Effect of Bone Graft on the Correlation between Clinical Bone Quality and CBCT-determined Bone Density: A Pilot Study.

AIM AND OBJECTIVE: The aim of this pilot study is to explore the possible correlation between radiographic bone density and clinical bone quality in edentulous implant sites with and without a history of bone grafting. MATERIALS AND METHODS: A retrospective evaluation of 273 surgically placed dental implants with adequate preoperative cone-beam computed tomography (CBCT) between 2017 and 2019. Misch classification was used to assess the bone quality, and CBCT grayscale values, utilizing Hounsfield units (HU), were used for radiographic bone density assessment. RESULTS: Sixty-six patients (mean age, 58 years; 43 [65%] female and 23 [35%] male) with 118 implant sites were included. A total of 38 sites with bone grafts were evaluated. Controlling for location, sites with previous bone graft had softer bone quality (p = 0.003) and greater bone density (p <0.001) compared to sites without previous bone grafts. A significant correlation existed between radiographic bone density and clinical bone quality (p ≤0.01). The magnitude of the relationship increased in the absence of bone graft (p <0.001) and became nonsignificant in sites with previous grafting. In sites with allograft, the relationship was not statistically different than those without bone graft (both p ≥0.07), while it was statistically different in sites with xenograft when sites assumed independent (p = 0.02). CONCLUSION: CBCT-determined radiographic bone density was correlated to clinical bone quality in the absence of previous bone grafting, while in the presence of previous bone graft, the radiographic bone density of the edentulous sites seemed to be not associated with the clinical bone density, especially in sites with history of xenograft bone grafting. CLINICAL SIGNIFICANCE: CBCT could be utilized to predict preoperative clinical bone quality in sites without previous bone grafting. When assessing sites with history of bone grafting, the CBCT should be interpreted with caution, especially if xenografts were used.

Treatment-resistant depression patients with baseline suicidal ideation required more treatments to achieve therapeutic response with ketamine/esketamine.

BACKGROUND: There is an urgent need to identify interventions to reduce suicidality. We investigated the antisuicidal effects of intravenous (IV) ketamine and intranasal (IN) esketamine among patients with treatment-resistant depression (TRD) in a historical cohort study. METHODS: The Quick Inventory of Depressive Symptomatology self-report (QIDS-SR) question 12 was used to measure suicidal ideation (SI). Cox proportional hazards models were used to evaluate associations between the number of treatments to response and baseline SI (yes, Q12 > 0 versus no, Q12 = 0), adjusting for covariates and modified baseline QIDS-SR score. We evaluated associations between the number of treatments to a 50 % reduction in SI score between IV and IN treatment. RESULTS: Fifty-two adults (62.5 % female, median age 49.1 years) received IV ketamine (71 %, n = 37) or IN esketamine (29 %, n = 15). Eighty-one percent of patients reported SI at baseline. Among those with baseline SI, 60 % had improved SI scores while 38 % did not change, and among those with no SI, 80 % did not change. After adjusting for covariates, the hazard ratios (HR) of response were significantly lower among those with baseline SI (HR = 0.36, 95 % CI, 0.14-0.92, p = 0.03). The number of treatments to achieve a 50 % reduction in SI score did not depend on group (IN esketamine vs. IV ketamine HR = 0.74 [95 % CI, 0.27-2.05]; p = 0.57). LIMITATIONS: Small sample size and lack of a placebo group. CONCLUSIONS: This study suggests that patients with baseline suicidal ideation require more treatments to achieve a response with ketamine or esketamine. The antisuicidal response seemed similar between IV ketamine and IN esketamine.

Change in neurocognitive functioning in patients with treatment-resistant depression with serial intravenous ketamine infusions: The Bio-K multicenter trial.

