Tongue-tie in the Neonatal Intensive Care Unit Compared to Healthy Newborns.

OBJECTIVE: We sought to characterize the prevalence of ankyloglossia in our neonatal intensive care unit (NICU) population and to determine characteristics of this cohort compared to infants in the birth center (BC). METHODS: Prospective data were collected using a standardized flow sheet. Breastfeeding infants undergoing evaluation for tongue-tie in the BC and NICU were included. Coryllos type, tip to frenulum length, tongue function, frequency of frenotomy, and breastfeeding outcomes were compared. RESULTS: Of 20,879 infants birthed at or admitted to the institution during the study period, there were fewer patients diagnosed with ankyloglossia in the BC compared to the NICU (3.3% BC vs. 5.4% NICU, p < 0.01). Of these, 163 underwent frenotomy: 86 in the BC and 77 in the NICU. For those undergoing frenotomy, gestational age (39.1 ± 1.3 BC, 34.4 ± 4.4 NICU, p < 0.01) and age at time of procedure (3.2 days BC, 29.2 NICU, p < 0.01) were the only demographic factors significantly different between the groups. There was no difference in Coryllos type or function score. In a subset of NICU infants with multiple assessments over time, function scores after frenotomy were significantly improved compared to pre-frenotomy (p < 0.01). CONCLUSION: Standard assessment tools appear to be appropriate for use in infants in the NICU, despite the higher rates of prematurity, low birth weights, and increased comorbidities. Assessment and intervention for tongue-tie can be one critical intervention to move these patients closer to oral feeding and discharge to home. LEVEL OF EVIDENCE: Level 3 Laryngoscope, 2024.

Risk Factors for Replacement of Tympanostomy Tubes After Surgical Removal for Pediatric Patients.

OBJECTIVES: Ear tube removal and patch myringoplasty are frequently performed. The indication and timing for surgery varies among otolaryngologists. This study identifies risk factors associated with the need for the replacement of tympanostomy tubes after tube removal and myringoplasty. STUDY DESIGN: Case series with chart review. SETTING: Single institution academic otolaryngology practice. METHODS: Patients younger than 12 years of age who underwent tympanostomy tube removal and myringoplasty at the University of Rochester Medical Center from March 2011 to September 2019. Patients with tympanostomy tube removal due to chronic otorrhea were excluded. RESULTS: One hundred sixty-one patients (230 ears) met inclusion criteria and had sufficient follow-up. Myringoplasty success after tube removal was 94.8%. Successful myringoplasty was associated with shorter tube duration (32 months) versus unsuccessful myringoplasty (40 months) (P = .02). Replacement tympanostomy tubes after myringoplasty occurred in 9.6% of ears. There was no difference in average patient age (P = .96) or duration of tubes (P = .74) in patients who required replacement of tympanostomy tubes versus patients who did not require tube replacement. Patients with a cleft abnormality were more likely to require tympanostomy tube replacement (P < .001). CONCLUSIONS: Most children do not need tubes replaced after removal. This study identified cleft abnormality as a factor that increased the need for replacement tubes. Longer tube durations of over 3 years negatively impacted myringoplasty success. Tympanostomy tube removal should be considered 2 to 3 years after placement in most patients with longer tube durations considered in children with a repaired cleft palate.

Perception and adaptation of receptive prosody in autistic adolescents.

A fundamental aspect of language processing is inferring others' minds from subtle variations in speech. The same word or sentence can often convey different meanings depending on its tempo, timing, and intonation-features often referred to as prosody. Although autistic children and adults are known to experience difficulty in making such inferences, the science remains unclear as to why. We hypothesize that detail-oriented perception in autism may interfere with the inference process if it lacks the adaptivity required to cope with the variability ubiquitous in human speech. Using a novel prosodic continuum that shifts the sentence meaning gradiently from a statement (e.g., "It's raining") to a question (e.g., "It's raining?"), we have investigated the perception and adaptation of receptive prosody in autistic adolescents and two groups of non-autistic controls. Autistic adolescents showed attenuated adaptivity in categorizing prosody, whereas they were equivalent to controls in terms of discrimination accuracy. Combined with recent findings in segmental (e.g., phoneme) recognition, the current results provide the basis for an emerging research framework for attenuated flexibility and reduced influence of contextual feedback as a possible source of deficits that hinder linguistic and social communication in autism.

