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We describe the clinical course of 4 infants infected with severe acute respiratory syndrome coronavirus 2. All were admitted to our tertiary care neonatal intensive care unit during the Omicron variant wave in our region. All 4 infants, who were less than 3 months of age, including three born prematurely, presented with critical illness. However, their clinical presentation varied considerably. Of them, two infants presented with apnea, one with respiratory distress, and one with gastrointestinal manifestation. Our experience with these four infants provides evidence for a severe form of disease and varied clinical presentation in neonates and young infants speculated to be infected with Omicron variant.

Acute Critical Event Debriefing (ACED) after cardiopulmonary arrests should be the standard of care. However, little literature exists on how to implement performance-focused ACED in healthcare. Based on a series of successful ACED implementations in a variety of our settings, we describe key learnings and propose best practices to aid clinicians and organizations in establishing a successful ACED program. Within this practical guide, we also present a novel, standardized debriefing tool (Hotwash) that has been adapted for a variety of clinical settings.

To examine the synergetic effects of ocean acidification (OA) and light intensity on the photosynthetic performance of marine diatoms, the marine centric diatom Thalassiosira weissflogii was cultured under ambient low CO2 (LC, 390 μatm) and elevated high CO2 (HC, 1000 μatm) levels under low-light (LL, 60 μmol m−2 s−1) or high-light (HL, 220 μmol m−2 s−1) conditions for over 20 generations. HL stimulated the growth rate by 128 and 99% but decreased cell size by 9 and 7% under LC and HC conditions, respectively. However, HC did not change the growth rate under LL but decreased it by 9% under HL. LL combined with HC decreased both maximum quantum yield (FV/FM) and effective quantum yield (ΦPSII), measured under either low or high actinic light. When exposed to UV radiation (UVR), LL-grown cells were more prone to UVA exposure, with higher UVA and UVR inducing inhibition of ΦPSII compared with HL-grown cells. Light use efficiency (α) and maximum relative electron transport rate (rETRmax) were inhibited more in the HC-grown cells when UVR (UVA and UVB) was present, particularly under LL. Our results indicate that the growth light history influences the cell growth and photosynthetic responses to OA and UVR.

This paper concerns Plato’s characterization of the body as the soul’s tool. I take perception as an example of the body’s usefulness. I explore the Timaeus’ view that perception provides us with models of orderliness. Then, I argue that perception of confusing sensible objects is necessary for our cognitive development too. Lastly, I consider the instrumentality relationship more generally and its place in Plato’s teleological worldview.

Background In North American countries national guidelines have strongly recommended formula over breastmilk for people with HIV because of concern for HIV transmission. However, data from resource-limited settings suggest the risk is less than 1% among virally suppressed people. Information regarding breastfeeding experience in high resource settings is lacking. Methods A retrospective multi-site study was performed for individuals with HIV who breastfed from 2014-2022 in the United States (8 sites) and Canada (3 sites). Descriptive statistics were used for data analysis. Results Among the 72 cases reported, most had been diagnosed with HIV and were on antiretroviral therapy (ART) prior to the index pregnancy and had undetectable viral loads at delivery. Most commonly reported reasons for choosing to breastfeed were health benefits, community expectations, and parent-child bonding. Median duration of breastfeeding was 24 weeks (range 1 day to 72 weeks). Regimens for infant prophylaxis and protocols for testing of infants and birthing parents varied widely among institutions. No neonatal transmissions occurred among the 94% of infants for whom results were available >= 6 weeks after weaning. Conclusions This study describes the largest cohort to date of people with HIV who breastfed in North America. Findings demonstrate high variability among institutions in policies, infant prophylaxis, and infant and parental testing practices. The study describes challenges in weighing the potential risks of transmission with personal and community factors. Finally, this study highlights the relatively small numbers of patients living with HIV who chose to breastfeed at any one location, and the need for further multi-site studies to identify best care practices.

