bluuebunny/crossref_metadata_2025 huggingface dataset:
Reduced Sensitivity to Tebuconazole in Botryosphaeria dothidea Isolates Collected from Major Apple Production Areas of China
Authors: Fan Kun , Fu Li , Liu Huimin , Qu Jianlu , Zhang Guofu , Zhang Shouan , Qiao Kang
Published: April 2022

China has the largest acreage and is the greatest producer of apples in the world. Apple ring rot (ARR) caused by Botryosphaeria dothidea is one of the major diseases affecting apple fruit production. Tebuconazole, a sterol demethylation-inhibiting (DMI) fungicide, has been increasingly applied to manage ARR in China. Resistance to tebuconazole in field populations of B. dothidea may be selected and accumulate to higher degrees over time. Establishment of tebuconazole sensitivity monitoring programs is critically important for resistance management and effective ARR control. However, the resistance level of B. dothidea to tebuconazole in China remains largely unknown. In this study, in vitro mycelial growth assays of B. dothidea in media amended with tebuconazole were conducted, and the sensitivity of B. dothidea to tebuconazole was determined with a set of 390 isolates collected from the major apple production provinces in China between 2006 and 2014. Results showed that the 50% effective concentration (EC50) value ranged from 0.011 to 0.918, 0.040 to 1.621, and 0.052 to 1.925 μg ml−1 with a median value of 0.194, 0.386, and 0.782 μg ml−1 in the isolates collected in 2006, 2010, and 2014, respectively. The frequency distribution of EC50 for tebuconazole was a nonnormal distribution (P < 0.05), suggesting that subpopulations with reduced sensitivity to tebuconazole had emerged in these B. dothidea isolates. The frequency distribution of the B. dothidea isolates collected in 2006 fit a unimodal curve and could be regarded as the baseline sensitivity to tebuconazole. The resistance levels increased over time with the average occurrence frequency of 43.3% and resistance index of 0.38. Positive cross-resistance was observed between tebuconazole and metconazole, which is another DMI fungicide, but multiple resistance was not detected between tebuconazole and non-DMI fungicides. Our results demonstrated that regular long-term resistance monitoring combining with prudent fungicide use should be implemented to prolong the lifespan of tebuconazole in management of ARR in apples.
A Quantitative PCR Assay for Detection and Quantification of Fusarium sambucinum
Authors: Thomas William J. , Borland Theodora G. , Bergl Darby D. , Claassen Briana J. , Flodquist Timothy A. , Montgomery Alexandria S. , Rivedal Hannah M. , Woodhall James , Ocamb Cynthia M. , Gent David H.
Published: April 2022

Fusarium sambucinum is an ascomycete that has been isolated from a broad range of plant hosts, including hop (Humulus lupulus L.), where it acts as a causal agent of Fusarium canker, a disease that can impact cone quality and yield in severe cases. Current diagnostic methods rely on isolation of the fungus from plant tissue, a time- and resource-intensive process with limited sensitivity, complicated by the potential presence of other Fusarium spp. that have been reported on hop. Our objective was to develop a rapid and sensitive diagnostic tool to detect and quantify F. sambucinum in plant tissues. Using a modified random amplified polymorphic DNA PCR assay, we identified a F. sambucinum-specific marker that serves as the target in a TaqMan (hydrolysis) probe quantitative PCR (qPCR) assay that can be used to detect F. sambucinum DNA in a background of plant DNA. When used to screen 52 isolates of F. sambucinum and isolates representing 13 other Fusarium spp., the assay was robust in detecting F. sambucinum while discriminating between F. sambucinum and closely related Fusarium spp., including F. venenatum. Furthermore, this assay reliably detects as little as 1 pg of F. sambucinum DNA in a background of total DNA from plant tissue. Within-sample comparisons of this qPCR assay with traditional cultural isolation methods demonstrated the greater sensitivity of the qPCR-based method for detection of F. sambucinum. When used to screen 220 asymptomatic stem samples, the qPCR assay detected F. sambucinum in 100 samples (45.5%); by comparison, F. sambucinum was detected in only 3 samples (1.4%) by culturing methods. Moreover, quantification of F. sambucinum DNA was possible for 60 of these samples, indicating the utility of the qPCR assay for early detection. This assay should be useful in diagnostic and epidemiological applications to detect and quantify F. sambucinum from multiple hosts and environmental samples.
Repeated Emergence of Sudden Oak Death in Oregon: Chronology, Impact, and Management
Authors: LeBoldus Jared M. , Navarro Sarah M. , Kline Norma , Ritokova Gabriela , Grünwald Niklaus J.
Published: April 2022

It has been two decades since the first detection of the sudden oak death pathogen Phytophthora ramorum in Oregon forests. Although the epidemic was managed since its first discovery in 2001, at least three invasions of three separate variants (clonal lineages), NA1, EU1, and NA2, are documented to have occurred to date. Control of this epidemic has cost over US$32 million from 2001 to 2020. This is dwarfed by the predicted cost of the closure to the Coos Bay export terminal, estimated at $58 million per year, if the epidemic was allowed to spread unchecked. Management efforts in Oregon have reduced inoculum and limited the spread of the pathogen. An outreach and citizen scientist program has been piloted to help in early detection efforts and search for disease-resistant tanoak. This feature article documents the repeated emergence, impact, costs, and lessons learned from managing this devastating invasive pathogen.
Impairment in Preextubation Alveolar Gas Exchange Is Associated With Postextubation Respiratory Support Needs in Infants After Cardiac Surgery
Authors: Scherer Bradley , Ghanayem Nancy , Guffey Danielle , Castro Danny , Cossbu Jorge , Afonso Natasha
Published: April 2022

OBJECTIVES:

To determine if indices of alveolar gas exchange preextubation predict postextubation respiratory support needs as well as the need for escalation of therapies following infant cardiac surgery.

