Snus is an oral tobacco product that originated in Sweden. Snus products are available as fine-cut loose tobacco or in pre-portioned porous "pouches." Some snus products undergo tobacco ...pasteurization during manufacturing, a process that removes or reduces nitrite-forming microbes, resulting in less tobacco-specific nitrosamine content in the product. Some tobacco companies and researchers have suggested that snus is potentially less harmful than traditional tobacco and thus a potential smoking cessation aid or an alternative to continued cigarette consumption. Although snus is available in various countries, limited information exists on snus variants from different manufacturers.
Moisture, pH, nicotine, and tobacco-specific N'-nitrosamines (TSNAs) were quantified in 64 snus products made by 10 manufacturers in the United States and Northern Europe (NE). Reported means, standard errors, and differences are least-square (LS) estimates from bootstrapped mixed effects models, which accounted for correlation among repeated measurements. Minor alkaloids and select flavors were also measured.
Among all product types, moisture (27.4%-59.5%), pH (pH 5.87-9.10), total nicotine (6.81-20.6 mg/g, wet), unprotonated nicotine (0.083-15.7 mg/g), and total TSNAs (390-4,910 ng/g) varied widely. The LS-mean unprotonated nicotine concentration of NE portion (7.72 mg/g, SE = 0.963) and NE loose (5.06 mg/g, SE = 1.26) snus were each significantly higher than US portion snus (1.00 mg/g, SE = 1.56). Concentrations of minor alkaloids varied most among products with the highest total nicotine levels. The LS-mean NNN+NNK were higher in snus sold in the US (1360 ng/g, SE = 207) than in NE (836 ng/g, SE = 132) countries. The most abundant flavor compounds detected were pulegone, eucalyptol, and menthol.
Physical and chemical characteristics of US and NE products labeled as snus can vary considerably and should not be considered "equivalent". Our findings could inform public health and policy decisions pertaining to snus exposure and potential adverse health effects associated with snus.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
A homologous series of bis-guanylhydrazone compounds decorated with hydrophobic functionalities bind and neutralize lipopolysaccharide (LPS) with a potency comparable to that of polymyxin B, a ...peptide antibiotic known to sequester LPS.
We have shown that lipopolyamines bind to the lipid A moiety of lipopolysaccharide, a constituent of Gram-negative bacterial membranes, and neutralize its toxicity in animal models of endotoxic shock. In an effort to identify non-polyamine scaffolds with similar endotoxin-recognizing features, we had observed an unusually high frequency of hits containing guanylhydrazone scaffolds in high-throughput screens. We now describe the syntheses and preliminary structure–activity relationships in a homologous series of bis-guanylhydrazone compounds decorated with hydrophobic functionalities. These first-generation compounds bind and neutralize lipopolysaccharide with a potency comparable to that of polymyxin B, a peptide antibiotic known to sequester LPS.
Abstract
We study the morphologies and structures of 57 dwarf galaxies that are representative of the general population of dwarf galaxies and compare their demographics to a sample of dwarf galaxies ...hosting optically selected active galactic nuclei (AGNs). The two samples span the same galaxy stellar mass (10
9
≲
M
⋆
/
M
⊙
≲ 10
9.5
) and color range, and the observations are well-matched in physical resolution. The fractions of irregular galaxies (14%) and early types/ellipticals (∼18%) are nearly identical among the two samples. However, among galaxies with disks (the majority of each sample), the AGN hosts almost always have a detectable (pseudo)bulge, while a large fraction of the non-AGN hosts are pure disk galaxies with no detectable (pseudo)bulge. Central point sources of light consistent with nuclear star clusters are detected in many of the non-AGN hosts. In contrast, central point sources detected in the AGN hosts are, on average, more than 2 orders of magnitude more luminous, suggesting the point sources in these objects are dominated by AGN light. The preference for (pseudo)bulges in dwarf AGN hosts may inform searches for massive black holes in dwarf galaxies and attempts to constrain the black hole occupation fraction, which, in turn, has implications for our understanding of black hole seeding mechanisms.
Smokeless tobacco (ST) products are widely used throughout the world and contribute to morbidity and mortality in users through an increased risk of cancers and oral diseases. Bacterial populations ...in ST contribute to taste, but their presence can also create carcinogenic, Tobacco-Specific N-nitrosamines (TSNAs). Previous studies of microbial communities in tobacco products lacked chemistry data (e.g. nicotine, TSNAs) to characterize the products and identify associations between carcinogen levels and taxonomic groups. This study uses statistical analysis to identify potential associations between microbial and chemical constituents in moist snuff products.
