bluuebunny/crossref_metadata_2025 huggingface dataset:
Bystander interventions in out-of-hospital cardiac arrest according to geographical area type
Authors: Christensen N , Folke F , Juul Joergensen A , Kollander Jakobsen L , Samsoee Kjoelbye J , Andelius L , Tofte Gregers M , Bundgaard Ringgren K , Torp-Pedersen C , Malta Hansen C
Published: May 2022

Funding Acknowledgements

Type of funding sources: Foundation. Main funding source(s): TrygFonden

Introduction

Bystander interventions and survival after out-of-hospital cardiac arrest (OHCA) have increased remarkably in Denmark over the last years. Even though 75% of all OHCA occur in residential areas, most interventions to increase bystander interventions have focused on public places. This study assessed bystander interventions (cardiopulmonary resuscitation [CPR] and defibrillation) according to area type.

Methods

We included bystander witnessed OHCAs from the Danish Cardiac Arrest Registry (2016-2019) with a known geographical location. Urban Atlas is an international data base covering 40% of Denmark, which uses satellite images to divide areas into different area types. In this study, Urban Atlas was used to identify and geocode OHCAs within the following subgroups: high density residential areas (defined as average degree of soil sealing >50%), low density residential areas (average degree of soil sealing <50%), public and industrial sites, nature, sport and leisure facilities, transportation (e.g. airport and railway stations), and fast transit roads.

Results

A total of 5,180 bystander witnessed OHCA were covered by Urban Atlas and included. The proportion of bystander interventions was lowest in residential areas where most OHCAs occurred (Figure 1). The proportion of bystander interventions was highest in sport and leisure areas and transportation sites. The proportion of bystander defibrillation increased 5-fold in transportation sites and 3-fold in sports and leisure sites compared with residential areas.

Conclusion

Patients with OHCA in transportation areas and sports and leisure areas were substantially more likely to receive bystander CPR and defibrillation, highlighting the success of initiatives to increase bystander interventions in public areas. Bystander defibrillation was lowest in residential areas supporting further efforts, such as smartphone activated volunteer responder activation, to improve bystander defibrillation in residential areas.
Mortality risk in cardiogenic shock: Head to head comparison CardShock vs IABP score depending on aetiology, the Shock CAT study
Authors: Garcia-Garcia C , Lopez T , Sanz E , Sanchez-Salado JC , Aboal J , Tomas C , Baneras J , Sionis A , Andrea R , Perez-Rodriguez M , Ruiz M , Pastor P , Buera I , Cediel G , Rueda F
Published: May 2022

Funding Acknowledgements

Type of funding sources: None.

Background

Mortality in cardiogenic shock (CS) remains very high. Several risk scores have been purposed to early stratification. The aetiology of CS could influence in the usefulness of different risk scores.

Purpose

The aim is to investigate in-hospital prognosis and mortality risk in CS patients comparing the prognostic accuracy of CardShock and IABP scores in a Mediterranean cohort depending on the CS aetiology.

Method

Shock CAT study was a multicentre, prospective, observational study conducted between December 2018 and December 2019 in eight public University hospitals in Catalonia (Spain), including CS patients due to acute coronary syndrome (ACS) and other aetiologies. Data on clinical presentation, biomarkers, management, including mechanical assistance support were analyzed. Cardshock and IABP score have been compared to assess 90-days mortality risk in a Mediterranean cohort.

Results

A total of 382 CS patients were included, mean age was 65.3 (SD 13.9) years and 75.1% were men. The most common cause of CS was ACS (61%, n=233); of them, 77.6% were STEMI, 9% developed mechanical complications and 19.4% primary ventricular fibrillation. STEMI patients were reperfused in 84.7% of cases, all with primary angioplasty. Main non-ACS aetiologies were severe acute heart failure, malignant arrhythmias and myocarditis. Mechanical assistance device was implanted in one third of patients (n=119), mainly intraaortic balloon pump (26.1%), ECMO in 7.8% and Impella CP in 4.5%. Average Cardshock score was 4.3 (SD 1.74) and mean IABP score was 2.2 (SD 1.61). In-hospital mortality was 33% (126 patients) and 90-days mortality was 37.3% (141 patients). Receiver-operating characteristic (ROC) curves demonstrated that IABP shock score had superior prognostic power for predicting 90-days mortality when compared with Cardshock score (area under the curve 0.72 vs 0.66) respectively, p=0.042; Figure 1. Although this superiority only was reached in ACS patients (area under the curve -AUC- 0.74 vs 0.66) respectively, p=0.047; because both scores were similar in non-ACS (AUC 0.64 vs 0.62, p=0.693), Figure 2.

Conclusions

Even though invasive management with STEMI reperfusion and mechanical assistance devices, cardiogenic shock in-hospital mortality remains 33% in a contemporary Mediterranean cohort. In this population, IABP shock score provided better 90-days mortality risk prediction than CardShock score, mainly in CS sue to ACS.
Soluble neprilysin and survival in critically ill patients
Authors: Lenz M , Krychtiuk KA , Brekalo M , Draxler DF , Pavo N , Hengstenberg C , Huber K , Huelsmann M , Heinz G , Wojta J , Speidl WS
Published: May 2022

Funding Acknowledgements

Type of funding sources: None.

Background

Critically ill patients admitted to an intensive care unit (ICU) exhibit a high mortality rate irrespective of the initial cause of hospitalization. Neprilysin, a neutral endopeptidase degrading an array of vasoactive peptides became a drug target within the treatment of heart failure with reduced ejection fraction.The aim of this study was to analyze whether circulating levels of neprilysin at ICU admission are associated with 30-day mortality.