DESIGN:

Retrospective chart review.

SETTING:

Pediatric cardiac ICU in a quaternary-care teaching hospital.

PATIENTS:

Infants less than 1 year old who underwent biventricular repair from January 2015 to December 2017.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

Preextubation alveolar-arterial gradient, oxygenation index, oxygen saturation index, Pao
2/Fio
2 ratio, and dead space ventilation (analyzed with both end-tidal carbon dioxide gradient and dead space fraction) were evaluated for each patient. All but dead space ventilation were associated with a higher level of noninvasive respiratory support immediately postextubation. Furthermore, impaired preextubation gas exchange was independently associated with escalation of respiratory support within the first 48-hour postextubation.

CONCLUSIONS:

Validated measures of alveolar gas exchange can be used as a tool to assess postextubation respiratory support needs including the risk of escalation of respiratory support in the first 48-hour postextubation. Prospective study with implementation of extubation guidelines, both for readiness and determination of early postextubation support, is needed to validate these findings.
The PANDORA Study: Prevalence and Outcome of Acute Hypoxemic Respiratory Failure in the Pre-COVID-19 Era
Authors: Villar Jesús , Mora-Ordoñez Juan M. , Soler Juan A. , Mosteiro Fernando , Vidal Anxela , Ambrós Alfonso , Fernández Lorena , Murcia Isabel , Civantos Belén , Romera Miguel A. , Mira Adrián , Díaz-Domínguez Francisco J. , Parrilla Dácil , Martínez-Carmona J. Francisco , Martínez Domingo , Pita-García Lidia , Robaglia Denis , Bueno-González Ana , Sánchez-Ballesteros Jesús , Pereyra Ángel E. , Hernández Mónica , Chamorro-Jambrina Carlos , Cobeta Pilar , González-Luengo Raúl I. , Montiel Raquel , Nogales Leonor , Fernández M. Mar , Arocas Blanca , Valverde-Montoro Álvaro , del Saz-Ortiz Ana M. , Olea-Jiménez Victoria , Añón José M. , Rodríguez-Suárez Pedro , Fernández Rosa L. , Fernández Cristina , Szakmany Tamas , González-Martín Jesús M. , Ferrando Carlos , Kacmarek Robert M. , Slutsky Arthur S. ,   for the Prevalence AND Outcome of acute hypoxemic Respiratory fAilure (PANDORA) Network
Published: April 2022

OBJECTIVES:

To establish the epidemiological characteristics, ventilator management, and outcomes in patients with acute hypoxemic respiratory failure (AHRF), with or without acute respiratory distress syndrome (ARDS), in the era of lung-protective mechanical ventilation (MV).

DESIGN:

A 6-month prospective, epidemiological, observational study.

SETTING:

A network of 22 multidisciplinary ICUs in Spain.

PATIENTS:

Consecutive mechanically ventilated patients with AHRF (defined as Pao
2/Fio
2 ≤ 300 mm Hg on positive end-expiratory pressure [PEEP] ≥ 5 cm H2O and Fio
2 ≥ 0.3) and followed-up until hospital discharge.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

Primary outcomes were prevalence of AHRF and ICU mortality. Secondary outcomes included prevalence of ARDS, ventilatory management, and use of adjunctive therapies. During the study period, 9,803 patients were admitted: 4,456 (45.5%) received MV, 1,271 (13%) met AHRF criteria (1,241 were included into the study: 333 [26.8%] met Berlin ARDS criteria and 908 [73.2%] did not). At baseline, tidal volume was 6.9 ± 1.1 mL/kg predicted body weight, PEEP 8.4 ± 3.1 cm H2O, Fio
2 0.63 ± 0.22, and plateau pressure 21.5 ± 5.4 cm H2O. ARDS patients received higher Fio
2 and PEEP than non-ARDS (0.75 ± 0.22 vs 0.59 ± 0.20 cm H2O and 10.3 ± 3.4 vs 7.7 ± 2.6 cm H2O, respectively [p < 0.0001]). Adjunctive therapies were rarely used in non-ARDS patients. Patients without ARDS had higher ventilator-free days than ARDS (12.2 ± 11.6 vs 9.3 ± 9.7 d; p < 0.001). All-cause ICU mortality was similar in AHRF with or without ARDS (34.8% [95% CI, 29.7–40.2] vs 35.5% [95% CI, 32.3–38.7]; p = 0.837).

CONCLUSIONS:

AHRF without ARDS is a very common syndrome in the ICU with a high mortality that requires specific studies into its epidemiology and ventilatory management. We found that the prevalence of ARDS was much lower than reported in recent observational studies.
Retrospective Review of Transpulmonary Pressure Guided Positive End-Expiratory Pressure Titration for Mechanical Ventilation in Class II and III Obesity
Authors: Liou Jesse , Doherty Daniel , Gillin Tom , Emberger John , Yi Yeonjoo , Cardenas Luis , Benninghoff Michael , Vest Michael , Deitchman Andrew
Published: April 2022

OBJECTIVES:

Acute respiratory distress syndrome is treated by utilizing a lung protective ventilation strategy. Obesity presents with additional physiologic considerations, and optimizing ventilator settings may be limited with traditional means. Transpulmonary pressure (PL) obtained via esophageal manometry may be more beneficial to titrating positive end-expiratory pressure (PEEP) in this population. We sought to determine the feasibility and impact of implementation of a protocol for use of esophageal balloon to set PEEP in obese patients in a community ICU.