This nonrandomized, multicenter, open-label clinical trial explored the impact of intravenous (IV) ketamine on cognitive function in adults (n = 74) with treatment-resistant depression (TRD). Patients received three IV ketamine infusions during the acute phase and, if remitted, four additional infusions in the continuation phase (Mayo site). Cognitive assessments using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) were conducted at baseline, end of the acute phase, and end of the continuation phase (Mayo site). Results showed a significant 53 % (39/74) remission rate in depression symptoms after the acute phase. In adjusted models, baseline language domain score was associated with a higher odd of remission (Odds Ratio, 1.09, 95 % CI = 1.03-1.17, p = 0.004) and greater improvement in MADRS at the end of the acute phase (ß =-0.97; 95 % CI, -1.74 to -0.20; P = 0.02). The likelihood of remission was not significantly associated with baseline immediate or delayed memory, visuospatial/constructional, or attention scores. In the continuation phase, improvements in immediate and delayed memory and attention persisted, with additional gains in visuospatial and language domains. Limitations included an open-label design, potential practice effects, and ongoing psychotropic medication use. Overall, the study suggests cognitive improvement, not deterioration, associated with serial IV ketamine administrations for TRD. These findings encourage future studies with larger sample sizes and longer follow-up periods to examine any potential for deleterious effect with recurrent ketamine use for TRD. Trial Registration: ClinicalTrials.gov: NCT03156504.

Multi-ancestry meta-analysis of tobacco use disorder identifies 461 potential risk genes and reveals associations with multiple health outcomes.

Tobacco use disorder (TUD) is the most prevalent substance use disorder in the world. Genetic factors influence smoking behaviours and although strides have been made using genome-wide association studies to identify risk variants, most variants identified have been for nicotine consumption, rather than TUD. Here we leveraged four US biobanks to perform a multi-ancestral meta-analysis of TUD (derived via electronic health records) in 653,790 individuals (495,005 European, 114,420 African American and 44,365 Latin American) and data from UK Biobank (ncombined = 898,680). We identified 88 independent risk loci; integration with functional genomic tools uncovered 461 potential risk genes, primarily expressed in the brain. TUD was genetically correlated with smoking and psychiatric traits from traditionally ascertained cohorts, externalizing behaviours in children and hundreds of medical outcomes, including HIV infection, heart disease and pain. This work furthers our biological understanding of TUD and establishes electronic health records as a source of phenotypic information for studying the genetics of TUD.

Establishment of a Labile Bound Copper Reference Interval in a Healthy Population via an Inductively Coupled Plasma Mass Spectrometry Dual Filtration-Based Assay.

CONTEXT.­: Clinical testing for Wilson disease (WD) is potentially challenging. Measuring the fraction of labile bound copper (LBC) to total copper may be a promising alternative diagnostic tool with better sensitivity and specificity than some current biomarker approaches. A dual filtration-based inductively coupled mass spectrometry (ICP-MS) assay to measure LBC in serum was developed. OBJECTIVE.­: To establish a reference interval for LBC and LBC to total copper (LBC fraction) in a healthy adult population, and to examine associations between total copper, LBC, and LBC fraction with age, sex, menopausal status, hormone replacement therapy, and supplement use. DESIGN.­: Serum samples were collected from healthy male (n = 110) and female (n = 104) patients between the ages of 19 and 80 years. Total copper and LBC were analyzed using ICP-MS. Results were used to calculate the LBC fraction. Reference intervals were calculated for the 2.5th and 97.5th percentiles for both LBC and LBC fraction. RESULTS.­: The reference intervals for LBC were determined to be 13 to 105 ng/mL and 12 to 107 ng/mL for female and male patients, respectively. The reference intervals for the LBC fraction were 1.0% to 8.1% and 1.2% to 10.5% for female and male patients, respectively. No significant associations were found regarding age, menopausal status, hormone replacement therapy, or vitamin and supplement use. CONCLUSIONS.­: Sex-specific reference intervals have now been established for LBC and LBC fraction. These data in conjunction with further testing of WD populations can be used to assess the sensitivity and specificity of LBC fraction in screening, monitoring, and diagnosis.

Efficacy of Ketamine with and without Lamotrigine in Treatment-Resistant Depression: A Preliminary Report.

Intravenous (IV) ketamine and FDA-approved intranasal (IN) esketamine are increasingly used for treatment-resistant depression (TRD). Preliminary studies have suggested a synergistic effect of ketamine and lamotrigine, although the data are inconclusive. Herein, we report the response to serial ketamine/esketamine treatment among patients with TRD with or without lamotrigine therapy. In this historical cohort study, we included adult patients with TRD who received serial IV racemic ketamine (0.5 mg/kg over 40-100 min) or IN esketamine (56/84 mg) treatments. A change in depressive symptoms was assessed using the 16-item Quick Inventory of Depressive Symptomatology self-report (QIDS-SR) scale. There were no significant differences in response or remission rates among the patients on or not on lamotrigine during the ketamine/esketamine treatments. For a percent change in the QIDS-SR from baseline, no interaction was found between the lamotrigine groups and treatment number (p = 0.70), nor the overall effect of the group (p = 0.38). There was a trend towards lower dissociation (based on the CADSS score) among current lamotrigine users, especially in patients who received IV ketamine. A major limitation is the limited number of patients taking lamotrigine (n = 13). This preliminary study provides insufficient evidence that continuing lamotrigine therapy attenuates the antidepressant effect of repeated ketamine/esketamine; however, there seems to be a signal toward attenuating dissociation with lamotrigine in patients receiving serial ketamine treatments. Further observational studies or randomized controlled trials are needed to replicate these findings.