Methods

In this single-center prospective observational study, 222 consecutive patients admitted to a tertiary ICU at a university hospital were included. Blood was drawn at admission and soluble neprilysin levels were measured using ELISA.

Results

In the total cohort, Soluble neprilysin levels did not differ according to survival status after 30 days as well as type of admission. However, in patients after surgery or heart valve intervention, 30-day survivors exhibited significantly lower circulating neprilysin levels as compared to those who died within 30 days (660.2, IQR: 156.4 – 2512.5 pg/ml versus 6532.6, IQR: 1840.1 – 10000.0 pg/ml; p=0.02). Soluble neprilysin predicted mortality independently from age, gender, and commonly used scores of risk-prediction (EuroSCORE II, STS-score, and SAPS II score). Additionally, soluble neprilysin was markedly elevated in patients with sepsis and septic shock (p<0.05).

Conclusion

At the time of ICU-admission, circulating levels of neprilysin independently predicted 30-day mortality in patients following cardiac surgery or heart valve intervention, but not in critically ill medical patients. Furthermore, patients suffering from sepsis and septic shock displayed significantly increased circulating neprilysin levels.
Prognostic impact of anemia in acute coronary syndrome patients
Authors: Carvalho P , Monteiro J , Carvalho C , Bernardo M , Fontes P , Mateus P , Goncalves F , Moreira I
Published: May 2022

Funding Acknowledgements

Type of funding sources: None.

Introduction

Anemia commonly accompanies acute coronary syndromes (ACS) and is associated with worst outcomes. Over the last decade several trials have investigated the prognostic impact of hemoglobin (Hb) levels in the context of acute coronary syndrome (ACS), both in the short-term, during hospitalization, and in the long-term, albeit mainly up to three months, with only a few trials assessing one-year outcomes.

Methods

This was a retrospective study of ACS patients admitted to a single center between October/2011 and September/2018, in whom Hb level was evaluated on admission. Anemia was defined as defined as Hb ≤ 13g/dL for males and Hb ≤ 12g/dl for females. Baseline characteristics, management, and outcomes were compared between patients with and without anemia. The primary endpoint, MACE, was a composite of acute coronary syndrome, stroke and global death events. The secondary endpoint was cardiovascular death.

Results

A total of 578 patients were selected, with a mean age of 66.7±13.1 years, 74.9% were male, 42.6% had a ST-Elevation Myocardial Infarction and 18.9% met criteria for anemia. These patients had more comorbidities: arterial hypertension (78.0% vs 60.6%; p=0.001), diabetes mellitus (25.7% vs 50.5%, p=0.001), peripheral artery disease (3.9% vs 10.1%, p=0.01) and were older (mean age 64.8±13.1 vs 72.1±11.0 years, p<0.001). The non-anemic group had a higher percentage of smokers and, during hospitalization, was more often submitted to percutaneous coronary angioplasty. Antithrombotic therapy given during hospitalization and on discharge was similar in both groups.

During a median follow-up of 41 months (IQR: 20-59), 91 patients (15.7%) died and 104 (18%) had a MACE event. In a multivariate regression analysis, after adjusting for possible confounders, anemia was an independent predictor of MACE events (HR 1.64, 95% CI: 1.07-2.50) and cardiovascular death (HR 2.24, 95% CI: 1.26-3.96).

Conclusion

Anemia is highly prevalent in the ACS setting and the presence of anemia was independently associated with worse outcomes, particularly mortality.
FGF-23 as a predictor of 6-month outcome and response to therapy in acute heart failure
Authors: Plonka J , Olejnik A , Wezyk-Wylegala N , Rzepiela L , Dabrowska K , Klus A , Gawrylak- Dryja E , Bil-Lula I , Gierlotka M
Published: May 2022

Funding Acknowledgements

Type of funding sources: Public grant(s) – National budget only. Main funding source(s): This work was supported by a grant from the Institute of Medical Sciences, Univeristy of Opole, Poland

Background

FGF-23 is a well-known marker for phosphate metabolism and independent risk marker for cardiovascular mortality. FGF-23 can stimulate pro-fibrotic factors in myocytes and finally promote cardiac fibrosis. There is also evidence that FGF-23 levels can predict the response to the therapies in acute heart failure (AHF) patients. The aim of the study was to assess whether FGF-23 level change during an episode of AHF as well as its long-term prognostic utility in population of AHF patients. Additionally, we also aimed to evaluate correlations of FGF-23 levels with the response to therapy.

Methods

We analysed 112 consecutive patients admitted to ICCU between June 2019 and January 2021 due to high-risk AHF. Guidelines guided therapy of heart failure was introduced. Blood samples were collected on admission, at discharge as well as at the 30-day. Patients were then followed-up for all-cause mortality and rehospitalisations due to heart failure.

Results

Patients (N=112; median age 68 years, 75% men, median left ventricular ejection fraction 30% [IQR 20-38%]) had median admission levels of FGF-23 = 1278 pg/ml [283-4429], Klotho protein = 670 pg/ml [501-851], NT-proBNP = 5361 ng/l [3019-13182], and GDF-15 = 4582 pg/ml [3028-9081]. FGF-23 decreased by 70% from admission to discharge (P<0.001) and then remain relatively stable up to 30-day. During median 478 days follow-up 40 patients (36%) died or were hospitalised due to heart failure - they were older, more often with new onset AHF, of ischaemic aetiology and diabetics. Patients with high levels of FGF-23 (in the 4th quartile, both on admission or at discharge) had higher mortality (Figure A and B). Model combining FGF-23, Klotho protein, NT-pro BNP, and GDF-15 adjusted for age and sex showed satisfactory predictive value of unfavourable prognosis in ROC analysis (Figure C).

