Non-invasive cumulus cell analysis can be applied for oocyte ranking and is useful for countries with legal restrictions on embryo generation or freezing

by Tom Adriaenssens, Inge Van Vaerenbergh, Lisbet Van Landuyt, Greta Verheyen, Michaël De Brucker, Michel Camus, Peter Platteau, Michel De Vos, Maria Reis, Elien Van Hecke, André Rosenthal, Johan Smitz

Research question

Can a strategy for scoring oocyte quality, based on cumulus cell (CC) gene expression, prioritize oocytes with the highest implantation potential, while limiting the number of embryos to be processed in culture and the number of supernumerary embryos to be vitrified?

Design

An interventional, blinded, prospective cohort study was retrospectively analyzed. In the original study, patients underwent a fresh Day3 single embryo transfer with embryos ranked based on morphology and CC gene expression (Aurora Test). The additional ranking of the embryos with the Aurora Test resulted in significant higher clinical pregnancy and live birth rates. Now it is investigated if the Aurora Test ranking could be applied to select oocytes. The effect of an Aurora Test based restriction to 2 and 3 2PN or MII oocytes on clinical pregnancy and other outcomes, was analyzed in two subsets of patients with all 2PN (n = 83) or all MII oocytes (n = 45) ranked.

Results

Considering only the top three ranked 2PN oocytes, 95% of the patients would have received a fresh SET on Day3 resulting in 65% clinical pregnancies. This was not different from the pregnancy rate obtained in a strategy using all oocytes but significantly reduced the need for vitrification of supernumerary embryos by 3-fold. Considering only top-ranked MII oocytes gave similar results.

Conclusions

In countries with legal restrictions on freezing of embryos, gene expression of CC can be used for the selective processing of oocytes and would thus decrease the twin pregnancy rate and workload, especially for embryo morphology scoring and transfers as the handling and processing of lower competence oocytes is prevented, while improving the ART outcome.

The significance of parental mentalizing for four-year-old children’s solitary pretend play

by Johanne Smith-Nielsen, Anne Christine Stuart, Katrine Isabella Wendelboe, Ida Egmose, Camilla Overbye Roos, Mette Skovgaard Væver

Background

Pretend play is a signature behavior of early childhood and is considered to reflect the child’s emerging symbolic function, enabling the interpretation of social signals, language development, and emotion understanding. While theory links parental mentalizing with children’s pretend play, only a few studies have investigated this association. These studies are limited to infancy and early toddlerhood, and child pretend play is assessed during play with an adult (social play). Based on the assumption that child solitary pretend play reflects the child’s ‘baseline’ pretend play ability, in this study, we investigated children’s pretend play at its peak, i.e., during the preschool age, without the facilitation of another player. The overall objective was to investigate if parental mentalizing increases pretend play complexity in children.

Methods

The sample consisted 99 Danish mothers and their 4-year-old children. Employing a cross-sectional design, we hypothesized that parental mental state language, as an indicator of ‘online’ mentalizing during interaction with the child, is a mechanism through which ‘offline’ mentalizing, measured as parental reflective functioning, is associated with child solitary pretend play. Child pretend play complexity was observed and coded with an adapted version of the 12-Step Play Scale. Maternal offline mentalizing was assessed with the Parental Reflective Functioning Questionnaire, and maternal online mentalizing was assessed by coding the mothers’ mental state language during interaction with the child using a modified version of the mind-mindedness coding scheme.

Results

While there was no direct effect of maternal offline reflective functioning on child pretend play, online mental state language mediated the link between offline maternal reflective functioning and child pretend play.

Conclusions

These results provide support for the theoretically assumed link between parental mentalizing and children’s capacity for pretend play. Furthermore, our study contributes to the literature on parental mentalization, suggesting that parental mentalizing facilitates child development only if the parent can translate this ability into ’mentalizing in action’.

