COVID-19, IP and access: will the current system of medical innovation and access to medicines meet global expectations?

The COVID-19 pandemic has exposed the fundamental flaws in the current system of medical innovation and access to medicines, which require urgent attention from the global community. This is prompted by the experience of the past decades, which has proven that this system was ineffective in securing adequate access to medicines for all. The understanding of the deficiencies of the existing system is crucial today, as it may help to design effective approaches for improving access. This article will also consider mechanisms that may be implemented by governments for the protection of public health. These include short-term mechanisms, such as compulsory licensing and government use, as well as the long-term design of a new innovation model, including state-coordinated research of medicines and open innovation. The current system should be reconsidered to ensure the prompt development of COVID-19 therapy accessible to everyone and full preparedness for the pandemics of the future

Differentiation of Foot-and-Mouth Disease-Infected pigs from Vaccinated Pigs Using Antibody-Detecting Sandwich ELISA

The presence of serum antibodies for nonstructural proteins of the foot-and-mouth disease virus (FMDV) can differentiate FMDV-infected animals from vaccinated animals. In this study, a sandwich ELISA was developed for rapid detection of the foot-and-mouth disease (FMD) antibodies; it was based on an Escherichia coli-expressed, highly conserved region of the 3ABC nonstructural protein of the FMDV O/TW/99 strain and a monoclonal antibody derived from the expressed protein. The diagnostic sensitivity of the assay was 98.4%, and the diagnostic specificity was 100% for naïve and vaccinated pigs; the detection ability of the assay was comparable those of the PrioCHECK and UBI kits. There was 97.5, 93.4 and 66.6% agreement between the results obtained from our ELISA and those obtained from the PrioCHECK, UBI and CHEKIT kits, respectively. The kappa statistics were 0.95, 0.87 and 0.37, respectively. Moreover, antibodies for nonstructural proteins of the serotypes A, C, Asia 1, SAT 1, SAT 2 and SAT 3 were also detected in bovine sera. Furthermore, the absence of cross-reactions generated by different antibody titers against the swine vesicular disease virus and vesicular stomatitis virus (VSV) was also highlighted in this assay's specificit

Building trust in real-world data: lessons from INSIGHT, the UK's health data research hub for eye health and oculomics

PURPOSE OF REVIEW: In this review, we consider the challenges of creating a trusted resource for real-world data in ophthalmology, based on our experience of establishing INSIGHT, the UK's Health Data Research Hub for Eye Health and Oculomics. RECENT FINDINGS: The INSIGHT Health Data Research Hub maximizes the benefits and impact of historical, patient-level UK National Health Service (NHS) electronic health record data, including images, through making it research-ready including curation and anonymisation. It is built around a shared 'north star' of enabling research for patient benefit. INSIGHT has worked to establish patient and public trust in the concept and delivery of INSIGHT, with efficient and robust governance processes that support safe and secure access to data for researchers. By linking to systemic data, there is an opportunity for discovery of novel ophthalmic biomarkers of systemic diseases ('oculomics'). Datasets that provide a representation of the whole population are an important tool to address the increasingly recognized threat of health data poverty. SUMMARY: Enabling efficient, safe access to routinely collected clinical data is a substantial undertaking, especially when this includes imaging modalities, but provides an exceptional resource for research. Research and innovation built on inclusive real-world data is an important tool in ensuring that discoveries and technologies of the future may not only favour selected groups, but also work for all patients

Structure of the CaMKIIδ/Calmodulin Complex Reveals the Molecular Mechanism of CaMKII Kinase Activation

Structural and biophysical studies reveal how CaMKII kinases, which are important for cellular learning and memory, are switched on by binding of Ca2+/calmodulin

An overview of the Phalaenopsis orchid genome through BAC end sequence analysis

<p>Abstract</p> <p>Background</p> <p><it>Phalaenopsis </it>orchids are popular floral crops, and development of new cultivars is economically important to floricultural industries worldwide. Analysis of orchid genes could facilitate orchid improvement. Bacterial artificial chromosome (BAC) end sequences (BESs) can provide the first glimpses into the sequence composition of a novel genome and can yield molecular markers for use in genetic mapping and breeding.</p> <p>Results</p> <p>We used two BAC libraries (constructed using the <it>Bam</it>HI and <it>Hin</it>dIII restriction enzymes) of <it>Phalaenopsis equestris </it>to generate pair-end sequences from 2,920 BAC clones (71.4% and 28.6% from the <it>Bam</it>HI and <it>Hin</it>dIII libraries, respectively), at a success rate of 95.7%. A total of 5,535 BESs were generated, representing 4.5 Mb, or about 0.3% of the <it>Phalaenopsis </it>genome. The trimmed sequences ranged from 123 to 1,397 base pairs (bp) in size, with an average edited read length of 821 bp. When these BESs were subjected to sequence homology searches, it was found that 641 (11.6%) were predicted to represent protein-encoding regions, whereas 1,272 (23.0%) contained repetitive DNA. Most of the repetitive DNA sequences were gypsy- and copia-like retrotransposons (41.9% and 12.8%, respectively), whereas only 10.8% were DNA transposons. Further, 950 potential simple sequence repeats (SSRs) were discovered. Dinucleotides were the most abundant repeat motifs; AT/TA dimer repeats were the most frequent SSRs, representing 253 (26.6%) of all identified SSRs. Microsynteny analysis revealed that more BESs mapped to the whole-genome sequences of poplar than to those of grape or <it>Arabidopsis</it>, and even fewer mapped to the rice genome. This work will facilitate analysis of the <it>Phalaenopsis </it>genome, and will help clarify similarities and differences in genome composition between orchids and other plant species.</p> <p>Conclusion</p> <p>Using BES analysis, we obtained an overview of the <it>Phalaenopsis </it>genome in terms of gene abundance, the presence of repetitive DNA and SSR markers, and the extent of microsynteny with other plant species. This work provides a basis for future physical mapping of the <it>Phalaenopsis </it>genome and advances our knowledge thereof.</p

