The impact of prenatal environment on postnatal life and performance: Future perspectives for prevention and treatment.

The present review aims to offer a non-comprehensive outline of the current state-of-the-art and future perspectives on management and therapeutic tools for intrauterine growth restriction (IUGR) and associated prenatal programming in both human and animal species. Animals are used as models for the study of phenomena related to IUGR, but also for research on prenatal therapies with the main objective of designing and developing preventive and therapeutic strategies. The research is currently paying attention on maternal-focused pharmacological treatments and nutritional strategies but also on fetal-focused treatments. Fetal-focused treatments, administered either directly at the fetus or by using infusion of umbilical cord, amniotic sac or placenta, which avoids the administration of substances at high doses to the mother for allowing their availability at the fetoplacental level. The results obtained in this area of research using large animals (rabbits, pigs and ruminants) have a dual interest, for translational biomedicine and for veterinary medicine and animal production.

Efficiency and demographics of a high-yield dairy ewe farm with two managing systems involving five or 10 lambings per year.

This study assessed milk productivity, demographic characteristics and workload distribution on a single high-yield dairy ewe farm in Spain (Avila, Spain; continental climate, latitude of 40.90 N, altitude of 900 m) over a 7-year period considering a transition from a herd management system involving five lambings per year (5LY) to a system involving 10 lambings per year (10LY). The 5LY system was practiced on the farm from 2010 to 2012 and the 10LY system from 2014 to 2015, with 2009 and 2013 being considered transition years. During this period, 27 415 lactations were recorded from an average of 3746 Lacaune sheep/year. Several productivity parameters were higher in 2014 to 2015 than in 2010 to 2012: milk yield/lactation (370±156 v. 349±185 l), lactation length (218±75 v. 192±75 days) and dry period length (53.5±38.3 v. 69.1±34.8 days) (all P<0.0001). During 2014 to 2015, investment in new lambing facilities was possible, workload was distributed more uniformly throughout the year, workload per worker was smaller, rate of ewe culling was lower (35.39±0.53% v. 42.51±7.51%), ewe longevity was greater and higher-order lactations were more numerous (P<0.0001). On the other hand, during 2010 to 2012, daily production was higher (1.73±1.66 v. 1.70±0.62 l/day; P=0.038), the interlambing period was shorter (283±50 v. 302±44 days; P<0.0001) and lambings/ewe per year were greater (1.42±0.01 v. 1.30±0.01; P<0.05). These results suggest that a 10LY herd management system can be compatible with profitability, productivity and good animal and worker's welfare on a high-yield dairy farm, and may even be associated with better outcomes than a 5LY system.

Bright nanowire single photon source based on SiV centers in diamond.

The practical implementation of many quantum technologies relies on the development of robust and bright single photon sources that operate at room temperature. The negatively charged silicon-vacancy (SiV-) color center in diamond is a possible candidate for such a single photon source. However, due to the high refraction index mismatch to air, color centers in diamond typically exhibit low photon out-coupling. An additional shortcoming is due to the random localization of native defects in the diamond sample. Here we demonstrate deterministic implantation of Si ions with high conversion efficiency to single SiV- centers, targeted to fabricated nanowires. The co-localization of single SiV- centers with the nanostructures yields a ten times higher light coupling efficiency than for single SiV- centers in bulk diamond. This enhanced photon out-coupling, together with the intrinsic scalability of the SiV- creation method, enables a new class of devices for integrated photonics and quantum science.

Influence of practitioner expertise during early pregnancy diagnosis on pregnancy loss rate: A controlled, blinded trial.

