Multigene phylogeny, bioactive properties, enzymatic and dye decolorization potential of selected marine fungi from brown algae and sponges of Mauritius.

Marine fungi represent an important proportion of the microbial diversity in the oceans. They are attractive candidates for biotechnological purposes and industrial applications. Despite an increasing interest in mycology, marine fungi associated with sponges and algae have been poorly studied in Mauritius. The objectives of this study were to: 1) use multigene phylogenetic analyses to identify isolated marine fungi; 2) determine the differences in the antimicrobial and antioxidant properties of the fungal extracts; and 3) assess their enzyme activities and dye decolorization potential. Five fungal isolates viz Aspergillus chevalieri, Aspergillus iizukae, Aspergillus ochraceus, Exserohilum rostratum and Biatriospora sp. were identified based on phylogenetic analyses. There was no significant difference in the antimicrobial properties of the liquid and solid media extracts unlike the antioxidant properties (p < 0.05). The solid media extract of Aspergillus chevalieri (F2-SF) had a minimum inhibitory concentration of 0.156 mg/ml against Staphylococcus aureus while Aspergillus ochraceus (F25-SF) had a minimum inhibitory concentration of 0.313 and 2.5 mg/ml against Enterococcus faecalis and Salmonella typhi. The solid media extract of Biatriospora sp. (F34-SF) had a minimum inhibitory concentration of 0.195 and 1.563 mg/ml against Bacillus cereus, Escherichia coli and Enterobacter cloacae. An IC50 of 78.92 ± 4.71 µg/ml in the 2,2-Diphenyl-1-picrylhydrazyl (DPPH) scavenging assay, ferric reducing antioxidant power (FRAP) value of 11.17 ± 0.20 mM Fe2+/g dry weight extract (DWE) and total phenolic content 360.35 ± 10.31 mg GAE/g DWE was obtained with the solid media extract of Aspergillus chevalieri (F2-SF). Aspergillus ochraceus (F25-SF) and Biatriospora sp. (F34-SF) solid media extracts showed lower IC50 values in the DPPH assay and higher total phenolic content as compared to the liquid media extracts. Aspergillus chevalieri was a good producer of the enzymes DNAse and lipase and had maximum percentage dye decolorization of 79.40 ± 17.72% on Congo red. An enzymatic index ≥ 2 was found for the DNAse and lipase and the maximum percentage dye decolorization of 87.18 ± 3.80% was observed with Aspergillus ochraceus on Methylene blue. Regarding Biatriospora sp., it was a moderate producer of the three enzymes amylase, DNAse and protease and had a maximum dye decolorization potential of 56.29 ± 6.51% on Crystal violet. This study demonstrates that Mauritian marine fungi possess good bioactive properties, enzymatic and dye decolorization potentials, that can potentially be considered for use in pharmaceutical and industrial applications.

Metabarcoding assessment of fungal diversity in brown algae and sponges of Mauritius.

Marine fungi are largely associated with second most inhabitants of the marine ecosystem such as sponges and algae. They are important colonizers and play vital ecological roles, such as nutrient cycling, organic matter decomposition, and symbiosis with other organisms. High throughput sequencing methods have been used successfully to reveal unknown fungal communities associated with a number of hosts particularly in the marine environment. However, the diversity of marine fungi associated with sponges and brown algae in Mauritius remains largely unknown. Traditional methods based on culturing do not provide reliable estimate of fungal diversity as only those that are able to grow under laboratory conditions are dominant; in addition, a large proportion of fungi, cultured in vitro remain most of the time unidentifiable, given that there are no sporulating structures to be examined morphologically. To overcome these limitations, we employed Illumina sequencing to unravel fungi species present in the sponges, Iotrochota sp. and Biemna sp. and the brown algae Turbinaria conoides, Sargassum pfeifferae, and Sargassum obovatum, collected from the north of Mauritius. Diversity analyses revealed that Biemna sp. had the highest diversity from the sampled sponges with fungi from 24 orders being recovered while from brown algae; Turbinaria conoides had the highest diversity with recovery of fungal taxa of the orders Botryosphaeriales, Chaetothyriales, Eurotiales, Hypocreales, and Mucorales with the latter four orders being common in both sampled algae and sponges. Beta diversity analyses revealed clustering only in the algae, Turbinaria conoides, and Sargassum pfeifferae and not in the co-occurring sponges, indicating that sampling location did not have much influence on fungal diversity. Our findings provide the first amplicon sequencing based insights of the fungal communities associated with macro-algae and sponges in Mauritius and supplements research on the fungal community existing in the oceans around the world.