We quantitatively analyzed 38 smokeless tobacco products for TSNAs using liquid chromatography with tandem mass spectrometry (LC-MS/MS), and nicotine using gas chromatography with mass spectrometry (GC-MS). Moisture content determinations (by weight loss on drying), and pH measurements were also performed. We used 16S rRNA gene sequencing to characterize the microbial composition, and additionally measured total 16S bacterial counts using a quantitative PCR assay.
Our findings link chemical constituents to their associated bacterial populations. We found core taxonomic groups often varied between manufacturers. When manufacturer and flavor were controlled for as confounding variables, the genus Lactobacillus was found to be positively associated with TSNAs. while the genera Enteractinococcus and Brevibacterium were negatively associated. Three genera (Corynebacterium, Brachybacterium, and Xanthomonas) were found to be negatively associated with nicotine concentrations. Associations were also investigated separately for products from each manufacturer. Products from one manufacturer had a positive association between TSNAs and bacteria in the genus Marinilactibacillus. Additionally, we found that TSNA levels in many products were lower compared with previously published chemical surveys. Finally, we observed consistent results when either relative or absolute abundance data were analyzed, while results from analyses of log-ratio-transformed abundances were divergent.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
A recent phylogenetic review of the genus Sebastes suggested the existence of a cryptic species of vermilion rockfish (Sebastes miniatus). To evaluate the geographical and bathymetric range of the ...Type 1 and Type 2 forms reported in that study, cytochrome b sequences were examined from 548 fish. Type 1 fish were found primarily south of Point Conception on reefs deeper than 100 m. Type 2 fish were common range-wide at sites shallower than 100 m. Reproductive isolation between the two types was tested using nine microsatellite loci. Estimates of genetic divergence were made using the fixation index (FST) and correspondence between haplotype and genotype was tested by Bayesian population assignment and multivariate plotting of individual genotypes. Microsatellite analyses gave strong support for the presence of two distinct groups of genotypes. All fish with Type 1 haplotypes and fish with Type 2 haplotypes from < 100 m depth had genotypes unique to their haplotype group. However, most (68%) fish with Type 2 haplotypes from > 100 m depth assigned strongly to the Type 1 genotype group. Morphometric comparisons between the two genotypic groups revealed significant differences at three of the six examined measurements. Differences in both genetics, depth of occurrence, and morphology suggest these are separate species. This observation along with evidence of depth segregation in many recent species pairs led us to hypothesize a speciation model for Sebastes spp. by which the loss or truncation of a depth-related ontogenetic migration can lead to the creation of reproductively isolated populations.
MR imaging is not routinely used to image the extracranial facial nerve. The purpose of this study was to determine the extent to which this nerve can be visualized with a CISS sequence and to ...determine the feasibility of using that sequence for locating the nerve relative to tumor.
Thirty-two facial nerves in 16 healthy subjects and 4 facial nerves in 4 subjects with parotid gland tumors were imaged with an axial CISS sequence protocol that included 0.8-mm isotropic voxels on a 3T MR imaging system with a 64-channel head/neck coil. Four observers independently segmented the 32 healthy subject nerves. Segmentations were compared by calculating average Hausdorff distance values and Dice similarity coefficients.
The primary bifurcation of the extracranial facial nerve into the superior temporofacial and inferior cervicofacial trunks was visible on all 128 segmentations. The mean of the average Hausdorff distances was 1.2 mm (range, 0.3-4.6 mm). Dice coefficients ranged from 0.40 to 0.82. The relative position of the facial nerve to the tumor could be inferred in all 4 tumor cases.
The facial nerve can be seen on CISS images from the stylomastoid foramen to the temporofacial and cervicofacial trunks, proximal to the parotid plexus. Use of a CISS protocol is feasible in the clinical setting to determine the location of the facial nerve relative to tumor.
