Substance abuse prevention infrastructure: a survey-based study of the organizational structure and function of the D.A.R.E. program

BACKGROUND: The only national drug abuse prevention delivery system that supports the rapid diffusion of new prevention strategies and includes uniform training and credentialing of instructors who are monitored for quality implementation of prevention programming is the Drug Abuse Resistance Education network (D.A.R.E.) linking community law enforcement to schools. Analysis of the organizational structure and function of D.A.R.E. provides an understanding of the essential parameters of this successful delivery system that can be used in the development of other types of national infrastructures for community-based prevention services. Information regarding organizational structure and function around funding issues, training, quality control and community relationships was gathered through telephone surveys with 50 state D.A.R.E. coordinators (including two major cities), focus groups with local D.A.R.E. officers and mentors, and interviews with national D.A.R.E. office staff. RESULTS: The surveys helped identify several strengths inherent in the D.A.R.E. program necessary for building a prevention infrastructure, including a well-defined organizational focus (D.A.R.E. America), uniform training and means for rapid dissemination (through its organized training structure), continuing education mechanisms (through the state and national conference and website), mechanisms for program monitoring and fidelity of implementation (formal and informal), branding and, for several states, predictable and consistent financing. Weaknesses of the program as currently structured include unstable funding and the failure to incorporate components for the continual upgrading of curricula reflecting research evidence and "principles of prevention". CONCLUSION: The D.A.R.E. organization and service delivery network provides a framework for the rapid dissemination of evidence-based prevention strategies. The major strength of D.A.R.E. is its natural affiliation to local law enforcement agencies through state coordinators. Through these affiliations, it has been possible for D.A.R.E. to become established nationally within a few years and internationally within a decade. Understanding how this structure developed and currently functions provides insights into how other such delivery systems could be developed

Acute Beetroot Juice Ingestion Increases Nitric Oxide Bioavailability Without Changing Oral Microbial Composition in Healthy Young Women

Dietary nitrate supplementation can elicit beneficial health and exercise performance effects. Oral microbiota are critical for the metabolism of exogenously consumed nitrate; however, limited data are available on the influence of dietary nitrate ingestion on bacterial taxa and in women. PURPOSE: To investigate if acute dietary nitrate ingestion alters the oral microbiota in young healthy women compared to a nitrate-depleted placebo. METHODS: In a randomized double-blinded crossover design, fifteen recreationally active women (mean ± SD: age 20 ± 1 years; body mass 63 ± 10 kg; height 1.68 ± 0.1 m) participated in two conditions to ingest nitrate-rich beetroot juice (BR; 12 mmol of nitrate) and nitrate-depleted beetroot juice (PL, negligible nitrate), 2.5 hours prior to a resting blood draw and buccal swab sample. Plasma [nitrate] and [nitrite] were analyzed using gas phase chemiluminescence. Buccal swab samples were used for DNA extraction and isolation. DNA was amplified using polymerase chain reaction targeting the V3 - V4 region of the 16S rRNA gene. Following index PCR, amplicons were pooled and sequenced using the iSeq Illumina NGS sequencer. Reads were clustered into amplicon sequence variants and analyzed for alpha and beta diversity and relative abundance. RESULTS: BR increased plasma [nitrate] (PL: 52 ± 14 µM vs. BR: 629 ± 132 µM, P \u3c 0.001) and plasma [nitrite] (PL: 276 ± 286 nM vs. BR: 703 ± 391 nM, P \u3c 0.001). One sample had insufficient DNA and thus, a subset of samples was analyzed for oral microbial composition (n = 14). Alpha (i.e., species richness or evenness) and beta diversity was not different between PL and BR (P \u3e 0.05). The relative abundance of the phylum and genus were not influenced by BR (P \u3e 0.05). CONCLUSION: Acute nitrate ingestion did not improve or worsen the composition of global or lower taxonomic levels of bacteria in young recreationally active women. These data indicate that acute nitrate ingestion is an intervention to rapidly increase nitric oxide bioavailability in young recreationally active women, which is an effect that did not require changes to the oral microbial community. Further research is required to understand the impact of dosing regimen and population on oral bacterial taxa and the efficacy of nitrate on nitrate-induced effects

Pharmacokinetic, neurochemical, stereological and neuropathological studies on the potential effects of paraquat in the substantia nigra pars compacta and striatum of male C57BL/6J mice

