Manipulating Ligand Density at the Surface of Polyoxovanadate-Alkoxide Clusters.

We present the post-synthetic modification of a polyoxovanadate-alkoxide (POV-alkoxide) cluster via the reactivity of its cationic form, [V6O7(OCH3)12]1+, with water. This result indicates that cluster oxidation increases the lability of bridging methoxide ligands, affording a ligand exchange reaction that serves to compensate for the increased charge of the cluster core. This synthetic advance affords the isolation of a series of POV-alkoxide clusters with varying degrees of µ2-O2- ligands incorporated at the surface, namely, [V6O8(OCH3)11], [V6O9(OCH3)10], and [V6O10(OCH3)9]. Characterization of the POV-alkoxide clusters is described; changes in the infrared and electronic absorption spectra are consistent with the oxidation of the cluster core. We also examine the consequences of ligand substitution on the redox properties of the series of POV-alkoxide clusters via cyclic voltammetry; decreased alkoxide ligand density translates to a cathodic shift of analogous redox events. Ligand substitution also increases comproportionation constants of the Lindqvist core, indicating electron exchange between vanadium centers is promoted in structures with greater numbers of µ2-O2- ligands.

Influences of sociodemographic characteristics and parental HPV vaccination hesitancy on HPV vaccination coverage in five US states.

BACKGROUND: In the United States (US), half of new human papillomavirus (HPV) infections occur among young people aged 15-24 years. Despite the effectiveness of HPV vaccination in protecting against HPV-associated cancers, its coverage among adolescents remains suboptimal. This study examined the association of sociodemographic characteristics and HPV vaccination hesitancy with HPV vaccination coverage in five US states with disproportionately low adolescent coverage rates compared to the national average. METHODS: Responses to an online Qualtrics survey from 926 parents of children aged 9-17 years in Arkansas, Mississippi, Missouri, Tennessee, and Southern Illinois in July 2021 were analyzed using multivariate logistic regression to estimate the association of sociodemographic characteristics and HPV vaccination hesitancy with HPV vaccination coverage. RESULTS: Of the parents, 78 % were female, 76 % were non-Hispanic White, 61.9 % lived in rural areas, 22 % were classified as HPV vaccine hesitant, and 42 % had vaccinated their oldest child between the ages of 9-17 years against HPV. Children of vaccine hesitant parents were less likely to have received any doses of the HPV vaccine than children of non-vaccine hesitant parents (AOR: 0.17, 95 % CI:0.11-0.27). Male children were less likely to have initiated the HPV vaccine series than female children (AOR: 0.70, 95 % CI:0.50-0.97). Older children (13-17 vs 9-12 years), receiving the meningococcal conjugate or most recent seasonal influenza vaccine were all associated with higher likelihoods of receiving any doses of the HPV vaccine (AOR: 6.01, 95 % CI:3.98-9.08; AOR: 2.24, 95 % CI:1.27-3.95; AOR: 2.41, 95 % CI:1.73-3.36, respectively). CONCLUSIONS: Adolescent HPV vaccination coverage remains low in our targeted states. Children's age, sex, and parental vaccine hesitancy were significantly associated with likelihood of HPV vaccination. These findings offer the opportunity for targeted interventions among parents in regions with low vaccine uptake and underscore the importance of developing and implementing strategies to address parental HPV vaccination hesitancy to improve uptake in the US.

AANEM - IFCN glossary of terms in neuromuscular electrodiagnostic medicine and ultrasound.

Modern neuromuscular electrodiagnosis (EDX) and neuromuscular ultrasound (NMUS) require a universal language for effective communication in clinical practice and research and, in particular, for teaching young colleagues. Therefore, the AANEM and the IFCN have decided to publish a joint glossary as they feel the need for an updated terminology to support educational activities in neuromuscular EDX and NMUS in all parts of the world. In addition NMUS has been rapidly progressing over the last years and is now widely used in the diagnosis of disorders of nerve and muscle in conjunction with EDX. This glossary has been developed by experts in the field of neuromuscular EDX and NMUS on behalf of the AANEM and the IFCN and has been agreed upon by electronic communication between January and November 2019. It is based on the glossaries of the AANEM from 2015 and of the IFCN from 1999. The EDX and NMUS terms and the explanatory illustrations have been updated and supplemented where necessary. The result is a comprehensive glossary of terms covering all fields of neuromuscular EDX and NMUS. It serves as a standard reference for clinical practice, education and research worldwide.

