Outcomes for Pediatric Oncology and Hematopoietic Stem Cell Transplantation Patients Who Undergo Tracheostomy Placement: A Pediatric Health Information System Database Cohort Study, 2009-2020.

OBJECTIVES: To describe the epidemiology, surgical complications, and long-term outcomes after tracheostomy in pediatric oncology and/or hematopoietic stem cell transplantation (HSCT) patients in U.S. Children's Hospitals. DESIGN: Retrospective cohort from the Pediatric Health information System (PHIS) database, 2009-2020. SETTING: The PHIS dataset incorporates data from 48 pediatric hospitals in the Children's Hospital Association. PATIENTS: Patients 0-21 years old with an oncologic diagnosis and/or underwent HSCT, received a tracheostomy, and were discharged from hospital between January 1, 2009, and December 31, 2020. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: There were 1061 patients included in the dataset, and 217 (20.5%) had undergone HSCT. The annual prevalence in tracheostomy usage did not change over the study period. The majority of patients (62.2%) underwent tracheostomy early (< 30 d) in the admission and those who underwent the procedure later (> 90 d) had a significant increase in mortality (52.6% vs. 17.6%; p < 0.001) and mechanical ventilation (MV) at discharge (51.9% vs. 24.5%; p < 0.001) compared with the early tracheostomy patients. Complications reported included tracheostomy site bleeding (< 1%) and infection (24%). The overall rate of MV at discharge was 32.6% and significantly associated with chronic lung (adjusted odds ratio [OR], 1.54; 95% CI, 1.03-2.32) and acute lung disease (OR, 2.18; 95% CI, 1.19-3.98). The overall rate of mortality was 19.6% within the cohort and significantly associated with HSCT (OR, 5.45; 95% CI, 3.88-7.70), diagnosis of sepsis (OR, 2.09; 95% CI, 1.28-3.41), and requirement for renal replacement therapy (OR, 2.76; 95% CI, 1.58-4,83). CONCLUSIONS: This study demonstrated a static prevalence of tracheostomy placement in the cohort population relative to the increasing trends in other reported groups. Regardless of underlying diagnosis, the study patients incurred substantial morbidity and mortality. However, tracheostomy specific complication rates were comparable with that of the general pediatric population and were not associated with increased odds of mortality within this population.

Results in clinical practice in the treatment of severe eosinophilic asthma with mepolizumab: a real-life study.

OBJECTIVE: Add-on therapy with monoclonal antibodies is the recommended therapy for severe asthmatic patients refractory to maintenance treatment. In randomized control trials, mepolizumab reduced the number of exacerbations, the need of oral corticosteroids (OCS), increased asthma control, and lung function in a population of uncontrolled severe eosinophilic asthmatic patients. In this piece of work, we aimed to assess mepolizumab efficacy and safety in a cohort of patients with severe eosinophilic asthma in real-life conditions. METHODS: A retrospective study was carried out at eight hospitals from Asturias (Spain). The sample included patients treated with mepolizumab from 1 January 2016 to 31 March 2019. Demographic and clinical variables were collected, including OCS use, asthma control, lung function, and exacerbation rate. RESULTS: Sixty-nine patients (72% women) with mean age 56 ± 13 years were included. Annual exacerbation rate decreased from 4.7 (SD 3.7) to 1.3 (SD 2.5) (p < 0.001). The number of patients requiring OCS treatment decreased from 25 patients (36%, mean prednisone dose = 18 mg/day) to 13 patients (19%, mean prednisone dose = 9 mg/day) (p < 0.001). Twelve patients (48%) stopped OCS treatment. Forced expired volume in one second (FEV1) as percentage increased from 68% (SD 20) to 76% (SD 21) (p < 0.001). Fifty-six patients (81%) were considered responders to mepolizumab. No serious adverse events were detected during the study period. CONCLUSIONS: Overall, this study demonstrates mepolizumab efficacy and safety in a cohort of patients with uncontrolled severe eosinophilic asthma in routine clinical practice.

