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Bone is an endocrine organ that participates in whole-body homeostasis. The biology of bone-derived osteokines, however, remains unclear. Liang et al. integrate experimental and computational methods to discover new osteokines, establish their cell of origin and target site, and study their role in aging and during mechanical stress. [ABSTRACT FROM AUTHOR]

Plastics can contain two types of organic contaminants; absorbed from ambient water, and already contained as additives. To investigate the bioaccumulation of these substances, we conducted two types of exposure experiments using mussels and polyethylene microplastics with absorbed PCBs and containing four types of additives (BDE209, DBDPE, UV327 and UV234). After dietary exposure for 15 days, significantly higher concentrations of total PCBs, UV327 and UV234 were detected in the gonad of exposed groups than in the control groups, respectively. However, no significant differences in BDE209 or DBDPE levels were observed between the control and exposure groups. Although a higher transfer ratio was shown for PCB congeners with octanol-water partition coefficients (logK ow) below 7, the ratio was lower for higher-hydrophobic PCBs with logK ow above 7. This suggests that higher hydrophobic compounds (not only highly chlorinated PCBs, but also BDE209 and DBDPE) tend not to desorb or leach from plastics. [Display omitted] • Microplastics containing PCBs and four additives were exposed to mussels. • Increases of PCBs, UV327 and UV234, and decreases of BDE209 and DBDPE were observed. • The transfer ratio of PCBs has elevated with increasing hydrophobicity. • However, the ratio decreased as hydrophobicity of PCBs became extremely high. • High hydrophobicity would disturb the migration of compounds from plastics to biota. [ABSTRACT FROM AUTHOR]

The global context of cooperative intelligent public transport systems (C-ITS) in Smart Cities calls for a solution that integrates the perspectives of the travelers, public administration, vehicle manufacturers and transport operators in the joint effort of standardization, interconnection and assimilation of emerging technologies to meet operational, safety and environmental objectives at metropolitan, national or international level. The article proposes a definition for the capabilities maturity levels of the mobility ecosystem, and functional architecture for the collaborative decision-making system for implementing the C-ITS in the future Smart Cities. The paper contributes to the literature and practice in four manners. The first one is enhancing the awareness and understanding of maturity capability model (CMM) for all the stakeholders throughout the mobility ecosystem, emphasizing the key capabilities required for each maturity level. The second way is manifested throughout public and private companies acting on the same territory in the mobility ecosystem assess the existing capabilities and collaborate for achieving a superior maturity level of mobility processes, stable and repeatable results. In addition, the third one, based on CMM, is that governments regulate, conduct and control, establishing a stable and mature processes institutionalization for C-ITS. Finally, the fourth practice is defining a C-ITS functional architecture for the future Smart Cities to support collaborative decision-making applied for public transport implementation in big Smart Cities with the final objective of increasing the citizen's quality of life. [ABSTRACT FROM AUTHOR]

Mastectomy with immediate reconstruction is a high-risk cohort for postoperative nausea and vomiting (PONV). Known risk factors for PONV include female gender, prior PONV history, nonsmoker, age < 50, and postoperative opioid exposure. The objective of this observational, cohort analysis was to determine whether a standardized preoperative protocol with nonopioid and anti-nausea multimodal medications would reduce the odds of PONV. After IRB approval, retrospective data were collected for patients undergoing mastectomy with or without a nodal resection, and immediate subpectoral tissue expander or implant reconstruction. Patients were grouped based on treatment: those receiving the protocol - oral a cetaminophen, p regabalin, c elecoxib, and transdermal s copolamine (APCS); those receiving none (NONE), and those receiving partial protocol (OTHER). Logistic regression models were used to compare PONV among treatment groups, adjusting for patient and procedural variables. Among 305 cases, the mean age was 47 years (21–74), with 64% undergoing a bilateral procedure and 85% having had a concomitant nodal procedure. A total of 44.6% received APCS, 30.8% received OTHER, and 24.6% received NONE. The APCS group had the lowest rate of PONV (40%), followed by OTHER (47%), and NONE (59%). Adjusting for known preoperative variables, the odds of PONV were significantly lower in the APCS group versus the NONE group (OR=0.42, 95% CI: 0.20, 0.88 p = 0.016). Premedication with a relatively inexpensive combination of oral non-opioids and an anti-nausea medication was associated with a significant reduction in PONV in a high-risk cohort. Use of a standardized protocol can lead to improved care while optimizing the patient experience. [ABSTRACT FROM AUTHOR]

