A diagnosis of syphilis following a radical circumcision for suspected penile cancer.

We present a case of a 70-year-old gentleman who was referred to our tertiary 2-week-wait penile cancer clinic with a penile mass that was ulcerated, painful and discharging. This was suspicious for penile cancer and a radical circumcision was performed to remove the diseased foreskin en bloc with the lesion that was arising from the inner foreskin. Histopathology did not reveal cancer; however, we identified spirochaetes in keeping with syphilis. This was confirmed on serology. The patient was referred to the genitourinary medicine team and treated with antibiotics. This case demonstrates a rare presentation of genital syphilis in an elderly gentleman initially referred with concerns of penile cancer. Although, rare, especially in this age group, syphilis should be considered as a differential diagnosis in a patient presenting with an ulcerated, discharging, firm penile mass, especially given that the incidence of syphilis has been rising in recent years.

Aging and brain free cholesterol concentration on amyloid-ß peptide accumulation in guinea pigs.

Alzheimer's disease is a complex multifactorial neurodegenerative disorder wherein age is a major risk factor. The appropriateness of the Hartley guinea pig (GP), which displays high sequence homologies of its amyloid-ß (Aß40 and Aß42) peptides, Mdr1 and APP (amyloid precursor protein) and similarity in lipid handling to humans, was appraised among 9-40 weeks old guinea pigs. Protein expression levels of P-gp (Abcb1) and Cyp46a1 (24(S)-hydroxylase) for Aß40, and Aß42 efflux and cholesterol metabolism, respectively, were decreased with age, whereas those for Lrp1 (low-density lipoprotein receptor related protein 1), Rage (receptor for advanced glycation endproducts) for Aß efflux and influx, respectively, and Abca1 (the ATP binding cassette subfamily A member 1) for cholesterol efflux, were unchanged among the ages examined. There was a strong, negative correlation of the brain Aß peptide concentrations and Abca1 protein expression levels with free cholesterol. The correlation of Aß peptide concentrations with Cyp46a1 was, however, not significant, and concentrations of the 24(S)-hydroxycholesterol metabolite revealed a decreasing trend from 20 weeks old toward 40 weeks old guinea pigs. The composite data suggest a role for free cholesterol on brain Aß accumulation. The decreases in P-gp and Lrp1 protein levels should further exacerbate the accumulation of Aß peptides in guinea pig brain.

Complications of Synthetic Midurethral Slings: Is There a Relevant Discrepancy Between Observational Data and Clinical Trials?

CONTEXT: The complications of synthetic midurethral slings (MUSs) in women with stress urinary incontinence (SUI) have become a globally debated issue. OBJECTIVE: To systematically review the short- and long-term complications of mesh slings reported in observational data compared with clinical trial data, to determine whether the complication rates from clinical trials reflects "real-world" observational data. EVIDENCE ACQUISITION: PubMed and Cochrane Library were searched. Methods as detailed in Preferred Reporting Items for Systematic Reviews and Meta-analyses and Cochrane Handbook for Systematic Reviews of Interventions were followed. EVIDENCE SYNTHESIS: Thirty registries/databases including 709 335 MUS procedures (1-22 yr of follow-up) were identified. MUS procedures were associated with intraoperative bladder perforation in 0.86-3.6%, urethral perforation in 0-0.1%, vascular injury in 0.04-0.1%, voiding lower urinary tract symptoms (LUTS) in 1.47-3.5%, vaginal exposure in 0.2-1.9%, and reoperation in up to 9% of cases. Forty-three randomised clinical trials were identified, including 6284 women who underwent MUS procedures and 2177 women who underwent other interventions (1-10 yr of follow-up). MUS procedures were associated with urinary tract perforation in 2.58%, vaginal injury in 1.43%, de novo voiding LUTS in 4.37%, de novo storage LUTS in 5.41%, mesh extrusion/exposure (vaginal/urinary tract) in 2.54%, dyspareunia in 2.26%, pain (pelvic/suprapubic/perineal) in 2.83%, and reoperation for complications required in 1.82% of cases. Meta-analyses of the randomised controlled trials revealed that retropubic MUSs were associated with more events of urinary tract perforation (risk ratio [RR] 9.81, 95% confidence interval [CI] 5.05-19.04, high certainty of evidence [COE]) and voiding LUTS (RR 1.57, 95% CI 1.19-2.07, high COE) than transobturator MUSs. MUSs were associated with more events of pain than mini-slings (RR 1.72, 95% CI 1.04-2.87, moderate COE). CONCLUSIONS: Short- and long-term data on complications of polypropylene mesh used for female SUI are fairly comparable when using outcome data from well-designed clinical trials or from less structured prospective or retrospective registries. Comparisons have to be made with caution since the two systems of data collection are inherently incomparable. This knowledge should be incorporated in the discussion on how to implement polypropylene mesh for female stress incontinence. PATIENT SUMMARY: In order to know whether mesh tapes used for treating stress incontinence work well and are safe, high-quality information is important. It appears that well-designed clinical studies give similar results to large registration databases. These data should be interpreted with caution in view of the different ways the information was collected. These results will help physicians and patients understand the risks of mesh tapes.

