United States-Mexico Border Disparities in Alcoholic Liver Disease Mortality: A Cross-Sectional Analysis 1999-2020.

BACKGROUND: US-Mexico (US-MX) border regions are impacted by socioeconomic disadvantages. Alcohol use disorder remains widely prevalent in US-MX border regions, which may increase the risk of alcoholic liver disease (ALD). GOALS: We aimed to characterize ALD mortality trends in border regions compared to non-border regions from 1999 to 2020 in the United States (US). METHODS: We performed a cross-sectional analysis using the CDC repository. We queried death certificates to find ALD-related deaths from 1999 to 2020, which included demographic information such as gender, race/ethnicity, and area of residence. We estimated age-adjusted mortality rates (AAMR) per 100,000 population and compared the AAMRs across border and non-border regions. We also explored yearly mortality shifts using log-linear regression models and calculated the average annual percentage change (AAPC) using the Monte Carlo permutation test. RESULTS: In all, 11,779 ALD-related deaths were identified in border regions (AAMR 7.29) compared with 361,523 in non-border regions (AAMR 5.03). Border male (AAMR 11.21) and female (AAMR 3.77) populations were higher compared with non-border male (AAMR 7.42) and female (2.85) populations, respectively. Border non-Hispanic populations (AAMR 7.53) had higher mortality compared with non-border non-Hispanic populations (4.79), while both populations experienced increasing mortality shifts (AAPC +1.7, P<0.001 and +3.1, P<0.001, respectively). Border metropolitan (AAMR 7.35) and non-metropolitan (AAMR 6.76) regions had higher mortality rates compared with non-border metropolitan (AAMR 4.96) and non-metropolitan (AAMR 5.44) regions. CONCLUSIONS: Mortality related to ALD was higher in border regions compared with non-border regions. Border regions face significant health disparities when comparing ALD-related mortality.

Eculizumab in myasthenia gravis: A review.

Eculizumab, a monoclonal antibody against complement C5, is a novel therapy to treat refractory myasthenia gravis (MG). The present review was undertaken to study the role of eculizumab in MG. This includes the drug's mechanism, pharmacokinetics, clinical trial findings, tolerability, side effects, safety, dosage, administration, and cost. An English-language search for relevant items was undertaken using Embase and PubMed from 1946 to present. Clinical trial registries/databases and websites were also searched for relevant data. Keywords were eculizumab and MG. The present review found 103 articles after initial screening. Current data support eculizumab as an effective, safe, and tolerable drug in cases of refractory MG. However, its cost can prevent it from being widely accessible to a majority of the general population.

Returning to work after dysvascular lower limb amputation-A novel multivariate approach to examine relative contributions of biopsychosocial predictors.

BACKGROUND: Returning to work is a key outcome of rehabilitation and social re-integration after lower limb amputation. It is important to understand what biopsychosocial factors contribute to returning to work after dysvascular amputation. OBJECTIVE: Examining relative contributions of functional and contextual predictors of returning to work in participants with lower limb amputation due to diabetes and other dysvascular diseases. STUDY DESIGN: Cross-sectional. METHODS: Return-to-work outcome, biopsychosocial characteristics including physical functioning, self-efficacy & perceived ability, and socioeconomical support data were collected from a purposive sample (n = 57) in a multi-state collaborative research network. Grouped Weighted Quantile Sum model analysis was conducted to evaluate relative contributions of biopsychosocial predictors. RESULTS: Less than 30% of the participants returned to work after their amputation. Physical functioning (odds ratio = 10.19; 95% CI 2.46-72.74) was the most important predictor group. Working before amputation, prosthetic mobility, and access to rehabilitation care were also identified as key factors associated with returning to work. CONCLUSIONS: Fewer than 1 in 3 participants with dysvascular amputation returned to work, despite an average age of only 54 years at the time of amputation. Physical functioning was shown to be the most important predictor, while socioeconomic factors such as a lack of access to care also contribute to not returning to work after dysvascular amputation.

Effects of double and triple bonds on the spatial representations of odorants in the rat olfactory bulb.

