Hospitalizations, emergency room visits and causes of death in 198 patients with permanent hypoparathyroidism: a retrospective Austrian study (2005-2022).

Objective: Chronic hypoparathyroidism (HP) is associated with acute and chronic complications, especially those related to hypocalcemia. We aimed to analyze details on hospital admissions and the reported deaths in affected patients. Design and methods: In a retrospective analysis, we reviewed the medical history of 198 patients diagnosed with chronic HP over a continuous period of up to 17 years at the Medical University Graz. Results: The mean age in our mostly female cohort (70.2%) was 62.6 ± 18.7 years. The etiology was predominantly postsurgical (84.8%). About 87.4% of patients received standard medication (oral calcium/vitamin D), 15 patients (7.6%) used rhPTH1-84/Natpar® and 10 patients (4.5%) had no/unknown medication. Two hundred and nineteen emergency room (ER) visits and 627 hospitalizations were documented among 149 patients, and 49 patients (24.7%) did not record any hospital admissions. According to symptoms and decreased serum calcium levels, 12% of ER (n = 26) visits and 7% of hospitalizations (n = 44) were likely attributable to HP. A subgroup of 13 patients (6.5%) received kidney transplants prior to the HP diagnosis. In eight of these patients, parathyroidectomy for tertiary renal hyperparathyroidism was the cause of permanent HP. The mortality was 7.8% (n = 12), and the causes of death appeared to be unrelated to HP. Although the awareness for HP was low, calcium levels were documented in 71% (n = 447) of hospitalizations. Conclusions: Acute symptoms directly related to HP did not represent the primary cause of ER visits. However, comorbidities (e.g. renal/cardiovascular diseases) associated with HP played a key role in hospitalizations and deaths. Significance statement: Hypoparathyroidism (HP) is the most common complication after anterior neck surgery. Yet, it remains underdiagnosed as well as undertreated, and the burden of disease and long-term complications are usually underestimated. There are few detailed data on emergency room (ER) visits hospitalizations and death in patients with chronic HP, although acute symptoms due to hypo-/hypercalcemia are easily detectable. We show that HP is not the primary cause for presentation but that hypocalcemia is a typical laboratory finding (when ordered) and thus may contribute to subjective symptoms. Patients often present with renal/cardiovascular/oncologic illness for which HP is known to be a contributing factor. A small but very special group (n = 13, 6.5%) are patients after kidney transplantations who showed a high ER hospitalization rate. Surprisingly, HP was never the cause for their frequent hospitalizations but rather the result of chronic kidney disease. The most frequent cause for HP in these patients was parathyroidectomy due to tertiary hyperparathyroidism. The causes of death in 12 patients appeared to be unrelated to HP, but we found a high prevalence of chronic organ damages/comorbidities related to it in this group. Less than 25% documented HP correctly in the discharge letters, which indicates a high potential for improvement.

A Comparison of the Representation of Women in Editor Positions at Major Medical Journals in 2021 vs 2011.

PURPOSE: There continues to be a disparity in the representation of women across medicine, including in editor positions at major medical journals. The authors repeated a study they had conducted in 2011 to compare the representation of women in editor-in-chief and editorial board member positions in 2011 and 2021. METHOD: The authors included in their analysis the 60 journals from their original 2011 study and the top 5 ranked journals by Journal Impact Factor in each of 12 disciplines in 2021. This led to the inclusion of 86 journals. The authors collected the names and genders of the editors-in-chief and editorial board members at these journals, using information provided by the journals and a Google search for the photos and/or pronouns of the remaining editors. They compared results across years (2021 vs 2011), editor positions, disciplines, Journal Impact Factors, and ranks. RESULTS: Twenty-two of the 90 editors-in-chief (24.4%) were women in 2021 compared with 10 of 63 (15.9%) in 2011, an increase of 8.5%. Of the 6,285 editorial board members, 1,756 were women (27.9%) in 2021 compared with 719 of 4,112 (17.5%) in 2011, an increase of 10.4%. Journals with women editors-in-chief gained 3.5 ranks and 9.1 points in Journal Impact Factor on average over this 10-year period, compared with no gain in rank and an increase of 4.7 points in Journal Impact Factor for journals with men editors-in-chief; both are statistically significant differences (P = .045 and P = .016, respectively). CONCLUSIONS: In almost all evaluated disciplines and editor positions, there was an increase in the percentage of women at top-ranked medical journals over a 10-year period. Despite this increase, improvements are still needed to accelerate the currently slow rate of change in these positions to enhance diversity, equity, and inclusion for women in medicine.