1. Diatoms of the Arctic Ocean annually experience extreme changes of light environment linked to photoperiodic cycles and seasonal variations of the snow and sea-ice cover extent and thickness which attenuate light penetration in the water column. Arctic diatom communities exploit this complex seasonal dynamic through a well-documented species succession during spring, beginning in sea-ice and culminating in massive phytoplankton blooms underneath sea-ice and in the marginal ice zone. The pattern of diatom taxa sequentially dominating this succession is relatively well conserved interannually, and taxonomic shifts seem to align with habitat transitions. 2. To understand whether differential photoadaptation strategies among diatom taxa explain these recurring succession sequences, we coupled lab experiments with field work in Baffin Bay at 67.5°N. Based on field data, we selected five diatom species typical of different ecological niches and measured their growth rates under light intensity ranges representative of their natural habitats. To characterize their photoacclimative responses, we sampled pigments and total particulate carbon, and conducted 14C-uptake photosynthesis response curves and variable fluorescence measurements. 3. We documented a gradient in species respective light intensity for maximal growth suggesting divergent light response plasticity, which for the most part align with species sequential dominance. Other photophysiological parameters supported this ecophysiological framing, although contrasts were always clear only between succession endmembers, Nitzschia frigida and Chaetoceros neogracilis. To validate that these photoacclimative responses are representative of in situ dynamics, we compared them to the chlorophyll a-specific light-limited slope (α*) and saturated rate of photosynthesis (P*M), monitored in Baffin Bay on sea-ice and planktonic communities. This complementary approach confirmed that unusual responses in α* and P*M as a function of light history intensity are similar between sentinel sympagic species N. frigida and natural ice-core communities. While no light-history-dependent trends were observed in planktonic communities, their α* and P*M values were in the range of measurements from our monospecific cultures. 4. Synthesis. Our results suggest that Arctic diatoms species photoadaptation strategy is tuned to the light environment of the habitats in which they dominate and indeed drives the seasonal taxonomic succession.

To enable rapid propagation of action potentials, axons are ensheathed by myelin, a multilayered insulating membrane formed by oligodendrocytes. Most of the myelin is generated early in development, resulting in the generation of long-lasting stable membrane structures. Here, we explored structural and dynamic changes in central nervous system myelin during development. To achieve this, we performed an ultrastructural analysis of mouse optic nerves by serial block face scanning electron microscopy (SBF-SEM) and confocal time-lapse imaging in the zebrafish spinal cord. We found that myelin undergoes extensive ultrastructural changes during early postnatal development. Myelin degeneration profiles were engulfed and phagocytosed by microglia using exposed phosphatidylserine as one “eat me” signal. In contrast, retractions of entire myelin sheaths occurred independently of microglia and involved uptake of myelin by the oligodendrocyte itself. Our findings show that the generation of myelin early in development is an inaccurate process associated with aberrant ultrastructural features that require substantial refinement.

