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Abstract Background Surfactant is a well-established therapy for preterm neonates affected by respiratory distress syndrome (RDS). The goals of different methods of surfactant administration are to reduce the duration of mechanical ventilation and the severity of bronchopulmonary dysplasia (BPD); however, the optimal administration method remains unknown. This study compares the effectiveness of the INtubate-RECruit-SURfactant-Extubate (IN-REC-SUR-E) technique with the less-invasive surfactant administration (LISA) technique, in increasing BPD-free survival of preterm infants. This is an international unblinded multicenter randomized controlled study in which preterm infants will be randomized into two groups to receive IN-REC-SUR-E or LISA surfactant administration. Methods In this study, 382 infants born at 24+0–27+6 weeks’ gestation, not intubated in the delivery room and failing nasal continuous positive airway pressure (nCPAP) or nasal intermittent positive pressure ventilation (NIPPV) during the first 24 h of life, will be randomized 1:1 to receive IN-REC-SUR-E or LISA surfactant administration. The primary outcome is a composite outcome of death or BPD at 36 weeks’ postmenstrual age. The secondary outcomes are BPD at 36 weeks’ postmenstrual age; death; pulse oximetry/fraction of inspired oxygen; severe intraventricular hemorrhage; pneumothorax; duration of respiratory support and oxygen therapy; pulmonary hemorrhage; patent ductus arteriosus undergoing treatment; percentage of infants receiving more doses of surfactant; periventricular leukomalacia, severe retinopathy of prematurity, necrotizing enterocolitis, sepsis; total in-hospital stay; systemic postnatal steroids; neurodevelopmental outcomes; and respiratory function testing at 24 months of age. Randomization will be centrally provided using both stratification and permuted blocks with random block sizes and block order. Stratification factors will include center and gestational age (24+0 to 25+6 weeks or 26+0 to 27+6 weeks). Analyses will be conducted in both intention-to-treat and per-protocol populations, utilizing a log-binomial regression model that corrects for stratification factors to estimate the adjusted relative risk (RR). Discussion This trial is designed to provide robust data on the best method of surfactant administration in spontaneously breathing preterm infants born at 24+0–27+6 weeks’ gestation affected by RDS and failing nCPAP or NIPPV during the first 24 h of life, comparing IN-REC-SUR-E to LISA technique, in increasing BPD-free survival at 36 weeks’ postmenstrual age of life. Trial registration ClinicalTrials.gov NCT05711966. Registered on February 3, 2023.

BackgroundHypoxic-ischemic encephalopathy (HIE) represents one of the major causes of neonatal death and long-term neurological disability. Both hypoxic-ischemic insults and therapeutic hypothermia (TH) can affect respiratory function. Currently, there is no evidence regarding optimal respiratory management in these infants.MethodsThis is a retrospective cohort study examining newborns with HIE treated with TH between January 2015 and September 2020. The study population was divided into two groups based on different respiratory assistance during TH: spontaneous breathing (Group A) or mechanical ventilation (Group B). The primary outcome of the study was the mean pCO2 ± SD evaluation during TH in ventilated and non-ventilated asphyxiated infants. The secondary outcome was the correlation between ventilation strategy and short-term neurologic outcome according to Rutherford et al.'s MRI scoring system.ResultsA total of 126 newborns were enrolled, 75 in Group A and 51 in Group B. Respiratory management was individualized, and volume guarantee (VG) ventilation was the first choice for ventilated infants. Group B infants showed more severe conditions at birth. During TH, ventilated infants showed optimal mean pCO2 comparable with those breathing spontaneously (40.6 mmHg vs. 42.3 mmHg, respectively, p 0.091), with no significant difference in pCO2 standard deviation between (7.7 mmHg vs. 8.1 mmHg, respectively, p 0.522). Mean pH, pH standard deviation, mean pO2, pO2 standard deviation, and mean respiratory rate also did not differ between groups. MRI patterns of brain injury predictive of abnormal neurodevelopmental outcomes were similar in both groups. Logistic regression analysis demonstrated that only umbilical cord arterial blood pH-affected MRI lesions were associated with poor neurodevelopmental outcomes (OR 1.505; CI 95% 1.069–2.117).ConclusionsInfants cooled after HIE should receive individualized respiratory management, not necessarily involving intubation. In those infants requiring mechanical ventilation, a volume-targeted strategy appeared to be effective in maintaining stable blood gas levels. Short-term neurological outcomes appeared comparable in ventilated and non-ventilated infants.