Adherence to unhealthy diets is associated with altered frontal gamma-aminobutyric acid and glutamate concentrations and grey matter volume: preliminary findings.

OBJECTIVES: Common mental disorders (CMD) are associated with impaired frontal excitatory/inhibitory (E/I) balance and reduced grey matter volume (GMV). Larger GMV (in the areas that are implicated in CMD-pathology) and improved CMD-symptomatology have been observed in individuals who adhere to high quality diets. Moreover, preclinical studies have shown altered neurometabolites (primarily gamma-aminobutyric acid: GABA and glutamate: GLU) in relation to diet quality. However, neurochemical correlates of diet quality and how these neurobiological changes are associated with CMD and with its transdiagnostic factor, rumination, is unknown in humans. Therefore, in this study, we examined the associations between diet quality and frontal cortex neuro-chemistry and structure, as well as CMD and rumination in humans. METHODS: Thirty adults were classified into high and low diet quality groups and underwent 1H-MRS to measure medial prefrontal cortex (mPFC) metabolite concentrations and volumetric imaging to measure GMV. RESULTS: Low (vs High) diet quality group had reduced mPFC-GABA and elevated mPFC-GLU concentrations, as well as reduced right precentral gyrus (rPCG) GMV. However, CMD and rumination were not associated with diet quality. Notably, we observed a significant negative correlation between rumination and rPCG-GMV and a marginally significant association between rumination and mPFC-GLU concentrations. There was also a marginally significant association between mPFC-GLU concentrations and rPCG-GMV. DISCUSSION: Adhering to unhealthy dietary patterns may be associated with compromised E/I balance, and this could affect GMV, and subsequently, rumination.

Sagnac-interferometer-based multiwavelength SOA fiber laser assisted by an intensity-dependent loss mechanism.

We demonstrate a Sagnac-interferometer-based multiwavelength fiber laser with an intensity-dependent loss (IDL) mechanism in the L-band region using a semiconductor optical amplifier (SOA) as the gain medium. The IDL mechanism flattens and stabilizes the multiwavelength spectrum. We also investigate the effect of rotation angles of polarization controllers (PCs) at different polarization devices on multiwavelength performance. At best settings, 31 lasing lines within 3 dB uniformity were generated with an extinction ratio (ER) of 17 dB. Adjusting the half-wave plate of PC1 and PC2 from 0° to 90° shifted the multiwavelength output by 0.01 nm and 0.072 nm, respectively. PC2 adjustment also affects the multiwavelength flatness as compared to PC1. Furthermore, the number of lasing lines and the ER were directly influenced by the SOA current.

Examining the relationships between cognition and auditory hallucinations: A systematic review.

OBJECTIVE: Auditory hallucinations (hearing voices) have been associated with a range of altered cognitive functions, pertaining to signal detection, source-monitoring, memory, inhibition and language processes. Yet, empirical results are inconsistent. Despite this, several theoretical models of auditory hallucinations persist, alongside increasing emphasis on the utility of a multidimensional framework. Thus, clarification of current evidence across the broad scope of proposed mechanisms is warranted. METHOD: A systematic search of the Web of Science, PubMed and Scopus databases was conducted. Records were screened to confirm the use of an objective behavioural cognitive task, and valid measurement of hallucinations specific to the auditory modality. RESULTS: Auditory hallucinations were primarily associated with difficulties in perceptual decision-making (i.e. reduced sensitivity/accuracy for signal-noise discrimination; liberal responding to ambiguity), source-monitoring (i.e. self-other and temporal context confusion), working memory and language function (i.e. reduced verbal fluency). Mixed or limited support was observed for perceptual feature discrimination, imagery vividness/illusion susceptibility, source-monitoring for stimulus form and spatial context, recognition and recall memory, executive functions (e.g. attention, inhibition), emotion processing and language comprehension/hemispheric organisation. CONCLUSIONS: Findings were considered within predictive coding and self-monitoring frameworks. Of concern was the portion of studies which - despite offering auditory-hallucination-specific aims and inferences - employed modality-general measures, and/or diagnostic-based contrasts with psychologically healthy individuals. This review highlights disparities within the literature between theoretical conceptualisations of auditory hallucinations and the body of rigorous empirical evidence supporting such inferences. Future cognitive investigations, beyond the schizophrenia-spectrum, which explicitly define and measure the timeframe and sensory modality of hallucinations, are recommended.

