Less Common Bacterial, Fungal and Viral Infections: Review of Management in the Pregnant Patient

This review is a comprehensive summary of treatment options for pregnant patients with less common bacterial, fungal, and viral infections. It offers guidance to clinicians based on the most recently published evidence-based research and expert recommendations. A search of MEDLINE (inception to March 2021) and the CDC website was performed. Liposomal amphotericin B is the preferred therapy for cryptococcosis, histoplasmosis, oesophageal candidiasis, and coccidioidomycosis, especially during the first trimester due to teratogenic concerns with azole antifungals. For oral candidiasis, clotrimazole troches or miconazole mucoadhesive buccal tablets are recommended. A β-lactam antimicrobial is preferred over doxycycline for various manifestations of Lyme disease and the drug of choice for pneumonia is trimethoprim/sulfamethoxazole. Acyclovir is the preferred antiviral for varicella zoster virus. Fluoroquinolones, macrolides, and aminoglycosides should be avoided if possible and there are alternate agents available for an effective treatment regimen. There is a scarcity of clinical data in pregnant patients with less common bacterial, fungal and viral infections. This population lacks definitive recommendations in many clinical practice guidelines. The key to optimizing therapy is a comprehensive review of the available evidence and a careful balance of risks and benefits before final treatment decisions

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure

The Science Performance of JWST as Characterized in Commissioning

This paper characterizes the actual science performance of the James Webb Space Telescope (JWST), as determined from the six month commissioning period. We summarize the performance of the spacecraft, telescope, science instruments, and ground system, with an emphasis on differences from pre-launch expectations. Commissioning has made clear that JWST is fully capable of achieving the discoveries for which it was built. Moreover, almost across the board, the science performance of JWST is better than expected; in most cases, JWST will go deeper faster than expected. The telescope and instrument suite have demonstrated the sensitivity, stability, image quality, and spectral range that are necessary to transform our understanding of the cosmos through observations spanning from near-earth asteroids to the most distant galaxies.Comment: 5th version as accepted to PASP; 31 pages, 18 figures; https://iopscience.iop.org/article/10.1088/1538-3873/acb29

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Expression of the inhibitory receptor subunit GABAA α2 in neurons and glia of zebrafish embryos

The inhibitory GABAA receptors regulate most regions of the nervous system. Identification of the cell types and tissues that express different GABAA receptor subunits could greatly benefit research into a variety of mental illnesses including epilepsy, drug abuse, anxiety disorders, depression, and schizophrenia. As part of a biotechniques course at SUNY Alfred State College of Technology, students identified regions in the nervous system of zebrafish embryos that expressed the GABAA α2 subunit. Students synthesized fluorescent mRNA in situ probes directed against the GABAA α2 subunit using a variety of technologies. First, students cloned a fragment of the GABAA α2 subunit gene from whole RNA using reverse transcription PCR. They then cloned the resulting cDNA into a plasmid vector. Utilizing this plasmid, students generated fluorescent in situ probes. Combining these in situ probes with antibodies specific to neurons and glia allowed students to determine which cell types express the GABAA α2 subunit. This project allowed students to carry out a modern biotechnology project from design to completion. Students generated previously unpublished data and produced stunning images while gaining practical skills applicable to both academic and industry research projects

Fibromyalgia and the therapeutic relationship: Where uncertainty meets attitude

BACKGROUND: Fibromyalgia remains underdiagnosed and suboptimally treated even though it affects an estimated 3.3% of Canadians. The present study examines knowledge and attitudinal challenges affecting optimal care

The wild world of Guinea Worms: A review of the genus Dracunculus in wildlife

Nematodes are an extremely diverse and speciose group of parasites. Adult dracunculoid nematodes (Superfamily Dracunculoidea) occur in the tissues and serous cavities of mammals, fish, reptiles, amphibians and birds. Of the dracunculid group, perhaps best known is Dracunculus medinensis, the human Guinea Worm. Considerable work has been done on D. medinensis; however recent infections in peri-domestic dogs and the finding of naturally-infected paratenic hosts (previously unreported for D. medinensis) indicate we still have much to learn about these parasites. Furthermore, among eight species in the Old World and six species in the New World there is a lack of general life history knowledge as well as questions on species occurrence, host diversity, and transmission dynamics. Herein, we provide a comprehensive review of the genus Dracunculus, in order of a theoretical evolutionary progression from reptilian to mammalian hosts. Species descriptions, where available, are provided but also show where gaps occur in our knowledge of various species. Additionally, many first reports of Dracunculus spp. were done prior to the development and use of molecular tools. This is especially important for this group of parasites as speciation based on morphology is only applicable to males of the genus, and males, given their size, are notoriously difficult to recover from definitive hosts. Therefore, we also discuss current molecular tools used in the investigation of this group of parasites. Given recent host-switching events, the dracunculids are of increasing importance and require further work to expand our understanding of this genus. Keywords: Dracunculus spp, Wildlife, Definitive host, Paratenic host, Intermediate hos