ImportanceWearing a face mask in school can reduce SARS-CoV-2 transmission but it may also lead to increased hand-to-face contact, which in turn could increase infection risk through self-inoculation.ObjectiveTo evaluate the effect of wearing a face mask on hand-to-face contact by children while at school.Design, Setting, and ParticipantsThis prospective randomized clinical trial randomized students from junior kindergarten to grade 12 at 2 schools in Toronto, Ontario, Canada, during August 2020 in a 1:1 ratio to either a mask or control class during a 2-day school simulation. Classes were video recorded from 4 angles to accurately capture outcomes.InterventionsParticipants in the mask arm were instructed to bring their own mask and wear it at all times. Students assigned to control classes were not required to mask at any time (grade 4 and lower) or in the classroom where physical distancing could be maintained (grade 5 and up).Main Outcomes and MeasuresThe primary outcome was the number of hand-to-face contacts per student per hour on day 2 of the simulation. Secondary outcomes included hand-to-mucosa contacts and hand-to-nonmucosa contacts. A mixed Poisson regression model was used to derive rate ratios (RRs), adjusted for age and sex with a random intercept for class with bootstrapped 95% CIs.ResultsA total of 174 students underwent randomization and 171 students (mask group, 50.6% male; control group, 52.4% male) attended school on day 2. The rate of hand-to-face contacts did not differ significantly between the mask and the control groups (88.2 vs 88.7 events per student per hour; RR, 1.00; 95% CI, 0.78-1.28; P = >.99). When compared with the control group, the rate of hand-to-mucosa contacts was significantly lower in the mask group (RR, 0.12; 95% CI, 0.07-0.21), while the rate of hand-to-nonmucosa contacts was higher (RR, 1.40; 95% CI, 1.08-1.82).Conclusions and RelevanceIn this clinical trial of simulated school attendance, hand-to-face contacts did not differ among students required to wear face masks vs students not required to wear face masks; however, hand-to-mucosa contracts were lower in the face mask group. This suggests that mask wearing is unlikely to increase infection risk through self-inoculation.Trial RegistrationClinicalTrials.gov Identifier: NCT04531254

BACKGROUND The COVID-19 pandemic has challenged the mental health of healthcare workers, increasing the rates of moral distress (MD) and moral injury (MI) in this population. OBJECTIVE This pilot study aimed to investigate the feasibility of a virtual reality (VR) scenario to examine MD among healthcare workers during COVID-19, and to use our mobile application for real-time longitudinal monitoring of stress, MD, and MI in the eight weeks following the VR scenario. METHODS Participants were immersed in a VR scenario consisting of a morally challenging situation related to shortage of life-saving equipment in the COVID-19 pandemic. During the scenario participants answered the Moral Injury Outcome Scale (MIOS), the Perceived Stress Scale (PSS) and had their physiological signals collected. After the scenario, we conducted a debriefing session to gather participants’ impressions and feelings of the experiment and performed content analysis. Participants were also instructed to use a mobile application for the following eight weeks for monitoring stress, MD, and mental health symptoms. We conducted Wilcoxon signed-rank tests on the PSS and MIOS scores to examine if the VR scenario could induce significant stress and MD. Additionally, we evaluated user experience and the sense of presence at the end of the scenario through semi-open-ended feedback and the Igroup Presence Questionnaire (IPQ), respectively. The qualitative feedback was summarized and categorized to offer an experiential perspective. We used PSS and MIOS scores and physiological signals collected during the VR scenario to create a data-driven machine learning model to evaluate MD. MIOS scores were clustered into respective severities using a support vector machine to classify MD. RESULTS There were no dropouts during the VR scenario. Statistical analyses revealed no significant difference in the MIOS and PSS scores between before and after the experiment (P=.11 and P=.22, respectively), suggesting that the experiment did not acutely induce significant levels of stress or MD. On the other hand, the content analysis revealed feelings of guilt, shame, and numbness, which corresponded to the experience of MD. Based on IPQ results, the VR scenario achieved an above average degree of overall presence, spatial presence, and involvement, and slightly below average realism. The classification model achieved an accuracy of 98.67±0.87% for classifying MD. Over half of the participants did not answer symptom surveys on the mobile app. CONCLUSIONS Our study demonstrated VR to be a feasible method to simulate the experience of morally challenging events and elicit genuine responses associated with MD, with high acceptability and tolerability. Future research could better define its efficacy in examining stress, MD, and MI both acutely and in the longer term. An improved participant strategy for mobile data capture is needed for future studies. CLINICALTRIAL ClinicalTrials.gov NCT05001542 INTERNATIONAL REGISTERED REPORT RR2-10.2196/32240

