In the US, states enacted nonpharmaceutical interventions, including school closure, to reduce the spread of coronavirus disease 2019 (COVID-19). All 50 states closed schools in March 2020 despite ...uncertainty if school closure would be effective.
To determine if school closure and its timing were associated with decreased COVID-19 incidence and mortality.
US population-based observational study conducted between March 9, 2020, and May 7, 2020, using interrupted time series analyses incorporating a lag period to allow for potential policy-associated changes to occur. To isolate the association of school closure with outcomes, state-level nonpharmaceutical interventions and attributes were included in negative binomial regression models. States were examined in quartiles based on state-level COVID-19 cumulative incidence per 100 000 residents at the time of school closure. Models were used to derive the estimated absolute differences between schools that closed and schools that remained open as well as the number of cases and deaths if states had closed schools when the cumulative incidence of COVID-19 was in the lowest quartile compared with the highest quartile.
Closure of primary and secondary schools.
COVID-19 daily incidence and mortality per 100 000 residents.
COVID-19 cumulative incidence in states at the time of school closure ranged from 0 to 14.75 cases per 100 000 population. School closure was associated with a significant decline in the incidence of COVID-19 (adjusted relative change per week, -62% 95% CI, -71% to -49%) and mortality (adjusted relative change per week, -58% 95% CI, -68% to -46%). Both of these associations were largest in states with low cumulative incidence of COVID-19 at the time of school closure. For example, states with the lowest incidence of COVID-19 had a -72% (95% CI, -79% to -62%) relative change in incidence compared with -49% (95% CI, -62% to -33%) for those states with the highest cumulative incidence. In a model derived from this analysis, it was estimated that closing schools when the cumulative incidence of COVID-19 was in the lowest quartile compared with the highest quartile was associated with 128.7 fewer cases per 100 000 population over 26 days and with 1.5 fewer deaths per 100 000 population over 16 days.
Between March 9, 2020, and May 7, 2020, school closure in the US was temporally associated with decreased COVID-19 incidence and mortality; states that closed schools earlier, when cumulative incidence of COVID-19 was low, had the largest relative reduction in incidence and mortality. However, it remains possible that some of the reduction may have been related to other concurrent nonpharmaceutical interventions.
Genome expression and stability are dependent on biological processes that control repetitive DNA sequences and nuclear compartmentalization. The phase separation of macromolecules has recently ...emerged as a major player in the control of biological pathways. Here, we summarize recent studies that collectively reveal intersections between phase separation, repetitive DNA elements, and nuclear compartments. These intersections modulate fundamental processes, including gene expression, DNA repair, and cellular lifespan, in the context of health and diseases such as cancer and neurodegeneration.
The function and stability of rDNA repeats is intimately linked to the phase separation of various nucleolar factors.By creating Cajal bodies or chromosome end shields, phase separation modulates the length of telomeres and their crosstalk with the DNA damage response.Intersections between phase-separated nuclear compartments and factors encoded by mobile genetic elements impact genome stability and cellular lifespan.Aberrant phase transition of factors linked to diseases, including cancer and neurodegeneration, intersects with repetitive DNA loci and their nuclear compartments.
The testing effect refers to improved memory after retrieval practice and has been researched primarily with visual stimuli. In two experiments, we investigated whether the testing effect can be ...replicated when the to-be-learned information is presented auditorily, or visually + auditorily. Participants learned Swahili-English word pairs in one of three presentation modalities - visual, auditory, or visual + auditory. This was manipulated between-participants in Experiment 1 and within-participants in Experiment2. All participants studied the word pairs during three study trials. Half of participants practiced recalling the English translations in response to the Swahili cue word twice before the final test whereas the other half simply studied the word pairs twice more. Results indicated an improvement in final test performance in the repeated test condition, but only in the visual presentation modality (Experiments 1 and 2) and in the visual + auditory presentation modality (Experiment 2). This suggests that the benefits of practiced retrieval may be limited to information presented in a visual modality.
