Vitalism and Naturopathy in Psychedelic Medicine.

Psychedelic therapy is witnessing a rapid rise in popularity both in clinical research and in the greater culture. Since it involves the use of drugs, psychology, and spirituality, professionals from a variety of backgrounds such as physicians, psychotherapists, chaplains, etc. are increasingly becoming interested or directly involved. In this article, the authors describe why naturopathic doctors, with additional training, are well suited to provide psychedelic therapy. Naturopathy is rooted in the non-materialistic metaphysics of vitalism, which is consistent with the concept of inner healing intelligence, which is widely accepted in the psychedelic therapy community. In addition to the compatible foundational philosophies, naturopaths also possess a wide range of clinical skills including herbalism, pharmacology, and counseling, among others, that can be directly applied to psychedelic therapy and integration.

Neurodevelopmental outcomes of preterm neonates receiving rescue inhaled nitric oxide in the first week of age: a cohort study.

OBJECTIVE: To assess the neurodevelopmental outcomes of preterm neonates who received inhaled nitric oxide (iNO) in the first week of age for hypoxaemic respiratory failure (HRF). METHODS: In this retrospective cohort study, we included neonates born at <29 weeks gestational age (GA) between January 2010 and December 2018 who had a neurodevelopmental assessment at 18-24 months corrected age (CA) at one of the Canadian Neonatal Follow-Up Network clinics. The primary outcome was neurodevelopmental impairment (NDI). We performed propensity score-matched analysis to compare the outcomes of those who received and did not receive iNO. RESULTS: Of the 5612 eligible neonates, 460 (8.2%) received iNO in the first week of age. Maternal age, receipt of antenatal corticosteroids, GA and birth weight were lower in the iNO group compared with the no-iNO group. Neonates in the iNO group had higher illness severity scores and higher rates of preterm prolonged rupture of membranes and were small for GA. Severe brain injury, bronchopulmonary dysplasia and mortality were higher in the iNO group. Of the 4889 survivors, 3754 (77%) neonates had follow-up data at 18-24 months CA. After propensity score matching, surviving infants who received rescue iNO were not associated with higher odds of NDI (adjusted OR 1.34; 95% CI 0.85 to 2.12). CONCLUSIONS: In preterm neonates <29 weeks GA with HRF, rescue iNO use was not associated with worse neurodevelopmental outcomes among survivors who were assessed at 18-24 months CA.

The differential associative relationship between early risk factors, neonatal morbidities and early neurodevelopmental outcome in preterm infants <29 weeks' gestation.

BACKGROUND: Very preterm infants of <29 weeks' gestation are at high risk for adverse neurodevelopment due to multiple risk factors in the early stages of life. There is little information regarding the associative effects of risk factors in early life, neonatal morbidities and subsequent neurodevelopmental outcomes. AIMS: Investigate the association of early neurodevelopmental outcomes, neonatal complications and the risk factors in the early hours of life in a cohort of preterm infants <29 weeks' gestational age. METHODS: We enrolled all surviving preterm neonates born at gestation <29 weeks between January 2015 and June 2021 in the University of Hong Kong-Shenzhen Hospital. Demographic and clinical characteristics were collected from a database of the neonatal intensive care unit. Neurodevelopmental outcomes of the survivors were evaluated using the Ages and Stages Questionnaire (ASQ-3) which were measured at the adjusted age of 12 to 18 months. The multivariate linear regression model was used to determine correlation presented as ß coefficient (ß) with 95 % confidence intervals (CI). RESULTS: In this cohort of 56 survivors <29 weeks' gestation, urine output within the first 12 h of life and Apgar score at 5 min were positively associated with different domains of ASQ-3 score, however male sex and highest fraction of inspired oxygen (FiO2) in the first 12 h of life were negatively related with at least one of neurocognitive domains of ASQ-3 at adjusted age of 12 to 18 months. During hospitalization, in addition to the frequency of packed red cell transfusions, the development of severe necrotizing enterocolitis was inversely associated with both neuromotor and neurocognitive skills (gross motor domain: ß = -16.93, CI: -32.04, -1.82; fine motor domain: ß = -16.42, CI: -28.82, -4.02; problem solving domain: ß = -13.14, CI: -24.45, -1.83; all P < 0.05), whereas severe intraventricular hemorrhage had adverse effects on gross motor only (ß = -13.04, CI: -24.42, -1.65; P = 0.03). Bronchopulmonary dysplasia and retinopathy of prematurity were not related with ASQ-3. CONCLUSIONS: In this small cohort study of very preterm neonates born at <29 weeks' gestation, risk factors in the early hours of life and neonatal morbidities during hospitalization had differential associative relationships with ASQ-3 at 12-18 months adjusted age. This information may be important for parental counseling and management including early diagnosis and intervention.

