Emergency department visits as a potential opportunity to promote primary care attachment and modify utilization patterns - results of a pilot study in Berlin, Germany.

BACKGROUND: Utilization by low acuity patients contributes to emergency department (ED) crowding. Both knowledge deficits about adequate care levels and access barriers in primary care are important promoters of such presentations. Concurrently, not having a general practitioner (GP) increases the likelihood of low-acuity ED utilization. This pilot study thus investigated feasibility, acceptance, and potential effects of an ED-delivered intervention for low-acuity patients with no regular primary care provider, consisting of an educational leaflet on acute care options and an optional GP appointment scheduling service. METHODS: Low-acuity ED consulters not attached to a GP were given an information leaflet about alternative care offers for acute health problems and offered optional personal appointment scheduling at a local GP practice. Patients were surveyed on demographics, medical characteristics, health care utilization, valuation of the intervention, and reasons for not being attached to a GP and visiting the ED. A follow-up survey was conducted after twelve months. Trends in health and health care utilization were evaluated. RESULTS: Between December 2020 and April 2022, n = 160 patients were enrolled, n = 114 were followed up. The study population was characterized by young age (mean 30.6 years) and predominantly good general health. Besides good health, personal mobility was a central reason for not being attached to a GP, but general preference for specialists and bad experiences with primary care were also mentioned. Most frequently stated motives for the ED consultation were subjective distress and anxiety, a belief in the superiority of the hospital, and access problems in primary care. The interventional offers were favorably valued, 52.5% (n = 84) accepted the GP appointment scheduling service offer. At follow-up, GP utilization had significantly increased, while there were no significant changes regarding utilization of other providers, including ED. An additional practice survey showed a 63.0% take-up rate for the appointment service. CONCLUSIONS: With this pilot study, we were able to show that a personalized appointment scheduling service seems to be a promising approach to promote GP attachment and increase primary care utilization in patients without a regular GP in a highly urbanized setting. Further larger-scale studies are needed to investigate potential quantitative effects on ED visits. TRIAL REGISTRATION: German Clinical Trials Register (DRKS00023480); date 2020/11/27.

Health care utilization of patients with acute abdominal pain before and after emergency department visits.

BACKGROUND: Acute abdominal pain (AAP) is a major driver for capacity-use in emergency departments (EDs) worldwide. Yet, the health care utilization of patients with AAP before and after the ED remains unclear. The primary objective of this study was to describe adult patients presenting to the ED with AAP and their outpatient care (OC) use before and after the ED. Secondary objectives included description of hospitalization rates, in-hospital mortality, ED re-visits, and exploration of potential risk factors for hospitalization and ED re-visits. METHODS: For the analysis, we combined routine hospital data from patients who visited 15 EDs in Germany in 2016 with their statutory health insurance OC claims data from 2014 to 2017. Adult patients were included based on a chief complaint or an ED diagnosis indicating unspecific AAP or the Manchester Triage System indicator "Abdominal pain in adults". Baseline characteristics, ED diagnosis, frequency and reason of hospitalization, frequency and type of prior-OC (prOC) use up to 3 days before and of post-OC use up to 30 days after the ED visit. MAIN RESULTS: We identified 28,085 adults aged ≥ 20 years with AAP. 39.8% were hospitalized, 33.9% sought prOC before the ED visit (48.6% of them were hospitalized) and 62.7% sought post-OC up to 30 days after the ED visit. Hospitalization was significantly more likely for elderly patients (aged 65 and above vs. younger; adjusted OR 3.05 [95% CI 2.87; 3.25]), prOC users (1.71 [1.61; 1.90]) and men (1.44 [1.37; 1.52]). In-hospital mortality rate was 3.1% overall. Re-visiting the ED within 30 days was more likely for elderly patients (1.32 [1.13; 1.55) and less likely for those with prOC use (0.37 [0.31; 0.44]). CONCLUSIONS: prOC use was associated with more frequent hospitalizations but fewer ED re-visits. ED visits by prOC patients without subsequent hospitalization may indicate difficulties of OC resources to meet the complex diagnostic requirements and expectations of this patient population. Fewer ED re-visits in prOC users indicate effective care in this subgroup.

