Differential Impacts of Endogenous Antioxidants on Clinical Symptoms and Cognitive Function in Acute and Chronic Schizophrenia Patients.

BACKGROUND: Impaired antioxidant defense is implicated in the pathophysiology of schizophrenia, and superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH) are 3 first-line endogenous antioxidants. Various cognitive functions decline differently during the schizophrenia course. The characteristic roles of the 3 antioxidants in clinical and cognitive profiles in acute and chronic phases of schizophrenia require study. METHODS: We recruited 311 patients with schizophrenia, including 92 acutely exacerbated patients who had been off antipsychotics for at least 2 weeks and 219 chronic patients who had been stable on medication for at least 2 months. Blood SOD, CAT, and GSH levels; clinical symptoms; and 9 cognitive test scores were measured. RESULTS: Blood CAT levels were higher in the acute patients than in the chronic patients, whereas SOD and GSH levels were similar to one another. Higher CAT levels were correlated with less positive symptoms, better working memory and problem solving in the acute phase, and less negative symptoms, less general psychopathology, better global assessment of function, and better cognitive function (in speed of processing, attention, problem solving) in the chronic period. Higher SOD levels were correlated with better global assessment of function in the acute phase and better speed of processing, working memory, and verbal learning and memory in the chronic period. GSH influenced neither clinical nor cognitive manifestations. CONCLUSIONS: This study showed that blood CAT affected different clinical and cognitive domains between acute and chronic stages of schizophrenia, SOD influenced cognitive functions in chronic state, but GSH affected none. Further studies are needed to explore the underlying mechanisms.

Spontaneous Co-Assembly of Cellulose Nanocrystals and TiO2 Nanorods Followed by Calcination to Form Cholesteric Inorganic Nanostructures.

Chiral nanomaterials possess unique electronic, magnetic, and optical properties that are relevant to a wide range of applications including photocatalysis, chiral photonics, and biosensing. A simple, bottom-up method to create chiral, inorganic structures is introduced that involves the co-assembly of TiO2 nanorods with cellulose nanocrystals (CNCs) in water. To guide experimental efforts, a phase diagram was constructed to describe how phase behavior depends on the CNCs/TiO2/H2O composition. A lyotropic cholesteric mesophase was observed to extend over a wide composition range as high as 50 wt % TiO2 nanorods, far exceeding other examples of inorganic nanorods/CNCs co-assembly. Such a high loading enables the fabrication of inorganic, free-standing chiral films through removal of water and calcination. Distinct from the traditional templating method using CNCs, this new approach separates sol-gel synthesis from particle self-assembly using low-cost nanorods.

Alcohol Addiction, Gut Microbiota, and Alcoholism Treatment: A Review.

Alcohol addiction is a leading risk factor for personal death and disability. In 2016, alcohol use caused 2.2% of female deaths and 6.8% of male deaths, and disability-adjusted life years (DALYs) were 2.3% in female and 8.9% in male. Individuals with alcohol use disorder are at high risk of anxiety, depression, impaired cognition performance, and illicit drug use and are comorbid with liver disease, such as alcoholic hepatitis and liver cirrhosis, which is a major cause of personal death and disability worldwide. Psychological interventions, such as cognitive behavior therapy and motivational interviewing, as well as medical treatments, such as disulfiram, naltrexone, acamprosate, and nalmefene, are used for the treatment of alcohol addiction in Europe and the United States. However, the effect of current interventions is limited, and the need for additional interventions is substantial. Alcohol use impairs the intestinal barrier and causes changes to the intestinal permeability as well as the gut microbiota composition. Emerging studies have tried to reveal the role of the gut-brain axis among individuals with alcohol use disorder with or without alcohol liver disease. Bacterial products penetrate the impaired intestinal barrier and cause central inflammation; changes to the gut microbiota impair enterohepatic circulation of bile acids; alcohol abuse causes shortage of vital nutrients such as thiamine. Several studies have suggested that probiotics, through either oral administration or fecal microbiota transplantation, increased intestinal levels of potentially beneficial bacteria such as bifidobacteria and lactobacilli, improving the levels of liver-associated enzymes in patients with mild alcoholic hepatitis, and demonstrating beneficial psychotropic effects on anxiety and depression. In addition to medications for alcohol addiction, gene editing therapy such as clustered regularly interspaced short palindromic repeats (CRISPRs) may be another potential research target. Alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH), which are associated with ADH and ALDH genes, are major enzymes involved in alcohol metabolism, and gene editing approaches may have the potential to directly modify specific genes to treat alcoholism caused by genetic defects. Further research is needed to study the effect of the combined treatment for alcohol addiction.

