Probing Ion-Receptor Interactions in Halide Complexes of Octamethyl Calix[4]Pyrrole.

Ion receptors are molecular hosts that bind ionic guests, often with great selectivity. The interplay of solvation and ion binding in anion host-guest complexes in solution governs the binding efficiency and selectivity of such ion receptors. To gain molecular-level insight into the intrinsic binding properties of octamethyl calix[4]pyrrole (omC4P) host molecules with halide guest ions, we performed cryogenic ion vibrational spectroscopy (CIVS) of omC4P in complexes with fluoride, chloride, and bromide ions. We interpret the spectra using density functional theory, describing the infrared spectra of these complexes with both harmonic and anharmonic second-order vibrational perturbation theory (VPT2) calculations. The NH stretching modes of the pyrrole moieties serve as sensitive probes of the ion binding properties, as their frequencies encode the ion-receptor interactions. While scaled harmonic spectra reproduce the experimental NH stretching modes of the chloride and bromide complexes in broad strokes, the high proton affinity of fluoride introduces strong anharmonic effects. As a result, the spectrum of F-·omC4P is not even qualitatively captured by harmonic calculations, but it is recovered very well by VPT2 calculations. In addition, the VPT2 calculations recover the intricate coupling of the NH stretching modes with overtones and combination bands of CH stretching and NH bending modes and with low-frequency vibrations of the omC4P macrocycle, which are apparent for all of the halide ion complexes investigated here. A comparison of the CIVS spectra with infrared spectra of solutions of the same ion-receptor complexes in d3-acetonitrile and d6-acetone shows how ion solvation changes the ion-receptor interactions for the different halide ions.

Competition between Water-Water Hydrogen Bonds and Water-π Bonds in Pyrene-Water Cluster Anions.

We present infrared spectra and density functional theory calculations of hydrated pyrene anion clusters with up to four water molecules. The experimental spectra were acquired by using infrared Ar messenger photodissociation spectroscopy. Water molecules form clusters on the surface of the pyrene, forming hydrogen bonds with the π-system. The structures of the water clusters and their interaction with the π-system are encoded in OH stretching vibrational modes. We find that the interactions between water molecules are stronger than the interactions between water molecules and the π-system. While all clusters show multiple conformers, three- and four-membered rings are the lowest energy structures in the larger hydrates.

Characteristics of constipation screening and assessment tools: a scoping review protocol.

INTRODUCTION: Constipation is a common and significant burden on individuals and healthcare systems. Accurate assessment of constipation severity and symptom improvement are vital aspects of caring for patients with constipation. Therefore, nurses and allied healthcare professionals should possess knowledge regarding the characteristics of constipation assessment tools (ie, aim, scope, definition of constipation, content, structure, mode, administration time and context of use). However, existing reviews summarising characteristics of tools have been restricted to chronic constipation and self-reported measures. Furthermore, they have not included literature published after 2011. This scoping review aims to identify and comprehensibly map the characteristics of available tools for screening and assessment of constipation in order to manage the nursing care need related to constipation within any healthcare or research context and any patient group. METHODS AND ANALYSIS: This review will include primary research articles, methodological papers and clinical guidelines using tools for constipation screening and assessment, pertinent to nursing care management. It is not limited to a specific population or healthcare setting. Databases to be searched include PubMed, Embase, CINAHL, ProQuest, ClinicalKey and Google Scholar. To identify grey literature, national health services in selected countries will be searched. Papers written in English, Nordic language or German will be included. The reviewers will independently review the retrieved citations against the inclusion criteria, and data from included papers will be extracted using a data extraction form developed for this review. The scoping review will be conducted following the Joanna Briggs Institute Guidelines. The results will be presented in a table accompanied by a narrative summary. ETHICS AND DISSEMINATION: Ethical approval is not required, as no individual patient data are included. Findings will be shared and discussed with relevant stakeholders and disseminated through peer-reviewed publications and conference presentations. The protocol is registered on Open Science Framework (registration number: osf.io/h2vzd).

