Chronic supplementation of a multi-ingredient herbal supplement increases speed of cognitive task performance alongside changes in the urinary metabolism of dopamine and the gut microbiome in cognitively intact older adults experiencing subjective memory decline: a randomized, placebo controlled, parallel groups investigation.

Background: The effects of herbs on brain function are often investigated in isolation, yet herbal preparations are often complex combinations of phytochemicals, designed to target widespread mechanisms. Objective: To assess the effects of chronic, 12 weeks, supplementation of a multi-ingredient herbal supplement (containing Bacopa monnieri, Gotu kola leaf, Turmeric whole powder, Reishi full spectrum, Rosemary, Cardamom, Holy Basil, Turmeric Wholistic™ extract, Green Tea & Seagreens) on cognitive function in older adults with subjective memory decline. Secondly, to investigate whether effects are underpinned by shifts in microbial composition and/or metabolism of the herbs. Methods: Male and female participants (N = 128) aged between 55-75 years completed lab-based cognitive assessments, and provided stool and urine samples, at baseline and then following 90 days of multi-ingredient herb, or placebo, supplementation. Results: Deficits in memory were observed in response to 90 days of multi-ingredient herbal supplement supplementation but the positive effects were all focused on speed of cognitive task performance, with an additional improvement in the false alarm rate on the rapid visual information processing task. These improvements coincided with an increased presence of tyrosine in the urinary metabolome and this may implicate the role of dopamine in these processing and/or motor speed increases. Finally, multi-ingredient herbal supplementation significantly reduced levels of 3 bacterial species in the gut microbiome and one of these, Sutterella, coincides with lower levels of constipation reported in the multi-ingredient herbal supplement condition. Conclusion: A multi-ingredient herbal supplement increases speed of cognitive task performance and increased metabolism of tyrosine suggests that this is modulated by increased dopaminergic activity. Reduced levels of Sutterella in the gut is associated with improved bowel movements of participants. Interpretation of the negative effects on memory are, however, stymied by an unequal randomization of participants into treatment groups pre- and post-COVID 19.Clinical trial registration: identifier NCT05504668.

Implementation readiness for evidence-based autism practices in school systems.

Background: The increase in the number of autistic children being identified has led to increased demand on public schools to provide high-quality services. Effectively scaling up evidence-based practice (EBP) use for autistic students is challenging, given the complicated organization of special education. Teachers have significant challenges implementing autism EBP with fidelity. Factors such as implementation leadership and climate and attitudes toward EBP are linked to successful EBP use and may vary at different levels of the education system. Examining mechanisms of successful implementation is a critical step to support scale-up. Method: In this observational study, conducted from September 2018 to March 2020, California school personnel (n = 2273) at multiple levels of the system completed surveys related to implementation climate, leadership, and attitudes toward EBP. Data were collected throughout California at the Special Education Local Plan Areas, County Office of Education, and district and school levels from educators and administrators working in public schools supporting autistic students. Multi-level modeling was conducted to characterize implementation readiness. Results: Overall, implementation climate and leadership scores are low across levels with regional levels rated more positively than districts or schools. Attitudes toward EBP were moderate, with those working in schools having the poorest ratings and specialists/trainers and related service providers (e.g., speech-language pathologists) having the highest ratings. Conclusions: Outcomes provide a unique opportunity to compare implementation factors across organizational levels with a large, statewide sample. These data provide guidance for developing implementation interventions at multiple levels of the education system to increase readiness for effective scale-up of autism EBP in schools. Personnel and leaders at different organizational levels may need differentiated training targeting improved implementation climate and leadership. Personnel within districts and schools may experience a particular benefit from leadership support for EBP implementation.

The increase in the number of autistic children being identified in schools is increasing. To address this, schools are trying to do a better job of using high-quality practices based on research. However, teachers have had difficulty using research-based strategies for autistic students the way the manuals indicate they should be used. This might be due to the complexity of the strategies or limited support from special education leadership and infrastructure. Research shows that leaders can be very important in helping teachers use effective strategies. Over 2200 school personnel in California, including administrators, professional development providers, teachers, and paraprofessionals completed surveys asking about how their leaders, schools, districts, and regions supported the use of research practices for autistic students. Overall, limited support is provided in special education, with regional agencies providing more support than districts or schools. These data suggest that school and district leaders need training in how to support educators in using autism-specific strategies.

