The mental health impacts of human-ecosystem-animal relationships: A systematic scoping review of Eco-, Planetary, and One Health approaches.

The threats to human and animal health, biodiversity conservation, and our living planet's future are ever-present and increasingly more severe due to climate change and environmental degradation. There is an emerging discourse exploring the mental health dimensions contained within these changes. To better understand and respond to these impacts requires novel and creative methodological approaches built on conceptual frameworks that integrate perspectives from the social and natural sciences. Three of the most influential interdisciplinary frameworks at the human-animal-ecosystem interface include: One Health, EcoHealth, and Planetary Health. These frameworks report mental health as an integral component within overall health-related outcomes. However, a comprehensive synthesis of the state of the literature that examines how mental health is explored within these approaches does not currently exist. A systematic scoping review was therefore conducted to obtain clear understandings of patterns, gaps, and broad themes, and to highlight future research needs and considerations. Standardized PRISMA guidelines, including explicitly defined inclusion/exclusion criteria and dual screening/extractions, were used. 13 papers were included: seven using the One Health Framework, with Planetary and EcoHealth each represented by three. Trends observed include a predominate focus on companion animals as interventions, "sense of place" used as a component of mental well-being, and non-physical health-related measurements of animal well-being as an outcome within One Health research. The lack in retrieved studies also highlight the dearth in literature on mental health as a pillar of these three well established frameworks. Compiling what is known in the evidence-base as a launching point for scientific engagement, this review describes guidance for investigators on how to conduct mental health research within these framework parameters so that future studies can elucidate mechanisms underpinning the intersections between the biosphere and human mental-health and data-driven interventions and policy recommendations that simultaneously address mental health and global change can be proposed and enacted.

Effect of food additives on key bacterial taxa and the mucosa-associated microbiota in Crohn's disease. The ENIGMA study.

Food additives have been linked to the pro-inflammatory microbial dysbiosis associated with Crohn's disease (CD) but the underlying ecological dynamics are unknown. Here, we examine how selection of food additives affects the growth of multiple strains of a key beneficial bacterium (Faecalibacterium prausnitzii), axenic clinical isolates of proinflammatory bacteria from CD patients (Proteus, Morganella, and Klebsiella spp.), and the consortia of mucosa-associated microbiota recovered from multiple Crohn's disease patients. Bacterial growth of the axenic isolates was evaluated using a habitat-simulating medium supplemented with either sodium sulfite, aluminum silicate, carrageenan, carboxymethylcellulose, polysorbate 80, saccharin, sucralose, or aspartame, intended to approximate concentrations found in food. The microbial consortia recovered from post-operative CD patient mucosal biopsy samples were challenged with either carboxymethylcellulose and/or polysorbate 80, and the bacterial communities compared to unchallenged consortia by 16S rRNA gene amplicon profiling. Growth of all F. prausnitzii strains was arrested when either sodium sulfite or polysorbate 80 was added to cultures at baseline or mid-exponential phase of growth, and the inhibitory effects on the Gram-negative bacteria by sodium sulfite were conditional on oxygen availability. The effects from polysorbate 80, saccharin, carrageenan, and/or carboxymethylcellulose on these bacteria were strain-specific. In addition to their direct effects on bacterial growth, polysorbate 80 and/or carboxymethylcellulose can drive profound changes in the CD mucosa-associated microbiota via niche expansion of Proteus and/or Veillonellaceae - both implicated in early Crohn's disease recurrence. These studies on the interaction of food additives with the enteric microbiota provide a basis for dietary management in Crohn's disease.

The unseen epidemic: trauma and loneliness in urban midlife women.

