Seasonality and Climatic Factors Associated With Human Rhinovirus/Enterovirus Nasopharyngeal Sample Positivity on Oahu, Hawai'i, 2016-2019.

INTRODUCTION: Globally, human rhinoviruses/enteroviruses (HRVs/ENTs), indistinguishable on many widely available molecular platforms, are among the leading causes of the common cold. Geographic and climatic factors impact the peak activity of these viruses. In temperate climates, the peak activity of HRV occurs during autumn and spring whereas that of ENT occurs during autumn and summer. Both viruses are thought to peak during the rainy season in tropical climates like Hawai'i; however, data remain limited. We describe HRV/ENT seasonality and evaluate the climatic factors associated with peak activity among respiratory viral samples processed on Oahu, Hawai'i. MATERIALS AND METHODS: We conducted a retrospective analysis of all respiratory specimens submitted to Tripler Army Medical Center for multiplex polymerase chain reaction testing between May 2016 and May 2019. Among HRV/ENT-positive samples, we recorded the month and year of positivity. Summative monthly positive detection was calculated with peak months above the mean. Associations between temperature, precipitation levels, relative humidity, and wind speed by week and the number of positive samples for HRV/ENT were evaluated using Poisson regression. This analysis was conducted via IRB exempt protocol number 19R18. RESULTS: During our study period, there were 7,143 nasopharyngeal respiratory samples sent for multiplex polymerase chain reaction testing, with 1,572 positive for HRV/ENT (22%). Nineteen percent of respiratory samples positive for HRV/ENT were additionally positive for one or more respiratory pathogens. The majority of HRV/ENT-positive samples arose from children < 5 years of age (n = 959, 61%). Peak months were February, March, May, August, November, and December. After controlling for lagged count and year, average wind speed was the only climatic factor significantly associated with HRV/ENT sample positivity. CONCLUSIONS: The peak monthly activity of HRV/ENT was similar to temperate climates with the exception of peak activity in February. Unlike other tropical climates, lower wind speed was associated with increased weekly HRV/ENT positivity and should be further explored as a transmission factor. Our study contributes to understanding the annual variability of HRV/ENT activity in tropical environments, which can inform clinician expectations regarding respiratory viral symptomatology in this region.

Comparing the Clinical Courses of Children With Human Rhinovirus/Enterovirus to Children With Other Respiratory Viruses in the Outpatient Setting.

BACKGROUND: While infections caused by rhinoviruses and enteroviruses are common among children, the entirety of their clinical impact remains elusive. We compared the clinical outcomes of children with rhinovirus/enterovirus infections to other common respiratory viruses in outpatient settings. METHODS: We conducted a retrospective analysis of nasopharyngeal samples singly positive for human rhinovirus/enterovirus (HRV/ENT), influenza A/B (FLU) or respiratory syncytial virus (RSV) from patients ≤17 years submitted for clinical testing via multiplex polymerase chain reaction between 2016 and 2019. We evaluated the following outpatient outcomes: days of respiratory symptoms before testing; visits for respiratory symptoms; receipt of a breathing treatment; receipt of antibiotics and hospital admission. Statistical analyses were conducted controlling for age and comorbid conditions. RESULTS: There were 1355 positive samples included in this analysis (HRV/ENT: n = 743, FLU: n = 303 and RSV: n = 309). Compared to HRV/ENT, children with FLU had 28% fewer days of respiratory symptoms (ß: -0.32; 95% confidence interval: -0.46 to -0.18; P < 0.001), fewer visits for respiratory symptoms, and significantly decreased odds of receiving a breathing treatment or antibiotics, and admission to the hospital. Children with RSV had a similar number of days of respiratory symptoms, outpatient visits and odds of hospital admission, but significantly increased odds of receiving a breathing treatment and antibiotics compared to those with HRV/ENT. CONCLUSION: Clinicians should have a high level of vigilance when managing children with positive respiratory viral testing for HRV/ENT given the potential for clinical outcomes similar to and, in some instances, worse than known highly pathogenic viruses.

Structural and biochemical analysis of phosphoethanolamine methyltransferase from the pine wilt nematode Bursaphelenchus xylophilus.

In free-living and parasitic nematodes, the methylation of phosphoethanolamine to phosphocholine provides a key metabolite to sustain phospholipid biosynthesis for growth and development. Because the phosphoethanolamine methyltransferases (PMT) of nematodes are essential for normal growth and development, these enzymes are potential targets of inhibitor design. The pine wilt nematode (Bursaphelenchus xylophilus) causes extensive damage to trees used for lumber and paper in Asia. As a first step toward testing BxPMT1 as a potential nematicide target, we determined the 2.05 Å resolution x-ray crystal structure of the enzyme as a dead-end complex with phosphoethanolamine and S-adenosylhomocysteine. The three-dimensional structure of BxPMT1 served as a template for site-directed mutagenesis to probe the contribution of active site residues to catalysis and phosphoethanolamine binding using steady-state kinetic analysis. Biochemical analysis of the mutants identifies key residues on the ß1d-α6 loop (W123F, M126I, and Y127F) and ß1e-α7 loop (S155A, S160A, H170A, T178V, and Y180F) that form the phosphobase binding site and suggest that Tyr127 facilitates the methylation reaction in BxPMT1.

