A Delphi panel to build consensus on assessing disease severity and disease progression in adult patients with hypophosphatasia in the United States.

BACKGROUND: Hypophosphatasia (HPP) is an inborn error of metabolism with a variable presentation. We conducted a modified Delphi panel to obtain expert consensus on knowledge gaps regarding disease severity and progression in adult patients with HPP. METHODS: Healthcare professionals (HCPs) with experience managing adult patients with HPP were recruited to participate in a 3-round Delphi panel (round 1: paper survey and 1:1 interview; rounds 2-3: email survey). Panelists rated the extent of their agreement with statements about disease severity and progression in adult patients with HPP. Consensus was defined as ≥ 80% agreement. RESULTS: Ten HCPs completed round 1; nine completed rounds 2 and 3. Consensus was reached on 46/120 statements derived from steering committee input. Disease severity markers in adult patients with HPP can be bone-related (recurrent/poorly healing fractures, pseudo-fractures, metatarsal fractures, osteomalacia) or involve dentition or physiologic/functional manifestations (use of mobility devices/home modifications, abnormal gait, pain). Disease progression markers can include recurrent/poorly healing low-trauma fractures, development of ectopic calcifications, and/or impairment of functional activity. Panelists supported the development of a tool to help assess disease severity in the clinic and track changes in severity over time. Panelists also highlighted the role of a multidisciplinary team, centers with expertise, and the need to refer patients when disease severity is not clear. CONCLUSIONS: These statements regarding disease severity, progression, and assessment methods address some knowledge gaps in adult patients with HPP and may be helpful for treating HCPs, although the small sample size affects the ability to generalize the healthcare provider experience.

Preeclampsia and risk of maternal pulmonary hypertension at high altitude in Bolivia.

Women with a history of preeclampsia (PE) have a greater risk of pulmonary arterial hypertension (PAH). In turn, pregnancy at high altitude is a risk factor for PE. However, whether women who develop PE during highland pregnancy are at risk of PAH before and after birth has not been investigated. We tested the hypothesis that during highland pregnancy, women who develop PE are at greater risk of PAH compared to women undergoing healthy highland pregnancies. The study was on 140 women in La Paz, Bolivia (3640m). Women undergoing healthy highland pregnancy were controls (C, n = 70; 29 ± 3.3 years old, mean±SD). Women diagnosed with PE were the experimental group (PE, n = 70, 31 ± 2 years old). Conventional (B- and M-mode, PW Doppler) and modern (pulsed wave tissue Doppler imaging) ultrasound were applied for cardiovascular íííassessment. Spirometry determined maternal lung function. Assessments occurred at 35 ± 4 weeks of pregnancy and 6 ± 0.3 weeks after birth. Relative to highland controls, highland PE women had enlarged right ventricular (RV) and right atrial chamber sizes, greater pulmonary artery dimensions and increased estimated RV contractility, pulmonary artery pressure and pulmonary vascular resistance. Highland PE women had lower values for peripheral oxygen saturation, forced expiratory flow and the bronchial permeability index. Differences remained 6 weeks after birth. Therefore, women who develop PE at high altitude are at greater risk of PAH before and long after birth. Hence, women with a history of PE at high altitude have an increased cardiovascular risk that transcends the systemic circulation to include the pulmonary vascular bed.

Microplastics in stomach contents of juvenile Patagonian blennies (Eleginops maclovinus).

Microplastics are one of the major environmental issues that need to be addressed because they are starting to impact food chains and are also affecting human populations. The size, colour, form, and abundance of microplastics in young blennies of the species Eleginops maclovinus were examined in the current study. While the stomach contents of 70 % of the studied individuals contained microplastics, 95 % of them included fibres. Individual size and the largest particle size that can be eaten, which ranges between 0.09 and 1.5 mm present no statistical correlation. The quantity of particles taken in by each individual does not change with size. The most present microfibers colours were blue and red. Sampled fibres were analysed with FT-IR and no natural fibres were detected, proving the synthetic origin of the detected particles. These findings suggest that protected coastlines create conditions that favour the encounter of microplastics increasing local wildlife exposure to microplastics, raising the danger of their ingestion with potential physiological, ecological, economical and human health consequences.

