bluuebunny/crossref_metadata_2025 huggingface dataset:
Acylcarnitines and Genetic Variation in Fat Oxidation Genes in HIV-infected, Antiretroviral-treated Children With and Without Myopathy
Authors: Kirmse Brian , Hobbs Charlotte , Aaron Lisa , Montepiedra Grace , Summar Marshall , Williams Paige L. , Smith Caitlin J. , Van Dyke Russell , Yu Chunli , Ryckman Kelli K. , Borkowsky William ,   for the Pediatric HIV/AIDS Cohort Study
Published: May 2022

Background:

Mitochondrial toxicity resulting in myopathy and lactic acidosis has been described in antiretroviral (ARV)-exposed patients. We hypothesized that myopathy in HIV-infected, ARV-treated children would be associated with metabolic (acylcarnitines) and genetic (variants in metabolic genes) markers of dysfunctional fatty acid oxidation (FAO).

Methods:

Acylcarnitine profiles (ACP) were analyzed for 74 HIV-infected children on nucleoside reverse transcriptase inhibitor (NRTI)-containing ARV. Thirty-seven participants with ≥2 creatine kinase measurements >500 IU (n = 18) or evidence of echocardiographic cardiomyopathy (n = 19) were matched with 37 participants without myopathy. Single nucleotide polymorphisms (SNPs) in FAO genes were also evaluated.

Results:

Abnormal ACP was 73% (95% CI: 56%–86%) and 62% (95% CI: 45%–78%) in the myopathic and nonmyopathic groups, respectively. No significant association was found between myopathy and having an abnormal ACP (OR = 2.10, P = 0.22). In univariate analysis, a 1-year increase in NRTI use was associated with a 20% increase in odds of at least 1 ACP abnormality [OR (95% CI) = 1.20 (1.03–1.41); P = 0.02), and a 1-year increase in protease inhibitor use was associated with 28% increase in the odds of having at least 1 ACP abnormality [OR (95% CI) = 1.28 (1.07–1.52); P = 0.006). Three SNPs, all in the gene for the carnitine transporter (SLC22A5), were associated with the cardiomyopathy phenotype.

Conclusion:

FAO appears to be altered in HIV-infected children with and without myopathy, but abnormal FAO does not fully explain myopathy in ARV-exposed children. Further study of SLC22A5 variation in ARV-exposed people is warranted carnitine transporter dysfunction-related cardiomyopathy may be treatable.
Hepatosplenic Cat Scratch Disease and Prolonged Fever: When To Add Corticosteroids?
Authors: Pérez Pérez Alicia , Fernández Miaja María , Díaz García Paula , García Suárez Laura , Rodríguez Pérez Mercedes , Rodríguez de la Rúa Victoria , Alonso Álvarez Maria Agustina
Published: May 2022

The indications for use of corticosteroids for persistent fever in cat scratch disease are controversial. We report the case of a 5-year-old boy diagnosed with systemic cat scratch disease, who presented with fever for 28 days and focal hepatosplenic lesions. He did not show improvement despite antibiotic treatment for 4 weeks, however, he became afebrile 24 hours after the administration of corticosteroids.
Early Childhood Providers' Perceptions of Effective Professional Development Components
Authors: Pfeiffer Danika , Feuerstein Julie , Herman Dana , Landa Rebecca
Published: May 2022

A research-to-practice gap exists between evidence-based practices (EBPs) and actual practices implemented with children with developmental disabilities (DD) in early childhood care and education (ECCE) settings. Many ECCE providers lack the training needed to support these children's learning. Ten center-based providers working in inclusive ECCE classrooms participated in the Early Achievements for Child Care Providers Professional Development (EA-CP PD) program to learn to deliver differentiated instruction to children with DD using EBPs. Post-PD focus groups assessed the training's impact on providers' perceptions of the PD program and implementation of the EA-CP instructional strategies. Results of qualitative analysis revealed providers' perceived benefit of job-embedded coaching to support their implementation of the instructional strategies and ability to enhance children's social–communication and language development. Providers desired greater involvement from ECCE directors. Implications are discussed for giving directors more explicit roles in providers' PD to support implementation and enhance child outcomes.
Do Physician Assistant Training Programs Adequately Prepare PAs to Address Nutritional Issues in Clinical Practice?
Authors: Wolf Corri , Mandel Ellen , Peniuta Morgan , Lazure Patrice , Smith Noël E. , Peterson Eric D. , Péloquin Sophie
Published: May 2022

Purpose

The purpose of this study was to determine physician assistants' (PAs') current level of confidence to engage in nutrition-related tasks and their satisfaction with the nutrition education they received in PA school.

Methods

To achieve this goal, a mixed-methods approach that consisted of 3 data collection phases (qualitative online discussions, quantitative survey, and qualitative interviews) was used to explore and measure PAs' perceptions of the education they received in PA school and through other sources and how confident they felt addressing nutrition-related issues in clinical practice.

Results

While 80% of PAs endorse the idea that PAs should be more involved in providing nutritional care to patients, the majority reported basic or no knowledge of the nutritional implications of chronic conditions (69%), inflammatory bowel disease (69%), nutritional needs over the lifespan (67%), and food allergies and intolerances (64%). Barriers to patient care included knowledge-related challenges when selecting lab tests based on patient profile (46%) and identifying needs based on various gastrointestinal diseases (67%) and when using diagnostic data to identify deficiencies (74%). Overall, 59% of PAs reported being slightly or very dissatisfied with the nutrition-related content in the curricula used to formally train PAs.