Supporting regional pandemic management by enabling self-service reporting—A case report

by Richard Gebler, Martin Lehmann, Maik Löwe, Mirko Gruhl, Markus Wolfien, Miriam Goldammer, Franziska Bathelt, Jens Karschau, Andreas Hasselberg, Veronika Bierbaum, Toni Lange, Katja Polotzek, Hanns-Christoph Held, Michael Albrecht, Jochen Schmitt, Martin Sedlmayr

Background

The COVID-19 pandemic revealed a need for better collaboration among research, care, and management in Germany as well as globally. Initially, there was a high demand for broad data collection across Germany, but as the pandemic evolved, localized data became increasingly necessary. Customized dashboards and tools were rapidly developed to provide timely and accurate information. In Saxony, the DISPENSE project was created to predict short-term hospital bed capacity demands, and while it was successful, continuous adjustments and the initial monolithic system architecture of the application made it difficult to customize and scale.

Methods

To analyze the current state of the DISPENSE tool, we conducted an in-depth analysis of the data processing steps and identified data flows underlying users’ metrics and dashboards. We also conducted a workshop to understand the different views and constraints of specific user groups, and brought together and clustered the information according to content-related service areas to determine functionality-related service groups. Based on this analysis, we developed a concept for the system architecture, modularized the main services by assigning specialized applications and integrated them into the existing system, allowing for self-service reporting and evaluation of the expert groups’ needs.

Results

We analyzed the applications’ dataflow and identified specific user groups. The functionalities of the monolithic application were divided into specific service groups for data processing, data storage, predictions, content visualization, and user management. After composition and implementation, we evaluated the new system architecture against the initial requirements by enabling self-service reporting to the users.

Discussion

By modularizing the monolithic application and creating a more flexible system, the challenges of rapidly changing requirements, growing need for information, and high administrative efforts were addressed.

Conclusion

We demonstrated an improved adaptation towards the needs of various user groups, increased efficiency, and reduced burden on administrators, while also enabling self-service functionalities and specialization of single applications on individual service groups.

Validated respiratory drug deposition predictions from 2D and 3D medical images with statistical shape models and convolutional neural networks

by Josh Williams, Haavard Ahlqvist, Alexander Cunningham, Andrew Kirby, Ira Katz, John Fleming, Joy Conway, Steve Cunningham, Ali Ozel, Uwe Wolfram

For the one billion sufferers of respiratory disease, managing their disease with inhalers crucially influences their quality of life. Generic treatment plans could be improved with the aid of computational models that account for patient-specific features such as breathing pattern, lung pathology and morphology. Therefore, we aim to develop and validate an automated computational framework for patient-specific deposition modelling. To that end, an image processing approach is proposed that could produce 3D patient respiratory geometries from 2D chest X-rays and 3D CT images. We evaluated the airway and lung morphology produced by our image processing framework, and assessed deposition compared to in vivo data. The 2D-to-3D image processing reproduces airway diameter to 9% median error compared to ground truth segmentations, but is sensitive to outliers of up to 33% due to lung outline noise. Predicted regional deposition gave 5% median error compared to in vivo measurements. The proposed framework is capable of providing patient-specific deposition measurements for varying treatments, to determine which treatment would best satisfy the needs imposed by each patient (such as disease and lung/airway morphology). Integration of patient-specific modelling into clinical practice as an additional decision-making tool could optimise treatment plans and lower the burden of respiratory diseases.

Exploring knowledge, perceptions, and practices of antimicrobials, and their resistance among medicine dispensers and community members in Kavrepalanchok District of Nepal

by Sabina Marasini, Sudim Sharma, Anjali Joshi, Surakshya Kunwar, Roshan Kumar Mahato, Archana Shrestha, Biraj Karmacharya

Background

Inappropriate use of antimicrobials is a global public health issue, particularly in developing countries, including Nepal, where over-the-counter sales and self-medication of antimicrobials are common.

Objectives

To explore knowledge, perceptions, and practices of antimicrobials and their resistance among medicine dispensers and community members in Nepal.

Methods

The study was conducted in three rural and five urban municipalities of the Kavrepalanchok district from May 2021 to August 2021. Data were collected using two qualitative approaches: In-Depth Interviews (IDIs) and Focus Group Discussions (FGDs). Data were analyzed using thematic analysis that combined deductive and inductive approaches to identify codes under pre-specified themes.

