Breast-feeding as protective factor against bronchopulmonary dysplasia in preterm infants.

Breast-feeding is associated with fewer comorbidities in very-low-birth-weight (VLBW) preterm infants. Bronchopulmonary dysplasia (BPD) of VLBW infants is a multifactorial pathology in which nutritional aspects may be of special importance. The aim of this study is to determine, in a cohort of VLBW infants, whether breast milk nutrition is associated with a reduced prevalence and severity of BPD. A retrospective study was conducted to record the intake of mother's own milk (MOM), pasteurised donor human milk or preterm formula milk in the first 2 weeks of postnatal life of 566 VLBW newborns at our hospital during the period January 2008-December 2021. After applying the relevant exclusion criteria, data for 489 VLBW infants were analysed; 195 developed some degree of BPD. Moderate or severe BPD is associated with less weight gain. Moreover, the preferential ingestion of breast milk in the first and second postnatal weeks had effects associated with lower OR for BPD, which were statistically demonstrable for mild (OR 0·16; 95 % CI 0·03, 0·71) and severe (OR 0·08; 95 % CI 0·009, 0·91) BPD. Breast-feeding during the first weeks of postnatal life is associated with a reduced prevalence of BPD, which is frequently associated with less weight gain as a result of greater respiratory effort with greater energy expenditure.

Extrauterine growth restriction and low energy intake during the early neonatal period of very low birth weight infants are associated with decreased lung function in childhood.

Premature birth, bronchopulmonary dysplasia or restrictive nutrition in the first weeks of postnatal life may have repercussions on lung development and affect long-term lung function outcomes. This prospective observational study is based on a cohort of 313 very low birth weight (VLBW) neonates, born between 1 January 2008 and 1 December 2016. The daily intake of calories, protein, fat and carbohydrates during the first week of life and evidence of inadequate weight gain (Δwt) until week 36 of gestational age (GA) were recorded. FEV1, FEF25-75 %, forced vital capacity (FVC) and the FEV1/FVC ratio were determined. The relations between these parameters were determined by regression analysis. Spirometric parameters were obtained for 141 children with a mean age of 9 years (95 % CI 7, 11); 69 of them (48·9 %) had presented wheezing episodes on more than three occasions. In addition, 60 (42·5 %) had a history of bronchopulmonary dysplasia. Of these, n 40 (66·6 %) had a history of wheezing. Significant association between protein/energy intake in the first week of life and the lung function parameters analysed was observed. Poor Δwt to GA week 36 was significantly associated with decreased mean pulmonary flow. Inadequate protein/energy intake in the first week of life of VLBW newborns and poor Δwt to week 36 of GA is associated with a significant worsening of lung function parameters.

A pragmatic strength and conditioning intervention for firefighters: Feasibility of the Tactical Athlete Resilience Program (TARP).

ISSUE ADDRESSED: Firefighting is physically and mentally taxing and recruits are expected to have optimal health and fitness. However, physical fitness tends to decline following initial training, placing firefighters at an increased risk for stress and injury. Efforts are needed to engage and support firefighters in maintaining adequate health and fitness to withstand the rigorous demands of their occupation. This study examined the feasibility of TARP, a pragmatic strength and conditioning intervention for metropolitan-based firefighters, delivered in collaboration with a professional National Rugby League club. METHODS: A mixed-methods approach was utilised to examine program implementation, recruitment and sample characteristics, intervention satisfaction and acceptability, and participants' response to the intervention. Evaluation measures included field notes taken during steering committee meetings, participant flow data, baseline and follow-up outcome measures, self-report questionnaires, and telephone interviews with a sample of participants. RESULTS: Participants (N = 113) were predominantly men (82%) with a mean age of 43 ± 9.3 years and BMI of 26.6 ± 2.9 kg/m2 . Program satisfaction was high (95% very satisfied or somewhat satisfied) among program completers (42% retention). Key strengths of the program included delivery through the professional sports club, quality of facilities and equipment, and scheduling flexibility. Future programs should consider incorporating education or training to support behaviour change maintenance and strategies to retain participants at follow-up. CONCLUSIONS: Results provide valuable insights into the design and delivery of interventions for firefighters and demonstrate the importance of strong partnerships between community stakeholders.

