Combining activity and grimace scores reflects perinatal stability in infants <32 weeks gestational age.

BACKGROUND: Over 95% of infants less than 32 weeks gestational age-very preterm infants (VPTI)-require cardiorespiratory support at birth. Clinical condition at birth is assessed by the Apgar score, but the precision and accuracy of activity and grimace has not been evaluated. We hypothesised activity and grimace could predict the level of cardiorespiratory support required for stabilisation. METHODS: Two hundred twenty-nine videos of VPTI resuscitations at Monash Children's Hospital and The Royal Women's Hospital, Melbourne were evaluated, with 78 videos eligible for assessment. Activity and grimace were scored (0, 1, or 2) by seven consultant neonatologists, with inter-rater reliability assessed. Activity and grimace were correlated with the maximum level of cardiorespiratory support required for stabilisation. RESULTS: Kendall's Coefficient of Concordance (W) showed strong interobserver agreement for activity (W = 0.644, p < 0.001) and grimace (W = 0.722, p < 0.001). Neither activity nor grimace independently predicted the level of cardiorespiratory support required. Combining activity and grimace showed non-vigorous infants (combined score <2) received more cardiorespiratory support than vigorous (combined score ≥ 2). CONCLUSION: Scoring of activity and grimace was consistent between clinicians. Independently, activity and grimace did not correlate with perinatal stabilisation. Combined scoring showed non-vigorous infants had greater resuscitation requirements. IMPACT: Our study evaluates the precision and accuracy of activity and grimace to predict perinatal stability, which has not been validated in infants <32 weeks gestational age. We found strong score agreement between assessors, indicating video review is a practical and precise method for grading of activity and grimace. Combined scoring to allow a dichotomous evaluation of infants as non-vigorous or vigorous showed the former group required greater cardiorespiratory support at birth.

Dexmedetomidine for analgesia and sedation in newborn infants receiving mechanical ventilation.

BACKGROUND: Dexmedetomidine is a selective alpha-2 agonist with minimal impact on the haemodynamic profile. It is thought to be safer than morphine or stronger opioids, which are drugs currently used for analgesia and sedation in newborn infants. Dexmedetomidine is increasingly being used in children and infants despite not being licenced for analgesia in this group. OBJECTIVES: To determine the overall effectiveness and safety of dexmedetomidine for sedation and analgesia in newborn infants receiving mechanical ventilation compared with other non-opioids, opioids, or placebo. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, CINAHL, and two trial registries in September 2023. SELECTION CRITERIA: We planned to include randomised controlled trials (RCTs) and quasi-RCTs evaluating the effectiveness of dexmedetomidine compared with other non-opioids, opioids, or placebo for sedation and analgesia in neonates (aged under four weeks) requiring mechanical ventilation. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were level of sedation and level of analgesia. Our secondary outcomes included days on mechanical ventilation, number of infants requiring additional medication for sedation or analgesia (or both), hypotension, neonatal mortality, and neurodevelopmental outcomes. We planned to use GRADE to assess the certainty of evidence for each outcome. MAIN RESULTS: We identified no eligible studies for inclusion. We identified four ongoing studies, two of which appear to be eligible for inclusion; they will compare dexmedetomidine with fentanyl in newborn infants requiring surgery. We listed the other two studies as awaiting classification pending assessment of full reports. One study will compare dexmedetomidine with morphine in asphyxiated newborns undergoing hypothermia, and the other (mixed population, age up to three years) will evaluate dexmedetomidine versus ketamine plus dexmedetomidine for echocardiography. The planned sample size of the four studies ranges from 40 to 200 neonates. Data from these studies may provide some evidence for dexmedetomidine efficacy and safety. AUTHORS' CONCLUSIONS: Despite the increasing use of dexmedetomidine, there is insufficient evidence supporting its routine use for analgesia and sedation in newborn infants on mechanical ventilation. Furthermore, data on dexmedetomidine safety are scarce, and there are no data available on its long-term effects. Future studies should address the efficacy, safety, and long-term effects of dexmedetomidine as a single drug therapy for sedation and analgesia in newborn infants.

