Evaluation and management of pediatric thyroid nodules and thyroid cancer at a single institution after adoption of the American Thyroid Association 2015 guidelines.

OBJECTIVES: The study purpose is to correlate clinical findings with rates of differentiated thyroid cancer (DTC) in a cohort of children presenting with thyroid nodules at a single institution since the adoption of the 2015 American Thyroid Association (ATA) Guidelines Task Force on Pediatric Thyroid Cancer. METHODS: Clinical, radiographic, and cytopathologic findings were retrospectively analyzed in a pediatric cohort (≤19 years) identified with ICD-10 codes for thyroid nodules and thyroid cancer from January 2017 until May 2021. RESULTS: We analyzed 183 patients with thyroid nodules. The mean patient age was 14 years (interquartile range 11-16) with a female (79.2 %) and white Caucasian (78.1 %) predominance. The overall DTC in our pediatric patient cohort was 12.6 % (23 out of 183). Most of the malignant nodules measured from 1-4 cm (65.2 %) with TI-RADS score of ≥4 (69.6 %). Among the fine-needle aspiration results (n=49), the highest frequency of DTC was within the malignant category (16.33 %), followed by suspicious for malignancy (6.12 %), then atypia or follicular lesion of undetermined significance (8.16 %), and lastly follicular lesion or neoplasm and benign with 4.08 % and 2.04 % respectively. Of the forty-four thyroid nodules that underwent surgical intervention, pathology was remarkable for 19 papillary thyroid carcinoma (43.18 %) and 4 follicular thyroid carcinoma (9.09 %). CONCLUSIONS: Based on the analysis of our pediatric cohort in the southeast region at a single institution, adoption of the 2015 ATA guidelines could lead to an increased accuracy in detecting DTC while reducing the number of patients requiring interventions, such as FNA biopsy and/or surgeries. Further, based on our small cohort, it would be reasonable for thyroid nodules 1 cm or less to be monitored clinically with physical exam and ultrasonography, with further therapeutic or diagnostic intervention considered based on concerning features or parental shared decision making.

Association between perceived social support and suicide ideation distress among psychiatric inpatients: The role of thwarted interpersonal needs.

INTRODUCTION: The interpersonal theory of suicide posits that thwarted belongingness (TB) and perceived burdensomeness (PB) are proximal risk factors for suicide ideation; however, there are mixed results regarding this hypothesis among psychiatric inpatients. OBJECTIVE: The current study examined the mediating role of TB and PB in the relationship between perceived social support (i.e., support from family, friends, a significant other, and total) and suicide ideation distress among psychiatric inpatients. METHODS: Participants (short-term psychiatric inpatients; N = 139) were administered self-report assessments cross-sectionally. RESULTS: Nonparametric mediation results indicated that the total (additive) indirect effects of TB and PB, in parallel, were significant in all models, yet there were only significant specific (unique) indirect effects of PB. CONCLUSION: TB and PB, in combination, may be proximal risk factors for suicide ideation distress among psychiatric inpatients with lower perceived social support from family, friends, a significant other, and in total. These findings are congruent with the interpersonal theory of suicide's propositions that the combination of TB and PB increases the risk for suicide ideation. Clinicians may consider using interventions that target increasing perceived social support and decreasing TB and PB (i.e., cognitive behavioral therapy and social skills training) for this population.

Deaf Individuals Who Report Having Good Balance Function Present with Significant Vestibular Deficits.

