Sustained deep-tissue voltage recording using a fast indicator evolved for two-photon microscopy.

Genetically encoded voltage indicators are emerging tools for monitoring voltage dynamics with cell-type specificity. However, current indicators enable a narrow range of applications due to poor performance under two-photon microscopy, a method of choice for deep-tissue recording. To improve indicators, we developed a multiparameter high-throughput platform to optimize voltage indicators for two-photon microscopy. Using this system, we identified JEDI-2P, an indicator that is faster, brighter, and more sensitive and photostable than its predecessors. We demonstrate that JEDI-2P can report light-evoked responses in axonal termini of Drosophila interneurons and the dendrites and somata of amacrine cells of isolated mouse retina. JEDI-2P can also optically record the voltage dynamics of individual cortical neurons in awake behaving mice for more than 30 min using both resonant-scanning and ULoVE random-access microscopy. Finally, ULoVE recording of JEDI-2P can robustly detect spikes at depths exceeding 400 µm and report voltage correlations in pairs of neurons.

A positively tuned voltage indicator for extended electrical recordings in the brain.

Genetically encoded voltage indicators (GEVIs) enable optical recording of electrical signals in the brain, providing subthreshold sensitivity and temporal resolution not possible with calcium indicators. However, one- and two-photon voltage imaging over prolonged periods with the same GEVI has not yet been demonstrated. Here, we report engineering of ASAP family GEVIs to enhance photostability by inversion of the fluorescence-voltage relationship. Two of the resulting GEVIs, ASAP4b and ASAP4e, respond to 100-mV depolarizations with ≥180% fluorescence increases, compared with the 50% fluorescence decrease of the parental ASAP3. With standard microscopy equipment, ASAP4e enables single-trial detection of spikes in mice over the course of minutes. Unlike GEVIs previously used for one-photon voltage recordings, ASAP4b and ASAP4e also perform well under two-photon illumination. By imaging voltage and calcium simultaneously, we show that ASAP4b and ASAP4e can identify place cells and detect voltage spikes with better temporal resolution than commonly used calcium indicators. Thus, ASAP4b and ASAP4e extend the capabilities of voltage imaging to standard one- and two-photon microscopes while improving the duration of voltage recordings.

Examination of orthodontic expenditures and trends in the United States from 1996 to 2016: disparities across demographics and insurance payers.

BACKGROUND: Orthodontics prevent and treat facial, dental, and occlusal anomalies. Untreated orthodontic problems can lead to significant dental public health issues, making it important to understand expenditures for orthodontic treatment. This study examined orthodontic expenditures and trends in the United States over 2 decades. METHODS: This study used data collected by the Medical Expenditure Panel Survey to examine orthodontic expenditures in the United States from 1996 to 2016. Descriptive statistics for orthodontic expenditures were computed and graphed across various groups. Trends in orthodontic expenditures were adjusted to the 2016 United States dollar to account for inflation and deflation over time. Sampling weights were applied in estimating per capita and total expenditures to account for non-responses in population groups. RESULTS: Total orthodontic expenditures in the United States almost doubled from $11.5 billion in 1996 to $19.9 billion in 2016 with the average orthodontic expenditure per person increasing from $42.69 in 1996 to $61.52 in 2016. Black individuals had the lowest per capita orthodontic visit expenditure at $30.35. Out-of-pocket expenses represented the highest total expenditure and although the amount of out-of-pocket expenses increased over the years, they decreased as a percentage of total expenditures. Public insurance increased the most over the study period but still accounted for the smallest percentage of expenditures. Over the course of the study, several annual decreases were interspersed with years of increased spending CONCLUSION: While government insurance expenditure increased over the study period, out of pocket expenditures remained the largest contributor. Annual decreases in expenditure associated with economic downturns and result from the reliance on out-of-pocket payments for orthodontic care. Differences in spending among groups suggest disparities in orthodontic care among the US population.

Social Network Analysis of COVID-19 Sentiments: Application of Artificial Intelligence.

