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Pediatrics in Review Oct 2023Allergic rhinitis (AR) affects more than 400 million people worldwide, making it 1 of the most prevalent chronic diseases. Childhood AR is increasing, and almost half of...
Allergic rhinitis (AR) affects more than 400 million people worldwide, making it 1 of the most prevalent chronic diseases. Childhood AR is increasing, and almost half of patients with AR develop symptoms before age 6 years. Although a diagnosis of AR is associated with higher socioeconomic status, underserved and urban populations have more indoor aeroallergen sensitizations and are likely underdiagnosed with AR, further exacerbating health-care disparities. AR negatively impacts quality of life, school performance, and overall health outcomes. Untreated AR in children increases the risk for poor asthma control, increased asthma severity, and exacerbations. Many patients believe that they have seasonal allergies only but in reality have both perennial and seasonal AR, which may change the approach to allergen avoidance measures and treatment recommendations. Pharmacotherapy of AR has expanded, with many intranasal corticosteroids, intranasal antihistamines, and second-generation oral antihistamines approved for pediatric use. Allergen immunotherapy, including both subcutaneous and sublingual forms, are approved for children and are disease modifying, potentially reducing further allergen sensitization and progression to asthma. Many of the currently available biological therapies indicated for pediatric asthma and/or atopic diseases reduce AR symptoms as well. Children with moderate to severe or refractory AR or those with comorbidities should be referred to allergists for diagnostic testing and expanded management options, including immunotherapy and potential biological treatment.
Topics: Humans; Child; Quality of Life; Rhinitis, Allergic; Rhinitis, Allergic, Seasonal; Histamine Antagonists; Allergens; Asthma; Desensitization, Immunologic; Histamine H1 Antagonists, Non-Sedating
PubMed: 37777655
DOI: 10.1542/pir.2022-005618 -
Fertility and Sterility Jul 2023To date, recurrent implantation failure (RIF) has no clear definition and no clearly identified impaired function. Hence, the term RIF is currently used somewhat... (Review)
Review
IMPORTANCE
To date, recurrent implantation failure (RIF) has no clear definition and no clearly identified impaired function. Hence, the term RIF is currently used somewhat haphazardly, on the basis of clinicians' judgment.
OBJECTIVE
International experts in reproductive medicine met on July 1, 2022, in Lugano, Switzerland, to review the different facets of RIF and define the diagnosis and its appropriate management.
EVIDENCE REVIEW
A systematic review without meta-analysis of studies published in English from January 2015 to May 2022.
FINDINGS
Data indicated that RIF has been largely overevaluated, overdiagnosed, and overtreated without sufficient critical assessment of its true nature. Our analyses show that true RIF is extremely uncommon-occurring in <5% of couples with infertility-and that reassurance and continued conventional therapies are warranted in most cases of assisted reproductive technology (ART) failure. Although the true biologic determinants of RIF may exist in a small subset of people with infertility, they elude the currently available tools for assessment. Without identification of the true underlying etiology(ies), it is reasonable not to assign this diagnosis to a patient until she has failed at least 3 euploid blastocyst transfers (or the equivalent number of unscreened embryo transfers, adjusted to the patient's age and corresponding euploidy rate). In addition, other factors should be ruled out that may contribute to her reduced odds of sustained implantation. In such cases, implantation failure should not be the only issue considered in case of ART failure because this may result from multiple other factors that are not necessarily repetitive or persistent. In reality, RIF impacting the probability of further ART success is a very rare occurrence.
CONCLUSION
True RIF is extremely uncommon, occurring in <5% of couples with infertility. Reassurance and continued conventional therapies are warranted in most cases. It would seem reasonable not to assign this diagnosis to a patient until she has failed at least 3 euploid embryo transfers (or the equivalent number of unscreened embryos, adjusted to her age).
RELEVANCE
Given the number of internationally recognized experts in the field present at the Lugano meeting 2022, our publication constitutes a consensus statement.
Topics: Humans; Female; Embryo Implantation; Embryo Transfer; Infertility; Reproductive Techniques, Assisted; Aneuploidy; Retrospective Studies
PubMed: 36822566
DOI: 10.1016/j.fertnstert.2023.02.014 -
EBioMedicine Sep 2023Patients diagnosed with environmental/occupational bronchiolitis obliterans (BO) over the last 2 decades often present with an indolent evolution of respiratory symptoms... (Review)
Review
Patients diagnosed with environmental/occupational bronchiolitis obliterans (BO) over the last 2 decades often present with an indolent evolution of respiratory symptoms without a history of high-level, acute exposure to airborne toxins. Exertional dyspnea is the most common symptom and standard clinical and radiographic evaluation can be non-diagnostic. Lung biopsies often reveal pathological abnormalities affecting all distal lung compartments. These modern cases of BO typically exhibit the constrictive bronchiolitis phenotype of small airway remodeling, along with lymphocytic inflammation. In addition, hypertensive-type remodeling of intrapulmonary vasculature, diffuse fibroelastosis of alveolar tissue, and fibrous thickening of visceral pleura are frequently present. The diagnosis of environmental/occupational BO should be considered in patients who present with subacute onset of exertional dyspnea and a history compatible with prolonged or recurrent exposure to environmental toxins. Important areas for future studies include development of less invasive diagnostic approaches and testing of novel agents for disease prevention and treatment.
