Imparting child nutritional assessment skills among medical students using hybrid problem-based learning approach in a community setting.

Background: Malnutrition affects up to a third of children in India, with severe and acute malnutrition prevalent among under five children. Nutritional assessment skills for detecting malnutrition in children in primary care settings are vital. Hybrid problem-based learning (HPBL) is an innovative, collaborative, and adaptable instructional learning strategy that can be used to teach medical students clinical skills in a community setting. Methods: A two-month quasi-experimental study was undertaken in a rural setting with third-year medical students. Faculty members were sensitized and subject experts developed a training module addressing the knowledge, attitude, communication, and practice domains. The students underwent a 3-week training module where pre-testing, case presentation, and group formation in first week, an anchoring lecture, tutorial and self-directed learning and role-play by students in subsequent week, and in last week, case discussion, post-testing, and feedback rounds were done. Results: In all domains, knowledge (3.8, 0.01), practice (4.3, 0.01), attitude and communication (3.7, 0.01), and proportional satisfactory responses, the HPBL approach resulted in a significant improvement in nutritional assessment competency. Teachers preferred the practical and engaging character of the approach, stating that doubts and questions were better addressed and that they would use it to teach similar topics. Conclusion: HPBL is an excellent teaching method for clinical skills, like nutritional assessment in simulated/field settings. The novel teaching-learning approach was well received by students and faculty members. Learning outcomes and satisfaction rates enhanced in students and faculty were encouraged to apply the approach to other topics.

The effectiveness of whey proteins in prevention and treatment of cancer: a review.

Cancer prevalence is rising rapidly around the globe, contributing immensely to the burden on health systems, hence the search for more effective and selective treatments still remains enticing. Whey, as a natural source, has received extensive focus in recent years because of its intriguing applications to health benefits. Growing consumer appreciation of the nutraceutical effects of whey components makes them an attractive field within cancer research. Whey is a valuable source of superior-quality proteins, lactose, vitamins, and minerals that contribute to proper nutrition as well as help hamper illness and even complement certain disease-related therapy prognosis. As a result, industry leaders and dairy producers are devising new ways to valorize it. Great emphasis on cancer prevention and treatment has been given to whey protein (WP) by the scientific community. WP intake has been proven to induce anti-cancer effects in various in vitro and in vivo studies. Nutritionists and dietitians are now enormously endorsing the role of WP in the therapeutic field, notably for cancer cachexia management. However, human intervention studies with WP are in their infancy and remain to be established with different tumor entities to provide valid proof of its ability to act as a coadjuvant in cancer treatment.

CBL-interacting protein kinase 25 contributes to root meristem development.

Co-ordination of auxin and cytokinin activities determines root meristem size during post-embryonic development. Calcineurin B-like proteins (CBLs) and their interacting protein kinases (CIPKs) constitute signaling modules that relay calcium signals. Here we report that CIPK25 is involved in regulating the root meristem size. Arabidopsis plants lacking CIPK25 expression displayed a short root phenotype and a slower root growth rate with fewer meristem cells. This phenotype was rescued by restoration of CIPK25 expression. CIPK25 interacted with CBL4 and -5, and displayed strong gene expression in the flower and root, except in the cell proliferation domain in the root apical meristem. Its expression in the root was positively and negatively regulated by auxin and cytokinin, respectively. The cipk25 T-DNA insertion line was compromised in auxin transport and auxin-responsive promoter activity. The cipk25 mutant line showed altered expression of auxin efflux carriers (PIN1 and PIN2) and an Aux/IAA family gene SHY2. Decreased PIN1 and PIN2 expression in the cipk25 mutant line was completely restored when combined with a SHY2 loss-of-function mutation, resulting in recovery of root growth. SHY2 and PIN1 expression was partially regulated by cytokinin even in the absence of CIPK25, suggesting a CIPK25-independent cytokinin signaling pathway(s). Our results revealed that CIPK25 plays an important role in the co-ordination of auxin and cytokinin signaling in root meristem development.

Primary Osteosarcoma in the Elderly Revisited: Current Concepts in Diagnosis and Treatment.

