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The loss of an estrous cycle is critical in any production system. Especially in artificial insemination programs in which the detection of estrus depends on the human factor. The detection of estrus, has been one of the limitations for the massive use of artificial insemination. Therefore, the application of estrus and ovulation synchronization methods is very important in reproductive management in cattle. The objective was to evaluate by ultrasonography two estrus synchronization protocols in beef cows (Aberdeen angus). The research was carried out at the Research and Production Center (CIP) Chuquibambilla of the National University of the Altiplano. The experiment was performed with 30 cows that were divided into two groups of 15 for the first protocol (T1-Ovsynch) and 15 animals for the second protocol (T2-CIDR-synch). The ovarian function for T1 was 50% for both the right and left ovary, while for T2 it was 75 and 25% for right and left ovary, respectively; Presence of corpus luteum (CL) was 75% of cows for T1 and 60% of cows for T2, the follicle growth rate was for T1 of 0.5 ± 0.87 mm and for T2 of 1.2 ± 0.74 mm; The maximum diameter of the ovarian follicle for TI was 8.09 ± 3.23 mm and for T2 of 10.2 ± 3.16 mm and the pregnancy rate for T1 was 33.3% and for T2 of 66.7%. In conclusion, ultrasonographic evaluation is a useful tool for evaluating estrus synchronization protocols. Real-time observation of the synchrony of the emergence of a new follicular wave (at the beginning of the treatments) and ovulation in both protocols, resulting in a higher pregnancy rate.

Advanced age is associated with an increased risk of vascular morbidity, attributable in part to impairments in new blood vessel formation. Mesenchymal stem cells (MSCs) have previously been shown to play an important role in neovascularization and deficie

The deregulation of copper homoeostasis can promote various diseases such as Menkes disease or hypertrophic cardioencephalomyopathy. We have recently synthesized solid copper(II) complexes ([Cu(His) 2 Cl 2 ] and [Cu(Ser) 2 ]), stable in physiological media and with potential as therapeutic agents. This report describes: i) the biocompatibility of these complexes at concentrations up to 100 μM using a differentiated Caco-2 cells model; ii) their transport across the intestinal epithelium using a transepithelial resistance assay and monitoring the amount of copper complexes at the apical and basolateral sides of the cells. The results suggest that the flow occurs through paracellular routes. The intracellular copper retention was <2.7% with no significant differences in intracellular copper content between 6 h and 48 h, suggesting an early copper retention process. Furthermore, this is the first evidence that demonstrates [Cu(His) 2 Cl 2 ] and [Cu(Ser) 2 ] induce transcriptional downregulation of the four major copper transporters (CTR1, DMT1, ATP7A, ATP7B), and the upregulation of the metallothionein gene expression. A remarkable finding was the increase in cytochrome c oxidase activity observed after the treatment of differentiated Caco-2 cells with copper(II) complexes at concentrations of 50-100 μM. The understanding of the transport mechanisms of these copper(II) complexes across the intestinal epithelium and of their subsequent biological activities could contribute to the development of optimal pharmaceutical formulations for the therapy of copper deficiency-related diseases., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

How parasites develop and survive, and how they stimulate or modulate host immune responses are important in understanding disease pathology and for the design of new control strategies. Microarray analysis and bulk RNA sequencing have provided a wealth of data on gene expression as parasites develop through different life-cycle stages and on host cell responses to infection. These techniques have enabled gene expression in the whole organism or host tissue to be detailed, but do not take account of the heterogeneity between cells of different types or developmental stages, nor the spatial organisation of these cells. Single-cell RNA-seq (scRNA-seq) adds a new dimension to studying parasite biology and host immunity by enabling gene profiling at the individual cell level. Here we review the application of scRNA-seq to establish gene expression cell atlases for multicellular helminths and to explore the expansion and molecular profile of individual host cell types involved in parasite immunity and tissue repair. Studying host-parasite interactions in vivo is challenging and we conclude this review by briefly discussing the applications of organoids (stem-cell derived mini-tissues) to examine host-parasite interactions at the local level, and as a potential system to study parasite development in vitro. Organoid technology and its applications have developed rapidly, and the elegant studies performed to date support the use of organoids as an alternative in vitro system for research on helminth parasites., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Purpose: G-CSF enhances colon cancer development. This study defines the prevalence and effects of increased G-CSF signaling in human colon cancers and investigates G-CSF inhibition as an immunotherapeutic strategy against metastatic colon cancer., Experimental Design: Patient samples were used to evaluate G-CSF and G-CSF receptor (G-CSFR) levels by IHC with sera used to measure G-CSF levels. Peripheral blood mononuclear cells were used to assess the rate of G-CSFR+ T cells and IFNγ responses to chronic ex vivo G-CSF. An immunocompetent mouse model of peritoneal metastasis (MC38 cells in C57Bl/6J) was used to determine the effects of G-CSF inhibition (αG-CSF) on survival and the tumor microenvironment (TME) with flow and mass cytometry., Results: In human colon cancer samples, the levels of G-CSF and G-CSFR are higher compared to normal colon tissues from the same patient. High patient serum G-CSF is associated with increases in markers of poor prognosis, (e.g., VEGF, IL6). Circulating T cells from patients express G-CSFR at double the rate of T cells from controls. Prolonged G-CSF exposure decreases T cell IFNγ production. Treatment with αG-CSF shifts both the adaptive and innate compartments of the TME and increases survival (HR, 0.46; P = 0.0237) and tumor T-cell infiltration, activity, and IFNγ response with greater effects in female mice. There is a negative correlation between serum G-CSF levels and tumor-infiltrating T cells in patient samples from women., Conclusions: These findings support G-CSF as an immunotherapeutic target against colon cancer with greater potential benefit in women., (©2023 American Association for Cancer Research.)

