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Printing is a promising manufacturing approach for the fabrication of flexible, large-area, custom sensor systems for applications such as wearable electronics and sensor labels. While printed examples of many physical and chemical sensors have been demonstrated, functionality useful for stand-alone systems such as high-resolution analog-to-digital conversion and wireless communication to address these sensors is not currently available in circuits printed entirely from solution. In order to retain the benefits of print manufacturing without sacrificing performance, a hybrid approach can be followed where printed and pre-fabricated devices are used together. In this report a mostly-printed wireless light and temperature sensor system that operates at 3.6 V and reports light and temperature readings wirelessly with a sensitivity of 0.7 °Cand 2.5 μWcm-2 at 500 nm respectively is demonstrated. The number of printed components was maximized and off-the-shelf microfabricated devices were only introduced where functionality is not currently achievable through printing. Onto a flexible polyester substrate, print processes were used to fabricate the bulk-heterojunction photodiode, thermistor, low-voltage operation multiplexing transistors, antenna, passives and interconnects, and silicon ICs are used for signal processing, memory and wireless communication. The printed components (sensors and transistors) were specifically developed to facilitate electrical integration into the hybrid system.

Bronchopulmonary dysplasia, the most prevalent chronic lung disease of prematurity, is often treated with glucocorticoids (GCs) such as dexamethasone (DEX), but their use is encumbered with several adverse somatic, metabolic, and neurologic effects. We previously reported that systemic delivery of the GC prodrug ciclesonide (CIC) in neonatal rats activated glucocorticoid receptor (GR) transcriptional responses in lung but did not trigger multiple adverse effects caused by DEX. To determine whether limited systemic metabolism of CIC was solely responsible for its enhanced safety profile, we treated neonatal rats with its active metabolite desisobutyryl-ciclesonide (Des-CIC). DEX but not Des-CIC caused a reduction in body weight as well as reduced insulin-like growth factor-1 serum levels and chronic hyperglycemia in neonatal rats. However, Des-CIC was as effective as DEX in reducing the expression of various bleomycin-induced proinflammatory cytokine mRNAs. In vitro studies with various cell types demonstrate the potent GR transactivation and transrepression activity of Des-CIC, although genome-wide transcriptomic analyses reveal differences in DEX vs. Des-CIC responses in neonatal rat lung and liver tissue. Des-CIC is a GR super-agonist as revealed by an in vitro coregulator peptide binding assay. In addition, molecular dynamics simulations revealed unique Des-CIC-dependent allosteric signaling pathways between specific residues in the GR ligand-binding domain and receptor surfaces interacting with coregulator peptides. Thus, Des-CIC is a potential novel selective GR modulator that could impart a favorable therapeutic index for CIC use for even modest durations of GC exposure which could have long-lasting adverse somatic, metabolic, or neurologic effects., (© The Author(s) 2024. Published by Oxford University Press on behalf of National Academy of Sciences.)

