Delineating organizational principles of the endogenous L-A virus by cryo-EM and computational analysis of native cell extracts.

The high abundance of most viruses in infected host cells benefits their structural characterization. However, endogenous viruses are present in low copy numbers and are therefore challenging to investigate. Here, we retrieve cell extracts enriched with an endogenous virus, the yeast L-A virus. The determined cryo-EM structure discloses capsid-stabilizing cation-π stacking, widespread across viruses and within the Totiviridae, and an interplay of non-covalent interactions from ten distinct capsomere interfaces. The capsid-embedded mRNA decapping active site trench is supported by a constricting movement of two flexible opposite-facing loops. tRNA-loaded polysomes and other biomacromolecules, presumably mRNA, are found in virus proximity within the cell extract. Mature viruses participate in larger viral communities resembling their rare in-cell equivalents in terms of size, composition, and inter-virus distances. Our results collectively describe a 3D-architecture of a viral milieu, opening the door to cell-extract-based high-resolution structural virology.

Behavior and circadian glucocorticoids in prepubertal monozygotic twins with birthweight differences: A prospective longitudinal cohort study on twin-to-twin transfusion syndrome patients.

BACKGROUND/OBJECTIVE: Low birthweight may have adverse sequelae in later life. Therefore, we analyzed behavioral difficulties and salivary glucocorticoid profiles in monozygotic twins with intra-twin birthweight differences due to twin-to-twin transfusion syndrome (TTTS). METHODS: 46 monozygotic TTTS twin pairs with birthweight differences of <1SDS (concordant; n=29) and ≥1SDS (discordant; n=17) were recruited at a mean age of 6.9 years for a prospective longitudinal cohort study. For glucocorticoid analysis, saliva samples were collected (at 7 h, 13 h, 18 h and 21 h) and analyzed with liquid chromatography-tandem mass spectrometry. Parents completed the Strengths and Difficulties Questionnaire. RESULTS: From the parents' perspective, the formerly smaller twins had statistically higher scores regarding hyperactivity (mean 4.63 vs 3.48, p=0.003) and emotional problems (mean 2.67 vs 2.02, p=0.042). Less catch-up growth (Δintra-twin height SDS 4 years of age - Δintra-twin birth length SDS) of the smaller twins was associated with higher scores for hyperactivity (Adj. R²=0.261, p<0.001, ß=-1.88, F(1.44)=16.86, n=46, f²=0.35), while smaller birthweight (Adj. R²=0.135, p=0.007, ß=-0,87, F(1.44)=8.03, n=46, f²=0.16) and birth length (Adj. R²=0.085, p=0.028, ß=-0,78, F(1.44)=5.19, n=46, f²=0.09) were associated with higher scores for peer problems. Greater Δintra-twin for cortisol (7 h: rho=0.337, p=0.029; cumulative: rho=0.458; p=0.024) and cortisone (7 h: rho=0.329, p=0.029; 13 h: rho=0.436, p=0.005) correlated with a greater Δintra-twin for conduct problems. In the discordant group, circa 1 SDS in head circumference persisted from birth (mean SDS: smaller twin -1.18, larger twin -0.08, p<0.001) to present (mean SDS: smaller twin -1.16, larger twin -0.14, p<0.001). CONCLUSION: Higher cortisol and cortisone concentrations in smaller twins were associated with higher scores for conduct problems. Lower birthweight and absent catch-up growth affected the parents' perspective on the smaller twins' behavior. They saw those children as more hyperactive, with more peer problems and emotional problems. Thus, it seems important to introduce regular check-ups where behavioral difficulties can be assessed, and assistance and advice can be given to the families. Due to the persisting smaller head circumference in the smaller discordant twins, this should be measured regularly.

Mass mortality of diadematoid sea urchins in the Red Sea and Western Indian Ocean.