DESIGN:

Retrospective cohort study of obese (body mass index [BMI] ≥ 35 kg/m2) patients undergoing individualized PEEP titration with esophageal manometry. Data were extracted from electronic health record, and Wilcoxon signed rank test was performed to determine whether there were differences in the ventilatory parameters over time.

SETTING:

Intensive care unit in a community based hospital system in Newark, Delaware.

PATIENTS:

Twenty-nine mechanically ventilated adult patients with a median BMI of 45.8 kg/m2 with acute respiratory distress syndrome (ARDS).

INTERVENTION:

Individualized titration of PEEP via esophageal catheter obtained transpulmonary pressures.

MEASUREMENTS AND MAIN RESULTS:

Outcomes measured include PEEP, oxygenation, and driving pressure (DP) before and after esophageal manometry at 4 and 24 hr. Clinical outcomes including adverse events (pneumothorax and pneumomediastinum), increased vasopressor use, rescue therapies (inhaled pulmonary vasodilators, extracorporeal membrane oxygenation, and new prone position), continuous renal replacement therapy, and tracheostomy were also analyzed. Four hours after PEEP titration, median PEEP increased from 12 to 20 cm H2O (p < 0.0001) with a corresponding decrease in median DP from 15 to 13 cm H2O (p = 0.002). Subsequently, oxygenation improved as median Fio
2 decreased from 0.8 to 0.6 (p < 0.0001), and median oxygen saturation/Fio
2 (S/F) ratio improved from 120 to 165 (p < 0.0001). One patient developed pneumomediastinum. No pneumothoraces were identified. Improvements in oxygenation continued to be seen at 24 hr, compared with the prior 4 hr mark, Fio
2 (0.6–0.45; p < 0.004), and S/F ratio (165–211.11; p < 0.001). Seven patients required an increase in vasopressor support after 4 hours. Norepinephrine and epinephrine were increased by 0.05 (± 0.04) µg/kg/min and 0.02 (± 0.01) µg/kg/min on average, respectively.

CONCLUSIONS:

PL-guided PEEP titration in obese patients can be used to safely titrate PEEP and decrease DP, resulting in improved oxygenation.
The relative effectiveness of fecal immunochemical test-based colorectal cancer screening to detect adenomas and cancer in different demographic and socioeconomic groups. A nationwide cohort study
Authors: Larsen Mette Bach , Søborg Bo , Njor Sisse Helle , Jensen Thomas Møller , Ingeholm Peter , Andersen Berit
Published: April 2022

Introduction

This study aimed at analyzing the relative effectiveness in removal of adenomas and detection of cancer of implementing colorectal cancer (CRC) screening in different demographic and socioeconomic groups.

Methods

This register-based retrospective cohort study included residents aged 50–72 years. Those randomly selected to be invited for CRC screening from 1 March 2014 to 30 June 2015 were classified as invited; those invited from 1 January 2016 to 31 December 2017 were classified as not yet invited. Strata-specific relative risks (RRs) of having adenomas removed and CRC detected were estimated.

Results

A total of 1 343 090 individuals were included. The RR of having adenomas removed were higher among men compared with women [RRwomen = 6.41 (95% confidence interval [CI]: 5.08–8.09), RRmen = 7.74 (95% CI: 6.16–9.73), P < 0.01] and among Danes compared with immigrants [RRDanes = 4.71 (95% CI: 3.73–5.93), RRWestern = 4.76 (95% CI: 3.39–6.69), RRnon-Western = 3.35 (95% CI: 2.39–4.69), P = 0.03]. Regarding detection of CRC, the effectiveness increased with increasing age ranging from RR = 1.53 (95% CI: 0.93– 2.51) to RR = 1.97 (95% CI: 1.22–3.17) (P = 0.04) and was higher among men compared with women (RRwomen = 1.75 (95% CI: 1.10–2.76), RRmen = 2.07 (95% CI: 1.32–3.26), P = 0.02.

Conclusion

Attention must be paid to the potential differences in screening effectiveness among diverse subpopulations; first, by securing equal opportunities for participation across subpopulations and second, by considering sex and age-specific screening programs.
Overcoming the Fukushima Wastewater Crisis: What the Japanese Authorities Could Do to Address Opposing Views
Authors: Ng Kwan Hoong , Yoong David , Gong Jiankun
Published: April 2022

In April 2021, the Japanese authorities’ announcement of their decision to release processed wastewater from the damaged Fukushima Daiichi nuclear power plant into the Pacific Ocean over 30 y, beginning in 2023, triggered strong domestic and international opposition. Failure to handle this situation tactfully can lead to public disorder, civil disobedience, loss of trust in the authorities, and even diplomatic sanctions. In this article, we explain the underlying reasons behind this resistance, and we offer some strategic methods that the Japanese authorities can deploy to address opposing views and overcome the Fukushima wastewater crisis.
The danger of underdiagnosing coronary microvascular disease in women
Authors: Behnke Lyn M.
Published: April 2022