Post-Anesthesia Cognitive Dysfunction in Mice Is Associated with an Age-Related Increase in Neuronal Intracellular [Ca2+]-Neuroprotective Effect of Reducing Intracellular [Ca2+]: In Vivo and In Vitro Studies.

Background: Postoperative cognitive dysfunction (POCD) is a common disorder after general anesthesia in elderly patients, the precise mechanisms of which remain unclear. Methods: We investigated the effect of isoflurane with or without dantrolene pretreatment on intracellular calcium concentration ([Ca2+]i), reactive oxygen species (ROS) production, cellular lactate dehydrogenase (LDH) leak, calpain activity, and cognitive function using the Morris water maze test of young (3 months), middle-aged (12-13 months), and aged (24-25 months) C57BL6/J mice. Results: Aged cortical and hippocampal neurons showed chronically elevated [Ca2+]i compared to young neurons. Furthermore, aged hippocampal neurons exhibited higher ROS production, increased LDH leak, and elevated calpain activity. Exposure to isoflurane exacerbated these markers in aged neurons, contributing to increased cognitive deficits in aged mice. Dantrolene pretreatment reduced [Ca2+]i for all age groups and prevented or significantly mitigated the effects of isoflurane on [Ca2+]i, ROS production, LDH leak, and calpain activity in aged neurons. Dantrolene also normalized or improved age-associated cognitive deficits and mitigated the cognitive deficits caused by isoflurane. Conclusions: These findings suggest that isoflurane-induced cytotoxicity and cognitive decline in aging are linked to disruptions in neuronal intracellular processes, highlighting the reduction of [Ca2+]i as a potential therapeutic intervention.

Connectome dysfunction in patients at clinical high risk for psychosis and modulation by oxytocin.

Abnormalities in functional brain networks (functional connectome) are increasingly implicated in people at Clinical High Risk for Psychosis (CHR-P). Intranasal oxytocin, a potential novel treatment for the CHR-P state, modulates network topology in healthy individuals. However, its connectomic effects in people at CHR-P remain unknown. Forty-seven men (30 CHR-P and 17 healthy controls) received acute challenges of both intranasal oxytocin 40 IU and placebo in two parallel randomised, double-blind, placebo-controlled cross-over studies which had similar but not identical designs. Multi-echo resting-state fMRI data was acquired at approximately 1 h post-dosing. Using a graph theoretical approach, the effects of group (CHR-P vs healthy control), treatment (oxytocin vs placebo) and respective interactions were tested on graph metrics describing the topology of the functional connectome. Group effects were observed in 12 regions (all pFDR < 0.05) most localised to the frontoparietal network. Treatment effects were found in 7 regions (all pFDR < 0.05) predominantly within the ventral attention network. Our major finding was that many effects of oxytocin on network topology differ across CHR-P and healthy individuals, with significant interaction effects observed in numerous subcortical regions strongly implicated in psychosis onset, such as the thalamus, pallidum and nucleus accumbens, and cortical regions which localised primarily to the default mode network (12 regions, all pFDR < 0.05). Collectively, our findings provide new insights on aberrant functional brain network organisation associated with psychosis risk and demonstrate, for the first time, that oxytocin modulates network topology in brain regions implicated in the pathophysiology of psychosis in a clinical status (CHR-P vs healthy control) specific manner.

Propofol directly binds and inhibits skeletal muscle ryanodine receptor 1 (RyR1).

