11 years; 62% had ischemic HF. The average number of ablations per patient was 13 ± 3. No protocol-defined safety events were associated with the procedure. One subject experienced a renal artery occlusion that was possibly related to the denervation procedure. Statistically significant reductions in N-terminal pro-B-type natriuretic peptide (NT-proBNP; 1530 ± 1228 vs 1428 ± 1844 ng/mL; P = .006) and 120-minute glucose tolerance test (11.2 ± 5.1 vs 9.9 ± 3.6; P = .026) were seen at 12 months, but there was no significant change in LVEF (28 ± 9% vs 29 ± 11%; P= .536), 6-minute walk test (384 ± 96 vs 391 ± 97 m; P= .584), or eGFR (52.6 ± 15.3 vs 52.3 ± 18.5 mL • min-1 • 1.73 m-2; P= .700). CONCLUSIONS: RDN was associated with reductions in NT-proBNP and 120-minute glucose tolerance test in HF patients 12 months after RDN treatment. There was no deterioration in other indices of cardiac and renal function in this small feasibility study.

Leadless Cardiac Pacemaker Implantation After Lead Extraction in Patients With Severe Device Infection.

BACKGROUND: Conventional pacemaker therapy is limited by short- and long-term complications, most notably device infection. Transcatheter pacing systems (TPS) may be beneficial in this kind of patients as they eliminate the need for a device pocket and leads and thus may reduce the risk of re-infection. METHODS: We assessed a novel procedure in 6 patients with severe device infection who were pacemaker dependent. After lead extraction a single chamber TPS was implanted into the right ventricle. RESULTS: Of the 6 patients who underwent lead extraction due to severe device infection at our institution, 3 were diagnosed with a pocket infection only, whereas the other 3 showed symptoms of both pocket and lead infection. Successful lead extraction and TPS implantation was accomplished in all patients. Four patients were bridged with a temporary pacemaker between 2 hours and 2 days after lead extraction, whereas 2 patients had the TPS implanted during the same procedure just before traditional pacemaker system removal. All patients stayed free of infection during the follow-up period of 12 weeks. An additional positron emission tomography scan was performed in each patient and indicated no signs of an infection around the TPS. CONCLUSION: Transcather pacemaker implantation was safe and feasible in 6 patients and did not result in re-infection even if implanted before removal of the infected pacemaker system within the same procedure. Therefore, implantation of a TPS may be an option for patients with severe device infection, especially in those with blocked venous access or who are pacemaker dependent.

Clinical safety of an MRI conditional implantable cardioverter defibrillator system: A prospective Monocenter ICD-Magnetic resonance Imaging feasibility study (MIMI).

BACKGROUND: The aim of this study was to evaluate the safety and efficacy of the Lumax 740(®) Implantable Cardioverter Defibrillator (ICD) system in patients undergoing a defined 1.5 Tesla (T) MRI. MATERIALS AND METHODS: Between November 2013 and April 2014, eighteen patients (age range, 41-78 years; mean age, 64 years) implanted with a Lumax 740(®) ICD system for at least 6 weeks before an MRI were enrolled into this single-center feasibility study. The local ethics committee approved the study before patients gave written informed consent. Patients underwent defined MRI 1.5T of the brain and lower lumbar spine with three safety follow-up evaluations obtained during the 3-month study period. Data were analyzed descriptively. Study endpoints were the absence of either MRI and pacing system related serious adverse device effects (SADE), or of a ventricular pacing threshold increase >0.5V, or of an R-wave amplitude attenuation < 50%, or of an R-wave amplitude < 5.0 mV at 1-month follow-up. The assessment of safety and efficacy was supported by recording of all adverse events, changes in pacing threshold, R-wave sensing, pacing impedances and in battery status. RESULTS: Sixteen patients completed the MRI and the follow-up period. As no SADE occurred, the SADE free rate was 100%. Freedom from ventricular pacing threshold increase was 100% (16/16; 95%CI: 82.9%; 100.0%). There were no significant differences between baseline and follow-up measurements of sensing amplitudes (-0.58 ± 2.07 mV, P = 0.239, -0.41 ± 1.04 mV, P = 0.133, and -0.25 ± 1.36 mV, P = 0.724, for immediately after, 1 month and 3 months after MRI scan, respectively) and pacing thresholds (-0.047 ± 0.18 V, P = 0.317, -0.019 ± 0.11 V, P = 0.490, and 0.075 ± 0.19 V, P = 0.070, for immediately after, 1 month and 3 months after MRI scan, respectively). Lead impedances after the MRI scan were significantly lower as compared with baseline values (-22.8 ± 21.69 Ω, P = 0.001, -21.62 ± 39.71 Ω, P = 0.040, and -33.68 ± 57.73 Ω, P = 0.018, for immediately after, 1 month and 3 months after MRI scan, respectively). CONCLUSION: MRI scans in patients with MRI conditional ICD system (Lumax 740(®) ) are feasible and can be performed safely under defined conditions in a hospital setting.

