Development of an Aptamer-Based Molecular Tool for Specifically Targeting Microglia via the CD64 Protein.

Microglial dysfunction has been identified as a key factor in the pathology of several traumatic and neurodegenerative diseases in the central nervous system. Due to the importance of microglia in various pathological processes, the development of molecular tools to target microglia may be of significance for the clinical diagnosis and treatment of these disorders. In this study, a DNA aptamer, ZH-1c, that binds microglia with high affinity was developed by cell-SELEX and truncated strategies. ZH-1c exhibits promising binding ability under physiological temperatures, high serum stability after being modified, and can be internalized by microglia. Also, the binding target of ZH-1c on microglia was identified as the transmembrane protein CD64, which increased in response to inflammatory stimulation via lipopolysaccharide and interferon-gamma, thus enhancing the affinity of ZH-1c for activated microglia. Based on the above experiments, the DNA aptamer ZH-1c exhibits great potential for the targeting of activated inflammatory microglia and may be suitable as a novel and effective molecular tool for diagnosis and microglia-targeted therapies.

A Pre-Implementation Enhancement Strategy to Increase the Yield of Training and Consultation for School-Based Behavioral Preventive Practices: a Triple-Blind Randomized Controlled Trial.

As the most common setting where youth access behavioral healthcare, the education sector frequently employs training and follow-up consultation as cornerstone implementation strategies to promote the implementation of evidence-based practices (EBPs). However, these strategies alone are not sufficient to promote desirable implementation (e.g., intervention fidelity) and youth behavioral outcomes (e.g., mitigated externalizing behaviors). Theory-informed pragmatic pre-implementation enhancement strategies (PIES) are needed to prevent the lackluster outcomes of training and consultation. Specifically, social cognitive theory explicates principles that inform the design of PIES content and specify mechanisms of behavior change (e.g., "intentions to implement" (ITI)) to target increasing providers' responsiveness to training and consultation. This triple-blind parallel randomized controlled trial preliminarily examined the efficacy of a pragmatic PIES based on social cognitive theories (SC-PIES) to improve implementation and youth behavioral outcomes from universal preventive EBPs in the education sector. Teachers from a diverse urban district were recruited and randomly assigned to the treatment (SC-PIES; ntreatment = 22) or active control condition (administrative meeting; ncontrol = 21). Based on the condition assigned, teachers received the SC-PIES or met with administrators before their EBP training. We assessed teachers' ITI, intervention fidelity, and youth behavioral outcome (academic engagement as an incompatible behavior to externalizing disorders) at baseline, immediately after training, and 6 weeks afterward. A series of ANCOVAs detected sizeable effects of SC-PIES, where teachers who received SC-PIES demonstrated significantly larger improvement in their ITI, intervention fidelity, and youth behaviors as compared to the control. Conditional analyses indicated that teachers' ITI partially mediated the effect of SC-PIES on intervention fidelity, which in turn led to improved youth behaviors. Findings suggest that theory-informed pragmatic PIES targeting providers' ITI can boost their responsiveness to implementation strategies, as reflected in improved implementation behaviors and youth behavioral outcomes. The results have implications for targeting motivational mechanisms of behavior change and situating preventive implementation strategies at the intersection between the preparation and active implementation stages of an implementation process. Limitations and implications for research and practice are discussed. Clinicaltrials.gov: NCT05240222. Registered on: 2/14/2022. Retrospectively registered.  https://clinicaltrials.gov/show/NCT05240222.

The Interaction Between General and Strategic Leadership and Climate on Their Multilevel Associations with Implementer Attitudes Toward Universal Prevention Programs for Youth Mental Health: A Cross-Sectional Study.

