Trends and Frequencies of Antibiotic Prescriptions for Acute Sinusitis Outpatient Visits in Adults.

OBJECTIVE: The objective of this study was to analyze the trends and frequency in which recommended first-line therapy, amoxicillin with or without clavulanate, was prescribed for acute sinusitis based on current otolaryngology and other gold standard guidelines, as well as analyze differences in prescription behaviors of otolaryngologists compared with non-otolaryngologists for outpatient adult acute sinusitis visits. METHODS: Weighted patient data from the National Ambulatory Medical Care Survey were analyzed to calculate visit rates and trends of antibiotic prescriptions for adults diagnosed with acute sinusitis from 2007 to 2019. Visits with multiple prescribed antibiotics or concomitant diagnoses requiring antibiotics were excluded. Each visit was classified based on the type of antibiotic prescribed. RESULTS: Acute sinusitis was diagnosed in 0.63% of all outpatient visits from 2007 to 2019 (95% confidence interval: 0.56%-0.71%). Amoxicillin had the greatest increase in prescription frequency (13.4%), whereas macrolides had the largest decrease in prescription frequency (13.9%). Among adult acute sinusitis outpatient visits in which antibiotics were prescribed, recommended first-line antibiotic therapy of amoxicillin-clavulanate or amoxicillin alone was prescribed in 40.4% of visits. The most common antibiotic prescribed was amoxicillin-clavulanate at otolaryngologist visits (20.5%) and macrolides at non-otolaryngologist visits (26.0%). A greater proportion of otolaryngologist visits resulted in no antibiotics prescribed for acute sinusitis (36.8% vs. 22.5%, p < 0.001). CONCLUSION: Otolaryngologists engage in watchful waiting more than non-otolaryngologists. Broader dissemination of existing guidelines for acute sinusitis treatment to non-Otolaryngologist (ENT) primary care specialties that take care of acute sinusitis to improve antibiotic stewardship and appropriate antibiotic selection is needed. LEVEL OF EVIDENCE: 4 Laryngoscope, 134:2622-2625, 2024.

Reflections and Critical Directions for Toilet Training in Applied Behavior Analysis.

Achieving toileting independence is a critical skill that yields several benefits of pressing social, developmental, and health-related importance. The seminal behavioral approach to toilet training established the conceptualization of continence and framework for toileting research thereafter. Contemporary researchers continue to evaluate toilet training procedures that produce efficacious outcomes for young children that closely align with current applied behavior analysis (ABA) ethics and standards of practice. Despite the overall success of behavior-analytic toileting approaches, there are critical directions still worthy of consideration and investigation. In this paper, we acknowledge the seminal roots and many of the contemporary contributions. We also critically reflect on current practices while proposing necessary areas to advance behavior-analytic toilet training research.

Anger treatment via CBAT delivered remotely: Outcomes on psychometric and self-monitored measures of anger.

Studies of anger treatment have often reported on reappraisal and relaxation techniques delivered in person to forensic and psychiatric samples. The present study evaluated an integrative programme of cognitive-behavioural affective therapy (CBAT) delivered remotely to chronic pain sufferers with comorbid anger. Volunteers (N = 54) were randomly assigned to either CBAT or an Emotional Education (EE) group, both receiving hour-long videorecorded sessions twice a week for 4 weeks plus weekly calls by telephone. At 1-month post-treatment, follow-up was conducted. Outcomes were measured using the Anger Parameters Scale (APS) and its five subscales (frequency, duration, intensity, latency and threshold) as well as daily self-monitored anger logs. As hypothesized, pre- to post-treatment decline in APS total scores was significant for CBAT, Hedges' g = 0.65, 95% CI [0.14, 1.16] but nonsignificant and small for EE, g = 0.17, CI [-0.41, 0.75]. At the primary endpoint (post-treatment), APS total scores were significantly lower for CBAT than for EE. Treatment gains were maintained till follow-up. On all five APS subscales, pre-post effect sizes were medium-sized for CBAT and generally small for EE. This picture was mirrored in the self-monitored frequency, duration and intensity of anger. Findings support the efficacy of CBAT over time, its comparative efficacy over EE and its ecological generalizability. Future research could expand sample size, reduce sample imbalance, extend follow-up and strengthen treatment potency with more sessions. The present study renews enthusiasm for teletherapy and is the first to demonstrate CBAT efficacy in treating maladaptive anger in the chronic pain population.