Mechanisms affecting the gut of preterm infants in enteral feeding trials: a nested cohort within a randomised controlled trial of lactoferrin.

OBJECTIVE: To determine the impact of supplemental bovine lactoferrin on the gut microbiome and metabolome of preterm infants. DESIGN: Cohort study nested within a randomised controlled trial (RCT). Infants across different trial arms were matched on several clinical variables. Bacteria and metabolite compositions of longitudinal stool and urine samples were analysed to investigate the impact of lactoferrin supplementation. SETTING: Thirteen UK hospitals participating in a RCT of lactoferrin. PATIENTS: 479 infants born <32 weeks' gestation between June 2016 and September 2017. RESULTS: 10 990 stool and 22 341 urine samples were collected. Analyses of gut microbiome (1304 stools, 201 infants), metabolites (171 stools, 83 infants; 225 urines, 90 infants) and volatile organic compounds (314 stools, 117 infants) were performed. Gut microbiome Shannon diversity at 34 weeks corrected age was not significantly different between infants in the lactoferrin (mean=1.24) or placebo (mean=1.06) groups (p=0.11). Lactoferrin receipt explained less than 1% variance in microbiome compositions between groups. Metabolomic analysis identified six discriminative features between trial groups. Hospital site (16%) and postnatal age (6%) explained the greatest variation in microbiome composition. CONCLUSIONS: This multiomic study identified minimal impacts of lactoferrin but much larger impacts of hospital site and postnatal age. This may be due to the specific lactoferrin product used, but more likely supports the findings of the RCT in which this study was nested, which showed no impact of lactoferrin on reducing rates of sepsis. Multisite mechanistic studies nested within RCTs are feasible and help inform trial interpretation and future trial design.

Harmful Choices, the Case of C, and Decision-Making Competence.

In this paper, we make the case that a person who is considering or has already made a decision that appears seriously harmful to that person should in some cases be judged incapable of making that decision because of the harmfulness of the decision. We focus on the English case of C of 2015. C refused life-saving dialysis. The hospital wanted her declared incompetent to make this decision under the English Mental Capacity Act of 2005. The Judge argued that the consequences for a person's welfare of their decision are irrelevant to the assessment of competence, a position labeled "internalism." This aligns with an assessment of decision-making competence on a strictly cognitivist model. However, internalism misrepresents decision-making. The outcomes of decision-making processes should be part and parcel of judgments of decision-making competence, and in some cases are necessary for any judgment of incompetence to be made.

Leveraging telehealth to evaluate infants with prodromal autism spectrum disorder characteristics using the telehealth evaluation of development for infants.

LAY ABSTRACT: Many families seeking early evaluations for autism spectrum disorder face long waitlists, must often travel to centers with appropriate expertise, and are frequently told by providers to "wait and see." This results in significant stress for families and delayed supports to infants and their caregivers who could benefit. This study evaluated whether telehealth could be used to identify and evaluate infants with early autism spectrum disorder characteristics in the first year of life. In this study, we evaluated 41 infants via telehealth using a standard set of probes and scored behavior related to social communication, play, imitation, and other developmental domains. We found the majority of infants demonstrated elevated likelihood of autism spectrum disorder on both parent-reported questionnaires and examiner-rated behavior. Caregiver ratings of the overall utility of the protocol used in this study were high. Overall, this study demonstrates the feasibility for telehealth-based approaches to evaluate infants' with elevated likelihood of autism spectrum disorder in the first year of life, which could help to improve families' access to care and to expand our capacity to conduct studies evaluating possible intervention supports.

Staff to staff transmission as a driver of healthcare worker infections with COVID-19.