An efficient removal approach for degradation of metformin from aqueous solutions with sulfate radicals.

Metformin consumption for diabetes treatment is increasing, leading to its presence in wastewater treatment plants where conventional methods cannot remove it. Therefore, this work aims to analyze the performance of advanced oxidation processes using sulfate radicals in the degradation of metformin from water. Experiments were performed in a photoreactor provided with a low-pressure Hg lamp, using K2S2O8 as oxidant and varying the initial metformin concentration (CA0), oxidant concentration (Cox), temperature (T), and pH in a response surface experimental design. The degradation percentages ranged from 26.1 to 87.3%, while the mineralization percentages varied between 15.1 and 64%. Analysis of variance (ANOVA) showed that the output variables were more significantly affected by CA0, Cox, and T. Besides, a reduction of CA0 and an increase of Cox up to 5000 µM maximizes the metformin degradation since the generation of radicals and their interaction with metformin molecules are favored. For the greatest degradation percentage, the first order apparent rate constant achieved was 0.084 min-1. Furthermore, while in acidic pH, temperature benefits metformin degradation, an opposite behavior is obtained in a basic medium because of recombination and inhibition reactions. Moreover, three degradation pathways were suggested based on the six products detected by HPLC-MS: N-cyanoguanidine m/z = 85; N,N-dimethylurea m/z = 89; N,N-dimethyl-cyanamide m/z = 71 N,N-dimethyl-formamide m/z = 74; glicolonitrilo m/z = 58; and guanidine m/z = 60. Finally, it was shown that in general the toxicity of the degradation byproducts was lower than the toxicity of metformin toward Chlamydomonas reinhardtii.

The onset of puberty in colony-housed male and female titi monkeys (Plecturocebus cupreus): Possible effects of oxytocin treatment during peri-adolescent development.

Oxytocin has been used to treat neurodevelopmental conditions in adolescent patients but possible effects on reproductive development have not been well investigated. The effects of daily intra-nasal oxytocin treatment (12-18 months of age) on puberty and fertility were studied in colony-housed, male and female titi monkeys (Plecturocebus cupreus). Body weight, urinary conjugated pregnanes and estrogens (defining cyclicity) in females, and androgens and sperm in urine of in males, were measured from 1 to 3 years of age to detect puberty. Serum testosterone was also measured in males at 13, 23 and 33 months of age and hemi-castration at 3 years of age enabled assessment of testicular morphometry and oxytocin receptor expression. An oxytocin treatment*time interaction suggested a minor, transient suppression in weight gain after treatment ended. Note that females weighed 10% less across all ages. Oxytocin-treated females exhibited early, spurious ovulations but neither regular cyclicity (≈30 months) nor pregnancies were affected by treatment. Oxytocin did not affect the pubertal increase in urinary androgen or the first appearance of sperm, which occurred as early as 15 months of age. Treatment did delay the puberty-associated rise in serum testosterone in males. All males were pubertal by 22 months and all females by 32 months of age. Although no major male or female fertility outcome was observed, oxytocin demonstrated some physiological effects through a delay of testosterone secretion in males, induction of precocious ovulation in females, and a suppression of general weight gain for the months following treatment.

Efectividad de la fisioterapia en el desarrollo motor de niños con osteogénesis imperfecta: una revisión sistemática / Effectiveness of physiotherapy in the motor development of children with osteogenesis imperfecta: A systematic review

