ACR appropriateness Criteria® infertility.
Appropriate imaging for women undergoing infertility workup depends upon the clinician's suspicion for potential causes of infertility. Transvaginal US is the preferred modality to assess the ovaries for features of polycystic ovary syndrome (PCOS), the leading cause of anovulatory infertility. For women who have a history or clinical suspicion of endometriosis, which affects at least one third of women with infertility, both MRI and pelvic US can provide valuable information. If tubal occlusion is suspected, whether due to endometriosis, previous pelvic inflammatory disease, or other cause, hysterosalpingogram (HSG) is the preferred method of evaluation. To assess for anatomic causes of recurrent pregnancy loss (RPL) such as Müllerian anomalies, synechiae, and leiomyomas, saline infusion sonohysterography, MRI and 3-D US are most appropriate. Up to 10% of women suffering recurrent pregnancy loss have a congenital Müllerian anomaly. When assessment of the pituitary gland is indicated, MRI is the imaging exam of choice.The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every three years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.


Overexpression of microRNA-5100 decreases the aggressive phenotype of pancreatic cancer cells by targeting PODXL.
Metastasis is the main cause of cancer-associated death, and metastasis of pancreatic cancer remains difficult to treat because of its aggressiveness. MicroRNAs (miRNAs) play crucial roles in the regulation of various human transcripts, and many miRNAs have been reported to correlate with cancer metastasis. We identified an anti-metastatic miRNA, miR-5100, by investigating differences in miRNA profiling between highly metastatic pancreatic cancer cells and their parental cells. Overexpression of miR-5100 inhibited colony formation (P<0.05), cell migration (P<0.0001) and invasion (P<0.0001) of pancreatic cancer cells. In addition, we identified a possible target of miR-5100, podocalyxin-like 1 (PODXL), and demonstrated miR-5100 directly binds to the 3' untranslated region of PODXL and post-transcriptionally regulates its expression in pancreatic cancer cells. Silencing PODXL resulted in diminished cell migration (P<0.0001) and invasion (P<0.05). We also clarified the close relationship between expression of PODXL in human pancreatic cancer specimens and liver metastasis (P=0.0003), and determined that post-operative survival was longer in the low-PODXL expression group than in the high-PODXL expression group (P<0.05). These results indicate that miR-5100 and PODXL have considerable therapeutic potential for anti-metastatic therapy and could be potential indicators for cancer metastases in patients with pancreatic cancer.


Late heartbeat-evoked potentials are associated with survival after cardiac arrest.
Cardiac arrest (CA) is a serious condition characterized by high mortality rates, even after initial successful resuscitation, mainly due to neurological damage. Whether brain-heart communication is associated with outcome after CA is unknown. Heartbeat-evoked brain potentials (HEPs) represent neurophysiological indicators of brain-heart communication. The aim of this study was to address the association between HEPs and survival after CA. HEPs were calculated from resting EEG/ECG in 55 CA patients 24 h after resuscitation. All patients were treated with targeted temperature management and a standardized sedation protocol during assessment. We investigated the association between HEP amplitude (180-320 ms, 455-595 ms, 860-1000 ms) and 6-month survival. Twenty-five of 55 patients (45%) were still alive at 6-month follow-up. Survivors showed a higher HEP amplitude at frontopolar and frontal electrodes in the late HEP interval than non-survivors. This effect remained significant after controlling for between-group differences in terms of age, Fentanyl dose, and time lag between resuscitation and EEG assessment. There were no group differences in heart rate or heart rate variability. Brain-heart communication, as reflected by HEPs, is associated with survival after CA. Future studies should address the brain-heart axis in CA.


Inhibition by neurotoxic phospholipases A2 of synaptosomal uptake of gamma-aminobutyric acid.
A comparison has been made of the abilities of several neurotoxic and nontoxic phospholipases A2 from snake venoms to inhibit the intake of gamma-aminobutyric acid into synaptosomes from rat cerebral cortex. The neurotoxic phospholipase A2 inhibited GABA uptake more than the nontoxic enzymes did. However, there was a poor correlation between the measured specific enzyme activity of a phospholipase A2 and its ability to inhibit the uptake of GABA.


Differential roles of PDGFR-alpha and PDGFR-beta in angiogenesis and vessel stability.
Preclinical and clinical evaluations of individual proangiogenic/arteriogenic factors for the treatment of ischemic myocardium and skeletal muscle have produced unfulfilled promises. The establishment of functional and stable arterial vascular networks may require combinations of different angiogenic and arteriogenic factors. Using in vivo angiogenesis and ischemic hind-limb animal models, we have compared the angiogenic and therapeutic activities of fibroblast growth factor 2 (FGF-2) in combinations with PDGF-AA and PDGF-AB, two members of the platelet-derived growth factor (PDGF) family, with distinct receptor binding patterns. We show that both PDGF-AA/FGF-2 and PDGF-AB/FGF-2 in combinations synergistically induce angiogenesis in the mouse cornea. FGF-2 up-regulates PDGFR-alpha and -beta expression levels in the newly formed blood vessels. Interestingly, PDGF-AB/FGF-2, but not PDGF-AA/FGF-2, is able to stabilize the newly formed vasculature by recruiting pericytes, and an anti-PDGFR-beta neutralizing antibody significantly blocks PDGF-AB/FGF-2-induced vessel stability. These findings demonstrate that PDGFR-beta receptor is essential for vascular stability. Similarly, PDGF-AB/FGF-2 significantly induces stable collateral growth in the rat ischemic hind limb. The high number of collaterals induced by PDGF-AB/FGF-2 leads to dramatic improvement of the paw's skin perfusion. Immunohistochemical analysis of the treated skeletal muscles confirms that a combination of PDGF-AB and FGF-2 significantly induces arteriogenesis in the ischemic tissue. A combination of PDGF-AB and FGF-2 would be optimal proangiogenic agents for the treatment of ischemic diseases.


