Development of a new age-appropriate, chewable tablet of mebendazole 500 mg for preventive chemotherapy of soil-transmitted helminth infections in pre-school and school-age children.

The aim of this study was to develop an age-appropriate tablet of mebendazole 500 mg to be used in large donation programs by the World Health Organization (WHO) for preventive chemotherapy of soil-transmitted helminth (STH) infections in pre-school and school-age children living in tropical and subtropical endemic areas. To that end, a new oral tablet formulation was developed that can be either chewed or given to young (≥1 year old) children by spoon after rapid disintegration to a soft mass with the addition of a small amount of water directly on the spoon. Although the tablet was manufactured using conventional fluid bed granulation, screening, blending, and compression processes, one of the main challenges was to combine properties of a chewable, dispersible, and regular (solid) immediate release tablet to meet the predefined requirements. The tablet disintegration time was below 120 s, allowing for administration by the "spoon method". The tablet hardness was higher (160-220 N) than normally applicable for chewable tablets, permitting shipment along a lengthy supply chain in a primary 200-tablet count bottle packaging. In addition, the resulting tablets are stable for 48 months in all climatic zones (I-IV). In this article, several aspects of the development of this unique tablet are described, including formulation, process development, stability, clinical acceptability testing, and regulatory filing.

Post-operative dysnatremia is associated with adverse early outcomes after surgery for congenital heart disease.

BACKGROUND: Dysnatremia is a common disorder in critically ill surgical children. The study's aim is to determine the prevalence of dysnatremia and its association with outcomes after surgery for congenital heart disease (CHD). METHODS: This is a single-center retrospective cohort study of children <18 years of age undergoing surgery for CHD between January 2012 and December 2014. Multivariable logistic regression analysis was used to evaluate the relationship between dysnatremia and outcomes during the perioperative period. A total of 1345 encounters met the inclusion criteria. RESULTS: The prevalence of pre- and post-operative dysnatremia were 10.2% and 47.1%, respectively. Hyponatremia occurred in 19.1%, hypernatremia in 25.6%. Hypernatremia at 24, 48, and 72 h post-operative was associated with increased hospital mortality (odds ratios (OR) [95% confidence intervals (CI)] 3.08 [1.16-8.17], p = 0.024; 4.35 [1.58-12], p = 0.0045; 4.14 [1.32-12.97], p = 0.0148, respectively. Hypernatremia was associated with adverse neurological events 3.39 [1.12-10.23], p = 0.0302 at 48 h post-operative. Hyponatremia was not associated with any adverse outcome in our secondary analysis. CONCLUSIONS: Post-operative dysnatremia is a common finding in this heterogeneous cohort of pediatric cardiac-surgical patients. Hypernatremia was more prevalent than hyponatremia and was associated with adverse early post-operative outcomes. IMPACT: Our study has shown that dysnatremia was highly prevalent in children after congenital heart surgery with hypernatremia associated with adverse outcomes including mortality. It is important to understand fluid and sodium regulation in the post-operative period in children with congenital heart disease to better address fluid overload and associated electrolyte imbalances and acute kidney injury. While clinicians are generally very aware of the importance of hyponatremia in critically ill children, similar attention should be given to hypernatremia in this population.

The role of CTNNB1 mutations and matrix metalloproteinases (MMPs) in anti-angiogenesis treatment of endometrial carcinoma.

OBJECTIVE: Treatment options and associated biomarkers for advanced and recurrent disease are limited. Endometrial cancers (ECs) with CTNNB1 exon 3 mutations appear to have preferential response to bevacizumab, an anti-angiogenesis treatment, though the mechanism of action is unknown. We aim to identify mediators of bevacizumab-responsive endometrial cancers. METHODS: We analyzed RNA expression from TCGA and protein expression from CPTAC to identify likely targets for ß-catenin overactivity. We then transiently and stably overexpressed ß-catenin in EC cells to confirm the results suggested by our in silico analysis. We performed corroborative experiments by silencing CTNNB1 in mutated cell lines to demonstrate functional specificity. We implanted transduced cells into xenograft models to study microvessel density. RESULTS: CTNNB1-mutated ECs were associated with increased ß-catenin and MMP7 protein abundance (P < 0.001), but not VEGF-A protein abundance. Overexpressing ß-catenin in EC cells did not increase VEGF-A abundance but did increase expression and secretion of MMP7 (P < 0.03). Silencing CTNNB1 in CTNNB1-mutated cells decreased MMP7 gene expression in EC (P < 0.0001). Microvessel density was not increased. CONCLUSIONS: These data provide a mechanistic understanding for bevacizumab-response in CTNNB1-mutated ECs demonstrated in GOG-86P. We hypothesize that overexpressed and secreted MMP7 potentially digests VEGFR-1, releasing VEGF-A, and increasing its availability. These activities may drive the formation of permeable vessels, which contributes to tumor progression, metastasis, and immune suppression. This mechanism is unique to EC and advocates for further clinical trials evaluating this treatment-related biomarker.