The syncope core management process in the emergency department: a consensus statement of the EUSEM syncope group.

The European Society of Cardiology issued updated syncope guidelines in 2018 which included recommendations for managing syncope in the emergency department (ED) setting. However, these guidelines lack detailed process-oriented instructions regarding the fact that ED syncope patients initially present with a transient loss of consciousness (TLOC), which can have a broad spectrum of causes. This study aims to establish a European consensus on the general process of the workup and care for patients with suspected syncope and provides rules for sufficient and systematic management of the broad group of syncope (initially presenting as TLOC) patients in the ED. A variety of European diagnostic and therapeutic standards for syncope patients were reviewed and summarized in three rounds of a modified Delphi process by the European Society for Emergency Medicine syncope group. Based on a consensus statement, a detailed process pathway is created. The primary outcome of this work is the presentation of a universal process pathway for the structured management of syncope patients in European EDs. The here presented extended event process chain (eEPC) summarizes and homogenizes the process management of European ED syncope patients. Additionally, an exemplary translation of the eEPC into a practice-based flowchart algorithm, which can be used as an example for practical use in the ED, is provided in this work. Syncope patients, initially presenting with TLOC, are common and pose challenges in the ED. Despite variations in process management across Europe, the development of a universally applicable syncope eEPC in the ED was successfully achieved. Key features of the consensus and eEPC include ruling out life-threatening causes, distinguishing syncope from nonsyncopal TLOCs, employing syncope risk stratification categories and based on this, making informed decisions regarding admission or discharge.

Linking CRISPR-Cas9 double-strand break profiles to gene editing precision with BreakTag.

Cas9 can cleave DNA in both blunt and staggered configurations, resulting in distinct editing outcomes, but what dictates the type of Cas9 incisions is largely unknown. In this study, we developed BreakTag, a versatile method for profiling Cas9-induced DNA double-strand breaks (DSBs) and identifying the determinants of Cas9 incisions. Overall, we assessed cleavage by SpCas9 at more than 150,000 endogenous on-target and off-target sites targeted by approximately 3,500 single guide RNAs. We found that approximately 35% of SpCas9 DSBs are staggered, and the type of incision is influenced by DNA:gRNA complementarity and the use of engineered Cas9 variants. A machine learning model shows that Cas9 incision is dependent on the protospacer sequence and that human genetic variation impacts the configuration of Cas9 cuts and the DSB repair outcome. Matched datasets of Cas9 and engineered variant incisions with repair outcomes show that Cas9-mediated staggered breaks are linked with precise, templated and predictable single-nucleotide insertions, demonstrating that a scission-based gRNA design can be used to correct clinically relevant pathogenic single-nucleotide deletions.

"I do not know the advantages of having a general practitioner" - a qualitative study exploring the views of low-acuity emergency patients without a regular general practitioner toward primary care.

BACKGROUND: Emergency departments (ED) worldwide have to cope with rising patient numbers. Low-acuity consulters who could receive a more suitable treatment in primary care (PC) increase caseloads, and lack of PC attachment has been discussed as a determinant. This qualitative study explores factors that contribute to non-utilization of general practitioner (GP) care among patients with no current attachment to a GP. METHOD: Qualitative semi-structured telephone interviews were conducted with 32 low-acuity ED consulters with no self-reported attachment to a GP. Participants were recruited from three EDs in the city center of Berlin, Germany. Data were analyzed by qualitative content analysis. RESULTS: Interviewed patients reported heterogeneous factors contributing to their PC utilization behavior and underlying views and experiences. Participants most prominently voiced a rare need for medical services, a distinct mobility behavior, and a lack of knowledge about the role of a GP and health care options. Views about and experiences with GP care that contribute to non-utilization were predominantly related to little confidence in GP care, preference for directly consulting medical specialists, and negative experiences with GP care in the past. Contrasting their reported utilization behavior, many interviewees still recognized the advantages of GP care continuity. CONCLUSION: Understanding reasons of low-acuity ED patients for GP non-utilization can play an important role in the design and implementation of patient-centered care interventions for PC integration. Increasing GP utilization, continuity of care and health literacy might have positive effects on patient decision-making in acute situations and in turn decrease ED burden. TRIAL REGISTRATION: German Clinical Trials Register: DRKS00023480; date: 2020/11/27.