Histamine is a biogenic amine implicated in various biological and pathological processes. Convenient cellular models are needed to screen and develop new antihistamine agents. This report aimed to characterize the response of neurons differentiated from mouse P19 embryonal carcinoma cells to histamine treatment, and to investigate the modulation of this response by antihistamine drugs, vegetal diamine oxidase, and catalase. The exposure of P19 neurons to histamine reduced cell viability to 65% maximally. This effect involves specific histamine receptors, since it was prevented by treatment with desloratadine and cimetidine, respectively, H 1 and H 2 antagonists, but not by the H 3 antagonist ciproxifan. RT-PCR analysis showed that P19 neurons express H 1 and H 2 receptors, and the H 3 receptor, although it seemed not involved in the histamine effect on these cells. The H 4 receptor was not expressed. H 1 and H 2 antagonists as well as vegetal diamine oxidase diminished the intracellular Ca 2+ mobilization triggered by histamine. The treatment with vegetal diamine oxidase or catalase protected against mortality and a significant reduction of H 2 O 2 level, generated from the cells under the histamine action, was found upon treatments with desloratadine, cimetidine, vegetal diamine oxidase, or catalase. Overall, the results indicate the expression of functional histamine receptors and open the possibility of using P19 neurons as model system to study the roles of histamine and related drugs in neuronal pathogenesis. This model is less expensive to operate and can be easily implemented by current laboratories of analysis and by Contract Research Organizations., (© 2023. The Author(s).)

Phubbing is when one uses their smartphone in a social interaction instead of interacting with the other individual(s) in their presence. Phubbing and being phubbed are growing concerns as the number of smartphones and frequency of smartphone use increases. This study assessed the relationships between phubbing, being phubbed, psychosocial constructs, and socially adverse personality traits among Hispanic emerging adult college students. Hispanic college students ( n  =  452) completed a survey assessing: sociodemographics, phubbing, being phubbed, depression, anxiety, stress, Machiavellianism, narcissism, psychopathy, and need for drama (interpersonal manipulation, impulsive outspokenness, persistent perceived victimhood). Hispanic emerging adult college students reported low-to-moderate levels of phubbing and being phubbed. Regarding phubbing findings, nomophobia (fear of separation from one's phone), interpersonal conflict, and problem acknowledgement were positively associated with negative affect. Moreover, interpersonal conflict, self-isolation, and problem acknowledgement were positively associated with interpersonal manipulation. Regarding being phubbed findings, perceived norms, feeling ignored, and interpersonal conflict were positively associated with persistent perceived victimhood. Findings indicate that Hispanic college students may use their smartphones in social settings to alleviate negative affect. Moreover, a virtual environment on a smartphone may be easier to manipulate and can be used to continue garnering attention and portraying oneself as the victim, fulfilling one's need for drama. Regarding exploratory mediations, phubbing and being phubbed mediated the relationships between multiple socially adverse personality traits and negative affect. The clinical implications of these results are discussed. Prospective studies are warranted to determine temporality., Supplementary Information: The online version contains supplementary material available at 10.1007/s12144-023-04767-y., Competing Interests: Conflict of interestThe Author(s) declare(s) that there is no conflict of interest., (© The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2023, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Objective: Laparoscopic Heller myotomy and Dor fundoplication has become the gold standard in treating esophageal achalasia and robotic surgical platform represents its natural evolution. The objective of our study was to assess durable long-term clinical outcomes in our cohort., Methods and Procedures: Between June 1, 1999 and June 30, 2019, 111 patients underwent minimally invasive treatment for achalasia (96 laparoscopically and 15 robotically). Fifty-two were males. Mean age was 49 years (20 - 96). Esophageal manometry confirmed the diagnosis. Fifty patients underwent pH monitoring study, with pathologic reflux in 18. Preoperative esophageal dilation was performed in 76 patients and 21 patients received botulin injection. Dysphagia was universally present, and mean duration was 96 months (5 - 480)., Results: Median operative time was 144 minutes (90 - 200). One patient required conversion to open approach. Four mucosal perforations occurred in the laparoscopic group and were repaired intraoperatively. Seven patients underwent completion esophageal myotomy and added Dor fundoplication. Upper gastrointestinal series was performed before discharge. Median hospital stay was 39 hours (24 - 312). Median follow up was 157 months (6 - 240), and dysphagia was resolved in 94% of patients. Seven patients required postoperative esophageal dilation., Conclusions: Minimally invasive Heller myotomy and Dor fundoplication are feasible. The operation is challenging, but excellent results hinge on the operative techniques and experience. The high dexterity, three-dimensional view, and the ergonomic movements of robotic surgery allow application of all the technical elements, achieving the best durable outcome for the patient. Robotic surgery is the natural evolution of minimally invasive treatment of esophageal achalasia., (© 2022 by SLS, Society of Laparoscopic & Robotic Surgeons.)

