Gut- and oral-dysbiosis differentially impact spinal- and bulbar-onset ALS, predicting ALS severity and potentially determining the location of disease onset.

BACKGROUND: Prior studies on the role of gut-microbiome in Amyotrophic Lateral Sclerosis (ALS) pathogenesis have yielded conflicting results. We hypothesized that gut- and oral-microbiome may differentially impact two clinically-distinct ALS subtypes (spinal-onset ALS (sALS) vs. bulbar-onset ALS (bALS), driving disagreement in the field. METHODS: ALS patients diagnosed within 12 months and their spouses as healthy controls (n = 150 couples) were screened. For eligible sALS and bALS patients (n = 36) and healthy controls (n = 20), 16S rRNA next-generation sequencing was done in fecal and saliva samples after DNA extractions to examine gut- and oral-microbiome differences. Microbial translocation to blood was measured by blood lipopolysaccharide-binding protein (LBP) and 16S rDNA levels. ALS severity was assessed by Revised ALS Functional Rating Scale (ALSFRS-R). RESULTS: sALS patients manifested significant gut-dysbiosis, primarily driven by increased fecal Firmicutes/Bacteroidetes-ratio (F/B-ratio). In contrast, bALS patients displayed significant oral-dysbiosis, primarily driven by decreased oral F/B-ratio. For sALS patients, gut-dysbiosis (a shift in fecal F/B-ratio), but not oral-dysbiosis, was strongly associated with greater microbial translocation to blood (r = 0.8006, P < 0.0001) and more severe symptoms (r = 0.9470, P < 0.0001). In contrast, for bALS patients, oral-dysbiosis (a shift in oral F/B-ratio), but not gut-dysbiosis, was strongly associated with greater microbial translocation to blood (r = 0.9860, P < 0.0001) and greater disease severity (r = 0.9842, P < 0.0001). For both ALS subtypes, greater microbial translocation was associated with more severe symptoms (sALS: r = 0.7924, P < 0.0001; bALS: r = 0.7496, P = 0.0067). Importantly, both sALS and bALS patients displayed comparable oral-motor deficits with associations between oral-dysbiosis and severity of oral-motor deficits in bALS but not sALS. This suggests that oral-dysbiosis is not simply caused by oral/bulbar/respiratory symptoms but represents a pathological driver of bALS. CONCLUSIONS: We found increasing gut-dysbiosis with worsening symptoms in sALS patients and increasing oral-dysbiosis with worsening symptoms in bALS patients. Our findings support distinct microbial mechanisms underlying two ALS subtypes, which have been previously grouped together as a single disease. Our study suggests correcting gut-dysbiosis as a therapeutic strategy for sALS patients and correcting oral-dysbiosis as a therapeutic strategy for bALS patients.

Acceptance of Illness Among Patients Pursuing Transplantation or Left Ventricular Assist Device.

Acceptance of illness is related to better mental health among patients with chronic illness; however, this construct has not been evaluated as part of routine transplantation evaluations. The purpose of this study was to create a brief measure of acceptance of illness for patients pursuing organ transplantation and examine how acceptance is related to distress. Retrospective medical record reviews were conducted for 290 patients who completed a routine psychosocial evaluation prior to transplant listing which included the Illness Acceptance Scale (IAS). Internal consistency for the IAS was excellent (Cronbach's alpha = .92). Illness acceptance was negatively correlated with depression, anxiety, and catastrophizing and was not related to health literacy or health numeracy. The IAS is a reliable and valid measure for patients who are pursuing thoracic transplant or left ventricular assist device. Clinicians may want to screen transplant candidates for illness acceptance and refer those with lower levels to psychological interventions.

Predictors of Alcohol Use after Bariatric Surgery.