Conclusion

Levels of FGF-23 on admission in patients with AHF are significantly elevated and lowers during appropriate effective therapy what indicates the utility of FGF-23 as a typical biomarker. High values of FGF-23 are associated with higher 6-month mortality. Reduction of the FGF-23 during hospitalization can serve as a marker of AHF compensation, thus FGF-23 could be a valuable tool for assessing response to treatment.
The impact of COVID-19 pandemic on type A aortic dissection care
Authors: Manla Y , Bhatnagar G , Aljabery Y , Kakar V , Bajwa G , Sanger S , Almahmeed W , Bafadel A , Khan U , Ahmed W , Gobolos L
Published: May 2022

Funding Acknowledgements

Type of funding sources: None.

Introduction

COVID-19 created a challenging situation for cardiac surgery and associated acute care programs around the world. While non-urgent cases might be postponed, operating on life-threatening conditions, including type A aortic dissection (TAAD), must be sustained despite the ongoing pandemic. Therefore, we investigated the impact of the COVID-19 pandemic on our urgent aortic program.

Methods

36 individuals presenting with TAAD in a single centre were analysed from the pre-pandemic period (2019, n=16) and the pandemic era (2020, n=20). Retrospective data review was conducted on patient characteristics, TAAD presenting symptoms, operative techniques, postoperative outcomes and length of stay. A comparison was made between both eras applying appropriate testing methods, and a p-value <0.05 was considered statistically significant.

Results

A 25% increase in TAAD referrals occurred during the pandemic era. Patients were featured by younger age of presentation in contrast to Western data (pre-pandemic group: 47.6 ± 18.7, and the pandemic group: 50.6 ± 16.2 years, p=0.6) but showed similar male predominance (4:1) in both groups. There was no statistical difference in baseline comorbidities between the groups. Length of hospital and intensive care unit stays were comparable between both groups. Low rates of postoperative complications were registered in both groups with no significant between-group difference.

Conclusion

Emergent surgical management remains essential in patients with TAAD regardless of the pandemic. Furthermore, temporary structural departmental re-configuration and optimal personal protective equipment utilisation warrant maintained satisfactory outcomes in such critical healthcare scenarios.
Patient mortality dynamics in intensive cardiac care: single department experience
Authors: Serpytis P , Striogaite G
Published: May 2022

Funding Acknowledgements

Type of funding sources: None.

Introduction

Intensive cardiac care is celebrating 60 years anniversary since description of a first coronary care unit by Dr. Desmond Julian in 1961. The establishment of such units was a breakthrough in diagnosis, treatment, and the development of critical care medicine. For the last 20 years our intensive cardiac care department has been a leading centre in its field in Lithuania, admitting over 4000 patients each year. Assessment of mortality in intensive cardiac care units is one of the main indicators of quality of healthcare provided.

Purpose

To examine the dynamics of mortality of patients treated in our intensive cardiac care department in 2000-2020.

Methods

The de-identified data set of patients who were treated in our intensive cardiac care department in 2000-2020 was gathered from medical records retrospectively. The set consisted of total number of patients treated in the department, the number of patients treated for ST-elevation myocardial infarction (STEMI), the number of patients treated for non-ST-elevation myocardial infarction (NSTEMI), the number of patients treated for pulmonary embolism (PE), and the number of patients who died in each of these groups. The analysis of collected data was performed using MS Excel, IBM SPSS Statistics 26.0 programs. Paired Student’s t-test and Chi-square test were applied. Results were considered statistically significant at p<0.05.

Results

The analysis population comprised 65583 patients who were treated between years 2000 and 2020 of which 15912 (24.26%) were treated for STEMI, 8609 (13.13%) for NSTEMI, and 1460 (2.23%) for PE. The overall patient mortality in 2000-2020 was 4.76%, patient mortality treated for STEMI was 8.07%, treated for NSTEMI – 4.88%, and treated for PE – 15.74%. Mortality was found to be significantly higher in the STEMI group than in the NSTEMI group (8.07% vs. 4.88%; p<0.001). Mortality in patients treated for STEMI in 2000-2005, 2006-2010, 2011-2015, and 2016-2020 were also found to be statistically significantly different (p=0.001) and consistently decreasing (9.2% vs. 8.0% vs. 7.3% vs. 7.0%). There were no statistically significant differences in the mortality of patients treated for NSTEMI and PE at different time periods (p>0.05) as observed in the STEMI group. Assessing all patients treated in 2000-2020, it was found that statistically significantly more patients died in 2016-2020 (5.2%) than in 2000-2015 (4.6%; p=0.01).

Conclusions

The highest mortality in patients treated in our intensive cardiac care department in 2000-2020 was observed in the group of patients treated for pulmonary embolism. A consistent decrease in mortality was observed in patients treated for ST-elevation myocardial infarction. The average total patient mortality rate in 2016-2020 was found to be statistically significantly higher than in the previous years.
Effect of modular cardiac rehabilitation on quality of life, exercise tolerance and psychological status in patients with myocardial infarction and COVID-19 infection
Authors: Bolatbekov BA , Trusheva KS , Baibolova MK , Kudaiberdieva GZ , Bolatbekova ZS , Kuramys S , Baimagambetov AK
Published: May 2022

Funding Acknowledgements

Type of funding sources: None.