Application of PCR-based diagnostic tools that target Enterocytozoon hepatopenaei for the molecular detection of a Vittaforma-like microsporidium that infects Penaeus vannamei from Costa Rica.

Several PCR methodologies are available for the detection of Enterocytozoon hepatopenaei (EHP) that target the SSU rRNA gene. However, these methodologies are reported as unsuitable for the detection of EHP due to specificity issues. Here, we report the applicability of two commonly used SSU rRNA methodologies for the detection of additional microsporidia from the genus Vittaforma that is present in cultured Penaeus vannamei from Costa Rica. The molecular detection of DNA of the novel microsporidia can only be achieved using SSU rRNA targeting methodologies and does not cross-react with the highly specific spore wall protein gene PCR detection method.

A Comparison of Baseline Procedures in Task Analyses.

Several methods for assessing baseline performance in chained tasks have been outlined in the literature, including the fixed-opportunity probe (FOP) and the multiple-opportunity probe (MOP). Concerns have been raised regarding how each of these methods might change the baseline performance of a task, affecting the interpretation of experimental control. The purpose of the current study was to conduct a within-subject comparison of both the FOP and MOP procedures for children with autism performing daily living and self-care skills. Results indicated that, for most participants, the MOP resulted in elevated performance during baseline compared to the FOP, and that for some participants the MOP resulted in acquisition prior to direct training. Because of the possibility that the FOP might result in suppressed baseline performance, it is recommended that in most cases clinicians and researchers use the MOP when assessing baseline performance in chained tasks in order to obtain the most accurate data.

Acceptability of Single-dose Clindamycin Gel for Bacterial Vaginosis: A Randomized Controlled Trial.

PURPOSE: The goal of this study was to assess the acceptability of a single-dose bioadhesive 2% clindamycin vaginal gel for bacterial vaginosis (BV). METHODS: This double-blind, placebo-controlled, randomized study compared a new clindamycin gel with placebo gel (2:1 ratio). The primary objective was efficacy; secondary objectives were safety and acceptability. Subjects were evaluated at screening, days 7 to 14 (Day 7-14), and days 21 to 30 (test-of-cure [TOC]). An acceptability questionnaire with 9 questions was administered at the Day 7-14 visit, and a subset of questions (#7-#9) was asked again at the TOC visit. At Visit 1, subjects were provided with a daily electronic diary (e-Diary) to collect information regarding study drug administration, vaginal discharge, odor, itching, and any other treatments used. Study site staff reviewed e-Diaries at the Day 7-14 and TOC visits. FINDINGS: A total of 307 women with BV were randomized to treatment (204 to the clindamycin gel group and 103 to the placebo gel group). Most (88.3%) reported at least one previously diagnosed BV episode, and more than one half (55.4%) had experience with other vaginal treatments for BV. At the TOC visit, almost all (91.1%) of the clindamycin gel subjects described their overall experience with the study drug as "satisfied" or "very satisfied," 95.8% indicated that they would be "likely" or "very likely" to use the product again if it became available after the study and they had BV again, and 93.7% would be "likely" or "very likely" to recommend their treatment to a friend who had BV. Almost all (90.2%) clindamycin-treated subjects responded that application was "clean" or "fairly clean," as opposed to "neither clean nor messy," "fairly messy," or "messy." Although 55.4% experienced leakage in the days after application, only 26.9% of those indicated that it was bothersome. Subjects receiving clindamycin gel also reported improvement in both odor and discharge, commencing shortly after dosing and continuing through the assessment period, regardless of whether they met the critical cure criteria. IMPLICATIONS: A single dose of a new bioadhesive 2% clindamycin vaginal gel showed rapid resolution of symptoms and was highly acceptable as a treatment for bacterial vaginosis. CLINICALTRIALS: gov identifier: NCT04370548.

