Rapidly improving ARDS differs clinically and biologically from persistent ARDS.

BACKGROUND: Rapidly improving acute respiratory distress syndrome (RIARDS) is an increasingly appreciated subgroup of ARDS in which hypoxemia improves within 24 h after initiation of mechanical ventilation. Detailed clinical and biological features of RIARDS have not been clearly defined, and it is unknown whether RIARDS is associated with the hypoinflammatory or hyperinflammatory phenotype of ARDS. The purpose of this study was to define the clinical and biological features of RIARDS and its association with inflammatory subphenotypes. METHODS: We analyzed data from 215 patients who met Berlin criteria for ARDS (endotracheally intubated) and were enrolled in a prospective observational cohort conducted at two sites, one tertiary care center and one urban safety net hospital. RIARDS was defined according to previous studies as improvement of hypoxemia defined as (i) PaO2:FiO2 > 300 or (ii) SpO2: FiO2 > 315 on the day following diagnosis of ARDS (day 2) or (iii) unassisted breathing by day 2 and for the next 48 h (defined as absence of endotracheal intubation on day 2 through day 4). Plasma biomarkers were measured on samples collected on the day of study enrollment, and ARDS phenotypes were allocated as previously described. RESULTS: RIARDS accounted for 21% of all ARDS participants. Patients with RIARDS had better clinical outcomes compared to those with persistent ARDS, with lower hospital mortality (13% vs. 57%; p value < 0.001) and more ICU-free days (median 24 vs. 0; p value < 0.001). Plasma levels of interleukin-6, interleukin-8, and plasminogen activator inhibitor-1 were significantly lower among patients with RIARDS. The hypoinflammatory phenotype of ARDS was more common among patients with RIARDS (78% vs. 51% in persistent ARDS; p value = 0.001). CONCLUSIONS: This study identifies a high prevalence of RIARDS in a multicenter observational cohort and confirms the more benign clinical course of these patients. We report the novel finding that RIARDS is characterized by lower concentrations of plasma biomarkers of inflammation compared to persistent ARDS, and that hypoinflammatory ARDS is more prevalent among patients with RIARDS. Identification and exclusion of RIARDS could potentially improve prognostic and predictive enrichment in clinical trials.

A realist evaluation of devices used for the prevention of heel pressure ulcers: An ethnographic study of clinical practice.

BACKGROUND: It is known that heel offloading devices are widely used in clinical practice for the prevention of heel pressure ulcers, even though there is a lack of robust, good quality evidence to inform their use. OBJECTIVE: To explore how and why heel offloading devices are used (or not used) and reasoning behind their use in population at high risk of developing heel pressure ulcers. METHODS: An ethnographic study was conducted as part of a realist evaluation in three orthopaedic wards in a large English hospital. Twelve observations took place, with 49 h and 35 min of patient care observed. A total of 32 patients were observed and 19 members of the nursing team were interviewed and in-depth interviews with the three ward managers were conducted. RESULTS: Although the focus of the study was on offloading devices, constant low pressure heel specific devices were also observed in use for pressure ulcer prevention, whilst offloading devices were perceived to be for higher risk patients or those already with a heel pressure ulcer. Nursing staff viewed leadership from the ward manager and the influence of the Tissue Viability Nurse Specialists as key mechanisms for the proactive use of devices. CONCLUSIONS: This study informs trial design as it has identified that a controlled clinical trial of both types of heel specific devices is required to inform evidence-based practice. Involving the ward managers and Tissue Viability Nurse Specialists during set up phase for clinical equipoise could improve recruitment. Tweetable abstract How, for whom, and in what circumstances do devices work to prevent heel pressure ulcers? Observations of clinical practice.

Development of a core outcome set for use in research evaluations of interventions for venous leg ulceration: International eDelphi consensus.