BACKGROUND: Vestibular and/or balance deficits are well documented in deaf individuals. In the adult population, poor vestibular and/or balance function can lead to activity limitations and increased risk of falling. An effective case history by health care providers to probe for potential balance concerns is necessary for appropriate referral; however, patients may not consistently report vestibular and balance symptoms. Currently, there is little information available as to how deaf individuals report these symptoms and how their reported balance ability relates to measures of balance and vestibular functions. PURPOSE: The aim of the current study was to evaluate self-perceived balance ability in participants who self-identify as either deaf or hearing, and compare these results to measures of balance and vestibular functions. RESEARCH DESIGN: This is a prospective, between-group design. STUDY SAMPLE: Data from 57 adults between the ages of 18 to 29 years who self-reported as deaf (39) or hearing (18) were evaluated. Participants completed the activities-specific balance confidence (ABC) scale, a brief case history, self-report rating of balance (SRRB), the Modified Clinical Test of Sensory Integration of Balance (mCTSIB), along with both ocular vestibular-evoked myogenic potentials (oVEMPs) and cervical vestibular-evoked myogenic potentials (cVEMPs). Only participants with SRRBs of good or excellent were included in the inferential analyses. RESULTS: Proportions of participants rating their balance ability as either good or excellent were similar between both groups, as were the results on the ABC scale. Statistical analyses revealed significant associations between the groups on both oVEMPs and cVEMPs. No significant differences were observed on sway velocities in any of the mCTSIB conditions; however, more than one-third of deaf participants had mCTSIB Condition 4-on foam, eyes closed-scores above 2 standard deviations of the hearing group. CONCLUSION: Deaf participants self-report similar ratings of balance ability as hearing participants despite significant differences in vestibular function. A relatively large subset of deaf participants had increased sway velocity on balance function testing that required increased reliance on vestibular cues. A thorough discussion of balance and vestibular symptoms should be completed when a patient who self-identifies as deaf is seen by a health care provider so that appropriate screenings or referrals can be completed as necessary.

Considering the impact of COVID-19 on suicide risk among individuals in prison and during reentry.

PURPOSE -: This paper mains to bring attention to the potential impact COVID-19 could have on suicide risk among individuals who are incarcerated and those reentering the community after incarceration (i.e. reentry), with particular emphasis on the USA, as well as provide possible solutions to mitigate suicide risk. DESIGN/METHODOLOGY/APPROACH -: This paper provides an overview of the association between the COVID-19 pandemic policies and suicide, the vulnerabilities specific to prisoners during the COVID-19 pandemic, relevant suicide risk factors among prisoners, the possible impact of COVID-19 on suicide risk during reentry and proposed solutions for moving forward to mitigate both risks for COVID-19 and suicide. FINDINGS -: This paper highlights that prisoners and individuals reentering the community are particularly vulnerable to COVID-19 and suicide risk and COVID-19-related stressors may further exacerbate known suicide risk factors (e.g. psychiatric symptoms, lack of positive social ties, low feelings of belonging, feelings of burden, economic problems) and suicidal thoughts and behaviors. This paper also discusses barriers (e.g. lack of funds, access to health and mental health care, COVID-19 testing and personal protective equipment) to managing COVID-19 and suicide risk within prisons and during reentry. ORIGINALITY/VALUE -: This paper provides a review of scalable solutions that could mitigate the impact of COVID-19 and suicide risk during this pandemic among prisoners and those reentering the community, such as psychoeducation, self-help stress management, telehealth services, increased access and reduced cost of phone calls, reduced or eliminated cost of soap and sanitization supplies in prisons and early release programs.

Decision-making ability in psychosis: a systematic review and meta-analysis of the magnitude, specificity and correlates of impaired performance on the Iowa and Cambridge Gambling Tasks.

