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Chitosan-Based Microparticle Encapsulated Acinetobacter baumannii Phage Cocktail in Hydrogel Matrix for the Management of Multidrug Resistant Chronic Wound Infection

Turk J Pharm Sci. 2022 Apr 29;19(2):187-195. doi: 10.4274/tjps.galenos.2021.72547.

ABSTRACT

OBJECTIVES: Multi-drug resistant bacteria have been implicated in various debilitating infections that have led to life loss. This study developed an approach to tackle multidrug resistant Acinetobacter baumannii infection in a chronic wound model through A. baumannii phage encapsulation with resuspension in hydrogel.

MATERIALS AND METHODS: Two isolates of A. baumannii-specific lytic phases ɸAB140 and ɸAB150 alone, in combination (cocktail) encapsulated within a chitosan (CS) microparticle was suspended in CS hydrogel and evaluated for their therapeutic efficacy to ensure bacterial clearance in A. baumannii induced diabetic wound infection. Microencapsulation of the phage was carried out using ionic gelation techniques Biological characterization via cell cytoxicity, in vivo wound healing, histology and histomorphometry was carried out.

RESULTS: Two characterized A. baumannii phages (ɸAB140 and ɸAB150), specific to twenty A. baumannii isolates, were isolated. The encapsulated CS microparticle hydrogel exhibited a pH of 5.77 ± 0.05. The wound size reduction was most pronounced in formulation C2, which showed statistically significant wound seize reduction on days 4 and 7, 56.79 ± 2.02% and 62.15 ± 5.11%, respectively. The optimized concentration of C2 was not toxic to the cells as it adequately supported cell growth with a proliferation rate of 215 ± 7.89% compared to control (107.32 ± 4.55%).

CONCLUSION: Microparticle carrier technology was used to show the lytic activity against multi drug-resistant A. baumannii. In vivo results showed significant wound size reduction that was most pronounced in formulation C2 on day 4.

PMID:35510310 | DOI:10.4274/tjps.galenos.2021.72547

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Building Causal Knowledge in Behavior Genetics

Behav Brain Sci. 2022 May 5:1-76. doi: 10.1017/S0140525X22000681. Online ahead of print.

ABSTRACT

Behavior genetics is a controversial science. For decades, scholars have sought to understand the role of heredity in human behavior and life-course outcomes. Recently, technological advances and the rapid expansion of genomic databases have facilitated the discovery of genes associated with human phenotypes like educational attainment and substance use disorders. To maximize the potential of this flourishing science, and to minimize potential harms, careful analysis of what it would mean for genes to be causes of human behavior is needed. In this paper, we advance a framework for identifying instances of genetic causes, interpreting those causal relationships, and applying them to advance causal knowledge more generally in the social sciences. Central to thinking about genes as causes is counterfactual reasoning, the cornerstone of causal thinking in statistics, medicine, and philosophy. We argue that within-family genetic effects represent the product of a counterfactual comparison in the same way as average treatment effects from randomized controlled trials (RCTs). Both average treatment effects from RCTs and within-family genetic effects are shallow causes: they operate within intricate causal systems (non-unitary), produce heterogeneous effects across individuals (non-uniform), and are not mechanistically informative (non-explanatory). Despite these limitations, shallow causal knowledge can be used to improve understanding of the etiology of human behavior and to explore sources of heterogeneity and fade-out in treatment effects.

PMID:35510303 | DOI:10.1017/S0140525X22000681

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Language abilities in preschool children with critical CHD: a systematic review

Cardiol Young. 2022 May 5:1-11. doi: 10.1017/S1047951122001330. Online ahead of print.

ABSTRACT

CONTEXT: Children with critical CHD are at risk for neurodevelopmental impairments, including delays in expressive and receptive language development. However, no study has synthesised the literature regarding language abilities in children with this condition.

OBJECTIVE: We summarised the literature regarding expressive and receptive language in preschool children with critical CHD.

DATA SOURCES: MEDLINE, Embase, Scopus, Child Development and Adolescent Studies, ERIC, PsycINFO, and CINAHL.

STUDY SELECTION: We included studies published between January, 1990 and 1 July, 2021, focused on children aged ≤5 years with critical CHD requiring a complex cardiac procedure at age <1 year. Language ability was documented using standardised, validated tools assessing both expressive and receptive language outcomes.

DATA EXTRACTION: Data (study, patient and language characteristics, and results) were extracted by two reviewers.

