Inhibition of nonsense-mediated mRNA decay may improve stop codon read-through therapy for Duchenne muscular dystrophy.

Duchene muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are genetic neuromuscular disorders that affect skeletal and cardiac muscle resulting from mutations in the dystrophin gene (DMD), coding for dystrophin protein. Read-through therapies hold great promise for the treatment of genetic diseases harboring nonsense mutations, such as DMD/BMD, as they enable a complete translation of the affected mRNA. However, to date, most read-through drugs have not achieved a cure for patients. One possible explanation for the limitation of these therapies for DMD/BMD is that they rely on the presence of mutant dystrophin mRNAs. However, the mutant mRNAs containing premature termination codons are identified by the cellular surveillance mechanism, the nonsense-mediated mRNA decay (NMD) process, and are degraded. Here, we show that the combination of read-through drugs together with known NMD inhibitors have a synergistic effect on the levels of nonsense-containing mRNAs, among them the mutant dystrophin mRNA. This synergistic effect may enhance read-through therapies' efficacy and improve the current treatment for patients.

Optimisation of a radio-frequency atomic magnetometer: a Uniform Design approach.

High-sensitivity operation of a radio-frequency atomic magnetometer (RF-AM) requires careful setting of the system parameters, including the lasers intensity and detuning, and the vapour cell temperature. The identification of the optimal operating parameters, which ensures high sensitivity, is typically performed empirically and is often a lengthy process, which is especially labour intensive if frequent retuning of the magnetometer is required to perform different tasks. This paper demonstrates an efficient approach to RF-AM performance optimisation which relies on an open-loop optimisation technique based on Uniform Design (UD). This paper specifically describes the optimisation of an unshielded RF-AM based on a 4-factor-12-level UD of the experimental parameters space. The proposed procedure is shown to lead to the efficient optimisation of the atomic magnetometer at different frequencies, and is applicable to both AC and DC sensitivity optimisation. The procedure does not require any detailed knowledge of the model underlying the operation of the RF-AM and is effective in reducing the number of experimental runs required for the optimisation. It is ideally suited to self-calibration of devices without human supervision.

The 'Tommy Atkins' mango genome reveals candidate genes for fruit quality.

BACKGROUND: Mango, Mangifera indica L., an important tropical fruit crop, is grown for its sweet and aromatic fruits. Past improvement of this species has predominantly relied on chance seedlings derived from over 1000 cultivars in the Indian sub-continent with a large variation for fruit size, yield, biotic and abiotic stress resistance, and fruit quality among other traits. Historically, mango has been an orphan crop with very limited molecular information. Only recently have molecular and genomics-based analyses enabled the creation of linkage maps, transcriptomes, and diversity analysis of large collections. Additionally, the combined analysis of genomic and phenotypic information is poised to improve mango breeding efficiency. RESULTS: This study sequenced, de novo assembled, analyzed, and annotated the genome of the monoembryonic mango cultivar 'Tommy Atkins'. The draft genome sequence was generated using NRGene de-novo Magic on high molecular weight DNA of 'Tommy Atkins', supplemented by 10X Genomics long read sequencing to improve the initial assembly. A hybrid population between 'Tommy Atkins' x 'Kensington Pride' was used to generate phased haplotype chromosomes and a highly resolved phased SNP map. The final 'Tommy Atkins' genome assembly was a consensus sequence that included 20 pseudomolecules representing the 20 chromosomes of mango and included ~ 86% of the ~ 439 Mb haploid mango genome. Skim sequencing identified ~ 3.3 M SNPs using the 'Tommy Atkins' x 'Kensington Pride' mapping population. Repeat masking identified 26,616 genes with a median length of 3348 bp. A whole genome duplication analysis revealed an ancestral 65 MYA polyploidization event shared with Anacardium occidentale. Two regions, one on LG4 and one on LG7 containing 28 candidate genes, were associated with the commercially important fruit size characteristic in the mapping population. CONCLUSIONS: The availability of the complete 'Tommy Atkins' mango genome will aid global initiatives to study mango genetics.

Reappraisal of the historical myopia epidemic in native Arctic communities.