Subcutaneous Double "Purse String Suture"-A Safe Method for Femoral Vein Access Site Closure after Leadless Pacemaker Implantation.

BACKGROUND: Leadless cardiac pacemaker (LCP) requires large-caliber venous sheaths for device placement. Sheath sizes for these procedures vary from 18- to 23-French (F). The most common complications are hematomas, pseudoaneurysms, and arteriovenous fistulas. Complete and secure closure of the venous access is an important step at the end of such a procedure. METHODS: We performed a retrospective analysis of all patients who had undergone LCP implantation at our institution. Patients and procedural characteristics as well as groin complications at 30 days and 3 months were evaluated. After sheath removal venous access sites were closed performing a so-called "purse-string" suture (PSS). RESULTS: Seventy-seven patients received an LCP at our institution. In 27 (35%) of these patients a heparin bolus was given at the beginning of the procedure. Anticoagulation therapy with phenprocoumon was present in 32 (40%) of patients. In 76 (98.7%) patients, the LCP was implanted without complications. In one (1.3%) patient a perforation occurred during implantation, which required surgical intervention. Access site complications occurred in three (3.9%) patients, two (2.6%) groin hematomas, and one (1.3%) arteriovenous fistula. The hematomas disappeared completely after 3 weeks, and the fistula was not detectable by ultrasound anymore after 4 weeks. CONCLUSION: Use of subcutaneous absorbable double PSS closure after removal of large-caliber venous sheaths is a safe technique to achieve immediate postprocedural hemostasis. Especially for sheath sizes with an inner diameter of 23F, this technique creates a very secure and also cosmetically appealing closure.

Influence of pseudo-resistance on the effect of renal denervation on 24-hour ambulatory blood pressure levels.

BACKGROUND: Renal denervation (RDN) is a promising treatment option in addition to medical antihypertensive treatment in patients suffering from resistant hypertension. Despite the growing interest in RDN, the negative result of the Symplicity HTN-3 trial led to a debate on the efficacy of RDN. METHODS: We systematically investigated the effects of RDN, evaluated by 24-hr ambulatory blood pressure measurements (ABPM), in a consecutive series of patients with resistant hypertension, which was defined by a mean office systolic blood pressure (SBP) >160 mm Hg (>150 mm Hg in patients with diabetes). Patients with a mean 24-hr SBP of less than 130 mm Hg at baseline were classified as pseudo-resistant, while all other patients were classified as true-resistant. After six months, we analyzed the response rates in true-resistant and in pseudo-resistant patients, respectively, by the means of 24-hr ABPM. Thereby, patients with a reduction of more than 5 mm Hg in 24-hr SBP were classified as responders. RESULTS: RDN was performed in 106 patients. By 24-hr ABPM, 20 patients (18.9%) were classified as pseudo-resistant patients. In this cohort, we only found two responders (response rate 10%) six months after RDN. By contrast, in true-resistant patients, the response rate was almost 60% and the mean BP reduction was -18.6/-9 mm Hg in 24-hr ABPM. CONCLUSIONS: We found a significant BP reduction in almost 60% of patients with true-resistant hypertension, but only in 10% in patients with pseudo-resistant hypertension. According to our results, patient selection seems to be crucial for acceptable response rates after RDN.

Coronary Pan-Ischemia as a First Sign of a Fulminant Host-Versus-Graft Reaction Eight Years After Orthotopic Heart Transplantation.

Acute graft rejection in patients after heart transplantation can cause arrhythmias and acute angina pectoris with electrocardiographic ST-segment elevation. We report a case of a 53-year old female patient who had undergone cardiac transplantation 8 years previously. She developed bradycardia with co-existent ST-segment elevation caused by a histologically proven acute graft rejection. After administration of methylprednisolone and immune absorption leading to initial clinical improvement, the patient died unexpectedly. The reasons remain unclear, but a degeneration of the conduction system as well as impaired blood flow in the right coronary caused by cellular and humoral rejection most likely have both contributed.

Gold-coated pacemaker implantation for a patient with type IV allergy to titanium.

