Effect of Radiological Tumor Thickness on Prognosis of Early Glottic-Squamous Cell Carcinoma Treated With Radiation.

OBJECTIVES: Tumor depth of invasion is a known prognostic factor in several head and neck cancers, but data on early laryngeal squamous cell carcinoma (SCC) are sparse. In this study, we aim to determine whether radiological tumor thickness serves as a prognostic factor in early SCC of the glottis treated with radiation. METHODS: One hundred thirty-two adult patients (age >18 years) underwent pretreatment computed tomography (CT) and were treated with radiation for pathologically proven early stage (T1 or T2) glottic SCC. Thirty-eight were excluded because the tumor could not be correctly identified on the CT scan, and an additional three patients because of insufficient data. RESULTS: The final cohort consisted of 91 patients, 84 (90.3%) men and 7 (9.7%) women aged 39.86-86.53 (mean 65.55 ± 12.76) years. Mean tumor thickness was 0.59 ± 0.19 cm in patients with T1 tumors and 0.79 ± 0.21 cm in patients with T2 tumors. The optimal cutoff value for 5-year disease-free survival (DFS), using the Youden index (sensitivity: 81.2%, specificity 65.3%), was 0.7 cm. A significant advantage in 5-year overall survival (OAS) and 5-year DFS for tumor thickness of <0.7 cm (P = 0.01 and P < 0.01, respectively) was found, these findings were consistent also when each stage was examined separately (T1 vs T2). CONCLUSION: Radiological tumor thickness appears to significantly predict OAS and DFS in early glottic SCC patients. IMPLICATION FOR PRACTICE: Tumor thickness may be considered as an auxiliary aid in deciding follow-up time and frequency, proper treatment, and determining prognosis.

Attachment relationship quality with mothers and fathers and child temperament: An individual participant data meta-analysis.

A growing body of research suggests that, compared with single parent-child attachment relationships, child developmental outcomes may be better understood by examining the configurations of child-mother and child-father attachment relationships (i.e., attachment networks). Moreover, some studies have demonstrated an above-chance level chance of concordance between the quality of child-mother and child-father attachment relationships, and child temperament has been offered as a plausible explanation for such concordance. To assess whether temperament plays a role in the development of different attachment network configurations, in this preregistered individual participant data meta-analysis we tested the degree to which the temperament dimension of negative emotionality predicts the number of secure, insecure-avoidant, insecure-resistant, and disorganized attachment relationships a child has with mother and father. Data included in the linear mixed effects analyses were collected from seven studies sampling 872 children (49% female; 83% White). Negative emotionality significantly predicted the number of secure (d = -0.12) and insecure-resistant (d = 0.11), but not insecure-avoidant (d = 0.04) or disorganized (d = 0.08) attachment relationships. Nonpreregistered exploratory analyses indicated higher negative emotionality in children with insecure-resistant attachment relationships with both parents compared to those with one or none (d = 0.19), suggesting that temperament plays a small yet significant role in child-mother/child-father insecure-resistant attachment relationships concordance. Taken together, results from this study prompt a more in-depth examination of the mechanism underlying the small yet significantly higher chance that children with increased negative emotionality have for developing multiple insecure-resistant attachment relationships. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Configurations of mother-child and father-child attachment relationships as predictors of child language competence: An individual participant data meta-analysis.

An individual participant data meta-analysis was conducted to test pre-registered hypotheses about how the configuration of attachment relationships to mothers and fathers predicts children's language competence. Data from seven studies (published between 1985 and 2014) including 719 children (Mage : 19.84 months; 51% female; 87% White) were included in the linear mixed effects analyses. Mean language competence scores exceeded the population average across children with different attachment configurations. Children with two secure attachment relationships had higher language competence scores compared to those with one or no secure attachment relationships (d = .26). Children with two organized attachment relationships had higher language competence scores compared to those with one organized attachment relationship (d = .23), and this difference was observed in older versus younger children in exploratory analyses. Mother-child and father-child attachment quality did not differentially predict language competence, supporting the comparable importance of attachment to both parents in predicting developmental outcomes.

Using virtual reality-based neurocognitive testing and eye tracking to study naturalistic cognitive-motor performance.

