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The excessive growth of harmful cyanobacteria, including Dolichospermum (formerly known as Anabaena), in freshwater bodies has become a pressing global concern. However, detailed information about the role of Dolichospermum in shaping bloom dynamics and producing cyanotoxins is limited. In this study, a bloom event dominated by Dolichospermum spp. at Detroit Lake (Oregon, USA) was examined from 2019 to 2021. In 2019, early summer cyanobacterial community succession reached up to 8.7 % of total phytoplankton abundance. Dolichospermum was the major microcystin (MC)-producing genus, with peak MC levels of 7.34 μg L -1 . The presence of MCs was strongly correlated with the abundance of Dolichospermum (r = 0.84, p < 0.05) and MC synthetase gene, mcyE-Ana (r = 0.63, p < 0.05). Metabolic analyses further showed that the presence of nif/pst genes linked to nitrogen and phosphorus metabolism was dominated by Dolichospermum from the bloom onset until September. In addition, the abundance of Dolichospermum was significantly correlated with the abundance of nitrogen-fixing nif-Ana gene (r = 0.62, p < 0.05). As the lake experienced a longer N and P scarcity period (May to September), the N 2 -fixing Dolichospermum was able to dominate over other non-fixing cyanobacteria present, including Microcystis and Planktothrix. Overall, our results facilitate a better understanding of the organism and will help working toward managing/predicting future blooms., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025. Published by Elsevier B.V.) more...

Harmful algal blooms caused by cyanobacteria threaten aquatic ecosystems, the economy, and human health. Previous work has tried to identify the mechanisms that allow blooms to form, focusing on the role of nutrients. However, little is known about how introduced nutrients influence gene expression in situ . To address this knowledge gap, we used in situ mesocosms initiated with water experiencing a Microcystis bloom. We added pulses of nutrients that are commonly associated with anthropogenic sources to the mesocosms for 72 hours and collected samples for metatranscriptomics to examine how the physiological function of Microcystis and bloom status changed. The addition of nitrogen (N) as urea, but not the addition of PO 4 , resulted in conspicuous bloom persistence for at least 9 days after the final introduction of nutrients. The addition of urea initially resulted in the upregulation of photosynthesis machinery, as well as phosphate, carbon, and N transport and metabolism. Once Microcystis presumably became N-replete, upregulation of amino acid metabolism, microcystin biosynthesis, and other processes associated with biomass generation occurred. These capacities coincided with the upregulation of toxin-antitoxin systems, CRISPR- cas genes, and transposases suggesting that phage defense and genome rearrangement are critical in bloom persistence. Overall, our results show the stepwise transcriptional response of a Microcystis bloom to the introduction of nutrients, specifically urea, as it is sustained in a natural setting. The transcriptomic shifts observed herein may serve as markers of the longevity of blooms while providing insight into why Microcystis blooms over other cyanobacteria.IMPORTANCEHarmful algal blooms represent a threat to human health and ecosystems. Understanding why blooms persist may help us develop warning indicators of bloom persistence and create novel mitigation strategies. Using mesocosm experiments initiated with water with an active bloom, we measured the stepwise transcription changes of the toxin-producing cyanobacterium Microcystis in response to the addition of nutrients that are important in causing blooms. We found that nitrogen (N), but not phosphorus, promoted bloom longevity. The initial introduction of N resulted in the upregulation of genes involved in photosynthesis and N import. At later times in the bloom, upregulation of genes involved in biomass generation, phage protection, genomic rearrangement, and toxin production was observed. Our results suggest that Microcystis first fulfills nutritional requirements before investing energy in pathways associated with growth and protection against competitors, which allowed bloom persistence more than a week after the final addition of nutrients. more...

