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Objective: Image-guided diagnosis and treatment of lung lesions is an active area of research. With the growing number of solutions proposed, there is also a growing need to establish a standard for the evaluation of these solutions. Thus, realistic phantom and preclinical environments must be established. Realistic study environments must include implanted lung nodules that are morphologically similar to real lung lesions under X-ray imaging., Methods: Various materials were injected into a phantom swine lung to evaluate the similarity to real lung lesions in size, location, density, and grayscale intensities in X-ray imaging. A combination of n-butyl cyanoacrylate (n-BCA) and ethiodized oil displayed radiopacity that was most similar to real lung lesions, and various injection techniques were evaluated to ensure easy implantation and to generate features mimicking malignant lesions., Results: The techniques used generated implanted nodules with properties mimicking solid nodules with features including pleural extensions and spiculations, which are typically present in malignant lesions. Using only n-BCA, implanted nodules mimicking ground glass opacity were also generated. These results are condensed into a set of recommendations that prescribe the materials and techniques that should be used to reproduce these nodules., Conclusions: Generated recommendations on the use of n-BCA and ethiodized oil can help establish a standard for the evaluation of new image-guided solutions and refinement of algorithms in phantom and animal studies with realistic nodules.

Objective: To analyze the impact of COVID-19 lockdown on serum glucose levels of pregnant women., Design: A retrospective analysis of O'Sullivan test in pregnant women who underwent COVID-19 lockdown compared to controls. SITE: Poniente Primary Health Care center in Córdoba (Spain)., Participants: 235 pregnant women from 23 +0 to 25 +0 weeks of gestation without diabetes mellitus., Interventions: Gestational diabetes mellitus screening with O'Sullivan test and 3-h oral glucose tolerance test., Main Measurements: Pregnant women who underwent gestational diabetes mellitus screening with O'Sullivan test before (control group) and during COVID-19 Lockdown (Lockdown group) in Córdoba (Spain) were investigated. Lockdown group was divided in early and late lockdown. An additional, control group from data of the same months of the Lockdown in the previous year were recorded to discarded seasonally (adjusted seasonally control) this group was also divided in early and late seasonally adjusted. A logistic regression model for O'Sullivan test has been performed to analyze potential cofounders. Kolgomorov-Smirnov and Kruskal-Wallis test comparing pregnant women who underwent COVID-19 lockdown with the two types of controls., Results: Statistically significant differences were found in serum glucose after O'Sullivan test between lockdown group and control group (123.51±26.02mg/dL and 112.86±31.28mg/dL; p=0.017). When early lockdown group and control group were compared no differences were found (119.64±26.18mg/dL vs. 112.86±31.28mg/dL; p>0.05) whereas differences were observed in late lockdown group and control group (127.22±25.59mg/dL vs. 112.86±31.28mg/dL; p=0.009). Statistical trends were also found between lockdown group and seasonally adjusted group and between lockdown and late seasonally adjusted group (p=0.089). A higher proportion of positive O'Suvillan pregnant women who were subsequently diagnosed with GDM were found in lockdown group compared to the seasonally adjusted control group (60% vs. 26.06% respectively; p<0.05)., Conclusions: The COVID-19 lockdown was associated with an increase in serum glucose levels after the O'Sullivan test as well as a higher GDM diagnosis risk in pregnant women. The findings of our study emphasize the essential requirement for comprehensive maternal services and the accessibility to community's health assets during future lockdown scenarios to pregnant women., (Copyright © 2024 The Author(s). Publicado por Elsevier España S.L.U. All rights reserved.)

Background and Aims: Cardiac fibrosis in response to injury leads to myocardial stiffness and heart failure. At the cellular level, fibrosis is triggered by the conversion of cardiac fibroblasts (CF) into extracellular matrix-producing myofibroblasts. miR-24-3p regulates this process in animal models. Here, we investigated whether miR-24-3p plays similar roles in human models., Methods and Results: Gain- and loss-of-function experiments were performed using human induced pluripotent stem cell-derived cardiomyocytes (hCM) and primary hCF under normoxic or ischaemia-simulating conditions. hCM-derived extracellular vesicles (EVs) were added to hCF. Similar experiments were performed using three-dimensional human cardiac microtissues and ex vivo-cultured human cardiac slices.hCF transfection with miR-24-3p mimic prevented TGFβ1-mediated induction of FURIN, CCND1 and SMAD4-miR-24-3p target genes participating in TGFβ1-dependent fibrinogenesis -, regulating hCF-to-myofibroblast conversion. hCM secreted miR-24-3p as EV cargo. hCM-derived EVs modulated hCF activation. Ischaemia-simulating conditions induced miR-24-3p depletion in hCM-EVs and microtissues. Similarly, hypoxia downregulated miR-24-3p in cardiac slices. Analyses of clinical samples revealed decreased miR-24-3p levels in circulating EVs in acute myocardial infarction (AMI) patients, compared with healthy subjects. Post-mortem RNAScope analysis showed miR-24-3p downregulation in myocardium from AMI patients, compared with patients who died from noncardiac diseases. Berberin, a plant-derived agent with miR-24-3p-stimulatory activity, increased miR-24-3p contents in hCM-EVs, downregulated FURIN, CCND1 and SMAD4, and inhibited fibrosis in cardiac microtissues., Conclusions: These findings suggest that hCM may control hCF activation through miR-24-3p secreted as EV cargo. Ischaemia impairs this mechanism, favouring fibrosis., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Objective: To examine the concordance rate of MRI findings with intraoperative and pathologic findings in patients with Placenta Accreta Spectrum (PAS), as well as the use of structured reporting, and their relationship to clinical outcomes., Methods: An IRB approved retrospective chart review was performed for patients with a history of cesarean delivery, a diagnosis of PAS on post-operative pathology report, and a placental MRI prior to delivery between 2008-2022. Concordance rates were calculated between final MRI, ultrasound, operative, and pathologic diagnoses, as well as impact on clinical outcomes. Quantitative variables were analyzed using a t-test. Categorical variables were analyzed using chi-squared and Fischer's exact tests., Results: A total of 59 patients met initial inclusion criteria. Of these 59 patients, 8 (13.6%) were interpreted using structured reporting. Discordance between preoperative imaging, operative findings and final pathology diagnoses were associated with increased blood loss, blood transfusion, ICU admission, and postpartum length of stay. Structured reporting was found to significantly reduce the amount of diagnostic discordance (p=.017) and was associated with decreased ICU admissions when utilized (p=.045)., Conclusions: Use of structured reporting in the interpretation of placental MRI may decrease the amount of discordance between imaging and intraoperative or pathologic diagnoses, which in our study is associated with improved patient outcomes including decreased blood loss and amount of blood transfused. Radiologists must be cognizant of key imaging features of PAS on MRI, as interpretation provides an opportunity to positively impact the quality and safety of patient care., Competing Interests: Declarations of competing interest None., (Copyright © 2024. Published by Elsevier Inc.)

Introduction: Ezetimibe inhibits cholesterol uptake by modulation of intestinal sterol absorption. Currently, although some studies have shown alterations in ezetimibe levels caused by alterations in the ABCG5 , ABCG8 , NPC1L1 or UGT1A1 genes, there are no pharmacogenetic guidelines to confirm these biomarkers. The aim of this work was to evaluate the effect of 49 variants in 22 pharmacogenes related to metabolism and transport., Methods: A total of 96 healthy volunteers from four bioequivalence clinical trials of ezetimibe as monotherapy or in combination with simvastatin were studied. Blood samples were extracted for unconjugated ezetimibe plasma quantification and genotyping., Results and Discussion: No association of metabolizing enzyme variants with ezetimibe pharmacokinetic parameters was found. The results show some trends in the univariate analysis for ABCB1 rs2032582 or ABCC2 rs2273697 and C max ( p univariate ( p uv ) = 0.056 and 0.087, respectively), which finally reach significance in the multivariate analysis ( p multivariate ( p mv ) = 0.049 and 0.048, respectively). Nevertheless, these results need to be validated in future studies., Competing Interests: FA-S and DO have been consultants or investigators in clinical trials sponsored by the following pharmaceutical companies: Abbott, Alter, Aptatargets, Chemo, Cinfa, FAES, Farmal' der, Ferrer, GlaxoSmithKline, Galenicum, Gilead, Italfarmaco, Janssen-Cilag, Kern, Moderna, MSD, Normon, Novartis, Servier, Silver Pharma, Teva and Zambon. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 González-Iglesias, Ochoa, Navares-Gómez, Zubiaur, Aldama, Torre, Ríos-Rodríguez, Soria-Chacartegui, Rodríguez-Lopez, Abad-Santos and Novalbos.)

