Implementing the practice of early skin-to-skin contact among infants ≥35 weeks gestation born vaginally: a quality improvement study.

BACKGROUND: Early skin-to-skin contact (SSC) at birth has been shown to improve neonatal outcomes due to enhanced cardiorespiratory stability, thermoregulation and breastfeeding success. LOCAL PROBLEM: The practice of early SSC was virtually non-existent in our delivery room (DR). METHODS AND INTERVENTIONS: The study was conducted in a newly established tertiary care teaching hospital in Western Rajasthan, India. We aimed to improve the median duration of early SSC from 0 min to at least 60 min over 24 weeks in our DR. A quality improvement (QI) team was formed, and all inborn infants ≥35 weeks born vaginally from 9 March 2017 were included. Using the tools of point-of-care QI, we found the lack of standard operating procedure, lack of knowledge among nursing staff regarding early SSC, routine shifting of all infants to radiant warmer, the practice of prioritising birthweight documentation and vitamin K administration as the major hindrances to early SSC. Various change ideas were implemented and tested sequentially through multiple plan-do-study-act (PDSA) cycles to improve the duration of early SSC. Interventions included framing a written policy for SSC, sensitising the nursing staff and resident doctors, actively delaying the alternate priorities, making early SSC a shared responsibility among paediatricians, obstetricians, nursing staff and family members, and continuing SSC in the recovery area of the DR complex. RESULTS: The duration of early SSC increased from 0 to 67 min without any additional resources. The practice of SSC got well established in the system as reflected by a sustained improvement of 63 min and 72 min, respectively, at the end of 2 months and 4 years after study completion. CONCLUSION: Using the QI approach, we established and sustained the practice of early SSC for more than 60 min in our unit by using system analysis and testing change ideas in sequential PDSA cycles.

Phenothiazine Embedded Dithiasmaragdyrins.

Two different types of novel phenothiazine-embedded dithiasmaragdyrins containing one phenothiazine ring, two thiophene rings and two pyrrole rings connected via three meso carbons and two direct bonds in the macrocyclic framework were synthesized over the sequence of synthetic steps starting with phenothiazine. Three examples of phenothiazine-embedded dithiasmaragdyrins were synthesized by condensing appropriate phenothiazine-based pentapyrrane with pentafluorobenzaldehyde and two examples of phenothiazine sulfone embedded dithiasmaragdyrins were synthesized by condensing phenothiazine-based diol with appropriate meso-aryl dipyrromethane under mild acid-catalysed conditions. 1D&2D NMR studies revealed that the thiophene rings adopted inverted orientation in phenothiazine sulfone embedded dithiasmaragdyrins whereas in phenothiazine-embedded dithiasmaragdyrins, the thiophene rings were in normal orientation. Both types of macrocycles exhibit nonaromatic absorption features and showed panchochromic absorption features in its neutral and protonated forms. The electrochemical studies indicated that the phenothiazine-embedded dithiasmaragdyrins were more electron-rich compared to phenothiazine sulfone embedded dithiasmaragdyrins. DFT studies revealed that both types of dithiasmaragdyrins exhibit significantly distorted structures and TD-DFT studies support the experimental observations.

Porphyrinoid framework embedded with polycyclic aromatic hydrocarbons: new synthetic marvels.

The highly conjugated tetrapyrrolic porphyrin macrocycle and its contracted and expanded congeners have been extensively used for a wide range of applications across diverse research domains because of their captivating and intriguing features. Over the years, the porphyrin framework and electronic properties of porphyrinoids have been modified and tuned by replacing one or more pyrrole ring(s) with five- and six-membered heterocycles/carbacycles, and their resulting properties have been explored. In recent times, polycyclic aromatic hydrocarbons (PAHs), such as biphenyl, terphenyl, naphthalene, anthracene, phenanthrene, fluorene, pyrene and dibenzo[g,p]chrysene, have been used to replace one or more pyrrole rings of porphyrinoids, and resulting polycyclic-aromatic-embedded porphyrinoids show unique features that differ from those of other modified porphyrinoids. The polycyclic aromatic hydrocarbons in the porphyrinoid macrocyclic framework induce different π-conjugation pathways in macrocycles, exhibit variable degrees of aromaticity from nonaromatic to aromatic and antiaromatic and provide a unique ligand environment to form stable coordination and organometallic complexes in which metals show uncommon oxidation states and unusual reactivity. This review presents an overview of the synthesis, coordination chemistry, structure and properties of various porphyrinoids with an embedded PAH that have been reported to date.

