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Jelaluddin Rumi was born in the year 1207 and until the age of thirty-seven was a brilliant scholar and popular teacher. But his life changed forever when he met the powerful wandering dervish, Shams of Tabriz, of whom Rumi said, \"What I had thought of before as God, I met today in a human being.\" From this mysterious and esoteric friendship came a new height of spiritual enlightenment. When Shams disappeared, Rumi began his transformation from scholar to artist, and his poetry began to fly. Today, the ecstatic poetry of Jelaluddin Rumi is more popular than ever, and Coleman Barks, through his musical and magical translations, has been instrumental in bringing this exquisite literature to devoted followers. Now, for the first time, Barks has gathered the essential poems of Rumi and put them together in this wonderful comprehensive collection that delights with playful energy and unequaled passion. The Essential Rumi offers the most beautiful rendering of the primary poetry of Rumi to both devoted enthusiasts and novice readers. Poems about everything from bewilderment, emptiness, and silence to flirtation, elegance, and majesty are presented with love, humor, warmth, and tenderness. Take in the words of Jelaluddin Rumi and feel yourself transported to the magical, mystical place of a whirling, ecstatic poet.

BackgroundSystemic inflammation amplifies neonatal hypoxic–ischemic (HI) brain injury. Azithromycin (AZ), an antibiotic with anti-inflammatory properties, improves sensorimotor function and reduces tissue damage after neonatal rat HI brain injury. The objective of this study was to determine if AZ is neuroprotective in two neonatal rat models of inflammation-amplified HI brain injury.Design/MethodsSeven-day-old (P7) rats received injections of toll-like receptor agonists lipopolysaccharide (LPS) or Pam3Cys-Ser-(Lys)4 (PAM) prior to right carotid ligation followed by 50 min (LPS + HI) or 60 min (PAM + HI) in 8% oxygen. Outcomes included contralateral forelimb function (forepaw placing; grip strength), survival, %Intact right hemisphere (brain damage), and a composite score incorporating these measures. We compared postnatal day 35 outcomes in controls and groups treated with three or five AZ doses. Then, we compared P21 outcomes when the first (of five) AZ doses were administered 1, 2, or 4 h after HI.ResultsIn both LPS + HI and PAM + HI models, AZ improved sensorimotor function, survival, brain tissue preservation, and composite scores. Benefits increased with five- vs. three-dose AZ and declined with longer initiation delay.ConclusionsPerinatal systemic infection is a common comorbidity of neonatal asphyxia brain injury and contributes to adverse outcomes. These data support further evaluation of AZ as a candidate treatment for neonatal neuroprotection.ImpactAZ treatment decreases sensorimotor impairment and severity of brain injury, and improves survival, after inflammation-amplified HI brain injury, and this can be achieved even with a 2 h delay in initiation.This neuroprotective benefit is seen in models of inflammation priming by both Gram-negative and Gram-positive infections.This extends our previous findings that AZ treatment is neuroprotective after HI brain injury in neonatal rats.

The neurological examination of critically ill neonates is largely limited to reflexive behavior. The exam often ignores sleep-wake physiology that may reflect brain integrity and influence long-term outcomes. We assessed whether polysomnography and concurrent cerebral near-infrared spectroscopy (NIRS) might improve prediction of 18-month neurodevelopmental outcomes. Term newborns with suspected seizures underwent standardized neurologic examinations to generate Thompson scores and had 12-hour bedside polysomnography with concurrent cerebral NIRS. For each infant, the distribution of sleep-wake stages and electroencephalogram delta power were computed. NIRS-derived fractional tissue oxygen extraction (FTOE) was calculated across sleep-wake stages. At age 18-22 months, surviving participants were evaluated with Bayley Scales of Infant Development (Bayley-III), 3rd edition. Twenty-nine participants completed Bayley-III. Increased newborn time in quiet sleep predicted worse 18-month cognitive and motor scores (robust regression models, adjusted r2 = 0.22, p = .007, and 0.27, .004, respectively). Decreased 0.5-2 Hz electroencephalograph (EEG) power during quiet sleep predicted worse 18-month language and motor scores (adjusted r2 = 0.25, p = .0005, and 0.33, .001, respectively). Predictive values remained significant after adjustment for neonatal Thompson scores or exposure to phenobarbital. Similarly, an attenuated difference in FTOE, between neonatal wakefulness and quiet sleep, predicted worse 18-month cognitive, language, and motor scores in adjusted analyses (each p < .05). These prospective, longitudinal data suggest that inefficient neonatal sleep-as quantified by increased time in quiet sleep, lower electroencephalogram delta power during that stage, and muted differences in FTOE between quiet sleep and wakefulness-may improve prediction of adverse long-term outcomes for newborns with neurological dysfunction.