One of the mechanisms by which cancer cells acquire hyperinvasive and migratory properties with progressive loss of epithelial markers is the epithelial-to-mesenchymal transition (EMT). We have previously reported that in different cancer types, including nonsmall cell lung cancer (NSCLC), the microRNA-183/96/182 cluster (m96cl) is highly repressed in cells that have undergone EMT. In the present study, we used a novel conditional m96cl mouse to establish that loss of m96cl accelerated the growth of Kras mutant autochthonous lung adenocarcinomas. In contrast, ectopic expression of the m96cl in NSCLC cells results in a robust suppression of migration and invasion in vitro, and tumor growth and metastasis in vivo. Detailed immune profiling of the tumors revealed a significant enrichment of activated CD8 + cytotoxic T lymphocytes (CD8 + CTLs) in m96cl-expressing tumors, and m96cl-mediated suppression of tumor growth and metastasis was CD8 + CTL-dependent. Using coculture assays with naïve immune cells, we show that m96cl expression drives paracrine stimulation of CD8 + CTL proliferation and function. Using tumor microenvironment-associated gene expression profiling, we identified that m96cl elevates the interleukin-2 (IL2) signaling pathway and results in increased IL2-mediated paracrine stimulation of CD8 + CTLs. Furthermore, we identified that the m96cl modulates the expression of IL2 in cancer cells by regulating the expression of transcriptional repressors Foxf2 and Zeb1, and thereby alters the levels of secreted IL2 in the tumor microenvironment. Last, we show that in vivo depletion of IL2 abrogates m96cl-mediated activation of CD8 + CTLs and results in loss of metastatic suppression. Therefore, we have identified a novel mechanistic role of the m96cl in the suppression of lung cancer growth and metastasis by inducing an IL2-mediated systemic CD8 + CTL immune response., (© 2022 Kundu et al.; Published by Cold Spring Harbor Laboratory Press.)

Purpose: To evaluate angle-corrected peak systolic cystic artery velocity (CAv) as a predictor of acute cholecystitis among patients presenting to the emergency department (ED) with right upper quadrant (RUQ) pain., Methods: In this IRB-approved and retrospective study, CAv was evaluated in 73 patients, 43 who underwent definitive treatment with cholecystectomy or percutaneous cholecystostomy and 30 control patients without clinical suspicion for cholecystitis. In addition to CAv, the following were reviewed by 3 radiologists: CBD diameter, cholelithiasis, impacted stone in the neck, sludge, gallbladder wall thickness > 3 mm, gallbladder transverse dimension ≥ 4 cm, longitudinal dimension ≥ 8 cm, tensile gallbladder fundus sign, pericholecystic fluid, pericholecystic echogenic fat, and sonographic Murphy sign., Results: Of the 43 patients who underwent definitive treatment, 25 had acute cholecystitis (34%) and 18 (25%) had chronic cholecystitis. Average CAv measurements were 50 ± 16 cm/s (acute), 28 ± 8 cm/s (chronic), and 22 ± 8 cm/s (control; p < 0.0001). In univariate analysis, among patients who underwent definitive therapy, CAv ≥ 40 cm/s, gallbladder wall thickness, stone impaction, GB long dimension ≥ 8 cm, and elevated WBC were associated with acute cholecystitis (p < 0.05). In multivariate analysis, CAv ≥ 40 cm/s was the only statistically significant variable (p = 0.016). CAv ≥ 40 cm/s alone had a PPV of 94.7% and overall accuracy of 81.4% in diagnosing acute cholecystitis., Conclusion: CAv ≥ 40 cm/s is highly associated with acute cholecystitis in patients presenting to the ED with RUQ pain., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Current diagnostic standards involve severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) detection in nasopharyngeal swabs (NPS), but saliva is an attractive and noninvasive option for diagnosis. The objectives were to determine the performance of saliva in comparison with NPS for detecting SARS-CoV-2 and to compare the optimized home brew reverse-transcription polymerase chain reaction (RT-PCR) with a commercial RT-PCR. Paired NPS and saliva specimens were prospectively collected and tested by RT-PCR from patients presenting at an emergency room with signs and symptoms compatible with coronavirus disease-2019. A total of 348 samples from 174 patients were tested by RT-PCR assays. Among 174 patients with symptoms, 63 (36%) were SARS-CoV-2 positive in NPS using the optimized home-brew PCR. Of these 63 patients, 61 (98%) were also positive in saliva. An additional positive SARS-CoV-2 saliva was detected in a patient with pneumonia. Kappa Cohen's coefficient agreement between NPS and saliva was 0.96 (95% confidence interval [CI], 0.90-0.99). Median Ct values in NPS versus saliva were 18.88 (interquartile range [IQR], 15.60-23.58; range, 11.97-38.10) versus 26.10 (IQR, 22.75-30.06; range, 13.78-39.22), respectively (p < .0001). The optimized home-brew RT-PCR demonstrated higher analytical and clinical sensitivity compared with the commercial RT-PCR assay. A high sensitivity (98%) and agreement (kappa 0.96) in saliva samples compared to NPS was demonstrated when using an optimized home-brew PCR even when the viral load in saliva was lower than in NPS. This noninvasive sample is easy to collect, requires less consumable and avoids discomfort to patients. Importantly, self-collection of saliva can diminish exposure to healthcare personnel., (© 2021 Wiley Periodicals LLC.)