IMPORTANCE: Posttraumatic stress disorder (PTSD) is prevalent, persistent, and disabling. Although psychotherapy and pharmacotherapy have proven efficacious in randomized clinical trials, geographic ...barriers impede rural veterans from engaging in these evidence-based treatments. OBJECTIVE: To test a telemedicine-based collaborative care model designed to improve engagement in evidence-based treatment of PTSD. DESIGN, SETTING, AND PARTICIPANTS: The Telemedicine Outreach for PTSD (TOP) study used a pragmatic randomized effectiveness trial design with intention-to-treat analyses. Outpatients were recruited from 11 Department of Veterans Affairs (VA) community-based outpatient clinics serving predominantly rural veterans. Inclusion required meeting diagnostic criteria for current PTSD according to the Clinician-Administered PTSD Scale. Exclusion criteria included receiving PTSD treatment at a VA medical center or a current diagnosis of schizophrenia, bipolar disorder, or substance dependence. Two hundred sixty-five veterans were enrolled from November 23, 2009, through September 28, 2011, randomized to usual care (UC) or the TOP intervention, and followed up for 12 months. INTERVENTIONS: Off-site PTSD care teams located at VA medical centers supported on-site community-based outpatient clinic providers. Off-site PTSD care teams included telephone nurse care managers, telephone pharmacists, telepsychologists, and telepsychiatrists. Nurses conducted care management activities. Pharmacists reviewed medication histories. Psychologists delivered cognitive processing therapy via interactive video. Psychiatrists supervised the team and conducted interactive video psychiatric consultations. MAIN OUTCOMES AND MEASURES: The primary outcome was PTSD severity as measured by the Posttraumatic Diagnostic Scale. Process-of-care outcomes included medication prescribing and regimen adherence and initiation of and adherence to cognitive processing therapy. RESULTS: During the 12-month follow-up period, 73 of the 133 patients randomized to TOP (54.9%) received cognitive processing therapy compared with 16 of 132 randomized to UC (12.1%) (odds ratio, 18.08 95% CI, 7.96-41.06; P < .001). Patients in the TOP arm had significantly larger decreases in Posttraumatic Diagnostic Scale scores (from 35.0 to 29.1) compared with those in the UC arm (from 33.5 to 32.1) at 6 (β = −3.81; P = .002) and 12 (β = −2.49; P = .04) months. Patients in the TOP arm also had significantly larger decreases in Posttraumatic Diagnostic Scale scores (from 35.0 to 30.1) compared with those in the UC arm (from 33.5 to 29.1) at 12 months (β = −2.49; P=.04). There were no significant group differences in the number of PTSD medications prescribed and adherence to medication regimens were not significant. Attendance at 8 or more sessions of cognitive processing therapy significantly predicted improvement in Posttraumatic Diagnostic Scale scores (β = −3.86 95% CI, −7.19 to −0.54; P = .02) and fully mediated the intervention effect at 12 months. CONCLUSIONS AND RELEVANCE: Telemedicine-based collaborative care can successfully engage rural veterans in evidence-based psychotherapy to improve PTSD outcomes. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00821678
Background: High (10–20 Hz) and low frequency (1–5 Hz) repetitive transcranial magnetic stimulation (rTMS) have been explored for possible therapeutic effects in the treatment of neuropsychiatric ...disorders. As part of a double-blind, placebo-controlled, crossover study evaluating the antidepressant effect of daily rTMS over the left prefrontal cortex, we evaluated changes in absolute regional cerebral blood flow (rCBF) after treatment with 1- and 20-Hz rTMS. Based on preclinical data, we postulated that high frequency rTMS would increase and low frequency rTMS would decrease flow in frontal and related subcortical circuits.
Methods: Ten medication-free, adult patients with major depression (eight unipolar and two bipolar) were serially imaged using
15O water and positron emission tomography to measure rCBF. Each patient was scanned at baseline and 72 hours after 10 daily treatments with 20-Hz rTMS and 10 daily treatments with 1 Hz rTMS given in a randomized order. TMS was administered over the left prefrontal cortex at 100% of motor threshold (MT). Significant changes in rCBF from pretreatment baseline were determined by paired
t test.
Results: Twenty-hertz rTMS over the left prefrontal cortex was associated only with increases in rCBF. Significant increases in rCBF across the group of all 10 patients were located in the prefrontal cortex (L > R), the cingulate gyrus (L ≫ R), and the left amygdala, as well as bilateral insula, basal ganglia, uncus, hippocampus, parahippocampus, thalamus, and cerebellum. In contrast, 1-Hz rTMS was associated only with decreases in rCBF. Significant decreases in flow were noted in small areas of the right prefrontal cortex, left medial temporal cortex, left basal ganglia, and left amygdala. The changes in mood following the two rTMS frequencies were inversely related (
r = −.78,
p < .005,
n = 10) such that individuals who improved with one frequency worsened with the other.