This retrospective study used data obtained from medical records of 530 stranded free-ranging harbor (Phoca vitulina), grey (Halichoerus grypus), harp (Pagophilus groenlandicus), and hooded seals (Cystophora cristata) presented to the Marine Mammal Stranding Center in Brigantine, New Jersey from January 1998 through December 2016. The objective was to identify hematological and plasma biochemical parameters of seals at time of presentation that were associated with successful rehabilitation and with duration of hospitalization using univariate and multivariate logistic regressions. At presentation, animals that subsequently survived rehabilitation had greater alkaline phosphatase activity and absolute lymphocyte and total calcium concentrations and lower blood urea nitrogen, sodium, chloride, phosphorus, and total bilirubin concentrations and lower aspartate aminotransferase and alanine aminotransferase activities than animals that eventually died or were euthanized while under care. Results suggest that young, actively growing animals are more likely to survive rehabilitation and that bloodwork consistent with dehydration, systemic disease, and exhaustion are negative prognostic indicators. These results provide prognostic indicators that may aid clinical decision-making for seals presented for rehabilitation.

In 2007, the University of British Columbia (UBC) was the first university in Canada to establish and adopt global access (GA) principles. Toward implementing these principles, UBC then identified a set of strategies for providing affordable access to new UBC-developed technologies throughout low- and middle-income countries and among vulnerable populations. In this perspective, we provide an update of UBC’s progress over the past 15 years made on several technologies that fall under the GA principles. The technologies reported on are wide-ranging, including an oral medication for the treatment of leishmaniasis; peptides for potential use against malaria, and various bacterial, viral and fungal infections; a portable vaccine cooler; a diagnostic technology to detect severe sepsis; and an SMS Messaging System to monitor and support patients with HIV, TB and COVID-19. We identify challenges faced by the researchers in implementing the GA principles for these technologies and potential solutions for overcoming them through creative licensing and partnerships with public and private sectors, governments, local companies, and communities. As the UBC example illustrates, universities across the globe have an opportunity to make a significant social impact on improving global health of vulnerable populations and on supporting local infrastructures for sustaining these improvements.

Objective: To compare obstetrical and neonatal outcomes in patients with p-PROM (preterm premature rupture of membranes) at less than 30 weeks of gestational age before and after the application of protocols developed on the basis of international guidelines and to identify local barriers and strategies for their implementation. Study design: Single and twin pregnancies with p-PROM

Surface biotinylation, proximity ligation assays and proteomics are used to identify surface markers of prostate-derived small extracellular vesicles.

Abstract This retrospective study used data obtained from medical records of 530 stranded free-ranging harbor (Phoca vitulina), grey (Halichoerus grypus), harp (Pagophilus groenlandicus), and hooded seals (Cystophora cristata) presented to the Marine Mammal Stranding Center in Brigantine, New Jersey from January 1998 through December 2016. The objective was to identify hematological and plasma biochemical parameters of seals at time of presentation that were associated with successful rehabilitation and with duration of hospitalization using univariate and multivariate logistic regressions. At presentation, animals that subsequently survived rehabilitation had greater alkaline phosphatase activity and absolute lymphocyte and total calcium concentrations and lower blood urea nitrogen, sodium, chloride, phosphorus, and total bilirubin concentrations and lower aspartate aminotransferase and alanine aminotransferase activities than animals that eventually died or were euthanized while under care. Results suggest that young, actively growing animals are more likely to survive rehabilitation and that bloodwork consistent with dehydration, systemic disease, and exhaustion are negative prognostic indicators. These results provide prognostic indicators that may aid clinical decision-making for seals presented for rehabilitation.

ABSTRACT: Objectives: The World Health Organization recommends mass drug administration (MDA) with azithromycin to eliminate trachoma as a public health problem. MDA decisions are based on prevalence estimates from two-stage cluster surveys. There is a need to mathematically evaluate current trachoma survey designs. Our study aimed to characterize the effects of the number of units sampled on the precision and cost of trachomatous inflammation–follicular (TF) estimates. Methods: A population of 30 districts was simulated to represent the breadth of possible TF distributions in Amhara, Ethiopia. Samples of varying numbers of clusters (14–34) and households (10–60) were selected. Sampling schemes were evaluated based on precision, proportion of incorrect and low MDA decisions made, and estimated cost. Results: The number of clusters sampled had a greater impact on precision than the number of households. The most efficient scheme depended on the underlying TF prevalence in a district. For lower prevalence areas (< 10%) the most cost-efficient design (providing adequate precision while minimizing cost) was 20 clusters of 20–30 households. For higher prevalence areas (> 10%), the most efficient design was 15–20 clusters of 20–30 households. Conclusions: For longer-running programs, using context-specific survey designs would allow for practical precision while reducing survey costs. Sampling 15 clusters of 20–30 households in suspected moderate-to-high prevalence districts and 20 clusters of 20–30 households in districts suspected to be near the 5% threshold appears to be a balanced approach.