PURPOSE: This study was developed to explain the extraordinary rise in myopia prevalence beginning after 1950 in Indigenous Arctic communities considering recent findings about the risk factors for school myopia development. Myopia prevalence changed drastically from a historical low of less than 3% to more than 50% in new generations of young adults following the Second World War. At that time, this increase was attributed to concurrent alterations in the environment and way of life which occurred in an aggressive programme of de-culturalization and re-acculturation through residential school programmes that introduced mental, emotional and physical stressors. However, the predominant idea that myopia was genetic in nature won the discussion of the day, and research in the area of environmental changes was dismissed. There may have also been an association between myopia progression and the introduction of extreme mental, emotional and physical stressors at the time. RECENT FINDINGS: Since 1978, animal models of myopia have demonstrated that myopiagenesis has a strong environmental component. Furthermore, multiple studies in human populations have shown since 2005 how myopia could be produced by a combination of limited exposure to the outdoors and heavy emphasis on academic subjects associated with intense reading habits. This new knowledge was applied in the present study to unravel the causes of the historical myopia epidemics in Inuit communities. SUMMARY: After reviewing the available published data on myopia prevalence in circumpolar Inuit populations in the 20th century, the most likely causes for the Inuit myopia epidemic were the combination of increased near work (from almost none to daily reading) and the move from a mostly outdoor to a much more indoor way of life, exacerbated by fewer hours of sunshine during waking hours, the lower illuminance in the Arctic and the extreme psychophysical stress due to the conditions in the Residential Schools.

An appetite for pests: Synanthropic insectivorous bats exploit cotton pest irruptions and consume various deleterious arthropods.

Conservation biological control (CBC) seeks to minimize the deleterious effects of agricultural pests by enhancing the efficiency of natural enemies. Despite the documented potential of insectivorous bats to consume pests, many synanthropic bat species are still underappreciated as beneficial species. We investigated the diet of Kuhl's pipistrelle (Pipistrellus kuhlii), a common synanthropic insectivorous bat that forages in urban and agricultural areas, to determine whether it may function as a natural enemy in CBC. Faecal samples of P. kuhlii were collected throughout the cotton-growing season from five roost sites near cotton fields located in a Mediterranean agroecosystem, Israel, and analyzed using DNA metabarcoding. Additionally, data on estimated abundance of major cotton pests were collected. We found that the diet of P. kuhlii significantly varied according to sites and dates and comprised 27 species of agricultural pests that were found in 77.2% of the samples, including pests of key economic concern. The dominant prey was the widespread cotton pest, the pink bollworm, Pectinophora gossypiella, found in 31% of the samples and in all the roosts. Pink bollworm abundance was positively correlated with its occurrence in the bat diet. Furthermore, the bats' dietary breadth narrowed, while temporal dietary overlap increased, in relation to increasing frequencies of pink bollworms in the diet. This suggests that P. kuhlii exploits pink bollworm irruptions by opportunistic feeding. We suggest that synanthropic bats provide important pest suppression services, may function as CBC agents of cotton pests and potentially contribute to suppress additional deleterious arthropods found in their diet in high frequencies.

Homozygous stop mutation in AHR causes autosomal recessive foveal hypoplasia and infantile nystagmus.

Herein we present a consanguineous family with three children affected by foveal hypoplasia with infantile nystagmus, following an autosomal recessive mode of inheritance. The patients showed normal electroretinography responses, no signs of albinism, and no anterior segment or brain abnormalities. Upon whole exome sequencing, we identified a homozygous mutation (c.1861C>T;p.Q621*) in the aryl hydrocarbon receptor (AHR) gene that perfectly co-segregated with the disease in the larger family. AHR is a ligand-activated transcription factor that has been intensively studied in xenobiotic-induced toxicity. Further, it has been shown to play a physiological role under normal cellular conditions, such as in immunity, inflammatory response and neurogenesis. Notably, knockout of the Ahr gene in mouse impairs optic nerve myelin sheath formation and results in oculomotor deficits sharing many features with our patients: the eye movement disorder in Ahr-/- mice appears early in development and presents as conjugate horizontal pendular nystagmus. We therefore propose AHR to be a novel disease gene for a new, recessively inherited disorder in humans, characterized by infantile nystagmus and foveal hypoplasia.

Non-ST-Elevation Myocardial Infarction with Non-significant Coronary Artery Disease as a Symptom of Occult or New Malignancy.