Implications of organophosphate pesticides on brain cells and their contribution toward progression of Alzheimer's disease.

The most widespread neurodegenerative disorder, Alzheimer's disease (AD) is marked by severe behavioral abnormalities, cognitive and functional impairments. It is inextricably linked with the deposition of amyloid ß (Aß) plaques and tau protein in the brain. Loss of white matter, neurons, synapses, and reactive microgliosis are also frequently observed in patients of AD. Although the causative mechanisms behind the neuropathological alterations in AD are not fully understood, they are likely influenced by hereditary and environmental factors. The etiology and pathogenesis of AD are significantly influenced by the cells of the central nervous system, namely, glial cells and neurons, which are directly engaged in the transmission of electrical signals and the processing of information. Emerging evidence suggests that exposure to organophosphate pesticides (OPPs) can trigger inflammatory responses in glial cells, leading to various cascades of events that contribute to neuroinflammation, neuronal damage, and ultimately, AD pathogenesis. Furthermore, there are striking similarities between the biomarkers associated with AD and OPPs, including neuroinflammation, oxidative stress, dysregulation of microRNA, and accumulation of toxic protein aggregates, such as amyloid ß. These shared markers suggest a potential mechanistic link between OPP exposure and AD pathology. In this review, we attempt to address the role of OPPs on altered cell physiology of the brain cells leading to neuroinflammation, mitochondrial dysfunction, and oxidative stress linked with AD pathogenesis.

Understanding the multifaceted role of miRNAs in Alzheimer's disease pathology.

Small non-coding RNAs (miRNAs) regulate gene expression by binding to mRNA and mediating its degradation or inhibiting translation. Since miRNAs can regulate the expression of several genes, they have multiple roles to play in biological processes and human diseases. The majority of miRNAs are known to be expressed in the brain and are involved in synaptic functions, thus marking their presence and role in major neurodegenerative disorders, including Alzheimer's disease (AD). In AD, amyloid beta (Aß) plaques and neurofibrillary tangles (NFTs) are known to be the major hallmarks. The clearance of Aß and tau is known to be associated with miRNA dysregulation. In addition, the ß-site APP cleaving enzyme (BACE 1), which cleaves APP to form Aß, is also found to be regulated by miRNAs, thus directly affecting Aß accumulation. Growing evidences suggest that neuroinflammation can be an initial event in AD pathology, and miRNAs have been linked with the regulation of neuroinflammation. Inflammatory disorders have also been associated with AD pathology, and exosomes associated with miRNAs are known to regulate brain inflammation, suggesting for the role of systemic miRNAs in AD pathology. Several miRNAs have been related in AD, years before the clinical symptoms appear, most of which are associated with regulating the cell cycle, immune system, stress responses, cellular senescence, nerve growth factor (NGF) signaling, and synaptic regulation. Phytochemicals, especially polyphenols, alter the expression of various miRNAs by binding to miRNAs or binding to the transcriptional activators of miRNAs, thus control/alter various metabolic pathways. Awing to the sundry biological processes being regulated by miRNAs in the brain and regulation of expression of miRNAs via phytochemicals, miRNAs and the regulatory bioactive phytochemicals can serve as therapeutic agents in the treatment and management of AD.

90 versus 60 min of early skin-to-skin contact on exclusive breastfeeding rate in healthy infants' ≥35 weeks: A randomised controlled trial.