Antecedentes y objetivo La osteogénesis imperfecta es una enfermedad rara cuya característica principal es la presencia de fragilidad ósea. Además, estos pacientes presentan bajo tono muscular, laxitud ligamentosa, esclerótica azul, retraso en el crecimiento, problemas dentales y alteraciones en el desarrollo motor. El objetivo del presente estudio es analizar la evidencia existente sobre el efecto de la fisioterapia en el desarrollo de la motricidad gruesa y fina en niños con osteogénesis imperfecta. Material y métodos Revisión sistemática cualitativa de ensayos clínicos y estudios observacionales sobre el tratamiento fisioterapéutico en niños con osteogénesis imperfecta publicados en revistas científicas. Se realizó la búsqueda bibliográfica en las bases informatizadas Medline, BASE, Cochrane, EBSCO, SCOPUS y Web of Science. Resultados Fueron identificados 102 artículos en las bases de datos informatizadas. Tras cribar los artículos con los criterios de inclusión establecidos en el presente trabajo y la eliminación de los duplicados fueron incluidos 4 artículos en este estudio. En estos 4 artículos se evaluó el riesgo de sesgo según el manual de revisiones sistemáticas de Cochrane. Se observaron mejoras en las variables fuerza muscular, función motora, fatiga, marcha, resistencia aeróbica y densidad ósea. Los resultados entre estudios son difíciles de comparar debido a su heterogeneidad. Conclusiones La fisioterapia puede mejorar la motricidad gruesa en niños con osteogénesis imperfecta. Es necesario un mayor número de estudios con una mejor calidad metodológica para confirmar con mayor evidencia los resultados (AU)

Background and objective Osteogenesis imperfecta is a rare disease with a low prevalence. It is characterized by a bone fragility increase. In addition, these patients present with low muscle tone, ligamental laxity, blue sclera, reduced physical growth, dental problems, and alterations in motor development. The aim of the present study is to know the effects of physiotherapy on fine and gross motor development in children with osteogenesis imperfecta. Methods Systematic review of clinical trials and observational studies on physiotherapeutic treatment in children with osteogenesis imperfecta. The computerized databases Medline, BASE, Cochrane, EBSCO, SCOPUS, and Web of Science were used in the literature search. Results One hundred and two articles were identified on the databases. After screening by inclusion criteria and removing duplicates, 4 articles were included in this study. In the 4 articles, bias risk was assessed according to the Cochrane Systematic Review Manual. Muscle strength, motor function, fatigue, gait, aerobic resistance, and bone density were improved with physiotherapy treatment. Results are difficult to compare due to the heterogeneity of the studies. Conclusions Physical therapy can improve gross motor skills in children with osteogenesis imperfecta. A larger number of studies with a better methodological quality are necessary to confirm the results with more evidence (AU)

Efectividad de la terapia bimanual intensiva en la motricidad gruesa y fina de niños con parálisis cerebral. Revisión sistemática / Effectiveness of intensive bimanual therapy in gross and fine motor skills in children with cerebral palsy. Systematic review

Introducción La parálisis cerebral provoca una serie de trastornos en la postura y el movimiento que puede dificultar el desarrollo de la motricidad gruesa y las habilidades manuales. La terapia bimanual intensiva se utiliza para mejorar el uso y la coordinación de los miembros superiores de los niños con parálisis cerebral. El objetivo fue analizar la evidencia de la terapia bimanual intensiva sobre la motricidad fina y gruesa en niños con parálisis cerebral. Material y método Se realizó una revisión sistemática siguiendo la normativa PRISMA en las bases de datos PubMed, Biblioteca Virtual en Salud, Cochrane Library, Web of Science y EBSCO. Además, se utilizó la herramienta Cochrane para la valoración de sesgo. La ultima búsqueda fue realizada el 20 de marzo de 2020. Resultados Un total de tres ensayos clínicos controlados aleatorizados y un ensayo cuasi aleatorizado (n = 112; edad media = 7,3 años) fueron seleccionados. La mayoría de los estudios presentaron un riesgo de sesgo poco claro en la generación y ocultación de la secuencia. Los resultados mostraron una mejoría en la función de la mano, la calidad de movimiento, en el tiempo de sincronización para los grupos que recibieron este tratamiento. Conclusión La terapia bimanual intensiva mejora la función de la mano, la calidad de movimiento y el tiempo de sincronización, además de la coordinación entre ambas manos (AU)