Synthetic glucocorticoids (sGCs) such as dexamethasone (DEX), while used to mitigate inflammation and disease progression in premature infants with severe bronchopulmonary dysplasia (BPD), are also associated with significant adverse neurologic effects such as reductions in myelination and abnormalities in neuroanatomical development. Ciclesonide (CIC) is a sGC prodrug approved for asthma treatment that exhibits limited systemic side effects. Carboxylesterases enriched in the lower airways convert CIC to the glucocorticoid receptor (GR) agonist des-CIC. We therefore examined whether CIC would likewise activate GR in neonatal lung but have limited adverse extra-pulmonary effects, particularly in the developing brain. Neonatal rats were administered subcutaneous injections of CIC, DEX or vehicle from postnatal days 1-5 (PND1-PND5). Systemic effects linked to DEX exposure, including reduced body and brain weight, were not observed in CIC treated neonates. Furthermore, CIC did not trigger the long-lasting reduction in myelin basic protein expression in the cerebral cortex nor cerebellar size caused by neonatal DEX exposure. Conversely, DEX and CIC were both effective at inducing the expression of select GR target genes in neonatal lung, including those implicated in lung-protective and anti-inflammatory effects. Thus, CIC is a promising, novel candidate drug to treat or prevent BPD in neonates given its activation of GR in neonatal lung and limited adverse neurodevelopmental effects. Furthermore, since sGCs such as DEX administered to pregnant women in pre-term labor can adversely affect fetal brain development, the neurological-sparing properties of CIC, make it an attractive alternative for DEX to treat pregnant women severely ill with respiratory illness, such as with asthma exacerbations or COVID-19 infections., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Glucocorticoid (GC) signaling via the glucocorticoid receptor (GR) is essential for lung maturation in mammals. Previous studies using global or conditional mouse model knockouts of the GR gene have established that GR-mediated signaling in the interstitial mesenchyme of the fetal lung is critical for normal lung development. Screens for downstream GC-targets in conditional mesenchymal GR deficient mouse lung (GRmesKO) identified Versican (Vcan), an important extracellular matrix component and cell proliferation regulator, as a potential GR-regulated target. We show that, of the five major VCAN isoforms, the VCAN-V1 isoform containing the GAGβ domain is the predominant VCAN isoform in the fetal mouse lung distal mesenchyme at both E16.5 and E18.5, whereas the GAGα-specific VCAN-V2 isoform was only localized to the smooth muscle surrounding proximal airways. Both Vcan-V1 mRNA and protein levels were strongly overexpressed in the GRmesKO lung at E18.5. Finally, we investigated the GC regulation of the ECM protease ADAMTS 12 and showed that Adamts 12 mRNA levels were markedly reduced at E18.5 in GRmesKO fetal mouse lung and were strongly induced by both cortisol and betamethasone in cultures of primary rat fetal lung fibroblasts. ADAMTS12 protein immunoreactivity was also strongly increased in the distal lung at E18.5, after dexamethasone treatment in utero. In summary, glucocorticoid signaling via GR represses GAGβ domain-containing VCAN isoforms in distal lung mesenchyme in vivo by repressing Vcan gene expression and, in part, by inducing the ECM protease ADAMTS12, thereby contributing to the control of ECM remodelling and lung cell proliferation prior to birth.

Preterm birth is characterized by severe lung immaturity that is frequently treated antenatally or postnatally with the synthetic steroid betamethasone. The underlying cellular targets and pathways stimulated by betamethasone in the fetal lung are poorly defined. In this study, betamethasone was compared with corticosterone in steroid-treated primary cultures of fetal rat lung fibroblasts stimulated for 6 hours and analyzed by whole-cell transcriptome sequencing and glucocorticoid (GC) receptor (GR) chromatin immunoprecipitation sequencing (ChIP-Seq) analysis. Strikingly, betamethasone stimulated a much stronger transcriptional response compared with corticosterone for both induced and repressed genes. A total of 483 genes were significantly stimulated by betamethasone or corticosterone, with 476 stimulated by both steroids, indicating a strong overlap in regulation. Changes in mRNA levels were confirmed by quantitative PCR for eight induced and repressed target genes. Pathway analysis identified cell proliferation and cytoskeletal/cell matrix remodeling pathways as key processes regulated by both steroids. One target, transglutaminase 2 (Tgm2), was localized to fetal lung mesenchymal cells. Tgm2 mRNA and protein levels were strongly increased in fibroblasts by both steroids. Whole-genome GR ChIP-Seq analysis with betamethasone identified GC response element-binding sites close to the previously characterized GR target genes Per1, Dusp1, Fkbp5, and Sgk1 and near the genes identified by transcriptome sequencing encoding Crispld2, Tgm2, Hif3α, and Kdr, defining direct genomic induction of expression in fetal lung fibroblasts via the GR. These results demonstrate that betamethasone stimulates specific genes and cellular pathways controlling cell proliferation and extracellular matrix remodeling in lung mesenchymal fibroblasts, providing a basis for betamethasone's treatment efficacy in preterm birth., (Copyright © 2019 Endocrine Society.)

Steroids are complex lipophilic molecules that have many actions in the body to regulate cellular, tissue and organ functions across the life-span. Steroid hormones such as cortisol, aldosterone, estradiol and testosterone are synthesised from cholesterol in specialised endocrine cells in the adrenal gland, ovary and testis, and released into the circulation when required. Steroid hormones move freely into cells to activate intracellular nuclear receptors that function as multi-domain ligand-dependent transcriptional regulators in the cell nucleus. Activated nuclear receptors modify expression of hundreds to thousands of specific target genes in the genome. Steroid hormone actions in the fetus include developmental roles in the respiratory system, brain, and cardiovascular system. The synthetic glucocorticoid steroid betamethasone is used antenatally to reduce the complications of preterm birth. Development of novel selective partial glucocorticoid receptor agonists may provide improved therapies to treat the respiratory complications of preterm birth and spare the deleterious effects of postnatal glucocorticoids in other organs., (© 2019 Elsevier Ltd. All rights reserved.)

