Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Roadmap on printable electronic materials for next-generation sensors

The dissemination of sensors is key to realizing a sustainable, ‘intelligent’ world, where everyday objects and environments are equipped with sensing capabilities to advance the sustainability and quality of our lives—e.g., via smart homes, smart cities, smart healthcare, smart logistics, Industry 4.0, and precision agriculture. The realization of the full potential of these applications critically depends on the availability of easy-to-make, low-cost sensor technologies. Sensors based on printable electronic materials offer the ideal platform: they can be fabricated through simple methods (e.g., printing and coating) and are compatible with high-throughput roll-to-roll processing. Moreover, printable electronic materials often allow the fabrication of sensors on flexible/stretchable/biodegradable substrates, thereby enabling the deployment of sensors in unconventional settings. Fulfilling the promise of printable electronic materials for sensing will require materials and device innovations to enhance their ability to transduce external stimuli—light, ionizing radiation, pressure, strain, force, temperature, gas, vapours, humidity, and other chemical and biological analytes. This Roadmap brings together the viewpoints of experts in various printable sensing materials—and devices thereof—to provide insights into the status and outlook of the field. Alongside recent materials and device innovations, the roadmap discusses the key outstanding challenges pertaining to each printable sensing technology. Finally, the Roadmap points to promising directions to overcome these challenges and thus enable ubiquitous sensing for a sustainable, ‘intelligent’ world

Reclaiming the Classics for a Diverse and Global World Through OER

In the 2019–20 academic year, I redesigned a course on the classics to make both the texts and the context in which they were taught more accessible for and relevant to the predominantly female students of Saint Mary’s College, Notre Dame. The course was re-centered on the dialogue between the ever-evolving and diverse cultures within Greece and the Roman empire and surrounding regions such as Egypt, Ethiopia, and Persia; issues caused by slavery and economic inequality; conceptions of gender roles and sexuality, race and ethnicity, and migration and citizenship; the troubling appropriation of classical motifs and texts by fascist groups in the twentieth century and some alt-right groups and sexual predators in the twenty-first century; and on recent initiatives meant to demonstrate the diversity of both Greek and Roman cultures through documentary, artistic, and archaeological evidence (particularly in the digital humanities and in museums and libraries).  I also wanted to make the course close to zero cost for students and to shift to digital texts which lent themselves to interactivity and social scholarship. Our librarian, Catherine Pellegrino, obtained multi-user e-books for modern reinterpretations of classical works still in copyright. A LibreTexts grant enabled the co-authors of this article—the course instructor (and lead author) and two paid student researchers—and a team of summer-employed student collaborators to edit, footnote, and create critical introductions and student activities for various key texts for the course. Many of these texts are now hosted on the LibreTexts OER platform.  Beta versions of enriched OER texts and activities were user tested in a synchronous hybrid virtual/physical classroom of twenty-five students, who were taking the course (HUST 292) in the fall semester of 2020

Differential prey capture success in ant lions (Myrmeleon immaculatus).

The predatory behavior of the ant lion larvae, Myrmeleon immaculatus was investigated using three different sizes of prey. Relationships between ant lion body size and pit structure, capture success and prey size, and capture time and prey size were investigated. A statistically significant relationship exists between ant lion body size and pit structure. In addition, small ant lions and large ant lions were found to differ signficantly in the sizes of prey they captured. However, the amount of time small and large ant lions spent capturing similar size prey did not differ. The results of this study indicate that although small and large ant lions invest the same amount of effort into prey capture, they do not receive equal energy return.http://deepblue.lib.umich.edu/bitstream/2027.42/54799/1/3240.pdfDescription of 3240.pdf : Access restricted to on-site users at the U-M Biological Station

Sodium chloride pica causing recurrent nephrolithiasis in a patient with iron deficiency anemia: a case report

Abstract Background Iron deficiency anemia is a common finding in women of child-bearing age. Pica, or the ingestion of non-food or non-nutritive items, is a well-known manifestation of iron deficiency. A high sodium diet increases risk for nephrolithiasis. We describe the case of a 31-year-old woman with recurrent calcium nephrolithiasis and anemia who ate ice chips as well as spoons of salt daily. Treatment of pica may prove effective in preventing recurrent nephrolithiasis. Case presentation A 31-year-old white woman with a past medical history of menorrhagia, anemia, and recurrent calcium nephrolithiasis presented for preoperative evaluation prior to ureterolithotomy. She described a daily pattern of eating continually from a cup of ice chips accompanied by multiple spoons of salt directly out of a salt shaker. These cravings had been present for many years, were bothersome to her, and interfered with her daily life. Laboratory findings revealed hemoglobin of 10.9 g/dL with ferritin of 3 ng/mL. History, physical, and laboratory data were consistent with pica secondary to iron deficiency anemia. She was prescribed orally administered ferrous sulfate 325 mg three times a day with meals. She continues to struggle with the symptoms of pica and orally administered supplementation. Conclusions It is important that clinicians consider the possible diagnosis of sodium chloride pica in patients with iron deficiency anemia and recurrent nephrolithiasis. Treatment of anemia and resolution of pica may prove effective in preventing future nephrolithiasis. Specific questioning about pica symptoms in patients with iron deficiency anemia and recurrent nephrolithiasis may be helpful diagnostically and therapeutically