Heart disease is the number one killer of women in the United States. Part of the difficulty with diagnosing heart disease in women is related to a disease process called coronary microvascular disease (CMVD; previously called syndrome X). Also known as nonobstructive coronary artery disease, CMVD is challenging to identify because often there is a lack of convincing evidence of an acute problem during evaluation. In these patients, the epicardial coronary arteries do not have visible blockages, and stress tests often are interpreted as normal or false positive. Therefore, symptomatic patients often are left undiagnosed, frustrated, and at risk of adverse cardiac events. Frequently, the only method of diagnosis is treatment of the symptoms. This information is provided to help advanced practice nurses and other clinicians diagnose and treat CMVD.
Dilemma of identifying congenital hemolytic anemias in primary care
Authors: Kleinert Dorothy , Seibert Diane C.
Published: April 2022

Anemia, the overall reduction of red blood cell (RBC) mass in an individual, occurs as a result of an underlying condition. It is probably the most common pathological state worldwide and can be acute, chronic, congenital, or acquired. It can be placed in one of three broad categories: blood loss, hypoproliferative, and hemolytic. The most common and easiest to correct is hypoproliferative anemia caused by nutritional deficiencies. The most common genetic anemias are caused by mutations on the alpha- or beta-globin genes, but there are other mutations that alter red cell membrane function or decrease the bone marrow's ability to manufacture RBCs. Understanding the mechanisms of anemia can help providers interpret the symptom(s)/presentation and guide the clinical workup. Nurse practitioners, especially those in primary care, should be able to recognize when a microcytic anemia is not caused by iron deficiency because these anemias are not corrected by iron supplementation and will need additional workup and referral to hematology.
Relationship of Nurses’ Professional Values and Attitudes With Their Professional Behaviors
Authors: Aciksoz Semra , Uzun Senay , Soylu Cakmak Fatma , Arslan Filiz , Isık Fikriye
Published: April 2022

The purpose of this cross-sectional study was to investigate the relationship of nurses’ professional values and attitudes with their professional behaviors. The sample of the study included the nurses (n = 235) at a hospital in Turkey. The results show that the importance given to professional values was high and that attitude toward the profession was positive; the importance given to professional values and positive attitude toward the profession increased in direct proportion to professional behaviors.
Utilizing a Learning Management System to Provide Nursing Professional Development
Authors: Long Elizabeth M. , Bellard Quentin
Published: April 2022

The provider unit involved in this project was based in a university setting within a school of nursing and serves both the university nursing faculty and nurses within the community. To support effective online content design principles, usability, a connection to the content, and a method for participants to provide sound feedback, a nurse planner for the unit and an instructional designer in the university collaborated to transition nursing professional development activities to an online format utilizing a learning management system. Virtual learning is viable and a potentially effective option to provide interactive and innovative professional development.
Connecting the DOTs in Clinical Orientation
Authors: Higgins Jennifer , Cantrell Faith , Runkel Natasha , Fitzgerald Stacy , Pyles Laurie , Skroch Alisa , Huston Joshua , Hammer Nathan
Published: April 2022

Newly hired nurses often complete orientation to the acute care setting with multiple preceptors, and communication about orientation progress has the potential to be disjointed. Traditionally, orientation has been tracked using various formats relying on pen and paper. The Daily Orientation Tracker or DOT, created by preceptors and nurse educators, has pushed communication into an accessible, user-friendly format found to be successful for the orientation of new nurses. Information about how the DOT was developed and implemented as well as data describing the empirical success of the DOT are shared.
IDH1/2 Mutations in Sinonasal Undifferentiated Carcinomas
Authors: Kakkar Aanchal , Rathor Amber , Ashraf Subiyathul Farah , Singh Varsha , Sikka Kapil , Jain Deepali
Published: April 2022

Sinonasal undifferentiated carcinoma (SNUC) is a rare, poorly defined sinonasal epithelial neoplasm from which several genetically defined entities are emerging. IDH1/2 mutations were recently identified in a subset of SNUC. However, the ideal method for the detection of these mutations remains to be established. Cases diagnosed as SNUC between 2010 and 2020 were retrieved. Immunohistochemistry was performed using IDH1/2 mutant-specific antibody MsMab-1. Quantitative real-time polymerase chain reaction (qPCR) was performed on genomic DNA extracted from formalin-fixed paraffin-embedded tissue using 2 kits to detect IDH1/2 mutations. Sanger sequencing was performed in a subset of cases. Thirty-eight cases of SNUC were identified, 18 of which showed IDH1/2 mutations by qPCR (47.4%). IDH2 R172K and R140x were most frequent, each seen in 6 cases (33.3%). Sanger sequencing identified IDH1/2 mutations in 4 out of 21 cases (19%) and did not detect mutations identified by qPCR in 7 cases. On immunohistochemistry, strong IDH positivity was present in 2 cases (5.3%), 1 of which had IDH2 mutation, while no mutation was detected in the other. Our results demonstrating IDH2 R172K and IDH2 R140x variants are a novel finding in SNUC. Immunohistochemistry and Sanger sequencing have low sensitivity for detection of IDH1/2 mutations, and qPCR-based assays may be utilized, particularly in resource-limited settings where access to sophisticated sequencing techniques are difficult.
Accessory Thyroid Tissue Detected Using 131I SPECT/CT Imaging
Authors: Tao Wilson Chun , Kang Owen , Russo Robert , Mansberg Robert
Published: April 2022

