Complementing model species with model clades.

Model species continue to underpin groundbreaking plant science research. At the same time, the phylogenetic resolution of the land plant Tree of Life continues to improve. The intersection of these two research paths creates a unique opportunity to further extend the usefulness of model species across larger taxonomic groups. Here we promote the utility of the Arabidopsis thaliana model species, especially the ability to connect its genetic and functional resources, to species across the entire Brassicales order. We focus on the utility of using genomics and phylogenomics to bridge the evolution and diversification of several traits across the Brassicales to the resources in Arabidopsis, thereby extending scope from a model species by establishing a "model clade". These Brassicales-wide traits are discussed in the context of both the model species Arabidopsis thaliana and the family Brassicaceae. We promote the utility of such a "model clade" and make suggestions for building global networks to support future studies in the model order Brassicales.

The contributions from the progenitor genomes of the mesopolyploid Brassiceae are evolutionarily distinct but functionally compatible.

The members of the tribe Brassiceae share a whole-genome triplication (WGT), and one proposed model for its formation is a two-step pair of hybridizations producing hexaploid descendants. However, evidence for this model is incomplete, and the evolutionary and functional constraints that drove evolution after the hexaploidy are even less understood. Here, we report a new genome sequence of Crambe hispanica, a species sister to most sequenced Brassiceae. Using this new genome and three others that share the hexaploidy, we traced the history of gene loss after the WGT using the Polyploidy Orthology Inference Tool (POInT). We confirm the two-step formation model and infer that there was a significant temporal gap between those two allopolyploidizations, with about a third of the gene losses from the first two subgenomes occurring before the arrival of the third. We also, for the 90,000 individual genes in our study, make parental subgenome assignments, inferring, with measured uncertainty, from which of the progenitor genomes of the allohexaploidy each gene derives. We further show that each subgenome has a statistically distinguishable rate of homoeolog losses. There is little indication of functional distinction between the three subgenomes: the individual subgenomes show no patterns of functional enrichment, no excess of shared protein-protein or metabolic interactions between their members, and no biases in their likelihood of having experienced a recent selective sweep. We propose a "mix and match" model of allopolyploidy, in which subgenome origin drives homoeolog loss propensities but where genes from different subgenomes function together without difficulty.

Leadership and early strategic response to the SARS-CoV-2 pandemic at a COVID-19 designated hospital in South Africa.

While many countries are preparing to face the COVID-19 pandemic, the reported cases in Africa remain low. With a high burden of both communicable and non-communicable disease and a resource-constrained public healthcare system, sub-Saharan Africa is preparing for the coming crisis as best it can. We describe our early response as a designated COVID-19 provincial hospital in Cape Town, South Africa (SA).While the first cases reported were related to international travel, at the time of writing there was evidence of early community spread. The SAgovernment announced a countrywide lockdown from midnight 26 March 2020 to midnight 30 April 2020 to stem the pandemic and save lives. However, many questions remain on how the COVID-19 threat will unfold in SA, given the significant informal sector overcrowding and poverty in our communities. There is no doubt that leadership and teamwork at all levels is critical in influencing outcomes.

Genomic Origin and Diversification of the Glucosinolate MAM Locus.

Glucosinolates are a diverse group of plant metabolites that characterize the order Brassicales. The MAM locus is one of the most significant QTLs for glucosinolate diversity. However, most of what we understand about evolution at the locus is focused on only a few species and not within a phylogenetic context. In this study, we utilize a micro-synteny network and phylogenetic inference to investigate the origin and diversification of the MAM/IPMS gene family. We uncover unique MAM-like genes found at the orthologous locus in the Cleomaceae that shed light on the transition from IPMS to MAM. In the Brassicaceae, we identify six distinct MAM clades across Lineages I, II, and III. We characterize the evolutionary impact and consequences of local duplications, transpositions, whole genome duplications, and gene fusion events, generating several new hypothesizes on the function and diversity of the MAM locus.