In this issue of Cell Metabolism , Lu et al. show that chronic liver disease increases the expression and activity of PP2Ac, a phosphatase that downregulates the excretion of lecithin-cholesterol aceyltransferase (LCAT). LCAT, a liver-derived enzyme, protects bone and prevents bone loss, and its lowered levels in progressive liver injury cause hepatic osteodystrophy (HOD) and worsen liver fibrosis. These discoveries open the possibility that recombinant LCAT may be a treatment for both HOD and liver fibrosis. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic seemingly is peaking now in New York City and has triggered significant changes to the standard management of gastrointestinal diseases. Priorities such as minimizing viral transmission, preserving personal protective equipment, and freeing hospital beds have driven unconventional approaches to managing gastroenterology (GI) patients. Conversion of endoscopy units to COVID units and redeployment of GI fellows and faculty has profoundly changed the profile of most GI services. Meanwhile, consult and procedural volumes have been reduced drastically. In this review, we share our collective experiences regarding how we have changed our practice of medicine in response to the COVID surge. Although we review our management of specific consults and conditions, the overarching theme focuses primarily on noninvasive measures and maximizing medical therapies. Endoscopic procedures have been reserved for those timely interventions that are most likely to be therapeutic. The role of multidisciplinary discussion, although always important, now has become critical. The support of our faculty and trainees remains essential. Local leadership can encourage well-being by frequent team check-ins and by fostering trainee development through remote learning. Advancing a clear vision and a transparent process for how to organize and triage care in the recovery phase will allow for a smooth transition to our new normal. [ABSTRACT FROM AUTHOR]

• Resolvin D4 mitigated the lung inflammation in LPS-injected mice. • Resolvin D4 maintained epithelial barrier function in LPS-induced cell injury. • Anti-inflammatory effects of Resolvin D4 may be mediated by sirtuin-3 signalling. Acute respiratory distress syndrome (ARDS) is a life-threatening condition involving severe lung inflammation. The excessive oxidative stress and persistent inflammation that occur in ARDS lead to decreased epithelial integrity and hypoxemia due to pulmonary edema via increased vascular permeability. Resolvin D4 (RvD4) is one of the lipid mediators that is biosynthesized from omega-3 polyunsaturated fatty acids. It plays a role in the resolution of inflammation and reduces oxidative stress and cell death. We investigated the therapeutic potential of the administration of RvD4 in a murine model of lipopolysaccharide (LPS)-induced ARDS. Concurrent with the intratracheal administration of LPS, RvD4 or saline was administered to mice via the caudal vein every 12 h. This treatment with RvD4 alleviated the LPS-induced infiltration of inflammatory cells in lungs, inhibited increased pulmonary vascular permeability, decreased the levels of IL-1β, IL-6, and TNF-α in bronchoalveolar lavage fluid (BALF), and suppressed the reduction of the expression levels of the tight junction protein, Zonula occludens-1 (Zo-1) and the NAD+-dependent deacetylase, Sirtuin-3 (Sirt3). In vitro experiments revealed that in LPS-stimulated BEAS-2B cells, treatment with RvD4 suppressed the increases in the expressions of pro-inflammatory cytokines and maintained the epithelial cell barrier function and cell viability. The silencing of SIRT3 abolished both the anti-inflammatory effect and the retention of cell integrity in BEAS-2B cells. Together these results indicate that treatment with RvD4 can (i) protect against LPS-induced lung injury by inhibiting inflammation, and (ii) maintain epithelial barrier function via a reduction in the downregulation of SIRT3. [ABSTRACT FROM AUTHOR]