INTRODUCTION: Venous leg ulceration (VLU) is a chronic, recurring condition with associated pain, malodour, impaired mobility and susceptibility to infection which in turn significantly impacts an individual's health-related quality of life. Randomised controlled trials (RCTs) aim to determine the efficacy of interventions to improve outcomes. To be useful, these outcomes should be consistently and fully reported across RCTs. A core outcome set (COS) is an agreed-upon standardised set of outcomes which should be, at a minimum, reported in all RCTs for a given indication including that of VLU. AIM: To gain consensus on which outcome domains and outcomes should be considered as core and therefore included in all RCTs of interventions in VLU treatment. METHOD: Two sequential, two round e-Delphi surveys were completed. The first gained consensus on core outcome domains and the second on core outcomes within those domains. Participants included: people with direct experience of having VLUs and their carers, healthcare professionals whose practice included VLU care and researchers within wound care (clinical, academic, industry). RESULTS: Five outcome domains; healing, pain, quality of life, resource use and adverse events, and 11 outcomes were rated as core by participants. The patient and not the limb or ulcer was the preferred unit of analysis for reporting. RECOMMENDATIONS: We recommend investigators report on all five outcome domains, regardless of the type of intervention being evaluated. Future research is needed to identify measurement methods for the 11 identified outcomes. We also recommend investigators follow the CONSORT guidelines (http://www.consort-statement.org/).

Chemical systems biology reveals mechanisms of glucocorticoid receptor signaling.

Glucocorticoids display remarkable anti-inflammatory activity, but their use is limited by on-target adverse effects including insulin resistance and skeletal muscle atrophy. We used a chemical systems biology approach, ligand class analysis, to examine ligands designed to modulate glucocorticoid receptor activity through distinct structural mechanisms. These ligands displayed diverse activity profiles, providing the variance required to identify target genes and coregulator interactions that were highly predictive of their effects on myocyte glucose disposal and protein balance. Their anti-inflammatory effects were linked to glucose disposal but not muscle atrophy. This approach also predicted selective modulation in vivo, identifying compounds that were muscle-sparing or anabolic for protein balance and mitochondrial potential. Ligand class analysis defined the mechanistic links between the ligand-receptor interface and ligand-driven physiological outcomes, a general approach that can be applied to any ligand-regulated allosteric signaling system.

Strongly baryon-dominated disk galaxies at the peak of galaxy formation ten billion years ago.

In the cold dark matter cosmology, the baryonic components of galaxies-stars and gas-are thought to be mixed with and embedded in non-baryonic and non-relativistic dark matter, which dominates the total mass of the galaxy and its dark-matter halo. In the local (low-redshift) Universe, the mass of dark matter within a galactic disk increases with disk radius, becoming appreciable and then dominant in the outer, baryonic regions of the disks of star-forming galaxies. This results in rotation velocities of the visible matter within the disk that are constant or increasing with disk radius-a hallmark of the dark-matter model. Comparisons between the dynamical mass, inferred from these velocities in rotational equilibrium, and the sum of the stellar and cold-gas mass at the peak epoch of galaxy formation ten billion years ago, inferred from ancillary data, suggest high baryon fractions in the inner, star-forming regions of the disks. Although this implied baryon fraction may be larger than in the local Universe, the systematic uncertainties (owing to the chosen stellar initial-mass function and the calibration of gas masses) render such comparisons inconclusive in terms of the mass of dark matter. Here we report rotation curves (showing rotation velocity as a function of disk radius) for the outer disks of six massive star-forming galaxies, and find that the rotation velocities are not constant, but decrease with radius. We propose that this trend arises because of a combination of two main factors: first, a large fraction of the massive high-redshift galaxy population was strongly baryon-dominated, with dark matter playing a smaller part than in the local Universe; and second, the large velocity dispersion in high-redshift disks introduces a substantial pressure term that leads to a decrease in rotation velocity with increasing radius. The effect of both factors appears to increase with redshift. Qualitatively, the observations suggest that baryons in the early (high-redshift) Universe efficiently condensed at the centres of dark-matter haloes when gas fractions were high and dark matter was less concentrated.

Breastfeeding challenges and opportunities during COVID-19 in Hong Kong.