Remote Advance Care Planning in the Emergency Department During COVID-19 Disaster: Program Development and Initial Evaluation.

BACKGROUND: The coronavirus disease 2019 pandemic caused an unprecedented surge of patients presenting to emergency departments and forced hospitals to adapt to provide care to patients safely and effectively. The purpose here was to disseminate a novel program developed under disaster conditions to address advance care planning communications. METHODS: A program development and initial evaluation was conducted for the Remote Goals of Care program, which was created for families to communicate patient goals of care and reduce responsibilities of those in the emergency department. RESULTS: This program facilitated 64 remote goals of care conversation, with 72% of conversations taking place remotely with families of patients who were unable to participate. These conversations included discussions of patient preferences for care, including code status, presence of caregivers or surrogates, understanding of diagnosis and prognosis, and hospice care. Initially, this program was available 24 hours per day, 7 days per week, with gradual reduction in hours as needs shifted. Seven nurses who were unable to work in corona-positive environments but were able to continue working remotely were utilized. Lessons learned include the need for speed and agility of response and the benefit of established relationships between traditionally siloed specialties. Additional considerations include available technology for patients and families and expanding the documentation abilities for remote nurses. A logic model was developed to support potential program replication at other sites. DISCUSSION: Upon initial evaluation, Remote Goals of Care Program was well received and demonstrated promise in decanting the responsibility of goals of care discussions from the emergency department to a calmer, remote setting. In future iterations, additional services and technology adjustments can be made to make this program more accessible to more patients and families. Other facilities may wish to replicate our Remote Goals of Care Program described here.

Olfactory Distraction for Management of Nausea in Palliative Care Patients.

Nausea is one of the most common and debilitating symptoms Palliative Care patients experience. This can be caused by the life-limiting illness itself, its complications, or its treatments. While there are many options for management, including anti-emetics and motility agents, patients may develop refractory nausea or even intolerance to these treatments. Drug interactions, sedation, extrapyramidal effects, serotonin syndrome, and prolonged QT intervals with risk factors for Torsades de Pointes may all preclude use of these medications. Olfactory distraction using alcohol swabs has supporting literature in the emergency care setting as a means of alleviating nausea in a safe and effective way. We present a case series of 3 patients admitted to a Northwell facility who were referred to the Palliative Care consult service for severe nausea. The patients had nausea of varying etiology and were successfully managed with inhalation of alcohol swabs. This is the first case series that looks into applying this intervention to the Palliative Care population as an easy-to-use, readily-available, and safe method to manage nausea.

The Virulence of Grief in the Pandemic: Bereavement Overload During COVID.

The COVID-19 pandemic brought about bereavement overload as a risk factor for complicated grief. Bereavement overload (BO) describes individuals' reactions to losses transpiring in a quick succession, without the time and opportunity for coping [9]. It can occur during catastrophic events and impact everyone experiencing the loss.With the high death toll from COVID-19, many people have lost multiple loved ones followed by an abbreviated grieving process due to the nature of the pandemic. This can have psychosocial impact on survivors for years. One of the evolving roles of Palliative Care within and after the pandemic should be to recognize those suffering from BO. Obtaining loss histories may identify those at risk of pathologic grief to provide preventive bereavement care.We present three cases encountered in our health system during the COVID-19 pandemic amongst a family member, a patient, and a healthcare provider. In each case the Palliative Care Team worked closely with these individuals to identify COVID-associated BO and helped them reconcile their unresolved grief to be able to move forward. These cases reflect only a fraction of those who experienced loss during the pandemic, but they illustrate how grief can be complicated by the pandemic for everyone involved.Palliative Care will have a crucial role moving forward, in treating the pandemic of complicated grief within the pandemic to adapt to the needs of all survivors, as we realize the effects of COVID will last long after its virulence has waned.

Antimicrobial properties of marine fungi from sponges and brown algae of Mauritius.