Sea urchins are primary herbivores on coral reefs, regulating algal biomass and facilitating coral settlement and growth.1,2,3,4,5,6,7,8,9,10,11,12 Recurring mass mortality events (MMEs) of Diadema species Gray, 1825 have been recorded globally,13,14,15,16,17,18,19,20,21,22,23 the most notorious and ecologically significant of which occurred in the Caribbean in 1983,14,17,19,20 contributing to the shift from coral to algal-dominated ecosystems.17,24,25 Recently, first evidence of Diadema setosum mass mortality was reported from the eastern Mediterranean Sea.23 Here, we report extensive mass mortalities of several diadematoid species inhabiting the Red Sea and Western Indian Ocean (WIO)26,27,28 including first evidence of mortalities in the genus Echinothrix Peters, 1853. Mortalities initiated in the Gulf of Aqaba on December 2022 and span the Red Sea, the Gulf of Oman, and the Western Indian Ocean (Réunion Island), with population declines reaching 100% at some sites. Infected individuals are characterized by spine loss and tissue necrosis, resulting in exposed skeletons (i.e., tests) and mortality. Molecular diagnostics of the 18S rRNA gene confirm the presence of a waterborne scuticociliate protozoan most closely related to Philaster apodigitiformis in infected specimens-identical to the pathogen found in the 2022 Caribbean mass mortality of Diadema antillarum.13,15,18 Collapse of these key benthic grazers in the Red Sea and Western Indian Ocean may lead to algal dominance over corals, threatening the stability of coral reefs on a regional scale.29,30,31,32 We issue a warning regarding the further expansion of mortalities and call for immediate monitoring and conservation efforts for these key ecological species.

Evaluation of anti-Fel d 1 IgY ingredient for pet food on growth performance in kittens.

Introduction: The domestic cat (Felis catus) is one of the most common pets. Worldwide, approximately one in five adults are sensitive to cat allergens. The major cat allergen is the secretoglobulin Fel d 1, which is primarily produced in the salivary and sebaceous glands. Chickens produce IgY antibodies, which are similar in structure to mammalian IgG. When chickens are exposed to Fel d 1, anti-Fel d 1-specific IgY (AFD1) is produced and is naturally concentrated in egg yolk. The aim of this study was to evaluate the tolerability, effects on growth and food consumption, and potential adverse effects of a chicken egg product ingredient containing AFD1 in kittens. Methods: This was a blinded, controlled study. Twenty-seven (27) eight-week old kittens were randomly assigned to three feeding groups containing 0 ppm AFD1 (Group 0), 8 ppm AFD1 (Group 1), and 16 ppm AFD1 (Group 2) for 84 days. Veterinary exams and bloodwork were performed on Day 42 and Day 84, and body weight and body condition score (BCS) were monitored weekly. Results: Throughout the study, there were no signs of nutritional deficiency or adverse clinical events in any of the subjects. Administration of a chicken egg product ingredient containing AFD1 in the diet (whether in coating or combination of coating and top dress) had no significant effect on body weight nor food consumption, and all subjects maintained a healthy Body Condition Score (BCS) throughout the study. Moreover, there were no biologically significant differences in the mean clinical chemistry and hematology parameters. Discussion: This study demonstrated that a diet formulated to contain up to 16 ppm AFD1, included in the coating and the top-dress of dry kitten food, was well tolerated, promoted adequate growth, and exhibited no adverse effects.

Structural connectivity of grandiose versus vulnerable narcissism as models of social dominance and subordination.

Social dominance and subordination have been linked to fronto-limbic and fronto-thalamic networks and are related to phenotypes such as grandiose vs. vulnerable narcissistic traits. The latter have been linked to clinical features such as empathy and emotional regulation. In this study we tested the hypotheses that narcissistic traits are associated with white matter integrity in fasciculus uncinate, cingulum, and anterior thalamic radiation (ATR). We applied the Pathological Narcissism Inventory (PNI) to assess narcissistic traits in a sample of 267 psychiatrically healthy individuals. We used 3 T MRI to acquire Diffusion Tensor Imaging data for analysis with TBSS in FSL applying TFCE to test for correlations of fractional anisotropy (FA) and PNI scales. We detected a significant positive correlation of PNI total and FA in the right posterior cingulum. PNI Vulnerability was significantly correlated with FA in the left anterior and right posterior cingulum. We did not find overall correlations with PNI Grandiosity, but additional analyses showed significant effects with FA of ATR. Our results strengthen network models for narcissism underlying both personality variation and pathology. Especially associations of narcissistic vulnerability within fronto-limbic tracts suggest overlaps within neural correlates of related phenotypes like neuroticism, social subordination, and negative emotionality.