Barriers to sustain breastfeeding could be time and place specific. Here, we summarise new and old challenges to breastfeeding during COVID-19 pandemic in Hong Kong, some of which were obtained from qualitative in-depth interviews with health-care professionals. We document how unnecessary massive mother-baby separations in hospitals and doubts in COVID-19 vaccine safety seriously harm breastfeeding. We also discuss how the trends and increase in acceptance of receiving post-natal care from family doctors, online-antenatal class, work-from-home policy and telemedicine implicate new strategies to protect, promote and support breastfeeding during and after the pandemic. The challenges from the COVID-19 pandemic on breastfeeding have revealed new opportunities to support breastfeeding in Hong Kong and similar settings where exclusive breastfeeding for 6 months is still not the norm.

Palbociclib-Induced Cellular Senescence Is Modulated by the mTOR Complex 1 and Autophagy.

Despite not dividing, senescent cells acquire the ability to synthesize and secrete a plethora of bioactive molecules, a feature known as the senescence-associated secretory phenotype (SASP). In addition, senescent cells often upregulate autophagy, a catalytic process that improves cell viability in stress-challenged cells. Notably, this "senescence-related autophagy" can provide free amino acids for the activation of mTORC1 and the synthesis of SASP components. However, little is known about the functional status of mTORC1 in models of senescence induced by CDK4/6 inhibitors (e.g., Palbociclib), or the effects that the inhibition of mTORC1 or the combined inhibition of mTORC1 and autophagy have on senescence and the SASP. Herein, we examined the effects of mTORC1 inhibition, with or without concomitant autophagy inhibition, on Palbociclib-driven senescent AGS and MCF-7 cells. We also assessed the pro-tumorigenic effects of conditioned media from Palbociclib-driven senescent cells with the inhibition of mTORC1, or with the combined inhibition of mTORC1 and autophagy. We found that Palbociclib-driven senescent cells display a partially reduced activity of mTORC1 accompanied by increased levels of autophagy. Interestingly, further mTORC1 inhibition exacerbated the senescent phenotype, a phenomenon that was reversed upon autophagy inhibition. Finally, the SASP varied upon inhibiting mTORC1, or upon the combined inhibition of mTORC1 and autophagy, generating diverse responses in cell proliferation, invasion, and migration of non-senescent tumorigenic cells. Overall, variations in the SASP of Palbociclib-driven senescent cells with the concomitant inhibition of mTORC1 seem to depend on autophagy.

Genotypic, proteomic, and phenotypic approaches to decipher the response to caspofungin and calcineurin inhibitors in clinical isolates of echinocandin-resistant Candida glabrata.

BACKGROUND: Echinocandin resistance represents a great concern, as these drugs are recommended as first-line therapy for invasive candidiasis. Echinocandin resistance is conferred by mutations in FKS genes. Nevertheless, pathways are crucial for enabling tolerance, evolution, and maintenance of resistance. Therefore, understanding the biological processes and proteins involved in the response to caspofungin may provide clues indicating new therapeutic targets. OBJECTIVES: We determined the resistance mechanism and assessed the proteome response to caspofungin exposure. We then evaluated the phenotypic impact of calcineurin inhibition by FK506 and cephalosporine A (CsA) on caspofungin-resistant Candida glabrata isolates. METHODS: Twenty-five genes associated with caspofungin resistance were analysed by NGS, followed by studies of the quantitative proteomic response to caspofungin exposure. Then, susceptibility testing of caspofungin in presence of FK506 and CsA was performed. The effects of calcineurin inhibitor/caspofungin combinations on heat stress (40°C), oxidative stress (0.2 and 0.4 mM menadione) and on biofilm formation (polyurethane catheter) were analysed. Finally, a Galleria mellonella model using blastospores (1 × 109 cfu/mL) was developed to evaluate the impact of the combinations on larval survival. RESULTS: F659-del was found in the FKS2 gene of resistant strains. Proteomics data showed some up-regulated proteins are involved in cell-wall biosynthesis, response to stress and pathogenesis, some of them being members of calmodulin-calcineurin pathway. Therefore, the impact of calmodulin inhibition was explored. Calmodulin inhibition restored caspofungin susceptibility, decreased capacity to respond to stress conditions, and reduced biofilm formation and in vivo pathogenicity. CONCLUSIONS: Our findings confirm that calmodulin-calcineurin-Crz1 could provide a relevant target in life-threatening invasive candidiasis.