Conclusions

The primary goal of every PA program is to prepare its graduates to be competent to enter clinical practice. Regarding nutrition, these data indicate that programs are failing to do so. PAs lack the confidence and ability to provide optimal nutritional care, which is staggering considering that nutrition is the first line of treatment in the prevention and management of numerous chronic diseases.
Vertical split fracture of the vertebral body following oblique lumbar interbody fusion
Authors: Hong Jong-Hwan , Han Moon-Soo , Lee Jung-Kil , Moon Bong Ju
Published: May 2022

Rationale:

Oblique lumbar interbody fusion (OLIF) is an effective and safe surgical technique widely used for treating spondylolisthesis; however, its use is controversial because of several associated complications, including endplate injury. We report a rare vertebral body fracture following OLIF in a patient with poor bone quality.

Patient concerns:

A 72-year-old male patient visited our clinic for 2 years with lower back pain, leg radiating pain, and intermittent neurogenic claudication.

Diagnoses:

Lumbar magnetic resonance imaging revealed L4-5 stenosis.

Intervention:

We performed OLIF with percutaneous pedicle screw fixation and L4 subtotal decompressive laminectomy. We resected the anterior longitudinal ligament partially for anterior column release and inserted a huge cage to maximize segmental lordosis. No complications during and after the operation were observed. Further, the radiating pain and back pain improved, and the patient was discharged. Two weeks after the operation, the patient visited the outpatient department complaining of sudden recurred pain, which occurred while going to the bathroom. Radiography and computed tomography revealed a split fracture of the L5 body and an anterior cage displacement. In revision of OLIF, we removed the dislocated cage and filled the bone cement between the anterior longitudinal ligament and empty disc space. Further, we performed posterior lumbar interbody fusion L4-5, and the screw was extended to S1.

Outcomes:

After the second surgery, back pain and radiating pain in the left leg improved, and he was discharged without complications.

Lesson:

In this case, owing to insufficient intervertebral space during L4-5 OLIF, a huge cage was used to achieve sufficient segmental lordosis after anterior column release, but a vertebral body coronal fracture occurred. In patients with poor bone quality and less flexibility, a huge cage and over-distraction could cause a vertebral fracture; hence, selecting an appropriate cage or considering a posterior approach is recommended.
Concurrent ascending colon adenocarcinoma and ileocecal tuberculosis
Authors: Park Sun Min , Kim Ji Hoon , Chong Yosep , Kang Won-Kyung
Published: May 2022

Rationale:

Few cases have been reported of the coexistence of tuberculosis and adenocarcinoma of the large bowel. We report a rare case of concurrent ascending colon adenocarcinoma and ileocecal tuberculosis, which were nearly indistinguishable from one another.

Patient concerns:

A 59-year-old man visited our clinic with dizziness and anorexia.

Diagnosis:

Computed tomography revealed a mass in the ascending colon with ill-defined nodules in the liver. A colon biopsy showed adenocarcinoma with multinucleated giant cells. The liver nodules were confirmed to be metastatic adenocarcinomas.

Interventions:

Ant tuberculosis medications were administered prior to surgery. Two weeks later, a laparoscopic right hemicolectomy and radiofrequency ablation of the liver were performed.

Outcomes:

The final pathology confirmed adenocarcinoma with chronic granulomatous inflammation and giant cells.

Lessons:

In this patient, the cancer was in an advanced stage and had no history of tuberculosis infection. Thus, in this case, the malignancy seemed to create the proper environment for either reactivation of a latent tuberculosis infection or, less likely, for the acquisition of a primary mycobacterial infection. In conclusion, clinicians should be aware of the possibility of concurrent colon adenocarcinoma and intestinal tuberculosis.
Current approach of primary bilateral adrenal hyperplasia
Authors: Delivanis Danae A. , Vassiliadi Dimitra A. , Tsagarakis Stylianos
Published: May 2022

Purpose of review

To discuss the most recent findings on the pathophysiology, the genetic and molecular causes of primary bilateral adrenal hyperplasia (PBAH). The diagnostic approach of patients with PBAH will also be presented in detail with an emphasis on the emerging diagnostic tools and finally, the treatment of PBAH will be discussed with an emphasis on the newest surgical and medical treatment approaches.

Recent findings

PBAH is a highly heterogeneous condition mostly detected incidentally on abdominal imaging. Based on the size of the nodules, PBAH is subdivided into primary bilateral macronodular adrenal hyperplasia (PBMAH) and micronodular adrenal hyperplasia. A substantial proportion of patients with PBMAH harbor a germline mutation of the armadillo repeat containing 5 tumor suppression gene and therefore genetic testing is strongly recommended. Measurements of plasma or urinary multisteroid profiles show promising results in that PBMAH has a distinctive plasma steroid fingerprint that can help in diagnosis and subtyping of PBMAH. Finally, although surgery is the mainstay of treatment of patients with PBAH, medical therapy is increasingly emerging as an alternative option.

