Biologics such as monoclonal antibodies are much more complex than small-molecule drugs, which raises challenging questions for the development and regulatory evaluation of follow-on versions of such ...biopharmaceutical products (also known as biosimilars) and their clinical use once patent protection for the pioneering biologic has expired. With the recent introduction of regulatory pathways for follow-on versions of complex biologics, the role of analytical technologies in comparing biosimilars with the corresponding reference product is attracting substantial interest in establishing the development requirements for biosimilars. Here, we discuss the current state of the art in analytical technologies to assess three characteristics of protein biopharmaceuticals that regulatory authorities have identified as being important in development strategies for biosimilars: post-translational modifications, three-dimensional structures and protein aggregation.
Alzheimer's Disease (AD) represents a major and rapidly growing burden to the healthcare ecosystem. A growing body of evidence indicates that cognitive, behavioral, sensory, and motor changes may ...precede clinical manifestations of AD by several years. Existing tests designed to diagnose neurodegenerative diseases, while well-validated, are often less effective in detecting deviations from normal cognitive decline trajectory in the earliest stages of the disease. In the quest for gold standards for AD assessment, there is a growing interest in the identification of readily accessible digital biomarkers, which harness advances in consumer grade mobile and wearable technologies. Topics examined include a review of existing early clinical manifestations of AD and a path to the respective sensor and mobile/wearable device usage to acquire domain-centric data towards objective, high frequency and passive digital phenotyping.
Anthocyanins are important health-promoting phytochemicals that are abundant in many fleshy fruits. Bilberry (Vaccinium myrtillus) is one of the best sources of these compounds. Here, we report on ...the expression pattern and functional analysis of a SQUAMOSA-class MADS box transcription factor, VmTDR4, associated with anthocyanin biosynthesis in bilberry. Levels of VmTDR4 expression were spatially and temporally linked with color development and anthocyanin-related gene expression. Virus-induced gene silencing was used to suppress VmTDR4 expression in bilberry, resulting in substantial reduction in anthocyanin levels in fully ripe fruits. Chalcone synthase was used as a positive control in the virus-induced gene silencing experiments. Additionally, in sectors of fruit tissue in which the expression of the VmTDR4 gene was silenced, the expression of R2R3 MYB family transcription factors related to the biosynthesis of flavonoids was also altered. We conclude that VmTDR4 plays an important role in the accumulation of anthocyanins during normal ripening in bilberry, probably through direct or indirect control of transcription factors belonging to the R2R3 MYB family.
Hidradenitis suppurativa (HS) is a complex chronic relapsing inflammatory condition anchored in the hair follicle wherein painful abscesses, nodules, and tunnels form under the skin with the ...potential for intermittent pus drainage and tissue scarring. Current estimates of incidence are 1-4% globally with the disease three times more prevalent in women and higher rates among Black populations. Patients with HS are also more likely to suffer from depression, anxiety, and loneliness underscoring the need for carefully approached strategies on disease awareness and interventions. Delays in formal diagnosis, which have been estimated at 7-10 years on average, impede timely provision of optimal care. Despite best intent, when patients present at a physician's office, stigmas relating to physical appearance can be exacerbated by negative interactions experienced by patients. In addition to long wait times and the dearth of available HS expert dermatology professionals, patients perceive heightened physician focus on two of the HS flare risk factors (smoking and body mass index BMI) as negatively impacting their care. Given the need for continual, personal, and sensitive patient support, herein we advocate for re-examination of approach to care and the leveraging of highly personalized digital support solutions. New medications which can directly or indirectly control elements of the disease and its comorbidities are also entering the marketplace. Collectively, we posit that these new developments provide opportunity for a holistic approach for patients with HS, leading to long-term engagement and improved outcomes.Hidradenitis suppurativa (HS) is a complex chronic relapsing inflammatory condition anchored in the hair follicle wherein painful abscesses, nodules, and tunnels form under the skin with the potential for intermittent pus drainage and tissue scarring. Current estimates of incidence are 1-4% globally with the disease three times more prevalent in women and higher rates among Black populations. Patients with HS are also more likely to suffer from depression, anxiety, and loneliness underscoring the need for carefully approached strategies on disease awareness and interventions. Delays in formal diagnosis, which have been estimated at 7-10 years on average, impede timely provision of optimal care. Despite best intent, when patients present at a physician's office, stigmas relating to physical appearance can be exacerbated by negative interactions experienced by patients. In addition to long wait times and the dearth of available HS expert dermatology professionals, patients perceive heightened physician focus on two of the HS flare risk factors (smoking and body mass index BMI) as negatively impacting their care. Given the need for continual, personal, and sensitive patient support, herein we advocate for re-examination of approach to care and the leveraging of highly personalized digital support solutions. New medications which can directly or indirectly control elements of the disease and its comorbidities are also entering the marketplace. Collectively, we posit that these new developments provide opportunity for a holistic approach for patients with HS, leading to long-term engagement and improved outcomes.