AIM: To compare the effect of 90 versus 60 min of early skin-to-skin contact (SSC) among vaginally born healthy infants ≥35 weeks of gestation on their exclusive breastfeeding rates and breastfeeding behaviour. METHODS: This parallel-group, open-label, randomised controlled trial enrolled healthy term and late preterm infants born vaginally. Infants in the intervention group received early SSC for 90 min compared to 60 min in the control group. The primary outcome was the proportion of infants on exclusive breastfeeding at 60 ± 12 h. RESULTS: One hundred ninety-eight mother-infant dyads were randomised (99 in each group). The infants in the 90-min SSC group were more likely to be exclusively breastfed at 60 ± 12 h as compared to the 60-min SSC group (RR, 95% CI-1.44, [1.15-1.79], p < 0.01). The modified infant breastfeeding assessment tool score at 60 ± 12 h was significantly higher in the 90-min SSC group (median [IQR]-9, [8, 10] versus 8 [7, 10], p = 0.03]. The proportion of infants on exclusive breastfeeding at 6, 10, and 14 weeks of age was also significantly higher in the 90-min SSC group (RR, 95% CI-1.39 [1.11-1.74], 1.36 [1.08-1.07], and 1.38 [1.08-1.75], respectively). CONCLUSION: Increasing the duration of early SSC showed a dose-response benefit on exclusive breastfeeding rates and breastfeeding behaviour. TRIAL REGISTRATION: CTRI/2018/09/015632, registered on 06/09/2018.

Periodic Rotation versus Continuous Application of Same Nasal Interface for Non-invasive Respiratory Support in Preterm Neonates: A Systematic Review and Meta-analysis.

OBJECTIVES: To review whether the periodic rotation of nasal mask with binasal prongs is superior to continuous application of either of the interfaces in preterm infants on non-invasive positive pressure respiratory support. METHOD: The authors searched Medline, CINAHL, Embase, Web of Science, and CENTRAL for randomized controlled trials (RCTs) comparing periodic rotation of the two interfaces (mask or prongs) against the continuous application of either, in preterm infants on nasal continuous positive airway pressure (nCPAP) or nasal intermittent positive pressure ventilation (NIPPV). They performed a random-effects meta-analysis using RevMan 5.4. The primary outcome was the incidence of moderate to severe nasal injury. Other outcomes included any nasal injury, need for invasive ventilation, duration of respiratory support, hospital stay, and mortality. RESULTS: Four RCTs (520 participants) were included. There was no difference in the incidence of moderate to severe nasal injury between periodic rotation vs. continuous nasal mask (3 RCTs, 293 participants; RR: 1.75, 95% CI: 0.73-4.19), or periodic rotation vs. continuous binasal prongs (3 RCTs, 296 participants; RR: 0.40, 95% CI: 0.14-1.11). Periodic rotation lowered the incidence of any grade nasal injury compared to continuous binasal prongs (RR: 0.61, 95% CI: 0.49-0.75) but not compared to continuous nasal mask (RR: 1.38, 95% CI: 0.92-2.06). Periodic rotation was associated with longer non-invasive respiratory support (compared to prongs) and prolonged hospital stay (compared to masks). There were no significant differences in other clinical outcomes. CONCLUSIONS: Among preterm infants receiving non-invasive respiratory support, periodically rotating a nasal mask with short binasal prongs may not be superior to the continuous application of nasal masks.

Levetiracetam versus Phenobarbitone for Management of Neonatal Seizures: A Systematic Review and Meta-analysis.