Introduction Cerebral palsy causes a range of posture and movement disorders that can make it difficult to develop gross motor skills and manual skills. Bimanual intensive therapy is used to improve the use and coordination of the upper limbs of children with cerebral palsy. The objective was to analyse the evidence of bimanual intensive therapy on fine and gross motor skills in children with cerebral palsy. Material and method A systematic review was carried out following the PRISMA rules in the databases PUBMED, Biblioteca virtual en salud, Cochrane library, Web of science and EBSCO platforms. To assess the risk of bias, the tool proposed by Cochrane was used. The last search was carried out on March 20, 2020. Results A total of 3 randomized controlled trials and 1 quasi-randomized trial (n = 112; mean age = 7.3 years) were selected. Most studies presented a risk of unclear bias in the generation and concealment of the sequence. The results showed an improvement in the function of the hand, the quality of movement, in the time of synchronization for the groups that received this treatment. Conclusion Bimanual intensive therapy improves the function of the hand, the quality of movement and the time of synchronization, as well as the coordination between the two hands (AU)

Physicochemical characterization of protein isolates of amaranth and common bean and a study of their compatibility with xanthan gum.

Vegetables are considered to be a sustainable source of promising biomaterials such as proteins and polysaccharides. In this study, four protein isolates (amaranth protein isolate API, amaranth globulin-rich protein isolate AGR, bean protein isolate BPI, and bean phaseolin-rich protein isolate BPR) were structurally characterized under different pH conditions (2-12) and their compatibility behavior with xanthan gum (XG) in aqueous medium was described. All protein isolates showed ß turn and ß sheet (78.24-81.11%), as the major secondary structures without statistically significant difference under the pH conditions surveyed. Protein isolates show solubility at pH ≤ 3 (40.4-85.1%) and pH ≥ 8 (57.6-99.9%) and surface hydrophobicity results suggest protein denaturation at pH ≤ 3. In the compatibility study, API/XG ratios between 1:1 and 5:1 at pH from 7 to 9 and the BPI/XG ratios from 1:1 to 20:1 at pH 7 form gels that do not require heating nor crosslinking agent addition. Zeta potential results, on the other hand, evidenced that formation of gels is driven by attractive electrostatic interaction of the charged regions of both biopolymers and intermolecular interactions such as hydrogen bonds.

Effect of Bacillus subtilis DSM 32315 under Different Necrotic Enteritis Models in Broiler Chickens: A Meta-Analysis of Five Independent Research Trials.

Challenge models are needed to understand the pathogenesis of necrotic enteritis (NE) and provide the basis of evaluating nonantibiotic feed-additive interventions. In the category of nonantibiotic feed additives, the application of probiotics to improve intestinal health and growth performance of broiler chickens in the face of an NE challenge has been well described. However, it is crucial to evaluate the consistency of specific probiotics for mitigating the disease challenge and improving performance. Therefore, a meta-analysis of five independent research trials was conducted with the objective of evaluating the effect of Bacillus subtilis DSM 32315 (probiotic) on body weight gain (BWG), feed conversion ratio (FCR), NE mortality, and lesion score (LS) of broiler chickens challenged with NE. These independent studies were conducted in three countries (the United States, Thailand, and Finland). The statistical analysis used fixed and random effects to estimate the mean effect size (MES) of the difference between NE-challenged birds (control) and NE-challenged probiotic-fed birds and the 95% confidence interval of MES. A meta-regression was performed to evaluate heterogeneity (MES variance) among studies. The statistical analysis was performed using a robust variance estimation strategy with a SAS macro. Probiotic-supplemented birds had a significantly higher BWG (MES = 1.04, P = 0.009) and a significantly lower FCR (MES = -1.39, P = 0.020), NE mortality (MES = -1.15, P = 0.012), and LS (MES = -1.29, P = 0.045). Response variables of BWG (Q = 2.81, P = 0.560) and NE mortality (Q = 5.60, P = 0.354) did not present heterogeneity. Heterogeneity was found for FCR (Q = 10.34, P = 0.035) and LS (Q = 16.13, P = 0.001). Overall, dietary supplementation of B. subtilis DSM 32315 significantly improved BWG and reduced FCR, mortality, and LS in a repeatable large-scale manner.

Sow performance in response to natural betaine fed during lactation and post-weaning during summer and non-summer months.