Pancreatic ductal adenocarcinoma (PDAC) is one of the most fatal cancers worldwide with high mortality, which is mainly due to the lack of reliable biomarkers for PDAC diagnosis/prognosis in the early stages and effective therapeutic strategies for the treatment. Cancer-derived small extracellular vesicles (sEVs), which carry various messages and signal biomolecules (e.g. RNAs, DNAs, proteins, lipids, and glycans) to constitute the key features (e.g. genetic and phenotypic status) of cancer cells, are regarded as highly competitive non-invasive biomarkers for PDAC diagnosis/prognosis. Additionally, new insights on the biogenesis and molecular functions of cancer-derived sEVs pave the way for novel therapeutic strategies based on cancer-derived sEVs for PDAC treatment such as inhibition of the formation or secretion of cancer-derived sEVs, using cancer-derived sEVs as drug carriers and for immunotherapy. This review provides a comprehensive overview of the most recent scientific and clinical research on the discovery and involvement of key molecules in cancer-derived sEVs for PDAC diagnosis/prognosis and strategies using cancer-derived sEVs for PDAC treatment. The current limitations and emerging trends toward clinical application of cancer-derived sEVs in PDAC diagnosis/prognosis and treatment have also been discussed.

Background Helping Babies Breathe (HBB) is a newborn resuscitation training program designed to reduce neonatal mortality in low- and middle-income countries. However, skills decay after initial training is a significant barrier to sustained impact. Objective To test whether a mobile app, HBB Prompt, developed with user-centred design, helps improve skills and knowledge retention after HBB training. Methods HBB Prompt was created during Phase 1 of this study with input from HBB facilitators and providers from Southwestern Uganda recruited from a national HBB provider registry. During Phase 2, healthcare workers (HCWs) in two community hospitals received HBB training. One hospital was randomly assigned as the intervention hospital, where trained HCWs had access to HBB Prompt, and the other served as control without HBB Prompt (NCT03577054). Participants were evaluated using the HBB 2.0 knowledge check and Objective Structured Clinical Exam, version B (OSCE B) immediately before and after training, and 6 months post-training. The primary outcome was difference in OSCE B scores immediately after training and 6 months post-training. Results Twenty-nine HCWs were trained in HBB (17 in intervention, 12 in control). At 6 months, 10 HCW were evaluated in intervention and 7 in control. In intervention and control respectively, the median OSCE B scores were: 7 vs. 9 immediately before training, 17 vs. 21 immediately after training, and 12 vs. 13 at 6 months after training. Six months after training, the median difference in OSCE B scores was -3 (IQR -5 to -1) in intervention and -8 (IQR -11 to -6) in control (p = 0.02). Conclusion HBB Prompt, a mobile app created by user-centred design, improved retention of HBB skills at 6 months. However, skills decay remained high 6 months after training. Continued adaptation of HBB Prompt may further improve maintenance of HBB skills.

A critical synthesis of the arguments made by Flexsenhar, Omerzu, Standhartinger and Brélaz, concerning the provenance of Paul’s letter to the Philippians, suggests: (1) ‘the whole of the praetorium’ referenced in 1.13 is a group of people working in an official provincial building, hence (2) in view of Paul’s incarceration awaiting imminent trial, this is probably in a provincial capital, (3) where a group of imperial slaves, who, following attested practice, identify themselves as ‘a household of Caesar’ (4.22), and originally from Philippi, have migrated to join the local congregation. Further critical consideration suggests, moreover, that, although Ephesus is a plausible location for the explanation of this data, Corinth is a still more powerful and economic explanation of this and related data points.

Circulating pancreatic ductal adenocarcinoma (PDAC) derived small extracellular vesicles (sEVs) are nano-sized membranous vesicles secreted from PDAC cells and released into surrounding body fluids, such as blood. The use of plasma-derived sEVs for cancer diagnosis is particularly appealing in biomedical research because the sEVs reflect some key features (

International audience; Photosynthesis in diatoms is performed using the same basic modules as cyanobacteria and plants. It can be regulated on multiple levels depending on the environmental cues, allowing diatoms to adjust their photosynthetic light reaction towards optimum whilst at the same time minimizing photodamage induced by light. In recent years, tremendous progress has been gained in understanding these acclimation processes, revealing several diatom-specific features. In this chapter, we trace several paths through the photosynthetic electron transport chain to optimize photosynthesis. We review how diatoms repair photoinactivated reaction centers and which mechanisms they have to preempt photodamage. Finally, photoprotection is set in an ecophysiological context, highlighting differences in photoprotection of diatoms from different habitats.