OBJECTIVES: To review whether levetiracetam is non-inferior to phenobarbitone as the first-choice antiseizure medication (ASM). METHODS: The authors searched Medline, Embase, Web of Science, Scopus, and Cochrane Library for randomized controlled trials (RCTs) published until May 31, 2023. RCTs comparing the efficacy and safety of levetiracetam and phenobarbitone as first-line ASM in neonatal seizures were included. Random effects meta-analysis was performed, and the Risk of Bias version 2 tool was used for quality assessment. RESULTS: Eleven RCTs enrolling 821 neonates [mostly term, with hypoxic-ischemic encephalopathy (HIE)] were included. There was no significant difference in seizure control between levetiracetam and phenobarbitone (10 RCTs, 786 participants; relative risk RR: 1.11; 95% CI: 0.79, 1.54; I2- 88%). Neonates in the levetiracetam group had a significantly lower incidence of hypotension (RR: 0.28; 95% CI: 0.09, 0.86), respiratory depression (RR: 0.36, 95% CI: 0.19, 0.66), and depressed sensorium (RR: 0.52, 95% CI: 0.27, 1.00). Three studies compared neurodevelopmental outcomes; however two of them were cross-over trials where infants received both drugs. Only one RCT enrolled pure cohorts and showed better neurodevelopment in the levetiracetam group at one month of age. CONCLUSIONS: With the limitation of very-low certainty evidence, the results of this systematic review suggest that levetiracetam may be non-inferior to phenobarbitone for managing neonatal seizures. Considering a better safety profile and marginally better neurodevelopment in the short term, levetiracetam may be considered an initial choice for managing neonatal seizures. REGISTRATION NUMBER: PROSPERO (CRD42023438018).

Understanding the neuronal synapse and challenges associated with the mitochondrial dysfunction in mild cognitive impairment and Alzheimer's disease.

Synaptic mitochondria are crucial for maintaining synaptic activity due to their high energy requirements, substantial calcium (Ca2+) fluctuation, and neurotransmitter release at the synapse. To provide a continuous energy supply, neurons use special mechanisms to transport and distribute healthy mitochondria to the synapse while eliminating the damaged mitochondria from the synapse. Along the neuron, mitochondrial membrane potential (ψ) gradient exists and is highest in the somal region. Lower ψ in the synaptic region renders mitochondria more vulnerable to oxidative stress-mediated damage. Secondly, mitochondria become susceptible to the release of cytochrome c, and mitochondrial DNA (mtDNA) is not shielded from the reactive oxygen species (ROS) by the histone proteins (unlike nuclear DNA), leading to activation of caspases and pronounced oxidative DNA base damage, which ultimately causes synaptic loss. Both synaptic mitochondrial dysfunction and synaptic failure are crucial factors responsible for Alzheimer's disease (AD). Furthermore, amyloid beta (Aß) and hyper-phosphorylated Tau, the two leading players of AD, exaggerate the disease-like pathological conditions by reducing the mitochondrial trafficking, blocking the bi-directional transport at the synapse, enhancing the mitochondrial fission via activating the mitochondrial fission proteins, enhancing the swelling of mitochondria by increasing the influx of water through mitochondrial permeability transition pore (mPTP) opening, as well as reduced ATP production by blocking the activity of complex I and complex IV. Mild cognitive impairment (MCI) is also associated with decline in cognitive ability caused by synaptic degradation. This review summarizes the challenges associated with the synaptic mitochondrial dysfunction linked to AD and MCI and the role of phytochemicals in restoring the synaptic activity and rendering neuroprotection in AD.

Sonographic assessment of diaphragmatic thickness and excursion to predict CPAP failure in neonates below 34 weeks of gestation: A prospective cohort study.

BACKGROUND: To evaluate the diagnostic accuracy of sonographic assessment of diaphragmatic dimensions and excursions in predicting Continuous Positive Airway Pressure (CPAP) failure in preterm neonates with respiratory distress. METHODS: Prospective cohort study among preterm neonates less than 34 weeks of gestation who were hemodynamically stable and either admitted with respiratory distress or who developed respiratory distress shortly after admission to the NICU and having Silverman-Anderson Score (SAS) ≥ 3/10 were included. We performed sonographic assessment of diaphragmatic dimensions and excursions before and one hour ±30 minutes after application of CPAP. 'CPAP failure' was defined as combined outcome of the need of surfactant and/or upgradation of respiratory support within first 72 hours after a trial of CPAP. Clinical parameters and diaphragmatic measurements were compared between CPAP failure and success groups. RESULTS: Of 62 participants, 20 (32%) failed CPAP. On binomial logistic regression (after adjustment for gestational age and birth weight), initial SAS, higher diaphragmatic excursion (both left and right, before and after CPAP application), lower left hemidiaphragm diaphragmatic thickness fraction (DTF) (before CPAP application) and lower right DTF (after CPAP application) were independent predictors of CPAP failure. However, the receiver-operating characteristics curves showed that excursions of right and left hemi-diaphragm both before and after CPAP application, had highest accuracies in predicting CPAP failure (AUC 0.84, 0.80 and 0.86, 0.78, respectively; p < .001). CONCLUSION: Diaphragmatic excursion can be a useful parameter to predict the failure of CPAP in preterm neonates with respiratory distress.