A 65-year-old man was scheduled for pacemaker implantation for symptomatic sick-sinus-syndrome (SSS). He suffered from multiple drug-allergies and allergies to several metals like quicksilver and titanium. Gold-coated pacemaker generators and polyurethane leads are effective in avoiding allergic reactions to pacing system components. Therefore, we decided to implant a custom-made gold-coated DDDR-pacemaker generator and polyurethane leads.

Renal denervation in the treatment of resistant arterial hypertension.

Patients with resistant arterial hypertension have an increased risk of stroke, myocardial infarction, heart failure, and chronic kidney disease. In many cases, limitations of pharmacological treatment like intolerance and adherence to the antihypertensive medications are present in the clinical setting. In this context, new treatment options like trans-femoral sympathetic renal nerve denervation is, even after publication of the Symplicity HTN-3 trial, a promising new treatment option.

Impact of route of access and stenosis subtype on outcome after transcatheter aortic valve replacement.

Introduction: Previous analyses have reported the outcomes of transcatheter aortic valve replacement (TAVR) for patients with low-flow, low-gradient (LFLG) aortic stenosis (AS), without stratifying according to the route of access. Differences in mortality rates among access routes have been established for high-gradient (HG) patients and hypothesized to be even more pronounced in LFLG AS patients. This study aims to compare the outcomes of patients with LFLG or HG AS following transfemoral (TF) or transapical (TA) TAVR. Methods: A total of 910 patients, who underwent either TF or TA TAVR with a median follow-up of 2.22 (IQR: 1.22-4.03) years, were included in this multicenter cohort study. In total, 146 patients (16.04%) suffered from LFLG AS. The patients with HG and LFLG AS were stratified according to the route of access and compared statistically. Results: The operative mortality rates of patients with HG and LFLG were found to be comparable following TF access. The operative mortality rate was significantly increased for patients who underwent TA access [odds ratio (OR): 2.91 (1.54-5.48), p = 0.001] and patients with LFLG AS [OR: 2.27 (1.13-4.56), p = 0.02], which could be corroborated in a propensity score-matched subanalysis. The observed increase in the risk of operative mortality demonstrated an additive effect [OR for TA LFLG: 5.45 (2.35-12.62), p < 0.001]. LFLG patients who underwent TA access had significantly higher operative mortality rates (17.78%) compared with TF LFLG (3.96%, p = 0.016) and TA HG patients (6.36%, p = 0.024). Conclusions: HG patients experienced a twofold increase in operative mortality rates following TA compared with TF access, while LFLG patients had a fivefold increase in operative mortality rates. TA TAVR appears suboptimal for patients with LFLG AS. Prospective studies should be conducted to evaluate alternative options in cases where TF is not possible.

Takotsubo syndrome before and during the COVID-19 pandemic in Austria: a retrospective cohort study (TOSCA-19).

AIMS: This study aims to investigate the prevalence of Takotsubo syndrome (TTS) as a percentage of the total number of acute coronary syndrome (ACS), including non-STE-elevation myocardial infarction and ST-elevation myocardial infarction, as well as the short-term outcome of TTS patients before and during the COVID-19 pandemic. METHODS AND RESULTS: We compared patients from two different periods: (i) Period 1 (before the COVID-19 pandemic): 1 March to 30 December 2019, and (ii) Period 2 (during the COVID-19 pandemic): 1 March to 30 December 2020. The retrospective database was created from the archives of the participating hospitals or electronic hospital systems by trained medical personnel. The subjects' medical history, cardiovascular risk factors, laboratory values, echocardiography findings, and an in-hospital outcome were variables of interest. Furthermore, propensity score matching analysis was performed to evaluate the short-term prognosis in TTS and ACS patients. Altogether six Austrian centres-(i) 3rd Medical Department of Cardiology and Intensive Care Medicine, Clinic Ottakring, Vienna, Austria; (ii) 5th Medical Department of Cardiology, Clinic Favoriten, Vienna, Austria; (iii) 2nd Medical Department, Hanusch Hospital, Vienna, Austria; (iv) University Clinic of Internal Medicine III, Cardiology and Angiology, Medical University of Innsbruck, Austria; (v) Department of Cardiology, University Hospital Graz, Graz, Austria; (vi) Department of Cardiology and Intensive Medicine, Kepler University Clinic, Linz, Austria-participated in the study. During period 1, 87 (3.5%) patients out of 2482 ACS patients had TTS in all participating centres. During period 2, 71 (2.7%) patients out of 2572 ACS patients had TTS in all participating centres. Accordingly, the prevalence of TTS remained stable irrespective of potential psychologic stress during the COVID pandemic. Furthermore, the baseline characteristics of TTS patients did not change during the COVID-19 pandemic. The prevalence of in-hospital complications [cardiogenic shock (4.6% vs. 4.3%, P = 0.925), ventricle thrombus (1.1% vs. 1.4%, P = 0.885) and in-hospital bleeding (3.4% vs. 1.4%, P = 0.417)] remained stable. The all-cause in-hospital mortality of TTS patients did not change during the COVID-19 pandemic [χ2 (2) = 0.058, P = 0.810]. Moreover, a propensity score matching analysis of all-cause in-hospital mortality between matched TTS and ACS patients showed higher in-hospital mortality in ACS patients during COVID-19 pandemic (P = 0.043). CONCLUSIONS: Despite the well-known increased psychologic stress during the COVID-19 pandemic, the prevalence of TTS during the COVID-19 pandemic and the short-term clinical outcome in Austria remained unimpacted.