This study explores the application of computer vision for enhancing the selection of rootstock-graft combinations and detecting diseases in grape seedlings. Computer vision has various applications in viticulture, but publications and research have not reported the use of computer vision in rootstock-graft selection, which defines the novelty of this research. This paper presents elements of the technology for applying computer vision to rootstock-graft combinations and includes an analysis of grape seedling cuttings. This analysis allows for a more accurate determination of the compatibility between rootstock and graft, as well as the detection of potential seedling diseases. The utilization of computer vision to automate the grafting process of grape cuttings offers significant benefits in terms of increased efficiency, improved quality, and reduced costs. This technology can replace manual labor and ensure economic efficiency and reliability, among other advantages. It also facilitates monitoring the development of seedlings to determine the appropriate planting time. Image processing algorithms play a vital role in automatically determining seedling characteristics such as trunk diameter and the presence of any damage. Furthermore, computer vision can aid in the identification of diseases and defects in seedlings, which is crucial for assessing their overall quality. The automation of these processes offers several advantages, including increased efficiency, improved quality, and reduced costs through the reduction of manual labor and waste. To fulfill these objectives, a unique robotic assembly line is planned for the grafting of grape cuttings. This line will be equipped with two conveyor belts, a delta robot, and a computer vision system. The use of computer vision in automating the grafting process for grape cuttings offers significant benefits in terms of efficiency, quality improvement, and cost reduction. By incorporating image processing algorithms and advanced robotics, this technology has the potential to revolutionize the viticulture industry. Thanks to training a computer vision system to analyze data on rootstock and graft grape varieties, it is possible to reduce the number of defects by half. The implementation of a semi-automated computer vision system can improve crossbreeding efficiency by 90%. Reducing the time spent on pairing selection is also a significant advantage. While manual selection takes between 1 and 2 min, reducing the time to 30 s using the semi-automated system, and the prospect of further automation reducing the time to 10–15 s, will significantly increase the productivity and efficiency of the process. In addition to the aforementioned benefits, the integration of computer vision technology in grape grafting processes brings several other advantages. One notable advantage is the increased accuracy and precision in pairing selection. Computer vision algorithms can analyze a wide range of factors, including size, shape, color, and structural characteristics, to make more informed decisions when matching rootstock and graft varieties. This can lead to better compatibility and improved overall grafting success rates.

Sleep disorders are particularly important in the development of children, affecting the emotional, behavioural, and cognitive spheres. The incidence of these disorders has been assessed in different types of populations, including patients with a history of premature birth, who, from the literature data, would seem to have an increased incidence of sleep disorders at school age. The aims of the present study are: (i.) to assess the presence of sleep disorders in a population of very preterm infants at 6–36 months who are at low risk of neurological impairments using the Italian version of the Sleep Disturbance Scale for Children (SDSC) adapted for this age group, and (ii.) to identify possible differences from a control group of term-born infants. A total of 217 low-risk preterm and 129 typically developing infants and toddlers were included in the study. We found no differences in the SDSC total and the factor scores between these two populations of infants. Low-risk preterm infants and toddlers showed similar incidences of sleep disorders to their term-born peers. Further clinical assessments will be needed to confirm these data at school age.

To improve our ability to monitor cellular responses to e.g. cytokines or drugs, Lönn et al have developed a semi-automated system for large-scale in situ proximity ligation assays (isPLA) in HaCAT keratinocyte cells. Their approach expands the scope for image-based single cell analyses by combining observations of protein interactions and modifications with morphological details of individual cells at high throughput.

Abstract Glioblastoma (GBM) is a brain malignancy characterized by invasiveness to the surrounding brain tissue and by stem-like cells, which propagate the tumor and may also regulate invasiveness. During brain development, polarity proteins, such as Par3, regulate asymmetric cell division of neuro-glial progenitors and neurite motility. We, therefore, studied the role of the Par3 protein (encoded by PARD3) in GBM. GBM patient transcriptomic data and patient-derived culture analysis indicated diverse levels of expression of PARD3 across and independent from subtypes. Multiplex immunolocalization in GBM tumors identified Par3 protein enrichment in SOX2-, CD133-, and NESTIN-positive (stem-like) cells. Analysis of GBM cultures of the three subtypes (proneural, classical, mesenchymal), revealed decreased gliomasphere forming capacity and enhanced invasiveness upon silencing Par3. GBM cultures with suppressed Par3 showed low expression of stemness (SOX2 and NESTIN) but higher expression of differentiation (GFAP) genes. Moreover, Par3 silencing reduced the expression of a set of genes encoding mitochondrial enzymes that generate ATP. Accordingly, silencing Par3 reduced ATP production and concomitantly increased reactive oxygen species. The latter was required for the enhanced migration observed upon silencing of Par3 as anti-oxidants blocked the enhanced migration. These findings support the notion that Par3 exerts homeostatic redox control, which could limit the tumor cell-derived pool of oxygen radicals, and thereby the tumorigenicity of GBM.