Results

A total of 16 In-depth interviews with medicine dispensers and 3 focus group discussions with community members were conducted. Knowledge regarding antimicrobial resistance varied among dispensers. Those with a prior educational background in pharmacy often had good knowledge about the causes and consequences of antimicrobial resistance. Meanwhile, consumers were less aware of antimicrobial resistance. Community members perceived antimicrobials as effective medicines but not long-term solution for treating diseases. They reported that dispensing without a prescription was common and that both consumers and dispensers were responsible for the inappropriate use of antimicrobials. On the contrary, several dispensers said that self-medication was common among the consumers, especially among more educated groups. The medicine dispensers and consumers expressed concerns about the weak enforcement of policies regarding pharmacy drug use and dispensing practices.

Conclusion

Promoting and strengthening the appropriate use of antimicrobials among medicine dispensers and community members is crucial. Bold policies and collective implementation of regulations could help combat antimicrobial resistance.

Primary care quality for older adults: Practice-based quality measures derived from a RAND/UCLA appropriateness method study

by Rebecca H. Correia, Darly Dash, Aaron Jones, Meredith Vanstone, Komal Aryal, Henry Yu-Hin Siu, Aquila Gopaul, Andrew P. Costa

We established consensus on practice-based metrics that characterize quality of care for older primary care patients and can be examined using secondary health administrative data. We conducted a two-round RAND/UCLA Appropriateness Method (RAM) study and recruited 10 Canadian clinicians and researchers with expertise relevant to the primary care of elderly patients. Informed by a literature review, the first RAM round evaluated the appropriateness and importance of candidate quality measures in an online questionnaire. Technical definitions were developed for each endorsed indicator to specify how the indicator could be operationalized using health administrative data. In a virtual synchronous meeting, the expert panel offered feedback on the technical specifications for the endorsed indicators. Panelists then completed a second (final) questionnaire to rate each indicator and corresponding technical definition on the same criteria (appropriateness and importance). We used statistical integration to combine technical expert panelists’ judgements and content analysis of open-ended survey responses. Our literature search and internal screening resulted in 61 practice-based quality indicators for rating. We developed technical definitions for indicators endorsed in the first questionnaire (n = 55). Following the virtual synchronous meeting and second questionnaire, we achieved consensus on 12 practice-based quality measures across four Priority Topics in Care of the Elderly. The endorsed indicators provide a framework to characterize practice- and population-level encounters of family physicians delivering care to older patients and will offer insights into the outcomes of their care provision. This study presented a case of soliciting expert feedback to develop measurable practice-based quality indicators that can be examined using administrative data to understand quality of care within population-based data holdings. Future work will refine and operationalize the technical definitions established through this process to examine primary care provision for older adults in a particular context (Ontario, Canada).

The impact of cineole treatment timing on common cold duration and symptoms: Non-randomized exploratory clinical trial

by Andreas Michalsen, Kim Goldenstein, Peter Kardos, Ludger Klimek, Jürgen Palm, Dajana Parganlija, Johannes Stöckl

Introduction

Common cold (CC) symptoms arise from an inflammatory response treatable with cineole and generally peak within two days, which complicates research implementation. We therefore explored the benefits of early cineole administration with enrolment of participants prior to CC onset.

Methods

Out of 522 adults enrolled in our phase IV, open-label, non-randomized, exploratory clinical trial (EudraCT No. 2020-000860-51), 329 developed a CC and used 200 mg cineole (Soledum^®, CNL-1976) t.i.d. for max. 15 (± 2) days. Primary endpoint was burden of disease based on the Wisconsin Upper Respiratory Symptom Survey (WURSS-11).

Results

Comparing three strata based on time to treatment (≤ 12 h, > 12 to ≤ 24 h and > 24 h), earliest treatment resulted in lowest AUC-WURSS (Spearman correlation coefficient of 0.36) and reduced the overall burden of disease by 38% (p Conclusions

Early intervention shows clinical benefits relevant for the effective treatment of CC with cineole.