The association between restricted intra-uterine growth and inadequate postnatal nutrition in very-low-birth-weight infants and their neurodevelopmental outcomes: a 50-month follow-up study.

Inadequate nutrition during a critical period of development - as is the case during gestation and the first days of life, especially in very-low-birth-weight (VLBW) infants, can impact on neurodevelopment and favour co-morbidities. In this study, we evaluate how neurodevelopment may be affected by intra-uterine growth (IUGR) restriction and by an inadequate intake of nutritional energy during the early neonatal period. A longitudinal cohort study was conducted to analyse the nutritional contributions received during the first week of life, among a population of 396 VLBW infants. Motor, cognitive, sensory and behavioural development was assessed at 14, 25, 33 and 50 months. The association between IUGR, postnatal energy restriction and neurodevelopment was examined using multivariate logistic regression techniques. Mild cognitive delay was observed in 35·6 % of neonates with IUGR and in 24 % of those with appropriate birth weight. IUGR is associated with behavioural disorder (OR 2·60; 95 % CI 1·25, 5·40) and delayed cognitive development (OR 2·64; 95 % CI 1·34, 5·20). Energy restriction during the first week of life is associated with visual deficiency (OR 2·96; 95 % CI 1·26, 6·84) and cerebral palsy (OR 3·05; CI 95 % 1·00, 9·54). In VLBW infants, IUGR is associated with behavioural disorder, while postnatal energy restriction is significantly associated with motor disorder, infantile cerebral palsy and sensory disorder.

Sensitivity and Specificity of the Newborn Infant Parasympathetic Evaluation Index in Pain Assessment of Very Low Birth Weight Infants.

OBJECTIVE: This article describes the results of a study investigating the sensitivity and specificity of the Newborn Infant Parasympathetic Evaluation (NIPE) index for detecting the physiological changes resulting from nociception in painful procedures in very low birth weight (VLBW) infants. STUDY DESIGN: A prospective observational study was carried on of 44 newborns at 23 to 32 weeks' gestational age. The sensitivity and specificity of the NIPE index are analyzed using a receiver operating characteristic curve. Most of the painful procedures performed were skin-lancing and venipunctures. Nonpainful procedures consist of no intervention, with an interval of at least 1 hour with painful procedures in each newborn. RESULTS: The accuracy of the NIPE index to diagnose mild nociceptive stimulation in VLBW newborns is 73.2%. CONCLUSION: The NIPE index is a useful technique for assessing nociceptive stimulation in newborns, presenting less observer-dependent variability than other pain assessment scales. KEY POINTS: · The NIPE index offers an objective assessment of pain.. · Moderate-high sensitivity of the NIPE index in the evaluation of pain in premature newborns.. · Painful procedures in VLBW newborns are reflected as a decrease in the NIPE score..

Caffeic acid phenethyl ester exerts apoptotic and oxidative stress on human multiple myeloma cells.

Caffeic acid phenethyl ester (CAPE) is a phenolic compound initially identified in bee glue. CAPE is reported to exhibit antitumor activity in many cancer models. However, the effect of CAPE on multiple myeloma (MM) is not well studied. We investigated the anti-myeloma effect of CAPE, and the data showed that CAPE inhibited the growth of human MM cells in a dose (1 ~ 30 µM) and time (24 ~72 h) dependent manner without altering the viability of normal human peripheral blood B cells. Stress and toxicity pathway analysis demonstrated that CAPE, in a dose- and time-related fashion, induced the expression of apoptotic and oxidative stress-response genes including growth arrest and DNA-damage inducible, alpha and gamma (GADD45A and GADD45G) and heme oxygenase-1. Apoptosis of MM cells by CAPE was further confirmed through flow cytometric analysis with up to 50% apoptotic cells induced by 50 µM CAPE within 24 h. Western blot analysis revealed the CAPE-induced activation of apoptosis executioner enzyme caspase-3, and corresponding cleavage of its downstream target poly(ADP-ribose)polymerase (PARP). The oxidative stress caused by CAPE cytotoxicity in MM cells was evaluated through measurement of reactive oxygen species (ROS) level, antioxidant intervention and glutathione depletion. The intracellular ROS level was not elevated by CAPE, but the pretreatment of antioxidant (N-acetyl cysteine) and glutathione synthesis inhibitor (buthionine sulfoximine) suggested that CAPE may cause oxidative stress by decrease of intracellular antioxidant level rather than over production of ROS. These data suggest that CAPE promotes apoptosis through oxidative stress in human multiple myeloma cells.