Prevention of foot ulcers in persons with diabetes at risk of ulceration: A systematic review and meta-analysis.

AIMS: Prevention of foot ulcers in persons with diabetes is important to help reduce the substantial burden on both individual and health resources. A comprehensive analysis of reported interventions is needed to better inform healthcare professionals about effective prevention. The aim of this systematic review and meta-analysis is to assess the effectiveness of interventions to prevent foot ulcers in persons with diabetes who are at risk thereof. MATERIALS AND METHODS: We searched the available scientific literature in PubMed, EMBASE, CINAHL, Cochrane databases and trial registries for original research studies on preventative interventions. Both controlled and non-controlled studies were eligible for selection. Two independent reviewers assessed risk of bias of controlled studies and extracted data. A meta-analysis (using Mantel-Haenszel's statistical method and random effect models) was done when >1 RCT was available that met our criteria. Evidence statements, including the certainty of evidence, were formulated according to GRADE. RESULTS: From the 19,349 records screened, 40 controlled studies (of which 33 were Randomised Controlled Trials [RCTs]) and 103 non-controlled studies were included. We found moderate certainty evidence that temperature monitoring (5 RCTs; risk ratio [RR]: 0.51; 95% CI: 0.31-0.84) and pressure-optimised therapeutic footwear or insoles (2 RCTs; RR: 0.62; 95% CI: 0.26-1.47) likely reduce the risk of plantar foot ulcer recurrence in people with diabetes at high risk. Further, we found low certainty evidence that structured education (5 RCTs; RR: 0.66; 95% CI: 0.37-1.19), therapeutic footwear (3 RCTs; RR: 0.53; 95% CI: 0.24-1.17), flexor tenotomy (1 RCT, 7 non-controlled studies, no meta-analysis), and integrated care (3 RCTs; RR: 0.78; 95% CI: 0.58-1.06) may reduce the risk of foot ulceration in people with diabetes at risk for foot ulceration. CONCLUSIONS: Various interventions for persons with diabetes at risk for foot ulceration with evidence of effectiveness are available, including temperature monitoring (pressure-optimised) therapeutic footwear, structured education, flexor tenotomy, and integrated foot care. With hardly any new intervention studies published in recent years, more effort to produce high-quality RCTs is urgently needed to further improve the evidence base. This is especially relevant for educational and psychological interventions, for integrated care approaches for persons at high risk of ulceration, and for interventions specifically targeting persons at low-to-moderate risk of ulceration.

Clinical and biomechanical effectiveness of foot-ankle exercise programs and weight-bearing activity in people with diabetes and neuropathy: A systematic review and meta-analysis.

BACKGROUND: Most interventions to prevent foot ulcers in people with diabetes do not seek to reverse the foot abnormalities that led to the ulcer. Foot-ankle exercise programs target these clinical and biomechanical factors, such as protective sensation and mechanical stress. Multiple RCTs exist investigating the effectiveness of such programs, but these have never been summarised in a systematic review and meta-analysis. METHODS: We searched the available scientific literature in PubMed, EMBASE, CINAHL, Cochrane databases and trial registries for original research studies on foot-ankle exercise programs for people with diabetes at risk of foot ulceration. Both controlled and non-controlled studies were eligible for selection. Two independent reviewers assessed the risk of bias of controlled studies and extracted data. Meta-analysis (using Mantel-Haenszel's statistical method and random effect models) was performed when >2 RCTs were available that met our criteria. Evidence statements, including the certainty of evidence, were formulated according to GRADE. RESULTS: We included a total of 29 studies, of which 16 were RCTs. A foot-ankle exercise programme of 8-12 weeks duration for people at risk of foot ulceration results in: (a) no increase or decrease risk of foot ulceration or pre-ulcerative lesion (Risk Ratio (RR): 0.56 (95% CI: 0.20-1.57)); (b) no increase or decrease risk of adverse events (RR: 1.04 (95% CI: 0.65-1.67)); (c) not increase or decrease barefoot peak plantar pressure during walking (Mean Difference (MD): -6.28 kPa (95% CI: -69.90-57.34)); (d) no increase or decrease health-related quality of life (no meta-analysis possible). Likely results in increases in ankle joint and first metatarsalphalangeal joint range of motion (MD: 1.49° (95% CI: -0.28-3.26)) may result in improvements in neuropathy signs and symptoms (MD: -1.42 (95% CI: -2.95-0.12)), may result in a small increase in daily steps in some people (MD: 131 steps (95% CI: -492-754)), and may not increase or decrease foot and ankle muscle strength and function (no meta-analysis was possible). CONCLUSIONS: In people at risk of foot ulceration, a foot-ankle exercise programme of 8-12 weeks duration may not prevent or cause diabetes-related foot ulceration. However, such a programme likely improves the ankle joint and first metatarsalphalangeal joint range of motion and neuropathy signs and symptoms. Further research is needed to strengthen the evidence base, and should also focus on the effects of specific components of foot-ankle exercise programs.

