Laser fluorescence assessment of dental caries arrest with two silver fluoride agents in patients with special needs- a preliminary report.

PURPOSE: While silver diamine fluoride has been used extensively for caries arrest and desensitising, silver fluoride (AgF) at neutral pH may also have value as a minimally invasive dental caries treatment. This study explored the effectiveness of two AgF products (AgF/KI and AgF/SnF2) when used in adult patients with special needs (SN) who had high caries risk and salivary gland hypofunction. METHODS: This split-mouth clinical study, over two appointments 3-months apart, compared the impact of a single application of AgF/KI (Riva Star Aqua, SDI) and AgF/SnF2 (Creighton Dental CSDS, Whiteley) on matched carious lesions in the same arch, by clinical visual-tactile (cVT) assessment of caries status and laser fluorescence (LF, DIAGNOdent) evaluation of bacterial load in the lesions, using repeated measures analysis. RESULTS: Twelve participants were recruited in the study. A total of 56 teeth (28 pairs) were included. Both AgF products gave a significant decrease in caries activity as measured by cVT (P < 0.0001) and LF (P = 0.0027). There were no statistically significant differences between the two AgF treatments, with response rates for improvements in active lesions of 92% in the AgF/KI arm, and 96% in the AgF/SnF2 arm. There was no effect of tooth type, lesion type, arch type, plaque metabolism and plaque area at the site level on outcomes, nor was there a clustering effect of sites in a patient level analysis. Overall, LF was superior to cVT for detecting lesions that still progressed despite treatment (P = 0.0027). CONCLUSION: A single application of AgF/KI or AgF/SnF2 has high predictability (over 90%) for achieving arrest in active caries lesions in adult patients with SN and high caries risk. Clinical assessment should use visual-tactile examination combined with LF readings to detect lesions that are still progressing and that require additional treatments. Future studies should compare these AgF modalities with SDF and explore factors such as time between applications and the need for repeated applications. TRIAL REGISTRATION: The study was registered with the Australian Clinical Trials Registry (ACTRN12621001139864p) on 23/08/2021.

Androgens and Urethral Health: How Hypogonadism Affects Postoperative Outcomes of Patients Undergoing Artificial Urinary Sphincter or Inflatable Penile Prosthesis Placement.

OBJECTIVE: To determine the role of androgens in penile and urethral health, we sought to understand what impact hypogonadism may have on artificial urinary sphincter (AUS) and inflatable penile prosthesis (IPP) outcomes. We hypothesize that patients with hypogonadism are at increased risk of reinterventions, complications, and infections. METHODS: We queried the TriNetX Global Database in March 2023 for patients receiving an AUS or IPP, looking at lifetime reintervention, complication, and infection rates. We conducted multiple comparisons: (1) eugonadal patients against hypogonadal patients, (2) hypogonadal patients on testosterone replacement therapy (TRT) against hypogonadal patients not on TRT, and (3) hypogonadal patients on TRT against eugonadal patients. RESULTS: Hypogonadal patients undergoing AUS had more complications (33.5% vs 28.3%), higher reintervention rates (27.7% vs 24.3%) and higher infection rates (7.3% vs 6.8%), albeit none reaching significance. Hypogonadal patients undergoing IPP had significantly higher infection rates (6.3% vs 4.4%, RR 1.5 (1.04, 2.04)) and reintervention rates (14.9% vs 11.9%, RR 1.3 (1.04, 1.61)), but not complication rates (21.9% vs 18.9%). When comparing patients with hypogonadism on TRT vs off TRT, there was not a significant difference in reinterventions, or complications, in AUS and IPP patients, but there were significantly more infections in IPP patients (7.0% vs 3.9%, RR 1.9 (1.002, 3.5)). CONCLUSION: Hypogonadal patients have more reinterventions, complications, and infections following urologic implant surgery, to varying levels of significance. TRT may not be completely protective to improve tissue health but with many limitations that should be explored in further research.

Diabetes and pancreatic cancer risk in a multiracial cohort.