The Efficacy of Botulinum Toxin in Pediatric Chronic Migraine: A Literature Review.

AIMS: To conduct a review of the literature on the use of botulinum toxin for the treatment of pediatric chronic migraine. METHODS: A review of the literature was performed using EMBASE, PubMed, and Cochrane/Ovid. Using our inclusion and exclusion criteria, we targeted any study, published before April 2020, evaluating the efficacy of botulinum toxin in migraineurs younger than 18 years. RESULTS: Seven studies were included: 2 retrospective analyses, 3 case series, a case report, and a randomized control trial. Studies included 1 to 125 patients, with the number of botulinum toxin treatments ranging from 1 to 11 treatments. The results of the randomized controlled trial showed nonsuperiority between placebo and botulinum toxin. Results of the other studies were generally favorable but were difficult to compare because of lack of standardization of botulinum toxin dosing, injection paradigm, frequency and duration of treatment, usage of accompanying prophylaxis, and variation in outcome measures across studies. There was low-quality evidence that botulinum toxin improved headache frequency and intensity, though some studies demonstrated efficacy in treatment with botulinum toxin. CONCLUSION: This review is the first of its kind, updating the literature on the efficacy of botulinum toxin in pediatric patients. Given evidence of its utility in treating pediatric migraines, off-label use should be considered in certain cases. Further study is warranted to better characterize injection paradigms and patient selection because of the limited and inconsistent data available.

Drug Delivery Approaches for the Treatment of Cervical Cancer.

Cervical cancer is a highly prevalent cancer that affects women around the world. With the availability of new technologies, researchers have increased their efforts to develop new drug delivery systems in cervical cancer chemotherapy. In this review, we summarized some of the recent research in systematic and localized drug delivery systems and compared the advantages and disadvantages of these methods.

A Hypoxia-Targeted Boron Neutron Capture Therapy Agent for the Treatment of Glioma.

PURPOSE: Boron neutron capture therapy (BNCT) has the potential to become a viable cancer treatment modality, but its clinical translation has been limited by the poor tumor selectivity of agents. To address this unmet need, a boronated 2-nitroimidazole derivative (B-381) was synthesized and evaluated for its capability of targeting hypoxic glioma cells. METHODS: B-381 has been synthesized from a 1-step reaction. Using D54 and U87 glioma cell lines, the in vitro cytotoxicity and cellular accumulation of B-381 has been evaluated under normoxic and hypoxic conditions compared to L-boronophenylalanine (BPA). Furthermore, tumor retention of B-381 was evaluated in vivo. RESULTS: B-381 had low cytotoxicity in normal and cancer cells. Unlike BPA, B-381 illustrated preferential retention in hypoxic glioma cells compared to normoxic glioma cells and normal tissues in vitro. In vivo, B-381 illustrated significantly higher long-term tumor retention compared to BPA, with 9.5-fold and 6.5-fold higher boron levels at 24 and 48 h, respectively. CONCLUSIONS: B-381 represents a new class of BNCT agents in which their selectivity to tumors is based on hypoxic tumor metabolism. Further studies are warranted to evaluate B-381 and similar compounds as preclinical candidates for future BNCT clinical trials for the treatment of glioma.

Ovos e larvas de helmintos nos sanitários de pré-escolas municipais de Sorocaba, SP e suas freqüências nas fezes das crianças / Helminth eggs and larvs in the water closet of some city nursery schools (Infant Educational Center) from Sorocaba, SP, Brazil, and their frequency in children feces

O objetivo desta pesquisa foi relacionar a presença de ovos e/ou larvas de helmintos em elementos dos sanitários com a freqüência dos mesmos nas fezes de seus usuários. Três amostras das fezes de 1050 crianças em idade pré-escolar, examinadas pelo método de sedimentaçäo, foram positivas para 184 ovos ou larvas de helmintos, em 162 crianças. Dos 465 elementos dos sanitários (assento, descarga, trinco, maçanetas e registro de torneira) de 12 pré-escolas municipais de Sorocaba examinados com fita adesiva transparente sobre lâmina de microscopia estavam contaminados, sendo encontrados l8 ovos de Ascaris lumbricoides, 1 de Enterobius vermicularis e 4 larvas de nematóides parcialmente alteradas. Näo houve correlaçäo significante entre a contaminaçäo de elementos de sanitários e das fezes de seus usuários