Ramipril is an angiotensin-converting enzyme inhibitor used for hypertension and heart failure management. To date, scarce literature is available on pharmacogenetic associations affecting ramipril. The goal of this study was to investigate the effect of 120 genetic variants in 34 pharmacogenes (i.e., genes encoding for enzymes like CYPs or UGTs and transporters like ABC or SLC) on ramipril pharmacokinetic variability and adverse drug reaction (ADR) incidence. Twenty-nine healthy volunteers who had participated in a single-dose bioequivalence clinical trial of two formulations of ramipril were recruited. A univariate and multivariate analysis searching for associations between genetic variants and ramipril pharmacokinetics was performed. SLCO1B1 and ABCG2 genotype-informed phenotypes strongly predicted ramipril exposure. Volunteers with the SLCO1B1 decreased function (DF) phenotype presented around 1.7-fold higher dose/weight-corrected area under the curve (AUC/DW) than volunteers with the normal function (NF) phenotype (univariate p-value [p uv ] < 0.001, multivariate p-value [p mv ] < 0.001, β = 0.533, R 2  = 0.648). Similarly, volunteers with ABCG2 DF + poor function (PF) phenotypes presented around 1.6-fold higher AUC/DW than those with the NF phenotype (p uv  = 0.011, p mv  < 0.001, β = 0.259, R 2  = 0.648). Our results suggest that SLCO1B1 and ABCG2 are important transporters to ramipril pharmacokinetics, and their genetic variation strongly alters its pharmacokinetics. Further studies are required to confirm these associations and their clinical relevance., (© 2024 The Author(s). Basic & Clinical Pharmacology & Toxicology published by John Wiley & Sons Ltd on behalf of Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).)

Summary: Monteggia fracture is a complex fracture consisting of a proximal ulna fracture with a dislocation of the radial head. This review article highlights the relevant anatomy, clinical evaluation, classification, surgical management, recent innovation, and advancements with treating these injuries. A thorough understanding of these fractures allows for detailed operative plans and reconstitution of normal anatomy., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Some evidence suggests that surgical minimally invasive (MIDCAB) and hybrid coronary revascularization (HCR) are safe and potentially effective at short-term follow-up. Data on long-term outcomes are more limited and inconclusive., Methods: Between February 2013 and December 2023, a total of 1997 patients underwent surgical coronary artery revascularization at our institution, of whom, 92 (4.7%) received left anterior mini-thoracotomy access (MIDCAB), either isolated (N = 78) or in combination with percutaneous coronary intervention (N = 14, HCR group)., Results: After a median follow-up of 75 months (range 3.1: 149 months), cardiac mortality was 0% while overall mortality was 3%, with one in-hospital mortality and two additional late deaths. Conversion to sternotomy happened in two patients (2.1%), and surgical re-explorations occurred in five patients (4.6%), of whom three for bleeding and two for graft failure. All patients received left internal mammary (LIMA) to left anterior descending artery (LAD) grafting (100%). In the HCR group, 10 patients (72%) showed percutaneous revascularization (PCI) after MIDCAB, showing PCI on a mean of 1.6 ± 0.6 vessels and implanting 2.1 ± 0.9 drug-eluting stents., Conclusions: MIDCAB, in isolation or in association with hybrid coronary revascularization, is associated with encouraging short- and long-term results in selected patients discussed within a dedicated heart-team.

Background: Blood glucose level variability has been associated with increased risk of complication in the postoperative setting of cardiovascular surgery. Although interesting for optimization of blood glucose management in this context, continuous blood glucose (CBG) devices can have a limited reliability in this context, in particular because of the use of paracetamol. The aim of this study was to evaluate the reliability of Dexcom G6®, a recently developed continuous glucose monitoring device., Methods: We performed a prospective, observational, non-randomized, single-centre study comparing Dexcom G6® CBG level monitoring with the standard methods routinely used in this context. The standard blood glucose values were paired to the time corresponding values measured with Dexcom G6®. Agreement between the two methods and potential correlation in case of paracetamol use were calculated., Results: From May 2020 to August 2021, 36 out of 206 patients operated for isolated coronary artery bypass grafting were enrolled; 673 paired blood glucose level were analyzed. Global agreement (ρc) was 0.85 (95% C.I.: 0.84-0.86), intensive care unit agreement was 0.78 (95%C.I.: 0.74-0.82) and ward agreement was 0.91 (95%C.I.: 0.89-0.93). In the diabetic population, it was 0.87 (95%C.I.: 0.85-0.90). When paracetamol was used, the difference was 0.02 mmol/l (95%C.I.: 0.29-0.33)., Conclusions: Dexcom G6 ® provides good blood glucose level accuracy in the postoperative context of cardiac surgery compared to the standard methods of measurements. The results are particularly reliable in the ward where the need for repeated capillary glucose measurements implies patient discomfort and time-consuming manipulations for the nursing staff., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Understanding how management influences forage nutritive value and grazer selection within grazing seasons is an ongoing effort for researchers and land managers globally. We used six, 65 ha pastures managed with patch-burn grazing and stocked with either cow-calf pairs (0.45-0.5 ha • AUM -1 ) or gestating ewes (0.4-0.48 ha • AUM-1) to explore how patterns in rangeland forage drive grazer selection in semi-arid rangeland over four summer grazing seasons at monthly intervals. We used near-infrared spectroscopy to determine nutritive value parameters from monthly forage clippings. We evaluated livestock performance as the average daily weight gains of each animal. We used mixed-effect models and ordination to compare patch and grazer types across the time-since-fire gradient and found that time-since-fire was significant for all measured variables. Cattle and sheep consistently preferred recently burned patches throughout grazing seasons. These recently burned patches typically contained available forage with higher crude protein and moisture content, lower biomass, and lower acid detergent fiber, acid detergent lignin, and neutral detergent fiber compared to intermediate time since fire patches and patches burned three years ago. Differences between patch-burn grazing with cattle and sheep were observed as additional patch contrasts for available biomass and crude protein, but grazer type and ecological site were not statistically significant factors for the nutritive value ordination. Our study indicates that patch-burn grazing is capable of imposing and maintaining heterogeneous, grazer selection, forage biomass, and nutritive value patterns desirable for heterogeneity focused land management, regardless of grazer type. These findings are especially relevant to the northern Great Plains where introduced grasses are homogenizing the structural environment of remaining rangelands. With prescribed fire currently an uncommon practice throughout the region, these findings provide a baseline of expectations for practitioners and land managers implementing patch-burn grazing and illustrate how grazing livestock can benefit from the patch contrast in forage nutritive value and biomass., Competing Interests: Declaration of competing interest We have no declared conflicts of interest regarding this manuscript or project., (Published by Elsevier Ltd.)