Outcomes for Children With Pulmonary Hypertension Undergoing Tracheostomy Placement: A Multi-Institutional Analysis.

OBJECTIVES: To describe epidemiology, interventions, outcomes, and the health services experience for a cohort of children with pulmonary hypertension (PH) who underwent tracheostomy placement and to identify risk factors for inhospital mortality and 30-day readmissions. DESIGN: Retrospective cohort study of the Pediatric Health Information System database. SETTING: Thirty-seven freestanding U.S. children's hospitals. PATIENTS: Patients 31 days to 21 years old who were discharged from the hospital between January 1, 2009, and December 31, 2017, with a diagnosis of primary or secondary PH, and who underwent tracheostomy placement. Outcomes were examined over a 2-year period from the time of discharge from the index encounter. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: There were 793 patients with PH who underwent tracheostomy placement. The overall inhospital mortality rate was 23.7%. Secondary PH due to congenital heart disease (CHD) was significantly associated with overall inhospital mortality (adjusted odds ratio [OR], 2.36; 95% CI, 1.38-4.04). The rate of 30-day readmissions for patients over the 2-year follow-up period was 33.3%. Tracheostomy during the index encounter and the diagnosis of secondary PH due to CHD were significantly associated with lower rates of 30-day readmissions (adjusted OR, 0.34; 95% CI, 0.19-0.61; and adjusted OR, 0.43; 95% CI, 0.24-0.77, respectively). CONCLUSIONS: In the context of expanding utilization of tracheostomy and long-term ventilation, children with PH are among the highest risk cohorts for extended and repeated hospitalization and death. Tracheostomy placement during the index encounter was associated with fewer 30-day readmissions over the 2-year follow-up period. Further understanding of which subgroups may benefit from earlier intervention and which subgroups are at highest risk may offer important clinical insight when considering optimal timing of tracheostomy and may enhance informed decision-making for all stakeholders.

Disease correction by AAV-mediated gene therapy in a new mouse model of mucopolysaccharidosis type IIID.

Gene therapy is a promising therapeutic alternative for Lysosomal Storage Disorders (LSD), as it is not necessary to correct the genetic defect in all cells of an organ to achieve therapeutically significant levels of enzyme in body fluids, from which non-transduced cells can uptake the protein correcting their enzymatic deficiency. Animal models are instrumental in the development of new treatments for LSD. Here we report the generation of the first mouse model of the LSD Muccopolysaccharidosis Type IIID (MPSIIID), also known as Sanfilippo syndrome type D. This autosomic recessive, heparan sulphate storage disease is caused by deficiency in N-acetylglucosamine 6-sulfatase (GNS). Mice deficient in GNS showed lysosomal storage pathology and loss of lysosomal homeostasis in the CNS and peripheral tissues, chronic widespread neuroinflammation, reduced locomotor and exploratory activity and shortened lifespan, a phenotype that closely resembled human MPSIIID. Moreover, treatment of the GNS-deficient animals with GNS-encoding adeno-associated viral (AAV) vectors of serotype 9 delivered to the cerebrospinal fluid completely corrected pathological storage, improved lysosomal functionality in the CNS and somatic tissues, resolved neuroinflammation, restored normal behaviour and extended lifespan of treated mice. Hence, this work represents the first step towards the development of a treatment for MPSIIID.

Methenamine's journey of 160 years: Repurposal of an old urinary antiseptic for treatment and hypoxic radiosensitization of cancers and glioblastoma.