The occurrence of cyanobacterial harmful algal blooms (cyanoHABs) is related to their physical and chemical environment. However, less is known about their associated microbial interactions and processes. In this study, cyanoHABs were analyzed as a microbial ecosystem, using 1 year of 16S rRNA sequencing and 70 metagenomes collected during the bloom season from Lake Okeechobee (Florida, USA). Biogeographical patterns observed in microbial community composition and function reflected ecological zones distinct in their physical and chemical parameters that resulted in bloom "hotspots" near major lake inflows. Changes in relative abundances of taxa within multiple phyla followed increasing bloom severity. Functional pathways that correlated with increasing bloom severity encoded organic nitrogen and phosphorus utilization, storage of nutrients, exchange of genetic material, phage defense, and protection against oxidative stress, suggesting that microbial interactions may promote cyanoHAB resilience. Cyanobacterial communities were highly diverse, with picocyanobacteria ubiquitous and oftentimes most abundant, especially in the absence of blooms. The identification of novel bloom-forming cyanobacteria and genomic comparisons indicated a functionally diverse cyanobacterial community with differences in its capability to store nitrogen using cyanophycin and to defend against phage using CRISPR and restriction-modification systems. Considering blooms in the context of a microbial ecosystem and their interactions in nature, physiologies and interactions supporting the proliferation and stability of cyanoHABs are proposed, including a role for phage infection of picocyanobacteria. This study displayed the power of "-omics" to reveal important biological processes that could support the effective management and prediction of cyanoHABs., Importance: Cyanobacterial harmful algal blooms pose a significant threat to aquatic ecosystems and human health. Although physical and chemical conditions in aquatic systems that facilitate bloom development are well studied, there are fundamental gaps in the biological understanding of the microbial ecosystem that makes a cyanobacterial bloom. High-throughput sequencing was used to determine the drivers of cyanobacteria blooms in nature. Multiple functions and interactions important to consider in cyanobacterial bloom ecology were identified. The microbial biodiversity of blooms revealed microbial functions, genomic characteristics, and interactions between cyanobacterial populations that could be involved in bloom stability and more coherently define cyanobacteria blooms. Our results highlight the importance of considering cyanobacterial blooms as a microbial ecosystem to predict, prevent, and mitigate them., Competing Interests: The authors declare no conflict of interest. more...

Cystic fibrosis (CF) is caused by mutations in the CF transmembrane conductance regulator (CFTR) gene, with F508del being the most prevalent mutation. The combination of CFTR modulators (potentiator and correctors) has provided benefit to CF patients carrying the F508del mutation; however, the safety and effectiveness of in utero combination modulator therapy remains unclear. We created a F508del ferret model to test whether ivacaftor/lumacaftor (VX-770/VX-809) therapy can rescue in utero and postnatal pathologies associated with CF. Using primary intestinal organoids and air-liquid interface cultures of airway epithelia, we demonstrate that the F508del mutation in ferret CFTR results in a severe folding and trafficking defect, which can be partially restored by treatment with CFTR modulators. In utero treatment of pregnant jills with ivacaftor/lumacaftor prevented meconium ileus at birth in F508del kits and sustained postnatal treatment of CF offspring improved survival and partially protected from pancreatic insufficiency. Withdrawal of ivacaftor/lumacaftor treatment from juvenile CF ferrets reestablished pancreatic and lung diseases, with altered pulmonary mechanics. These findings suggest that in utero intervention with a combination of CFTR modulators may provide therapeutic benefits to individuals with F508del. This CFTR-F508del ferret model may be useful for testing therapies using clinically translatable endpoints. more...

Speciation leads to adaptive changes in organ cellular physiology and creates challenges for studying rare cell-type functions that diverge between humans and mice. Rare cystic fibrosis transmembrane conductance regulator (CFTR)-rich pulmonary ionocytes exist throughout the cartilaginous airways of humans 1,2 , but limited presence and divergent biology in the proximal trachea of mice has prevented the use of traditional transgenic models to elucidate ionocyte functions in the airway. Here we describe the creation and use of conditional genetic ferret models to dissect pulmonary ionocyte biology and function by enabling ionocyte lineage tracing (FOXI1-Cre ERT2 ::ROSA-TG), ionocyte ablation (FOXI1-KO) and ionocyte-specific deletion of CFTR (FOXI1-Cre ERT2 ::CFTR L/L ). By comparing these models with cystic fibrosis ferrets 3,4 , we demonstrate that ionocytes control airway surface liquid absorption, secretion, pH and mucus viscosity-leading to reduced airway surface liquid volume and impaired mucociliary clearance in cystic fibrosis, FOXI1-KO and FOXI1-Cre ERT2 ::CFTR L/L ferrets. These processes are regulated by CFTR-dependent ionocyte transport of Cl - and HCO 3 - . Single-cell transcriptomics and in vivo lineage tracing revealed three subtypes of pulmonary ionocytes and a FOXI1-lineage common rare cell progenitor for ionocytes, tuft cells and neuroendocrine cells during airway development. Thus, rare pulmonary ionocytes perform critical CFTR-dependent functions in the proximal airway that are hallmark features of cystic fibrosis airway disease. These studies provide a road map for using conditional genetics in the first non-rodent mammal to address gene function, cell biology and disease processes that have greater evolutionary conservation between humans and ferrets., (© 2023. The Author(s).) more...