Purpose of the study: Marine fungi of Mauritius have been poorly studied. There are numerous reports on the bioactive secondary metabolites that are produced by fungi around the world. Yet, research on the molecular characterisation and the pharmaceutical potential of marine fungi in Mauritius is rather scanty. Method: The samples, which consisted of three sponges Haliclona sp., Iotrochota sp. and Biemna sp. and two brown algae Turbinaria conoides and Sargassum portierianum, were collected in the North of Mauritius during winter. No sporulating structures were observed from the fungal cultures making morphological analysis impossible. The molecular characterisation of the selected isolates was carried out by the amplification of the ITS regions and phylogenetic analysis. The antimicrobial properties were then determined using the disc diffusion and the minimum inhibitory concentration (MIC) assay. Results: Genus level identification was made from molecular data and for some isolates, species-level identification was even possible. Twelve fungi that showed the best antimicrobial properties were identified as Peniophora sp., Aspergillus cristatus, Acremonium sp., Cordyceps memorabilis, Aspergillus ochraceus, Biscogniauxia sp., Aspergillus keratitidis, Exserohilum rostratum, Chromocleista sp., Nigrospora oryzae, Aspergillus flavipes and Mycosphaerella. The lowest MIC result of 0.0098 mg/mL was obtained with Chromocleista sp. mycelium extract against Staphylococcus aureus. The MIC of the mycelium extracts was lower than the broth extracts for most isolates indicating that the antimicrobial compounds are not secreted. Conclusion: Marine fungi from the Mauritian waters have immense potential in the search for natural products against antibiotic-resistant bacteria.

Crosstalk Between CD11b and Piezo1 Mediates Macrophage Responses to Mechanical Cues.

Macrophages are versatile cells of the innate immune system that perform diverse functions by responding to dynamic changes in their microenvironment. While the effects of soluble cues, including cytokines and chemokines, have been widely studied, the effects of physical cues, including mechanical stimuli, in regulating macrophage form and function are less well understood. In this study, we examined the effects of static and cyclic uniaxial stretch on macrophage inflammatory and healing activation. We found that cyclic stretch altered macrophage morphology and responses to IFNγ/LPS and IL4/IL13. Interestingly, we found that both static and cyclic stretch suppressed IFNγ/LPS induced inflammation. In contrast, IL4/IL13 mediated healing responses were suppressed with cyclic but enhanced with static stretch conditions. Mechanistically, both static and cyclic stretch increased expression of the integrin CD11b (αM integrin), decreased expression of the mechanosensitive ion channel Piezo1, and knock down of either CD11b or Piezo1 through siRNA abrogated stretch-mediated changes in inflammatory responses. Moreover, we found that knock down of CD11b enhanced the expression of Piezo1, and conversely knock down of Piezo1 enhanced CD11b expression, suggesting the potential for crosstalk between integrins and ion channels. Finally, stretch-mediated differences in macrophage activation were also dependent on actin, since pharmacological inhibition of actin polymerization abrogated the changes in activation with stretch. Together, this study demonstrates that the physical environment synergizes with biochemical cues to regulate macrophage morphology and function, and suggests a role for CD11b and Piezo1 crosstalk in mechanotransduction in macrophages.

Mild catalytic defects of tert rs61748181 polymorphism affect the clinical presentation of chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is a disorder of accelerated lung aging. Multiple pieces of evidence support that the aging biomarker short telomeres, which can be caused by mutations in telomerase reverse transcriptase (TERT), contribute to COPD pathogenesis. We hypothesized that short telomere risk-associated single nucleotide polymorphisms (SNPs) in TERT, while not able to drive COPD development, nonetheless modify the disease presentation. We set out to test the SNP carrying status in a longitudinal study of smokers with COPD and found that rapid decline of FEV1 in lung function was associated with the minor allele of rs61748181 (adjusted odds ratio 2.49, p = 0.038). Biochemical evaluation of ex vivo engineered human cell models revealed that primary cells expressing the minor allele of rs61748181 had suboptimal telomere length maintenance due to reduced telomerase catalytic activity, despite having comparable cell growth kinetics as WT-TERT expressing cells. This ex vivo observation translated clinically in that shorter telomeres were found in minor allele carriers in a sub-population of COPD patients with non-declining lung function, over the 5-year period of the longitudinal study. Collectively, our data suggest that functional TERT SNPs with mild catalytic defects are nonetheless implicated in the clinical presentation of COPD.