BACKGROUND: High rates of healthcare worker (HCW) infections due to COVID-19 have been attributed to several factors, including inadequate personal protective equipment (PPE), exposure to a high density of patients with COVID-19, and poor building ventilation. We investigated an increase in the number of staff COVID-19 infections at our hospital to determine the factors contributing to infection and to implement the interventions required to prevent subsequent infections. METHODS: We conducted a single-centre retrospective cohort study of staff working at a tertiary referral hospital who tested positive for SARS-CoV-2 between 25 January 2020 and 25 November 2020. The primary outcome was the source of COVID-19 infection. RESULTS: Of 45 staff who returned a positive test result for SARS-CoV-2, 19 were determined to be acquired at our hospital. Fifteen (15/19; 79% [95% CI: 54-94%]) of these were identified through contact tracing and testing following exposures to other infected staff and were presumed to be staff-to-staff transmission, including an outbreak in 10 healthcare workers (HCWs) linked to a single ward that cared for COVID-19 patients. The staff tearoom was identified as the likely location for transmission, with subsequent reduction in HCW infections and resolution of the outbreak following implementation of enhanced control measures in tearoom facilities. No HCW contacts (0/204; 0% [95% CI: 0-2%]) developed COVID-19 infection following exposure to unrecognised patients with COVID-19. CONCLUSION: Unrecognised infections among staff may be a significant driver of HCW infections in healthcare settings. Control measures should be implemented to prevent acquisition from other staff as well as patient-staff transmission.

Highly accurate long-read HiFi sequencing data for five complex genomes.

The PacBio® HiFi sequencing method yields highly accurate long-read sequencing datasets with read lengths averaging 10-25 kb and accuracies greater than 99.5%. These accurate long reads can be used to improve results for complex applications such as single nucleotide and structural variant detection, genome assembly, assembly of difficult polyploid or highly repetitive genomes, and assembly of metagenomes. Currently, there is a need for sample data sets to both evaluate the benefits of these long accurate reads as well as for development of bioinformatic tools including genome assemblers, variant callers, and haplotyping algorithms. We present deep coverage HiFi datasets for five complex samples including the two inbred model genomes Mus musculus and Zea mays, as well as two complex genomes, octoploid Fragaria × ananassa and the diploid anuran Rana muscosa. Additionally, we release sequence data from a mock metagenome community. The datasets reported here can be used without restriction to develop new algorithms and explore complex genome structure and evolution. Data were generated on the PacBio Sequel II System.

General practitioners and decision-making capacity assessment: the experiences and educational needs of New Zealand general practitioners.

BACKGROUND: Assessing decision-making capacity to health care is within the scope of practice for all doctors, yet the experience of GPs in this area is unknown. OBJECTIVE: To explore the experiences, perspectives, approaches and challenges for GPs in New Zealand when conducting decision-making capacity assessments. METHODS: Qualitative study design comprising individual in-depth semi-structured interviews conducted with a convenience sample of GPs. Interview transcripts were transcribed verbatim and analysed using a thematic analysis approach. RESULTS: Twelve participants were recruited. The following themes emerged: (i) GPs' roles and responsibilities in decision-making capacity assessments; (ii) GPs lack formal training, knowledge, and confidence in decision-making capacity assessments; (iii) the legal interface of decision-making capacity assessments; (iv) GPs' relationships with specialists and the resulting impact on their confidence in decision-making capacity assessments; and (v) opportunities to improve GPs' knowledge and confidence in decision-making capacity assessments. CONCLUSIONS: GPs take responsibility for decision-making capacity assessments; however, assessments can be complex. There is a need to develop specific curriculum and training resources for GPs to improve their clinical skills and legal knowledge in decision-making capacity assessments.

What do doctors know about assessing decision-making capacity?

AIMS: To survey hospital doctors (HDs) and general practitioners (GPs) on what they know about assessing capacity, and to determine their educational needs. METHOD: A mixed-methods, cross-sectional survey was administered to a convenience sample of HDs and GPs. Respondents were asked about their roles, the prevalence of older patients they had seen, specific questions about capacity assessment, difficulties encountered and their preferred format for further education. RESULTS: 152/980 (15%) HDs and 74/4,000 (2%) GPs responded. Most had been concerned about a patient's capacity in the past year, but had not received training in assessing capacity since graduation. The average responder scored below 70% on knowledge questions. Lack of legal knowledge and time pressures were among difficulties encountered. One-third of respondents lacked confidence to assess capacity to a standard high enough to present in court. Many doctors were willing to improve their skills, requesting tutorials or short courses. CONCLUSION: Respondents demonstrated gaps in their knowledge on assessing capacity, and a lack of confidence in their opinions. The findings of this survey suggest that further clinical and legal education of doctors in performing capacity assessments would be valuable.