BACKGROUND: The coronavirus disease (COVID-19) pandemic led to substantial public discussion. Understanding these discussions can help institutions, governments, and individuals navigate the pandemic. OBJECTIVE: The aim of this study is to analyze discussions on Twitter related to COVID-19 and to investigate the sentiments toward COVID-19. METHODS: This study applied machine learning methods in the field of artificial intelligence to analyze data collected from Twitter. Using tweets originating exclusively in the United States and written in English during the 1-month period from March 20 to April 19, 2020, the study examined COVID-19-related discussions. Social network and sentiment analyses were also conducted to determine the social network of dominant topics and whether the tweets expressed positive, neutral, or negative sentiments. Geographic analysis of the tweets was also conducted. RESULTS: There were a total of 14,180,603 likes, 863,411 replies, 3,087,812 retweets, and 641,381 mentions in tweets during the study timeframe. Out of 902,138 tweets analyzed, sentiment analysis classified 434,254 (48.2%) tweets as having a positive sentiment, 187,042 (20.7%) as neutral, and 280,842 (31.1%) as negative. The study identified 5 dominant themes among COVID-19-related tweets: health care environment, emotional support, business economy, social change, and psychological stress. Alaska, Wyoming, New Mexico, Pennsylvania, and Florida were the states expressing the most negative sentiment while Vermont, North Dakota, Utah, Colorado, Tennessee, and North Carolina conveyed the most positive sentiment. CONCLUSIONS: This study identified 5 prevalent themes of COVID-19 discussion with sentiments ranging from positive to negative. These themes and sentiments can clarify the public's response to COVID-19 and help officials navigate the pandemic.

Two infants with bilateral renal agenesis who were bridged by chronic peritoneal dialysis to kidney transplantation.

Bilateral renal agenesis is associated with severe oligohydramnios and was considered incompatible with postnatal life due to severe pulmonary hypoplasia. The use of renal replacement therapy was limited by significant morbidity and mortality associated with dialysis in very young infants with major pulmonary pathology. In the United States, there is a tremendous controversy about whether or not the use of prenatal amniotic fluid infusions provides a benefit to fetuses with bilateral renal agenesis. One of the critical issues identified is that there are, as yet, no children reported who had achieved long-term survival. Previous reports all indicated these children died shortly after birth or after unsuccessful peritoneal dialysis. We present two infants with a prenatal diagnosis of bilateral renal agenesis whose mothers elected to undergo prenatal amnioinfusions. One was born at 28 weeks with a birthweight of 1230 g and the other born at 34 weeks with a birthweight of 1940 g. We present the details of both cases, with initial management on chronic peritoneal dialysis, which started shortly after birth, as a bridge to living related kidney transplants.

Profile of Orthodontic Use across Demographics.

OBJECTIVES: Population-based studies have focused on patients' rendering of orthodontic treatment due to their malocclusion and medical needs. However, there is a scarcity of data from national sources on the prevalence of orthodontic visits and associated patient characteristics, as well as their effect on dental health. This study evaluated the demographic differences of orthodontic patients and examined the association between orthodontics use and risk of periodontal disease and oral surgical intervention. METHODS: This study used data collected from the 2019 Medical Expenditure Panel Survey. Descriptive statistics were used to evaluate socio-demographics and covariates by the use of orthodontics. Chi-square tests were used to assess demographic differences among respondents who stated whether or not they used orthodontics. Logistic regression models were then used to examine the association of orthodontics and oral health outcomes. RESULTS: The sample size was 12,422, of which 491 respondents indicated a usage of orthodontics. There were significant differences among demographic variables (p < 0.05) that included 61.1% females, 60.8% Whites, 67.6% participants under the age of 18 years old, and a family total income of $100,000 or more (52.7%). After controlling for socio-demographics and covariates, individuals who used orthodontics were less likely to have periodontal disease (AOR = 0.623, 95% CI = 0.610 to 0.637) and tooth extractions (AOR = 0.071, 95% CI = 0.070 to 0.073) than those who did not. CONCLUSIONS: Our findings indicate orthodontics usage was higher in females, younger patients, and Whites, highlighting the possible demographic disparities in orthodontics use. Additionally, those who used orthodontics were less likely to have oral health issues.

Elemental mercury poisoning presenting as hypertension in a young child.