Cytokine storm of a different flavour: The different cytokine signature of SARS-CoV-2, the cause of COVID-19, from the original SARS outbreak.

Here we present a case series of three patients with COVID-19 (coronavirus disease 2019) who had a cytokine panel that revealed elevation of interleukin-6 (IL-6) but normal levels of interleukin-10 (IL-10), interferon-gamma (INF-γ) and interleukin-8 (IL-8), in contrast to the cytokine signature described in severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS). We also documented evidence of a compromised T-cell IFN-γ response in two of these patients.

Pulmonary Embolism and Increased Levels of d-Dimer in Patients with Coronavirus Disease.

We report 3 patients with coronavirus disease who had a decline in respiratory status during their hospital course that responded well to intravenous steroids and interleukin-6 receptor antagonist therapy. These patients later showed development of persistent hypoxia with increased levels of d-dimer levels and were given a diagnosis of pulmonary embolisms.

What Can Lexical Tone Training Studies in Adults Tell Us about Tone Processing in Children?

A growing number of studies on the acquisition of lexical tone by adult learners have revealed that factors such as language background, musical experience, cognitive abilities, and neuroanatomy all play a role in determining tone learning success. On the basis of these findings, it has been argued that the effectiveness of tone learning in adulthood depends on individual differences in these factors. However, it is not clear whether similar individual differences play an analogous role in tone learning in childhood. Indeed, relatively few studies have made comparisons between how adults and children learn lexical tones. Here, we review recent developments for tone learning in both adults and children. The review covers tone training in a range of contexts, including in naive listeners, in native speakers of other tone languages, in listeners with varying levels of musical experience, and in individuals with speech and hearing disorders. Finally, we discuss the parallels between adult and child tone learning, and provide recommendations concerning how findings in adult tone training can provide insights into tone learning for children by accommodating the needs of individual learners.

Placentation in watersnakes I: Placental histology and development in North American Nerodia (Colubridae: Natricinae).

As part of a broad survey of placental structure, function, and evolution in reptilian sauropsids paraffin-section histology was used to study microscopic anatomy of the uterus and fetal membranes of three species of North American watersnakes (Nerodia: Colubridae). The pre-ovulatory uterus is poorly vascularized with inactive shell glands. These shell glands are activated during vitellogenesis but regress during pregnancy. Two placentas develop through apposition of the uterine lining to the chorioallantois and the yolk sac omphalopleure. Fetal and maternal components of the chorioallantoic placenta are progressively vascularized during development. Their epithelia are attenuated, but (contrary to a previous report), epithelia of neither the uterus nor the chorion are eroded. The fetal portion of the yolk sac placenta is an omphalallantois, formed of avascular omphalopleure, isolated yolk mass, and allantois. This placenta is progressively replaced by chorioallantoic placenta during mid- to late-development through depletion of the isolated yolk mass. The chorioallantoic placenta is anatomically specialized for maternal-fetal gas exchange, and its expansion during development reflects the growing needs of the fetus for gas exchange. The yolk sac placenta is morphologically unsuited for gas exchange, but may serve other functions in maternal-fetal exchange.

Comparison of documentation of patient reported adverse drug reactions on both paper-based medication charts and electronic medication charts at a New Zealand hospital.

AIM: Known adverse drug reactions (ADRs) can have profound effects on disease states, as well as prescribing practice. Therefore, the correct and complete documentation of each individual patient's ADR history, upon hospital admission, is important in optimising that individual patient's pharmacotherapy. This study investigated the documentation of ADRs at a tertiary New Zealand hospital, on both paper-based medication charts and electronic medication charts to quantify both the number of ADRs patients self-report, as well as the differences between recording of that information in electronic and paper-based charting systems. METHOD: Following ethical approval, inpatient medication charts on the general medical ward (electronic prescribing), or the general surgical ward (paper-based medication charts) were viewed for documented ADRs-as reported by each patient on admission. Consecutive patient charts (and electronic clinical management system) were viewed until 50 patients from each ward, each with at least one documented ADR, (in any of the information sources) were obtained. Patient demographic information, ADR history and discrepancies between information sources were determined. RESULTS: In both wards 114 patients were reviewed in order to find 50 patients with documented ADRs. In the medical ward (electronic) 44 (90%) patients had discrepancies in ADR information between different information sources and in the surgical ward (paper) this occurred in 49 (98%) patients. CONCLUSION: A large number of patients self-report ADRs. Full documentation of patient reported ADRs is required to adequately inform future prescribing decisions. Discrepancies between ADR information recorded in different information systems exist, but information sharing between electronic and non-electronic sources could be prioritised in order to allow full and complete information to be collected, stored and utilised; and reduce the current inadequacies.