Social network interventions for health behaviours and outcomes: A systematic review and meta-analysis

Background There has been a growing interest in understanding the effects of social networks on health-related behaviour, with a particular backdrop being the emerging prominence of complexity or systems science in public health. Social network interventions specifically use or alter the characteristics of social networks to generate, accelerate, or maintain health behaviours. We conducted a systematic review and meta-analysis to investigate health behaviour outcomes of social network interventions. Methods and findings We searched eight databases and two trial registries from 1990 to May 28, 2019, for English-language reports of randomised controlled trials (RCTs) and before-and-after studies investigating social network interventions for health behaviours and outcomes. Trials that did not specifically use social networks or that did not include a comparator group were excluded. We screened studies and extracted data from published reports independently. The primary outcome of health behaviours or outcomes at ≤6 months was assessed by random-effects meta-analysis. Secondary outcomes included those measures at >6–12 months and >12 months. This study is registered with the International Prospective Register of Systematic Reviews, PROSPERO: CRD42015023541. We identified 26,503 reports; after exclusion, 37 studies, conducted between 1996 and 2018 from 11 countries, were eligible for analysis, with a total of 53,891 participants (mean age 32.4 years [SD 12.7]; 45.5% females). A range of study designs were included: 27 used RCT/cluster RCT designs, and 10 used other study designs. Eligible studies addressed a variety of health outcomes, in particular sexual health and substance use. Social network interventions showed a significant intervention effect compared with comparator groups for sexual health outcomes. The pooled odds ratio (OR) was 1.46 (95% confidence interval [CI] 1.01–2.11; I2 = 76%) for sexual health outcomes at ≤6 months and OR 1.51 (95% CI 1.27–1.81; I2 = 40%) for sexual health outcomes at >6–12 months. Intervention effects for drug risk outcomes at each time point were not significant. There were also significant intervention effects for some other health outcomes including alcohol misuse, well-being, change in haemoglobin A1c (HbA1c), and smoking cessation. Because of clinical and measurement heterogeneity, it was not appropriate to pool data on these other behaviours in a meta-analysis. For sexual health outcomes, prespecified subgroup analyses were significant for intervention approach (p 6 months) for sexual health outcomes. Intervention effects for drug risk outcomes at each time point were not significant. There were also significant intervention effects for some other health outcomes including alcohol misuse, well-being, change in HbA1c, and smoking cessation

The Mitochondrial Genomes of the Nudibranch Mollusks, Melibe leonina and Tritonia diomedea, and Their Impact on Gastropod Phylogeny.

The phylogenetic relationships among certain groups of gastropods have remained unresolved in recent studies, especially in the diverse subclass Opisthobranchia, where nudibranchs have been poorly represented. Here we present the complete mitochondrial genomes of Melibe leonina and Tritonia diomedea (more recently named T. tetraquetra), two nudibranchs from the unrepresented Cladobranchia group, and report on the resulting phylogenetic analyses. Both genomes coded for the typical thirteen protein-coding genes, twenty-two transfer RNAs, and two ribosomal RNAs seen in other species. The twelve-nucleotide deletion previously reported for the cytochrome oxidase 1 gene in several other Melibe species was further clarified as three separate deletion events. These deletions were not present in any opisthobranchs examined in our study, including the newly sequenced M. leonina or T. diomedea, suggesting that these previously reported deletions may represent more recently divergent taxa. Analysis of the secondary structures for all twenty-two tRNAs of both M. leonina and T. diomedea indicated truncated d arms for the two serine tRNAs, as seen in some other heterobranchs. In addition, the serine 1 tRNA in T. diomedea contained an anticodon not yet reported in any other gastropod. For phylogenetic analysis, we used the thirteen protein-coding genes from the mitochondrial genomes of M. leonina, T. diomedea, and seventy-one other gastropods. Phylogenetic analyses were performed for both the class Gastropoda and the subclass Opisthobranchia. Both Bayesian and maximum likelihood analyses resulted in similar tree topologies. In the Opisthobranchia, the five orders represented in our study were monophyletic (Anaspidea, Cephalaspidea, Notaspidea, Nudibranchia, Sacoglossa). In Gastropoda, two of the three traditional subclasses, Opisthobranchia and Pulmonata, were not monophyletic. In contrast, four of the more recently named gastropod clades (Vetigastropoda, Neritimorpha, Caenogastropoda, and Heterobranchia) were all monophyletic, and thus appear to be better classifications for this diverse group