Trivial trauma and delayed rupture of a normal spleen: a case report.
Although a majority of splenic ruptures present acutely with a known mechanism of injury, a minority of patients present days to weeks following trauma with a delayed rupture. Also uncommon is the atraumatic rupture, the vast majority of which occur in patients with underlying splenic pathology. A handful of cases of apparently spontaneous rupture of a normal spleen are reported; however, there is debate about whether these actually represent delayed ruptures following a history of trauma that is not elicited. Although a few cases of delayed rupture of the spleen following trivial trauma have been reported, the majority of these present evidence of an underlying disease process. We found only two such cases that documented a normal spleen and three cases where underlying splenic pathology was not reported. We review the literature and discuss the phenomenon of delayed rupture of the normal spleen following trivial trauma. A 27-year-old Caucasian man with no underlying splenic pathology presented with splenic rupture one week after playfully wrestling with his partner. The patient did not present at the time of the injury and only recalled it upon repeated questioning after computed tomography diagnosis. This case lends support to the theory that the normal spleen can rupture some time after trivial trauma, which seems like a more plausible explanation than rupture without cause. However, given the dearth of similar reports in the literature, the possibility remains that the association we have observed is not causational.


Osteoarthritis: new insights. Part 1: the disease and its risk factors.
Osteoarthritis is the most common form of arthritis, affecting millions of people in the United States. It is a complex disease whose etiology bridges biomechanics and biochemistry. Evidence is growing for the role of systemic factors (such as genetics, dietary intake, estrogen use, and bone density) and of local biomechanical factors (such as muscle weakness, obesity, and joint laxity). These risk factors are particularly important in weight-bearing joints, and modifying them may present opportunities for prevention of osteoarthritis-related pain and disability. Major advances in management to reduce pain and disability are yielding a panoply of available treatments ranging from nutriceuticals to chondrocyte transplantation, new oral anti-inflammatory medications, and health education. This article is part 1 of a two-part summary of a National Institutes of Health conference. The conference brought together experts on osteoarthritis from diverse backgrounds and provided a multidisciplinary and comprehensive summary of recent advances in the prevention of osteoarthritis onset, progression, and disability. Part 1 focuses on a new understanding of what osteoarthritis is and on risk factors that predispose to disease occurrence. It concludes with a discussion of the impact of osteoarthritis on disability.


Efficacy and tolerability of an herbal formulation for weight management.
The clinical effects and tolerability of a novel herbal formulation comprising the extracts of Sphaeranthus indicus and Garcinia mangostana were assessed in two similarly designed randomized, double-blind, placebo-controlled, clinical trials in 100 human subjects with a body mass index (BMI) between 30 and 40 kg/m². Participants were randomized into two groups receiving either 400 mg of herbal blend twice daily or two identical placebo capsules. All subjects received three meals (2000 kcal/day) throughout the study and walked 5 days a week for 30 min. The primary outcome was reduction in body weight. Secondary outcomes were reduction in BMI and in waist and hip circumference. Serum glycemic, lipid, and adiponectin levels were also measured. Ninety-five subjects completed the trials, and data from these two studies were pooled and analyzed. At study conclusion (8 weeks), statistically significant reductions in body weight (5.2 kg; P<.0001), BMI (2.2 kg/m²; P<.0001), as well as waist (11.9 cm; P<.0001) and hip circumferences (6.3 cm; P=.0001) were observed in the herbal group compared with placebo. An increase in serum adiponectin concentration was also found in the herbal group versus placebo (P=.0008) at study conclusion along with reductions in fasting blood glucose (12.2%, P=.01), cholesterol (13.8%, P=.002), and triglyceride (41.6%, P<.0001) concentrations. No changes were seen across organ function panels, multiple vital signs, and no major adverse events were reported. The minor adverse events were equally distributed between the two groups. Our findings suggest that the herbal blend appears to be a well-tolerated and effective ingredient for weight management.


Effect of heparin concentration and infusion rate on the patency of arterial catheters.
In a prospective randomized controlled trial involving 470 arterial catheters in 470 children, we studied the effect of changing either the concentration or the flow rate of a heparin infusion. Although catheters tended to remain patent longer with a flow rate of 2 ml/h rather than 1 ml/h, the difference was not statistically significant. Increasing the heparin concentration from 1 to 5 U/ml significantly prolonged catheter patency.


Ab initio molecular dynamics of proton networks in narrow polymer electrolyte pores.
It is well established that proton conductivity in fuel cell membrane materials such as Nafion decreases strongly with decreasing water content. Proton transport in almost dry membranes is thought to proceed through narrow channels. In the present work we investigate proton structure and dynamics in two narrow cylindrical pores, which differ by their radius and the spacing of SO(3)H groups inside the channel. Pores are modelled through eight CF(3)CF(3) and four CF(3)SO(3)H entities in a helical arrangement. The water content λ (the ratio between the number of water molecules and the number of sulfonic acid groups) in the pores varies between 2.5 and 4.5. We observe a transition from the undissociated acid at very low λ through more or less localized H(3)O(+) entities to more delocalized H(5)O(2)(+) entities for the investigated range of λ. In the narrower pore, where S-S distances vary in a more favourable range (between 6 and 8.5 Å) than in the wider pore, we find that the molecular mobility is significantly higher, even at a rather high density of water molecules inside the pore.


The influence of boundary conditions on the accuracy of diffusion theory in time-resolved reflectance spectroscopy of biological tissues.
The applicability of diffusion theory for the determination of tissue optical properties from time-resolved reflectance spectroscopy is investigated. Analytical expressions from diffusion theory using the three most commonly assumed boundary conditions at the air-tissue interface are compared with time-resolved Monte Carlo simulations and measurements on tissue phantoms. The effects of the choice of the boundary conditions on the accuracy of the findings for the optical parameters are quantified, and criteria for accurate curve-fitting algorithms are developed.