The Association Between Thyroid Stimulating Hormone and Depression: A Historical Cohort Study.

OBJECTIVE: To investigate the association between thyroid-stimulating hormone (TSH) and clinically relevant depression (CRD) in a population-based study. PATIENTS AND METHODS: Adult patients (≥18 years of age) who received care at Mayo Clinic in Rochester, Minnesota, and completed a TSH and Patient Health Questionnaire - 9 (PHQ-9) within 6 months of each other, between July 8, 2017, and August 31, 2021, were included. Demographics, medical comorbidities, thyroid function laboratory data, psychotropic medications, presence of primary thyroid disorder, thyroid hormone replacement (T4 and/or T3), and mood disorder diagnoses (using International Classification of Diseases, 10th version, Clinical Modifications codes) were extracted electronically. The primary outcome, CRD, was defined as a PHQ-9 score greater than or equal to 10. Logistic regression analysis was conducted to assess the association between TSH categories (low ≤0.3 mIU/L; normal >0.3-4.2 mIU/L; high >4.2 mIU/L) and CRD. RESULTS: The cohort included 29,034 patients, mean age 51.4 years, 65% females, 89.9% White, and a mean body mass index of 29.9 kg/m2. The mean ± standard deviation for TSH was 3.0±8.5 mIU/L, and the mean PHQ-9 score was 6.3±6.2. After adjustment, the odds of CRD were significantly higher among the low TSH category (odds ratio, 1.37; 95% CI, 1.18-1.57; P<.001) compared with the normal TSH category, especially in people 70 years of age or younger compared with people older than 70 years of age. Subgroup analysis did not show an increase in odds of CRD among patients with subclinical/overt hypothyroidism/hyperthyroidism (after adjustment). CONCLUSION: In this large population-based cross-sectional study, we report that low TSH was associated with higher odds of depression. Future longitudinal cohort studies are needed to investigate the relationship between thyroid dysfunction and depression as well as sex differences.

Correction: Joseph et al. Efficacy of Ketamine with and without Lamotrigine in Treatment-Resistant Depression: A Preliminary Report. Pharmaceuticals 2023, 16, 1164.

In the original publication [...].

Prevention of external auditory canal exostosis in the Colorado whitewater community.

CONTEXT: External auditory canal exostoses (EACE) are bony formations that develop insidiously in the auditory meatus from chronic exposure to cold water and, in severe cases, require surgery. This condition has been understudied in the whitewater kayakers and not yet studied in the riverboarding population. Precautions such as earplugs are thought to prevent the formation of EACE because they mechanically block cold water from contacting the sensitive skin in the external auditory canal; however, earplugs are not commonly utilized by athletes. Inquiring about hobbies and the use of protective equipment can be done during osteopathic physicians' preventive care visits. OBJECTIVES: This article aims to determine the prevalence of EACE in Colorado whitewater athletes and their attitudes about wearing ear protection before and after an educational intervention directed at increasing awareness and prevention of EACE. METHODS: In July 2020, participants of this cross-sectional study completed a 10-min survey that collected demographics, whitewater experience, and perceptions of EACE, followed by an educational intervention. Participant ears were photographed utilizing a digital otoscope to assess EACE, and severity ratings were categorized into one of four occlusion levels: none (0%), mild (<25%), moderate (25-75%), or severe (>75%). Spearman correlation coefficients and Wilcoxon signed-rank tests were utilized to assess changes in attitudes before and after the educational intervention. RESULTS: Eighty-one participants (mean [SD] age = 36.3 [12.6] years, 25.9% female) completed the study: 74 kayakers and seven riverboarders. After the intervention, 60.5% (49/81) (p<0.001) reported greater understanding of EACE and 75.0% (60/80) were more likely to wear ear protection (p<0.001). Most (58.0%, 47/81) never wore ear protection. Of the 61 (75.0%) participants with at least one ear severity rating, most (55.7%, 34/61) had moderate EACE, 29.5% (18/61) had no to mild EACE, and 14.8% (9/61) had severe EACE (p<0.001). Impaired hearing was the biggest barrier to utilizing ear protection (51.6%, 33/64). CONCLUSIONS: Our results suggested that the educational intervention improved understanding of EACE and may increase utilization of ear protection in this population. Such prevention efforts may lead to better health of whitewater paddlers by reducing the incidence of EACE. Encouraging osteopathic physicians to inquire about hobbies and protective equipment during primary care preventive visits is essential to help keep athletes in the river doing what they love for longer, contributing to a healthier and happier whole person.