Guidelines on the prevention of foot ulcers in persons with diabetes (IWGDF 2023 update).

AIMS: This is the 2023 International Working Group on the Diabetic Foot guideline on the prevention of foot ulcers in persons with diabetes, which updates the 2019 guideline. This guideline is targeted at clinicians and other healthcare professionals. MATERIALS AND METHODS: We followed the Grading of Recommendations, Assessment, Development and Evaluations methodology to devise clinical questions and critically important outcomes in the PICO format, to conduct a systematic review of the medical-scientific literature including, where appropriate, meta-analyses, and to write recommendations and their rationale. The recommendations are based on the quality of evidence found in the systematic review, expert opinion where (sufficient) evidence was not available, and a weighing of the desirable and undesirable effects of an intervention, as well as patient preferences, costs, equity, feasibility and applicability. RESULTS: We recommend screening a person with diabetes at very low risk of foot ulceration annually for the loss of protective sensation and peripheral artery disease, and screening persons at higher risk at higher frequencies for additional risk factors. For preventing a foot ulcer, educate persons at-risk about appropriate foot self-care, educate not to walk without suitable foot protection, and treat any pre-ulcerative lesion on the foot. Educate moderate-to-high risk people with diabetes to wear properly fitting, accommodative, therapeutic footwear, and consider coaching them to monitor foot skin temperature. Prescribe therapeutic footwear that has a demonstrated plantar pressure relieving effect during walking, to help prevent plantar foot ulcer recurrence. Consider advising people at low-to-moderate risk to undertake a, preferably supervised, foot-ankle exercise programme to reduce ulcer risk factors, and consider communicating that a total increase in weight-bearing activity of 1000 steps/day is likely safe with regards to risk of ulceration. In people with non-rigid hammertoe with pre-ulcerative lesion, consider flexor tendon tenotomy. We suggest not to use a nerve decompression procedure to help prevent foot ulcers. Provide integrated foot care for moderate-to-high-risk people with diabetes to help prevent (recurrence of) ulceration. CONCLUSIONS: These recommendations should help healthcare professionals to provide better care for persons with diabetes at risk of foot ulceration, to increase the number of ulcer-free days and reduce the patient and healthcare burden of diabetes-related foot disease.

High-Resolution Spectroscopy and Selective Photoresponse of Cryogenically Cooled Green Fluorescent Protein Chromophore Anions.

By time-resolved action spectroscopy of cryogenically cooled molecular ions, we have achieved a remarkable vibrational resolution in the photoresponse of the deprotonated green fluorescent protein (GFP) chromophore, a key molecular unit in the bioimaging of living cells. We define four characteristic spectral regions of the S0-S1 band with competing electronic and nuclear decay channels. We determine the energy barrier toward internal conversion to be ∼250 cm-1. This inhibits internal conversion and hence statistical fragmentation near the S0-S1 band origin, which is identified at 481.51 ± 0.15 nm (20768 ± 6 cm-1). The origin is red-shifted by only 221 cm-1 compared to that of wild-type GFP at 77 K. This, together with a striking agreement between the vibronic profiles of the protein and its chromophore, suggests their similar photophysics. In combination with theory, the data reveal the coexistence of mutually energy-borrowing mechanisms between nuclei and electrons mediated by specific vibrational modes.