To identify factors which may help or hinder decision-making ability in people with psychosis, we did a systematic review and meta-analysis of their performance on the Iowa and Cambridge Gambling Tasks. Analysis of 47 samples found they had moderately poorer performance than healthy individuals (N = 4264, g = -0.57, 95% confidence interval (CI) -0.66 to -0.48). Few studies (k = 8) used non-psychotic clinical comparator groups, although very low-quality evidence (k = 3) found people with bipolar disorder may perform better. Negative symptoms (k = 13, N = 648, r = -0.17, 95% CI -0.26 to -0.07) and lower IQ (k = 11, N = 525, r = 0.20, 95% CI 0.29-0.10), but not positive symptoms (k = 10, N = 512, r = -0.01, 95% CI -0.11 to 0.08), each had small-moderate associations with poorer decision-making. Lower quality evidence suggested general symptoms, working memory, social functioning, awareness of emotional responses to information, and attentional bias towards gain are associated with decision-making, but not education, executive functioning or overall symptoms. Meta-regression suggested an inverse association between decision-making and depression severity (k = 6, Q = 6.41, R2 100%, p = 0.01). Those taking first-generation (k = 6, N = 305, g = -0.17, 95% CI -0.40 to 0.06, p = 0.147) or low-dose antipsychotics (k = 5, N = 442, g = -0.19, 95% CI -0.44 to 0.06, p = 0.139) had unimpaired decision-making. Although meta-regression found no linear association between dose and performance, non-reporting of the dose was common and associated with larger impairments (k = 46, Q = 4.71, R2 14%, p = 0.03). Those supporting people with psychosis to make decisions, including treatment decisions, should consider the potential effect of these factors. Interventionist-causal trials are required to test whether reducing antipsychotic dose and treating anxiety and depression can improve decision-making in this group.

A man who collapsed after using the internet.

Recognising prolonged seated immobility as a provoking factor in the development of venous thromboembolism can influence management including duration of anticoagulation therapy.

In-vitro melanoma models: invasive growth is determined by dermal matrix and basement membrane.

A critical first step in the metastatic progression of cutaneous melanoma, invasive growth into the dermal compartment, would ideally be studied in the proper three-dimensional tissue microenvironment. In this study, we compared the growth and behavior of four melanoma cell lines originating from primary and metastatic human cutaneous melanomas (AN, RU, M14, and WK) in in-vitro human skin equivalents (HSEs) generated with four different dermal matrices: human fibroblast-seeded rat tail collagen, human fibroblast-derived matrix (FDM), noncellular human de-epidermized dermis (DED), and a novel fully cellular human DED with an intact pre-existent basement membrane. Melanoma cells showed proliferation in all HSEs, indicating that the microenvironment formed in all HSEs studied here allows the growth of melanoma cells in concert with epidermal keratinocytes for multiple weeks in vitro. Melanoma cells did not affect epidermal proliferation and terminal differentiation. Growth of melanoma cells in the dermal compartment, as a measure of invasive potential, differs markedly between the four types of in-vitro human melanoma models. Notably, the growth of melanoma cells in the dermal matrix was observed in all HSEs cultured with cell lines originating from metastatic melanoma, except for cDED-based HSEs, and the growth of melanoma cells of nonmetastatic origin was observed in the dermal compartment of FDM-based HSEs. Our results show that the type of dermal equivalent and the presence of an intact basement membrane should be taken into consideration when studying melanoma invasion using in-vitro HSEs.

Solventless High Throughput Manufacturing of Poly(butylene terephthalate) Nanofibers.

Nanofibers possess high surface area to volume ratios and are particularly attractive for a variety of applications including tissue regeneration, drug delivery, fiber-reinforced composites, filtration, and protective clothing. Though the production of nanofibers from common thermoplastic polymers is relatively well-demonstrated, processing constraints have limited high throughput manufacturing of nanofibers from high performance polymers. This has in turn limited broad technological exploitation of polymer nanofibers in areas such as hot chemical filtration or high-performance lightweight composites for aerospace and defense applications. We report here that nanofibers can be produced in a solventless high throughput process from polymers such as poly(butylene terephthalate) (PBT) using a newly developed technology termed "Forcespinning" that employs centrifugal force to attenuate fibers. Our investigations also show that these nanofibers have a high crystallinity and enhanced molecular orientation which is important for realizing desirable physical and chemical properties of many high-performance polymer fibers.

Dual use of amphiphilic macromolecules as cholesterol efflux triggers and inhibitors of macrophage athero-inflammation.