DAF-16 and TCER-1 Facilitate Adaptation to Germline Loss by Restoring Lipid Homeostasis and Repressing Reproductive Physiology in C. elegans.

Elimination of the proliferating germline extends lifespan in C. elegans. This phenomenon provides a unique platform to understand how complex metazoans retain metabolic homeostasis when challenged with major physiological perturbations. Here, we demonstrate that two conserved transcription regulators essential for the longevity of germline-less adults, DAF-16/FOXO3A and TCER-1/TCERG1, concurrently enhance the expression of multiple genes involved in lipid synthesis and breakdown, and that both gene classes promote longevity. Lipidomic analyses revealed that key lipogenic processes, including de novo fatty acid synthesis, triglyceride production, desaturation and elongation, are augmented upon germline removal. Our data suggest that lipid anabolic and catabolic pathways are coordinately augmented in response to germline loss, and this metabolic shift helps preserve lipid homeostasis. DAF-16 and TCER-1 also perform essential inhibitory functions in germline-ablated animals. TCER-1 inhibits the somatic gene-expression program that facilitates reproduction and represses anti-longevity genes, whereas DAF-16 impedes ribosome biogenesis. Additionally, we discovered that TCER-1 is critical for optimal fertility in normal adults, suggesting that the protein acts as a switch supporting reproductive fitness or longevity depending on the presence or absence of the germline. Collectively, our data offer insights into how organisms adapt to changes in reproductive status, by utilizing the activating and repressive functions of transcription factors and coordinating fat production and degradation.

Correction: DAF-16 and TCER-1 Facilitate Adaptation to Germline Loss by Restoring Lipid Homeostasis and Repressing Reproductive Physiology in C. elegans.

[This corrects the article DOI: 10.1371/journal.pgen.1005788.].

Germline signals deploy NHR-49 to modulate fatty-acid ß-oxidation and desaturation in somatic tissues of C. elegans.

In C. elegans, removal of the germline extends lifespan significantly. We demonstrate that the nuclear hormone receptor, NHR-49, enables the response to this physiological change by increasing the expression of genes involved in mitochondrial ß-oxidation and fatty-acid desaturation. The coordinated augmentation of these processes is critical for germline-less animals to maintain their lipid stores and to sustain de novo fat synthesis during adulthood. Following germline ablation, NHR-49 is up-regulated in somatic cells by the conserved longevity determinants DAF-16/FOXO and TCER-1/TCERG1. Accordingly, NHR-49 overexpression in fertile animals extends their lifespan modestly. In fertile adults, nhr-49 expression is DAF-16/FOXO and TCER-1/TCERG1 independent although its depletion causes age-related lipid abnormalities. Our data provide molecular insights into how reproductive stimuli are integrated into global metabolic changes to alter the lifespan of the animal. They suggest that NHR-49 may facilitate the adaptation to loss of reproductive potential through synchronized enhancement of fatty-acid oxidation and desaturation, thus breaking down some fats ordained for reproduction and orchestrating a lipid profile conducive for somatic maintenance and longevity.

Reducing Prenatal Phthalate Exposure Through Maternal Dietary Changes: Results from a Pilot Study.

Diet is a major source of exposure to certain phthalates, a class of environmental chemicals associated with endocrine disruption in animal models and humans. Several studies have attempted to lower phthalate exposure through carefully designed dietary interventions, with inconsistent results. We conducted a dietary intervention pilot study with the objective to lower phthalate exposure in low-income pregnant women, a particularly vulnerable population. Ten pregnant women consumed a provided diet consisting of mostly fresh, organic foods for 3 days. We collected urine samples before, during, and after the intervention and conducted semi-structured interviews to assess the feasibility and acceptability of the intervention. We used repeated measures ANOVA and paired t-tests to assess differences in urinary phthalate metabolite concentrations across the study, focusing on the metabolites of di-2-ethylhexyl phthalate (DEHP), a phthalate of particular interest, and their molar sum (∑DEHP). Phthalate metabolite concentrations did not change appreciably during the intervention period. We observed no significant difference in ∑DEHP metabolite concentrations across the three time periods (F = 0.21; adjusted p value = 0.65), and no reduction during the intervention as compared to baseline (t = -1.07, adjusted p value = 0.51). Results of interviews indicated that participants were not motivated to make dietary changes to potentially reduce chemical exposures outside of the study. Despite the small sample size, our results suggest that promoting dietary changes to lower phthalate exposure may not be an effective public health measure. Reducing the use of phthalates in food processing and packaging may be a better solution to lowering exposure on a population level.