AIMS: To determine the relationship of diabetes with pancreatic cancer incidence among African American and Whites of similar socio-economic status. METHODS: Using the Southern Community Cohort Study, we conducted a follow-up during 2002-2015 of pancreatic cancer incidence of 73,378 mostly low-income participants aged 40-79 years; 15,913 reported diabetes at baseline. Multivariable Cox analysis controlling for sex, family history of pancreatic cancer, BMI, smoking status, alcohol consumption, education, income and other important covariates, and with age as the timescale was used. RESULTS: Totally, 265 incident pancreatic cancer cases were observed. Pancreatic cancer risk was increased among those with diabetes (HR 1.54, CI 1.16-2.05), with similar increases among African Americans (HR 1.51, CI 1.08-2.11) and Whites (HR 1.78, CI 1.00-3.16). No trend in risk was observed for diabetes duration among those with diabetes, with HRs of 1.39 (0.91-2.11), 2.31 (1.51-3.54) and 1.23 (0.80-1.89) for <5, 5-9 and 10+ years duration, respectively. African Americans were at increased risk of pancreatic cancer (HR = 1.40, 95% CI 1.05-1.87), which persisted after adjusting for diabetes (HR 1.36, CI 1.02-1.81). The effect sizes for other pancreatic cancer risk factors with pancreatic cancer were similar by diabetes status, although a stronger association with low BMI was evident among those with diabetes. CONCLUSIONS: Diabetes increases pancreatic cancer risk similarly among African Americans and Whites in this Southern U.S.

Online Health Information for Penile Prosthesis Implants Lacks Quality and Is Unreadable to the Average US Patient.

BACKGROUND: Online health information (OHI) has become widely accessible and affects patient decisions regarding their healthcare. The purpose of this study was to assess the readability, quality, and accuracy of information available to patients online about penile prosthesis implants (PPIs). METHODS: We performed a Google search using the keywords "penile implant" and "penile prosthesis." The first 30 search results for both terms were analyzed, and advertisements, news articles, duplicates, and videos were excluded. Websites were categorized as institutional, commercial, and personal/patient support. Readability of each website was determined using the Flesch-Kincaid grade level (FKGL) readability formula within the readable tool. Quality was measured by Health On the Net (HON) certification status and the DISCERN scoring method. For website accuracy, a score of 1-4 (1=0-25%, 2=25-50%, 3=50-75%, and 4=75-100%) was assigned. RESULTS: Forty-four websites met the criteria (23 institutional, 12 commercial, and 9 personal/patient support). The mean total FKGL score was 9.55. No statistical difference was detected between mean FKGL for each website category (p=0.69). Only eight websites (18%) scored ≤8th-grade reading level (average US adult level), while 36 (82%) were >8th-grade level. Mean total DISCERN sum score was 39.74/75, with no statistical difference in mean DISCERN score between website types (p=0.08). Over half (55%) of the websites were defined as "very poor" or "poor" quality by DISCERN scoring. Mean total overall quality rating was 2.67/5. HON certification was verified for only nine websites (20%). Twenty-five percent of websites were classified as 0-25% accurate, 23% were 25-50% accurate, 30% were 50-75% accurate, and 23% were 75-100% accurate. CONCLUSION: Most information on the Internet about PPIs is reasonably accurate; however, the majority of websites are deficient in quality and unreadable to the average patient, irrespective of website type.

Building and strengthening relationships between academic departments/divisions of emergency medicine and rural and regional emergency departments.

OBJECTIVES: Make recommendations on approaches to building and strengthening relationships between academic departments or divisions of Emergency Medicine and rural and regional emergency departments. METHODS: A panel of leaders from both rural and urban/academic practice environments met over 8 months. Draft recommendations were developed from panel expertise as well as survey data and presented at the 2018 Canadian Association of Emergency Physicians (CAEP) Academic Symposium. Symposium feedback was incorporated into final recommendations. RESULTS: Seven recommendations emerged and are summarized below: 1)CAEP should ensure engagement with other rural stakeholder organizations such as the College of Family Physicians of Canada and the Society of Rural Physicians of Canada.2)Engagement efforts require adequate financial and manpower resources.3)Training opportunities should be promoted.4)The current operational interface between the academic department of Emergency Medicine and the emergency departments in the catchment area must be examined and gaps addressed as part of building and strengthening relationships.5)Initial engagement efforts should be around projects with common value.6)Academic Departments should partner with and support rural scholars.7)Academic departments seeking to build or strengthen relationships should consider successful examples from elsewhere in the country as well as considering local culture and challenges. CONCLUSION: These recommendations serve as guidance for building and strengthening mutually beneficial relationships between academic departments or divisions of Emergency Medicine and rural and regional emergency departments.