Abstract Background Unplanned intensive care unit readmission within 72 hours is an established metric of hospital care quality. However, it is unclear what factors commonly increase the risk of intensive care unit readmission in surgical patients. The objective of this study was to evaluate predictors of readmission among a diverse sample of surgical patients and develop an accurate and clinically applicable nomogram for prospective risk prediction. Methods We retrospectively evaluated patient demographic characteristics, comorbidities, and physiologic variables collected within 48 hours before discharge from a surgical intensive care unit at an academic center between April 2010 and July 2015. Multivariable regression models were used to assess the association between risk factors and unplanned readmission back to the intensive care unit within 72 hours. Model selection was performed using lasso methods and validated using an independent data set by receiver operating characteristic area under the curve analysis. The derived nomogram was then prospectively assessed between June and August 2017 to evaluate the correlation between perceived and calculated risk for intensive care unit readmission. Results Among 3,109 patients admitted to the intensive care unit by general surgery (34%), transplant (9%), trauma (43%), and vascular surgery (14%) services, there were 141 (5%) unplanned readmissions within 72 hours. Among 179 candidate predictor variables, a reduced model was derived that included age, blood urea nitrogen, serum chloride, serum glucose, atrial fibrillation, renal insufficiency, and respiratory rate. These variables were used to develop a clinical nomogram, which was validated using 617 independent admissions, and indicated moderate performance (area under the curve: 0.71). When prospectively assessed, intensive care unit providers' perception of respiratory risk was moderately correlated with calculated risk using the nomogram (ρ: 0.44; P <.001), although perception of electrolyte abnormalities, hyperglycemia, renal insufficiency, and risk for arrhythmias were not correlated with measured values. Conclusion Intensive care unit readmission risk for surgical patients can be predicted using a simple clinical nomogram based on 7 common demographic and physiologic variables. These data underscore the potential of risk calculators to combine multiple risk factors and enable a more accurate risk assessment beyond perception alone. [ABSTRACT FROM AUTHOR]

Purpose kV radiotherapy treatment calculations are based on flat, homogenous, full-scatter reference conditions. However, clinical treatments often include surface irregularities and inhomogeneities, causing uncertainty. Therefore, confirmation of actual delivered doses in vivo is valuable. The current study evaluates, and implements, radiochromic film and micro silica bead TLD for in vivo kV dosimetry. Methods The kV energy and dose response of EBT3 film and silica bead TLD was established and uncertainty budgets determined. In vivo dosimetry measurements were made for a consecutive series of 30 patients using the two dosimetry systems. Results Energy dependent calibration factors were required for both dosimetry systems. The standard uncertainty estimate for in vivo measurement with film was 1.7% and for beads was 1.5%. The mean measured dose was −2.1% for film and −2.6% for beads compared to prescription. Deviations up to −9% were found in cases of large surface irregularity, or with underlying air cavities or bone. Dose shielding by beads could be clinically relevant at low kV energies and superficial depths. Conclusions Both film and beads may be used to provide in vivo verification of delivered doses in kV radiotherapy, particularly for complex situations that are not well represented by standard reference condition calculations. [ABSTRACT FROM AUTHOR]