Kirchhoff's Laws and Hepatic Clearance, Well-Stirred Model - Is There Common Ground?

Clearance concepts are extensively applied in drug development and drug therapy. The well-stirred model (WSM) of hepatic elimination is the most widely adopted physiologic model in pharmacokinetics owing to its simplicity. A common feature of this organ model is its use to relate hepatic clearance of a compound to the physiologic variables: organ blood flow rate, binding within blood, and hepatocellular metabolic and excretory activities. Recently, Kirchhoff's laws of electrical network have been applied to organ clearance (Pachter et al., 2022; Benet and Sodhi, 2023) with the claim that they yield the same equation for hepatic clearance as the WSM, and that the equation is independent of a mechanistic model. This commentary analyzes this claim and shows that implicit in the application of Kirchhoff's approaches are the same assumptions as those of the WSM. Concern is also expressed in the interpretation of permeability or transport parameters and related equations, as well as the inappropriateness of the corresponding equation defining hepatic clearance. There is no value, and some dangers, in applying Kirchhoff's electrical laws to organ clearance. SIGNIFICANCE STATEMENT: This commentary refutes this claim by Pachter et al. (2022), and Benet and Sodhi, (2023), who suggest that the well-stirred model (WSM) of hepatic elimination, the most widely applied physiologic model of hepatic clearance, provides the same equation as Kirchhoff's laws of electrical network that is independent of a physiologic model. A careful review shows that the claim is groundless and fraught with errors. We conclude that there is no place for the application of Kirchhoff's laws to organ clearance models.

A large dermoid cyst of the spermatic cord.

Dermoid cysts of the spermatic cord are rare, with only a few adult cases published in the literature. We report a patient with a 10cm inguinal mass referred to us for a suspected paratesticular sarcoma. Imaging suggested a cyst but, due to the recent increase in size, the cyst contents were evacuated and the cyst wall was biopsied. Histopathology revealed a dermoid cyst, which is a benign variant of cystic teratomas. Histopathological examination was required here due to the uncertainty. Careful interpretation was required, as cystic teratomas very occasionally undergo a malignant transformation.

A comparative study of pilomatricoma and epidermoid cyst with ultrasound.

AIM: To explore and compare the ultrasonic (US) features of pilomatricoma (PM) and epidermoid cyst (EC) in the differential diagnosis and improve the accuracy of US diagnosis of PM. MATERIALS AND METHODS: Three hundred and nine patients who underwent US examination before surgery with a histopathological diagnosis of PM or EC after surgery were analysed retrospectively. The patients were categorised into the training and validation sets according to the inspection times. Univariate analysis was undertaken on the US and clinical features of PM and statistically significant variables (p<0.05) were included in the multivariate logistic regression model to establish a diagnostic model. RESULTS: The results demonstrated that the multivariate logistic regression model for PM was statistically significant (p<0.001). The risk factors included posterior echo attenuation and hypoechoic halos (odds ratio [OR] = 9.277, 10.254) and the protective factors included age, diameter thickness, and posterior echo enhancement (OR=0.936, 0.302, 0.156). The performance of the diagnostic model was tested using the training set (area under the receiver operating characteristic curve [AUC] = 0.974, 95% confidence interval [CI] = 0.955-0.994) and the validation set (AUC = 0.967, 95% CI = 0.926-1.000), which demonstrated good discriminant ability. CONCLUSIONS: The diagnostic accuracy for PM was higher than that for EC when the nodule is characterised by posterior echo attenuation, hypoechoic halos, smaller thickness, and younger age. The US diagnostic model developed may be used to guide the diagnosis of PM.