Calciphylaxis is a rare disease characterized by calcification of the middle layer of small arteries and arterioles, causing secondary cuta-neous ischemia. The diagnosis is clinical but may be confirmed by histological examination. The optimal treatment is not exactly known, although there is consensus that a multifactorial approach is required. This report is regarding the case of a female patient with a kidney transplant requiring peritoneal dialysis, in the late postoperative period of partial parathyroidectomy due to severe hyperparathyroidism, with refractory hypocalcemia and severe calciphylaxis, subsequently treated with intralesional sodium thiosulfate due to initial intoler-ance to intravenous thiosulfate treatment. J Drugs Dermatol. 2023;22(12):e28-e30.&nbsp; &nbsp;&nbsp; doi:10.36849/JDD.7362e.

Background: The quality of a myocardial protection of a single-dose del Nido cardioplegia versus multiple dose blood-based cardioplegia on myocardial injury, outcomes and operative times in patients undergoing minimally invasive aortic valve replacement is basically unreported., Methods and Results: Preoperative and post-operative data, as well as technical details from isolated minimally invasive aortic valve replacements, performed using single-dose or multiple-dose cardioplegia were prospectively collected and retrospectively analysed. A total of 110 patients undergoing minimally invasive valve replacements at our institution composed two groups: 55 patients in the blood cardioplegia group (BloCa) and 55 in the del Nido group (DeNiCa). The two-matched groups were comparable in terms of preoperative variables. In the DeNiCa group, there was a statistically significant less need for cardiac defibrillation after aortic cross-clamp release ( p  < 0.001). Moreover, the BloCa group received intraoperatively more blood transfusions ( p  = 0.001) and more insulin administration for higher glucose levels ( p  < 0.001). The BloCa group showed higher intraoperative lactate levels ( p  = 0.01). Need for post-operative inotropic and vasoactive support, Creatine Kinase-MB levels after 6 and 12 h, onset of post-operative atrial fibrillation and length of stay were similar. No deaths occurred in neither groups., Conclusion: Single-dose del Nido cardioplegia in the setting of minimally invasive aortic surgery seems to offer adequate myocardial protection, comparable to multiple dose hematic cardioplegia. It has been documented a lower peri-operative need of defibrillation after cross-clamp release, lactate- and glucose peak values, as well as less blood transfusions compared to blood cardioplegic strategy., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Introduction: Humeral shaft fractures can be treated non-operatively or operatively. The optimal management is subject to debate. The aim was to compare non-operative and operative treatment of a humeral shaft fracture in terms of fracture healing, complications, and functional outcome., Methods: Databases of Embase, Medline ALL, Web-of-Science Core Collection, and the Cochrane Central Register of Controlled Trials (CENTRAL) were systematically searched for publications reporting clinical and functional outcomes of humeral shaft fractures after non-operative treatment with a functional brace or operative treatment by intramedullary nailing (IMN; antegrade or retrograde) or plate osteosynthesis (open plating or minimally invasive). A pooled analysis of the results was performed using MedCalc., Results: A total of 173 studies, describing 11,868 patients, were included. The fracture healing rate for the non-operative group was 89% (95% confidence interval (CI) 84-92%), 94% (95% CI 92-95%) for the IMN group and 96% (95% CI 95-97%) for the plating group. The rate of secondary radial nerve palsies was 1% in patients treated non-operatively, 3% in the IMN, and 6% in the plating group. Intraoperative complications and implant failures occurred more frequently in the IMN group than in the plating group. The DASH score was the lowest (7/100; 95% CI 1-13) in the minimally invasive plate osteosynthesis group. The Constant-Murley and UCLA shoulder score were the highest [93/100 (95% CI 92-95) and 33/35 (95% CI 32-33), respectively] in the plating group., Conclusion: This study suggests that even though all treatment modalities result in satisfactory outcomes, operative treatment is associated with the most favorable results. Disregarding secondary radial nerve palsy, specifically plate osteosynthesis seems to result in the highest fracture healing rates, least complications, and best functional outcomes compared with the other treatment modalities., (© 2023. The Author(s).)

Background: Thoracic endovascular aortic repair (TEVAR) has become a standard treatment for acute and chronic thoracic aorta diseases. We analyzed long-term outcomes and risk factors of TEVAR procedures according to the aortic pathology., Methods: Demographics, indications, technical details, and outcomes of patients undergoing TEVAR procedures in our institutions were prospectively collected and retrospectively analyzed. Overall survival was determined using Kaplan-Meier methods while log-rank tests were used to compare the survival between groups. Cox regression analysis was used to identify risk factors., Results: Between June 2002 and April 2020, 116 patients underwent TEVAR for different thoracic aorta diseases. Among them, 47 patients (41%) underwent TEVAR for aneurysmatic aortic disease, 26 (22%) for type-B aortic dissection, 23 (20%) for penetrating aortic ulcer, 11 (9%) after previous type-A dissection treatment, and 9 (8%) for traumatic aortic injury. Patients with posttraumatic aortic injury were younger (P < 0.01) with less hypertension (P < 0.01), diabetes (P < 0.01), and prior cardiac surgery (P < 0.01). Survival was different based on indication for TEVAR (log rank 0.024). Patients after previous type-A dissection treatment had the worst survival rate (50% at 5 years) while survival for aneurysmatic aortic disease was 55% at 5 years. No late death occurred in the traumatic group. Cox-regression model identified independent predictors for mortality: age (hazard ratio [HR]: 1.05, 95% confidence interval [CI]: 1.01-1.09, P = 0.006), male gender (HR: 3.2, 95% CI: 1.1-9.2, P = 0.028), moderate chronic obstructive pulmonary disease (HR: 2.1, 95% CI: 1.02-4.55, P = 0.043), previous cardiac surgery (HR: 2.1, 95% CI: 1.008-4.5, P = 0.048), and treatment indication for aneurysm (HR: 2.6, 95% CI: 1.2-5.2, P = 0.008)., Conclusions: TEVAR is a safe and effective procedure with excellent long-term results in case of traumatic aortic injury. The overall long-term survival is affected by aortic pathology, associated comorbidities, gender, and previous cardiac surgery., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: The COVID-19 pandemic entailed cutting off the usual access to hospitals, denying patients daily visits from their relatives and friends. The standard communication between medical staff and relatives also suffered, with a perceived negative impact on overall care. We developed an electronic communication solution to re-establish a proactive daily communication with patients' families., Methods: The communication software allowed families to receive daily interprofessional (medical, nursing, and physiotherapy) updates by text message, on patients' postoperative clinical state. Appreciation and performance of this communication was evaluated through a prospective randomised study. Two groups were compared (group D, 32 patients "Digital" receiving daily SMS, and group S, 16 patients "Standard" without SMS), assessing satisfaction through dedicated surveys under COVID-19 restrictions. Moreover, private outgoing vs. incoming communication flow between patients and their relatives (phone calls and text messages, for both groups) were analysed at different timeframes of the postoperative hospital stay., Results: Mean age of the population was 66 ± 7 years for both groups. The digital communication service was successfully adopted in group D in all cases, sending overall 155 communications (4.84 per patient). Calls received from relatives were 13 in group D vs. 22 in group S (0.4 vs. 1.4 calls per patient, p  = 0.002). Patients' outgoing vs. incoming traffic flow was equal in the two groups for every timeframe (first two postoperative days vs. the rest), independently from digital communication. Comparing satisfaction of communication (from 1 to 7), level of information and understandability resulted in 6.7 in group D vs. 5.6 in group S ( p  = 0.004). Appreciation of digital communication was highest during the first three postoperative days., Conclusion: The restrictions caused by the COVID-19 pandemic generated simple and effective ideas on digital solutions for interprofessional communication. Offering this digital service, which complements rather than replace the classic communication, eased the need of the families to be informed and significantly enhanced the overall satisfaction regarding the healthcare service., Summary: The COVID-19 pandemic has interrupted access to hospital patients and cut off physical contact, denying patients, their families, and medical staff the necessary constant communication about the progress of their stay. It has become necessary, therefore, to compensate for the lack of "physical" face-to-face interaction by introducing innovative digital communication solutions. Our interprofessional project aims to assess the overall satisfaction and acceptance of digital communication service between the hospital and the families, updating on postoperative clinical condition of patients. Specifically, the introduction of a digital communication module attached to the electronic patient record allows relatives to be informed on a daily basis. The development of this module/software enabled families to receive daily, interprofessional and proactive digital updates, on their relative ones' postoperative stay., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Pozzoli, Zurfluh, Schulz, Bianchi, Giuffrida, Crivelli, Torre, Ferrari and Demertzis.)