Effect of botulinum toxin type A on muscular temporomandibular disorder: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Botulinum toxin type A (BTX-A) is increasingly used to manage painful temporomandibular disorders (TMD). However, the effect of BTX-A on muscular TMD remains unclear. OBJECTIVE: To assess the efficacy, safety and optimal dose of BTX-A for treating TMD. METHODS: We conducted systematic literature searches in MEDLINE, Embase, Web of Science, ClinicalTrials.gov and Cochrane Library until March 2023. We extracted data from randomized controlled trials (RCTs) that evaluated the efficacy and safety of BTX-A in treating muscular TMD. We performed a meta-analysis using a random-effects model. RESULTS: Fifteen RCTs involving 504 participants met the inclusion criteria. BTX-A was significantly more effective than placebo in reducing pain intensity, as measured on a 0-10 scale, at 1 month (MD [95% CI] = -1.92 [-2.87, -0.98], p < .0001) and 6 months (MD [95% CI] -2.08, [-3.19 to -0.98]; p = .0002). A higher dosage of BTX-A (60-100 U bilaterally) was associated with a greater reduction in pain at 6 months (MD [95% CI] = -2.98 [-3.52, -2.44]; p < .001). BTX-A also resulted in decreased masseter muscle intensity (µV) (MD [95% CI] = -44.43 [-71.33, -17.53]; p = .001) at 1 month and occlusal force (kg) at 3 months (MD [95% CI] = -30.29 [-48.22 to -12.37]; p = .0009). There was no significant difference in adverse events between BTX-A and placebo. CONCLUSIONS: BTX-A is a safe and effective treatment for reducing pain and improving temporomandibular muscle and joint function in muscular TMD patients. A bilateral dose of 60-100 U might be an optimal choice for treating muscular TMD pain.

A bibliometric study of worldwide scientific literature on somatopsychics (1913‒2022).

OBJECTIVES: This investigation aims to analyze the characteristics and development of literature and advocate to include "Somatopsychic" as a Medical Subject Headings (MeSH) term. BACKGROUND: The interplay between physiological processes and psychological conditions, commonly referred to as "Somatopsychic," has garnered increasing attention in scientific literature over the years. METHODS: Somatopsychic-related research from the Scopus database using (Text word) and (MeSH) features. Publications were collected on Mar 22, 2023. The publication output was then analyzed using the R package's bibliometrics (Biblioshiny) and VOSviewer. RESULTS: In this study, search results for "somatopsychic" using (MeSH) resulted in a predictable return of 0 articles. Meanwhile, based on a search with (Text word), this study retrieved 306 documents for an unlimited period (and yielded published articles between 1913 and 2022). The analysis also revealed that 3,176 authors contributed to publications related to somatopsychic, with the United States ranking first in terms of authorship. In addition, the study presented a co-word network that illustrated frequent co-occurrence of particular keywords within somatopsychic research. CONCLUSION: This study reveals that somatopsychic-related publications are becoming increasingly prevalent. Adding somatopsychic as a dedicated term to the MeSH thesaurus of the National Library of Medicine would assist in indexing and retrieving the most pertinent literature on this topic (Tab. 3, Fig. 5, Ref. 51).

Efficacy of adjunctive octenidine hydrochloride as compared to chlorhexidine and placebo as adjuncts to instrumentation in stage I-II periodontitis: A double-blinded randomized controlled trial.

OBJECTIVES: This randomized, controlled, double-blinded clinical trial aimed to evaluate the efficacy of octenidine hydrochloride and chlorhexidine mouthwashes as adjuncts to instrumentation in stage I-II periodontitis patients. METHODS: Forty-five patients with mild-to-moderate periodontitis were randomly allocated to three groups: 0.1% octenidine dihydrochloride (OCT), placebo, and 0.12% chlorhexidine (CHX) mouthwashes. Patients were instructed to use the mouthwash after instrumentation for twice a day up to 3 weeks. Periodontal parameters such as probing pocket depth (PPD), clinical attachment loss (CAL), O'Leary plaque index (PI), Loe and Silness gingival index (GI), Lobene stain index (SI), and oral soft tissue changes were recorded at baseline and once every week for 3 weeks. The visual analogue scale (VAS) was also recorded as a self-administered questionnaire at the end of the study. The one-way ANOVA was used to compare VAS scores between the groups. The repeated measures ANOVA and post hoc Newman-Keuls tests were used to assess the differences in the periodontal parameters between groups at different time intervals. The Kruskal-Wallis test was used to compare the mean SI. RESULTS: There was a significant reduction in the mean GI of the OCT and CHX groups compared to placebo (p < 0.05). OCT usage resulted in significantly less staining, according to mean SI, when compared to CHX. Furthermore, VAS scores revealed that OCT was significantly the preferred mouthwash (p < 0.01). CONCLUSION: Adjunctive octenidine hydrochloride may be an alternative to chlorhexidine in its ability to control the periodontal parameters in patients with stage I-II periodontitis. Further larger studies are necessary to confirm these findings.