BACKGROUND: Connectedness and attachment are vital parts of humanity. Loneliness, a state of distress in reaction to perceived detachment and isolation, is reported by over one-third of U.S. adults and is associated with numerous physical and mental health consequences. What contributes to loneliness, especially in women and minority populations, is poorly understood, but this population is also at greater risk for abuse and trauma. Our study aimed to further understand loneliness in urban midlife women and to explore the relationship that may exist with trauma(s). METHODS: To identify primacies for mental health care, female midlife participants (N=50) of a long-standing urban community-based cohort focused on health improvement completed a one-time audiotaped interview with both quantitative assessments and a qualitative interview. Loneliness was assessed by the UCLA 3-item Loneliness Scale. Using semi-structured interviews, open-ended questions facilitated a discussion regarding mental health needs and experiences. Interview transcripts were coded and analyzed following a grounded theory methodology. Themes around loneliness and trauma emerged. The transcripts were coded using the same methodology and coders as the individual interviews. Twenty women participated in two optional focus groups. RESULTS: Participants had a mean age of 50, with the majority identifying as Black/African American (N=37) and unemployed (N=33). Three themes emerged regarding perceived causes of loneliness: trauma, the burden of responsibilities for others, and secondary to unhealthy relationships. Loneliness associated with trauma will be explored here; other themes are beyond the scope of this paper and will be discussed in subsequent analyses. Quantitative results suggest that physical abuse (loneliness scores 5.4 vs. 4.0, p=0.003), as well as emotional abuse and neglect (loneliness scores 5.6 vs. 4.4, p=0.01), were associated with greater loneliness. CONCLUSION: In urban midlife low-income women, lifetime physical abuse and emotional abuse/neglect are associated with increased feelings of loneliness. Qualitative data provide insight into how participants viewed their traumatic histories, ways in which the trauma has ongoing influence, and how they experience loneliness. Though further investigation is needed, trauma-informed approaches should be considered in both primary care and mental health settings with a focus on mitigating loneliness and providing appropriate support and trauma treatment.

Distinctive gut microbiomes of ankylosing spondylitis and inflammatory bowel disease patients suggest differing roles in pathogenesis and correlate with disease activity.

BACKGROUND: Multiple studies have confirmed dysbiosis in ankylosing spondylitis (AS) and inflammatory bowel disease (IBD); however, due to methodological differences across studies, it has not been possible to determine if these diseases have similar or different gut microbiomes. RESULTS: In this study, faecal and intestinal biopsies were obtained from 33 Australian AS patients (including 5 with concomitant IBD, 'AS-IBD'), 59 IBD patients and 105 healthy controls. Stool samples were also obtained from 16 Italian AS patients and 136 Swedish AS patients. Focusing on the Australian cohort, AS, AS-IBD and IBD patients differed from one another and from healthy controls in both alpha and beta diversity. AS patients with and without clinical IBD could be distinguished from one another with moderate accuracy using stool microbiome (AUC=0.754). Stool microbiome also accurately distinguished IBD patients from healthy controls (AUC=0.757). Microbiome composition was correlated with disease activity measured by BASDAI and faecal calprotectin (FCP) levels. Enrichment of potentially pathogenic Streptococcus was noted in AS, AS-IBD and IBD patients. Furthermore, enrichment of another potentially pathogenic genus, Haemophilus, was observed in AS, AS-IBD, IBD, AS patients with increased BASDAI, and IBD patients with faecal calprotectin >100 µg/mg. Apart from these genera, no other taxa were shared between AS and IBD patients. CONCLUSIONS: In conclusion, the distinct gut microbiome of AS and AS-IBD patients compared to IBD patients and healthy controls is consistent with immunological and genetic evidence suggesting that the gut plays a different role in driving AS compared with IBD. However, enrichment of two potentially pathogenic genera in both diseases suggests that the presence of a shared/common microbial trigger of disease cannot be discounted.

High fat diet-induced obesity prolongs critical stages of the spermatogenic cycle in a Ldlr-/-.Leiden mouse model.

Obesity can disturb spermatogenesis and subsequently affect male fertility and reproduction. In our study, we aim to elucidate at which cellular level of adult spermatogenesis the detrimental effects of obesity manifest. We induced high fat diet (HFD) obesity in low-density lipoprotein receptor knock-out Leiden (Ldlr-/-.Leiden) mice, and studied the morphological structure of the testes and histologically examined the proportion of Sertoli cells, spermatocytes and spermatids in the seminiferous tubules. We examined sperm DNA damage and chromatin condensation and measured plasma levels of leptin, testosterone, cholesterol and triglycerides. HFD-induced obesity caused high plasma leptin and abnormal testosterone levels and induced an aberrant intra-tubular organisation (ITO) which is associated with an altered spermatids/spermatocytes ratio (2:1 instead of 3:1). Mice fed a HFD had a higher level of tubules in stages VII + VIII in the spermatogenic cycle. The stages VII + VII indicate crucial processes in spermatogenic development like initiation of meiosis, initiation of spermatid elongation, and release of fully matured spermatids. In conclusion, HFD-induced obese Ldlr-/-.Leiden mice develop an aberrant ITO and alterations in the spermatogenic cycle in crucial stages (stages VII and VII). Thereby, our findings stress the importance of lifestyle guidelines in infertility treatments.