High-resolution genomic analysis to investigate the impact of the invasive brushtail possum (<i>Trichosurus vulpecula</i>) and other wildlife on microbial water quality assessments

by Marie Moinet, Lynn Rogers, Patrick Biggs, Jonathan Marshall, Richard Muirhead, Megan Devane, Rebecca Stott, Adrian Cookson

Escherichia coli are routine indicators of fecal contamination in water quality assessments. Contrary to livestock and human activities, brushtail possums (Trichosurus vulpecula), common invasive marsupials in Aotearoa/New Zealand, have not been thoroughly studied as a source of fecal contamination in freshwater. To investigate their potential role, Escherichia spp. isolates (n = 420) were recovered from possum gut contents and feces and were compared to those from water, soil, sediment, and periphyton samples, and from birds and other introduced mammals collected within the Mākirikiri Reserve, Dannevirke. Isolates were characterized using E. coli-specific real-time PCR targeting the uidA gene, Sanger sequencing of a partial gnd PCR product to generate a gnd sequence type (gST), and for 101 isolates, whole genome sequencing. Escherichia populations from 106 animal and environmental sample enrichments were analyzed using gnd metabarcoding. The alpha diversity of Escherichia gSTs was significantly lower in possums and animals compared with aquatic environmental samples, and some gSTs were shared between sample types, e.g., gST535 (in 85% of samples) and gST258 (71%). Forty percent of isolates gnd-typed and 75% of reads obtained by metabarcoding had gSTs shared between possums, other animals, and the environment. Core-genome single nucleotide polymorphism (SNP) analysis showed limited variation between several animal and environmental isolates (Escherichia clones are shared between possums, other wildlife, water, and the wider environment. These findings support the potential role of possums as contributors to fecal contamination in Aotearoa/New Zealand freshwater. Our study deepens the current knowledge of Escherichia populations in under-sampled wildlife. It presents a successful application of high-resolution genomic methods for fecal source tracking, thereby broadening the analytical toolbox available to water quality managers. Phylogenetic analysis of isolates and profiling of Escherichia populations provided useful information on the source(s) of fecal contamination and suggest that comprehensive invasive species management strategies may assist in restoring not only ecosystem health but also water health where microbial water quality is compromised.

Risk of major myopia-associated non-communicable ocular health disorders in Ghana

by Samuel Kyei, Rexford Kwasi Gyaami, John Baptist Abowine, Ebenezer Zaabaar, Kofi Asiedu, Samuel Bert Boadi-Kusi, Jacob Mensah Mesuh, Frank Assiamah, Anthony Armah, Patience Ansomah Ayerakwah

Objective

To assess the differential association of myopia with major non-communicable ocular diseases in an African clinical cohort.

Methods

A five-year hospital-based retrospective study of myopia cases. Patients’ folders, Optical Coherence Tomography scans, and fundus photographs were reviewed for the abstraction of relevant data. Only records that employed recognized standards and classification systems for diagnosing and staging the various ocular conditions were included. Demographic characteristics, non-cycloplegic objective refractive findings, and non-communicable eye diseases were retrieved from the records. Myopia-associated risk factors were then determined using logistic regression and correlation.

Results

Some 16018 patients (32027 eyes) met the inclusion criteria for at least one eye comprising 50.8% males (n = 8137) and 49.2% females (n = 7881). The mean age of the patients was 43.14 ± 17.88 years (range: 2–98 years). The mean spherical equivalent± Standard deviation for myopia was -2.30±3.23 DS (range: -0.50 to -25DS). Binary logistic regression analysis showed that myopic eyes had a higher odd of AC (OR, 0.53; 95% CI, 0.50–0.57), POAG (OR, 6.0; 95% CI, 5.26–6.82), DR (OR, 10.70; 95% CI, 3.91–29.27) and cataracts (OR, 20; 95% CI, 15.32–26.20) but not dry eye (OR, 0.74, 95% CI, 0.68–0.81), macular degeneration and pterygium (OR, 0.36; 95% CI, 0.32–0.40).

Conclusion

Africans with myopia are more at risk of developing allergic conjunctivitis, cataracts, POAG, and DR but not for dry eye, macular degeneration, and pterygium.