Introduction

COVID-19 worsens the prognosis in patients with cardiovascular diseases, including myocardial infarction (MI). In connection with this, cardiac rehabilitation (CR) programs must be adapted for this category of post-infarction patients. Little is known on effect of CR on quality of life and anxiety and depression in patients with MI and COVID-19.

Objective

The aim of the study was to evaluate the use of a modular CR program on quality of life, excercise tolerance, anxiety and depression in post-infarction patients recovered from COVID-19 infection during a pandemic.

Methods

Overall, 86 patients with previous COVID-19 infection were included in this prospective longitudinal study. We evaluated the parameters of quality of life according to the Seattle questionnaire, exercise tolerance according to the six-minute walk test, and the depression and anxiety rating scale (HADS) before and after applying the modular CR program.

Results

According to the computed tomography (CT) classification, the severity class of lung lesions was: grade CT1 -23%, CT2-48%, CT3-23% and CT4-6%. When assessing the quality of life before the start of the modular CR -74% complained of episodic attacks of angina pectoris, while at the end of the CR, only 5% of had chest pain (p<0.05). Tolerance to physical activity according to the 6-minute walk test improved significantly from 245 ± 3.6 meters before CR to 355 ± 5.1 meters in dynamics (p=0.012). The depression and anxiety reduced significantly (p=0.0023) after CR: before the onset of modular CR 55% of patients were depressed in and 69% exhibited anxiety; after CR, depression in 10.4% of patients had depression and 7% - anxiety.

Conclusions

The use of a modular CR program in postinfarction patients with COVID-19 improves the quality of life, exercise tolearnce and psychological status.
Kounis syndrome leading to triple-vessel coronary artery ischaemia due to simultaneous coronary spasm, plaque erosion, and multiple stent thrombosis: a case report
Authors: Yamamoto Hiroyuki , Otake Hiromasa , Tanimura Kosuke , Hirata Ken-ichi
Published: May 2022

Background

Kounis syndrome (KS) is an acute coronary syndrome (ACS) induced by allergic reactions. Currently, there are three variants of KS based on the mechanism and onset of ACS. We report a rare case of KS, wherein ACS was caused by all KS variants.

Case summary

A 68-year-old man with a history of percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction of the left anterior descending artery 16 days ago underwent a staged PCI for the mid-left circumflex artery (LCx) stenosis under optical coherence tomography (OCT) guidance using low-molecular-weight dextran (LMWD). During OCT examination, the LMWD induced an anaphylactic reaction. The patient was immediately administered medications to manage the anaphylaxis; however, he complained of chest discomfort. Coronary angiography and subsequent intravascular ultrasound revealed a newly developed coronary thrombus in the proximal LCx. Furthermore, coronary spasm or multiple stent thromboses occurred sequentially in all coronary arteries, resulting in triple-vessel coronary artery ischaemia. Balloon angioplasty was performed under intra-aortic balloon pumping, which could rescue the patient. The patient was discharged without any complications 11 days post-KS, under a 7-day anti-histamine regimen. No further cardiovascular events had occurred by 1-year follow-up.

Discussion

This case documented the clinical course of KS caused by LMWD, wherein all KS variants occurred sequentially. Early recognition of KS and appropriate management with anaphylaxis medication and balloon angioplasty under mechanical circulatory support effectively prevent vascular morbidity. Interventionalists should be aware of this rare and serious complication of PCI.
Iatrogenic pacemaker-induced ventricular arrhythmia: a case report
Authors: Pooranachandran Vivetha , Hodson Tim , Nicolson Will , Ng Ghulam Andre
Published: May 2022

Background

Minimizing right ventricular (RV) pacing to reduce the progression of heart failure is an established practice. Proprietary algorithms to reduce unnecessary RV pacing have been incorporated into both simple and complex cardiac pacemaker devices, for reducing the possibility of heart failure and arrhythmias.

Case summary

We present a case of a 43-year-old male implanted with a dual-chamber primary prevention implantable cardioverter-defibrillator (AUTOGEN EL, Boston Scientific) for sudden cardiac death. At the time of implant, the patient had hypertrophic cardiomyopathy with mild left ventricular (LV) systolic impairment, and sinus rhythm with intact atrioventricular (AV) conduction. The patient developed progression of his disease with symptoms (dyspnoea) and LV impairment. This led to a decision to activate the minimal RV pacing algorithm (RYTHMIQ™). A deterioration in AV conduction caused intrinsic ventricular beats to fall in the atrial blanking period, and subsequent VVI backup pacing resulted in R on T pacing. This induced ventricular arrhythmia. RYTHMIQ™ was subsequently deactivated, and the patient has had no further device-induced arrhythmias.

Discussion

Numerous studies have demonstrated the adverse effect of RV pacing on LV function. Minimizing RV pacing is, therefore, encouraged in individuals with intact AV conduction. However, underlying conduction abnormalities must be assessed prior to activating algorithms designed to minimize RV pacing. This case demonstrates the importance of careful intracardiac electrogram interpretation and individual case-based device programming, to avoid device-induced complications.
Wearable cuffless blood pressure monitoring devices: a systematic review and meta-analysis
Authors: Islam Sheikh Mohammed Shariful , Chow Clara K , Daryabeygikhotbehsara Reza , Subedi Narayan , Rawstorn Jonathan , Tegegne Teketo , Karmakar Chandan , Siddiqui Muhammad U , Lambert Gavin , Maddison Ralph
Published: May 2022

Aims

High blood pressure (BP) is the commonest modifiable cardiovascular risk factor, yet its monitoring remains problematic. Wearable cuffless BP devices offer potential solutions; however, little is known about their validity and utility. We aimed to systematically review the validity, features and clinical use of wearable cuffless BP devices.