Patients undergoing bariatric surgery are at risk for devloping an alcohol use disorder (AUD). The purpose of this study was to investigate pre-surgical psychosocial risk factors for post-surgical alcohol consumption and hazardous drinking. Participants (N = 567) who underwent bariatric surgery between 2014 and 2017 reported their post-surgical alcohol use. Information was collected from the pre-surgical evaluation including history of alcohol use, psychiatric symptoms, and maladaptive eating behaviors (i.e., binge eating, purging, and emotional eating). Younger age and pre-surgical alcohol use predicted post-surgical alcohol use and hazardous drinking. In addition, higher levels of depressive symptoms and maladaptive eating patterns predicted post-surgical binge drinking. Clinicians conducting pre-surgical psychosocial evaluations should be aware of the multiple risk factors related to post-surgical problematic alcohol use. Future research should evaluate whether preventive interventions for high-risk patients decrease risk for post-surgical alcohol misuse.

Improved visible-blindness of AlGaN deep ultraviolet photodiode with monolithically integrated angle-insensitive Fabry-Perot filter.

Despite the rapidly increasing demand for accurate ultraviolet (UV) detection in various applications, conventional Si-based UV sensors are less accurate due to disruption by visible light. Recently, Ga(Al)N-based photodiodes have attracted great interest as viable platforms that can avoid such issues because their wide bandgap enables efficient detection of UV light and they are theoretically blind to visible and infrared light. However, the heteroepitaxy of a Ga(Al)N layer on sapphire substrates inevitably leads to defects, and the Ga(Al)N photodiode (PD) becomes not perfectly insensible to visible light. Employment of a dielectric stacked UV pass filter is possible to avoid unwanted absorption of visible light, but the angle-dependent pass band limits the detection angle. Here, we have demonstrated the Ag-Al2O3 Fabry-Perot UV pass filter-integrated AlGaN ultraviolet photodiode. The inherent optical extinction characteristics of Ag was utilized to design the fabrication-tolerant UV pass filter with a peak transmittance at ∼325 nm. As the angle of incidence increased, the peak transmission decreased from 45% to 10%, but the relative transmission spectrum remained almost unchanged. By integrating these filters, the visible light rejection ratio (responsivity for 315 nm light to responsivity for 405 nm light) was improved by a factor of 10, reaching a value of 106 at angles of up to 80 degrees.

Intimate partner violence and barriers to mental health care for ethnically diverse populations of women.

Ethnically diverse populations of women, particularly survivors of intimate partner violence (IPV), experience many barriers to mental health care. The search terms ''women'' and ''domestic violence or IPV'' and ''mental health care'' were used as a means to review the literature regarding barriers to mental health care and minority women. Abstracts chosen for further review included research studies with findings on women of one or more ethnic minority groups, potential barriers to accessing mental health care, and a nonexclusive focus on IPV. Fifty-five articles were selected for this review. Identified barriers included a variety of patient, provider, and health system/community factors. Attention to the barriers to mental health care for ethnically diverse survivors of IPV can help inform the development of more effective strategies for health care practice and policy.

Income Inequality and the Differential Effect of Adverse Childhood Experiences in US Children.

OBJECTIVE: Adverse childhood experiences (ACEs) can affect health and development across the life course. Despite a general understanding that adversity is associated with lower income, we know less about how ACEs manifest at different income levels and how these income-related patterns affect children's health and development. METHODS: Data from the 2011 to 2012 National Survey of Children's Health were used to examine the prevalence of 9 ACEs in US children, across 4 levels of household income, and in relationship to 5 parent-reported measures of child health. Bivariate analyses and multivariable logistic regression models were used to examine the associations between number of ACEs and children's health outcomes on the basis of the 4 income groups. RESULTS: When partitioned according to income strata, the proportion of children who experienced ACEs showed a steep income gradient, particularly for children who experienced ≥4 ACEs. The linear gradient across income groups was less pronounced for each specific ACE, with several ACEs (experience of divorce, drug and alcohol exposure, parental mental illness) showing high reported prevalence in all but the highest income group. Multivariate analysis showed a consistent income-related gradient for each of the health outcomes. However, higher income was not necessarily found to be a protective factor against ACEs. CONCLUSIONS: ACEs are distributed across the income ladder and not just concentrated below the poverty level. This suggests that a more comprehensive policy strategy that includes targeted as well as universal interventions is warranted.