Mass mortality of the invasive alien echinoid Diadema setosum (Echinoidea: Diadematidae) in the Mediterranean Sea.

The sea urchin Diadema setosum is an ecological key species across its range, particularly on coral reefs. In 2006 D. setosum was first observed in the Mediterranean Sea, and since, it has proliferated to occupy the entire Levantine Basin. Here we report the mass mortality of the invasive D. setosum in the Mediterranean Sea. This is the first report of D. setosum mass mortality. The mortality spans over 1000 km along the Levantine coast of Greece and Turkey. The current mortality shows similar pathologies to previously reported Diadema mass mortality events, suggesting pathogenic infection as the cause of mortalities. Maritime transport, local currents, and fish predation of infected individuals may distribute pathogens at varying geographical scales. Due to the proximity of the Levantine Basin to the Red Sea, the risk of pathogen transport to the native Red Sea D. setosum population is imminent-with potentially catastrophic consequences.

Building the foundation for a modern patient-partnered infrastructure to study temporomandibular disorders.

Background: Conflicting reports from varying stakeholders related to prognosis and outcomes following placement of temporomandibular joint (TMJ) implants gave rise to the development of the TMJ Patient-Led RoundTable initiative. Following an assessment of the current availability of data, the RoundTable concluded that a strategically Coordinated Registry Network (CRN) is needed to collect and generate accessible data on temporomandibular disorder (TMD) and its care. The aim of this study was therefore to advance the clinical understanding, usage, and adoption of a core minimum dataset for TMD patients as the first foundational step toward building the CRN. Methods: Candidate data elements were extracted from existing data sources and included in a Delphi survey administered to 92 participants. Data elements receiving less than 75% consensus were dropped. A purposive multi-stakeholder sub-group triangulated the items across patient and clinician-based experience to remove redundancies or duplicate items and reduce the response burden for both patients and clinicians. To reliably collect the identified data elements, the identified core minimum data elements were defined in the context of technical implementation within High-performance Integrated Virtual Environment (HIVE) web-application framework. HIVE was integrated with CHIOS™, an innovative permissioned blockchain platform, to strengthen the provenance of data captured in the registry and drive metadata to record all registry transaction and create a robust consent network. Results: A total of 59 multi-stakeholder participants responded to the Delphi survey. The completion of the Delphi surveys followed by the application of the required group consensus threshold resulted in the selection of 397 data elements (254 for patient-generated data elements and 143 for clinician generated data elements). The infrastructure development and integration of HIVE and CHIOS™ was completed showing the maintenance of all data transaction information in blockchain, flexible recording of patient consent, data cataloging, and consent validation through smart contracts. Conclusion: The identified data elements and development of the technological platform establishes a data infrastructure that facilitates the standardization and harmonization of data as well as perform high performance analytics needed to fully leverage the captured patient-generated data, clinical evidence, and other healthcare ecosystem data within the TMJ/TMD-CRN.

Enabling cryo-EM density interpretation from yeast native cell extracts by proteomics data and AlphaFold structures.

In the cellular context, proteins participate in communities to perform their function. The detection and identification of these communities as well as in-community interactions has long been the subject of investigation, mainly through proteomics analysis with mass spectrometry. With the advent of cryogenic electron microscopy and the "resolution revolution," their visualization has recently been made possible, even in complex, native samples. The advances in both fields have resulted in the generation of large amounts of data, whose analysis requires advanced computation, often employing machine learning approaches to reach the desired outcome. In this work, we first performed a robust proteomics analysis of mass spectrometry (MS) data derived from a yeast native cell extract and used this information to identify protein communities and inter-protein interactions. Cryo-EM analysis of the cell extract provided a reconstruction of a biomolecule at medium resolution (∼8 Å (FSC = 0.143)). Utilizing MS-derived proteomics data and systematic fitting of AlphaFold-predicted atomic models, this density was assigned to the 2.6 MDa complex of yeast fatty acid synthase. Our proposed workflow identifies protein complexes in native cell extracts from Saccharomyces cerevisiae by combining proteomics, cryo-EM, and AI-guided protein structure prediction.