Pulmonary Paecilomyces in a Diabetic Patient.
Paecilomyces species are among the most frequent saprophytes. Two species namely Paecilomyces lilacinus and Paecilomyces variotii are the most frequently isolated species from humans. Fungemia, endocarditis peritonitis, osteomyelitis and rarely pneumonia have been reported. We report a 74-year old diabetic woman with Paecilomyces variotii pneumonia. Paecilomyces variotii is a rare cause of pneumonia and in our knowledge, our case is the first case of pleural effusion due to this fungus.


Drought-induced forest decline: causes, scope and implications.
A large number of episodes of forest mortality associated with drought and heat stress have been detected worldwide in recent decades, suggesting that some of the world's forested ecosystems may be already responding to climate change. Here, we summarize a special session titled 'Drought-induced forest decline: causes, scope and implications' within the 12th European Ecological Federation Congress, held in Ávila (Spain) from 25 to 29 September 2011. The session focused on the interacting causes and impacts of die-off episodes at the community and ecosystem levels, and highlighted recent events of drought- and heat-related tree decline, advances in understanding mechanisms and in predicting mortality events, and diverse consequences of forest decline. Talks and subsequent discussion noted a potentially important role of carbon that may be interrelated with plant hydraulics in the multi-faceted process leading to drought-induced mortality; a substantial and yet understudied capacity of many forests to cope with extreme climatic events; and the difficulty of separating climate effects from other anthropogenic changes currently shaping forest dynamics in many regions of the Earth. The need for standard protocols and multi-level monitoring programmes to track the spatio-temporal scope of forest decline globally was emphasized as critical for addressing this emerging environmental issue.


A glucagon-like endocrine pathway in Drosophila modulates both lipid and carbohydrate homeostasis.
The regulation of energy homeostasis is fundamental to all organisms. The Drosophila fat body serves as a repository for both triglycerides and glycogen, combining the energy storage functions of mammalian adipose and hepatic tissues, respectively. Here we show that mutation of the Drosophila adipokinetic hormone receptor (AKHR), a functional analog of the mammalian glucagon receptor, leads to abnormal accumulation of both lipid and carbohydrate. As a consequence of their obese phenotypes, AKHR mutants are markedly starvation resistant. We show that AKHR is expressed in the fat body, and, intriguingly, in a subset of gustatory neurons that mediate sweet taste. Genetic rescue experiments establish that the metabolic phenotypes arise exclusively from the fat body AKHR expression. Behavioral experiments demonstrate that AKHR mutants are neither sedentary nor hyperphagic, suggesting the metabolic abnormalities derive from a genetic propensity to retain energy stores. Taken together, our results indicate that a single endocrine pathway contributes to both lipid and carbohydrate catabolism in the Drosophila fat body.


Semi-supervised Machine Learning with MixMatch and Equivalence Classes.
Semi-supervised methods have an increasing impact on computer vision tasks to make use of scarce labels on large datasets, yet these approaches have not been well translated to medical imaging. Of particular interest, the MixMatch method achieves significant performance improvement over popular semi-supervised learning methods with scarce labels in the CIFAR-10 dataset. In a complementary approach, Nullspace Tuning on equivalence classes offers the potential to leverage multiple subject scans when the ground truth for the subject is unknown. This work is the first to (1) explore MixMatch with Nullspace Tuning in the context of medical imaging and (2) characterize the impacts of the methods with diminishing labels. We consider two distinct medical imaging domains: skin lesion diagnosis and lung cancer prediction. In both cases we evaluate models trained with diminishing labeled data using supervised, MixMatch, and Nullspace Tuning methods as well as MixMatch with Nullspace Tuning together. MixMatch with Nullspace Tuning together is able to achieve an AUC of 0.755 in lung cancer diagnosis with only 200 labeled subjects on the National Lung Screening Trial and a balanced multi-class accuracy of 77% with only 779 labeled examples on HAM10000. This performance is similar to that of the fully supervised methods when all labels are available. In advancing data driven methods in medical imaging, it is important to consider the use of current state-of-the-art semi-supervised learning methods from the greater machine learning community and their impact on the limitations of data acquisition and annotation.


Fine Mapping and Functional Analysis Reveal a Role of SLC22A1 in Acylcarnitine Transport.
Genome-wide association studies have identified a signal at the SLC22A1 locus for serum acylcarnitines, intermediate metabolites of mitochondrial oxidation whose plasma levels associate with metabolic diseases. Here, we refined the association signal, performed conditional analyses, and examined the linkage structure to find coding variants of SLC22A1 that mediate independent association signals at the locus. We also employed allele-specific expression analysis to find potential regulatory variants of SLC22A1 and demonstrated the effect of one variant on the splicing of SLC22A1. SLC22A1 encodes a hepatic plasma membrane transporter whose role in acylcarnitine physiology has not been described. By targeted metabolomics and isotope tracing experiments in loss- and gain-of-function cell and mouse models of Slc22a1, we uncovered a role of SLC22A1 in the efflux of acylcarnitines from the liver to the circulation. We further validated the impacts of human variants on SLC22A1-mediated acylcarnitine efflux in vitro, explaining their association with serum acylcarnitine levels. Our findings provide the detailed molecular mechanisms of the GWAS association for serum acylcarnitines at the SLC22A1 locus by functionally validating the impact of SLC22A1 and its variants on acylcarnitine transport.