Background In the era of highly potent illicit opioids, such as fentanyl and carfentanil, injectable opioid agonist treatment (iOAT) is an effective treatment for those with severe and treatment-refractory opioid use disorder. Untreated opioid use disorder in pregnancy can lead to maternal and neonatal morbidity and mortality. There are currently limited reports on the use of iOAT in pregnant women. The in-patient setting may provide an opportunity to pregnant women for stabilization with iOAT where first line therapies have been ineffective. Case summary We report a case of a pregnant individual who engaged in daily intravenous fentanyl who was admitted to the hospital at 29 weeks gestation for stabilization with iOAT, methadone, and slow-release oral morphine. Before admission, she endured 6 opioid overdoses in her pregnancy and continued to use illicit intravenous opioids in the community despite high dose methadone combined with slow-release oral morphine. Her withdrawal symptoms and cravings were ameliorated with hydromorphone 90 mg IM/IV BID, methadone 135 mg daily, and morphine sulfate sustained release 600 mg daily. With this regimen, she was able to reduce her intravenous fentanyl use to a single episode during her hospitalization. She completed her pregnancy in hospital, delivering a full-term live infant after receiving comprehensive prenatal care. Discussion This case report highlights iOAT as an option during pregnancy and describes the in-patient setting as appropriate to retain high-risk patients in care. This approach may benefit those who are refractory to standard opioid agonist treatment, the numbers of whom may be rising as tolerance to the illicit supply increases.

I argue that, according to Plato, the body is the sole cause of psychic disorders. This view is expressed at Timaeus 86b in an ambiguous sentence that has been widely misunderstood by translators and commentators. The goal of this article is to offer a new understanding of Plato’s text and view. In the first section, I argue that although the body is the result of the gods’ best efforts, their sub-optimal materials meant that the soul is constantly vulnerable to the body’s influences. In the second section, I argue that every psychic disorder is a disruption of the motions of the inner psychic circles by the body; moreover, I defend my translation of 86b. In the final section, I argue that the goal of education is to restore the circles to their original orbits, and I disarm a possible objection that bad education is also a cause of psychic disorder.

Introduction Rh sensitization occurs when Rh(D)-negative women develop anti-Rh(D) antibodies following exposure through pregnancy or transfusion. Rh disease may cause jaundice, anemia, neurological impairment, and death. It is rare in countries where Rh Immune Globulin (RhIg) is used. Canadian Rh sensitization and disease rates are unknown. Methods This survey-based study was conducted using a Canadian Paediatric Surveillance Program questionnaire sent to Canadian paediatricians and paediatric subspecialists to solicit Rh disease cases from May 2016 to June 2018. Paediatricians reported Rh-positive infants ≤ 60 days of age, born to Rh-negative mothers with RhD sensitization. Results Sixty-two confirmed cases of infants affected by Rh(D) sensitization were reported across Canada. The median gestational age of neonates was term, age at presentation was 2 hours, and hemoglobin at presentation was 137.5 g/L (33 to 203 g/L). The median peak bilirubin and phototherapy duration were 280 µmol/L (92 to 771 µmol/L), and 124 hours, respectively. Thirty (48%) infants received Intravenous immune globulin (IVIG) (median two doses). Seventeen (27%) received one to three simple transfusions; 10 (16%) required exchange transfusions. Six (10%) infants presented with acute bilirubin encephalopathy, and less than five presented with seizures. Fourteen mothers with affected infants were born outside of Canada. Discussion Rh disease continues to exist in Canada. Additional efforts are needed to raise awareness of Rh disease, prevent disease, and minimize sequelae when it does occur. The ongoing global burden of Rh Disease, as well as the possibility of emerging Rh immunoglobulin refusal are among factors that could be taken into consideration in future prevention efforts.