BACKGROUND: Malignancy is a known risk factor for venous thromboembolism; however, the association with arterial thromboembolic events remains unclear. OBJECTIVES: To examine the association between non-ST-elevation myocardial infarction (NSTEMI) and non-significant coronary artery disease (CAD) and the presence of new or occult malignancy. METHODS: An observational cohort, single-center study was performed 2010-2015. Adult patients with NSTEMI, who underwent coronary angiography and had no significant coronary lesion, were included. Using propensity score matching, we created a 2:1 matched control group of adults with NSTEMI, and significant coronary artery disease. Risk factors for new or occult malignancy were assessed using multivariate backward stepwise logistic regression analysis. The primary outcome was new or occult malignancy, defined as any malignancy diagnosed in the 3 months prior and 6 months following the myocardial infarction (MI). RESULTS: During the study period, 174 patients who presented with MI with non-obstructive coronary arteries were identified. The matched control group included 348 patients. There was no significant difference in the group demographics, past medical history, or clinical presentation. The incidence of new or occult malignancy in the study group was significantly higher (7/174, 4% vs. 3/348, 0.9%, P = 0.019). NSTEMI with non-significant CAD was an independent risk factor for occult malignancy (odds ratio [OR] 4.6, 95% confidence interval [95%CI] 1.1-18.7). Other risk factors included active smoking (OR 11.2, 95%CI 2.5-49.1) and age (OR 1.1, 95%CI 1.03-1.17). CONCLUSIONS: NSTEMI with non-significant CAD may be a presenting or early marker of malignancy and warrants further investigation.

Mango (Mangifera indica L.) germplasm diversity based on single nucleotide polymorphisms derived from the transcriptome.

BACKGROUND: Germplasm collections are an important source for plant breeding, especially in fruit trees which have a long duration of juvenile period. Thus, efforts have been made to study the diversity of fruit tree collections. Even though mango is an economically important crop, most of the studies on diversity in mango collections have been conducted with a small number of genetic markers. RESULTS: We describe a de novo transcriptome assembly from mango cultivar 'Keitt'. Variation discovery was performed using Illumina resequencing of 'Keitt' and 'Tommy Atkins' cultivars identified 332,016 single-nucleotide polymorphisms (SNPs) and 1903 simple-sequence repeats (SSRs). Most of the SSRs (70.1%) were of trinucleotide with the preponderance of motif (GGA/AAG)n and only 23.5% were di-nucleotide SSRs with the mostly of (AT/AT)n motif. Further investigation of the diversity in the Israeli mango collection was performed based on a subset of 293 SNPs. Those markers have divided the Israeli mango collection into two major groups: one group included mostly mango accessions from Southeast Asia (Malaysia, Thailand, Indonesia) and India and the other with mainly of Floridian and Israeli mango cultivars. The latter group was more polymorphic (FS=-0.1 on the average) and was more of an admixture than the former group. A slight population differentiation was detected (FST=0.03), suggesting that if the mango accessions of the western world apparently was originated from Southeast Asia, as has been previously suggested, the duration of cultivation was not long enough to develop a distinct genetic background. CONCLUSIONS: Whole-transcriptome reconstruction was used to significantly broaden the mango's genetic variation resources, i.e., SNPs and SSRs. The set of SNP markers described in this study is novel. A subset of SNPs was sampled to explore the Israeli mango collection and most of them were polymorphic in many mango accessions. Therefore, we believe that these SNPs will be valuable as they recapitulate and strengthen the history of mango diversity.

The effect of nocturnal CPAP therapy on the intraocular pressure of patients with sleep apnea syndrome.

