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Background: Many patients with bipolar disorder (BD) do not respond to or have difficulties tolerating lithium and/or other mood stabilizing agents. There is a need for personalized treatments based on biomarkers in guiding treatment options. The calcium voltage-gated channel CACNA1C is a promising candidate for developing personalized treatments. CACNA1C is implicated in BD by genome-wide association studies and several lines of evidence suggest that targeting L-type calcium channels could be an effective treatment strategy. However, before such individualized treatments can be pursued, biomarkers predicting treatment response need to be developed., Methods: As a first step in testing the hypothesis that CACNA1C genotype is associated with serum levels of CACNA1C, we conducted ELISA measures on serum samples from 100 subjects with BD and 100 control subjects., Results: We observed significantly higher CACNA1C (p < 0.01) protein levels in subjects with BD. The risk single nucleotide polymorpshism (SNP) (rs11062170) showed functional significance as subjects homozygous for the risk allele (CC) had significantly greater CACNA1C protein levels compared to subjects with one (p = 0.013) or no copies (p = 0.009). We observed higher somatostatin (SST) (p < 0.003) protein levels and lower levels of the clock protein aryl hydrocarbon receptor nuclear translocator-like (ARTNL) (p < 0.03) and stress signaling factor corticotrophin releasing hormone (CRH) (p < 0.001) in BD. SST and period 2 (PER2) protein levels were associated with both alcohol dependence and lithium response., Conclusions: Our findings represent the first evidence for increased serum levels of CACNA1C in BD. Along with altered levels of SST, ARNTL, and CRH our findings suggest CACNA1C is associated with circadian rhythm and stress response disturbances in BD., Competing Interests: Declaration of competing interest The authors have no competing financial interests to disclose., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Sleep disturbances are highly prevalent in depressive episodes and are linked to higher mood severity and suicidal behaviors. Slow wave sleep (SWS) and REM sleep are compromised in depression. Current evidence suggests that rapid antidepressant effects of intravenous (IV) ketamine in patients with treatment-resistant depression (TRD) is mediated by its effects on SWS and REM sleep. Sleep phenotypes may help predict ketamine response., Method: In this observational study, we investigated differences in rates of response among sleep phenotypes defined by QIDS-SR in a cohort of patients with TRD (n = 52) treated with IV ketamine or intranasal (IN) esketamine. Also, we explored a neurovegetative symptoms of atypical depression (NVSAD) phenotype and its association between response and change in QIDS-SR following the treatment with IV ketamine/IN esketamine., Results: 94 % of patients reported sleep difficulties and 62 % reported more than one sleep phenotype with middle and early insomnia being the most prevalent. Individuals with baseline hypersomnia showed higher response rates and more pronounced improvements on their QIDS-SR score. Additionally, 15 % of patients presented with NVSAD phenotype; the majority of whom achieved response and had higher reductions on QIDS-SR. A trend towards faster response was identified for hypersomnia and atypical depression phenotypes., Limitations: Observational study design and lack of a placebo group., Conclusions: Our data indicate that patients with TRD who have baseline hypersomnia and atypical depression features experienced a more substantial reduction in depressive symptoms and are more likely to achieve response with ketamine/esketamine. This could serve as a future predictor for clinical response., Competing Interests: Declaration of competing interest BS has received research grant support from the Mayo Clinic, the NNDC Momentum grant (unrelated to this study) and BD2 (Breakthrough Discoveries for thriving with bipolar disorder). JLVV has received grant-in-kind support from Assurex Health (unrelated to this study). Dr. Kung received payment for a recorded CME presentation about transcranial magnetic stimulation by Psychopharmacology Institute. Other authors report no potential conflicts of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: During the COVID-19 outbreak, video appointments became a popular method for health care delivery, particularly in the early stages of the pandemic. Although Mayo Clinic aimed to reduce face-to-face (F2F) appointments to prevent the spread of the virus, some patients continued seeing their health care providers in person. In the later stages of the pandemic, many patients became comfortable with video appointments, even if they were initially hesitant. However, a subset of patients continued to avoid video appointments. It is not yet clear what sociodemographic factors may be associated with this group of patients., Objective: This cross-sectional study aimed to examine demographic and social determinant of health (SDoH) factors associated with persistent nonusers of video appointments among a sample of patients within a multistate health care organization. We also explored patient beliefs about the use of video for health care appointments., Methods: We conducted a 1-time cross-sectional paper survey, mailed between July and December 2022, of patients matching the eligibility criteria: (1) aged ≥18 years as of April 2020, (2) Mayo Clinic Midwest, Florida, or Arizona patient, (3) did not use video appointment services during April-December 2020 but attended F2F appointments in the departments of primary care and psychiatry/psychology. The survey asked patients, "Have you ever had a video appointment with a healthcare provider?" "Yes" respondents were defined as "users" (adapted to video appointments), and "no" respondents were defined as "persistent nonusers" of video appointments. We analyzed demographics, SDoH, and patient beliefs toward video appointments in 2 groups: persistent nonusers of video appointments and users. We used chi-square and 2-tailed t tests for analysis., Results: Our findings indicate that patients who were older, lived in rural areas, sought care at Mayo Clinic Midwest, and did not have access to the patient portal system were likely to be persistent nonusers of video appointments. Only 1 SDoH factor (not having a disability, handicap, or chronic disease) was associated with persistent nonuse of video appointments. Persistent nonusers of video appointments held personal beliefs such as discomfort with video communication, difficulty interpreting nonverbal cues, and personal preference for F2F appointments over video., Conclusions: Our study identified demographic (older age and rural residence), sociodemographic factors (not having a disability, handicap, or chronic disease), and personal beliefs associated with patients' decisions to choose between video versus F2F appointments for health care delivery. Health care institutions should assess patients' negative attitudes toward technology prior to introducing them to digital health care services. Failing to do so may result in its restricted usage, negative patient experience, and wasted resources. For patients who hold negative beliefs about technology but are willing to learn, a "digital health coordinator" could be assigned to assist with various digital health solutions., (©Pravesh Sharma, Celia Kamath, Tabetha A Brockman, Anne Roche, Pamela Sinicrope, Ruoxiang Jiang, Paul A Decker, Vanessa Pazdernik, Christi Patten. Originally published in JMIR Formative Research (https://formative.jmir.org), 24.01.2024.)