Requirement of KISS1 secretion for multiple organ metastasis suppression and maintenance of tumor dormancy.
The KISS1 protein suppresses metastasis of several tumor models without blocking orthotopic tumor growth, but the mechanism remains elusive. For its role in human sexual maturation, KISS1 protein is secreted and processed to kisspeptins, which bind to the G protein-coupled receptor GPR54. We tested the hypothesis that KISS1 secretion is required for metastasis suppression via GPR54. KISS1 containing an internal FLAG epitope with (KFM) or without (KFMdeltaSS) a signal sequence was transfected into C8161.9 human melanoma cells, which do not express endogenous KISS1. Whole-cell lysates and conditioned medium from C8161.9(KFM) and C8161.9(KFMdeltaSS) cells were collected and analyzed for kisspeptins by immunoprecipitation and enzyme-linked immunosorbent assay. GPR54 levels were measured using real-time reverse transcription-polymerase chain reaction. The ability of conditioned medium from C8161.9(KFM) and C8161.9(KFMdeltaSS) cells to stimulate calcium mobilization in GPR54-expressing Chinese hamster ovary cells (CHO-G) and in C8161.9 cells was evaluated. Metastasis was monitored in athymic mice (groups of 10 per experiment) that were injected with C8161.9(KFM) or C8161.9(KFMdeltaSS) cells labeled with enhanced green fluorescent protein. Survival of mice injected with C8161.9 or C8161.9(KFM) cells was analyzed by Kaplan-Meier methods. Full-length KFM and KFMdeltaSS were detected in whole-cell lysates of C8161.9(KFM) and C8161.9(KFMdeltaSS) cells, respectively, but kisspeptins were detected only in conditioned medium of C8161.9(KFM) cells. In vivo, C8161.9(KFM), but not C8161.9(KFMdeltaSS), cells were suppressed for metastasis to lung, eye, kidney, and bone, with corresponding differences in mouse survival (median > 120 versus 42 days). C8161.9(KFM) cells seeded mouse lungs but did not form macroscopic metastases. Conditioned medium from C8161.9(KFM), but not C8161.9(KFMdeltaSS), cells stimulated calcium mobilization in CHO-G cells. GPR54 expression was low in C8161.9 cells, which were not stimulated by conditioned medium from C8161.9(KFM) cells. KISS1 secretion was required for multiple organ metastasis suppression and for maintenance of disseminated cells in a dormant state. The absence of GPR54 expression in C8161.9 cells (whose metastatic spread was suppressed by KFM) suggests that metastasis suppression is not mediated through this receptor. The results imply the existence of another KISS1 receptor and/or paracrine signaling. The findings raise the possibility that soluble KISS1, kisspeptins, or mimetics could be used to maintain tumor dormancy, rendering treatment of already disseminated tumor cells (i.e., micrometastases) a legitimate target.


[Characterization of the kinase activity of bovine adrenal pyruvate dehydrogenase complex].
In the presence of [gamma-32P]ATP the bovine adrenal pyruvate dehydrogenase complex accepts the label simultaneously and becomes inactivated. This suggests the existence of kinase in the composition of the complex as is typical of the complexes from other animal sources. The Pi is incorporated into the subunit with molecular weight of 42 000. The kinase activity of the adrenal pyruvate dehydrogenase complex is high: within the first 20 sec of incubation with ATP the inactivation is as high as 60%. The pH optimum for kinase is around 7.3. The apparent Km value for ATP with 50 mM KCl is 7 microM; that in the absence of KCl is 10 microM. ADP is a competitive inhibitor of kinase with respect to ATP (Ki = 100 microM), when K+ are present in the medium. Thiamine pyrophosphate and pyruvate decrease the rate of pyruvate dehydrogenase complex inactivation.


Medicine use from birth to age two years: the 2004 Pelotas (Brazil) Birth Cohort study.
To describe medicine use by children at three, 12 and 24 months of age. Cross-sectional study using data from the 2004 Pelotas Birth Cohort (Southern Brazil), including: 3,985 children at three months, 3,907 children at 12 months, and 3,868 children at 24 months of age. The outcome investigated was use of medicine in the 15 days preceding the interview. Information on independent variables (medicine used, who indicated it, how it was obtained, periodicity of use, and therapeutic group) were collected using a standardized questionnaire administered during a home interview with the child's parents. Prevalence of medicine use at three, 12, and 24 months was 65.0% (95% CI: 63.5;66.5), 64.4% (95% CI: 62.9;65.9), and 54.7% (95% CI: 53.1;56.2), respectively. As age increased, there was a reduction in the total number of medicines used and an increase in self-medicine, which reached 34% at 24 months. Furthermore, frequency of sporadic medicine use increased, while that of continuous use decreased. Medicine was purchased mainly using private resources, with roughly 10% of drugs being purchased through the Brazilian National Health Care System. The profile of medicine types used also changed with age. The type of medicine most frequently used were dermatological products (36%) at three months; respiratory system drugs (24%) at 12 months; and analgesics (26%) at 24 months of age. Compared to three months, medicine use at 24 months was characterized by decreased use of digestive tract and metabolism drugs, drugs for the sensory organs, cardiovascular system drugs, and dermatological products, and an increase in systemic anti-infectious drugs, medicine for the skeletomuscular and respiratory systems, analgesics, insecticides, and repellents. Medicine use in this cohort was high and indicates the need for prioritizing rational use of medicine in early life.


Challenges to medications development in treating alcohol dependence: an international perspective.
Few medications for treating alcohol dependence exist. Greater partnership is needed between academia and the pharmaceutical industry to develop, licence and market efficacious medications for treating alcohol dependence. Methodologies that span the divide between preclinical and large-scale clinical studies need to be developed in order to provide sufficient information on safety, toleration, drug-interaction profile and efficacy, with which to guide development decisions. Due to the heterogeneous nature of alcohol dependence, the effort of developing an efficacious medication is likely to be enhanced by clearer choices about the characteristics of the population. Careful consideration of potential mechanism of action of the putative therapeutic medication should enable the appropriate choice of drinking endpoint. The pharmaceutical industry in collaboration with academia might need to develop new approaches to determining appropriate treatment endpoints with regulatory bodies. The investment risk to industry should be appraised not only in terms of the rather poor results of previous marketing efforts but with a view to the opportunity to penetrate a potentially enormous and largely untapped market.