Alpha-1 antitrypsin deficiency (AATD) is the most common genetic cause and risk factor for chronic obstructive pulmonary disease, but the field lacks a large-animal model that allows for longitudinal assessment of pulmonary function. We hypothesized that ferrets would model human AATD-related lung and hepatic disease. AAT-knockout (AAT-KO) and PiZZ (E342K, the most common mutation in humans) ferrets were generated and compared with matched controls using custom-designed flexiVent modules to perform pulmonary function tests, quantitative computed tomography (QCT), bronchoalveolar lavage (BAL) proteomics, and alveolar morphometry. Complete loss of AAT (AAT-KO) led to increased pulmonary compliance and expiratory airflow limitation, consistent with obstructive lung disease. QCT and morphometry confirmed emphysema and airspace enlargement, respectively. Pathway analysis of BAL proteomics data revealed inflammatory lung disease and impaired cellular migration. The PiZ mutation resulted in altered AAT protein folding in the liver, hepatic injury, and reduced plasma concentrations of AAT, and PiZZ ferrets developed obstructive lung disease. In summary, AAT-KO and PiZZ ferrets model the progressive obstructive pulmonary disease seen in AAT-deficient patients and may serve as a platform for preclinical testing of therapeutics including gene therapy. more...

We report the first complete genome of Microcystis aeruginosa from North America. A harmful bloom that occurred in the Caloosahatchee River in 2018 led to a state of emergency declaration in Florida. Although strain FD4 was isolated from this toxic bloom, the genome did not have a microcystin biosynthetic gene cluster., (Copyright © 2020 Urakawa et al.) more...

Cystic fibrosis (CF) is characterized by increased mucus viscosity and delayed mucociliary clearance that contributes to progressive decline of lung function. Mucus in the respiratory and GI tract is excessively adhesive in the presence of airway dehydration and excess extracellular Ca2+ upon mucin release, promoting hyperviscous, densely packed mucins characteristic of CF. Therapies that target mucins directly through ionic interactions remain unexploited. Here we show that poly (acetyl, arginyl) glucosamine (PAAG), a polycationic biopolymer suitable for human use, interacts directly with mucins in a Ca2+-sensitive manner to reduce CF mucus viscoelasticity and improve its transport. Notably, PAAG induced a linear structure of purified MUC5B and altered its sedimentation profile and viscosity, indicative of proper mucin expansion. In vivo, PAAG nebulization improved mucociliary transport in CF rats with delayed mucus clearance, and cleared mucus plugging in CF ferrets. This study demonstrates the potential use of a synthetic glycopolymer PAAG as a molecular agent that could benefit patients with a broad array of mucus diseases. more...

Cystic fibrosis (CF) is a multiorgan disease caused by mutations in the cystic fibrosis transmembrane conductance regulator ( CFTR ). In patients with CF, abnormalities initiate in several organs before birth. However, the long-term impact of these in utero pathologies on disease pathophysiology is unclear. To address this issue, we generated ferrets harboring a VX-770 (ivacaftor)-responsive CFTR G551D mutation. In utero VX-770 administration provided partial protection from developmental pathologies in the pancreas, intestine, and male reproductive tract. Homozygous CFTR G551D/G551D animals showed the greatest VX-770-mediated protection from these pathologies. Sustained postnatal VX-770 administration led to improved pancreatic exocrine function, glucose tolerance, growth and survival, and to reduced mucus accumulation and bacterial infections in the lung. VX-770 withdrawal at any age reestablished disease, with the most rapid onset of morbidity occurring when withdrawal was initiated during the first 2 weeks after birth. The results suggest that CFTR is important for establishing organ function early in life. Moreover, this ferret model provides proof of concept for in utero pharmacologic correction of genetic disease and offers opportunities for understanding CF pathogenesis and improving treatment., (Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.) more...