Anthriporphyrinoids: Design, Synthesis, and Reactivity towards Diels-Alder Reaction.

A series of non-aromatic anthripentaphyrins containing an anthracene unit, two thiophenes, and two pyrrole rings as a part of a macrocyclic framework connected via three meso-carbons were synthesized. The crystal structure of one of the anthripentaphyrins revealed that the two thiophene rings were in an inverted orientation, and the macrocycle adopts a nonplanar Z-like ruffled structure. These anthriporphyrinoids act as dienes and undergo Diels-Alder reaction with dienophiles to form stable non-aromatic Diels-Alder adducts.

Systematic rotation versus continuous application of 'nasal prongs' or 'nasal mask' in preterm infants on nCPAP: a randomized controlled trial.

To compare whether alternate rotation of nasal mask with nasal prongs every 8 h as compared to continuous use of either interface alone decreases the incidence of nasal injury in preterm infants receiving nasal Continuous Positive Airway Pressure (nCPAP). This was an open-label, three-arm, stratified randomized controlled trial where infants < 35 weeks receiving nCPAP were randomized into three groups using two different nasal interfaces (continuous prongs group, continuous mask group, and rotation group). All infants were assessed for nasal injury six hours post-removal of nCPAP using grading suggested by Fischer et al. The nursing care was uniform across all three groups. Intention-to-treat analysis was done. Fifty-seven infants were enrolled, with nineteen in each group. The incidence of nasal injury was 42.1% vs. 47.4% vs. 68.4% in the rotation group, continuous mask, and continuous prongs groups, respectively (P = 0.228). On adjusted analysis (gestational age, birth weight, and duration of nCPAP therapy), the incidence of nasal injury was significantly less in the rotation group as compared to continuous prongs group (Adjusted Odds Ratio [AOR], 95% confidence interval [CI]; 0.10 [0.01-0.69], P = 0.02) and a trend towards lesser nasal injury as compared to continuous mask group (AOR, 95% CI; 0.15 [0.02-1.08], P = 0.06). However, there was no significant difference in incidence of nasal injuries between continuous prongs versus continuous mask group (P = 0.60). The need for surfactant, nCPAP failure rate, duration of nCPAP, and common neonatal co-morbidities were similar across all three groups.   Conclusion: Systematic rotation of nasal mask with nasal prongs significantly reduced nasal injury among preterm infants on nCPAP as compared to continuous use of nasal prongs alone without affecting nCPAP failure rate.   Trial registration: CTRI/2019/01/017320, registered on 31/01/2019. What is Known: • Use of nasal mask as an interface for nasal Continuous Positive Airway Pressure decreases nasal injury as compared to nasal prongs. What is New: • Rotation of nasal prongs and nasal mask interfaces alternately every 8 h may reduce the nasal injury even further as compared to either interface alone.

Viscoplastic Modeling of Surface Relief Grating Growth on Isotropic and Preoriented Azopolymer Films.

We report on solving of two intriguing issues concerning the inscription of surface relief gratings within azopolymer thin films under irradiation with SS, PP and RL interference patterns. For this, we utilize the orientation approach and viscoplastic modeling in combination with experimental results, where the change in surface topography is acquired in situ during irradiation with modulated light. First, the initial orientation state of polymer backbones is proved to be responsible for the contradictory experimental reports on the efficiency of the SS interference pattern. Different orientation states can influence not only the phase of SS grating but also its height, which is experimentally confirmed by using special pretreatments. Second, the faster growth of gratings inscribed by the RL interference pattern is shown to be promoted by a weak photosoftening effect. Overall, the modeled results are in good agreement with the order of relative growth efficiency: RL-PP-SS.