Cognitive Dysfunction: Feasibility of a Brief Intervention to Help Breast Cancer Survivors.

BACKGROUND: Many cancer survivors experience cancer-related cognitive dysfunction (CRCD), which is believed to be the result of multiple contributing biologic, situational, and personal factors. Efficacious, clinically implementable interventions addressing the multifactorial nature of CRCD are needed. OBJECTIVES: This study evaluated the feasibility of an intervention to help breast cancer survivors mitigate the effects of modifiable factors that contribute to CRCD and improve cognitive functioning. METHODS: A single-group pre-/post-test design was used. Treatment fidelity was tracked to evaluate implementability; attendance rates, experience surveys, and homework engagement were used to characterize acceptability. Pre- and post-test cognitive functioning, stress, fatigue, and mood were measured to evaluate preliminary efficacy. FINDINGS: The intervention was implementable and acceptable to participants. Participants made statistically significant improvements.

Novel strain-level resolution of Crohn's disease mucosa-associated microbiota via an ex vivo combination of microbe culture and metagenomic sequencing.

The mucosa-associated microbiota is widely recognized as a potential trigger for Crohn's disease pathophysiology but remains largely uncharacterised beyond its taxonomic composition. Unlike stool microbiota, the functional characterisation of these communities using current DNA/RNA sequencing approaches remains constrained by the relatively small microbial density on tissue, and the overwhelming amount of human DNA recovered during sample preparation. Here, we have used a novel ex vivo approach that combines microbe culture from anaerobically preserved tissue with metagenome sequencing (MC-MGS) to reveal patient-specific and strain-level differences among these communities in post-operative Crohn's disease patients. The 16 S rRNA gene amplicon profiles showed these cultures provide a representative and holistic representation of the mucosa-associated microbiota, and MC-MGS produced both high quality metagenome-assembled genomes of recovered novel bacterial lineages. The MC-MGS approach also produced a strain-level resolution of key Enterobacteriacea and their associated virulence factors and revealed that urease activity underpins a key and diverse metabolic guild in these communities, which was confirmed by culture-based studies with axenic cultures. Collectively, these findings using MC-MGS show that the Crohn's disease mucosa-associated microbiota possesses taxonomic and functional attributes that are highly individualistic, borne at least in part by novel bacterial lineages not readily isolated or characterised from stool samples using current sequencing approaches.

Multispecialty tracheostomy experience.

INTRODUCTION: Tracheostomy is a common surgical procedure used to create a secure airway in patients, now performed by a variety of specialties, with a notable rise in critical care environments. It is unclear whether this rise is seen in units with large head and neck surgery departments, and how practice in such units compares with the rest of the UK. METHODS: A three-year retrospective audit was carried out between anaesthetic, surgical and critical care departments. All tracheostomy procedures were recorded anonymously. RESULTS: A total of 523 tracheostomies were performed, 66% of which were in men. The mean patient age was 60 years. The majority (83%) were elective, performed for various indications, while the remaining 17% were emergency tracheostomies performed for pending airway obstruction. A fifth of the tracheostomies were percutaneous procedures. Most emergency tracheostomies (78%) were performed by otolaryngology. Three cricothyroidotomies were performed within critical care and theatres. Complications related to tracheostomy occurred in 47 cases (9%), most commonly lower respiratory tract infection. The mean time to decannulation was 12.8 days. CONCLUSIONS: This paper discusses the findings of a comprehensive, multispecialty audit of tracheostomy experience in a large health board, with over 150 tracheostomies performed annually. Elective cases form the majority although there is a significant case series of emergency tracheostomies performed for a range of pathologies. Around a quarter of those requiring tracheostomy ultimately died, mostly as a result of advanced cancer.

A survey of pediatric cochlear implant recipients as young adults.

