Stringent nonpharmaceutical interventions (NPIs) such as lockdowns and border closures are not currently recommended for pandemic influenza control. New Zealand used these NPIs to eliminate ...coronavirus disease 2019 during its first wave. Using multiple surveillance systems, we observed a parallel and unprecedented reduction of influenza and other respiratory viral infections in 2020. This finding supports the use of these NPIs for controlling pandemic influenza and other severe respiratory viral threats.
Background
New Zealand's (NZ) complete absence of community transmission of influenza and respiratory syncytial virus (RSV) after May 2020, likely due to COVID‐19 elimination measures, provided a ...rare opportunity to assess the impact of border restrictions on common respiratory viral infections over the ensuing 2 years.
Methods
We collected the data from multiple surveillance systems, including hospital‐based severe acute respiratory infection surveillance, SHIVERS‐II, ‐III and ‐IV community cohorts for acute respiratory infection (ARI) surveillance, HealthStat sentinel general practice (GP) based influenza‐like illness surveillance and SHIVERS‐V sentinel GP‐based ARI surveillance, SHIVERS‐V traveller ARI surveillance and laboratory‐based surveillance. We described the data on influenza, RSV and other respiratory viral infections in NZ before, during and after various stages of the COVID related border restrictions.
Results
We observed that border closure to most people, and mandatory government‐managed isolation and quarantine on arrival for those allowed to enter, appeared to be effective in keeping influenza and RSV infections out of the NZ community. Border restrictions did not affect community transmission of other respiratory viruses such as rhinovirus and parainfluenza virus type‐1. Partial border relaxations through quarantine‐free travel with Australia and other countries were quickly followed by importation of RSV in 2021 and influenza in 2022.
Conclusion
Our findings inform future pandemic preparedness and strategies to model and manage the impact of influenza and other respiratory viral threats.
...she brings us along on the journey of her own life, from a childhood as a minister's daughter, through the challenges of growing up in the grip of a patriarchal purity culture, to the adult ...realization that she had everything she needed inside her all along. Through these intertwined journeys, Cleveland also shares the gift of her soul-searching and its fruits - self-love, the knowledge that God is who we need God to be and how to bring a 2-foot statue home on an airplane. Throughout this thought-provoking, revealing and challenging book, Cleveland elucidates the lessons she learned, and continues to learn, as she embraces the God of the side-eye, of thick thighs, of the intimate knowledge of loss, mistreatment, suffering, and making a way out of no way Like Christian in A Pilgrim's Progress, we are invited along for the journey in God Is a Black Woman as the author breaks from her past in an effort to find "Life!
Kidney organoids have potential uses in disease modelling, drug screening and regenerative medicine. However, novel cost-effective techniques are needed to enable scaled-up production of kidney cell ...types
We describe here a modified suspension culture method for the generation of kidney micro-organoids from human pluripotent stem cells. Optimisation of differentiation conditions allowed the formation of micro-organoids, each containing six to ten nephrons that were surrounded by endothelial and stromal populations. Single cell transcriptional profiling confirmed the presence and transcriptional equivalence of all anticipated renal cell types consistent with a previous organoid culture method. This suspension culture micro-organoid methodology resulted in a three- to fourfold increase in final cell yield compared with static culture, thereby representing an economical approach to the production of kidney cells for various biological applications.
Intracranial stenosis is one of the most common etiologies of stroke. To our knowledge, no randomized clinical trials have compared balloon-expandable stent treatment with medical therapy in ...symptomatic intracranial arterial stenosis.
To evaluate the efficacy and safety of the balloon-expandable stent plus medical therapy vs medical therapy alone in patients with symptomatic intracranial stenosis (≥70%).
VISSIT (the Vitesse Intracranial Stent Study for Ischemic Stroke Therapy) trial is an international, multicenter, 1:1 randomized, parallel group trial that enrolled patients from 27 sites (January 2009-June 2012) with last follow-up in May 2013.
Patients (N = 112) were randomized to receive balloon-expandable stent plus medical therapy (stent group; n = 59) or medical therapy alone (medical group; n = 53).
a composite of stroke in the same territory within 12 months of randomization or hard transient ischemic attack (TIA) in the same territory day 2 through month 12 postrandomization. A hard TIA was defined as a transient episode of neurological dysfunction caused by focal brain or retinal ischemia lasting at least 10 minutes but resolving within 24 hours. Primary safety measure: a composite of any stroke, death, or intracranial hemorrhage within 30 days of randomization and any hard TIA between days 2 and 30 of randomization. Disability was measured with the modified Rankin Scale and general health status with the EuroQol-5D, both through month 12.