Background: Anxiety and depression are frequently comorbid yet phenotypically distinct. This study identifies differences in the clinically observable phenome across a wide variety of physical and mental disorders comparing patients with diagnoses of depression without anxiety, anxiety without depression, or both depression and anxiety., Methods: Using electronic health records for 14 994 participants with depression and/or anxiety in the Mayo Clinic Biobank, a phenotype-based phenome-wide association study (Phe 2 WAS) was performed to test for differences between these groups across a broad range of clinical diagnoses observed in the electronic health record. Additional analyses were performed to determine the temporal sequencing of diagnoses., Results: Compared to patients diagnosed only with anxiety, those diagnosed only with depression were more likely to have diagnoses of obesity (OR 1.75; p = 1 × 10 -27 ), sleep apnea (OR 1.71; p = 1 × 10 -22 ), and type II diabetes (OR 1.74; p = 9 × 10 -18 ). Compared to those diagnosed only with depression, those diagnosed only with anxiety were more likely to have diagnoses of palpitations (OR 1.91; p = 2 × 10 -25 ), benign skin neoplasms (OR 1.61; p = 2 × 10 -17 ), and cardiac dysrhythmias (OR 1.45; p = 2 × 10 -12 ). Patients with comorbid depression and anxiety were more likely to have diagnoses of other mental health disorders, substance use disorders, sleep problems, and gastroesophageal reflux relative to isolated depression., Conclusions: While depression and anxiety are closely related, this study suggests that phenotypic distinctions exist between depression and anxiety. Improving phenotypic characterization within the broad categories of depression and anxiety could improve the clinical assessment of depression and anxiety.

Background: Alcohol is the most abused substance among adults in the United States. The COVID-19 pandemic impacted patterns of alcohol use, but data are conflicting, and previous studies are largely limited to cross-sectional analyses. Objective: This study aimed to longitudinally assess sociodemographic and psychological correlates of changes in three patterns of alcohol use (number of alcoholic drinks, drinking regularity, and binge drinking) during COVID-19. Methods: We studied changes in self-reported drinking behaviors in 222,195 Mayo Clinic patients over 21 years of age (58.1% female and 41.9% male) between April 1, 2019, and March 30, 2021. Logistic regression models were used to estimate associations between patient characteristics and change in alcohol consumption. Results: Sociodemographically younger age, White race, having a college degree, and living in a rural area were associated with increased alcohol use regularity (all p  < .05). Younger age, male, White, high-school education or less, living in a more deprived neighborhood, smoking, and living in a rural area were associated with increases in number of alcohol drinks (all p  ≤ .04) and binge drinking (all p  ≤ .01). Increased anxiety scores were associated with increased number of drinks, while depression severity was associated with both increased drinking regularity and increased number of drinks (all p  ≤ .02) independent of sociodemographic characteristics. Conclusion: Our study showed that both sociodemographic and psychological characteristics were associated with increased alcohol consumption patterns during the COVID-19 pandemic. Our study highlights specific target groups previously not described in the literature for alcohol interventions based on sociodemographic and psychological characteristics.