PURPOSE OF REVIEW: Osteosarcoma is mostly seen in bones of children and young adults. When it occurs in older persons, the tumor is considered secondary usually complicating Paget disease or irradiated bone. However, there is a second incidence peak of primary osteosarcoma later in life when these tumors occur de novo. This article describes the clinical, imaging, and treatment of POS in older patients, including demographic data of patients from our institution. FINDINGS: We present our experience with 920 cases of osteosarcoma that were seen between 1984 and 2003 at the University of Texas MD Anderson Cancer Center in Houston, TX, USA. Among the 868 primary osteosarcoma of bones, there were 100 (11.52%), which comprised 69% of the tumors in patients over the age of 50 years. Older patients with primary osteosarcoma tend to have relatively more common axial skeleton involvement, have more distant disease, and are difficult to treat because of concomitant comorbidities. Despite that, most adult patients treated with chemotherapy have shown good results with longer disease-free survival. A lytic bone lesion seen in radiographs of elderly patients should include primary osteosarcoma among differential diagnoses. Radical surgery and chemotherapy seem to ensure long-term disease-free survival in most cases. The elderly patients with POS in pelvis, spine, and upper extremities and those with distant disease (metastases) have worse prognosis.

Interlocked benzenes in triangular π-architectures: anchoring groups dictate ion binding and transmission.

Macrocyclic compounds like crown ethers, calixarenes, etc. are well explored in the literature as receptors for alkali metal ions. In most of these studies, the size of the macrocyclic cavity has evolved as the prominent determining criterion for the selective binding of various ions. However, approaches to systematically tailor the ion transport properties via the interplay of topological as well as electronic properties of the hosts are rarely addressed. Herein, we investigate the performance of [2.2.2]PCPs ([2.2.2]paracyclophane and [2.2.2]paracyclophene) and cyclohexaphenylene (CHP) as receptors for the alkali ions, Li+, Na+ and K+. The three macrocycles differ in terms of the groups (ethylene, vinylene and phenylene) anchoring the three benzene rings into triangular three-dimensional architectures, thereby providing opportunities for controlling the topological and the electronic features of the cavities. Based on electronic structure calculations, we predict that PCPs and CHP could be used in conjunction with dehydrobenzoannulenes that possess similar triangular π-architectures in two-dimensions to achieve selective ion transmission. Furthermore, an extended network of CHP, graphenylene, is shown for the first time to be potentially useful in energy storage applications in lithium ion batteries akin to graphyne and graphdiyne. The ion binding properties of graphenylenes would be rather interesting to investigate experimentally for energy applications, particularly in the context of the recent successful synthesis of one of the members of the graphenylene family. Overall, we have attempted to provide a unified description of the cationic interactions with 2D and 3D triangular π-architectures, describing the utility of materials like graphyne, graphdiyne and graphenylene for ion sensing and separation and energy storage applications.

Characterization of Physiologic (18)F FSPG Uptake in Healthy Volunteers.

Purpose To evaluate the normal biodistribution and kinetics of (S)-4-(3-[18F]fluoropropyl)-l-glutamic acid ((18)F FSPG) in healthy volunteers and to compare (18)F FSPG mean and maximum standardized uptake values (SUVmean and SUVmax, respectively) with those of (18)F fluorodeoxyglucose (FDG) across a variety of organs. Materials and Methods This protocol was reviewed and approved by all appropriate regulatory authorities. An 8-mCi (±10%) dose of (18)F FSPG was given to five subjects (three women, two men), and seven whole-body positron emission tomography (PET) scans were performed 5, 10, 20, 30, 45, 150, and 240 minutes after injection. Regions of interest were analyzed on the resultant (18)F FSPG images to evaluate the kinetics of this radiotracer. The images obtained 45 minutes after injection were used to measure SUVmean and SUVmax in additional regions of the body. These values were compared with similar values obtained with (18)F FDG PET published previously. Descriptive statistics, including average and standard deviation across the five subjects, were used. (18)F FSPG SUVmean and SUVmax were compared. Results On the (18)F FSPG images obtained 45 minutes after injection, there was only low-grade background activity in the majority of analyzed regions. Prominent activity was seen throughout the pancreas. Clearance of the radiotracer through the kidneys and collection in the bladder also were seen. SUV quantification shows notable differences between (18)F FSPG and (18)F FDG in the pancreas ((18)F FSPG SUVmean, 8.2; (18)F FDG SUVmean, 1.3), stomach ((18)F FSPG SUVmax, 3.6; (18)F FDG SUVmax, 1.6), and brain ((18)F FSPG SUVmean, 0.08; (18)F FDG SUVmean, 7.8). The kinetic data showed rapid clearance of the radiotracer from the blood pool and most organs, except the pancreas. Conclusion (18)F FSPG is a PET radiopharmaceutical characterized by rapid clearance from most healthy tissues, except the pancreas and kidneys. A consistent biodistribution pattern was observed with low background uptake. The physiologic uptake of this new radiotracer throughout the body is described in more detail, which is important for improved interpretative accuracy and understanding potential clinical applications. (©) RSNA, 2016.