Background: Cell therapy has been proposed as part of the therapeutic arsenal to assist bone formation and remodeling in the early stages of osteonecrosis of the femoral head. The purpose of this study is to determine the effects of intraosseous inoculation of mesenchymal stem cells on bone formation and remodeling in an established experimental model of osteonecrosis of the femoral head in immature pigs., Methods: Thirty-one 4-week-old immature Yorkshire pigs were used. Experimental osteonecrosis of the femoral head was created in the right hip of all included animals ( n   =  31). The month after surgery, hip and pelvis radiographs were taken to confirm osteonecrosis of the femoral head. Four animals were excluded following surgery. Two groups were established: (A) mesenchymal stem cell-treated group ( n   =  13) and (B) saline-treated group ( n   =  14). One month after surgery the mesenchymal stem cell-group received an intraosseous injection of 10  ×  10 6 mesenchymal stem cell (5 cc) and the saline-treated group of 5 cc of physiological saline solution. Osteonecrosis of the femoral head progression was assessed by monthly X-rays (1-, 2-, 3- and 4-months post-surgery). The animals were sacrificed 1 or 3 months following the intraosseous injection. Repair tissue and osteonecrosis of the femoral head were histologically evaluated immediately after sacrifice., Results: At time of sacrifice, radiographic images showed evident osteonecrosis of the femoral head with associated severe femoral head deformity in 11 of the 14 animals (78%) in the saline group and in only 2 of the 13 animals (15%) in the mesenchymal stem cell group. Histologically, the mesenchymal stem cell group showed less osteonecrosis of the femoral head and less flattening. In the saline group, there was pronounced femoral head flattening and the damaged epiphyseal trabecular bone was largely replaced with fibrovascular tissue., Conclusion: Intraosseous mesenchymal stem cells inoculation improved bone healing and remodeling in our immature pig osteonecrosis of the femoral head model. This work supports further investigation to determine whether mesenchymal stem cells enhance the healing process in immature osteonecrosis of the femoral head.

Aims of the Study: We evaluated the clinical outcome and the hemodynamic and freedom from structural valve degeneration of two standard aortic bioprostheses. Methods: Clinical results, echocardiographic findings and follow-up data of patients operated for isolated or combined aortic valve replacement with the Perimount or the Trifecta bioprosthesis were prospectively collected, retrospectively analysed and compared. We weighted all the analyses by the inverse of the propensity of choosing either valves. Results: Between April 2015 and December 2019, 168 consecutive patients (all comers) underwent aortic valve replacement with Trifecta (n = 86) or Perimount (n = 82) bioprostheses. Mean age was 70.8 ± 8.6 and 68.8 ± 8.6 years for the Trifecta and Perimount groups, respectively ( p = 0.120). Perimount patients presented a greater body mass index (27.6 ± 4.5 vs. 26.0 ± 4.2; p = 0.022), and 23% of them suffered from angina functional class 2-3 (23.2% vs. 5.8%; p = 0.002). Mean ejection fraction was 53.7 ± 11.9% (Trifecta) and 54.5 ± 10.4% (Perimount) ( p = 0.994), with mean gradients of 40.4 ± 15.9 mmHg (Trifecta) and 42.3 ± 20.6 mmHg (Perimount) ( p = 0.710). Mean EuroSCORE-II was 7 ± 11% and 6 ± 9% for the Trifecta and Perimount group, respectively ( p = 0.553). Trifecta patients more often underwent isolated aortic valve replacement (45.3% vs. 26.8%; p = 0.016) and annulus enlargement (10.5% vs. 2.4%; p = 0.058). All-cause mortality at 30 days was 3.5% (Trifecta) and 8.5% (Perimount), ( p = 0.203) while new pacemaker implantation (1.2% vs. 2.5%; p = 0.609) and stroke rate (1.2% vs. 2.5%; p = 0.609) were similar. Acute MACCE were observed in 5% (Trifecta) and 9% (Perimount) of patients with an unweighted OR of 2.22 (95%CI 0.64-7.66; p = 0.196) and a weighted OR of 1.10 (95%CI: 0.44-2.76, p = 0.836). Cumulative survival at 24 months was 98% (95%CI: 0.91-0.99) and 96% (95%CI: 0.85-0.99) for Trifecta and Perimount groups, respectively (log-rank test; p = 0.555). The 2-year freedom from MACCE was 94% (95%CI: 0.65-0.99) for Trifecta and 96% (95%CI: 0.86-0.99) for Perimount (log-rank test; p = 0.759, HR 1.46 (95%CI: 0.13-16.48)) in the unweighted analysis (not estimable in the weighted analysis). During the follow-up (median time: 384 vs. 593 days; p = 0.0001) there were no re-operations for structural valve degeneration. Mean valve gradient at discharge was lower for Trifecta across all valve sizes (7.9 ± 3.2 vs. 12.1 ± 4.7 mmHg; p < 0.001), but the difference did not persist during follow-up (8.2 ± 3.7 mmHg for Trifecta, 8.9 ± 3.6 mmHg for Perimount; p = 0.224); Conclusions: Postoperative outcome and mid-term follow-up were similar. An early better hemodynamic performance was detected for the Trifecta valve but did not persist over time. No difference in the reoperation rate for structural valve degeneration was found.

To address the antimicrobial resistance (AMR) crisis, governments around the world have created action plans to optimize antimicrobial use (AMU). These plans include antimicrobial stewardship (AMS) that encompasses educational programs for healthcare workers. We discuss these programs in sub-Saharan Africa, including the opportunities and challenges arising from a highly constrained healthcare environment., (Published by Elsevier Ltd.)

Background: Recommendations for the diagnosis of pulmonary embolism are available for healthcare providers. Yet, real practice data show existing gaps in the translation of evidence-based recommendations. This is a study to assess the effect of a computerised decision support system (CDSS) with an enhanced design based on best practices in content and reasoning representation for the diagnosis of pulmonary embolism., Design: Randomised preclinical pilot study of paper-based clinical scenarios in the diagnosis of pulmonary embolism. Participants were clinicians (n=30) from three levels of experience: medical students, residents and physicians. Participants were randomised to two interventions for the diagnosis of pulmonary embolism: a didactic lecture versus a decision tree via a CDSS. The primary outcome of diagnostic pathway concordance (derived as a ratio of the number of correct diagnostic decision steps divided by the ideal number of diagnostic decision steps in diagnostic algorithms) was measured at baseline (five clinical scenarios) and after either intervention for a total of 10 clinical scenarios., Results: The mean of diagnostic pathway concordance improved in both study groups: baseline mean=0.73, post mean for the CDSS group=0.90 (p<0.001, 95% CI 0.10-0.24); baseline mean=0.71, post mean for didactic lecture group=0.85 (p<0.001, 95% CI 0.07-0.2). There was no statistically significant difference between the two study groups or between the three levels of participants., Interpretation: A computerised decision support system designed for both content and reasoning visualisation can improve clinicians' diagnostic decision-making., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Antimicrobial resistance (AMR) is a global health issue disproportionately affecting low- and middle-income countries. In Tanzania, multi-drug-resistant bacteria (MDR) are highly prevalent in clinical and community settings, inhibiting effective treatment and recovery from infection. The burden of AMR can be alleviated if antimicrobial stewardship (AMS) programs are coordinated and incorporate local knowledge and systemic factors. AMS includes the education of health providers to optimise antimicrobial use to improve patient outcomes while minimising AMR risks. For programmes to succeed, it is essential to understand not just the awareness of and receptiveness to AMR education, but also the opportunities and challenges facing health professionals. We conducted in-depth interviews ( n = 44) with animal and human health providers in rural northern Tanzania in order to understand their experiences around AMR. In doing so, we aimed to assess the contextual factors surrounding their practices that might enable or impede the translation of knowledge into action. Specifically, we explored their motivations, training, understanding of infections and AMR, and constraints in daily practice. While providers were motivated in supporting their communities, clear issues emerged regarding training and understanding of AMR. Community health workers and retail drug dispensers exhibited the most variation in training. Inconsistencies in understandings of AMR and its drivers were apparent. Providers cited the actions of patients and other providers as contributing to AMR, perpetuating narratives of blame. Challenges related to AMR included infrastructural constraints, such as a lack of diagnostic testing. While health and AMR-specific training would be beneficial to address awareness, equally important, if not more critical, is tackling the challenges providers face in turning knowledge into action.