Microbial coexistence through chemical-mediated interactions.

Many microbial functions happen within communities of interacting species. Explaining how species with disparate growth rates can coexist is important for applications such as manipulating host-associated microbiota or engineering industrial communities. Here, we ask how microbes interacting through their chemical environment can achieve coexistence in a continuous growth setup (similar to an industrial bioreactor or gut microbiota) where external resources are being supplied. We formulate and experimentally constrain a model in which mediators of interactions (e.g. metabolites or waste-products) are explicitly incorporated. Our model highlights facilitation and self-restraint as interactions that contribute to coexistence, consistent with our intuition. When interactions are strong, we observe that coexistence is determined primarily by the topology of facilitation and inhibition influences not their strengths. Importantly, we show that consumption or degradation of chemical mediators moderates interaction strengths and promotes coexistence. Our results offer insights into how to build or restructure microbial communities of interest.

Proteogenomic characterization and integrative analysis of glioblastoma multiforme.

Glioblastoma multiforme (GBM), the most aggressive and lethal primary brain tumor, is characterized by very low life expectancy. Understanding the genomic and proteogenomic characteristics of GBM is essential for devising better therapeutic approaches.Here, we performed proteomic profiling of 8 GBM and paired normal brain tissues. In parallel, comprehensive integrative genomic analysis of GBM was performed in silico using mRNA microarray and sequencing data. Two whole transcript expression profiling cohorts were used - a set of 3 normal brain tissues and 22 glioma tissue samples and a cohort of 5 normal brain tissues and 49 glioma tissue samples. A validation cohort included 529 GBM patients from The Cancer Genome Atlas datasets. We identified 36 molecules commonly changed at the level of the gene and protein, including up-regulated TGFBI and NES and down-regulated SNCA and HSPA12A. Single amino acid variant analysis identified 200 proteins with high mutation rates in GBM samples. We further identified 14 differentially expressed genes with high-level protein modification, among which NES and TNC showed differential expression at the protein level. Moreover, higher expression of NES and TNC mRNAs correlated with shorter overall survival, suggesting that these genes constitute potential biomarkers for GBM.

YAP regulates cell proliferation, migration, and steroidogenesis in adult granulosa cell tumors.

The Hippo signaling pathway has been implicated as a conserved regulator of organ size in both Drosophila and mammals. Yes-associated protein (YAP), the central component of the Hippo signaling cascade, functions as an oncogene in several malignancies. Ovarian granulosa cell tumors (GCT) are characterized by enlargement of the ovary, excess production of estrogen, a high frequency of recurrence, and the potential for malignancy and metastasis. Whether the Hippo pathway plays a role in the pathogenesis of GCT is unknown. This study was conducted to examine the expression of YAP in human adult GCTs and to determine the role of YAP in the proliferation and steroidogenesis of GCT cells. Compared with age-matched normal human ovaries, GCT tissues exhibited higher levels of YAP expression. YAP protein was predominantly expressed in the nucleus of tumor cells, whereas the non-tumor ovarian stromal cells expressed very low levels of YAP. YAP was also expressed in cultured primary human granulosa cells and in KGN and COV434 GCT cell lines. siRNA-mediated knockdown of YAP in KGN cells resulted in a significant reduction in cell proliferation (P<0.001). Conversely, overexpression of wild type YAP or a constitutively active YAP (YAP1) mutant resulted in a significant increase in KGN cell proliferation and migration. Moreover, YAP knockdown reduced FSH-induced aromatase (CYP19A1) protein expression and estrogen production in KGN cells. These results demonstrate that YAP plays an important role in the regulation of GCT cell proliferation, migration, and steroidogenesis. Targeting the Hippo/YAP pathway may provide a novel therapeutic approach for GCT.