Structured inquiry-based learning: Drosophila GAL4 enhancer trap characterization in an undergraduate laboratory course.

We have developed and tested two linked but separable structured inquiry exercises using a set of Drosophila melanogaster GAL4 enhancer trap strains for an upper-level undergraduate laboratory methods course at Bucknell University. In the first, students learn to perform inverse PCR to identify the genomic location of the GAL4 insertion, using FlyBase to identify flanking sequences and the primary literature to synthesize current knowledge regarding the nearest gene. In the second, we cross each GAL4 strain to a UAS-CD8-GFP reporter strain, and students perform whole mount CNS dissection, immunohistochemistry, confocal imaging, and analysis of developmental expression patterns. We have found these exercises to be very effective in teaching the uses and limitations of PCR and antibody-based techniques as well as critical reading of the primary literature and scientific writing. Students appreciate the opportunity to apply what they learn by generating novel data of use to the wider research community.

Theoretical study of novel azo-tetraphenylporphyrins: potential photovoltaic materials.

A density functional theory study was performed to analyze the electron donor-acceptor properties of the cis and trans isomers of a novel azobenzene-containing tetraphenylporphyrin (TPPN2PhC14H29) with different substituents (Br or TMS). In general, the trans isomers are better electron acceptors than the correspondent cis homologues. Their UV-vis spectra were also obtained and a comparison with available experimental results is included. According to these results, the azo compounds reported here are promising materials for the elaboration of dye-sensitized solar cells because their HOMO-LUMO gaps are close to 2 eV. Moreover, the energy of the high intensity absorption bands also fulfills the requirements needed for the operation of a solar cell built with TiO2 and the I(-)/I3(-) pair.

Role of Notch signaling in establishing the hemilineages of secondary neurons in Drosophila melanogaster.

The secondary neurons generated in the thoracic central nervous system of Drosophila arise from a hemisegmental set of 25 neuronal stem cells, the neuroblasts (NBs). Each NB undergoes repeated asymmetric divisions to produce a series of smaller ganglion mother cells (GMCs), which typically divide once to form two daughter neurons. We find that the two daughters of the GMC consistently have distinct fates. Using both loss-of-function and gain-of-function approaches, we examined the role of Notch signaling in establishing neuronal fates within all of the thoracic secondary lineages. In all cases, the 'A' (Notch(ON)) sibling assumes one fate and the 'B' (Notch(OFF)) sibling assumes another, and this relationship holds throughout the neurogenic period, resulting in two major neuronal classes: the A and B hemilineages. Apparent monotypic lineages typically result from the death of one sibling throughout the lineage, resulting in a single, surviving hemilineage. Projection neurons are predominantly from the B hemilineages, whereas local interneurons are typically from A hemilineages. Although sibling fate is dependent on Notch signaling, it is not necessarily dependent on numb, a gene classically involved in biasing Notch activation. When Numb was removed at the start of larval neurogenesis, both A and B hemilineages were still generated, but by the start of the third larval instar, the removal of Numb resulted in all neurons assuming the A fate. The need for Numb to direct Notch signaling correlated with a decrease in NB cell cycle time and may be a means for coping with multiple sibling pairs simultaneously undergoing fate decisions.