Ovotesticular disorders of sex development in FGF9 mouse models of human synostosis syndromes

In mice, male sex determination depends on FGF9 signalling via FGFR2c in the bipotential gonads to maintain the expression of the key testis gene SOX9. In humans, however, while FGFR2 mutations have been linked to 46,XY disorders of sex development (DSD), the role of FGF9 is unresolved. The only reported pathogenic mutations in human FGF9, FGF9S99N and FGF9R62G, are dominant and result in craniosynostosis (fusion of cranial sutures) or multiple synostoses (fusion of limb joints). Whether these synostosis-causing FGF9 mutations impact upon gonadal development and DSD etiology has not been explored. We therefore examined embryonic gonads in the well-characterized Fgf9 missense mouse mutants, Fgf9S99N and Fgf9N143T, which phenocopy the skeletal defects of FGF9S99N and FGF9R62G variants, respectively. XY Fgf9S99N/S99N and XY Fgf9N143T/N143T fetal mouse gonads showed severely disorganized testis cords and partial XY sex reversal at 12.5\ua0days post coitum (dpc), suggesting loss of FGF9 function. By 15.5 dpc, testis development in both mutants had partly recovered. Mitotic analysis in vivo and in vitro suggested that the testicular phenotypes in these mutants arise in part through reduced proliferation of the gonadal supporting cells. These data raise the possibility that human FGF9 mutations causative for dominant skeletal conditions can also lead to loss of FGF9 function in the developing testis, at least in mice. Our data suggest that, in humans, testis development is largely tolerant of deleterious FGF9 mutations which lead to skeletal defects, thus offering an explanation as to why XY DSDs are rare in patients with pathogenic FGF9 variants

Study protocol for Healthy Conversations @ Playgroup: a multi-site cluster randomized controlled trial of an intervention to promote healthy lifestyle behaviours in young children attending community playgroups

Background: Early childhood is a critical window for preventing obesity and chronic disease. Yet, 1 in 4 Australian children aged 5 years and under are affected by overweight or obesity; and significant proportions of children under 5 years fail to meet guidelines for diet quality, physical activity (PA), screen time, and sleep. Consequently, effective interventions to promote healthy lifestyle behaviors and prevent obesity during early childhood are needed. Community playgroups provide an opportunity for parents, carers, and children to meet in a safe and relaxed environment to play and share information. The structure, low cost and reach of playgroups provide a unique platform to engage parents in a scalable program to promote healthful lifestyle behaviors and prevent childhood obesity. However, the evidence base for the effectiveness of health promotion programs delivered in community playgroup settings is limited and lacking credible evidence from rigorously conducted randomized controlled trials. Methods: The Healthy Conversations @ Playgroup randomized controlled trial (RCT) aims to address the underlying behavioral risk factors for obesity by helping parents take effective steps to improve their child’s dietary, PA, screen time, and sleep behaviors. The intervention program comprises 10 “healthy conversations” led by a trained peer facilitator, designed to increase parents’ behavioral capability and self-efficacy to implement autonomy-supportive parenting practices. The program will be delivered biweekly during regularly scheduled playgroup sessions over 10-weeks. Effectiveness will be tested in a 2-arm cluster RCT involving 60 community playgroups in three states across Australia. After baseline assessments, participating playgroups will be randomly allocated to either intervention or wait-list control conditions. Primary outcomes (vegetable intake, discretionary foods, daily PA, screen time, sleep duration, and body mass index [BMI] z-score) will be assessed at baseline, immediately post-intervention (10-weeks; T2) and 6-months post-intervention (T3). Outcomes will be assessed for differential change at T2 and T3. Discussion: The Healthy Conversations @ Playgroup trial will rigorously evaluate a novel peer-led intervention program to promote healthful lifestyle behaviors and prevent obesity in children and families attending community playgroups. If effective, the program could be immediately scaled-up and delivered in community playgroups across Australia. Trial registration: Trial registered 22nd January 2021 with the Australian and New Zealand Clinical Trials Registry (ACTRN12621000055808).</p

Mutant NR5A1/SF-1 in patients with disorders of sex development shows defective activation of the SOX9 TESCO enhancer

International audienceNuclear receptor subfamily 5 group A member 1/Steroidogenic factor 1 (NR5A1; SF-1; Ad4BP) mutations cause 46,XY disorders of sex development (DSD), with phenotypes ranging from developmentally mild (e.g., hypospadias) to severe (e.g., complete gonadal dysgenesis). The molecular mechanism underlying this spectrum is unclear. During sex determination, SF-1 regulates SOX9 (SRY [sex determining region Y]-box 9) expression. We hypothesized that SF-1 mutations in 46,XY DSD patients affect SOX9 expression via the Testis-specific Enhancer of Sox9 core element, TESCO. Our objective was to assess the ability of 20 SF-1 mutants found in 46,XY DSD patients to activate TESCO. Patient DNA was sequenced for SF-1 mutations and mutant SF-1 proteins were examined for transcriptional activity, protein expression, sub-cellular localization and in silico structural defects. Fifteen of the 20 mutants showed reduced SF-1 activation on TESCO, 11 with atypical sub-cellular localization. Fourteen SF-1 mutants were predicted in silico to alter DNA, ligand or cofactor interactions. Our study may implicate aberrant SF-1-mediated transcriptional regulation of SOX9 in 46,XY DSDs