A controlled field trial was conducted to assess the potential influence of practitioner inexperience during early pregnancy diagnosis with ultrasound (PD-US) on the risk of pregnancy loss. A veterinarian with more than 10 years' experience in PD-US (Vet-A) and a veterinarian with fewer than 12 months' experience at the start of the study (Vet-B) visited the same dairy farm once a week for 33 and 26 weeks, respectively. The two veterinarians did not interact with each other at any time during the study, nor did they know that their data would later be used in this study. Using the same farm scanner, they performed PD-US at 28-34 day after breeding, together diagnosing 915 pregnancies. All cows were re-checked at 49-56 day after artificial insemination, and cows no longer pregnant were recorded as having suffered pregnancy loss. Although Vet-A and Vet-B diagnosed a similar proportion of pregnancies (58.44 ± 16% vs 56.96 ± 18%, p > .05), the rate of pregnancy loss was significantly higher among cows diagnosed by Vet-B (10.41 ± 11.2% vs 4.87 ± 9.0, p = .029). In addition, among cows diagnosed by Vet-B, the rate of pregnancy loss was significantly higher among cows diagnosed, while he had fewer than 12 months' PD-US experience (11.17 ± 12.14%) than among cows that he diagnosed later (7.14 ± 11.01%, p = .038); in fact, this latter loss rate was comparable to that among cows diagnosed by Vet-A during the same period (3.51 ± 9.83%, p = .620). These results suggest that inexperience with PD-US during the late embryonic period can increase risk of early pregnancy loss, supporting the need for proper training.

Development of subcutaneous fat in Spanish and Latin American children and adolescents: Reference values for biceps, triceps, subscapular and suprailiac skinfolds.

Subcutaneous fat skinfolds represent a reliable assessment instrument of adiposity status. This study provides current percentile references for four subcutaneous skinfolds (biceps, triceps, subscapular, suprailiac) applicable to children and adolescents in Spain and in Latin American countries where data are scarce. The design consisted of a cross-sectional multicenter study performed with identical methods in 5 countries (Argentina, Cuba, Mexico, Spain and Venezuela). Total sample comprised 9163 children and youths (boys 4615 - girls 4548) aged 6-18 years, healthy and without apparent pathologies. Percentiles 3, 5, 10, 25, 50, 75, 90, 95 and 97 were calculated by the LMS method. Sexual dimorphism was assessed using the t-test and age differences with ANOVA. Normalized growth percentile references were obtained according to sex and age for each skinfold. The mean values of four skinfolds were significantly greater in girls than boys (p<0.001) and, in both sexes, all skinfolds show statistical differences through age (p<0.001) with different magnitudes. Except triceps in girls, peaks between 11 and 12 years of age are more noticeable in boys than in girls. Although the general model of growth is known, the skinfold measurements show variability among populations and differences of magnitude are presented according to the analyzed population. Therefore, these age and sex-specific reference percentile values for biceps, triceps, subscapular and suprailiac skinfolds, derived from a large sample of Spanish and Latin American children and adolescents, are a useful tool for adiposity diagnosis in this population for which no reference values were available.

Early postpartum administration of equine chorionic gonadotropin to dairy cows calved during the hot season: Effects on fertility after first artificial insemination.

Heat stress reduces fertility of high-producing dairy cows, and early administration of equine chorionic gonadotropin (eCG) may improve it. Here, 401 heat-stressed, high-producing dairy cows on a single commercial farm were given eCG (500 UI, n = 214) or saline (n = 187) on days 11-17 after calving, and the effects on fertility after the first artificial insemination (AI) were assessed. On post-partum day 96.34 ± 9.88, all cows were inseminated after a "double short Cosynch" synchronization protocol. Ovarian activity and uterine status were checked by ultrasound on the day of eCG administration and every 7 days thereafter for a total of 3 weeks; checks were also performed during synchronization, and 7 days after AI. On post-partum day 30, cytobrush uterine cytology was performed to check for subclinical endometritis. Pregnancy status was checked on days 30 and 60 after AI. The eCG and control groups did not differ significantly in terms of average lactations per cow (2.33 ± 1.34), days in milk at first AI (96.33 ± 9.88), average milk yield at AI (41.38 ± 7.74 L), or the particular inseminator or bull used for AI. The eCG and control groups showed increasing ovarian activity with time, with approximately 75% of cows in both groups showing a corpus luteum at the beginning of the synchronization protocol. On post-partum day 30, 17.4% of eCG cows and 22.9% of control cows showed subclinical endometritis. Cows treated with eCG showed a tendency toward lower hyperecogenic intraluminal content (16.8 vs. 21.4%, P = 0.15), but ovarian activity during the synchronization protocol was similar between eCG and control groups, with 91% of animals in both groups showing luteolysis after prostaglandin application and 88% showing ovulation after the last administration of gonadotropin-releasing hormone. Fertility was similar between the two groups at both time points after AI (30 days, 34.9 vs. 31.8%; 60 days, 30.6 vs. 28.5%; P > 0.2). These results suggest that early postpartum eCG administration does not improve fertility of heat-stressed dairy cows as long as 60 days after AI. Other strategies may be more effective at mitigating the ability of post-partum heat stress to reduce fertility of high-producing dairy cows.