The metal cation chelating capacity of astaxanthin. Does this have any influence on antiradical activity?

In this Density Functional Theory study, it became apparent that astaxanthin (ASTA) may form metal ion complexes with metal cations such as Ca⁺², Cu⁺², Pb⁺², Zn⁺², Cd⁺² and Hg⁺². The presence of metal cations induces changes in the maximum absorption bands which are red shifted in all cases. Therefore, in the case of compounds where metal ions are interacting with ASTA, they are redder in color. Moreover, the antiradical capacity of some ASTA-metal cationic complexes was studied by assessing their vertical ionization energy and vertical electron affinity, reaching the conclusion that metal complexes are slightly better electron donors and better electron acceptors than ASTA.

Bridging the gap between attitudes and action: A qualitative exploration of clinician and exercise professional's perceptions to increase opportunities for exercise counselling and referral in cancer care.

OBJECTIVE: This study aimed to 1) understand factors impacting the implementation of exercise communication and referral, and 2) explore integrated clinical approaches to exercise communication and referral in cancer care. METHODS: Seven focus groups (N = 53) were conducted with clinicians and exercise professionals throughout Sydney, Australia. A sub-sample of participants (n = 9) attended a half-day workshop to identifying best practice approaches for moving forward. Data were analysed using thematic content analysis. RESULTS: Two themes emerged: 1) Factors impacting the knowledge-to-action gap, inclusive of limited exercise specific knowledge and training opportunities, funding structure, and current referral process, and 2) Recommendations for a consistent and efficient way forward, detailing the need for oncologist-initiated communication, distribution of cancer-exercise resources, and access to exercise professionals with cancer expertise. CONCLUSIONS: This study identified factors (e.g., cancer-exercise specific training, integration of exercise physiologists) influencing exercise counselling and referral. A potential implementation-referral approach accounting for these factors and how to incorporate exercise into a standard model of cancer care, is described. Future testing is required to determine feasibility and practicality of these approaches. PRACTICAL IMPLICATIONS: A pragmatic model is provided to guide implementation-referral, inclusive of oncologist-initiated communication exchange, relevant resources, and access to exercise professionals with cancer expertise.

Information flow, cell types and stereotypy in a full olfactory connectome.

The hemibrain connectome provides large-scale connectivity and morphology information for the majority of the central brain of Drosophila melanogaster. Using this data set, we provide a complete description of the Drosophila olfactory system, covering all first, second and lateral horn-associated third-order neurons. We develop a generally applicable strategy to extract information flow and layered organisation from connectome graphs, mapping olfactory input to descending interneurons. This identifies a range of motifs including highly lateralised circuits in the antennal lobe and patterns of convergence downstream of the mushroom body and lateral horn. Leveraging a second data set we provide a first quantitative assessment of inter- versus intra-individual stereotypy. Comparing neurons across two brains (three hemispheres) reveals striking similarity in neuronal morphology across brains. Connectivity correlates with morphology and neurons of the same morphological type show similar connection variability within the same brain as across two brains.

Density functional theory study of the magnetic circular dichroism spectra of molybdenyl complexes.

We report a density functional theory (DFT) study of the magnetic circular dichroism (MCD) spectra for four molybdenyl complexes: [MoOCl(4)](-), [MoO(S(2)C(2)H(4))(2)](-), [(Tp*)MoO(bdt)], and [(L3S)MoO(bdt)] (Tp* = hydrotris (3,5-dimethyl-1-pyrazolyl) borate; L3S = (2-dimethylethane-thiolate)bis(3,5-dimethylpyrazolyl)-methane; bdt =1,2-benzenedithiolate). The simulation of the temperature dependent MCD-bands (C-terms) that give rise to the spectra was performed using a method based on time-dependent DFT. In this method, the C-parameters are calculated by including spin-orbit perturbations. On the basis of the theoretical calculations, new or additional assignments are made for the MCD spectra of the complexes; specially for [(L3S)MoO(bdt)], for which case only tentative assignments of the excitations have been proposed in recent years.