Methenamine (hexamethylenetetramine, hexamine, urotropine) is a compound discovered in 1859, which is still currently being used as a urinary antiseptic. Methenamine is highly soluble in water and polar solvents, and its molecular constitution is similar to adamantane compounds with tetrahedral cage like structure. In acidic conditions, methenamine decomposes to formaldehyde and ammonia. Recently, methenamine has gained a renewal of interest due to antibiotic-resistant bacteria urinary tract infections; interestingly, bacteria cannot gain resistance to formaldehyde. In 1968, David and Burkitt reported remarkable regression of four Burkitt Lymphoma patients in eight subjects who were treated with septicemine (a solution containing 6.3 g of methenamine iodomethylate and 1 g of methenamine sodium benzoate in 100 cc distilled water). Unfortunately, these striking observations did not gain interest in the medical community; despite experimental models that showed that methenamine synergized with hyperthermia, radiation, and chemotherapy to block cancer growth. As the hypoxic core of tumours have an acidic pH, it would be plausible to expect that methenamine would selectively target dormant, non-proliferative, and treatment-resistant cancer clones in large tumours. Moreover, previous data suggests that methenamine can be safely used intravenously and for treatment of infections of the central nervous system. It may therefore be an effective adjuvant in treatment of systemic cancers and glioblastoma.

From epidemiology and neurometabolism to treatment: Vitamin D in pathogenesis of glioblastoma Multiforme (GBM) and a proposal for Vitamin D + all-trans retinoic acid + Temozolomide combination in treatment of GBM.

Here we review tumoricidal efficacy of Vitamin D analogues in glioblastoma multiforme (GBM) and potential synergisms with retinoic acid and temozolomide based on epidemiological and cellular studies. Epidemiological data suggest that winter birth is associated with higher risk of GBM, and GBM debulking in the winter enhanced mortality, which may relate with lower exposure to sunlight essential to convert cholecalciferol to Vitamin D. Comparative studies on blood bank specimens revealed that higher prediagnosis levels of calcidiol are associated with lower risk of GBM in elderly men. Supplemental Vitamin D reduced mortality in GBM patients in comparison to nonusers. Expression of Vitamin D Receptor is associated with a good prognosis in GBM. Conversely, Vitamin D increases glial tumor synthesis of neutrophins NGF and NT-3, the low affinity neurotrophin receptor p75NTR, IL-6 and VEGF, which may enhance glioma growth. Antitumor synergisms between temozolomide and Vitamin D and Vitamin D with Vitamin A derivatives were observed. Hence, we hypothesize that Calcitriol + ATRA (All-Trans Retinoic Acid) + Temozolomide - CAT combination might be a safer approach to benefit from Vitamin D in the management of high-grade glial tumors. Adding acetazolomide to this protocol may reduce the risk of pseudotumor cerebri, as both Vitamin D and Vitamin A excess may cause intracranial hypertension; this approach may provide further benefit as acetazolomide also exhibits anticancer activity.

Can shoulder range of movement be measured accurately using the Microsoft Kinect sensor plus Medical Interactive Recovery Assistant (MIRA) software?

BACKGROUND: This study compared the accuracy of measuring shoulder range of movement (ROM) with a simple laptop-sensor combination vs. trained observers (shoulder physiotherapists and shoulder surgeons) using motion capture (MoCap) laboratory equipment as the gold standard. METHODS: The Microsoft Kinect sensor (Microsoft Corp., Redmond, WA, USA) tracks 3-dimensional human motion. Ordinarily used with an Xbox (Microsoft Corp.) video game console, Medical Interactive Recovery Assistant (MIRA) software (MIRA Rehab Ltd., London, UK) allows this small sensor to measure shoulder movement with a standard computer. Shoulder movements of 49 healthy volunteers were simultaneously measured by trained observers, MoCap, and the MIRA device. Internal rotation was assessed with the shoulder abducted 90° and external rotation with the shoulder adducted. Visual estimation and MIRA measurements were compared with gold standard MoCap measurements for agreement using Bland-Altman methods. RESULTS: There were 1670 measurements analyzed. The MIRA evaluations of all 4 cardinal shoulder movements were significantly more precise, with narrower limits of agreement, than the measurements of trained observers. MIRA achieved ±11° (95% confidence interval [CI], 8.7°-12.6°) for forward flexion vs. ±16° (95% CI, 14.6°-17.6°) by trained observers. For abduction, MIRA showed ±11° (95% CI, 8.7°-12.8°) against ±15° (95% CI, 13.4°-16.2°) for trained observers. MIRA attained ±10° (95% CI, 8.1°-11.9°) during external rotation measurement, whereas trained observers only reached ±21° (95% CI, 18.7°-22.6°). For internal rotation, MIRA achieved ±9° (95% CI, 7.2°-10.4°), which was again better than TOs at ±18° (95% CI, 16.0°-19.3°). CONCLUSIONS: A laptop combined with a Microsoft Kinect sensor and the MIRA software can measure shoulder movements with acceptable levels of accuracy. This technology, which can be easily set up, may also allow precise shoulder ROM measurement outside the clinic setting.