PBAH is a poorly studied and therefore a challenging disease to diagnose and treat. Hopefully with these newest diagnostic and therapeutic tools, a more comprehensive approach will be adopted.
Utilization of Antitumor Necrosis Factor Biologics in Very Early Onset Inflammatory Bowel Disease: A Multicenter Retrospective Cohort Study From North America
Authors: Kerur Basavaraj , Fiedler Karoline , Stahl Marisa , Hyams Jeffrey , Stephens Michael , Lu Ying , Pfefferkorn Marian , Alkhouri Raza , Strople Jennifer , Kelsen Judith , Siebold Leah , Goyal Alka , Rosh Joel R. , LeLeiko Neal , Van Limbergen Johan , Guerrerio Anthony L. , Maltz Ross M. , Karam Lina , Crowley Eileen , Griffiths Anne M. , Heyman Melvin B. , Deneau Mark , Benkov Keith , Noe Joshua , Moulton Dedrick , Pappa Helen , Galanko Joseph , Snapper Scott , Muise Aleixo M. , Kappelman Michael D. , Benchimol Eric I.
Published: May 2022

Background:

Research on the utilization and effectiveness of antitumor necrosis factor (TNF) biologics in children with very early onset inflammatory bowel disease (VEOIBD) is urgently needed. Here we describe anti-TNF use and durability in a multicenter cohort.

Methods:

We performed a retrospective cohort study of patients diagnosed with VEOIBD (<6 years) between 2008 and 2013 at 25 North American centers. We performed chart abstraction at diagnosis and 1, 3, and 5 years after diagnosis. We examined the rate of initiation and durability of infliximab and adalimumab and evaluated associations between treatment durability and the following covariates with multivariate Cox proportional hazard regression: age at diagnosis, sex, disease duration, disease classification, and presence of combined immunomodulatory treatment versus monotherapy.

Results:

Of 294 children with VEOIBD, 120 initiated treatment with anti-TNF therapy and 101 had follow-up data recorded [50% Crohn disease (CD), 31% ulcerative colitis (UC), and 19% IBD unclassified (IBD-U)]. The cumulative probability of anti-TNF treatment was 15% at 1 year, 30% at 3 years, and 45% at 5 years from diagnosis; 56 (55%) were treated between 0 and 6 years old. Anti-TNF durability was 90% at 1 year, 75% at 3 years, and 55% at 5 years. The most common reason for discontinuation of anti-TNF were loss of response in 24 (57%) children. Children with UC/IBD-U had lower durability than those with CD (hazard ratio [HR] 0.17; 95% confidence interval [CI], 0.06–0.51; P = 0.001).

Conclusions:

Utilization and durability of anti-TNF in VEOIBD is relatively high and comparable with older children. Having Crohn disease (compared with UC/IBD-U) is associated with greater durability.
Impact of Pancreatic Enzymes on Enteral Fat and Nitrogen Absorption in Short Bowel Syndrome
Authors: Sainath Nina N. , Bales Christina , Brownell Jefferson N. , Pickett-Blakely Octavia , Sattar Aisha , Stallings Virginia A.
Published: May 2022

Objectives:

Patients with short bowel syndrome (SBS) can have a high morbidity rate. To minimize morbidity, enteral autonomy is the primary goal in clinical management of patients with SBS. This is often difficult to achieve because of significant malabsorption. To date, there are limited therapies that improve absorption in patients with SBS. The impact of pancreatic enzyme replacement treatment on enteral absorption has not been studied in this population and was the primary aim of this study.

Subjects/methods:

This was an interventional study in 11 subjects (6 pediatric subjects ages 4.0–17.9 years, 5 adult subjects 18–75 years) that compared enteral absorption in each subject before and after pancreatic enzyme medication (Creon). Coefficient of fat absorption (CFA) and coefficient of nitrogen absorption (CNA) were used as markers of enteral absorption of fat and protein, respectively.

Results:

There was no statistically significant mean change in CFA and CNA before and after pancreatic enzyme medication therapy. Six subjects demonstrated an increase in CFA and 8 subjects demonstrated an increase in CNA after the use of pancreatic enzyme medication therapy.

Conclusions:

There was no statistically significant improvement in enteral fat and protein absorption in the cohort as a whole, though several subjects demonstrated an improvement. These results suggest that some patients with SBS may benefit from treatment with pancreatic enzymes. Further studies are needed to better evaluate the effect of pancreatic enzyme therapy on enteral absorption in subjects with SBS and to characterize factors that may predict a positive response.
Bariatric Surgery
Authors: Ranjit Rajesh , Alexandrovna Lapik Irina , Minkailovna Gapparova Kamilat , Vladimirovich Galchenko Alexey
Published: May 2022

Today, bariatric surgery is the most effective treatment of obesity. Restrictive surgeries are aimed at reducing the volume of the stomach. Such operations have the least adverse effects in terms of the physiology of digestion. However, they are less effective in losing weight. Mixed operations (gastric bypass surgery, biliopancreatic diversion) decrease the volume of the stomach and the length of the small intestine. Mixed operations tend to provide more pronounced results in a short time. However, by seriously disrupting the digestion and absorption of the food, they may result in severe micronutrient deficiencies. The assimilation of lipophilic substances is severely impaired as the biliopancreatic system is almost disconnected from the digestive tract. Furthermore, the assimilations of not only fats and essential fatty acids but also all fat-soluble vitamins are interrupted. In most cases, these patients need to take high-dose micronutrient supplements for their whole life. Usually, deficiencies of vitamins A, D, E, C, and vitamins of group B, especially B1, B6, B12, niacin, and folate, as well as iron, calcium, phosphate, magnesium, zinc, copper, and selenium, are found after operations. Restrictive operations, although less traumatic for the digestive system, significantly disrupt the digestion and absorption of nutrients, especially those in which the stomach plays a significant role in its digestion. These are proteins, folate, niacin, vitamin B12, iron, and copper. Bariatric surgical procedures are like a double-edged sword. They can be highly effective in the treatment of obesity and related complications; nevertheless, they are surgeries with serious potential for complications.
Doris Howes Calloway
Authors: King Janet C. , Kretsch Molly J. , Butte Nancy F. , Murphy Suzanne P. , Yates Allison A. , Blackburn Mary L.
Published: May 2022