Natural human behavior arises from continuous interactions between the cognitive and motor domains. However, assessments of cognitive abilities are typically conducted using pen and paper tests, i.e., in isolation from "real life" cognitive-motor behavior and in artificial contexts. In the current study, we aimed to assess cognitive-motor task performance in a more naturalistic setting while recording multiple motor and eye tracking signals. Specifically, we aimed to (i) delineate the contribution of cognitive and motor components to overall task performance and (ii) probe for a link between cognitive-motor performance and pupil size. To that end, we used a virtual reality (VR) adaptation of a well-established neurocognitive test for executive functions, the 'Color Trails Test' (CTT). The VR-CTT involves performing 3D reaching movements to follow a trail of numbered targets. To tease apart the cognitive and motor components of task performance, we included two additional conditions: a condition where participants only used their eyes to perform the CTT task (using an eye tracking device), incurring reduced motor demands, and a condition where participants manually tracked visually-cued targets without numbers on them, incurring reduced cognitive demands. Our results from a group of 30 older adults (>65) showed that reducing cognitive demands shortened completion times more extensively than reducing motor demands. Conditions with higher cognitive demands had longer target search time, as well as decreased movement execution velocity and head-hand coordination. We found larger pupil sizes in the more cognitively demanding conditions, and an inverse correlation between pupil size and completion times across individuals in all task conditions. Lastly, we found a possible link between VR-CTT performance measures and clinical signatures of participants (fallers versus non-fallers). In summary, performance and pupil parameters were mainly dependent on task cognitive load, while maintaining systematic interindividual differences. We suggest that this paradigm opens the possibility for more detailed profiling of individual cognitive-motor performance capabilities in older adults and other at-risk populations.

Reconsidering routine admission for children under age 3 undergoing partial tonsillectomy: a prospective study.

BACKGROUND: Partial Tonsillectomy (PT) is an alternative method to treat sleep disordered breathing (SDB) and/or obstructive sleep apnea (OSA). The current guidelines do not differentiate it from traditional tonsillectomy. Thus, children younger than 3 years old undergoing PT are admitted for surveillance similar to traditional tonsillectomy due to possible postoperative complications. The aim of this study is to assess the risks of PT in children 3 years old and younger, compared to older children. METHODS: Children underwent inpatient partial tonsillectomy and/or adenoidectomy, due to SDB/OSA, from 2018 to 2020. A special protocol was designed, including follow-up at 2-, 4-, 6-, 8- and 24-h after surgery. Variables analyzed included visual analogue pain score, oral intake, oxygen saturation, pulse rate, postoperative hemorrhage, urine output, temperature, analgesics and fluid administration. Furthermore, major interventions were recorded. Comparison of all variables between children younger than 3 years old with older children was performed. RESULTS: Ninety-two children were included; mean age of the whole cohort was 44.5 ± 21.9 months. Thirty-five (38%) children were 3-years old or younger and n = 57 (62%) were older than 3 years old, with no significant statistical difference in sex (p = 0.22). Mean age in the younger group was 25.7 ± 6.9 months, and 56.1 ± 20.1 months in the older group. In total we had 7 children with post-operative complications; 4 with fever, 3 with low intake. There were no major interventions recorded in either group. The complications were more common in the older group (n = 5) than the younger group (n = 2) without a statistical significance (p = 0.59). There were no differences in VAS, use of painkillers, oral intake, urine output, oxygen saturation and tachycardia among the two groups. CONCLUSION: This study supports that children undergoing ambulatory PT may be at low risk of complications, regardless of age.

Powered Intracapsular Tonsillotomy and Adenoidectomy in Infants ≤36 Months Compared to Older Children: A Retrospective Analysis.

OBJECTIVES: To evaluate the safety and outcomes of powered intracapsular tonsillotomy and adenoidectomy (PITA) for the treatment of sleep disordered breathing in infants up to 36 months of age compared to older children. METHODS: This retrospective analysis included children who underwent PITA from 2013 to 2019 at a single tertiary care medical center. The patients were divided into 2 groups: up to 36 months, and 36 to 72 months. The data were collected from electronic medical records and from a telephone survey based on a modified version of the OSA-18 questionnaire. Post-operative complications, and short- and long-term outcomes were compared. RESULTS: A total of 48 patients met the inclusion criteria for the main study group (up to 36 months of age). They were compared to 59 children 36 to 72 months of age. There were no differences in subjective outcomes between age groups (P = .65). There were no differences in the frequency of post-operative complications between age groups (P = .8) or in the number of hospitalization days (P = .91). CONCLUSION: The short- and long-term outcomes and safety of PITA for the treatment of sleep disordered breathing in infants up to 36 months of age are similar to those of older children.