Long-Lived, Transferred Crystalline Silicon Carbide Nanomembranes for Implantable Flexible Electronics.
Implantable electronics are of great interest owing to their capability for real-time and continuous recording of cellular-electrical activity. Nevertheless, as such systems involve direct interfaces with surrounding biofluidic environments, maintaining their long-term sustainable operation, without leakage currents or corrosion, is a daunting challenge. Herein, we present a thin, flexible semiconducting material system that offers attractive attributes in this context. The material consists of crystalline cubic silicon carbide nanomembranes grown on silicon wafers, released and then physically transferred to a final device substrate (e.g., polyimide). The experimental results demonstrate that SiC nanomembranes with thicknesses of 230 nm do not experience the hydrolysis process (i.e., the etching rate is 0 nm/day at 96 °C in phosphate-buffered saline (PBS)). There is no observable water permeability for at least 60 days in PBS at 96 °C and non-Na+ ion diffusion detected at a thickness of 50 nm after being soaked in 1× PBS for 12 days. These properties enable Faradaic interfaces between active electronics and biological tissues, as well as multimodal sensing of temperature, strain, and other properties without the need for additional encapsulating layers. These findings create important opportunities for use of flexible, wide band gap materials as essential components of long-lived neurological and cardiac electrophysiological device interfaces.


Improving Stem Cell Delivery to the Trabecular Meshwork Using Magnetic Nanoparticles.
Glaucoma is a major cause of blindness and is frequently associated with elevated intraocular pressure. The trabecular meshwork (TM), the tissue that primarily regulates intraocular pressure, is known to have reduced cellularity in glaucoma. Thus, stem cells, if properly delivered to the TM, may offer a novel therapeutic option for intraocular pressure control in glaucoma patients. For this purpose, targeted delivery of stem cells to the TM is desired. Here, we used magnetic nanoparticles (Prussian blue nanocubes [PBNCs]) to label mesenchymal stem cells and to magnetically steer them to the TM following injection into the eye's anterior chamber. PBNC-labeled stem cells showed increased delivery to the TM vs. unlabeled cells after only 15-minute exposure to a magnetic field. Further, PBNC-labeled mesenchymal stem cells could be delivered to the entire circumference of the TM, which was not possible without magnetic steering. PBNCs did not affect mesenchymal stem cell viability or multipotency. We conclude that this labeling approach allows for targeted, relatively high-efficiency delivery of stem cells to the TM in clinically translatable time-scales, which are necessary steps towards regenerative medicine therapies for control of ocular hypertension in glaucoma patients.


Phase Angle as a Reliable Biomarker of Frailty to Predict Postoperative Outcomes in Patients Undergoing Off-Pump Coronary Artery Grafting: A Prospective Observational Study.
To elucidate the association between phase angle (PA) and a composite adverse outcome in patients requiring off-pump coronary artery bypass grafting (OPCAB). A prospective observational study. High-volume single center. A total of 229 adult patients who underwent OPCAB from May 2019 to October 2020. Each patient underwent bioelectrical impedance analysis, including PA assessment before surgery (PApre), immediately postoperatively (PApost), and 1 day postoperatively (PAPOD1), using an Inbody S10. Frailty index and nutritional assessments also were obtained before surgery. Patient outcomes were assessed using a composite adverse outcome comprising death, myocardial infarction, revascularization, new-onset atrial fibrillation, acute kidney injury, stroke, postoperative pulmonary complications, wound complications, sepsis, reoperation, and/or delirium occurring during hospitalization and over the following year. Patients for whom composite adverse outcomes were reported had lower PApre than those without complications (5.4 ± 0.9 v 6.0 ± 0.9, p < 0.001). The PA was significantly associated with in-hospital and 1-year composite postoperative outcomes. The odds ratios (OR, [95% confidence interval]) for PApre by time were in-hospital complications (0.435 [0.314, 0.604], p < 0.001; 1-year complications: 0.459 [0.330, 0.638], p < 0.001) and PAPOD1 (OR, in-hospital complications: 0.400 [0.277, 0.576], 1-year complications: 0.429 [0.298, 0.619], p < 0.001). The PApre was significantly associated with days alive and out of hospital until 1 year. The cut-off value of PApre for optimal prediction of in-hospital complications was 6.0 (area under the curve: 0.691 [0.623-0.758], p < 0.001). Low PA as an indicator of frailty is associated with adverse postoperative outcomes after OPCAB. Low PA may be employed as a noninvasive and practical tool for the prediction of prognosis in patients with coronary artery disease.


Immunological Aspects Involved in the Degeneration of Cryopreserved Arterial Allografts.
Introduction: Cryopreserved arterial allografts have remained an option in patients requiring distal revascularization or associated with vascular infection, in the absence of a valid autogenous saphenous vein. The objective of this study is to describe the different clinical, anatomopathological, and immunological findings related to vascular transplant rejection. Methods: In a prospective trial, 35 patients who underwent cryopreserved allogeneic arterial bypass were studied, including demographics and conduit patency. Anti-HLA antibody production was stablished prior to the surgery, 7 days, 1, 3 months, and every 3 months since. Clinical and ultrasound evaluation was added after the first month. Donor HLA-typing was retrieved whenever available, allowing for the characterization and quantification of donor specific antibodies. Cytotoxic crossmatch test was also performed. A second group of patients with allograft degenerations registered during the follow up period was studied. In this group, exclusively for aneurysm description and histopathological analysis, they were included those degenerated vascular transplants from the original series, but also those implanted prior to the beginning of the study and degraded during follow up. Results: All patients studied displayed an increase in anti-HLA antibodies one month after the intervention, regarding bypass patency. In total, 14 patients fulfilled requirements for the study of donor specific antibodies, equally showing IgG production detectable one month after surgery. The presence of complement-fixing antibodies was also confirmed. Antibody levels were not related to graft degeneration. No specific immune markers able to predict aneurysmal development and evolution were found. From the original group, 3 patients suffered aneurysmal degeneration during follow up, together with 9 bypasses previously implanted. Average time until the first degeneration was 33 ± 19.7 months, with 30.6 ± 17.7 and 54.5 ± 2.5 months for a second and third degeneration, when occurring. Therefore, subsequent vascular transplants frequently augmented the time for new degenerations, despite increasing sensibilization. Samples from eight degenerated allografts were available for analysis, unexpectedly showing inflammatory infiltrate in only four cases and immune complex deposition in 7. Conclusions: Immune response against vascular transplants was confirmed in all cases, but chronic rejection did not necessarily provoke bypass degradation or reduced the time for new aneurysms to develop in subsequent allografts.