Plasma neurofilament light chain (NfL) reference interval determination in an Age-stratified cognitively unimpaired cohort.

BACKGROUND AND AIMS: Neurofilament light chain (NfL) is an emerging biomarker of neurodegenerative disease progression. As plasma NfL increases with age, characterization of NfL concentrations in an age-stratified cognitively unimpaired population was assessed. MATERIALS AND METHODS: EDTA-plasma samples were measured using the Simoa® NF-light™ Advantage Kit assay. One-sided reference intervals were established from 1100 cognitive normal individuals (588 male, 512 female) aged 20 to 95 years. Of those, 927 samples were obtained from the Mayo Clinic Study of Aging cohort (age > 50 years), and the remainder (age < 50 years) were obtained from individuals without known neurological conditions. All samples were from individuals without known chronic kidney disease, stroke or myocardial infarction, and a body mass index < 30 kg/m2. RESULTS: The 97.5th percentile limits for the following age ranges (in years) were (pg/mL): 20 s: ≤8.4, 30 s: ≤11.4, 40 s: ≤15.4, 50 s: ≤20.8, 60 s: ≤28.0, 70 s: ≤37.9, 80+: ≤51.2. Sex had no significant effect on reference intervals. Observed NfL concentrations increased at a rate of 3.1 % per year of age. CONCLUSIONS: Characterization of the rate of NfL concentration increase and decade-wide reference intervals from a neurologically well-characterized patient population will aid in interpretation of NfL during the clinical evaluation of a potential neurodegenerative disease.

Education, Knowledge, and Practice Characteristics of Cannabis Physicians: A Survey of the Society of Cannabis Clinicians.

Context: Medical cannabis use has increased in recent years despite being a federally illegal drug in the United States. States with medical cannabis use laws require patients to be certified by physicians. However, little is known about the education, knowledge, and practice characteristics of physicians who recommend and supervise patients' use of medical cannabis. Objective: This study assessed how U.S. physicians who practice cannabis medicine are educated, self-assess their knowledge, and describe their practice. Methods: In fall 2017, a 57-item, electronic survey was sent to all members of the Society of Cannabis Clinicians. Because California has had legalized medical cannabis for longer than any other state, we analyzed responses for 14 items between California and non-California physicians. Results: Of 282 surveyed, 133 were eligible and 45 completed the survey. Of those, multiple medical specialties were represented. Only one physician received education during medical school about cannabis medicine, but physicians gained knowledge through conferences (71%, 32/45), the medical literature (64%, 29/45), and websites (62%, 28/45). Just over half (56%, 20/45) felt that there was sufficient information available to practice cannabis medicine. Of the 37 who answered the knowledge question, most felt knowledgable about cannabinoids (78%, 29/37) and the endocannabinoid system (76%, 28/37). There was a wide variation in the number of cannabis recommendations provided by physicians over the course of their practice career (median 1200; interquartile range, 100-5000), and most provided condition-specific treatment (69%, 31/45) and dosing recommendations (62%, 28/45). The majority (81%, 30/37) of physicians received referrals from mainstream medical providers. No differences were found between California and non-California physicians, except more women were from California (p=0.02). Conclusions: The use of medical cannabis continues to increase in the United States and globally. All states that allow medical cannabis require a physician's recommendation, yet few states require specific clinical training. Findings of this study suggest the need for more formal education and training of physicians in medical school and residency, more opportunities for cannabis-related continuing medical education for practicing physicians, and clinical and basic science research that will inform best practices in cannabis medicine.

