Lynch syndrome: from detection to treatment Williams, Madeleine H; Hadjinicolaou, Andreas V; Norton, Benjamin C ...
Frontiers in oncology,
05/2023, Letnik:
13
Journal Article
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Lynch syndrome (LS) is an inherited cancer predisposition syndrome associated with high lifetime risk of developing tumours, most notably colorectal and endometrial. It arises in the context of ...pathogenic germline variants in one of the mismatch repair genes, that are necessary to maintain genomic stability. LS remains underdiagnosed in the population despite national recommendations for empirical testing in all new colorectal and endometrial cancer cases. There are now well-established colorectal cancer surveillance programmes, but the high rate of interval cancers identified, coupled with a paucity of high-quality evidence for extra-colonic cancer surveillance, means there is still much that can be achieved in diagnosis, risk-stratification and management. The widespread adoption of preventative pharmacological measures is on the horizon and there are exciting advances in the role of immunotherapy and anti-cancer vaccines for treatment of these highly immunogenic LS-associated tumours. In this review, we explore the current landscape and future perspectives for the identification, risk stratification and optimised management of LS with a focus on the gastrointestinal system. We highlight the current guidelines on diagnosis, surveillance, prevention and treatment and link molecular disease mechanisms to clinical practice recommendations.
Sunscreens are topical preparations containing one or more compounds that filter, block, reflect, scatter, or absorb ultraviolet (UV) light. Part 2 of this review focuses on the environmental, ...ecological effects and human toxicities that have been attributed to UV filters.
Literature review using NIH databases (eg, PubMed and Medline), FDA and EPA databases, Google Scholar, the Federal Register, and the Code of Federal Regulations (CFR).
This was a retrospective literature review that involved many different types of studies across a variety of species. Comparison between reports is limited by variations in methodology and criteria for toxicity.
In vivo and in vitro studies on the environmental and biological effects of UV filters show a wide array of unanticipated adverse effects on the environment and exposed organisms. Coral bleaching receives considerable attention from the lay press, but the scientific literature identifies potential toxicities of endocrine, neurologic, neoplastic and developmental pathways. These effects harm a vast array of aquatic and marine biota, while almost no data supports human toxicity at currently used quantities (with the exception of contact allergy). Much of these data are from experimental studies or field observations; more controlled environmental studies and long-term human use data are limited. Several jurisdictions have prohibited specific UV filters, but this does not adequately address the dichotomy of the benefits of photoprotection vs lack of eco-friendly, safe, and FDA-approved alternatives.
A glossary of pandemic-related terms Norton, Benjamin B.; Morens, David M.; Norton, Scott A.
Journal of the American Academy of Dermatology,
03/2021, Letnik:
84, Številka:
3
Journal Article
Absorption imaging of a single atom Streed, Erik W; Jechow, Andreas; Norton, Benjamin G ...
Nature communications,
2012-Jul-03, Letnik:
3, Številka:
1
Journal Article
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Absorption imaging has played a key role in the advancement of science from van Leeuwenhoek's discovery of red blood cells to modern observations of dust clouds in stellar nebulas and Bose-Einstein ...condensates. Here we show the first absorption imaging of a single atom isolated in a vacuum. The optical properties of atoms are thoroughly understood, so a single atom is an ideal system for testing the limits of absorption imaging. A single atomic ion was confined in an RF Paul trap and the absorption imaged at near wavelength resolution with a phase Fresnel lens. The observed image contrast of 3.1 (3)% is the maximum theoretically allowed for the imaging resolution of our set-up. The absorption of photons by single atoms is of immediate interest for quantum information processing. Our results also point out new opportunities in imaging of light-sensitive samples both in the optical and X-ray regimes.
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Although cochlear implant (CI) technology has allowed for the partial restoration of hearing over the last few decades, persistent challenges (e.g., poor performance in noisy ...environments and limited ability to decode intonation and music) remain. The “electrode–neuron gap” is inherent to these challenges and poses the most significant obstacle to advancing past the current plateau in CI performance. We propose the development of a “neuro-regenerative nexus”—a biological interface that doubly preserves native spiral ganglion neurons (SGNs) while precisely directing the growth of neurites arising from transplanted human pluripotent stem cell (hPSC)-derived otic neuronal progenitors (ONPs) toward the native SGN population. We hypothesized that the Polyhedrin Delivery System (PODS®-recombinant human brain-derived neurotrophic factor rhBDNF) could stably provide the adequate BDNF concentration gradient to hPSC-derived late-stage ONPs to facilitate otic neuronal differentiation and directional neurite outgrowth. To test this hypothesis, a finite element model (FEM) was constructed to simulate BDNF concentration profiles generated by PODS®-rhBDNF based on initial concentration and culture device geometry. For biological validation of the FEM, cell culture experiments assessing survival, differentiation, neurite growth direction, and synaptic connections were conducted using a multi-chamber microfluidic device. We were able to successfully generate the optimal BDNF concentration gradient to enable survival, neuronal differentiation toward SGNs, directed neurite extension of hPSC-derived SGNs, and synaptogenesis between two hPSC-derived SGN populations. This proof-of-concept study provides a step toward the next generation of CI technology.