Emerging literature has highlighted the importance of discerning general and strategic organizational context (OC) factors (e.g., leadership and climate) and their interaction effect on individual implementation behaviors (e.g., attitudes toward evidence-based practices; EBPs) in youth mental healthcare. This study aimed to examine how leadership and climate (general and strategic) are associated with implementer attitudes toward EBPs across the individual and organizational levels and their interaction effect in schools. A series of multilevel models (MLMs) were fitted on a diverse sample of schools actively implementing universal prevention programs for youth mental health (441 implementers from 52 schools). The organization-level aggregates and individual educators' perceptions of general and strategic leadership and climate, and their interaction terms, were entered as level-2 and level-1 predictors of four attitudinal dimensions (Requirement, Openness, Appeal, and Divergence) based on their level of measurement. At the organizational level, higher levels of strategic leadership and climate, but not their general counterparts, were consistently associated with more favorable attitudes in all four dimensions. At the individual/within-school level, higher levels of perceived general and strategic leadership and climate were associated with more favorable attitudes of Requirement and Openness. At the organizational/between-school level, general climate moderated the positive effect of strategic climate on implementers' perception of appeal and divergence of EBPs. Our findings indicate that leaders should make data-based decisions to allocate resources on strategic and/or general leadership and climate to foster favorable staff attitudes toward EBPs based on the level of measurement, implementation-specificity, and attitudinal dimensions.

Two O-Methyltransferases Mediate Multiple Methylation Steps in the Biosynthesis of Coumarins in Cnidium monnieri.

Coumarins with methoxy groups such as osthole (1), xanthotoxin (2), bergapten (3), and isopimpinellin (4) are typical bioactive ingredients of many medicinal plants. The methylation steps remain widely unknown. Herein, we report the discovery of two methyltransferases in the biosynthesis of O-methyl coumarins in Cnidium monnieri by transcriptome mining, heterologous expression, and in vitro enzymatic assays. The results reveal that (i) CmOMT1 catalyzes the methylation of osthenol (8) as the final step in the biosynthesis of 1, (ii) CmOMT2 shows the highest efficiency and preference for methylating xanthotoxol (11) to form 2, and (iii) CmOMT1 and CmOMT2 also efficiently transform bergaptol (10) and 8-hydroxybergapten (13) into 3 or 4, suggesting the CmOMTs mediate multistep methylations in the biosynthesis of linear furanocoumarins in C. monnieri.

Particle electrode materials dependent tetrabromobisphenol A degradation in three-dimensional biofilm electrode reactors.

The completely biological degradation of Tetrabromobisphenol A (TBBPA) contaminant is challenging. Bio-electrochemical systems are efficient to promote electrons transfer between microbes and pollutants to improve the degradation of refractory contaminants. In particular, three-dimensional biofilm electrode reactors (3DBERs), integrating the biofilm with particle electrodes, represent a novel bio-electrochemical technology with superior treatment performances. In this study, the electroactive biofilm is cultured and acclimated on two types of particle electrodes, granular activated carbon (GAC) and granular zeolite (GZ), to degrade the target pollutant TBBPA in 3DBERs. Compared to GZ, GAC materials are more favorable for biofilm formation in terms of high specific surface area and good conductivity. The genus of Thauera is efficiently enriched on both GAC and GZ particles, whose growth is promoted by the electricity. By applying 5 V voltage, TBBPA can be removed by over 95% in 120 min whether packing GAC or GZ particle electrodes in 3DBERs. The synergy of electricity and biofilm in TBBPA degradation was more significant in GAC packed 3DBER, because the improved microbial activity by electrical stimulation accelerates debromination rate and hence the decomposition of TBBPA. Applying electricity also promotes TBBPA degradation in GZ packed 3DBER mainly due to the enhanced electrochemical effects. Roles of particle electrode materials in TBBPA removal are distinguished in this work, bringing new insights into refractory wastewater treatment by 3DBERs.

[Research progresses on PGC-1α, a key energy metabolic regulator].

Disturbance of the energy balance, when the energy intake exceeds its expenditure, is a major risk factor for the development of metabolic syndrome (MS). The peroxisome proliferator activated receptor γ (PPARγ) coactivator-1α (PGC-1α) functions as a key regulator of energy metabolism and has become a hotspot in current researches. PGC-1α sensitively responds to the environmental stimuli and nutrient signals, and further selectively binds to different transcription factors to regulate various physiological processes, including glucose metabolism, lipid metabolism, and circadian clock. In this review, we described the gene and protein structure of PGC-1α, and reviewed its tissue-specific function in the regulation of energy homeostasis in various mammalian metabolic organs, including liver, skeletal muscle and heart, etc. At the meanwhile, we summarized the application of potential small molecule compounds targeting PGC-1α in the treatment of metabolic diseases. This review will provide theoretical basis and potential drug targets for the treatment of metabolic diseases.

Chronic exposure to green light aggravates high-fat diet-induced obesity and metabolic disorders in male mice.