Ion implantation for deterministic single atom devices.

We demonstrate a capability of deterministic doping at the single atom level using a combination of direct write focused ion beam and solid-state ion detectors. The focused ion beam system can position a single ion to within 35 nm of a targeted location and the detection system is sensitive to single low energy heavy ions. This platform can be used to deterministically fabricate single atom devices in materials where the nanostructure and ion detectors can be integrated, including donor-based qubits in Si and color centers in diamond.

An integrated diamond nanophotonics platform for quantum-optical networks.

Efficient interfaces between photons and quantum emitters form the basis for quantum networks and enable optical nonlinearities at the single-photon level. We demonstrate an integrated platform for scalable quantum nanophotonics based on silicon-vacancy (SiV) color centers coupled to diamond nanodevices. By placing SiV centers inside diamond photonic crystal cavities, we realize a quantum-optical switch controlled by a single color center. We control the switch using SiV metastable states and observe optical switching at the single-photon level. Raman transitions are used to realize a single-photon source with a tunable frequency and bandwidth in a diamond waveguide. By measuring intensity correlations of indistinguishable Raman photons emitted into a single waveguide, we observe a quantum interference effect resulting from the superradiant emission of two entangled SiV centers.

iCarer: AAL for the Informal Carers of the Elderly.

In the context of the long-term care for older adults, informal carers play a key role. Daily competing priorities or a care-skills deficit may lead them to stress, anxiety and/or depression. The iCarer project (AAL-2012-5-239) proposes the design and implementation of a cloud-inspired personalised and adaptive platform which will offer support to informal carers of older adults with cognitive impairment. By means of a holistic approach comprising technologies and services addressing the intelligent and interactive monitoring of activities, knowledge management for personalised guidance and orientation, virtual interaction, e-learning, care coordination facilities and social network services, iCarer aims to reduce the informal carer stress and to enhance the quality of care they provide, thus improving their quality of life. The iCarer platform will be evaluated through a multi-centre non-controlled study (4 months; 48 homes located in England and in Slovenia). Currently the iCarer project is completing the development work. The evaluation trial is expected to start in August 2015.

A reliable method to quantify sildenafil and its metabolite N-demethylsildenafil by HPLC in plasma of children.

The aim of this study was to develop a simple method for quantifying plasma levels of sildenafil and its metabolite by liquid chromatography with a C18 reverse-phase column and UV detection. For both compounds, linearity was assessed in the range from 10 and 1 000 ng · ml-1 and had correlation coefficients of r=0.995 and r=0.997 for sildenafil and its metabolite, respectively. The inter- and intra-day coefficients of variation was<5.3%. The limits of detection and quantification were 1 and 10 ng · ml-1. Drug levels were determined satisfactorily in two patients. A simple and reliable method was developed for use in children with Pulmonary Arterial Hypertension under treatment with sildenafil.

Broncoscopia pediátrica: de dónde venimos, hacia dónde vamos / Paediatric bronchoscopy: from where we came from, to where we are going

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Antenatal and postnatal management of congenital cystic adenomatoid malformation.