Background: In this longitudinal cohort study, we examined the socio-demographic and psychological predictors of alcohol use initiation during the COVID-19 pandemic in a sample of never alcohol users aged ≥21 prior to COVID-19., Methods: Our study population consisted of 56 930 patients aged ≥21, as of 30 March 2019 were collected from a pre-COVID period of 1 year before 31 March 2020, and during-COVID, a period between 1 April 2020 and 30 March 2021. Univariable and multivariable logistic regression models were utilized to examine the roles of socio-demographic variables (gender, age, education, Area Deprivation Index and rural residence) changes in anxiety and depression severity as predictors of alcohol use initiation., Results: Age, gender, race, ethnicity, education and rural status were significant predictors in multivariable analysis. A subgroup analysis showed neither anxiety nor depression had a significant association with alcohol use initiation., Conclusion: Women, younger individuals, those living in a rural area and people who smoke cigarettes were more likely to initiate alcohol use during the pandemic. Our study has public health and clinical implications such as the need for targeted alcohol use screening and intervention for vulnerable individuals., (© The Author(s) 2020. Published by Oxford University Press on behalf of Faculty of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Aims: Brain-derived neurotrophic factor (BDNF) levels may be associated with alcohol use disorders (AUD) and alcohol consumption, correlate with sleep disturbance and be influenced by sex differences and sex hormones. These associations have not been examined in a single sample accounting for all these factors., Methods: Data from 190 participants (29.4% female) with AUD were utilized. Sleep quality, craving intensity, depression, anxiety and alcohol consumption were assessed using the Pittsburgh Sleep Quality Index (PSQI), Penn Alcohol Craving Scale (PACS), Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder-7 (GAD-7) and Timeline Follow Back for 90 days(TLFB 90). Inventory of Drug Taking Situations (IDTS) assessed the tendency to drink in positive/negative emotional states. Serum BDNF (sBDNF) and plasma sex hormones (estrogen, progesterone, testosterone, FSH and SHBG) were measured. Pearson correlation analyses were used to examine the association between sBDNF and these measures in the entire sample and in men and women separately. Higher order interaction effects between these factors were evaluated for their association with sBDNF using a backward selection model., Results: No significant correlations between sBDNF levels and sex hormones, PSQI, PHQ-9, PACS, IDTS scores and alcohol consumption were found (all P-values > 0.05). sBDNF levels were negatively correlated with GAD-7 scores in men (r = -0.1841; P = 0.03). When considering all quadratic and two-way interactions among PSQI, PHQ-9, GAD-7, mean and max drinks/day, number of drinking days, heavy drinking days, and sex no higher order moderating effects of sBDNF levels were found., Conclusion: Our study revealed no significant associations between sBDNF and alcohol measures, sleep, depression and sex hormones suggesting limited utility as a biomarker., (© The Author(s) 2023. Medical Council on Alcohol and Oxford University Press. All rights reserved.)

Background: Kidney stones are a highly prevalent disease worldwide. Additionally, both environmental and occupational exposure to Pb and Cd continue to be prevalent globally and can result in renal toxicity. The objective of this study was to examine the potential presence of Pb and Cd in kidney stones, and to assess for correlation with demographic factors including smoking, gender, age, and kidney stone matrix composition., Methods: Patient kidney stones (n = 96) were analyzed using Fourier transform infrared spectroscopy to identify the stone constituents. Cd and Pb concentrations (µg/g) were determined by inductively coupled plasma mass spectrometry. Cd and Pb concentrations were correlated using bivariable and multivariable statistical analysis with demographic factors (age, gender, smoking status), and kidney stone composition., Results: Kidney stone Cd (median 0.092 µg/g, range 0.014 to 2.46) and Pb concentrations (median 0.95 µg/g, range 0.060 to 15.4) were moderately correlated (r = 0.56, P < 0.0001). Cd concentrations were positively associated with patient history of smoking, patient age, and calcium oxalate monohydrate levels while negatively associated with struvite and uric acid/uric acid dihydrate. Pb concentrations were positively associated with females and apatite levels while negatively associated with uric acid/uric acid dihydrate. After holding constant other stone type composition levels, smoking status, and age, both Pb and Cd were positively associated with apatite and negatively associated with uric acid/uric acid dihydrate, struvite, and calcium carbonate., Conclusions: Cd and Pb kidney stone concentrations are associated with specific kidney stone types. Cd and Pb kidney stone concentrations are both associated with smoking., (© American Association for Clinical Chemistry 2022. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

This study evaluated advanced pulmonary ultrasonography training for COVID-19 lung examination. Students completed identical pretests and post-tests and a survey. Changes were found for individual questions and overall scores (all P≤.02), specifically image identification, previous material, and COVID-19 questions. Students were receptive to the training for education and future practice (P<.001), and they felt capable using ultrasound for diagnosis and management of COVID-19 patients. Pulmonary ultrasonography training should be considered for the medical school curriculum., (Copyright 2023 by the Missouri State Medical Association.)