Background: Obesity is often associated with comorbidities that limit remnant liver recovery after hepatectomy. The extent to which obesity, in the absence of comorbidities, impacts surgical risk after hepatectomy is unknown. We hypothesized that an obese population without major comorbidities would not be at increased risk of adverse outcomes after hepatectomies., Methods: We performed a retrospective analysis identifying patients who underwent hepatectomies from the American College of Surgeons National Surgical Quality Improvement Program data set 2005-2017. Outcomes of interest included the following: mortality, any morbidity, critical care complications, and failure to discharge home. Body mass index (BMI) was the primary variable of interest, grouped as ≥35 and <35 based on bivariate tests of associations with candidate cut-off points. In attempt to isolate the effect of obesity on outcomes among patients "without major comorbidities" (WOC), we included patients without diabetes, chronic obstructive pulmonary disease, renal insufficiency, and nonsmokers; remaining patients were grouped as "with major comorbidities" (WC). Multivariable logistic regression was used to test whether obesity is independently associated with the outcomes of interest after adjustment for other covariates., Results: A total of 36,396 patients were included. There were 13,754 patients in the WOC group and 22,642 in the WC group. Among patients in the WOC group, the adjusted odds of mortality were 2.2 times higher for patients with a BMI ≥35 versus a BMI <35. Among the patients in the WC group, a BMI ≥35 was not a statistically significant predictor of mortality after adjustment for other covariates. Obese patients had increased odds of each outcome among the WOC group., Conclusions: Our hypothesis was refuted by these data. In fact, the adverse effect of obesity was more evident among healthy patients., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Support of somatic growth is a fundamental requirement of tissue-engineered valves. However, efforts thus far have been unable to maintain this support long term. A key event that will determine the valve's long-term success is the extent to which healthy host tissue remodeling can occur on the valve soon after implantation. The construct's phenotypic-status plays a critical role in accelerating tissue remodeling and engineered valve integration with the host via chemotaxis. In the current study, human bone-marrow-derived mesenchymal stem cells were utilized to seed synthetic, biodegradable scaffolds for a period of 8 days in rotisserie culture. Subsequently, cell-seeded scaffolds were exposed to physiologically relevant oscillatory shear stresses (overall mean, time-averaged shear stress, ~7.9 dynes/cm 2 ; overall mean, oscillatory shear index, ~0.18) for an additional 2 weeks. The constructs were found to exhibit relatively augmented endothelial cell expression (CD31; compared to static controls) but concomitantly served to restrict the level of the activated smooth muscle phenotype (α-SMA) and also produced very low stem cell secretion levels of fibronectin ( p < 0.05 compared to static and rotisserie controls). These findings suggest that fluid-induced oscillatory shear stresses alone are important in regulating a healthy valve phenotype of the engineered tissue matrix. Moreover, as solid stresses could lead to increased α-SMA levels, they should be excluded from conditioning during the culture process owing to their associated potential risks with pathological tissue remodeling. In conclusion, engineered valve tissues derived from mesenchymal stem cells revealed both a relatively robust valvular phenotype after exposure to physiologically relevant scales of oscillatory shear stress and may thereby serve to accelerate healthy valve tissue remodeling in the host post-implantation., (Copyright © 2020 Gonzalez, Perez-Nevarez, Mirza, Perez, Lin, Hsu, Caobi, Raymond, Gomez Hernandez, Fernandez-Lima, George and Ramaswamy.)

The growing demand for a sustainable leather industry with a low environmental impact has prompted the development of alternative vegetable-based materials. In this study, a biodegradable mushroom-based leather derived from the fruiting body of Phellinus ellipsoideus is investigated. The biodegradable leather proves to be thermally stable up to 250 °C. The mechanically robust macrostructure combines a tensile strength of 1.2 MPa and ductility (101% strain at break) attributed to the natural balance of chitin (0.3) and proteins (0.7) constituting the mycelium fibers. The chitin-protein system results in an intrinsic scratch-resistant structure with exciting damping properties in a low frequency range. Enhanced damping capabilities within 5-20 Hz (tan δ: 0.1-0.20) are attributed to the macrostuctural alignment of the mycelium under cyclic tension. Whereas, increasing frequencies >20 Hz induce micromolecular interactions between chitin and proteins within the fibers. Exposure of the bioleather to acidic (pH 4, 5) and basic (pH 8, 9) media demonstrated the selective dissolution of proteins (basic) and chitin (acid) components within the mycelium, opening an opportunity for tunable mechanical response. Reducing the protein content induced an increase in stiffness and strength (pH 8 and 9), while reducing its chitin component showed variable ductility (pH 4 and 5). Owing to the entirely natural composition of the mushroom leather, intrinsic antifungal and antibacterial properties found in the mycelium resist fungal invasion and bacterial growth. Thus, this study displays the unique morphology-property relationship of a biodegradable mushroom leather, proving its potential as a fully sustainable and environmentally friendly alternative.

Aim: The aim of this review paper is to summarize recent developments and research in robotics, relevant to the field of ankle rehabilitation, to overview new findings and determine the actual state of the art. Method: The literature search was performed using scientific and medical databases (Scopus, PubMed and Web of Science) and other websites related to robots used in the area of ankle rehabilitation, analysing studies from 1950s to present. Information about the mechanical and kinematic specifications, actuation and stage of development was extracted from the selected literature. Results: Several types of rehabilitation robots have been considered, and they were classified depending on their architecture and design features. We we found that, regardless of the differences in architectures, only a few of them have been commercialized. The majority of rehabilitation robots designs allows plantarflexion-dorsiflexion movements. Unless some exceptions, most of the wearable robots do not allow the adduction-abduction movement. Neither the physical appearance of the robot nor the user's perception towards it has not regularly been taken into account in the design stage. This limits the possibility of successful commercialization. Conclusions: Up to the present moment, the main challenges in the field of robot rehabilitation are the lack of unique rehabilitation protocols capable to fulfil the needs of all types of patients and the additional resources to measure the effectiveness of proposals that have not yet been commercialized. Nonetheless, we have mentioned above three areas were the challenges in design are more pressing. The first one is the robot architecture, which still presents some incommodities nowadays to emulate the ankle joint movement in a natural way. Thus, the displacements experienced by the axes in the joint must be adaptable to each patient and a wide range of pathologies. Moreover, many proposals are not been conceived to the purpose of commercialization, and even less to become an object of personal use.Implications for rehabilitationThis review states that the use of robotic devices for ankle rehabilitation is a consolidated paradigm in the ankle's rehabilitation.Platform-based robots allow to do complex and specialized spatial movements and these architectures endow the device with high stiffness, a balanced force distribution and better adaptability to the mechanical properties of human ankle joints. Unless some exceptions, most of the wearable robots do not allow the adduction-abduction movement.For a full integration of these technologies in the ankle's rehabilitation field, more clinical evaluations are needed.Regardless of the potential of robotic devices in rehabilitation, only a few of them have been commercialized.