Parameters of anger as related to sensory-affective components of pain.

OBJECTIVES: Comorbid with chronic pain are negative emotions, anger being particularly salient. To evaluate specific relationships between pain and anger, the present study deconstructed anger into five parameters and dichotomized pain into sensory vs. affective components. Hypotheses were (i) anger parameters would be significantly and positively correlated with affective pain more so than with sensory pain, and (ii) individual parameters would be differentially related to pain components. METHODS: The Anger Parameters Scale (APS) was used to rate five parameters of anger: frequency, duration, intensity, latency, and threshold. Also rated was the physical sensation of pain and the degree of distress from pain. The volunteer sample comprised n=51 chronic pain patients, varying in ethnicity/race and educational level. RESULTS: Descriptive statistics revealed: APS total M=71.52, SD=16.68, Sensory pain M=6.27, SD=2.15, Affective pain M=5.76, SD=2.28. Sensory and affective pain were highly correlated, r=0.70. APS total was significantly associated with affective pain (r=+0.28) but hardly with sensory pain (r=0.12). Two anger parameters significantly correlated with affective pain: anger frequency (r=+0.30, p<0.05) and anger threshold (r=+0.33, p<0.05). Secondarily, certain educational levels (but not gender and ethnicity/race) were associated with significantly higher APS total scores. CONCLUSIONS: Scores for all variables were in the mid-range. As hypothesized, anger was more strongly correlated with distress/suffering of pain than with physical sensation of pain, though both pain components were closely coupled. Specific findings regarding frequency and threshold imply that being angry often and being oversensitive to provocation are associated with greater distress in this context. In deconstructing anger and dichotomizing pain, the present study extends previous research by elaborating on what aspects of anger are most related to which components of pain. Moreover, certain educational levels with higher levels of anger may need special attention. Further research could examine if treatment of anger might lead to corresponding changes in chronic pain.

Single-Dose, Bioadhesive Clindamycin 2% Gel for Bacterial Vaginosis: A Randomized Controlled Trial.

OBJECTIVE: To assess efficacy and safety of a single-dose vaginal clindamycin gel for bacterial vaginosis treatment. METHODS: We conducted a double-blind, placebo-controlled, randomized study comparing clindamycin gel with placebo (2:1 ratio). Entry required clinical diagnosis of bacterial vaginosis, that is, all four Amsel's criteria, without other genital infections. Nugent scores of 7-10 were required for efficacy assessment, per updated 2019 U.S. Food and Drug Administration guidance. Patients were evaluated at screening, day 7-14, and day 21-30 (test of cure). Clinical cure was defined as resolution of three of four Amsel's criteria. Bacteriologic cure was defined as Nugent score lower than 4. Therapeutic cure was both clinical and bacteriologic cure. Primary outcome was clinical cure at the test-of-cure visit. Secondary endpoints were clinical cure at day 7-14, and bacteriologic and therapeutic cures at day 7-14 and test of cure. A sample size of 188 patients in the clindamycin group compared with 94 patients in the placebo group had 90% power to detect statistically significant difference (P=.05, 2-tailed). RESULTS: Participants were seen between July 9, 2020, and November 12, 2020. Of 307 randomized women, 56.0% were Black and 88.3% reported one or more previous bacterial vaginosis episodes. In the modified intention-to-treat population, 70.5% of patients in the clindamycin group and 35.6% in the placebo group achieved clinical cure at test of cure (primary outcome) (difference of 34.9, 95% CI 19.0-50.8), as did 77.5% of patients in the clindamycin group and 42.6% of patients in the placebo group in the per-protocol population (difference of 34.9, 95% CI 17.0-52.7). Statistically significant differences between groups were seen for all secondary endpoints. Clinical cure rate in patients in the clindamycin group with more than three bacterial vaginosis episodes in the prior year was 70.0%. Approximately 15% (15.3%) of patients in the clindamycin group experienced one or more treatment-emergent adverse events related to study treatment, as did 9.7% of patients in the placebo group. The most frequent treatment-related, treatment-emergent adverse event was vulvovaginal candidiasis. CONCLUSION: A new, single-dose clindamycin vaginal gel was highly effective, with excellent safety, in women disproportionately affected by bacterial vaginosis, with Nugent scores of 7-10 at study entry. FUNDING SOURCE: The study was funded by Daré Bioscience, Inc. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov, NCT04370548.