Possible clinical implications of the structural variations between the tympanic membrane quadrants.

Introduction: Retraction pockets and marginal perforations of the pars tensa of the tympanic membrane (TM) are most commonly found at superior posterior quadrant (SPQ). The patulous Eustachian tube tends to manifest in the same quadrant. Variation in the structure of the TM may explain these observations. Material and Methods: A line defined by the manubrium was used to divide the pars tensa into anterior and posterior portions. A transverse line centered on the umbo divides the pars tensa into superior and inferior parts, resulting in four quadrants. Surface areas of each of the TM quadrants were measured in a sample of 23 human adult formalin-fixed temporal bones. The TMs were completely excised, faced medially, and placed against graph paper to maintain scale measurements, photoed, and measured.TM thickness was measured on a different set of 20 human temporal bones (TB) preparations with normal external and middle ears. Four random loci were chosen from each pars tensa's TM quadrant. The thickness was measured using high-magnification power microscopy. Results: The SPQ was the largest and thinnest of the four quadrants. It occupies 31% of the pars tensa area. It is 69 µm as compared to approximately 85 µm in the other quadrants. The radial lines between the umbo and the annulus are in descending order from superior posterior toward the anterior-superior radials. Conclusion: The SPQ has the largest vibratory area and is the thinnest of the four TM quadrants. Variation in the thickness of the middle, fibrous layer accounts for the variation in the thickness of the TM. These findings may explain the tendency of pathologies related to Eustachian tube dysfunction to preferentially manifest in or originate from the SPQ.

Correction: Dagan et al. A Lifespan Development Theory of Insecure Attachment and Internalizing Symptoms: Integrating Meta-Analytic Evidence via a Testable Evolutionary Mis/Match Hypothesis. Brain Sci. 2021, 11, 1226.

In the original article [...].

Gli1 Regulates the Postnatal Acquisition of Peripheral Nerve Architecture.

Peripheral nerves are organized into discrete compartments. Axons, Schwann cells (SCs), and endoneurial fibroblasts (EFs) reside within the endoneurium and are surrounded by the perineurium, a cellular sheath comprised of layers of perineurial glia (PNG). SC secretion of Desert Hedgehog (Dhh) regulates this organization. In Dhh nulls, the perineurium is deficient and the endoneurium is subdivided into small compartments termed minifascicles. Human Dhh mutations cause a neuropathy with similar defects. Here we examine the role of Gli1, a canonical transcriptional effector of hedgehog signaling, in regulating peripheral nerve organization in mice of both genders. We identify PNG, EFs, and pericytes as Gli1-expressing cells by genetic fate mapping. Although expression of Dhh by SCs and Gli1 in target cells is coordinately regulated with myelination, Gli1 expression unexpectedly persists in Dhh null EFs. Thus, Gli1 is expressed in EFs noncanonically (i.e., independent of hedgehog signaling). Gli1 and Dhh also have nonredundant activities. Unlike Dhh nulls, Gli1 nulls have a normal perineurium. Like Dhh nulls, Gli1 nulls form minifascicles, which we show likely arise from EFs. Thus, Dhh and Gli1 are independent signals: Gli1 is dispensable for perineurial development but functions cooperatively with Dhh to drive normal endoneurial development. During development, Gli1 also regulates endoneurial extracellular matrix production, nerve vascular organization, and has modest, nonautonomous effects on SC sorting and myelination of axons. Finally, in adult nerves, induced deletion of Gli1 is sufficient to drive minifascicle formation. Thus, Gli1 regulates the development and is required to maintain the endoneurial architecture of peripheral nerves.SIGNIFICANCE STATEMENT Peripheral nerves are organized into distinct cellular/ECM compartments: the epineurium, perineurium, and endoneurium. This organization, with its associated cellular constituents, is critical for the structural and metabolic support of nerves and their response to injury. Here, we show that Gli1, a transcription factor normally expressed downstream of hedgehog signaling, is required for the proper organization of the endoneurium but not the perineurium. Unexpectedly, Gli1 expression by endoneurial cells is independent of, and functions nonredundantly with, Schwann Cell-derived Desert Hedgehog in regulating peripheral nerve architecture. These results further delineate how peripheral nerves acquire their distinctive organization during normal development, and highlight mechanisms that may regulate their reorganization in pathologic settings, including peripheral neuropathies and nerve injury.