Community partnerships within a novel dental school urgent care center: Student perceptions.

PURPOSE/OBJECTIVES: Oral health inequities and limited access to care cause patients to seek dental treatment in hospital emergency departments. In addition, conventional clinic models and curricular limitations may result in inadequate experiences for students learning urgent dental care. The aim of the current study was to investigate student perceptions of a novel dental school urgent care clinic model. METHODS: A mixed-methods, cross-sectional study design was used to survey third-year and fourth-year students at a Midwest dental school in spring 2020 about their experiences providing patient care in the school's internal urgent care center. Along with a structured curriculum, the urgent care clinic model incorporates an on-site partnership with a community health center and a hospital emergency department affiliation that serves as a referral base to provide students with their learning experiences. RESULTS: Of 81 students, 78 completed the survey (96% response rate). The majority of students treated 50 or more patients. From their urgent care experiences, a majority of students felt prepared to manage patients with acute dental pain and swelling (72/77, 94%), and reported a better understanding of interprofessional collaborations in dentistry (42/77, 55%) and the importance of providing urgent dental care to underserved patients (72/77, 94%). Most students (64/75, 85%) were more likely to offer urgent dental care services to underserved populations in future practice. CONCLUSION: This collaborative school-based urgent care clinic model incorporating community partnerships provided transformative learning experiences, positively impacted student perceptions of their learning, and influenced future practice behaviors related to urgent dental care.

Success Predictors For Third-Year Osteopathic Medical Students on National Standardized Examinations: A Family Medicine Clerkship Course Study.

CONTEXT: Medical education institutions often use community-based sites and preceptors during students' third and fourth years for clinical training. However, differences in the sites, preceptors, assessment methods, and students may result in variations in clinical training, potentially affecting educational outcomes. During clerkships at A.T. Still University School of Osteopathic Medicine in Arizona, all students are evaluated by several methods for each required clerkship course. Required assessments include the clinical preceptor's evaluation, online coursework specific to each clerkship, patient log documentation, and the Comprehensive Osteopathic Medical Achievement Test (COMAT) relevant to that clerkship. OBJECTIVE: To evaluate which methods of student assessment in a family medicine clerkship course were most predictive of the future success of students on national standardized examinations. METHODS: Third-year osteopathic medical students from a single class who had completed the Comprehensive Osteopathic Medical Licensing Examination (COMLEX)-USA Level 2-Cognitive Evaluation (CE) and 2-Performance Evaluation (PE) and the COMAT were included in the study. Scores on the examinations were used as success benchmarks. Analysis of 4 categories of predictor variables-clerkship site, previous student performance, preceptor evaluation, and clerkship coursework assessment (ie, assignment scores and log numbers)-was used to predict success on the national standardized examinations. RESULTS: Ninety-nine of 105 students were eligible for inclusion. No associations were found between examination scores and clerkship site or log numbers (all P≥.10). Correlations were found for previous student performance (ie, grade point average for first-year and second-year coursework) and all examinations except COMLEX-USA Level 2-PE (r=0.56-0.74, all P<.001), and between total score in family medicine clerkship coursework and COMLEX-USA Level 2-CE and COMAT scores (r=0.28-0.39, all P≤.006). Correlations were also found between preceptor evaluation (total score and subscore on medical knowledge) and all assessed national standardized examinations (r=0.20-0.34, all P<.049). CONCLUSION: Our results suggest that analysis of predictor variables in clerkship courses can reasonably predict success on national standardized examinations and may be useful for early identification of struggling students who may need additional support to perform well on the examinations.

Impact of experiential learning on dental students' training in nitrous oxide inhalation sedation.