<i>Metarhizium</i> spp. isolates effective against Queensland fruit fly juvenile life stages in soil

by Madita Prince, Aimee C. McKinnon, Diana Leemon, Tim Sawbridge, John Paul Cunningham

Queensland fruit fly, Bactrocera tryoni, Froggatt (Diptera: Tephritidae) is Australia’s primary fruit fly pest species. Integrated Pest Management (IPM) has been adopted to sustainably manage this polyphagous species with a reduced reliance on chemical pesticides. At present, control measures are aimed at the adult stages of the fly, with no IPM tools available to target larvae once they exit the fruit and pupate in the soil. The use of entomopathogenic fungi may provide a biologically-based control method for these soil-dwelling life stages. The effectiveness of fungal isolates of Metarhizium and Beauveria species were screened under laboratory conditions against Queensland fruit fly. In bioassays, 16 isolates were screened for pathogenicity following exposure of third-instar larvae to inoculum-treated vermiculite used as a pupation substrate. The best performing Metarhizium sp. isolate achieved an average percentage mortality of 93%, whereas the best performing Beauveria isolate was less efficient, with an average mortality of 36%. Susceptibility to infection during different development stages was investigated using selected fungal isolates, with the aim of assessing all soil-dwelling life stages from third-instar larvae to final pupal stages and emerging adults. Overall, the third larval instar was the most susceptible stage, with average mortalities between 51–98% depending on the isolate tested. Moreover, adult mortality was significantly higher when exposed to inoculum during pupal eclosion, with mortalities between 56–76% observed within the first nine days post-emergence. The effect of temperature and inoculum concentration on insect mortality were assessed independently with candidate isolates to determine the optimum temperature range for fungal biological control activity and the rate required for application in field conditions. Metarhizium spp. are highly efficacious at killing Queensland fruit fly and have potential for use as biopesticides to target soil-dwelling and other life stages of B. tryoni.

The incredible shrinking puffin: Decreasing size and increasing proportional bill size of Atlantic puffins nesting at Machias Seal Island

by Heather L. Major, Joy E. Rivers, Quinn B. Carvey, Antony W. Diamond

Climate change imposes physiological constraints on organisms particularly through changing thermoregulatory requirements. Bergmann’s and Allen’s rules suggest that body size and the size of thermoregulatory structures differ between warm and cold locations, where body size decreases with temperature and thermoregulatory structures increase. However, phenotypic plastic responses to malnutrition during development can result in the same patterns while lacking fitness benefits. The Gulf of Maine (GOM), located at the southern end of the Labrador current, is warming faster than most of the world’s oceans, and many of the marine species that occupy these waters exist at the southern edge of their distributions including Atlantic puffins (Fratercula arctica; hereafter “puffin”). Monitoring of puffins in the GOM, at Machias Seal Island (MSI), has continued annually since 1995. We asked whether changes in adult puffin body size and the proportional size of bill to body have changed with observed rapid ocean warming. We found that the size of fledgling puffins is negatively related to sea surface temperature anomalies (warm conditions = small fledgers), adult puffin size is related to fledgling size (small fledgers = small adults), and adult puffins have decreased in size in recent years in response to malnutrition during development. We found an increase in the proportional size of bill to wing chord, likely in response to some mix of malnutrition during development and increasing air temperatures. Although studies have assessed clinal variation in seabird morphology with temperature, this is the first study addressing changes in seabird morphology in relation to ocean warming. Our results suggest that puffins nesting in the GOM have morphological plasticity that may help them acclimate to ocean warming.

Convergence and divergence in mortality: A global study from 1990 to 2030

by David Atance, M. Mercè Claramunt, Xavier Varea, Jose Manuel Aburto

An empirical question that has motivated demographers is whether there is convergence or divergence in mortality/longevity around the world. The epidemiological transition is the starting point for studying a global process of mortality convergence. This manuscript aims to provide an update on the concept of mortality convergence/divergence. We perform a comprehensive examination of nine different mortality indicators from a global perspective using clustering methods in the period 1990-2030. In addition, we include analyses of projections to provide insights into prospective trajectories of convergence clubs, a dimension unexplored in previous work. The results indicate that mortality convergence clubs of 194 countries by sex resemble the configuration of continents. These five clubs show a common steady upward trend in longevity indicators, accompanied by a progressive reduction in disparities between sexes and between groups of countries. Furthermore, this paper shows insights into the historical evolution of the convergence clubs in the period 1990-2020 and expands their scope to include projections of their expected future evolution in 2030.