Although the importance of diet quality was identified more than 120 years ago, it was nearly 60 years before the specific quantitative nutrient needs for humans were determined. Dr Doris Howes Calloway, a nutrition professor at the University of California in Berkeley, established a metabolic unit for studying human nutrient requirements. This article reviews the early origins of human nutrition research and the unique contributions of Dr Calloway worldwide.
Report From the Field: Public Health Equity Through Innovative Multisector Data Sharing
Authors: Tanner Clare , Strzyzykowski Trevor , Mannor Kara , Hendricks-Sturrup Rachele
Published: May 2022

Context:

Data sharing across sectors for the purpose of driving health equity is a particularly innovative yet emerging concept in public health practice and research, although the extent to which public health entities engage in multisector data sharing and initiatives is currently underexplored. This practice report examines the nature and extent to which public health entities are sharing data across sectors in ways that are innovative and supportive of their organizational missions to promote community health equity and well-being.

Program:

As a program office of the Robert Wood Johnson Foundation, Data Across Sectors for Health (DASH) seeks to promote and support data sharing systems leveraged toward equitable improvements to health.

Implementation:

We pilot tested, revised, and disseminated the 2021 All In National Inventory, a survey implemented to scan the environment to track progress and challenges in the field of data sharing, and feed lessons learned back into communities to cultivate further public health innovations involving shared data and infrastructure development.

Evaluation:

Use case development, engaging communities to cocreate shared data systems.

Discussion:

Findings show public health plays a pivotal role in innovation to share data across sectors to serve as a community health improvement foundation. While public health often leads these initiatives to improve health and promote health equity, national data suggest there is much room for improvement in incorporating equitable data sharing practice.
The Public Health National Center for Innovations: An Initial Qualitative Evaluation
Authors: Siegfried Alexa L. , Kennedy Mallory , Gonick Shannon A. , Liotta Madeleine
Published: May 2022

Context:

The Public Health National Center for Innovations (PHNCI) was launched in 2015 as a division of the Public Health Accreditation Board (PHAB) to serve as a hub for fostering public health innovation and transformation.

Objectives:

We explored perspectives of key informants to assess PHNCI's work in its first 5 years, including implementation of activities, outputs, accomplishments, and opportunities.

Design:

This qualitative study involved a Web site review; secondary document review; 15 interviews with 17 key informants purposively sampled from 2 groups—PHNCI and PHAB staff and leadership (PHNCI respondents), and external partners and collaborators (external respondents); and thematic analysis of qualitative data.

Setting:

United States.

Results:

PHNCI implemented its planned activities over the past 5 years—including grant programs and learning communities; large-scale public health initiatives; conferences, events, and convenings; webinar trainings; and resources, tools, and materials—resulting in more than 150 outputs. According to key informants, PHNCI's major accomplishments were as follows: contributed to an increased understanding and awareness of innovation in the public health field; provided grants and learning communities to support innovation; developed and disseminated materials to help practitioners innovate; established partnerships and promoted cross-sector collaboration; supported systems transformation; incorporated innovation into public health accreditation; and focused efforts to advance health equity.

Conclusions:

Going forward, PHNCI should continue to prioritize its core activities that support public health innovation and transformation; expand its work by addressing innovation in new public health topic areas; strengthen and expand its cross-sector work, partnerships, and activities to advance health equity and antiracism; and increase its visibility and reach, particularly within other sectors. Continued commitment and leadership are important for strengthening the capacity of the public health system to innovate, respond to ongoing and emerging public health threats and challenges, and advance health equity.
Characteristics of office workers who benefit most from interventions for preventing neck and low back pain: a moderation analysis
Authors: Akkarakittichoke Nipaporn , Jensen Mark P. , Newman Andrea K. , Waongenngarm Pooriput , Janwantanakul Prawit
Published: May 2022

Introduction:

Neck and low back pain are significant health problem in sedentary office workers. Active break and postural shift interventions has been proved to reduce the incidence of new onset of both neck and low back pain.

Objectives:

To identify variables that moderate the effects of active breaks and postural shift interventions on the development of neck and low back pain in office workers.

Methods:

Using data from a 3-arm (active break, postural shift, and control group) cluster randomized controlled trial (N = 193), we evaluated the moderating effects of age, job position, education level, sex, perceived psychological work demands, number of working hours, and using a chair with lumbar support on the benefits of 2 interventions designed to prevent the development of neck and low back pain in office workers. Moderation analyses were conducted using the Hayes PROCESS macro, with post hoc Johnson–Neyman techniques and logistic regressions.

Results:

Significant interactions between intervention groups and 3 moderators assessed at baseline emerged. For the prevention of neck pain, the effect of the active break intervention was moderated by the number of working hours and the effect of the postural shift intervention was moderated by the level of perceived psychological work demands and the number of working hours. For the prevention of low back pain, the effect of postural shift intervention was moderated by having or not having a chair with lumbar support.