PURPOSE/OBJECTIVES: Competence in nitrous oxide/oxygen (N2 O/O2 ) inhalation sedation is expected of dental graduates, but applying what is learned through didactic instruction to patient care can be challenging without firsthand experience. Therefore, the purpose of the current study was to evaluate the impact of experiential learning on dental students' confidence and sense of preparedness for administration of N2 O/O2 . METHODS: A biphasic, mixed methods study was conducted at a Midwestern dental school and included 2 cohorts of dental students. In Phase 1 (spring 2019), a cross-sectional study design was used to survey outgoing third-year and fourth-year students who received didactic N2 O/O2 instruction alone. In Phase 2 (summer 2019), a nonrandomized, preintervention-postintervention study design was used to survey incoming third-year students before and after a hands-on N2 O/O2 laboratory exercise. RESULTS: Of the 79 Phase 1 students (99% response rate), all believed a firsthand learning experience with N2 O/O2 during didactic learning would increase their confidence and preparedness when administering to a patient (both P < .001). Of the 41 Phase 2 students (100% response rate), after the lab exercise, all felt that firsthand experience enhanced classroom instruction and increased confidence and preparedness when administering N2 O to a patient (all P < .001). Fifty-six (71%) Phase 1 and 39 (80%) Phase 2 students believed classroom instruction alone was inadequate to prepare them to administer N2 O/O2 (both P < .001). CONCLUSIONS: Our results strongly suggest that experiential learning of N2 O/O2 inhalation sedation through a hands-on laboratory exercise should be incorporated into the predoctoral curricula of dental schools.

Assessing Competency in Family Medicine Residents Using the Osteopathic Manipulative Medicine Mini-Clinical Evaluation Exercise.

CONTEXT: The Mini-Clinical Evaluation Exercise (Mini-CEX) is one example of a direct observation tool used for workplace-based skills assessment. The Mini-CEX has been validated as a useful formative evaluation tool in graduate medical education. However, no Mini-CEX has been reported in the literature that specifically assesses the osteopathic manipulative medicine (OMM) skills of family medicine residents. Therefore, the authors created and studied an OMM Mini-CEX to fill this skills assessment gap. OBJECTIVE: To determine whether the OMM Mini-CEX is perceived as an effective evaluation tool for assessing the OMM core competencies of family medicine residents. METHODS: Faculty and residents of The Wright Center for Graduate Medical Education National Family Medicine Residency program participated in the study. Each resident was evaluated at least once using the OMM Mini-CEX. Surveys were used to assess faculty and resident perceptions of the usefulness and effectiveness of the OMM Mini-CEX for assessing OMM competencies. RESULTS: Eighty-one responses were received during 2 survey cycles within a 7-month period. The internal consistency of the survey responses had a high reliability (Cronbach α=0.93). Considering respondents who agreed that they had a clear understanding of the general purpose of a Mini-CEX, the perceived effectiveness score for the OMM Mini-CEX was higher among those who agreed that a Mini-CEX was a useful part of training than among those who disagreed or were unsure of its usefulness (median score, 4.0 vs 3.4, respectively; P=.047). CONCLUSIONS: The results suggest the OMM Mini-CEX can be a useful direct observation evaluation tool to assess OMM core competencies in family medicine residents. Additional research is needed to determine its perceived effectiveness in other clinical specialties and in undergraduate medical education.

Effects of pressure applied during standardized spinal mobilizations on peripheral skin blood flow: A randomised cross-over study.

BACKGROUND: Peripheral skin blood flow (SBF) changes during and after spinal mobilization (SM), evaluated with laser Doppler flowmetry, may document physiological responses associated with SM. OBJECTIVES: To document variations in SBF during and after application of an SM and evaluate influence of pressure on SBF by applying the same standardized SM with 3 different nonnoxious pressures. DESIGN: Cross-over design with 4 interventions on 4 different days: control (no touch) and 3 SMs applied rhythmically at 5%, 40%, or 80% of pain pressure threshold (sham SM, low-pressure SM, or high-pressure SM, respectively). METHOD: Thirty-two individuals participated. The inspiratory gasp (IG) test was our positive control of vasoconstriction through excitation of the skin sympathetic nervous activity (SSNA). Each session comprised 5 phases: (1) baseline at the end of a 20-min acclimatization, (2) IG test, (3) post-IG phase, (4) SM phase or no manual contact for control, and (5) post-SM phase. A Biopac MP36 system collected SBF data, and a Novel Pliance-X system recorded pressure data. RESULTS/FINDINGS: Equal and significant bilateral vasodilation occurred during application of unilateral sham SM, low-pressure SM, and high-pressure SM. Post-SM significant vasodilation persisted after high-pressure SM. CONCLUSIONS: The current study is the first to describe bilateral peripheral SBF changes occurring during and 5 min after application of standardized SMs. Our post-SM vasodilation suggests involvement of mechanisms other than the putative SSNA-excitatory mechanism proposed with skin conductance measurements. Persistence of post-SM vasodilation following only high-pressure SM suggests possible pressure-dependent mechanisms. However, further research is warranted to clarify our findings.