AANEM - IFCN Glossary of Terms in Neuromuscular Electrodiagnostic Medicine and Ultrasound.

Modern neuromuscular electrodiagnosis (EDX) and neuromuscular ultrasound (NMUS) require a universal language for effective communication in clinical practice and research and, in particular, for teaching young colleagues. Therefore, the AANEM and the IFCN have decided to publish a joint glossary as they feel the need for an updated terminology to support educational activities in neuromuscular EDX and NMUS in all parts of the world. In addition NMUS has been rapidly progressing over the last years and is now widely used in the diagnosis of disorders of nerve and muscle in conjunction with EDX. This glossary has been developed by experts in the field of neuromuscular EDX and NMUS on behalf of the AANEM and the IFCN and has been agreed upon by electronic communication between January and November 2019. It is based on the glossaries of the AANEM from 2015 and of the IFCN from 1999. The EDX and NMUS terms and the explanatory illustrations have been updated and supplemented where necessary. The result is a comprehensive glossary of terms covering all fields of neuromuscular EDX and NMUS. It serves as a standard reference for clinical practice, education and research worldwide. HIGHLIGHTS: Optimal terminology in neuromuscular electrodiagnosis and ultrasound has been revisited. A team of international experts have revised and expanded a standardized glossary. This list of terms serves as standard reference for clinical practice, education and research.

A Novel Etchant System for Orthodontic Bracket Bonding.

Orthodontic treatment is widely used to correct irregular teeth and/or jaw discrepancies to improve oral function and facial aesthetics. However, it is frequently associated with enamel damage that include chipping, demineralisation, and white spot formation. So far, current bonding systems that can maintain shear bond strengths (SBS) suitable for clinical performance are unable to limit enamel demineralisation, adhesive remnants and damage caused on removal of brackets after treatment. This study reports a novel "safe enamel etch" clinically viable procedure that was accomplished via application of novel etchant pastes developed with ß-tricalcium phosphate and monocalcium phosphate monohydrate powders mixed with citric acid (5 M) or phosphoric acid (37% PA) to yield BCA and BPA etchants respectively. Although enamel etched with clinically used PA gel yielded higher SBS than the BCA/BPA etchants, it exhibited greater adhesive remnants with evidence of enamel damage. In contrast, the experimental etchants resulted in unblemished enamel surfaces with zero or minimal adhesive residue and clinically acceptable SBS. Furthermore, the BPA etchant caused lower enamel decalcification with extensive calcium-phosphate precipitation. The study conclusively showed that BPA facilitated in vitro enamel adhesion without detrimental effects of the aggressive PA gel with potential for remineralisation and saving time at the post-debonding step.

Tumourigenic canine osteosarcoma cell lines associated with frizzled-6 up-regulation and enhanced side population cell frequency.

An increased serum alkaline phosphatase concentration is known to be associated with a negative prognosis in canine and human osteosarcoma. To expand upon previous studies regarding the biological relevance of increased serum alkaline phosphatase as a negative prognostic factor, xenogeneic heterotopic transplants were performed using six canine primary osteosarcoma cell lines generated from patients with differing serum alkaline phosphatase concentrations (three normal and three increased). Three of the six cell lines were capable of generating tumours and tumour formation was independent of the serum alkaline phosphatase status of the cell line. Microarray analysis identified 379 genes as being differentially expressed between the tumourigenic and non-tumourigenic cell lines. Frizzled-6 was upregulated to the greatest extent (7.78-fold) in tumourigenic cell lines compared with non-tumourigenic cell lines. Frizzled-6, a co-receptor for Wnt ligands has been associated with enhanced tumour-initiating cells and poor prognosis for other tumours. The increased expression of frizzled-6 was confirmed by quantitative reverse transcription polymerase chain reaction (QPCR) and Western blot analysis. Additionally, the tumourigenic cell lines also had an increase in the percentage of side population cells compared with non-tumourigenic cell lines (5.89% versus 1.58%, respectively). There were no differences in tumourigenicity, frizzled-6 or percentage of side population cells noted between osteosarcoma cell lines generated from patients of differing serum alkaline phosphatase concentration. However, to our knowledge this is the first study to identified frizzled-6 as a possible marker of osteosarcoma cell populations with enhanced tumourigenicity and side population cells. Future work will focus on defining the role of frizzled-6 in osteosarcoma tumourigenesis and tumour-initiating cells.