Conclusions:

The study findings can be used to help determine who might benefit the most from 2 treatments that can reduce the risk of developing neck and low back pain in sedentary workers and may also help us to understand the mechanisms underlying the benefits of these interventions.
Tele-Untethered: Telemedicine Without Waiting Rooms
Authors: Meyer Brett C. , Perrinez Emily S. , Payne Keith , Carreño Shivon , Partridge Brittany , Braunlich Brian , Tangney Jeff , Sylwestrzak Marc , Kremer Brendan , Kane Christopher J. , Longhurst Christopher A.
Published: May 2022

Background and Objectives:

Telemedicine bridges the gap between care needs and provider availability. The value of telemedicine can be eclipsed by long wait times, especially if patients are stuck in virtual waiting rooms. UCSD Tele-Untethered allows patients to join visits without waiting in virtual waiting rooms. Tele-Untethered uses a text-to-video link to improve clinic flow, decrease virtual waiting room reliance, improve throughput, and potentially improve satisfaction.

Methods:

This institutional review board (IRB)-approved quality improvement pilot (IRB #210364QI) included patients seen in a single vascular neurology clinic, within the pilot period, if they had a smartphone/cell phone, and agreed to participate in a flexible approach to telehealth visits. Standard work was disseminated (patient instructions, scripting, and workflows). Patients provided a cell phone number to receive a text link when the provider was ready to see them. Metrics included demographics, volumes, visit rates, percentage seen early/late, time savings, and satisfaction surveys.

Results:

Over 2.5 months, 22 patients were scheduled. Of those arriving, 76% were “Tele-Untethered” and 24% were “Standard Telemedicine.” Text-for-video link was used for 94% of Tele-Untethered. Fifty-five percent were seen early. There was a 55-minute-per-session time savings.

Conclusion:

This UCSD Tele-Untethered pilot benefitted patients by allowing scheduling flexibility while not being tied to a “virtual waiting room.” It benefited providers as it allowed them to see patients in order/not tied to exact times, improved throughput, and saved time. Even modest time savings for busy providers, coupled with Lean workflows, can provide critical value. High Tele-Untethered uptake and use of verbal check-in highlight that patients expect flexibility and ease of use. As our initial UCSD Tele-Untethered successes included patient flexibility and time savings for patients and providers, it can serve as a model as enterprises strive for optimal care and improved satisfaction. Expansion to other clinic settings is underway with a mantra of “UCSD Tele-Untethered: Your provider can see you now.”
Resolution of Misleading COVID-19 Vaccination–Related Nodal and Splenic FDG Uptake in the Follow-up Study
Authors: Bhimaniya Sudhir , Jahromi Amin
Published: May 2022

Newly diagnosed low-grade bilateral breast lymphoma in 63-year-old woman demonstrated intense FDG uptake in the left axillary lymph nodes and the spleen, concerning for lymphomatous involvement. Subsequent ultrasound-guided biopsy did not demonstrate any pathologic left axillary lymph nodes. Further investigation revealed COVID-19 vaccination in the left arm, 5 days prior to the 18F-FDG PET/CT study. Six-month follow-up 18F-FDG PET/CT showed resolution of the intense FDG uptake in the left axillary lymph nodes and spleen without any treatment, suggesting a self-remitting acute local and systemic immune response to COVID-19 vaccination.
Hemodynamic Response to Acute Volume Load and Endomyocardial NO-synthase Gene Expression in Heart Transplant Recipients
Authors: Kobediona Monika , Bartunek Jozef , Delrue Leen , Van Durme Frederik , Lau Chirik Wah , Moya Ana , Verstreken Sofie , Heggermont Ward , Dierckx Riet , Goethals Marc , Vanderheyden Marc
Published: May 2022

Background.

A pulmonary capillary wedge pressure (PCWP) >18 mm Hg following volume load has been proposed as a partition value for the detection of heart failure with preserved ejection fraction. As hemodynamic changes in filling pressures (FP) have been attributed to a nitric oxide (NO)-mediated rightward shift of the pressure-volume relationship, we investigated the hemodynamic response to volume load in heart transplant recipients (HTx) and examined the role of inducible NO synthase (iNOS) gene expression on diastolic function changes.

Methods.

In 36 HTx, FPs were measured before and after volume load, following which Starling curves were constructed using PCWP and cardiac index (CI). Patients were categorized into those with normal (group A, n = 21) and abnormal hemodynamics (group B, n = 15, PCWP >15 mm Hg at rest or >18 mm Hg following volume load). For the establishment of the potential role of NO, endomyocardial iNOS gene expression level was measured.

Results.

Except for PCWP (P < 0.001) and mean pulmonary artery pressure (P < 0.001) no differences in age, baseline characteristics, and ejection fraction were observed between both groups, and volume load significantly increased PCWP in both groups (group A: P < 0.001 and group B: P < 0.001) without any change in heart rate. Interestingly, volume load significantly increased CI in group A (P < 0.001) but not in group B (P = 0.654), and the Starling curves revealed a higher CI at any given PCWP in group A together with significantly higher iNOS gene expression (P = 0.009).

Conclusions.

In HTx, volume load increases FP and unmasks the presence of left ventricular diastolic dysfunction. Interestingly, following saline load group B shows a blunted Starling response, with higher PCWP and lack of CI increase at any given PCWP. The higher iNOS gene expression level in group A suggests a potential role of NO as mediator of diastolic function.
Longitudinal Evaluation of Cytopenias in the Renal Transplant Population
Authors: Johnson Aileen C. , Karadkhele Geeta , Magua Wairimu , Vasanth Payas , Larsen Christian P.
Published: May 2022

Background.

