Multimodal Biomarkers That Predict the Presence of Gleason Pattern 4: Potential Impact for Active Surveillance.

PURPOSE: Latent grade group ≥2 prostate cancer can impact the performance of active surveillance protocols. To date, molecular biomarkers for active surveillance have relied solely on RNA or protein. We trained and independently validated multimodal (mRNA abundance, DNA methylation, and/or DNA copy number) biomarkers that more accurately separate grade group 1 from grade group ≥2 cancers. MATERIALS AND METHODS: Low- and intermediate-risk prostate cancer patients were assigned to training (n=333) and validation (n=202) cohorts. We profiled the abundance of 342 mRNAs, 100 DNA copy number alteration loci, and 14 hypermethylation sites at 2 locations per tumor. Using the training cohort with cross-validation, we evaluated methods for training classifiers of pathological grade group ≥2 in centrally reviewed radical prostatectomies. We trained 2 distinct classifiers, PRONTO-e and PRONTO-m, and validated them in an independent radical prostatectomy cohort. RESULTS: PRONTO-e comprises 353 mRNA and copy number alteration features. PRONTO-m includes 94 clinical, mRNAs, copy number alterations, and methylation features at 14 and 12 loci, respectively. In independent validation, PRONTO-e and PRONTO-m predicted grade group ≥2 with respective true-positive rates of 0.81 and 0.76, and false-positive rates of 0.43 and 0.26. Both classifiers were resistant to sampling error and identified more upgrading cases than a well-validated presurgical risk calculator, CAPRA (Cancer of the Prostate Risk Assessment; P < .001). CONCLUSIONS: Two grade group classifiers with superior accuracy were developed by incorporating RNA and DNA features and validated in an independent cohort. Upon further validation in biopsy samples, classifiers with these performance characteristics could refine selection of men for active surveillance, extending their treatment-free survival and intervals between surveillance.

Implementation of self-monitoring of blood glucose for patients with insulin-dependent diabetes at a rural non-communicable disease clinic in Neno, Malawi.

BACKGROUND: Self-monitoring of blood glucose (SMBG) is a widely accepted standard of practice for management of insulin-dependentdiabetes, yet is largely unavailable in rural sub-Saharan Africa (SSA). This prospective cohort study is the first known report ofimplementation of SMBG in a rural, low-income country setting. OBJECTIVES: To evaluate adherence and change in clinical outcomes with SMBG implementation at two rural hospitals in Neno, Malawi. METHODS: Forty-eight patients with type 1 and insulin-dependent type 2 diabetes were trained to use glucometers and logbooks. Participantsmonitored preprandial glucose daily at rotating times and overnight glucose once a week. Healthcare providers were trained to evaluateglucose trends, and adjusted insulin regimens based on results. Adherence was measured as the frequency with which patients checked anddocumented blood glucose at prescribed times, while clinical changes were measured by change in glycated haemoglobin (HbA1c) over a6-month period. RESULTS: Participants brought their glucometers and logbooks to the clinic 95 - 100% of the time. Adherence with measuring glucose valuesand recording them in logbooks eight times a week was high (mean (standard deviation) 69.4% (15.7) and 69.0% (16.6), respectively). MeanHbA1c decreased from 9.0% (75 mmol/mol) at enrolment to 7.8% (62 mmol/mol) at 6 months (mean difference 1.2% (95% confidenceinterval (CI) 0.6 - 2.0; p=0.0005). The difference was greater for type 1 diabetes (1.6%; 95% CI 0.6 - 2.7; p=0.0031) than for type 2 diabetes(0.9%; 95% CI 0.1 - 1.9; p=0.0630). There was no documented increase in hypoglycaemic events, and no hospitalisations or deaths occurred. CONCLUSION: SMBG is feasible for patients with insulin-dependent diabetes in a rural SSA population, and may be associated with improvedHbA1c levels. Despite common misconceptions, all patients, regardless of education level, can benefit from SMBG. Further research onlong-term retention of SMBG activities and the benefits of increasing frequency of monitoring is warranted.

Remote robotic percutaneous coronary intervention: An animal feasibility study.