Outcomes of the Bethesda system for reporting thyroid cytopathology in community- vs. institution-performed cytology.

OBJECTIVES: Despite the important role of the community in the assessment and risk stratification of patients with thyroid nodules, evidence-based data on the Bethesda System for Reporting Thyroid Cytopathology (BSRTC) performance in community clinics is lacking. We aim to evaluate BSRTC performance of aspirations taken in community clinics compared with primary referral center. METHODS: Patients who underwent thyroid surgery between 2013 and 2018 at our institution were divided according to the fine needle aspirations (FNA) settings: community FNA (cFNA) vs. institutional FNA (iFNA). Demographics, BSRTC results and final pathology were collected. Diagnostic values were calculated for BSRTC categories (sensitivity, specificity, positive predictive value [PPV], and negative predictive value [NPV]), and were compared between the groups. RESULTS: A total of 268 nodules were included in the study; 77% (207) cFNA and 23% (61) iFNA. Patients in the community were younger (51.7 ± 15.1 vs. 56.6 years±14.8, p = 0.03) and with less epidemiology risk factors for thyroid cancer (1.9% vs 13.1%, p < 0.001). cFNA malignancy rate for BSRTC I-VI was 0%, 6.4%, 11.8%, 32.1%, 91.6% and 93.8% respectively. Best sensitivity was found for BSRTC III-VI in both groups (88% and 83%, cFNAs and iFNAs, respectively). Overall best performance was obtained for BSRTC V-VI for both groups (cfNA: 85%, 97%, 93%, 94% and 93%; iFNAs: 81%, 100%, 100%, 87% and 91%, for sensitivity, specificity, PPV, NPV and accuracy, respectively). CONCLUSIONS: Community-performed FNAs demonstrate acceptable BSRTC distribution and malignancy rates, comparable with a primary referral academic hospital. This supports the universality of the BSRTC 2017 and its recommendations also in the community.

Early attachment networks to multiple caregivers: History, assessment models, and future research recommendations.

Early attachment has been commonly hypothesized to predict children's future developmental outcomes, and robust evidence relying on assessments of single caregiver-child attachment patterns has corroborated this hypothesis. Nevertheless, most often children are raised by multiple caregivers, and they tend to form attachment bonds with more than one of them. In this paper, we briefly describe the conceptual and empirical roots underlying the notion of attachment networks to multiple caregivers. We detail potential reasons for research focusing on a single caregiver (most often mothers, but recently also fathers) and the historical attempts to establish a more ecologically valid assessment of attachment to multiple caregivers. Finally, we describe a recently developed organizational framework that includes testable models on which future research may rely for assessing the predictive power of attachment networks to multiple caregivers on children's developmental outcomes.

A Lifespan Development Theory of Insecure Attachment and Internalizing Symptoms: Integrating Meta-Analytic Evidence via a Testable Evolutionary Mis/Match Hypothesis.