Effect of low pH on growth and shell mechanical properties of the Peruvian scallop Argopecten purpuratus (Lamarck, 1819).

Dissolution of anthropogenic CO2 modifies seawater pH, leading to ocean acidification, which might affect calcifying organisms such as bivalve mollusks. Along the Peruvian coast, however, natural conditions of low pH (7.6-8.0) are encountered in the habitat of the Peruvian scallop (Argopecten purpuratus), as a consequence of the nearby coastal upwelling influence. To understand the effects of low pH in a species adapted to these environmental conditions, an experiment was performed to test its consequences on growth, calcification, dissolution, and shell mechanical properties in juvenile Peruvian scallops. During 28 days, scallops (initial mean height = 14 mm) were exposed to two contrasted pH conditions: a control with unmanipulated seawater presenting pH conditions similar to those found in situ (pHT = 7.8) and a treatment, in which CO2 was injected to reduce pH to 7.4. At the end of the experiment, shell height and weight, and growth and calcification rates were reduced about 6%, 20%, 9%, and 10% respectively in the low pH treatment. Mechanical properties, such as microhardness were positively affected in the low pH condition and crushing force did not show differences between pH treatments. Final soft tissue weights were not significantly affected by low pH. This study provides evidence of low pH change shell properties increasing the shell microhardness in Peruvian scallops, which implies protective functions. However, the mechanisms behind this response need to be studied in a global change context.

Thermo-Mechanical and Fungi Treatment as an Alternative Lignin Degradation Method for Bambusa oldhamii and Guadua angustifolia Fibers.

Different strategies have been used to degrade the molecular structure of lignins in natural fibers. Both chemical and biological processes can obtain different types of lignins for industrial use. In this study, a variation of the spectral intensity of the thermo-mechanical and fungi-modified Bambusa oldhamii (giant bamboo) and Guadua angustifolia Kunt fibers were examined via Fouriertransform infrared spectroscopy. The giant bamboo and Guadua angustifolia Kunt specimens were modified using a non-chemical alternative steam pressure method for degrading lignins, followed by mechanical sieving to obtain fibers of different lengths. The obtained fibers were treated with the Fusarium incarnatum-equiseti MF18MH45591 strain in a 21 d degradation process. The samples were subjected to Fouriertransform infrared spectroscopy before and after the strain treatment. The intensity variation was found to be in the spectral range of 1200 cm-1 to 1800 cm-1, in which lignin components are commonly found in most plant species. A multivariate analysis of the principal components of the treated and untreated control samples confirmed the changes in the spectral region of interest, which were associated with the thermo-mechanical and fungal treatment.

Climate vulnerability assessment of key fishery resources in the Northern Humboldt Current System.

The Northern Humboldt Current System sustains one of the most productive fisheries in the world. However, climate change is anticipated to negatively affect fish production in this region over the next few decades, and detailed analyses for many fishery resources are unavailable. We implemented a trait-based Climate Vulnerability Assessment based on expert elicitation to estimate the relative vulnerability of 28 fishery resources (benthic, demersal, and pelagic) to the impacts of climate change by 2055; ten exposure factors (e.g., temperature, salinity, pH, chlorophyll) and 13 sensitivity attributes (biological and population-level traits) were used. Nearly 36% of the species assessed had "high" or "very high" vulnerability. Benthic species were ranked the most vulnerable (gastropod and bivalve species). The pelagic group was the second most vulnerable; the Pacific chub mackerel and the yellowfin tuna were amongst the most vulnerable pelagic species. The demersal group had the relatively lowest vulnerability. This study allowed identification of vulnerable fishery resources, research and monitoring priorities, and identification of the key exposure factors and sensitivity attributes which are driving that vulnerability. Our findings can help fishery managers incorporate climate change into harvest level and allocation decisions, and assist stakeholders plan for and adapt to a changing future.