OBJECTIVES: The purpose of this study was to explore the feasibility and safety of robotic PCI performed using an off-siteremote-control system in an animal model. BACKGROUND: Access to primary percutaneous coronary intervention (PCI) remains a challenge in acute myocardial infarction management. The combination of telemedicine and robotic PCI allow the potential delivery of primary PCI to remote locations without the delay of transfer. METHODS: This single-center prospective pilot preclinical feasibility study compared robotic PCI with remote PCI on swine across three stages (adjacent room, different floor of the same building, two different buildings). Latency up to 1,000 ms was introduced into the operating environment to simulate decreased network quality (blinded to operator). The primary outcome measures were technical success and acute safety. The secondary outcome measures included lesion wiring time, procedural time and qualitative scoring of the PCI experience by the operator. RESULTS: Across 52 experiments in 15 animals, technical success was 100%. No procedural complications occurred during the study. No significant difference in lesion treatment time was detected between stages (p = .11) and between time per target vessel when latency up to 1,000 ms was introduced (p = .58). Injected delay >250 ms had the greatest impact on procedure perceived lag. Longer procedure time was associated with lower procedure impact score, regardless of injected latency. CONCLUSIONS: Remote robotic PCI was feasible and safe in an animal model. Procedural duration was acceptable and unaffected by network latency. Future studies are needed to determine the safety and feasibility of remote PCI in humans.

"Always Events® " just another quality improvement tool or is it?

INTRODUCTION: Always Events® are defined as "those aspects of the care experience that should always occur when patients, their family members or other care partners, and service users interact with health care professionals and the health care system". It is a quality improvement methodology that starts by asking our patients the simple question "what matters to you?" and then through coproduction, works out a way to achieve this. METHODS AND RESULTS: This article tells our story and highlights the value of undertaking an Always Event® within the Radiology department at Warrington and Halton Hospitals. It will demonstrate how this approach combines research, an evaluation of findings and implementation of those findings within a very short timeframe. Embedded within the article are comments from our staff, volunteers and patients which reflect upon their experiences, our limitations, the outcomes we achieved and the impact it has had upon our patients and staff. CONCLUSION AND IMPLICATIONS FOR PRACTICE: It was important to our patients that they would be informed of how long they would wait for their examination once they booked in at x-ray reception. By undertaking an Always Event® this process is now embedded in our departments everyday activities with over 90% of our patients now being informed of their waiting time. This continued collaboration has really emphasised the value of listening to our patients, and the benefits this can lead to. It has also encouraged a positive research culture within our department (optimisation studies, working with industry, quality projects), helping to progress our profession and resulting in a quality service for our patients.

Effects of quorum quenching on temporal succession of activated sludge microbial community in a membrane bioreactor.

AIMS: Quorum quenching (QQ) is an attractive strategy for mitigating biofouling in membrane bioreactors (MBRs). However, the effects of QQ on the activated sludge (AS) process have not been adequately evaluated. This study investigated the long-term effects of QQ on a laboratory-scale anoxic-oxic MBR, focusing on AS performance and microbial community. METHODS AND RESULTS: Anoxic-oxic MBRs with and without QQ were operated for 91 days. QQ did not affect COD and TN removal efficiencies over the experimental period, during which its activity remained >90%. QQ reduced floc size by approximately 8% but had no effect on biomass concentration. AS microbial communities were regularly analysed using massively parallel sequencing. AS bacterial communities were temporally dynamic irrespective of QQ presence, for example, a temporal increase in bacterial diversity and a temporal decay of community similarity. QQ counteracted the temporal change in diversity and the temporal distance-community decay. Community comparison revealed that QQ changed the successional trajectory of the AS community at a late period, because it decelerated temporal changes of specific members, such as Thiothrix and Sphingomonadaceae*. Correlation networks revealed that QQ increased network clustering, complexity and density. The combined results suggest that the tighter microbial association by QQ increased the community resistance. CONCLUSIONS: QQ can enhance the diversity and stability of the AS community in MBR by counteracting the innate temporal change in community structure. SIGNIFICANCE AND IMPACT OF THE STUDY: Our findings are useful for the further advancement of QQ-based strategies in engineered microbial environments.

Laparoscopic reoperation for pediatric recurrent inguinal hernia after previous laparoscopic repair.