Objective: Ketamine has been redeveloped as a rapid-acting antidepressant for treatment-resistant depression (TRD). There is a paucity of literature comparing subanesthetic intravenous (IV) ketamine and US Food and Drug Administration (FDA)-approved intranasal (IN) esketamine for TRD in real-world clinical settings. We compared the efficacy and time to achieve remission/response with repeated ketamine and esketamine., Methods: An observational study of adults with TRD received up to 6 IV ketamine (0.5 mg/kg over 40 minutes) or up to 8 IN esketamine (56- or 84-mg) treatments from August 17, 2017, to June 24, 2021. Depressive symptoms were measured utilizing the 16-item Quick Inventory of Depressive Symptomatology self-report (QIDS-SR) before and 24 hours after treatment. Cox proportional hazard models were used to evaluate associations between time to response ( ≥ 50% change in QIDS-SR score) and remission (QIDS-SR score ≤ 5)., Results: Sixty-two adults (median age = 50 years, 65% female) received IV ketamine (76%, n = 47) or IN esketamine (24%, n = 15). Neither baseline-to-endpoint change in QIDS-SR score nor response/remission rates were significantly different between groups. Time to remission, defined as number of treatments (adjusting for age, body mass index [BMI], sex, and baseline QIDS-SR score), was faster for IV versus IN treatment (HR = 5.0, P  = .02)., Conclusions: Intravenous ketamine and intranasal esketamine showed similar rates of response and remission in TRD patients, but the number of treatments required to achieve remission was significantly lower with IV ketamine compared to IN esketamine. These findings need to be investigated in a randomized control trial comparing these two treatment interventions., (© Copyright 2023 Physicians Postgraduate Press, Inc.)

Lithium has been a cornerstone treatment for bipolar disorder (BD). Despite descriptions in the literature regarding associations between long-term lithium therapy (LTLT) and development of a thyroid disorder (overt/subclinical hypo/hyperthyroidism, thyroid nodule, and goiter) in BD, factors such as time to onset of thyroid abnormalities and impact on clinical outcomes in the course of illness have not been fully characterized. In this study we aimed to compare clinical characteristics of adult BD patients with and without thyroid disorders who were on LTLT. We aimed to identify the incidence of thyroid disorders in patients with BD on LTLT and response to lithium between patients with and without thyroid disorders in BD. The Cox proportional model was used to find the median time to the development of a thyroid disorder. Our results showed that up to 32% of patients with BD on LTLT developed a thyroid disorder, of which 79% developed hypothyroidism, which was corrected with thyroid hormone replacement. We did not find significant differences in lithium response between patients with or without thyroid disorders in BD. Findings from this study suggest that patients with BD and comorbid thyroid disorders when adequately treated have a response to lithium similar to patients with BD and no thyroid disorders.

Aims: The objective of this study is to longitudinally assess sociodemographic and psychological correlates of increased alcohol use during the coronavirus disease of 2019 (COVID-19) period among adolescents and young adults., Methods: Pre-COVID period is defined as the 1-year period on or before 31 March 2020, and during-COVID period is defined as the period from 1st April 2020 to 30 March 2021. Univariable logistic regression models are used to evaluate the association of demographic characteristics, Area Deprivation Index (ADI), rurality, changes in Patient Health Questionnaire (PHQ-9) and Generalized Anxiety Disorder (GAD-7) scale severity, and the risk of increased alcohol consumption (binge drinking, number of drinks and drinking regularity) from pre-COVID to during-COVID period., Results and Conclusion: Our study found that worsened anxiety symptoms, older age, being in college and current cigarette smoking status were associated with increased alcohol use among youth during the pandemic year. Socioeconomic position (measured by ADI) and rural status were not found to be associated with increased alcohol use among adolescents and young adults., (© The Author(s) 2022. Medical Council on Alcohol and Oxford University Press. All rights reserved.)

Background: Gadolinium-based contrast agents (GBCAs) and Iodinated contrast media are widely utilized to increase medical imaging sensitivity. With predominant renal elimination, the potential for the incorporation of contrast agent derived gadolinium and iodine into kidney stones remains largely uncharacterized. The study objective was to measure gadolinium and iodine concentrations within kidney stones. Observed elemental concentrations were correlated with prior contrast agent administration, kidney stone composition, age, gender, and smoking status., Methods: Kidney stones from 96 patients were analyzed by Fourier Transform Infrared Spectroscopy to determine stone composition. Residual kidney stone material was digested and analyzed by Inductively Coupled Plasma Mass Spectrometry to determine gadolinium and iodine concentrations. Univariable and multivariable lognormal linear regression were performed to study the relationship between kidney stone element concentrations and contrast agent administration, kidney stone composition, age, gender, and smoking status., Results: Median iodine and gadolinium stone concentrations were 6.4 (range 0.6-3997) and 0.1 (range ≤0.013-113.5) µg/g respectively. Elevated gadolinium was strongly associated with GBCA history with a hazard rate of 2.20 (95 % CI 1.14-3.25 P < 0.001). Gadolinium was positively associated with smoking, as well as stones comprised of apatite and calcium oxalate. Iodine concentrations were negatively associated with uric acid stones., Conclusion: Gadolinium, but not iodine, concentrations in kidney stones was strongly correlated with contrast exposure history. Stone matrix composition and demographic factors, particularly smoking, can influence observed kidney stone elemental concentrations. Additional studies are needed to determine if exposure to gadolinium and iodine promote the formation of stone matrix and/or reflect exposure history., (Copyright © 2022 Elsevier GmbH. All rights reserved.)