A qualitative study of the background and in-hospital medicolegal response to female burn injuries in India.

BACKGROUND: Most burns happen in low- and middle-income countries. In India, deaths related to burns are more common in women than in men and occur against a complex background in which the cause - accidental or non-accidental, suicidal or homicidal - is often unclear. Our study aimed to understand the antecedents to burns and the problem of ascribing cause, the sequence of medicolegal events after a woman was admitted to hospital, and potential opportunities for improvement. METHODS: We conducted semi-structured interviews with 33 women admitted to two major burns units, their families, and 26 key informant doctors, nurses, and police officers. We used framework analysis to examine the context in which burns occurred and the sequence of medicolegal action after admission to hospital. RESULTS: Interviewees described accidents, attempted suicide, and attempted homicide. Distinguishing between these was difficult because the underlying combination of poverty and cultural precedent was common to all and action was contingent on potentially conflicting narratives. Space constraint, problems with cooking equipment, and inflammable clothing increased the risk of accidental burns, but coexisted with household conflict, gender-based violence, and alcohol use. Most burns were initially ascribed to accidents. Clinicians adhered to medicolegal procedures, the police carried out their investigative requirements relatively rapidly, but both groups felt vulnerable in the face of the legal process. Women's understandable reticence to describe burns as non-accidental, the contested nature of statements, their perceived history of changeability, the limited quality and validity of forensic evidence, and the requirement for resilience on the part of clients underlay a general pessimism. CONCLUSIONS: The similarities between accident and intention cluster so tightly as to make them challenging to distinguish, especially given women's understandable reticence to describe burns as non-accidental. The contested status of forensic evidence and a reliance on testimony means that only a minority of cases lead to conviction. The emphasis should be on improving documentation, communication between service providers, and public understanding of the risks of burns.

Explainable artificial intelligence approaches for brain-computer interfaces: a review and design space.

Objective.This review paper provides an integrated perspective of Explainable Artificial Intelligence (XAI) techniques applied to Brain-Computer Interfaces (BCIs). BCIs use predictive models to interpret brain signals for various high-stake applications. However, achieving explainability in these complex models is challenging as it compromises accuracy. Trust in these models can be established by incorporating reasoning or causal relationships from domain experts. The field of XAI has emerged to address the need for explainability across various stakeholders, but there is a lack of an integrated perspective in XAI for BCI (XAI4BCI) literature. It is necessary to differentiate key concepts like explainability, interpretability, and understanding, often used interchangeably in this context, and formulate a comprehensive framework.Approach.To understand the need of XAI for BCI, we pose six key research questions for a systematic review and meta-analysis, encompassing its purposes, applications, usability, and technical feasibility. We employ the PRISMA methodology-preferred reporting items for systematic reviews and meta-analyses to review (n = 1246) and analyse (n = 84) studies published in 2015 and onwards for key insights.Main results.The results highlight that current research primarily focuses on interpretability for developers and researchers, aiming to justify outcomes and enhance model performance. We discuss the unique approaches, advantages, and limitations of XAI4BCI from the literature. We draw insights from philosophy, psychology, and social sciences. We propose a design space for XAI4BCI, considering the evolving need to visualise and investigate predictive model outcomes customised for various stakeholders in the BCI development and deployment lifecycle.Significance.This paper is the first to focus solely on reviewing XAI4BCI research articles. This systematic review and meta-analysis findings with the proposed design space prompt important discussions on establishing standards for BCI explanations, highlighting current limitations, and guiding the future of XAI in BCI.