Synthesis and Studies of Fused Benzo-Benzisapphyrins.

A series of rare examples of fused benzo-benzisapphyrins were synthesized readily by (3 + 2) condensation of benzodipyrrole-derived diol and para-benzitripyrrane in the presence of 0.5 equiv of TFA in CH2Cl2 under inert atmosphere conditions accompanied by DDQ oxidation in open air. The crude compounds were separated by basic alumina column chromatography and afforded pure fused benzo-benzisapphyrins in 20-22% yields. The fused sapphyrins were characterized in detail by high-resolution mass spectrometry (HRMS) and one-dimensional (1D) and two-dimensional (2D) NMR spectroscopy. The 1H NMR spectra recorded at both 298 and at 233 K clearly exhibited the presence of a strong diatropic ring current in benzo-benzisapphyrins, and the macrocycles are of aromatic nature. The DFT-optimized structure of benzo-benzisapphyrin revealed that the macrocycle was planar to a great extent due to the rigid structure of the dibenzopyrrole moiety, and the NICS(0) value of -11.2 ppm supports the aromatic nature of macrocycles. The absorption spectra of benzo-benzisapphyrins showed three weak Q bands approximately in the region of 650-900 nm and a strong Soret band at 480 nm, along with a shoulder band at ∼510 nm. The diprotonated derivative generated by the addition of excess TFA to the benzo-benzisapphyrin macrocycle exhibited bathochromically shifted absorption bands compared to the free base macrocycle.

Synthesis and Studies of Di(p-Benzi)Decaphyrin and Di(9,10-Anthracenyl)Decaphyrin.

Two novel macrocycles, di(p-benzi)decaphyrin and di(9,10-anthracenyl)decaphyrin have been synthesized by condensing appropriate p-phenylene based pentapyrrane or 9,10-anthracenyl based pentapyrrane with pentafluorobenzaldehyde under acid catalyzed conditions. The pentapyrrane precursors were synthesized over sequence of steps starting with commercially available 1,4-dibromobenzene and 9,10-dibromoanthracene. The decaphyrin macrocycles were freely soluble in common organic solvents and characterized and studied by HR-MS, 1D and 2D NMR, absorption, cyclic voltammetry and computational techniques. The 1 H NMR spectra of both decaphyrins were almost similar with very few resonances, indicating their symmetrical nature in solution and the position of chemical shifts of various protons supports nonaromatic nature of decaphyrins. The DFT optimized structures revealed that both decaphyrins showed a doubly twisted figure of eight conformation and the p-phenylene rings in di(p-benzi)decaphyrin and anthracenyl rings in di(9,10-anthracenyl)decaphyrin did not participate in π-delocalization with rest of the respective decaphyrin macrocycle. Both decaphyrins showed sharp intense band in the region of 400-500 nm and a broad band in the region of 600-900 nm. The absorption bands of di(p-benzi)decaphyrin were significantly red shifted compared to di(9,10-anthracenyl)decaphyrin. The protonated derivatives of decaphyrins generated by addition of TFA to the toluene solution of decaphyrins showed distinct changes in colour and absorption spectral bands. The redox studies indicated that both decaphyrins are electron rich and undergo easier oxidations. The electrochemical and computational studies revealed that HOMO-LUMO energy gap was less in di(p-benzi)decaphyrin compared to di(9,10-anthracenyl)decaphyrin supporting the bathochromic shifts of absorption bands in di(p-benzi)decaphyrin. TD-DFT studies were in agreement with the experimental observations.