Mercury intoxication is an uncommon cause of hypertension in children and can mimic several other diseases, such as pheochromocytoma and vasculitis. Mercury intoxication can present as a diagnostic challenge because levels of catecholamines may be elevated, suggesting that the etiology is a catecholamine-secreting tumor. Once acrodynia is identified as a primary symptom, a 24-hour urine mercury level can confirm the diagnosis. Inclusion of mercury intoxication in the differential diagnosis early on can help avoid unnecessary and invasive diagnostic tests and therapeutic interventions. We discuss a case of mercury intoxication in a 3-year-old girl presenting with hypertension and acrodynia, without a known history of exposure. Chelation therapy successfully treated our patient's mercury intoxication. However, it was also necessary to concurrently treat her hypertension and the pain associated with her acrodynia. Because there were no known risk factors for mercury poisoning in this case, and because ritual use of mercury is common in much of the United States, we recommend high clinical suspicion and subsequent testing in all cases of acrodynia.

Case report: Diarrhea-associated hemolytic uremic syndrome in the Era of COVID-19.

Over the past two years, a growing number of SARS-CoV-2 infection-associated clinical pediatric phenotypes have been identified, including a hemolytic uremic syndrome (HUS) form of thrombotic microangiopathy. Oregon's high prevalence of Shiga toxin-producing Escherichia coli (STEC) infections gives it a unique perspective to discuss the impact of COVID-19 and HUS. We seek to highlight SARS-CoV-2 as a potential new infectious etiology of severe diarrhea-associated HUS, based on two cases from Portland, Oregon, occurring in non-COVID-19 immunized children. The first case is a previously healthy ten-year-old who presented with SARS-CoV-2 infection and bloody diarrhea after an appendectomy, followed by full-blown oligo-anuric HUS. Second is a previously healthy six-year-old who presented with short-lived bloody diarrhea, rapidly evolving to HUS, and who tested positive for COVID-19 via polymerase chain reaction and STEC toxins one and two. These two cases highlight two main points. First, SARS-CoV-2 must be included in the differential diagnosis of diarrhea-associated HUS, either as the sole agent or concurrent with a STEC infection. Second, when managing STEC gastroenteritis the recommendation has been to maintain excellent hydration as a strategy to prevent the progression to oligo-anuric acute kidney injury and HUS. This strategy may need to be re-evaluated in a patient with SARS-CoV-2 infection or co-infection.

Comparing oral health behaviours of men and women in the United States.

OBJECTIVE: This study used a national database to update and examine current differences in men's and women's oral health and oral health behaviours in the United States. METHODS: Data from the National Health and Nutrition Examination Survey for the 2017-2018 cycle were used to explore the relationship between males and females and their oral health. Multivariate analyses assessed for gender differences in oral health behaviors between genders after controlling for sample demographic characteristics. RESULTS: The final sample consisted of 4,741 participants. Males tended to have fewer dental visits, worse perception of their gum and tooth health, poorer flossing habits, and more root caries. Females were more proactive in visiting dentists and displayed a greater awareness of oral health. Females were less likely to report discussing oral cancer screening with their dentist even though they were screened more often. On examination, males were more often advised to seek urgent dental care than females. All these differences were statistically significant at p<0.05, although the effect size for examination variables was small (Phi <0.1). CONCLUSIONS: Oral health and oral health behaviours demonstrate gender differences with men reporting poorer oral health, poorer oral hygiene habits, and fewer dental visits. These findings suggest gender-targeted strategies have the potential to improve oral health and reduce gender-related disparities. CLINICAL SIGNIFICANCE: This study found that women exhibit better oral health practices and behaviours. These differences may cause a disproportionate burden of oral disease in men and highlight the need for dentists, hygienists, and those interested in dental public health to develop gender-specific strategies to address these inequalities.

An Exploration of the Use and Impact of Preventive Measures on Skin Cancer.