AbstractThe pharmacokinetics and neurotoxicity of paraquat dichloride (PQ) were assessed following once weekly administration to C57BL/6J male mice by intraperitoneal injection for 1, 2 or 3 weeks at doses of 10, 15 or 25mg/kg/week. Approximately 0.3% of the administered dose was taken up by the brain and was slowly eliminated, with a half-life of approximately 3 weeks. PQ did not alter the concentration of dopamine (DA), homovanillic acid (HVA) or 3,4-dihydroxyphenylacetic acid (DOPAC), or increase dopamine turnover in the striatum. There was inconsistent stereological evidence of a loss of DA neurons, as identified by chromogenic or fluorescent-tagged antibodies to tyrosine hydroxylase in the substantia nigra pars compacta (SNpc). There was no evidence that PQ induced neuronal degeneration in the SNpc or degenerating neuronal processes in the striatum, as indicated by the absence of uptake of silver stain or reduced immunolabeling of tyrosine-hydroxylase-positive (TH+) neurons. There was no evidence of apoptotic cell death, which was evaluated using TUNEL or caspase 3 assays. Microglia (IBA-1 immunoreactivity) and astrocytes (GFAP immunoreactivity) were not activated in PQ-treated mice 4, 8, 16, 24, 48, 96 or 168h after 1, 2 or 3 doses of PQ.In contrast, mice dosed with the positive control substance, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP; 10mg/kg/dose×4 doses, 2h apart), displayed significantly reduced DA and DOPAC concentrations and increased DA turnover in the striatum 7 days after dosing. The number of TH+ neurons in the SNpc was reduced, and there were increased numbers of degenerating neurons and neuronal processes in the SNpc and striatum. MPTP-mediated cell death was not attributed to apoptosis. MPTP activated microglia and astrocytes within 4h of the last dose, reaching a peak within 48h. The microglial response ended by 96h in the SNpc, but the astrocytic response continued through 168h in the striatum.These results bring into question previous published stereological studies that report loss of TH+ neurons in the SNpc of PQ-treated mice. This study also suggests that even if the reduction in TH+ neurons reported by others occurs in PQ-treated mice, this apparent phenotypic change is unaccompanied by neuronal cell death or by modification of dopamine levels in the striatum

Heart Rate and Energy Expenditure Concurrent Validity of Identical Garmin Wrist Watches During Moderately Heavy Resistance Training

Consistent with previous years, ACSM has found that wearable technology and resistance training (RT) are two of the top 5 fitness trends in 2023. Our lab recently found that wrist-worn devices, such as Garmin Instinct, are neither valid nor reliable at measuring average or maximal heart rate (HR) or estimating energy expenditure (EE) following light intensity circuit RT. We postulated that the errors may have been due to the device’s algorithms assuming higher intensity during RT. PURPOSE: The purpose of this study was to determine the concurrent validity of identical Garmin Instinct wrist-watches to record valid measures of average and maximal HR as well as estimated EE following moderately heavy RT. METHODS: Twenty-one adult participants completed this study (n=10 female, n=11 male). Two Garmin Instinct wrist-watches were evaluated, along with the Polar H10 chest strap and Cosmed K5 portable metabolic unit as the criterion devices for average/maximal HR and EE, respectively. Participants completed 8 supersets of the reverse lunge and shoulder press exercises using dumbbells at a light (4 sets) and moderately heavy (4 sets) intensity with 1 superset of 6 repetitions per exercise (12 repetitions per superset) and 1 min rest between supersets. Data were analyzed for validity (Mean Absolute Percent Error [MAPE] and Lin’s Concordance Coefficient [CCC]), with predetermined thresholds of MAPE\u3c10% and CCC\u3e0.70. A one-way repeated measures ANOVA with Sidak post-hoc test was used to determine differences (p\u3c0.05). RESULTS: The identical Garmin Instinct devices were not considered valid for average HR (MAPE range: 36.5-81.6%; CCC range: 0.07-0.18), maximal HR (MAPE range: 18.6-18.8%; CCC range: 0.15-0.31), or estimated EE (MAPE range: 14.0-16.4%; CCC range: 0.08-0.32) compared to the criterion references. The devices were significantly different than each other for average HR (p=0.005), maximal HR (p\u3c0.001), and estimated EE (p\u3c0.0001). CONCLUSION: The wearable wrist-worn devices tested herein should not be utilized for accurate measurements of HR or EE during RT, and there are even differences between identical devices. People who RT while using these devices should do so with caution if wishing to utilize them for physiological measures

Rating of Perceived Exertion, Average Heart Rate, and Energy Expenditure Following Indoor and Outdoor Moderately Heavy Superset Resistance Training