BackgroundInflammation contributes to neonatal hypoxic–ischemic brain injury pathogenesis. We evaluated the neuroprotective efficacy of azithromycin, a safe, widely available antibiotic with anti-inflammatory properties, in a neonatal rodent hypoxic–ischemic brain injury model.MethodsSeven-day-old rats underwent right carotid artery ligation followed by 90-min 8% oxygen exposure; this procedure elicits quantifiable left forepaw functional impairment and right cerebral hemisphere damage. Sensorimotor function (vibrissae-stimulated forepaw placing, grip strength) and brain damage were compared in azithromycin- and saline-treated littermates 2–4 weeks later. Multiple treatment protocols were evaluated (variables included doses ranging from 15 to 45 mg/kg; treatment onset 15 min to 4 h post-hypoxia, and comparison of 1 vs. 3 injections).ResultsAll azithromycin doses improved function and reduced brain damage; efficacy was dose dependent, and declined with increasing treatment delay. Three azithromycin injections, administered over 48 h, improved performance on both function measures and reduced brain damage more than a single dose.ConclusionIn this neonatal rodent model, azithromycin improved functional and neuropathology outcomes. If supported by confirmatory studies in complementary neonatal brain injury models, azithromycin could be an attractive candidate drug for repurposing and evaluation for neonatal neuroprotection in clinical trials.

BackgroundEnriched language exposure may benefit infants in the neonatal intensive care unit. We hypothesized that changes in neonatal electroencephalogram (EEG) coherence during sleep, in response to maternal voice exposure, predict language development.MethodsConvalescent neonates underwent 12-h polysomnography. A recording of the mother’s voice was randomized to continuous playback in the first or second 6 h. We calculated the imaginary coherence (ICOH—a measure of functional connectivity) between EEG leads. Spearman correlations were computed between ICOH and 18-month Bayley-III language scores.ResultsThirty-five neonates were included (N = 18 33-to-<35 weeks gestation; N = 17 ≥ 35 weeks). Predictive value of ICOH during neonatal non-rapid eye movement (NREM) sleep was left lateralized, and varied with gestational age and voice playback. ICOH in the left-hemispheric (C3-Cz; T3-Cz) channels across multiple EEG frequency bands was associated with 18-month language scores (rho = −0.34 to −0.48). The association was driven by neonates born at 33–34 weeks gestation, and a trend suggested a possible effect of maternal voice at some EEG frequencies. Right hemisphere ICOH (C4-Cz; T4-Cz) was not associated with language outcome.ConclusionsLeft-hemispheric EEG functional connectivity during neonatal NREM sleep shows early signs of physiologic asymmetry that may predict language development. We speculate that sleep analyses could have unique prognostic value.ImpactDuring neonatal NREM sleep, EEG functional connectivity predicts future language development.Left temporal and central EEG coherence—specifically the imaginary component of coherence—is predictive, whereas the same analysis from the right hemisphere is not.These results appear to vary according to the infant’s gestational age, and a trend suggests they may be enhanced by measuring functional connectivity during exposure to the mother’s voice.These findings identify early evidence of physiologic differentiation within the cerebral hemispheres and raise the possibility that neonatal NREM sleep has a role to play in language development.

Acute postasphyxial encephalopathy around the time of birth remains a major cause of death and disability. The possibility that hypothermia may be able to prevent or lessen asphyxial brain injury is a “dream revisited”. In this review, a historical perspective is provided from the first reported use of therapeutic hypothermia for brain injuries in antiquity, to the present day. The first uncontrolled trials of cooling for resuscitation were reported more than 50 y ago. The seminal insight that led to the modern revival of studies of neuroprotection was that after profound asphyxia, many brain cells show initial recovery from the insult during a short “latent” phase, typically lasting ~6 h, only to die hours to days later during a “secondary” deterioration phase characterized by seizures, cytotoxic edema, and progressive failure of cerebral oxidative metabolism. Studies designed around this conceptual framework showed that mild hypothermia initiated as early as possible before the onset of secondary deterioration, and continued for a sufficient duration to allow the secondary deterioration to resolve, is associated with potent, long-lasting neuroprotection. There is now compelling evidence from randomized controlled trials that mild induced hypothermia significantly improves intact survival and neurodevelopmental outcomes to midchildhood.

Objective Among neonates with acute symptomatic seizures, we evaluated whether the inability to take full feeds at the time of hospital discharge from neonatal seizure admission is associated with worse neurodevelopmental outcomes, after adjusting for relevant clinical variables. Methods This prospective, nine‐center study of the Neonatal Seizure Registry (NSR) assessed characteristics of infants with seizures, including evidence of brainstem injury on magnetic resonance imaging (MRI), mode of feeding upon discharge, and developmental outcomes at 12, 18, and 24 months. The inability to take oral feeds was identified through a review of medical records. Brainstem injury was identified through a central review of neonatal MRIs. Developmental outcomes were assessed with the Warner Initial Developmental Evaluation of Adaptive and Functional Skills (WIDEA‐FS) at 12, 18, and 24 months corrected age. Results Among 276 infants, inability to achieve full oral feeds was associated with lower total WIDEA‐FS scores (160.2 ± 25.5 for full oral feeds vs. 121.8 ± 42.9 for some/no oral feeds at 24 months, p < 0.001). At 12 months, a gastrostomy tube was required for 23 of the 49 (47%) infants who did not achieve full oral feeds, compared with 2 of the 221 (1%) who took full feeds at discharge (p < 0.001). Conclusions The inability to take full oral feeds upon hospital discharge is an objective clinical sign that can identify infants with acute symptomatic neonatal seizures who are at high risk for impaired development at 24 months.