Conclusions: These data indicate that 2 weeks of daily 20-Hz rTMS over the left prefrontal cortex at 100% MT induce persistent increases in rCBF in bilateral frontal, limbic, and paralimbic regions implicated in depression, whereas 1-Hz rTMS produces more circumscribed decreases (including in the left amygdala). These data demonstrate frequency-dependent, opposite effects of high and low frequency rTMS on local and distant regional brain activity that may have important implications for clinical therapeutics in various neuropsychiatric disorders.
Abstract only
Introduction:
Emergency medical services (EMS) are an important link in the chain of care for patients experiencing time-sensitive cardiovascular emergencies, including ST-segment ...elevation myocardial infarction (STEMI). Recent quality initiatives have focused on reducing delays in STEMI care in both the prehospital and in-hospital environments. For instance, “door-to-balloon times” are tracked to ensure minimal delays from the time a STEMI patient enters a hospital to revascularization. In the prehospital realm, comparably less research has investigated factors contributing to delays in care for STEMI patients. Prolonged “scene times” - the time spent with a patient prior to transport - represents one area where focus is needed.
Methods:
As part of an ongoing initiative, EMS providers are encouraged to limit scene times to under 20 minutes for STEMI patients. We queried data from the Minnesota State Emergency Medical Services Regulatory Bureau (EMSRB) to ascertain what percentage of EMS encounters involving STEMI patients within the state’s MNSTAR EMS database between 2018 and 2021 had a scene time of greater than 20 minutes. Encounters involving helicopter emergency medical services (HEMS) were excluded.
Results:
Between 2018 and 2021, there were a total of 5178 STEMI patient encounters meeting eligibility criteria. Approximately 67.6% (n~3501) of patient encounters involved a scene time less than or equal to 20 minutes. Rural communities were associated with prolonged scene times when compared with metropolitan communities.
Conclusions:
Our preliminary analysis of EMS data from Minnesota shows one-third of STEMI encounters had scene times greater than 20 minutes. Thus, reducing prehospital scene times by EMS may be one method to streamline the care for STEMI patients. Further research should investigate what factors influence EMS crews to spend more than 20 minutes on scene with STEMI patients.
Most electronic cigarettes (e-cigarettes) contain a solution of propylene glycol/glycerin and nicotine, as well as flavors. E-cigarettes and their associated e-liquids are available in numerous ...flavor varieties. A subset of the flavor varieties include coffee, tea, chocolate, and energy drink, which, in beverage form, are commonly recognized sources of caffeine. Recently, some manufacturers have begun marketing e-liquid products as energy enhancers that contain caffeine as an additive.
A Gas Chromatography-Mass Spectrometry (GC-MS) method for the quantitation of caffeine in e-liquids was developed, optimized and validated. The method was then applied to assess caffeine concentrations in 44 flavored e-liquids from cartridges, disposables, and refill solutions. Products chosen were flavors traditionally associated with caffeine (ie, coffee, tea, chocolate, and energy drink), marketed as energy boosters, or labeled as caffeine-containing by the manufacturer.
Caffeine was detected in 42% of coffee-flavored products, 66% of tea-flavored products, and 50% of chocolate-flavored e-liquids (limit of detection LOD - 0.04 µg/g). Detectable caffeine concentrations ranged from 3.3 µg/g to 703 µg/g. Energy drink-flavored products did not contain detectable concentrations of caffeine. Eleven of 12 products marketed as energy enhancers contained caffeine, though in widely varying concentrations (31.7 µg/g to 9290 µg/g).
E-liquid flavors commonly associated with caffeine content like coffee, tea, chocolate, and energy drink often contained caffeine, but at concentrations significantly lower than their dietary counterparts. Estimated daily exposures from all e-cigarette products containing caffeine were much less than ingestion of traditional caffeinated beverages like coffee.
This study presents an optimized and validated method for the measurement of caffeine in e-liquids. The method is applicable to all e-liquid matrices and could potentially be used to ensure regulatory compliance for those geographic regions that forbid caffeine in e-cigarette products. The application of the method shows that caffeine concentrations and estimated total caffeine exposure from e-cigarette products is significantly lower than oral intake from beverages. However, because very little is known about the effects of caffeine inhalation, e-cigarette users should proceed with caution when using caffeine containing e-cigarette products. Further research is necessary to determine associated effects from inhaling caffeine.
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