Uncoupling CD4+ TIL-Mediated Tumor Killing from JAK-Signaling in Melanoma.

PURPOSE: Impaired MHCI-presentation and insensitivity to immune effector molecules are common features of immune checkpoint blockade (ICB)-resistant tumors and can be, respectively, associated with loss of ß2 microglobulin (B2M) or impaired IFNγ signaling. Patients with ICB-resistant tumors can respond to alternative immunotherapies, such as infusion of autologous tumor-infiltrating lymphocytes (TIL). CD4+ T cells can exert cytotoxic functions against tumor cells; however, it is unclear whether CD4+ T-cell responses can be exploited to improve the clinical outcomes of patients affected by ICB-resistant tumors. EXPERIMENTAL DESIGN: Here, we exploited CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9 gene editing to reproduce immune-resistant tumor phenotypes via gene knockout (KO). To determine the role of cytotoxic CD4+ TILs in ICB-resistant tumors, we investigated CD4+ TIL-mediated cytotoxicity in matched pairs of TILs and autologous melanoma cell lines, used as a model of patient-specific immune-tumor interaction. Around 40% of melanomas constitutively express MHC Class II molecules; hence, melanomas with or without natural constitutive MHC Class II expression (MHCIIconst+ or MHCIIconst-) were used. RESULTS: CD4+ TIL-mediated cytotoxicity was not affected by B2M loss but was dependent on the expression of CIITA. MHCIIconst+ melanomas were killed by tumor-specific CD4+ TILs even in the absence of IFNγ-mediated MHCII upregulation, whereas IFNγ was necessary for CD4+ TIL-mediated cytotoxicity against MHCIIconst- melanomas. Notably, although tumor-specific CD4+ TILs did not kill JAK1KO MHCIIconst- melanomas even after IFNγ stimulation, sensitivity to CD4+ TIL-mediated cytotoxicity was maintained by JAK1KO MHCIIconst+ melanomas. CONCLUSIONS: In conclusion, our data indicate that exploiting tumor-specific cytotoxic CD4+ TILs could help overcome resistance to ICB mediated by IFNγ-signaling loss in MHCIIconst+ melanomas. See related commentary by Betof Warner and Luke, p. 3829.

Prenatal and early childhood predictors of intelligence quotient (IQ) in 7-year-old Danish children from the Odense Child Cohort.

BACKGROUND: Cognitive development measured as intelligence quotient can predict socioeconomic markers in adulthood. It is therefore of interest to determine predictors of childhood intelligence quotient. AIM: To assess intelligence quotient scores based on standardised Danish age-appropriate scores and to evaluate potential predictors of intelligence quotient. MATERIALS: At 7 years of age children in the Odense Child Cohort completed an abbreviated version of the Wechsler intelligence scale for children 5th edition consisting of four subtests (vocabulary, similarities, block design and matrix reasoning) from which the full scale intelligence quotient and verbal comprehension index were estimated. Potential predictors from pregnancy through childhood were collected from questionnaires, birth records and clinical examinations. METHODS: Intelligence quotient scores were investigated through descriptive statistics and linear regression models. RESULTS: The mean full scale intelligence quotient among 1375 children was 99.1 (95% confidence interval 98.5; 99.8) points. Higher full scale intelligence quotient scores were observed in girls 100.8 (95% confidence interval 100.0; 101.8) compared to boys 97.6 (96.7; 98.4), and in children of mothers with high and intermediate education 101.7 (100.4; 103.1) and 99.6 (98.7; 100.5), respectively, compared to low education 96.1 (94.9; 97.3). In linear regression analyses, longer maternal education and child sex (girls) remained strong predictors of intelligence quotient at age 7 years. In addition, paternal education, child head circumference and longer duration of breastfeeding were associated with higher intelligence quotient, whereas maternal overweight and obesity before pregnancy was associated with lower intelligence quotient. CONCLUSIONS: Mean intelligence quotient scores were comparable to the standardised mean intelligence quotient of 100 point of Danish peers. It is important to follow up these children to determine which predictors persist into adulthood.