As the primary Ca 2+ release channel in skeletal muscle sarcoplasmic reticulum (SR), mutations in the type 1 ryanodine receptor (RyR1) or its binding partners underlie a constellation of muscle disorders, including malignant hyperthermia (MH). In patients with MH mutations, exposure to triggering drugs such as the halogenated volatile anesthetics biases RyR1 to an open state, resulting in uncontrolled Ca 2+ release, sarcomere tension and heat production. Restoration of Ca 2+ into the SR also consumes ATP, generating a further untenable metabolic load. When anesthetizing patients with known MH mutations, the non-triggering intravenous general anesthetic propofol is commonly substituted for triggering anesthetics. Evidence of direct binding of anesthetic agents to RyR1 or its binding partners is scant, and the atomic-level interactions of propofol with RyR1 are entirely unknown. Here, we show that propofol decreases RyR1 opening in heavy SR vesicles and planar lipid bilayers, and that it inhibits activator-induced Ca 2+ release from SR in human skeletal muscle. In addition to confirming direct binding, photoaffinity labeling using m- azipropofol (AziP m ) revealed several putative propofol binding sites on RyR1. Prediction of binding affinity by molecular dynamics simulation suggests that propofol binds at least one of these sites at clinical concentrations. These findings invite the hypothesis that in addition to propofol not triggering MH, it may also be protective against MH by inhibiting induced Ca 2+ flux through RyR1.

Hippocampal Glutamate, Resting Perfusion and the Effects of Cannabidiol in Psychosis Risk.

Background: Preclinical and human data suggest that psychosis onset involves hippocampal glutamatergic dysfunction, driving hyperactivity and hyperperfusion in a hippocampal-midbrain-striatal circuit. Whether glutamatergic dysfunction is related to cerebral perfusion in patients at clinical high risk (CHR) for psychosis, and whether cannabidiol (CBD) has ameliorative effects on glutamate or its relationship with perfusion remains unknown. Methods: Using a double-blind, parallel-group design, 33 CHR patients were randomized to a single 600 mg dose of CBD or placebo; 19 healthy controls did not receive any drug. Proton magnetic resonance spectroscopy was used to measure glutamate concentrations in left hippocampus. We examined differences relating to CHR status (controls vs placebo), effects of CBD (placebo vs CBD), and linear between-group effects, such that placebo>CBD>controls or controls>CBD>placebo. We also examined group × glutamate × cerebral perfusion (measured using Arterial Spin Labeling) interactions. Results: Compared to controls, CHR-placebo patients had significantly lower hippocampal glutamate (P =.015) and a significant linear relationship was observed across groups, such that glutamate was highest in controls, lowest in CHR-placebo, and intermediate in CHR-CBD (P =.031). Moreover, there was a significant interaction between group (controls vs CHR-placebo), hippocampal glutamate, and perfusion in the putamen and insula (P FWE =.012), with a strong positive correlation in CHR-placebo vs a negative correlation in controls. Conclusions: Our findings suggest that hippocampal glutamate is lower in CHR patients and may be partially normalized by a single dose of CBD. Furthermore, we provide the first in vivo evidence of an abnormal relationship between hippocampal glutamate and perfusion in the striatum and insula in CHR.

Disfunción de la [Ca 2+] diastólica en cardiomiocitos aislados de pacientes chagásicos / Dysfunction of diastolic [Ca2+] in cardiomyocytes isolated from chagasic patients

Introducción y objetivos. La enfermedad de Chagas es un mal endémico en Latinoamérica, causado por el parásito Trypanosoma cruzi, que generalmente afecta al funcionamiento del corazón. Estudiamos la regulación del calcio intracelular en cardiomiocitos de pacientes chagásicos con diversos grados de deterioro funcional. Métodos. Se utilizaron microelectrodos selectivos para el calcio para determinar simultáneamente la concentración diastólica de calcio ([Ca2+]d) y el potencial de membrana en biopsias endomiocárdicas de pacientes chagásicos y controles. Resultados. La [Ca2+]d aumentó el 123, el 295 y el 738% en los pacientes chagásicos de los grupos funcionales I, II y III, respectivamente, respecto a los controles. El potencial de membrana mostró una parcial despolarización de un 6% en el grupo funcional I, el 10% en el II y el 22% en el III respecto a los controles. La [Ca2+]d se revirtió parcialmente con 1-[6-[[(17ß)-3-metoxiestra-1,3,5(10)-trieno-17-il]amino]hexil]-1H-pirrole-2,5-diona (U-73122), antagonista de la betafosfolipasa C, y 2-aminoetoxidifenil borato (2-APB), inhibidor de los receptores de inositol 1,4,5-trifosfato. La fenilefrina, fármaco que induce una rápida elevación del contenido intracelular del inositol 1,4,5-trifosfato, incrementó la [Ca2+]d en cardiomiocitos controles y chagásicos, que fue mayor en los cardiomicitos chagásicos y se inhibió por 2-APB. Conclusiones. En cardiomiocitos de pacientes chagásicos hay una disfunción de la regulación de la [Ca2+]d correlacionada con las alteraciones cardiacas observadas en las diferentes fases de la enfermedad. Esta perturbación en dicha regulación se asocia, aparentemente, a una alteración en la regulación del mediador intracelular inositol 1,4,5-trifosfato (AU)