Topics: Humans; Bronchiolitis Obliterans; Biopsy; Dyspnea; Phenotype
PubMed: 37598462
DOI: 10.1016/j.ebiom.2023.104760 -
RSC Advances Nov 2023Recently, there has been a significant increase in academic and industrial interest in self-healing polymers (SHPs) due to their remarkable ability to regenerate... (Review)
Review
Recently, there has been a significant increase in academic and industrial interest in self-healing polymers (SHPs) due to their remarkable ability to regenerate scratched surfaces and materials of astronomical significance. Scientists have been inspired by the magical repairing mechanism of the living world. They transformed the fiction of self-healing into reality by designing engrossing polymeric materials that could self-repair mechanical abrasions repeatedly. As a result, the durability of the materials is remarkably improved. Thus, the idea of studying SHPs passively upholds economic and environmental sustainability. However, the critical areas of self-healing (including healing efficiency, healing mechanism, and thermo-mechanical property changes during healing) are under continuous scientific improvisation. This review highlights recent notable advances of SHPs for application in regenerating scratched surfaces with various distinctive underlying mechanisms. The primary focus of the work is aimed at discussing the impact of SHPs on scratch-healing technology. Beyond that, insights regarding scratch testing, methods of investigating polymer surfaces, wound depths, the addition of healing fillers, and the environmental conditions maintained during the healing process are reviewed thoroughly. Finally, broader future perspectives on the challenges and prospects of SHPs in healing surface scratches are discussed.
PubMed: 38046629
DOI: 10.1039/d3ra06676b -
Nature Communications Nov 2023Introspective agents can recognize the extent to which their internal perceptual experiences deviate from the actual states of the external world. This ability, also...
Introspective agents can recognize the extent to which their internal perceptual experiences deviate from the actual states of the external world. This ability, also known as insight, is critically required for reality testing and is impaired in psychosis, yet little is known about its cognitive underpinnings. We develop a Bayesian modeling framework and a psychophysics paradigm to quantitatively characterize this type of insight while people experience a motion after-effect illusion. People can incorporate knowledge about the illusion into their decisions when judging the actual direction of a motion stimulus, compensating for the illusion (and often overcompensating). Furthermore, confidence, reaction-time, and pupil-dilation data all show signatures consistent with inferential adjustments in the Bayesian insight model. Our results suggest that people can question the veracity of what they see by making insightful inferences that incorporate introspective knowledge about internal distortions.
Topics: Humans; Perceptual Distortion; Illusions; Bayes Theorem; Psychophysics; Psychotic Disorders; Motion Perception
PubMed: 38030601
DOI: 10.1038/s41467-023-42813-2 -
Expert Review of Anti-infective Therapy 2023Chagas disease, caused by parasite , is the most important neglected tropical disease in the Americas. Two drugs are available for treatment, but access to them is... (Review)
Review
INTRODUCTION
Chagas disease, caused by parasite , is the most important neglected tropical disease in the Americas. Two drugs are available for treatment, but access to them is challenging, in part due to complex diagnostic algorithms. These are stage-dependent, involve multiple tests, and are ill-adapted to the reality of vast areas where the disease is endemic. Molecular and serologic tools are used to detect acute and chronic infections, with the performance of the latter showing geographic differences. Breakthroughs in the development of new diagnostic tools include the validation of a loop-mediated isothermal amplification assay for acute infections (-LAMP), and the regional validation of several rapid diagnostic tests (RDTs) for chronic infection, which simplify testing in resource-limited settings. The literature search was carried out in the MEDLINE database until 1 August 2023.
AREAS COVERED
This review outlines existing algorithms, and proposes new ones focused on point-of-care testing.
EXPERT OPINION
Integrating point-of-care testing into existing diagnostic algorithms in certain endemic areas will increase access to timely diagnosis and treatment. However, additional research is needed to validate the use of these techniques across a wider geography, and to better understand the cost-effectiveness of their large-scale implementation.