Neonatal Feeding Behavior as a Complex Dynamical System.

The requirements of evidence-based practice in 2017 are motivating new theoretical foundations and methodological tools for characterizing neonatal feeding behavior. Toward that end, this article offers a complex dynamical systems perspective. A set of critical concepts from this perspective frames challenges faced by speech-language pathologists and allied professionals: when to initiate oral feeds, how to determine the robustness of neonatal breathing during feeding and appropriate levels of respiratory support, what instrumental assessments of swallow function to use with preterm neonates, and whether or not to introduce thickened liquids. In the near future, we can expect vast amounts of new data to guide evidence-based practice. But unless practitioners are able to frame these issues in a systems context larger than the individual child, the availability of "big data" will not be effectively translated to clinical practice.

MANBA, CXCR5, SOX8, RPS6KB1 and ZBTB46 are genetic risk loci for multiple sclerosis.

A recent genome-wide association study reported five loci for which there was strong, but sub-genome-wide significant evidence for association with multiple sclerosis risk. The aim of this study was to evaluate the role of these potential risk loci in a large and independent data set of ≈ 20,000 subjects. We tested five single nucleotide polymorphisms rs228614 (MANBA), rs630923 (CXCR5), rs2744148 (SOX8), rs180515 (RPS6KB1), and rs6062314 (ZBTB46) for association with multiple sclerosis risk in a total of 8499 cases with multiple sclerosis, 8765 unrelated control subjects and 958 trios of European descent. In addition, we assessed the overall evidence for association by combining these newly generated data with the results from the original genome-wide association study by meta-analysis. All five tested single nucleotide polymorphisms showed consistent and statistically significant evidence for association with multiple sclerosis in our validation data sets (rs228614: odds ratio = 0.91, P = 2.4 × 10(-6); rs630923: odds ratio = 0.89, P = 1.2 × 10(-4); rs2744148: odds ratio = 1.14, P = 1.8 × 10(-6); rs180515: odds ratio = 1.12, P = 5.2 × 10(-7); rs6062314: odds ratio = 0.90, P = 4.3 × 10(-3)). Combining our data with results from the previous genome-wide association study by meta-analysis, the evidence for association was strengthened further, surpassing the threshold for genome-wide significance (P < 5 × 10(-8)) in each case. Our study provides compelling evidence that these five loci are genuine multiple sclerosis susceptibility loci. These results may eventually lead to a better understanding of the underlying disease pathophysiology.

Pediatric Respiratory Syncytial Virus Hospitalizations and Respiratory Support After the COVID-19 Pandemic.