Synergistic response to oncogenic mutations defines gene class critical to cancer phenotype.

Understanding the molecular underpinnings of cancer is of critical importance to the development of targeted intervention strategies. Identification of such targets, however, is notoriously difficult and unpredictable. Malignant cell transformation requires the cooperation of a few oncogenic mutations that cause substantial reorganization of many cell features and induce complex changes in gene expression patterns. Genes critical to this multifaceted cellular phenotype have therefore only been identified after signalling pathway analysis or on an ad hoc basis. Our observations that cell transformation by cooperating oncogenic lesions depends on synergistic modulation of downstream signalling circuitry suggest that malignant transformation is a highly cooperative process, involving synergy at multiple levels of regulation, including gene expression. Here we show that a large proportion of genes controlled synergistically by loss-of-function p53 and Ras activation are critical to the malignant state of murine and human colon cells. Notably, 14 out of 24 'cooperation response genes' were found to contribute to tumour formation in gene perturbation experiments. In contrast, only 1 in 14 perturbations of the genes responding in a non-synergistic manner had a similar effect. Synergistic control of gene expression by oncogenic mutations thus emerges as an underlying key to malignancy, and provides an attractive rationale for identifying intervention targets in gene networks downstream of oncogenic gain- and loss-of-function mutations.

Changes in heart rate variability during TOVA testing in patients with major depressive disorder.

AIM: The aim of this study was to identify major depressive disorder (MDD) based on heart rate variability (HRV) during tests of variables of attention (TOVA). METHOD: Forty-five MDD patients without cardiovascular disease and 45 controls matched by age and gender participated in this study. RESULTS: Compared to the controls, the MDD group had lower resting HRV parameters, more omissions and variability and longer response times on TOVA, and failure of attention employment to decrease HRV. CONCLUSIONS: The resting HRV parameters may provide easily measured, clinically useful ways to identify patients with MDD and to monitor their progress in treatment.

A 30-Year-Old Woman with an 8-Week History of Anxiety, Depression, Insomnia, and Mild Cognitive Impairment Following COVID-19 Who Responded to Accelerated Bilateral Theta-Burst Transcranial Magnetic Stimulation Over the Prefrontal Cortex.

BACKGROUND This report is of a 30-year-old woman with an 8-week history of anxiety, depression, insomnia, and mild cognitive impairment following COVID-19 infection, who responded to accelerated bilateral theta-burst transcranial magnetic stimulation (TBS) over the prefrontal cortex. CASE REPORT A previously healthy 30-year-old woman visited our psychiatric clinic for symptoms including anxiety, depression, insomnia, and brain fog (mild cognitive impairment) for more than 8 weeks after being diagnosed with COVID-19 on May 9, 2022. Continuous TBS of the right dorsolateral prefrontal cortex (DLPFC), followed by intermittent TBS of the left DLPFC, was performed twice daily over 5 days for a total of 10 sessions. The Beck Depression Inventory (BDI), Hamilton Depression Rating Scale (HAMD), Beck Anxiety Inventory (BAI), Pittsburgh Sleep Quality Index (PSQI), and subsets of the Wechsler Memory Scale (WMS)-Third Edition were administered at baseline and at the end of treatment. After 10 sessions of treatment, her BAI, BDI, HAMD, PSQI, WMS-Logical Memory, WMS-Faces, WMS-Verbal Paired Associates, and WMS-Family Pictures scores had improved from 4, 18, 10, 14, 8, 10, 12, and 8, respectively, to 0, 7, 1, 10, 15, 15, 15, and 10, respectively. CONCLUSIONS Accelerated TBS over the bilateral DLPFC may ameliorate long-COVID-associated neuropsychiatric symptoms. Additional trials are warranted to evaluate the effect of neuropsychiatric symptoms following COVID-19.

Accelerated theta-burst transcranial magnetic stimulation of the bilateral dorsolateral prefrontal cortex in a patient with post-traumatic stress disorder and major depressive disorder: Case report.

