Generation of Vascularized Brain Organoids to Study Neurovascular Interactions

The recently developed brain organoids have been used to recapitulate the processes of brain development and related diseases. However, the lack of vasculatures, which regulate neurogenesis, brain disorders, and aging process, limits the utility of brain organoids. In this study, we induced vessel and brain organoids respectively, and then fused two types of organoids together to obtain vascularized brain organoids. The fused brain organoids were engrafted with robust vascular network-like structures, and exhibited increased number of neural progenitors, in line with the possibility that vessels regulate neural development. Fusion organoids also contained functional blood-brain-barrier (BBB)-like structures, as well as microglial cells, a specific population of immune cells in the brain. The incorporated microglia responded actively to immune stimuli to the fused brain organoids. Thus, the fusion organoids established in this study allow modeling interactions between the neuronal and non-neuronal components in vitro, in particular the vasculature and microglia niche.

Invasive Candidiasis in Hospitalized Patients with Major Burns

Background: Invasive candidiasis (IC) is a major cause of morbidities and mortality in patients hospitalized with major burns. This study investigated the incidence of IC in this specific population and analyzed the possible risk factors. Materials and Methods: We retrospectively analyzed data from the National Health Insurance Research Database (NHIRD) of Taiwan. We identified 3582 patients hospitalized with major burns on over 20% of their total body surface area (TBSA) during 2000–2013; we further analyzed possible risk factors. Result: IC was diagnosed in 452 hospitalized patients (12.6%) with major burns. In the multivariate analysis, patients older than 50 years (adjusted odds ratio (OR) = 1.96, 95% confidence interval (CI) 1.36–2.82), those of female sex (adjusted OR = 1.33, 95% CI 1.03–1.72), those with burns on the head (adjusted OR = 1.33, 95% CI 1.02–1.73), and those with burns over a greater TBSA had higher risks of IC. Conclusion: Treating IC is crucial in healthcare for major burns. Our study suggests that several risk factors are associated with IC in patients hospitalized with major burns, providing reliable reference value for clinical decisions.

Women's COPD

Chronic obstructive pulmonary disease (COPD) is no longer a respiratory disease that predominantly affects men, to the point where the prevalence among women has equaled that of men since 2008, partly due to their increasing exposure to tobacco and to biomass fuels. Indeed, COPD has become the leading cause of death in women in the USA. A higher susceptibility of female to smoking and pollutants could explain this phenomenon. Besides, the clinical presentation appears different among women with more frequent breathlessness, anxiety or depression, lung cancer (especially adenocarcinoma), undernutrition and osteoporosis. Quality of life is also more significantly impaired in women. The theories advanced to explain these differences involve the role of estrogens, smaller bronchi, impaired gas exchange in the lungs and smoking habits. Usual medications (bronchodilators, ICS) demonstrated similar trends for exacerbation prevention and lung function improvement in men and women. There is an urgent need to recognize the increasing burden of COPD in women and therefore to facilitate global improvements in disease management (smoking cessation, pulmonary rehabilitation…) in half of the population. Nevertheless, important limitations to the treatment of women with COPD include greater under-diagnosis than in men, fewer spirometry tests and medical consultations. In conclusion there is an urgent need to recognize the increasing burden of COPD in women and therefore to facilitate globally improvements in disease management in this specific population.

Inclusion and Exclusion

In this chapter, the authors explore the practice of inclusion as it relates to the education of deaf and hard of hearing (d/hh) students. Using the current situation in Jamaica as a microcosm, it is argued that for this specific population of students it may be necessary to reframe and redefine the notion of inclusion more broadly. For example, the authors argue that as a result of the specific cultural, linguistic, and academic needs of d/hh students, a more traditional approach to inclusion may in fact result in isolation and less access to content and skills. Inclusion that considers how deaf education classrooms may include accessible language, the Deaf community, families of d/hh children, and Deaf role models may be more appropriate for this population.

Menstrual irregularity as a biological limit to early pregnancy awareness

US state legislatures have proposed laws to prohibit abortion once the earliest embryonic electrical activity is detectable (fetal “heartbeat”). On average, this occurs roughly 6 wk after the last menstrual period. To be eligible for abortion, people must recognize pregnancy very early in gestation. The earliest symptom of pregnancy is a missed period, and irregular menstrual cycles—which occur frequently—can delay pregnancy detection past the point of fetal cardiac activity. In our analysis of 1.6 million prospectively recorded menstrual cycles, cycle irregularity was more common among young women, Hispanic women, and women with common health conditions, such as diabetes and polycystic ovary syndrome. These groups face physiological limitations in detecting pregnancy before fetal cardiac activity. Restriction of abortion this early in gestation differentially affects specific population subgroups, for reasons outside of individual control.