Laryngeal Ultrasound Detects Vocal Fold Immobility in Adults: A Systematic Review.

Laryngeal ultrasound (US) is becoming widely accepted for assessing true vocal fold immobility (TVFI), a potential complication of laryngeal and thyroid surgery. The objective of this project is to perform a systematic review and meta-analysis of pooled evidence surrounding laryngeal US as a modality for diagnosing TVFI in adults at risk for the condition in comparison to laryngoscopy as a gold standard. Medical subject heading terms were used to search MEDLINE, Embase, Google Scholar, Web of Science, and the Cochrane Library for relevant citations from January 1, 2000, to June 30, 2020. Studies were included if they involved patients 16 years and older, where laryngeal US was compared to laryngoscopy for TVFI. Studies were excluded if there were insufficient data to compute a sensitivity/specificity table after attempting to contact the authors. Case reports, and case series were also excluded. The initial search returned 1357 citations. Of these, 109 were selected for review utilizing the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Thirty citations describing 6033 patients were included in the final meta-analysis. A bivariate random effects meta-analysis was performed, revealing a pooled sensitivity for laryngeal US of 0.95 (95% confidence interval [CI] 0.88-0.98), a specificity of 0.99 (95% CI 0.97-0.99), and a diagnostic odds ratio of 1328.2 (95% CI 294.0-5996.5). The area under the curve of the hierarchical summary receiver operating characteristic curve was 0.99 (95% CI 0.98-1.00). Laryngeal US demonstrates high sensitivity and specificity for detecting VFI in the hands of clinicians directly providing care to patients.

Assessment of Vocal Cord Motion Using Laryngeal Ultrasound in Children: A Systematic Review and Meta-Analysis.

OBJECTIVES: Laryngeal ultrasound is a nonirradiating, noninvasive method for assessing the upper airway in children. This systematic review and meta-analysis examine available evidence for accuracy of laryngeal ultrasound in diagnosing vocal cord immobility in infants and children after surgery and trauma affecting the vocal cords. DESIGN: Medical subject heading terms were used to search MEDLINE, Embase, Google Scholar, Web of Science, and the Cochrane Library for relevant citations. Publications from January 1, 2000, to June 30, 2020 were included in the search strategy. Study inclusion criteria consisted of randomized control trials and nonrandomized retrospective or prospective observational studies where vocal cord motion was evaluated by laryngeal ultrasound and compared with a reference test. Studies were excluded if there was insufficient data to compute a sensitivity/specificity table. Case reports, case series less than 10, and manuscripts not published in English were also excluded. PATIENTS: Studies which included subjects younger than or equal to 18 years were considered for full article review. SETTINGS: No restrictions on study settings were imposed in this systematic review. MEASUREMENTS AND MAIN RESULTS: The initial search returned 1,357 citations. After de-duplication, abstract, and full review, eight citations were included in the final meta-analysis. A bivariate random-effects meta-analysis was performed, which revealed a pooled sensitivity for laryngeal ultrasound in detecting vocal cord immobility of 91% (95% CI, 83-95%), specificity of 97% (95% CI, 82-100%), diagnostic odds ratio 333.56 (95% CI, 34.00-3,248.71), positive likelihood ratio 31.58 (95% CI, 4.50-222.05), and negative likelihood ratio 0.09 (95% CI, 0.05-0.19). CONCLUSIONS: Laryngeal ultrasound demonstrates high sensitivity and specificity for detecting vocal cord motion in children in a wide range of clinical settings. Laryngeal ultrasound offers a low-risk imaging option for assessing vocal cord function in children compared with the current gold standard of laryngoscopy.