Detection of pathogens has become increasingly important, especially in the face of outbreaks and epidemics all over the world. Nucleic acid detection techniques provide a solid base to detect and identify pathogens. In recent years, magnetic sensors and magnetic labels have become of more interest due to their simplicity of use, low cost, and versatility. In this work, we have used the isothermal DNA amplification technique of rolling circle amplification (RCA) in combination with oligo-functionalized magnetic nanoparticles. Detection of RCA products takes place through specific binding between magnetic nanoparticles and RCA products. Upon binding, the relaxation frequency of the nanoparticle changes. This change was measured using an AC susceptometer. We showcase that the RCA time can be reduced for a quicker assay when performing the RCA on the surface of micrometer-sized beads, which consequently increases the hydrodynamic volume of the RCA products. This, in turn, increases the Brownian relaxation frequency shift of the nanoparticles upon binding. We performed optimization work to determine the ideal quantity of micrometer-sized particles, oligo-functionalized nanoparticles, and the amplification time of the RCA. We show that the detection of 0.75 fmol of preamplification synthetic target is possible with only 20 min of amplification time. Finally, we showcase the high specificity of the assay, as the functionalized nanoparticles are unable to bind to amplified DNA that does not match their labels. Overall, this paves the way for a simple bioassay that can be used without expensive laboratory equipment for detection of pathogens in outbreak settings and clinics around the world., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Objective: Transcatheter aortic valve replacement (TAVR) through alternative access routes is indicated in patients with severe aortic valve stenosis and diseased peripheral arteries. We analysed and compared the outcome of patients undergoing transapical (TA) and direct transaortic (TAO) TAVR procedures. Methods: Preoperative characteristics, procedural details, and thirty-day outcome of patients undergoing transapical (TA-TAVR group) and direct transaortic (TAO-TAVR group) TAVR procedures were prospectively collected and retrospectively analysed. Results: From March 2012 to March 2022, 81 TA and 82 TAO-TAVR (total: 163 cases) were performed with balloon-expanding (n = 120; 73.6%) and self-expandable (n = 43; 26.4%) valves. The mean age was 79.7 ± 6.2 and 81.9 ± 6.7 years for the TA- and TAO-TAVR groups, respectively (p = 0.032). Females were more represented in the TAO-TAVR group (56% vs. 32%; p = 0.003) while TA-TAVR patients showed a higher prevalence of previous vascular surgery (20% vs. 6%; p = 0.01), previous cardiac surgery (51% vs. 3.6%; p < 0.001), and porcelain aorta (22% vs. 5%; p = 0.001). The mean ejection fraction was 49.0 ± 14.6% (TA) and 53.5 ± 12.2% (TAO) (p = 0.035) while mean gradients were 35.6 ± 13.2 mmHg (TA) and 40.4 ± 16.1 mmHg (TAO) (p = 0.045). The median EuroSCORE-II was 5.0% (IQR: 3.0−11.0) and 3.9% (IQR: 2.5−5.4) for the TA- and TAO-TAVR groups, respectively (p = 0.005). The procedural time was shorter for TA procedures (97 min (IQR: 882−118) vs. 102 min (IQR: 88−129); p = 0.133). Mortality at day 30 was 6% in both groups (p = 1.000); the permanent pacemaker implantation rate was similar (8.6% vs. 9.7%; p = 1.000), and hospital stay was shorter for the TAO group (8 days (IQR: 6−11) vs. 10 days (IQR: 7−13); p = 0.025). Conclusions: Our results show that transapical and direct transaortic TAVR in high-risk patients with diseased peripheral arteries provide satisfactory clinical results with similar thirty-day outcomes.

Background: Mitral annular calcification (MAC) may represent a significant challenge for heart surgeons with an extremely high perioperative risk during mitral valve (MV) surgery. The risk is further increased when patients fail to be eligible for any percutaneous treatment, particularly because circumferential calcifications involving the anterior leaflet suggest a critical obstruction of the left ventricular outflow tract (LVOT)., Objectives: The objective of this study was to evaluate residual mitral regurgitation (MR) after surgical mitral valve replacement using a Sapien 3 Ultra (Edwards Lifesciences, CA, USA) transcatheter aortic valve implantation (TAVI) prosthesis, reinforced with a pericardial skirt, in high-risk selected patients with severe MAC., Methods: Since 2020, five high-risk patients (mean age 70 years; 63-76; four women) with severe mitral disease in the context of severe MAC (computed tomography-based mean MAC Score 8.2 ± 1.1) were operated on after we adopted this novel technique. The operations were performed under general anesthesia, using a transapical TAVI delivery system to position the Sapien 3 in the mitral position under direct vision. To reinforce and avoid paravalvular leakages, a pericardial skirt was previously sewn around the prosthesis, securing it to the annulus and perivalvular atrial surface., Results: Sapien 3 Ultra implantation was successful without residual MR in all five patients (mild paravalvular leak in one case). Four patients had a 29-mm valve implanted, while one had a 26-mm valve implanted. Predilatation of the native annulus was never performed. Perfusion and clamping times were 134 ± 53 mins and 108 ± 43 mins, respectively. The presence of the pericardial skirt reduced the risk of leakage between the prosthesis and the rigid calcium surface, with final mean and maximal gradients of the TAVI prosthesis of 4.1 and 10.8 mmHg, respectively. There were no left ventricular outflow tract obstructions (mean LVOT gradient of 8 ± 1 mmHg). All patients were discharged, and neither mortality nor prosthetic dysfunction, nor residual mitral regurgitation was recorded. During follow-up, the last patient treated (MAC Score 10, severe calcification of the mitro-aortic junction) returned to our attention with a significant recurrent jet originating from the anterolateral commissure, currently medically treated, given the prohibitive redo risk., Conclusion: Direct open surgical implantation of the Sapien 3 valve can be safely done in patients with severe MAC in dedicated centers. Reinforcing the TAVI prosthesis by sewing a pericardial skirt led to satisfactory perioperative and early postoperative results, reducing paravalvular leakages. Complex anatomies have a CERTAIN risk of recurrence., Competing Interests: Author EF is a consultant for Edwards Lifesciences. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Pozzoli, Torre, Pedrazzini, Demertzis and Ferrari.)

An attractive approach to increase the aqueous apparent solubility of poorly soluble drugs is to formulate them in their amorphous state. In the present study, celecoxib, a poorly soluble drug, was successfully loaded into mesoporous magnesium carbonate (MMC) in its amorphous state via a solvent evaporation method. Crystallization of celecoxib was suppressed, and no reaction with the carrier was detected. The MMC formulation was evaluated in vitro and in vivo in terms of oral bioavailability. Celebra®, a commercially available formulation, was used as a reference. The two celecoxib formulations were orally administrated in male rats (average of n = 6 animals per group), and blood samples for plasma were taken from all animals at different time points after administration. There was no statistical difference (p > 0.05) in AUCinf between the two formulations. The results showed that MMC may be a promising drug delivery excipient for increasing the bioavailability of compounds with solubility-limited absorption.

