Public Perceptions of Treating Opioid Use Disorder With Deep Brain Stimulation: Comment Analysis Study.

BACKGROUND: The number of opioid-related deaths in the United States has more than tripled over the past 7 years, with a steep increase beginning at the same time as the COVID-19 pandemic. There is an urgent need for novel treatment options that can help alleviate the individual and social effects of refractory opioid use disorder (OUD). Deep brain stimulation (DBS), an intervention that involves implanting electrodes in the brain to deliver electrical impulses, is one potential treatment. Currently in clinical trials for many psychiatric conditions, including OUD, DBS's use for psychiatric indications is not without controversy. Several studies have examined ethical issues raised by using DBS to counter treatment-resistant depression, obsessive-compulsive disorder, and eating disorders. In contrast, there has been limited literature regarding the use of DBS for OUD. OBJECTIVE: This study aims to gain empirical neuroethical insights into public perceptions regarding the use of DBS for OUD, specifically via the analysis of web-based comments on news media stories about the topic. METHODS: Qualitative thematic content analysis was performed on 2 Washington Post newspaper stories that described a case of DBS being used to treat OUD. A total of 292 comments were included in the analysis, 146 comments from each story, to identify predominant themes raised by commenters. RESULTS: Predominant themes raised by commenters across the 2 samples included the hopes and expectations with treatment outcomes, whether addiction is a mental health disorder, and issues related to resource allocation. Controversial comments regarding DBS as a treatment method for OUD seemingly decreased when comparing the first printed newspaper story to the second. In comparison, the number of comments relating to therapeutic need increased over time. CONCLUSIONS: The general public's perspectives on DBS as a treatment method for OUD elucidated themes via this qualitative thematic content analysis that include overarching sociopolitical issues, positions on the use of technology, and technological and scientific issues. A better understanding of the public perceptions around the use of DBS for OUD can help address misinformation and misperceptions about the use of DBS for OUD, and identify similarities and differences regarding ethical concerns when DBS is used specifically for OUD compared to other psychiatric disorders.

The Incidence of Amyotrophic Lateral Sclerosis in Ohio 2016-2018: The Ohio Population-Based ALS Registry.

INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is a fatal, neuromuscular disease with no cure. ALS incidence rates have not been assessed specifically in Ohio, yet the state contains both metropolitan and rural areas with a variety of environmental factors that could contribute to disease etiology. We report the incidence of ALS in Ohio residents diagnosed from October 2016 through September 2018. METHODS: We engaged practitioners from 9 Ohio sites to identify newly diagnosed ALS patients and to complete case report forms with demographic and clinical information. ALS was diagnosed according to the Awaji criteria and classified as either definite, probable, or possible. We developed a method to estimate missing cases using a Poisson regression model to impute cases in counties with evidence of undercounting. RESULTS: We identified 333 newly diagnosed ALS patients residing in Ohio during the 2-year index period and found incidence rates varied in the 88 state counties. After incorporating the estimated 27% of missing cases, the corrected crude annual incidence was 1.96/100,000 person-years, and the age- and gender-standardized incidence was 1.71/100,000 person-years (standardized to the 2010 US census). DISCUSSION/CONCLUSION: The estimated Ohio incidence of ALS is overall similar to that reported in other states in the USA. This study reveals a geospatial variation in incidence within the state, and areas with higher rates warrant future investigation.

Identifying aerosolized cyanobacteria in the human respiratory tract: A proposed mechanism for cyanotoxin-associated diseases.

Cyanobacteria produce harmful toxins that have been associated with several acute conditions and chronic human diseases, like gastroenteritis, non-alcoholic liver disease, and amyotrophic lateral sclerosis. Aerosol from waterbodies appears to be a likely mechanism for exposure. We conducted a study of human biospecimens focused on the cyanobacterial aerosilization process by evaluating the extent to which cyanobacteria can invade the human respiratory tract. Our study suggests that humans routinely inhale aerosolized cyanobacteria, which can be harbored in the nostrils and the lungs. Using PCR, cyanobacteria were found at high frequencies in the upper respiratory tract (92.20%) and central airway (79.31%) of our study subjects. Nasal swabs were not predictive of bronchoalveolar lavage (BAL) when detecting inhaled cyanobacteria. Interestingly, we found no evidence that time of year was a significant factor for cyanobacteria positivity (BAL cytology p = 1.0 and PCR p = 1.0); (nasal swab cytology p = 0.051 and PCR p = 0.65). Additionally, we found that proximity to a waterbody was not a significant factor for cyanobacteria positivity in BAL and nasal swabs collected during cyanobacteria bloom season [May-October] (p = 0.46 and p = 0.38). These data suggest that cyanobacteria exposure may be a prevalent and chronic phenomenon not necessarily restricted to waterbodies alone. Sources of indoor exposure warrant future investigation. Given the widespread prevalence of cyanobacterial exposure in the airway, investigation of the aerosol spread of cyanotoxins, more specifically, is warranted. Our findings are consistent with the hypothesis that aerosol is a significant route for cyanobacteria exposure, and thus a likely route of transmission for cyanotoxin-associated human diseases.