Introducción de vídeojuegos en el tratamiento convencional de la ambliopía funcional / Incorporation of videogames into the conventional treatment for functional amblyopia

RESUMEN Objetivo: Valorar la efectividad del vídeojuego en educandos que padecen ambliopía funcional. Métodos: Se confeccionó la historia clínica de cada paciente, la cual incluyó la revisión oftalmológica completa, la evaluación de la agudeza visual con la prueba adecuada a cada edad, y se evaluó la presencia de supresión mediante la prueba de filtro rojo y las luces de Worth. Cada prueba se realizó de forma individual según el tipo y la severidad de la ambliopía, y se le indicó la refracción correspondiente. Los pacientes se dividieron en dos grupos: al grupo A se le aplicó la terapia tradicional de la ambliopía, y al grupo B se le siguió la misma pauta que un tratamiento tradicional de ambliopía, pero con la introducción de vídeojuegos. Resultados: Se observó en el grupo A un predominio de los pacientes con agudeza visual inicial entre 0,2 - 0,4 (50 %), la cual se incrementó en dos líneas o más en el (55 %); sin embargo, en el grupo B la agudeza inicial entre 0,2 - 0,4 fue de 56,5 %. Los resultados sensoriales seis meses posteriores al tratamiento, según cada grupo de estudio, mostraron en el grupo B una reducción de la supresión en el 91,3 %, y en el grupo A de un 75 %. Conclusión: La terapia visual combinada con vídeojuego es efectiva; mejora la agudeza visual; elimina y reduce la supresión, por lo que constituye una herramienta que complementa la terapia visual tradicional de la ambliopía.

ABSTRACT Objective: Assess the effectiveness of videogames for students suffering from functional amblyopia. Methods: A clinical record was developed for each patient, which included complete ophthalmological examination, visual acuity evaluation with the suitable test for each age, and determination of the presence of suppression by the red filter test and the Worth lights test. Each test was conducted individually according to the type and severity of amblyopia, and the corresponding refraction was indicated. The patients were divided into two groups: Group A received traditional amblyopia therapy, whereas Group B underwent traditional amblyopia treatment combined with the incorporation of videogames. Results: Group A showed a predominance of patients with initial visual acuity between 0.2 - 0.4 (50%), which increased two lines or more in 55%. However, in Group B initial visual acuity ranged between 0.2 - 0.4 in 56.5%. Six months after treatment, sensory results were 91.3% suppression reduction in Group B and 75% in Group A. Conclusion: Visual therapy proved effective when combined with videogames: visual acuity improved and suppression was reduced. It is thus a suitable tool to complement the traditional visual therapy for amblyopia.

Eficacia en el diagnóstico y tratamiento del síndrome de Brown / Efficacy of the diagnosis and treatment of Brown syndrome

RESUMEN Objetivo: Identificar las características clínicas y los criterios quirúrgicos en el síndrome de Brown. Métodos: Se realizó un estudio descriptivo retrospectivo a 15 pacientes con el diagnóstico de síndrome de Brown, quienes acudieron a la Consulta de Visión Binocular del Hospital Infantil Sur "Dr. Antonio María Béguez César". Se incluyeron los niños con edades entre 2 a 7 años, con el diagnóstico definido de síndrome de Brown; se realizó exploración motora y sensorial completa y se evaluó el ojo afectado, el tipo de síndrome de Brown que tenía el paciente, las características clínicas y los criterios quirúrgicos tenidos en cuenta para resolver una conducta adecuada. Resultados: En la muestra estudiada el 66,5 por ciento de los pacientes tuvo afectado el ojo derecho con un síndrome de Brown leve; el 73 por ciento estuvo en ortotropía y el 73,3 por ciento no fue quirúrgico. Conclusión: Los pacientes con síndrome de Brown leve que permanecen en ortotropía, sin tortícolis y sin depresión en aducción, no requieren intervención quirúrgica(AU)

ABSTRACT Objective: Identify the clinical characteristics of and surgical criteria for Brown syndrome. Methods: A retrospective descriptive study was conducted of 15 patients diagnosed with Brown syndrome attending the binocular vision service at Dr. Antonio María Béguez César South University Children's Hospital. The sample included children aged 2-7 years with a definite diagnosis of Brown syndrome. Complete motor and sensory exploration was done, and evaluation was performed of the affected eye, Brown syndrome type, clinical characteristics and surgical criteria considered to select the appropriate management. Results: 66.5 percent of the study sample had their right eye affected by mild Brown syndrome, 73 percent were orthotropic, and 73.3 percent were not surgical cases. Conclusion: Patients with mild Brown syndrome who remained orthotropic, without torticollis or adduction depression, did not require surgical intervention(AU)

Amino acid-level signal-to-noise analysis of incidentally identified variants in genes associated with long QT syndrome during pediatric whole exome sequencing reflects background genetic noise.