Impacto de la presentación tardía al servicio de Urgencias por cólico renal agudo en los resultados bioquímicos y clínicos / Impact of a delayed presentation to the emergency department for acute renal colic on biochemical and clinical outcomes

Introducción y objetivo Verificar el impacto en los resultados bioquímicos y clínicos de la demora en acudir al servicio de Urgencias (SU) ante un cólico renal agudo. Materiales y métodos Los datos se recogieron retrospectivamente en 3 instituciones de 2 países europeos, desde el 1 de enero hasta el 30 de abril del 2020. Se incluyó a los pacientes que acudieron a Urgencias con un cólico renal unilateral o bilateral causado por urolitiasis confirmada por imagen durante el periodo de estudio. La consulta en el SU después de 24 h desde el inicio de los síntomas se consideró tardía. Los pacientes que acudieron antes de las 24 h desde el inicio de los síntomas se incluyeron en el grupo A y los pacientes que se presentaron después de las 24 h se adjudicaron al grupo B. Se compararon los parámetros clínicos y bioquímicos, así como el manejo recibido por cada paciente. Resultados Se analizó a 397 pacientes que acudieron a Urgencias con urolitiasis confirmada (grupo A, n = 199; grupo B, n = 198). La mediana (RIC) de demora hasta la consulta fue de 2 días (1,5-4). En el momento de la consulta, no se encontraron diferencias estadísticamente significativas entre los 2 grupos de pacientes en cuanto a los síntomas como fiebre y dolor en el flanco, o la mediana de los niveles séricos de creatinina, proteína C reactiva y leucocitos. No se encontraron diferencias en cuanto al tratamiento conservador o quirúrgico. Conclusiones La demora > 24 h hasta acudir al SU no se asocia a un empeoramiento de los parámetros bioquímicos ni de los resultados clínicos. La mayoría de los pacientes con dolor lumbar agudo no siempre necesitan acudir de forma inmediata a urgencias, pudiendo ser tratados en consultas externas (AU)

Introduction and objective To verify the impact of delay on biochemical and clinical outcomes for patients presenting to the emergency department (ED) with acute renal colic. Materials and methods Data were retrospectively collected from 3 institutions of 2 European countries between 01 January and 30 April 2020. Patients who presented to the ED with unilateral or bilateral renal colic caused by urolithiasis confirmed by imaging tests during the study period were included. A presentation after 24 hours since the onset of symptoms was considered a delay. Patients presenting before 24 hours from the symptom onset were included in Group A, while the patients presenting after 24 hours in Group B. Clinical and biochemical parameters and management were compared. Results 397 patients who presented to ED with confirmed urolithiasis were analyzed (Group A, n = 199; Group B, n = 198. The median (IQR) delay in presentation was 2 days (1,5-4). At presentation, no statistically significant differences were found amongst the 2 groups of patients regarding presenting symptoms such as fever and flank pain, and the median serum levels of creatinine, C reactive protein and white blood cells. No differences were found in terms of conservative or operative management. Conclusions Delay in consultation >24 hours is not associated with worsening biochemical parameters and clinical outcomes. Most patients with acute loin pain do not necessarily need urgent attendance to the ED and may be managed in the outpatients (AU)

Impact of a delayed presentation to the emergency department for acute renal colic on biochemical and clinical outcomes.