Further evaluation of functional analysis screening methods in early autism intervention.

A goal of some functional analysis (FA) variations is to reduce assessment time while still maintaining efficacy. This may be especially important when conducting FAs in early intervention programs, where time is a crucial commodity. To that end, we evaluated a model for using the results of the no-interaction condition as a screening for behavioral function and to guide selection of FA test conditions with 20 participants (22 assessments) aged 3 to 7 years old. We used the no-interaction condition to develop hypotheses for both automatic reinforcement and socially mediated reinforcement. The outcome of the no-interaction condition guided the selection of test conditions for the remainder of the FA. We also incorporated methods from prior FA studies (e.g., divided attention) to modify the test conditions. We obtained differentiated results in 91% of assessments, all within 70 min and, as such, extended evidence that an FA can be completed in little time without sacrificing efficacy.

Analysis of Online Patient Education Materials on Rhinoplasty.

Objective: Are education materials available online appropriate for patients seeking information before rhinoplasty? Study Design: Google.com and YouTube.com were searched for patient education information on rhinoplasty procedures. Of the first 100 results, 75 articles and 75 videos met the inclusion criteria. Each article's readability was scored using six previously validated readability scores to determine patient's ability to comprehend the text, while each video was scored using the Journal of the American Medical Association (JAMA) benchmark criteria and the Global Quality Score (GQS) to measure source reliability and educational value, respectively. Results: Analysis of the readability of the 75 articles yielded an average grade reading level of 10.31 (range 5-20; 95% confidence interval, 9.83-10.79), while video analysis found videos authored by physicians were significantly more reliable (PJAMA < 0.001) and had a significantly higher educational value (PGQS < 0.001). Patient education videos were found to be more reliable than patient experience videos (PJAMA = 0.01). Conclusions: The average reading level for text information on rhinoplasty is higher than the recommended 5th-grade reading level and educational videos authored by physicians are more reliable and contain higher educational value yet lack important information.

Distribution of Paycheck Protection Program to otolaryngology practices during the COVID-19 pandemic.

BACKGROUND: The Coronavirus disease of 2019 (COVID-19) has impacted physician practices in many ways with some ENT clinics reporting around a 50% drop in completed scheduled ENT visits during the first wave of the pandemic compared to 2019. AIMS: This study surveyed first round PPP loan disbursement to otolaryngology practices in the United States in response to COVID-19. METHODS: A cross-sectional study was conducted using publicly available data published on PPP by the SBA. Otolaryngology clinics receiving loans greater than $0.15M were filtered using the following terms: "otolaryngology", "otolaryngologist","sinus", "head and neck", "throat", "ENT", and "facial plastic". 481 ENT clinics that received loans greater than $0.15 M from the Paycheck Protection Program (PPP) were identified. Loan amount, business type, geographicregion, owner race, owner gender, and the number of jobs per business were recorded for each clinic. Chi-square analysis was performed to determine significance (P < 0.05) of each characteristic. RESULTS: Loan distribution was significantly different based on jobs reported (P < .001) and business type (P < .001). 100% of loans ranging from $0.15 M to $0.35 M went to micro and small practices whereas 33% of medium-sized practices received loans greater than $1 M. Higher proportions of Subchapter corporations (60.00%) received smaller loans of $0.15 to $0.35 M than Limited Liability Companies (39.13%) and Corporations (51.69%) which generally employ more people. DISCUSSION: Loan distribution was significantly different between businesses based on jobs reported (P < 0.001), with micro/small practices recieving smaller loans than their medium counterparts. All large businesses recived loans in in excess of $2 M. This suggests proportional distribution of loans in accordance with jobs reported. CONCLUSION: This study suggests PPP funding was objectively distributed to ENT clinics based on staff size. LEVEL OF EVIDENCE: Level 4.