Density functional theory study of the electron paramagnetic resonance parameters and the magnetic circular dichroism spectrum for model compounds of dimethyl sulfoxide reductase.

We report a density functional theory (DFT) study of electron paramagnetic resonance (EPR) parameters for complexes modeling the paramagnetic center Mo(V) of the molybdoenzyme dimethyl sulfoxide reductase. We pay special attention to the Mo-OH link to find the most likely geometry and orientation of the metal center in the enzyme and provide an analysis of the physical origin of the g-values in terms of magnetically induced orbital mixing. We also present a study of the magnetic circular dichroism (MCD) spectrum for a complex that models the Mo(V) center of the enzyme. The calculation of the MCD-parameters that give rise to the spectrum was performed using a newly implemented method based on time-dependent DFT. On the basis of the theoretical calculations, it was possible to give a full assignment of the bands of the MCD spectrum for the enzyme.

Connectomics Analysis Reveals First-, Second-, and Third-Order Thermosensory and Hygrosensory Neurons in the Adult Drosophila Brain.

Animals exhibit innate and learned preferences for temperature and humidity-conditions critical for their survival and reproduction. Leveraging a whole-brain electron microscopy volume, we studied the adult Drosophila melanogaster circuitry associated with antennal thermo- and hygrosensory neurons. We have identified two new target glomeruli in the antennal lobe, in addition to the five known ones, and the ventroposterior projection neurons (VP PNs) that relay thermo- and hygrosensory information to higher brain centers, including the mushroom body and lateral horn, seats of learned and innate behavior. We present the first connectome of a thermo- and hygrosensory neuropil, the lateral accessory calyx (lACA), by reconstructing neurons downstream of heating- and cooling-responsive VP PNs. A few mushroom body-intrinsic neurons solely receive thermosensory input from the lACA, while most receive additional olfactory and thermo- and/or hygrosensory PN inputs. Furthermore, several classes of lACA-associated neurons form a local network with outputs to other brain neuropils, suggesting that the lACA serves as a hub for thermo- and hygrosensory circuitry. For example, DN1a neurons link thermosensory PNs in the lACA to the circadian clock via the accessory medulla. Finally, we survey strongly connected downstream partners of VP PNs across the protocerebrum; these include a descending neuron targeted by dry-responsive VP PNs, meaning that just two synapses might separate hygrosensory inputs from motor circuits. These data provide a comprehensive first- and second-order layer analysis of Drosophila thermo- and hygrosensory systems and an initial survey of third-order neurons that could directly modulate behavior.

Complete Connectomic Reconstruction of Olfactory Projection Neurons in the Fly Brain.

Nervous systems contain sensory neurons, local neurons, projection neurons, and motor neurons. To understand how these building blocks form whole circuits, we must distil these broad classes into neuronal cell types and describe their network connectivity. Using an electron micrograph dataset for an entire Drosophila melanogaster brain, we reconstruct the first complete inventory of olfactory projections connecting the antennal lobe, the insect analog of the mammalian olfactory bulb, to higher-order brain regions in an adult animal brain. We then connect this inventory to extant data in the literature, providing synaptic-resolution "holotypes" both for heavily investigated and previously unknown cell types. Projection neurons are approximately twice as numerous as reported by light level studies; cell types are stereotyped, but not identical, in cell and synapse numbers between brain hemispheres. The lateral horn, the insect analog of the mammalian cortical amygdala, is the main target for this olfactory information and has been shown to guide innate behavior. Here, we find new connectivity motifs, including axo-axonic connectivity between projection neurons, feedback, and lateral inhibition of these axons by a large population of neurons, and the convergence of different inputs, including non-olfactory inputs and memory-related feedback onto third-order olfactory neurons. These features are less prominent in the mushroom body calyx, the insect analog of the mammalian piriform cortex and a center for associative memory. Our work provides a complete neuroanatomical platform for future studies of the adult Drosophila olfactory system.

The connectome of the adult Drosophila mushroom body provides insights into function.