Electrochemical On-line ICP-MS in Electrocatalysis Research.

Electrocatalyst degradation due to dissolution is one of the major challenges in electrochemical energy conversion technologies such as fuel cells and electrolysers. While tendencies towards dissolution can be grasped considering available thermodynamic data, the kinetics of material's stability in real conditions is still difficult to predict and have to be measured experimentally, ideally in-situ and/or on-line. On-line inductively coupled plasma mass spectrometry (ICP-MS) is a technique developed recently to address exactly this issue. It allows time- and potential-resolved analysis of dissolution products in the electrolyte during the reaction under dynamic conditions. In this work, applications of on-line ICP-MS techniques in studies embracing dissolution of catalysts for oxygen reduction (ORR) and evolution (OER) as well as hydrogen oxidation (HOR) and evolution (HER) reactions are reviewed.

ALKBH5-induced demethylation of mono- and dimethylated adenosine.

RNA contains methylated A-base derivatives. A methylation to m6A and then demethylation regulate homeostasis in mRNA. It is assumed that m6A is mainly demethylated by the α-ketoglutarate dependent oxidase ALKBH5. Here we show that ALKBH5 also demethylates the dimethylated adenosine m62A, which is a non-canonical base present in ribosomal RNA.

Electrifying model catalysts for understanding electrocatalytic reactions in liquid electrolytes.

Electrocatalysis is at the heart of our future transition to a renewable energy system. Most energy storage and conversion technologies for renewables rely on electrocatalytic processes and, with increasing availability of cheap electrical energy from renewables, chemical production will witness electrification in the near future1-3. However, our fundamental understanding of electrocatalysis lags behind the field of classical heterogeneous catalysis that has been the dominating chemical technology for a long time. Here, we describe a new strategy to advance fundamental studies on electrocatalytic materials. We propose to 'electrify' complex oxide-based model catalysts made by surface science methods to explore electrocatalytic reactions in liquid electrolytes. We demonstrate the feasibility of this concept by transferring an atomically defined platinum/cobalt oxide model catalyst into the electrochemical environment while preserving its atomic surface structure. Using this approach, we explore particle size effects and identify hitherto unknown metal-support interactions that stabilize oxidized platinum at the nanoparticle interface. The metal-support interactions open a new synergistic reaction pathway that involves both metallic and oxidized platinum. Our results illustrate the potential of the concept, which makes available a systematic approach to build atomically defined model electrodes for fundamental electrocatalytic studies.

The Common Intermediates of Oxygen Evolution and Dissolution Reactions during Water Electrolysis on Iridium.

Understanding the pathways of catalyst degradation during the oxygen evolution reaction is a cornerstone in the development of efficient and stable electrolyzers, since even for the most promising Ir based anodes the harsh reaction conditions are detrimental. The dissolution mechanism is complex and the correlation to the oxygen evolution reaction itself is still poorly understood. Here, by coupling a scanning flow cell with inductively coupled plasma and online electrochemical mass spectrometers, we monitor the oxygen evolution and degradation products of Ir and Ir oxides in situ. It is shown that at high anodic potentials several dissolution routes become possible, including formation of gaseous IrO3 . On the basis of experimental data, possible pathways are proposed for the oxygen-evolution-triggered dissolution of Ir and the role of common intermediates for these reactions is discussed.

N6-methyladenosine (m6A) recruits and repels proteins to regulate mRNA homeostasis.

RNA modifications are integral to the regulation of RNA metabolism. One abundant mRNA modification is N6-methyladenosine (m6A), which affects various aspects of RNA metabolism, including splicing, translation and degradation. Current knowledge about the proteins recruited to m6A to carry out these molecular processes is still limited. Here we describe comprehensive and systematic mass-spectrometry-based screening of m6A interactors in various cell types and sequence contexts. Among the main findings, we identified G3BP1 as a protein that is repelled by m6A and positively regulates mRNA stability in an m6A-regulated manner. Furthermore, we identified FMR1 as a sequence-context-dependent m6A reader, thus revealing a connection between an mRNA modification and an autism spectrum disorder. Collectively, our data represent a rich resource and shed further light on the complex interplay among m6A, m6A interactors and mRNA homeostasis.