Methods and results

We searched MEDLINE, Embase, IEEE Xplore and the Cochrane Database till December 2019 for studies that reported validating cuffless BP devices. We extracted information about study characteristics, device features, validation processes, and clinical applications. Devices were classified according to their functions and features. We defined devices with a mean systolic BP (SBP) and diastolic BP (DBP) biases of <5 mmHg as valid as a consensus. Our definition of validity did not include assessment of device measurement precision, which is assessed by standard deviation of the mean difference—a critical component of ISO protocol validation criteria. Study quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies version 2 tool. A random-effects model meta-analysis was performed to summarise the mean biases for SBP and DBP across studies. Of the 430 studies identified, 16 studies (15 devices, 974 participants) were selected. The majority of devices (81.3%) used photoplethysmography to estimate BP against a reference device; other technologies included tonometry, auscultation and electrocardiogram. In addition to BP and heart rate, some devices also measured night-time BP (n = 5), sleep monitoring (n = 3), oxygen saturation (n = 3), temperature (n = 2) and electrocardiogram (n = 3). Eight devices showed mean biases of <5 mmHg for SBP and DBP compared with a reference device and three devices were commercially available. The meta-analysis showed no statistically significant differences between the wearable and reference devices for SBP (pooled mean difference = 3.42 mmHg, 95% CI: −2.17, 9.01, I2 95.4%) and DBP (pooled mean = 1.16 mmHg, 95% CI: −1.26, 3.58, I2 87.1%).

Conclusion

Several cuffless BP devices are currently available using different technologies, offering the potential for continuous BP monitoring. The variation in standards and validation protocols limited the comparability of findings across studies and the identification of the most accurate device. Challenges such as validation using standard protocols and in real-life settings must be overcome before they can be recommended for uptake into clinical practice.
Environmental Adaptation of Risk Preferences
Authors: Di Falco Salvatore , Vieider Ferdinand M
Published: May 2022

We present incentivised panel data measuring risk preferences of subsistence farmers from across Ethiopia and pair them with rainfall data. We use these data to test the hypothesis that risk preferences may adapt to the environment of the decision maker. We find that rainfall shocks decrease risk tolerance for the same individuals over time. We also find that historical rainfall characteristics and geographical features can explain 40% of the variation in preferences across individuals. The time-changing effects are perfectly aligned with the geographical effects we document, painting a unified and highly coherent picture. This provides the first real-world evidence that preferences may systematically adapt to the environment of the decision maker.
Serum Concentrations of Losartan Metabolites Correlate With Improved Physical Function in a Pilot Study of Prefrail Older Adults
Authors: Lee Jessica L , Zhang Cissy , Westbrook Reyhan , Gabrawy Mariann M , Nidadavolu Lolita , Yang Huanle , Marx Ruth , Wu Yuqiong , Anders Nicole M , Ma Lina , Bichara Marcela-Dávalos , Kwak Min-Ji , Buta Brian , Khadeer Mohammed , Yenokyan Gayane , Tian Jing , Xue Qian-Li , Siragy Helmy M , Carey Robert M , de Cabo Rafael , Ferrucci Luigi , Moaddel Ruin , Rudek Michelle A , Le Anne , Walston Jeremy D , Abadir Peter M
Published: May 2022

Losartan is an oral antihypertensive agent that is rapidly metabolized to EXP3174 (angiotensin-subtype-1-receptor blocker) and EXP3179 (peroxisome proliferator-activated receptor gamma [PPARγ] agonist), which was shown in animal studies to reduce inflammation, enhance mitochondrial energetics, and improve muscle repair and physical performance. We conducted an exploratory pilot study evaluating losartan treatment in prefrail older adults (age 70–90 years, N = 25). Participants were randomized to control (placebo) or treatment (daily oral losartan beginning at 25 mg per day and increasing every 8 weeks) for a total of 6 months. Fatigue, hyperkalemia, and hypotension were the most observed side effects of losartan treatment. Participants in the losartan group had an estimated 89% lower odds of frailty (95% confidence interval [CI]: 18% to 99% lower odds, p = .03), with a 0.3-point lower frailty score than the placebo group (95% CI: 0.01–0.5 lower odds, p = .04). Frailty score was also negatively associated with serum losartan and EXP3179 concentrations. For every one standard deviation increase in EXP3179 (ie, 0.0011 ng/μL, based on sample values above detection limit) and EXP3174 (ie, 0.27 ng/μL, based on sample values above detection limit), there was a 0.0035 N (95% CI: 0.0019–0.0051, p < .001) and a 0.0027 N (95% CI: 0.00054–0.0043, p = .007) increase in average knee strength, respectively.
Proteome-Wide Discovery of Cortical Proteins That May Provide Motor Resilience to Offset the Negative Effects of Pathologies in Older Adults
Authors: Buchman Aron S , Yu Lei , Klein Hans-Ulrich , Zammit Andrea R , Oveisgharan Shahram , Grodstein Francine , Tasaki Shinya , Levey Allan I , Seyfried Nicholas T , Bennett David A
Published: May 2022

Background

Motor resilience proteins have not been identified. This proteome-wide discovery study sought to identify proteins that may provide motor resilience.