Association of sildenafil use with age-related macular degeneration:a retrospective cohort study

Objective: Despite significant advances in clinical care and understanding of the underlying pathophysiology, age-related macular degeneration (AMD)—a major cause of global blindness—lacks effective treatment to prevent the irreversible degeneration of photoreceptors leading to central vision loss. Limited studies suggest phosphodiesterase type 5 (PDE5) inhibitors, such as sildenafil, may prevent AMD by increasing retinal blood flow. This study explores the potential association between sildenafil use and AMD risk in men with erectile dysfunction using UK data. Methods and analysis: Using the UK’s IQVIA Medical Research Data, the study analysed 31 575 men prescribed sildenafil for erectile dysfunction and no AMD history from 2007 to 2015, matched with a comparator group of 62 155 non-sildenafil users in a 1:2 ratio, over a median follow-up of approximately three years. Results: The primary outcome was the incidence of AMD in the two groups. The study found no significant difference in AMD incidence between the sildenafil users and the non-users, with an adjusted hazard ratio (HR) of 0.99 (95% CI 0.84 to 1.16), after accounting for confounders such as age, ethnicity, Townsend deprivation quintile, body mass index category, and diagnosis of hypertension and type 2 diabetes. Conclusion: The study results indicated no significant association between sildenafil use and AMD prevention in UK men with erectile dysfunction, suggesting sildenafil’s protective effect on AMD is likely insignificant

Structural basis of fumarate hydratase deficiency

Fumarate hydratase catalyzes the stereospecific hydration across the olefinic double bond in fumarate leading to L-malate. The enzyme is expressed in mitochondrial and cytosolic compartments, and participates in the Krebs cycle in mitochondria, as well as in regulation of cytosolic fumarate levels. Fumarate hydratase deficiency is an autosomal recessive trait presenting as metabolic disorder with severe encephalopathy, seizures and poor neurological outcome. Heterozygous mutations are associated with a predisposition to cutaneous and uterine leiomyomas and to renal cancer. The crystal structure of human fumarate hydratase shows that mutations can be grouped into two distinct classes either affecting structural integrity of the core enzyme architecture, or are localized around the enzyme active site

Aberrant KDM5B expression promotes aggressive breast cancer through MALAT1 overexpression and downregulation of hsa-miR-448

Relative expression of KDM5B, MALAT1, SNAIL, Vimentin and miR 448 normalized against GAPDH in MCF10A WT, MCF10A OE, MDA-MB-231 WT and MDA-MB-231 KD cells. Data are representative of 3 independent experiments and analyzed by student’s t-test. All data are shown as mean ± SEM. WT, wild type; OE, KDM5B overexpressed; KD, knockdown using shKDM5B clone II. (DOCX 519 kb

Traffic agents for improving QoS in mixed infrastructure and ad hoc modes wireless LAN

As an important complement to infrastructured wireless networks, mobile ad hoc networks (MANET) are more flexible in providing wireless access services, but more difficult in meeting different quality of service (QoS) requirements for mobile customers. Both infrastructure and ad hoc network structures are supported in wireless local area networks (WLAN), which can offer high data-rate wireless multimedia services to the mobile stations (MSs) in a limited geographical area. For those out-of-coverage MSs, how to effectively connect them to the access point (AP) and provide QoS support is a challenging issue. By mixing the infrastructure and the ad hoc modes in WLAN, we propose in this paper a new coverage improvement scheme that can identify suitable idle MSs in good service zones as traffic agents (TAs) to relay traffic from those out-of-coverage MSs to the AP. The service coverage area of WLAN is then expanded. The QoS requirements (e.g., bandwidth) of those MSs are considered in the selection process of corresponding TAs. Mathematical analysis, verified by computer simulations, shows that the proposed TA scheme can effectively reduce blocking probability when traffic load is light

Pentaquark baryon production at the Relativistic Heavy Ion Collider

Production of pentaquark $\Theta^+$ baryons in central relativistic heavy ion collisions is studied in a kinetic model. Assuming that a quark-gluon plasma is produced in the collisions, we first determine the number of $\Theta^+$ produced from the quark-gluon plasma using a parton coalescence model, and then take into consideration its production and absorption in subsequent hadronic matter via the reactions $KN\leftrightarrow\Theta$, $KN\leftrightarrow\pi\Theta$, and \piN\leftrightarrow\bar K\Theta. We find that although the final $\Theta^+$ number is affected by hadronic interactions, it remains sensitive to the initial number of $\Theta^+$ produced from the quark-gluon plasma, particularly in the case of a small $\Theta^+$ width as imposed by the $K^+N$ and $K^+d$ scattering data. Because of small baryon chemical potential in the hot dense matter produced in these collisions, the number of produced anti-$\Theta$ is only slightly smaller than that of $\Theta^+$.Comment: 6 pages, 2 figures, revised version, to appear in PL