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.

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.

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®.

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.

Gold nanoparticles (AuNP) exert immunostimulatory and protective effects in shrimp (Litopenaeus vannamei) against Vibrio parahaemolyticus.

Gold nanoparticles (AuNP) stimulate immune responses in mammals but they have not been tested in species of relevance in aquaculture. In this study the immunostimulant and protective potential of orally administered AuNP against V. parahaemolyticus, the causative agent of Acute Hepatopancreatic Necrosis Disease, was determined in shrimp. Synthetized AuNP (18.57 ±â€¯4.37 nm) were moderately dispersed with a negative ζ potential of -10.3 ±â€¯0.208 mV (pH = 7). AuNP were administered (single dose) at 0.2, 2, and 20 µg/g feed in shrimp. Hemolymph samples were withdrawn daily for 6 days. Hemolymph or hemocytes were used to determine total hemocyte counts, immune-related enzymatic activities, and expression of immune-relevant genes. Hepatopancreas was sampled for the analysis of AuNP biodistribution and histological examination. Survival was recorded daily. No mortality or toxicity signs in hepatopancreas were found. AuNP were detected in hepatopancreas. Early (24-48 h) immunostimulation was mainly related to immune gene up-regulation. Upon a challenge with V. parahaemolyticus, survival was higher (80%) and histopathological damages were lower in shrimp treated with the 2 µg/g dose when compared to the control. Therefore orally administered AuNP are proposed as immunostimulants that protect shrimp against V. parahaemolyticus infection.

Managing the farmscape for connectivity increases conservation value for tropical bird species with different forest-dependencies.

Land clearing for agricultural use is a primary driver of biodiversity loss and fragmentation of natural ecosystems. Restoring natural habitat connectivity by retaining quality habitats and increasing on-farm tree cover contributes to species' mobility and persistence in agricultural landscapes. Nonetheless, remarkably few studies have quantified the impacts of on-farm practices for species' mobility measured as functional connectivity within the context of farm and broader spatial levels of landscape organization. We tested how adding and removing trees in different configurations on a farm comprised of coffee plantations and cattle pastures can help evaluate species' mobility at the farmscape level (an area comprising the farm plus a 1.5 km buffer area). We coupled bird capture data and scenario modeling to assess species mobility of five neotropical bird species with distinct life history characteristics representing a gradient of forest dependency. We used seven years of mist-netting data to estimate species habitat affinity and to predict species mobility using the Circuitscape model across a 4371 ha farmscape in Costa Rica. Circuitscape allowed us to estimate changes in movement probability and relative changes in resistance to movement that species experience during dispersal (measured as resistance distance and passage area through which species can move) under four farmscape management scenarios. The four land-use scenarios included: (a) the 2011 farmscape land-use composition and configuration, b) converting all existing live fences to post-and-wire fence lines in the farm c) converting simplified coffee agroforests to multistrata coffee agroforests in the farm, and d) placing multistrata live fences around the perimeter of every parcel and roads on the farm. Model results suggest that existing multistrata live fences maintain the sporadic movement of all five species irrespective of forest dependence. Likewise, adding multistrata live fences around individual fields presents a more efficient strategy for increasing species mobility than multistrata coffee agroforestry systems in the assessed farmscape, by doubling the passage areas available to all species, although it created labyrinths with "dead-ends" for two species. While retaining large habitat patches remains important for conservation, managing on-farm connectivity complements these efforts by increasing movement probability and reducing dispersal resistance for forest-dependent bird species.

Effects of supplemental methionine sources in finishing pig diets on growth performance, carcass characteristics, cutting yields, and meat quality.