Cytopenias, a common complication for immunosuppressed patients, are known to be associated with adverse transplant outcomes. However, there is little information on cytopenias in recipients treated with the costimulation blockade agent, belatacept.

Methods.

We compared cytopenia incidence and manifestations in patients undergoing kidney transplant at Emory University Hospital on tacrolimus and belatacept. To reduce selection bias, the tacrolimus group was narrowed to include only patients eligible for belatacept.

Results.

Of 1651 patients transplanted between 2009 and 2019, 187 (11%) experienced severe anemia, 309 (19%) experienced leukopenia, and 62 (4%) thrombocytopenia. On multivariable regressions, deceased-donor transplant, cytomegalovirus viremia, and thymoglobulin treatment were associated with risk of developing leukopenia, anemia, and thrombocytopenia. High-risk cytomegalovirus status was also associated with development of leukopenia and anemia. Additionally, azathioprine was associated with development of anemia, and both tacrolimus therapy and Caucasian race were associated with thrombocytopenia. Longitudinal quantifications of hematologic cell lines over the first-year posttransplant were extracted from generalized linear models fit using splines. Only hemoglobin range was significantly different between groups (greater in belatacept patients). Plots of mean cell count for each group suggest an earlier recovery from posttransplant anemia in belatacept patients.

Conclusions.

Belatacept patients are not at increased risk of cytopenia but may have improved recovery from posttransplant anemia.
Vegetables and rhizospheres as the reservoir for extensively drug-resistant (XDR) Pseudomonas aeruginosa
Authors: Sakthivel Ambreetha , Mathee Kalai , Dananjeyan Balachandar
Published: May 2022

Pseudomonas aeruginosais an urgent threat pathogen due to its evolving resistance to multiple antibiotics. Agricultural soil and plants are the vast reservoirs of this much-dreaded opportunistic bacterium. A few human isolates of P. aeruginosa are known to infect plants and insects. However, there is no report on the occurrence of multi-drug resistant P. aeruginosa in edible vegetable crops. This study compared 18 P. aeruginosa isolates from the rhizosphere and endophytic niches of four different vegetable crops (cucumber, tomato, eggplant, and chili) with three known clinical strains. All the isolates were tested for virulence traits such as resistance to various antibiotics classes, motility, biofilm, and production of virulence factors (rhamnolipid, pyocyanin, hemolysin, proteases, and lipases). Hierarchical clustering based on Ward minimum variance with Manhattan distance matrix grouped the strains into three clusters based on their phenotypic traits. Strains were exhibiting the highest virulence co-clustered with the human pathogenic isolates. These strains were resistant to cephalosporins, aminoglycosides, macrolides, nitrofurans, tetracyclines, and sulfonamides. These extensively drug-resistant (XDR) strains were only susceptible to polymyxin (colistin) and quinolone (cephalosporin). This study shows that the virulence traits are shared between plant- and human-isolates of P. aeruginosa. More importantly, the occurrence of XDR strains in vegetable crops is a serious global threat.
Nitrofurantoin-resistant Escherichia coli in the UK: genetic determinants, diversity, and undetected occurrences
Authors: Wan Yu , Mills Ewurabena , Leung Rhoda C. Y. , Vieira Ana , Jauneikaite Elita , Zhi Xiangyun , Croucher Nicholas , Ellington Matthew J. , Sriskandan Shiranee
Published: May 2022

Background

Antimicrobial resistance in enteric or urinary E. coli might predispose invasive E. coli infection and bacteraemia. Nitrofurantoin resistance occurs in <6% of UK urinary E. coli isolates, however, 2018 national recommendations to prescribe nitrofurantoin for uncomplicated urinary tract infection (UTI) raised concerns for increased prevalence of nitrofurantoin-resistant E. coliin the future. Therefore, we investigated mechanisms of nitrofurantoin resistance in UK E. coli isolates and assessed their occurrences in a large dataset of E. coli genomes.

Methods

To elucidate chromosomal and acquired genetic determinants of nitrofurantoin resistance in E. coli, we analysed whole-genome sequences of nine randomly selected nitrofurantoin-resistant UTI E. coli isolates from West London. We then performed targeted analysis of 12,412 E. coli genomes collected from across the UK and predicted nitrofurantoin susceptibility from identified genotypes.

Results

Using comparative genomics, we found known and novel point mutations or insertion sequences (ISs) in chromosomal genes encoding oxygen-insensitive nitroreductases NfsA and NfsB in the nine isolates. Most of these genetic alterations resulted in gene inactivation. We also identified the same kinds of mutations in NfsA, NfsB, and their associated enzyme RibE in a number of 12,412 E. coli genomes. We also observed homoplasic mutations in all these proteins. By contrast, multidrug efflux pump OqxAB, which confers resistance when horizontally transferred, was only encoded by one genome.