INTRODUCTION AND OBJECTIVE: To verify the impact of delay on biochemical and clinical outcomes for patients presenting to the emergency department (ED) with acute renal colic. MATERIALS AND METHODS: Data were retrospectively collected from three institutions of two European countries between 01 January and 30 April 2020. Patients who presented to the ED with unilateral or bilateral renal colic caused by urolithiasis confirmed by imaging tests during the study period were included. A presentation after 24 h since the onset of symptoms was considered a delay. Patients presenting before 24 h from the symptom onset were included in Group A, while the patients presenting after 24 h in Group B. Clinical and biochemical parameters and management were compared. RESULTS: A total of 397 patients who presented to ED with confirmed urolithiasis were analyzed (Group A, n = 199; Group B, n = 198. The median (IQR) delay in presentation was 2 days (1,5-4). At presentation, no statistically significant differences were found amongst the two groups of patients regarding presenting symptoms such as fever and flank pain, and the median serum levels of creatinine, C reactive protein and white blood cells. No differences were found in terms of conservative or operative management. CONCLUSION: Delay in consultation >24 h is not associated with worsening biochemical parameters and clinical outcomes. Most patients with acute loin pain do not necessarily need urgent attendance to the ED and may be managed in the outpatients.

The Gender Euphoria Scale (GES): a protocol for developing and validating a tool to measure gender euphoria in transgender and gender diverse individuals.

Background: Gender euphoria (i.e., a positive feeling associated with one's gender identity, expression, or affirmation) is widely discussed among transgender and gender diverse (hereafter referred to as trans) individuals. However, as a construct, gender euphoria has never been formally measured and has rarely been empirically studied. Hence, this protocol paper illustrates our process for developing and validating a new tool to measure gender euphoria, known as the Gender Euphoria Scale (GES), for use with trans populations. Methods: Deductive methods including findings from previous research and a review of existing measures, together with inductive methods such as expert feedback and focus groups with trans individuals, were used to generate a preliminary item pool for the GES. Pilot testing with trans community members and mental health clinicians was then used to refine items and develop a preliminary scale. Trans participants involved in an ongoing longitudinal study (TRANSform) were invited to complete the scale alongside measures of personality and gender factors to assess validity. Participants were then invited to complete the scale two weeks after initial completion to assess the test-retest reliability of the scale. The next stage in the scale development process will be to examine the dimensionality of the GES using exploratory factor analytic techniques. The scale will then be assessed for internal consistency, temporal stability, discriminant validity, and convergent validity. Conclusion: This paper outlines the development and characterization of a novel tool to measure gender euphoria for the first time. The GES will facilitate research opportunities to better understand the nature of gender euphoria and its influences, and may be used clinically to examine relationships between gender euphoria and gender affirming interventions. Hence, we expect the GES to make a significant contribution to both research and clinical practice with trans communities.

Significance of the Vitamin D Receptor on Crosstalk with Nuclear Receptors and Regulation of Enzymes and Transporters.

The vitamin D receptor (VDR), in addition to other nuclear receptors, the pregnane X receptor (PXR) and constitutive androstane receptor (CAR), is involved in the regulation of enzymes, transporters and receptors, and therefore intimately affects drug disposition, tissue health, and the handling of endogenous and exogenous compounds. This review examines the role of 1α,25-dihydroxyvitamin D3 or calcitriol, the natural VDR ligand, on activation of the VDR and its crosstalk with other nuclear receptors towards the regulation of enzymes and transporters, notably many of the cytochrome P450s including CYP3A4 and sulfotransferase 2A1 (SULT2A1) as well as cholesterol 7α-hydroxylase (CYP7A1). Moreover, the VDR upregulates the intestinal channel, TRPV6, for calcium absorption, LDL receptor-related protein 1 (LRP1) and receptor for advanced glycation end products (RAGE) in brain for ß-amyloid peptide efflux and influx, the sodium phosphate transporters (NaPi), the apical sodium-dependent bile acid transporter (ASBT) and organic solute transporters (OSTα-OSTß) for bile acid absorption and efflux, respectively, the renal organic anion transporter 3 (OAT3) and several of the ATP-binding cassette protein transporters-the multidrug resistance protein 1 (MDR1) and the multidrug resistance-associated proteins (MRPs). Hence, the role of the VDR is increasingly being recognized for its therapeutic potential and pharmacologic activity, giving rise to drug-drug interactions (DDI). Therapeutically, ligand-activated VDR shows anti-inflammatory effects towards the suppression of inflammatory mediators, improves cognition by upregulating amyloid-beta (Aß) peptide clearance in brain, and maintains phosphate, calcium, and parathyroid hormone (PTH) balance and kidney function and bone health, demonstrating the crucial roles of the VDR in disease progression and treatment of diseases.