Rationale: Aging in the heart is a gradual process, involving continuous changes in cardiovascular cells, including cardiomyocytes (CMs), namely cellular senescence. These changes finally lead to adverse organ remodeling and resulting in heart failure. This study exploits CMs from human induced pluripotent stem cells (iCMs) as a tool to model and characterize mechanisms involved in aging. Methods and Results: Human somatic cells were reprogrammed into human induced pluripotent stem cells and subsequently differentiated in iCMs. A senescent-like phenotype (SenCMs) was induced by short exposure (3 hours) to doxorubicin (Dox) at the sub-lethal concentration of 0.2 µM. Dox treatment induced expression of cyclin-dependent kinase inhibitors p21 and p16, and increased positivity to senescence-associated beta-galactosidase when compared to untreated iCMs. SenCMs showed increased oxidative stress, alteration in mitochondrial morphology and depolarized mitochondrial membrane potential, which resulted in decreased ATP production. Functionally, when compared to iCMs, SenCMs showed, prolonged multicellular QTc and single cell APD, with increased APD variability and delayed afterdepolarizations (DADs) incidence, two well-known arrhythmogenic indexes. These effects were largely ascribable to augmented late sodium current (I NaL ) and reduced delayed rectifier potassium current (Ikr). Moreover sarcoplasmic reticulum (SR) Ca 2+ content was reduced because of downregulated SERCA2 and increased RyR2-mediated Ca 2+ leak. Electrical and intracellular Ca 2+ alterations were mostly justified by increased CaMKII activity in SenCMs. Finally, SenCMs phenotype was furtherly confirmed by analyzing physiological aging in CMs isolated from old mice in comparison to young ones. Conclusions: Overall, we showed that SenCMs recapitulate the phenotype of aged primary CMs in terms of senescence markers, electrical and Ca 2+ handling properties and metabolic features. Thus, Dox-induced SenCMs can be considered a novel in vitro platform to study aging mechanisms and to envision cardiac specific anti-aging approach in humans., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Inappropriate wound healing (WH) management can cause significant comorbidities, especially in patients affected by chronic and metabolic diseases, such as diabetes. WH involves several different, partially overlapping processes, including hemostasis, inflammation, cell proliferation, and remodeling. Oxidative stress in WH contributes to WH impairment because of the overexpression of radical oxygen species (ROS) and nitrogen species (RNS). This study aimed to evaluate the in vitro antioxidative action of a gel containing a Propionibacterium extract (Emorsan ® Gel) and assess its skin re-epithelialization properties in a mouse model of WH. The scavenging effects of the bacterial extract were assessed in vitro through the ABTS and DPPH assays and in L-929 murine fibroblasts. The effects of the Emorsan ® Gel were studied in vivo in a murine model of WH. After WH induction, mice were treated daily with vehicle or Emorsan ® Gel for 6 or 12 days. According to the in vitro tests, the Propionibacterium extract exerted an inhibitory effect on ROS and RNS, consequently leading to the reduction in malondialdehyde (MDA) and nitrite levels. Before proceeding with the in vivo study, the Emorsan ® Gel was verified to be unabsorbed. Therefore, the observed effects could be ascribed to a local action. The results obtained in vivo showed that through local reduction of oxidative stress and inflammation (IL-1β, TNF-α), the Emorsan ® Gel significantly reduced the infiltration of mast cells into the injured wound, leading to the amelioration of symptoms such as itch and skin irritation. Therefore, the Emorsan ® Gel improved the speed and percentage of wound area closure by improving the tissue remodeling process, prompting vascular-endothelial growth factor (VEGF) and transforming growth factor (TGF)- β production and reducing the expression of adhesion molecules. Emorsan ® Gel, by its ability to inhibit free radicals, could reduce local inflammation and oxidative stress, thus enhancing the speed of wound healing.

The current cardiac surgical landscape, with the expansion of minimally invasive operations, ECMO, and some interventional therapies, requires a thorough knowledge of peripheral cannulation techniques. In particular, venous cannulation may appear trivial and complication-free, but this does not reflect the reality. A venous cannulation which is not perfectly performed can lead to serious life-threatening complications in several steps. The technique we describe step by step is the current gold standard in terms of safety and efficacy: from the use of ultrasound for ultrasound-guided puncture to safe advancement of super stiff guidewires by means of a sentinel catheter, and concluding with smooth insertion of the venous cannula over the stiff guidewire up to the SVC. Moreover, a list of bailout maneuvers to solve complications is presented along with a report of institutional clinical experience since the adoption of this technique., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Pozzoli, Torre, Toto, Theologou, Ferrari and Demertzis.)

(1) Introduction: Intraoperative preservation solutions for saphenous vein grafts may influence the endothelial structure and increase the risk of graft failure after coronary surgery. The aim of the study was to compare the efficacy of three solutions in maintaining the endothelial cell integrity of venous segments. (2) Methods: We tested the efficacy of physiological saline solution (PSS), heparinized autologous blood (HAB) and DuraGraft ® in preserving the endothelium of vein segments by evaluating the degree of endothelial cell apoptosis. Two incubation times (2 and 4 h from harvesting) were used for each solution. The quantification of apoptotic cells was computed as the intensity nuclei/intensity area ratio. (3) Results: After 2 h of ischemia, the degree of apoptosis decreased progressively across the use of DuraGraft, HAB and PSS ( p = 0.004), although only the difference between DuraGraft and PSS yielded a statistical significance ( p = 0.002). After 4 h, a similar decrease in apoptosis was shown across the three media; however, statistical significance was not reached. The analysis of the elapsed time (2 or 4 h of incubation) showed that this was a relevant factor in maintaining the endothelial structural integrity independently from the storage solution (test for interaction of media and time p = 0.010). (4) Conclusion: Within 2 h of incubation, endothelial structural integrity depended on the incubating medium. DuraGraft better protected the SVG against ischemic-induced apoptosis when compared to saline solution. Prolonged ischemia was associated with extended endothelium damage and none of the studied solutions protected the vein graft.

Land-use and land-cover change associated with agriculture is one of the main drivers of biodiversity loss. In heavily modified agricultural landscapes, grazing lands may be the only areas that can provide essential resources for native grassland species. Management decisions, such as choice of livestock species, affect the extent to which grazing lands provide suitable habitat for native species such as pollinators.Our study compared how sheep versus cattle herbivory affected floral resources and butterfly abundance across low-diversity, former Conservation Reserve Program (CRP) pastures managed with patch-burn grazing.Across all years (2017-2019), flowering species richness and abundance were significantly higher in cattle pastures than sheep pastures. On average, we recorded 6.9 flowering species/transect in cattle pastures and 3.8 flowering species/transect in sheep pastures. The average floral abundance per transect was 1278 stems/transect in cattle pastures and 116 stems/transect in pastures grazed by sheep.Similarly, we observed higher butterfly species richness, diversity, and abundance in cattle than in sheep pastures. In cattle pastures, we observed an average of 75 butterflies and 6.75 species per transect, compared with an average of 52 butterflies and 3.37 species per transect in sheep pastures. However, the butterfly community composition did not significantly differ between grazing treatments likely because agricultural-tolerant, habitat generalists comprised the majority of the butterfly community. Five generalist butterflies comprised 92.3% of observations; Colias philodice was the most abundant (61% of observations). Speyeria idalia and Danaus plexippus , two butterflies of conservation concern, comprised less than 0.5% of butterfly observations.Our results, which are among the first attempt quantifying butterfly use of post-CRP fields grazed by livestock, show that increased precipitation and cattle grazing promoted higher forb abundance and richness. However, additional interventions may be needed to enhance floral resources to sustain and improve pollinator diversity in these landscapes., Competing Interests: None declared., (© 2022 The Authors. Ecology and Evolution published by John Wiley & Sons Ltd.)