Neuroleptic Malignant Syndrome in Children with Autism Spectrum Disorder (ASD): A Case Report and Brief Review of Recent Literature

Neuroleptic malignant syndrome (NMS) is a rare, life-threatening, idiosyncratic adverse reaction to antipsychotic drugs. Despite the increasing rates in the prescription of antipsychotics in pediatric patients with autism spectrum disorder (ASD), little is known about the occurrence and hallmarks of NMS in this specific population. NMS appears to be part of the larger catatonia domain, based on the frequent relationship between ASD and catatonia, on the shared, when not overlapping, clinical features with malignant catatonia, and on the effectiveness of catatonia treatments on the NMS/MC symptoms. The intrinsic difficulties of exploring NMS in ASD in controlled studies accounts for the subsequent lack of available information. Based on recent reports and on our case report, clinical features of NMS in the pediatric ASD population appear to be the same as the non-ASD population. Further studies are needed to confirm these results.

QTc Intervals Are Prolonged in Late Preterm and Term Neonates during Therapeutic Hypothermia but Normalize Afterwards

Background: There are anecdotal reports on reversible QTc prolongation during therapeutic hypothermia (TH) for moderate to severe neonatal encephalopathy after asphyxia. As the QTc interval is a relevant biomarker for pharmacovigilance during medication development, a structured search and review on published neonatal QTc values to generate reference values is warranted to facilate medication development in this specific population. Methods: A structured search and literature assessment (PubMed, Embase, and Google Scholar) with ‘Newborn/Infant, QT and hypothermia’ was conducted (October 2021). Retrieved individual values were converted to QTc (Bazett) over postnatal age (day 1–7). Results: We retrieved 94 QTc intervals (during TH (n = 50, until day 3) or subsequent normothermia (n = 44, day 4–7)) in 33 neonates from 6 publications. The median (range) of QTc intervals during TH was 508 (430–678), and 410 (317–540) ms afterwards (difference 98 ms, or +28 ms/°C decrease). Four additional cohorts (without individual QTc intervals) confirmed the pattern and magnitude of the effect of body temperature on the QTc interval. Conclusions: We highlighted a relevant non-maturational covariate (°C dependent TH) and generated reference values for the QTc interval in this specific neonatal subpopulation. This knowledge on QTc during TH should be considered and integrated in neonatal medication development.

Distinct characteristics of multisystem inflammatory syndrome in children in Poland

During the winter months of 2020/2021 a wave of multisystem inflammatory syndrome in children (MIS-C) emerged in Poland. We present the results of a nationwide register aiming to capture and characterise MIS-C with a focus on severity determinants. The first MIS-C wave in Poland was notably high, hence our analysis involved 274 children. The group was 62.8% boys, with a median age of 8.8 years. Besides one Asian, all were White. Overall, the disease course was not as severe as in previous reports, however. Pediatric intensive care treatment was required for merely 23 (8.4%) of children, who were older and exhibited a distinguished clinical picture at hospital admission. We have also identified sex-dependent differences; teenage boys more often had cardiac involvement (decreased ejection fraction in 25.9% vs. 14.7%) and fulfilled macrophage activation syndrome definition (31.0% vs. 15.2%). Among all boys, those hospitalized in pediatric intensive care unit were significantly older (median 11.2 vs. 9.1 years). Henceforth, while ethnicity and sex may affect MIS-C phenotype, management protocols might be not universally applicable, and should rather be adjusted to the specific population.

End-of-life Comfort Evaluation, is Clinic Enough? A Retrospective Cohort Study of Combined Comfort Evaluation with Analgesia/Nociception Index and Clinic in non-Communicative Patients

Background: Comfort evaluation is one of the major challenges in the palliative care setting, particularly when it comes to non-communicative patients. For this specific population, validated tools for comfort evaluation are scarce and healthcare professionals have to rely on their clinical sense and experience. Objectives: To provide arguments for the use of Analgesia/Nociception Index (ANI) monitoring in order to improve clinical comfort evaluation. Methods: We conducted a retrospective cohort study of non-communicative patients at the end of their lives whose comfort was evaluated clinically and with ANI. We focused on the coherence or discordance of clinical and ANI evaluations and on pharmacological interventions driven by them. Results: 58 evaluations from 33 patients were analyzed. Clinical and demographic characteristics were highly variable. Simultaneous clinical and ANI evaluations were concordant in 45 measurements (77.58%), leading mostly to no treatment modification when indicating comfort and to increasing anxiolytic or pain-relief treatments when indicating discomfort. Thirteen (22.41%) evaluations were discordant, leading mostly to treatment incrementation. Conclusion: We suggest that the ANI monitor is a reliable tool in the palliative setting and may help provide patients with the best symptom relief and the most appropriate therapeutics.