Sclerostin in the development of osteoarthritis: A mini review.

Wnt signalling plays an important role in bone and cartilage metabolism. Activation of Wnt signalling promotes bone formation but cartilage degradation. Sclerostin (SOST) can inhibit Wnt signalling. It is expressed by chondrocytes in the articular cartilage and osteocytes in the subchondral bone. Since osteoarthritis (OA) is a joint degenerative disease involving both bone and joint compartments, SOST may have a role in mediating the progression of this disease. This review examined the current literature on the role of SOST in the pathogenesis of OA and its usefulness as a biomarker of OA. Most studies agree that SOST is upregulated as a rescue mechanism in OA to prevent further degenerative changes of the joint. It antagonises inflammation-induced cartilage catabolism while preserving chondrocyte anabolic activities. It also prevents abnormal bone mineralisation and osteophyte formation. However, studies on the performance of SOST as a biomarker to detect and stage OA are limited. Further studies are required to determine whether SOST can be a biomarker or therapeutic target for OA.

In Defense of Current Concepts and Applications of Clearance in Drug Development and Therapeutics.

Clearance is one of the most widely quoted and applied pharmacokinetic concepts in drug development and therapy. Its foundations and associated models of drug elimination are well embedded and accepted within the scientific community. Recently, however, the prevailing views that have held us in good stead for the past almost 50 years have been challenged with the argument that organ clearance should not be based on elimination rate, now defined by extraction across the liver divided by incoming or systemic concentration, as in current practice, but rather, by the mean concentration of drug within the blood in the organ, which is model-dependent. We argue that all needed parameters already exist, and that the proposed new approach to organ clearance is confusing and unnecessary. SIGNIFICANCE STATEMENT: Clearance concepts are widely applied in drug development and therapy. Historically, hepatic clearance has been defined as the ratio of rate of elimination divided by ingoing blood concentration. Recently, this approach has been challenged arguing that clearance should be referenced to blood concentration within the liver extrapolation (IVIVE). There is no need for additional, a feature that corresponds to intrinsic clearance of the chosen clearance model, a widely accepted parameter in physiologically based pharmacokinetic (PBPK) and in vitro to in vivo extrapolation (IVIVE). There is no need for additional, confusing clearance terms, which offer no material benefit.

Measuring Amyloid-ß Peptide Concentrations in Murine Brain with Improved ELISA Assay.

The amyloid-ß (Aß) peptides of 40 and 42 amino acids that are implicated in Alzheimer's disease may potentially aggregate into toxic oligomers and form neuritic plaques. The enzyme-linked immunosorbent assay (ELISA) is a facile method used for the determination of Aß concentrations in biological matrices, namely plasma, cerebrospinal fluid, and brain. The method is mostly used for the measurement of Aß concentrations in transgenic mice, but it is unknown whether the ELISA method is suitable for measuring low, endogenous levels of Aß in the brains of wild-type mice. The Aß ELISA kit manufacturer recommends use of 5 M guanidine hydrochloride (GuHCl), a protein-denaturing agent, for homogenization of the brain tissue, followed by dilution back down to 0.1 M to avoid quenching by GuHCl. Components of brain matrices and GuHCl that could interfere with the quantitation have not been investigated. In this article, we describe an improved method involving homogenization of mouse brain with 1 M instead of 5 M GuHCl, reducing the dilution factor by 5× to provide a higher sensitivity. The modified ELISA assay is improved for the quantitation of brain Aß peptides in wild-type mice, where Aß peptide levels are much lower than those in transgenic mouse models. © 2021 Wiley Periodicals LLC.

Multicentre study of hospitalised patients with sports- and recreational cycling-related traumatic brain injury in Hong Kong.