Evaluating bowel movements, self-initiations, and problem behavior with the emergence of urinary continence.

Much of the research evaluating toilet training interventions for children with ASD has focused on urinations as the primary dependent variable. As a result, the effects that toilet training interventions targeting urinations may have on other related dependent variables remains unclear. We conducted a retrospective analysis of data obtained by Perez et al. (2020), who evaluated the effects of a treatment package on urinary continence in children with ASD. We examined the relation between the emergence of urinary continence and multiple nontargeted dependent variables: bowel movements, self-initiation correspondence, percentage of appropriate urinations that were self-initiated, self-initiation rate, and problem behavior. Results showed that improvements in urinary continence were strongly correlated with improvements in all nontargeted dependent variables. Implications for future research and clinical practice are discussed.

A Novel Parent Questionnaire for the Detection of Seizures in Children of Spanish-Speaking Families.

BACKGROUND: We developed and validated a Spanish seizure screen for children based on a previously validated English seizure screen that could be administered by a trained research assistant in a 2-step process, approximating the clinical diagnostic process of a pediatric epilepsy specialist. This questionnaire was designed to study seizure prevalence in a research population of children at risk for epilepsy. METHODS: Spanish-speaking parents of children 6 months to 17 years old were recruited from the pediatric neurology clinics at Boston Medical Center and interviewed using a computerized questionnaire. A computerized algorithm of parent responses rendered a seizure classification of positive or negative. Blinded to questionnaire results, pediatric neurologists served as the diagnostic gold standard, ranking each patient event using a 4-level scale based on clinical history and examination: (1) not likely, (2) indeterminate, (3) probable, and (4) almost certain where rankings of 3 or 4 lead to a diagnosis of seizure. RESULTS: The questionnaire was completed by 163 enrolled parents. The seizure screen demonstrated a 94.2% sensitivity and 93.7% specificity for identifying seizures. The positive predictive value was 87.5%, and the negative predictive value was 97.2%. CONCLUSIONS: This pediatric seizure questionnaire was both sensitive and specific for detecting clinically confirmed seizures. This tool may be useful to clinicians and researchers in screening large populations of children, decreasing the time and cost of added neurologic assessments.

Functional analysis and operant treatment of food guarding in a pet dog.

The present study extended functional analysis (FA) methodology to human-directed resource guarding in a dog in an in-home setting. The subject underwent four conditions including control, attention, escape, and tangible, arranged in a modified FA. The results indicated multiply controlled resource guarding (i.e., escape, attention, and tangible functions). The experimenter then conducted a treatment evaluation involving three function-based treatments in a concurrent multiple baseline design. Resource guarding decreased to zero levels in treatments for each maintaining contingency. Treatment effects were maintained when the subject was tested with an owner, with an untrained handler, a highly preferred treat, in an untrained setting, as well as after 2 weeks in the absence of training. Behavior analytic techniques may hold promise for lasting behavior change for resource guarding in domestic dogs, and should be examined in other populations and with other canine problem behavior.

An extension of commonly used toilet-training procedures to children with autism spectrum disorder.

The current study evaluated a toilet-training treatment package described by Greer et al. (2016) with children diagnosed with autism spectrum disorder (ASD). Most of the current research on toilet-training interventions for children with ASD are replications and modifications of Azrin and Foxx (1971) or (more recently) LeBlanc et al. (2005). However, these procedures are composed of components that are not included in studies with typically developing (TD) children. For example, Greer et al. evaluated the effectiveness of three typical components within a toilet-training package, mostly with TD participants: a 30-min sit schedule, placing participants in underwear, and differential reinforcement. The primary purpose of the current study was to replicate and extend the treatment package described by Greer et al. to children with ASD. A secondary purpose was to evaluate modifications necessary for individualized toilet training when the commonly used components were ineffective. The results of Greer et al. were replicated for 11 participants with ASD in the current study, suggesting that intensive toileting interventions (e.g., interventions requiring overcorrection, reprimands, and dense sit schedules) may only be necessary for a subset of individuals with ASD.

Direct vasoactive effects of the chromogranin A (CHGA) peptide catestatin in humans in vivo.