Expression of mutant telomerase in immortal telomerase-negative human cells results in cell cycle deregulation, nuclear and chromosomal abnormalities and rapid loss of viability.
We have reconstituted wild type or mutant telomerase activity in two human cell lines that lack constitutive expression of both core subunits of the enzyme and maintain telomeres by a telomerase-independent mechanism (ALT cells). Wild type telomerase RNA and four telomerase RNAs with single point mutations in their template domain were used to express enzymes specifying different telomeric DNA sequences. Expression of wild type telomerase for up to 32 days had no detectable effect on cell growth or viability. In contrast, cells expressing mutant telomerases had slower growth rate, abnormal cell cycle and reduced viability. Dramatically aberrant nuclei, typical of cells undergoing mitotic catastrophe, and large numbers of fused chromosomes were also characteristic of these populations. Notably, all phenotypes were apparent within the first few cell divisions after expression of the enzymes. Unlike wild type, mutant telomerase activity was progressively selected against with cell culturing, and this correlated with the disappearance of cells with aberrant phenotypes. Our results suggest that even very limited synthesis of mutated sequences can affect telomere structure in human cells, and that the toxicity of mutant telomerases is due to telomere malfunction.


A case of isolated ACTH deficiency who developed autoimmune-mediated hypothyroidism and impaired water diuresis during glucocorticoid replacement therapy.
A case of isolated ACTH deficiency who developed autoimmune-mediated hypothyroidism and still showed impaired water diuresis during glucocorticoid replacement therapy is reported. A 45-year-old woman was initially admitted for nausea, vomiting, and general malaise. Her serum sodium and plasma osmolality, ACTH and cortisol values were low, but her urine osmolality was high. Other pituitary hormone levels, thyroid hormone levels, and a computed tomogram of the pituitary gland were normal. The patient was treated with hydrocortisone and followed in the outpatient clinic; however, she was lost to follow up 18 months after admission. Three years later she presented with hypoglycemia and hyponatremia. Her serum or plasma ACTH, FT3, FT4, cortisol levels were low and her serum TSH level was high. Pituitary stimulation tests revealed a blunted response of ACTH to CRH and an exaggerated response of TSH to TRH. Plasma ADH was inappropriately high, and a water-loading test revealed impaired water diuresis and poor suppression of ADH. Although ADH was suppressed, impaired water diuresis was observed in the water loading test after hydrocortisone supplementation. Thyroxine supplementation completely normalized the water diuresis. Her outpatient clinic medical records revealed a gradual increase in TSH levels during follow up, indicating that she had developed hypothyroidism during glucocorticoid replacement therapy. The hyponatremia on the first admission was due to glucocorticoid deficiency, whereas the hyponatremia on the second admission was due to combined deficiencies of glucocorticoid and thyroid hormones.


Intense THz source based on BNA organic crystal pumped at Ti:sapphire wavelength.
We report on high-energy terahertz pulses by optical rectification (OR) in the organic crystal N-benzyl-2-methyl-4-nitroaniline (BNA) directly pumped by a conventional Ti:sapphire amplifier. The simple scheme provides an optical-to-terahertz conversion efficiency of 0.25% when pumped by collimated laser pulses with a duration of 50 fs and a central wavelength of 800 nm. The generated radiation spans frequencies between 0.2 and 3 THz. We measured the damage threshold, as well as the dependency of the conversion efficiency on the pump fluence, pump wavelength, and pulse duration.


FMLP-induced enzyme release from neutrophils: a role for intracellular calcium.
The ability of the chemotactic peptide N-formylmethionyl-leucyl-phenylalanine (FMLP) to stimulate beta-glucuronidase release and 45Ca2+ release from rabbit neutrophils was studied. FMLP stimulated enzyme release from cytochalasin B-treated cells either in the presence or the absence of extracellular calcium. Depletion of cell calcium, by exposure to either ethyleneglycol-bis(beta-aminoethylether)-N,N'-tetraacetic acid or the calcium ionophore A23187, blocked the ability of FMLP to stimulate enzyme release and 45Ca2+ release in the absence of extracellular calcium. The ability of A23187 to lower the 45Ca2+ content of neutrophils, to block FMLP-stimulated 45Ca2+ release, and to inhibit FMLP-stimulated enzyme release in the absence of calcium was dose dependent over the same concentration range (10(-8) to 10(-6) M A23187) for all three actions. In contrast, FMLP stimulated enzyme release from A23187-treated cells, provided that extracellular calcium was present. This secretory response was normal as judged by cell ultrastructure and FMLP dose-response relationships. It is concluded that A23187 depletes a pool of intracellular calcium usually released by FMLP and that release of calcium from this pool is necessary for initiation of enzyme secretion in the absence of extracellular calcium.