Cardiovascular endurance and psychosocial health predict short- and long-term BMI-SDS reduction: results from the CHILT III program.

This longitudinal study analyzes data from the Children's Health Interventional Trial (CHILT) III, an 11-month juvenile multicomponent weight management program. The objective is to identify predictors of changes in body mass index standard deviation scores (BMI-SDS), so as to further enable the advancement of existing interventions with sustained impact. This study's sample consists of 237 children and adolescents with obesity (8-17 years, 54% girls) participating in the CHILT III program between 2003 and 2021. Anthropometrics, demographics, relative cardiovascular endurance (W/kg), and psychosocial health (i.e., physical self-concept and self-worth) were assessed at program entry ([Formula: see text]), end ([Formula: see text]), and one-year follow-up ([Formula: see text]; n = 83). From [Formula: see text] to [Formula: see text], the mean BMI-SDS was reduced by -0.16 ± 0.26 units (p < 0.001). Media use and cardiovascular endurance at baseline and improvements in endurance and self-worth over the course of the program predicted changes in BMI-SDS (adj. R2 = 0.22, p < 0.001). From [Formula: see text] to [Formula: see text], mean BMI-SDS increased ([Formula: see text], p = 0.005). Changes in BMI-SDS from [Formula: see text] to [Formula: see text] were associated with parental education, improvements in cardiovascular endurance and physical self-concept, and BMI-SDS, media use, physical self-concept, and endurance level at program end (adj. R2 = 0.39, p < 0.001).  Conclusions: This study highlights the need for comprehensive, sustainable weight management approaches, in order to sustain the initial treatment benefits. In this context, improvements in cardiovascular endurance and psychosocial health could be essential strategies to pursue in practice, as they significantly predicted reductions in BMI-SDS - both pre- to post-intervention and at follow-up. TRIAL REGISTRATION: DRKS00026785; date of registration: 13.10.202, retrospectively registered. WHAT IS KNOWN: • Childhood obesity is associated with the onset of noncommunicable diseases, many of which are likely to carry into adulthood. Thus, effective weight management strategies for affected children and their families are vital. However, achieving lasting positive health outcomes with multidisciplinary weight management programs remains challenging. WHAT IS NEW: • According to this study, short- and longer-term BMI-SDS reductions are associated to cardiovascular endurance and psychosocial health. These factors should therefore be given even greater consideration in weight management strategies, as they may be important not only in themselves but also for long-term weight loss (maintenance).

How dental teams can help patients with temporomandibular disorders receive general dental care: An International Delphi process.

BACKGROUND: Many patients with temporomandibular disorders (TMD) find it difficult to undergo dental care due to challenges caused by their condition, previous temporomandibular joint surgery or invasive dental procedures, and the impact of comorbid conditions. Managing routine dental care for some patients with TMD can be seen as challenging by some dental practitioners. OBJECTIVE: The objective of this study was to work with patients experiencing TMD and clinicians to co-produce recommendations aimed at helping general dentists to provide routine dental care for patients with TMD. METHODS: A modified Delphi process was used to co-produce recommendations. Six patients experiencing TMD, patient advocates and seven clinicians took part, including international TMD clinicians. Two meetings were held with patient participants, mediated by a trained facilitator. Recommendations suggested by patient participants were distributed to clinicians who were asked to add additional suggestions, but not to modify patients' recommendations unless to aid clarity. Additional themes were identified from the existing literature, and the recommendations were then reviewed by the International Network for Orofacial Pain and Related Disorders Methodology (INfORM) consortium. RESULTS: Recommendations were given to support patients before, during and after dental treatment. Participants identified specific and practical recommendations to help patients with TMD receive routine dental care, but also emphasised the need for professionals to listen sensitively to patients' concerns and work with patients in an empathetic and non-judgmental way. CONCLUSION: These recommendations, co-developed with patients experiencing TMD, should help dental professionals to provide supportive general dental care for patients with TMD.

Direct observation of motor protein stepping in living cells using MINFLUX.