RESULTS: Seventeen studies were included. Among children 2-5 years old with critical CHD, there were statistically significant deficits in overall (standardised mean difference: -0.46; 95 % confidence interval: -0.56, -0.35), expressive (standardised mean difference: -0.45;95 % confidence interval: -0.54, -0.37), and receptive (standardised mean difference: -0.32; 95 % confidence interval: -0.40, -0.23) language compared to normative data. Results reported as medians were similar to meta-analysis findings. Subgroup analysis showed that children with univentricular physiology had lower language scores than children with biventricular physiology.

CONCLUSIONS: Preschool children with critical CHD had statistically significantly lower language outcomes compared to expected population norms. Healthcare professionals should test early and often for language deficits, referring to individually tailored supports.

PMID:35510297 | DOI:10.1017/S1047951122001330

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Interim Analysis of STREAMLINE® Surgical System Clinical Outcomes in Eyes with Glaucoma

Clin Ophthalmol. 2022 Apr 27;16:1313-1320. doi: 10.2147/OPTH.S358871. eCollection 2022.

ABSTRACT

PURPOSE: To characterize the clinical outcomes of a novel ab interno minimally invasive procedure with the STREAMLINE® Surgical System for creation of incisional goniotomies and canal of Schlemm viscodilation in eyes with mild to severe primary open-angle glaucoma (POAG).

METHODS: In a prospective, single-arm, first-in-human case series, 20 eyes of 20 subjects with mild to severe POAG underwent creation of incisional goniotomies and canal of Schlemm viscodilation following phacoemulsification cataract extraction after washout of all intraocular pressure (IOP)-lowering medications. The angle surgery portion was performed with a single-use handpiece tipped with a microcannula that creates precise goniotomies through the trabecular meshwork into the canal of Schlemm and delivers a small volume of ophthalmic viscosurgical device directly into the canal via precise catheterization. Outcomes in this interim analysis included mean reduction in IOP and medications through 6 months of follow-up, as well as the proportion of eyes achieving IOP reduction ≥20% from baseline.

RESULTS: At month 6, mean IOP reduction of ≥20% from baseline was achieved in 89.5% of eyes (17/19). Mean (standard deviation) medicated IOP at screening was 16.3 (3.6) mmHg and unmedicated baseline IOP (after washout) was 23.5 (2.5) mmHg. Mean IOP was significantly reduced from baseline through 6 months of follow-up to 14.7 (2.4) mmHg (p<0.001), representing an IOP reduction of 8.8 mmHg (36.9%). Overall, 57.9% (11/19) of eyes decreased dependence on IOP-lowering medications by at least one medication, and 42.1% (8/19) were medication free. Mean medication use was reduced from 2.0 (0.8) at screening to 1.1 (1.1) at 6 months (p<0.001). Three eyes had transient IOP spikes treated with topical medications.

CONCLUSION: The creation of incisional goniotomies and canal of Schlemm viscodilation safely and effectively reduced IOP and the need for IOP-lowering medications by both clinically and statistically significant magnitudes in eyes with mild to severe POAG undergoing concomitant phacoemulsification cataract extraction through the first 6 months of follow-up.

PMID:35510271 | PMC:PMC9058234 | DOI:10.2147/OPTH.S358871

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Genetic diversity of European maize landraces: Dataset on the molecular and phenotypic variation of derived doubled-haploid populations

Data Brief. 2022 Apr 12;42:108164. doi: 10.1016/j.dib.2022.108164. eCollection 2022 Jun.

ABSTRACT

Genetic variation is the basis of selection, evolution and breeding. Maize landraces represent a rich source of allelic diversity, but their efficient utilization in breeding and research has been hampered by their heterogeneous and heterozygous nature and insufficient information about most accessions. While molecular inventories of germplasm repositories are growing steadily, linking these data to meaningful phenotypes for quantitative traits is challenging. Here, we present comprehensive molecular and phenotypic data for ∼1,000 doubled-haploid (DH) lines derived from three pre-selected European maize landraces. Due to their full homozygosity, the DH lines can be multiplied ad libitum and represent a powerful biological resource available to the community. The DH lines allow high-precision phenotyping in repeated experiments and reveal the full additive genetic variance of the population. The DH lines were evaluated for nine agronomically important, quantitative traits in multi-environment field trials comprising seven locations and two years. The DH populations revealed high genetic variance and high heritability for the analysed traits. The DH lines were genotyped with 600k SNP markers. After stringent quality filtering 500k markers remained for further analyses. This is the largest resource of landrace derived DH material in maize, unprecedented in its structure and dimension. The presented data are ideal for linking molecular variation to meaningful phenotypes. They can be used for genome-wide association studies, genomic prediction, and population genetic analyses as well as for developing and testing statistical methods. All plant material is available to the community for conducting additional experiments, extending the panel of traits and environments, and for testing the landrace-derived lines in combination with other genetic material.