Genetic profiling of rat gliomas and cardiac schwannomas from life-time radiofrequency radiation exposure study using a targeted next-generation sequencing gene panel

by Ashley M. Brooks, Andrea Vornoli, Ramesh C. Kovi, Thai Vu T. Ton, Miaofei Xu, Ahmed Mashal, Eva Tibaldi, Federica Gnudi, Jian-Liang Li, Robert C. Sills, John R. Bucher, Daniele Mandrioli, Fiorella Belpoggi, Arun R. Pandiri

The cancer hazard associated with lifetime exposure to radiofrequency radiation (RFR) was examined in Sprague Dawley (SD) rats at the Ramazzini Institute (RI), Italy. There were increased incidences of gliomas and cardiac schwannomas. The translational relevance of these rare rat tumors for human disease is poorly understood. We examined the genetic alterations in RFR-derived rat tumors through molecular characterization of important cancer genes relevant for human gliomagenesis. A targeted next-generation sequencing (NGS) panel was designed for rats based on the top 23 orthologous human glioma-related genes. Single-nucleotide variants (SNVs) and small insertion and deletions (indels) were characterized in the rat gliomas and cardiac schwannomas. Translational relevance of these genetic alterations in rat tumors to human disease was determined through comparison with the Catalogue of Somatic Mutations in Cancer (COSMIC) database. These data suggest that rat gliomas resulting from life-time exposure to RFR histologically resemble low grade human gliomas but surprisingly no mutations were detected in rat gliomas that had homology to the human IDH1 p.R132 or IDH2 p.R172 suggesting that rat gliomas are primarily wild-type for IDH hotspot mutations implicated in human gliomas. The rat gliomas appear to share some genetic alterations with IDH1 wildtype human gliomas and rat cardiac schwannomas also harbor mutations in some of the queried cancer genes. These data demonstrate that targeted NGS panels based on tumor specific orthologous human cancer driver genes are an important tool to examine the translational relevance of rodent tumors resulting from chronic/life-time rodent bioassays.

Morphological and ultrastructural investigation of the posterior atlanto-occipital membrane: Comparing children with Chiari malformation type I and controls

by Vijay M. Ravindra, Lorraina Robinson, Hailey Jensen, Elena Kurudza, Evan Joyce, Allison Ludwick, Russell Telford, Osama Youssef, Justin Ryan, Robert J. Bollo, Rajiv R. Iyer, John R. W. Kestle, Samuel H. Cheshier, Daniel S. Ikeda, Qinwen Mao, Douglas L. Brockmeyer

Introduction

The fibrous posterior atlanto-occipital membrane (PAOM) at the craniocervical junction is typically removed during decompression surgery for Chiari malformation type I (CM-I); however, its importance and ultrastructural architecture have not been investigated in children. We hypothesized that there are structural differences in the PAOM of patients with CM-I and those without.

Methods

In this prospective study, blinded pathological analysis was performed on PAOM specimens from children who had surgery for CM-I and children who had surgery for posterior fossa tumors (controls). Clinical and radiographic data were collected. Statistical analysis included comparisons between the CM-I and control cohorts and correlations with imaging measures.

Results

A total of 35 children (mean age at surgery 10.7 years; 94.3% white) with viable specimens for evaluation were enrolled: 24 with CM-I and 11 controls. There were no statistical demographic differences between the two cohorts. Four children had a family history of CM-I and five had a syndromic condition. The cohorts had similar measurements of tonsillar descent, syringomyelia, basion to C2, and condylar-to-C2 vertical axis (all p>0.05). The clival-axial angle was lower in patients with CM-I (138.1 vs. 149.3 degrees, p = 0.016). Morphologically, the PAOM demonstrated statistically higher proportions of disorganized architecture in patients with CM-I (75.0% vs. 36.4%, p = 0.012). There were no differences in PAOM fat, elastin, or collagen percentages overall and no differences in imaging or ultrastructural findings between male and female patients. Posterior fossa volume was lower in children with CM-I (163,234 mm³ vs. 218,305 mm³, p Conclusions

In patients with CM-I, the PAOM demonstrates disorganized architecture compared with that of control patients. This likely represents an anatomic adaptation in the presence of CM-I rather than a pathologic contribution.