Clinical factors and echocardiographic techniques related to the presence, size, and location of acoustic windows for leadless cardiac pacing.

AIMS: Temporary leadless cardiac pacing using ultrasound energy is feasible in patients. An implantable left ventricular stimulation system being developed for cardiac resynchronization therapy transfers energy from a subcutaneous transmitter to an endocardial receiver through tissue free of interfering lung or rib ('acoustic window'). The aim was to use transthoracic echocardiography to evaluate acoustic window (AW) locations and sizes to determine the implant site for a transmitter, and to investigate clinical predictors of AW location and size. METHODS AND RESULTS: Inclusion criteria were ejection fraction ≤35%, and New York Heart Association functional class III or IV. Acoustic windows were evaluated in intercostal spaces (ICSs) measured in the supine, right lateral, sitting, and standing position during normal respiration and held inspiration. Among 42 patients, at least one adequate AW (≥2 cm(2)) was identified in 41, 19 patients had adequate AWs in 2 ICSs and 20 patients had adequate AWs in 3. Acoustic window areas were generally smallest in the lateral position with held inspiration and largest in the standing position with normal respiration. Patients with ischaemic cardiomyopathy compared with non-ischaemic cardiomyopathy had smaller heart size [left ventricular end-systolic volume index (LVESVI) 78 ± 38 mL/m(2) vs. 104 ± 46 mL/m(2), P = 0.03] but larger AWs in the right lateral position (11.4 ± 6.5 cm(2) vs. 7.3 ± 3.4 cm(2), P = 0.01) and standing position (14.0 ± 7.2 cm(2) vs. 9.4 ± 3.3 cm(2), P = 0.02). CONCLUSIONS: Adequate AWs were present in nearly all patients. Despite smaller hearts, ischaemic cardiomyopathy patients had adequate AWs. A simple procedure performed as an adjunct to pre-implant echocardiography can screen patients and identify transmitter implant locations for an ultrasound-mediated leadless pacing system.

A dynamic and chamber-specific mitochondrial remodeling in right ventricular hypertrophy can be therapeutically targeted.

OBJECTIVES: The right ventricle fails quickly after increases in its afterload (ie, pulmonary hypertension) compared with the left ventricle (ie, systemic hypertension), resulting in significant morbidity and mortality. We hypothesized that the poor performance of the hypertrophied right ventricle is caused, at least in part, by a suboptimal mitochondrial/metabolic remodeling. METHODS/RESULTS: We studied mitochondrial membrane potential, a surrogate for mitochondrial function, in human (n = 11) and rat hearts with physiologic (neonatal) and pathologic (pulmonary hypertension) right ventricular hypertrophy in vivo and in vitro. Mitochondrial membrane potential is higher in the normal left ventricle compared with the right ventricle but is highest in the hypertrophied right ventricle, both in myocardium and in isolated cardiomyocytes (P < .01). Mitochondrial membrane potential correlated positively with the degree of right ventricular hypertrophy in vivo and was recapitulated in phenylephrine-treated neonatal cardiomyocytes, an in vitro model of hypertrophy. The phenylephrine-induced mitochondrial hyperpolarization was reversed by VIVIT, an inhibitor of the nuclear factor of activated T lymphocytes, a transcription factor regulating the expression of several mitochondrial enzymes during cardiac development and hypertrophy. The clinically used drug dichloroacetate, known to increase the mitochondria-based glucose oxidation, reversed both the phenylephrine-induced mitochondrial hyperpolarization and nuclear factor of activated T lymphocytes (NFAT) activation. In Langendorff perfusions, dichloroacetate increased rat right ventricular inotropy in hypertrophied right ventricles (P < .01) but not in normal right ventricles, suggesting that mitochondrial hyperpolarization in right ventricular hypertrophy might be associated with its suboptimal performance. CONCLUSIONS: The dynamic changes in mitochondrial membrane potential during right ventricular hypertrophy are chamber-specific, associated with activation of NFAT, and can be pharmacologically reversed leading to improved contractility. This mitochondrial remodeling might provide a framework for development of novel right ventricle-specific therapies.