Osteosarcoma tissues and cell lines from patients with differing serum alkaline phosphatase concentrations display minimal differences in gene expression patterns.

Serum alkaline phosphatase (ALP) concentration is a prognostic factor for osteosarcoma in multiple studies, although its biological significance remains incompletely understood. To determine whether gene expression patterns differed in osteosarcoma from patients with differing serum ALP concentrations, microarray analysis was performed on 18 primary osteosarcoma samples and six osteosarcoma cell lines from dogs with normal and increased serum ALP concentration. No differences in gene expression patterns were noted between tumours or cell lines with differing serum ALP concentration using a gene-specific two-sample t-test. Using a more sensitive empirical Bayes procedure, defective in cullin neddylation 1 domain containing 1 (DCUN1D1) was increased in both the tissue and cell lines of the normal ALP group. Using quantitative PCR (qPCR), differences in DCUN1D1 expression between the two groups failed to reach significance. The homogeneity of gene expression patterns of osteosarcoma associated differing serum ALP concentrations are consistent with previous studies suggesting serum ALP concentration is not associated with intrinsic differences of osteosarcoma cells.

Risk of hemoptysis in cystic fibrosis clinical trials: A retrospective cohort study.

BACKGROUND: Cystic fibrosis (CF) is characterized by airway infection and inflammation resulting in respiratory complications including hemoptysis. The objectives of this study were to characterize the risk of hemoptysis attributable to underlying disease and in the presence of standard of care therapy. METHODS: This retrospective cohort study estimated hemoptysis rates overall and by relevant risk factors utilizing adverse event data from longitudinal prospective CF clinical trials. RESULTS: Of the 1008 participants, 73% were ≤18 years old; of 929 with available spirometry, 27% had an FEV1<70% predicted. During the average 8.2 months of follow-up, 8% experienced ≥1 hemoptysis events (95% CI: 6%, 10%). Of the 125 events, 76% were mild in severity and only 9% were serious. Hemoptysis rates were greater among adults than children, those with FEV1<70% predicted, and participants infected with P. aeruginosa but not with S. aureus. CONCLUSIONS: Hemoptysis is a common adverse event among CF clinical trial participants, and particularly in adults with more severe lung disease. These results can be used to predict event occurrence in future clinical trials.

Long-term treatment with oral N-acetylcysteine: affects lung function but not sputum inflammation in cystic fibrosis subjects. A phase II randomized placebo-controlled trial.

PURPOSE: To evaluate the effects of oral N-acetylcysteine (NAC), which replenishes systemic glutathione, on decreasing inflammation and improving lung function in CF airways. METHODS: A multicenter, randomized, double-blind proof of concept study in which 70 CF subjects received NAC or placebo orally thrice daily for 24 weeks. ENDPOINTS: primary, change in sputum human neutrophil elastase (HNE) activity; secondary, FEV(1) and other clinical lung function measures; and safety, the safety and tolerability of NAC and the potential of NAC to promote pulmonary hypertension in subjects with CF. RESULTS: Lung function (FEV(1) and FEF(25-75%)) remained stable or increased slightly in the NAC group but decreased in the placebo group (p=0.02 and 0.02). Log(10) HNE activity remained equal between cohorts (difference 0.21, 95% CI -0.07 to 0.48, p=0.14). CONCLUSIONS: NAC recipients maintained their lung function while placebo recipients declined (24 week FEV1 treatment effect=150 mL, p<0.02). However no effect on HNE activity and other selected biomarkers of neutrophilic inflammation were detected. Further studies on mechanism and clinical outcomes are warranted.