Background: Surgical aortic valve replacement with rapid deployment bioprosthesis guarantees good hemodynamic results but carries the risk of paravalvular leaks. To address this issue, an annulus stabilization technique has been recently developed., Methods: Clinical and hemodynamic parameters from patients treated for aortic valve replacement with the rapid deployment bioprosthesis and a concomitant annulus stabilization technique were prospectively collected and retrospectively analyzed. Echocardiographic data at discharge and at 1-year follow-up were collected and analysed., Results: A total of 57 patients (mean age 74.3 ± 6.1 years) with symptomatic aortic valve stenosis underwent aortic valve replacement with the rapid deployment bioprosthesis and concomitant annulus stabilization technique (mean valve size: 23.8 ± 1.9 mm). Combined procedures accounted for 56.1%. Hospital mortality was 1.8% and a new pacemaker for conduction abnormalities was implanted in 10 patients. The pre-discharge echocardiographic control showed absence of paravalvular leaks of any degree in all patients with mean valve gradient of 9.6 ± 4.0 mmHg. The 1-year echocardiographic control confirmed the good valve hemodynamic (mean gradient of 8.0 ± 2.8 mmHg) and absence of leaks., Conclusion: In this preliminary clinical experience, the annulus stabilization technique prevents postoperative paravalvular leaks after rapid deployment aortic valve implantation, up to 1-year postoperatively. Studies on larger series are of paramount importance to confirm the long-term efficacy of this new surgical technique.

Visual detection of rolling circle amplification products (RCPs) has been achieved by specific aggregation with magnetic nanoparticles. The method presented here reliably generates aggregates in 1.5 h; these are visible to the naked eye in samples containing at least 0.4 fmol of RCPs. In addition, alternate current susceptometry and absorbance spectroscopy have also been used to quantify the amplified products. The specificity of the detection method was tested, and no non-specific aggregation was detected in samples containing up to 20 fmol of non-complementary amplified DNA. This method is a versatile tool for detecting pathogenic DNA in point-of-care diagnostics, with no readout equipment required. However, chips and automated assays can be used in conjugation with the developed method since detection and quantification can be achieved by commercially available readout instruments., Competing Interests: The authors declare no competing financial interest., (© 2021 The Authors. Published by American Chemical Society.)

In the current work, mesoporous magnesium carbonate (MMC) was used to suppress crystallization of the poorly soluble drug celecoxib (CXB). This resulted in both a higher dissolution rate and supersaturation of the substance in vitro as well as an increased transfer of CXB over a Caco-2 cell membrane mimicking the membrane in the small intestine. The CXB flux over the cell membrane showed a linear behavior over the explored time period. These results indicate that MMC may be helpful in increasing the bioavailability and obtaining a continuous release of CXB, and similar substances, in vivo. Neusilin US2 was used as a reference material and showed a more rapid initial release with subsequent crystallization of the incorporated CXB in the release media. The presented results form the foundation of future development of MMC as a potential carrier for poorly soluble drugs.

Introduction: In the early phase of the coronavirus disease 2019 (COVID-19) pandemic, United States Emergency Medical Services (EMS) experienced a decrease in calls, and at the same time, an increase in out-of-hospital deaths. This finding led to a concern for the implications of potential delays in care for the obstetric population., Hypothesis/problem: This study examines the impact of the pandemic on prehospital care amongst pregnant women., Methods: A retrospective observational study was conducted comparing obstetric-related EMS activations in Maryland (USA) during the pandemic (March 10-July 20, 2020) to a pre-pandemic period (March 10-July 20, 2019). Comparative analysis was used to analyze the difference in frequency and acuity of calls between the two periods., Results: There were fewer obstetric-related EMS encounters during the pandemic compared to the year prior (daily average during the pandemic 12.5 [SD = 3.8] versus 14.6 [SD = 4.1] pre-pandemic; P <.001), although the percent of total female encounters remained unchanged (1.6% in 2020 versus 1.5% in 2019; P = .091). Key indicators of maternal status were not significantly different between the two periods. African-American women represented a disproportionately high percentage of obstetric-related activations (36.2% in 2019 and 34.8% in 2020)., Conclusions: In this state-wide analysis of EMS calls in Maryland early in the pandemic, no significant differences existed in the utilization of EMS by pregnant women. Prehospital EMS activations amongst pregnant women in Maryland only decreased slightly without an increase in acuity. Of note, over-representation by African-American women compared to population statistics raises concern for broader systemic differences in access to obstetric care.

Within agricultural landscapes, native bees often rely on limited natural and seminatural lands to provide the majority of the food and nesting resources that sustain them. To understand better how management can affect pollinators in these seminatural areas, we compared how sheep or cattle herbivory influenced floral resources and bee communities in low-diversity, former Conservation Reserve Program (CRP) pastures managed with patch-burn grazing. We sampled bee communities and floral resources three times per season in 2017, 2018, and 2019. We used plant-pollinator line transect sampling and collected bees and counted all flowering stems within 1 m. Across all years, we found that floral abundance, floral richness, floral diversity (Simpson's) and bee richness and abundance were significantly higher in cattle pastures compared to sheep. In cattle pastures, 46 native bee species plus honey bees interacted with 25 of 68 available flowering forbs. In sheep pastures, we recorded 14 native bee species and honey bees interacted with 10 of 34 flowering species. Native bee abundance and native bee richness were best explained by models that included an interaction of floral richness and year. Overall, our results suggest that season-long sheep grazing in low-diversity grasslands greatly reduces available floral resources and correlates with much lower bee abundance and native bee diversity. Given the importance of pollinators to natural and agricultural systems, it is imperative that we take proactive actions to increase forb richness and native flower abundance in seminatural lands to maintain a more diverse and resilient bee community that can continue to support pollination services and global food security., (© 2021 by the Ecological Society of America.)

We aimed to analyze the outcome and identify predictors of hospital mortality in patients with refractory cardiac arrest (CA) complicating acute coronary syndromes (ACS) and requiring veno-arterial extracorporeal membrane oxygenation (VA-ECMO) treatment. Between Jan-2005 and Dec-2019, 51 patients underwent urgent VA-ECMO implantation for CA in ACS. Patients were divided in two groups: "in-hospital" cardiac arrest (IHCA) and "out-of-hospital" cardiac arrest (OHCA). Prospectively collected data were retrospectively analyzed and compared between groups. Predictors for hospital mortality were investigated. IHCA and OHCA patients were 32 (62.7%) and 19 (37.3%), respectively. The groups differed for: male gender (72% vs 95%; p = 0.070), lactate peak level (8.5 ± 4.3vs10.7 ± 2.9; p = 0.023), total elapsed time from CA to VA-ECMO implantation in both groups (p < 0.001) and elapsed time from CA (IHCA group) or hospital arrival (OHCA group) to VA-ECMO implantation (38 min vs 80 min; p = 0.001). At logistic regression analysis, concomitant lactate level greater than 8.0 mmol/L and elapsed time from CA to VA-ECMO ≥ 30 min were predictors of increased mortality (OR 3.9; 95% CI 1.19-12.79; p = 0.025) for the entire population. In-hospital mortality was 60.8% (31/51 patients): 68.4% in OHCA group and 56.2% in IHCA group. No risk factors related to 30-day mortality resulted significant at univariable analysis. When rapidly instituted, VA-ECMO improves survival in patients with refractory cardiac arrest allowing coronary syndrome treatment. The association of an elapsed time from CA to VA-ECMO implantation longer than 30 min and a preoperative lactate peak level over 8.0 mmol/L predict a poor outcome, independently from being IHCA or OHCA., (© 2021. The Japanese Society for Artificial Organs.)