PURPOSE: Recurrence is a concerning area in pediatric inguinal hernia repair. Various laparoscopic repair methods are available to treat recurrent pediatric inguinal hernia. We analyzed previous laparoscopic hernia repairs and report the outcomes of laparoscopic inguinal hernia reoperations in patients with recurrent inguinal hernia. METHODS: Fifty-one patients who presented for recurrent inguinal hernia after laparoscopic hernia repair from September 2012 to May 2017 were retrospectively evaluated. Previous laparoscopic procedures were analyzed with respect to sac removal (removal vs. leaving in place), suture material (absorbable vs. nonabsorbable), and high ligation method (purse string vs. multiple stitches). We removed the hernia sac from all patients and performed suture repair of the muscular arch of the internal inguinal ring using nonabsorbable material. RESULTS: All patients (38 male, 13 female) had indirect inguinal hernias. No conversion to open surgery occurred. Forty-three (84.3%) patients developed recurrence within 1 year after the previous operation [mean 8.7 ± 6.9 (range 3-33) months]. Twenty patients had concurrent hydroceles (39.2%); 16 were cord hydroceles and 4 were canal of Nuck hydroceles. In the previous operations, the hernia sac was not removed in 100% (51/51) of patients, absorbable suture material was used in 58.8% (30/51), and purse string high ligation was performed in 88.2% (45/51). No re-recurrence developed during a mean follow-up of 25.0 ± 12.6 (range 13-54) months. CONCLUSION: Laparoscopic reoperation with hernia sac removal and suture repair of the muscular arch of the internal inguinal ring with nonabsorbable material is an effective operation with few recurrences and complications.

Outcomes of decentralizing hypertension care from district hospitals to health centers in Rwanda, 2013-2014.

SETTING: Three district hospitals (DHs) and seven health centers (HCs) in rural Rwanda. OBJECTIVE: To describe follow-up and treatment outcomes in stage 1 and 2 hypertension patients receiving care at HCs closer to home in comparison to patients receiving care at DHs further from home. DESIGN: A retrospective descriptive cohort study using routinely collected data involving adult patients aged ⩾18 years in care at chronic non-communicable disease clinics and receiving treatment for hypertension at DH and HC between 1 January 2013 and 30 June 2014. RESULTS: Of 162 patients included in the analysis, 36.4% were from HCs. Patients at DHs travelled significantly further to receive care (10.4 km vs. 2.9 km for HCs, P < 0.01). Odds of being retained were significantly lower among DH patients when not adjusting for distance (OR 0.11, P = 0.01). The retention effect was consistent but no longer significant when adjusting for distance (OR 0.18, P = 0.10). For those retained, there was no significant difference in achieving blood pressure targets between the DHs and HCs. CONCLUSION: By removing the distance barrier, decentralizing hypertension management to HCs may improve long-term patient retention and could provide similar hypertension outcomes as DHs.

Lactococcus lactis KR-050L extract suppresses house dust mite induced-atopic skin inflammation through inhibition of keratinocyte and mast cell activation.

AIMS: Atopic dermatitis (AD) is a chronic inflammatory skin disease, with a steadily increasing prevalence. Lactic acid bacteria (LAB) have been widely used in the food industry and are an attractive option for preventing and treating allergic skin diseases. We previously isolated new LABs including Lactococcus lactis KR-050L from Gajuknamu kimchi, and showed the anti-inflammatory effects of extract of L. lactis KR-050L culture broth (LLK). In this study, we investigated the effects of LLK on AD. METHODS AND RESULTS: For the in vitro study, we used human keratinocytes (HaCaT) and mast cells (RBL-2H3). In vivo study, we investigated the effects of LLK on Dermatophagoides farinae extract (DFE) and 2,4-dinitrochlorobenzene (DNCB)-induced atopic skin inflammation in mice. LLK suppressed expression of pro-inflammatory cytokines and chemokines by down-regulation of p38 MAPK, STAT1 and nuclear translocation of NF-κB in keratinocytes. Topical application of LLK suppressed AD symptoms based on reduction in ear thickness, serum IgE levels and immune cell infiltration. Furthermore, LLK inhibited serum histamine levels and mast cells infiltration in vivo, and reduced mast cells activation in vitro. CONCLUSIONS: These results suggest that LLK inhibits AD symptoms through inhibition of keratinocytes and mast cells activation. SIGNIFICANCE AND IMPACT OF THE STUDY: LLK is a potential therapeutic candidate for AD treatment.