Making inferences about the computations performed by neuronal circuits from synapse-level connectivity maps is an emerging opportunity in neuroscience. The mushroom body (MB) is well positioned for developing and testing such an approach due to its conserved neuronal architecture, recently completed dense connectome, and extensive prior experimental studies of its roles in learning, memory, and activity regulation. Here, we identify new components of the MB circuit in Drosophila, including extensive visual input and MB output neurons (MBONs) with direct connections to descending neurons. We find unexpected structure in sensory inputs, in the transfer of information about different sensory modalities to MBONs, and in the modulation of that transfer by dopaminergic neurons (DANs). We provide insights into the circuitry used to integrate MB outputs, connectivity between the MB and the central complex and inputs to DANs, including feedback from MBONs. Our results provide a foundation for further theoretical and experimental work.

Theoretical study of the oxidation reaction and electron spin resonance parameters involving sulfite oxidase.

We present a density functional theory (DFT) study on the conversion of sulfite to sulfate with a model complex representing the active site of the molybdenum-containing enzyme sulfite oxidase (SO). This study considers the attack of the sulfur lone pair from SO(3)(2-) on the equatorial oxo ligand of the model complex as the initial step in the oxidation process. The good agreement between our energy profile and data derived from experimental kinetic parameters provides some support for the reaction mechanism of the oxidative half-reaction of SO proposed in this study. The enzymatic reductive half-reaction involves the formation of an Electron Spin Resonance (ESR) active Mo(V) species. Experimentally, differences in ESR parameters (g-values and (1)H hyperfine coupling constant) of the low- and high-pH forms of the enzyme have been found. The current study also presents DFT-based calculations on ESR parameters for three model complexes representing the paramagnetic center Mo(V) of SO in its possible low- and high-pH forms. We provide an analysis of the magnetic orbital coupling responsible for the calculated g-values. Finally, we suggest how the conformation and hydrogen bonding interactions of the hydroxyl ligand can explain the different ESR parameters at low- and high-pH.

A theoretical study of the magnetic circular dichroism spectrum for sulfite oxidase based on time-dependent density functional theory.

We present a theoretical study of the temperature-dependent magnetic circular dichroism (MCD) spectrum for complexes modeling the molybdoenzyme sulfite-oxidase (1) in its Mo(V) oxidation state. The theoretical study was based on a newly implemented time-dependent density functional method that takes into account first-order perturbations due to spin-orbit coupling and a constant magnetic field. It was possible, on the basis of the theoretical calculations, to give a full assignment of the MCD spectrum for 1 and interpret the C term of each band in the experimental MCD spectrum in terms of spin-orbit couplings between specific excited states and between excited states and the ground state.

Glomerular maps without cellular redundancy at successive levels of the Drosophila larval olfactory circuit.

BACKGROUND: Drosophila larvae possess only 21 odorant-receptor neurons (ORNs), whereas adults have 1,300. Does this suggest that the larval olfactory system is built according to a different design than its adult counterpart, or is it just a miniature version thereof? RESULTS: By genetically labeling single neurons with FLP-out and MARCM techniques, we analyze the connectivity of the larval olfactory circuit. We show that each of the 21 ORNs is unique and projects to one of 21 morphologically identifiable antennal-lobe glomeruli. Each glomerulus seems to be innervated by a single projection neuron. Each projection neuron sends its axon to one or two of about 28 glomeruli in the mushroom-body calyx. We have discovered at least seven types of projection neurons that stereotypically link an identified antennal-lobe glomerulus with an identified calycal glomerulus and thus create an olfactory map in a higher brain center. CONCLUSIONS: The basic design of the larval olfactory system is similar to the adult one. However, ORNs and projection neurons lack cellular redundancy and do not exhibit any convergent or divergent connectivity; 21 ORNs confront essentially similar numbers of antennal-lobe glomeruli, projection neurons, and calycal glomeruli. Hence, we propose the Drosophila larva as an "elementary" olfactory model system.