Broadening the examination of sociocultural constructs relevant to African-American colorectal cancer screening.

The importance of sociocultural constructs as influences on cancer attitudes and screening has been established in the literature. This paper reports on the efforts to explore alternatives to sociocultural constructs previously associated with African-American cancer screening, but with low acceptance among community members or incomplete measurement (empowerment and collectivism) and develop a measure for a recently identified construct of interest (privacy). We report preliminary psychometric data on these sociocultural scales and their associations with cancer attitudes. African-Americans (N = 1021), 50-75 years of age participated in this study. Participants were identified via a listed sample and completed a telephone survey administered via call center. Sociocultural attitudes were assessed using items identified through computerized database searches, reviewed by advisory panels, edited and tested using cognitive response strategies. Cancer screening pros and cons, cancer worry, perceived cancer risk, colorectal cancer (CRC) screening subjective norms, and perceived self-efficacy for colorectal cancer screening (CRCS) were also assessed. Confirmatory factor analyses and multivariate analyses were conducted to provide support for the validity of the constructs and to understand the associations among the selected sociocultural constructs (empowerment, collectivism, and privacy) and cancer beliefs and attitudes (CRC perceived benefits and barriers, perceived risks, subjective norms, and perceived behavioral control/self-efficacy). Consistent with the literature, the factor analytic model (RMSEA for the model was .062; 90% CI: .060-.065) provided support for the empowerment, collectivism, and privacy constructs. The modified collectivism and privacy scales had acceptable reliability. The privacy scale demonstrated the strongest associations with measures of cancer beliefs and attitudes. The implication of the findings and need for further scale development activities is discussed.

Canine osteosarcoma cell lines from patients with differing serum alkaline phosphatase concentrations display no behavioural differences in vitro.

Osteosarcoma is an aggressive malignancy and represents the most frequent primary bone malignancy of dogs and humans. Prognostic factors reported for osteosarcoma include tumour size, presence of metastatic disease and serum alkaline phosphatase (ALP) concentration at the time of diagnosis. To date, there have been no studies to determine whether the behaviour of osteosarcoma cells differ based on serum ALP concentration. Here, we report on the generation of six canine osteosarcoma cell lines from osteosarcoma-bearing dogs with differences in serum ALP concentration. To determine whether in vitro behaviour differs between primary osteosarcoma cell lines generated from patients with normal or increased serum ALP, assays were performed to evaluate proliferation, migration, invasion and chemosensitivity. There were no significant differences in cell proliferation, migration, invasion or chemosensitivity between cell lines associated with normal or increased serum ALP concentration.

Disassociation of verbal learning and hippocampal volume in type 2 diabetes and major depression.

OBJECTIVE: The purpose of this study was to examine the relationship between verbal learning and memory performance and hippocampal volume in subjects with co-morbid type 2 diabetes and major depression compared with healthy control subjects and subjects with type 2 diabetes alone. METHODS: Twenty four subjects with type 2 diabetes and 20 subjects with type 2 diabetes and major depression were recruited from endocrinology clinics and were compared with 32 healthy control subjects recruited from the community. Subjects were scanned on a 1.5 T GE scanner, and hippocampal volumes were measured using Freesurfer. The California Verbal Learning Test assessed learning and memory. Significant predictors of verbal learning performance (e.g., age, gender, education, blood pressure, stroke risk, hemoglobin A1c, and hippocampal volume) were determined using a stepwise linear regression. RESULTS: Subjects with diabetes and depression had significantly worse performance on verbal list learning compared with healthy control subjects. Hippocampal volume was a strong predictor of performance in healthy control subjects, and age and hippocampal volume were strong predictors in subjects with type 2 diabetes alone. Age alone was a significant predictor of verbal learning performance in subjects with diabetes and depression. CONCLUSIONS: The relationship between hippocampal volume and performance on the California Verbal Learning Test is decoupled in subjects with type 2 diabetes and major depression and this decoupling may contribute to poor verbal learning and memory performance in this study population.