Lake Okeechobee, FL, USA, has been subjected to intensifying cyanobacterial blooms that can spread to the adjacent St. Lucie River and Estuary via natural and anthropogenically-induced flooding events. In July 2016, a large, toxic cyanobacterial bloom occurred in Lake Okeechobee and throughout the St. Lucie River and Estuary, leading Florida to declare a state of emergency. This study reports on measurements and nutrient amendment experiments performed in this freshwater-estuarine ecosystem (salinity 0-25 PSU) during and after the bloom. In July, all sites along the bloom exhibited dissolved inorganic nitrogen-to-phosphorus ratios < 6, while Microcystis dominated (> 95%) phytoplankton inventories from the lake to the central part of the estuary. Chlorophyll a and microcystin concentrations peaked (100 and 34 μg L-1, respectively) within Lake Okeechobee and decreased eastwards. Metagenomic analyses indicated that genes associated with the production of microcystin (mcyE) and the algal neurotoxin saxitoxin (sxtA) originated from Microcystis and multiple diazotrophic genera, respectively. There were highly significant correlations between levels of total nitrogen, microcystin, and microcystin synthesis gene abundance across all surveyed sites (p < 0.001), suggesting high levels of nitrogen supported the production of microcystin during this event. Consistent with this, experiments performed with low salinity water from the St. Lucie River during the event indicated that algal biomass was nitrogen-limited. In the fall, densities of Microcystis and concentrations of microcystin were significantly lower, green algae co-dominated with cyanobacteria, and multiple algal groups displayed nitrogen-limitation. These results indicate that monitoring and regulatory strategies in Lake Okeechobee and the St. Lucie River and Estuary should consider managing loads of nitrogen to control future algal and microcystin-producing cyanobacterial blooms., Competing Interests: The authors have declared that no competing interests exist. more...

Rationale: Classical interpretation of cystic fibrosis (CF) lung disease pathogenesis suggests that infection initiates disease progression, leading to an exuberant inflammatory response, excessive mucus, and ultimately bronchiectasis. Although symptomatic antibiotic treatment controls lung infections early in disease, lifelong bacterial residence typically ensues. Processes that control the establishment of persistent bacteria in the CF lung, and the contribution of noninfectious components to disease pathogenesis, are poorly understood., Objectives: To evaluate whether continuous antibiotic therapy protects the CF lung from disease using a ferret model that rapidly acquires lethal bacterial lung infections in the absence of antibiotics., Methods: CFTR (cystic fibrosis transmembrane conductance regulator)-knockout ferrets were treated with three antibiotics from birth to several years of age and lung disease was followed by quantitative computed tomography, BAL, and histopathology. Lung disease was compared with CFTR-knockout ferrets treated symptomatically with antibiotics., Measurements and Main Results: Bronchiectasis was quantified from computed tomography images. BAL was evaluated for cellular differential and features of inflammatory cellular activation, bacteria, fungi, and quantitative proteomics. Semiquantitative histopathology was compared across experimental groups. We demonstrate that lifelong antibiotics can protect the CF ferret lung from infections for several years. Surprisingly, CF animals still developed hallmarks of structural bronchiectasis, neutrophil-mediated inflammation, and mucus accumulation, despite the lack of infection. Quantitative proteomics of BAL from CF and non-CF pairs demonstrated a mucoinflammatory signature in the CF lung dominated by Muc5B and neutrophil chemoattractants and products., Conclusions: These findings implicate mucoinflammatory processes in the CF lung as pathogenic in the absence of clinically apparent bacterial and fungal infections. more...

The cystic fibrosis (CF) field is the beneficiary of five species of animal models that lack functional cystic fibrosis transmembrane conductance regulator (CFTR) channel. These models are rapidly informing mechanisms of disease pathogenesis and CFTR function regardless of how faithfully a given organ reproduces the human CF phenotype. New approaches of genetic engineering with RNA-guided nucleases are rapidly expanding both the potential types of models available and the approaches to correct the CFTR defect. The application of new CRISPR/Cas9 genome editing techniques are similarly increasing capabilities for in vitro modeling of CFTR functions in cell lines and primary cells using air-liquid interface cultures and organoids. Gene editing of CFTR mutations in somatic stem cells and induced pluripotent stem cells is also transforming gene therapy approaches for CF. This short review evaluates several areas that are key to building animal and cell systems capable of modeling CF disease and testing potential treatments., (Copyright © 2017 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.) more...