Congenital thoracic malformations (CTMs) are a heterogeneous group of rare disorders that may involve the airways or lung parenchyma. The authors have focused on the condition that causes the most controversy, namely, congenital cystic adenomatoid malformation (CCAM). The reported incidence is 3.5 and 0.94 per 10,000 live births for CTMs and CCAMs respectively. Ultrasound is the antenatal imaging modality of choice for screening for CCAMs whilst magnetic resonance imaging is complimentary for morphological and volumetric evaluation of the foetal lung. Most CCAMs are detected antenatally with only a small proportion presenting postnatally. Only a few CCAMs cause foetal problems, with foetal hydrops being the best predictor of death. Although many CCAMs regress during pregnancy, most remain detectable postnatally by CT scans. Surgical excision of symptomatic lesions is relatively straightforward, but management of asymptomatic lesions is controversial. Some surgeons adopt a "wait and see" approach operating only on those patients who develop symptoms, but others operate on asymptomatic patients usually within the first year of life. Due to the potential of malignant transformation, children should have long term follow up. There is an urgent need to delineate the natural history of antenatally detected CCAMs to guide future management.

Congenital diaphragmatic hernia.

Infants with congenital diaphragmatic hernia (CDH) have significant mortality and long-term morbidity. Only 60-70% survive and usually those in high-volume centres. The current Task Force, therefore, has convened experts to evaluate the current literature and make recommendations on both the antenatal and post-natal management of CDH. The incidence of CDH varies from 1.7 to 5.7 per 10,000 live-born infants depending on the study population. Antenatal ultrasound scanning is routine and increasingly complemented by the use of magnetic resonance imaging. For isolated CDH, antenatal interventions should be considered, but the techniques need vigorous evaluation. After birth, management protocols are often used and have improved outcome in nonrandomised studies, but immediate intubation at birth and gentle ventilation are important. Pulmonary hypertension is common and its optimal management is crucial as its severity predicts the outcome. Usually, surgery is delayed to allow optimal medical stabilisation. The role of minimal invasive post-natal surgery remains to be further defined. There are differences in opinion about whether extracorporeal membrane oxygenation improves outcome. Survivors of CDH can have a high incidence of comorbidities; thus, multidisciplinary follow-up is recommended. Multicentre international trials are necessary to optimise the antenatal and post-natal management of CDH patients.

Molecular and catalytic properties of the aldehyde dehydrogenase of Gluconacetobacter diazotrophicus, a quinoheme protein containing pyrroloquinoline quinone, cytochrome b, and cytochrome c.

Several aldehyde dehydrogenase (ALDH) complexes have been purified from the membranes of acetic acid bacteria. The enzyme structures and the chemical nature of the prosthetic groups associated with these enzymes remain a matter of debate. We report here on the molecular and catalytic properties of the membrane-bound ALDH complex of the diazotrophic bacterium Gluconacetobacter diazotrophicus. The purified ALDH complex is a heterodimer comprising two subunits of 79.7 and 50 kDa, respectively. Reversed-phase high-pressure liquid chromatography (HPLC) and electron paramagnetic resonance spectroscopy led us to demonstrate, for the first time, the unequivocal presence of a pyrroloquinoline quinone prosthetic group associated with an ALDH complex from acetic acid bacteria. In addition, heme b was detected by UV-visible light (UV-Vis) spectroscopy and confirmed by reversed-phase HPLC. The smaller subunit bears three cytochromes c. Aliphatic aldehydes, but not formaldehyde, were suitable substrates. Using ferricyanide as an electron acceptor, the enzyme showed an optimum pH of 3.5 that shifted to pH 7.0 when phenazine methosulfate plus 2,6-dichlorophenolindophenol were the electron acceptors. Acetaldehyde did not reduce measurable levels of the cytochrome b and c centers; however, the dithionite-reduced hemes were conveniently oxidized by ubiquinone-1; this finding suggests that cytochrome b and the cytochromes c constitute an intramolecular redox sequence that delivers electrons to the membrane ubiquinone.

The quinohaemoprotein alcohol dehydrogenase from Gluconacetobacter xylinus: molecular and catalytic properties.