Many naturally occurring volatile chemicals that are detected through the sense of smell contain unsaturated (double or triple) carbon-carbon bonds. These bonds can affect odors perceived by humans, yet in a prior study of unsaturated hydrocarbons we found only very minor effects of unsaturated bonds. In the present study, we tested the possibility that unsaturated bonds affect the recognition of oxygen-containing functional groups, because humans perceive odor differences between such molecules. We therefore compared spatial activity patterns across the entire glomerular layer of the rat olfactory bulb evoked by oxygen-containing odorants differing systematically in the presence, position, number, and stereochemistry of unsaturated bonds. We quantified activity patterns by mapping [(14)C]2-deoxyglucose uptake into anatomically standardized data matrices, which we compared statistically. We found that the presence and number of unsaturated bonds consistently affected activity patterns, with the largest effect related to the presence of a triple bond. Effects of bond saturation included a loss of activity in glomeruli strongly activated by the corresponding saturated odorants and/or the presence of activity in areas not stimulated by the corresponding saturated compounds. The position of double bonds also affected patterns of activity, but cis vs. trans configuration had no measurable impact in all five sets of stereoisomers that we studied. These results simultaneously indicate the importance of interactions between carbon-carbon bond types and functional groups in the neural coding of odorant chemical information and highlight the emerging concept that the rat olfactory system is more sensitive to certain types of chemical differences than others.

Differential responses to branched and unsaturated aliphatic hydrocarbons in the rat olfactory system.

In an effort to understand mammalian olfactory processing, we have been describing the responses to systematically different odorants in the glomerular layer of the main olfactory bulb of rats. Previously, we demonstrated chemotopically organized and distinct olfactory responses to a homologous series of straight-chained alkanes that consisted of purely hydrocarbon structures, indicating that hydrocarbon chains could serve as molecular features in the combinatorial coding of odorant information. To better understand the processing of hydrocarbon odorants, we now have examined responses to other types of chemical changes in these kinds of molecules, namely, branching and carbon-carbon bond saturation. To this end, we used the [14C]2-deoxyglucose method to determine glomerular responses to a group of eight-carbon branched alkane isomers, unsaturated octenes (double-bonded), and octynes (triple-bonded). In contrast to the differential responses we observed previously for straight-chained alkanes of differing carbon number, the rat olfactory system was not particularly sensitive to these variations in branching and bond saturation. This result was unexpected, given the distinct molecular conformations and property profiles of the odorants. The similarity in activity patterns was paralleled by a similarity in spontaneous perceptual responses measured using a habituation assay. These results demonstrate again the functional relationship between bulbar activity patterns and odor perception. The results further suggest that the olfactory system does not respond equally to all aspects of odorant chemistry, functioning as a specific, rather than a general, chemical analysis system.

Long hydrocarbon chains serve as unique molecular features recognized by ventral glomeruli of the rat olfactory bulb.

In an effort to understand mammalian olfactory processing, we have been describing the responses to systematically different odorants in the glomerular layer of the main olfactory bulb of rats. To understand the processing of pure hydrocarbon structures in this system, we used the [(14)C]2-deoxyglucose method to determine glomerular responses to a homologous series of alkanes (from six to 16 carbons) that are straight-chained hydrocarbons without functional groups. We found two rostral regions of activity evoked by these odorants, one lateral and one medial, that were observed to shift ventrally with increasing alkane carbon chain length. Furthermore, we successfully predicted that the longest alkanes with carbon chain length greater than our previous odorant selections would stimulate extremely ventral glomerular regions where no activation had been observed with the hundreds of odorants that we had previously studied. Overlaps in response profiles were observed in the patterns evoked by alkanes and by other aliphatic odorants of corresponding carbon chain length despite possessing different oxygen-containing functional groups, which demonstrated that hydrocarbon chains could serve as molecular features in the combinatorial coding of odorant information. We found a close and predictable relationship among the molecular properties of odorants, their induced neural activity, and their perceptual similarities.

Functional mapping of the rat olfactory bulb using diverse odorants reveals modular responses to functional groups and hydrocarbon structural features.

In an effort to understand the olfactory code of rats, we collected more than 1,500,000 measurements of glomerular activity in response to 54 odorants selected to provide differences in functional groups and hydrocarbon structure. Each odorant evoked a unique response pattern by differentially stimulating clusters of glomeruli, called modules. Odorants sharing specific aspects of their structure activated the same modules, allowing us to relate responses to structure across approximately 80% of the glomerular layer. The most obvious relationship was between the presence of particular oxygen-containing functional groups and the activity of glomeruli within dorsal modules. Functional group-specific responses were observed for odorants possessing a wide range of hydrocarbon structure, including aliphatic, cyclic, and aromatic features. Even formic acid and acetone, the simplest odorants possessing acid or ketone functional groups, respectively, stimulated modules specific for these functional groups. At the same time, quantitative analysis of pattern similarities revealed relationships in activation patterns between odorants of similar hydrocarbon structure. The odorant responses were reliable enough to allow us to predict accurately specific aspects of odorant molecular structure from the evoked glomerular activity pattern, as well as predicting the location of glomerular activity evoked by novel odorants.