Patterns in refractive error and treatment delay in keratoconus–An Australian study

by Samantha Bobba, Alanna Wood, John Males, Yves Kerdraon

Keratoconus is the most common primary corneal ectasia and is associated with significant morbidity. In its early stages, keratoconus is often asymptomatic, making the identification of subclinical disease challenging. Refractive error is a parameter that is documented at most routine optometry visits, yet interestingly, changes in refraction of keratoconic patients over time have not yet been studied and compared with the general population. Early diagnosis of keratoconus facilitates timely referral for treatments such as corneal collagen cross-linking, which has been shown to slow disease progression. In this context, documenting delays between initial presentation to the optometrist and referral for collagen-cross-linking as well as comparing the trends in visual acuity and refractive error between keratoconic and non-keratoconic patients over time are particularly relevant.

Cytomegalovirus detection is associated with ICU admission in non-AIDS and AIDS patients with <i>Pneumocystis jirovecii</i> pneumonia

by Alexandre Perret, Marion Le Marechal, Raphaele Germi, Daniele Maubon, Cécile Garnaud, Johan Noble, Aude Boignard, Loïc Falque, Mathieu Meunier, Théophile Gerster, Olivier Epaulard

Objectives

Cytomegalovirus (CMV) is frequently detected in lung and/or blood samples of patients with Pneumocystis jirovecii pneumonia (PJP), although this co-detection is not precisely understood. We aimed to determine whether PJP was more severe in case of CMV detection.

Methods

We retrospectively included all patients with a diagnosis of PJP between 2009 and 2020 in our centre and with a measure of CMV viral load in blood and/or bronchoalveolar lavage (BAL). PJP severity was assessed by the requirement for intensive care unit (ICU) admission.

Results

The median age of the 249 patients was 63 [IQR: 53–73] years. The main conditions were haematological malignancies (44.2%), solid organ transplantations (16.5%), and solid organ cancers (8.8%). Overall, 36.5% patients were admitted to ICU. CMV was detected in BAL in 57/227 patients; the 37 patients with viral load ≥3 log copies/mL were more frequently admitted to ICU (78.4% vs 28.4%, p Conclusions

PJP is more severe in the case of concomitant CMV detection. This may reflect either the deleterious role of CMV itself, which may require antiviral therapy, or the fact that patients with CMV reactivation are even more immunocompromised.

Efficacy of early cardiac rehabilitation after acute myocardial infarction: Randomized clinical trial protocol

by Caroline Schon, Amanda Felismino, Joceline de Sá, Renata Corte, Tatiana Ribeiro, Selma Bruno

The acute myocardial infarction (AMI) present high mortality rate that may be reduced with cardiac rehabilitation. Despite its good establishment in outpatient care, few studies analyzed cardiac rehabilitation during hospitalization. Thus, this study aims to clarify the safety and efficacy of early cardiac rehabilitation after AMI. This will be a clinical, controlled, randomized trial with blind outcome evaluation and a superiority hypothesis. Twenty-four patients with AMI will be divided into two groups (1:1 allocation ratio). The intervention group will receive an individualized exercise-based cardiac rehabilitation protocol during hospitalization and a semi-supervised protocol after hospital discharge; the control group will receive conventional care. The primary outcomes will be the cardiac remodeling assessed by cardiac magnetic resonance imaging, functional capacity assessed by maximal oxygen consumption, and cardiac autonomic balance examined via heart rate variability. Secondary outcomes will include safety and the total exercise dose provided during the protocol. Statistical analysis will consider the intent-to-treat analysis. Trial registration. Trial registration number: Brazilian Registry of Clinical Trials (ReBEC) (RBR- 9nyx8hb).