Gluconacetobacter xylinus possesses a constitutive membrane-bound oxidase system for the use of ethanol. Its alcohol dehydrogenase complex (ADH) was purified to homogeneity and characterized. It is a 119-kDa heterodimer (68 and 41 kDa subunits). The peroxidase reaction confirmed the presence of haem C in both subunits. Four cytochromes c per enzyme were determined by pyridine hemochrome spectroscopy. Redox titrations of the purified ADH revealed the presence of four haem c redox centers, with apparent mid-point potential values (Em(7)) of -33, +55, +132 and +310 mV, respectively. The ADH complex contains one mol of pyrroloquinoline quinone as determined by HPLC. The enzyme was purified in full reduced state; oxidation was induced by potassium ferricyanide and substrate restores full reduction. Activity responses to pH were sharp, showing two distinct optimal pH values (i.e. pH 5.5 and 6.5) depending on the electron acceptor used. Purified ADH oxidizes primary alcohols (C2-C6) but not methanol. Noteworthy, aliphatic aldehydes (C1-C4) were also good substrates. Myxothiazol and antymicin A were powerful inhibitors of the purified ADH complex, most likely acting at the ubiquinone acceptor site in subunit II.

The management of tracheobronchial obstruction in children.

Tracheobronchial obstruction is very uncommon in children and small infants. Stenosis and malacia, either congenital or acquired, are probably the most frequent diagnosis in this setting. Clinical symptoms are common to both airway anomalies and bronchoscopy plays a crucial role in the diagnostic work-up. Management is complex and surgeons involved in it should be familiar with multiple surgical and endoscopical techniques. Symptomatic short tracheal stenosis are best treated by means of resection and reconstruction, although endoscopic dilation or laser resection can be tried first in selected cases. In long tracheal stenosis, slide tracheoplasty is the surgical procedure of choice. Tracheobronchial malacia is usually self-limiting by the age of 3 years and most cases show mild symptoms that can be treated conservatively. In a small group of patients airway compromise is severe enough to require surgical or endoscopical treatment. Aortopexy or tracheostomy are the classic treatments for congenital tracheomalacia, but increasing experience with endoscopic airway stent placement in children is making this technique more attractive and popular. Acquired tracheomalacia is usually caused by a long-standing tracheostomy and if decannulation is impaired surgical treatment is mandatory.

Surgical management of severe suprastomal cricotracheal collapse complicating pediatric tracheostomy.

OBJECTIVE: Suprastomal tracheal collapse may interfere with decannulation in tracheostomized patients. The purposes of the study are to evaluate the role of tracheotomy technique in the ethiology of suprastomal cricotracheal collapse and to report our results in the treatment of this complication. METHODS: A retrospective review of children showing severe suprastomal collapse during the period 1990-2007, in a tertiary care children's hospital, was performed. Medical records were assessed for the following data: sex, age, original indication for tracheotomy, surgical technique, endoscopic findings, type of surgical correction, complications, result, and follow-up. RESULTS: Fourteen patients were included in the study, nine girls and five boys. Average age at tracheotomy was 17 months (range: 21 days-8 years), and prolonged ventilatory support was the most common indication (57%). Horizontal H-type tracheotomy was the most frequent technique in patients with suprastomal collapse (n=9), whereas only one patient with a vertical tracheotomy showed this complication (p<0.05). In every case bronchoscopy disclosed a suprastomal tracheal obstruction of at least 50% of the lumen. Mean age at surgical decannulation was 38 months (range: 12-147 months). Two surgical techniques have been used in the treatment of suprastomal collapse: anterior cricotracheal suspension (n=13) and reconstruction with autologous cartilage graft (n=1). All the patients were successfully decannulated although in one case two procedures were required. No recurrence has been observed during long-term follow-up (mean: 8.6 years). CONCLUSIONS: Endoscopical examination is essential for the diagnosis of suprastomal collapse and to rule out other causes of decannulation failure. In our experience, the tracheotomy technique seems to have an ethiologic role, and anterior cricotracheal suspension is a simple and effective procedure in the treatment of this tracheostomy related complication.