Objectives: The aims of this naturalistic study are to examine psychiatric rehospitalization rates in geriatric compared to nongeriatric patients who receive electroconvulsive therapy (ECT) and to characterize the sustained effectiveness of ECT for treatment of depression., Methods: Retrospective review of electronic medical records at a tertiary care center for patients with major depressive disorder who received an acute course of ECT at an index psychiatric hospitalization over a 5-year period. Data for subsequent psychiatric and primary care encounters were ascertained by chart review. Outcomes of interest included between-group differences in rates of psychiatric rehospitalization, time to rehospitalization, rates of other types of clinical follow-up care, and effect of demographic variables on clinical outcome., Results: Of 482 total patients, there were 210 (44%) geriatric patients (≥65 years). These patients experienced lower overall rates of psychiatric rehospitalization after ECT (6.2% vs 22%; P < 0.0001) compared to the nongeriatric group. Cox proportional hazard models indicated that older age, assessed both as a dichotomous and continuous variable, was associated with lower risk of rehospitalization. The majority (76.9%) of detected rehospitalizations among geriatric patients occurred within 6 months. In comparison, rates of outpatient primary care and psychiatric follow-up after ECT did not differ as a function of age., Conclusions: Our findings suggest that geriatric patients with major depression receive greater long-term benefit from an acute course of ECT than do nongeriatric patients. Much more research is needed on this topic to rigorously evaluate the long-term efficacy of ECT in geriatric populations. more...

Introduction: Patients with borderline personality disorder (BPD) often struggle with treatment-resistant depression. To date, few studies have specifically assessed the rate of improvement of depressive symptoms during an acute inpatient hospitalization in patients who screen positive for BPD compared with those who do not., Methods: A sample of 245 psychiatric inpatients was divided into 2 groups on the basis of whether or not they tested positive on the McLean Screening Instrument for Borderline Personality Disorder (MSI-BPD). Hamilton Depression Rating Scale (Ham-D) scores were compared from admission to discharge., Results: At admission, the MSI-BPD group (n=64) endorsed significantly more depressive symptoms than the MSI-BPD group (n=181), as measured by higher mean Ham-D scores (34.1 vs. 30.3, P=0.0002). Although both groups demonstrated improvements in Ham-D scores by discharge, the MSI-BPD group showed a markedly more robust change (22.1 vs. 18.2, P=0.002). This effect remained significant using a propensity score model to account for differences in baseline characteristics between the 2 groups (22.1 vs. 18.8, P=0.022)., Conclusions: These findings suggest that patients who test positive on this BPD screening tool tend to be admitted in greater distress and to subsequently improve more robustly in the setting of an inpatient hospitalization. This finding lends support to the theory that the depressive symptoms associated with borderline personality pathology emerge in the context of interpersonal hypersensitivity and relationship instability and therefore that the holding environment of the hospital can result in rapid improvement. more...

Objective: Within a practice-based collaborative care program for depression, we examined associations between positive baseline screens for comorbid mental and behavioral health problems, depression remission and utilization after 1 year., Methods: This observational study of 1507 depressed adults examined baseline screens for hazardous drinking (Alcohol Use Disorders Identification Test score ≥ 8), severe anxiety (Generalized Anxiety Disorder 7-item score ≥ 15) and bipolar disorder [Mood Disorders Questionnaire (MDQ) positive screen]; 6-month depression remission; primary care, psychiatric, emergency department (ED) and inpatient visits 1 year postbaseline; and multiple covariates. Analyses included logistic and zero-inflated negative binomial regression., Results: At unadjusted baseline, 60.7% had no positive screens beyond depression, 31.5% had one (mostly severe anxiety), 6.6% had two and 1.2% had all three. In multivariate models, positive screens reduced odds of remission versus no positive screens [e.g., one screen odds ratio (OR) = 0.608, p = .000; all three OR = 0.152, p = .018]. Screening positive for severe anxiety predicted more postbaseline visits of all types; severe anxiety plus hazardous drinking predicted greater primary care, ED and inpatient; severe anxiety plus MDQ and the combination of all three positive screens both predicted greater psychiatric visits (all p < .05). Regression-adjusted utilization patterns varied across combinations of positive screens., Conclusions: Positive screens predicted lower remission. Severe anxiety and its combinations with other positive screens were common and generally predicted greater utilization. Practices may benefit from assessing collaborative care patients presenting with these screening patterns to determine resource allocation., (Copyright © 2014 Elsevier Inc. All rights reserved.) more...