800 IU versus 400 IU per day of vitamin D3 in term breastfed infants: a randomized controlled trial from an LMIC.

This open-label, block-randomized controlled trial compared the effect of 800 IU/day and 400 IU/day of oral vitamin D3 supplementation in reducing vitamin D insufficiency (VDI) among healthy-term breastfed infants at 14 weeks of postnatal age. All eligible infants were randomized to receive either 800 or 400 IU/day of oral vitamin D3 (starting within the first week until 14 weeks). The primary outcome was the proportion of infants with VDI (25-OH-D < 20 ng/ml) at 14 weeks. Secondary outcomes were vitamin D deficiency (VDD, < 12 ng/ml), severe VDD (< 5 ng/ml), anthropometry, biochemical or clinical rickets, and any adverse events related to vitamin D toxicity (VDT). Among 102 enrolled infants, the distribution of baseline variables (including cord 25-OH-D levels; 13.0 versus 14.2 ng/ml) was similar in both groups. On intention-to-treat analysis, the proportions of infants with VDI at 14 weeks were significantly lower in the 800 IU group compared to those in the 400 IU group [24% versus 55%; RR 0.44; 95% CI: 0.25-0.76]. The proportions of infants with elevated parathormone (6% versus 26.5%; p = 0.012) and severe VDD (0% versus 12.2%; p = 0.033) were significantly lower in the 800 IU group. Clinical rickets developed in three (6.2%) infants in the 400 IU group. No infant developed VDT.      Conclusions: Daily oral supplementation with 800 IU of vitamin D3 resulted in an almost 50% reduction in the proportion of infants with VDI and prevented the occurrence of severe VDD at 14 weeks of age compared to 400 IU with no evidence of vitamin D toxicity.     Trial Registration: Clinical Trial Registry of India (CTRI/2019/02/017374). What is Known: • Breastfeeding is the ideal source of nutrition for healthy-term breastfed infants; however, vitamin D content of breastmilk is suboptimal. • AAP recommends daily oral supplementation of 400 IU of vitamin D to all healthy-term breastfed infants; however, trials from high-income countries support insufficiency of this dose in maintaining serum 25-OH-D levels >20 ng/ml with no such information from low-middle-income countries. What is New: • 800 IU/day of oral vitamin D3 supplementation among term breastfed infants significantly reduces vitamin D insufficiency at 14 weeks' age as compared to the recommended dose of 400 IU/day. • This higher supplemental dose is safe with no evidence of vitamin D toxicity.

Synthesis and Studies of Structural Isomers of meso-Fused Dicarbahexaphyrins.

Two close structurally related isomers of nonaromatic meso-fused dicarbahexaphyrins were synthesized by condensing one equivalent of fluorene based tripyrrane with one equivalent of pentafluorobenzaldehyde in CH2 Cl2 under BF3 .OEt2 catalyzed conditions. The cis and trans isomers of meso-fused dicarbahexaphyrins were separated by preparative thin-layer chromatography and isolated pure macrocycles as green solids in 6-7% yields. NMR spectra of cis and trans isomers are quite distinct from each other and trans isomer was very symmetric and showed fewer resonances than cis isomer in NMR. The NMR study supported the nonaromatic nature of both cis and trans isomers of meso-fused dicarbahexaphyrins. DFT optimized structures revealed that the cis isomer adopted a singly twisted puckered conformation whereas the trans isomer displayed a saddle like conformation. Both cis and trans isomers almost showed similar nonaromatic absorption features with slight differences in their peak maxima. However, the protonated derivative of cis isomer showed absorption bands in visible-NIR region with bands extended upto 1000 nm whereas the trans isomer showed strong bands in the visible region. Both cis and trans macrocycles were easier to oxidize and reduce and TD-DFT studies corroborated with the experimental findings.

25% Dextrose Versus 24% Sucrose for Heel Lancing in Preterm Infants: A Noninferiority RCT.