Catestatin is a bioactive peptide of chromogranin A (CHGA) that is co-released with catecholamines from secretory vesicles. Catestatin may function as a vasodilator and is diminished in hypertension. To evaluate this potential vasodilator in vivo without systemic counterregulation, we infused catestatin to target concentrations of approximately 50, approximately 500, approximately 5000 nM into dorsal hand veins of 18 normotensive men and women, after pharmacologic venoconstriction with phenylephrine. Pancreastatin, another CHGA peptide, was infused as a negative control. After preconstriction to approximately 69%, increasing concentrations of catestatin resulted in dose-dependent vasodilation (P = 0.019), in female subjects (to approximately 44%) predominantly. The EC(50) (approximately 30 nM) for vasodilation induced by catestatin was the same order of magnitude to circulating endogenous catestatin (4.4 nM). No vasodilation occurred during the control infusion with pancreastatin. Plasma CHGA, catestatin, and CHGA-to-catestatin processing were then determined in 622 healthy subjects without hypertension. Female subjects had higher plasma catestatin levels than males (P = 0.001), yet lower CHGA precursor concentrations (P = 0.006), reflecting increased processing of CHGA-to-catestatin (P < 0.001). Our results demonstrate that catestatin dilates human blood vessels in vivo, especially in females. Catestatin may contribute to sex differences in endogenous vascular tone, thereby influencing the complex predisposition to hypertension.

Three femoral fixation devices for anterior cruciate ligament reconstruction: comparison of fixation on the lateral cortex versus the anterior cortex.

PURPOSE: To evaluate the biomechanical properties of 3 anterior cruciate ligament (ACL) reconstruction femoral fixation devices in a porcine model with implantation on both the lateral femoral cortex and the anterior femoral cortex. METHODS: ACL reconstructions with an 8-mm porcine tendon graft were performed on 48 porcine femurs with the EndoButton CL (Smith & Nephew, Andover, MA), ToggleLoc with ZipLoop technology (Biomet Sports Medicine, Warsaw, IN), or EZLoc (Biomet Sports Medicine). In 8 specimens for each implant, the femoral tunnel was drilled from the 10:30 surgical position out the lateral cortex. In another 8 specimens for each implant, the tunnel was drilled from the 10:30 position to a standardized anterior femoral surface. Cyclic testing was performed on an MTS testing machine (MTS, Eden Prairie, MN) from 50 N to 450 N for 2,000 cycles, followed by load-to-failure testing in specimens that survived. The cortical thickness and location of the implant exit were recorded. RESULTS: In the lateral femur group, 0 of the EZLoc devices, 2 of the ToggleLoc devices, and 3 of the EndoButtons completed cyclic testing. In the anterior femur group, 1 of the EZLoc devices, 5 of the ToggleLoc devices, and 5 of the EndoButtons completed cyclic testing (P = .012). In the anterior femur group, the ToggleLoc exhibited higher 2,000-cycle elongation (5.46 +/- 1 mm) than the EndoButton (3.55 +/- 0.6 mm) (P = .005). The EndoButton showed a higher first failure load (1,190.9 +/- 150.0 N) than the ToggleLoc (912.6 +/- 82.4 N) (P = .007). The anterior cortex (1.4 mm) was thinner than the lateral cortex (1.7 mm) (P = .0002). CONCLUSIONS: The EndoButton provided the strongest ACL femoral fixation with significantly less graft-implant elongation and significantly higher failure loads. It was also shown in a porcine model that implants on the anterior cortical surface perform better than those on the lateral surface. Increased cortical thickness, in the range tested, was not associated with improved implant performance in the porcine model. CLINICAL RELEVANCE: The EndoButton provided the best ACL femoral fixation of the devices tested.

Genetic variation within adrenergic pathways determines in vivo effects of presynaptic stimulation in humans.