Purpose: Laparoscopic fundoplication is now a cornerstone in the treatment of gastro-esophageal reflux disease (GERD) with sliding hernia. The best outcomes are achieved in those patients who have some response to medical treatment compared to those who do not. Robotic fundoplication is considered a novel approach in treating GERD with large paraesophageal hiatal hernias. Our goal was to examine the feasibility of this technique., Methods: Seventy patients (23 males and 47 females) with mean age 64 y old (22-92), preoperatively diagnosed with a large paraesophageal hiatal hernia, were treated with a robotic approach. Biosynthetic tissue absorbable mesh was applied for hiatal closure reinforcement. Fifty-eight patients underwent total fundoplication, 11 patients had partial fundoplication, and one patient had a Collis-Nissen fundoplication for acquired short esophagus., Results: All procedures were completed robotically, without laparoscopic or open conversion. Mean operative time was 223 min (180-360). Mean length of stay was 38 h (24-96). Median follow-up was 29 mo (7-51). Moderate postoperative dysphagia was noted in eight patients, all of which resolved after 3 mo without esophageal dilation. No mesh-related complications were detected. There were six hernia recurrences. Four patients were treated with redo-robotic fundoplication, and two were treated medically., Conclusions: The success of robotic fundoplication depends on adhering to a few important technical principles. In our experience, the robotic surgical treatment of gastroesophageal reflux disease with large paraesophageal hernias may afford the surgeon increased dexterity and is feasible with comparable outcomes compared with traditional laparoscopic approaches., Competing Interests: Conflicts of Interest: The authors declare no conflict of interest., (© 2020 by JSLS, Journal of the Society of Laparoscopic & Robotic Surgeons.)

Purpose: The aim of this study was to evaluate the clinical performance of the ACR's Ultrasound Liver Reporting and Data System (US LI-RADS™) for detecting hepatocellular carcinoma (HCC) in patients at high risk for HCC., Methods: In this retrospective, multicenter study, 2,050 patients at high risk for HCC (1,078 men and 972 women; mean age, 57.7 years) at five sites in the United States had undergone screening liver ultrasound from January 2017 to February 2018, and US LI-RADS observation categories and visualization scores were assigned on a clinical basis. Ultrasound reports and patient records were retrospectively reviewed and follow-up imaging studies and/or pathologic reports recorded. Descriptive statistics were generated, and multivariate logistic regression analysis was used to analyze the relationship of clinical and reader-based predictors of limited visualization. Diagnostic performance data were calculated in the subset of patients with confirmatory testing., Results: The most common indications for HCC screening were cirrhosis (n = 1,054 [51.4%]), noncirrhotic hepatitis B virus infection (n = 555 [27.1%]), and noncirrhotic hepatitis C virus infection (n = 234 [11.4%]). US LI-RADS observation categories assigned were US-1 (negative) in 90.4% (n = 1,854), US-2 (subthreshold) in 4.6% (n = 95), and US-3 (positive) in 4.9% (n = 101). Visualization scores were A (no or minimal limitations) in 76.8% (n = 1,575), B (moderate limitations) in 18.9% (n = 388), and C (severe limitations) in 4.2% (n = 87). Confirmatory tests, including multiphase contrast-enhanced CT or MRI (n = 331) or histopathology (n = 18), were available for 349 patients (17.0%). The sensitivity of US LI-RADS in this subset of patients was 82.4%, specificity was 74.2%, positive predictive value was 35.3%, and negative predictive value was 96.1%., Conclusions: Approximately 90% of US LI-RADS screening examinations were negative, 5% subthreshold, and 5% positive. Visualization scores were diagnostically acceptable in the vast majority (>95%) of examinations. US LI-RADS emphasized sensitivity and negative predictive value, which are key characteristics of a screening test., (Copyright © 2019 American College of Radiology. Published by Elsevier Inc. All rights reserved.)

Purpose: To examine the impact of targeted efforts to increase the number of female speakers at the Society of Interventional Radiology (SIR) Annual Scientific Meeting (ASM) by reporting gender trends for invited faculty in 2017/2018 vs 2016., Materials and Methods: Faculty rosters for the 2016, 2017, and 2018 SIR ASMs were stratified by gender to quantify female representation at plenary sessions, categorical courses, symposia, self-assessment modules, and "meet-the-expert" sessions. Keynote events, scientific abstract presentations, and award ceremonies were excluded. In 2017, the SIR Annual Meeting Committee issued requirements for coordinators to invite selected women as speakers. Session coordinators are responsible for issuing speaker invitations, and invited speakers have the option to decline., Results: Years 2017 and 2018 showed increases in female speaker representation, with women delivering 13% (89 of 687) and 14% (85 of 605) of all assigned presentations, compared with 9% in 2016 (46 of 514; P = .03 and P = .01, respectively). Gender diversity correlated with the gender of the session coordinator(s). When averaged over a 3-year period, female speakers constituted 7% of the speaker roster (112 of 1,504 presentations) for sessions led by an all-male coordinator team, compared with 36% (108 of 302) for sessions led by at least 1 female coordinator (P < .0001). Results of the linear regression model confirmed the effect of coordinator team gender composition (P < .0001)., Conclusions: Having a woman as a session coordinator increased female speaker participation, which suggests that the inclusion of more women as coordinators is one mechanism for achieving gender balance at scientific meetings., (Copyright © 2019 SIR. Published by Elsevier Inc. All rights reserved.)