Attachment scholars have long argued that insecure attachment patterns are associated with vulnerability to internalizing symptoms, such as depression and anxiety symptoms. However, accumulating evidence from the past four decades, summarized in four large meta-analyses evaluating the link between insecure attachment subtypes and internalizing symptoms, provide divergent evidence for this claim. This divergent evidence may be accounted for, at least in part, by the developmental period under examination. Specifically, children with histories of deactivating (i.e., insecure/avoidant) but not hyperactivating (i.e., insecure/resistant) attachment patterns in infancy and early childhood showed elevated internalizing symptoms. In contrast, adolescents and adults with hyperactivating (i.e., insecure/preoccupied) but not deactivating (i.e., insecure/dismissing) attachment classifications showed elevated internalizing symptoms. In this paper, we summarize findings from four large meta-analyses and highlight the divergent meta-analytic findings that emerge across different developmental periods. We first present several potential methodological issues that may have contributed to these divergent findings. Then, we leverage clinical, developmental, and evolutionary perspectives to propose a testable lifespan development theory of attachment and internalizing symptoms that integrates findings across meta-analyses. According to this theory, subtypes of insecure attachment patterns may be differentially linked to internalizing symptoms depending on their mis/match with the developmentally appropriate orientation tendency toward caregivers (in childhood) or away from them (i.e., toward greater independence in post-childhood). Lastly, we offer future research directions to test this theory.

Eight-month follow-up of olfactory and gustatory dysfunctions in recovered COVID-19 patients.

PURPOSE: To investigate the recovery of loss of smell and taste among recovered COVID-19 patients. MATERIALS AND METHODS: This cross-sectional follow-up study is a sequel to a study by Biadsee et al. Among the previous study population of 128 non-hospitalized patients, positive for COVID-19 by reverse transcription-polymerase chain reaction (RT-PCR), 97 patients participated in a survey designed for this study. Information and data regarding loss of smell and taste, rate of recovery, xerostomia, and additional symptoms; (Cough, Myalgia, Weakness, Rhinorrhea, Nasal congestion) were collected. RESULTS: A total of 43 men and 54 women were included. Mean age was 37.5 years (range 19-74). Mean follow-up was 229 days (range 191-253). Sixty-five patients reported gustatory dysfunction during the disease of which 61.5% reported full recovery, 38.5% partial recovery. Of 65 patients who reported olfactory impairment during the disease, 52% had full recovery and 48% reported partial recovery of olfactory function. Complete recovery of olfactory function was positively associated with full recovery of gustatory function (p = 0.01). Gender did not significantly affect the recovery of OD and GD (p = 0.45, p = 0.90, respectively). Patients who experienced olfactory dysfunction as an initial symptom had lower rates of olfactory complete recovery (p = 0.043). CONCLUSION: After a mean follow-up of 229 days, complete recovery of smell and taste functions occurred in 52% and 61.5%, respectively. However, dysfunction persisted in 48%-38.5% of patients.

It takes a village: a call for engaging attachment with adjunct disciplines to clarify "in-house" clinical conundrums.

Researchers have long discussed the rich clinical applications of attachment theory. Specifically, clinicians have been compelled by the idea that insecure attachment, broadly speaking, may bring about stressful (real or perceived) interpersonal experiences that increases risk for internalizing symptoms. However, recent meta-analyses examining the links between attachment representations and internalizing symptoms have challenged this assumption, highlighting the importance of considering insecure attachment subtypes in understanding one's vulnerability for internalizing symptoms. Here we expand on this special issue's target papers and propose that, despite an increase in citation impact of clinically relevant attachment research, there are still core theoretical and methodological questions left unanswered. We highlight three clinical conundrums: (1) hyperactivating, but not deactivating, attachment is linked to increased internalizing symptoms in adolescence and adulthood; (2) the magnitude of the associations between insecure attachment subtypes and internalizing symptoms varies depending on the developmental period; and (3) self-reported, but not narrative-based, deactivating attachment is associated with increased internalizing symptoms. We call for engagement with adjunct academic disciplines to elucidate these issues. These clinical conundrums have important ethical implications regarding how we understand insecure attachment and necessitate close theoretical and empirical attention before attachment findings can truly inform clinical practice.

'Golden' exosomes as delivery vehicles to target tumors and overcome intratumoral barriers: in vivo tracking in a model for head and neck cancer.