Methods

We studied the brains of older decedents with annual motor testing, postmortem brain pathologies, and proteome-wide data. Parkinsonism was assessed using 26 items of a modified United Parkinson Disease Rating Scale. We used linear mixed-effect models to isolate motor resilience, defined as the person-specific estimate of progressive parkinsonism after controlling for age, sex, and 10 brain pathologies. A total of 8 356 high-abundance proteins were quantified from dorsal lateral prefrontal cortex using tandem mass tag and liquid chromatography–mass spectrometry.

Results

There were 391 older adults (70% female), mean age 80 years at baseline and 89 years at death. Five proteins were associated with motor resilience: A higher level of AP1B1 (Estimate −0.504, SE 0.121, p = 3.12 × 10−5) and GNG3 (Estimate −0.276, SE 0.068, p = 4.82 × 10−5) was associated with slower progressive parkinsonism. By contrast, a higher level of TTC38 (Estimate 0.140, SE 0.029, p = 1.87 × 10−6), CARKD (Estimate 0.413, SE 0.100, p = 3.50 × 10−5), and ABHD14B (Estimate 0.175, SE 0.044, p = 6.48 × 10−5) was associated with faster progressive parkinsonism. Together, these 5 proteins accounted for almost 25% of the variance of progressive parkinsonism above the 17% accounted for by 10 indices of brain pathologies.

Discussion

Cortical proteins may provide more or less motor resilience in older adults. These proteins are high-value therapeutic targets for drug discovery that may lead to interventions that maintain motor function despite the accumulation of as yet untreatable brain pathologies.
Functional analysis of rare genetic variants in complement factor I in advanced age-related macular degeneration
Authors: Java Anuja , Pozzi Nicola , Schroeder Molly C , Hu Zheng , Huan Tianxiao , Seddon Johanna M , Atkinson John
Published: May 2022

Factor I (FI) is a serine protease inhibitor of the complement system. Heterozygous rare genetic variants in complement factor I (CFI) are associated with advanced age-related macular degeneration (AMD). The clinical impact of these variants is unknown since a majority have not been functionally characterized and are classified as ‘variants of uncertain significance’ (VUS). This study assessed the functional significance of VUS in CFI. Our previous cross-sectional study using a serum-based assay demonstrated that CFI variants in advanced AMD can be categorized into three types. Type 1 variants cause a quantitative deficiency of FI. Type 2 variants demonstrate a qualitative deficiency. However, Type 3 variants consist of VUS that are less dysfunctional than Types 1 and 2 but are not as biologically active as wild type (WT). In this study, we employed site-directed mutagenesis followed by expression of the recombinant variant and a comprehensive set of functional assays to characterize nine Type 3 variants that were identified in 37 individuals. Our studies establish that the expression of the recombinant protein compared with WT is reduced for R202I, Q217H, S221Y and G263V. Further, G362A and N536K, albeit expressed normally, have significantly less cofactor activity. These results led to re-categorization of CFI variants R202I, Q217H, S221Y and G263V as Type 1 variants and to reclassification of N536K and G362A as Type 2. The variants K441R, Q462H and I492L showed no functional defect and remained as Type 3. This study highlights the utility of an in-depth biochemical analysis in defining the pathologic and clinical implications of complement variants underlying AMD.
Tracing genetic connections of ancient Hungarians to the 6th–14th century populations of the Volga-Ural region
Authors: Szeifert Bea , Gerber Dániel , Csáky Veronika , Langó Péter , Stashenkov Dmitrii A , Khokhlov Aleksandr A , Sitdikov Ayrat G , Gazimzyanov Ilgizar R , Volkova Elizaveta V , Matveeva Natalia P , Zelenkov Alexander S , Poshekhonova Olga E , Sleptsova Anastasiia V , Karacharov Konstantin G , Ilyushina Viktoria V , Konikov Boris A , Sungatov Flarit A , Kolonskikh Alexander G , Botalov Sergei G , Grudochko Ivan V , Komar Oleksii , Egyed Balázs , Mende Balázs G , Türk Attila , Szécsényi-Nagy Anna
Published: May 2022

Most of the early Hungarian tribes originated from the Volga-Kama and South-Ural regions, where they were composed of a mixed population based on historical, philological and archaeological data. We present here the uniparental genetic makeup of the mediaeval era of these regions that served as a melting pot for ethnic groups with different linguistic and historical backgrounds. Representing diverse cultural contexts, the new genetic data originate from ancient proto-Ob-Ugric people from Western Siberia (6th–13th century), the pre-Conquest period and subsisting Hungarians from the Volga-Ural region (6th–14th century) and their neighbours. By examining the eastern archaeology traits of Hungarian prehistory, we also study their genetic composition and origin in an interdisciplinary framework. We analyzed 110 deep-sequenced mitogenomes and 42 Y-chromosome haplotypes from 18 archaeological sites in Russia. The results support the studied groups’ genetic relationships regardless of geographical distances, suggesting large-scale mobility. We detected long-lasting genetic connections between the sites representing the Kushnarenkovo and Chiyalik cultures and the Carpathian Basin Hungarians and confirmed the Uralic transmission of several East Eurasian uniparental lineages in their gene pool. Based on phylogenetics, we demonstrate and model the connections and splits of the studied Volga-Ural and conqueror groups. Early Hungarians and their alliances conquered the Carpathian Basin around 890 AD. Re-analysis of the Hungarian conquerors’ maternal gene pool reveals numerous surviving maternal relationships in both sexes; therefore, we conclude that men and women came to the Carpathian Basin together, and although they were subsequently genetically fused into the local population, certain eastern lineages survived for centuries.
Harnessing stakeholder knowledge for the collaborative development of Mobulid bycatch mitigation strategies in tuna fisheries
Authors: Cronin Melissa R , Croll Donald A , Hall Martin A , Lezama-Ochoa Nerea , Lopez Jon , Murua Hilario , Murua Jefferson , Restrepo Victor , Rojas-Perea Stefany , Stewart Joshua D , Waldo Jennifer L , Moreno Gala
Published: May 2022