Light is involved in many critical physiological or biochemical processes of human beings, such as visual sensing and the production of vitamin D. Recent studies have showed that the lights of different wavelengths have a profound influence in life activities. For example, blue light promotes alertness, whereas green light (GL) induces sleep in mice. On the other hand, metabolic homeostasis is regulated by a variety of factors, including dietary habits and light exposure. Our study aims to study whether certain wavelength of light would affect metabolic status of mice. Mice were divided into normal diet-fed group and high-fat diet (HFD)-fed group, and then exposed to various colors of the light. Physiological parameters, such as body weight, food intake and water drinking were regularly measured. Glucose tolerance test and pyruvate tolerance test were simultaneously performed. After mice were humanely sacrificed, liver histology and serologic analysis were performed for detecting lipid levels. We found that GL group showed obvious glucose intolerance and increased levels of serum and liver lipid contents compared to white light group. Meanwhile, the expression levels of lipid metabolism-related genes were almost down-regulated in liver. Furthermore, melatonin receptor-1b and thyroid hormone receptor-ß expression levels were significantly lowered in liver of GL-treated obese mice, suggesting that these hormone pathways may mediate the changes of lipid metabolism. Our data indicate that GL has a detrimental effect on the energy metabolism and aggravates HFD-induced obesity in mice. In addition to malnutrition, the colors of the lights also have a profound influence in the metabolic homeostasis and should be taken into consideration in the therapy of metabolic disorders.

A precision-based approach to implement evidence-based interventions for students with externalizing behaviors in developing countries: A single case experimental study in China.

The prevalence of externalizing behaviors imposes a far-reaching negative impact on students' social, behavioral, and academic outcomes, which constitute a public health issue in low-resource and populous developing countries (e.g., China). Compared to the "one-size-fits-all" approach (OSFA; forcing a single evidence-based intervention [EBI] on any struggling students) that is prevalent in many countries, a precision-based approach (e.g., Student Intervention Matching System; SIMS) to intervention programming can better meet students' heterogeneous needs by matching individual characteristics to active components of EBIs. But precision-based approaches cannot fulfill their potential in developing countries unless the contextual implementation barriers (e.g., high student-teacher ratio) are remedied with attention to feasibility, acceptability, and cultural compatibility. This collaborative pilot study with Chinese school stakeholders examined the efficacy, feasibility, acceptability, and cultural compatibility of SIMS to match behavioral EBIs to students with externalizing behaviors. A concurrent multiple-baseline across-participant design was used with six students (three dyads). Visual and quantitative analyses evidenced the superior efficacy of SIMS in improving externalizing behaviors compared to the OSFA approach. Social validity data endorsed the feasibility, acceptability, and cultural compatibility of SIMS and the matched EBIs perceived by school stakeholders (educators, students, and parents). Implications, limitations, and future directions for adapting precision-based approaches in low-resource and populous countries were discussed. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Heimler syndrome with a complaint of blurred vision caused by compound heterozygous variants in PEX1.

INTRODUCTION: Heimler syndrome (HS) is a rare disorder that includes sensorineural hearing loss (SNHL), nail abnormalities, and enamel hypoplasia. Patients with this syndrome can also exhibit ocular manifestations. At present, only a few cases of HS have been reported, existing knowledge of this syndrome is limited, and many cases have been misdiagnosed or even missed. This is the first report of Heimler syndrome with blurred vision as the first complaint, which was diagnosed by genetic analysis in the ophthalmology department. CASE DESCRIPTION: An 8-year-old girl complained of bilateral visual blur and night blindness from birth. Ophthalmic examinations revealed bilateral retinitis pigmentosa with cystoid macular edema, visual impairment with hyperopia and astigmatism. Hearing test revealed bilateral severe sensorineural hearing loss. Dental examinations revealed enamel hypoplasia. In addition, whole-exome sequencing (WES) identified two pathogenic variants in PEX1: the previously reported missense variant c.2966T > C (p.I989 T), and the novel frameshift variant c.1671_1672del (p.G558Sfs*33). CONCLUSION: Heimler syndrome is caused by compound heterozygous PEX1 pathogenic variants, c.2966T > C (p.I989 T) and c.1671_1672del (p.G558Sfs*33), which contributed to the diversity of clinical and genetic profiles in this patient. The main clinical manifestations include bilateral retinitis pigmentosa with cystoid macular edema, sensorineural hearing loss, and enamel hypoplasia. Systemic examinations are suggested for patients suspected of having pigmentary retinal dystrophy, especially combined with hearing-related impairments. Genetic testing can help us to make a definitive diagnosis.