Importance: After the COVID-19 pandemic, there was a surge of pediatric respiratory syncytial virus (RSV) infections, but national data on hospitalization and intensive care unit use and advanced respiratory support modalities have not been reported. Objective: To analyze demographics, respiratory support modes, and clinical outcomes of children with RSV infections at tertiary pediatric hospitals from 2017 to 2023. Design, Setting, and Participants: This cross-sectional study evaluated children from 48 freestanding US children's hospitals registered in the Pediatric Health Information System (PHIS) database. Patients 5 years or younger with RSV from July 1, 2017, to June 30, 2023, were included. Each season was defined from July 1 to June 30. Prepandemic RSV seasons included 2017 to 2018, 2018 to 2019, and 2019 to 2020. The postpandemic season was delineated as 2022 to 2023. Exposure: Hospital presentation with RSV infection. Main Outcomes and Measures: Data on emergency department presentations, hospital or intensive care unit admission and length of stay, demographics, respiratory support use, mortality, and cardiopulmonary resuscitation were analyzed. Postpandemic season data were compared with prepandemic seasonal averages. Results: A total of 288 816 children aged 5 years or younger (median [IQR] age, 8.9 [3.3-21.5] months; 159 348 [55.2%] male) presented to 48 US children's hospitals with RSV from July 1, 2017, to June 30, 2023. Respiratory syncytial virus hospital presentations increased from 39 698 before the COVID-19 pandemic to 94 347 after the pandemic (P < .001), with 86.7% more hospitalizations than before the pandemic (50 619 vs 27 114; P < .001). In 2022 to 2023, children were older (median [IQR] age, 11.3 [4.1-26.6] months vs 6.8 [2.6-16.8] months; P < .001) and had fewer comorbidities (17.6% vs 21.8% of hospitalized patients; P < .001) than during prepandemic seasons. Advanced respiratory support use increased 70.1% in 2022 to 2023 (9094 vs 5340; P < .001), and children requiring high-flow nasal cannula (HFNC) or noninvasive ventilation (NIV) were older than during prepandemic seasons (median [IQR] age for HFNC, 6.9 [2.7-16.0] months vs 4.6 [2.0-11.7] months; for NIV, 6.0 [2.1-16.5] months vs 4.3 [1.9-11.9] months). Comorbid conditions were less frequent after the pandemic across all respiratory support modalities (HFNC, 14.9% vs 19.1%, NIV, 22.0% vs 28.5%, invasive mechanical ventilation, 30.5% vs 38.0%; P < .001). Conclusions and Relevance: This cross-sectional study identified a postpandemic pediatric RSV surge that resulted in markedly increased hospital volumes and advanced respiratory support needs in older children with fewer comorbidities than prepandemic seasons. These clinical trends may inform novel vaccine allocation to reduce the overall burden during future RSV seasons.

Safety of the immediate use of nonsteroidal anti-inflammatory drugs after adult craniotomy for tumor.

OBJECTIVE: Poor pain control has a negative impact on postoperative recovery and patient satisfaction. However, overzealous pain management, particularly with opioids, can confound serial neurological assessments, increase morbidity, and predispose patients to long-term dependence. Nonsteroidal anti-inflammatory drugs (NSAIDs) are effective in treating postoperative pain and can limit opioid intake, but their use has been limited in patients undergoing craniotomy for brain tumor resection due to concerns of an increased hemorrhage risk. Herein, the authors aim to 1) address the safety of NSAID use in the immediate postoperative setting and 2) determine whether NSAID administration decreases opioid use following craniotomy for tumor resection in adult patients. METHODS: The authors conducted a retrospective cohort study of patients 18 years and older with an estimated glomerular filtration rate ≥ 60 ml/min/body surface area who had undergone craniotomy for tumor resection at their institution between 2019 and 2021. NSAID use in the first 48 hours following surgery was recorded. Primary outcomes were postoperative hemorrhage requiring a return to the operating room before hospital discharge and within 30 days of surgery. Secondary outcomes were more-than-minimal hemorrhage that did not require reoperation, acute kidney injury, and total opioid use within 48 hours after craniotomy. RESULTS: Among 1765 reviewed patient records, 1182 were eligible for inclusion in this analysis. Amid these records were 114 patients (9.6%) who had received at least one dose of an NSAID within 48 hours of their craniotomy. Four (0.3%) patients experienced bleeding requiring a return to operating room, one of whom was from the NSAID-treated group (RR 3.12, 95% CI 0.33-29.77, p = 0.30). No significant difference in nonoperative intracranial hemorrhage (RR 1.34, 95% CI 0.54-3.35, p = 0.53), postoperative acute kidney injury, or clinically significant extracranial bleeding was found between the NSAID and no-NSAID groups. Patients in the NSAID group had significantly higher oral morphine equivalent use (median 68 vs 30, p < 0.001). CONCLUSIONS: Postoperative NSAID use following craniotomy for tumor resection was not associated with an increased risk of hemorrhage requiring a return to the operating room. The authors noted higher opioid use in the patients treated with NSAIDs, which may reflect underlying reasons for the decision to treat patients with NSAIDs in the immediate postoperative period. These data warrant further investigation of NSAIDs as a safe, opioid-sparing postoperative pain management strategy in patients with normal kidney function who are undergoing intracranial tumor resection.