Benign sinonasal masses: a clinicopathological and radiological profile.
Benign nasal and paranasal sinus masses are commonly encountered in clinical practice. Though benign, certain nasal polyps, fungal sinusitis, hemangiomas and fibro-osseous tumors can present with locally destructive features and deformities, mimicking malignancies at once. This study was carried out to recognize the great variety of benign nasal lesions and their frequency in our region. A retrospective chart analysis of cases presenting as mass in nose and paranasal sinus that underwent surgery over three years duration at our institute was done. A provisional diagnosis was made after clinical assessment and radiological investigations, but the final diagnosis was established after histopathological examination. A total 331 cases presented as masses in nose and paranasal sinus presented during the period. The clinicopathological examination aided by endoscopic and imaging studies revealed the non neoplastic benign masses in 293 and neoplastic masses in 38. Polyps were the commonest lesions constituting 70% cases followed by rhinosporidiosis in 10%. Fungal sinusitis, squamous papillomas, hemangiomas and inverted papillomas were found to be in order of 4.5%, 4%, 3.5% and 3% respectively. Rare cases like "rhinooto- cereberal" form of mucormycosis, angiomyoma, and psammomatoid ossifying fibroma were also observed in the study. Most of the nasal polyps/fungal sinusitis can be diagnosed clinically. However many a times Computer tomography (CT) scan and biopsy are necessary to differentiate them from each other and treatment plan. Certain benign tumors have high potential for malignant transformation while others can present with locally destructive features and deformities.


Effect of different doses of chlorthalidone on blood pressure, serum potassium, and serum urate.
Chlorthalidone given to 40 hypertensive women significantly decreased blood pressure and serum potassium levels and increased the serum urate concentration. There were no individual correlations between the reduction in blood pressure and the decrease in serum potassium or the increase in serum urate. A reduction in dosage from 50 mg daily to 50 mg three times a week produced no significant changes in the diastolic or mean blood pressures though the systolic blood pressure was moderately increased. Concomitantly, serum potassium increased and serum urate decreased significantly on the lower chlorthalidone dose. We conclude that high doses of oral diuretics compared with lower ones are of limited further benefit and may increase the risk of clinically significant hypokalaemia and hyperuricaemia.


[Pharma-clinics. How I treat ... periungual warts].
Warts are common benign lesions for which no specific antiviral treatment is available. In some cases, patients and doctors can be put off by poor results. Before selecting any treatment for peri- and subungual warts, it is of utmost importance to bear in mind the risk of damaging the nail matrix. This paper reviews the advantages and inconveniences of the current available treatments in this location.


Presence of key findings in the medical record prior to a documented high-risk diagnosis.
Failure or delay in diagnosis is a common preventable source of error. The authors sought to determine the frequency with which high-information clinical findings (HIFs) suggestive of a high-risk diagnosis (HRD) appear in the medical record before HRD documentation. A knowledge base from a diagnostic decision support system was used to identify HIFs for selected HRDs: lumbar disc disease, myocardial infarction, appendicitis, and colon, breast, lung, ovarian and bladder carcinomas. Two physicians reviewed at least 20 patient records retrieved from a research patient data registry for each of these eight HRDs and for age- and gender-compatible controls. Records were searched for HIFs in visit notes that were created before the HRD was established in the electronic record and in general medical visit notes for controls. 25% of records reviewed (61/243) contained HIFs in notes before the HRD was established. The mean duration between HIFs first occurring in the record and time of diagnosis ranged from 19 days for breast cancer to 2 years for bladder cancer. In three of the eight HRDs, HIFs were much less likely in control patients without the HRD. In many records of patients with an HRD, HIFs were present before the HRD was established. Reasons for delay include non-compliance with recommended follow-up, unusual presentation of a disease, and system errors (eg, lack of laboratory follow-up). The presence of HIFs in clinical records suggests a potential role for the integration of diagnostic decision support into the clinical workflow to provide reminder alerts to improve the diagnostic focus.


Postural balance and functional independence of elderly people according to gender and age: cross-sectional study.
Aging causes changes in men and women. Studies have shown that women have worse postural balance and greater functional dependence than men, but there is no consensus regarding this. The aim of this study was to compare the balance and functional independence of elderly people according to sex and age, and to evaluate the association between postural balance and the number of drugs taken. Cross-sectional at a state university. 202 elderly people were evaluated regarding balance (Berg Scale), independence (Barthel Index), age, sex, number of medications and physical activity. The subjects comprised 117 women (70.2 ± 5.6 years old) and 85 men (71.1 ± 6.9 years old). For balance, there was no significant difference regarding sex, but there was a difference regarding age (P < 0.0001). For functional independence, there was a difference regarding sex (P = 0.003), but not regarding age. The variables of age, medications and physical activity were significant for predicting the Berg score. For the Barthel index, only age and sex were significant. Elderly people who took three or more medications/day showed higher risk of falling than those who took up two drugs/day (odds ratio = 5.53, P < 0.0001, 95% confidence interval, 2.3-13.0). There was no sexual difference in relation to postural balance. However, people who were more elderly presented a high risk of falling. Functional dependence was worse among females. There was an association between the number of medication drugs and risk of falling.


A role for NF-kappa B binding motifs in the differential induction of chemokine gene expression in human corneal epithelial cells.
The interleukin (IL)-8 promoter possesses a NF-kappa B-binding site with affinity to p50p65 and p65p65 complexes while the monocyte chemoattractant protein (MCP)-1 promoter's NF-kappa B-binding site has exclusive affinity to p50p65 heterodimers. The purpose of this study was to determine whether the two NF-kappa B sites play a role in the capacity of tumor necrosis factor (TNF)-alpha-stimulated human corneal epithelial cells (HCECs) to produce nanogram amounts of IL-8 in the absence of MCP-1 synthesis. IL-8 and MCP-1 promoters were cloned into luciferase reporter vectors. Site-directed mutagenesis of wild-type promoters was used to mutate the NF-kappa B-binding motif in the wild-type IL-8 reporter plasmid into a motif with exclusive affinity to p50p65 and to mutate the NF-kappa B binding motif in the wild-type MCP-1 reporter plasmid into a motif with affinity to p65p65. Luciferase activity was determined after transfection of reporter vector constructs into TNF-alpha-stimulated HCECs. The chromatin immunoprecipitation assay was used to confirm binding of NF-kappa B subunits to IL-8 and MCP-1 promoters in vivo. Promoters with affinity to p65p65 homodimers were active in driving the expression of the reporter gene, whereas promoters with affinity to p50p65 heterodimers did not induce significant reporter gene expression. Incorporation of a CCAAT enhancer-binding protein (C/EBP)-binding site immediately upstream of p65p65-binding sites significantly enhanced promoter activity. The results suggest that the interaction of p65p65 homodimers and C/EBP transcriptional factors with IL-8 promoters and not MCP-1 promoters account for the capacity of HCECs to produce IL-8 selectively, in the absence of MCP-1 production.