Supplemental methionine (Met) is widely used within the swine industry; however, data are limited regarding the effect of Met sources on carcass cutability and meat quality. The objective was to determine the effects of L-Met (LM, 99%), DL-Met (DLM, 99%), or calcium salt of DL-Met hydroxyl analog (MHA, 84%) in finishing pig diets on carcass characteristics and meat quality. At 9 weeks of age, pigs (N = 240) were allocated to 60 single-sex pens for a four-phase finishing trial that lasted 104 d. Pigs were fed a common grower diet until day 56 where pens were randomly allotted to one of the three experimental diets. For the remaining 7 wk of the finisher phase, pigs (BW = 79.9 ±â€…0.80 kg) were fed diets containing LM, DLM, or MHA, with the supplemental Met source providing 25% of standardized ileal digestible (SID) Met + cysteine (Cys) requirement based on 65% bioefficacy for MHA in comparison with LM or DLM. One pig per pen was slaughtered at the study conclusion (on day 104), and the left sides of carcasses were fabricated into subprimal cuts to determine carcass-cutting yields. Loin quality including proximate composition and shear force were measured. Hot carcass weight was not different (P = 0.34) between treatments (LM 104.5 kg; DLM 103.0 kg; MHA 101.5 kg), moreover, loin eye area was not different (P = 0.98) between treatments (LM 52.65 cm²; DLM 52.49 cm²; MHA 52.81 cm²). Boneless carcass-cutting yield was not different (P = 0.56) between treatments (LM 54.97 kg; DLM 54.82 kg; MHA 54.52 kg). Loin pH was not different (P = 0.24) between treatments (LM 5.45; DLM 5.48; MHA 5.45). However, drip loss tended to be reduced (P = 0.11) by the DLM treatment (5.58%) compared with LM (7.03%) and MHA (6.68%) treatments. Shear force was not different (P = 0.85) between treatments (LM 3.03 kg; DLM 3.06 kg; MHA 3.10 kg). However, cook loss tended to be reduced (P = 0.06) by the DLM treatment (16.20%) compared with LM (18.18%) and MHA (18.50%) treatments. These data suggest that only minimal differences in carcass cutability and meat quality can be attributed to Met source in finishing pig diets when using 65% bioefficacy for MHA relative to L-Met or DL-Met.

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.

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.

Cytotoxic and antioxidant activities of selected Lamiales species from Mexico.

CONTEXT: Methanol extracts obtained from eight species belonging to four families of the Lamiales order native to Mexico were investigated for biological action. OBJECTIVE: Cytotoxicity and antioxidant activity of methanol extracts have been investigated. MATERIALS AND METHODS: Cytotoxic activity was evaluated by the sulphorhodamine B protein staining assay against KB (nasopharyngeal), HEp-2 (larynx), HF-6 (colon), MCF7 (breast), PC-3 (prostate), and Ca Ski (cervix) carcinoma cell lines. To analyze the antioxidant activity, common stable radicals chromogens, 2,2-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid (ABTS+) and DPPH (1,1-diphenyl-2-picrylhydrazyl) were used. The ferric reducing antioxidant power (FRAP) and the total phenolic content of the samples were also determined. RESULTS: Some of the extracts, such as Limosella aquatica L. (Scrophulariaceae), Mimulus glabratus Kunth. (Phrymaceae), Pedicularis mexicana Zucc. ex Benth. (Orobanchaceae), and Penstemon campanulatus (Cav.) Willd. (Plantaginaceae) displayed remarkably selective cytotoxic activity. However, the extract from Veronica americana (Raf.) Schwein (Plantaginaceae) showed the highest activity with IC50 values of 1.46 and 0.169 g/ µL on PC-3 and HF-6 cells, respectively. With the exception of M. glabratus, all the extracts showed different degrees of antioxidant activity with IC50 values from 0.89 up to 1.8 in the ABTS assay; from 0.49 up to 1.25 mg/mL in the DPPH assay and with the FRAP evaluation, 36 to 68 equivalents in mM of FeSO4. V. americana also showed the highest antoxidant activity with IC50 values from 0.491 and 0.892 mg/mL, on DPPH and ABTS assays, respectively. DISCUSSION AND CONCLUSION: These findings demonstrated that the species studied have great potential cytotoxic and antioxidant activity.

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.

State of the art and recommendations. Kangaroo mother care: application in a high-tech environment.

UNLABELLED: Since Kangaroo Mother Care (KMC) was developed in Colombia in the 1970s, two trends in clinical application emerged. In low income settings, the original KMC model is implemented. This consists of continuous (24 h/day, 7 days/week) and prolonged mother/parent-infant skin-to-skin contact; early discharge with the infant in the kangaroo position; (ideally) exclusive breastfeeding; and, adequate follow-up. In affluent settings, intermittent KMC with sessions of one or a few hours skin-to-skin contact for a limited period is common. As a result of the increasing evidence of the benefits of KMC for both infants and families in all intensive care settings, KMC in a high-tech environment was chosen as the topic for the first European Conference on KMC, and the clinical implementation of the KMC model in all types of settings was discussed at the 7th International Workshop on KMC. Kangaroo Mother Care protocols in high-tech Neonatal Intensive Care Units (NICU) should specify criteria for initiation, kangaroo position, transfer to/from KMC, transport in kangaroo position, kangaroo nutrition, parents' role, modification of the NICU environment, performance of care in KMC, and KMC in case of infant instability. CONCLUSION: Implementation of the original KMC method, with continuous skin-to-skin contact whenever possible, is recommended for application in high-tech environments, although scientific evaluation should continue.