PMID:35510267 | PMC:PMC9058946 | DOI:10.1016/j.dib.2022.108164

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Ultrasonic Assessment of Cancellous Bone Based on the Two-Wave Phenomenon

Adv Exp Med Biol. 2022;1364:119-143. doi: 10.1007/978-3-030-91979-5_6.

ABSTRACT

The investigation of cancellous bone using ultrasound measurements is not an easy task due to the solid complex trabecular structure filled with fluid-like bone marrow. It is expected that the ultrasound propagated in cancellous bone contains valuable information about the complex structure. In this chapter, the methods to derive useful information by the two-wave phenomenon-based ultrasonic assessment of cancellous bone is introduced. First, the measurements and mathematical descriptions of the two-wave phenomenon are presented in Sect. 6.1. Here, a conventional mathematical method to understand the phenomenon and fundamental results of the experimental measurements are introduced. Next, in Sect. 6.2, the computational simulation methods using models representing real bone structures, the numerical or statistical separation techniques of the two waves, and machine learning techniques for deriving material information are discussed. Finally, in Sect. 6.3, the results and the current limitations of the clinical assessment with a device using the two-wave phenomenon are introduced.

PMID:35508873 | DOI:10.1007/978-3-030-91979-5_6

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Reduning Injection versus Neuraminidase Inhibitors in the Treatment of Influenza: A Systematic Review and Meta-Analysis

Chin J Integr Med. 2022 May 4. doi: 10.1007/s11655-022-3524-9. Online ahead of print.

ABSTRACT

OBJECTIVE: To perform a systematic review to assess the effectiveness and safety of Reduning Injection versus neuraminidase inhibitors in treatment of influenza.

METHODS: The MEDLINE, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), Chinese Bio-medical Literature and Retrieval System (Sinomed), China National Knowledge Infrastructure Database (CNKI), China Science and Technology Journal Database (VIP), Wanfang Data Knowledge Service Platform and ClinicalTrails.gov were systematically searched from inception dates to May 2021 for randomized controlled trials (RCTs) exploring Reduning Injection alone or in combination with neuraminidase inhibitors in patients with influenza. Statistical analysis was performed using RevMan 5.4 and Stata 15.1. The qualities of the involved studies were assessed by the risk of bias according to the Cochrane handbook. The evidence quality of each outcome was evaluated by GRADEpro GDT.

RESULTS: Twelve trials with 1,460 patients were included. The included studies had a certain unclear or high risk of bias. Reduning Injection appeared to be more effective in shortening the fever clearance time (MD: -16.20 h, 95% CI: -19.40 to -12.99, 7 trials, 814 patients, I2=94%, very low certainty), fever alleviation time (MD: -4.09 h, 95% CI: -4.22 to -3.96, 3 trials, 366 patients, I2=0%, low certainty), cough alleviation time (MD: -21.34 h, 95% CI: -41.56 to -1.11, 2 trials, 228 patients, I2=89%, very low certainty), fatigue alleviation time (MD: -31.83 h, 95% CI: -36.88 to -26.77, 2 trials, 270 patients, I2=0%, low certainty), sore throat alleviation time (MD: -28.66 h, 95% CI: -32.23 to -25.10, 1 trial, 150 patients, low certainty), and improving the total effective rate (RR: 1.15, 95% CI: 1.06 to 1.25, 10 trials, 1,074 patients, I2=76%, very low certainty). Besides, Reduning Injection seemed generally safe.

CONCLUSIONS: This study provided low or very low evidence indicating Reduning Injection may be effective in the treatment of influenza and might be safe. Further rigorously designed studies are needed to confirm the effectiveness and safety of Reduning Injection and support it as a recommendation for influenza.

PMID:35508864 | DOI:10.1007/s11655-022-3524-9

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Changes in Refractive Error Under COVID-19: A 3-Year Follow-up Study

Adv Ther. 2022 May 4. doi: 10.1007/s12325-022-02150-0. Online ahead of print.

ABSTRACT

INTRODUCTION: To investigate changes in refractive error in schoolchildren before and during the coronavirus disease 2019 (COVID-19) pandemic.

METHODS: This study included 2792 students, who underwent a 3-year follow-up from 2018 to 2020. All participants underwent yearly noncycloplegic refraction and ocular examinations. Time-related changes in sphere, cylinder, and spherical equivalent (SE) measurements in both genders were analyzed.