Dynamic measurements of molecular machines can provide invaluable insights into their mechanism, but these measurements have been challenging in living cells. Here, we developed live-cell tracking of single fluorophores with nanometer spatial and millisecond temporal resolution in two and three dimensions using the recently introduced super-resolution technique MINFLUX. Using this approach, we resolved the precise stepping motion of the motor protein kinesin-1 as it walked on microtubules in living cells. Nanoscopic tracking of motors walking on the microtubules of fixed cells also enabled us to resolve the architecture of the microtubule cytoskeleton with protofilament resolution.

Effect of Lifestyle Interventions during Pregnancy on Maternal Leptin, Resistin and Offspring Weight at Birth and One Year of Life.

Lifestyle during pregnancy impacts the health of the mother and child. However, the extent to which physical activity affects maternal biomarkers and factors that might influence birth weight remains unclear. We analysed data from two lifestyle interventions in which the effects of an exercise programme (2x/week, 60-90 min) on the course of pregnancy with regard to adipokines and offspring were evaluated. A total of 70 women participated in this study (45, intervention group; 25, control group). Anthropometric data and maternal fasting serum leptin and resistin levels were measured at three time points (approximately 14th (T1), 24th (T2), and 36th (T3) weeks of gestation). Neonatal/child data were retrieved from screening examinations. Independent of the intervention, we found a positive correlation between the fat mass at T1 and both leptin and resistin levels at all time points. Leptin level was significantly higher in the control group at T3; however, no differences between the groups were found for resistin. The birth weight was influenced by the birth length, fat mass at T1/T3, and resistin level at T2. The BMI-SDS at one year of age was influenced by maternal fat-free mass at T3 and resistin at T1/T2. Even if these results can only be interpreted cautiously, lifestyle interventions during pregnancy are important in promoting maternal and child health. Further randomised controlled trials and translational studies are warranted to clarify the underlying mechanisms.

Disparities in COVID-19 related health literacy, knowledge, and the assessment of the measures taken in Germany: a cross-sectional study.

Aim: Health literacy is necessary to access, understand, assess, and apply information on COVID-19. Studies have shown that health literacy is unequally distributed across social groups. This study aimed to analyze the differences in COVID-19-related health literacy (hereinafter referred to as "COV-19-HL"), knowledge about COVID-19, and the assessment of the measures taken regarding the sociodemographic characteristics as well as the influence of COV-19-HL on knowledge and assessments. Subject and methods: The study used the data obtained from the cross-sectional online survey "Digital divide in relation to health literacy during the COVID-19 pandemic." The data covers 1570 participants aged ≥18 years in Germany between April 29, 2020 and May 8, 2020. To analyze the differences by way of sociodemographic variables, t-tests and analyses of variance were carried out. Multivariate logistic regression models were used to determine the effect of COV-19-HL on knowledge and the assessment of measures. Results: The overall COV-19-HL was high with an average value of 37.4 (with 50 representing the highest COV-19-HL). COV-19-HL and knowledge about COVID-19 were slightly lower in men, migrants, people with low subjective social status, and with low education. Government requirements and recommendations were rated as more effective by women, older people, and individuals with a chronic illness. The chance of better knowledge about COVID-19 and rating measures as effective increased with higher COV-19-HL. Conclusion: The findings of this study show that COV-19-HL and knowledge about the virus are unequally distributed in Germany. Health communication should strengthen pandemic-related health literacy that is tailored to specific target groups.

An Imbalance in the Force: The Need for Standardized Benchmarks for Molecular Simulation.

Force fields (FFs) for molecular simulation have been under development for more than half a century. As with any predictive model, rigorous testing and comparisons of models critically depends on the availability of standardized data sets and benchmarks. While such benchmarks are rather common in the fields of quantum chemistry, this is not the case for empirical FFs. That is, few benchmarks are reused to evaluate FFs, and development teams rather use their own training and test sets. Here we present an overview of currently available tests and benchmarks for computational chemistry, focusing on organic compounds, including halogens and common ions, as FFs for these are the most common ones. We argue that many of the benchmark data sets from quantum chemistry can in fact be reused for evaluating FFs, but new gas phase data is still needed for compounds containing phosphorus and sulfur in different valence states. In addition, more nonequilibrium interaction energies and forces, as well as molecular properties such as electrostatic potentials around compounds, would be beneficial. For the condensed phases there is a large body of experimental data available, and tools to utilize these data in an automated fashion are under development. If FF developers, as well as researchers in artificial intelligence, would adopt a number of these data sets, it would become easier to compare the relative strengths and weaknesses of different models and to, eventually, restore the balance in the force.