The Diagnosis and Management of Recurrent Ischemic Priapism, Priapism in Sickle Cell Patients, and Non-Ischemic Priapism: An AUA/SMSNA Guideline.

PURPOSE: Priapism is a persistent penile erection that continues hours beyond, or is unrelated to, sexual stimulation and results in a prolonged and uncontrolled erection. Given its time-dependent and progressive nature, priapism is a situation that both urologists and emergency medicine practitioners must be familiar with and comfortable managing. METHODOLOGY: A comprehensive search of the literature on acute ischemic priapism and non-ischemic priapism (NIP) was performed by Emergency Care Research Institute for articles published between January 1, 1960 and May 1, 2020. A search of the literature on NIP, recurrent priapism, prolonged erection following intracavernosal vasoactive medication, and priapism in patients with sickle cell disease was conducted by Pacific Northwest Evidence-based Practice Center for articles published between 1946 and February 19, 2021. Searches identified 4117 potentially relevant articles, and 3437 of these were excluded at the title or abstract level for not meeting inclusion criteria. Full texts for the remaining 680 articles were ordered, and ultimately 203 unique articles were included in the report. RESULTS: This Guideline provides a clinical framework for the treatment (non-surgical and surgical) of NIP, recurrent ischemic priapism, and priapism in patients with sickle cell disease. The treatment of patients with a prolonged erection following intracavernosal vasoactive medication is also included. The AUA guideline on the diagnosis of priapism and the treatment of acute ischemic priapism was published in 2021. CONCLUSIONS: All patients with priapism should be evaluated emergently to identify the sub-type of priapism (acute ischemic versus non-ischemic) and those with an acute ischemic event should be provided early intervention when indicated. NIP is not an emergency and treatment must be based on patient objectives, available resources, and clinician experience. Management of recurrent ischemic priapism requires treatment of acute episodes and a focus on future prevention of an acute ischemic event. Sickle cell disease patients presenting with an acute ischemic priapism event should initially be managed with a focus on urologic relief of the erection; standard sickle cell assessment and interventions should be considered concurrent with urologic intervention. Treatment protocols for a prolonged, iatrogenic erection must be differentiated from protocols for true priapism.

Activation of Crtc2/Creb1 in skeletal muscle enhances weight loss during intermittent fasting.

The Creb-Regulated Transcriptional Coactivator (Crtc) family of transcriptional coregulators drive Creb1-mediated transcription effects on metabolism in many tissues, but the in vivo effects of Crtc2/Creb1 transcription on skeletal muscle metabolism are not known. Skeletal muscle-specific overexpression of Crtc2 (Crtc2 mice) induced greater mitochondrial activity, metabolic flux capacity for both carbohydrates and fats, improved glucose tolerance and insulin sensitivity, and increased oxidative capacity, supported by upregulation of key metabolic genes. Crtc2 overexpression led to greater weight loss during alternate day fasting (ADF), selective loss of fat rather than lean mass, maintenance of higher energy expenditure during the fast and reduced binge-eating during the feeding period. ADF downregulated most of the mitochondrial electron transport genes, and other regulators of mitochondrial function, that were substantially reversed by Crtc2-driven transcription. Glucocorticoids acted with AMPK to drive atrophy and mitophagy, which was reversed by Crtc2/Creb1 signaling. Crtc2/Creb1-mediated signaling coordinates metabolic adaptations in skeletal muscle that explain how Crtc2/Creb1 regulates metabolism and weight loss.

The adverse impact of COVID-19 on men's health.