PURPOSE: Few studies have documented that nocturnal continuous positive airway pressure (CPAP) therapy is associated with an increase in intraocular pressure (IOP) in patients with severe obstructive sleep apnea syndrome (OSAS). We re-examined the effect of CPAP therapy on the IOP of OSAS patients. METHODS: The IOP of two different groups of newly diagnosed OSAS patients was compared at their first sleep lab exam without CPAP treatment (non-CPAP treated group; n = 20) and at the second sleep lab exam with CPAP treatment (CPAP treated group; n = 31). The sleep lab exam (sleep period: from 11:00 p.m. until 6:00 a.m.) included IOP measurements, a complete ophthalmologic exam, and nocturnal hemodynamic recordings. The IOP was measured serially using rebound tonometer (IOP; ICARE® PRO) performed while in sitting and supine positions before, during, and after the sleep period. We compared the difference in IOP of CPAP and non-CPAP groups. RESULTS: The mean IOP of the CPAP and non-CPAP groups measured in sitting position before the sleep period was 13.33 ± 2.04 mmHg and 14.02 ± 2.44 mmHg, respectively (p = 0.9). Assuming a supine position for 1 minute significantly increased the IOP by 1.93 mmHg and 2.13 mmHg for both the non-CPAP and CPAP groups (paired t-test; p = 0.02, p = 0.001 respectively), but this IOP rise showed no difference between the two groups. The IOP increased significantly further after 7 hours of sleep in the supine position, and the mean IOP of the CPAP and non-CPAP groups was 19.2 ± 5.68 mmHg and 19.69 ± 5.61 mmHg respectively (independent t-test; p = 0.74). The rise in IOP for both groups was not correlated with any hemodynamic parameters. Three OSAS patients with glaucoma treated with CPAP had mean IOP of 23.75 mmHg after 7 hours of sleep. CONCLUSIONS: OSAS patients have a significant rise in IOP during the sleep period when comparing measurements before and after the sleep period; however, CPAP therapy did not affect the measured IOP. The presented findings suggest that in terms of IOP, CPAP is safe for non-glaucomatous patients, but this may not hold true for glaucomatous patients.

Seventeen years since rimonabant's downfall: reassessing its suicidality risk profile.

Targeting the cannabinoid type 1 receptor (CB1) is a clinically validated antiobesity therapeutic approach. The only such drug approved, rimonabant, was launched in 2006 in Europe but subsequently rejected by the US Food and Drug Administration (FDA) in 2007. The FDA cited the increased risk of suicidality in its opposition to rimonabant's approval, leading to the drug's eventual worldwide withdrawal and the abandonment of this class of therapeutics. Seventeen years later, a new class of CB1-targeting drugs is emerging, but the impact of the 2007 FDA decision remains a formidable obstacle to its clinical development. We revisit the suicidality data presented by the FDA in light of the evolution of suicidality assessment and cross-reference this with the data in the subsequently published clinical trials. We conclude that the publicly available data do not support the FDA's conclusion that the use of rimonabant was associated with an increase in the risk of suicidality.

Induction of stomatal opening following a night-chilling event alleviates physiological damage in mango trees.

Chilling events have become more frequent with climate change and are a significant abiotic factor causing physiological damage to plants and, consequently, reducing crop yield. Like other tropical and subtropical plants, mango (Mangifera indica L.) is particularly sensitive to chilling events, especially if they are followed by bright sunny days. It was previously shown that in mango leaves stomatal opening is restricted in the morning following a night-chilling event. This impairment results in restraint of carbon assimilation and subsequently, photoinhibition and reactive oxygen species production, which leads to chlorosis and in severe cases, cell death. Our detailed physiological analysis showed that foliar application of the guard cell H+-ATPase activator, fusicoccin, in the morning after a cold night, mitigates the physiological damage from 'cold night-bright day' abiotic stress. This application restored stomatal opening, thereby enabling gas exchange, releasing the photosynthetic machinery from harmful excess photon energy, and improving the plant's overall physiological state. The mechanisms by which plants react to this abiotic stress are examined in this work. The foliar application of compounds that cause stomatal opening as a potential method of minimizing physiological damage due to night chilling is discussed.

Gene architecture is a determinant of the transcriptional response to bulky DNA damages.

Bulky DNA damages block transcription and compromise genome integrity and function. The cellular response to these damages includes global transcription shutdown. Still, active transcription is necessary for transcription-coupled repair and for induction of damage-response genes. To uncover common features of a general bulky DNA damage response, and to identify response-related transcripts that are expressed despite damage, we performed a systematic RNA-seq study comparing the transcriptional response to three independent damage-inducing agents: UV, the chemotherapy cisplatin, and benzo[a]pyrene, a component of cigarette smoke. Reduction in gene expression after damage was associated with higher damage rates, longer gene length, and low GC content. We identified genes with relatively higher expression after all three damage treatments, including NR4A2, a potential novel damage-response transcription factor. Up-regulated genes exhibit higher exon content that is associated with preferential repair, which could enable rapid damage removal and transcription restoration. The attenuated response to BPDE highlights that not all bulky damages elicit the same response. These findings frame gene architecture as a major determinant of the transcriptional response that is hardwired into the human genome.