BACKGROUND: Catecholamines govern stress blood pressure responses. Catecholaminergic responses may be partially genetic and contribute to the complex heritability of hypertension. METHODS AND RESULTS: To evaluate catecholaminergic responses without systemic counterregulation, we infused graded concentrations of tyramine, an indirect presynaptic norepinephrine releaser, into dorsal hand veins of 49 normotensive men and women of 5 ethnicities. Vascular responses were coupled to common (minor allele frequency >10%) single-nucleotide polymorphisms at adrenergic target loci within presynaptic pathways. Significance was set at P<0.003 after Bonferroni correction. Generalized analysis of molecular variance (GAMOVA) was performed to determine whether genetic admixture contributed to results. Venoconstriction progressed to 47% with increasing concentrations of tyramine (0.129 to 25.8 mmol/L; P<0.001). Family history of hypertension (P<0.001) and female sex (P=0.02) predicted blunted tyramine responses. Two genetic loci significantly predicted vascular response: chromogranin B, which encodes a protein that catalyzes catecholamine vesicle formation (CHGB, exon 4, Glu348Glu; P=0.002), and cytochrome b-561 (CYB561, intron 1, C719G; P<0.001), an electron shuttle for catecholamine synthesis. Stepwise regression suggested important effects for the CHGB locus, with polymorphisms for the vacuolar-ATPase beta-subunit (ATP6V1B1, exon 1, Ile30Thr) and flavin-containing monooxygenase-3 (FMO3, exon 3, Lys158Glu, P=0.002). GAMOVA did not show a significant relationship between overall genetic profile and hand-vein constriction (P=0.29), which indicates that population stratification did not contribute to this phenotype. CONCLUSIONS: Locally infused tyramine produced dose-dependent pressor responses, predicted by family history of hypertension, sex, and genetic variants at loci, particularly CHGB, that encode the biosynthesis, storage, and metabolism of catecholamines. Such variants may influence the complex heritability of adrenergic responses and perhaps hypertension.

Extracellular signal-regulated kinase (ERK)-dependent gene expression contributes to L1 cell adhesion molecule-dependent motility and invasion.

The cell adhesion molecule L1 has been implicated in a variety of motile processes, including neurite extension, cerebellar cell migration, extravasation, and metastasis. Homophilic or heterophilic L1 binding and concomitant signaling have been shown to promote cell motility in the short term. In this report, L1 is also shown to induce and maintain a motile and invasive phenotype by promoting gene transcription. In the presence of serum or platelet-derived growth factor, L1 promotes heightened and sustained activation of the extracellular signal-regulated kinase pathway. Activation of this pathway then induces the expression of motility- and invasion-associated gene products, including the beta(3)-integrin subunit, small GTPases, and the cysteine proteases cathepsin-L and -B. Induction of integrin alpha(v)beta(3) and rac-1 is shown to contribute directly to L1-dependent haptotaxis, whereas induction of cathepsins-L and -B promotes matrix invasion. This study provides a novel translational mechanism to account for the association between L1 expression and motile processes involved in metastasis and development.

Alphav-integrin utilization in human beta-cell adhesion, spreading, and motility.

The role of individual integrins in human beta-cell development and function is largely unknown. This study describes the contribution of alpha(v)-integrins to human beta-cell adhesion, spreading, and motility. Developmental differences in alpha(v)-integrin utilization are addressed by comparing the responses of adult and fetal beta-cells, and vitronectin is used as a substrate based on its unique pattern of expression in the developing pancreas. Fetal and adult beta-cells attached equally to vitronectin and integrin alpha(v)beta(5) was found to support the adhesion of both mature and immature beta-cell populations. Fetal beta-cells were also observed to spread and migrate on vitronectin, and integrin alpha(v)beta(1) was found to be essential for these responses. In contrast to their fetal counterparts, adult beta-cells failed to either spread or migrate and this deficit was associated with a marked down-regulation of alpha(v)beta(1) expression in adult islet preparations. The integrin alpha(v)beta(3) was not found to support significant beta-cell attachment or migration. Based on our findings, we conclude that integrins alpha(v)beta(5) and alpha(v)beta(1) are important mediators of human beta-cell adhesion and motility, respectively. By supporting fetal beta-cell migration, alpha(v)beta(1) could play an important role in early motile processes required for islet neogenesis.