Background: Theta-burst transcranial magnetic stimulation has demonstrated promising effectiveness as treatment for post-traumatic stress disorder (PTSD) and depression. However, the effect of accelerated theta-burst stimulation (TBS) in comorbid with PTSD and depression remains unknown. Case presentation: We report a case of a 25-year-old woman with PTSD and depression whose symptoms markedly improved after continuous TBS of the right dorsolateral prefrontal cortex (DLPFC) and intermittent TBS (iTBS) over the left DLPFC, and then with 20 min break before the 2nd iTBS session. Conclusions: Accelerated TBS over the bilateral DLPFC may improve severe PTSD and depression. Accelerated TBS may have more improvement of depression symptoms than PTSD symptoms. Further trials are warranted to investigate the effect and safety for patients with complicated PTSD and depression.

Influence of Sex Differences on Serum Lipid Profiles among Habitual Coffee Drinkers: Evidence from 23,072 Taiwan Biobank Participants.

The bioactive compounds of coffee are involved in lipid metabolism, and sex differences may play an important role. This study aimed to evaluate the influence of sex differences on serum lipid profiles among habitual coffee drinkers. We conducted a nationwide cross-sectional study of 23,628 adults using data obtained from the Taiwan Biobank database. Adults who drank more than one cup of coffee per day and those who drank less than one cup per day were compared with non-drinkers. After adjusting for baseline demographics and lifestyle, a generalized linear model was used to estimate the change in serum lipid profiles in men and women and in postmenopausal and premenopausal women among different coffee-drinking behaviors. We found that habitual coffee consumption changed the serum lipid profiles of men and women. Further, coffee drinkers had higher serum total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and lower serum triglyceride levels than non-drinkers. Compared with premenopausal women, both men and postmenopausal women had increased serum total cholesterol and low-density lipoprotein cholesterol levels. Menopausal status may play an important role in modulating the effect of habitual coffee intake on dyslipidemia. Moreover, premenopausal women potentially benefit more from habitual coffee drinking than men and postmenopausal women.

The associations between cognitive functions and TSNAX genetic variations in patients with schizophrenia.

BACKGROUND: The translin-associated factor X (TSNAX) gene, located adjacent to the DISC1 gene, has been implicated in schizophrenia. While cognitive impairment determines long-term the functional outcome of schizophrenia, the role of TSNAX in cognitive dysfunction of schizophrenia patients remains elusive. This study aimed to explore the genetic effect of TSNAX on cognitive functions of schizophrenia. METHODS: We recruited 286 chronic schizophrenia patients who had been stabilized with antipsychotics for at least 2 months and genotyped three TSNAX SNPs (rs1630250, rs766288, rs6662926). Clinical symptoms and seven cognitive domains were assessed. The score of cognitive tests was standardized to T score. RESULTS: Clinical symptoms were similar among genotypes of all the three SNPs. The GLM analysis demonstrated that TSNAX genetic polymorphisms influenced cognitive function of schizophrenia patients after adjustment for gender, age, and education. The patients with the rs1630250 C/G genotype performed better than the G/G homozygotes in the Trail Making A (p = 0.034). Those with the rs766288 G/T genotype also performed better than the G/G homozygotes in the Trail Making A (p = 0.012). The patients with the G/G genotype of rs6662926 also performed better than the C/C homozygotes in verbal learning and memory test (p = 0.044). CONCLUSIONS: This study suggests that the TSNAX gene variation may influence the cognitive functions of the patients with schizophrenia.

Sex and age disparities in the influence of tobacco smoking on depression: Evidence from the Taiwan Biobank.

INTRODUCTION: The global tobacco epidemic poses a notable challenge to global health due to its association with various tobacco-related diseases. Although tobacco smoking is associated with depression, the exact mechanism by which tobacco smoking increases the risk of depression is unclear. This study explored the potential effects of tobacco smoking on depression. METHODS: We used data in the analysis from the Taiwan Biobank of 27916 individuals recruited from 2015 to 2020. To investigate the associations between tobacco use and depression, the results of the depression-measuring subscale of the Patient Health Questionnaire-4 as well as data on participants' tobacco consumption and other relevant covariates, were analyzed. RESULTS: Participants who smoked were more likely to report depression than those who did not smoke (AOR=1.50; 95% CI: 1.21-1.86). Furthermore, depression was significantly higher in women who smoked than in their male counterparts (females: AOR=1.68; 95% CI: 1.27-2.23, and males: AOR=1.32; 95% CI: 0.96-1.80). Women aged <55 years and who smoked were more likely to report depression, whereas this trend was not observed in those aged ≥55 years (<55 years: AOR=1.75; 95% CI: 1.23-2.48), and ≥55 years: AOR=1.58; 95% CI: 0.97-2.56). CONCLUSIONS: Tobacco smoking is a significant factor associated with depression, particularly in younger women. The increasing prevalence of tobacco use for years among younger women in Taiwan might contribute to shifts in the associations between depression and tobacco use in women.