Topics: Humans; Chagas Disease; Trypanosoma cruzi; Point-of-Care Testing; Rapid Diagnostic Tests; Algorithms
PubMed: 37933443
DOI: 10.1080/14787210.2023.2279110 -
Journal of General Internal Medicine Dec 2023Observational research can be strengthened by examining potential dose-response relationships that correlate a clinical intervention with a patient outcome. Despite... (Review)
Review
Observational research can be strengthened by examining potential dose-response relationships that correlate a clinical intervention with a patient outcome. Despite being a classic criterion for establishing causality, dose-response testing can be difficult to interpret in clinical medicine due to multiple diverse pitfalls. This review introduces a cautionary framework for investigators considering dose-response relationships in observational research to support evidence-based medicine. Each pitfall is illustrated with a specific example relevant when analyzing a dose-response relationship. Several pitfalls stem from faulty interpretation including confounding by indication and fallible range selection. Additional pitfalls relate to improper analysis including fitting a nonlinear model and misclassification error. Further pitfalls arise in special situations including subjective self-report and artifacts from survival bias. These caveats are common sources of misunderstanding in analyses that examine the link between varying exposures and the intensity of clinical outcomes. Awareness of specific pitfalls, we suggest, might help advance the conduct, application, and translation of dose-response relationships in observational research to inform evidence-based medical care.
Topics: Humans; Causality; Bias
PubMed: 37783979
DOI: 10.1007/s11606-023-08395-x -
Biotechnology Advances 2024The bioprocessing industry is undergoing a significant transformation in its approach to quality assurance, shifting from the traditional Quality by Testing (QbT) to... (Review)
Review
The bioprocessing industry is undergoing a significant transformation in its approach to quality assurance, shifting from the traditional Quality by Testing (QbT) to Quality by Design (QbD). QbD, a systematic approach to quality in process development, integrates quality into process design and control, guided by regulatory frameworks. This paradigm shift enables increased operational efficiencies, reduced market time, and ensures product consistency. The implementation of QbD is framed around key elements such as defining the Quality Target Product Profile (QTPPs), identifying Critical Quality Attributes (CQAs), developing Design Spaces (DS), establishing Control Strategies (CS), and maintaining continual improvement. The present critical analysis delves into the intricacies of each element, emphasizing their role in ensuring consistent product quality and regulatory compliance. The integration of Industry 4.0 and 5.0 technologies, including Artificial Intelligence (AI), Machine Learning (ML), Internet of Things (IoT), and Digital Twins (DTs), is significantly transforming the bioprocessing industry. These innovations enable real-time data analysis, predictive modelling, and process optimization, which are crucial elements in QbD implementation. Among these, the concept of DTs is notable for its ability to facilitate bi-directional data communication and enable real-time adjustments and therefore optimize processes. DTs, however, face implementation challenges such as system integration, data security, and hardware-software compatibility. These challenges are being addressed through advancements in AI, Virtual Reality/ Augmented Reality (VR/AR), and improved communication technologies. Central to the functioning of DTs is the development and application of various models of differing types - mechanistic, empirical, and hybrid. These models serve as the intellectual backbone of DTs, providing a framework for interpreting and predicting the behaviour of their physical counterparts. The choice and development of these models are vital for the accuracy and efficacy of DTs, enabling them to mirror and predict the real-time dynamics of bioprocessing systems. Complementing these models, advancements in data collection technologies, such as free-floating wireless sensors and spectroscopic sensors, enhance the monitoring and control capabilities of DTs, providing a more comprehensive and nuanced understanding of the bioprocessing environment. This review offers a critical analysis of the prevailing trends in model-based bioprocessing development within the sector.
Topics: Biotechnology; Machine Learning; Quality Control; Artificial Intelligence; Internet of Things
PubMed: 38754797
DOI: 10.1016/j.biotechadv.2024.108378 -
Proceedings of the National Academy of... Oct 2023Houston TX experienced a widely known failure of its police forensic laboratory. This gave rise to the Houston Forensic Science Center (HFSC) as a separate entity to...
Houston TX experienced a widely known failure of its police forensic laboratory. This gave rise to the Houston Forensic Science Center (HFSC) as a separate entity to provide forensic services to the City of Houston. HFSC is a very large forensic laboratory and has made significant progress at remediating the past failures and improving public trust in forensic testing. HFSC has a large and robust blind testing program, which has provided many insights into the challenges forensic laboratories face. HFSC's journey from a notoriously failed lab to a model also gives perspective to the resource challenges faced by all labs in the country. Challenges for labs include the pervasive reality of poor-quality evidence. Also that forensic laboratories are necessarily part of a much wider system of interdependent functions in criminal justice making blind testing something in which all parts have a role. This interconnectedness also highlights the need for an array of oversight and regulatory frameworks to function properly. The major essential databases in forensics need to be a part of blind testing programs and work is needed to ensure that the results from these databases are indeed producing correct results and those results are being correctly used. Last, laboratory reports of "inconclusive" results are a significant challenge for laboratories and the system to better understand when these results are appropriate, necessary and most importantly correctly used by the rest of the system.
Topics: Humans; Crime; Forensic Medicine; Forensic Sciences; Police; Criminal Law
PubMed: 37782808
DOI: 10.1073/pnas.2303592120