Novel insights into bulky DNA damage formation and nucleotide excision repair from high-resolution genomics.

DNA damages compromise cell function and fate. Cells of all organisms activate a global DNA damage response that includes a signaling stress response, activation of checkpoints, and recruitment of repair enzymes. Especially deleterious are bulky, helix-distorting damages that block transcription and replication. Due to their miscoding nature, these damages lead to mutations and cancer. In human cells, bulky DNA damages are repaired by nucleotide excision repair (NER). To date, the basic mechanism of NER in naked DNA is well defined. Still, there is a fundamental gap in our understanding of how repair is orchestrated despite the packaging of DNA in chromatin, and how it is coordinated with active transcription and replication. The last decade has brought forth huge advances in our ability to detect and assay bulky DNA damages and their repair at single nucleotide resolution across the human genome. Here we review recent findings on the effect of chromatin and DNA-binding proteins on the formation of bulky DNA damages, and novel insights on NER, provided by the recent application of genomic methods.

Novel cannabinoid receptor 1 inverse agonist CRB-913 enhances efficacy of tirzepatide, semaglutide, and liraglutidein the diet-induced obesity mouse model.

OBJECTIVE: Incretin receptor agonists are now standard of care in treating obesity. Their efficacy and tolerability might be further improved by combining them with compounds that offer orthogonal mechanisms of action. The cannabinoid type 1 receptor (CB1R) is a clinically validated therapeutic target in obesity, and several experimental CB1R inverse agonists have been shown to induce weight loss. METHODS: This study characterizes a novel CB1R inverse agonist (CRB-913) with similar preclinical potency to rimonabant but markedly reduced brain penetration. CRB-913 was tested as monotherapy and in combination with tirzepatide, semaglutide, or liraglutide in the diet-induced obesity (DIO) mouse model for body weight reduction. RESULTS: CRB-913 demonstrated enhanced plasma exposure (3.8-fold larger area under the curvelast ) and reduced brain levels (9.5-fold lower area under the curvelast ) than rimonabant. CRB-913 monotherapy yielded a dose-dependent decrease in body weight in DIO mice reaching -22% within 18 days. In further DIO studies in combination with tirzepatide, semaglutide, or liraglutide, CRB-913 (2.5 mg/kg) resulted in -32.6%, -28.8%, and -16.8% decreases in body weight on Day 18, respectively, with concomitant improvements in body fat content, liver triglycerides, and liver fat deposits. CONCLUSIONS: CRB-913 in combination with incretin analogues could deliver meaningful improvements over current standards of care for obesity and related conditions.

Promoter insertion leads to polyembryony in mango - a case of convergent evolution with citrus.

Sexual reproduction in plants is the main pathway for creating new genetic combinations in modern agriculture. In heterozygous plants, after the identification of a plant with desired traits, vegetative propagation (cloning) is the primary path to create genetically uniform plants. Another natural plant mechanism that creates genetically uniform plants (clones) is apomixis. In fruit crops like citrus and mango, sporophytic apomixis results in polyembryony, where seeds contain multiple embryos, one of which is sexually originated and the others are vegetative clones of the parent mother tree. Utilizing the mango genome and genetic analysis of a diverse germplasm collection, we identified MiRWP as the gene that causes polyembryony in mango. There is a strong correlation between a specific insertion in the gene's promoter region and altered expression in flowers and developing fruitlets, inducing multiple embryos. The MiRWP gene is an ortholog of CitRWP that causes polyembryony in citrus. Based on the data, we speculate that promoter insertion events, which occurred independently in citrus and mango, induced nucellar embryogenesis. The results suggest convergent evolution of polyembryony in the two species. Further work is required to demonstrate the utility of these genes (mango and citrus) in other biological systems as a tool for the clonal production of other crops.