OBJECTIVES: To identify the influence of pediatric cochlear implantation on long term communication modality, education, and income. METHODS: A telephone survey was conducted with 56 young adults who had received cochlear implants (CI) as children. The participants were, on average, 10.6 (SD = 64) when they received their CI and 21 (SD = 2.29) when they participated in this study. All of the participants used a unilateral CI at the time of the survey. Where applicable, survey results were compared to the general population of similar aged individuals in Ontario using chi-squared tests of proportionality. RESULTS: Participants (49/56, 88%) indicated that they used their CI all waking hours and 75% (42/56) reported using spoken language as their primary mode of communication. They attended post-secondary school at higher rates than the general population (χ2(1) = 14.35, p < .001); a wide range of study areas were identified with a greater proportion involved in fine arts than the general population (χ2(1) = 25.50, p < .001). The rates of employment in this group were below general rates (χ2(1) = 21.87, p < .001). However, those who were employed reported salaries similar to their hearing peers. CONCLUSION: The findings from this study suggest that young adults who received a unilateral CI in childhood typically continue to use their CIs to support spoken language. Their increased rates of post-secondary education are encouraging and they may be choosing unique areas of study. Longer term studies are required to further investigate lower rates of employment in this cohort.

32 year follow up of patients following atrial redirection surgery for transposition of the great arteries.

OBJECTIVE: A significant body of patients who have undergone Mustard or Senning procedure require lifelong follow up. In this retrospective review, we examined the cohort of such patients currently attending our center. DESIGN: Patients who had undergone either Mustard or Senning procedure were identified. We retrospectively reviewed medical records, recorded demographic information and data regarding the clinical state, NHYA class, cardiopulmonary exercise testing, NT-proBNP measurement, and recent cardiac MRI findings. RESULTS: Forty-six patients were identified, the mean age was 32.2 years (± 6.1 years), 67.4% were male. Thirty-two patients (69.6%) had undergone a Senning procedure. The median length of the follow-up was 32 years. Thirty-two patients (69.6%) were NHYA class 1. The mean VO2max achieved was 24.2 ± 5.8 mL/min/kg. The mean NT-proBNP was 266.4 pg/mL (± 259.9 pg/mL). The mean right ventricular end-diastolic volume (RVEDV) was 212.4 mL ± 73.1 mL (indexed 114.2 mL/m2  ± 34.4 mL/m2 ). The mean right ventricular ejection fraction (RVEF) was 53.7% ± 7.9%. The mean left ventricular end-diastolic volume (LVEDV) was 161.5 mL ± 73.7 mL (indexed 87.8 mL/m2  ± 41.1 mL/m2 ). The mean left ventricular ejection fraction (LVEF) was 59.8% ± 5.7%. There was a significant correlation between right ventricular (RV) size on MRI and NT-proBNP level. CONCLUSIONS: We present a relatively well cohort of patients with overall favorable long-term outcome. The majority of patients are NHYA class 1 and the systemic right ventricular function appears to be well preserved as assessed by MRI. The exercise tolerance is reduced, with the majority of patients achieving around 60% of the estimated VO2max . Regular specialist follow-up and assessment with advanced imaging at regular intervals remain important for this group.

Lingual Squamous Cell Carcinoma in Two Horses.

Squamous cell carcinoma (SCC) is one of the most common malignant neoplasms in horses, but lingual SCC has seldom been reported. On separate occasions, a 12-year-old American Quarter Horse mare and an 18-year-old American Saddlebred stallion were presented to the Auburn University Large Animal Teaching Hospital for evaluation of weight loss, dysphagia, and ptyalism. Evaluation of each horse included physical examination, skull radiographs, oral examination, complete blood count and serum biochemistry profile, endoscopic evaluation of the mouth, and biopsy of tissue from a lesion found on the tongue. Histopathologic assessment of tissue harvested from the lingual lesions led to a diagnosis of SCC in each case. The diagnosis prompted euthanasia for one horse, but radiation therapy appeared to delay the progression of the lesion in the other horse.

What Trauma Looks Like for Incarcerated Men: A Study of Men's Lifetime Trauma Exposure in Two State Prisons.