Objective. The primary purposes of this study were to determine the extent to which multitasking affects the speed and accuracy with which Doctor of Pharmacy students identify prescription errors and ...whether there is a relationship between students’ self-perception of their multitasking ability and their actual ability.
Methods. One hundred twenty-one second-year pharmacy students enrolled in the required course Introduction to Dosage Forms spent one week in an experimental (multitasking) condition and one week in a control (undistracted) condition. Subjects were given 10 minutes to check 10 prescriptions and record any identified filling errors. A cellular phone was placed in each room. Subjects in the experimental (multitasking) condition answered a call from a researcher posing as a talkative customer during the prescription-checking task while subjects in the control condition were not interrupted by a cell phone call during the task. Subjects’ completion times and accuracy were recorded.
Results. When subjects were multitasking, they took significantly longer to complete the prescription-checking task than when they were not multitasking. Furthermore, when subjects were multitasking, they scored significantly lower on the prescription-checking task than when they were not multitasking. Finally, students’ self-perceptions of their multitasking abilities were not related to the speed with which they completed the prescription-checking task nor to their accuracy.
Conclusion. Multitasking negatively affects speed and accuracy of prescription verification in student pharmacists. Our procedure can be used as an in-class activity to demonstrate the limits of attention and to shape how future pharmacists practice.
To examine the incidence, mortality, and health care use related to neonatal herpes simplex virus (HSV) infection.
A retrospective longitudinal cohort study using a multistate Medicaid claims ...database. We identified neonates hospitalized with HSV infection from 2009 to 2015 by using discharge diagnosis codes and managed them for 6 months after discharge. Incidence rates were corrected for the imperfect sensitivity and specificity of thediagnosis codes for identifying HSV infection.
Of 2 107 124 births from 2009 to 2015, 900 neonates were identified with HSV infection, with a corrected incidence rate of 4.5 (95% confidence interval CI: 4.2-4.8) per 10 000 births. The yearly disease incidence increased by 56%, from 3.4 (95% CI: 2.8-4.2) per 10 000 births (or 1 in 2941 births) in 2009 to 5.3 (95% CI: 4.6-6.1) per 10 000 births (or 1 in 1886 births) in 2015 (
< .001). Of the 900 neonates with HSV infection, 54 (6.0% 95% CI: 4.4%-7.6%) died during the index hospitalization; there was no increase in the yearly mortality rate. Of the 692 (81.2%) infants with follow-up data, 316 (45.7%) had an emergency department visit, and 112 (16.2%) had a hospital readmission. Total payments at 6 months amounted to $60 620 431, a median of $87 602 per case of neonatal HSV infection.
We observed an increase in neonatal HSV infection incidence over a recent 7-year period in a Medicaid population. Associated health care use and payments were substantial. Public health interventions targeting disease prevention and early diagnosis are needed.
RNA-binding proteins play fundamental roles in the regulation of molecular processes critical to cellular and organismal homeostasis. Recent studies have identified the RNA-binding protein Ataxin-2 ...as a genetic determinant or risk factor for various diseases including spinocerebellar ataxia type II (SCA2) and amyotrophic lateral sclerosis (ALS), amongst others. Here, we first discuss the increasingly wide-ranging molecular functions of Ataxin-2, from the regulation of RNA stability and translation to the repression of deleterious accumulation of the RNA-DNA hybrid-harbouring R-loop structures. We also highlight the broader physiological roles of Ataxin-2 such as in the regulation of cellular metabolism and circadian rhythms. Finally, we discuss insight from clinically focused studies to shed light on the impact of molecular and physiological roles of Ataxin-2 in various human diseases. We anticipate that deciphering the fundamental functions of Ataxin-2 will uncover unique approaches to help cure or control debilitating and lethal human diseases.