The purpose of the current study was to assess knowledge and attitudes about human papillomavirus (HPV) and HPV vaccination for oropharyngeal cancer (OPC) prevention in first-year through fourth-year dental students., Methods: In this cross-sectional quantitative study, surveys assessed knowledge and attitudes about HPV, HPV-related OPC, and HPV vaccination of incoming first-year dental students (D1), outgoing first- and second-year dental students (D1-D2), and outgoing third- and fourth-year dental students (D3-D4). After completing a 40-item pre-training knowledge and attitude assessment survey, a one-time, one-hour national HPV training session was conducted. An 8-item attitudinal post-survey was completed after training., Results: Of 173 participants (75.9% response rate), over 85% did not know that the rate of HPV is not highest among women in their 30s, and only 11% to 28% knew that smoking-associated OPC is more deadly than HPV-associated OPC. While participants overall expressed willingness to administer the HPV vaccine, the willingness of dental students to do so in their future practice tapered off progressively through dental school year categories ( p < 0.001). Among outgoing D1-D4 students, the one-hour HPV training increased participants' self-perceived ability to describe the burden of HPV disease, discuss the importance of HPV vaccination for cancer prevention, and provide needed HPV vaccination information to parents (all p ≤ 0.004)., Conclusions: Understanding deficits in dental student knowledge and attitudes across the 4 years of dental school may help dental educators better understand the timing and content needed for effective HPV training in the dental school curriculum to reduce HPV-associated OPC prevalence.

Context: Many medical schools have a distributed model for clinical clerkship education, challenging our ability to determine student gaps during clinical education. With the graduating class of 2017, A.T. Still University's School of Osteopathic Medicine in Arizona (ATSU-SOMA) began requiring additional online curricula for all clerkship courses., Objectives: To determine whether third year and fourth year students receiving ATSU-SOMA's online curricula during core clerkships performed better overall on national standardized examinations than students from previous years who had not received the curricula, and whether scores from online coursework correlated with outcomes on standardized examinations as possible early predictors of success., Methods: This retrospective cohort study analyzed existing data (demographics and assessments) from ATSU-SOMA classes of 2017-2020 (curriculum group) and 2014-2016 (precurriculum group). The effect of the curriculum on national standardized examinations (Comprehensive Osteopathic Medical Achievement Test [COMAT] and Comprehensive Osteopathic Medical Licensing Examination of the United States [COMLEX-USA]) was estimated using augmented inverse probability weighting (AIPW). Correlations between assignment scores and national standardized examinations were estimated using linear regression models., Results: The curriculum group had 405 students with a mean (standard deviation [SD]) age of 25.7 (±3.1) years. Two hundred and fifteen (53.1%) students in the curriculum group were female and 190 (46.9%) were male. The precurriculum group had 308 students (mean ± SD age, 26.4 ± 4.2 years; 157 [51.0%] male; 151 [49.0%] female). The online curriculum group had higher COMAT clinical subject exam scores in obstetrics and gynecology, osteopathic principles and practice (OPP), psychiatry, and surgery (all p≤0.04), as well as higher COMLEX-USA Level 2-Cognitive Evaluation (CE) family medicine and OPP subscores (both p≤0.03). The curriculum group had a 9.4 point increase in mean total COMLEX-USA Level 2-CE score (p=0.08). No effect was found for the curriculum overall on COMAT mean or COMLEX-USA Level 2-Performance Evaluation scores (all p≥0.11). Total coursework scores in each core clerkship, excluding pediatrics, were correlated with COMAT mean score (all adjusted p≤0.03). Mean scores for five of the seven assignment types in core clerkships, excluding evidence based medicine types, were positively correlated with COMAT mean scores (all adjusted p≤0.049). All assignment types correlated with COMLEX-USA Level 2-CE total score (all adjusted p≤0.04), except interprofessional education (IPE)., Conclusions: Results from this study of 713 students from ATSU-SOMA suggested that our online curriculum supplemented clinic based learning during clerkship courses and improved student outcomes on national standardized examinations., (© 2021 Kelli Glaser et al., published by De Gruyter, Berlin/Boston.)

Context: Osteopathic manipulative treatment reduces symptoms in patients with headache disorders, but the underlying mechanisms are unclear., Objective: To evaluate blood flow in the intracranial and extracranial vasculature before and after occipitoatlantal decompression (OAD) using Doppler ultrasonography., Methods: Healthy, first-year osteopathic medical students from A.T. Still University's Kirksville College of Osteopathic Medicine participated in a randomized, single-blinded, two-period, two-treatment crossover study. The participants were randomly assigned to 1 of 2 treatment interventions: OAD or sham touch. After one week, participants returned to have the other intervention performed. Blood flow parameters-peak systolic velocity (PSV) and end-diastolic velocity (EDV)-in the middle cerebral artery (MCA), internal carotid artery (ICA), and vertebral artery (VA) were evaluated before, immediately after, 5 minutes after, and 10 minutes after treatment. Differences in PSV, EDV, heart rate (HR), and blood pressure (BP) for both interventions were analyzed for the four time points using mixed-effects models., Results: Thirty healthy medical students (11 men, 19 women; mean age, 24 years) participated in this study. EDV increased after OAD in the MCA, ICA, and VA (all p<0.001); no change occurred after sham touch (all p>0.05). EDV was greater for all post-treatment timepoints after OAD in the MCA, ICA, and VA than after sham touch (all p<0.001). Although baseline PSV in the MCA measured before treatment was different between treatment interventions (p=0.01), no difference was found between interventions at any post-treatment time point (all p>0.59). Changes in PSV in the ICA and VA and for HR and BP did not depend on treatment intervention (p>0.06)., Conclusion: Increases in EDV occurred in major cranial arteries after OAD but not after sham touch, indicating that OAD improves blood flow to the brain. The exact mechanism of this increase is unknown; however, it can be explained by either parasympathetic stimulation through the secretion of vasodilating neurotransmitters or by a decrease in external tissue pressure on ICA and VA, with the resulting flow causing further dilation in the MCA.