Background: Skin cancer is the most common form of cancer, and both clinical and epidemiological data link cumulative solar dosages and the number of sunburns to skin cancer. Each year, more than 5.4 million new cases of skin cancer are diagnosed, incurring a significant health and financial burden. Recommended preventive measures for skin cancer include the use of sunscreen, sun avoidance, and protective clothing. This study used a national database to examine the association of preventive measures with the prevalence of skin cancer, specifically analyzing the preventive measures of sunscreen use, staying in the shade, and wearing long-sleeved shirts. The second aim was to determine which characteristics, if any, correlated with using prevention measures. Methods: This study analyzed data from the National Health and Nutritional Examination Survey 2015−2016 cycle to examine the association of three preventive measures (using sunscreen, staying in the shade, and wearing long-sleeved shirts) with skin cancer. Logistic regression and chi-square tests were utilized to examine the relationship between skin cancer and these prevention methods. Results: Sunscreen use (OR = 3.752; p < 0.05) was statistically associated with a lower prevalence of skin cancer, while wearing long-sleeved shirts (OR = 6.911; p = 0.064) and staying in the shade (OR = 0.646; p = 0.481) did not emerge as factors significantly associated with a lower prevalence after controlling for gender, race/ethnicity, marital status, income, health insurance, and general health. Additionally, men and individuals of color were less likely to use sunscreen. Conclusion: Sunscreen use was associated with a lower prevalence of skin cancer, while wearing long-sleeved shirts and staying in the shade was not significantly linked to lower rates of skin cancer, suggesting that these measures may not be as effective as sunscreen for preventing skin cancer. Men and individuals of color were significantly less likely to use sunscreen. These findings can help guide future education efforts and research regarding skin cancer prevention and suggest the need to develop male-oriented programs to mitigate the gender disparity in employing sun-protection measures.

Relationships between ENDS-Related Familial Factors and Oral Health among Adolescents in the United States.

The influence of familial and social environments plays a significant role in Electronic Nicotine Delivery System (ENDS) use and may contribute to poor oral health among adolescents. This study utilized the Population Assessment of Tobacco and Health (PATH) database and included youths aged 12 to 17 years who reported no history of dental health issues at baseline. Adjusted odds ratios (AOR) were used to examine the association between END-related familial factors and oral health among adolescents in the United States, with statistical significance set at p < 0.05. The sample consisted of 3892 adolescents (weighted N = 22,689,793). Parents' extremely negative reaction towards ENDS when they found their children using ENDS (AOR = 0.309) was connected to a lower risk of oral health issues. The findings suggest that clinicians and policymakers need to consider the roles of these factors when developing strategies to improve oral health outcomes.

Alpha 2-macroglobulin capture allows detection of mast cell chymase in serum and creates a reservoir of angiotensin II-generating activity.

Human chymase is a highly efficient angiotensin II-generating serine peptidase expressed by mast cells. When secreted from degranulating cells, it can interact with a variety of circulating antipeptidases, but is mostly captured by alpha(2)-macroglobulin, which sequesters peptidases in a cage-like structure that precludes interactions with large protein substrates and inhibitors, like serpins. The present work shows that alpha(2)-macroglobulin-bound chymase remains accessible to small substrates, including angiotensin I, with activity in serum that is stable with prolonged incubation. We used alpha(2)-macroglobulin capture to develop a sensitive, microtiter plate-based assay for serum chymase, assisted by a novel substrate synthesized based on results of combinatorial screening of peptide substrates. The substrate has low background hydrolysis in serum and is chymase-selective, with minimal cleavage by the chymotryptic peptidases cathepsin G and chymotrypsin. The assay detects activity in chymase-spiked serum with a threshold of approximately 1 pM (30 pg/ml), and reveals native chymase activity in serum of most subjects with systemic mastocytosis. alpha(2)-Macroglobulin-bound chymase generates angiotensin II in chymase-spiked serum, and it appears in native serum as chymostatin-inhibited activity, which can exceed activity of captopril-sensitive angiotensin-converting enzyme. These findings suggest that chymase bound to alpha(2)-macroglobulin is active, that the complex is an angiotensin-converting enzyme inhibitor-resistant reservoir of angiotensin II-generating activity, and that alpha(2)-macroglobulin capture may be exploited in assessing systemic release of secreted peptidases.

Men and Oral Health: A Review of Sex and Gender Differences.