Prevalence of autoimmune diseases in in-patients with schizophrenia: nationwide population-based study.

BACKGROUND: The association between autoimmune diseases and schizophrenia has rarely been systematically investigated. AIMS: To investigate the association between schizophrenia and a variety of autoimmune diseases and to explore possible gender variation in any such association. METHOD: Taiwan's National Health Insurance Research Database was used to identify 10 811 hospital in-patients with schizophrenia and 108 110 age-matched controls. Univariate and multiple logistic regression analyses were performed, separately, to evaluate the association between autoimmune diseases and schizophrenia. We applied the false discovery rate to correct for multiple testing. RESULTS: When compared with the control group, the in-patients with schizophrenia had an increased risk of Graves' disease (odds ratio (OR) = 1.32, 95% CI 1.04-1.67), psoriasis (OR = 1.48, 95% CI 1.07-2.04), pernicious anaemia (OR = 1.71, 95% CI 1.04-2.80), celiac disease (OR = 2.43, 95% CI 1.12-5.27) and hypersensitivity vasculitis (OR = 5.00, 95% CI 1.64-15.26), whereas a reverse association with rheumatoid arthritis (OR = 0.52, 95% CI 0.35-0.76) was also observed. Gender-specific variation was found for Sjögren syndrome, hereditary haemolytic anaemia, myasthenia gravis, polymyalgia rheumatica and dermatomyositis. CONCLUSIONS: Schizophrenia was associated with a greater variety of autoimmune diseases than was anticipated. Further investigation is needed to gain a better understanding of the aetiology of schizophrenia and autoimmune diseases.

The effectiveness and safety of adjunctive aripiprazole in Taiwanese patients with antidepressant-refractory major depressive disorder: a prospective, open-label trial.

There is currently no published clinical trial on the safety and effectiveness of aripiprazole in Taiwanese patients with treatment-refractory major depressive disorder. We were interested in determining the applicability of current recommended doses of aripiprazole as an adjunct to antidepressant therapy in this population. We conducted a prospective, open-label nonrandomized, 4-week flexibly dosed (2.5-5 mg/d) trial with aripiprazole augmentation in 9 Taiwanese patients who had a history of nonresponse to at least 2 adequate courses of antidepressant therapy with different types of antidepressants. The primary end point for clinical effectiveness was mean change in the 17-item Hamilton Rating Scale for Depression at the end of the 4-week trial. Secondary end points for clinical effectiveness included mean change in Beck Depression Inventory and Beck Anxiety Inventory scores. The Systematic Assessment of Treatment Emergent Events-General Inquiry was used to assess adverse effects. All patients completed the trial and responded to treatment; the remission rate was 77.8%. The mean daily dose of adjunctive aripiprazole was 4.2 mg. Common treatment-emergent adverse events included insomnia and sedation (33.3%) and akathisia (22.2%). We found high effectiveness despite a lower mean daily dose of adjunctive aripiprazole (4.2 mg) when compared with previously reported findings; however, we also observed a higher frequency of treatment-emergent adverse effects. Additional studies are required to ascertain whether there are ethnic differences in the pharmacokinetics and/or pharmacodynamics of aripiprazole in treatment-refractory depression.

The Relationship between Habitual Coffee Drinking and the Prevalence of Metabolic Syndrome in Taiwanese Adults: Evidence from the Taiwan Biobank Database.

Previous studies revealed inconsistent results between coffee drinking and metabolic syndrome (MetS). The aim of the study was to evaluate the relationship between habitual coffee drinking and the prevalence of MetS among men and women. We conducted a nationwide, cross-sectional study using 23,073 adults obtained from the Taiwan Biobank database (mean ± SD (range) age, 54.57 ± 0.07 (30-79) years; 8341 men and 14,731 (63.8%) women). Adults who drank more than one cup of coffee per day (n = 5118) and those who drank less than one cup per day (n = 4515) were compared with nondrinkers (n = 13,439). Multivariate logistic regression models were used to evaluate the risk of MetS between the two groups. Separate models were also estimated for sex-stratified and habitual coffee-type-stratified (black coffee (BC), coffee with creamer (CC), and coffee with milk (CM)) subgroup analyses. The MetS diagnosis was based on at least three of the five metabolic abnormalities. Coffee drinkers (≥1 cup/day) had a significantly lower prevalence of MetS than nondrinkers (AOR (95% CI): 0.80 (0.73-0.87)). Women who drank any amount of coffee and any type of coffee were more likely to have a significantly lower prevalence of MetS than nondrinkers. Only men who drank more than one cup of coffee per day or black coffee drinkers were more likely to have a lower prevalence of MetS. Our study results indicate that adults with habitual coffee drinking behaviors of more than one cup per day were associated with a lower prevalence of MetS. Moreover, women could benefit from habitual coffee drinking of all three coffee types, whereas men could only benefit from drinking BC.