Secular Trend of Self-Concept in the Context of Childhood Obesity-Data from the CHILT III Programme, Cologne.

Juvenile obesity is associated with a lower self-concept. Given the continued prevalence of obesity, we examined the secular trend of body mass index standard deviation score (BMI-SDS) and self-concept in participants of a German weight management programme (n = 242, 53.3% female, mean age 12.5 ± 2.1 years, mean BMI-SDS 2.45 ± 0.46) over a period of 15 years. Anthropometric data, physical fitness (watt/kg), and demographic data were assessed. The years 2005 to 2020 were grouped into six sections containing a mean of n = 40 participants. The questionnaire for the assessment of self and competence in children (FSK-K) was used to assess the following domains: "scholastic competence", "social competence", "physical appearance", "global self-worth", and "behavioural conduct". No significant between-group differences in self-assessment across self-concept domains were found. In all time periods, heavier children assigned the lowest rating to physical appearance. Social competence increased with higher physical fitness. Even though no negative trend in the self-concept of children with obesity was found in this cohort, the findings confirmed an association between juvenile overweight/obesity and lower physical self-concept, and between a better social competence and increasing physical fitness. Accompanying psychosocial care, therefore, rightly remains an important pillar of obesity therapy.

Diagnostic Accuracy of 99mTc-Sestamibi SPECT/CT for Characterization of Solid Renal Masses.

Our objective was to assess the diagnostic accuracy of 99mTc-sestamibi SPECT/CT for characterizing solid renal masses. Methods: Imaging and clinical records of patients who underwent 99mTc-sestamibi SPECT/CT for clinical work-up of their solid renal masses from September 2018 to October 2021 were retrospectively reviewed. Histopathology formed the reference standard, and the diagnoses were categorized as malignant/concerning (renal cell carcinomas [RCCs] other than chromophobe histology) and benign/nonconcerning (oncocytic tumors including chromophobe RCC, other benign diagnoses) to calculate the sensitivity and specificity of 99mTc-sestamibi SPECT/CT and contrast-enhanced CT (ceCT). The clinical reads of the SPECT/CT images were used for visual classification of the lesions. Additionally, the SPECT images were manually segmented to obtain the maximum and mean counts of the lesion and adjacent renal cortex and maximum and mean lesion Hounsfield units. Results: 99mTc-sestamibi SPECT/CT was performed on 42 patients with 62 renal masses. A histopathologic diagnosis was available for 27 patients (18 male, 9 female) with 36 solid renal masses. ceCT findings were available for 20 of these patients. The most commonly identified single histologic type was clear cell RCC (13/36; 36.1%). Oncocytic tumors were the most common group of nonconcerning lesions (15/36), with oncocytoma as the predominant histologic type (n = 6). The sensitivity and specificity of SPECT/CT for diagnosing a nonconcerning lesion were 66.7% and 89.5%, respectively, compared with 10% and 75%, respectively, for ceCT. The lesion-to-kidney ratios for maximum and mean counts and maximum lesion Hounsfield units showed significant differences between the 2 groups (P < 0.05). The lesion-to-kidney mean count ratio at a cutoff of 0.46 showed a sensitivity and specificity of 87.5% and 86.67%, respectively, for detecting nonconcerning lesions, which was significantly higher than that of ceCT. Conclusion: The current literature on the utility of 99mTc-sestamibi SPECT/CT for characterization of solid renal masses is limited. We offer additional evidence of the incremental value of 99mTc-sestamibi SPECT/CT over ceCT for differentiating malignant or aggressive renal tumors from benign or indolent ones, thereby potentially avoiding overtreatment and its associated complications. Quantitative assessment can further increase the diagnostic accuracy of SPECT/CT and may be used in conjunction with visual interpretation.