Patient-reported outcome is associated with health care costs in patients with ischaemic heart disease and arrhythmia.

AIMS: Systematic use of patient-reported outcomes (PROs) have the potential to improve quality of care and reduce costs of health care services. We aimed to describe whether PROs in patients diagnosed with heart disease are directly associated with health care costs. METHODS AND RESULTS: A national cross-sectional survey including PROs at discharge from a heart centre with 1-year follow-up using data from national registers. We included patients with either ischaemic heart disease (IHD), arrhythmia, heart failure (HF), or valvular heart disease (VHD). The Hospital Anxiety and Depression Scale, the heart-specific quality of life, the EuroQol five-dimensional questionnaire, and the Edmonton Symptom Assessment Scale were used. The economic analysis was based on direct costs including primary, secondary health care, and medical treatment. Patient-reported outcomes were available from 13 463 eligible patients out of 25.241 [IHD (n = 7179), arrhythmia (n = 4322), HF (n = 987), or VHD (n = 975)]. Mean annual total direct costs in all patients were €23 228 (patients with IHD: €19 479, patients with arrhythmia: €21 076, patients with HF: €34 747, patients with VDH: €48 677). Hospitalizations contributed overall to the highest part of direct costs. For patients discharged with IHD or arrhythmia, symptoms of anxiety or depression, worst heart-specific quality of life or health status, and the highest symptom burden were associated with increased economic expenditure. We found no associations in patients with HF or VHD. CONCLUSION: Patient-reported outcomes at discharge from a heart centre were associated with direct health care costs in patients with IHD and arrhythmia. REGISTRATION: ClinicalTrials.gov: NCT01926145.

Distal symmetrical polyneuropathy is present in all individuals with diabetes and foot ulcers - and does not associate with healing time.

We estimated the occurrence of diabetic neuropathy using six different diagnostic modalities in individuals with newly diagnosed diabetic foot ulcers (DFUs) and assessed the association with DFU healing time. All individuals with DFU had distal symmetrical polyneuropathy. Presence of neuropathy did not associate with ulcer healing time (p ≥ 0.12).

Flexor Tendon Tenotomy Treatment of the Diabetic Foot: A Multicenter Randomized Controlled Trial.

OBJECTIVE: The aim of this study was to evaluate the effects of needle flexor tendon tenotomy treatment of the diabetic hammertoe deformity. RESEARCH DESIGN AND METHODS: A multicenter randomized controlled trial of individuals with diabetes and ulcers or impending ulcers associated with hammertoes was performed between 1 November 2019 and 31 March 2021. Participants were stratified by the presence of ulcers or impending ulcers. Participants were randomly assigned to tenotomy and standard nonsurgical treatment or to standard nonsurgical treatment alone. Primary outcomes were time to ulcer healing and progression from impending ulcer to active ulcer. RESULTS: Of 224 screened participants with diabetes, 95 (59.0% men) were included. The mean follow-up was 291 ± 70 days, 28 (29.5%) had type 1 diabetes, mean diabetes (presented with 25-75% quartile) duration was 20 (13-26) years, and mean age was 67.7 ± 9.8 years. Of the included participants, 16 had ulcers, of whom 8 were randomly assigned to intervention. Of the remaining 79 with impending ulcers, 39 were randomly assigned to intervention. For participants with ulcers, healing rates favored tenotomy (100% vs. 37.5%, P = 0.026) as did time to ulcer healing (P = 0.04). For those with impending ulcers, incidence of progression to an active ulcer was lower (1 vs. 7, P = 0.028) and the number of ulcer-free days higher (P = 0.043) in the tenotomy group. No serious adverse events were recorded. CONCLUSIONS: This randomized study showed that the simple procedure of needle flexor tendon tenotomy was effective and safe when treating and preventing ulcers associated with the diabetic hammertoe deformity.