Work-life balance and welfare.

OBJECTIVES: An online survey and focus groups were conducted, providing qualitative information on the work-life balance of psychiatrists and trainees in Australasia. METHODS: An invitation to participate in an anonymous online welfare survey was emailed to all the Royal Australian and New Zealand College of Psychiatrists trainees, Fellows, and Affiliates. Following this, nine focus groups were held across Australia and New Zealand. RESULTS: Responses received were thematically analysed. The emergent patterns are presented in this report. CONCLUSIONS: Our research suggests that work-life balance can be subjectively and objectively measured. There are phases of good and bad work-life balance, depending on stage of career and other commitments. Work-life balance may be an indicator of the health of individuals and organisations. Due to its complexity, with intrinsic and extrinsic factors involved, solutions are unlikely to be simple. Further studies are needed to substantiate our findings.

Discharging Mrs. Fox: A Team-Based Interprofessional Collaborative Standardized Patient Encounter.

INTRODUCTION: In 2003, the Institute of Medicine recommended that interprofessional education be incorporated into the training programs of health care professionals. However, many logistical challenges hinder formal interprofessional learning in health care profession programs. METHODS: This resource is a 3-hour interprofessional small-group session designed for health professions student teams to engage in a standardized patient encounter, each team member contributing a profession-specific perspective to create a collaborative care plan across five discharge decisions. The activity includes a simulated standardized patient encounter and debrief session wherein students discuss the role of bias and communication and create a collaborative care plan. RESULTS: Following the activity, participants were surveyed about the value of the educational experience. Over 12 months, 106 students (81 medicine, nine nursing, 16 pharmacy) participated in the interprofessional activity. Eighty-four students responded to the postevent survey (79% response rate). Students were confident that the experience helped them integrate profession-specific knowledge, create a shared care plan, and understand how interprofessional collaboration contributes to quality care. The debriefing session and interprofessional interaction were an integral component of the experience. DISCUSSION: This resource is a feasible interprofessional small-group activity that has been implemented without excessive faculty time or institutional resources. It is adaptable to institutional needs, local resources, level of trainee, and professions. The session provides interprofessional students the opportunity to engage with one another and with the patient in a collaborative decision-making activity focused around a critical transition of care.

Whole-genome characterization of chemoresistant ovarian cancer.

Patients with high-grade serous ovarian cancer (HGSC) have experienced little improvement in overall survival, and standard treatment has not advanced beyond platinum-based combination chemotherapy, during the past 30 years. To understand the drivers of clinical phenotypes better, here we use whole-genome sequencing of tumour and germline DNA samples from 92 patients with primary refractory, resistant, sensitive and matched acquired resistant disease. We show that gene breakage commonly inactivates the tumour suppressors RB1, NF1, RAD51B and PTEN in HGSC, and contributes to acquired chemotherapy resistance. CCNE1 amplification was common in primary resistant and refractory disease. We observed several molecular events associated with acquired resistance, including multiple independent reversions of germline BRCA1 or BRCA2 mutations in individual patients, loss of BRCA1 promoter methylation, an alteration in molecular subtype, and recurrent promoter fusion associated with overexpression of the drug efflux pump MDR1.

Clinic type and patient characteristics affecting time to resolution after an abnormal cancer-screening exam.

BACKGROUND: Research shows that multilevel factors influence healthcare delivery and patient outcomes. The study goal was to examine how clinic type [academic medical center (AMC) or federally qualified health center (FQHC)] and patient characteristics influence time to resolution (TTR) among individuals with an abnormal cancer-screening test enrolled in a patient navigation (PN) intervention. METHODS: Data were obtained from the Ohio Patient Navigation Research Project, a group-randomized trial of 862 patients from 18 clinics in Columbus, Ohio. TTR of patient after an abnormal breast, cervical, or colorectal screening test and the clinics' patient and provider characteristics were obtained. Descriptive statistics and Cox shared frailty proportional hazards regression models of TTR were used. RESULTS: The mean patient age was 44.8 years and 71% of patients were white. In models adjusted for study arm, FQHC patients had a 39% lower rate of resolution than AMC patients (P = 0.004). Patient factors of having a college education, private insurance, higher income, and being older were significantly associated with lower TTR. After adjustment for factors that substantially affected the effect of clinic type (patient insurance status, education level, and age), clinic type was not significantly associated with TTR. CONCLUSIONS: These results suggest that TTR among individuals participating in PN programs are influenced by multiple socioeconomic patient-level factors rather than clinic type. Consequently, PN interventions should be tailored to address socioeconomic status factors that influence TTR. IMPACT: These results provide clues regarding where to target PN interventions and the importance of recognizing predictors of TTR according to clinic type.