Associations among educators' beliefs, intervention fidelity, and student outcomes in school-wide positive behavior interventions, and supports: A school-level moderated mediation analysis.

Existing literature has established the effectiveness of school-wide positive behavioral interventions and supports (SWPBIS) for improving school-level student behavioral and academic outcomes. Implementation of SWPBIS in uncontrolled settings is often suboptimal, leading to lackluster outcomes. Researchers have developed and validated several implementation strategies to improve individual-level implementation determinants (e.g., educators' supportive beliefs) to promote the successful delivery of universal programs (e.g., SWPBIS). However, empirical studies are needed to explore the mechanisms of change through which school-level educators' beliefs influence their delivery of SWPBIS. This school-level quasi-experimental study tested a mediational mechanism of change where changes in educators' beliefs work through their intervention fidelity of SWPBIS to influence student outcomes. We delivered the Supportive Belief Intervention (a school-wide implementation strategy used before training to promote educators' supportive beliefs about SWPBIS) and then Tier 1 SWPBIS training to 81 elementary schools serving diverse student populations. At the start of the academic year, school-level educators' beliefs were assessed before the Supportive Belief Intervention. At the end of the academic year, educators' beliefs, intervention fidelity, and rates of student reading proficiency and suspension were assessed. Conditional process analyses with nonparametric bootstrapping (mediational and first stage moderated mediational models) revealed that, at the school level, a larger increase in educators' supportive beliefs was associated with enhanced SWPBIS fidelity and better corollary student outcomes (increased reading proficiency and reduced suspension), while student socioeconomic status moderated the size of the mediation effect. Implications for research and practices about the implementation of SWPBIS and school context were discussed. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Inter-Organizational Alignment and Implementation Outcomes in Integrated Mental Healthcare for Children and Adolescents: A Cross-Sectional Observational Study.

Background: Integrated care involves care provided by a team of professionals, often in non-traditional settings. A common example worldwide is integrated school-based mental health (SBMH), which involves externally employed clinicians providing care at schools. Integrated mental healthcare can improve the accessibility and efficiency of evidence-based practices (EBPs) for vulnerable populations suffering from fragmented traditional care. However, integration can complicate EBP implementation due to overlapping organizational contexts, diminishing the public health impact. Emerging literature suggests that EBP implementation may benefit from the similarities in the implementation context factors between the different organizations in integrated care, which we termed inter-organizational alignment (IOA). This study quantitatively explored whether and how IOAs in general and implementation context factors are associated with implementation outcomes in integrated SBMH. Methods: SBMH clinicians from community-based organizations (CBOs; nclinician=27) and their proximal student-support school staff (nschool=99) rated their schools and CBOs (clinician only) regarding general (organizational culture and molar climate) and implementation context factors (Implementation Climate and Leadership), and nine common implementation outcomes (e.g., treatment integrity, service access, acceptability). The levels of IOA were estimated by intra-class correlations (ICCs). We fitted multilevel models to estimate the standalone effects of context factors from CBOs and schools on implementation outcomes. We also estimated the 2-way interaction effects between CBO and school context factors (i.e., between-setting interdependence) on implementation outcomes. Results: The IOA in general context factors exceeded those of implementation context factors. The standalone effects of implementation context factors on most implementation outcomes were larger than those of general context factors. Similarly, implementation context factors between CBOs and schools showed larger 2-way interaction effects on implementation outcomes than general context factors. Conclusions: This study preliminarily supported the importance of IOA in context factors for integrated SBMH. The findings shed light on how IOA in implementation and general context factors may be differentially associated with implementation outcomes across a broad array of integrated mental healthcare settings.

Inter-organizational alignment and implementation outcomes in integrated mental healthcare for children and adolescents: a cross-sectional observational study.