Salinization and sedimentation drive contrasting assembly mechanisms of planktonic and sediment-bound bacterial communities in agricultural streams.

Agriculture is the most dominant land use globally and is projected to increase in the future to support a growing human population but also threatens ecosystem structure and services. Bacteria mediate numerous biogeochemical pathways within ecosystems. Therefore, identifying linkages between stressors associated with agricultural land use and responses of bacterial diversity is an important step in understanding and improving resource management. Here, we use the Mississippi Alluvial Plain (MAP) ecoregion, a highly modified agroecosystem, as a case study to better understand agriculturally associated drivers of stream bacterial diversity and assembly mechanisms. In the MAP, we found that planktonic bacterial communities were strongly influenced by salinity. Tolerant taxa increased with increasing ion concentrations, likely driving homogenous selection which accounted for ~90% of assembly processes. Sediment bacterial phylogenetic diversity increased with increasing agricultural land use and was influenced by sediment particle size, with assembly mechanisms shifting from homogenous to variable selection as differences in median particle size increased. Within individual streams, sediment heterogeneity was correlated with bacterial diversity and a subsidy-stress relationship along the particle size gradient was observed. Planktonic and sediment communities within the same stream also diverged as sediment particle size decreased. Nutrients including carbon, nitrogen, and phosphorus, which tend to be elevated in agroecosystems, were also associated with detectable shifts in bacterial community structure. Collectively, our results establish that two understudied variables, salinity and sediment texture, are the primary drivers of bacterial diversity within the studied agroecosystem, whereas nutrients are secondary drivers. Although numerous macrobiological communities respond negatively, we observed increasing bacterial diversity in response to agricultural stressors including salinization and sedimentation. Elevated taxonomic and phylogenetic bacterial diversity likely increases the probability of detecting community responses to stressors. Thus, bacteria community responses may be more reliable for establishing water quality goals within highly modified agroecosystems that have experienced shifting baselines.

A plug-and-play aptamer diagnostic platform based on linear dichroism spectroscopy.

A plug-and-play sandwich assay platform for the aptamer-based detection of molecular targets using linear dichroism (LD) spectroscopy as a read-out method has been demonstrated. A 21-mer DNA strand comprising the plug-and-play linker was bioconjugated onto the backbone of the filamentous bacteriophage M13, which gives a strong LD signal due to its ready alignment in linear flow. Extended DNA strands containing aptamer sequences that bind the protein thrombin, TBA and HD22, were then bound to the plug-and-play linker strand via complementary base pairing to generate aptamer-functionalised M13 bacteriophages. The secondary structure of the extended aptameric sequences required to bind to thrombin was checked using circular dichroism spectroscopy, with the binding confirmed using fluorescence anisotropy measurements. LD studies revealed that this sandwich sensor design is very effective at detecting thrombin down to pM levels, indicating the potential of this plug-and-play assay system as a new label-free homogenous detection system based on aptamer recognition.

The REDUCED trial: a cluster randomized trial for REDucing the utilization of CEsarean delivery for dystocia.