The Role of Humor Production and Perception in the Daily Life of Couples: An Interest-Indicator Perspective.

In established relationships, are couples who are funny more satisfied with each other, or are satisfied couples more able to see the funny side of their partners? Much research has examined the evolutionary function of humor in relationship initiation, but not in relationship maintenance. Using a dyadic daily-diary study composed of college students from Singapore, results showed that relationship quality was positively associated with same-day humor production and perception. Importantly, and consistent with an interest-indicator perspective in which humor exchanges communicate relationship interest, relationship quality was also positively associated with next-day humor production and perception, and across both sexes. Results also indicated some support for a sexual-selection perspective in which humor exchanges predicted only same- and next-day satisfaction, but not commitment. Our findings suggest that humor can ultimately function as a strategy to monitor and maintain established relationships.

Early neurodevelopmental outcomes of extreme preterm infants exposed to paracetamol: a retrospective cohort study.

BACKGROUND: Paracetamol is commonly used for analgesia and patent ductus arteriosus (PDA) treatment in preterm infants. We aimed to evaluate early neurodevelopmental outcomes of extreme preterm infants exposed to paracetamol during their neonatal admission. METHODS: This retrospective cohort study included surviving infants born at <29 weeks gestation, or with a birth weight of <1000 grams. Neurodevelopmental outcomes studied were early cerebral palsy (CP) or high risk of CP diagnosis, Hammersmith Infant Neurological Examination (HINE) score and Prechtl General Movement Assessment (GMA) at 3-4 months corrected age. RESULTS: Two hundred and forty-two infants were included, of which 123 were exposed to paracetamol. After adjusting for birth weight, sex and chronic lung disease, there were no significant associations between paracetamol exposure and early CP or high risk of CP diagnosis (aOR 1.46, 95% CI 0.61, 3.5), abnormal or absent GMA (aOR 0.82, 95% CI 0.37, 1.79) or HINE score (adjusted ß -0.19, 95% CI -2.39, 2.01). Subgroup analysis stratifying paracetamol exposure into <180 mg/kg or ≥180 mg/kg cumulative dose found that neither had significant effects on outcomes. CONCLUSIONS: In this cohort of extreme preterm infants, no significant association was found between exposure to paracetamol during the neonatal admission and adverse early neurodevelopment. IMPACT: Paracetamol is commonly used in the neonatal period for analgesia and patent ductus arteriosus treatment in preterm infants, although prenatal paracetamol use has been associated with adverse neurodevelopmental outcomes. Exposure to paracetamol during the neonatal admission was not associated with adverse early neurodevelopment at 3-4 months corrected age in this cohort of extreme preterm infants. The findings from this observational study is consistent with the small body of literature supporting the lack of association between neonatal paracetamol exposure and adverse neurodevelopmental outcomes in preterm infants.

Automated oxygen delivery for preterm infants with respiratory dysfunction.