Thyroid ectopia has been described as a rare congenital anomaly, characterized by the presence of a thyroid gland in locations other than the orthotopic pretracheal location. The prevalence of accessory thyroid tissue in patients undergoing postablative radioiodine therapy in a 12-month period at a tertiary hospital nuclear medicine department was assessed. Fifty-seven patients were treated between September 2020 and September 2021. Retrospective analysis identified the presence and location of all accessory thyroid tissue separate from the orthotopic pretracheal thyroid gland. Accessory thyroid tissue was present in 21.1% (12/57) of the patients. Accessory thyroid tissue was most commonly located in the lingual region.
FAP-Targeted Radionuclide Therapy of Advanced Radioiodine-Refractory Differentiated Thyroid Cancer With Multiple Cycles of 177Lu-FAPI-46
Authors: Fu Hao , Huang Jingxiong , Sun Long , Wu Hua , Chen Haojun
Published: April 2022

Many recent studies began to explore the therapeutic potential of FAP-targeted radionuclide therapy for refractory cancers. In this case, we presented the experience of multiple cycles of 177Lu-FAPI-46 radionuclide therapy in a 34-year-old man with radioiodine-refractory differentiated thyroid cancer (RAIR-DTC). Intense radiotracer uptake was observed in RAIR-DTC metastatic lesions on the pretreatment 68Ga-FAPI PET/CT and posttherapeutic scintigraphy. Follow-up examinations after 4 cycles of 177Lu-FAPI-46 treatment revealed stable metastatic lesions, resulting in stable disease. This case demonstrated the potential feasibility of 177Lu-FAPI-46 in the treatment of advanced RAIR-DTC; further research on improving the FAP-targeting vector may be necessary.
Effects of a Physically Active Lifestyle Modification (PALM) Program for Independent Taiwanese Older Adults
Authors: Kuo Chang-Chih , Shyu Hui-Jen , Park Daniel , Tsai Pei-Chun , Li Yu-Hsien
Published: April 2022

This pilot study investigated a manualized lifestyle-based intervention, Physically Active Lifestyle Modification (PALM) program, designed to increase physical activity in the daily life routines of Taiwanese older adults and improve their quality of life. Thirty older adults who attended a Senior Citizens Learning Camp in Taiwan participated in the program. Quantitative measures and qualitative interviews were employed to study the intervention's effect on quality of life and to capture participants' subjective experiences in the program. Results revealed significant improvement in both physical and mental component summary of the RAND 36-Item Short Form Health Survey. Interview data revealed 4 key themes: change in action, self-awareness of occupational pattern, acquisition of health information, and social participation.
Relative Importance of Physical Activity and Body Composition on Insulin Resistance in Older Adult Population
Authors: Tsai Pao-Feng , Wang Chih-Hsuan , Hunt Caralise W. , Watts Sarah O. , Ware Katilya S.
Published: April 2022

This secondary data analysis project examined the relative importance of physical activity (PA) and body composition on homeostatic model assessment of insulin resistance (HOMA-IR) in older adults and investigated possible racial and/or ethnic differences in these relationships. The analysis included 717 participants from the 2017-2018 National Health and Nutrition Examination Survey study who were 55 years of age or older without diabetes. Results show that HOMA-IR increased with increasing levels of recreational PA, with 1 exception: HOMA-IR decreased with increasing levels of recreational PA in individuals with lower body mass index levels. Racial/ethnic differences in these relationships were identified.
Dysbiosis of the Female Murine Gut Microbiome Exacerbates Neutrophil-mediated Vascular Allograft Injury by Affecting Immunoregulation by Acetate
Authors: Rey Kevin M. , Tam Franklin F. , Enns Winnie , Rahim Javaria F. , Safari Kwestan , Guinto Elizabeth , Van Rossum Thea , Brinkman Fiona S.L. , Choy Jonathan C.
Published: April 2022

Background.

The gut microbiota affects immune responses that cause organ transplant rejection, but the mechanisms by which this occurs remain poorly understood.

Methods.

We have examined, in a murine model, how disruption of the gut microbiota with antibiotics early in life alters this microbial community later in life to affect immune responses that injure vascular allografts.

Results.

Analysis of 16S rRNA and whole genome sequencing of the gut microbiota demonstrated that early life disruption of this microbial community with antibiotics caused a reduction in taxa and enzymatic genes involved in the synthesis of acetate, an immunoregulatory metabolite in mice and humans. When allograft vascular injury was examined, early life disruption of the gut microbiota increased neutrophil accumulation and related medial injury of transplanted arteries. Normalizing the gut microbiota by co-housing and oral administration of acetate prevented neutrophil-mediated vascular allograft injury.

Conclusions.

Dysbiosis of the gut microbiome that reduces its production of the immunoregulatory metabolite acetate exacerbates neutrophil-mediated allograft vascular injury.
Diagnosis and analysis of unexplained cases of childhood encephalitis in Australia using metatranscriptomic sequencing
Authors: Li Ci-Xiu , Burrell Rebecca , Dale Russell C. , Kesson Alison , Blyth Christopher C. , Clark Julia E. , Crawford Nigel , Jones Cheryl A. , Britton Philip N. , Holmes Edward C.
Published: April 2022