Toenail mercury Levels are associated with amyotrophic lateral sclerosis risk.

INTRODUCTION: Mercury is a neurotoxic metal that is potentially a risk factor for amyotrophic lateral sclerosis (ALS). Consumption of methylmercury contaminated fish is the primary source of US population exposure to mercury. METHODS: We used inductively coupled plasma mass spectrometry to measure levels of mercury in toenail samples from patients with ALS (n = 46) and from controls (n = 66) as a biomarker of mercury exposure. RESULTS: Patients with ALS had higher toenail mercury levels (odds ratio 2.49, 95% confidence interval 1.18-5.80, P = 0.024) compared with controls, adjusted for age and sex. We also estimated the amount of mercury consumed from finfish and shellfish and found toenail mercury levels elevated overall among patients with ALS and controls in the top quartile for consumption (P = 0.018). DISCUSSION: Biomarker data show that ALS is associated with increased with mercury levels, which were related to estimated methylmercury intake via fish. Replication of these associations in additional populations is warranted. Muscle Nerve, 2018.

The Potential Role of BMAA in Neurodegeneration.

Neurodegenerative diseases are a major public health issue throughout the world with devastating effects on patients and families. Sporadic forms of neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis are generally thought to develop as a consequence of genetic susceptibility and environmental influences. A number of environmental triggers have been identified in association with amyotrophic lateral sclerosis and Parkinson's disease. We discuss the role of ß-methylamino-L-alanine in the development of neurodegeneration and the potential importance of this neurotoxin as a risk for neurodegeneration.

Assessing Cyanobacterial Harmful Algal Blooms as Risk Factors for Amyotrophic Lateral Sclerosis.

Reoccurring seasonal cyanobacterial harmful algal blooms (CHABs) persist in many waters, and recent work has shown links between CHAB and elevated risk of amyotrophic lateral sclerosis (ALS). Quantifying the exposure levels of CHAB as a potential risk factor for ALS is complicated by human mobility, potential pathways, and data availability. In this work, we develop phycocyanin concentration (i.e., CHAB exposure) maps using satellite remote sensing across northern New England to assess relationships with ALS cases using a spatial epidemiological approach. Strategic semi-analytical regression models integrated Landsat and in situ observations to map phycocyanin concentration (PC) for all lakes greater than 8 ha (n = 4117) across the region. Then, systematic versions of a Bayesian Poisson Log-linear model were fit to assess the mapped PC as a risk factor for ALS while accounting for model uncertainty and modifiable area unit problems. The satellite remote sensing of PC had strong overall ability to map conditions (adj. R2, 0.86; RMSE, 11.92) and spatial variability across the region. PC tended to be positively associated with ALS risk with the level of significance depending on fixed model components. Meta-analysis shows that when average PC exposure is 100 µg/L, an all model average odds ratio is 1.48, meaning there is about a 48% increase in average ALS risk. This research generated the first regionally comprehensive map of PC for thousands of lakes and integrated robust spatial uncertainty. The outcomes support the hypothesis that cyanotoxins increase the risk of ALS, which helps our understanding of the etiology of ALS.

Medical history of chemotherapy or immunosuppressive drug treatment and risk of amyotrophic lateral sclerosis (ALS).