BACKGROUND: Many preterm infants require respiratory support to maintain an optimal level of oxygenation, as oxygen levels both below and above the optimal range are associated with adverse outcomes. Optimal titration of oxygen therapy for these infants presents a major challenge, especially in neonatal intensive care units (NICUs) with suboptimal staffing. Devices that offer automated oxygen delivery during respiratory support of neonates have been developed since the 1970s, and individual trials have evaluated their effectiveness. OBJECTIVES: To assess the benefits and harms of automated oxygen delivery systems, embedded within a ventilator or oxygen delivery device, for preterm infants with respiratory dysfunction who require respiratory support or supplemental oxygen therapy. SEARCH METHODS: We searched CENTRAL, MEDLINE, CINAHL, and clinical trials databases without language or publication date restrictions on 23 January 2023. We also checked the reference lists of retrieved articles for other potentially eligible trials. SELECTION CRITERIA: We included randomised controlled trials and randomised cross-over trials that compared automated oxygen delivery versus manual oxygen delivery, or that compared different automated oxygen delivery systems head-to-head, in preterm infants (born before 37 weeks' gestation). DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our main outcomes were time (%) in desired oxygen saturation (SpO2) range, all-cause in-hospital mortality by 36 weeks' postmenstrual age, severe retinopathy of prematurity (ROP), and neurodevelopmental outcomes at approximately two years' corrected age. We expressed our results using mean difference (MD), standardised mean difference (SMD), and risk ratio (RR) with 95% confidence intervals (CIs). We used GRADE to assess the certainty of evidence. MAIN RESULTS: We included 18 studies (27 reports, 457 infants), of which 13 (339 infants) contributed data to meta-analyses. We identified 13 ongoing studies. We evaluated three comparisons: automated oxygen delivery versus routine manual oxygen delivery (16 studies), automated oxygen delivery versus enhanced manual oxygen delivery with increased staffing (three studies), and one automated system versus another (two studies). Most studies were at low risk of bias for blinding of personnel and outcome assessment, incomplete outcome data, and selective outcome reporting; and half of studies were at low risk of bias for random sequence generation and allocation concealment. However, most were at high risk of bias in an important domain specific to cross-over trials, as only two of 16 cross-over trials provided separate outcome data for each period of the intervention (before and after cross-over). Automated oxygen delivery versus routine manual oxygen delivery Automated delivery compared with routine manual oxygen delivery probably increases time (%) in the desired SpO2 range (MD 13.54%, 95% CI 11.69 to 15.39; I2 = 80%; 11 studies, 284 infants; moderate-certainty evidence). No studies assessed in-hospital mortality. Automated oxygen delivery compared to routine manual oxygen delivery may have little or no effect on risk of severe ROP (RR 0.24, 95% CI 0.03 to 1.94; 1 study, 39 infants; low-certainty evidence). No studies assessed neurodevelopmental outcomes. Automated oxygen delivery versus enhanced manual oxygen delivery There may be no clear difference in time (%) in the desired SpO2 range between infants who receive automated oxygen delivery and infants who receive manual oxygen delivery (MD 7.28%, 95% CI -1.63 to 16.19; I2 = 0%; 2 studies, 19 infants; low-certainty evidence). No studies assessed in-hospital mortality, severe ROP, or neurodevelopmental outcomes. Revised closed-loop automatic control algorithm (CLACfast) versus original closed-loop automatic control algorithm (CLACslow) CLACfast allowed up to 120 automated adjustments per hour, whereas CLACslow allowed up to 20 automated adjustments per hour. CLACfast may result in little or no difference in time (%) in the desired SpO2 range compared to CLACslow (MD 3.00%, 95% CI -3.99 to 9.99; 1 study, 19 infants; low-certainty evidence). No studies assessed in-hospital mortality, severe ROP, or neurodevelopmental outcomes. OxyGenie compared to CLiO2 Data from a single small study were presented as medians and interquartile ranges and were not suitable for meta-analysis. AUTHORS' CONCLUSIONS: Automated oxygen delivery compared to routine manual oxygen delivery probably increases time in desired SpO2 ranges in preterm infants on respiratory support. However, it is unclear whether this translates into important clinical benefits. The evidence on clinical outcomes such as severe retinopathy of prematurity are of low certainty, with little or no differences between groups. There is insufficient evidence to reach any firm conclusions on the effectiveness of automated oxygen delivery compared to enhanced manual oxygen delivery or CLACfast compared to CLACslow. Future studies should include important short- and long-term clinical outcomes such as mortality, severe ROP, bronchopulmonary dysplasia/chronic lung disease, intraventricular haemorrhage, periventricular leukomalacia, patent ductus arteriosus, necrotising enterocolitis, and long-term neurodevelopmental outcomes. The ideal study design for this evaluation is a parallel-group randomised controlled trial. Studies should clearly describe staffing levels, especially in the manual arm, to enable an assessment of reproducibility according to resources in various settings. The data of the 13 ongoing studies, when made available, may change our conclusions, including the implications for practice and research.

Oxygen saturation levels and retinopathy of prematurity in extremely preterm infants - a case control study.

PURPOSE: To investigate the association of risk factors, including oxygen exposure, for developing retinopathy of prematurity (ROP) in preterm infants at increased risk of ROP. METHODS: A case-control study was conducted where each infant born at < 28 weeks gestation with ROP was matched with another without ROP over five years (July 2015 - June 2020). Clinical information about the infants was collected from electronic medical records, including method of oxygen delivery, oxygen saturation (SpO2), fraction of inspired oxygen (FiO2) and mean airway pressure (MAP) measurements. MATLAB was used for a time-averaged analysis. Stata/SE 16.0 was used for statistical analysis. RESULTS: 123 ROP/non-ROP pairs were included in this study. The time-averaged SpO2 analysis showed non-ROP group spent more time in hyperoxia than the ROP group (p < 0.001). The non-ROP group had lower respiratory severity scores and analysis when FiO2 > 21% showed that were was no difference in SpO2 between the two groups when the infants were receiving oxygen support. Conditional logistic regressions showed neonatal surgery significantly increased the risk of ROP (OR = 1.4347, p = 0.010), while the influence of birthweight (odds ratio of 0.9965, p = 0.001) and oxygen exposure (OR = 0.9983, p = 0.012) on ROP outcome was found to be negligible as their odds ratios indicated no influence. CONCLUSIONS: At times when infants were receiving respiratory support (FiO2 > 21%) the SpO2 data indicated no difference in SpO2 between the ROP and non-ROP groups. Analysis of clinical variables found that neonatal surgery increased the odds of developing ROP.