Development of a transgenic early flowering pear (Pyrus communis L.) genotype by RNAi silencing of PcTFL1-1 and PcTFL1-2.

Trees require a long maturation period, known as juvenile phase, before they can reproduce, complicating their genetic improvement as compared to annual plants. 'Spadona', one of the most important European pear (Pyrus communis L.) cultivars grown in Israel, has a very long juvenile period, up to 14 years, making breeding programs extremely slow. Progress in understanding the molecular basis of the transition to flowering has revealed genes that accelerate reproductive development when ectopically expressed in transgenic plants. A transgenic line of 'Spadona', named Early Flowering-Spadona (EF-Spa), was produced using a MdTFL1 RNAi cassette targeting the native pear genes PcTFL1-1 and PcTFL1-2. The transgenic line had three T-DNA insertions, one assigned to chromosome 2 and two to chromosome 14 PcTFL1-1 and PcTFL1-2 were completely silenced, and EF-Spa displayed an early flowering phenotype: flowers developed already in tissue culture and on most rooted plants 1-8 months after transfer to the greenhouse. EF-Spa developed solitary flowers from apical or lateral buds, reducing vegetative growth vigor. Pollination of EF-Spa trees generated normal-shaped fruits with viable F1 seeds. The greenhouse-grown transgenic F1 seedlings formed shoots and produced flowers 1-33 months after germination. Sequence analyses, of the non-transgenic F1 seedlings, demonstrated that this approach can be used to recover seedlings that have no trace of the T-DNA. Thus, the early flowering transgenic line EF-Spa obtained by PcTFL1 silencing provides an interesting tool to accelerate pear breeding.

Ambient illuminance, retinal dopamine release and refractive development in chicks.

Form deprivation and low illuminance of ambient light are known to induce myopia in chicks. Low concentrations of retinal dopamine, a light-driven neurohormone, was previously shown to be associated with form deprivation myopia. In the present study we examined the dependence of retinal dopamine release in chicks on illuminance during light-dark cycles and in continuous light, and the role of retinal dopamine release in illuminance dependent refractive development. Newly hatched chicks (n = 166) were divided into two experimental groups, a dopamine (n = 88) and a refraction group (n = 78). Both groups were further divided into six illumination groups for exposure of chicks to illuminances of 50, 500 or 10,000 lux of incandescent illumination (referred to throughout as low, medium, and high illuminance, respectively), either under a light-dark cycle with lights on between 7 AM and 7 PM or under continuous illumination. For the dopamine experiment, chicks were euthanized and vitreous was extracted on day 14 post-hatching at 7, 8 AM and 1 PM. Vitreal dihydroxyphenylacetic acid (DOPAC) and dopamine concentrations were quantified by high-performance liquid chromatography coupled to electrochemical detection. For the refraction experiment, chicks underwent refraction, keratometry and A-scan ultrasonography on days 30, 60 and 90 post-hatching, and each of those measurements was correlated with vitreal DOPAC concentration measured at 1 PM (representing the index of retinal dopamine release). The results showed that under light-dark cycles, vitreal DOPAC concentration was strongly correlated with log illuminance, and was significantly correlated with the developing refraction, corneal radius of curvature, and axial length values. On day 90, low vitreal DOPAC concentrations were associated with myopia (-2.41 ± 1.23 D), flat cornea, deep anterior and vitreous chambers, and thin lens. Under continuous light, vitreal DOPAC concentrations measured at 1 PM in the low, medium, and high illuminance groups did not differ from the concentrations measured at 8 AM. On day 90, low DOPAC concentrations were associated with emmetropia (+0.63 ± 3.61), steep cornea, and shallow vitreous chamber. We concluded that ambient light over a log illuminance range of 1.69-4 is linearly related to vitreal DOPAC concentration. Under both light-dark cycles and continuous light, the intensity of ambient light regulates the release of retinal dopamine. Refractive development is associated with illuminance dependent dopamine release.

Light Intensity in Nursery Schools: A Possible Factor in Refractive Development.