Mechanical hyperalgesia and neuropathic pain qualities impart risk for chronic postoperative pain after total knee replacement.

Total knee replacement (TKR) is the gold-standard treatment for end-stage chronic osteoarthritis pain, yet many patients report chronic postoperative pain after TKR. The search for preoperative predictors for chronic postoperative pain following TKR has been studied with inconsistent findings. This study investigates the predictive value of quantitative sensory testing (QST) and PainDETECT for postoperative pain 3, 6, and 12 months post-TKR. We assessed baseline and postoperative (3- and 6-months) QST measures in 77 patients with knee OA (KOA) and 41 healthy controls, along with neuropathic pain scores in patients (PainDETECT). QST parameters included pressure pain pressure threshold (PPT), pain tolerance threshold (PTT), conditioned pain modulation (CPM), and temporal summation (TS) using cuff algometry, alongside mechanical hyperalgesia, and mechanical temporal summation to repeated pinprick stimulation. Compared to healthy controls, KOA patients at baseline demonstrated hyperalgesia to pinprick stimulation at the medial OA-affected knee and cuff pressure on the ipsilateral calf. Lower cuff algometry PTT and mechanical pinprick hyperalgesia were associated with baseline KOA pain intensity. Moreover, baseline pinprick pain hyperalgesia explained 25% of variance in pain intensity 12 months post-TKR and preoperative neuropathic pain scores also captured 30% and 20% of the variance in postoperative pain at 6- and 12-months, respectively. A decrease in mechanical pinprick hyperalgesia from before surgery to 3 months after TKR was associated with lower postoperative pain at the 12 months post-TKR follow-up, and vice-versa. Our findings suggest that preoperative pinprick hyperalgesia and PainDETECT neuropathic-like pain symptoms show predictive value for the development of chronic post-TKR pain.

Prognostic value of preoperative mechanical hyperalgesia and neuropathic pain qualities for postoperative pain after total knee replacement.

BACKGROUND: Total knee replacement (TKR) is the gold standard treatment for end-stage chronic osteoarthritis pain, yet many patients report chronic postoperative pain after TKR. The search for preoperative predictors for chronic postoperative pain following TKR has been studied with inconsistent findings. METHODS: This study investigates the predictive value of quantitative sensory testing (QST) and PainDETECT for postoperative pain 3, 6 and 12 months post-TKR. We assessed preoperative and postoperative (3 and 6 months) QST measures in 77 patients with knee OA (KOA) and 41 healthy controls, along with neuropathic pain scores in patients (PainDETECT). QST parameters included pressure pain pressure threshold (PPT), pain tolerance threshold (PTT), conditioned pain modulation (CPM) and temporal summation (TS) using cuff algometry, alongside mechanical hyperalgesia and temporal summation to repeated pinprick stimulation. RESULTS: Compared to healthy controls, KOA patients at baseline demonstrated hyperalgesia to pinprick stimulation at the medial knee undergoing TKR, and cuff pressure at the calf. Lower cuff algometry PTT and mechanical pinprick hyperalgesia were associated with preoperative KOA pain intensity. Moreover, preoperative pinprick pain hyperalgesia explained 25% of variance in pain intensity 12 months post-TKR and preoperative neuropathic pain scores also captured 30% and 20% of the variance in postoperative pain at 6 and 12 months respectively. A decrease in mechanical pinprick hyperalgesia from before surgery to 3 months after TKR was associated with lower postoperative pain at the 12 months post-TKR follow-up. CONCLUSION: Our findings suggest that preoperative pinprick hyperalgesia and neuropathic-like pain symptoms show predictive value for the development of chronic post-TKR pain. SIGNIFICANCE STATEMENT: This study's findings hold significant implications for chronic pain management in knee osteoarthritis patients, particularly those undergoing total knee replacement surgery (TKR). Mechanical hyperalgesia and neuropathic pain-like characteristics predict postoperative pain 1 year after TKR, emphasizing the importance of understanding pain phenotypes in OA for selecting appropriate pain management strategies. The normalization of hyperalgesia after surgery correlates with better long-term outcomes, further highlighting the therapeutic potential of addressing abnormal pain processing mechanisms pre- and post-TKR.