Youth with bipolar disorder (BD) and those with severe, non-episodic irritability (severe mood dysregulation, SMD) show face-emotion labeling deficits. These groups differ from healthy volunteers (HV) in neural responses to emotional faces. It is unknown whether awareness is required to elicit these differences. We compared activation in BD (N=20), SMD (N=18), and HV (N=22) during "Aware" and "Non-aware" priming of shapes by emotional faces. Subjects rated how much they liked the shape. In aware, a face (angry, fearful, happy, neutral, blank oval) appeared (187 ms) before the shape. In non-aware, a face appeared (17 ms), followed by a mask (170 ms), and shape. A Diagnosis-by-Awareness-by-Emotion ANOVA was not significant. There were significant Diagnosis-by-Awareness interactions in occipital regions. BD and SMD showed increased activity for non-aware vs. aware; HV showed the reverse pattern. When subjects viewed angry or neutral faces, there were Emotion-by-Diagnosis interactions in face-emotion processing regions, including the L precentral gyrus, R posterior cingulate, R superior temporal gyrus, R middle occipital gyrus, and L medial frontal gyrus. Regardless of awareness, BD and SMD differ in activation patterns from HV and each other in multiple brain regions, suggesting that BD and SMD are distinct developmental mood disorders., (Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.) more...

Background: Children with bipolar disorder (BD) or severe mood dysregulation (SMD) show behavioural and neural deficits during facial emotion processing. In those with other psychiatric disorders, such deficits have been associated with reduced attention to eye regions while looking at faces., Methods: We examined gaze fixation patterns during a facial emotion labelling task among children with pediatric BD and SMD and among healthy controls. Participants viewed facial expressions with varying emotions (anger, fear, sadness, happiness, neutral) and emotional levels (60%, 80%, 100%) and labelled emotional expressions., Results: Our study included 22 children with BD, 28 with SMD and 22 controls. Across all facial emotions, children with BD and SMD made more labelling errors than controls. Compared with controls, children with BD spent less time looking at eyes and made fewer eye fixations across emotional expressions. Gaze patterns in children with SMD tended to fall between those of children with BD and controls, although they did not differ significantly from either of these groups on most measures. Decreased fixations to eyes correlated with lower labelling accuracy in children with BD, but not in those with SMD or in controls., Limitations: Most children with BD were medicated, which precluded our ability to evaluate medication effects on gaze patterns., Conclusion: Facial emotion labelling deficits in children with BD are associated with impaired attention to eyes. Future research should examine whether impaired attention to eyes is associated with neural dysfunction. Eye gaze deficits in children with BD during facial emotion labelling may also have treatment implications. Finally, children with SMD exhibited decreased attention to eyes to a lesser extent than those with BD, and these equivocal findings are worthy of further study. more...

Background: The role of the promoter polymorphism (5HTTLPR) of the serotonin transporter gene (SLC6A4) in psychiatric illnesses has been studied extensively. Serotonergic function also regulates many central nervous system, including appetite and feeding behaviors. The 5HTTLPR short allele was found to be associated with increased body mass index and obesity risk among the general population. No data is available to support generalizability of such association among psychiatric population., Methods: We examined the relationship between BMI and the 5HTTLPR genotype in a large sample of 1831 psychiatric patients at Mayo Clinic, Rochester, Minnesota, using a retrospective chart review., Results: Average BMI among groups with the short/short (28.29 ± 7.27 kg/m(2)), the short/long (28.07 ± 6.45 kg/m(2)) and the long/long (28.15 ± 7.51 kg/m(2)) genotypes of 5HTTLPR were not statistically different. This negative association persisted even with the sub-analysis of the Caucasians. However, we observed an increased rate of obesity among our psychiatric patient sample compared to the general population of Minnesota (36.6% versus 27.6%, p=0.0001 for males, 30.3% versus 24.4%, p=0.0001 for females). Also, sub-analysis showed female inpatients to have a significantly higher average BMI than outpatients (28.64 ± 8.08 kg/m(2) versus 27.13 ± 6.92 kg/m(2), p=0.026). This confirmed a significant association between mental health disorder and BMI., Limitations: Retrospective study design with limited control for potential confounders., Conclusions: In this large sample of psychiatric patients we found no significant association between 5HTTLPR genotype and BMI, which is different from the case with general population reported in the literature., (Published by Elsevier B.V.) more...