BACKGROUND: To reduce cesarean delivery rates in nulliparous women, guidelines for diagnosing nonprogressive labor have been developed by the National Institute of Child Health and Human Development, the American College of Obstetricians and Gynecologists, and the Society for Maternal-Fetal Medicine. These are mainly based on data from the Consortium for Safe Labor study. The guidelines have not been tested in a clinical trial, so the efficacy and safety of this new approach is uncertain. OBJECTIVE: This study aimed to assess whether adoption of new guidelines for diagnosing nonprogressing labor would reduce cesarean delivery rates. STUDY DESIGN: We conducted a cluster randomized controlled trial of a knowledge translation program of the guidelines in 26 Canadian hospitals (13 control sites and 13 intervention sites). The sites included all intrapartum care sites in Alberta that perform cesarean delivery and deliver at least 70 nulliparous women annually. The baseline period started on January 1, 2015. The intervention was initiated at the first intervention site in January 2017. The follow-up period began at the first intervention site in February 2017 and lasted till February 2020. The primary outcome was the rate of cesarean delivery in nulliparous women with vertex presentation in labor at term. The secondary outcomes included spontaneous vaginal birth and maternal and neonatal safety. The main data source for the primary and secondary outcomes was the Alberta Perinatal Health Program database. The cesarean delivery rates were assessed using repeated measures mixed effects logistic regression applied to individual births. RESULTS: The analysis was based on 45,193 deliveries at intervention sites and 43,725 deliveries at control sites. There was no evidence of a decrease in the rate of cesarean delivery in association with the intervention (baseline-adjusted odds ratio, 0.94; 95% confidence interval [0.85-1.05]; P=.259). The rate of spontaneous vaginal delivery increased slightly (baseline-adjusted odds ratio, 1.10; 95% confidence interval, [1.01-1.18]; P=.024). We did not observe any differences in adverse maternal or neonatal outcomes. CONCLUSION: Cesarean delivery rates in nulliparous women were not reduced by the application of recent guidelines for the diagnosis of nonprogressive labor. Spontaneous vaginal delivery-a secondary outcome-was increased in the intervention group. The intervention appears to be safe.

Fostering Hope: Comprehensive Accessible Mother-Infant Dyad Care for Neonatal Abstinence (CAIN).

Hospital and community healthcare providers have expressed concerns around the continuity and quality of care for infants with neonatal abstinence syndrome (NAS) during hospitalization and transition home. This qualitative study explored the experiences of hospital and community-based healthcare providers and identified themes related to the management of NAS for mothers and infants. Healthcare providers that cared for women with substance use disorders and/or cared for newborns with NAS in a large urban setting in Canada met inclusion criteria for this study and were interviewed in groups or as individuals. Interview transcripts were reviewed iteratively using inductive thematic analysis to identify an overarching theme linked with primary themes. In total, 45 healthcare providers were interviewed. Qualitative analysis of their experiences derived the overarching theme of hope with five primary themes being: mother/infant, mental health, system, judgement, and knowledge. The study identified gaps in NAS care including fear, stigma, and language. This research demonstrates that programs and interventions that work with mothers and newborns with NAS must foster hope in mothers, families, and in the extended care provider team and improve communication between hospital and community networks.

Outcomes of infants with hypoxic-ischemic encephalopathy during COVID-19 pandemic lockdown in Canada: a cohort study.

PURPOSE: To evaluate change in the severity of hypoxic-ischemic encephalopathy (HIE) and associated morbidities between pre- and during COVID-19 pandemic periods in Canada. METHODS: We conducted a retrospective cohort study extracting the data from level-3 NICUs participating in Canadian Neonatal Network (CNN). The primary outcome was a composite of death in the first week after birth and/or stage 3 HIE (Sarnat and Sarnat). Secondary outcomes included rate and severity of HIE among admitted neonates, overall mortality, brain injury on magnetic resonance imaging (MRI), neonates requiring resuscitation, organ dysfunction, and therapeutic hypothermia (TH) usage. We included 1591 neonates with gestational age ≥ 36 weeks with HIE during the specified periods: pandemic cohort from April 1st to December 31st of 2020; pre-pandemic cohort between April 1st and December 31st of 2017, 2018, and 2019. We calculated the odds ratio (OR) and confidence intervals (CI). RESULTS: We observed no significant difference in the primary outcome (15% vs. 16%; OR 1.08; 95%CI 0.78-1.48), mortality in the first week after birth (6% vs. 6%; OR 1.10, 95%CI 0.69-1.75), neonates requiring resuscitation, organ dysfunction, TH usage, or rate of brain injury. In the ad hoc analysis, per 1000 live births, there was an increase in the rate of infants with HIE and TH use. CONCLUSIONS: Severity of HIE, associated morbidities, and mortality were not significantly different during the pandemic lockdown compared to a pre-pandemic period in Canada. Anticipated risks and difficulties in accessing healthcare have not increased the mortality and morbidities in neonates with HIE in Canada.