A recent population-based analysis demonstrated lower risk of the lethal degenerative neuromuscular disease, amyotrophic lateral sclerosis (ALS) associated with history of the use of 'antineoplastic agents' and 'immunosuppressants'. To see if this finding was generalizable to other ALS cohorts, we examined associations between use of these agents and ALS risk in an independent case-control study of n = 414 ALS patients and n = 361 controls in an Eastern US population. Controls were sampled from the general population and among non-neurodegenerative disease patients. A history of chemotherapy treatment was significantly associated with a decreased ALS risk (OR 0.46, 95% CI 0.22-0.89, P = 0.026). We did not observe an association between risk of ALS and immunosuppressant therapy use (OR 0.78, 95% CI 0.50-1.02, P = 0.23). Analyses were adjusted for age, gender, and smoking. Our results support the prior report for chemotherapy treatment and lead to further discussion of the underlying mechanism.

Environmental and Occupational Exposures and Amyotrophic Lateral Sclerosis in New England.

BACKGROUND: Recent data provide support for the concept that potentially modifiable exposures are responsible for sporadic amyotrophic lateral sclerosis (ALS). OBJECTIVE: To evaluate environmental and occupational exposures as risk factors for sporadic ALS. METHODS: We performed a case-control study of ALS among residents of New England, USA. The analysis compared questionnaire responses from 295 patients with a confirmed ALS diagnosis to those of 225 controls without neurodegenerative illness. RESULTS: Self-reported job- or hobby-related exposure to one or more chemicals, such as pesticides, solvents, or heavy metals, increased the risk of ALS (adjusted OR 2.51; 95% CI 1.64-3.89). Industries with a higher toxicant exposure potential (construction, manufacturing, mechanical, military, or painting) were associated with an elevated occupational risk (adjusted OR 3.95; 95% CI 2.04-8.30). We also identified increases in the risk of ALS associated with frequent participation in water sports, particularly waterskiing (adjusted OR 3.89; 95% CI 1.97-8.44). Occupation and waterskiing both retained independent statistical significance in a composite model containing age, gender, and smoking status. CONCLUSIONS: Our study contributes to a growing body of literature implicating occupational- and hobby-related toxicant exposures in ALS etiology. These epidemiologic study results also provide motivation for future evaluation of water-body-related risk factors.

A cognitive behavioral intervention (HOBSCOTCH) improves quality of life and attention in epilepsy.

OBJECTIVE: Cognitive difficulties in epilepsy are common and add to disability beyond seizures alone. A self-management intervention targeting cognitive dysfunction was developed and assessed for whether it improves quality of life, objective memory, and mood in adults with epilepsy. METHODS: The HOme Based Self-management and COgnitive Training CHanges lives (HOBSCOTCH) program was developed to incorporate (1) psychoeducation, (2) self-awareness training, (3) compensatory strategies, and (4) application of these strategies in day-to-day life using problem solving therapy. Adults aged 18-65 years with epilepsy (n=66) were randomized into 3 groups, to receive 8 weeks of HOBSCOTCH, with (H+) or without (H) additional working memory training on a commercial gaming device, or to a waitlisted control group. The primary outcome was quality of life (Quality of Life in Epilepsy scale, QOLIE-31) with secondary outcomes of objective cognition measured with the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and depression (as measured by PHQ9 and NDDIE). RESULTS: Both intervention arms showed a significant improvement in quality of life, as compared with controls who demonstrated a decline in QOLIE-31 scores. There was significant improvement in objective cognitive performance among the intervention groups, most notably in attention, compared with the waitlisted controls. There was no significant change in depression scores. SIGNIFICANCE: The HOBSCOTCH program significantly improved quality of life and appeared to be an effective intervention to address cognitive dysfunction in adults with epilepsy. Further studies are needed to assess the generalizability and cost-effectiveness of this intervention.

The Epidemiology of Amyotrophic Lateral Sclerosis in New Hampshire, USA, 2004-2007.

BACKGROUND/AIMS: Trends in disease incidence and mortality can provide clues to disease etiology. Previously, we described a town in New Hampshire (N.H.), USA, with 25 times the expected incidence rate of amyotrophic lateral sclerosis (ALS). This study aimed to describe the incidence and mortality of ALS across the state to assess rates relative to other states and industrialized nations. METHOD: A retrospective review of records from regional ALS centers, clinics and ALS organizations was conducted to obtain demographics and diagnostic details for patients diagnosed with ALS or primary lateral sclerosis in N.H. from January 2004 to December 2007. Data on mortality from review of death certificates were obtained for a similar time frame. RESULTS: We identified 113 N.H. residents diagnosed with ALS in 2004-2007, yielding an age-standardized incidence rate ranging from 1.3 to 2.2 per 100,000 of the population per year. During the same period, the standardized mortality rate per 100,000 varied from 2.6 to 3.5. ALS was more common among men (ratio 1.6:1), who were more likely than women to have an earlier age at onset (59 ± 14.2 vs. 65 ± 11.8 years, p = 0.01). CONCLUSION: While localized areas in N.H. with high ALS incidence rates have been reported previously, the overall incidence and mortality rates of ALS in N.H. are similar to those in other industrialized nations.