BACKGROUND: Integrated care involves care provided by a team of professionals, often in non-traditional settings. A common example worldwide is integrated school-based mental health (SBMH), which involves externally employed clinicians providing care at schools. Integrated mental healthcare can improve the accessibility and efficiency of evidence-based practices (EBPs) for vulnerable populations suffering from fragmented traditional care. However, integration can complicate EBP implementation due to overlapping organizational contexts, diminishing the public health impact. Emerging literature suggests that EBP implementation may benefit from the similarities in the implementation context factors between the different organizations in integrated care, which we termed inter-organizational alignment (IOA). This study quantitatively explored whether and how IOA in general and implementation context factors are associated with implementation outcomes in integrated SBMH. METHODS: SBMH clinicians from community-based organizations (CBOs; nclinician = 27) and their proximal student-support school staff (nschool = 99) rated their schools and CBOs (clinician only) regarding general (organizational culture and molar climate) and implementation context factors (Implementation Climate and Leadership), and nine common implementation outcomes (e.g., treatment integrity, service access, acceptability). The levels of IOA were estimated by intra-class correlations (ICCs). We fitted multilevel models to estimate the standalone effects of context factors from CBOs and schools on implementation outcomes. We also estimated the 2-way interaction effects between CBO and school context factors (i.e., between-setting interdependence) on implementation outcomes. RESULTS: The IOA in general context factors exceeded those of implementation context factors. The standalone effects of implementation context factors on most implementation outcomes were larger than those of general context factors. Similarly, implementation context factors between CBOs and schools showed larger 2-way interaction effects on implementation outcomes than general context factors. CONCLUSIONS: This study preliminarily supported the importance of IOA in context factors for integrated SBMH. The findings shed light on how IOA in implementation and general context factors may be differentially associated with implementation outcomes across a broad array of integrated mental healthcare settings.

Brief School-Based Interventions Targeting Student Mental Health or Well-Being: A Systematic Review and Meta-Analysis.

Brief, school-based mental health interventions hold promise for reducing barriers to mental health support access, a critical endeavor in light of increasing rates of mental health concerns among youth. However, there is no consensus on whether or not brief school-based interventions are effective at reducing mental health concerns or improving well-being. This systematic review and meta-analysis aims to provide consensus and determine directions for future work. Articles were included if they examined a brief (≤ four sessions or 240 min of intervention time) psychosocial intervention, were conducted within a Pre-K through 12th-grade school setting, included at least one treatment outcome evaluating mental health or well-being, and were published since 2000. A total of 6,702 papers were identified through database searching, of which 81 papers (k studies = 75) were ultimately selected for inclusion. A total of 40,498 students were included across studies and a total of 75 unique interventions were examined. A total of 324 effect sizes were extracted. On average, interventions led to statistically significant improvements in mental health/well-being outcomes versus control conditions up to one-month (g = .18, p = .004), six-month (g = .15, p = .006), and one-year (g = .10, p = .03) post-intervention. There may be benefits to brief school-based interventions from a preventative public health standpoint; future research may focus on how to optimize their real-world utility. Prospero pre-registration: CRD42021255079.

Discovery of a novel class of boron-based antibacterials with activity against gram-negative bacteria.

Gram-negative bacteria cause approximately 70% of the infections in intensive care units. A growing number of bacterial isolates responsible for these infections are resistant to currently available antibiotics and to many in development. Most agents under development are modifications of existing drug classes, which only partially overcome existing resistance mechanisms. Therefore, new classes of Gram-negative antibacterials with truly novel modes of action are needed to circumvent these existing resistance mechanisms. We have previously identified a new a way to inhibit an aminoacyl-tRNA synthetase, leucyl-tRNA synthetase (LeuRS), in fungi via the oxaborole tRNA trapping (OBORT) mechanism. Herein, we show how we have modified the OBORT mechanism using a structure-guided approach to develop a new boron-based antibiotic class, the aminomethylbenzoxaboroles, which inhibit bacterial leucyl-tRNA synthetase and have activity against Gram-negative bacteria by largely evading the main efflux mechanisms in Escherichia coli and Pseudomonas aeruginosa. The lead analogue, AN3365, is active against Gram-negative bacteria, including Enterobacteriaceae bearing NDM-1 and KPC carbapenemases, as well as P. aeruginosa. This novel boron-based antibacterial, AN3365, has good mouse pharmacokinetics and was efficacious against E. coli and P. aeruginosa in murine thigh infection models, which suggest that this novel class of antibacterials has the potential to address this unmet medical need.

Long-Term Follow-up of 64 Patients With Idiopathic Subglottic Stenosis: Treatment Pathways, Outcomes, and Impact of Serial Intralesional Steroid Injections.