A Family-Centered, Multidisciplinary Clinic for Early Diagnosis of Neurodevelopmental Impairment and Cerebral Palsy in China-A Pilot Observation.

Background: Comprehensive multidisciplinary assessment of neurodevelopmental outcomes of high-risk neonates may have significant challenges in low- and middle-income countries, in addition to socio-cultural barriers. We aimed to compare the time to diagnosis of neurodevelopmental impairment (NDI) and cerebral palsy (CP) in preterm neonates (<29 weeks) at a multidisciplinary assessment and care (MDAC) clinic with that of a conventional high-risk infant follow-up clinic in China. Methods: All eligible surviving very preterm neonates born at <29 weeks gestation at the University of Hong Kong-Shenzhen Hospital between January 2015 and December 2019 were followed up in conventional (2015-2017) and MDAC (2018-2020) clinics up to 2 years corrected age with clinical demographic information collected in a prospective database. The MDAC team used standardized developmental assessments. The rates and timing of diagnosing NDI and CP in two epochs were compared. Results: The rates of NDI and CP were not different in two epochs [NDI: 12 (50%) vs. 12 (41%); CP: 3 (12%) vs. 2 (7%) of 24 and 29 surviving infants assessed in conventional and MDAC clinics, respectively]. Infants in the MDAC clinic were diagnosed with NDI and CP earlier than those in the pre-MDAC epoch (6 vs. 14 months corrected age, respectively, P < 0.05). Conclusion: High-risk preterm neonates can be followed more effectively in a family-centered, child-friendly multidisciplinary clinic, leading to an earlier diagnosis of NDI and CP. Early counseling and interventions could be implemented accordingly.

Pulmonary artery dopplers for early prediction of risk for bronchopulmonary dysplasia in extremely low birth weight babies.

OBJECTIVE: The early abnormal pulmonary vasoreactivity observed in babies at risk of Bronchopulmonary dysplasia (BPD) increases the pulmonary vascular resistance. This can be assessed non-invasively using Time to Peak Velocity:Right Ventricular Ejection Time ratio (TPV:RVET) measured from pulmonary artery Doppler waveform obtained using echocardiogram. We postulate that screening for this early can predict BPD in this cohort. The objective of the study was to determine the utility of TPV:RVET in early prediction of BPD in Extremely Low Birth Weight (ELBW) babies born less than 1250grams Birth Weight. METHODS: This was a single-center retrospective cohort study of ELBW babies born<29 weeks over 4 year period who had echocardiogram between 7-21 days of life. TPV:RVET ratio was measured from pulmonary artery Doppler waveform obtained using echocardiogram. The main outcome was BPD at 36 weeks corrected gestation. The predictive ability of TPV:RVET (cut off 0.34) for subsequent development of BPD was analyzed using ROC. RESULTS: Of 589 ELBW<29 weeks, 207 babies were eligible. BPD was found in 60.4%. The TPV:RVET at 0.34 had sensitivity 76.8% (95%CI 68.4-83.9), specificity 85.4% (95%CI 75.8-92.2), positive predictive value 88.9% (95%CI 81.4-94.1), negative predictive value 70.7% (95%CI 60.7-79), and ROC area 0.811 (95%CI 0.757-0.864). Odds ratio of having BPD for TPV:RVET at 0.34 was 19.9 (95%CI 8.19-48.34) and increased by 1.07 (95%CI 1.05-1.09) with every additional days of mechanical ventilation. TPV:RVET ratio had 92.75% inter-observer agreement with kappa 0.83. CONCLUSION: TPV:RVET ratio is a good and reliable early screening tool for subsequent development of BPD in ELBW babies with substantial inter-observer agreement.

Tracheostomies in term and preterm infants: A single-center Canadian retrospective cohort.