A sealed abdominal interface was positioned below the diaphragm (the "NeoVest") to apply synchronized and proportional negative pressure ventilation (NPV) and was compared to positive pressure ventilation (PPV) using neurally adjusted ventilatory assist (NAVA). Both modes were controlled by the diaphragm electrical activity (Edi).Eleven rabbits (mean weight 2.9 kg) were instrumented, tracheotomized, and ventilated with either NPV or PPV (sequentially) with different loads (resistive, dead space, acute lung injury). Assist with either PPV or NPV was titrated to reduce Edi by 50%.In order to achieve a 50% reduction in Edi, NPV required slightly more negative pressure (-8 to -12 cm HIt is feasible to apply NPV sub-diaphragmatically in synchrony and in proportion to Edi in an animal model of respiratory distress.Negative pressure ventilation (NPV), for example, the "Iron Lung," may offer advantages over positive pressure ventilation. In the present work, we describe the "NeoVest," a system consisting of a sealed abdominal interface and a ventilator that applies NPV in synchrony and in proportion to the diaphragm electrical activity (Edi).

Extremely preterm infants are prone to hyperbilirubinemia and its sequelae. Currently recommended thresholds for initiating phototherapy in these newborns are consensus-based (CB).A multi-site retrospective cohort study of 642 infants born at 24Among infants born 24We provide statistically derived pre-phototherapy TSB levels that may clarify patterns of pre-phototherapy TSB levels in extremely preterm infants.We present statistically derived pre-phototherapy total serum bilirubin levels in a cohort of extremely preterm infants. Most of these preterm infants received phototherapy-some at below currently published thresholds. There are notable differences between our statistically derived pre-phototherapy TSB levels and currently published lower limit TSB thresholds for phototherapy. Our study results assist in the understanding of pre-phototherapy TSB levels in extremely preterm infants.

The nosocomial spread of Mycobacterium tuberculosis from a healthcare worker with infectious pulmonary tuberculosis disease to patients remains a risk in the healthcare environment, including neonatal intensive care units. In this paper, we outlined a protocol for neonates exposed to tuberculosis in a neonatal intensive care unit that includes skin testing, chest X-ray imaging, and prophylactic isoniazid. Neonatal patients were followed up with tuberculosis skin testing at both three months corrected age and two months postexposure. To our knowledge, this is the first Canadian study to illustrate a protocol following tuberculosis exposure in a neonatal intensive care unit for exposed neonates.

A retrospective study was conducted at our institution of all patients who delivered between May 2016 and April 2017. A change of practice had been instituted, which involved obstetricians testing for Neisseria gonorrhoeae and Chlamydia trachomatis universally in the first and third trimesters. Medical records were reviewed for N. gonorrhoeae and C. trachomatis results and for risk factors traditionally associated with sexually transmitted infections (STIs). A substantial proportion of patients (10.7%) had not undergone screening during pregnancy. We also identified third-trimester cases of infection in asymptomatic patients who had no traditional risk factors STI acquisition, which raised the question of optimal timing for STI screening during pregnancy.

International audience; Light harvesting and photochemistry is performed by photosystems coupled to specific antennae embedded in the thylakoid membrane, a common principle across diatoms, plants and green algae. Still, unique features of diatoms within this common principle have been unraveled in recent decades, likely resulting from the complex evolutionary history of diatoms. These unique features are found in (i) the lipid composition of the thylakoid membrane, ii) the spatial organization of the light harvesting complexes, and iii) their protein and pigment composition. This chapter summarizes current knowledge of these three specific features, with a focus on structural and functional properties.