Encephalitis is most often caused by a variety of infectious agents identified through diagnostic tests utilizing cerebrospinal fluid. We investigated the clinical characteristics and potential aetiological agents of unexplained encephalitis through metagenomic sequencing of residual clinical samples from multiple tissue types and independent clinical review. Forty-three specimens were collected from 18 encephalitis cases with no cause identified by the Australian Childhood Encephalitis study. Samples were subjected to total RNA sequencing (‘metatranscriptomics’) to determine the presence and abundance of potential pathogens, and to describe the possible aetiologies of unexplained encephalitis. Using this protocol, we identified five RNA and two DNA viruses associated with human infection from both non-sterile and sterile sites, which were confirmed by PCR. These comprised two human rhinoviruses, two human seasonal coronaviruses, two polyomaviruses and one picobirnavirus. Human rhinovirus and seasonal coronaviruses may be responsible for five of the encephalitis cases. Immune-mediated encephalitis was considered likely in six cases and metatranscriptomics did not identify a possible pathogen in these cases. The aetiology remained unknown in nine cases. Our study emphasizes the importance of respiratory viruses in the aetiology of unexplained child encephalitis and suggests that non-central-nervous-system sampling in encephalitis clinical guidelines and protocols could improve the diagnostic yield.
Digging deeper into GWAS signal using GRIN implicates additional genes contributing to suicidal behavior
Authors: Sullivan Kyle A. , Lane Matthew , Cashman Mikaela , Miller J. Izaak , Pavicic Mirko , Walker Angelica M. , Cliff Ashley , Romero Jonathon , Qin Xuejun , Lindquist Jennifer , Mullins Niamh , Docherty Anna , Coon Hilary , Ruderfer Douglas M. ,   International Suicide Genetics Consortium,   VA Million Veteran Program,   MVP Suicide Exemplar Workgroup, Garvin Michael R. , Pestian John P. , Ashley-Koch Allison E. , Beckham Jean C. , McMahon Benjamin , Oslin David W. , Kimbrel Nathan A. , Jacobson Daniel A. , Kainer David
Published: April 2022

Genome-wide association studies (GWAS) identify genetic variants underlying complex traits but are limited by stringent genome-wide significance thresholds. Here we dramatically relax GWAS stringency by orders of magnitude and apply GRIN (Gene set Refinement through Interacting Networks), which increases confidence in the expanded gene set by retaining genes strongly connected by biological networks from diverse lines of evidence. From multiple GWAS summary statistics of suicide attempt, a complex psychiatric phenotype, GRIN identified additional genes that replicated across independent cohorts and retained genes that were more biologically interrelated despite a relaxed significance threshold. We present a conceptual model of how these retained genes interact through neurobiological pathways to influence suicidal behavior and identify existing drugs associated with these pathways that would not have been identified under traditional GWAS thresholds. We demonstrate that GRIN is a useful community resource for improving the signal to noise ratio of GWAS results.
Weight-normative messaging predominates on TikTok – a qualitative content analysis
Authors: Minadeo Marisa , Pope Lizzy
Published: April 2022

Tiktok is a social media platform with many adolescent and young adult users. Food, nutrition, and weight-related posts are popular on TikTok, yet there is little understanding of the content of these posts, and whether nutrition-related content is presented by experts. The objective was to identify key themes in food, nutrition, and weight-related posts on TikTok. 1000 TikTok videos from 10 popular nutrition, food, and weight-related hashtags each with over 1 billion views were downloaded and analyzed using template analysis. The one-hundred most viewed videos were downloaded from each of the ten chosen hashtags. Two coders then coded each video for key themes. Key themes included the glorification of weight loss in many posts, the positioning of food to achieve health and thinness, and the lack of expert voices providing nutrition information. The majority of posts presented a weight-normative view of health, with less than 3% coded as weight-inclusive. Most posts were created by white, female adolescents and young adults. Nutrition-related content on TikTok is largely weight normative, and may contribute to disordered eating behaviors and body dissatisfaction in the young people that are TikTok’s predominant users. Helping users discern credible nutrition information, and eliminate triggering content from their social media feeds may be strategies to address the weight-normative social media content that is so prevalent.
Aperiodic brain activity and response to anesthesia vary in disorders of consciousness
Authors: Maschke Charlotte , Duclos Catherine , Owen Adrian M. , Jerbi Karim , Blain-Moraes Stefanie
Published: April 2022

The analysis of human EEG has traditionally focused on oscillatory power, which is characterized by peaks above an aperiodic component in the power spectral density. This study investigates the aperiodic EEG component of individuals in a disorder of consciousness (DOC); how it changes in response to exposure to anesthesia; and how it relates to the brain’s information richness and criticality. High-density EEG was recorded from 43 individuals in a DOC, with 16 of these individuals undergoing a protocol of propofol anesthesia. The aperiodic component was defined by the spectral slope of the power spectral density. Our results demonstrate that the EEG aperiodic component is more informative about the participants’ level of consciousness than the oscillatory component. Importantly, the pharmacologically induced change in the spectral slope from 30-45 Hz positively correlated with individual’s pre-anesthetic level of consciousness. The pharmacologically induced loss of information-richness and criticality was associated with individual’s pre-anesthetic aperiodic component. During exposure to anesthesia, the aperiodic component was correlated with 3-month recovery status for individuals with DOC. The aperiodic EEG component has been historically neglected; this research highlights the necessity of considering this measure for the assessment of individuals in DOC and future research that seeks to understand the neurophysiological underpinnings of consciousness.
SARS-CoV-2 detection in wastewater as an early warning: the case of metropolitan area of the city of Buenos Aires (AMBA)
Authors: Barrio Alejandro , Borro Verónica , Cicchino Marcelo , Morón Adriana , Coronel Lorena , Vuolo Juan , Mayón Paula , Moroz Ayelén , Maisa Paula , Alcántara Sebastián , Torras María , Cervini Marcos , Arzeno Martín , Godoy Cristian , Campillay Diego , Filiel Nestor , Salas Ana , Salvio Paula
Published: April 2022

Agua y Saneamientos Argentinos S.A. (AySA) delivers essential services as drinking water production and wastewater treatment for more than 14.5 million inhabitants of Buenos Aires Metropolitan Area (AMBA), Argentina, and collects residual liquids of 8.5 million through 16,178 km network. Since the very moment the World Health Organization (WHO) declared the COVID-19 pandemic, AySA developed a methodology to determine SARS-CoV-2 viral genetic load in untreated wastewater as an epidemiological surveillance tool, based on international experiences. In order to monitor viral load in the representative areas of the sewage collection system, more than 1500 samples where concentrated, by using an adapted ultracentrifugation method followed by RNA extraction and quantitative reverse transcription polymerase chain reaction (RT-qPCR), to measure the target Orf1ab gene of SARS-CoV-2 in our molecular microbiology laboratory.