Plastic bronchitis can cause fatal airway obstruction. An 85-year-old woman with no medical history presented to the emergency department of our hospital with progressing respiratory failure and hemoptysis. Bronchoscopy revealed a fibrin-type cast thrombus in the trachea, and plastic bronchitis was diagnosed. Initial treatment involved airway thrombus removal, and the patient survived. However, bleeding persisted for 6 days, and respiratory status showed slight improvement despite ventilatory management. Steroids were administered for concomitant acute respiratory distress syndrome, and there was marked improvement in both airway hemorrhage and respiratory failure. The patient was extubated, the steroid dose was reduced, and no rebleeding was observed. The patient was discharged from the hospital 1 month after the onset of symptoms. Blood tests were positive for the myeloperoxidase-anti-neutrophil cytoplasmic antibody; however, no biopsy was performed, and no specific symptoms were observed. A definitive diagnosis was therefore not reached. The causes of plastic bronchitis are numerous, and there are no standardized diagnostic criteria or treatment guidelines for this condition. The present case suggests that steroids may be effective in some patients with plastic bronchitis. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to determine the incremental yield of prenatal exome sequencing over chromosomal microarray or G-banding karyotype in fetuses with: (1) intrauterine growth restriction related to placental insufficiency or (2) short long bones, in isolated and nonisolated instances for both scenarios.Data Sources: Data were collected via electronic searches for relevant citations from January 2010 to April 10, 2022 in MEDLINE, Embase, Web of Science, and Cochrane, and using relevant bibliographies and data generated in-house.Study Eligibility Criteria: Included were prospective or retrospective cohort studies and/or case series with: (1) n>5 cases of short long bones and/or intrauterine growth restriction undergoing prenatal sequencing with a clearly defined phenotype including assessment of placental function; (2) testing based on prenatal phenotype only; (3) a nondiagnostic chromosomal microarray/karyotype; and (4) known results of genetic testing.Methods: Incremental yield was calculated for each study and as a pooled value for the aforementioned groups using a random-effects model. Results were displayed in forest plots with 95% confidence intervals. Heterogeneity was assessed statistically using Higgins' I2. Publication bias was assessed graphically using funnel plots. Quality assessment was performed using modified Standards for Reporting of Diagnostic Accuracy criteria (International Prospective Register of Systematic Reviews registration number CRD42022324680).Results: Nineteen studies were included (n=452 cases). The apparent incremental yields with prenatal sequencing were: (1) 4% (95% confidence interval, -5.0 to 12; I2=0%) in isolated intrauterine growth restriction with evidence of placental insufficiency, (2) 30% (95% confidence interval, 13-47; I2=1%) in intrauterine growth restriction with additional structural anomalies, (3) 48% (95% confidence interval, 26-70; I2=73%) in isolated short long bones, and (4) 68% (95% confidence interval, 58-77; I2=51%) in short long bones with additional skeletal anomalies. Of the 37 short long bone cases with a diagnosis, 32 had a skeletal dysplasia, with thanatophoric dysplasia and osteogenesis imperfecta being the most common (both 21.6% [n=8/37]). In fetuses with short long bones and additional skeletal features, osteogenesis imperfecta was the most common diagnosis (28% [n=57/204]). Where documented, the inheritance patterns were de novo in 75.4% (n=150) of cases.Conclusion: Prenatal sequencing adds substantially to incremental yield over chromosomal microarray in fetuses with short long bones or multisystem intrauterine growth restriction. Robust studies are required to assess the utility of fetal sequencing in isolated intrauterine growth restriction with evidence of placental insufficiency, which cannot be recommended on the basis of current evidence. [ABSTRACT FROM AUTHOR]

Introduction: The objectives of this study were firstly to determine the proportion of placental pathology in fetuses affected by trisomy 21 (T21) using current pathological descriptive terminology and secondly to examine if a correlation existed between the finding of an abnormal umbilical artery Doppler (UAD) waveform, the presence of T21 and defined placental pathological categories.Methods: This case-control study assessed singleton fetuses with karyotypically confirmed trisomy 21 where placental histopathology had been conducted from 2003 to 2015 inclusive, within a university tertiary obstetric centre. This was compared with unselected normal singleton control pregnancies matched within a week of gestation at delivery. Data included birthweight centiles and placental histopathology. Comparisons of Doppler findings across placental pathological categories were performed using statistical analysis.Results: 104 cases were analysed; 52 cases of trisomy 21 and 52 controls. Fetal vascular malperfusion (48.1% vs. 5.8%, p = 0.001) and maturation defects (39.2% vs. 15.7%, p = 0.023) were more common in trisomy 21 placentas. Compared with controls, trisomy 21 fetuses were more likely to have shorter umbilical cords (p = 0.001) and had more UAD abnormalities. Amongst T21 pregnancies, umbilical artery Doppler abnormalities are associated with the presence of maternal vascular malperfusion.Discussion: Fetal vascular malperfusion and maturation defects are more common in trisomy 21 placentas. Abnormal umbilical artery Doppler waveforms are more common in T21 and are associated with maternal vascular malperfusion. Placental disease may explain the increased rate of intrauterine death in T21. [ABSTRACT FROM AUTHOR]