NLRP3 and AIM2 inflammasomes exacerbate the pathogenic Th17 cell response to eggs of the helminth Schistosoma mansoni.

Infection with the helminth Schistosoma mansoni can cause exacerbated morbidity and mortality via a pathogenic host CD4 T cell-mediated immune response directed against parasite egg antigens, with T helper (Th) 17 cells playing a major role in the development of severe granulomatous hepatic immunopathology. The role of inflammasomes in intensifying disease has been reported; however, neither the types of caspases and inflammasomes involved, nor their impact on the Th17 response are known. Here we show that enhanced egg-induced IL-1ß secretion and pyroptotic cell death required both caspase-1 and caspase-8 as well as NLRP3 and AIM2 inflammasome activation. Schistosome genomic DNA activated AIM2, whereas reactive oxygen species, potassium efflux and cathepsin B, were the major activators of NLRP3. NLRP3 and AIM2 deficiency led to a significant reduction in pathogenic Th17 responses, suggesting their crucial and non-redundant role in promoting inflammation. Additionally, we show that NLRP3- and AIM2-induced IL-1ß suppressed IL-4 and protective Type I IFN (IFN-I) production, which further enhanced inflammation. IFN-I signaling also curbed inflammasome- mediated IL-1ß production suggesting that these two antagonistic pathways shape the severity of disease. Lastly, Gasdermin D (Gsdmd) deficiency resulted in a marked decrease in egg-induced granulomatous inflammation. Our findings establish NLRP3/AIM2-Gsdmd axis as a central inducer of pathogenic Th17 responses which is counteracted by IFN-I pathway in schistosomiasis.

Experiential learning through Program Evaluation: Assessing external barriers to Bridgehaven attendance.

This cross-sectional study was conducted as an experiential project in a graduate Program Evaluation class. We worked together as a team to solve difficulties that occurred when evaluating a program for the first time, including overcoming initial fears and identifying the appropriate focus. The goal of this study was to identify the most common barriers to attendance at Bridgehaven Mental Health Services, a community-based outpatient program tailored to aid in the transition from hospitals to community living. External barriers to attendance were examined by an adapted version of the Structural Barriers to Clinic Attendance Scale (SCBA) and a researcher-created qualitative measure. Between-group t-tests and non-parametric analyses indicated that a far walk from the bus stop and negative perceptions of staff behavior were significant external barriers to Bridgehaven attendance among 42 adult members with severe mental illness. Additionally, themes from the qualitative data revealed that 74.7% of members viewed other obligations and appointments as barriers to their attendance. About half of the members surveyed indicated the positive impact of groups on attendance. Overall findings revealed the importance of considering external barriers, particularly issues related to transportation, scheduling, and social perceptions when identifying solutions to declining attendance rates. Through the process of conducting this study, we learned invaluable skills (e.g., problem-solving, teamwork, collaboration, and flexibility) that will carry with us as we evaluate programs in the future.

Diagnostic Dilemma in Fatal Paraquat Poisoning: An Autopsy Case Report.

Paraquat is a highly toxic agent used as an herbicide worldwide. Despite its easy and widespread availability, data regarding cases of paraquat poisoning in India is limited. Diagnosis often becomes difficult without a clear history, owing to its rather nonspecific and varying presentation. In the present case, a 22-year-old man was brought with a history of high-grade fever, sore throat, and oral ulcers for around a week. He was symptomatically treated at multiple hospitals and was worked up for suspected diagnoses like diphtheria and influenza (H1N1). Later during treatment, it was revealed that "Paraxzone" was procured online by the patient himself two weeks before the onset of his symptoms. Thence, the treatment regimen was modified following suspicion of paraquat poisoning. However, the delay in diagnosis led to the worsening his condition, and the patient succumbed to death due to pulmonary and renal complications after 16 days of survival. The postmortem examination, supplemented with histopathological evaluation, supported the diagnosis of paraquat poisoning. Paraquat poisoning can mimic a myriad of clinical conditions. Thorough history taking, a high degree of suspicion, and collaborative work with the investigating agency are of paramount importance while dealing with cases of suspected paraquat poisoning in hospital settings.