Exosomes are promising vectors for anti-tumor therapy, due to their biocompatibility, low immunogenicity, and innate ability to interact with target cells. However, promoting clinical application of exosome-based therapeutics requires elucidation of key issues, including exosome biodistribution, tumor targeting and accumulation, and the ability to overcome tumor barriers that limit the penetration of various nano-carriers and drugs. Here, we examined these parameters in exosomes derived from mesenchymal stem cells (MSC-exo) and from the A431 squamous cell carcinoma line (A431-exo), which both have potential use in cancer therapy. Using our novel technique combining gold nanoparticle (GNP) labeling of exosomes and non-invasive computed tomography imaging (CT), we longitudinally and quantitatively tracked the two intravenously-injected exosome types in A431 tumor-bearing mice. CT imaging up to 48 h and subsequent ex vivo analysis revealed tumor homing abilities of both exosome types, yet there was significantly higher tumor accumulation of MSC-exo as compared to A431-exo. Moreover, MSC-exo demonstrated the ability to penetrate the tumor and distribute throughout its bulk, while non-encapsulated GNPs remained concentrated at the tumor periphery. Histological analysis showed penetration of MSC-exo not only into the tumor tissue, but also into tumor cell cytoplasm. While the proportion of biodistribution between organs at 48 h was similar for both exosome types, more rapid clearance was indicated for A431-exo. Thus, our findings demonstrate an effect of exosome type on tumor targeting abilities and biodistribution, and suggest that MSC-exo may have superior abilities for tumor-targeted therapy.

Configurations of mother-child and father-child attachment as predictors of internalizing and externalizing behavioral problems: An individual participant data (IPD) meta-analysis.

An unsettled question in attachment theory and research is the extent to which children's attachment patterns with mothers and fathers jointly predict developmental outcomes. In this study, we used individual participant data (IPD) meta-analysis to assess whether early attachment networks with mothers and fathers are associated with children's internalizing and externalizing behavioral problems. Following a pre-registered protocol, data from 9 studies and 1,097 children (mean age: 28.67 months) with attachment classifications to both mothers and fathers were included in analyses. We used a linear mixed effects analysis to assess differences in children's internalizing and externalizing behavioral problems as assessed via the average of both maternal and paternal reports based on whether children had two, one, or no insecure (or disorganized) attachments. Results indicated that children with an insecure attachment relationship with one or both parents were at higher risk for elevated internalizing behavioral problems compared with children who were securely attached to both parents. Children whose attachment relationships with both parents were classified as disorganized had more externalizing behavioral problems compared to children with either one or no disorganized attachment relationship with their parents. Across attachment classification networks and behavioral problems, findings suggest (a) an increased vulnerability to behavioral problems when children have insecure or disorganized attachment to both parents, and (b) that mother-child and father-child attachment relationships may not differ in the roles they play in children's development of internalizing and externalizing behavioral problems.

Does secure base script knowledge mediate associations between observed parental caregiving during childhood and adult romantic relationship quality and health?

Increasingly, attachment representations are being assessed via secure base script knowledge - the degree to which individuals show awareness of the temporal-causal schema that summarizes the basic features of seeking and receiving effective support from caregivers during times of need. Limited research has assessed the links between secure base script knowledge and aspects of adult functioning and the role that secure base script knowledge may play in accounting for associations between early caregiving quality and adulthood functioning. We used follow-up assessments of the NICHD Study of Early Child Care and Youth Development cohort (N = 585) to examine whether secure base script knowledge at age 18 years: (a) is associated with later romantic relationship quality, depressive symptoms, and body mass index (BMI) at age 26 years, and (b) mediates expected associations between the quality of maternal and paternal sensitivity across the first 15 years of life and age-26 outcomes. More access to, and elaborated knowledge of the secure base script predicted less extreme hostility with romantic partners, and better emotional and physical health. Moreover, secure base script knowledge mediated the links between early maternal and paternal sensitivity and both later romantic partner hostility and depressive symptoms, but not BMI.

Convergent validity and stability of secure base script knowledge from young adulthood to midlife.

Attachment theory posits that early experiences with caregivers are made portable across development in the form of mental representations of attachment experiences. These representations, the secure base script included, are thought to be stable across time. Here, we present data from two studies. Study 1 (N = 141) examined the degree of empirical convergence between the two major measures of secure base script knowledge in Study 2, we examined stability of secure base script knowledge from late adolescence to midlife combining data from both a high- and normative-risk cohort (N = 113). Study 1 revealed evidence for convergent validity (r = .50) and Study 2 revealed moderate rank-order stability (r = .43), which was not moderated by cohort risk status. Results support the validity of secure base script knowledge assessments and prediction that attachment representations show moderate stability across early adulthood and into midlife.