INTRODUCTION: Cycling is associated with a greater risk of traumatic brain injury (TBI) than other recreational activities. This study aimed to investigate the epidemiology of sports-related TBI in Hong Kong and to examine predictors for recreational cycling-induced intracranial haemorrhage. METHODS: This retrospective multicentre study included patients diagnosed with sports-related TBI in public hospitals in Hong Kong from 2015 to 2019. Computed tomography scans were reviewed by an independent assessor. The primary endpoint was traumatic intracranial haemorrhage. The secondary endpoint was an unfavourable Glasgow Outcome Scale (GOS) score at discharge from hospital. RESULTS: In total, 720 patients were hospitalised with sports-related TBI. The most common sport was cycling (59.2%). The crude incidence of cycling-related TBI was 1.1 per 100 000 population. Cyclists were more likely to exhibit intracranial haemorrhage and an unfavourable GOS score, compared with patients who had TBI because of other sports. Although 47% of cyclists had intracranial haemorrhage, only 15% wore a helmet. In multivariate analysis, significant predictors for intracranial haemorrhage were age ≥60 years, antiplatelet medication, moderate or severe TBI, and skull fracture. Among 426 cyclists, 375 (88%) had mild TBI, and helmet wearing was protective against intracranial haemorrhage, regardless of age, antiplatelet medication intake, and mechanism of injury. Of 426 cyclists, 31 (7.3%) had unfavourable outcomes on discharge from hospital. CONCLUSIONS: The incidence of sports-related TBI is low in Hong Kong. Although cycling-related head injuries carried greater risks of intracranial haemorrhage and unfavourable outcomes compared with other sports, most cyclists experienced good recovery. Helmet wearing among recreational cyclists with mild TBI was protective against intracranial haemorrhage and skull fracture.

Impact of age, hypercholesterolemia, and the vitamin D receptor on brain endogenous ß-amyloid peptide accumulation in mice.

Age, hypercholesterolemia, and vitamin D deficiency are risk factors that increase the brain accumulation of pathogenic ß-amyloid peptides (40 and 42), precursors leading to Alzheimer's disease (AD) in humans. The relative changes accompanying aging, high cholesterol, and/or treatment of calcitriol, active vitamin D receptor (VDR) ligand, under normal physiology are unknown. We examined these relative changes in C57BL/6 mice of ages 2, 4-8, and more than 10 months old, which were fed a normal or high fat / high cholesterol diet and treated with calcitriol, active ligand of the vitamin D receptor (0 or 2.5 µg/kg ×4, intraperitoneally, every other day to elicit cholesterol lowering in liver). Aß40 but not Aß42 accumulation in brain and lower P-glycoprotein (P-gp) and neprilysin protein expressions for Aß efflux and degradation, respectively, were found to be associated with aging. But there was no trend for BACE1 (ß-secretase 1, a cholesterol-sensitive enzyme) toward Aß synthesis with age. In response to calcitriol treatment, P-gp was elevated, mitigating partially the age-related changes. Although age-dependent decreasing trends in mRNA expression levels existed for Cyp46a1, the brain cholesterol processing enzyme, whose inhibition increases BACE1 and ApoE to facilitate microglia Aß degradation, mRNA changes for other cholesterol transporters: Acat1 and Abca1, and brain cholesterol levels remained unchanged. There was no observable change in the mRNA expression of amyloid precursor protein (APP) and the influx (RAGE) and efflux (LRP1) transporters with respect to age, diet, or calcitriol treatment. Overall, aging poses as a risk factor contributing to Aß accumulation in brain, and VDR-mediated P-gp activation partially alleviates the outcome.

[Feasibility, efficacy and safety of transbrachial access for interventional therapy on paravalvular leak post surgical valve replacement].