OBJECTIVE: To describe treatment pathways and long-term outcomes in 64 patients with idiopathic subglottic stenosis (iSGS), including the impact of serial intralesional steroid injection (SILSI) on degree of stenosis, need for subsequent operation, and patient-reported outcome measures. METHODS: Retrospective review of 64 female patients with iSGS undergoing varied management approaches, 57 of whom underwent SILSI as at least part of their care. Treatment pathways included SILSI only, endoscopic intervention followed by SILSI only, endoscopic interventions only, endoscopic intervention followed by SILSI followed by need for repeat endoscopic intervention, open surgery, and tracheotomy. Outcomes assessed included subjectively estimated percent airway stenosis, dyspnea index (DI), modified medical research council (MMRC) dyspnea scale, voice handicap index-10 (VHI-10), number of operative and office-based procedures performed, need for subsequent operative intervention, and inter-operative interval. RESULTS: Treatment pathways included SILSI alone (n = 6), endoscopic intervention(s) followed by SILSI only (n = 31), SILSI followed by additional endoscopic or office-based procedures (n = 16), open surgery (n = 3), and tracheostomy (n = 4). 57 of 64 patients underwent SILSI as at least part of their treatment. Inter-operative interval was increased after starting SILSI. Of patients undergoing SILSI, those with more procedures or shorter inter-operative interval prior to SILSI were more likely to return to the operating room. Estimated stenosis, DI, MMRC, and VHI-10 decreased with SILSI. Stenosis was not correlated with DI, MMRC, or VHI-10, though DI was correlated with both MMRC and VHI-10 score. CONCLUSION: Of 57 patients undergoing SILSI, 37 did not require further operative intervention. Improvements in inter-operative interval, dyspnea, and voice were observed across patients. Randomized trials to identify which patients may benefit most from SILSI are warranted.

LINC01278 Induces Autophagy to Inhibit Tumour Progression by Suppressing the mTOR Signalling Pathway.

Uveal melanoma (UM) is an aggressive intraocular malignant tumour that is closely related to autophagic dysfunction. We aimed to identify autophagy-related long noncoding RNAs (lncRNAs) to elucidate the molecular mechanism of UM. Here, we show that LINC01278 is a new potential biomarker with clinical prognostic value in UM through bioinformatics analysis. Application of an autophagy inhibitor (3-MA) and an autophagy agonist (MG-132) indicated that LINC01278 can inhibit UM cell proliferation, migration, and invasion by inducing autophagy. A xenograft nude mouse model was used to examine the tumorigenesis of UM cells in vivo. Mechanistically, LINC01278 can inhibit the mTOR signalling pathway to activate autophagy, as shown by experiments with an mTOR agonist (MHY1485) and mTOR inhibitor (rapamycin) treatment. Our findings indicate that LINC01278 functions as a tumour suppressor by inhibiting the mTOR signalling pathway to induce autophagy. Targeting the LINC01278-mTOR axis might be a novel and promising therapeutic approach for UM.

Comparison of Free Flap Outcomes at a University Hospital versus County Hospital Setting for Head and Neck Reconstruction.

Introduction Patients at public county hospitals often have poorer access to healthcare with advanced disease on presentation. These factors, along with limited resources at county hospitals, may have an impact on outcomes for patients requiring complex head and neck reconstruction. Objective To delineate differences in the frequency of complications in two different care settings, a public county hospital and a private university hospital. Methods Retrospective review of otolaryngology patients at a university hospital compared with a publicly-funded county hospital. The main outcome measure was major complications including total flap loss or unplanned reoperation in 30 days. Secondary outcome measures included medical complications, partial flap loss, and unplanned hospital readmission in 30 days. Results In the county hospital sample ( n = 58) free flap failure or reoperation occurred in 20.7% of the patients, and minor complications, in 36.2% of the patients. In the university hospital sample ( n = 65) flap failure or reoperation occurred in 9.2% of the patients, and minor complications, in 12.3% of the patients. Patients at the private hospital who had surgery in the oropharynx were least likely to have minor complications. Conclusion Patients at the county hospital had a higher but not statistically significant difference in flap failure and reoperation than those at a university hospital, although the county hospital experienced more minor postoperative complications. This is likely multifactorial, and may be related to poorer access to primary care preoperatively, malnutrition, poorly controlled or undiagnosed medical comorbidities, and differences in hospital resources.