BACKGROUND: Two studies were conducted to evaluate the effects of dietary natural betaine on sow reproductive performance during summer (Exp. 1) and non-summer months (Exp. 2). Treatments were designed as a 2 × 2 factorial arrangement with factors including dietary betaine (0 or 0.2%) and period of supplementation (lactation or post-weaning until 35 days post-insemination). In Exp. 1, 322 and 327 sows and in Exp. 2, 300 and 327 sows representing young (parity 1 and 2) and mature (parity 3 to 6) sows, respectively, were used. RESULTS: In Exp. 1, supplementation of betaine during lactation increased sow body weight losses (- 11.95 vs. -14.63 kg; P = 0.024), reduced feed intake (4.12 vs. 4.28 kg/d; P = 0.052), and tended to reduce percentage of no-value pigs (P = 0.071). Betaine fed post-weaning reduced weaning-to-estrus interval (5.75 vs. 6.68 days; P = 0.054) and farrowing rate (86.74% vs. 91.36%; P = 0.060), regardless of parity group. Post-hoc analysis with sows clustered into 3 parity groups (1, 2 and 3, and 4+) indicated that betaine fed in lactation to parity 4+ sows (P = 0.026) and betaine fed post-weaning to parity 1 sows increased the number of pigs born in the subsequent cycle (P ≤ 0.05). In Exp. 2, betaine fed during lactation tended to reduce the weaning-to-estrus interval (6.64 vs. 7.50 days; P = 0.077) and farrowing rate (88.23% vs. 83.54%; P = 0.089), regardless of parity group. Feeding betaine post-weaning reduced number of pigs born (13.00 vs. 13.64; P = 0.04) and pigs born alive (12.30 vs. 12.82; P = 0.075), regardless of parity group. CONCLUSIONS: Using 0.2% betaine during the non-summer months did not benefit sow performance. During the summer, betaine supplementation in lactation increased subsequent litter size in parity 4+ sows. Betaine fed during the post-weaning period reduced the wean-to-estrus interval and farrowing rate, increased total number of pigs born for parity 1 sows and reduced total number of pigs born to parity 4+ sows. Further research is needed to determine if the detrimental effects on feed intake and farrowing rate may be correlated and depend on dietary betaine level.

Reference values of leukocyte and lymphocytes populations in umbilical cord and capillary blood in healthy Mexican newborns

INTRODUCTION: In newborns, dramatic changes occur in the blood and bone marrow during the first hours; there are rapid fluctuations in the quantities of leukocytes populations. In this work, we investigated leukocytes subsets counts in two types of blood samples (cord blood and capillary blood) extracted from healthy newborns. METHODS: Blood samples from Mexican neonates were collected by Instituto Nacional de Pediatría with written informed consent. For all samples we determined leukocytes populations; neutrophils, monocytes, total lymphocytes, and populations: T CD3+ cells, TCD4+ cells, T CD8+ cells, B CD19+ cells and NK CD16+56 cells by flow cytometry. We used the Mann-Whitney U test to compare leukocytes of cord and capillary blood; also to analyze the differences between gender and we obtained reference values of the cord and capillary blood in neonates. RESULTS: We observed higher absolute counts and frequencies of total lymphocyte in capillary blood compared with cord blood. In absolute numbers, the capillary blood showed significant differences in neutrophils, monocytes, lymphocytes, T CD3+ cells, T CD4+ cells, T CD8+ cells, B CD19+ cells, and NK cells; no significant differences were observed between genders. DISCUSSION: Our data contribute to newborn Mexican reference values for all these populations of leukocytes. We found that the dispersal range differs between the two types of blood, suggesting a different fate in the immune response. Immunophenotyping of the blood cell population to identify these cells is an essential tool in the diagnosis and follow-up of neonates with immunodeficiencies and other immune disorders

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Efectos de los sistemas de posicionamiento sobre la función respiratoria del niño con parálisis cerebral: una revisión sistemática / Effects of positioning systems on the respiratory function of children with cerebral palsy: A systematic review