Conclusions

Chromosomal de novo mutations and ISs are main causes of nitrofurantoin resistance in UK E. coli. Prevalence of nitrofurantoin resistance should be monitored among urine, blood, and enteric isolates as nitrofurantoin exposure increases.
Microbial community of MX80 bentonite and their interaction with iron
Authors: Gilmour Katie , Davie Colin , Gray Neil
Published: May 2022

MX80 bentonite has been selected as the buffer and backfill in a proposed method of long-term deep geological storage of nuclear waste. Extensive studies have been carried out on the geomechanical properties of MX80; however, it is not clear what effect microbes will have on its ability to function as an effective barrier. Specifically, in the UK, as carbon steel waste canisters will contribute iron oxides and rust products to the immediate environment, iron-reducing bacteria are of interest. Iron-reducing bacteria can reduce structural or external Fe (III) to Fe (II) and some species are adapted to high temperatures and low water availability, in keeping with conditions within the waste repository. Indigenous iron-interacting bacteria have been identified in compacted MX80 and microbially-influenced iron-reduction was observed in groundwater salinity up to 0.45M NaCl. Experiments investigating gas production, and silica-solubilising abilities of this community were carried out. Further experiments in pressurised test cells investigated microbial activities at the clay / steel interface. Significant increases in hydrogen production were observed when microbes were present, and biogenically influenced changes in structure and appearance of MX80 were seen in all experiments. Additionally, silica release occurred, likely coupled to metal / microbe interactions. Corrosion products differed depending on microbial presence following incubation in test cells. Biogenic transformation of clay minerals through iron reduction or release of silica to groundwater could significantly impact the geomechanical properties of MX80, as indicated by observed changes in clay plasticity, and ultimately this could affect the behavior of the material as a barrier.
Investigation of the influence of plant tissue damage on the attachment of Listeria to fresh salad produce
Authors: Alsharif Asma
Published: May 2022

Vegetables and fruits are an important for a healthy life due to them containing nutritionally important minerals and vitamins. Green salads (spinach, lettuce) are popular convenience consumer products, however evidence is increasing that these ready to eat salads have been identified as a source of foodborne illness. There are many pathogenic bacteria which are transmitted by food that can cause serious disease. One of the most important is Listeria monocytogenesbecause it can cause invasive infections and especially because of its ability to grow at low (food refrigeration) temperatures. The aim of this study is to investigate whether compounds released from damaged fresh salad leave have an effect on Listeria growth and virulence. The results in this report show that Listeria was highly responsive to the salad extracts and that growth and biofilm formation were both increased compared to un-supplemented control cultures. Plant derived chemicals also stimulated Listeria growth in serum-SAPI medium. The results also showed that Listeria treated with salad extract was more virulent in a Galleria mellonella infection model.
Clostridioides difficile surveillance at the University Hospital in Košice reveals high prevalence of the ribotype 176
Authors: Čurová Katarína , Toporová Annamária , Krůtová Marcela , Novotný Martin , Ambro Ĺuboš , Kamlárová Anna , Hockicko Ján , Siegfried Leonard
Published: May 2022

Background

Clostridioides difficile infection (CDI) has become a serious health problem worldwide in recent years, the severity of which lies in the ability to spread epidemically in hospitals and in frequent diseases relapses. CDI Surveillance was performed at the Louis Pasteur University Hospital in Košice from January to February 2020 to analyse the molecular characteristics ofC. difficile(CD) isolates from local patients with CDI.

Methods

CDI was initially diagnosed using the C. difficile rapid test (for enzyme GDH and toxin A/B). A total of 36 stool samples (29 GDH and toxin positive, 7 GDH positive and toxin negative) were cultured anaerobically on selective media (Brazier’s agar). Culture was positive for CD in 31 samples. Bacterial DNA was extracted from all CD isolates. Genes tcdA, tcdB, cdtA and cdtB encoding toxin A, toxin B and binary toxin were detected by multiplex PCR and ribotypes of CD were analysed by capillary electrophoresis-based PCR.

Results

Molecular typing showed that toxin A as well as toxin B was confirmed in 30 of 31 isolates, binary toxin in 18 isolates. Ribotype 176, characterized by production of all 3 toxins, was the most prevalent and was detected in 18 isolates (58%). Toxin A and toxin B producing ribotypes 001, 014 and 020 were also confirmed.

Conclusion

The high incidence of epidemic ribotype 176 with higher capacity to spread in a hospital setting emphasises the need to implement strict epidemic measures and the importance of implementing continuous surveillance programmes for CDI in Slovakia.
Molecular and cellular insight into Escherichia coli SslE and its role during biofilm maturation
Authors: Corsini Paula , Wang Sunjun , Rehman Saima , Fenn Katherine , Sagar Amin , Sirovica Slobodan , Cleaver Leanne , Edwards-Gayle Charlotte , Mastroianni Giulia , Dorgan Ben , Sewell Lee , Lynham Steven , Iuga Dinu , Franks Trent , Jarvis James , Carpenter Guy , Curtis Michael , Bernado Pau , Darbari Vidya , Garnett James
Published: May 2022

Escherichia coli is a Gram-negative bacterium that colonizes the human intestine and virulent strains can cause severe diarrhoeal and extraintestinal diseases. The protein SslE is secreted by a range of pathogenic and some commensal E. colistrains. It can degrade mucins in the intestine, promotes biofilm maturation and in virulent strains, it is a major determinant of infection, although how it carries out these functions is not well understood. Here we examine SslE from the E. coli Waksman and H10407 strains and using electron microscopy (EM), small angle X-ray scattering (SAXS), nuclear magnetic resonance (NMR) spectroscopy and biochemical analyses we show that SslE has a highly dynamic structure in solution. We also directly observe acidification within mature biofilms, describe a mechanism where SslE forms unique functional fibres under these conditions and determine that these SslE aggregates can bind cellulose, a major exopolysaccharide of many E. coli biofilms. Our data indicates that the spatial organization of SslE polymers and local pH are critical for biofilm maturation and SslE is a key factor that drives persistence of SslE-secreting bacteria during acidic stress.
Heterogenous susceptibility to R-pyocins in populations of Pseudomonas aeruginosa sourced from cystic fibrosis lungs
Authors: Mei Madeline , Thomas Jacob , Diggle Stephen
Published: May 2022