PURPOSE OF REVIEW: The COVID-19 pandemic has led to devastating health outcomes across the world. Initially thought to primarily affect the respiratory system, there is now clear and abundant evidence that COVID-19 can impact upon the male genitourinary system and overall men's health. In this review article, we explore the potential mechanisms by which COVID-19 specifically affects men and we review the literature examining the adverse effects of the disease on men's health. RECENT FINDINGS: Studies suggest that men are at higher risk for severe COVID-19 infection and death. COVID-19 infection has a negative impact on men's health including worsening semen parameters, potentially lower testosterone levels, and an increased risk of erectile dysfunction. SUMMARY: COVID-19 is a highly pathogenic virus that exerts adverse effects upon the male genitourinary system in myriad ways. The COVID-19 infection can impact serum testosterone, fertility, sexual function, and mental health. Fortunately, the COVID-19 vaccine is safe and effective in preventing COVID-19 infection and many of these sequelae.

Voluntary sustainability standards could significantly reduce detrimental impacts of global agriculture.

Voluntary sustainability standards (VSS) are stakeholder-derived principles with measurable and enforceable criteria to promote sustainable production outcomes. While institutional commitments to use VSS to meet sustainable procurement policies have grown rapidly over the past decade, we still have relatively little understanding of the (i) direct environmental benefits of large-scale VSS adoption; (ii) potential perverse indirect impacts of adoption; and (iii) implementation pathways. Here, we illustrate and address these knowledge gaps using an ecosystem service modeling and scenario analysis of Bonsucro, the leading VSS for sugarcane. We find that global compliance with the Bonsucro environmental standards would reduce current sugarcane production area (-24%), net tonnage (-11%), irrigation water use (-65%), nutrient loading (-34%), and greenhouse gas emissions from cultivation (-51%). Under a scenario of doubled global sugarcane production, Bonsucro adoption would further limit water use and greenhouse gas emissions by preventing sugarcane expansion into water-stressed and high-carbon stock ecosystems. This outcome was achieved via expansion largely on existing agricultural lands. However, displacement of other crops could drive detrimental impacts from indirect land use. We find that over half of the potential direct environmental benefits of Bonsucro standards under the doubling scenario could be achieved by targeting adoption in just 10% of global sugarcane production areas. However, designing policy that generates the most environmentally beneficial Bonsucro adoption pathway requires a better understanding of the economic and social costs of VSS adoption. Finally, we suggest research directions to advance sustainable consumption and production.

The view of Hong Kong parents on secondary use of dried blood spots in newborn screening program.

BACKGROUND: Residual dried blood spots (rDBS) from newborn screening programmes represent a valuable resource for medical research, from basic sciences, through clinical to public health. In Hong Kong, there is no legislation for biobanking. Parents' view on the retention and use of residual newborn blood samples could be cultural-specific and is important to consider for biobanking of rDBS. OBJECTIVE: To study the views and concerns on long-term storage and secondary use of rDBS from newborn screening programmes among Hong Kong Chinese parents. METHODS: A mixed-method approach was used to study the views and concerns on long-term storage and secondary use of rDBS from newborn screening programmes among Hong Kong Chinese parents of children 0-3 years or expecting parents through focus groups (8 groups; 33 participants) and a survey (n = 1012, 85% mothers) designed with insights obtained from the focus groups. We used framework analysis to summarise the themes as supportive factors, concerns and critical arguments for retention and secondary use of rDBS from focus group discussion. We used multiple logistic regression to assess factors associated with support for retention and secondary use of rDBS in the survey. RESULTS: Both in focus groups and survey, majority of parents were not aware of the potential secondary use of rDBS. Overall secondary use of rDBS in medical research was well accepted by a large proportion of Hong Kong parents, even if all potential future research could not be specified in a broad consent. However parents were concerned about potential risks of biobanking rDBS including leaking of data and mis-use of genetic information. Parents wanted to be asked for permission before rDBS are stored and mainly did not accept an "opt-out" approach. The survey showed that parents born in mainland China, compared to Hong Kong born parents, had lower awareness of newborn screening but higher support in biobanking rDBS. Higher education was associated with support in rDBS biobanking only among fathers. CONCLUSION: Long-term storage and secondary use of rDBS from newborn screening for biomedical research and a broad consent for biobanking of rDBS are generally acceptable to Hong Kong parents given their autonomy is respected and their privacy is protected, highlighting the importance of an accountable governance and a transparent access policy for rDBS biobanks.