PURPOSE: Increased levels of outdoor light have been found to be associated causally with decreased rates of myopia. The goal of this study was to measure the effect of indoor nursery school light intensity on refraction of preschool children in Israel. METHODS: A total of 1596 children aged 4 to 5 years from 27 nursery schools were examined. Light intensity was tested with a luxmeter device (Lux) inside and outside the nursery school. Noncycloplegic refractions were measured with the PlusOptix vision A09 screening device. Data analysis was performed using Pearson coefficients, chi-square tests for proportions and ANOVA tests by tertiles of illuminance. RESULTS: This study included 1131 kindergarten children with a mean age of 4.87 ±â€Š0.33 years, of which 571 were female (50.5%). The mean light intensity of the low, medium, and high intensity groups differed significantly (ANOVA P < 0.001) at 359 ±â€Š2.64 lux (range 264-431), 490 ±â€Š2.21 lux (range 432-574), and 670.76 ±â€Š3.73 lux (range 578-804), respectively. Mean spherical equivalent (SE) was +0.56 ±â€Š0.03D for the low-intensity group, +0.73 ±â€Š0.03D for the medium-intensity group, and +0.89 ±â€Š0.03D for the high-intensity group (ANOVA P < 0.001). The low-intensity group had 42.1% of children with zero refraction or less, while the high-intensity group had 19.3%. CONCLUSIONS: In the nursery schools, lower amounts of illumination were associated with less hyperopic refractive error. As the low hyperopic reserve is a risk factor for developing myopia, this finding needs to be followed up to establish whether this association reflects a causal relationship, which could be modulated for the prevention of myopia.

Impact of the COVID-19 Pandemic on Infectious Diseases in Brazil: A Case Study on Dengue Infections.

Brazil is known for being a breeding ground for emerging infectious diseases (EIDs), such as Zika, dengue, and chikungunya. Given that it has been one of the countries most affected by the SARS-CoV-2 pandemic, this article aims to analyze the impact that the COVID-19 pandemic has had on the burden of infectious diseases in Brazil, especially that of dengue. Brazil is a unique territory with a heterogeneous population living in a tropical, wet climate favorable to infectious diseases. In addition, despite being one of the largest emerging economies in the world, the country has been exposed to political instability and a public health system that suffers from large funding shortfalls and a lack of coherent regulation. The findings from this study are multilayered. Firstly, as cases of COVID-19 rose at the start of the pandemic, cases of dengue declined drastically. This may be due, in part, to factors such as seasonal climate and distancing measures. Furthermore, the findings indicate that the diversion of resources away from dengue and other infectious diseases, and mobilization for COVID-19 testing and treatment, likely resulted in a serious underreporting of dengue. While Brazil has incorporated some of the lessons learned from past EID experience in responding to the COVID-19 pandemic, the analysis highlights how the country's structural problems present pitfalls in the epidemiological fight. It was concluded that in a country such as Brazil, where infectious disease outbreaks are only a matter of time, pandemic preparedness should be prioritized over pandemic response.

Effective bubble-based testing for SARS-CoV-2 using swab-pooling.

OBJECTIVES: Despite the success in developing COVID-19 vaccines, containment of the disease is obstructed worldwide by vaccine production bottlenecks, logistics hurdles, vaccine refusal, transmission through unvaccinated children, and the appearance of new viral variants. This underscores the need for effective strategies for identifying carriers/patients, which was the main aim of this study. METHODS: We present a bubble-based PCR testing approach using swab-pooling into lysis buffer. A bubble is a cluster of people who can be periodically tested for SARS-CoV-2 by swab-pooling. A positive test of a pool mandates quarantining each of its members, who are then individually tested while in isolation to identify the carrier(s) for further epidemiological contact tracing. RESULTS: We tested an overall sample of 25 831 individuals, divided into 1273 bubbles, with an average size of 20.3 ± 7.7 swabs/test tube, obtaining for all pools (≤37 swabs/pool) a specificity of 97.5% (lower bound 96.6%) and a sensitivity of 86.3% (lower bound 78.2%) and a post hoc analyzed sensitivity of 94.6% (lower bound 86.7%) and a specificity of 97.2% (lower bound 96.2%) in pools with ≤25 swabs, relative to individual testing. DISCUSSION: This approach offers a significant scale-up in sampling and testing throughput and savings in testing cost, without reducing sensitivity or affecting the standard PCR testing laboratory routine. It can be used in school classes, airplanes, hospitals, military units, and workplaces, and may be applicable to future pandemics.