Our lab recently found that light intensity circuit resistance training outdoors had a significantly lower perception of effort (RPE) compared to indoor resistance training, despite no physiological differences in heart rate and energy expenditure. However, no study has examined other intensities or set schemes in differing environmental settings. PURPOSE: To determine how indoor or outdoor environments effect rating of perceived exertion (RPE) following light and moderately heavy intensity superset resistance training in recreationally resistance trained adults. METHODS: Twenty-three adult participants completed this study (n=10 female, n=13 male; age: 26.1±8.8 yrs; height: 172.2±9.5 cm; mass: 73.4±18.7 kg; RT experience: 5.3±4.8 yrs). Participants wore devices to measure heart rate (Polar H10 chest strap) and energy expenditure (Cosmed K5 Portable Metabolic Cart). Randomly in indoor and outdoor settings, participants completed 4 supersets of the reverse lunge and shoulder press exercises using dumbbells at a light (2 sets) and moderately heavy (2 sets) intensity with 1 superset of 6 repetitions per exercise (12 repetitions per superset) and 1 min rest between supersets. The OMNI Rating of Perceived Exertion Scale for Resistance Exercise 0-10 RPE scale was used following each superset. A paired T-test was used to determine differences between environmental setting (pRESULTS: No significant differences were observed between indoor and outdoor environments for average heart rate (129.4±17.2 and 127.8±23.3 bpm, p=0.67), energy expenditure (30.6±11.5 and 28.3±9.9 kcals; p=0.06), as well as RPE during light intensity (2.9±0.9 and 2.9±0.8 arbitrary units/AU’s, p=0.70) and moderately heavy intensity (6.5±1.7 and 6.3±1.5 AU’s, p=0.27) supersets. CONCLUSION: In recreationally resistance trained adults, light intensity and moderately heavy intensity superset resistance training in indoor or outdoor settings does not alter heart rate, energy expenditure, or perceived effort

Costa Rica Rift hole deepened and logged

During Leg 111 of the Ocean Drilling Program, scientists on the drilling vessel JOIDES Resolution studied crustal structure and hydrothermal processes in the eastern equatorial Pacific. Leg 111 spent 43 days on its primary objective, deepening and logging Hole 5048, a deep reference hole in 5.9-million-year-old crust 200 km south of the spreading axis of the Costa Rica Rift. Even before Leg 111 , Hole 5048 was the deepest hole drilled into the oceanic crust, penetrating 274.5 m of sediments and 1,075.5 m of pillow lavas and sheeted dikes to a total depth of 1,350 m below sea floor (mbsf). Leg 111 deepened the hole by 212.3 m to a total depth of 1,562.3 mbsf (1,287.8 m into basement), and completed a highly successful suite of geophysical logs and experiments, including sampling of borehole waters

Evolutionary Action Score of TP53 Identifies High-Risk Mutations Associated with Decreased Survival and Increased Distant Metastases in Head and Neck Cancer

TP53 is the most frequently altered gene in head and neck squamous cell carcinoma, with mutations occurring in over two-thirds of cases, but the prognostic significance of these mutations remains elusive. In the current study, we evaluated a novel computational approach termed evolutionary action (EAp53) to stratify patients with tumors harboring TP53 mutations as high or low risk, and validated this system in both in vivo and in vitro models. Patients with high-risk TP53 mutations had the poorest survival outcomes and the shortest time to the development of distant metastases. Tumor cells expressing high-risk TP53 mutations were more invasive and tumorigenic and they exhibited a higher incidence of lung metastases. We also documented an association between the presence of high-risk mutations and decreased expression of TP53 target genes, highlighting key cellular pathways that are likely to be dysregulated by this subset of p53 mutations that confer particularly aggressive tumor behavior. Overall, our work validated EAp53 as a novel computational tool that may be useful in clinical prognosis of tumors harboring p53 mutations

The Role of Genetic Variation Near Interferon-Kappa in Systemic Lupus Erythematosus

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by increased type I interferons (IFNs) and multiorgan inflammation frequently targeting the skin. IFN-kappa is a type I IFN expressed in skin. A pooled genome-wide scan implicated the IFNK locus in SLE susceptibility. We studied IFNK single nucleotide polymorphisms (SNPs) in 3982 SLE cases and 4275 controls, composed of European (EA), African-American (AA), and Asian ancestry. rs12553951C was associated with SLE in EA males (odds ratio = 1.93, P = 2.5 × 10−4), but not females. Suggestive associations with skin phenotypes in EA and AA females were found, and these were also sex-specific. IFNK SNPs were associated with increased serum type I IFN in EA and AA SLE patients. Our data suggest a sex-dependent association between IFNK SNPs and SLE and skin phenotypes. The serum IFN association suggests that IFNK variants could influence type I IFN producing plasmacytoid dendritic cells in affected skin