Bronchopulmonary dysplasia and neurobehavioural outcomes at birth and 2 years in infants born before 30 weeks.

OBJECTIVE: To identify neurobehavioural risks in preterm infants with bronchopulmonary dysplasia (BPD) prior to hospital discharge. DESIGN AND PATIENTS: Longitudinal study of 676 newborns born before 30 weeks of gestation. SETTING: Nine university NICUs affiliated with six universities. All were Vermont Oxford Network (VON) participants. PATIENTS AND INTERVENTIONS: Infants were enrolled in the Neonatal Neurobehavior and Outcomes in Very Preterm Infants Study from April 2014 to June 2016. Prospective medical record reviews, VON definitions and criteria, and maternal interviews were used to collect maternal and neonatal medical variables and socioenvironmental data. MAIN OUTCOME MEASURES: NICU Network Neurobehavioral Scale (NNNS) at the time of hospital discharge; Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III) and Gross Motor Function Classification System at 2 years' corrected age. RESULTS: Infants with moderate/severe BPD were less attentive (Wald χ2 9.68, p=0.008), more lethargic (Wald χ2 9.91, p=0.007), with increased non-optimal reflexes (Wald χ2 7.37, p=0.025). Infants with moderate/severe BPD were more likely to have Bayley-III language and motor scores <85 (adjusted OR (aOR) 1.74, 95% CI 1.06 to 2.85, and aOR 2.06, 95% CI 1.10 to 3.85). Infants with both moderate/severe and mild BPD were more likely to have a cerebral palsy diagnosis (aOR 2.96, 95% CI 1.34 to 6.54, and aOR 2.81, 95% CI 1.32 to 5.99). CONCLUSIONS: BPD severity presents risks for poor neurodevelopment at NICU discharge and at age 2 years. Early identification of poorly regulated behaviour can provide critical information for early preventive and targeted interventions with potential to improve long-term outcomes.

The antioxidant Rutin counteracts the pathological impact of α-synuclein on the enteric nervous system in vitro.

Motoric disturbances in Parkinson's disease (PD) derive from the loss of dopaminergic neurons in the substantia nigra. Intestinal dysfunctions often appear long before manifestation of neuronal symptoms, suggesting a strong correlation between gut and brain in PD. Oxidative stress is a key player in neurodegeneration causing neuronal cell death. Using natural antioxidative flavonoids like Rutin, might provide intervening strategies to improve PD pathogenesis. To explore the potential effects of micro (mRutin) compared to nano Rutin (nRutin) upon the brain and the gut during PD, its neuroprotective effects were assessed using an in vitro PD model. Our results demonstrated that Rutin inhibited the neurotoxicity induced by A53T α-synuclein (Syn) administration by decreasing oxidized lipids and increasing cell viability in both, mesencephalic and enteric cells. For enteric cells, neurite outgrowth, number of synaptic vesicles, and tyrosine hydroxylase positive cells were significantly reduced when treated with Syn. This could be reversed by the addition of Rutin. nRutin revealed a more pronounced result in all experiments. In conclusion, our study shows that Rutin, especially the nanocrystals, are promising natural compounds to protect neurons from cell death and oxidative stress during PD. Early intake of Rutin may provide a realizable option to prevent or slow PD pathogenesis.

Parkinson mice show functional and molecular changes in the gut long before motoric disease onset.

BACKGROUND: There is increasing evidence that Parkinson's disease (PD) might start in the gut, thus involving and compromising also the enteric nervous system (ENS). At the clinical onset of the disease the majority of dopaminergic neurons in the midbrain is already destroyed, so that the lack of early biomarkers for the disease represents a major challenge for developing timely treatment interventions. Here, we use a transgenic A30P-α-synuclein-overexpressing PD mouse model to identify appropriate candidate markers in the gut before hallmark symptoms begin to manifest. METHODS: Based on a gait analysis and striatal dopamine levels, we defined 2-month-old A30P mice as pre-symptomatic (psA30P), since they are not showing any motoric impairments of the skeletal neuromuscular system and no reduced dopamine levels, but an intestinal α-synuclein pathology. Mice at this particular age were further used to analyze functional and molecular alterations in both, the gastrointestinal tract and the ENS, to identify early pathological changes. We examined the gastrointestinal motility, the molecular composition of the ENS, as well as the expression of regulating miRNAs. Moreover, we applied A30P-α-synuclein challenges in vitro to simulate PD in the ENS. RESULTS: A retarded gut motility and early molecular dysregulations were found in the myenteric plexus of psA30P mice. We found that i.e. neurofilament light chain, vesicle-associated membrane protein 2 and calbindin 2, together with the miRNAs that regulate them, are significantly altered in the psA30P, thus representing potential biomarkers for early PD. Many of the dysregulated miRNAs found in the psA30P mice are reported to be changed in PD patients as well, either in blood, cerebrospinal fluid or brain tissue. Interestingly, the in vitro approaches delivered similar changes in the ENS cultures as seen in the transgenic animals, thus confirming the data from the mouse model. CONCLUSIONS: These findings provide an interesting and novel approach for the identification of appropriate biomarkers in men.