Catalyst Stability Benchmarking for the Oxygen Evolution Reaction: The Importance of Backing Electrode Material and Dissolution in Accelerated Aging Studies.

In searching for alternative oxygen evolution reaction (OER) catalysts for acidic water splitting, fast screening of the material intrinsic activity and stability in half-cell tests is of vital importance. The screening process significantly accelerates the discovery of new promising materials without the need of time-consuming real-cell analysis. In commonly employed tests, a conclusion on the catalyst stability is drawn solely on the basis of electrochemical data, for example, by evaluating potential-versus-time profiles. Herein important limitations of such approaches, which are related to the degradation of the backing electrode material, are demonstrated. State-of-the-art Ir-black powder is investigated for OER activity and for dissolution as a function of the backing electrode material. Even at very short time intervals materials like glassy carbon passivate, increasing the contact resistance and concealing the degradation phenomena of the electrocatalyst itself. Alternative backing electrodes like gold and boron-doped diamond show better stability and are thus recommended for short accelerated aging investigations. Moreover, parallel quantification of dissolution products in the electrolyte is shown to be of great importance for comparing OER catalyst feasibility.

Stability limits of tin-based electrocatalyst supports.

Tin-based oxides are attractive catalyst support materials considered for application in fuel cells and electrolysers. If properly doped, these oxides are relatively good conductors, assuring that ohmic drop in real applications is minimal. Corrosion of dopants, however, will lead to severe performance deterioration. The present work aims to investigate the potential dependent dissolution rates of indium tin oxide (ITO), fluorine doped tin oxide (FTO) and antimony doped tin oxide (ATO) in the broad potential window ranging from -0.6 to 3.2 VRHE in 0.1 M H2SO4 electrolyte. It is shown that in the cathodic part of the studied potential window all oxides dissolve during the electrochemical reduction of the oxide - cathodic dissolution. In case an oxidation potential is applied to the reduced electrode, metal oxidation is accompanied with additional dissolution - anodic dissolution. Additional dissolution is observed during the oxygen evolution reaction. FTO withstands anodic conditions best, while little and strong dissolution is observed for ATO and ITO, respectively. In discussion of possible corrosion mechanisms, obtained dissolution onset potentials are correlated with existing thermodynamic data.

Stability and Activity of Non-Noble-Metal-Based Catalysts Toward the Hydrogen Evolution Reaction.

A fundamental understanding of the behavior of non-noble based materials toward the hydrogen evolution reaction is crucial for the successful implementation into practical devices. Through the implementation of a highly sensitive inductively coupled plasma mass spectrometer coupled to a scanning flow cell, the activity and stability of non-noble electrocatalysts is presented. The studied catalysts comprise a range of compositions, including metal carbides (WC), sulfides (MoS2 ), phosphides (Ni5 P4 , Co2 P), and their base metals (W, Ni, Mo, Co); their activity, stability, and degradation behavior was elaborated and compared to the state-of-the-art catalyst platinum. The non-noble materials are stable at HER potentials but dissolve substantially when no current is flowing. Through pre- and post-characterization of the catalysts, explanations of their stability (thermodynamics and kinetics) are discussed, challenges for the application in real devices are analyzed, and strategies for circumventing dissolution are suggested. The precise correlation of metal dissolution with applied potential/current density allows for narrowing down suitable material choices as replacement for precious group metals as for example, platinum and opens up new ways in finding cost-efficient, active, and stable new-generation electrocatalysts.

Platinum recycling going green via induced surface potential alteration enabling fast and efficient dissolution.

The recycling of precious metals, for example, platinum, is an essential aspect of sustainability for the modern industry and energy sectors. However, due to its resistance to corrosion, platinum-leaching techniques rely on high reagent consumption and hazardous processes, for example, boiling aqua regia; a mixture of concentrated nitric and hydrochloric acid. Here we demonstrate that complete dissolution of metallic platinum can be achieved by induced surface potential alteration, an 'electrode-less' process utilizing alternatively oxidative and reductive gases. This concept for platinum recycling exploits the so-called transient dissolution mechanism, triggered by a repetitive change in platinum surface oxidation state, without using any external electric current or electrodes. The effective performance in non-toxic low-concentrated acid and at room temperature is a strong benefit of this approach, potentially rendering recycling of industrial catalysts, including but not limited to platinum-based systems, more sustainable.