Design and feasibility of a memory intervention with focus on self-management for cognitive impairment in epilepsy.

The aim of this study was to assess the feasibility of a self-management intervention targeting cognitive dysfunction to improve quality of life and reduce memory-related disability in adults with epilepsy. The intervention incorporates (1) education on cognitive function in epilepsy, (2) self-awareness training, (3) compensatory strategies, and (4) application of these strategies in day-to-day life using problem-solving therapy. In addition to the behavioral modification, formal working memory training was conducted by utilizing a commercially available program in a subgroup of patients. Our findings suggest that a self-management intervention targeting cognitive dysfunction was feasible for delivery to a rural population with epilepsy, with 13 of 16 enrolled participants completing the 8-session program. Qualitative data indicate high satisfaction and subjective improvement in cognitive functioning in day-to-day life. These findings provide support for further evaluation of the efficacy of this intervention through a randomized controlled trial.

Detection of cyanotoxins, ß-N-methylamino-L-alanine and microcystins, from a lake surrounded by cases of amyotrophic lateral sclerosis.

A cluster of amyotrophic lateral sclerosis (ALS) has been previously described to border Lake Mascoma in Enfield, NH, with an incidence of ALS approximating 25 times expected. We hypothesize a possible association with cyanobacterial blooms that can produce ß-N-methylamino-L-alanine (BMAA), a neurotoxic amino acid implicated as a possible cause of ALS/PDC in Guam. Muscle, liver, and brain tissue samples from a Lake Mascoma carp, as well as filtered aerosol samples, were analyzed for microcystins (MC), free and protein-bound BMAA, and the BMAA isomers 2,4-diaminobutyric acid (DAB) and N-(2-aminoethyl)glycine (AEG). In carp brain, BMAA and DAB concentrations were 0.043 µg/g ± 0.02 SD and 0.01 µg/g ± 0.002 SD respectively. In carp liver and muscle, the BMAA concentrations were 1.28 µg/g and 1.27 µg/g respectively, and DAB was not detected. BMAA was detected in the air filters, as were the isomers DAB and AEG. These results demonstrate that a putative cause for ALS, BMAA, exists in an environment that has a documented cluster of ALS. Although cause and effect have not been demonstrated, our observations and measurements strengthen the association.

Development of a small-scale bioreactor method to monitor the molecular diversity and environmental impacts of bacterial biofilm communities from an acid mine drainage impacted creek.

Shamokin Creek is a tributary of the Susquehanna River in central Pennsylvania that is heavily impacted by the acid mine drainage (AMD) caused by the oxidation of pyrite from the region's extensive anthracite coal mining industry. Recent studies have begun to characterize the microbial communities present in this and other AMD-impacted waters, but varying environmental conditions have complicated attempts to determine the ecological impacts of individual bacterial species within these communities. This study developed a small-scale biofilm reactor protocol that allowed us to simultaneously monitor the development of bacterial biofilm communities in AMD-impacted creek collected water using terminal restriction fragment length polymorphism (T-RFLP) analysis of 16S rRNA genes, while assessing the impacts that the developing biofilms were having on water quality. Our analysis confirmed that the diversity and composition of these small in situ biofilm communities could be monitored using molecular methods, and indicated the possible presence of many taxa frequently found in AMD environments, including Sulfobacillus, Nitrospira, Desulfovibrio, Geobacter, and Leptothrix species. A significant increase in the total sulfate was observed in the bioreactor, and as most likely due to the accumulation of sulfur-oxidizing bacteria such as Sulfobacillus in the biofilms. This system will allow us to study the microbial ecology of Shamokin Creek through controlled experiments that will ultimately integrate microscopic, molecular, physiological and chemical analyses, and that can be utilized to develop more effective and cost-efficient environmental remediation techniques for AMD-impacted areas.