OBJECTIVES: To compare the efficacy of 25% dextrose with 24% sucrose for heel-lance analgesia in preterm infants admitted to the NICU. METHODS: In this noninferiority, double-blind, randomized controlled trial, preterm infants born at 28 weeks and 0 days to 35 weeks and 6 days of gestation who were due for a scheduled heel-lance procedure were enrolled. Infants randomly assigned to the intervention arm received 0.5 mL 25% dextrose, whereas infants in the active control group received 0.5 mL 24% sucrose orally just 2 minutes before the heel-lance procedure. The primary outcome was Premature Infant Pain Profile (PIPP) score 30 seconds after the procedure. Secondary outcomes included PIPP scores at 60 and 120 seconds, PIPP-Revised scores at 30, 60, and 120 seconds, and any adverse events. RESULTS: Sixty-four infants were enrolled (32 in each group). The mean (SD) PIPP score at 30 seconds was 6.41 (2.56) in the dextrose group and 7.03 (2.23) in the sucrose group (mean difference, -0.63 (95% confidence interval, -1.85 to 0.60; P = .31). The upper margin of the confidence interval did not cross the predefined noninferiority margin of 2. The mean PIPP scores at 60 (5.03 [2.18] vs 5.39 [1.48]) and 120 (4.75 [1.97] vs 4.94 [1.46]) seconds were also similar. The PIPP-Revised scores between the 2 groups at all time intervals were comparable. One infant in the intervention group had a transient coughing episode. CONCLUSIONS: In preterm infants under intensive care, 25% dextrose is noninferior to 24% sucrose for heel-lance analgesia as assessed by PIPP score.

Ameliorative role of naringenin against lead-induced genetic damage and oxidative stress in cultured human lymphocytes.

Lead (Pb) is a ubiquitous toxic heavy metal that is known to induce damage to major macromolecules (lipids, proteins, and nucleic acids) by enhancing the level of reactive oxygen species (ROS). Naringenin, a predominant flavonoid primarily found in citrus fruits has attained increasing attention due to its various pharmacological properties. Thus, the present investigation aimed to explore the ameliorative role of naringenin against Pb-induced toxicity in human peripheral blood lymphocytes (PBLs) under in vitro conditions. For this purpose, PBLs were exposed to Pb (350 µg/ml) alone as well in combination with naringenin (10 and 30 µg/ml). Sister chromatid exchange (SCE) and alkaline comet assay were used as genotoxic indices to evaluate the genotoxic and antigenotoxic activity of Pb and naringenin, respectively. Lipid peroxidation (LPO), glutathione peroxidase (GPx), catalase (CAT), superoxide dismutase (SOD), and reduced glutathione (GSH) assays were used as oxidative damage markers. The results revealed that Pb induced a significant (p < 0.05) increase in genetic and oxidative damage as compared with the untreated sample whereas the treatment of cells along with naringenin (10 and 30 µg/ml) and Pb (350 µg/ml) caused a significant reduction in genetic damage and elevation in SOD, GPx, and CAT activities and GSH level, accompanied by a significant reduction in LPO level as compared with Pb alone treated sample. So, the present investigation revealed that naringenin might be used as a protective agent against Pb-induced toxicity due to its antigenotoxic and antioxidative properties.

Bis-(Fluorene)-Embedded Hexaphyrins.

The polyaromatic hydrocarbon containing expanded porphyrins, bis-(fluorene)-embedded hexaphyrins, were synthesized by condensing fluorene-based tripyrrane with pentafluorobenzaldehyde in CH2Cl2 in the presence of 1 equiv of BF3·OEt2 under an inert atmosphere followed by oxidation with DDQ in open air at room temperature. The reaction worked only when 1 equiv of BF3·OEt2 was added to the reaction mixture under concentrated reaction conditions. The bis-(fluorene)-embedded macrocycles were characterized and studied by high-resolution mass spectrometry (HRMS), nuclear magnetic resonance (NMR), absorption, electrochemical, and density functional theory (DFT)/time-dependent (TD)-DFT techniques. In 1H NMR, the hexaphyrins showed a few broad unresolved resonances at room temperature, but the NMR spectra were well-resolved at lower temperatures, indicating that the hexaphyrins were very flexible. The DFT-optimized structures indicated that the two fluorene units at the crossing point of the figure-eight loop makes an angle of ∼79.73° with each other, the fluorene moieties maintained their own planarity, and one of the fluorene moieties was not involved in conjugation with the rest of the macrocycle. The absorption spectra of hexaphyrins showed one intense sharp band in the higher energy region and a broad band in the lower energy region. The electrochemical studies indicated that expanded hexaphyrins are relatively electron-rich and showed three easier oxidations and one reduction. The DFT/TD-DFT studies are in agreement with the experimental observations.