Towards universal Kangaroo Mother Care: recommendations and report from the First European conference and Seventh International Workshop on Kangaroo Mother Care.

UNLABELLED: The hallmark of Kangaroo Mother Care (KMC) is the kangaroo position: the infant is cared for skin-to-skin vertically between the mother's breasts and below her clothes, 24 h/day, with father/substitute(s) participating as KMC providers. Intermittent KMC (for short periods once or a few times per day, for a variable number of days) is commonly employed in high-tech neonatal intensive care units. These two modalities should be regarded as a progressive adaptation of the mother-infant dyad, ideally towards continuous KMC, starting gradually and progressively with intermittent KMC. The other components in KMC are exclusive breastfeeding (ideally) and early discharge in kangaroo position with strict follow-up. Current evidence allows the following general statements about KMC in affluent and low-income settings: KMC enhances bonding and attachment; reduces maternal postpartum depression symptoms; enhances infant physiologic stability and reduces pain, increases parental sensitivity to infant cues; contributes to the establishment and longer duration of breastfeeding and has positive effects on infant development and infant/parent interaction. Therefore, intrapartum and postnatal care in all types of settings should adhere to a paradigm of nonseparation of infants and their mothers/families. Preterm/low-birth-weight infants should be regarded as extero-gestational foetuses needing skin-to-skin contact to promote maturation. CONCLUSION: Kangaroo Mother Care should begin as soon as possible after birth, be applied as continuous skin-to-skin contact to the extent that this is possible and appropriate and continue for as long as appropriate.

Vasoactive and antioxidant activities of plants used in Mexican traditional medicine for the treatment of cardiovascular diseases.

This study demonstrated that the aqueous extracts of plants employed in Mexican traditional medicine for the treatment of cardiovascular diseases are able to modify the tone of arterial smooth muscle. Agastache mexicana (Kunth) Lint & Epling (Labiatae), Chenopodium murale L. (Chenopodiaceae), Chirantodendron pentadactylon Larreat (Sterculiaceae), Dracocephalum moldavica L. (Labiatae), Psittacanthus calyculatus G. Don (Loranthaceae), Prunus serotina ssp. capuli (Cav. ex Spreng) McVaugh (Rosaceae), and Sechium edule Sw. (Cucurbitaceae) contain secondary metabolites that promote vascular relaxation and display antioxidant activities. As expected, their antioxidant effects showed a significant correlation with the polyphenolics content. However, a lower correlation was found between the antioxidant activity and the maximum vasodilatory effect, suggesting that the vasodilatation elicited by the plant extracts could be only partly attributed to their antioxidant properties. The extract of P. calyculatus, which displayed a maximum vasorelaxant effect that was higher than that of acetylcholine, induced endothelium-dependent vasodilatation. Futhermore, the vasorelaxant response to the P. calyculatus extract was reduced after adding an inhibitor of soluble guanylate cyclase activity, providing evidence that the NO/cGMP pathway is involved. On the other hand, the extracts of Bocconia frutescens L. (Papaveraceae), Magnolia grandiflora L. (Magnoliaceae), and Solanum rostratum Dunal (Solanaceae) induced concentration-dependent contraction of rat aortic rings, suggesting that these plants have potential health benefits for the treatment of ailments such as venous insufficiency. The pharmacological activities of the extracts studied provide scientific support for their ethnomedical use.

State of the art and recommendations. Kangaroo mother care: application in a high-tech environment.

UNLABELLED: Since Kangaroo Mother Care (KMC) was developed in Colombia in the 1970s, two trends in clinical application emerged. In low-income settings, the original KMC modelis implemented. This consists of continuous (24 h/day; 7 days/week) and prolonged mother/parent-infant skin-to-skin contact; early discharge with the infant in the kangaroo position; (ideally) exclusive breastfeeding and, adequate follow up. In affluent settings, intermittent KMC with sessions of one or a few hours skin-to-skin contact for a limited period is common. As a result of the increasing evidence of the benefits of KMC for both infants and families in all intensive care settings, KMC in a high-tech environment was chosen as the topic for the first European Conference on KMC, and the clinical implementation of the KMC modelin all types of settings was discussed at the 7th International Workshop on KMC Kangaroo Mother Care protocols in high-tech Neonatal Intensive Care Units (NICU) should specify criteria for initiation, kangaroo position, transfer to/from KMC, transport in kangaroo position, kangaroo nutrition, parents'role, modification of the NICU environment, performance of care in KMC, and KMCin case of infant instability. CONCLUSION: Implementation of the original KMC method, with continuous skin-to-skin contact whenever possible, is recommended for application in high-tech environments, although scientific evaluation should continue.