OBJECTIVE: To examine patient characteristics, hospital course, and medical outcomes of neonatal tracheostomy at a single center. DESIGN: Retrospective cohort study. SETTING: Level III neonatal intensive care units (NICUs) in Edmonton, Canada. PATIENTS: Infants admitted to NICU who underwent tracheostomy between January 2013 and December 2017 inclusive. MAIN OUTCOME MEASURES: Hospital course, discharge, and 3-year post-tracheostomy outcomes were compared between preterm infants <29 weeks gestation and infants with congenital anomalies. RESULTS: Forty-three infants were identified; seven were lost to follow-up and excluded. Of the 36 analyzed, 86% survived to discharge. At discharge, 13% were decannulated, 36% required no mechanical ventilation, and 52% required mechanical ventilation. Median hospitalization was 295 days. At 3 years post-tracheostomy, 97% were alive. Proportions of infants with tracheostomy in situ was 80%, 73%, and 60% at 1, 2, and 3 years post tracheostomy. Tracheostomy incidence was 2.7% for preterm infants <29 weeks gestational age with 55% for subglottic stenosis. All preterm infants received postnatal steroids. Preterm infants underwent tracheostomy at later chronological age (123 vs. 81 days, p < 0.001), but similar corrected gestational age (42 + 5 vs. 51 + 2 weeks, p = 0.095). Preterm infants had more intubation attempts (17 vs. 4, p < 0.001), total extubations (8 vs. 2, p < 0.001), and days on ventilation before tracheostomy (100 vs. 78, p < 0.001). CONCLUSIONS: Infants who underwent tracheostomy in a Canadian public healthcare setting demonstrated decreasing tracheostomy dependence and high survival post tracheostomy, despite prolonged hospitalization. Preterm infants had more intubation and extubation events which may have contributed to airway injury.

Tracheal Reconstruction for Congenital Tracheal Stenosis: A 950-Gram Neonate.

Congenital tracheal stenosis is a rare but life-threatening malformation of the trachea. Surgical reconstruction is high risk, and not frequently performed in neonates born of extreme prematurity and low birth weight. We present the case of an extremely premature 950-gram neonate with severe congenital tracheal stenosis who underwent tracheal reconstruction. Complete repair, with no residual stenosis, was achieved with slide tracheoplasty without the need for cardiopulmonary bypass.

Ultrarapid detection of SARS-CoV-2 RNA using a reverse transcription-free exponential amplification reaction, RTF-EXPAR.

A rapid isothermal method for detecting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for COVID-19, is reported. The procedure uses an unprecedented reverse transcription-free (RTF) approach for converting genomic RNA into DNA. This involves the formation of an RNA/DNA heteroduplex whose selective cleavage generates a short DNA trigger strand, which is then rapidly amplified using the exponential amplification reaction (EXPAR). Deploying the RNA-to-DNA conversion and amplification stages of the RTF-EXPAR assay in a single step results in the detection, via a fluorescence read-out, of single figure copy numbers per microliter of SARS-CoV-2 RNA in under 10 min. In direct three-way comparison studies, the assay has been found to be faster than both RT-qPCR and reverse transcription loop-mediated isothermal amplification (RT-LAMP), while being just as sensitive. The assay protocol involves the use of standard laboratory equipment and is readily adaptable for the detection of other RNA-based pathogens.

Flow Linear Dichroism of Protein-Membrane Systems.

Linear dichroism (LD) is the differential absorbance of light polarized parallel and perpendicular to an orientation direction. Any oriented sample will show a signal in its electronic as well as vibrational transitions. Model membrane small unilamellar vesicles or liposomes provide an oriented system when they are subject to shear flow in a Couette or other type of flow cell. Anything, including peptides and proteins, that is bound to the liposome also gives an LD signal whereas unbound analytes are invisible. Flow LD is the ideal technique for determining the orientation of different chromophores with respect to the membrane normal. To illustrate the power of the method, data for diphenyl hexatriene, fluorene, antimicrobial peptides (aurein 2.5 and gramicidin), are considered as well as another common chromophore, fluorene, often used to increase the hydrophobicity and hence membrane binding of peptides. How LD can be used both for geometry, structure analysis and probing kinetic processes is considered. Kinetic analysis usually involves identifying binding (appearance of an LD signal), insertion (sign change), often followed by loss of signal, if the inserted protein or peptide disrupts the membrane .

Left hypoplastic lung and hemoptysis-rare familial unilateral pulmonary vein atresia.

Unilateral pulmonary vein atresia (UPVA) is a rare congenital vascular malformation with obliteration of the pulmonary vein. We present a case series of three siblings with variable presentation of UPVA. We suggest a dominant genetic cause based on different paternity. Identifying genetic etiology would contribute to early diagnosis and screening.

Combining bacteriophage engineering and linear dichroism spectroscopy to produce a DNA hybridisation assay.