An ERK5-PFKFB3 axis regulates glycolysis and represents a therapeutic vulnerability in pediatric diffuse midline glioma.

Metabolic reprogramming in pediatric diffuse midline glioma is driven by gene expression changes induced by the hallmark histone mutation H3K27M, which results in aberrantly permissive activation of oncogenic signaling pathways. Previous studies of diffuse midline glioma with altered H3K27 (DMG-H3K27a) have shown that the RAS pathway, specifically through its downstream kinase, extracellular-signal-related kinase 5 (ERK5), is critical for tumor growth. Further downstream effectors of ERK5 and their role in DMG-H3K27a metabolic reprogramming have not been explored. We establish that ERK5 is a critical regulator of cell proliferation and glycolysis in DMG-H3K27a. We demonstrate that ERK5 mediates glycolysis through activation of transcription factor MEF2A, which subsequently modulates expression of glycolytic enzyme PFKFB3. We show that in vitro and mouse models of DMG-H3K27a are sensitive to the loss of PFKFB3. Multi-targeted drug therapy against the ERK5-PFKFB3 axis, such as with small-molecule inhibitors, may represent a promising therapeutic approach in patients with pediatric diffuse midline glioma.

Insights on the neural basis of motor plasticity induced by theta burst stimulation from TMS-EEG.

Transcranial magnetic stimulation (TMS) is a useful tool to induce and measure plasticity in the human brain. However, the cortical effects are generally indirectly evaluated with motor-evoked potentials (MEPs) reflective of modulation of cortico-spinal excitability. In this study, we aim to provide direct measures of cortical plasticity by combining TMS with electroencephalography (EEG). Continuous theta-burst stimulation (cTBS) was applied over the primary motor cortex (M1) of young healthy adults, and we measured modulation of (i) MEPs, (ii) TMS-induced EEG evoked potentials (TEPs), (iii) TMS-induced EEG synchronization and (iv) eyes-closed resting EEG. Our results show the expected cTBS-induced decrease in MEP size, which we found to be paralleled by a modulation of a combination of TEPs. Furthermore, we found that cTBS increased the power in the theta band of eyes-closed resting EEG, whereas it decreased single-pulse TMS-induced power in the theta and alpha bands. In addition, cTBS decreased the power in the beta band of eyes-closed resting EEG, whereas it increased single-pulse TMS-induced power in the beta band. We suggest that cTBS acts by modulating the phase alignment between already active oscillators; it synchronizes low-frequency (theta and/or alpha) oscillators and desynchronizes high-frequency (beta) oscillators. These results provide novel insight into the cortical effects of cTBS and could be useful for exploring cTBS-induced plasticity outside of the motor cortex.

Is the secure base phenomenon evident here, there, and anywhere? A cross-cultural study of child behavior and experts' definitions.