An economic analysis of robotic versus laparoscopic surgery for endometrial cancer: costs, charges and reimbursements to hospitals and professionals.

OBJECTIVE: To determine the actual costs, charges, and reimbursements associated with robotic vs. laparoscopic surgery for endometrial cancer. METHODS: Data were collected from hospital billing records, MD professional group billing records, tumor registry, and medical records on operations performed by a single surgeon from one institution between 2008 and 2010. For comparison, surgical groups were matched based on age, histology, and stage of disease over the same time period. RESULTS: Of 54 patients, 27 underwent robotic surgery (RS) and 27 had laparoscopic surgery (LS). The median age was 57 years. There were no statistically significant differences between the groups based on age, stage, and histology. The hospital charges for RS were higher at $64,266 vs. $55,130 for LS (p=0.036). However, the reimbursement to the hospital was not statistically different at $13,003 for RS and $10,245 for LS (p=0.29). Operating suite, room and board, anesthesia, post anesthesia care unit, and pathology accounted for over 90% of hospital charges. The surgeon charges for RS and LS were $6824 and $6327, respectively (p=0.033) and the anesthesiologist charges were $4049 and $2985, respectively (p=0.001). However, there were no differences in reimbursement to the surgeon (p=0.74) and anesthesiologist (p=0.84) between the two operative approaches. CONCLUSIONS: Our data showed that the direct costs and charges associated with robotic surgery were higher compared to laparoscopic surgery. However, actual reimbursements to the hospital, surgeon, and anesthesiologist were not significantly different between the two surgical approaches.

Bio-oil from photosynthetic microalgae: case study.

Microalgae possess the potential to produce bio-oils, carbohydrates, protein, amino acids and other value added products, each of which increase its value as a crop. Unfortunately, proven systems do not yet exist for commercial scale production. System designs have generally not adequately accounted for water and energy use at scale, as well as byproduct markets, and thus yielded systems that are both unaffordable and unsustainable. We address energy and water use by presenting a straightforward microalga-to-bio-oil production process and then characterize system performance using steady-state water and energy balances. Practical limitations to commercial production of bio-oils from photosynthetic microalgae are proposed and conclusions drawn regarding system potential for assumed biomass productivities. As this is a theoretical analysis of a generic process and in practice many of the bottlenecks presented remain to be solved, it is our intent that the analysis framework presented herein can be applied to future systems that propose such solutions.

Improving the coordination of care for low back pain patients by creating better links between acute and community services.

This paper reports on the development of a care-pathway to improve service linkages between the acute setting and community health services in the treatment of low back pain. The pathway was informed by two processes: (1) a literature review based on best-practice guidelines in the assessment, treatment and continuity of care for low back pain patients; and (2) consultation with staff and key stakeholders. Stakeholders from both the acute and community sectors comprised the Working Group, who identified central areas of concern to be addressed in the care-pathway, with the goal of preventing chronicity of low back pain and reducing emergency department presentations. The main outcomes achieved include: the development of a new care-coordinator role, which would support a greater focus on integration between acute and community sectors for low back pain patients; identifying the need to screen at-risk patients; implementation of the SCTT (Service Coordination Tool Templates) tool as a system of referral across the acute and community settings; and agreement on the need to develop an evidence-based self-management program to be offered to low back pain patients. The benefits and challenges of implementing this care pathway are discussed.

What gets in the way of clinical contact? Student perceptions of barriers to patient contact.