There is a broad scientific consensus that amyotrophic lateral sclerosis (ALS) is caused by gene-environment interactions. Mutations in genes underlying familial ALS (fALS) have been discovered in only 5-10% of the total population of ALS patients. Relatively little attention has been paid to environmental and lifestyle factors that may trigger the cascade of motor neuron death leading to the syndrome of ALS, although exposure to chemicals including lead and pesticides, and to agricultural environments, smoking, certain sports, and trauma have all been identified with an increased risk of ALS. There is a need for research to quantify the relative roles of each of the identified risk factors for ALS. Recent evidence has strengthened the theory that chronic environmental exposure to the neurotoxic amino acid β-N-methylamino-L-alanine (BMAA) produced by cyanobacteria may be an environmental risk factor for ALS. Here we describe methods that may be used to assess exposure to cyanobacteria, and hence potentially to BMAA, namely an epidemiologic questionnaire and direct and indirect methods for estimating the cyanobacterial load in ecosystems. Rigorous epidemiologic studies could determine the risks associated with exposure to cyanobacteria, and if combined with genetic analysis of ALS cases and controls could reveal etiologically important gene-environment interactions in genetically vulnerable individuals. more...

CONTEXT Youth with bipolar disorder (BD) and those with severe, nonepisodic irritability (severe mood dysregulation [SMD]) exhibit amygdala dysfunction during facial emotion processing. However, studies have not compared such patients with each other and with comparison individuals in neural responsiveness to subtle changes in facial emotion; the ability to process such changes is important for social cognition. To evaluate this, we used a novel, parametrically designed faces paradigm. OBJECTIVE To compare activation in the amygdala and across the brain in BD patients, SMD patients, and healthy volunteers (HVs). DESIGN Case-control study. SETTING Government research institute. PARTICIPANTS Fifty-seven youths (19 BD, 15 SMD, and 23 HVs). MAIN OUTCOME MEASURE Blood oxygenation level-dependent data. Neutral faces were morphed with angry and happy faces in 25% intervals; static facial stimuli appeared for 3000 milliseconds. Participants performed hostility or nonemotional facial feature (ie, nose width) ratings. The slope of blood oxygenation level-dependent activity was calculated across neutral-to-angry and neutral-to-happy facial stimuli. RESULTS In HVs, but not BD or SMD participants, there was a positive association between left amygdala activity and anger on the face. In the neutral-to-happy whole-brain analysis, BD and SMD participants modulated parietal, temporal, and medial-frontal areas differently from each other and from that in HVs; with increasing facial happiness, SMD patients demonstrated increased, and BD patients decreased, activity in the parietal, temporal, and frontal regions. CONCLUSIONS Youth with BD or SMD differ from HVs in modulation of amygdala activity in response to small changes in facial anger displays. In contrast, individuals with BD or SMD show distinct perturbations in regions mediating attention and face processing in association with changes in the emotional intensity of facial happiness displays. These findings demonstrate similarities and differences in the neural correlates of facial emotion processing in BD and SMD, suggesting that these distinct clinical presentations may reflect differing dysfunctions along a mood disorders spectrum. more...

Objective: Child and adult bipolar patients show both behavioral deficits in face emotion processing and abnormal amygdala activation. However, amygdala function in pediatric relative to adult bipolar patients has not been compared directly. The authors used functional MRI to compare amygdala activity during a face processing task in children and adults with bipolar disorder and in healthy comparison subjects., Method: Amygdala responses to emotional facial expressions were examined in pediatric (N=18) and adult (N=17) bipolar patients and in healthy child (N=15) and adult (N=22) volunteers. Participants performed a gender identification task while viewing fearful, angry, and neutral faces., Results: In response to fearful faces, bipolar patients across age groups exhibited right amygdala hyperactivity relative to healthy volunteers. However, when responses to all facial expressions were combined, pediatric patients exhibited greater right amygdala activation than bipolar adults and healthy children., Conclusions: Amygdala hyperactivity in response to fearful faces is present in both youths and adults with bipolar disorder. However, compared with bipolar adults and healthy child volunteers, pediatric bipolar patients showed amygdala hyperactivity in response to a broad array of emotional faces. Thus, abnormal amygdala activation during face processing appears to be more pervasive in children than in adults with bipolar disorder. Longitudinal studies are needed to elucidate the mechanisms of this developmental difference, thus facilitating developmentally sensitive diagnosis and treatment. more...