Sex and gender related health disparities in oral health remain an underappreciated and often over looked aspect of well-being. The goal of this narrative review is to identify sex and gender related oral health disparities by summarizing the current literature related to differences in oral health between men and women. The review identified that men are more likely to: ignore their oral health, have poorer oral hygiene habits, and experience higher rates of periodontal disease, oral cancer, and dental trauma. Men also visit dentists less frequently and compared to women seek oral treatment more often for an acute problem and less often for disease prevention. Women exhibit more positive attitudes about dental visits, greater oral health literacy, and demonstrate better oral health behaviors than men. Men disproportionately develop periodontal diseases due to a combination of biological and gender related reasons including immune system factors, hormone differences, poorer oral hygiene behaviors, and greater tobacco use. There is a male to female ratio of 2:1 for oral cancer, largely attributable to more tobacco use, heavier use of alcohol, and longer sun exposure. Minority men experience a disproportionate burden of oral health disparities because of both their gender and race/ethnic identities. In conclusion, this review identifies several differences between men and women related to oral health and highlights the need for further research to better understand these disparities and how to incorporate them into developing prevention, education and treatment strategies to improve oral health in men.

Predicting all-cause 90-day hospital readmission for dental patients using machine learning methods.

INTRODUCTION: Hospital readmission rates are an indicator of the health care quality provided by hospitals. Applying machine learning (ML) to a hospital readmission database offers the potential to identify patients at the highest risk for readmission. However, few studies applied ML methods to predict hospital readmission. This study sought to assess ML as a tool to develop prediction models for all-cause 90-day hospital readmission for dental patients. METHODS: Using the 2013 Nationwide Readmissions Database (NRD), the study identified 9260 cases for all-cause 90-day index admission for dental patients. Five ML classification algorithms including decision tree, logistic regression, support vector machine, k-nearest neighbors, and artificial neural network (ANN) were implemented to build predictive models. The model performance was estimated and compared by using area under the receiver operating characteristic curve (AUC), and accuracy, sensitivity, specificity, and precision. RESULTS: Hospital readmission within 90 days occurred in 1746 cases (18.9%). Total charges, number of diagnosis, age, number of chronic conditions, length of hospital stays, number of procedures, primary expected payer, and severity of illness emerged as the top eight important features in all-cause 90-day hospital readmission. All models had similar performance with ANN (AUC = 0.743) slightly outperforming the rest. CONCLUSION: This study demonstrates a potential annual saving of over $500 million if all of the 90-day readmission cases could be prevented for 21 states represented in the NRD. Among the methods used, the prediction model built by ANN exhibited the best performance. Further testing using ANN and other methods can help to assess important readmission risk factors and to target interventions to those at the greatest risk.

Health Disparities Associated with Females Reporting Human Papillomavirus Infection in the United States.

Few studies provide detailed findings about the health disparities of women being told by a physician whether they have ever had a human papillomavirus (HPV) infection. This study sought to characterize the prevalence and characteristics associated with women age 18 to 59 years in the United States who report being told they were infected with HPV. This study used data from the National Health and Nutritional Examination Survey. Descriptive statistics were computed on study variables and multiple logistic regression analyses were conducted to explore the association of the study variables with the outcome variable. Sampling weights were applied to produce national estimates of prevalence. The sample consisted of 1,669 females, representative of 75,107,170 females in the United States population. Around 11.5% reported being told that they had an HPV infection, of which 60.9% were White, and 82.9% were born in the United States. White women are 2.0 times more likely to be told they have HPV than Asian women and 2.8 times more likely than Black women. United States-born women were 2.1 times more likely told they had an HPV infection than those foreign born. This study found that among U.S. women, less than 12% reported ever having been told they have had an HPV infection. Epidemiologic findings suggest gaps between ever being told of a previous infection and being diagnosed with a clinically relevant HPV infection. Despite epidemiologic data indicating higher HPV prevalence among those less educated and women of color, these groups were less likely to report ever being told they have an HPV infection than White women, and those with a college degree suggesting communication gaps among these subgroups about HPV infection that might exist. Strategies to address potential gaps in communication among these subgroups can potentially reduce the economic burden and health disparities related to HPV infection.

In an era of uncertainty: Impact of COVID-19 on dental education.