Effect of Lactobacillus fermentum MCC2760-Based Probiotic Curd on Hypercholesterolemic C57BL6 Mice.

Lactobacillus fermentum MCC2760 is a probiotic strain proven earlier for cholesterol-reducing and anti-inflammatory properties in vitro and in vivo. This study investigates L. fermentum MCC2760-based probiotic curd in high-cholesterol diet (HCD)-fed C57BL6 mice. The mice were grouped into normal diet control, high-cholesterol diet control, normal diet with probiotic supplementation, and high-cholesterol diet with probiotic supplementation. Control groups and treatment groups were supplemented with market curd and probiotic curd, respectively, via oral gavage for eight weeks. The probiotic count was maintained at 10.95 log CFU/mL in the developed probiotic curd. The HCD group showed an increase in feed intake and body weight. Reduction in the levels of serum cholesterol, triglycerides, low-density lipoprotein cholesterol, glucose, aspartate aminotransferase, and alanine transaminase was observed in probiotic-supplemented groups. The probiotic-supplemented group resulted in an increase in Lactobacillus spp. count along with reduced pathogen count in the feces. Probiotic supplementation also showed a reduction in the bacterial translocation count in mesenteric adipose tissue. Expression of inflammatory markers by qPCR showed the decline in the fold change of TNF-α, IL-6, and IL-12 and elevation in the fold change of IL-10 in the adipose tissue of the probiotic-treated group. Probiotic supplementation also improved the expression of GLP-1, ZO-1, and CB2 in the intestine. They were thus possibly playing a role in the enhancement of barrier function. Histopathological sections showed improvement in the cellular infiltration and pathological indications due to the high-cholesterol diet intake. Our study also confirmed that probiotics could increase serum antioxidant enzymes in treated groups, showing their beneficial antioxidant activity. It suggests the anti-inflammatory, antioxidant effect, and gut barrier function of the given probiotic formulation, which ameliorate hypercholesterolemia.

Distribution and determinants of submandibular gland involvement in oral cavity squamous cell carcinoma.

INTRODUCTION: Though the submandibular gland (SMG) is routinely sacrificed for several reasons during neck dissection in patients undergoing curative surgery for oral cavity cancers, it might be an innocent bystander and should be considered for preservation. This study aimed to identify the incidence, different patterns of invasion, and risk factors of SMG involvement in oral cavity squamous cell carcinoma (SCC). METHODS: This was a retrospective study of the patients who underwent upfront curative surgery for a biopsy-proven oral cavity SCC. A consistent protocol-based treatment strategy was followed during the study period. Data about clinical profile including demographics, clinical and histology details, and treatment profile were extracted and analysed. RESULTS: A total of 303 patients underwent unilateral and bilateral neck dissections contributing 79.2% (n = 240) and 20.8% (n = 63) of patients respectively. The common primary sites were buccal mucosa (n = 129, 42.5%), tongue (n = 100, 33.0%) and alveolar gingiva (n = 52, 17.2%). A total of four SMGs showed tumor involvement resulting in a prevalence of 1.09% per neck dissection (n = 366) and 1.32% per patient (n = 303). Of these four cases of SMG involvement, one patient with alveolar cancer had direct tumor invasion while the other three (alveolar cancer - two, tongue cancer - one) patients had neck node metastasis. CONCLUSION: The present study confirms a very low incidence of SMG involvement in patients with oral cavity cancer who undergo neck dissection. It is often observed in patients with high neck node burden (≥N2 disease and the presence of extracapsular spread) or direct invasion by the primary tumor.

The Peritoneum: What Nuclear Radiologists Need to Know.