OBJECTIVE: While it is understood that high rates of trauma exposure are common among incarcerated male populations, there is limited data on the nature of the trauma exposure. This study sought to develop foundational knowledge about the trauma experiences of incarcerated men in order to provide a basis for further theory building in this area. METHOD: This study used a quantitative-qualitative approach to examine the trauma histories of a randomly selected sample of 67 men incarcerated in the Missouri Department of Corrections. RESULTS: The analyses revealed several patterns among study participants, including near universal trauma exposure in adolescence with the most frequent exposures involving witnessing or being proximate to violent deaths of family and friends. The mean age of exposure for all trauma exposure types measured was 17 years old. We found that for this group of incarcerated men, trauma exposures in childhood tended to result more from community violence than child maltreatment (e.g., abuse and neglect by caregivers). CONCLUSION: The study results suggested that further research may be needed into the effects of close proximity to violent death during this particular window in adolescent development. Neuroscience research has shown that this is a "sensitive period" in brain development with potential negative outcomes in early adulthood, including emotional regulation deficits that can potentially lead to increased risk of arrest. Further research on trauma exposure within this population is needed both to appropriately serve men while in prison or in the process of reentering society and to support efforts to reduce mass incarceration.

Breastfeeding: a key modulator of gut microbiota characteristics in late infancy.

The objective of this study was to investigate the impact of the most commonly cited factors that may have influenced infants' gut microbiota profiles at one year of age: mode of delivery, breastfeeding duration and antibiotic exposure. Barcoded V3/V4 amplicons of bacterial 16S-rRNA gene were prepared from the stool samples of 52 healthy 1-year-old Australian children and sequenced using the Illumina MiSeq platform. Following the quality checks, the data were processed using the Quantitative Insights Into Microbial Ecology pipeline and analysed using the Calypso package for microbiome data analysis. The stool microbiota profiles of children still breastfed were significantly different from that of children weaned earlier (P<0.05), independent of the age of solid food introduction. Among children still breastfed, Veillonella spp. abundance was higher. Children no longer breastfed possessed a more 'mature' microbiota, with notable increases of Firmicutes. The microbiota profiles of the children could not be differentiated by delivery mode or antibiotic exposure. Further analysis based on children's feeding patterns found children who were breastfed alongside solid food had significantly different microbiota profiles compared to that of children who were receiving both breastmilk and formula milk alongside solid food. This study provided evidence that breastfeeding continues to influence gut microbial community even at late infancy when these children are also consuming table foods. At this age, any impacts from mode of delivery or antibiotic exposure did not appear to be discernible imprints on the microbial community profiles of these healthy children.

Music Perception Testing Reveals Advantages and Continued Challenges for Children Using Bilateral Cochlear Implants.

A modified version of the child's Montreal Battery of Evaluation of Amusia (cMBEA) was used to assess music perception in children using bilateral cochlear implants. Our overall aim was to promote better performance by children with CIs on the cMBEA by modifying the complement of instruments used in the test and adding pieces transposed in frequency. The 10 test trials played by piano were removed and two high and two low frequency trials added to each of five subtests (20 additional). The modified cMBEA was completed by 14 children using bilateral cochlear implants and 23 peers with normal hearing. Results were compared with performance on the original version of the cMBEA previously reported in groups of similar aged children: 2 groups with normal hearing (n = 23: Hopyan et al., 2012; n = 16: Polonenko et al., 2017), 1 group using bilateral cochlear implants (CIs) (n = 26: Polonenko et al., 2017), 1 group using bimodal (hearing aid and CI) devices (n = 8: Polonenko et al., 2017), and 1 group using unilateral CI (n = 23: Hopyan et al., 2012). Children with normal hearing had high scores on the modified version of the cMBEA and there were no significant score differences from children with normal hearing who completed the original cMBEA. Children with CIs showed no significant improvement in scores on the modified cMBEA compared to peers with CIs who completed the original version of the test. The group with bilateral CIs who completed the modified cMBEA showed a trend toward better abilities to remember music compared to children listening through a unilateral CI but effects were smaller than in previous cohorts of children with bilateral CIs and bimodal devices who completed the original cMBEA. Results confirmed that musical perception changes with the type of instrument and is better for music transposed to higher rather than lower frequencies for children with normal hearing but not for children using bilateral CIs. Overall, the modified version of the cMBEA revealed that modifications to music do not overcome the limitations of the CI to improve music perception for children.

The working alliance, beliefs about the supervisor, and counseling self-efficacy: Applying the relational efficacy model to counselor supervision.