Activated vascular wall macrophages can rapidly internalize modified lipoproteins and escalate the growth of atherosclerotic plaques. This article proposes a biomaterials-based therapeutic intervention for depletion of non-regulated cholesterol accumulation and inhibition of inflammation of macrophages. Macromolecules with high scavenger receptor (SR)-binding activity were investigated for SR-mediated delivery of agonists to cholesterol-trafficking nuclear liver-X receptors. From a diverse feature space of a family of amphiphilic macromolecules of linear and aromatic mucic acid backbones modified with varied aliphatic chains and conjugated with differentially branched poly(ethylene glycol), a key molecule (carboxyl-terminated, C12-derivatized, linear mucic acid backbone) was selected for its ability to preferentially bind scavenger receptor A (SR-A) as the key target. At a basal level, this macromolecule suppressed the pro-inflammatory signaling of activated THP-1 macrophages while competitively lowering oxLDL uptake in vitro through scavenger receptor SRA-1 targeting. To further deplete intracellular cholesterol, the core macromolecule structure was exploited to solubilize a hydrophobic small molecule agonist for nuclear Liver-X Receptors, which regulate the efflux of intracellular cholesterol. The macromolecule-encapsulated agonist system was found to reduce oxLDL accumulation by 88% in vitro in comparison to controls. in vivo studies were designed to release the macromolecules (with or without encapsulated agonist) to injured carotid arteries within Sprague Dawley rats fed a high fat diet, conditions that yield enhanced cholesterol accumulation and macrophage recruitment. The macromolecules lowered intimal levels of accumulated cholesterol (50% for macromolecule alone; 70% for macromolecule-encapsulated agonist) and inhibited macrophage retention (92% for macromolecule; 96% for macromolecule-encapsulated agonist; 4 days) relative to non-treated controls. Thus, this study highlights the promise of designing bioactive macromolecule therapeutics based on scavenger receptor targeting, for potential management of vascular arterial disease.

Efficient intracellular siRNA delivery by ethyleneimine-modified amphiphilic macromolecules.

New materials that can bind and deliver oligonucleotides such as short interfering RNA (siRNA) without toxicity are greatly needed to fulfill the promise of therapeutic gene silencing. Amphiphilic macromolecules (AMs) were functionalized with linear ethyleneimines to create cationic AMs capable of complexing with siRNA. Structurally, the parent AM is formed from a mucic acid backbone whose tetra-hydroxy groups are alkylated with 12-carbon aliphatic chains to form the hydrophobic component of the macromolecule. This alkylated mucic acid is then mono-functionalized with poly(ethylene glycol) (PEG) as a hydrophilic component. The resulting AM contains a free carboxylic acid within the hydrophobic domain. In this work, linear ethyleneimines were conjugated to the free carboxylic acid to produce an AM with one primary amine (1N) or one primary amine and four secondary amines (5N). Further, an AM with amine substitution both to the free carboxylic acid in the hydrophobic domain and also to the adjacent PEG was synthesized to produce a polymer with one primary amine and eight secondary amines (9N), four located on each side of the AM hydrophobic domain. All amine-functionalized AMs formed nanoscale micelles but only the 5N and 9N AMs had cationic zeta potentials, which increased with increasing number of amines. All AMs exhibited less inherent cytotoxicity than linear polyethyleneimine (L-PEI) at concentrations of 10 µM and above. By increasing the length of the cationic ethyleneimine chain and the total number of amines, successful siRNA complexation and cellular siRNA delivery was achieved in a malignant glioma cell line. In addition, siRNA-induced silencing of firefly luciferase was observed using complexes of siRNA with the 9N AM and comparable to L-PEI, yet showed better cell viability at higher concentrations (above 10 µM). This work highlights the promise of cationic AMs as safe and efficient synthetic vectors for siRNA delivery. Specifically, a novel polymer (9N) was identified for efficient siRNA delivery to cancer cells and will be further evaluated.

Preferential cellular uptake of amphiphilic macromolecule-lipid complexes with enhanced stability and biocompatibility.