Computed tomography in patients with sepsis presenting to the emergency department: exploring its role in light of patient outcomes.

OBJECTIVES: This study aimed to explore the role of CT in septic patients presenting to the emergency department (ED). MATERIALS AND METHODS: We performed a retrospective secondary analysis of 192 septic patients from a prospective observational study, i.e., the "LIFE POC" study. Sepsis was diagnosed in accordance with the Sepsis-3 definition. Clinical and radiological data were collected from the hospital administration and radiological systems. Information on mortality and morbidity was collected. Time-to-CT between CT scan and sepsis diagnosis (ttCTsd) was calculated. Diagnostic accuracy was assessed with the final sepsis source as reference standard. The reference standard was established through the treating team of the patient based on all available clinical, imaging, and microbiological data. RESULTS: Sixty-two of 192 patients underwent a CT examination for sepsis focus detection. The final septic source was identified by CT in 69.4% (n = 43). CT detected septic foci with 81.1% sensitivity (95% CI, 68.0-90.6%) and 55.6% specificity (95% CI, 21.2-86.3%). Patients with short versus long ttCTsd did not differ in terms of mortality (16.1%, n = 5 vs 9.7, n = 3; p = 0.449), length of hospital stay (median 16 d, IQR 9 d 12 h-23 d 18 h vs median 13 d, IQR 10 d 00 h-24 d 00 h; p = 0.863), or duration of intensive care (median 3d 12 h, IQR 2 d 6 h-7 d 18 h vs median 5d, IQR 2 d-11 d; p = 0.800). CONCLUSIONS: Our findings show a high sensitivity of CT in ED patients with sepsis, confirming its relevance in guiding treatment decisions. The low specificity suggests that a negative CT requires further ancillary diagnostic tests for focus detection. The timing of CT did not affect morbidity or mortality outcomes. CLINICAL RELEVANCE STATEMENT: In patients with sepsis who present to the ED, CT can be used to identify infectious foci on the basis of clinical suspicion, but should not be used as a rule-out test. Scientific evidence for the optimal timing of CT beyond clinical decision-making is currently missing, as potential mortality benefits are clouded by differences in clinical severity at the time of ED presentation. KEY POINTS: • In patients with sepsis who present to the ED, CT for focus identification has a high sensitivity and can thereby be valuable for patient management. • As the specificity is considerably lower, a thorough microbiological assessment is important in these cases. • The timing of CT did not affect morbidity and mortality outcomes in this study, which might be due to variability in clinical severity at the time of ED presentation.

Biomarkers Improve Diagnostics of Sepsis in Adult Patients With Suspected Organ Dysfunction Based on the Quick Sepsis-Related Organ Failure Assessment (qSOFA) Score in the Emergency Department.

OBJECTIVES: Consensus regarding biomarkers for detection of infection-related organ dysfunction in the emergency department is lacking. We aimed to identify and validate biomarkers that could improve risk prediction for overt or incipient organ dysfunction when added to quick Sepsis-related Organ Failure Assessment (qSOFA) as a screening tool. DESIGN: In a large prospective multicenter cohort of adult patients presenting to the emergency department with a qSOFA score greater than or equal to 1, admission plasma levels of C-reactive protein, procalcitonin, adrenomedullin (either bioavailable adrenomedullin or midregional fragment of proadrenomedullin), proenkephalin, and dipeptidyl peptidase 3 were assessed. Least absolute shrinkage and selection operator regression was applied to assess the impact of these biomarkers alone or in combination to detect the primary endpoint of prediction of sepsis within 96 hours of admission. SETTING: Three tertiary emergency departments at German University Hospitals (Jena University Hospital and two sites of the Charité University Hospital, Berlin). PATIENTS: One thousand four hundred seventy-seven adult patients presenting with suspected organ dysfunction based on qSOFA score greater than or equal to 1. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The cohort was of moderate severity with 81% presenting with qSOFA = 1; 29.2% of these patients developed sepsis. Procalcitonin outperformed all other biomarkers regarding the primary endpoint (area under the curve for receiver operating characteristic [AUC-ROC], 0.86 [0.79-0.93]). Adding other biomarkers failed to further improve the AUC-ROC for the primary endpoint; however, they improved the model regarding several secondary endpoints, such as mortality, need for vasopressors, or dialysis. Addition of procalcitonin with a cutoff level of 0.25 ng/mL improved net (re)classification by 35.2% compared with qSOFA alone, with positive and negative predictive values of 60.7% and 88.7%, respectively. CONCLUSIONS: Biomarkers of infection and organ dysfunction, most notably procalcitonin, substantially improve early prediction of sepsis with added value to qSOFA alone as a simple screening tool on emergency department admission.