Evaluation of the Neonate with Seizures.

Neonatal seizures are common, occurring in 2 to 5 of 1,000 live births in the United States. The neonatal brain is thought to be predisposed toward seizures due to a combination of excessive excitatory and deficient inhibitory neuronal activity. The seizures tend to be focal or multifocal without secondary generalization, resulting in subtle seizure appearance. There are five main categories of neonatal seizures: focal clonic, focal tonic, myoclonic, subtle, and generalized tonic. An electroencephalogram is recommended to diagnose and treat neonatal seizures due to poor reliability of the clinical examination. Causes of neonatal seizures are broad, including trauma, structural brain anomalies, infections, metabolic disorders, drug withdrawal or intoxication, and neonatal epilepsy syndromes. Treatment of neonatal seizures involves management of cardiorespiratory status, correction of metabolic derangements, and antiepileptics as needed. The most common antiepileptics used in neonates are phenobarbital, levetiracetam, and fosphenytoin. The long-term risk of neurodevelopmental disability varies depending upon the etiology of neonatal seizures. Close attention to developmental milestones and neurology follow-up is recommended for all neonates with seizures. [Pediatr Ann. 2020;49(7):e292-e298.].

Postoperative Care Pathways Following Lumbar Total Disc Replacement: Results of a Modified Delphi Approach.

STUDY DESIGN: A modified Delphi method was used to establish consensus. Subject matter experts were invited to participate as the expert panel. Best practice statements were distributed to the panel. Panel members were asked to mark "agree" or "disagree" after a series of statements during several rounds until either consensus could be obtained or the practice method was deemed unable to achieve consensus. OBJECTIVE: Lumbar total disc replacement (TDR) is acknowledged as an alternative to spinal fusion in appropriately selected patients. There is a lack of unanimity on the appropriate postoperative patient protocols and rehabilitation expectations for the procedure. The long-term viability of Lumbar TDR, further adoption in the community setting and specific patient outcomes are contingent on the existence of appropriate postoperative recovery programs. SUMMARY OF BACKGROUND DATA: Currently there are no established methods for postoperative care following lumbar TDR. Establishing a postoperative clinical pathway algorithm may improve patient outcomes with respect to lumbar TDR. METHOD: A lumbar TDR expert panel of 22 spine surgeons employed a modified Delphi method to drive consensus on postoperative care following single-level Lumbar TDR. The panel first reviewed literature and guidelines relevant to postoperative care following lumbar TDR. Panel members considered 21 survey questions intended to determine "standard-practice" postoperative care recommendations for patients who have undergone lumbar TDR for the initial recovery phase (0-4 wk) and rehabilitation (4-20 wk). Each panel member participated in a round of anonymous voting followed by a group discussion. Consensus was defined as 80% agreement or higher among the respondents. RESULTS: Consensus was achieved in 11 of the 21 survey questions. There was a high degree of consensus around the key goals for both the initial recovery and rehabilitation phases, ceased use of narcotics for pain management by 4 weeks postoperative, unrestricted walking immediately following surgery, timelines for physical therapy (within 2-4 wk) and return to work based on level of activity (as early as 1 wk postoperative). Lack of agreement included the use of back bracing and timing of postoperative visits. Generally, panel members felt that patient expectations regarding return to function were different following lumbar TDR versus fusion and warrant further study. CONCLUSION: Surgeon and patient alignment around postoperative expectations may significantly affect the long-term results of lumbar TDR. This surgeon consensus study found agreement for immediate postoperative ambulation, rapid reduction in opioids within the first month, and early return to work. When expectations are appropriately set with patients preoperatively, both provider and patient have shared goals in the return-to-function process. LEVEL OF EVIDENCE: 5.

Impact of protein kinase CK2 inhibitors on proliferation and differentiation of neural stem cells.

BACKGROUND: Protein kinases play central roles in cell and tissue development. Protein kinase CK2, an ubiquitously expressed serine/threonine kinase has severe impacts on embryo- and spermatogenesis. Since its role in neurogenesis has so far only been investigated in very few studies, we analysed the role of CK2 in neural stem cells by using two specific inhibitors. METHODS: Neural stem cells were isolated from the subventricular zone of neonatal mice, using a neurosphere approach. Proliferation of the neurospheres, as well as their differentiation was investigated with and without inhibition of CK2. Changes in proliferation were assessed by counting the number and measuring the diameter of the neurospheres. Furthermore, the absolute cell numbers within the neurospheres were estimated. Differentiation was induced by retinoic acid in single cells after dissociation of the neurospheres. CK2 was inhibited at consecutive time points after induction of the differentiation process. RESULTS: CK2 inhibition reduced the amount and size of proliferating neurospheres dose dependently. Adding the CK2 inhibitor CX-4945 at the start of differentiation we observed a dose-dependent effect of CX-4945 on cell viability and glia cell differentiation. Adding quinalizarin, a second CK2 inhibitor, at the start of differentiation led to an elevated level of apoptosis, which was accompanied by a reduced neural differentiation. Adding the CK2 inhibitors at 72 h after the start of differentiation had no effect on stem cell differentiation. Conclusion: Inhibition of CK2 influences early gliogenesis in a time point and concentration dependent manner. GENERAL SIGNIFICANCE: The use of a CK2 inhibitor significantly affects the neural stem cell niche.