Structural insights into the recognition of cisplatin and AAF-dG lesion by Rad14 (XPA).

Nucleotide excision repair (NER) is responsible for the removal of a large variety of structurally diverse DNA lesions. Mutations of the involved proteins cause the xeroderma pigmentosum (XP) cancer predisposition syndrome. Although the general mechanism of the NER process is well studied, the function of the XPA protein, which is of central importance for successful NER, has remained enigmatic. It is known, that XPA binds kinked DNA structures and that it interacts also with DNA duplexes containing certain lesions, but the mechanism of interactions is unknown. Here we present two crystal structures of the DNA binding domain (DBD) of the yeast XPA homolog Rad14 bound to DNA with either a cisplatin lesion (1,2-GG) or an acetylaminofluorene adduct (AAF-dG). In the structures, we see that two Rad14 molecules bind to the duplex, which induces DNA melting of the duplex remote from the lesion. Each monomer interrogates the duplex with a ß-hairpin, which creates a 13mer duplex recognition motif additionally characterized by a sharp 70° DNA kink at the position of the lesion. Although the 1,2-GG lesion stabilizes the kink due to the covalent fixation of the crosslinked dG bases at a 90° angle, the AAF-dG fully intercalates into the duplex to stabilize the kinked structure.

Dissolution of Platinum in the Operational Range of Fuel Cells.

One of the most important practical issues in low-temperature fuel-cell catalyst degradation is platinum dissolution. According to the literature, it initiates at 0.6-0.9 VRHE, whereas previous time- and potential-resolved inductively coupled plasma mass spectrometry (ICP-MS) experiments, however, revealed dissolution onset at only 1.05 VRHE. In this manuscript, the apparent discrepancy is addressed by investigating bulk and nanoparticulated catalysts. It is shown that, given enough time for accumulation, traces of platinum can be detected at potentials as low as 0.85 VRHE. At these low potentials, anodic dissolution is the dominant process, whereas, at more positive potentials, more platinum dissolves during the oxide reduction after accumulation. Interestingly, the potential and time dissolution dependence is similar for both types of electrode. Dissolution processes are discussed with relevance to fuel-cell operation and plausible dissolution mechanisms are considered.

An approach to aminonaphthoquinone ansamycins using a modified Danishefsky diene.

A robust and scalable synthesis of a novel, cyano-substituted Danishefsky-type diene and its use in the Diels-Alder reaction with various dienophiles is reported. The diene allows for the rapid construction of highly substituted aminonaphthoquinones that occur in numerous ansamycin antibiotics.

Long-term survival after surgical critical illness: the impact of prolonged preceding organ support therapy.

OBJECTIVE: To identify the prognostic importance of preceding invasive ventilation, renal replacement therapy, and catecholamine therapy for long-term survivors after surgical critical illness. SUMMARY BACKGROUND DATA: Nothing is known about the effect of preceding intensive care unit (ICU)-related therapies on long-term outcome. METHODS: We performed a retrospective analysis of prospectively collected data of an ICU patient cohort linked to a local database. Adult patients (n = 1462) admitted to a 12-bed ICU between 1993 and 2005, who had an ICU length of stay of more than 4 days, were followed up until the end of the second year after ICU admission. Hazard function was explored by Weibull modeling and likelihood ratio tests. Cox-type structured hazard regression models were used to analyze linear, nonlinear, or time-varying associations of therapeutic variables with 2-year survival time of a patient subgroup, which had survived the period of high hazard. RESULTS: Hazard rate declined exponentially up to day 195 after ICU admission, and became constant thereafter. A total of 808 patients reached this stable stage of their disease forming the study population. Of these patients, 648 (80.2%) were still alive at the end of the second year after ICU admission. Underlying diseases were major determinants for long-term outcome. Long-term mortality was significantly associated with the acute extent of physiological derangement during ICU stay (maximum Apache II score), but was independent from the duration of preceding invasive organ support. CONCLUSION: In surgical patients with a prolonged ICU length of stay, an exorbitant mortality exists for about half a year after ICU admission. Later on, life expectancy of surviving patients is largely determined by the underlying disease and, to a minor degree, by the acute extent of homeostatic disturbance during ICU stay. The duration of preceding invasive therapies does not limit long-term survival.