Social anhedonia, communication, and marital satisfaction in newlywed couples.

OBJECTIVE: Social anhedonia is associated with disinterest in social interactions and poor relationship functioning, yet little is known about the specific mechanisms underlying associations between social anhedonia and romantic relationship behaviors and satisfaction. We examined the links between social anhedonia, perceptions of conflict communication patterns, and marital satisfaction. METHOD: The current research examined the role of social anhedonia on marital quality and functioning longitudinally across a year in a sample of 100 newlywed couples using an actor-partner interdependence framework. RESULTS: Social anhedonia was negatively associated with own and partner's marital satisfaction. It was also negatively associated with constructive communication and positively associated with destructive communication. Furthermore, cross-sectional mediation analyses showed that communication patterns mediated the social anhedonia-satisfaction link. CONCLUSIONS: Taken together, these findings suggest that social anhedonia is likely to lead to lower marital satisfaction, partly through its effect on communication between partners.

The long and short of mistress relationships: Sex-differentiated mate preferences reflect a compromise of mating ideals.

OBJECTIVE: Evolved mate preferences have taken center stage in evolutionary psychology research, yet this literature has been fairly muted on mate preferences for extrapair partners. Here, we examined the mate preferences for mistress relationships (the traits that men prioritize in a mistress and mistresses prioritize in their male partners) and compared these preferences to those of short- and long-term relationships. METHOD: In two studies (NStudy 1a  = 104, NStudy 1b  = 191), we derived dimensions of mate preferences through exploratory factor analyses. In subsequent studies (NStudy 2  = 219, NStudy 3  = 101), we employed a budget allocation paradigm, where participants designed their ideal mates for different relationship types (short-term, long-term, and mistress relationships). RESULTS: Whereas men focused on fulfilling short-term mating ideals (by prioritizing physical attractiveness) in a mistress relationship, women focused on fulfilling long-term (but also some short-term) mating ideals (prioritizing both physical attractiveness and social status) for a mistress relationship. CONCLUSION: Findings indicate that mistress relationships reflect a compromise of men's and women's (conflicting) mating ideals and contribute to an understanding of relationships that are neither completely short- nor long-term in nature.

Deep Learning System Outperforms Clinicians in Identifying Optic Disc Abnormalities.

BACKGROUND: The examination of the optic nerve head (optic disc) is mandatory in patients with headache, hypertension, or any neurological symptoms, yet it is rarely or poorly performed in general clinics. We recently developed a brain and optic nerve study with artificial intelligence-deep learning system (BONSAI-DLS) capable of accurately detecting optic disc abnormalities including papilledema (swelling due to elevated intracranial pressure) on digital fundus photographs with a comparable classification performance to expert neuro-ophthalmologists, but its performance compared to first-line clinicians remains unknown. METHODS: In this international, cross-sectional multicenter study, the DLS, trained on 14,341 fundus photographs, was tested on a retrospectively collected convenience sample of 800 photographs (400 normal optic discs, 201 papilledema and 199 other abnormalities) from 454 patients with a robust ground truth diagnosis provided by the referring expert neuro-ophthalmologists. The areas under the receiver-operating-characteristic curves were calculated for the BONSAI-DLS. Error rates, accuracy, sensitivity, and specificity of the algorithm were compared with those of 30 clinicians with or without ophthalmic training (6 general ophthalmologists, 6 optometrists, 6 neurologists, 6 internists, 6 emergency department [ED] physicians) who graded the same testing set of images. RESULTS: With an error rate of 15.3%, the DLS outperformed all clinicians (average error rates 24.4%, 24.8%, 38.2%, 44.8%, 47.9% for general ophthalmologists, optometrists, neurologists, internists and ED physicians, respectively) in the overall classification of optic disc appearance. The DLS displayed significantly higher accuracies than 100%, 86.7% and 93.3% of clinicians (n = 30) for the classification of papilledema, normal, and other disc abnormalities, respectively. CONCLUSIONS: The performance of the BONSAI-DLS to classify optic discs on fundus photographs was superior to that of clinicians with or without ophthalmic training. A trained DLS may offer valuable diagnostic aid to clinicians from various clinical settings for the screening of optic disc abnormalities harboring potentially sight- or life-threatening neurological conditions.