Lyme disease is the most frequently reported zoonotic tick-borne disease worldwide, and the number of infected humans is increasing. Lyme disease (or Lyme borreliosis) is an affection caused by the spirochete Borrelia burgdorferi, sensu lato. Lyme disease is also reported as a variety of misleading clinical symptomatologies. Infected patient's blood serology is the most currently test used for its diagnosis. However, serology has a low sensitivity, which ranges from 34% to 70%. Thus, there are numerous subsequent false-negative diagnoses despite an active clinical infection profile. Therefore, alternative and more sensitive techniques are required to detect the antigens or nucleic acids of Borrelia. Actually, the most appropriate methodological approach seems to be the polymerase chain reaction (PCR). However, PCR will detect the only "visible" part available of the targeted DNA presence in the blood of the infected patients. Consequently PCR alone will not be conclusive enough to reach the final diagnosis. Considering the ability of Borrelia to invade host cells, we hypothesize that a selective lysis of all blood cells should improve the diagnostic sensitivity of the detection of Borrelia by PCR in whole blood, and subsequently reduce the false-negative diagnostic rate, thus improving the patient's diagnosis and therapeutic management. [ABSTRACT FROM AUTHOR]

Background Patients with advanced cancer and an abdominal surgical emergency pose a dilemma, because rescue surgery may be futile. This study defines morbidity and mortality rates and identifies preoperative risk factors that may predict outcome. Methods The National Surgical Quality Improvement Program database was queried for patients with disseminated cancer undergoing emergent abdominal surgery (2005–2012). Preoperative variables were used for prediction models for 30-day major morbidity and mortality. A tree model and logistic regression were used to find factors associated with outcomes. A training dataset was analyzed and then model performance was evaluated on a validation dataset. Results Study patients had an overall 30-day major morbidity and mortality rate of 48.8% and 26%, respectively. The classification tree model for prediction for a morbidity involved the following variables: sepsis, albumin, functional status, and transfusion (misclassification rate, 36%). The tree model for mortality showed that an American Society of Anesthesiologists (ASA) score of 4 or 5 with a dependent functional status to be predictive of mortality (misclassification rate, 24%). There was agreement between models for predictive variables. Conclusion The decision to operate for an abdominal emergency in the setting of disseminated cancer is difficult. Our study confirms the high risk for morbidity and mortality in this population. Preoperative factors including sepsis, increased ASA class, low serum albumin level, and patient functional dependence all predict poor outcomes. [ABSTRACT FROM AUTHOR]

Abstract: Background: To improve medication-taking behavior, it is important to identify factors that may contribute to suboptimal compliance and persistence with osteoporosis medications. Objective: The purpose of this descriptive analysis was to identify concurrent prescription medication use (number and type) among women receiving daily or weekly oral bisphosphonate therapy. Methods: Patient prescription data were collected from November 1999 to June 2004 from a US patient claims database accessed through Wolters Kluwer Health (formerly NDC Health), which represents >65 million patients annually. Women aged ≥50 years who were receiving daily or weekly oral bisphosphonate medication during the study months were included. Concomitant medications were defined based on ≥14 days of prescription supply in the same month as bisphosphonate therapy. Data were examined to determine the frequency with which certain drugs and drug classes were prescribed concomitantly with bisphosphonates. Each study month was treated independently to assess concomitant medication use. Results: Over the study period, the number of female bisphosphonate recipients in the database increased from 78,909 to 250,286. At the end of the study, 16.2%, 12.2%, 8.7%, and 19.1% of bisphosphonate recipients were prescribed 3, 4, 5, or ≥6 concomitant medications, respectively. The most commonly prescribed concomitant drug classes were cholesterol reducers, diuretics, β-blockers, calcium channel blockers, synthetic thyroid hormones, angiotensin-converting enzyme inhibitors, systemic analgesics/anti-inflammatory drugs, and antispasmodics/antisecretory drugs. From July 2001 until the end of the study, the number of concomitant medications was higher for women receiving daily bisphosphonates than for those receiving weekly bisphosphonates, 4.16 versus 3.77 as of June 2004. In addition, the mean number of concomitant medications prescribed increased with age: in the aged 50 to 64 years cohort, the aged 65 to 74 years cohort, and the aged ≥75 years cohort, the mean number was 3.09, 3.62, and 3.97, respectively, as of June 2004. Conclusion: This analysis suggests that women prescribed bisphosphonates have a high medication burden, with the majority of patients (56%) taking ≥3 concomitant prescription medications. [Copyright &y& Elsevier]