The peritoneum is the largest and most complex serous membrane in the human body. The peritoneal membrane is composed of a layer of mesothelium supported by a thin layer of connective tissue. The peritoneum is one continuous sheet, forming two layers and a potential space between them - the peritoneal cavity- which is subdivided into multiple communicating spaces containing small amount of serous fluid that facilitates frictionless movement of mobile intraabdominal viscera. Peritoneum also contributes to fluid exchange mechanism and plays a role in immune response. The peritoneum is subject to many neoplastic and non-neoplastic processes including infections, trauma, developmental and inflammatory processes. Different Nuclear Medicine imaging techniques can be used to diagnose peritoneal diseases, most of these techniques can be customized depending on the clinical scenario and expected findings. Peritoneal scintigraphy can detect abnormal peritoneal communication or compartmentalization. Several nuclear medicine techniques can help characterize intraperitoneal fluid collections and differentiate sterile from infected fluid. PET imaging plays an important role in imaging of different neoplastic and non-neoplastic peritoneal pathologies. Nuclear radiologists need to be familiar with peritoneal anatomy and pathology to interpret peritoneal findings in dedicated peritoneal nuclear medicine imaging studies, as part of more general nuclear medicine scans, or on CT or MRI component of hybrid imaging studies. The purpose of this article is to review the normal peritoneal anatomy, various pathologic processes involving the peritoneum, and different nuclear medicine and hybrid imaging techniques that can help detect, characterize, and follow up peritoneal pathology.

Initial evaluation of (4S)-4-(3-[18F]fluoropropyl)-L-glutamate (FSPG) PET/CT imaging in patients with head and neck cancer, colorectal cancer, or non-Hodgkin lymphoma.

PURPOSE: (4S)-4-(3-[18F]Fluoropropyl)-L-glutamic acid ([18F]FSPG) measures system xC- transporter activity and shows promise for oncologic imaging. We present data on tumor uptake of this radiopharmaceutical in human subjects with head and neck cancer (HNC), colorectal cancer (CRC), and non-Hodgkin lymphoma (NHL). METHODS: A total of 15 subjects with HNC (n = 5), CRC (n = 5), or NHL (n = 5) were recruited (mean age 66.2 years, range 44-87 years). 301.4 ± 28.1 MBq (8.1 ± 0.8 mCi) of [18F]FSPG was given intravenously to each subject, and 3 PET/CT scans were obtained 0-2 h post-injection. All subjects also had a positive [18F]FDG PET/CT scan within 1 month prior to the [18F]FSPG PET scan. Semi-quantitative and visual comparisons of the [18F]FSPG and [18F]FDG scans were performed. RESULTS: [18F]FSPG showed strong uptake in all but one HNC subject. The lack of surrounding brain uptake facilitated tumor delineation in the HNC patients. [18F]FSPG also showed tumor uptake in all CRC subjects, but variable uptake in the NHL subjects. While the absolute [18F]FDG SUV values were comparable or higher than [18F]FSPG, the tumor-to-background SUV ratios were greater with [18F]FSPG than [18F]FDG. CONCLUSIONS: [18F]FSPG PET/CT showed promising results across 15 subjects with 3 different cancer types. Concordant visualization was mostly observed between [18F]FSPG and [18F]FDG PET/CT images, with some inter- and intra-individual uptake variability potentially reflecting differences in tumor biology. The tumor-to-background ratios were greater with [18F]FSPG than [18F]FDG in the cancer types evaluated. Future studies based on larger numbers of subjects and those with a wider array of primary and recurrent or metastatic tumors are planned to further evaluate the utility of this novel tracer.

Clinical Evaluation of (4S)-4-(3-[18F]Fluoropropyl)-L-glutamate (18F-FSPG) for PET/CT Imaging in Patients with Newly Diagnosed and Recurrent Prostate Cancer.

PURPOSE: (4S)-4-(3-[18F]Fluoropropyl)-L-glutamic acid (18F-FSPG) is a radiopharmaceutical for PET imaging of system xC - activity, which can be upregulated in prostate cancer. We present data on the first evaluation of patients with newly diagnosed or recurrent prostate cancer with this radiopharmaceutical. EXPERIMENTAL DESIGN: Ten patients with primary and 10 patients with recurrent prostate cancer were enrolled in this prospective multicenter study. After injection of 300 MBq of 18F-FSPG, three whole-body PET/CT scans were obtained. Visual analysis was compared with step-section histopathology when available as well as other imaging studies and clinical outcomes. Metabolic parameters were measured semiquantitatively. Expression levels of xCT and CD44 were evaluated by IHC for patients with available tissue samples. RESULTS: 18F-FSPG PET showed high tumor-to-background ratios with a relatively high tumor detection rate on a per-patient (89%) and per-lobe (87%) basis. The sensitivity was slightly higher with imaging at 105 minutes in comparison with 60 minutes. The maximum standardized uptake values (SUVmax) for cancer was significantly higher than both normal (P < 0.005) and benign pathology (P = 0.011), while there was no significant difference between normal and benign pathology (P = 0.120). In the setting of recurrence, agreement with standard imaging was demonstrated in 7 of 9 patients (78%) and 13 of 18 lesions (72%), and revealed true local recurrence in a discordant case. 18F-FSPG accumulation showed moderate correlation with CD44 expression. CONCLUSIONS: 18F-FSPG is a promising tumor imaging agent for PET that seems to have favorable biodistribution and high cancer detection rate in patients with prostate cancer. Further studies are warranted to determine the diagnostic value for both initial staging and recurrence, and how it compares with other investigational radiotracers and conventional imaging modalities.