Impact of smoking on donor site following rectus flap harvest for head and neck reconstruction.

OBJECTIVES: The rectus abdominis myocutaneous free flap has been widely used as a reconstructive option in head and neck reconstruction with great success. Challenging the popular assumption, this study sought to examine the effects of smoking on donor site complications in this population. METHODS: Multi-institution retrospective study of 103 patients (50 active smokers, 28 former and 25 never smoked). RESULTS: Overall complication rate was 14.5 %. Hernia rate 4.8 %, evisceration 0 %, dehiscence 2.9 %, infection 6.7 %. Smoking history did not significantlly influence complication rates (chi square test, p = 0.33). Abdominal wall closure technique also did not influence the complication rate (chi square test, p = 0.58). CONCLUSIONS: The rectus abdomonis myocutaneous free flap has an acceptable complication rate that does not appear to be influenced by smoking history. While patients should be counseled regarding smoking cessation, smoking habits should not delay treatment nor obviate consideration of rectus flap utilization.

Diversity and Biosynthetic Potential of Fungi Isolated from St. John's Island, Singapore.

Adaptation to a wide variety of habitats allows fungi to develop unique abilities to produce diverse secondary metabolites with diverse bioactivities. In this study, 30 Ascomycetes fungi isolated from St. John's Island, Singapore were investigated for their general biosynthetic potential and their ability to produce antimicrobial secondary metabolites (SMs). All the 30 fungal isolates belong to the Phylum Ascomycota and are distributed into 6 orders and 18 genera with Order Hypocreales having the highest number of representative (37%). Screening for polyketide synthase (PKS) and nonribosomal peptide synthetase (NRPS) genes using degenerate PCR led to the identification of 23 polyketide synthases (PKSs) and 5 nonribosomal peptide synthetases (NRPSs) grouped into nine distinct clades based on their reduction capabilities. Some of the identified PKSs genes share high similarities between species and known reference genes, suggesting the possibility of conserved biosynthesis of closely related compounds from different fungi. Fungal extracts were tested for their antimicrobial activity against S. aureus, Methicillin-resistant S. aureus (MRSA), and Candida albicans. Bioassay-guided fractionation of the active constituents from two promising isolates resulted in the isolation of seven compounds: Penilumamides A, D, and E from strain F4335 and xanthomegnin, viomellein, pretrichodermamide C and vioxanthin from strain F7180. Vioxanthin exhibited the best antibacterial activity with IC50 values of 3.0 µM and 1.6 µM against S. aureus and MRSA respectively. Viomellein revealed weak antiproliferative activity against A549 cells with an IC50 of 42 µM. The results from this study give valuable insights into the diversity and biosynthetic potential of fungi from this unique habitat and forms a background for an in-depth analysis of the biosynthetic capability of selected strains of interest with the aim of discovering novel fungal natural products.

Use of extracorporeal membrane oxygenation in massive amlodipine overdose.

Calcium-channel blocker overdose can result in profound vasoplegia and cardiogenic shock, which can quickly spiral into multi-organ failure and death. In this case report, we discuss two separate cases of massive amlodipine overdose with polydrug intoxication (Patient A: amlodipine and quetiapine; Patient B: amlodipine, fluoxetine and zopiclone), both of which were complicated by life-threatening vasoplegic shock refractory to supportive therapy (endotracheal intubation, fluid resuscitation, activated charcoal, vasopressors and inotropes), multimodal antidotes (calcium and hyper-insulinemic euglycemic therapy) and even second-line treatment (methylene blue and therapeutic plasma exchange). Despite exhausting all therapeutic options, resuscitation remained futile with no clinical response elicited until veno-arterial extracorporeal membrane oxygenation (ECMO) salvage therapy was initiated in both cases as a bridge-to-recovery. Albumin dialysis was also commenced to further enhance elimination of amlodipine given its high plasma protein-binding properties. Both patients improved drastically once perfusion to vital organs was maintained by ECMO and eventually survived with good neurological outcomes and preserved cardiac contractility on discharge. This case report supports the growing evidence that although ECMO support represents a potentially life-saving salvage therapy for refractory poisoning-induced shock, escalation to ECMO must be considered and instituted early before irreversible multi-organ failure sets in to ensure good clinical outcomes.