Nonepithelial ovarian cancer - the current clinical practice in the Nordic countries. Survey from the surgical subcommittee of the Nordic society of gynecological oncology (NSGO).

BACKGROUND: Nonepithelial ovarian cancer (NEOC) represents a wide variety of rare tumors. They are often diagnosed at an early stage and have a good prognosis compared to epithelial ovarian cancer. In the Nordic countries, the total annual number of patients diagnosed with ovarian cancer, Fallopian tube cancer or primary peritoneal carcinoma (hereafter ovarian cancer) was 2281 in 2014-2018, of which 3-10% were NEOC. International guidelines for diagnosis, treatment and follow-up have been developed. We present the results of a survey, aiming at clarifying current clinical practice in the Nordic countries. MATERIAL AND METHODS: Between 09.2020 and 02.2021 a 33-question electronic survey was distributed to 22 hospitals in Finland, Sweden, Norway, Iceland and Denmark via the Nordic Society of Gynecological Oncology (NSGO) National Representatives. Data were collected in a secure web-based software platform. The questionnaire focused on demographics, diagnosis, treatment and follow-up programs. RESULTS: Twenty-one (95,4%) centers completed the survey. A total of 155 annual new NEOC cases treated in the Nordic countries were reported, corresponding to approximately 7% of all ovarian cancer cases. Most centers measured some or all of the recommended biomarkers routinely. Vaginal ultrasound and computed tomography (CT) were the preferred imaging modalities. The majority of centers conducted multidisciplinary team (MDT) meetings. The primary reported treatment was surgery. In 65% of centers, lymph node dissection was only performed in cases with suspicious lymph nodes. Surveillance was usually offered > four years. DISCUSSION: Despite, the presence of clinical European guidelines, variation in the current clinical practice amongst participating centers adhering to national guidelines was observed. Prospective clinical national research programs are sparse, and an enhanced cooperation in the Nordic countries toward development of a Nordic guideline and database is highly warranted and a prerequisite for future research, preferably in cooperation with the larger international groups.

Novel topical allogeneic bone-marrow-derived mesenchymal stem cell treatment of hard-to-heal diabetic foot ulcers: a proof of concept study.

AIM: The aim of this study was to investigate safety of treating diabetic foot ulcers with a topically administered mesenchymal stem cell product. METHOD: Individuals with diabetes, peripheral neuropathy, toe blood pressure > 39 mmHg and non-infected foot ulcers with duration of four to fifty-two weeks were screened. Participants were treated with a one-time application of a topically applied allogeneic cellular product containing CD362 enriched mesenchymal stem cells suspended in a collagen solution. Participants were subsequently followed for seven months to gather information on adverse event and serious adverse events. RESULTS/DISCUSSION: A total of sixteen individuals were screened, of whom two were included. The included participants incurred a total of seven adverse events and one serious adverse event. Increased exudation from the treated diabetic foot ulcer was observed for both participants and a connection to investigational medicinal product was suspected. The increased exudation was resolved within one week after application of investigational medicinal product, without any further complications. The serious adverse event consisted of a hospital admission due to neurological symptoms, which were assumed to be caused by hypoglycemia, with no suspected correlation to the investigational medicinal product. None of the other observed adverse events were suspected to be associated with the investigational medicinal product. CONCLUSION: This study presents data from two individuals with a diabetic foot ulcer treated with a novel topical mesenchymal stem cell product. An adverse event observed for both participants was suspected to be associated to the investigational medicinal product, i.e., increased exudation, which was resolved within one week, did not lead to further complications and can easily be remedied by choosing bandages with higher absorption capacity or increasing frequency of bandage changes. This study lays the groundwork for further large scale randomized clinical studies. TRIAL REGISTRATION: EudraCT number 2015-005580-16. Registered 12/06-2018.

The memories that people would save or erase differ from their most positive and negative memories on function, emotion and correspondence with the life script.