Single-Center Experience Using Marginal Liver Grafts in Korea.

BACKGROUND: Liver transplantation (LT) is an established therapeutic modality for patients with end-stage liver disease. The use of marginal donors has become more common worldwide due to the sharp increase in recipients, with a consequent shortage of suitable organs. We analyzed our single-center experience over the last 8 years in LT to evaluate the outcomes of using so-called "marginal donors." METHODS: We retrospectively analyzed the database of all LTs performed at our institution from 2009 to 2017. Only patients undergoing deceased-donor LTs were analyzed. Marginal grafts were defined as livers from donors >60 years of age, livers from donors with serum sodium levels >155 mEq, graft steatosis >30%, livers with cold ischemia time ≥12 hours, livers from donors who were hepatitis B or C virus positive, livers recovered from donation after cardiac death, and livers split between 2 recipients. Patients receiving marginal grafts (marginal group) were compared with patients receiving standard grafts (standard group). RESULTS: A total of 106 patients underwent deceased-donor LT. There were 55 patients in the standard group and 51 patients in the marginal group. There were no significant differences in terms of age, sex, Model for End-Stage Liver Disease score, underlying liver disease, presence of hepatocellular carcinoma, and hospital stay between the 2 groups. Although the incidence of acute cellular rejection, cytomegalovirus infection, and postoperative complications was similar between the 2 groups, the incidence of early allograft dysfunction was higher in the marginal group. With a median follow-up of 26 months, the 1-, 3-, and 5-year overall and graft (death-censored) survivals in the marginal group were 85.5%, 75%, and 69.2% and 85.9%, 83.6%, and 77.2%, respectively. Patient overall survival and graft survival (death-censored) were significantly lower in the marginal group (P = .023 and P = .048, respectively). On multivariate analysis, receiving a marginal graft (hazard ratio [HR], 4.862 [95% confidence interval (CI), 1.233-19.171]; P = .024) and occurrence of postoperative complications (HR, 4.547 [95% CI, 1.279-16.168]; P = .019) were significantly associated with worse patient overall survival. Also, when factors associated with marginal graft were analyzed separately, graft steatosis >30% was independently associated with survival (HR, 5.947 [95% CI, 1.481-23.886]; P = .012). CONCLUSIONS: Patients receiving marginal grafts showed lower but acceptable overall survival and graft survival. However, because graft steatosis >30% was independently associated with worse survival, caution must be exercised when using this type of marginal graft by weighing the risk and benefits.

Closing the gap: decentralising mental health care to primary care centres in one rural district of Rwanda.

Setting: Programmes that integrate mental health care into primary care settings could reduce the global burden of mental disorders by increasing treatment availability in resource-limited settings, including Rwanda. Objective: We describe patient demographics, service use and retention of patients in care at health centres (HC) participating in an innovative primary care integration programme, compared to patients using existing district hospital-based specialised out-patient care. Design: This was a retrospective cohort study using routinely collected data from six health centres and one district hospital from October 2014 to March 2015. Results: Of 709 patients, 607 were cared for at HCs; HCs accounted for 88% of the total visits for mental disorders. Patients with psychosis used HC services more frequently, while patients with affective disorders were seen more frequently at the district hospital. Of the 68% of patients who returned to care within 90 days of their first visit, 76% had a third visit within a further 90 days. There were no significant differences in follow-up rates between clinical settings. Conclusion: This study suggests that a programme of mentorship for primary care nurses can facilitate the decentralisation of out-patient mental health care from specialised district hospital mental health services to HCs in rural Rwanda.