Adverse Clinical Events at the Injection Site Are Exceedingly Rare After Reported Radiopharmaceutical Extravasation in Patients Undergoing 99mTc-MDP Whole-Body Bone Scintigraphy: A 12-Year Experience.

The deleterious effects of high-dose radiation on normal tissue are sometimes extrapolated to diagnostic (SPECT and PET) radiopharmaceutical extravasation (RPE). It has been hypothesized that diagnostic RPE can have gradually evolving local tissue injury and a potentially increased risk of local dermatologic or oncologic diseases over a longer period. However, data on clinical adverse events after diagnostic RPE are limited. Therefore, our primary aim was to study the occurrence of short-term and long-term clinical adverse events in patients who underwent 99mTc-methylene diphosphonate (99mTc-MDP) whole-body bone scintigraphy (WBBS) with reported RPE. Methods: The records of 99mTc-MDP WBBS performed from June 2010 to January 2022 were retrospectively examined for RPE documented in the scan reports. The clinical records of patients with a documented RPE were extensively reviewed for any related short-term adverse events (within 2 wk of the WBBS: local symptoms and care sought for local dermatologic or musculoskeletal issues) and long-term adverse events (until the last follow-up: local deleterious effects and related consults for dermatology, plastic surgery, oncology, or orthopedics). Results: Retrospective review of the records of 31,679 99mTc-MDP WBBS studies showed RPE documented in 118 (0.37%). Medical records were not retrievable for 22 patients, yielding a final cohort of 96 patients with reported RPE. The median follow-up was 18.9 mo (interquartile range, 7.8-45.7 mo). Short-term events were noted in 4 patients, of whom one was asymptomatic. Of the 3 symptomatic patients, 2 experienced mild discomfort at the injection site, and 1 had tender swelling. Three of the 4 events were in patients who had a prior intravenous contrast extravasation for contrast-enhanced CT performed earlier during the day and a 99mTc-MDP injection later at the same site, likely leading to RPE. None of the long-term local events had any plausible link with the RPE event. Conclusion: Reported RPE was rare, and 3 patients (0.009%) had short-term local symptoms, all of which were likely related to the prior higher-volume intravenous contrast extravasation. The smaller-volume diagnostic radiopharmaceutical injections for WBBS are highly unlikely to cause local symptoms on their own. No patient had any long-term adverse event with a plausible link to the RPE.

Functionalized C3-Symmetric Building Blocks-The Chemistry of Triaminotrimesic Acid.

A series of C3-symmetric fully substituted benzenes were prepared based on alkyl triamino-benzene-tricarboxylates. Starting with a one step-synthesis, the alkyl triamino-benzene-tricarboxylates were synthesized using the corresponding cyanoacetates. The reactivity of these electronically sophisticated compounds was investigated by the formation of azides, the click reaction of the azides and a Sandmeyer-like reaction. Caused by the low stability of triaminobenzenes, direct N-alkylation was rarely reported. The use of the stable alkyl triamino-benzene-tricarboxylates allowed us total N-alkylation under standard alkylation conditions. The molecular structures of the C3-symmetric structures have been corroborated by an X-ray analysis.

Lighting up Nobel Prize-winning studies with protein intrinsic disorder.

Intrinsically disordered proteins and regions (IDPs and IDRs) and their importance in biology are becoming increasingly recognized in biology, biochemistry, molecular biology and chemistry textbooks, as well as in current protein science and structural biology curricula. We argue that the sequence → dynamic conformational ensemble → function principle is of equal importance as the classical sequence → structure → function paradigm. To highlight this point, we describe the IDPs and/or IDRs behind the discoveries associated with 17 Nobel Prizes, 11 in Physiology or Medicine and 6 in Chemistry. The Nobel Laureates themselves did not always mention that the proteins underlying the phenomena investigated in their award-winning studies are in fact IDPs or contain IDRs. In several cases, IDP- or IDR-based molecular functions have been elucidated, while in other instances, it is recognized that the respective protein(s) contain IDRs, but the specific IDR-based molecular functions have yet to be determined. To highlight the importance of IDPs and IDRs as general principle in biology, we present here illustrative examples of IDPs/IDRs in Nobel Prize-winning mechanisms and processes.