Quantifying Variability of Manual Annotation in Cryo-Electron Tomograms.

Although acknowledged to be variable and subjective, manual annotation of cryo-electron tomography data is commonly used to answer structural questions and to create a "ground truth" for evaluation of automated segmentation algorithms. Validation of such annotation is lacking, but is critical for understanding the reproducibility of manual annotations. Here, we used voxel-based similarity scores for a variety of specimens, ranging in complexity and segmented by several annotators, to quantify the variation among their annotations. In addition, we have identified procedures for merging annotations to reduce variability, thereby increasing the reliability of manual annotation. Based on our analyses, we find that it is necessary to combine multiple manual annotations to increase the confidence level for answering structural questions. We also make recommendations to guide algorithm development for automated annotation of features of interest.

Abnormal visual experience during development alters the early stages of visual-tactile integration.

Visual experience during the critical periods in early postnatal life is necessary for the normal development of the visual system. Disruption of visual input during this period results in amblyopia, which is associated with reduced activation of the striate and extrastriate cortices. It is well known that visual input converges with other sensory signals and exerts a significant influence on cortical processing in multiple association areas. Recent work in healthy adults has also shown that task-relevant visual input can modulate neural excitability at very early stages of information processing in the primary somatosensory cortex. Here we used electroencephalography to investigate visual-tactile interactions in adults with abnormal binocular vision due to amblyopia and strabismus. Results showed three main findings. First, in comparison to a visually normal control group, participants with abnormal vision had a significantly lower amplitude of the P50 somatosensory event related potential (ERP) when visual and tactile stimuli were presented concurrently. Second, the amplitude of the P100 somatosensory ERP was significantly greater in participants with abnormal vision. These results indicate that task relevant visual input does not significantly influence the excitability of the primary somatosensory cortex, instead, the excitability of the secondary somatosensory cortex is increased. Third, participants with abnormal vision had a higher amplitude of the P1 visual ERP when a tactile stimulus was presented concurrently. Importantly, these results were not modulated by viewing condition, which indicates that the impact of amblyopia on crossmodal interactions is not simply related to the reduced visual acuity as it was evident when viewing with the unaffected eye and binocularly. These results indicate that the consequences of abnormal visual experience on neurophysiological processing extend beyond the primary and secondary visual areas to other modality-specific areas.

Should doxylamine-pyridoxine be used for nausea and vomiting of pregnancy?

Doxylamine-pyridoxine is the first-line agent for the treatment of nausea and vomiting of pregnancy (NVP) according to Canadian guidelines, and this combination is commonly prescribed to pregnant women. There is limited evidence that doxylamine-pyridoxine is more effective than pyridoxine alone. There is stronger support for the safety of pyridoxine monotherapy than for the combination of doxylamine-pyridoxine during pregnancy, and some conflicting evidence links doxylamine-pyridoxine use to pyloric stenosis and childhood malignancies. The role of doxylamine-pyridoxine as the first-line pharmacological treatment for NVP in Canada should be reconsidered.

La combinaison doxylamine-pyridoxine constitue l'agent de première intention à utiliser pour la prise en charge de la nausée et des vomissements de la grossesse (NVG), selon les lignes directrices canadiennes traitant de la question, et cette combinaison est couramment prescrite aux femmes enceintes. Les données qui indiquent que la combinaison doxylamine-pyridoxine est plus efficace que la pyridoxine utilisée seule sont limitées. En fait, les données qui soutiennent l'innocuité de la monothérapie à la pyridoxine pendant la grossesse sont plus solides que les données qui soutiennent celle de la combinaison doxylamine-pyridoxine; de plus, certaines données contradictoires établissent des liens entre la combinaison doxylamine-pyridoxine et les tumeurs malignes de l'enfance et la sténose du pylore. Le rôle de la combinaison doxylamine-pyridoxine à titre de traitement pharmacologique de première intention pour contrer la nausée et les vomissements de la grossesse au Canada devrait être remis en question.