Preprocedure: 1)We recommend that providers should be familiar with the operation of their specific ultrasound machine prior to initiation of a vascular access procedure. 2)We recommend that providers should use a high-frequency linear transducer with a sterile sheath and sterile gel to perform vascular access procedures. 3)We recommend that providers should use two-dimensional ultrasound to evaluate for anatomical variations and absence of vascular thrombosis during preprocedural site selection. 4)We recommend that providers should evaluate the target blood vessel size and depth during preprocedural ultrasound evaluation., Techniques: General Techniques 5) We recommend that providers should avoid using static ultrasound alone to mark the needle insertion site for vascular access procedures. 6)We recommend that providers should use real-time (dynamic), two-dimensional ultrasound guidance with a high-frequency linear transducer for central venous catheter (CVC) insertion, regardless of the provider's level of experience. 7)We suggest using either a transverse (short-axis) or longitudinal (long-axis) approach when performing real-time ultrasound-guided vascular access procedures. 8)We recommend that providers should visualize the needle tip and guidewire in the target vein prior to vessel dilatation. 9)To increase the success rate of ultrasound-guided vascular access procedures, we recommend that providers should utilize echogenic needles, plastic needle guides, and/or ultrasound beam steering when available. Central Venous Access Techniques 10) We recommend that providers should use a standardized procedure checklist that includes the use of real-time ultrasound guidance to reduce the risk of central line-associated bloodstream infection (CLABSI) from CVC insertion. 11)We recommend that providers should use real-time ultrasound guidance, combined with aseptic technique and maximal sterile barrier precautions, to reduce the incidence of infectious complications from CVC insertion. 12)We recommend that providers should use real-time ultrasound guidance for internal jugular vein catheterization, which reduces the risk of mechanical and infectious complications, the number of needle passes, and time to cannulation and increases overall procedure success rates. 13)We recommend that providers who routinely insert subclavian vein CVCs should use real-time ultrasound guidance, which has been shown to reduce the risk of mechanical complications and number of needle passes and increase overall procedure success rates compared with landmark-based techniques. 14)We recommend that providers should use real-time ultrasound guidance for femoral venous access, which has been shown to reduce the risk of arterial punctures and total procedure time and increase overall procedure success rates. Peripheral Venous Access Techniques 15) We recommend that providers should use real-time ultrasound guidance for the insertion of peripherally inserted central catheters (PICCs), which is associated with higher procedure success rates and may be more cost effective compared with landmark-based techniques. 16)We recommend that providers should use real-time ultrasound guidance for the placement of peripheral intravenous lines (PIV) in patients with difficult peripheral venous access to reduce the total procedure time, needle insertion attempts, and needle redirections. Ultrasound-guided PIV insertion is also an effective alternative to CVC insertion in patients with difficult venous access. 17)We suggest using real-time ultrasound guidance to reduce the risk of vascular, infectious, and neurological complications during PIV insertion, particularly in patients with difficult venous access. Arterial Access Techniques 18)We recommend that providers should use real-time ultrasound guidance for arterial access, which has been shown to increase first-pass success rates, reduce the time to cannulation, and reduce the risk of hematoma development compared with landmark-based techniques. 19)We recommend that providers should use real-time ultrasound guidance for femoral arterial access, which has been shown to increase first-pass success rates and reduce the risk of vascular complications. 20)We recommend that providers should use real-time ultrasound guidance for radial arterial access, which has been shown to increase first-pass success rates, reduce the time to successful cannulation, and reduce the risk of complications compared with landmark-based techniques., Postprocedure: 21) We recommend that post-procedure pneumothorax should be ruled out by the detection of bilateral lung sliding using a high-frequency linear transducer before and after insertion of internal jugular and subclavian vein CVCs. 22)We recommend that providers should use ultrasound with rapid infusion of agitated saline to visualize a right atrial swirl sign (RASS) for detecting catheter tip misplacement during CVC insertion. The use of RASS to detect the catheter tip may be considered an advanced skill that requires specific training and expertise., Training: 23) To reduce the risk of mechanical and infectious complications, we recommend that novice providers should complete a systematic training program that includes a combination of simulation-based practice, supervised insertion on patients, and evaluation by an expert operator before attempting ultrasound-guided CVC insertion independently on patients. 24)We recommend that cognitive training in ultrasound-guided CVC insertion should include basic anatomy, ultrasound physics, ultrasound machine knobology, fundamentals of image acquisition and interpretation, detection and management of procedural complications, infection prevention strategies, and pathways to attain competency. 25)We recommend that trainees should demonstrate minimal competence before placing ultrasound-guided CVCs independently. A minimum number of CVC insertions may inform this determination, but a proctored assessment of competence is most important. 26)We recommend that didactic and hands-on training for trainees should coincide with anticipated times of increased performance of vascular access procedures. Refresher training sessions should be offered periodically. 27)We recommend that competency assessments should include formal evaluation of knowledge and technical skills using standardized assessment tools. 28)We recommend that competency assessments should evaluate for proficiency in the following knowledge and skills of CVC insertion: (a) Knowledge of the target vein anatomy, proper vessel identification, and recognition of anatomical variants; (b) Demonstration of CVC insertion with no technical errors based on a procedural checklist; (c) Recognition and management of acute complications, including emergency management of life-threatening complications; (d) Real-time needle tip tracking with ultrasound and cannulation on the first attempt in at least five consecutive simulation. 29)We recommend a periodic proficiency assessment of all operators should be conducted to ensure maintenance of competency., (© 2019 Society of Hospital Medicine.)