This research was developed for a period that lasted from January 01 to June 02, 2021, in order to anticipate to the current second wave. The results achieved have demonstrated that changes in SARS-CoV-2 RNA are satisfactorily related to local epidemiological data for COVID-19. The association of variables is statistically significant when analyzing data from four large wastewater treatment plants, (R2 > 0.5 and p-value < 0.05), obtaining significant correlations between log10 viral genomic load and log10 positive cases reported one and two weeks later after samples were analyzed.

From the results obtained, it is concluded that the virus sewage system levels were a good predictor of clinical cases to be diagnosed in the immediate future and it is feasible to use this methodology, at local level, as an additional tool for decision-making in public health strategy.

Highlights

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Development of an integrated molecular sampling, analysis and detection system that can alert about the circulation of SARS-CoV-2.

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Early warning of infected population.

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First laboratory in a public water company to develop a monitoring method in Argentina.

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Use of poly aluminum chloride (PAC) as a coagulant in the viral concentration stage.
Determinants of motivated behavior are linked to fatigue and its perturbation by SARS-CoV-2 vaccination
Authors: Stolz David S. , Luebber Finn , Lange Tanja , Borgwardt Stefan , Ziemann Malte , Riemekasten Gabriela , Rupp Jan , Müller-Pinzler Laura , Paulus Frieder M. , Krach Sören
Published: April 2022

Background

Fatigue has an adaptive function and serves as a temporary signal to rest and save energy often in response to immune activation. It may, however, also persist in a pathological condition incurring significant burden. While subjective symptoms and scientific consensus indicate that both physical and mental determinants of motivated behavior are affected in fatigue, the underlying processes are rarely examined using objective, task-based indicators.

Methods

In three consecutive studies, including validation (N = 48) and reliability assessments (N = 27), we use an experimental task to jointly objectify reward learning and effort execution as two determinants of behavioral motivation. In addition, we tested how fatigue and its acute perturbation in response to immune activation after SARS-CoV-2 vaccination are linked to these task-based indicators of motivation in a longitudinal cross-over design (N = 55).

Results

The validation study showed the utility of the experimental task for simultaneously assessing learning, effort exertion, and its regulation based on subjective confidence. The reliability assessment over a one-week period indicated that symptoms of fatigue and task behavior are highly reliable and that repetition effects have little impact on motivated behavior. Finally, in the vaccination trial, we found significant links between fatigue and task behavior. Baseline levels of fatigue predicted how effort is gauged in dependence of current confidence about reward outcomes, and state perturbations of fatigue in the context of the SARS-CoV-2 vaccination reduced confidence during learning. Importantly, task success was significantly lower in subjects who reported high fatigue at baseline and who additionally experienced stronger increase in fatigue in response to vaccination.

Discussion

Our results demonstrate that the experimental task allows to jointly assess determinants of motivated behavior, and to link its constituent processes to subjective fatigue. This suggests that our understanding of fatigue and its perturbation due to acute immune activation can benefit from objective, task-based indicators of the underlying motivational mechanisms. Future studies could build on these findings to further deepen the understanding of neurobehavioral mechanisms underlying fatigue in the context of immune activation.
Pronounced Regional Variation in Esketamine and Ketamine Prescribing to US Medicaid Patients
Authors: Aguilar Alexia G. , Beauregard Burke A. , Conroy Christopher P. , Khatiwoda Yashoda T. , Horsford Shantia M. E. , Nichols Stephanie D. , Piper Brian J.
Published: April 2022

Background

Ketamine, and its isomer esketamine are useful for treatment resistant depression (depression not responsive to traditional antidepressants). Compared to other antidepressants, ketamine and esketamine lack a therapeutic delay and do not increase risk of suicidality in adolescents. Esketamine gained FDA approval in March of 2019.

Objective

This study aimed to geographically characterize ketamine and esketamine prescriptions in the United States among Medicaid patients.

Methods

Ketamine and esketamine prescription rate data per state per quarter were obtained from the Medicaid State Drug Utilization Database for 2019-2020. Total prescription rates per year for ketamine and esketamine were obtained for 2009-2020.

Results

Between 2009-2020, ketamine prescribing rates peaked in 2013 followed by a general decline. For ketamine and esketamine prescriptions in 2019, Montana and Indiana showed significantly higher prescription rates, respectively, relative to the national average. A total of 21 states prescribed neither ketamine or esketamine in 2019. Since its approval, esketamine prescriptions have surpassed those of ketamine. There was a 121.3% increase in esketamine prescriptions from 2019 to 2020. Ten states prescribed neither ketamine or esketamine in 2020.