ANTECEDENTES Y OBJETIVO: Los niños con parálisis cerebral suelen presentar afectación del sistema respiratorio por debilidad muscular. Varios enfoques terapéuticos se han introducido para mejorar este problema, destacando el uso ergonómico en los sistemas de posicionamiento para mejorar el deterioro neuromuscular debido al mal posicionamiento y que conduce a alteraciones respiratorias. El objetivo de este estudio es analizar la evidencia existente sobre el efecto de diferentes sistemas de posicionamiento en la función respiratoria de niños con parálisis cerebral. MATERIAL Y MÉTODOS: Revisión sistemática de ensayos clínicos siguiendo las recomendaciones PRISMA en las bases de datos PubMed, PEDro, SciELo y Science Direct. Se utilizó la escala PEDro para la validez interna de los estudios y la herramienta propuesta por Cochrane para la valoración de los riesgos de sesgo. La búsqueda fue electrónica y manual. RESULTADOS: Se identificaron 26 estudios, de los que 7 fueron seleccionados para la revisión. Se encontraron resultados significativos en la función pulmonar al emplear asiento adaptado anterior, órtesis de tobillo y pie y sistema de posicionamiento nocturno. El empleo de una silla de ruedas con diferentes adaptaciones supuso mejoras en la función respiratoria, sin resultados estadísticamente significativos. CONCLUSIONES: Los sistemas de posicionamiento pueden mejorar la función respiratoria de los niños con parálisis cerebral. Existen diferentes procedimientos de intervención y de evaluación de los sistemas de posicionamiento destinados a la función respiratoria

BACKGROUND AND OBJECTIVE: Children with cerebral palsy usually have respiratory system involvement due to muscle weakness. Several therapeutic uses have been introduced to solve this problem, including the use of ergonomics in positioning systems to improve neuromuscular deterioration due to poor positioning and leading to respiratory disorders. The objective is to analyse the evidence on the effect of different positioning systems on the respiratory function of children diagnosed with cerebral palsy. MATERIAL AND METHODS: Systematic review of clinical trials following the PRISMA recommendations in PubMed, PEDro, SciELo and Science Direct databases. The PEDro scale was used for the internal validity of the studies and the tool proposed by Cochrane for the assessment of risk of bias. RESULTS: Twenty-six studies were identified, of which 7 were selected for review. Significant results were found in lung function using anterior adaptive seating, ankle foot orthosis and a night positioning system. By contrast, the use of a wheelchair with different adaptations resulted in improvements in respiratory function without statistically significant results. CONCLUSIONS: Positioning systems can improve the respiratory function of children with cerebral palsy. There are different procedures for intervention and evaluation of positioning systems for respiratory function

EndoPredict® in early hormone receptor-positive, HER2-negative breast cancer.

PURPOSE: Evaluating consecutive early breast cancer patients, we analyzed both the impact of EndoPredict® on clinical decisions as well as clinico-pathological factors influencing the decision to perform this gene expression test. METHODS: Hormone receptor (HR)-positive and human epidermal growth factor receptor 2 (HER2)-negative early breast cancer patients treated between 2011 and 2016 were included in this study to investigate the role of EndoPredict® (EPclin) in the treatment of early breast cancer. A main study aim was to analyze the changes in therapy recommendations with and without EPclin. In addition, the impact of clinico-pathological parameters for the decision to perform EPclin was examined by Pearson's chi-squared test (χ2-test) and Fisher's exact test as well as univariate and multivariate logistic regressions. RESULTS: In a cohort of 869 consecutive early HR-positive, HER-negative breast cancer patients, EPclin was utilized in 156 (18.0%) patients. EPclin led to changes in therapy recommendations in 33.3% (n = 52), with both therapy escalation in 19.2% (n = 30) and de-escalation in 14.1% (n = 22). The clinico-pathological factors influencing the use of EPclin were age (P < 0.001, odds ratio [OR] 0.498), tumor size (P = 0.011, OR 0.071), nodal status (P = 0.021, OR 1.674), histological grade (P = 0.043, OR 0.432), and Ki-67 (P < 0.001, OR 3.599). CONCLUSIONS: EPclin led to a change in therapy recommendations in one third of the patients. Clinico-pathological parameters such as younger age, smaller tumor size, positive nodal status, intermediate histological grade and intermediate Ki-67 had a significant influence on the use of EndoPredict®.