PURPOSE/OBJECTIVES: The coronavirus disease 2019 (COVID-19) pandemic arguably represents the worst public health crisis of the 21st century. However, no empirical study currently exists in the literature that examines the impact of the COVID-19 pandemic on dental education. This study evaluated the impact of COVID-19 on dental education and dental students' experience. METHODS: An anonymous online survey was administrated to professional dental students that focused on their experiences related to COVID-19. The survey included questions about student demographics, protocols for school reopening and student perceptions of institutional responses, student concerns, and psychological impacts. RESULTS: Among the 145 respondents, 92.4% were pre-doctoral dental students and 7.6% were orthodontic residents; 48.2% were female and 12.6% students lived alone during the school closure due to the pandemic. Students' age ranged from 23 to 39 years. Younger students expressed more concerns about their emotional health (P = 0.01). In terms of the school's overall response to COVID-19, 73.1% students thought it was effective. The majority (83%) of students believed that social distancing in school can minimize the development of COVID-19. In general, students felt that clinical education suffered after transitioning to online but responded more positively about adjustments to other online curricular components. CONCLUSIONS: The COVID-19 pandemic significantly impacted dental education. Our findings indicate that students are experiencing increased levels of stress and feel their clinical education has suffered. Most students appear comfortable with technology adaptations for didactic curriculum and favor masks, social distancing, and liberal use of sanitizers.

Prediction of 30-Day Hospital Readmissions for All-Cause Dental Conditions using Machine Learning.

INTRODUCTION: It is unknown whether patients admitted for all-cause dental conditions (ACDC) are at high risk for hospital readmission, or what are the risk factors for dental hospital readmission. OBJECTIVE: We examined the prevalence of, and risk factors associated with, 30-day hospital readmission for patients with an all-cause dental admission. We applied artificial intelligence to develop machine learning (ML) algorithms to predict patients at risk of 30-day hospital readmission. METHODS: This study used data extracted from the 2013 Nationwide Readmissions Database (NRD). There were a total of 11,341 cases for all-cause index admission for dental patients admitted to the hospitals. Descriptive statistics were used to analyze patient characteristics. This study applied five techniques to build risk prediction models and to identify risk factors. Model performance was evaluated using area under the receiver operating characteristic curve (AUC), and accuracy, sensitivity, specificity and precision. RESULTS: There were 11% of patients admitted for ACDC readmitted within 30 days of hospital discharge. On average, the total charge per patient was $131,004 for those with 30-day readmission (n=1254) and $69,750 for those without readmission (n=10,087). Factors significantly associated with 30-day hospital readmission included total charges, number of diagnoses, age, number of chronic conditions, length of hospital stays, number of procedures, Medicare insurance and Medicaid insurance, and severity of illness. Model performance from all methods was similar with the artificial neural network showing the highest AUC of 0.739. CONCLUSION: Our results demonstrate that readmission after hospitalization with ACDC is fairly common. If one-third of the 30-day readmission cases can be avoided, there is a potential annual saving of over $25 million among the twenty-one states represented in the NRD. The ML algorithms can predict hospital readmission in dental patients and should be further tested to aid the reduction of hospital readmission and enhancement of patient-centered care.

Teaching Pediatric Peritoneal Dialysis Globally through Virtual Simulation.

BACKGROUND AND OBJECTIVES: Despite the increasing prevalence of childhood kidney disease worldwide, there is a shortage of clinicians trained to provide peritoneal dialysis (PD). E-learning technologies may provide a solution to improve knowledge in PD. We describe the development of a virtual PD simulator and report the first 22 months of online usage. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: The PD simulator was developed and released on OPENPediatrics in January of 2016. A prospective study of international, multidisciplinary healthcare providers was conducted from January of 2016 through October of 2017. User action data were analyzed with descriptive statistics and linear regression. Paired t tests compared user pre- and post-test scores. User satisfaction was assessed by survey. RESULTS: The simulator was accessed by 1066 users in 70 countries. Users spent a median of 35 minutes (interquartile range [IQR] 14-84) in the simulator. Users who completed the structured learning curriculum (n=300) spent a median of 85 minutes (IQR 46-95), and those who completed the entire simulator (n=63) spent a median of 122 minutes (IQR 69-195). Users who completed the simulator were more likely to scroll through text and access the simulator in multiple sessions. The 300 users that completed testing showed statistically significant increases in the post- versus pretest scores, with a mean increase of 36.4 of 100 points, SD 19.9 (95% confidence interval, 34.1 to 38.6, P<0.001). Eighty-seven percent (20 of 23) of survey respondents felt the simulator was relevant to their clinical practice, and 78% (18 of 23) would recommend it to others. CONCLUSIONS: This is the first reported virtual PD simulator. Increased test scores were observed between pre- and post-tests by clinicians who completed testing, across disciplines, training levels, and resource settings.