PIAS1 activates the expression of smooth muscle cell differentiation marker genes by interacting with serum response factor and class I basic helix-loop-helix proteins.

Although a critical component of vascular disease is modulation of the differentiated state of vascular smooth muscle cells (SMC), the mechanisms governing SMC differentiation are relatively poorly understood. We have previously shown that E-boxes and the ubiquitously expressed class I basic helix-loop-helix (bHLH) proteins, including E2-2 and E12, are important in regulation of the SMC differentiation marker gene, the SM alpha-actin gene. The aim of the present study was to identify proteins that bind to class I bHLH proteins in SMC and modulate transcriptional regulation of SMC differentiation marker genes. Herein we report that members of the protein inhibitor of activated STAT (PIAS) family interact with class I bHLH factors as well as serum response factor (SRF). PIAS1 interacted with E2-2 and E12 based on yeast two-hybrid screens, mammalian two-hybrid assays, and/or coimmunoprecipitation assays. Overexpression of PIAS1 significantly activated the SM alpha-actin promoter and mRNA expression, as well as SM myosin heavy chain and SM22alpha, whereas a small interfering RNA for PIAS1 decreased activity of these promoters, as well as endogenous mRNA expression, and SRF binding to SM alpha-actin promoter within intact chromatin in cultured SMC. Of significance, PIAS1 bound to SRF and activated SM alpha-actin promoter expression in wild-type but not SRF(-/-) embryonic stem cells. These results provide novel evidence that PIAS1 modulates transcriptional activation of SMC marker genes through cooperative interactions with both SRF and class I bHLH proteins.

The effect of opiates on the activity of human placental aromatase/CYP19.

Aromatase, cytochrome P450 19, is a key enzyme in the biosynthesis of estrogens by the human placenta. It is also the major placental enzyme that metabolizes the opiates L-acetylmethadol (LAAM), methadone, and buprenorphine (BUP). Methadone and BUP are used in treatment of the opiate addict and are competitive inhibitors of testosterone conversion to estradiol (E(2)) and 16alpha-hydroxytestosterone (16-OHT) to estriol (E(3)) by aromatase. The aim of this investigation is to determine the effect of 20 opiates, which can be administered to pregnant patients for therapeutic indications or abused, on E(2) and E(3) formation by placental aromatase. Data obtained indicated that the opiates increased, inhibited, or had no effect on aromatase activity. Their effect on E(3) formation was more pronounced than that on E(2) due to the lower affinity of 16-OHT than testosterone to aromatase. The K(i) values for the opiates that inhibited E(3) formation were sufentanil, 7 +/- 1 microM; LAAM, 13 +/- 8 microM; fentanyl, 25 +/- 5 microM; oxycodone, 92 +/- 22 microM; codeine, 218 +/- 69 microM; (+)-pentazocine, 225 +/- 73 microM. The agonists morphine, heroin, hydromorphone, oxymorphone, hydrocodone, propoxyphene, meperidine, levorphanol, dextrorphan, and (-)-pentazocine and the antagonists naloxone and naltrexone caused an increase in E(3) formation by 124-160% of control but had no effect on E(2) formation. Moreover, oxycodone and codeine did not inhibit E(2) formation and the IC(50) values for fentanyl, sufentanil, and (+)-pentazocine were >1000 microM. It is unlikely that the acute administration of the opiates that inhibit estrogen formation would affect maternal and/or neonatal outcome. However, the effects of abusing any of them during the entire pregnancy are unclear at this time.