Prostate cancer derived prostatic acid phosphatase promotes an osteoblastic response in the bone microenvironment.

Approximately 90 % of patients who die of prostate cancer (PCa) have bone metastases, often promoting osteoblastic lesions. We observed that 88 % of castration-resistant PCa (CRPC) bone metastases express prostatic acid phosphatase (PAP), a soluble secreted protein expressed by prostate epithelial cells in predominately osteoblastic (n = 18) or osteolytic (n = 15) lesions. Additionally, conditioned media (CM) of an osteoblastic PCa xenograft LuCaP 23.1 contained significant levels of PAP and promoted mineralization in mouse and human calvaria-derived cells (MC3T3-E1 and HCO). To demonstrate that PAP promotes mineralization, we stimulated MC3T3-E1 cells with PAP and observed increased mineralization, which could be blocked with the specific PAP inhibitor, phosphonic acid. Furthermore, the mineralization promoted by LuCaP 23.1 CM was also blocked by phosphonic acid, suggesting PAP is responsible for the mineralization promoting activity of LuCaP 23.1. In addition, gene expression arrays comparing osteoblastic to osteolytic CRPC (n = 14) identified betacellulin (BTC) as a gene upregulated during the osteoblastic response in osteoblasts during new bone formation. Moreover, BTC levels were increased in bone marrow stromal cells in response to LuCaP 23.1 CM in vitro. Because new bone formation does occur in osteoblastic and can occur in osteolytic CRPC bone metastases, we confirmed by immunohistochemistry (n = 36) that BTC was highly expressed in osteoblasts involved in new bone formation occurring in both osteoblastic and osteolytic sites. These studies suggest a role for PAP in promoting the osteoblastic reaction in CRPC bone metastases and identify BTC as a novel downstream protein expressed in osteoblasts during new bone formation.

Re-analysis of safety data supporting doxylamine use for nausea and vomiting of pregnancy.

Antihistamines are commonly used to treat nausea and vomiting of pregnancy (NVP). We re-analyzed the 24 primary studies cited in a 1997 meta-analysis that concluded antihistamine use for NVP was safe as they had been studied in more than 200,000 participating women and the pooled odds ratio for congenital malformations was 0.76 (95% confidence interval [CI]: 0.60-0.94). Our analysis of this meta-analysis showed that 139,414 women were included in 22 original studies involving antihistamines, 129,108 of which were in studies involving doxylamine. In these studies, 23,485 women were exposed to antihistamines, 14,624 of which were exposed to doxylamine. The summary relative risk (cohort studies) and odds ratio (case-control studies) for congenital malformations from antihistamine exposure were 1.09 (95% CI: 1.01-1.18) and 1.04 (95% CI: 0.91-1.19), and for doxylamine exposure, the summary relative risk and odds ratio were 0.94 (95% CI: 0.80-1.10) and 1.07 (95% CI: 0.93-1.23), respectively. Although not a new systematic review, our re-analysis demonstrates that the safety data for antihistamines, and doxylamine in particular, are based on many fewer than 200,000 participating women and exposures, and that doxylamine use is not associated with a decreased risk of malformations as previously reported.

Genomic comparison of Salmonella typhimurium DT104 with non-DT104 strains.

DT104 emerged as a new branch of Salmonella typhimurium with resistance to multiple antimicrobials. To reveal some general genomic features of DT104 for clues of evolutionary events possibly associated with the emergence of this relatively new type of this pathogen, we mapped 11 independent DT104 strains and compared them with non-DT104 S. typhimurium strains. We found that all 11 DT104 strains contained three insertions absent in non-DT104 strains, i.e., the previously reported ST104, ST104B and ST64B. However, SGI-1, a genomic island known to be responsible for DT104 multidrug resistance, was not present in all DT104 strains examined in this study: one DT104 strain did not contain SGI-1 but carried a 144 kb plasmid, suggesting possible evolutionary relationships between the two DNA elements in the development of antimicrobial resistance.