Objective: To investigate the feasibility, efficacy and safety of transbrachial access for interventional therapy on prosthetic paravalvular leak (PVL) post surgical valve replacement. Methods: This is a retrospective study. Patients with PVL after surgical valve replacement who underwent interventional therapy via the brachial artery approach in Structural heart disease center of Fuwai hospital between August 2017 and October 2019, were included. All patients underwent puncture of the brachial artery under local anesthesia, angiography and transcatheter closure procedure were performed. The procedure was performed under transthoracic echocardiography (TTE) guidance. Baseline data, operation data and pre-and post-operative TTE examination results were collected and analyzed. Postoperative complications were recorded and operational adverse events were obtained during follow up in the outpatient department after discharge. The operation success rate was calculated, which was defined as the degree of perivalvular regurgitation decrease by 1 grade and above according to TTE without interfering the valve movement and coronary artery blood flow within 30 days after occluder placement. Results: A total of 10 patients were enrolled in this study, the mean age was (57.5±14.6) years, and 6 patients were males. There were 7 cases with aortic PVL, and 3 cases with mitral PVL. Except for one patient who was converted to the femoral vein-transseptal approach, the other 9 patients were successfully implanted with the devices via the brachial artery approach. The operation time was (103.3±34.0) minutes, and there was no need for rigorous bed rest after the operation. The median hospital stay was 7.5 (3.0, 9.8) days. The operation success rate was 9/10 via the brachial artery approach. The differences in the degree of perivalvular regurgitation, New York Heart Association (NYHA) classification, left ventricular end diastolic diameter and left atrial diameter before and after operation were statistically significant (all P<0.05). One case developed new hemolysis with renal insufficiency on the second day after procedure and discharged after successful dialysis. Another case experienced complication of brachial artery pseudoaneurysm after procedure and discharged after successful treatment with thrombin injection. The mean follow-up time was (14.3±7.9) months. During the follow-up, NYHA classification remained as Ⅰ/Ⅱ in 9 patients, no operational adverse events were observed. Conclusions: Transbrachial access for interventional therapy on PVL post surgical valve replacement is a feasible, effective, and safe procedure. It has the advantages of simplifying the operation process and reducing postoperative bed rest time.

Paeonol inhibits proliferation and induces cell apoptosis of human T24 and 5637 bladder cancer cells in vitro and in vivo

Purpose Paeonol is a natural chemical medicine derived from the bark of peony root, which has been found to inhibit tumor activity in various tumor cell lines, and can play a synergistic anti-tumor effect with chemotherapy or radiotherapy. Methods We used paeonol to act on human bladder cancer T24 and 5637 cells, and established xenograft tumor in nude mice by subcutaneous injection of T24 cells. Results CCK-8 assay and plate cloning experiments showed that paeonol could inhibit the proliferation of T24 and 5637 cells in vitro. The results of flow cytometry and the detection of BAX, Bcl-2 and Caspase-3 proteins suggested that paeonol can induce apoptosis of T24 and 5637 cells in vitro. Tumor formation, TUNEL detection and immunohistochemical results of Ki67, BAX, Bcl-2 and Caspase-3 in nude mice showed that paeonol could inhibit T24 cell proliferation and induce apoptosis in vivo, thus inhibiting tumor growth. Further research revealed that paeonol could reduce phosphorylation expression of PI3K and AKT in T24 and 5637 cells. Conclusion We confirmed that paeonol could inhibit proliferation and induce apoptosis of human bladder cancer T24 and 5637 cells in vitro and in vivo, inhibit the growth of T24 tumor-forming nude mice, and possibly play a role by inhibiting the PI3K/AKT signaling pathway, so as to provide a potential therapeutic drug for bladder cancer (AU)

Custom, spray coated receive coils for magnetic resonance imaging.

We have developed a process for fabricating patient specific Magnetic Resonance Imaging (MRI) Radio-frequency (RF) receive coil arrays using additive manufacturing. Our process involves spray deposition of silver nanoparticle inks and dielectric materials onto 3D printed substrates to form high-quality resonant circuits. In this paper, we describe the material selection and characterization, process optimization, and design and testing of a prototype 4-channel neck array for carotid imaging. We show that sprayed polystyrene can form a low loss dielectric layer in a parallel plate capacitor. We also demonstrate that by using sprayed silver nanoparticle ink as conductive traces, our devices are still dominated by sample noise, rather than material losses. These results are critical for maintaining high Signal-to-Noise-Ratio (SNR) in clinical settings. Finally, our prototype patient specific coil array exhibits higher SNR (5 × in the periphery, 1.4 × in the center) than a commercially available array designed to fit the majority of subjects when tested on our custom neck phantom. 3D printed substrates ensure an optimum fit to complex body parts, improve diagnostic image quality, and enable reproducible placement on subjects.