Formation of the mouse cerebellum is initiated in the embryo and continues for a few weeks after birth. Double-mutant mice lacking platelet-derived growth factor C (PDGF-C) and that are heterozygous for platelet-derived growth factor receptor alpha (Pdgfc-/-; PdgfraGFP/+) develop cerebellar hypoplasia and malformation with loss of cerebellar lobes in the posterior vermis. This phenotype is similar to those observed in Foxc1 mutant mice and in a human neuroimaging pattern called Dandy Walker malformation. Pdgfc-Pdgfra mutant mice also display ependymal denudation in the fourth ventricle and gene expression changes in cerebellar meninges, which coincide with the first visible signs of cerebellar malformation. Here, we show that PDGF-C/PDGFRα signalling is a critical component in the network of molecular and cellular interactions that take place between the developing meninges and neural tissues, and which are required to build a fully functioning cerebellum.

IntroductionUreaplasma (U.) and Mycoplasma (M.) species have been related to pregnancy complications (including preterm birth) and worse neonatal outcomes. The aim of our work is to evaluate neurodevelopmental outcomes in preterm infants born to mothers with Ureaplasma/Mycoplasma colonization during pregnancy.MethodsPreterm infants with gestational age (GA) of ≤ 30 weeks were included in a retrospective follow-up study. To evaluate the effects of maternal vaginal colonization, we divided preterm infants into two groups: exposed and unexposed infants. All infants were assessed at 24 ± 3 months of age using Griffith’s Mental Developmental Scales (GMDS).ResultsAmong 254 preterm infants, only 32 infants (12.6%) were exposed to U. /M. colonization during pregnancy. Exposed infants and unexposed ones had a similar Griffith′s Developmental Quotient (106 ± 27.2 vs. 108.9 ± 19.5, respectively), without significant differences (p = 0.46). However, exposed infants had a significantly poorer outcome than their unexposed peers in terms of locomotor abilities (100.7 ± 28.3 exposed vs. 111.5 ± 26.1 unexposed, p = 0.03).ConclusionFor visual and hearing impairment, exposed and unexposed infants had similar incidences of cognitive and motor impairment. However, exposed infants had significantly lower locomotor scores than unexposed peers.

Adenine nucleotide translocases (ANTs) and uncoupling proteins (UCPs) are known to facilitate proton leak across the inner mitochondrial membrane. However, it remains to be unravelled whether UCP2/3 contribute to significant amount of proton leak in vivo. Reports are indicative of UCP2 dependent proton-coupled efflux of C4 metabolites from the mitochondrial matrix. Previous studies have suggested that UCP2/3 knockdown (KD) contributes to increased ANT-dependent proton leak. Here we investigated the hypothesis that interaction exists between the UCP2 and ANT2 proteins, and that such interaction is regulated by the cellular metabolic demand. Protein-protein interaction was evaluated using reciprocal co-immunoprecipitation and in situ proximity ligation assay. KD of ANT2 and UCP2 was performed by siRNA in human embryonic kidney cells 293A (HEK293A) cells. Mitochondrial and cellular respiration was measured by high-resolution respirometry. ANT2-UCP2 interaction was demonstrated, and this was dependent on cellular metabolism. Inhibition of ATP synthase promoted ANT2-UCP2 interaction whereas high cellular respiration, induced by adding the mitochondrial uncoupler FCCP, prevented interaction. UCP2 KD contributed to increased carboxyatractyloside (CATR) sensitive proton leak, whereas ANT2 and UCP2 double KD reduced CATR sensitive proton leak, compared to UCP2 KD. Furthermore, proton leak was reduced in double KD compared to UCP2 KD. In conclusion, our results show that there is an interaction between ANT2-UCP2, which appears to be dynamically regulated by mitochondrial respiratory activity. This may have implications in the regulation of mitochondrial efficiency or cellular substrate utilization as increased activity of UCP2 may promote a switch from glucose to fatty acid metabolism.