Contexte : Les programmes qui intègrent les soins de santé mentale dans les structures de soins de santé primaires pourraient réduire le fardeau mondial des troubles mentaux en augmentant la disponibilité du traitement dans des contextes de ressources limitées, notamment au Rwanda.Objectif : Nous décrivons les caractéristiques démographiques des patients, leur utilisation des services et la rétention des patients en traitement dans les centres de santé (HC) participant à un programme innovant d'intégration dans les soins de santé primaires, comparés aux patients recourant aux consultations spécialisées existantes, basées dans les hôpitaux de district.Schéma : Une étude rétrospective de cohorte basée sur des données recueillies en routine dans six centres de santé et dans un hôpital de district, entre octobre 2014 et mars 2015.Résultats : De 709 patients, 607 ont été soignés dans les HC et les HC ont totalisé 88% de l'ensemble des consultations pour troubles mentaux. Les patients atteints de psychose ont plus souvent utilisé les services des HC, tandis que les patients atteints de troubles affectifs ont été plus souvent vus à l'hôpital de district. De 68% des patients qui sont revenus dans les 90 jours suivant leur première consultation, 76% ont eu une troisième consultation au cours des 90 jours suivants. Il n'y a pas eu de différences significatives en termes de taux de suivi entre les deux contextes cliniques.Conclusion : Cette étude suggère qu'un programme de tutorat destiné aux infirmiers de soins de santé primaires peut faciliter la décentralisation de la prise en charge de la santé mentale en consultation externe des services de santé mentale des hôpitaux spécialisés de district vers les HC dans le Rwanda rural.

Marco de referencia: Los programas que integran la atención de la salud mental al entorno de la atención primaria podrían reducir la carga mundial de morbilidad por trastornos mentales, al aumentar la disponibilidad del tratamiento en los medios con escasos recursos, por ejemplo en Rwanda.Objetivo: Se describen las características demográficas, la utilización de los servicios y la retención en la atención, de los pacientes atendidos en los centros de salud que participan en un programa innovador de atención primaria y se comparan con los pacientes que acuden a la consulta ambulatoria especializada que se presta en un hospital distrital.Método: Fue este un estudio de cohortes retrospectivo a partir de los datos recogidos de manera sistemática en seis centros de salud y un hospital distrital, de octubre del 2014 a marzo del 2015.Resultados: De los 709 pacientes, se atendieron 607 en los centros de salud y estos centros realizaron el 88% del total de consultas por trastornos mentales. Los pacientes con trastornos psicóticos utilizaban con mayor frecuencia los servicios en los centros de salud, pero los pacientes con trastornos del afecto se atendían con mayor frecuencia en el hospital distrital. El 68% de los pacientes regresaron al servicio de atención en los 90 días que siguieron a su primera consulta y el 76% de ellos acudió a una tercera consulta en los siguientes 90 días. No se observaron diferencias significativas en las tasas de seguimiento en los diferentes entornos clínicos.Conclusión: Los resultados del presente estudio ponen de manifiesto que un programa tutorial dirigido al personal de enfermería de los centros de atención primaria puede facilitar la descentralización de la atención ambulatoria de los pacientes con trastornos de salud mental, desde el hospital distrital con servicios especializados hacia los centros de salud en zonas rurales de Rwanda.

Molecular and clinical characterization of human respiratory syncytial virus in South Korea between 2009 and 2014.

Respiratory syncytial virus (RSV) can cause serious respiratory infections, second only to influenza virus. In order to know RSV's genetic changes we examined 4028 respiratory specimens from local hospital outpatients in Gyeonggi Province, South Korea over six consecutive years by real-time one-step RT-PCR; 183 patients were positive for RSV infection. To investigate the specific distribution of RSV genotypes, we performed partial sequencing of the glycoprotein gene. Of the 131 RSV-A specimens sequenced, 61 (43·3%) belonged to the ON1 genotype, 66 (46·8%) were NA1 genotype, 3 (2·1%) were GA5 genotype, and 1 (0·7%) belonged to the GA1 genotype. Of the 31 RSV-B specimens sequenced, 29 were BA9 genotype (87·9%) and 2 were BA10 genotype (6·1%). The most common clinical symptoms were fever, cough, nasal discharge, and phlegm; multiple logistic regression analysis showed that RSV-positive infection on pediatric patients was strongly associated with cough (OR = 2·8, 95% CI 1·6-5·1) and wheezing (OR = 2·8, 95% CI 1·7-4·4). The ON1 genotype was significantly associated with phlegm (OR = 11·8, 95% CI 3·8-46·7), while the NA1 genotype was associated with the pediatric patients' gender (males, OR = 2·4, 95% CI 1·1-5·4) and presence of chills (OR = 5·1, 95% CI 1·1-27·2). RSV subgroup B was showed association with nasal obstruction (OR = 4·6, 95% CI 1·2-20·0). The majority of respiratory virus coinfections with RSV were human rhinovirus (47·2%). This study contributes to our understanding of the molecular epidemiological characteristics of RSV, which promotes the potential for improving RSV vaccines.