Manta and devil rays (Mobulids) face several immediate threats, including incidental capture in industrial tropical tuna fisheries. As a result, efforts have emerged to avoid or mitigate Mobulid bycatch in these fisheries. However, many mitigation efforts fail to incorporate fisher expertise from the outset, potentially leading to interventions that are not viable. Here, we combine survey and focus group data to synthesize knowledge of Mobulid bycatch and mitigation ideas in Eastern Pacific Ocean purse seine fisheries. Primary obstacles for mitigating Mobulid bycatch, according to respondents, are: (1) an inability to sight Mobulids before capture, (2) the lack of specific equipment on board, and (3) the difficulty of releasing large individuals; we suggest that the latter two can be addressed by simple operational modifications. We also find that Mobulids are most likely to be sighted by fishers after capture, suggesting that this is an important time in the fishing operation for bycatch mitigation interventions that ensure Mobulids survive capture. To address this, we share creative ideas brought by fishers for avoidance of Mobulids. This study provides a model of how to incorporate stakeholder input in the design of bycatch technology in large-scale fisheries and could inform similar efforts around the world.
Shared and Unique Effects of Long-Term Administration of Methylphenidate and Atomoxetine on Degree Centrality in Medication-Naïve Children With Attention-Deficit/Hyperactive Disorder
Authors: Fu Zhao , Yuan Jing , Pei Xuyao , Zhang Kangfuxi , Xu Chenyang , Hu Na , Xie Rao , Zhao Yilu , Wang Yufeng , Yang Li , Cao Qingjiu
Published: May 2022

Background

Although methylphenidate (MPH) and atomoxetine (ATX) can improve clinical symptoms and functional impairments in attention deficit/hyperactive disorder (ADHD), the underlying psychopharmacological mechanisms have not been clearly elucidated. Therefore, we aimed to explore the shared and unique neurologic basis of these 2 medications in alleviating the clinical symptoms and functional impairments observed in ADHD.

Methods

Sixty-seven ADHD and 44 age-matched children with typical development were included and underwent resting-state functional magnetic resonance imaging scans at baseline. Then patients were assigned to MPH, ATX, or untreated subgroups, based on the patients’ and their parents’ choice, for a 12-week follow-up and underwent a second functional magnetic resonance imaging scan. The treatment effect on degree centrality (DC) was identified and correlated with clinical symptoms and functional impairments in the ADHD group.

Results

Both MPH and ATX normalized the DC value in extensive brain regions mainly involving fronto-cingulo-parieto-cerebellum circuits. However, ATX showed limited significant effects on the cerebellum compared with ADHD at baseline. The improvements in clinical symptoms were correlated with increased DC in the right inferior temporal gyrus in both MPH and ATX subgroups but showed opposite effects. The alleviation of functional impairments in the school/learning domain negatively correlated with decreased DC in the bilateral cerebellum after MPH treatment, and the family functional domain positively correlated with decreased DC in the cerebellum and negatively correlated with decreased DC in the postcentral gyrus after ATX treatment.

Conclusions

Both MPH and ATX can normalize abnormal brain functions that mainly involve the fronto-cingulo-parieto-cerebellum circuit in ADHD. Furthermore, the 2 medications showed shared and unique effects on brain functions to alleviate clinical symptoms and functional impairment.
Medically Attended Illness due to Respiratory Syncytial Virus Infection Among Infants Born in the United States Between 2016 and 2020
Authors: Gantenberg Jason R , van Aalst Robertus , Zimmerman Nicole , Limone Brendan , Chaves Sandra S , La Via William V , Nelson Christopher B , Rizzo Christopher , Savitz David A , Zullo Andrew R
Published: May 2022

Background

Respiratory syncytial virus (RSV) is a leading cause of infant hospitalization in the United States. Preterm infants and those with select comorbidities are at highest risk of RSV-related complications. However, morbidity due to RSV infection is not confined to high-risk infants. We estimated the burden of medically attended (MA) RSV-associated lower respiratory tract infection (LRTI) among infants in the United States.

Methods

We analyzed commercial (MarketScan Commercial [MSC], Optum Clinformatics [OC]), and Medicaid (MarketScan Medicaid [MSM]) insurance claims data for infants born between April 2016 and February 2020. Using both specific and sensitive definitions of MA RSV LRTI, we estimated the burden of MA RSV LRTI during infants’ first RSV season, stratified by gestational age, comorbidity status, and highest level of medical care associated with the MA RSV LRTI diagnosis.

Results

According to the specific definition 75.0% (MSC), 78.6% (MSM), and 79.6% (OC) of MA RSV LRTI events during infants’ first RSV season occurred among term infants without known comorbidities.