The effect of intraoperative intrathecal opioid administration on the length of stay and postoperative pain control for patients undergoing lumbar interbody fusion.

PURPOSE: In an effort to control postoperative pain more effectively in spinal fusion patients, intraoperative intrathecal morphine (ITM) administration is gaining popularity and acceptance with clinicians. This study seeks to determine the impact of intraoperative intrathecal opioid (ITO) administration following lumbar fusion surgery on postoperative pain and length of hospitalization as primary outcomes. Secondary outcomes will investigate postoperative opioid intake and side effects. METHODS: The retrospective analysis of collected data was performed. The study compared patients undergoing one- or two-level transforaminal interbody fusions between 2019 and 2021 who intraoperatively received two different ITO doses (n = 89) vs. the reference group (n = 48) that did not receive ITO. The patients in the ITO group received either 0.2 mg (n = 44) of duramorph or 0.2 mg duramorph + 50 mcg fentanyl (n = 45). The effect of ITO was evaluated for the first four postoperative days (POD) on pain scores (visual analog scale), length of stay (LOS, hours) and opioid requirement (MED, morphine equivalent dose). RESULTS: In the ITO group, a significant reduction of postoperative pain scores (t(99) = 4.3, p < 0.001) and opioid intake (t(70) = 2.49, p = 0.015) was noted on POD1. Cohen's d effect sizes were 0.76 and 0.50, meaning that postoperative pain and MED intake were reduced by about ¾ to ½ standard deviations (SD) in the ITO group. Further, multivariate regression models revealed that ITO administration predicted lower postoperative pain scores for the two PODs (ß = - 0.83, p < 0.001; ß = - 0.63, p = 0.022) and MED intake for the first two PODs (ß = - 20.8, p = 0.047; ß = - 16.4, p = 0.030). Mean LOS was 15.4 h less in the ITO group (mean ± SD, 63.4 ± 37.1 vs. 78.8 ± 39.6, p = 0.10). CONCLUSIONS: In conclusion, our study provides results in a large sample of patients undergoing transforaminal lumbar fusions. The results demonstrated that ITO administration is effective in reducing POD1 pain scores and POD1-2 opioid requirement while not increasing the risk of any opioid-related side effects.

The adverse association between stimulant use for attention deficit hyperactivity disorder (ADHD) and semen parameters.

This study examined the relationship between stimulant medications used for the treatment of attention deficit hyperactivity disorder and semen parameters. We performed a retrospective cohort study at a large, academic institution between 2002 and 2020. We included men with a semen analysis without prior spermatotoxic medication use, empiric medical therapy exposure or confounding medical diagnoses (varicocele, Klinefelter's syndrome, cryptorchidism, cystic fibrosis, diabetes, cancer or cancer-related treatment, and azoospermia). Men were stratified by stimulant exposure (methylphenidate or amphetamines). A multivariable linear regression was fit to assess the association between individual semen parameters, age, stimulant exposure and non-stimulant medication use. Of 8,861 men identified, 106 men had active prescriptions for stimulants within 90 days prior to semen testing. After controlling for age and exposure to non-stimulant medications, stimulant use was associated with decreased total motile sperm count (ß: -18.00 mil/ejaculate and standard error: 8.44, p = 0.033) in the setting of decreased semen volume (ß: -0.35 ml, and standard error: 0.16, p = 0.035), but not sperm concentration, motility and morphology. These findings suggest a role for reproductive physicians and mental health providers to consider counselling men on the potential negative impact of stimulants prescribed for attention deficit hyperactivity disorder on semen volume during fertility planning.

First record of Tmesiphantes Simon, 1892 (Araneae, Theraphosidae) in Peru: a new species and its phylogenetic placement.