Previous studies have demonstrated that intravitreal delivery of brain-derived neurotrophic factor (BDNF) by injection of recombinant protein or by gene therapy can alleviate retinal ganglion cell ...(RGC) loss after optic nerve injury. BDNF gene therapy can improve RGC survival in experimental models of glaucoma, the leading cause of irreversible blindness worldwide. However, the therapeutic efficacy of BDNF supplementation alone is time limited at least in part due to BDNF receptor downregulation. Tropomyosin-related receptor kinase-B (TrkB) downregulation has been reported in many neurological diseases including glaucoma, potentially limiting the effect of sustained or repeated BDNF delivery.Here, we characterize a novel adeno-associated virus (AAV) gene therapy (AAV2 TrkB-2A-mBDNF) that not only increases BDNF production but also improves long-term neuroprotective signaling by increasing expression of the BDNF receptor (TrkB) within the inner retina. This approach leads to significant and sustained elevation of survival signaling pathways ERK and AKT within RGCs over 6 months and avoids the receptor downregulation which we observe with treatment with AAV2 BDNF alone. We validate the neuroprotective efficacy of AAV2 TrkB-2A-mBDNF in a mouse model of optic nerve injury, where it outperforms conventional AAV2 BDNF or AAV2 TrkB therapy, before showing powerful proof of concept neuroprotection of RGCs and axons in a rat model of chronic intraocular pressure (IOP) elevation. We also show that there are no adverse effects of the vector on retinal structure or function as assessed by histology and electroretinography in young or aged animals. Further studies are underway to explore the potential of this vector as a candidate for progression into clinical studies to protect RGCs in patients with glaucoma and progressive visual loss despite conventional IOP-lowering treatment.
Bone is a highly vascularized and resilient organ with innate healing abilities, however some bone injuries overwhelm these attributes and require intervention, such as bone tissue engineering ...strategies. Combining biomaterials and growth factors, such as bone morphogenetic protein 2 (BMP2), is one of the most commonly used tissue engineering strategies. However, use of BMP2 has been correlated with negative clinical outcomes including aberrant inflammatory response, poor quality bone, and ectopic bone.
In the present study, a novel poly-n-acetyl glucosamine (pGlcNAc, trade name Talymed) scaffold was utilized in addition to the commonly used acellular collagen sponge (ACS) BMP2 delivery system in a murine calvarial defect model to investigate whether the innate properties of Talymed can reduce the noted negative bone phenotypes associated with BMP2 treatment.
Comparison of murine calvarial defect healing between ACS with and without Talymed revealed that there was no measurable healing benefit for the combined treatment. Healing was most effective utilizing the traditional acellular collagen sponge with a reduced dose of BMP2.
The results of this investigation lead to the conclusion that excessive dosing of BMP2 may be responsible for the negative clinical side effects observed with this bone tissue engineering strategy. Rather than augmenting the currently used ACS BMP2 bone wound healing strategy with an additional anti-inflammatory scaffold, reducing the dose of BMP2 used in the traditional delivery system results in optimal healing without the published negative side effects of BMP2 treatment.
We investigated whether the previously established effect of mood on episodic memory generalizes to semantic memory and whether mood affects metacognitive judgments associated with the retrieval of ...semantic information. Sixty‐eight participants were induced into a happy or sad mood by viewing and describing IAPS images. Following mood induction, participants saw a total of 200 general knowledge trivia items (50 open‐ended and 50 multiple‐choice after each of two mood inductions) and were asked to provide a metacognitive judgment about their knowledge for each item before providing a response. A sample trivia item is: Author – – To kill a mockingbird. Results indicate that mood affects the retrieval of semantic information, but only when the participant believes they possess the requested semantic information; furthermore, this effect depends upon the presence of retrieval cues. In addition, we found that mood does not affect the likelihood of different metacognitive judgments associated with the retrieval of semantic information, but that, in some cases, having retrieval cues increases accuracy of these metacognitive judgments. Our results suggest that semantic retrieval processes are minimally susceptible to the influence of affective state but does not preclude the possibility that affective state may influence encoding of semantic information.
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