Conclusions

Term infants without known comorbidities account for up to 80% of the MA RSV LRTI burden in the United States during infants’ first RSV season. Future prevention efforts should consider all infants.
Investigations into the emergent properties of gene-to-phenotype networks across cycles of selection: a case study of shoot branching in plants
Authors: Powell Owen M , Barbier Francois , Voss-Fels Kai P , Beveridge Christine , Cooper Mark
Published: May 2022

Predictive breeding is now widely practised in crop improvement programmes and has accelerated selection response (i.e. the amount of genetic gain between breeding cycles) for complex traits. However, world food production needs to increase further to meet the demands of the growing human population. The prediction of complex traits with current methods can be inconsistent across different genetic, environmental and agronomic management contexts because the complex relationships between genomic and phenotypic variation are not well accounted for. Therefore, developing gene-to-phenotype network models for traits that integrate the knowledge of networks from systems biology, plant and crop physiology with population genomics has been proposed to close this gap in predictive modelling. Here, we develop a gene-to-phenotype network for shoot branching, a critical developmental pathway underpinning harvestable yield for many crop species, as a case study to explore the value of developing gene-to-phenotype networks to enhance understanding of selection responses. We observed that genetic canalization is an emergent property of the complex interactions among shoot branching gene-to-phenotype network components, leading to the accumulation of cryptic genetic variation, reduced selection responses and large variation in selection trajectories across populations. As genetic canalization is expected to be pervasive in traits, such as grain yield, that result from interactions among multiple genes, traits, environments and agronomic management practices, the need to model traits in crop improvement programmes as outcomes of gene-to-phenotype networks is highlighted as an emerging opportunity to advance our understanding of selection response and the efficiency of developing resilient crops for future climates.
A systematic review to describe patterns of animal and human viral research in Rwanda
Authors: Dutuze M Fausta , Byukusenge Maurice , Shyaka Anselme , Christofferson Rebecca C
Published: May 2022

Rwanda is located in the Central East African region where several viral pathogens with global importance were originally described, including human immunodeficiency virus (HIV), Ebola, Zika, Rift Valley Fever (RVF), dengue and a long list of other neglected tropical viral pathogens. Due to many factors, this region has the potential to become a global hotspot for viral emergence. In Rwanda, viral diseases are underreported and the question is whether this is due to the absence of these viruses or a lack of investigation. Like many developing countries, capabilities in Rwanda need improvement despite research efforts throughout the years. This review describes the status of human and animal virus research in Rwanda and identifies relevant research and operational gaps. A comprehensive search was conducted in PubMed for virus research in Rwanda: 233 primary studies on viruses/viral diseases are indexed with connection to Rwanda. From 1958 to 2020, yearly publications generally increased and HIV/acquired immunodeficiency syndrome is the most studied virus. Compared with human viruses, few studies focus on animal and/or zoonotic viruses. The occurrence of the current severe acute respiratory syndrome coronavirus 2 pandemic shows strengthening warning and surveillance systems is critical to efficient preparedness and response. We recommend investment in human capacity, laboratory facilities and research to inform policy for viral surveillance in Rwanda.
The competition for India’s antitrust jurisdiction: Competition Commission versus sectoral regulators
Authors: Singh Madhavi
Published: May 2022

A string of judgments by Indian courts have downgraded the Competition Commission of India’s position in the adjudicatory hierarchy by requiring it to await the findings of sectoral regulators before initiating its own investigation. This article argues that the reasons advanced for deferring the Commission’s jurisdiction are erroneous. Further, the judicial test for deferral of the Commission’s jurisdiction is fraught with deficiencies and would inordinately delay or de facto divest the Commission of its jurisdiction. Some recent cases are trying to break away from this trend. One final battle though remains to be fought. With the emergence of competition issues in data protection and privacy related cases and the imminent establishment of data regulator(s) in India, the Commission will soon have an opportunity to push courts to re-examine and re-interpret existing judicial principles and reclaim its relative position in the adjudicatory hierarchy.
Matrix Extension of the CompactDry™ “Nissui” YMR for Enumeration of Yeasts and Molds in Dried Cannabis Flower: AOAC Performance Tested MethodSM 092002
Authors: Hamilton Lauren , Klavins Anna , Malherbe Rianna , Youngblood Jessa , Ito Yusuke , Hsiung Andre
Published: May 2022

Background

CompactDry™ Yeast/Mold Rapid (YMR) is a ready-to-use dry media sheet using a chromogenic medium with selective agents for the enumeration of yeasts and molds in a variety of food products after incubation at 25 ± 1°C for 3 days. The method is certified as AOAC Performance Tested MethodSM 092002.

Objective

The CompactDry YMR method was validated for a matrix extension to cannabis flower through the AOAC Emergency Response Validation process.

Methods

The performance of the CompactDry YMR was compared to Dichloran Rose Bengal Chloramphenicol (DRBC) agar for the enumeration of yeasts and molds in cannabis flower. Matrix data were normalized by log10 transformation, and performance indicators included repeatability, difference of means (DOM), and inclusivity/exclusivity.

Results

The results demonstrated that the CompactDry YMR method is equivalent to the DRBC agar method at 72 h of incubation. In the independent laboratory validation study, there was no significant difference in detection, enumeration, or repeatability between the CompactDry YMR method and DRBC agar at 72 h. Eighteen inclusivity and 16 exclusivity strains specific to cannabis plant materials that were not evaluated in the original CompactDry YMR method validation were tested in this study. All inclusivity organisms produced typical colonies on the CompactDry YMR. The two exclusivity bacterial strains that showed growth on CompactDry YMR at 72 h were inoculated at a high concentration.

Conclusions

CompactDry YMR is equivalent in performance to traditional culture media detection methods of yeasts and molds.

Highlights

CompactDry YMR will streamline dried cannabis flower testing.