Cost and utilization analysis of concurrent versus staged testicular prosthesis implantation for radical orchiectomy

by Vi Nguyen, Arman Walia, Joshua J. Horns, Niraj Paudel, Aditya Bagrodia, Darshan P. Patel, Tung-Chin Hsieh, James M. Hotaling

Purpose

American Urological Association guidelines recommend testicular prosthesis discussion prior to orchiectomy. Utilization may be low. We compared outcomes and care utilization between concurrent implant (CI) and staged implant (SI) insertion after radical orchiectomy.

Materials & methods

The MarketScan Commercial claims database (2008–2017) was queried for men ages >18 years who underwent radical orchiectomy for testicular mass, stratified as orchiectomy with no implant, CI, or SI. 90-day outcomes included rate of reoperation, readmission, emergency department (ED) presentation, and outpatient visits. Regression models provided rate ratio comparison.

Results

8803 patients (8564 no implant, 190 CI, 49 SI; 2.7% implant rate) were identified with no difference in age, Charlson Comorbidity Index, insurance plan, additional cancer treatment, or metastasis. Median perioperative cost at orchiectomy (+/- implant) for no implant, CI, and SI were $5682 (3648–8554), $7823 (5403–10973), and $5380 (4130–10521), respectively (p Conclusions

CI placement has less total perioperative cost, lower explant rate, and similar postoperative utilization to SI.

Screening for antibacterial and cytotoxic activities of Sri Lankan marine sponges through microfractionation: Isolation of bromopyrrole alkaloids from <i>Stylissa massa</i>

by Lakmini Kosgahakumbura, Jayani Gamage, Luke P. Robertson, Taj Muhammad, Björn Hellman, Ulf Göransson, Prabath Jayasinghe, Chamari Hettiarachchi, Paco Cárdenas, Sunithi Gunasekera

Sri Lanka is a biodiversity hotspot and one of the richest geographical locations of marine sponges in the Indian ocean. However, the most extensive taxonomical study on Sri Lankan sponge biodiversity dates back ~100 years and only a limited number of studies have been conducted on sponge natural products. In the current study, 35 marine sponge specimens (collected from 16 sponge habitats around Sri Lanka) were identified, microfractionated and evaluated for antibacterial and anticancer assays. In total, 30 species were characterized, of which 19 species gave extracts with antibacterial and/or cytotoxic activities. Microfractionated organic extract of Aciculites orientalis gave the most potent antibacterial activity against Staphylococcus aureus and strongest lymphoma cell toxicity was exhibited by the organic extract of Acanthella sp. Guided by the molecular ion peaks in the bioactive fractions, large-scale extraction of Stylissa massa led to the isolation of three bromopyrrole alkaloids, sceptrin, hymenin and manzacidin A/C. Of these, sceptrin exhibited broad spectrum antibacterial activity against both Escherichia coli and S. aureus (MIC of 62.5 μM against both species). Based on natural product literature, seven promising species were identified as understudied. Their further exploration may lead to the discovery of structurally novel compounds.

Endorsement of COVID-19 misinformation among criminal legal involved individuals in the United States: Prevalence and relationship with information sources

by Xiaoquan Zhao, Aayushi Hingle, Cameron C. Shaw, Amy Murphy, Breonna R. Riddick, Rochelle R. Davidson Mhonde, Bruce G. Taylor, Phoebe A. Lamuda, Harold A. Pollack, John A. Schneider, Faye S. Taxman

Criminal legal system involvement (CLI) is a critical social determinant of health that lies at the intersection of multiple sources of health disparities. The COVID-19 pandemic exacerbates many of these disparities, and specific vulnerabilities faced by the CLI population. This study investigated the prevalence of COVID-19-related misinformation, as well as its relationship with COVID-19 information sources used among Americans experiencing CLI. A nationally representative sample of American adults aged 18+ (N = 1,161), including a subsample of CLI individuals (n = 168), were surveyed in February-March 2021. On a 10-item test, CLI participants endorsed a greater number of misinformation statements (M = 1.88 vs. 1.27) than non-CLI participants, p