[Surgical decannulation of children with suprastomal collapse: review of our experience]. / Decanulación quirúrgica en el tratamiento del colapso traqueal supraestomal: revisión de nuestra experiencia.

BACKGROUND: Suprastomal tracheal collapse (STC) may interfere with decannulation in tracheostomized patients. AIM: To evaluate the role of tracheotomy technique in the ethiology of STC, and to analyze our results in the treatment of this complication. PATIENTS AND METHODS: We have studied the clinical charts of tracheostomized patients in our Unit, between 1990 and 2006, who showed significant STC impairing decannulation. The following data have been taken into account: sex, age, tracheotomy indication, surgical technique, endoscopic findings, type of surgical correction, complications, result, and follow-up. RESULTS: Thirteen patients have showed STC, nine girls and four boys. Average age when tracheotomy was performed was 18 months, and extended ventilatory support was the most common indication (61,5%). Tracheotomy with lateral flaps was the most frequent technique in this group of patients with STC (8 cases), whereas only one patient in whom an anterior vertical tracheal incision was performed showed this complication. In every case bronchoscopy disclosed a suprastomal tracheal obstruction of at least 50% of the lumen. Mean age when surgical decannulation was performed was 36 months (range, 12-147). Two surgical techniques have been used in the treatment of STC: anterior cricoid suspension (12 patients) and reconstruction with autologous cartilage graft (one case). A satisfactory result has been achieved in 92% of cases (one patient showed persistent collapse and the same procedure was repeated). Mean follow-is 8,6 years (range, 2 months-12 years). CONCLUSIONS: STC is a type of acquired tracheomalacia and presents in around 10% of tracheostomized patients. Bronchoscopy is essential for diagnosis and to rule out other causes of failure in decannulation. Tracheotomy technique seems to have an ethiologic role, and our preferred treatment, when sufficient cartilaginous support is present, is anterior cricoid suspension.

[Management of congenital tracheomalacia: a single institution experience]. / Traqueomalacia congénita: análisis de nuestra serie.

INTRODUCTION: Congenital tracheomalacia (CTM) is a rare disease causing tracheal wall collapse when breathing. Herein, we show our experience in the management of this type of airway anomaly, settling the indications for surgical or endoscopic treatment. PATIENTS AND METHODS: We have performed a retrospective study, from 1991 to 2003, of patients with a bronchoscopic diagnosis of CTM or bronchomalacia (BM). We have analyzed the following facts: sex, age, indication of the initial bronchoscopy, ethiology, clinical group, anatomic type, associated malformations, treatment modality, complications, results, and time of follow-up. RESULTS: 46 patients have been included in this study: 25 boys (54%) and 21 girls (45%). Mean age at diagnosis has been 11 months. The indications for diagnostic bronchoscopy have been: respiratory distress (24%), lung athelectasia (24%), stridor (21%), congenital tracheoesophageal fistula (11%), extubation failure (11%), apneic spells (6%), and recurrent pneumonia (2%). Secondary CTM has been much more frequent (82%) than the primary type (17%). Patients have been classified into 3 groups according to the severity of symptoms: group I--mild symptoms (7 patients); group II---moderate (22); and group III, severe (17). Tracheomalacia was diagnosed in 26 cases (56%), bronchomalacia in 12 (26%) and tracheobronchomalacia in 8 patients (17%). Almost all the patients (95%) have showed other associated malformations. Medical treatment has been instituted in 29 patients (63%), 15 cases (32%) have been managed surgically or endoscopically, and in 2 cases no treatment was tried because of their critical clinical status. In addition, in 17 patients (37%) an antireflux surgical procedure was performed. Satisfactory results have been achieved in 72% of treated patients, fair results were obtained in 4 (9%), and a poor outcome occurred in 2 (4,5%). Another 8 patients have died during follow-up due to unrelated causes. 36 patients (78%) are alive with a mean follow-up period of 5,3 years. CONCLUSIONS: Most patients with CTM can he treated conservatively though spontaneous resolution may he expected after the first year of life. Surgical or endoscopical procedures are indicated in those patients with severe respiratory symptoms.