An outbreak of norovirus infection associated with fermented oyster consumption in South Korea, 2013.

An acute gastroenteritis (AGE) outbreak was reported in May 2013 in Gyeonggi Province, South Korea. Eight students who had eaten breakfast on 21 May 2013 at a high-school restaurant exhibited AGE symptoms. Our case-control study showed that a strong association was observed between AGE symptoms and fermented oyster consumption. Virological studies also indicated that noroviruses (NoVs) were detected from both clinical samples and fermented oyster samples, and multiple different genotypes (genogroups GII.4, GII.11 and GII.14) of NoVs were present in both samples. The nucleotide sequence similarity between the strains found in the clinical samples and those in the fermented oysters was more than 99·5%. Therefore, to prevent further outbreaks, proper management of raw oysters is necessary and the food industry should be aware of the risk of viral gastroenteritis posed by fermented oysters contaminated with NoVs.

Modified maximum tangential stress criterion for fracture behavior of zirconia/veneer interfaces.

The veneering porcelain sintered on zirconia is widely used in dental prostheses, but repeated mechanical loadings may cause a fracture such as edge chipping or delamination. In order to predict the crack initiation angle and fracture toughness of zirconia/veneer bi-layered components subjected to mixed mode loadings, the accuracy of a new and traditional fracture criteria are investigated. A modified maximum tangential stress criterion considering the effect of T-stress and critical distance theory is introduced, and compared to three traditional fracture criteria. Comparisons to the recently published fracture test data show that the traditional fracture criteria are not able to properly predict the fracture initiation conditions in zirconia/veneer bi-material joints. The modified maximum tangential stress criterion provides more accurate predictions of the experimental results than the traditional fracture criteria.

Loss of serum response factor induces microRNA-mediated apoptosis in intestinal smooth muscle cells.

Serum response factor (SRF) is a transcription factor known to mediate phenotypic plasticity in smooth muscle cells (SMCs). Despite the critical role of this protein in mediating intestinal injury response, little is known about the mechanism through which SRF alters SMC behavior. Here, we provide compelling evidence for the involvement of SRF-dependent microRNAs (miRNAs) in the regulation of SMC apoptosis. We generated SMC-restricted Srf inducible knockout (KO) mice and observed both severe degeneration of SMCs and a significant decrease in the expression of apoptosis-associated miRNAs. The absence of these miRNAs was associated with overexpression of apoptotic proteins, and we observed a high level of SMC death and myopathy in the intestinal muscle layers. These data provide a compelling new model that implicates SMC degeneration via anti-apoptotic miRNA deficiency caused by lack of SRF in gastrointestinal motility disorders.

A small subunit processome protein promotes cancer by altering translation.

Dysregulation of ribosome biogenesis or translation can promote cancer, but the underlying mechanisms remain unclear. UTP18 is a component of the small subunit processome, a nucleolar multi-protein complex whose only known function is to cleave pre-ribosomal RNA to yield the 18S ribosomal RNA component of 40S ribosomal subunits. Here, we show that UTP18 also alters translation to promote stress resistance and growth, and that UTP18 is frequently gained and overexpressed in cancer. We observed that UTP18 localizes to the cytoplasm in a subset of cells, and that serum withdrawal increases cytoplasmic UTP18 localization. Cytoplasmic UTP18 associates with the translation complex and Hsp90 to upregulate the translation of IRES-containing transcripts such as HIF1a, Myc and VEGF, thereby inducing stress resistance. Hsp90 inhibition decreases cytoplasmic UTP18 and UTP18-induced increases in translation. Importantly, elevated UTP18 expression correlates with increased aggressiveness and decreased survival in numerous cancers. Enforced UTP18 overexpression promotes transformation and tumorigenesis, whereas UTP18 knockdown inhibits these processes. This stress adaptation mechanism is thus co-opted for growth by cancers, and its inhibition may represent a promising new therapeutic target.

Early exposure to bisphenol A alters neuron and glia number in the rat prefrontal cortex of adult males, but not females.