PTK6 inhibits autophagy to promote uveal melanoma tumorigenesis by binding to SOCS3 and regulating mTOR phosphorylation.

Autophagy dysfunction is one of the common causes of tumor formation and plays an important role in uveal melanoma (UM). However, little is known about the regulatory mechanisms of autophagy in UM. Here, we show that PTK6 can promote the proliferation, migration, and invasion of UM cells by inhibiting autophagy. SOCS3 can inhibit the proliferation, migration, and invasion of UM cells. Overexpression of SOCS3 can partially rescue the PTK6-induced promotion of UM cell proliferation, migration, and invasion. Mechanistically, PTK6 can bind to SOCS3, and SOCS3 can downregulate the expression of PTK6. Furthermore, PTK6 can upregulate the phosphorylation of mTOR to inhibit autophagy. Taken together, our findings demonstrate the functions of PTK6 and SOCS3 in UM cells and targeting the SOCS3-PTK6 signaling axis might be a novel and promising therapeutic strategy for patients with UM.

Rates of Detecting Thyroid Nodules Recommended for Biopsy with Ultrasound: Are All Indications Equal?

Background: The use of thyroid ultrasound increases yearly, adding to costs and overdetection of clinically irrelevant nodules. We investigated which indications most commonly prompt referral for thyroid ultrasound and the diagnostic utility by indication. Methods: We performed a retrospective observational cohort study of adults (≥18 years) undergoing an initial dedicated thyroid ultrasound between 2017 and 2019 at a tertiary academic center. Indicated reasons for referral were categorized into suspected palpable nodule (SPN), compressive symptoms (CS), metabolic symptoms (MS), screening due to high-risk factors, follow-up of incidental finding on other imaging, and combination of factors. Percentage of ultrasounds with an identifiable nodule and with a nodule recommended for biopsy was compared by indication. Separate logistic regression models were used to identify factors associated with finding any nodule and a biopsy-recommended nodule. Results: Among the 1739 patients included, the most common indication for thyroid ultrasound was SPN (40%), followed by incidental imaging (28%), CS (13%), combination (11%), MS (6%), and high-risk factors (2%). Overall, 62% of ultrasounds identified a nodule. Ultrasounds performed for incidental findings had the highest rate of nodule identification (94%), compared with 55%, 39%, and 43%, for SPN, CS, and MS, respectively (p < 0.05). Only 27% of ultrasounds identified a biopsy-recommended nodule. Nodules found incidentally had the highest rate of biopsy-recommended nodules at 55%. Rates of biopsy-recommended nodules for SPN, CS, and MS were 21%, 6%, and 10%, respectively. Logistic regression demonstrated that compared with patients referred for an SPN, those with incidental nodules were 10 times more likely to have a nodule found on ultrasound (odds ratio [OR] = 10.6 [CI 7.0-16.0]), while those referred for CS were half as likely to have a nodule (OR = 0.5 [CI 0.4-0.7]). Similar factors were associated with identification of biopsy-recommended nodules. Conclusions: Of all new dedicated thyroid ultrasounds, only a quarter find biopsy-recommended nodules, and nearly 40% do not identify a nodule at all. Notably, only 55% of ultrasounds done for SPN found a nodule. Ultrasound for CS and MS had the lowest rates of detecting nodules. Providing clear guidance on when to order thyroid ultrasounds can help reduce unnecessary health care utilization and potential overtreatment.

Upending the shortages crisis: A national survey of school psychology recruitment.

School psychology is experiencing a shortages crisis. There is also lack of national data regarding current recruitment practices. Understanding these practices is essential to overcome these personnel shortages. In this national study, 151 school psychology programs within the US and its territories were surveyed. Participants were chosen from a national comprehensive list of school psychology programs compiled by the research team. The survey was created through a detailed review of relevant literature and distributed by email using Qualtrics. Various recruitment strategy domains were examined. Findings suggest that program representatives perceived program location to be most important and program cost the least important for students choosing their programs. Furthermore, respondents indicated a general consensus regarding the importance of establishing a recruitment pipeline. Moreover, programs within smaller communities appeared to be more involved in recruitment pipeline efforts. Descriptives for recruitment strategy domains are presented and implications are discussed. (PsycInfo Database Record (c) 2022 APA, all rights reserved).