Dynamic simulation technology is integrated with mass balance concepts and compartment-flux diagramming to create computer models that estimate contaminant export from watersheds over long and short-term futures under alternative simulated policies of watershed management. The Watershed Ecosystem Nutrient Dynamics (WEND) model, applied to developed watersheds with a mix of urban, agricultural, and forest land-uses, predicted phosphorus (P) export from three watersheds; a 275,000 ha dairy/urban watershed, a 77,000 ha poultry/urban watershed, and a 23,000 ha swine dominated watershed. Urban, agricultural, and forestry activities contribute to P export in different proportions. In all cases the P imports to the watershed exceed total export and P accumulates in watershed soils. Long-term future P export patterns are compared for several watershed management strategies that range from encouragement of rapid urban growth to aggressive environmental protection. The specific response of each watershed to imposed management is unique, but management strategies designed to reduce export of P over the long-term need to consider options that promote P input/output balance. Using this same approach, the Watershed Ecosystem Bacterial Dynamics (WEBD) model assesses the dynamics of bacterial populations in a small case-study watershed over an annual cycle as influenced by dairy farm management actions. WEND and WEBD models integrate the diversity of activities and stakeholders interested in the watershed and promote development of a more holistic understanding of watershed function. Model outputs are designed to assist watershed policy-makers, managers, and planners to explore potential future impacts of management/policy decisions. more...

Objective: To articulate a framework for supporting individuals with behavioral challenges following brain injury, to describe a state-funded clinical intervention program established to provide community support to individuals with challenging behaviors following brain injury using such a framework, to present data from which it can be concluded that such a program is cost-effective, and to offer policy recommendations., Design: Retrospective analysis of cost data and living arrangements for individuals with behavioral challenges served for a period of 3-4 years through the New York State Home and Community-Based Services Traumatic Brain Injury (HCBS-TBI) Waiver program and the State Behavioral Resource Project., Subjects: 80 individuals with TBI and severe behavioral challenges that included criminal behavior, physical threats, assault and physical aggression, sexually inappropriate behavior, substance abuse, refusal to participate in intervention programs, and psychiatric disturbances, all of whom were at least 2 years postinjury (X = 7.33 years postinjury)., Results: The majority of individuals (82% of the 1996 cohort; 89% of the 1997 cohort) with challenging behaviors were living successfully in their home communities 3-4 years after the initiation of behavioral supports. In addition, the costs of serving these individuals decreased in the first year of community integration and for that last year that a cost analysis was completed., Conclusions: Many individuals with behavioral impairments can be supported successfully in community settings, so long as those supports are flexibly implemented to meet the changing needs of those individuals. Moreover, even with intensive supports, it is cost-effective to serve this population in the community. more...

This article examines Medicaid waivers to provide services to adults with traumatic brain injury (TBI) who are Medicaid eligible in the community and who would otherwise be placed in nursing homes or who meet nursing home levels of care. Medicaid waivers for individuals with TBI were addressed through a review of six TBI Waivers (Colorado, Idaho, Kansas, New York, Rhode Island, and Vermont). A summary of the services covered by the waivers is provided. Review of the data suggests two processes, obtaining a waiver and implementing a waiver. Four characteristics were linked to obtaining waivers (a) social-medical-political climate, (b) similarity to other waivers, (c) ability to strengthen access and reduce barriers, and (d) expenditure of resources. Similarly, four theoretical characteristics were posited to be associated with managing waivers: (a) cost effectiveness, developmental process of waiver implementation, (c) ability to improve access and reduce barriers, and (d) expenditure of resources to manage the waiver. more...

Limited diversity was found among cyanobionts from a cultivated population of cycads at a field site in Florida. All isolates were classified as Nostoc but were different from the one Nostoc species found in the soil. These cyanobacteria were root endophytes of several plants of Zamia integrifolia and one of Dioon. The isolates were similar morphologically and in their reactions to four fluorescein isothiocyanate conjugated lectins. Electrophoretic protein profiles and zymograms distinguished one cyanobiont and the soil Nostoc. A tenacious Anabaena epiphyte was also discovered inhabiting the surfaces of root nodules. more...