Purpose: To investigate the current state of gender diversity among invited coordinators at the Society of Interventional Radiology (SIR) Annual Scientific Meeting and to compare the academic productivity of female interventional radiologists to that of invited male coordinators., Materials and Methods: Faculty rosters for the SIR Annual Scientific Meetings from 2015 to 2017 were stratified by gender to quantify female representation among those asked to lead and coordinate podium sessions. To quantify academic productivity and merit, H-index, publications, and authorship by females over a 6-year period (2012-2017) were statistically compared to that of recurring male faculty., Results: From 2015 to 2017, women held 7.1% (9/126), 4.3%, (8/188), and 13.7% (27/197) of the available coordinator positions for podium sessions, with no representation at the plenary sessions, and subject matter expertise was concentrated in economics and education. Academic productivity of the top quartile of published female interventional radiologists was statistically similar to that of the invited male faculty (H-index P = .722; total publications P = .689; and authorship P = .662)., Conclusions: This study found that senior men dominate the SIR Annual Scientific Meeting, with few women leading or coordinating the podium sessions, despite their established academic track record., (Copyright © 2019. Published by Elsevier Inc.)

Purpose: To evaluate the association between imaging and clinical features and visualization scores, as specified by American College of Radiology (ACR) Ultrasound Liver Imaging Reporting and Data System (LI-RADS), on hepatocellular carcinoma (HCC) screening ultrasound examinations., Methods: In this dual-center retrospective study, HCC screening ultrasound reports containing ultrasound elastography measurements (January to September, 2017) were reviewed. Ultrasound point shear wave elastography and 2-dimensional shear wave elastography were used to assess liver stiffness; median shear wave velocity was translated to METAVIR fibrosis scoring, per previously published data. Reports were analyzed for subject age, sex, reason for HCC screening, spleen size, fibrosis scores, and assigned ultrasound visualization scores. Jonckheere-Terpstra trend and Kendall's tau-b coefficient analyses were performed., Results: 714 subjects (mean age 55; 51% male, 49% female) were included. 308 (43%) subjects had clinically declared cirrhosis; 406 (57%) did not. Majority (535, 75%) of exams were adequate (Visualization Score A), 156 (22%) moderately limited (Visualization Score B), and 23 (3%) severely limited (Visualization Score C). Increasing spleen size and patient age were associated with worsening visualization scores (p < 0.001). Suboptimal visualization was also associated with clinically significant fibrosis (≥ F2) by elastography (Kendall's tau-b = 0.181, p < 0.001) and clinically declared cirrhosis (Kendall's tau-b = 0.433, p < 0.001). There was no association with patient sex., Conclusion: Using ACR Ultrasound LI-RADS visualization score assessment, majority (75%) of HCC screening exams were diagnostically adequate, and only 3% were severely limited. Sonoelastographic diagnosis of clinically significant fibrosis, as well as clinical cirrhosis, increased patient age, and spleen size, were associated with greater diagnostic limitations.

Copper coordinated with amino acid residues is essential for the function of many proteins. In addition, copper complexed to free l-Histidine, as [Cu(His) 2 ], is used in the treatment of the neurodegenerative Menkes disease and of cardioencephalomyopathy. This study was aimed to coordinate copper(II) with four small ligands (l-Serine, l-Histidine, Urea and Biuret) and to evaluate structural features, stability, antioxidant activity and neuronal compatibility of the resulting complexes. All complexes were synthesized with CuCl 2 and purified by precipitation in alcohol. Elemental composition, X-rays diffraction and FTIR indicated that the complexes were in form of [Cu(ligand) 2 ] and exhibited tridentate (l-Histidine), bidentate (l-Serine and Biuret) or monodentate (Urea) coordination with copper. UV-Vis absorbance profiles in physiologically relevant solutions and cyclic voltammetry revealed that, contrarily to [Cu(Urea) 2 Cl 2 ] and [Cu(Biuret) 2 Cl 2 ], the [Cu(Ser) 2 ] and [Cu(His) 2 Cl 2 ] complexes were stable in different media including water, physiological saline and intestinal-like solutions. All complexes and their ligands had antioxidant capacity as evaluated by DPPH (1,1-diphenyl-2,2-picrylhydrazyl) and DPD (N,N-diethyl-p-phenylenediamine) methods, and the [Cu(His) 2 Cl 2 ] complex was the most potent. Neuronal compatibility was assessed through cell viability measurements using cultured neurons derived from mouse P19 stem cells. Although only [Cu(His) 2 Cl 2 ] showed a good neurocompatibility (about 90% at concentrations up to 200 μM), the cytotoxicity of the other copper complexes was lower compared to equivalent concentrations of CuCl 2 . These findings open new perspectives for the use of these copper complexes as antioxidants and possibly as therapeutic agents for neurodegenerative diseases. Furthermore, study of these complexes may help to improve chelation therapy for copper dysfunctions., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Introduction: Community-acquired Staphylococcus aureus (SA) bacteraemia is a common cause of hospitalisation in children. The occurrence of secondary foci (SF) of SA infection is associated with higher morbidity and mortality., Objectives: To identify risk factors for SF of infection in children with community-acquired SA bacteraemia., Material and Methods: Prospective cohort. All children aged from 30 days to 16 years admitted to a paediatric referral hospital between January 2010 and December 2016 for community-acquired infections, with SA isolated in blood cultures, were included. Microbiological, demographic and clinical characteristics were compared, with or without SF infection after 72hours of hospitalisation., Results: A total of 283 patients were included, 65% male (n=184), with a median age of 60 months (IQR: 30-132). Seventeen per cent (n=48) had at least one underlying disease and 97% (n=275) had some clinical focus of infection, the most common being: osteoarticular 55% (n=156) and soft tissue abscesses 27% (n=79). A total of 65% (n=185) were resistant to methicillin. A SF of infection was found in 16% of patients (n=44). The SF identified were pneumonia 73% (n=32), osteoarticular 11% (n=5), soft tissue 11% (n=5) and central nervous system 5% (n=2). In the multivariate analysis, the persistence of positive blood cultures after the fifth day (OR: 2.40, 95%CI: 1.07-5.37, P<0.001) and sepsis (OR: 17.23, 95%CI 5.21-56.9, P<0.001) were predictors of SF. There was no association with methicillin sensitivity., Conclusions: In this cohort, methicillin-resistant SA infections predominated. The occurrence of SF of infection was associated with the persistence of bacteraemia after the fifth day and sepsis on admission., (Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.)