Introduction and objectives: Chagas is an endemic disease in Latin America, caused by the parasite Trypanosoma cruzi, which usually affects the functioning of the heart. We have studied the regulation of intracellular calcium in cardiomyocytes isolated from chagasic patients with different degrees of heart dysfunction. Methods: Calcium selective microelectrodes were used to simultaneously measure diastolic calcium concentration ([Ca2+]d) and resting membrane potential in endomyocardial biopsies obtained from chagasic patients and controls. Results: The [Ca2+]d increased by 123%, 295%, and 738% in chagasic patients in functional class I, II, and III, respectively, in relation to controls. Membrane potential showed a partial depolarization of 6% in functional class I, 10% in functional class II, and 22% in functional class III, compared to control values. Alteration in the [Ca2+]d was partially reverted by 1-[6-[[(17ß)-3-metoxyestra-1,3,5(10)-trien-17-yl] amino]hexyl]-1H-pyrrole-2,5-dione (U-73122), a b-phospholipase C antagonist, and by 2-aminoethoxydiphenyl- borate (2-APB), an inositol 1,4,5-trisphosphate receptor blocker. Phenylephrine, an agent that induces a rapid transient increase in 1,4,5-trisphosphate intracellular content, produced a rise in [Ca2+]d, higher in chagasic cardiomyocytes than in controls, and its effect was fully inhibited by 2-APB. Conclusions: In cardiomyocytes from chagasic patients there is a dysfunction of the regulation of the [Ca2+]d, which correlates with the cardiac abnormalities observed in the different stages of the disease. This disturbance in the regulation of intracellular calcium appears to be associated with alterations in the regulation of intracellular messenger inositol 1,4,5-trisphosphate (AU)

Estudo da funçäo simpático-adrenal em crianças submetidas a cirurgia cardíaca com hipotermia de superfície, perfusäo limitada e parada circulatória / Simpathoadrenal function during cardiac surgery in children using the technique of surface cooling: limited cardiopulmonary bypass and circulatory arrest

Os níveis de catecolamina plasmática foram medidos em 20 crianças (idade média de 6,00 ñ 5,86 meses; peso médio 5,3 ñ 1,82 kg), durante a correçäo de defeitos cardíacos congênitos, usando-se a hipotermia de superfície (26-C), perfusäo cardiopulmonar limitada e parada circulatória (15-C). Adrenalina e noradrenalina plasmática foram dosadas em amostras sangüíneas arteriais seriadas, usando-se a cromatografia. A hipotermia de superfície produziu um significante aumento de ambas as catecolaminas. Durante o resfriamento central, os níveis caíram devido à hemodiluiçäo. Após o período de parada circulatória (23/64 minutos, média de 41,3), ocorreu um aumento das catecolaminas plasmáticas, que persistiu durante o reaquecimento. Após o reaquecimento, as catecolaminas plasmáticas permaneceram elevadas até o final do ato cirúrgico. Nossos resultados mostram que a técnica de hipotermia de superfície, perfusäo cardiopulmonar limitada e parada circulatória, sob as nossas condiçöes de anestesia, produziu significante aumento da concentraçäo de adrenalina e noradrenalina plasmática, porém o significado biológico é, ainda, inseguro