Abstract Understanding marine animal stranding patterns can aid rehabilitation efforts and evaluations of ecosystem health. The goal of this retrospective study was to identify factors associated with outcome of marine animals presented to a rehabilitation facility in Brigantine, New Jersey, USA. Records of 4819 phocids, cetaceans, and sea turtles were reviewed. Taxa, age, sex, season, and outcome (natural death, euthanasia, transfer to another facility, and successful release) were recorded for each case. Binary logistic regression was employed to identify predictors associated with release, and a multivariate logistic regression model was developed to evaluate whether the association between taxa and chance of release persisted after adjustment for the other variables. Phocids were most likely to strand during winter. Phocids and sea turtles that stranded alive were more likely to be released than to die under care or be euthanized. Taxa, age, and season were all significantly associated with the probability of release. These results provide a reference for phocid, cetacean, and sea turtle stranding and rehabilitation in part of the mid-Atlantic region. Critical evaluation of wildlife rehabilitation is indicated to audit the success of efforts and to assess threats to free-ranging populations.

The article considers the possibilities of using the artificial intelligence in horticulture and viticulture. At present, the artificial intelligence technologies are actively used in agriculture, which make it possible to effectively determine crop yields, automate the cropping and storage of agricultural produce, determine the condition of the soil, the composition and effective use of fertilizers, identify plant diseases and bring weeds under control using recognition methods. The use of the artificial intelligence methods in horticulture and viticulture has its own specific features: firstly, robotic complexes for harvesting cherries, apricots, apples, peaches and grapes; and secondly, the identification of fruit diseases by means photo recognition using neural networks’ machine learning.

Officers are searching and arresting vehicle occupants without a warrant with increasing regularity. For justification, this Article demonstrates, lower courts across the country unconstitutionally expand the scope of the Fourth Amendment's automobile exception--often in the context of a positive dog alert. But Supreme Court jurisprudence specifically limits the scope of the automobile exception to warrantless searches of cars and their containers. In other words, the probable cause underlying the automobile exception allows police to search a vehicle and its containers--nothing more. Despite that clear guidance, this Article argues that a growing number of lower courts nationwide unconstitutionally rely on the probable cause associated with the automobile exception to warrantlessly search vehicle occupants or, alternatively, warrantlessly arrest vehicle occupants. Specifically, this Article identifies those courts that interpret the automobile exception to additionally authorize two overarching categories of warrantless investigative activity: (1) searching vehicle occupants, and (2) arresting vehicle occupants. Each category, in the order presented by this Article, progressively unmoors the automobile exception from its constitutional foundation by broadly expanding the probable cause standard necessary to search a vehicle to permit further warrantless investigation. In response, this Article asserts that the probable cause associated with the automobile exception is limited to searching cars and does not justify searching people--much less seizing people. Those investigative actions, the Article concludes, each require an independent exception to the warrant requirement supported by separate probable cause., INTRODUCTION I. CARS, DOGS, AND THE FOURTH AMENDMENT A. Automobile Exception B. Dogs and Probable Cause 1. The Fourth Amendment Implications of a Dog Sniff 2. Dog Alerts and Probable [...]

¿Cuánto ha aportado el campo de la historia ambiental latinoamericana a la historiografía de la región?, ¿qué tanto le ha importado a la historiografía ambiental latinoamericana incidir en la historiografía de la región?, ¿podría tejerse esta relación con mayor provecho para ambas? Este escrito le habla al público de la Historia desde una lectura crítica de la historiografía ambiental latinoamericana. Sugiere que ésta le ha indicado a la Historia la relevancia de una agencia histórica más amplia y compleja, pero a menudo se ha conformado con narrativas previsibles de limitado atractivo para historiadores sin intereses explícitos hacia la relación entre sociedades y ecosistemas. Argumenta que, al entrar en los últimos años a una etapa más madura, la historiografía ambiental latinoamericana ha abierto el camino hacia mejores preguntas sobre temas fundamentales de la historiografía latinoamericana, interrogantes y objetos que resultan renovadores tanto conceptual como metodológicamente. Aborda, a manera de ejemplos, los asuntos de la cuestión agraria y la construcción del Estado nacional, señalando sin embargo que persiste una necesidad de documentar y sistematizar mejor la metodología de la historia ambiental. Las Conclusiones avanzan hacia la hipótesis de que el Antropoceno, como lugar de controversia epistemológica y de desafío metodológico, puede representar un terreno de contribución original de la historia ambiental a la historiografía latinoamericana.