Heart failure and cardiovascular disorders represent the leading cause of death in diabetic patients. Here we present a systematic review of the main mechanisms underlying the development of diabetic cardiomyopathy. We also provide an excursus on the relative contribution of cardiomyocytes, fibroblasts, endothelial and smooth muscle cells to the pathophysiology of heart failure in diabetes. After having described the preclinical tools currently available to dissect the mechanisms of this complex disease, we conclude with a section on the most recent updates of the literature on clinical management. • We present a systematic overview of the main mechanisms underlying the development of heart failure in diabetes. • We examine the role of cardiomyocytes, fibroblasts, endothelial and smooth muscle cells in diabetic cardiomyopathy. • We describe the preclinical tools currently available to dissect in vivo the mechanisms of this complex disease. • A section on the most recent updates on the clinical management of heart failure in diabetic patients concludes the review. [ABSTRACT FROM AUTHOR]

Endowed with sympathetic and peptidergic nerves, the vertebrate skeleton is under constant surveillance by the nervous system. In addition to pituitary hormone secretion, centrally regulated sympathetic release, as elegantly demonstrated by Karsenty and colleagues, integrate to control both components of skeletal remodeling, osteoblastic bone formation, and osteoclastic bone resorption. [Copyright &y& Elsevier]

Low-dose aspirin has been demonstrated to reduce the incidence of preeclampsia and fetal growth restriction in at-risk populations. Its role in low-risk populations is as yet unknown. Novel preeclampsia screening tests are emerging that can predict the risk of the development of preeclampsia from as early as 11 weeks of gestation. It may be more efficacious, acceptable, and cost-effective to prescribe low-dose aspirin to all pregnant women from the first trimester as opposed to performing a screening test in the first instance. There is variation in opinion: the American College of Obstetricians and Gynecologists suggests the use of aspirin only in women who are at risk of preeclampsia, based on patient history; the National Institute for Health and Clinical Excellence, UK, and the US Preventative Services Task Force recommend the use of low-dose aspirin if there is 1 major or 2 moderate risk factors. This point-counterpoint discussion shall address (1) controversies regarding the real impact of low-dose aspirin; (2) controversies in the actual guidelines among the different national societies; (3) controversies regarding emerging preeclampsia screening tests in terms of cost-effectiveness and efficacy, and (4) points in favor of the provision of universal vs screened-positive women. [ABSTRACT FROM AUTHOR]

Background: The hedgehog pathway inhibitor sonidegib demonstrated meaningful tumor shrinkage in more than 90% of patients with locally advanced basal cell carcinoma (BCC) or metastatic BCC in the BCC Outcomes with LDE225 Treatment study.Objective: This report provides long-term follow-up data collected up to 12 months after the last patient was randomized.Methods: In this multicenter, randomized, double-blind phase II study, patients were randomized 1:2 to sonidegib 200 or 800 mg. The primary end point was objective response rate assessed by central review.Results: Objective response rates in the 200- and 800-mg arms were 57.6% and 43.8% in locally advanced BCC and 7.7% and 17.4% in metastatic BCC, respectively. Among the 94 patients with locally advanced BCC who responded, only 18 progressed or died and more than 50% had responses lasting longer than 6 months. In addition, 4 of 5 responders with metastatic BCC maintained an objective response. Grade 3/4 adverse events and those leading to discontinuation were less frequent with sonidegib 200 versus 800 mg (38.0% vs 59.3%; 27.8% vs 37.3%, respectively).Limitations: No placebo or comparator arms were used because sonidegib demonstrated efficacy in advanced BCC in a phase I study, and the hedgehog pathway inhibitor vismodegib was not yet approved.Conclusion: With longer follow-up, sonidegib demonstrated sustained tumor responses in patients with advanced BCC. [ABSTRACT FROM AUTHOR]