The new ESC acute coronary syndrome guideline and its impact in the CPU and emergency department setting.

The new guideline on acute coronary syndrome (ACS) of the European Society of Cardiology (ESC) replaces two separate guidelines on ST-elevation myocardial infarction (STEMI) and non-ST-elevation (NSTE) ACS. This change of paradigm reflects the experts view that the ACS is a continuum, starting with unstable angina and ending in cardiogenic shock or cardiac arrest due to severe myocardial ischemia. Secondary, partly non-atherosclerotic-caused myocardial infarctions ("type 2") are not integrated in this concept.With respect to acute care in the setting of emergency medicine and the chest pain unit structures, the following new aspects have to be taken into account:1. New procedural approach as "think A.C.S." meaning "abnormal ECG," "clinical context," and "stable patient"2. New recommendation regarding a holistic approach for frail patients3. Revised recommendations regarding imaging and timing of invasive strategy in suspected NSTE-ACS4. Revised recommendations for antiplatelet and anticoagulant therapy in STEMI5. Revised recommendations for cardiac arrest and out-of-hospital cardiac arrest6. Revised recommendations for in-hospital management (starting in the CPU/ED) and ACS comorbid conditionsIn summary, the changes are mostly gradual and are not based on extensive new evidence, but more on focused and healthcare process-related considerations.

Effects of Different SARS-CoV-2 Testing Strategies in the Emergency Department on Length of Stay and Clinical Outcomes: A Randomised Controlled Trial.

The turn-around-time (TAT) of diagnostic and screening measures such as testing for SARS-CoV-2 can affect a patient's length of stay (LOS) in the hospital as well as the emergency department (ED). This, in turn, can affect clinical outcomes. Therefore, a reliable and time-efficient SARS-CoV-2 testing strategy is necessary, especially in the ED. In this randomised controlled trial, n = 598 ED patients presenting to one of three university hospital EDs in Berlin, Germany, and needing hospitalisation were randomly assigned to two intervention groups and one control group. Accordingly, different SARS-CoV-2 testing strategies were implemented: rapid antigen and point-of-care (POC) reverse transcription polymerase chain reaction (rtPCR) testing with the Roche cobas® Liat® (LIAT) (group one n = 198), POC rtPCR testing with the LIAT (group two n = 197), and central laboratory rtPCR testing (group three, control group n = 203). The median LOS in the hospital as an inpatient across the groups was 7 days. Patients' LOS in the ED of more than seven hours did not differ significantly, and furthermore, no significant differences were observed regarding clinical outcomes such as intensive care unit stay or death. The rapid and POC test strategies had a significantly (p < 0.01) shorter median TAT (group one 00:48 h, group two 00:21 h) than the regular central laboratory rtPCR test (group three 06:26 h). However, fast SARS-CoV-2 testing strategies did not reduce ED or inpatient LOS significantly in less urgent ED admissions. Testing strategies should be adjusted to the current circumstances including crowding, SARS-CoV-2 incidences, and patient cohort. This trial is registered with DRKS00023117.

[Black box: Attenders with psychosocial needs in the emergency department]. / Blackbox: Psychosoziale Fälle in der Notaufnahme.