There is need for closer examination of how counselors' efficacy beliefs develop and function within actual counseling or supervisory relationships. We adapted Lent and Lopez's (2002) model of relational efficacy beliefs to the context of counseling supervision, examining possible linkages of counselors' self-efficacy to beliefs about how their supervisor perceives their (counselors') efficacy (termed relation-inferred self-efficacy [RISE]), beliefs about the supervisor's efficacy (other-efficacy), and perceptions of the supervisory working alliance. Two hundred forty graduate student counselors completed the relational efficacy belief measures in relation to a particularly challenging client on their caseloads. Path analysis findings suggested that the hypothesized model provided good fit to the data. In particular, counselors' RISE beliefs regarding their supervisors were well-predicted by the supervisory working alliance, other-efficacy beliefs about the supervisor, amount of clinical experience, and perceived client distress level. RISE beliefs (along with amount of clinical experience), in turn, predicted counselors' self-efficacy. In addition, the strength of the relationship between RISE and counselor self-efficacy was moderated by other-efficacy, suggesting that supervisors' clinical credibility, from the perspective of their supervisees, plays an important role in their ability to promote the efficacy of their supervisees. (PsycINFO Database Record

Prevalence of left ventricular hypertrabeculation/noncompaction among children with sickle cell disease.

OBJECTIVES: Incidence of sickle cell disease (SCD) in Ireland has dramatically increased. Disease survival has also steadily improved however cardiovascular manifestations remain important causes of morbidity. These include reports of left ventricular hypertrabeculation (LVHT)/noncompaction. We sought to investigate the prevalence of LVHT among a large cohort of children with SCD. METHODS: We retrospectively reviewed the records of all patients with a diagnosis of SCD who had undergone surveillance echocardiography at Our Lady's Children's Hospital Crumlin (OLCHC) from 1998 to 2015. Demographics, hemoglobin phenotype and treatment information was recorded. LV systolic function, evidence of LVHT, and possible pulmonary arterial hypertension was assessed. RESULTS: Two hundred thirty-six patients had echocardiograms available for interpretation. One hundred twenty-one (51.3%) were female; mean age was 11.3 years (± 4.1 years). Twenty-six patients (11%) had features of LVHT on echocardiography. Eleven patients (4.7%) had borderline features of LVHT. Mean LVEDD across the whole cohort was 4.2 ± 0.69 cm, LVEDD z-score of 1.44 ± 1.9, and mean LVSF was 37.3% ±15.7%. There were no significant differences in terms of age, LVEDD, LVEDD z-score, or LVSF between patients with and those without LVHT. CONCLUSIONS: The prevalence of LVHT/noncompaction in children with SCD is lower than the adult population and LV systolic function is well preserved throughout our patient group. The mechanism behind the development of LVHT in this population remains speculative. Further work is required in this field. Sickle cell patients require longitudinal evaluation to ascertain changes in left ventricular function and the presence of LVHT/noncompaction.

Variable cartilage degradation in mice with diet-induced metabolic dysfunction: food for thought.

OBJECTIVE: Human cohort studies have demonstrated a role for systemic metabolic dysfunction in osteoarthritis (OA) pathogenesis in obese patients. To explore the mechanisms underlying this metabolic phenotype of OA, we examined cartilage degradation in the knees of mice from different genetic backgrounds in which a metabolic phenotype was established by various dietary approaches. DESIGN: Wild-type C57BL/6J mice and genetically modified mice (hCRP, LDLr-/-. Leiden and ApoE*3Leiden.CETP mice) based on C57BL/6J background were used to investigate the contribution of inflammation and altered lipoprotein handling on diet-induced cartilage degradation. High-caloric diets of different macronutrient composition (i.e., high-carbohydrate or high-fat) were given in regimens of varying duration to induce a metabolic phenotype with aggravated cartilage degradation relative to controls. RESULTS: Metabolic phenotypes were confirmed in all studies as mice developed obesity, hypercholesteremia, glucose intolerance and/or insulin resistance. Aggravated cartilage degradation was only observed in two out of the twelve experimental setups, specifically in long-term studies in male hCRP and female ApoE*3Leiden.CETP mice. C57BL/6J and LDLr-/-. Leiden mice did not develop HFD-induced OA under the conditions studied. Osteophyte formation and synovitis scores showed variable results between studies, but also between strains and gender. CONCLUSIONS: Long-term feeding of high-caloric diets consistently induced a metabolic phenotype in various C57BL/6J (-based) mouse strains. In contrast, the induction of articular cartilage degradation proved variable, which suggests that an additional trigger might be necessary to accelerate diet-induced OA progression. Gender and genetic modifications that result in a humanized pro-inflammatory state (human CRP) or lipoprotein metabolism (human-E3L.CETP) were identified as important contributing factors.