Bacteriocins are proteinaceous antimicrobials produced by bacteria which are active against other strains of the same species. R-type pyocins are phage tail-like bacteriocins produced by Pseudomonas aeruginosa. Due to their anti-pseudomonal activity, R-pyocins have potential as therapeutics in infection. P. aeruginosa is a Gram-negative opportunistic pathogen and is particularly problematic for individuals with cystic fibrosis (CF). P. aeruginosa from CF lung infections develop increasing resistance to antibiotics, making new treatment approaches essential. P. aeruginosa populations become phenotypically and genotypically diverse during infection, however, little is known of the efficacy of R-pyocins against heterogeneous populations. R-pyocins vary by subtype (R1-R5), distinguished by binding to different residues on the lipopolysaccharide (LPS). Each type varies in killing spectrum, and each strain produces only one R-type. To evaluate the prevalence of different R-types, we screened P. aeruginosastrains from the International Pseudomonas Consortium Database (IPCD) and from our biobank of CF strains. We found that (i) R1-types were the most prevalent R-type among strains from respiratory sources; (ii) there are a large number of strains lacking R-pyocin genes, and (iii) isolates collected from the same patient have the same R-type. We then assessed the impact of diversity on R-pyocin susceptibility and found a heterogenous response to R-pyocins within populations, likely due to differences in the LPS core. Our work reveals that heterogeneous populations of microbes exhibit variable susceptibility to R-pyocins and highlights that there is likely heterogeneity in response to other types of LPS-binding antimicrobials, including phage.
Multi-omics analysis of the specialised metabolism of two novel Pseudonocardia spp. isolated from the deep Southern Ocean
Authors: Parra Jonathan , Duncan Katherine R.
Published: May 2022

Multidrug-resistant pathogens have become a global threat. In this context, filamentous Actinobacteria has been proven to be an exceptional source of antimicrobial metabolites. In particular, rare actinomycetes isolated from marine environments have been proposed as a potential source of yet untapped specialised metabolites. In this study, two novel species, Pseudonocardia abyssalis sp. nov. and Pseudonocardia oceani sp. nov, isolated from deep Southern Ocean sediments are described, both in terms of their phenotypic and genomic characterization. Furthermore, the genomic architecture, with a focus on Biosynthetic Gene Cluster (BGC), across eight strains belonging to the two novel species were investigated. A total of 14 Gene Cluster Families (GCF) were identified, of which five GCFs comprise BGCs from both species, and nine were specific to each species. Moreover, a correlation of GCFs to phylogeny was observed. Following genome analysis, a comparative mass-spectrometry based metabolomics analysis was carried out with one strain from each new species, as well as Pseudonocardia ammonioxydans and Pseudonocardia sediminis, also of marine origin. The metabolomics profiles agreed with the GCF distribution, where a group of ubiquitous metabolites were produced by both new Pseudonocardia spp., while groups of species-specific metabolites were also detected. This metabolic-repertoire was found to be elicitated through the addition of N-acetyl glucosamine (GlcNAc), revealing chemically-inducible bioactivity against the fungi Candida albicas and multidrug-resistant Candida auris. These results showcase the power of a combined genomic-metabolomics approach to investigate rare-actinomycetes from understudied locations and have uncovered a wealth of both biosynthetic and chemical diversity for further investigation.
Diversity Analysis and Genome Mining of Microbial 16S rRNA Gene and Metagenomic Data for the Discovery of Novel Antibiotics
Authors: Giard Josephine , Pratscher Jennifer , Kerr Leena
Published: May 2022

There is an urgent need for new antimicrobials due to constantly advancing antimicrobial resistance. Here, we worked with environmental samples from diverse habitats including different savannah and forest soils, volcanic caves, and termite mounds and assessed their microbial communities for the potential of biosynthesis of secondary metabolites. We analysed and compared microbial composition by applying the QIIME2 pipeline to 16S rRNA gene data. We focused on the abundance of Actinobacteria and Streptomyces as they are important producers of antimicrobials. Out of the samples analysed, the highest abundance of Actinobacteria was found in termite mound and volcanic cave samples. Moreover, the termite mound samples also had the highest abundance of Streptomyces. When comparing microbial composition, soil samples and termite mound samples each formed their own clusters, but volcanic cave samples appeared more dispersed. We assessed the antimicrobial potential of a subset of samples by analysing metagenomic data to predict biosynthetic gene clusters (BGCs) using antiSMASH5.2.0, which resulted in over 800 hits per sample. This number was narrowed down by evaluating identified BGCs based on antimicrobial potential, completeness, size, presence/absence of regulatory and transport-related genes, and dissimilarity with known BGCs. This resulted in an average of 20 BGCs per sample. These BGCs will be subjected to further sequence-based analyses before attempting heterologous expression. Following successful expression, antimicrobial potential will be assessed by screening for growth inhibition of multidrug resistant E.coli strains and the ESKAPE pathogens.