The aim of this study was to evaluate the feasibility of applying the polymer-induced liquid-precursor (PILP) method to enhance silver diamine fluoride (SDF) therapy. One hundred forty micrometer deep artificial caries lesions were treated with (A) 38% SDF solution and (B) 38% SDF containing poly-L-aspartic acid (pASP). Changes in the nanomechanical profile across the lesion were evaluated. Hydrated artificial lesions had a low reduced elastic modulus (0.3 GPa) and nanohardness (0.02 GPa) region extending about 100 μm into the lesion, with a gradual linear increase to about 168 μm where the values plateaued to around 18 GPa/1.0 GPa. Topical application of SDF resulted in significantly recovered properties (p<0.001). SDF containing pASP resulted in greater nanomechanical properties compared to SDF alone, showing similar sloped regions up to 96 μm, then SDF alone dropped while SDF containing pASP continued at a modest slope until reaching normal at 144 μm. This nanoindentation study shows enhanced SDF therapy using the PILP method.

This study evaluated soft-embalmed human cadavers for ultrasound needle-guidance training. Second-year medical students used peripherally inserted central catheter (PICC) line and central line models and a Thiel-embalmed cadaver for training and provided feedback. Most (85%) agreed the cadaver was useful. There were positive correlations between performing the PICC line (r=0.44, P=.11) and central line (r=0.63, P=.03) procedures on a cadaver and in a clinical setting. Thiel-embalmed cadavers may provide important hands-on training., (Copyright 2020 by the Missouri State Medical Association.)

The current study evaluated an interprofessional approach involving medical students and nurses for learning vascular access with ultrasonography. Vascular access laboratories included needle-guidance training and provided an efficient way to master technically difficult venipuncture cases. Most agreed ultrasound technology was useful for these venipuncture cases. Participants felt prepared to perform venipuncture using ultrasonography in a clinical setting after training. Such laboratories should be considered for interprofessional learning of difficult procedures in the medical school curriculum., (Copyright 2020 by the Missouri State Medical Association.)

Context: Inversion tables are used as treatment for back pain, but there is a lack of agreement on systemic effects of inversion., Objective: To assess intracranial pressure (ICP) and cerebral blood flow using ultrasonography during inversion table tilt., Methods: Optic nerve sheath diameter (ONSD), heart rate (HR), blood pressure, internal carotid artery (ICA) and middle cerebral artery (MCA) blood flow of participants were measured in 3 positions: supine before inversion, during inversion with head down, and supine post-inversion. ONSD was evaluated with ocular ultrasonography and blood flow (ICA and MCA) with Doppler ultrasonography., Results: The ONSD changed significantly between the supine position, at 3 min of inversion, and after returning to supine position (all P < .001). The post-inversion HR was less than pre-inversion (P = .03) and 3-min inversion HR (P = .003). There were significant changes in ICA and MCA flow caused by inversion, which affected blood flow velocity, resistance, and pulsatility index (all P ≤ .005)., Conclusion: Inversion caused significant changes in ICP and blood flow. Thus, increased chance of complications may exist when using inversion as a therapeutic tool or during surgical procedures in patients with previous history of elevated ICP. These results demonstrate that inversion therapy should be used with caution., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Context: Discrepancies in ambulatory blood mercury sphygmomanometers pressure readings exist between automated blood pressure machines and manual mercury sphygmomanometers. For patients with elevated blood pressure, consistent blood pressure readings between these methods are important across all body mass index (BMI) levels., Objective: To determine the relationship between automated and manual blood pressure readings and the effect of BMI in patients with an elevated automated blood pressure reading., Methods: Automated and manual blood pressure readings (using the same arm) were collected from July 2014 to December 2016 across community-oriented primary care clinics in New York City for a retrospective medical record review. Automated systolic blood pressure (SBP) readings greater than 140 mm Hg or diastolic blood pressure (DBP) readings greater than 90 mm Hg were qualifying criteria for a manual blood pressure assessment. The difference in automated blood pressure readings relative to a manual blood pressure reading was assessed overall and for any relationship with BMI using linear regression and analysis of variance., Results: Data from 281 patients (166 [59%] women, 115 [41%] men; mean [SD] age of 57 [12.6] years) were assessed. For SBP, automated readings had an overall mean that was 8.0% greater than manual readings (P<.001). This relative difference decreased linearly by 2.7 points (95% CI, 1.0-4.4) for each 10-unit increase in BMI (P=.002). For DBP, automated readings had an overall mean that was 4.5% greater than manual readings (P<.001). This relative difference followed a quadratic relationship with BMI (P=.01), where the downward curve peaked at 6.6% (95% CI, 4.5-8.7) for a BMI of 35. When BMI was grouped into 4 categories, (normal weight, overweight, obese, and morbidly obese), morbidly obese patients had a smaller mean percentage SBP difference (4.3% [95% CI, 1.5-7.1]) compared with the other 3 categories (8.6% [95% CI, 7.2-9.9], P=.007). No relative differences between automated and manual methods for DBP were found among the BMI categories (P=.11)., Conclusions: The current study found significant differences between automated and manual blood pressure readings. The relationship of these differences with BMI was also statistically significant, but their clinical significance remains inconclusive. Because manual blood pressure readings may have clinical value when evaluating or treating a patient with elevated blood pressure, better adherence to proper technique may improve accuracy.