Conclusion

Despite the effectiveness of ketamine and esketamine for treatment resistant depression, their use among Medicaid patients was limited and variable in many areas of the US.
Vaping preferences of individuals who vaporise dry herb cannabis, cannabis liquids and cannabis concentrates
Authors: Morgan Jody , Gschwend Grace , Houston Matilda , Jones Alison , Kelso Celine
Published: April 2022

In 2019 an estimated 200 million people aged 15-64 used cannabis, making cannabis the most prevalent illicit substance worldwide. The last decade has seen a significant expansion in the cannabis vaporiser market, introducing cannabis vaporisation as a common administration method alongside smoking and ingestion. Despite reports of increased prevalence of cannabis vaporisation there has been little research into the use of these devices. To remedy the current dearth of data in this area this study utilised an anonymous online survey of individuals who self-reported past cannabis vaporisation. The respondents (N=557) were predominantly young (<35 years) and male. Most (91.4%) stated they had ever vaped dry herb cannabis, 59.1% reported vaporisation of cannabis oil or liquids, and 34.0% reported vaporisation of cannabis concentrates. This study identifies the types of vaporisation devices (including brands and models) employed by cannabis vapers, as well as the vaporisation temperatures and puff durations commonly used for dry herb, cannabis liquids and cannabis concentrates. To the best of our knowledge, this is the first time the usual operating temperatures of these vaporisation devices and user specific consumption patterns such as puff duration have been reported for cannabis vaping. This information will allow for more realistic experimental conditions in research settings.
Effects of the introduction of interprofessional conferences on the intensive care unit: Comparison of the length of stay in the intensive care unit before and after the introduction of interprofessional conferences
Authors: Watanabe Daichi , Uranaka Keiichi , Asazawa Kyouko , Akimoto Takako , Ohnuma Hironori
Published: April 2022

Recently, interprofessional team medicine has been practiced to achieve medical safety and improve patient outcomes. This study evaluated the effects of interprofessional conferences on intensive care units (ICUs) by comparing outcomes before and after their introduction. This study was conducted at a single center and included 1,765 patients who were admitted to the ICU between April 2017 and March 2019. There were 898 patients in the group before the introduction of conferences (before group) and 867 patients in the group after the introduction of conferences (after group). The interprofessional conferences involved physicians, nurses, physical therapists, nutritionists, and pharmacists. Data were extracted from the medical records. The primary outcome measure was the ICU length of stay (LOS). The secondary outcome measures were hospital LOS and rehabilitation and nutrition started within 48 hours of ICU admission. These outcomes were compared before and after the introduction of interprofessional conferences. The adjusted variables were gender, age, body mass index, ICU readmission, outcome, Barthel index at admission, and disease (classified by the International Statistical Classification of Diseases and Related Health Problems 10th edition). The ICU LOS (regression coefficient: -0.08; 95% confidence interval [CI]: -0.13 to -0.04) and hospital LOS (regression coefficient: -2.96; 95% CI: -5.20 to -0.72) were significantly shorter in after group than in the before group. Moreover, the proportion of patients who commenced nutrition (odds ratio [OR]: 1.45; 95% CI: 1.14 to 1.84) and rehabilitation (OR: 0.77; 95% CI: 0.51 to 1.17) within 48 hours of ICU admission was significantly higher in the after group than in the before group. Interprofessional conferences effectively reduced the ICU LOS and hospital LOS and improved the likelihood of commencing nutrition and rehabilitation within 48 hours of ICU admission.
Critical Arterial Stenosis Revisited
Authors: Archie Joseph P
Published: April 2022

Introduction

Stenosis of an organ/tissue primary artery can produce ischemia or only reduce blood flow reserve. Despite incomplete hemodynamic understanding of critical arterial stenosis, degree of diameter stenosis continues to be an index for patient management. This study aims to use the law of conservation of energy to quantitate the arterial pressure gradient produced by stenosis, determine organ/tissue perfusion pressure, blood flow and reserve as a function of degree of diameter stenosis and determine ischemic critical diameter stenosis.

Methods

The three-component model is parallel stenotic artery and collateral arteries supplying an organ/tissue. The three hemodynamic variables are blood pressure, blood flow and frictional percent diameter stenosis. Two new non-dimensional variables, K and C, are introduced to simplify understanding. K is the magnitude of arterial diameter stenosis produced energy dissipation. C is the magnitude of potential collateral blood flow. Conservation of energy analysis of arterial stenosis gives the pressure gradient produced and stenosis vascular resistance. Organs/tissues intrinsically autoregulate blood flow when perfusion pressure is greater than threshold value. Model energy analysis defines collateral vascular resistance and gives perfusion pressure, blood flow and reserve as a function of diameter stenosis. Results are illustrated in both pressure-stenosis domain and blood flow-stenosis domain. Renal and internal carotid artery (ICA) stenosis numerical results are in cm/gram/sec (CGS) units.

Results

The magnitude of arterial stenosis energy dissipation is proportional to K, a fourth power function of stenosis diameter with a steep slope between 65% and 80%, (K = 67 to 625). Organs/tissues without collaterals, C = 0, have specific critical arterial stenosis values within this range. For a renal artery with average diameter and blood flow critical stenosis is 74% (K = 233). Organ tissues with collateral blood flow potential equal to their normal resting blood flow have C = 1.0. Those with poor collaterals, C < 1, have critical stenosis from 65% to 99% depending on collateral magnitude, 0 < C < 1. In this group critical ischemic ICA stenosis begins at 70% and up to 99%, (K = 132 to ∞). Organ/tissues with good collateral circulation, C > 1, do not have ischemic critical stenosis, including the ICA. However, in these patients stenosis progression reduces blood flow reserve.

Conclusion

Arterial stenosis may or may not produce an ischemic critical value for specific organ/tissue supplied depending on the magnitude of collateral circulation.