Leadership and early strategic response to the SARS-CoV-2 pandemic at a COVID-19 designated hospital in South Africa

While many countries are preparing to face the COVID-19 pandemic, the reported cases in Africa remain low. With a high burden of both communicable and non-communicable disease and a resource-constrained public healthcare system, sub-Saharan Africa is preparing for the coming crisis as best it can. We describe our early response as a designated COVID-19 provincial hospital in Cape Town, South Africa (SA).While the first cases reported were related to international travel, at the time of writing there was evidence of early community spread. The SA government announced a countrywide lockdown from midnight 26 March 2020 to midnight 30 April 2020 to stem the pandemic and save lives. However, many questions remain on how the COVID-19 threat will unfold in SA, given the significant informal sector overcrowding and poverty in our communities. There is no doubt that leadership and teamwork at all levels is critical in influencing outcomes

Targeting mitochondrial translation by inhibiting DDX3: a novel radiosensitization strategy for cancer treatment.

DDX3 is a DEAD box RNA helicase with oncogenic properties. RK-33 is developed as a small-molecule inhibitor of DDX3 and showed potent radiosensitizing activity in preclinical tumor models. This study aimed to assess DDX3 as a target in breast cancer and to elucidate how RK-33 exerts its anti-neoplastic effects. High DDX3 expression was present in 35% of breast cancer patient samples and correlated with markers of aggressiveness and shorter survival. With a quantitative proteomics approach, we identified proteins involved in the mitochondrial translation and respiratory electron transport pathways to be significantly downregulated after RK-33 or DDX3 knockdown. DDX3 localized to the mitochondria and DDX3 inhibition with RK-33 reduced mitochondrial translation. As a consequence, oxygen consumption rates and intracellular ATP concentrations decreased and reactive oxygen species (ROS) increased. RK-33 antagonized the increase in oxygen consumption and ATP production observed after exposure to ionizing radiation and reduced DNA repair. Overall, we conclude that DDX3 inhibition with RK-33 causes radiosensitization in breast cancer through inhibition of mitochondrial translation, which results in reduced oxidative phosphorylation capacity and increased ROS levels, culminating in a bioenergetic catastrophe.

Talar Fractures and Dislocations: A Radiologist's Guide to Timely Diagnosis and Classification.

The talus, the second largest tarsal bone, has distinctive imaging characteristics and injury patterns. The predominantly extraosseous vascular supply of the talus predisposes it to significant injury in the setting of trauma. In addition, the lack of muscular attachments and absence of a secondary blood supply can lead to subsequent osteonecrosis. Although talar fractures account for less than 1% of all fractures, they commonly result from high-energy trauma and may lead to complications and long-term morbidity if not recognized and managed appropriately. While initial evaluation is with foot and ankle radiographs, computed tomography (CT) is often performed to evaluate the extent of the fracture, displacement, comminution, intra-articular extension, and associated injuries. Talar fractures are divided by anatomic region: head, neck, and body. Talar head fractures can be treated conservatively if nondisplaced, warranting careful radiographic and CT evaluation to assess rotation, displacement, and extension into the neck. The modified Hawkins-Canale classification of talar neck fractures is most commonly used due to its simplicity, usefulness in guiding treatment, and prognostic value, as it correlates associated malalignment with risk of subsequent osteonecrosis. Isolated talar body fractures may be more common than previously thought. The Sneppen classification further divides talar body fractures into osteochondral talar dome, lateral and posterior process, and shear and crush comminuted central body fractures. Crush comminuted central body fractures carry a poor prognosis due to nonanatomic reduction, bone loss, and subsequent osteonecrosis. Lateral process fractures can be radiographically occult and require a higher index of suspicion for successful diagnosis. Subtalar dislocations are often accompanied by fractures, necessitating postreduction CT. Familiarity with the unique talar anatomy and injury patterns is essential for radiologists to facilitate appropriate and timely management.

Efficacy and safety of ipratropium bromide/albuterol delivered via Respimat inhaler versus MDI.