Development of a PNGase Rc Column for Online Deglycosylation of Complex Glycoproteins during HDX-MS.

Protein glycosylation is one of the most common PTMs and many cell surface receptors, extracellular proteins, and biopharmaceuticals are glycosylated. However, HDX-MS analysis of such important glycoproteins has so far been limited by difficulties in determining the HDX of the protein segments that contain glycans. We have developed a column containing immobilized PNGase Rc (from Rudaea cellulosilytica) that can readily be implemented into a conventional HDX-MS setup to allow improved analysis of glycoproteins. We show that HDX-MS with the PNGase Rc column enables efficient online removal of N-linked glycans and the determination of the HDX of glycosylated regions in several complex glycoproteins. Additionally, we use the PNGase Rc column to perform a comprehensive HDX-MS mapping of the binding epitope of a mAb to c-Met, a complex glycoprotein drug target. Importantly, the column retains high activity in the presence of common quench-buffer additives like TCEP and urea and performed consistent across 114 days of extensive use. Overall, our work shows that HDX-MS with the integrated PNGase Rc column can enable fast and efficient online deglycosylation at harsh quench conditions to provide comprehensive analysis of complex glycoproteins.

Byzantine Empire Economic Growth: Did Past Climate Change Play a Role?

Different chronicles of the Byzantine Empire's history have noted various economic data gleaned from historical documents and accounts of the Empire's existence. I provide conjectures on approximate real GDP per capita for the Empire over its existence from AD 300 to 1453. I use these to investigate whether climate forcing variables are associated with real GDP per capita fluctuations. Some hypotheses on factors that would have affected Byzantine economic performance are tested using climate/environmental factors in time series regression. The results support and confirm some findings on how the Byzantine economy may have been affected by periods of regional climate change. Supplementary Information: The online version contains supplementary material available at 10.1007/s10745-022-00343-3.

A Home Care Regimen With Oral-B iO Toothbrush and Targeted Clean Brush Head to Reduce Peri-Implant Mucositis.

OBJECTIVE: This practice-based case series evaluated the effects of the Oral-B® iO™ oscillatingrotating (O-R) electric toothbrush with the novel Targeted Clean™ brush head as part of a home care regimen on the health of the tissues surrounding implant-borne fixed restorations. METHODS: Eight generally healthy, nonsmoking patients withj peri-implant mucositis in at least one implant site and moderate-to-high plaque levels who had not had a professional cleaning in 3 months and were not currently using an O-R toothbrush were recruited from the author's practice. Fixed implant restorations on these eight patients were evaluated for plaque and gingival inflammation (erythema, swelling, and bleeding on probing [BOP]). In collaboration with the dental hygiene team, the patients were introduced to specific protocols for implant maintenance utilizing the Oral-B iO O-R brush and the Targeted Clean brush head. After 6 weeks, the patients were re-evaluated. Clinical findings with photographs and probing as well as the impact of the intervention on each patient's motivation and compliance in maintaining oral hygiene at home were recorded. RESULTS: After 6 weeks, implant sites with baseline peri-implant mucositis demonstrated no BOP or other signs of infl ammation and reduced plaque scores. The patients' home care compliance and motivation to maintain effective oral hygiene around their implants saw a substantial improvement. CONCLUSIONS: The Oral-B iO O-R electric toothbrush with the novel Targeted Clean brush head, used as part of a home care regimen, markedly reduced peri-implant mucositis around fixed implant restorations among all eight patients in this case series. Key factors were the patient owning their disease pattern and the doctor/hygienist collaboration and use of education protocols to help improve the patients' home care compliance and motivation.