OBJECTIVES: The aims are (a) assessment of the prevalence of psychosocial emergencies in the emergency department (ED), (b) determination of the proportion of cases not coded as diagnosis (unreported cases), and (c) characterization of identified patients. METHODS: In a retrospective study, psychosocial emergencies in one week were identified from routine documentation of the central ED of the Charité - Universitätsmedizin Berlin, Charité Campus Mitte (CCM). After exclusion of planned admitted cases, 862 patients were included in the study. The identified psychosocial emergencies were descriptively analyzed with regard to their sociodemographic and clinical characteristics and compared with other emergencies. RESULTS: The prevalence of psychosocial emergencies in the reported period was 11.9% (n = 103). A large proportion of psychosocial emergencies were not coded (35.9%) or not fully coded (20.4%) as an ICD diagnosis (unreported cases). There was a statistically relevant difference in gender distribution with a significantly higher proportion of males among psychosocial emergencies (70.9%) compared to other emergencies (50.7%; p < 0.0001). The two most common treatment causes among psychosocial emergencies were substance abuse (66.0%) and homelessness (20.4%). CONCLUSIONS: This study shows a relevant proportion of psychosocial emergencies among all treatments in ED routine data and a high proportion of cases not captured in the coded diagnoses. EDs thus represent an important point of contact for vulnerable patient groups but standardized screening and identification are still lacking.

Management of syncope in the Emergency Department: a European prospective cohort study (SEED).

BACKGROUND AND IMPORTANCE: In 2018, the European Society of Cardiology (ESC) produced syncope guidelines that for the first-time incorporated Emergency Department (ED) management. However, very little is known about the characteristics and management of this patient group across Europe. OBJECTIVES: To examine the prevalence, clinical presentation, assessment, investigation (ECG and laboratory testing), management and ESC and Canadian Syncope Risk Score (CSRS) categories of adult European ED patients presenting with transient loss of consciousness (TLOC, undifferentiated or suspected syncope). DESIGN: Prospective, multicentre, observational cohort study. SETTINGS AND PARTICIPANTS: Adults (≥18 years) presenting to European EDs with TLOC, either undifferentiated or thought to be of syncopal origin. MAIN RESULTS: Between 00:01 Monday, September 12th to 23:59 Sunday 25 September 2022, 952 patients presenting to 41 EDs in 14 European countries were enrolled from 98 301 ED presentations (n = 40 sites). Mean age (SD) was 60.7 (21.7) years and 487 participants were male (51.2%). In total, 379 (39.8%) were admitted to hospital and 573 (60.2%) were discharged. 271 (28.5%) were admitted to an observation unit first with 143 (52.8%) of these being admitted from this. 717 (75.3%) participants were high-risk according to ESC guidelines (and not suitable for discharge from ED) and 235 (24.7%) were low risk. Admission rate increased with increasing ESC high-risk factors; 1 ESC high-risk factor; n = 259 (27.2%, admission rate=34.7%), 2; 189 (19.9%; 38.6%), 3; 106 (11.1%, 54.7%, 4; 62 (6.5%, 60.4%), 5; 48 (5.0%, 67.9%, 6+; 53 (5.6%, 67.9%). Furthermore, 660 (69.3%), 250 (26.3%), 34 (3.5%) and 8 (0.8%) participants had a low, medium, high, and very high CSRS respectively with respective admission rates of 31.4%, 56.0%, 76.5% and 75.0%. Admission rates (19.3-88.9%), use of an observation/decision unit (0-100%), and percentage high-risk (64.8-88.9%) varies widely between countries. CONCLUSION: This European prospective cohort study reported a 1% prevalence of syncope in the ED. 4 in 10 patients are admitted to hospital although there is wide variation between country in syncope management. Three-quarters of patients have ESC high-risk characteristics with admission percentage rising with increasing ESC high-risk factors.

Oral anticoagulation in heart failure complicated by atrial fibrillation: A nationwide routine data study.