Background: Historically, in an effort to evaluate and manage the rising cost of healthcare employers assess the direct cost burden via medical health claims and measures that yield clear data. Health related indirect costs are harder to measure and are often left out of the comprehensive overview of health expenses to an employer. Presenteeism, which is commonly referred to as an employee at work who has impaired productivity due to health considerations, has been identified as an indirect but relevant factor influencing productivity and human capitol. The current study evaluated presenteeism among employees of a large United States health care system that operates in six locations over a four-year period and estimated loss productivity due to poor health and its potential economic burden., Methods: The Health-Related Productivity Loss Instrument (HPLI) was included as part of an online Health Risk Appraisal (HRA) administered to employees of a large United States health care system across six locations. A total of 58 299 HRAs from 22 893 employees were completed and analyzed; 7959 employees completed the HRA each year for 4 years. The prevalence of 22 specific health conditions and their effects on productivity areas (quantity of work, quality of work, work not done, and concentration) were measured. The estimated daily productivity loss per person, annual cost per person, and annual company costs were calculated for each condition by fitting marginal models using generalized estimating equations. Intra-participant agreement in reported productivity loss across time was evaluated using κ statistics for each condition., Results: The health conditions rated highest in prevalence were allergies and hypertension (high blood pressure). The conditions with the highest estimated daily productivity loss and annual cost per person were chronic back pain, mental illness, general anxiety, migraines or severe headaches, neck pain, and depression. Allergies and migraines or severe headaches had the highest estimated annual company cost. Most health conditions had at least fair intra-participant agreement (κ ≥ 0.40) on reported daily productivity loss., Conclusions: Results from the current study suggested a variety of health conditions contributed to daily productivity loss and resulted in additional annual estimated costs for the health care system. To improve the productivity and well-being of their workforce, employers should consider presenteeism data when planning comprehensive wellness initiatives to curb productivity loss and increase employee health and well-being during working hours.

Oral size perception is not veridical, and there is disagreement on whether this nonveridicality tends to underestimate or overestimate size. Further, being hungry has been shown to affect oral size perception. In this study, we investigated the effect of hunger on oral size perception. Overall, being hungry had a small but significant effect on oral size perception and seemed to support that oral size perception tends to underestimate the size of objects. Both hungry and sated participants tended to underestimate the size of intraoral objects, but hungry participants underestimated to a significantly lesser degree. Unlike previous research, this tendency was independent of the order and number of assessments of size. We, therefore, offer a novel explanation for these findings: Oral size perception is modulated by a hierarchy of Bayesian predictions, and being hungry changes the priors in these predictions.

Context: Accurate determination of transverse process displacement in the horizontal plane requires accurate transverse process landmark localization followed by accurate discrimination of asymmetry by the examiner's palpating digits., Objective: To determine whether the accurate localization of transverse process landmarks influences overall accuracy of asymmetry determination in third-year osteopathic medical students evaluating covered lumbar spine models., Methods: A class of third-year osteopathic medical students was split into 2 groups and asked to determine whether the right transverse processes of covered lumbar spine models were anterior or posterior relative to the left transverse process. The marked model group (group A) was provided covered models with black dots on the fabric covers over the transverse process landmarks, while the covered models given to the students in the unmarked model group (group B) had no markings. Both groups were asked to assess asymmetry differences from L1 to L5 on 2 models. Landmarks were randomized for asymmetry (ranging from 2 mm to 6 mm) and direction (anterior or posterior on the right side). The number of correct responses was modeled as a binomial random variable in a generalized linear model to compare the effects of marked vs unmarked models on accuracy of palpation. The predicted probability of correctly determining the direction of the asymmetry and 95% CIs were calculated., Results: The probability of correctly identifying the direction of asymmetry was 0.89 (95% CI, 0.87-0.91) for group A and 0.74 (95% CI, 0.71-0.78) for group B, a 15 percentage point difference (OR, 1.2; 95% CI, 1.1-1.3; P<.001). Assuming accurate perception of digit asymmetry and accurate localization of landmarks are independent and correct answers are given only if both events occur, then students were more likely to accurately perceive digit asymmetry (0.89) than accurately localize landmarks (0.83=0.74/0.89). Overall, more students accurately identified the direction of asymmetry when the right transverse process was anterior (0.87; 95% CI, 0.84-0.90) than when it was posterior (0.81; 95% CI, 0.77-0.84) (OR, 1.6; 95% CI, 1.2-2.1; P=.001)., Conclusions: Student palpation accuracy was better when transverse process landmark localization was provided on the lumbar spine models than when it was not. Students were more likely to accurately perceive digit asymmetry than accurately localize the landmarks. Improving palpation accuracy requires developing educational methods to improve both accurate landmark localization and accurate digit asymmetry perception.