Screening for Functional Cognition in Postacute Care and the Improving Medicare Post-Acute Care Transformation (IMPACT) Act of 2014.

Occupational therapists have a long history of assessing functional cognition, defined as the ability to use and integrate thinking and performance skills to accomplish complex everyday activities. In response to passage of the Improving Medicare Post-Acute Care Transformation (IMPACT) Act of 2014 (Pub. L. 113-185), the American Occupational Therapy Association has been advocating that the Centers for Medicare and Medicaid Services consider functional cognition for inclusion in routine patient assessment in postacute care settings, with important implications for occupational therapy. These efforts have the potential to increase referrals to occupational therapy, emphasize the importance of addressing functional cognition in occupational therapy practice, and support the value of occupational therapy in achieving optimal postacute care outcomes.

Development of Multiwell-Plate Methods Using Pure Cultures of Methanogens To Identify New Inhibitors for Suppressing Ruminant Methane Emissions.

Hydrogenotrophic methanogens typically require strictly anaerobic culturing conditions in glass tubes with overpressures of H2 and CO2 that are both time-consuming and costly. To increase the throughput for screening chemical compound libraries, 96-well microtiter plate methods for the growth of a marine (environmental) methanogen Methanococcus maripaludis strain S2 and the rumen methanogen Methanobrevibacter species AbM4 were developed. A number of key parameters (inoculum size, reducing agents for medium preparation, assay duration, inhibitor solvents, and culture volume) were optimized to achieve robust and reproducible growth in a high-throughput microtiter plate format. The method was validated using published methanogen inhibitors and statistically assessed for sensitivity and reproducibility. The Sigma-Aldrich LOPAC library containing 1,280 pharmacologically active compounds and an in-house natural product library (120 compounds) were screened against M. maripaludis as a proof of utility. This screen identified a number of bioactive compounds, and MIC values were confirmed for some of them against M. maripaludis and M. AbM4. The developed method provides a significant increase in throughput for screening compound libraries and can now be used to screen larger compound libraries to discover novel methanogen-specific inhibitors for the mitigation of ruminant methane emissions.IMPORTANCE Methane emissions from ruminants are a significant contributor to global greenhouse gas emissions, and new technologies are required to control emissions in the agriculture technology (agritech) sector. The discovery of small-molecule inhibitors of methanogens using high-throughput phenotypic (growth) screening against compound libraries (synthetic and natural products) is an attractive avenue. However, phenotypic inhibitor screening is currently hindered by our inability to grow methanogens in a high-throughput format. We have developed, optimized, and validated a high-throughput 96-well microtiter plate assay for growing environmental and rumen methanogens. Using this platform, we identified several new inhibitors of methanogen growth, demonstrating the utility of this approach to fast track the development of methanogen-specific inhibitors for controlling ruminant methane emissions.

Multimodal Regulation Orchestrates Normal and Complex Disease States in the Retina.

Regulation of biological processes occurs through complex, synergistic mechanisms. In this study, we discovered the synergistic orchestration of multiple mechanisms regulating the normal and diseased state (age related macular degeneration, AMD) in the retina. We uncovered gene networks with overlapping feedback loops that are modulated by nuclear hormone receptors (NHR), miRNAs, and epigenetic factors. We utilized a comprehensive filtering and pathway analysis strategy comparing miRNA and microarray data between three mouse models and human donor eyes (normal and AMD). The mouse models lack key NHRS (Nr2e3, RORA) or epigenetic (Ezh2) factors. Fifty-four total miRNAs were differentially expressed, potentially targeting over 150 genes in 18 major representative networks including angiogenesis, metabolism, and immunity. We identified sixty-eight genes and 5 miRNAS directly regulated by NR2E3 and/or RORA. After a comprehensive analysis, we discovered multimodal regulation by miRNA, NHRs, and epigenetic factors of three miRNAs (miR-466, miR1187, and miR-710) and two genes (Ell2 and Entpd1) that are also associated with AMD. These studies provide insight into the complex, dynamic modulation of gene networks as well as their impact on human disease, and provide novel data for the development of innovative and more effective therapeutics.