RESULTS: The myopic sphere (- 0.78 ± 1.83 vs. – 1.03 ± 1.91 D; P = 0.025) and SE (- 1.04 ± 1.90 vs. – 1.32 ± 1.99 D; P = 0.015) progressed significantly from 2018 to 2019. Female participants had a significantly greater change in SE than male participants (P < 0.05), and the low hyperopia, emmetropia, and mild myopia groups significantly deteriorated (P < 0.001) from 2018 to 2019. Significant differences in sphere change (- 0.21 ± 0.97 vs. – 0.36 ± 0.96 D; P < 0.001) and SE change (- 0.23 ± 0.99 vs. – 0.38 ± 0.98 D; P < 0.001) were noted between 2019-2018 and 2020-2019, respectively. The respective changes in cylinder were statistically similar (- 0.03 ± 0.53 vs. – 0.05 ± 0.62 D; P = 0.400).

CONCLUSIONS: The refractive status of schoolchildren showed an increasing myopic shift trend before and during the COVID-19 pandemic. The low hyperopia, emmetropia, and mild myopia groups were more sensitive to environmental changes during COVID-19 than before. The myopic shift was greater in female participants than male participants.

PMID:35508845 | DOI:10.1007/s12325-022-02150-0

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Probing individual-level structural atrophy in frontal glioma patients

Neurosurg Rev. 2022 May 4. doi: 10.1007/s10143-022-01800-9. Online ahead of print.

ABSTRACT

Although every glioma patient varies in tumor size, location, histological grade and molecular biomarkers, non-tumoral morphological abnormalities are commonly detected by a statistical comparison among patient groups, missing the information of individual morphological alterations. In this study, we introduced an individual-level structural abnormality detection method for glioma patients and proposed several abnormality indexes to depict individual atrophy patterns. Forty-five patients with a glioma in the frontal lobe and fifty-one age-matched healthy controls participated in the study. Individual structural abnormality maps (SAM) were generated using patients’ preoperative T1 images, by calculating the degree of deviation of voxel volume in each patient with the normative model built from healthy controls. Based on SAM, a series of individual abnormality indexes were computed, and their relationship with glioma characteristics was explored. The results demonstrated that glioma patients showed unique non-tumoral atrophy patterns with overlapping atrophy regions mainly located at hippocampus, parahippocampus, amygdala, insula, middle temporal gyrus and inferior temporal gyrus, which are closely related to the human cognitive functions. The abnormality indexes were associated with several molecular biomarkers including isocitrate dehydrogenase (IDH) mutation, 1p/19q co-deletion and telomerase reverse transcriptase (TERT) promoter mutation. Our study provides an effective way to access the individual-level non-tumoral structural abnormalities in glioma patients, which has the potential to significantly improve individualized precision medicine.

PMID:35508819 | DOI:10.1007/s10143-022-01800-9

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Monitoring SARS-CoV-2 in the Wastewater and Rivers of Tapachula, a Migratory Hub in Southern Mexico

Food Environ Virol. 2022 May 4. doi: 10.1007/s12560-022-09523-2. Online ahead of print.

ABSTRACT

The COVID-19 pandemic has been monitored by applying different strategies, including SARS-CoV-2 detection with clinical testing or through wastewater-based epidemiology (WBE). We used the latter approach to follow SARS-CoV-2 dispersion in Tapachula city, located in Mexico’s tropical southern border region. Tapachula is a dynamic entry point for people seeking asylum in Mexico or traveling to the USA. Clinical testing facilities for SARS-CoV-2 monitoring are limited in the city. A total of eighty water samples were collected from urban and suburban rivers and sewage and a wastewater treatment plant over 4 months in Tapachula. We concentrated viral particles with a PEG-8000-based method, performed RNA extraction, and detected SARS-CoV-2 particles through RT-PCR. We considered the pepper mild mottle virus as a fecal water pollution biomarker and analytical control. SARS-CoV-2 viral loads (N1 and N2 markers) were quantified and correlated with official regional statistics of COVID-19 bed occupancy and confirmed cases (r > 91%). Our results concluded that WBE proved a valuable tool for tracing and tracking the COVID-19 pandemic in tropical countries with similar water temperatures (21-29 °C). Monitoring SARS-CoV-2 through urban and suburban river water sampling would be helpful in places lacking a wastewater treatment plant or water bodies with sewage discharges.

PMID:35508751 | DOI:10.1007/s12560-022-09523-2