The tarantula genus Tmesiphantes Simon, 1892 includes 20 valid species distributed in Argentina and Brazil. These spiders are distinguished from other Theraphosinae genera by the presence of an incrassate femur III, more evident in males, urticating hair types III and IV on the abdominal dorsum, few cuspules on the labium (0 to 30), maxillae with a maximum of 200 cuspules and sternum rounded. From recent examination of material from Peru, we discovered specimens that share all the morphological characters of Tmesiphantes, but did not fit with any known species. In the present study T. intiyaykuy sp. nov. is diagnosed, described, and illustrated. This new species resembles T. caymmii in the circular patch with stiff setae on midventral abdomen but can be distinguished by the shape of the palpal bulb and spermathecae. Also, we performed a phylogenetic analysis using morphological characters to infer the taxonomic placement of the new species. The analysis included 26 terminal species and 36 characters. Representatives of Tmesiphantes formed a monophyletic group and T. intiyaykuy sp. nov. is close related with T. caymmii. A dichotomous identification key and a geographic distribution map were constructed for recognized species of Tmesiphantes.

Isolation and Characterization of Galloylglucoses Effective against Multidrug-Resistant Strains of Escherichia coli and Klebsiella pneumoniae.

The search for new antibiotics against multidrug-resistant (MDR), Gram-negative bacteria is crucial with respect to filling the antibiotics development pipeline, which is subject to a critical shortage of novel molecules. Screening of natural products is a promising approach for identifying antimicrobial compounds hosting a higher degree of novelty. Here, we report the isolation and characterization of four galloylglucoses active against different MDR strains of Escherichia coli and Klebsiella pneumoniae. A crude acetone extract was prepared from Paeonia officinalis Linnaeus leaves, and bioautography-guided isolation of active compounds from the extract was performed by liquid-liquid extraction, as well as open column, flash, and preparative chromatographic methods. Isolated active compounds were characterized and elucidated by a combination of spectroscopic and spectrometric techniques. In vitro antimicrobial susceptibility testing was carried out on E. coli and K. pneumoniae using 2 reference strains and 13 strains hosting a wide range of MDR phenotypes. Furthermore, in vivo antibacterial activities were assessed using Galleria mellonella larvae, and compounds 1,2,3,4,6-penta-O-galloyl-ß-d-glucose, 3-O-digalloyl-1,2,4,6-tetra-O-galloyl-ß-d-glucose, 6-O-digalloyl-1,2,3,4-tetra-O-galloyl-ß-d-glucose, and 3,6-bis-O-digalloyl-1,2,4-tri-O-galloyl-ß-d-glucose were isolated and characterized. They showed minimum inhibitory concentration (MIC) values in the range of 2-256 µg/mL across tested bacterial strains. These findings have added to the number of known galloylglucoses from P. officinalis and highlight their potential against MDR Gram-negative bacteria.

Comparative effectiveness of heel-specific medical devices for the prevention of heel pressure ulcers: A systematic review.

BACKGROUND: Pressure ulcers (PUs) impact on patient's quality of life and are costly for healthcare providers. Heels are a particular concern due to specific risk factors. Relative effectiveness of medical devices, e.g., dressings, off-loading devices, heel cushioning devices, to reduce PU development is unknown. METHODS: Systematic review of the effectiveness of heel-specific medical devices for the prevention of heel PU (HPU)s. Database searches were performed from inception to June 2021 for RCTs. The primary outcome was incidence of new HPUs. Trials were assessed for risk of bias and data analysed with risk ratios, mean difference or hazard ratios as appropriate. RESULTS: Fifteen RCTs (4724 participants) were identified. Dressings, as constant low pressure (CLP) devices vs standard care: eight trials (very low quality) showed no-significant difference in effectiveness (RR 0.31, 95%CI 0.10 to 1.01). Off-loading devices vs standard care: three trials (low quality), showed significant reduction in development of Category≥1 HPUs (RR 0.20, 95%CI 0.05 to 0.80) two trials (medium quality), showed significant reduction in development of Category≥2 HPUs (RR 0.08, 95%CI 0.01 to 0.67). Comparisons between off-loading devices: two trials (low quality) showed no clear difference in HPU incidence. In a paediatric post-surgical population, one trial of off-loading device and one of a dressing (CLP device), both versus standard care, showed no clear difference in HPU incidence (RR 0.19 95%CI 0.02 to 1.55 and RR 0.89 95%CI 0.56 to 1.42 respectively). CONCLUSIONS: Off-loading devices may reduce HPU incidence, from low-quality evidence. There is insufficient evidence to suggest that dressings reduce HPU incidence.