Objective To determine precooling attributes possibly predicting death in infants with hypoxic-ischaemic encephalopathy (HIE) despite therapeutic cooling. Methods Eighty-five consecutive infants of ≥36 weeks' gestation who received cooling for HIE were reviewed. Logistic regression analysis was performed using precooling clinical and laboratory variables with death related to HIE during the first 9 months of life as the primary outcome. Results Thirteen (15%) of the 85 infants died during 9–18 months of follow-up despite cooling. 27 of the 85 were asystolic at birth but only 12 had Apgar scores of zero at both 5 and 10 min. Univariate analysis identified Apgar scores of zero at 5 and 10 min, pH <6.7, base deficit >22 mmol/l, and absent spontaneous movement as significantly associated with death during the first 9 months despite cooling. On multivariate analysis, only the Apgar score of zero at 10 min (p<0.001, OR 51.7, 95% CI 9.9 to 269.5) remained significantly associated with the primary outcome of death from HIE. Of the 12 infants who were asystolic at and beyond 10 min of life, nine died from HIE, two had spastic quadriparesis and global delay at 18–24 months, and one had extensive encephalomalacia on brain MRI during follow-up. Conclusions Of the selected precooling variables, only the 10 min Apgar score is independently associated with death despite therapeutic cooling in infants with HIE. Infants who remain asystolic at 10 min and beyond are unlikely to survive despite cooling, and the rare survivor is likely to have severe disability.

Background Whole body cooling (WBC) cools different parts of the brain uniformly, and selective head cooling (SHC) cools the superficial brain more than the deeper brain structures. In this study, the authors hypothesised that the hypoxic–ischaemic lesions on brain MRI following cooling would differ between modalities of cooling. Aim To compare the frequency, distribution and severity of hypoxic–ischaemic lesions on brain MRI between SHC or WBC. Methods In a single centre retrospective study, 83 infants consecutively cooled using either SHC (n=34) or WBC (n=49) underwent brain MRI. MRI images were evaluated by a neuroradiologist, who was masked to clinical parameters and outcomes, using a basal ganglia/watershed (BG/W) scoring system. Higher scores (on a scale of 0 to 4) were given for more extensive injury. The score has been reported to be predictive of neuromotor and cognitive outcome at 12 months. Results The two groups were similar for severity of depression as assessed by a history of an intrapartum sentinel event, Apgar scores, initial blood pH and base deficit and early neurological examination. However, abnormal MRI was more frequent in the SHC group (SHC 25 of 34, 74% vs WBC 22 of 49, 45%; p=0.0132, OR 3.4, 95% CI 1.3 to 8.8). Infants from the SHC group also had more severe hypoxic–ischaemic lesions (median BG/W score: SHC 2 vs WBC 0, p=0.0014). Conclusions Hypoxic–ischaemic lesions on brain MRI following therapeutic cooling were more frequent and more severe with SHC compared with WBC.

Background: In neonatal rats, early post-hypoxia-ischemia (HI) administration of the omega-3 fatty acid docosahexaenoic acid (DHA) improves sensorimotor function, but does not attenuate brain damage. Objective: To determine if DHA administration in addition to hypothermia, now standard care for neonatal asphyxial brain injury, attenuates post-HI damage and sensorimotor deficits. Methods: Seven-day-old (P7) rats underwent right carotid ligation followed by 90 min of 8% O 2 exposure. Fifteen minutes later, pups received injections of DHA 2.5 mg/kg (complexed to 25% albumin) or equal volumes of albumin. After a 1-hour recovery, pups were cooled (3 h, 30°C). Sensorimotor and pathology outcomes were initially evaluated on P14. In subsequent experiments, sensorimotor function was evaluated on P14, P21, and P28; histopathology was assessed on P28. Results: At P14, left forepaw function scores (normal: 20/20) were near normal in DHA + hypothermia-treated animals (mean ± SD 19.7 ± 0.7 DHA + hypothermia vs. 12.7 ± 3.5 albumin + hypothermia, p < 0.0001) and brain damage was reduced (mean ± SD right hemisphere damage 38 ± 17% with DHA + hypothermia vs. 56 ± 15% with albumin + hypothermia, p = 0.003). Substantial improvements on three sensorimotor function measures and reduced brain damage were evident up to P28. Conclusion: Unlike post-HI treatment with DHA alone, treatment with DHA + hypothermia produced both sustained functional improvement and reduced brain damage after neonatal HI.