The SARS-Cov-2 pandemic placed a dramatic burden on managed healthcare and perhaps nowhere as evident as in neurological and psychiatric disease care. This said, the duration of the pandemic mandated ...adaptability of the entire care system and the oft-vaunted benefits of telehealth and telemedicine were subjected to deep scrutiny at scale. Positive experiences were reported by both patients and providers from routine check-ups, to use of cognitive behavioral therapy associated with mental disorders, and management of complex diseases such as multiple sclerosis and other neurological and psychiatric conditions. Integration into standard care looks likely in the post pandemic era with many healthcare systems moving to expand reimbursement categories and develop equitable incentive models for developers and providers. In this commentary we share perspective on how the future of care may evolve through hybrid delivery models, and the advent of new therapeutic approaches which can address pain points identified during the pandemic.
Atmospheric dimethylsulfide (DMSa), continually derived from the world's oceans, is a feed gas for the tropospheric production of new sulfate particles, leading to cloud condensation nuclei that ...influence the formation and properties of marine clouds and ultimately the Earth's radiation budget. Previous studies on the Great Barrier Reef (GBR), Australia, have indicated coral reefs are significant sessile sources of DMSa capable of enhancing the tropospheric DMSa burden mainly derived from phytoplankton in the surface ocean; however, specific environmental evidence of coral reef DMS emissions and their characteristics is lacking. By using on-site automated continuous analysis of DMSa and meteorological parameters at Heron Island in the southern GBR, we show that the coral reef was the source of occasional spikes of DMSa identified above the oceanic DMSa background signal. In most instances, these DMSa spikes were detected at low tide under low wind speeds, indicating they originated from the lagoonal platform reef surrounding the island, although evidence of longer-range transport of DMSa from a 70 km stretch of coral reefs in the southern GBR was also observed. The most intense DMSa spike occurred in the winter dry season at low tide when convective precipitation fell onto the aerially exposed platform reef. This co-occurrence of events appeared to biologically shock the coral resulting in a seasonally aberrant extreme DMSa spike concentration of 45.9 nmol m−3 (1122 ppt). Seasonal DMS emission fluxes for the 2012 wet season and 2013 dry season campaigns at Heron Island were 5.0 and 1.4 µmol m−2 day−1, respectively, of which the coral reef was estimated to contribute 4 % during the wet season and 14 % during the dry season to the dominant oceanic flux.
A 2020 World Health Organization report underscored the impact of rising healthcare spending globally and questioned the long-term economic sustainability of current funding models. Increases in ...costs associated with care of late-stage irreversible diseases and the increasing prevalence of debilitating neurodegenerative disorders, coupled with increases in life expectancy are likely to overload the healthcare systems in many nations within the next decade if not addressed. One option for sustainability of the healthcare system is a change in emphasis from illness to wellness centered care. An attractive model is the P4 (Predictive, Preventative, Personalized and Participatory) medicine approach. Recent advances in connected health technology can help accelerate this transition; they offer prediction, diagnosis, and monitoring of health-related parameters. We explain how to integrate such technologies with conventional approaches and guide public health policy toward wellness-based care models and strategies to relieve the escalating economic burdens of managed care.
Thermal tolerance tests on Acropora millepora, a common Indo-Pacific hard coral, have shown that adult corals can acquire increased thermal tolerance by shuffling existing type C to type D ...Symbiodinium zooxanthellae when subjected to increased seawater temperatures. We report here dimethylsulphoniopropionate (DMSP) concentrations in A. millepora and examine links between DMSP concentrations, zooxanthellae clade, and bleaching tolerance. DMSP analysis on native and transplanted corals from three locations in the Great Barrier Reef indicated that the lower thermal tolerance in type C zooxanthellae coincided with variable DMSP concentrations, whilst the more thermal tolerant type D zooxanthellae had more stable areal DMSP concentrations as seawater temperatures increased. Our results suggest this increased thermal tolerance in type D zooxanthellae may reflect the ability of these coral symbionts to conserve their antioxidant DMSP levels to relatively constant concentrations, enabling the coral to overcome the build-up of oxygen free radicals in the cytoplasm of A. millepora. A conceptual diagram illustrates how the antioxidants DMS (P) participate in the bleaching process by scavenging oxygen free radicals and form DMSO, thus moderating coral bleaching and increasing thermotolerance.
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