Background: Infants in the newborn intensive care unit (NICU) often receive medications or nutritional support for extended periods. Due to the fragility of veins, central lines are often used. Adverse outcomes from central lines such as infections and line dislodgements, where the line terminates in a peripheral vessel rather than centrally, can drastically increase infant morbidity and mortality. Although evidence exists addressing the specialized needs of premature or smaller infants, there is far less evidence regarding infants that are larger, more physiologically complex, and have longer stays., Purpose: Using evidence-based practice strategies, we examined the literature for central line maintenance practices specific to the NICU population and created a care maintenance bundle to reduce infection and line dislodgement rates. Furthermore, we examined implementation of this bundle., Methods/search Strategy: A systematic search of PubMed, Cochrane Library, and CINAHL provided evidence for a practice change for central line maintenance for our nontunneled central lines. During project implementation, infection and dislodgement rates for both tunneled and nontunneled lines were examined in order have a control and intervention group., Findings/results: Prior to central line maintenance bundle implementation, there were 19 total incidences of central line dislodgements and 5 central line infections (14 dislodgements and 4 infections were from nontunneled lines, 5 dislodgements and 1 infection from a tunneled line). Postintervention there were 1 total dislodgement and 4 central line infections (the dislodgement was from a nontunneled line and all infections were from tunneled lines)., Implications for Practice: Although research has shown frequent, scheduled dressing changes using the chlorhexidine patch decreases infection rates, the risk of dislodgement and skin breakdown for NICU infants outweighs the potential benefit of decreased infection., Implications for Research: Further research is needed to determine whether this central line maintenance bundle would be beneficial for tunneled central lines.

Severe skin injury after extracorporeal shock wave lithotripsy (ESWL) is rare. We describe two patients who suffered full thickness skin burns following ESWL for renal calculi. One patient was treated conservatively and the other underwent debridement with skin grafting. We speculate that failure of the thermostatic mechanism of the lithotripter, leading to overheating of the water-filled cushion, resulted in this very rare adverse event. Proper preoperative patient counseling regarding the risk of serious burn injuries will help to avoid potential litigation.

Fifteen patients underwent subcapsular orchiectomy with placement of an intracapsular testicular prosthesis for hormonal treatment of symptomatic Stage D carcinoma of the prostate. Serum testosterone decreased to castration levels, and the intracapsular prosthesis was often indistinguishable from a normal testicle postoperatively. This new technique of castration may be considered an alternative in those patients reluctant to undergo other forms of orchiectomy.

This is a report of a case of gastroschisis and prune belly syndrome in a black male infant, the second born of dizygotic twins. This infant died of sepsis secondary to peritonitis that developed from a leaking gastrostomy site.

This retrospective review is the first to compare recurrence rates of calculi of the bladder following each of the three common methods. In 39 patients with bladder calculi and indwelling catheters, the recurrence rate of calculi of the bladder within two years was significantly greater following litholapaxy (44.1 per cent) or EHL (50.0 per cent) than vesicolithotomy (7.4 per cent). The average stone-free interval was shorter after litholapaxy (18.4 months) or EHL (13.8 months) than vesicolithotomy (70.8 months).

We report on a patient with systemic blastomycosis who presented with acute epididymitis that was followed by the appearance of typical skin and pulmonary lesions. An excellent clinical response was obtained with ketoconazole, a new oral antifungal agent. Only 2 cases of systemic blastomycosis that were treated with ketoconazole have been reported and neither patient had genitourinary involvement. The diagnosis and treatment of systemic blastomycosis with genitourinary involvement, and ketoconazole as the treatment of fungal infections are discussed.

The enzyme-linked immunosorbent assay (ELISA) measured urine and serum levels of O antigen-specific IgA against Escherichia coli in five women prone to recurrent Esch. coli cystitis and in 20 normal women. Serial urine and serum samples were taken from the five women during Esch. coli infections and during uninfected intervals, while a single urine and serum sample was obtained from the 20 normal women. Elevation of any class of serum immunoglobulins for patients with uncomplicated Esch. coli cystitis was absent. A local antigen-specific immunological response, predominantly of the IgA class, was present during Esch. coli cystitis. There was no significant difference (P greater than 0.1) in the urinary or serum levels of any class of immunoglobulins between the recurrent cystitis group when uninfected and the normal women. There was a significant increase (P less than 0.001) in the levels of urinary IgA and secretory IgA during Esch. coli cystitis as compared with the same women when uninfected or with normal women. A deficiency in the local immunological response of women prone to recurrent Esch. coli cystitis is not supported by our data.