Maintenance of the enteric stem cell niche by bacterial lipopolysaccharides? Evidence and perspectives.

The enteric nervous system (ENS) has to respond to continuously changing microenvironmental challenges within the gut and is therefore dependent on a neural stem cell niche to keep the ENS functional throughout life. In this study, we hypothesize that this stem cell niche is also affected during inflammation and therefore investigated lipopolysaccharides (LPS) effects on enteric neural stem/progenitor cells (NSPCs). NSPCs were derived from the ENS and cultured under the influence of different LPS concentrations. LPS effects upon proliferation and differentiation of enteric NSPC cultures were assessed using immunochemistry, flow cytometry, western blot, Multiplex ELISA and real-time PCR. LPS enhances the proliferation of enteric NSPCs in a dose-dependent manner. It delays and modifies the differentiation of these cells. The expression of the LPS receptor toll-like receptor 4 on NSPCs could be demonstrated. Moreover, LPS induces the secretion of several cytokines. Flow cytometry data gives evidence for individual subgroups within the NSPC population. ENS-derived NSPCs respond to LPS in maintaining at least partially their stem cell character. In the case of inflammatory disease or trauma where the liberation and exposure to LPS will be increased, the expansion of NSPCs could be a first step towards regeneration of the ENS. The reduced and altered differentiation, as well as the induction of cytokine signalling, demonstrates that the stem cell niche may take part in the LPS-transmitted inflammatory processes in a direct and defined way.

Long-term effects of traumatic injuries to incisors and periodontal tissues during childhood: a retrospective study.

AIM: The purpose of this study was to investigate the incidence of dentoalveolar growth disturbances, loss of teeth and esthetic impairment after the end of growth following traumatic injuries to incisors and periodontal tissues during childhood. MATERIALS AND METHODS: 41 patients having sustained dentoalveolar trauma before age 10 and who were now at least aged 16 years, and a total of 68 traumatized teeth were documented by clinical examination, dental casts and photographs. We determined the three-dimensional position of the traumatized teeth on the casts, as well as the traumatized teeth's pulp sensibility, percussive sound and sensitivity, shape and color. RESULTS: 82% of the traumatized teeth were in the upper dentition. 45% of the traumatized teeth experienced subluxation, nearly 30% luxation, 16% avulsion. At the time of the follow-up examination (mean 17.0 years post-trauma), 57% of the traumatized teeth were still in situ. Immediately after trauma 7.4% of the teeth were lost; up to 16 years post-trauma 35.6% of the teeth were lost because of failed root canal filling, root resorption or ankylosis. We observed no functional deviations. Dentoalveolar growth disturbances were rare. Three teeth were markedly discolored. CONCLUSION: Following dentoalveolar trauma during childhood, negative effects on growth, function and esthetics can be minimized by timely interdisciplinary treatment and by follow-up controls until the end of growth to achieve an outcome satisfying both the patient and clinician.

The clinical application of hyaluronic acid in gingivitis therapy.

OBJECTIVE: The efficacy of a topical application of hyaluronic acid (HA) was tested for treating gingivitis. METHOD AND MATERIALS: Sixty nonsmoking outpatients in good general condition, with clinical signs of gingivitis, were included in the study. Forty patients (HA group, 20 men, 20 women; age: 32.8 +/- 11.3 years) used a spray containing HA 5 times daily over a period of 1 week. The control group consisted of 20 patients (10 men, 10 women; age: 31.3 +/- 9.3 years). The clinical parameters DMF-T (decayed, missed, filled teeth) index, approximal plaque index, sulcus bleeding index, papilla bleeding index, and gingival crevicular fluid were measured at baseline (T1), after 3 days (T2), and after 7 days (T3). RESULTS: A reduction in the sulcus bleeding index of the HA group (T1: 72.9 +/- 19.5%) to 50.3 +/- 21.1% was noted at T2, and at T3 the sulcus bleeding index was 40.7 +/- 23.0%. The papilla bleeding index values of the HA group were 1.6 at T1, 1.0 at T2, and 0.7 at T3. The gingival crevicular fluid showed significant reductions in the HA group. At T1 the recorded mean value was 16.3, at T2 it was 11.8, and at T3 it was 7.9. Only insignificant changes were observed in the respective indices of the control group. There were no significant alterations in the plaque values of either group throughout the study period. CONCLUSION: The results obtained by this study demonstrate that the topical application of an HA-containing preparation represents a potentially useful adjunct in the therapy of gingivitis, although its use does not diminish the need for plaque reduction as a primary therapeutic measure.