BACKGROUND: This nationwide routine data analysis evaluates if oral anticoagulant (OAC) use in patients with heart failure (HF) and atrial fibrillation (AF) leads to a lower mortality and reduced readmission rate. Superiority of new oral anticoagulants (NOACs), compared to vitamin K antagonists (VKA), was analyzed for these endpoints. METHODS: Anonymous data of patients with a health insurance at the Allgemeine Ortskrankenkasse and a claims record for hospitalization with the main diagnosis of HF and secondary diagnosis of AF (2017-2019) were included. A hospital stay in the previous year was an exclusion criterion. Mortality and readmission for all-cause and stroke/intracranial bleeding (ICB) were analyzed 91-365 days after the index hospitalization. Kaplan-Meier survival curves and multivariable Cox regression models were used to evaluate the impact of medication on outcome. RESULTS: 180,316 cases were included [81 years (IQR 76-86), 55.6% female, CHA2DS2-VASc score ≥ 2 (96.81%)]. In 80.6%, OACs were prescribed (VKA: 21.7%; direct factor Xa inhibitors (FXaI): 60.0%; direct thrombin inhibitors (DTI): 3.4%; with multiple prescriptions per patient included). Mortality rate was 19.1%, readmission rate was 29.9% and stroke/ICB occurred in 1.9%. Risk of death was lower with any OAC (HR 0.77, 95% CI [0.75-0.79]) but without significant differences in OAC type (VKA: HR 0.73, [0.71-0.76]; FXaI: HR 0.77, [0.75-0.78]; DTI: HR 0.71, [0.66-0.77]). The total readmission rate (HR 0.97, [0.94 to 0.99]) and readmission for stroke/ICB (HR 0.71, [0.65-0.77]) was lower with OAC. CONCLUSIONS: Nationwide data confirm a reduction in mortality and readmission rate in HF-AF patients taking OACs, without NOAC superiority.

Common Complications and Cardiopulmonary Resuscitation in Patients with Left Ventricular Assist Devices: A Narrative Review.

Heart failure remains a major global burden regarding patients' morbidity and mortality and health system organization, logistics, and costs. Despite continual advances in pharmacological and resynchronization device therapy, it is currently well accepted that heart transplantation and mechanical circulatory support represent a cornerstone in the management of advanced forms of this disease, with the latter becoming an increasingly accepted treatment modality due to the ongoing shortage of available donor hearts in an ever-increasing pool of patients. Mechanical circulatory support strategies have seen tremendous advances in recent years, especially in terms of pump technology improvements, indication for use, surgical techniques for device implantation, exchange and explantation, and postoperative patient management, but not in the field of treatment of critically ill patients and those undergoing cardiac arrest. This contemporary review aims to summarize the collected knowledge of this topic with an emphasis on complications in patients with left ventricular assist devices, their treatment, and establishing a clear-cut algorithm and the latest recommendations regarding out-of-hospital or emergency department management of cardiac arrest in this patient population.

K6-linked ubiquitylation marks formaldehyde-induced RNA-protein crosslinks for resolution.

Reactive aldehydes are produced by normal cellular metabolism or after alcohol consumption, and they accumulate in human tissues if aldehyde clearance mechanisms are impaired. Their toxicity has been attributed to the damage they cause to genomic DNA and the subsequent inhibition of transcription and replication. However, whether interference with other cellular processes contributes to aldehyde toxicity has not been investigated. We demonstrate that formaldehyde induces RNA-protein crosslinks (RPCs) that stall the ribosome and inhibit translation in human cells. RPCs in the messenger RNA (mRNA) are recognized by the translating ribosomes, marked by atypical K6-linked ubiquitylation catalyzed by the RING-in-between-RING (RBR) E3 ligase RNF14, and subsequently resolved by the ubiquitin- and ATP-dependent unfoldase VCP. Our findings uncover an evolutionary conserved formaldehyde-induced stress response pathway that protects cells against RPC accumulation in the cytoplasm, and they suggest that RPCs contribute to the cellular and tissue toxicity of reactive aldehydes.

Patients pathways before and after treatments in emergency departments: A retrospective analysis of secondary data in Germany.

Increasing emergency department (ED) utilization induces considerable pressure on ED staff and organization in Germany. Reasons for certain ED attendances are seen partly in insufficient continuity of care outside of hospitals. To explore the health care patterns before and after an ED attendance in Germany, we used claims data from nine statutory health insurance funds, covering around 25 % of statutory health insurees (1). We descriptively analyzed ED attendances for adult patients in 2016 according to their sociodemographic characteristics and diagnoses (2). Based on the ED attendance as initial event, we investigated health care provider utilization 180 days before and after the respective ED treatment and are presented by means of Sankey diagrams. In total, 4,757,536 ED cases of 3,164,343 insured individuals were analyzed. Back pain was the most frequent diagnosis in outpatient ED cases (5.0 %), and 80.2 % of the patients visited primary care physicians or specialists 180 days before and 78.8 % 180 days after ED treatment. Among inpatient cases, heart failure (4.6 %) was the leading diagnosis and 74.6 % used primary care physicians or specialists 180 days before and 65.1 % 180 days after ED treatment. The ED re-attendance slightly increased for back pain (4.9 % to 7.9 %) and decreased for heart failure (13.4 % to 12.6 %).