Nucleic acid detection is an important part of our bio-detection arsenal, with the COVID-19 pandemic clearly demonstrating the importance to healthcare of rapid and efficient detection of specific pathogenic sequences. As part of the drive to establish new DNA detection methodologies and signal read-outs, here we show how linear dichroism (LD) spectroscopy can be used to produce a rapid and modular detection system for detecting quantities of DNA from both bacterial and viral pathogens. The LD sensing method exploits changes in fluid alignment of bionanoparticles (bacteriophage M13) engineered with DNA stands covalently attached to their surfaces, with the read-out signal induced by the formation of complementary duplexes between DNA targets and two M13 bionanoparticles. This new sandwich assay can detect pathogenic material down to picomolar levels in under 1 minute without amplification, as demonstrated by the successful sensing of DNA sequences from a plant virus (Potato virus Y) and an ampicillin resistance gene, ampR.

Diatom Assemblage Changes in Agricultural Alluvial Plain Streams and Application for Nutrient Management.

In large, alluvial floodplains dominated by agriculture, small streams have the potential to experience nutrient enrichment affecting algal assemblage structure and metabolism. Nutrient enrichment is largely driven by application of nutrients and altered hydrologic regimes. To inform stressor-response-based nutrient reduction goals for agricultural alluvial plain streams, diatom assemblages were sampled from 25 streams located within the Mississippi Alluvial Plain (MAP) with various land management practices and associated P and N inputs. From August through September 2015, epidendric diatom assemblage samples were collected from instream woody debris. Field nutrient gradients were skewed toward higher concentrations, and ranges of previously reported diatom assemblage response thresholds indicative of oligotrophic conditions were not well represented. Ordination analysis identified a gradient in species composition associated with increasing P and decreasing dissolved oxygen. A significant shift in diatom assemblage structure occurred when total P concentrations in the MAP streams exceeded 0.12 mg L-. Phosphorus-enriched systems were represented by a distinct set of indicator species, lower abundances of ubiquitous species, greater abundances of highly tolerant species, and greater abundances of high-P indicator species. No relationships were observed among diatom assemblage measures or traits with increasing N. Current results do not address potential criteria for identifying high-quality, oligotrophic streams. However, measures of diatom assemblage structure have potential for helping set benchmarks to reduce nutrient impacts and monitor effects of agricultural best management practices on MAP streams.

Engineering the flagellar type III secretion system: improving capacity for secretion of recombinant protein.

BACKGROUND: Many valuable biopharmaceutical and biotechnological proteins have been produced in Escherichia coli, however these proteins are almost exclusively localised in the cytoplasm or periplasm. This presents challenges for purification, i.e. the removal of contaminating cellular constituents. One solution is secretion directly into the surrounding media, which we achieved via the 'hijack' of the flagellar type III secretion system (FT3SS). Ordinarily flagellar subunits are exported through the centre of the growing flagellum, before assembly at the tip. However, we exploit the fact that in the absence of certain flagellar components (e.g. cap proteins), monomeric flagellar proteins are secreted into the supernatant. RESULTS: We report the creation and iterative improvement of an E. coli strain, by means of a modified FT3SS and a modular plasmid system, for secretion of exemplar proteins. We show that removal of the flagellin and HAP proteins (FliC and FlgKL) resulted in an optimal prototype. We next developed a high-throughput enzymatic secretion assay based on cutinase. This indicated that removal of the flagellar motor proteins, motAB (to reduce metabolic burden) and protein degradation machinery, clpX (to boost FT3SS levels intracellularly), result in high capacity secretion. We also show that a secretion construct comprising the 5'UTR and first 47 amino acidsof FliC from E. coli (but no 3'UTR) achieved the highest levels of secretion. Upon combination, we show a 24-fold improvement in secretion of a heterologous (cutinase) enzyme over the original strain. This improved strain could export a range of pharmaceutically relevant heterologous proteins [hGH, TrxA, ScFv (CH2)], achieving secreted yields of up to 0.29 mg L-1, in low cell density culture. CONCLUSIONS: We have engineered an E. coli which secretes a range of recombinant proteins, through the FT3SS, to the extracellular media. With further developments, including cell culture process strategies, we envision further improvement to the secreted titre of recombinant protein, with the potential application for protein production for biotechnological purposes.