Amphiphilic macromolecules (AM) were electrostatically complexed with a 1:1 ratio of 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) and 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) to form AM-lipid complexes with drug delivery applications. The complexes exist as AM-coated liposomes and their drug delivery properties can be tuned by altering the AM-lipid weight ratio. The complexation and tuning are achieved in a simple, efficient, and scalable manner. The gradual increase in lipid ratios concurrently increased the zeta potential of the complexes, which directly correlates to increased cell uptake of the complexes in vitro with preferential uptake noted in BT-20 carcinoma cells versus normal fibroblasts. Increasing AM content increased complex steric stability in the presence of serum proteins and reduced the inherent cytotoxicity towards fibroblasts in vitro. AM-lipid complexes solubilized paclitaxel and showed drug-mediated, dose-dependent cytotoxicity towards target BT-20 cells in vitro. AM-lipid complexes make good candidates as drug delivery systems due to their tunable zeta potential, steric stability, inherently low cytotoxicity, and ability to load and deliver insoluble chemotherapeutic agents. Significantly, their preferential uptake in a carcinoma cell line over normal cells in vitro demonstrates a unique, passive targeting approach to delivery anti-cancer therapeutics.

Controllable inhibition of cellular uptake of oxidized low-density lipoprotein: structure-function relationships for nanoscale amphiphilic polymers.

A family of anionic nanoscale polymers based on amphiphilic macromolecules (AMs) was developed for controlled inhibition of highly oxidized low-density lipoprotein (hoxLDL) uptake by inflammatory macrophage cells, a process that triggers the escalation of a chronic arterial disease called atherosclerosis. The basic AM structure is composed of a hydrophobic portion formed from a mucic acid sugar backbone modified at the four hydroxyls with lauroyl groups conjugated to hydrophilic poly(ethylene glycol) (PEG). The AM structure-activity relationships were probed by synthesizing AMs with six key variables: length of the PEG chain, carboxylic acid location, type of anionic charge, number of anionic charges, rotational motion of the anionic group, and PEG architecture. All AM structures were confirmed by nuclear magnetic resonance spectroscopy and their ability to inhibit hoxLDL uptake in THP-1 human macrophage cells was compared in the absence and presence of serum. We report that AMs with one, rotationally restricted carboxylic acid within the hydrophobic portion of the polymer was sufficient to yield the most effective AM for inhibiting hoxLDL internalization by THP-1 human macrophage cells under serum-containing conditions. Further, increasing the number of charges and altering the PEG architecture in an effort to increase serum stabilization did not significantly impair the ability of AMs to inhibit hoxLDL internalization, suggesting that selected modifications to the AMs could potentially promote multifunctional characteristics of these nanoscale macromolecules.

Acetylation of PAMAM dendrimers for cellular delivery of siRNA.

BACKGROUND: The advancement of gene silencing via RNA interference is limited by the lack of effective short interfering RNA (siRNA) delivery vectors. Rational design of polymeric carriers has been complicated by the fact that most chemical modifications affect multiple aspects of the delivery process. In this work, the extent of primary amine acetylation of generation 5 poly(amidoamine) (PAMAM) dendrimers was studied as a modification for the delivery of siRNA to U87 malignant glioma cells. RESULTS: PAMAM dendrimers were reacted with acetic anhydride to obtain controlled extents of primary amine acetylation. Acetylated dendrimers were complexed with siRNA, and physical properties of the complexes were studied. Dendrimers with up to 60% of primary amines acetylated formed approximately 200 nm complexes with siRNA. Increasing amine acetylation resulted in reduced polymer cytotoxicity to U87 cells, as well as enhanced dissociation of dendrimer/siRNA complexes. Acetylation of dendrimers reduced the cellular delivery of siRNA which correlated with a reduction in the buffering capacity of dendrimers upon amine acetylation. Confocal microscopy confirmed that escape from endosomes is a major barrier to siRNA delivery in this system. CONCLUSION: Primary amine acetylation of PAMAM dendrimers reduced their cytotoxicity to U87 cells, and promoted the release of siRNA from dendrimer/siRNA complexes. A modest fraction (approximately 20%) of primary amines of PAMAM can be modified while maintaining the siRNA delivery efficiency of unmodified PAMAM, but higher degrees of amine neutralization reduced the gene silencing efficiency of PAMAM/siRNA delivery vectors.