Atorvastatin (ATO) was commonly used to lower blood cholesterol, but it caused harmful effects to organs, including the liver. Thymoquinone (TQ), a prominent constituent of Nigella sativa, has antioxidant, antiinflammatory, antiapoptotic, antimicrobial, and anticancer activity. The current study investigated the mechanism of ATO-induced hepatotoxicity, whether posttreatment TQ could reverse ATO-induced hepatic injury, and the mechanism of action of TQ as a hepatoprotective agent. Forty adult male Sprague Dawley rats were divided into four equal groups: control, TQ-treated, ATO-treated, and combined ATO/TQ-treated. Rats were treated for 8 weeks and 10 days and euthanized by cervical dislocation 3 days after the last treatment. Blood samples and livers were tested for liver enzymes, oxidative stress, and apoptosis markers and used for histopathological and ultrastructural examination. The ATO-treated group showed an increase in liver enzymes, decreases in reduced glutathione and catalase, and increases in the malondialdehyde lipid peroxidation marker, protein carbonylation, and caspase 3 activity. Posttreatment TQ in the ATO/TQ-treated group seemed to reverse these changes. Histopathological and ultrastructural examination supported these data. Results from the current study suggested that posttreatment TQ may reverse oxidative stress injury in rat liver produced by ATO, suggesting a potential clinical application of using TQ to prevent ATO-induced hepatic injury.

Study Objective: To determine if teenage patients receiving prenatal care in an adolescent-focused clinic, emphasizing long-acting reversible contraception (LARC) using motivational interviewing techniques, had higher rates of uptake of postpartum LARC than a control group., Design and Setting: Retrospective cohort study comparing young women who received prenatal care in an adolescent-focused setting with those enrolled in standard prenatal care., Participants: Adolescents between the ages of 13 and 17 years receiving prenatal care within the Maricopa Integrated Health safety-net system between 2007 and 2014., Interventions: Motivational interviewing within the context of adolescent-focused prenatal care., Main Outcome Measures: Rates of uptake of LARC within 13 postpartum weeks., Results: The adjusted rate of LARC for adolescent-focused prenatal care participants by 13 weeks postpartum was 38% (95% confidence interval [CI], 29%-47%) compared with 18% (95% CI, 11%-28%) for standard care participants, with an adjusted odds ratio of LARC use of 2.8 (95% CI, 1.5-5.2). Among patients who received adolescent-focused prenatal care, most (27% vs 12.7%) were using an intrauterine device as opposed to an implantable contraceptive device., Conclusion: Participation in an adolescent-focused antepartum setting using motivational interviewing to emphasize postpartum LARC resulted in nearly 3 times higher rates of uptake compared with standard prenatal care., (Copyright © 2016 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.)

Objective: Evidence suggests people experience an oral size illusion and commonly perceive oral size inaccurately; however, the nature of the illusion remains unclear. The objectives of the present study were to confirm the presence of an oral size illusion, determine the magnitude (amount) and direction (underestimation or overestimation) of the illusion, and determine whether immediately prior cross-modal perceptual experiences affected the magnitude and direction., Design: Participants (N=27) orally assessed 9 sizes of stainless steel spheres (1/16 in to 1/2 in) categorized as small, medium, or big, and matched them with digital and visual reference sets. Each participant completed 20 matching tasks in 3 assessments. For control assessments, 6 oral spheres were matched with reference sets of same-sized spheres. For primer-control assessments, similar to control, 6 matching tasks were preceded by cross-modal experiences of the same-sized sphere. For experimental assessments, 8 matching tasks were preceded by a cross-modal experience of a differently sized sphere., Results: For control assessments, small and medium spheres were consistently underestimated, and big spheres were consistently overestimated. For experimental assessments, magnitude and direction of the oral size illusion varied according to the size of the sphere used in the cross-modal experience., Conclusion: Results seemed to confirm an oral size illusion, but direction of the illusion depended on the size of the object. Immediately prior cross-modal experiences influenced magnitude and direction of the illusion, suggesting that aspects of oral perceptual experience are dependent upon factors outside of oral perceptual anatomy and the properties of the oral stimulus., (Copyright © 2015 Elsevier Ltd. All rights reserved.)