Efficacy of Repetitive Transcranial Magnetic Stimulation in Patients With Methamphetamine Use Disorder: A Systematic Review and Meta-Analysis of Double-Blind Randomized Controlled Trials.

Background: Repetitive transcranial magnetic stimulation (rTMS) has demonstrated therapeutic potential for treating patients with methamphetamine use disorder (MUD). However, the most effective target and stimulation frequency of rTMS for treating MUD remains unclear. This meta-analysis explored the effect of rTMS on MUD. Methods: In this study, PubMed, Cochrane Systematic Reviews, and the Cochrane Collaboration Central Register of Controlled Clinical Trials were searched electronically for double-blind randomized controlled trials that used rTMS for treating MUD. We used published trials to investigate the efficacy of rTMS in MUD up to March 5, 2022, and pooled studies using a random-effect model to compare rTMS treatment effects. Patients who were diagnosed with MUD according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders were recruited. Clinical craving scores between baseline and after rTMS were compared using the standardized mean difference (SMD) with 95% confidence intervals (CIs). The heterogeneity of the included trials was evaluated through a visual inspection of funnel plots and the I2 statistic. Results: We identified seven trials with 462 participants with MUD that met the inclusion criteria. All the studies evaluated craving scores, with rTMS demonstrating a more significant effect than the sham treatment on reducing craving scores (SMD = 0.983, CI = 0.620-1.345, p ≤ 0.001). A subgroup meta-analysis revealed that intermittent theta-burst stimulation (iTBS) had a greater positive effect than 10-Hz rTMS. A metaregression revealed that the SMDs increased with the increase in baseline craving scores, whereas they decreased with the increase in the proportion of men and duration of abstinence. Conclusion: The meta-analysis suggests that rTMS may be associated with treatment effect on craving symptoms in patients with MUD. iTBS may have a greater positive effect on craving reduction than 10-z rTMS.

A CMOS ASIC Design for SiPM Arrays.

Our lab has previously reported on novel board-level readout electronics for an 8×8 silicon photomultiplier (SiPM) array featuring row/column summation technique to reduce the hardware requirements for signal processing. We are taking the next step by implementing a monolithic CMOS chip which is based on the row-column architecture. In addition, this paper explores the option of using diagonal summation as well as calibration to compensate for temperature and process variations. Further description of a timing pickoff signal which aligns all of the positioning (spatial channels) pulses in the array is described. The ASIC design is targeted to be scalable with the detector size and flexible to accommodate detectors from different vendors. This paper focuses on circuit implementation issues associated with the design of the ASIC to interface our Phase II MiCES FPGA board with a SiPM array. Moreover, a discussion is provided for strategies to eventually integrate all the analog and mixed-signal electronics with the SiPM, on either a single-silicon substrate or multi-chip module (MCM).

Defining Environmental Health Literacy.

"Environmental Health Literacy" (EHL) is embraced as important for improving public health by preventing disability and disease from our environment. This study aimed to determine knowledge and skill items identified by Environmental Health (EH) professionals as being associated with EHL and to understand how these items rank by importance. Such a coordinated effort to tease out skills and knowledge needed for EHL had not previously been made. We utilized a mixed-methods approach of semi-structured interviews of 24 EH professionals and a quantitative survey with 275 EH professionals across the United States. Interviews identified 37 skill and 69 knowledge items, which were used to create the survey questions. Survey results indicate 32 knowledge items and six skill items considered essential by >50% of respondents where consensus was reached between professional groups (chi square test: p > 0.05). We further identified six knowledge items, which >70% of EH professionals agreed were essential for EHL. The identification of these knowledge and skill items sets the stage for further research that includes exploring agreement with more diverse stakeholders, developing comprehensive measures of EHL and evaluation of methods and materials designed to improve EHL.