AIMS: Students clearly need to have direct clinical contact with patients during their training. However, students complain that the opportunities for this are inadequate. This study aims to describe students' perceptions of internal and external factors that may impede clinical contact. METHODS: A questionnaire was developed from a literature review and a focus group discussion. Participants were medical students who had just completed their fourth year at Otago University, Wellington, where the curriculum is integrated with clinical contact. Questionnaire responses included Likert scale scores and written responses to open questions. RESULTS: Sixty-four percent of the year group participated (45/70). Likert scale responses were categorised into high scoring (three or more; with a maximum of five) and low scoring (two or less) and into "internal" (13) and "external" (12) factors. Sixty-nine percent of respondents endorsed six or more high-scoring items. No significant differences were found between internal and external barriers, but female students were significantly more likely to endorse internal factors. Forty-nine percent of students commented in response to the open questions that direction to appropriate patients by a supervisor would help. CONCLUSIONS: Students identified a number of barriers to clinical contact with patients. This research suggests that access to clinical contact could be improved.

Neural stem cells in the subventricular zone are a source of astrocytes and oligodendrocytes, but not microglia.

The developmental origin of microglia remains a controversial subject. While it is generally accepted that primitive fetal macrophages that migrate from the yolk sac to the brain become microglia, it also has been argued that there is a second source of microglia that are of neuroectodermal lineage. To determine whether progenitors in the dorsolateral subventricular zone (SVZDL) are capable of producing microglia as well as macroglia, we infected perinatal rat SVZDL cells with a mixture of two replication-deficient retroviruses, placed these progenitors in vitro and then varied the media formulations to promote microglial differentiation. Mixed macroglial clones were obtained, but no heterogeneous clones containing microglia were observed, regardless of the media components. Among the macroglial clones, we observed every possible combination of type 1 astrocyte and O-2A lineage cells. Some clones were homogeneous and contained cells belonging to a single macroglial lineage. Other clonal clusters were heterogeneous and were comprised of type 1 astrocytes and oligodendrocytes, type 1 and type 2 astrocytes, or type 2 astrocytes and oligodendrocytes. Of 130 clones examined, where we used triple immunofluorescence with antibodies that recognize microglia, 2 clonal clusters contained OX-42+ microglia that were retrovirally labeled, but all of the cells in those clones expressed the microglial marker and none expressed either GFAP or O4. In addition, we isolated neural stem cells from the perinatal SVZDL and assessed their capacity to generate macroglia and microglia. Confirming and extending our previous analyses, neural stem cells generated homogeneous and heterogeneous macroglial clones, but they did not generate microglia. We conclude that brain macroglia and microglia do not share a common precursor, even though the neural stem cells in the SVZDL cells can produce neurons, astrocytes and oligodendrocytes. Therefore, the microglia that reside in the SVZDL are immigrants from nonneural precursors.

The molecular basis for the lack of immunostimulatory activity of vertebrate DNA.

Macrophages and B cells are activated by unmethylated CpG-containing sequences in bacterial DNA. The lack of activity of self DNA has generally been attributed to CpG suppression and methylation, although the role of methylation is in doubt. The frequency of CpG in the mouse genome is 12.5% of Escherichia coli, with unmethylated CpG occurring at approximately 3% the frequency of E. coli. This suppression of CpG alone is insufficient to explain the inactivity of self DNA; vertebrate DNA was inactive at 100 micro g/ml, 3000 times the concentration at which E. coli DNA activity was observed. We sought to resolve why self DNA does not activate macrophages. Known active CpG motifs occurred in the mouse genome at 18% of random occurrence, similar to general CpG suppression. To examine the contribution of methylation, genomic DNAs were PCR amplified. Removal of methylation from the mouse genome revealed activity that was 23-fold lower than E. coli DNA, although there is only a 7-fold lower frequency of known active CpG motifs in the mouse genome. This discrepancy may be explained by G-rich sequences such as GGAGGGG, which potently inhibited activation and are found in greater frequency in the mouse than the E. coli genome. In summary, general CpG suppression, CpG methylation, inhibitory motifs, and saturable DNA uptake combined to explain the inactivity of self DNA. The immunostimulatory activity of DNA is determined by the frequency of unmethylated stimulatory sequences within an individual DNA strand and the ratio of stimulatory to inhibitory sequences.