Rapid exome sequencing and adjunct RNA studies confirm the pathogenicity of a novel homozygous ASNS splicing variant in a critically ill neonate.

Rapid genomic diagnosis programs are transforming rare disease diagnosis in acute pediatrics. A ventilated newborn with cerebellar hypoplasia underwent rapid exome sequencing (75 h), identifying a novel homozygous ASNS splice-site variant (NM_133436.3:c.1476+1G>A) of uncertain significance. Rapid ASNS splicing studies using blood-derived messenger RNA from the family trio confirmed a consistent pattern of abnormal splicing induced by the variant (cryptic 5' splice-site or exon 12 skipping) with absence of normal ASNS splicing in the proband. Splicing studies reported within 10 days led to reclassification of c.1476+1G>A as pathogenic at age 27 days. Intensive care was redirected toward palliation. Cost analyses for the neonate and his undiagnosed, similarly affected deceased sibling, demonstrate that early diagnosis reduced hospitalization costs by AU$100,828. We highlight the diagnostic benefits of adjunct RNA testing to confirm the pathogenicity of splicing variants identified via rapid genomic testing pipelines for precision and preventative medicine.

Docosahexaenoic Acid and Bronchopulmonary Dysplasia in Preterm Infants.

BACKGROUND: Studies in animals and in humans have suggested that docosahexaenoic acid (DHA), an n-3 long-chain polyunsaturated fatty acid, might reduce the risk of bronchopulmonary dysplasia, but appropriately designed trials are lacking. METHODS: We randomly assigned 1273 infants born before 29 weeks of gestation (stratified according to sex, gestational age [<27 weeks or 27 to <29 weeks], and center) within 3 days after their first enteral feeding to receive either an enteral emulsion providing DHA at a dose of 60 mg per kilogram of body weight per day or a control (soy) emulsion without DHA until 36 weeks of postmenstrual age. The primary outcome was bronchopulmonary dysplasia, defined on a physiological basis (with the use of oxygen-saturation monitoring in selected infants), at 36 weeks of postmenstrual age or discharge home, whichever occurred first. RESULTS: A total of 1205 infants survived to the primary outcome assessment. Of the 592 infants assigned to the DHA group, 291 (49.1% by multiple imputation) were classified as having physiological bronchopulmonary dysplasia, as compared with 269 (43.9%) of the 613 infants assigned to the control group (relative risk adjusted for randomization strata, 1.13; 95% confidence interval [CI], 1.02 to 1.25; P=0.02). The composite outcome of physiological bronchopulmonary dysplasia or death before 36 weeks of postmenstrual age occurred in 52.3% of the infants in the DHA group and in 46.4% of the infants in the control group (adjusted relative risk, 1.11; 95% CI, 1.00 to 1.23; P=0.045). There were no significant differences between the two groups in the rates of death or any other neonatal illnesses. Bronchopulmonary dysplasia based on a clinical definition occurred in 53.2% of the infants in the DHA group and in 49.7% of the infants in the control group (P=0.06). CONCLUSIONS: Enteral DHA supplementation at a dose of 60 mg per kilogram per day did not result in a lower risk of physiological bronchopulmonary dysplasia than a control emulsion among preterm infants born before 29 weeks of gestation and may have resulted in a greater risk. (Funded by the Australian National Health and Medical Research Council and others; Australian New Zealand Clinical Trials Registry number, ACTRN12612000503820 .).

Assessment of breath sounds at birth using digital stethoscope technology.

Newborn transition is a phase of complex change involving lung fluid clearance and lung aeration. We aimed to use a digital stethoscope (DS) to assess the change in breath sound characteristics over the first 2 h of life and its relationship to mode of delivery. A commercially available DS was used to record breath sounds of term newborns at 1-min and 2-h post-delivery via normal vaginal delivery (NVD) or elective caesarean section (CS). Sound analysis was conducted, and two comparisons were carried out: change in frequency profiles over 2 h, and effect of delivery mode. There was a significant drop in the frequency profile of breath sounds from 1 min to 2 h with mean (SD) frequency decreasing from 333.74 (35.42) to 302.71 (47.19) Hz, p < 0.001, and proportion of power (SD) in the lowest frequency band increasing from 0.27 (0.11) to 0.37 (0.15), p < 0.001. At 1 min, NVD infants had slightly higher frequency than CS but no difference at 2 h.Conclusion: We were able to use DS technology in the transitioning infant to depict significant changes to breath sound characteristics over the first 2 h of life, reflecting the process of lung aeration.What is Known:• Lung fluid clearance and lung aeration are critical processes that facilitate respiration and mode of delivery can impact this• Digital stethoscopes offer enhanced auscultation and have been used in the paediatric population for the assessment of pulmonary and cardiac soundsWhat is New:• This is the first study to use digital stethoscope technology to assess breath sounds at birth• We describe a change in breath sound characteristics over the first 2 h of life and suggest a predictive utility of this analysis to predict the development of respiratory distress in newborns prior to the onset of symptoms.