Outside-the-(cavity-prep)-box thinking.

Direct placement restorative materials must interface with tooth structures that are often compromised by caries or trauma. The material must seal the interface while providing sufficient strength and wear resistance to assure function of the tooth for, ideally, the lifetime of the patient. Needed are direct restorative materials that are less technique-sensitive than current resin-based composite systems while having improved properties. The ideal material could be successfully used in areas of the world with limited infrastructure. Advances in our understanding of the interface between the restoration adhesive system and the stages of carious dentin can be used to promote remineralization. Application of fracture mechanics to adhesion at the tooth-restoration interface can provide insights for improvement. Research in polymer systems suggests alternatives to current composite resin matrix systems to overcome technique sensitivity, while advances in nano- and mesoparticle reinforcement and alignment in composite systems can increase material strength, toughness, and wear resistance, foreshadowing dental application.

Changes in tumour vessel density upon treatment with anti-angiogenic agents: relationship with response and resistance to therapy.

BACKGROUND: We examine how changes in a surrogate marker of tumour vessel density correlate with response and resistance to anti-angiogenic therapy. METHODS: In metastatic renal cancer patients treated with anti-angiogenic tyrosine kinase inhibitors, arterial phase contrast-enhanced computed tomography was used to simultaneously measure changes in: (a) tumour size, and (b) tumour enhancement (a surrogate marker of tumour vessel density) within individual lesions. RESULTS: No correlation between baseline tumour enhancement and lesion shrinkage was observed, but a reduction in tumour enhancement on treatment was strongly correlated with reduction in lesion size (r=0.654, P<0.0001). However, close examination of individual metastases revealed different types of response: (1) good vascular response with significant tumour shrinkage, (2) good vascular response with stabilisation of disease, (3) poor vascular response with stabilisation of disease and (4) poor vascular response with progression. Moreover, contrasting responses between different lesions within the same patient were observed. We also assessed rebound vascularisation in tumours that acquired resistance to treatment. The amplitude of rebound vascularisation was greater in lesions that had a better initial response to therapy (P=0.008). INTERPRETATION: Changes in a surrogate marker of tumour vessel density correlate with response and resistance to anti-angiogenic therapy. The data provide insight into the mechanisms that underlie response and resistance to this class of agent.

Activation of the canonical Wnt/ß-catenin signalling pathway is rare in canine malignant melanoma tissue and cell lines.

Canine malignant melanoma is a highly aggressive tumour associated with a poor overall survival rate due to both local disease recurrence and its highly metastatic nature. Similar to advanced melanoma in man, canine oral melanoma is poorly responsive to conventional anti-cancer therapies. The lack of sustainable disease control warrants investigation of novel therapies, preferably targeting features specific to the tumour and different from normal cells. The Wnt signalling pathway is known to contribute to melanocytic lineage development in vertebrates and perturbation of the Wnt/ß-catenin pathway has been implicated in numerous cancer types. Alterations of the Wnt/ß-catenin pathway are suggested to occur in a subset of human melanomas, although the precise role of the Wnt/ß-catenin pathway in melanoma is yet to be defined. This study investigates the activation status of the canonical Wnt/ß-catenin pathway in canine malignant melanoma and its potential as a therapeutic target for treating this disease. The data indicate that canonical Wnt/ß-catenin pathway activation is a rare event in canine oral malignant melanoma tissue and canine malignant melanoma cell lines.

Atrial giant cell myocarditis: a distinctive clinicopathologic entity.