BACKGROUND: Due to rapid expansion of clinical genetic testing, an increasing number of genetic variants of undetermined significance and unclear diagnostic value are being identified in children. Variants found in genes associated with heritable channelopathies, such as long QT syndrome (LQTS), are particularly difficult to interpret given the risk of sudden cardiac death associated with pathologic mutations. OBJECTIVE: The purpose of this study was to determine whether variants in LQTS-associated genes from whole exome sequencing (WES) represent disease-associated biomarkers or background genetic "noise." METHODS: WES variants from Baylor Genetics Laboratories were obtained for 17 LQTS-associated genes. Rare variants from healthy controls were obtained from the GnomAD database. LQTS case variants were extracted from the literature. Amino acid-level mapping and signal-to-noise calculations were conducted. Clinical history and diagnostic studies were analyzed for WES subjects evaluated at our institution. RESULTS: Variants in LQTS case-associated genes were present in 38.3% of 7244 WES probands. There was a similar frequency of variants in the WES and healthy cohorts for LQTS1-3 (11.2% and 12.9%, respectively) and LQTS4-17 (27.1% and 38.4%, respectively). WES variants preferentially localized to amino acids altered in control individuals compared to cases. Based on amino acid-level analysis, WES-identified variants are indistinguishable from healthy background variation, whereas LQTS1 and 2 case-identified variants localized to clear pathologic "hotspots." No individuals who underwent clinical evaluation had clinical suspicion for LQTS. CONCLUSION: The prevalence of incidentally identified LQTS-associated variants is ∼38% among WES tests. These variants most likely represent benign healthy background genetic variation rather than disease-associated mutations.

Effects of residential summer camp on body mass index and body composition in type 1 diabetes.

BACKGROUND: Body mass index (BMI) and fat mass may be higher in children with diabetes compared to healthy peers. It is not certain how diabetic children respond to exercise and diet interventions. OBJECTIVE: To investigate the effect of summer camp on BMI and body composition in children with type 1 diabetes. METHODS: Five hundred eighty-six children (5-19 years, 518 with type 1 diabetes, 68 without diabetes) were followed while attending camp. BMI z-scores (BMIz) and body composition (bioelectrical impedance analysis) were measured at the beginning and end of each 19-day session. Diet and activity were directly supervised, blood glucose closely monitored. A nested diabetic/non-diabetic sib pair analysis was also conducted. Changes in BMIz and percent fat mass (%FM) were the primary outcomes. Findings were confirmed by analysis of data from 612 campers (549 with diabetes) the following summer. RESULTS: At entry, campers with diabetes had higher BMIz and %FM. They tended to gain BMIz (0.04 ± 0.01) whereas non-diabetic campers lost (-0.16 ± 0.11, P < .0001). BMIz increases were positively correlated with precamp hemoglobin A1c values. The differences in initial values and changes in BMIz remained when campers with diabetes were compared to their siblings. All experienced a similar reduction in %FM. Similar results were obtained the following summer. CONCLUSIONS: Children with diabetes may, therefore, accrue more lean body tissue with increased exercise and a healthy diet than those without diabetes. This effect is greatest in those with initially poor metabolic control.

MR and CT arthrography of the hip.

CT arthrography (CTa) and MR arthrography (MRa) are useful tools for the investigation of intra-articular hip disease. They are minimally invasive techniques with a very low rate of complications and can be performed safely. CTa or MRa can be performed after an intra-articular injection of diluted contrast, but both techniques can also be performed after a single injection. As radiologists we should be able to address the surgeon's questions and work together to standardize terminology and classifications systems for accurate reporting. This update emphasizes radiological findings with a clinical perspective. CTa and MRa allow the precise diagnosis of labral tears, loose bodies, and intra-articular ligaments (capsular and ligamentum teres). The use of careful technique and a tailored protocol has improved our ability to detect and describe cartilage lesions. This is essential because knowledge of the status of the cartilage may dictate a specific surgical approach, and when cartilage lesions are extensive, they are a negative prognostic indicator for arthroscopic treatment.