Identifying outcomes reported in trials of interventions in venous leg ulceration for a core outcome set development: A scoping review.

BACKGROUND: Venous leg ulceration is a chronic, recurring, condition causing significant patient morbidity. Randomised controlled trials evaluating treatments for venous leg ulceration provide evidence for clinical decision-making. For trial findings to be useful, outcomes measured need to be clinically meaningful, and consistently and fully reported across trials. A core outcome set is an agreed and standardised set of outcomes which should be, as a minimum, reported in all trials for a given indication. AIM: To identify the outcome domains and outcomes reported in trials of interventions for venous leg ulceration. METHODS: A scoping review of the literature was carried out. Randomised controlled trials within Cochrane systematic reviews looking at venous leg ulceration interventions and qualitative studies exploring venous leg ulceration were included. RESULTS: The review identified 807 outcomes from randomised controlled trials and 15 outcomes from qualitative studies, and these were grouped into 11 outcome domains: healing, patient reported symptoms, clinician reported symptoms, carer reported symptoms, life impacts, clinical signs, clinical measurement, performance of the intervention, resource use (supplies and clinician time) and adverse events. The outcome domain 'healing' included 111 outcomes, 'symptoms' 109, 'life impacts' 30, 'clinical signs' 88, 'clinical measurement' 184, 'performance of the intervention' 58, 'resource use' 52 and 'adverse events' 190. CONCLUSION: The scoping review identified a large number of outcomes (n = 822) across 11 related outcome domains, supporting the need for a core outcome set.

Acute Ischemic Priapism: An AUA/SMSNA Guideline.

PURPOSE: Priapism is a persistent penile erection that continues hours beyond, or is unrelated to, sexual stimulation and results in a prolonged and uncontrolled erection. Given its time-dependent and progressive nature, priapism is a situation that both urologists and emergency medicine practitioners must be familiar with and comfortable managing. Acute ischemic priapism, characterized by little or no cavernous blood flow and abnormal cavernous blood gases (ie, hypoxic, hypercarbic, acidotic) represents a medical emergency and may lead to cavernosal fibrosis and subsequent erectile dysfunction. MATERIALS AND METHODS: A comprehensive search of the literature was performed by Emergency Care Research Institute for articles published between January 1, 1960 and May 1, 2020. Searches identified 2948 potentially relevant articles, and 2516 of these were excluded at the title or abstract level for not meeting inclusion criteria for any key question. Full texts for the remaining 432 articles were reviewed, and ultimately 137 unique articles were included in the report. RESULTS: This Guideline was developed to inform clinicians on the proper diagnosis and surgical and non-surgical treatment of patients with acute ischemic priapism. This Guideline addresses the role of imaging, adjunctive laboratory testing, early involvement of urologists when presenting to the emergency room, discussion of conservative therapies, enhanced data for patient counseling on risks of erectile dysfunction and surgical complications, specific recommendations on intracavernosal phenylephrine with or without irrigation, the inclusion of novel surgical techniques (eg, tunneling), and early penile prosthesis placement. CONCLUSIONS: All patients with priapism should be evaluated emergently to identify the sub-type of priapism (acute ischemic versus non-ischemic) and those with an acute ischemic event should be provided early intervention. Treatment of the acute ischemic patient must be based on patient objectives, available resources, and clinician experience. As such, a single pathway for managing the condition is oversimplified and no longer appropriate. Using a diversified approach, some men may be treated with intracavernosal injections of phenylephrine alone, others with aspiration/irrigation or distal shunting, and some may undergo non-emergent placement of a penile prosthesis.