Modelling variations of emergency attendances using data on community mobility, climate and air pollution.

Air pollution is associated with morbidity and mortality worldwide. We investigated the impact of improved air quality during the economic lockdown during the SARS-Cov2 pandemic on emergency room (ER) admissions in Germany. Weekly aggregated clinical data from 33 hospitals were collected in 2019 and 2020. Hourly concentrations of nitrogen and sulfur dioxide (NO2, SO2), carbon and nitrogen monoxide (CO, NO), ozone (O3) and particulate matter (PM10, PM2.5) measured by ground stations and meteorological data (ERA5) were selected from a 30 km radius around the corresponding ED. Mobility was assessed using aggregated cell phone data. A linear stepwise multiple regression model was used to predict ER admissions. The average weekly emergency numbers vary from 200 to over 1600 cases (total n = 2,216,217). The mean maximum decrease in caseload was 5 standard deviations. With the enforcement of the shutdown in March, the mobility index dropped by almost 40%. Of all air pollutants, NO2 has the strongest correlation with ER visits when averaged across all departments. Using a linear stepwise multiple regression model, 63% of the variation in ER visits is explained by the mobility index, but still 6% of the variation is explained by air quality and climate change.

An extended Tudor domain within Vreteno interconnects Gtsf1L and Ago3 for piRNA biogenesis in Bombyx mori.

Piwi-interacting RNAs (piRNAs) direct PIWI proteins to transposons to silence them, thereby preserving genome integrity and fertility. The piRNA population can be expanded in the ping-pong amplification loop. Within this process, piRNA-associated PIWI proteins (piRISC) enter a membraneless organelle called nuage to cleave their target RNA, which is stimulated by Gtsf proteins. The resulting cleavage product gets loaded into an empty PIWI protein to form a new piRISC complex. However, for piRNA amplification to occur, the new RNA substrates, Gtsf-piRISC, and empty PIWI proteins have to be in physical proximity. In this study, we show that in silkworm cells, the Gtsf1 homolog BmGtsf1L binds to piRNA-loaded BmAgo3 and localizes to granules positive for BmAgo3 and BmVreteno. Biochemical assays further revealed that conserved residues within the unstructured tail of BmGtsf1L directly interact with BmVreteno. Using a combination of AlphaFold modeling, atomistic molecular dynamics simulations, and in vitro assays, we identified a novel binding interface on the BmVreteno-eTudor domain, which is required for BmGtsf1L binding. Our study reveals that a single eTudor domain within BmVreteno provides two binding interfaces and thereby interconnects piRNA-loaded BmAgo3 and BmGtsf1L.

The sex-specific factor SOA controls dosage compensation in Anopheles mosquitoes.

The Anopheles mosquito is one of thousands of species in which sex differences play a central part in their biology, as only females need a blood meal to produce eggs. Sex differentiation is regulated by sex chromosomes, but their presence creates a dosage imbalance between males (XY) and females (XX). Dosage compensation (DC) can re-equilibrate the expression of sex chromosomal genes. However, because DC mechanisms have only been fully characterized in a few model organisms, key questions about its evolutionary diversity and functional necessity remain unresolved1. Here we report the discovery of a previously uncharacterized gene (sex chromosome activation (SOA)) as a master regulator of DC in the malaria mosquito Anopheles gambiae. Sex-specific alternative splicing prevents functional SOA protein expression in females. The male isoform encodes a DNA-binding protein that binds the promoters of active X chromosomal genes. Expressing male SOA is sufficient to induce DC in female cells. Male mosquitoes lacking SOA or female mosquitoes ectopically expressing the male isoform exhibit X chromosome misregulation, which is compatible with viability but causes developmental delay. Thus, our molecular analyses of a DC master regulator in a non-model organism elucidates the evolutionary steps that lead to the establishment of a chromosome-specific fine-tuning mechanism.