Enrollment was halted by the sponsor after negative results from another trial prompted an early analysis of outcomes, which suggested futility after 112 patients of a planned sample size of 250 were enrolled. The 30-day primary safety end point occurred in more patients in the stent group (14/58; 24.1% 95% CI, 13.9%-37.2%) vs the medical group (5/53; 9.4% 95% CI, 3.1%-20.7%) (P = .05). Intracranial hemorrhage within 30 days occurred in more patients in the stent group (5/58; 8.6% 95% CI, 2.9%-19.0%) vs none in the medical group (95% CI, 0%-5.5%) (P = .06). The 1-year primary outcome of stroke or hard TIA occurred in more patients in the stent group (21/58; 36.2% 95% CI, 24.0-49.9) vs the medical group (8/53; 15.1% 95% CI, 6.7-27.6) (P = .02). Worsening of baseline disability score (modified Rankin Scale) occurred in more patients in the stent group (14/58; 24.1% 95% CI, 13.9%-37.2%) vs the medical group (6/53; 11.3% 95% CI, 4.3%-23.0%) (P = .09).The EuroQol-5D showed no difference in any of the 5 dimensions between groups at 12-month follow-up.
Among patients with symptomatic intracranial arterial stenosis, the use of a balloon-expandable stent compared with medical therapy resulted in an increased 12-month risk of added stroke or TIA in the same territory, and increased 30-day risk of any stroke or TIA. These findings do not support the use of a balloon-expandable stent for patients with symptomatic intracranial arterial stenosis.
clinicaltrials.gov Identifier: NCT00816166.
Atrial fibrillation (AF) is associated with increased inward-rectifier current activity that may stabilize atrial rotors maintaining the arrhythmia. Left atrial (LA) structures are important for AF ...maintenance, but previous studies have mostly evaluated changes in the right atrium. MicroRNA-1 (miR-1) reciprocally regulates inwardly rectifying potassium channel (Kir)2.1 expression in coronary disease, contributing to arrhythmogenesis.
This study sought to evaluate changes in miR-1 and Kir2 subunit expression in relation to I(K1) alterations in LA of patients with persistent AF.
Atrial tissue was obtained from 62 patients (31 with AF) undergoing mitral valve repair or bypass grafting. Currents were recorded from isolated cells. Proteins were quantified from immunoblots. mRNA and miR-1 levels were measured with real-time polymerase chain reaction. Immunohistochemistry was applied to localize connexin (Cx) 43.
I(K1) density was increased in LA cells from patients with AF (at -100 mV: -5.9 +/- 1.3 vs. -2.7 +/- 0.7 sinus rhythm, P <.05). There was a corresponding increase in Kir2.1 protein expression, but no change in other Kir or Cx proteins. Expression of inhibitory miR-1 was reduced by approximately 86% in tissue samples of AF patients. Kir2.1 mRNA was significantly increased. No change in Cx43 localization occurred. Ex vivo tachystimulation of human atrial slices up-regulated Kir2.1 and down-regulated miR-1, suggesting a primary role of atrial rate in miR-1 down-regulation and I(K1) up-regulation.
miR-1 levels are greatly reduced in human AF, possibly contributing to up-regulation of Kir2.1 subunits, leading to increased I(K1). Because up-regulation of inward-rectifier currents is important for AF maintenance, these results provide potential new insights into molecular mechanisms of AF with potential therapeutic implications.
Congenital heart defects can be caused by mutations in genes that guide cardiac lineage formation. Here, we show deletion of NKX2-5, a critical component of the cardiac gene regulatory network, in ...human embryonic stem cells (hESCs), results in impaired cardiomyogenesis, failure to activate VCAM1 and to downregulate the progenitor marker PDGFRα. Furthermore, NKX2-5 null cardiomyocytes have abnormal physiology, with asynchronous contractions and altered action potentials. Molecular profiling and genetic rescue experiments demonstrate that the bHLH protein HEY2 is a key mediator of NKX2-5 function during human cardiomyogenesis. These findings identify HEY2 as a novel component of the NKX2-5 cardiac transcriptional network, providing tangible evidence that hESC models can decipher the complex pathways that regulate early stage human heart development. These data provide a human context for the evaluation of pathogenic mutations in congenital heart disease.
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