Autobiographical remembering is a dynamic process in which narrators construct their life story from single memories. What is included in or deleted from the life story depends on many factors. Here, we examined the functions, emotions and correspondence with the life script for the memories that people desire to save or erase from their past. We asked people to generate either the two memories they were most likely to save and erase or the two memories they regarded as their most positive and negative memories. Then everyone rated those memories on function, emotion and correspondence with the life script. Overall, we found save and erase memories corresponded less with the life script relative to most positive and most negative memories though they were similarly emotionally intense. Additionally, erase memories were more associated with shame and less with social functions than most negative memories, whereas most negative memories to a higher degree involved the death of significant others, albeit being similarly traumatic. These findings have important implications for theory about autobiographical memory, and possible clinical relevance.

Gender differences in patient-reported outcomes in patients with acute myocardial infarction.

AIMS: Women report worse health-related patient-reported outcomes (PROs) compared with men following acute myocardial infarction (AMI). However, this association is not well established when accounting for demographic and clinical patient characteristics at discharge. This knowledge is essential for clinicians when planning individualised care for patients following AMI. The aim of this study is to examine whether gender is associated with health-related PROs at discharge from a Danish heart centre, combining PROs with data from the national health and administrative registries. METHODS AND RESULTS: A cross-sectional study of 2131 patients with AMI discharged from a Danish heart centre responding to the following health-related PRO questionnaires: the Health-survey Short-Form-12 (SF-12), generating a physical component summary (PCS) and a mental component summary (MCS) score; the HeartQoL, providing a global, emotional, and physical score; the EuroQol five-dimensional questionnaire (EQ-5D-5L) and the EQ visual analogue scale (EQ VAS); the Hospital Anxiety and Depression Scale (HADS), generating an anxiety and depression score (HADS-A and HADS-D); the Edmonton Symptom Assessment Scale (ESAS); the Brief Illness Perception Questionnaire (B-IPQ). Patient-reported outcomes were linked to registry-based information adjusting for potential demographic and clinical confounding factors. In adjusted regression models, women reported worse health-related PROs compared with men in SF-12 PCS and SF-12 MCS, HeartQoL global, the HeartQoL emotional and HeartQoL physical score, EQ-5D-5L and EQ VAS, the HADS-A, ESAS, and in six out of eight B-IPQ items. CONCLUSIONS: Women reported worse health-related PROs compared with men. Health-related PROs have the potential to be further investigated to facilitate a more individualised healthcare follow-up after AMI.

Identifying Valid Algorithms for Number of Lines of Anti-Neoplastic Therapy in the Danish National Patient Registry Among Patients with Advanced Ovarian, Gastric, Renal Cell, Urothelial, and Non-Small Cell Lung Cancer Attending a Danish University Hospital.

PURPOSE: To develop algorithms to identify number of lines of anti-neoplastic therapy per patient based on the Danish National Patient Registry (DNPR) and identify which algorithm has the highest percentage agreement with a reference standard of documentation in medical records. PATIENTS AND METHODS: We included 179 patients diagnosed between January 1, 2012, and December 31, 2016, with stage II, III, or IV urothelial cell carcinoma or stage III or IV epithelial ovarian cancer, gastric adenocarcinoma, renal cell carcinoma, or non-small cell lung cancer (NSCLC). We developed two algorithms for number of lines of anti-neoplastic therapy based on dates and treatment codes (eg, "treatment with cisplatin" or "cytostatic treatment") in the DNPR. First, to denote a change in line of therapy the "Time-based algorithm" used the number of days between consecutive administrations. Second, the "Drug-based algorithm" used information on drug names if available or the number of days between consecutive administrations if no drug names were specified. We calculated the percentage agreement between the algorithms setting the number of allowed days between consecutive administrations from 28 to 50 and the reference standard - information on anti-neoplastic therapy drugs abstracted from medical records and subsequently coded according to lines of anti-neoplastic therapy. RESULTS: For the "Time-based algorithm", the highest percentage agreement with the reference standard was found when using <45 days between consecutive administrations (67.6%; 95% CI: 60.1-73.8%). However, the percentage agreement was higher for the "Drug-based algorithm" using <45 days between consecutive administrations for registrations where the drug name was unspecified (90.5%; 95% CI: 85.0-93.7%). CONCLUSION: The algorithm for number of lines of anti-neoplastic therapy that had the highest percentage agreement with the reference standard (medical records) incorporated both registration of specific drug names and <45 days between consecutive administrations if the drug name was unspecified in routinely recorded data from DNPR.