The evolutionary rationale offered by Bowlby implies that secure base relationships are common in child-caregiver dyads and thus, child secure behavior observable across diverse social contexts and cultures. This study offers a test of the universality hypothesis. Trained observers in nine countries used the Attachment Q-set to describe the organization of children's behavior in naturalistic settings. Children (N = 547) were 10-72 months old. Child development experts (N = 81) from all countries provided definitions of optimal child secure base use. Findings indicate that children from all countries use their mother as a secure base. Children's organization of secure base behavior was modestly related to each other both within and across countries. Experts' descriptions of the optimally attached child were highly similar across cultures.

Preterm infant swallowing of thin and nectar-thick liquids: changes in lingual-palatal coordination and relation to bolus transit.

Tongue-soft palate coordination and bolus head pharyngeal transit were studied by means of postacquisition kinematic analysis of videofluoroscopic swallowing images of ten preterm infants referred from hospital NICUs due to poor oral feeding and suspicion of aspiration. Sequences of coordinated tongue-soft palate movements and bolus transits during swallows of thin-consistency and nectar-thick-consistency barium were digitized, and time series data were used to calculate continuous relative phase, a measure of coordination. During swallows of nectar-thick compared to thin barium, tongue-soft palate coordination was more likely to be antiphase, bolus head pharyngeal transit time was longer, and coordination was significantly correlated with bolus head pharyngeal transit. Analysis of successive swallows indicated that tongue-soft palate coordination variability decreased with nectar-thick but not with thin-consistency barium. Together, the results suggest that slower-moving bolus transits may promote greater opportunity for available sensory information to be used to modulate timing of tongue-soft palate movements so that they are more effective for pumping liquids.

Surgical resection of recurrent intramedullary subependymoma of the cervical spinal cord.

Spinal subependymomas (SE) are rare, often indolent benign tumors presenting most frequently as intramedullary tumors in the cervical spine or cervicothoracic junction. When symptomatic, patients often present with years of sensory changes, weakness, paresthesias, or bowel and bladder dysfunction. Preoperatively, SE are difficult to distinguish radiographically from ependymomas or astrocytomas; however, it is important to make the distinction intraoperatively as complete resection can be curative. Here the authors present a rare case of recurrent, symptomatic cervical subependymoma which underwent gross-total resection and discussion of management strategies and outcomes of all SE at their institution.

Performance changes in National Collegiate Athletic Association Division I women basketball players during a competitive season: starters vs. nonstarters.

The effects of playing time on performance changes were examined in National Collegiate Athletic Association Division I women basketball players. Twelve basketball players (age = 20.6 ± 1.5 years; height = 178.0 ± 8.2 cm; weight = 74.1 ± 8.1 kg) were assessed before (PRE) and at the end of the regular basketball season (POST). Assessments included squat power; vertical jump (VJ) power; 20-second lower-body reaction test; 3 line drills; and subjective measures of energy, focus, fatigue, and alertness. Pre- to postseason comparisons were made between starters (28.3 ± 5.2 minutes per game) and nonstarters (NSs) (8.3 ± 5.3 minutes per game). Data were analyzed for clinical significance using an approach based on the magnitude of change. Results revealed that starters were likely to have greater increases in absolute VJ peak power and relative VJ peak power (87.9 and 90.7%, respectively) and they were likely (81.6%) to have a greater average squat power than NSs. Subjective measures of energy, focus, and alertness were possibly (72.9%), very likely (97.3%), and likely (79.2%) to be lower in starters compared with NSs, respectively. Other performance measures showed unclear differences between starters and NSs. Pearson's product-moment correlation analysis revealed significant (p < 0.05) inverse correlations between playing time and Δ focus (r = -0.79) among all players. In conclusion, significant improvements in VJ performance and average squat power were seen in starters compared with NSs, despite greater decreases in energy, focus, and alertness. In this study, the monitoring of sport-specific performance changes pre and post season showed that performance measures can be maintained throughout an National Collegiate Athletic Association Division I women basketball season.