Maternal sepsis is an obstetric emergency and a leading cause of maternal morbidity and mortality. Early recognition in a pregnant or postpartum patient can be a challenge as the normal physiologic changes of pregnancy may mask the signs and symptoms of sepsis. Bedside assessment tools may aid in the detection of maternal sepsis. Timely and targeted antibiotic therapy and fluid resuscitation are critical for survival in patients with suspected sepsis. Once diagnosed, a search for etiologies and early application of source control measures will further reduce harms. If the patient is in septic shock or not responding to initial treatment, multidisciplinary consultation and escalation of care is necessary. Health care professionals should be aware of the unique complications of sepsis in critically ill pregnant and postpartum patients, and measures to prevent poor outcomes in this population. Adverse pregnancy outcomes may occur in association with sepsis, and should be anticipated and prevented when possible, or managed appropriately when they occur. Using a standardized approach to the patient with suspected sepsis may reduce maternal morbidity and mortality., Competing Interests: Financial Disclosure Dr. Shields is the Principal Investigator of an AHRQ grant for developing a simulation course on maternal cardiac arrest; provided volunteer expert testimony to KJS law; was an examiner for the ABOG specialty certifying exam; is a member of Varda5, LLC, a consulting company for patient safety and quality initiatives; is a member of Body Wisdom S.A., LLC, a wellness company; and is a member of Overlevende, LLC, for personal assets. The other authors did not report any potential conflicts of interest., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc.)

Adolescents have access to a wide range of cannabis products with patterns of use becoming increasingly diverse. This study aimed to identify subgroups of adolescents in the general population who use similar types of cannabis and their association with psychotic experiences. Data on cannabis use were obtained from 467 adolescents aged between 16 and 17 years. Latent class analysis (LCA) identified groups of adolescents based on the type of cannabis used in the past 12 months. Univariate analysis explored differences in socio-demographics, substance use and mental health symptoms between groups. Multivariate analysis examined associations between class membership and psychotic experiences controlling for frequency and amount of cannabis. Finally, we explored the association between motives for cannabis and class membership using multi-nominal logistic regression. LCA identified 3 classes of adolescents: (i) herbal only (47.9%); (ii) skunk only (20.8%) and (3) mixed use (31.3%). Relative to non-users, skunk only use was associated with a 2-fold increase in paranoia (OR = 2.45, 95% CI = 1.29-4.63), along with, sleep disturbance and anxiety. Monthly cannabis use and consuming 2 or more joints on one occasion was associated with a 2-fold increase in hallucinations (OR = 2.2; 95% CI = 1.0-4.8 and OR = 1.9; 95% CI = 1.2-3.2), but did not reach the Bonferroni corrected p-value. Expansion and conformity motives differentiated the mixed cannabis class from the herbal only class. The findings suggest that different subgroups of cannabis users exist in adolescence as defined by the type of cannabis consumed and are differentially related to psychotic experiences and motives for use., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

This work explores several issues of importance for the development of a diagnostic method based on circle-to-circle amplification (C2CA) and oligonucleotide-functionalized magnetic nanoparticles. Firstly, the performance of the detection method was evaluated in terms of sensitivity and speed. Synthetic target sequences for Newcastle disease virus and Salmonella were used as model sequences. The sensitivity of the C2CA assay resulted in detection of 1 amol of starting DNA target with a total amplification time of 40 min for both target sequences. Secondly, the functionalization of the nanoparticles was evaluated in terms of robustness and stability. The functionalization was shown to be very robust, and the stability test showed that 92% of the oligos were still attached on the particle surface after three months of storage at 4 °C. Altogether, the results obtained in this study provide a strong foundation for the development of a quick and sensitive diagnostic assay.

Objective: To evaluate the association of sex and pregnancy status with rates of naloxone administration during opioid overdose-related emergency department (ED) visits by using the Nationwide Emergency Department Sample., Methods: A retrospective cohort study was conducted using the Nationwide Emergency Department Sample 2016 and 2017 data sets. Eligible records included men and women, 15-49 years of age, with an opioid overdose-related ED visit; records for women were stratified by pregnancy status (International Classification of Diseases, Tenth Revision O codes). A multivariable logistic regression model was used to assess the primary outcome of naloxone administration (Current Procedural Terminology code: J2310). Secondary outcomes included subsequent admission and mortality. A subgroup analysis compared pregnant women who did receive naloxone compared with those who did not receive naloxone., Results: Records from 443,714 men, 304,364 nonpregnant women, and 25,056 pregnant women were included. Nonpregnant women had lower odds for naloxone administration (1.70% vs 2.10%; adjusted odds ratio [aOR] 0.86 [95% CI 0.83-0.89]) and mortality (2.21% vs 2.99%; aOR 0.71 [95% CI 0.69-0.73]) but higher odds of subsequent admission (30.22% vs 27.18%; aOR 1.04 [95% CI 1.03-1.06]) compared with men. Pregnant women had lower odds for naloxone administration (0.27% vs 1.70%; aOR 0.16 [95% CI 0.13-0.21]) and mortality (0.41% vs 2.21%; aOR 0.28 [95% CI 0.23-0.35]) but higher odds of subsequent admission (40.50% vs 30.22%; aOR 2.04 [95% CI 2.00-2.10]) compared with nonpregnant women. Pregnant women who received naloxone had higher odds of mortality (14% vs 0.39%; aOR 6.30 [95% CI 2.11-18.78]) compared with pregnant women who did not receive naloxone. Pregnant women who did not receive naloxone were more likely to have Medicaid as their expected insurance payer, be in the lowest quartile of median household income for residence ZIP codes, and have a concurrent mental health diagnosis compared with pregnant women who did receive naloxone., Conclusion: Reproductive-aged women who are nonpregnant and pregnant were less likely to receive naloxone during opioid overdose-related ED visits compared with reproductive-aged men. Naloxone administration for reproductive-aged women should be prioritized in the efforts to reduce opioid- and pregnancy-related morbidity and mortality in the United States., Competing Interests: Financial Disclosure The authors did not report any potential conflicts of interest., (Copyright © 2021 by the American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.)

We studied Ulva lactuca to determine its potential for bioremediation of coastal watersheds. We cultured Ulva in orthogonal combinations of two salinities and three nutrient concentrations for six weeks, and then measured its growth, photosynthesis, chlorophyll fluorescence, nitrogen, carbon and phosphorus tissue concentrations, and carbon and nitrogen uptake pathways. Our findings show that Ulva was negatively affected by decreased salinity but these effects were ameliorated by the addition of nutrients to the water, such as would be expected from freshwater runoff during heavy rain events. Also, increased nutrients resulted in altered nitrogen (NH 4 + vs. NO 3 - ) and carbon (HCO 3 - vs. CO 2 ) uptake pathways, which can allow Ulva to retain its bloom potential even under reduced salinities. Together, our study suggests that Ulva is an ideal species to grow for the purpose of bioremediation of coastal bays and estuaries, even during storms that freshen the surface waters and increase nutrients., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Understanding the binding mechanism between probe-functionalized magnetic nanoparticles (MNPs) and DNA targets or amplification products thereof is essential in the optimization of magnetic biosensors for the detection of DNA. Herein, the molecular interaction forming hybrid structures upon hybridization between DNA-functionalized magnetic nanoparticles, exhibiting Brownian relaxation, and rolling circle amplification products (DNA-coils) is investigated by the use of atomic force microscopy in a liquid environment and magnetic biosensors measuring the frequency-dependent magnetic response and the frequency-dependent modulation of light transmission. This approach reveals the qualitative and quantitative correlations between the morphological features of the hybrid structures with their magnetic response. The suppression of the high-frequency peak in the magnetic response and the appearance of a new peak at lower frequencies match the formation of larger sized assemblies upon increasing the concentration of DNA-coils. Furthermore, an increase of the DNA-coil concentration induces an increase in the number of MNPs per hybrid structure. This study provides new insights into the DNA-MNP binding mechanism, and its versatility is of considerable importance for the mechanistic characterization of other DNA-nanoparticle biosensor systems.