Previous work has shown that exposure to bisphenol A (BPA) during early development can alter sexual differentiation of the brain in rodents, although few studies have examined effects on areas of the brain associated with cognition. The current study examined if developmental BPA exposure alters the total number of neurons and glia in the medial prefrontal cortex (mPFC) in adulthood. Pregnant Long-Evans rats were orally exposed to 0, 4, 40, or 400-µg/kg BPA in corn oil throughout pregnancy. From postnatal days 1 to 9, pups were given daily oral doses of oil or BPA, at doses corresponding to those given during gestation. Brains were examined in adulthood, and the volume of layers 2/3 and layers 5/6 of the mPFC was parcellated. The density of neurons and glia in these layers was quantified stereologically with the optical disector, and density was multiplied by volume for each animal. Males exposed to 400-µg/kg BPA were found to have increased numbers of neurons and glia in layers 5/6. Although there were no significant effects of BPA in layers 2/3, the pattern of increased neuron number in males exposed to 400-µg/kg BPA was similar to that seen in layers 5/6. No effects of BPA were seen in females or in males exposed to the other doses of BPA. This study indicates that males are more susceptible to the long-lasting effects of BPA on anatomy of the mPFC, an area implicated in neurological disorders.

Concurrent hepatic artery and portal vein thrombosis after orthotopic liver transplantation with preserved allografts.

In contrast to early HAT, late HAT has an insidious clinical presentation. Nevertheless, biliary and vascular reconstructions in this late setting are unlikely to improve outcome. Patent portal flow makes an important contribution to the viability of liver in case of late HAT while the allograft reconstitutes intrahepatic arterial flow through neovascularization. Concurrent HAT with PVT without immediate graft necrosis is extremely rare, and allograft and patient survival are seemingly impossible without retransplantation. In fact, hepatopetal arterial and portal venous neovascularization are known albeit obscure phenomena that can preserve posttransplant hepatic function under the extenuating circumstances of complete interruption of blood flow to the graft. We describe two such cases that developed combined HAT and PVT more than six months after OLT with perfect preservation of graft function. The survival of allografts in our cases was due to extensive hepatopetal arterial and portal venous collateralization. Simultaneous HAT and PVT after OLT are rare events and almost uniformly fatal, if they occur early. Due to paucity of such cases, however, underlying mechanisms and etiology remain elusive, and despite radiological diagnosis of these complications, there is no way to predict these events in the wake of stable graft function.

Incidental renal cell carcinoma originating from a native kidney after en-bloc resection for adrenal carcinoma in a kidney transplant recipient.

BACKGROUND: Renal transplantation is the best treatment for patients with end-stage renal disease. Although there is significantly increased risk of malignancy after renal transplantation, carcinoma of the native kidney is very rare, and moreover, the risk of endocrinologic malignancy after renal transplantation is lower than in the general population and adrenal cortical carcinoma extremely rare. We report a case of incidental renal cell carcinoma originating from a native kidney after en-bloc resection for adrenal carcinoma in a kidney transplant recipient. CASE REPORT: A 57 year-old male patient had undergone living-donor kidney transplantation for chronic renal failure from hypertension 15 years earlier and had a right adrenal tumor diagnosed on surveillance abdomen-pelvis computerized tomography. Based on 24-hour catecholamine laboratory findings, nonfunctioning tumor was suspected. The planned en-bloc resection of right adrenal gland and right native kidney combining the perirenal tissue and Gerota fascia was performed, because the tumor was suspicious for malignancy and could possibly invade the perirenal tissue or right kidney. On the final pathology, combined adrenal cortical carcinoma and incidental renal cell carcinoma was confirmed. Renal cell carcinoma was papillary, type I, and stage T1N0M0. Adrenal cortical carcinoma was 7.6 × 6.5 cm in size, had marked nuclear atypia, and was grade IV/IV. Mitotic counts were >10 per high-power field, but it had no capsular invasion or vascular invasion, and free resection margin was confirmed. In the preoperative period, he had taken immunosuppressants FK506 and mycophenolate sodium, but after combined carcinomas were confirmed, the regimen of combination of immunosuppressants was changed to sirolimus with low-dose FK506 and half-dose mycophenolate sodium.