We compared the efficacy and safety of ipratropium bromide/albuterol delivered via Respimat inhaler, a novel propellant-free inhaler, versus chlorofluorocarbon (CFC)-metered dose inhaler (MDI) and ipratropium Respimat inhaler in patients with COPD. This was a multinational, randomized, double-blind, double-dummy, 12-week, parallel-group, active-controlled study. Patients with moderate to severe COPD were randomized to ipratropium bromide/albuterol (20/100mcg) Respimat inhaler, ipratropium bromide/albuterol MDI [36mcg/206mcg (Combivent Inhalation Aerosol MDI)], or ipratropium bromide (20mcg) Respimat inhaler. Each medication was administered four times daily. Serial spirometry was performed over 6h (0.15min, then hourly) on 4 test days. The primary efficacy variable was forced expiratory volume in 1s (FEV(1)) change from test day baseline at 12 weeks. A total of 1209 of 1480 randomized, treated patients completed the study; the majority were male (65%) with a mean age of 64 yrs and a mean screening pre-bronchodilator FEV(1) (percent predicted) of 41%. Ipratropium bromide/albuterol Respimat inhaler had comparable efficacy to ipratropium bromide/albuterol MDI for FEV(1) area under the curve at 0-6h (AUC(0-6)), superior efficacy to ipratropium Respimat inhaler for FEV(1) AUC(0-4) and comparable efficacy to ipratropium Respimat inhaler for FEV(1) AUC(4-6). All active treatments were well tolerated. This study demonstrates that ipratropium bromide/albuterol 20/100mcg inhaler administered four times daily for 12 weeks had equivalent bronchodilator efficacy and comparable safety to ipratropium bromide/albuterol 36mcg/206mcg MDI, and significantly improved lung function compared with the mono-component ipratropium bromide 20 mcg Respimat inhaler. [Clinical Trial Identifier Number: NCT00400153].

Abdominal tuberculosis: the problem of diagnostic delay.

Abdominal tuberculosis can be difficult to diagnose. In order to minimize diagnostic delay, an audit study showed that the Mantoux test and/or culture of ascitic fluid did not reveal tuberculosis immediately. Laparoscopy/laparotomy with Ziel-Nielson staining and culture of tissue biopsy always confirmed the diagnosis. It is suggested that biopsy should be the first line in investigating patients suspected of having abdominal tuberculosis.

Measuring the adequacy of home care for frail elders.

Community elders (N = 330) were interviewed by telephone twice at baseline using both computer-assisted telephone interviews (CATI) and nurse clinicians, and at four-month follow-up using CATI to collect alternative paraprofessional home care adequacy measures. Measurement format influenced both reliability and observed levels of adequacy but alternative adequacy measures converged and were not closely linked to functional status. The predictive validity of measures based on clinical standards with respect to health outcomes was also demonstrated. These findings support emerging approaches in primary care and home health quality measurement that consider multiple dimension of user response to formal and informal care.

The administration of eligibility for community long-term care.

Eligibility assessment systems for community long-term care vary widely across current programs funded by states and Medicaid and in proposals to expand federal funding. Improved equity and efficiency in both current and proposed programs will require better specification of eligibility criteria, timing and setting of assessments, language of assessment items, training of assessors, procedures for appeal and review, and consideration of the costs of care management. Recent research and demonstrations provide models and technology for more uniform approaches in national programs.

Integrating care for the geriatric patient. Examples from the Social HMO (SHMO).

Managing the care of geriatric patients with chronic disease focuses attention on the functional impairments that place these patients at risk in the home environment. Maintaining patients in their preferred home settings requires physicians to coordinate effective discharge planning and long-term community care resources. A service coordinator or case manager can play a key role in coordinating the broad array of services needed, as well as linking the providers involved. A coordinated acute and long-term care service delivery system is described, with examples from the Social HMO (SHMO). Data are presented on SHMO enrollee demographic characteristics, chronic disease conditions and functional levels, as well as data on care plans, utilization and costs. A case example illustrates how ongoing medical and long-term care are integrated. Implications for geriatric care and HMO practice are discussed, with recommendations for improving geriatric care in the next generation of SHMO sites.

Across the great divide. Integrating acute, post-acute and long-term care.

The importance of integrating acute, post-acute and long-term care is underscored by analyses of the extent of medical complexity among the SHMO enrollee population that qualified for a long-term care benefit on functional (not medical) criteria. In the SHMO programs, initiatives to promote integration of services at all levels of care have largely come from the care management units. Integrative practices will vary in different organizational settings. Examples from two very different SHMO sites illustrate how integrative practices are implemented. It is concluded that in order to serve adequately a medically complex and functionally impaired elder population a key function of care management is to develop cooperative relationships, and mechanisms for information exchange, with providers at all system levels, reaching across the great divide between the acute and long-term care systems.