Light Driven Ultrafast Bioinspired Molecular Motors: Steering and Accelerating Photoisomerization Dynamics of Retinal.

Photoisomerization of retinal protonated Schiff base in microbial and animal rhodopsins are strikingly ultrafast and highly specific. Both protein environments provide conditions for fine-tuning the photochemistry of their chromophores. Here, by combining time-resolved action absorption spectroscopy and high-level electronic structure theory, we show that similar control can be gained in a synthetically engineered retinal chromophore. By locking the dimethylated retinal Schiff base at the C11═C12 double bond in its trans configuration (L-RSB), the excited-state decay is rendered from a slow picosecond to an ultrafast subpicosecond regime in the gas phase. Steric hindrance and pretwisting of L-RSB are found to be important for a significant reduction in the excited-state energy barriers, where isomerization of the locked chromophore proceeds along C9═C10 rather than the preferred C11═C12 isomerization path. Remarkably, the accelerated excited-state dynamics also becomes steered. We show that L-RSB is capable of unidirectional 360° rotation from all-trans to 9-cis and from 9-cis to all-trans in only two distinct steps induced by consecutive absorption of two 600 nm photons. This opens a way for the rational design of red-light-driven ultrafast molecular rotary motors based on locked retinal chromophores.

The Unequal Effects of the COVID-19 Pandemic on Political Interest Representation.

The COVID-19 pandemic is viewed by many as the biggest global crisis since WWII and had profound effects on the daily lives of people and decision-making worldwide. Using the pandemic as a system-wide agenda shock, we employ a difference-in-differences design to estimate its causal effects on inequalities in political access, and social media prominence among business interests and NGOs. Our argument is twofold. First, the urgency and uncertainty of crises incentivized decision-makers to privilege providing access to business groups over securing inclusivity in the types of interests consulted. Second, NGOs compensated by increasing prominence in public communications. Our analysis of data from over 10,000 interest groups from over 100 countries registered in the European Union supports these hypotheses. Business interests successfully capitalized on the crisis in insider access, while NGOs increased prominence on social media. The results have wider implications for understanding how large-scale crises affect inequalities in representation. Supplementary Information: The online version contains supplementary material available at 10.1007/s11109-022-09842-x.

The clinical course and mortality of persons with diabetic Charcot foot.

INTRODUCTION: The aim was to study the mortality and the clinical course of diabetic Charcot foot. METHODS: This was a retrospective cohort study including all persons with diabetes and a Charcot diagnosis from 2000 to 2016. RESULTS: In the mortality sub-study, 164 persons had the Charcot diagnosis, 52 (31.1%) died in the follow-up period. The mortality rate was 4.6/100 person-years at risk. Rate ratios for death were insignificantly different among smokers and non-smokers, among persons with type 1 and type 2 diabetes, among persons with a diabetes duration below or above ten years and among persons with a glycated haemoglobin (HbA1c) level above or below 60 mmol/mol after adjustment for age and gender. In the clinical course sub-study, 114 persons with Charcot were identified whereof 97 (85%) had an active Charcot. The duration from start of symptoms to diagnosis was ten weeks, the treatment period was 7.5 months and 46 (40%) had bony prominences (rocker bottom) in the planta at follow-up. CONCLUSIONS: The mortality rate among persons with Charcot was 4.6/person-years at risk, which was unaffected by smoking, diabetes type, diabetes duration and HbA1c level. The persons with Charcot had a long delay from symptom onset to diagnosis, a long treatment period and often developed complications. FUNDING: This research did not receive any specific grant from funding agencies in the public, commercial or not-for-profit sectors. TRIAL REGISTRATION: not relevant.