Emergency department 'outbreak rostering' to meet challenges of COVID-19.

The COVID-19 outbreak has posed unique challenges to the emergency department rostering. Additional infection control, the possibility of quarantine of staff and minimising contact among staff have significant impact on the work of doctors in the emergency department. Infection of a single healthcare worker may require quarantine of close contacts at work. This may thus affect a potentially large number of staff. As such, we developed an Outbreak Response Roster. This Outbreak Response Roster had fixed teams of doctors working in rotation, each team that staff the emergency department in turn. Members within teams remained constant and were near equally balanced in terms of manpower and seniority of doctors. Each team worked fixed 12 hours shifts with as no overlapping of staff or staggering of shifts. Handovers between shifts were kept as brief as possible. All these were measures to limit interactions among healthcare workers. With the implementation of the roster, measures were also taken to bolster the psychological wellness of healthcare workers. With face-to-face contact limited, we also had to maintain clear, open channels for communication through technology and continue educating residents through innovative means.

Outcomes of Two Trials of Oxygen-Saturation Targets in Preterm Infants.

BACKGROUND: The safest ranges of oxygen saturation in preterm infants have been the subject of debate. METHODS: In two trials, conducted in Australia and the United Kingdom, infants born before 28 weeks' gestation were randomly assigned to either a lower (85 to 89%) or a higher (91 to 95%) oxygen-saturation range. During enrollment, the oximeters were revised to correct a calibration-algorithm artifact. The primary outcome was death or disability at a corrected gestational age of 2 years; this outcome was evaluated among infants whose oxygen saturation was measured with any study oximeter in the Australian trial and those whose oxygen saturation was measured with a revised oximeter in the U.K. trial. RESULTS: After 1135 infants in Australia and 973 infants in the United Kingdom had been enrolled in the trial, an interim analysis showed increased mortality at a corrected gestational age of 36 weeks, and enrollment was stopped. Death or disability in the Australian trial (with all oximeters included) occurred in 247 of 549 infants (45.0%) in the lower-target group versus 217 of 545 infants (39.8%) in the higher-target group (adjusted relative risk, 1.12; 95% confidence interval [CI], 0.98 to 1.27; P=0.10); death or disability in the U.K. trial (with only revised oximeters included) occurred in 185 of 366 infants (50.5%) in the lower-target group versus 164 of 357 infants (45.9%) in the higher-target group (adjusted relative risk, 1.10; 95% CI, 0.97 to 1.24; P=0.15). In post hoc combined, unadjusted analyses that included all oximeters, death or disability occurred in 492 of 1022 infants (48.1%) in the lower-target group versus 437 of 1013 infants (43.1%) in the higher-target group (relative risk, 1.11; 95% CI, 1.01 to 1.23; P=0.02), and death occurred in 222 of 1045 infants (21.2%) in the lower-target group versus 185 of 1045 infants (17.7%) in the higher-target group (relative risk, 1.20; 95% CI, 1.01 to 1.43; P=0.04). In the group in which revised oximeters were used, death or disability occurred in 287 of 580 infants (49.5%) in the lower-target group versus 248 of 563 infants (44.0%) in the higher-target group (relative risk, 1.12; 95% CI, 0.99 to 1.27; P=0.07), and death occurred in 144 of 587 infants (24.5%) versus 99 of 586 infants (16.9%) (relative risk, 1.45; 95% CI, 1.16 to 1.82; P=0.001). CONCLUSIONS: Use of an oxygen-saturation target range of 85 to 89% versus 91 to 95% resulted in nonsignificantly higher rates of death or disability at 2 years in each trial but in significantly increased risks of this combined outcome and of death alone in post hoc combined analyses. (Funded by the Australian National Health and Medical Research Council and others; BOOST-II Current Controlled Trials number, ISRCTN00842661, and Australian New Zealand Clinical Trials Registry number, ACTRN12605000055606.).