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.

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.