Our study demonstrates that the generation of in vitro neurotrophin concentration gradients facilitates survival, neuronal differentiation toward auditory neurons, and directed neurite extension of human pluripotent stem cell-derived auditory neurons. These findings are indispensable to designing a bioactive cochlear implant, in which stem cell-derived neurons are integrated into a cochlear implant electrode strip, as the strategy will confer directional neurite growth from the transplanted cells in the inner ear. This study is the first to present the concept of a “neuro-regenerative nexus” congruent with a bioactive cochlear implant to eliminate the electrode-neuron gap—the most significant barrier to next-generation cochlear implant technology.
Trapped ions are a leading system for realizing quantum information processing (QIP). Most of the technologies required for implementing large-scale trapped-ion QIP have been demonstrated, with one ...key exception: a massively parallel ion-photon interconnect. Arrays of microfabricated phase Fresnel lenses (PFL) are a promising interconnect solution that is readily integrated with ion trap arrays for large-scale QIP. Here we show the first imaging of trapped ions with a microfabricated in-vacuum PFL, demonstrating performance suitable for scalable QIP. A single ion fluorescence collection efficiency of 4.2±1.5% was observed. The depth of focus for the imaging system was 19.4±2.4 μm and the field of view was 140±20 μm. Our approach also provides an integrated solution for high-efficiency optical coupling in neutral atom and solid-state QIP architectures.
The concept of emerging diseases is well understood; however, the concept of emerging injuries is not. We describe the introduction of two species of lionfish, native to the Indian and Pacific ...Oceans, into the warm shallow coastal waters of the Western Atlantic Ocean and the Caribbean Sea. Lionfish thrive in the same coastal waters that attract recreational swimmers, snorkelers, and divers. Because lionfish have ornate colors, people often swim close to have a better look. Lionfish have venomous spines and, in a defensive reaction, frequently envenomate curious humans. The fish are voracious predators and disrupt the coral ecosystems of the Atlantic. Furthermore, their range is spreading through a combination of lack of natural predators and the expansion of hospitable warm waters into higher latitudes as part of climate change.
We report the successful treatment of poxvirus lesions in two juvenile American flamingos (Phoenicopterus ruber) with experimental low-dose intralesional ribavirin injection. In the first flamingo, ...the size and location of a beak verrucosity interfered with feeding, and after multiple surgical interventions, an experimental therapy of low-dose intralesional ribavirin was implemented with close blood parameter monitoring to minimize any potential side effects due to systemic antiviral administration. The second flamingo had a poxvirus lesion on the tibiotarsus, which recurred after unsuccessful conservative medical treatment and surgical intervention and a course of intralesional ribavirin therapy was implemented. Regression of the lesions in both flamingos commenced within 3 days of ribavirin treatment resulting in complete resolution within 6 weeks of onset of ribavirin treatment.
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Barrett’s oesophagus is a pathological condition whereby the normal oesophageal squamous mucosa is replaced by specialised, intestinal-type metaplasia, which is strongly linked to chronic ...gastro-oesophageal reflux. A correct endoscopic and histological diagnosis is pivotal in the management of Barrett’s oesophagus to identify patients who are at high risk of progression to neoplasia. The presence and grade of dysplasia and the characteristics of visible lesions within the mucosa of Barrett’s oesophagus are both important to guide the most appropriate endoscopic therapy. In this review, we provide an overview on the management of Barrett’s oesophagus, with a particular focus on recent advances in the diagnosis and recommendations for endoscopic therapy to reduce the risk of developing oesophageal adenocarcinoma.
Research on the otolith organs remains inconclusive.
This study seeks to further elucidate utricular function in patients with Meniere's disease (MD) in three ways: (1) We aimed to disambiguate the ...role of the Subjective Visual Vertical (SVV) and Ocular Vestibular Evoked Myogenic Potential (o-VEMP) tests regarding which utricular subsystem each is measuring. (2) We sought to characterize the acute and chronic state of MD by identifying differences in the relationship of SVV and o-VEMP results across patients with acute and chronic MD. (3) We attempted to find a machine-learning algorithm that could predict acute versus chronic MD using SVV and o-VEMP.
A prospective study with ninety subjects.
(1) SVV and o-VEMP tests were found to have a moderate linear relationship in patients with acute MD, suggesting each test measures a different utricular subsystem. (2) Regression analyses statistically differed across the two patient populations, suggesting that SVV results were normalized in chronic MD patients. (3) Logistic regression and Naïve Bayes algorithms were found to predict acute and chronic MD accurately.
A better understanding of what diagnostic tests measure will lead to a better classification system for MD and more targeted treatment options in the future.
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