Phalloplasty, or creation of the penis, is one of the steps in gender confirming surgery for a female-to-male patient and for males with absence or malformation of the penis. Here, the most common techniques for phalloplasty, along with the pre-operative and post-operative care are discussed.

Advanced age is associated with an increased risk of vascular morbidity, attributable in part to impairments in new blood vessel formation. Mesenchymal stem cells (MSCs) have previously been shown to play an important role in neovascularization and deficiencies in these cells have been described in aged patients. Here we utilize single cell transcriptional analysis to determine the effect of aging on MSC population dynamics. We identify an age-related depletion of a subpopulation of MSCs characterized by a pro-vascular transcriptional profile. Supporting this finding, we demonstrate that aged MSCs are also significantly compromised in their ability to support vascular network formation in vitro and in vivo. Finally, aged MSCs are unable to rescue age-associated impairments in cutaneous wound healing. Taken together, these data suggest that age-related changes in MSC population dynamics result in impaired therapeutic potential of aged progenitor cells. These findings have critical implications for therapeutic cell source decisions (autologous versus allogeneic) and indicate the necessity of strategies to improve functionality of aged MSCs.

Gender differences in alcohol, tobacco, and other drugs use in Mexico are rapidly disappearing. This study explores the possible relationship between engaging in romantic relationships on substance use offers and the moderating effects of gender among a group of adolescents (N = 432) living in Guadalajara, Jalisco, Mexico. The data used to test these relationships were collected through self-administered surveys in 2010. OLS regressions were estimated, predicting substance offers. The results demonstrate an association between having been in a relationship and receiving substance use offers in the previous 12 months. Having had a boyfriend/girlfriend had a significant influence on the offers received by adolescent females, but not for males.

Reduced gene dosage of ribosomal protein subunits has been implicated in 5q- myelodysplastic syndrome and Diamond Blackfan anemia, but the cellular and pathophysiologic defects associated with these conditions are enigmatic. Using conditional inactivation of the ribosomal protein S6 gene in laboratory mice, we found that reduced ribosomal protein gene dosage recapitulates cardinal features of the 5q- syndrome, including macrocytic anemia, erythroid hypoplasia, and megakaryocytic dysplasia with thrombocytosis, and that p53 plays a critical role in manifestation of these phenotypes. The blood cell abnormalities are accompanied by a reduction in the number of HSCs, a specific defect in late erythrocyte development, and suggest a disease-specific ontogenetic pathway for megakaryocyte development. Further studies of highly purified HSCs from healthy patients and from those with myelodysplastic syndrome link reduced expression of ribosomal protein genes to decreased RBC maturation and suggest an underlying and common pathophysiologic pathway for additional subtypes of myelodysplastic syndrome.

Slow firing septal neurons modulate hippocampal and neocortical functions. Electrophysiologically, it is unclear whether slow firing neurons belong to a homogeneous neuronal population. To address this issue, whole-cell patch recordings and neuronal reconstructions were performed on rat brain slices containing the medial septum/diagonal band complex (MS/DB). Slow firing neurons were identified by their low firing rate at threshold (<5 Hz) and lack of time-dependent inward rectification (Ih). Unsupervised cluster analysis was used to investigate whether slow firing neurons could be further classified into different subtypes. The parameters used for the cluster analysis included latency for first spike, slow after-hyperpolarizing potential, maximal frequency and action potential (AP) decay slope. Neurons were grouped into three major subtypes. The majority of neurons (55%) were grouped as cluster I. Cluster II (17% of neurons) exhibited longer latency for generation of the first action potential (246.5+/-20.1 ms). Cluster III (28% of neurons) exhibited higher maximal firing frequency (25.3+/-1.7 Hz) when compared with cluster I (12.3+/-0.9 Hz) and cluster II (11.8+/-1.1 Hz) neurons. Additionally, cluster III neurons exhibited faster action potentials at suprathreshold. Interestingly, cluster II neurons were frequently located in the medial septum whereas neurons in cluster I and III appeared scattered throughout all MS/DB regions. Sholl's analysis revealed a more complex dendritic arborization in cluster III neurons. Cluster I and II neurons exhibited characteristics of "true" slow firing neurons whereas cluster III neurons exhibited higher frequency firing patterns. Several neurons were labeled with a cholinergic marker, Cy3-conjugated 192 IgG (p75NTR), and cholinergic neurons were found to be distributed among the three clusters. Our findings indicate that slow firing medial septal neurons are heterogeneous and that soma location is an important determinant of their electrophysiological properties. Thus, slow firing neurons from different septal regions have distinct functional properties, most likely related to their diverse connectivity.

We report the first known case of chronic relapsing thrombotic thrombocytopenic purpura associated with adult-onset Still's disease. The patient presented with diffuse arthralgias, sore throat, and a maculopapular rash involving the trunk and extremities; she was hospitalized with fever and confusion. Thrombocytopenia, renal failure, and microangiopathic hemolytic anemia developed within several days. After a diagnosis of thrombotic thrombocytopenic purpura was made, she responded well to a series of plasma exchanges. Evaluation for infection, autoimmune disorders, and malignancy was negative. She was discharged to home in good condition, with normal renal function and normal platelet count. Two more episodes of TTP developed 7 and 9 months after the first hospitalization. The diagnosis of adult-onset Still's disease was then determined on the basis of clinical and laboratory criteria. She was successfully treated with plasma exchange, prednisone, and azathioprine. She later had splenectomy and has subsequently been without recurrence of thrombotic thrombocytopenic purpura for 2 years.