BACKGROUND: Giant cell myocarditis (GCM) typically causes fulminant heart failure, arrhythmias, or heart block, necessitating aggressive immunosuppression, ventricular assist device insertion, or cardiac transplantation. We describe a novel variant of GCM, primarily involving the atria, that displays distinctive clinical features and follows a more benign course than ventricular GCM. METHODS AND RESULTS: We identified 6 patients (median age 67.5 years, 4 male) with atrial GCM in our pathology consultation practices from 2010 to 2012. Clinical history, imaging, and pathology materials were reviewed. Clinically, 4 patients had atrial fibrillation, 1 had acute heart failure, and 1 had incidental disease at autopsy. Among the 5 living patients, echocardiography revealed severe atrial dilatation (5 cases), mitral/tricuspid regurgitation (5), atrial mural thrombus (3), atrial wall thickening (2), and atrial hypokinesis (2). Ventricular function was preserved in all 5. Histological review of surgically resected atria showed giant cell and lymphocytic infiltrates, lymphocytic myocarditis-like foci, cardiomyocyte necrosis, and cardiomyocyte hypertrophy in all cases. Other features included interstitial fibrosis (5), poorly-formed granulomas (4), eosinophils (4), neutrophils (1), and vasculitis (1). Treatment consisted of steroids and cyclosporine (1), pacemaker placement for sick sinus syndrome (1), and supportive care (3). All 5 living patients returned to baseline exercise tolerance after 6 to 16 weeks of follow-up. CONCLUSIONS: Atrial GCM represents a distinct clinicopathologic entity with a more favorable prognosis than classic ventricular GCM. This disorder should be included in the differential diagnosis of atrial dilatation, particularly when associated with atrial wall thickening. The utility of immunomodulatory therapy for this condition remains unknown.

The PBRN initiative: transforming new technologies to improve patient care.

The NIDCR-supported Practice-based Research Network initiative presents dentistry with an unprecedented opportunity by providing a pathway for modifying and advancing the profession. It encourages practitioner participation in the transfer of science into practice for the improvement of patient care. PBRNs vary in infrastructure and design, and sustaining themselves in the long term may involve clinical trial validation by regulatory agencies. This paper discusses the PBRN concept in general and uses the New York University College of Dentistry's Practitioners Engaged in Applied Research and Learning (PEARL) Network as a model to improve patient outcomes. The PEARL Network is structured to ensure generalizability of results, data integrity, and to provide an infrastructure in which scientists can address clinical practitioner research interests. PEARL evaluates new technologies, conducts comparative effectiveness research, participates in multidisciplinary clinical studies, helps evaluate alternative models of healthcare, educates and trains future clinical faculty for academic positions, expands continuing education to include "benchmarking" as a form of continuous feedback to practitioners, adds value to dental schools' educational programs, and collaborates with the oral health care and pharmaceutical industries and medical PBRNs to advance the dental profession and further the integration of dental research and practice into contemporary healthcare (NCT00867997, NCT01268605).

Prenatal exposure to MDMA alters noradrenergic neurodevelopment in the rat.

3,4-methylenedioxymethamphetamine (MDMA; ecstasy) binds with high affinity to the norepinephrine transporter (NET), making the noradrenergic system a potential target during fetal exposure. Recent data indicate that adult rats that had been prenatally exposed to MDMA display persistent deficits in working memory and attention; behaviors consistent with abnormal noradrenergic signaling in the forebrain. The present study was designed to investigate whether prenatal exposure to MDMA from embryonic days 14-20 affects the structure and/or function of the noradrenergic system of the rat on postnatal day 21. Offspring that were prenatally exposed to MDMA exhibited an increase in noradrenergic fiber density in the prelimbic region of the prefrontal cortex and the CA1 region of the hippocampus that was not accompanied by an increase in the number of noradrenergic neurons in the locus coeruleus. Direct tissue autoradiography using tritiated nisoxetine demonstrated that while NET binding was not altered in the prelimbic cortex, the dentate gyrus, or the locus coeruleus, it was increased in the CA1, CA2, and CA3 regions of the hippocampus. Basal levels of norepinephrine were increased in the prefrontal cortex and the nucleus accumbens of MDMA-exposed rats, as compared to saline-treated controls. These findings indicate that prenatal exposure to MDMA results in structural changes in the noradrenergic system as well as functional alterations in NE neurotransmission in structures that are critical in attentional processing.