Park Access Among School-Age Youth in the United States.
Fewer than 30% of U.S. youth meet the recommendation to be active ≥ 60 minutes/day. Access to parks may encourage higher levels of physical activity. To examine differences in park access among U.S. school-age youth, by demographic characteristics and urbanicity of block group. Park data from 2012 were obtained from TomTom, Incorporated. Population data were obtained from the 2010 U.S. Census and American Community Survey 2006-2010. Using a park access score for each block group based on the number of national, state or local parks within one-half mile, we examined park access among youth by majority race/ethnicity, median household income, median education, and urbanicity of block groups. Overall, 61.3% of school-age youth had park access--64.3% in urban, 36.5% in large rural, 37.8% in small rural, and 35.8% in isolated block groups. Park access was higher among youth in block groups with higher median household income and higher median education. Urban youth are more likely to have park access. However, park access also varies by race/ethnicity, median education, and median household. Considering both the demographics and urbanicity may lead to better characterization of park access and its association with physical activity among youth.


FRET monitoring of a nonribosomal peptide synthetase.
Nonribosomal peptide synthetases (NRPSs) are multidomain enzyme templates for the synthesis of bioactive peptides. Large-scale conformational changes during peptide assembly are obvious from crystal structures, yet their dynamics and coupling to catalysis are poorly understood. We have designed an NRPS FRET sensor to monitor, in solution and in real time, the adoption of the productive transfer conformation between phenylalanine-binding adenylation (A) and peptidyl-carrier-protein domains of gramicidin synthetase I from Aneurinibacillus migulanus. The presence of ligands, substrates or intermediates induced a distinct fluorescence resonance energy transfer (FRET) readout, which was pinpointed to the population of specific conformations or, in two cases, mixtures of conformations. A pyrophosphate switch and lysine charge sensors control the domain alternation of the A domain. The phenylalanine-thioester and phenylalanine-AMP products constitute a mechanism of product inhibition and release that is involved in ordered assembly-line peptide biosynthesis. Our results represent insights from solution measurements into the conformational dynamics of the catalytic cycle of NRPSs.


The relation between personal relative deprivation and the urge to gamble among gamblers is moderated by problem gambling severity: a meta-analysis.
One psychosocial factor that has been identified to motivate gambling is personal relative deprivation (PRD), which refers to resentment stemming from the belief that one is deprived of a desired and deserved outcome compared to some referent. Although several lines of evidence point to a positive association between PRD and the urge to gamble, the factors that might moderate this relation have yet to be investigated. Through a quantitative research synthesis, we sought to test (a) the overall relation between PRD and gambling urges among people reporting recent gambling experience, and (b) whether this relation is moderated by problem gambling severity. Meta-analysis revealed that, overall, higher self-reported PRD was associated with stronger urges to gamble (r=.26). A meta-regression revealed that, across studies, the strength of this relation depended on problem gambling severity, such that the relation between PRD and gambling urges was stronger among samples higher in average problem gambling severity. This pattern was corroborated by an analysis of the aggregated individual participant data (N=857), such that PRD predicted gambling urges only among participants higher in problem gambling severity. The potential practical implications and limitations of these results are discussed.


Treatment utilization and unmet treatment need among Hispanics following brief intervention.
In a large randomized trial examining ethnic differences in response to a brief alcohol intervention following an alcohol-related injury, we showed that Hispanics, but not non-Hispanics, were more likely to reduce alcohol intake in comparison with treatment as usual (Addiction 105:62, 2010). The current study evaluates whether the observed improvements in drinking outcomes previously reported among Hispanics following brief intervention might be related to prior or subsequent treatment utilization. This study is a secondary analysis of data collected in a randomized clinical trial that evaluated ethnic differences in the effect of a brief motivational intervention (BMI) on alcohol use among medical inpatients admitted for alcohol-related injury. For this study, statistical analyses were carried out to compare alcohol use, alcohol problems, treatment utilization, and unmet treatment need between Hispanic (n = 537) and non-Hispanic White (n = 668) inpatients. In addition, we examined the relationship between prior treatment utilization and unmet treatment need and alcohol use outcomes following brief intervention and the impact of brief intervention on subsequent treatment utilization and unmet treatment need. In comparison with non-Hispanic Whites, Hispanics at baseline reported heavier drinking, more alcohol problems, greater unmet treatment need, and lower rates of treatment utilization. Among Hispanics, multilevel analyses showed that prior treatment utilization or unmet treatment need did not moderate the effect of BMI on alcohol outcomes. Furthermore, BMI did not significantly impact subsequent treatment utilization or unmet treatment need among Hispanics. Finally, treatment utilization and unmet treatment need at 6 months were not significant mediators between BMI and alcohol use outcomes at follow-up. The benefits of brief intervention among Hispanics do not appear to be better explained by subsequent engagement in mutual help groups or formal substance abuse treatment. Prior history of treatment, regardless of the severity of alcohol problems, does not appear to influence the impact of brief intervention on alcohol use among Hispanics. These findings support prior results reporting the benefits of brief intervention among Hispanics and demonstrate that these improvements are not related to prior or subsequent treatment utilization.


A Scoping Review of the Maternal Role at Older Age; Perceptions and Occupations.
Motherhood is a meaningful life role among adult women. Occupations within the maternal role of younger mothers have been well documented, but less is known regarding the maternal-role at older age. This review aimed to describe the occupations, activities, and perceptions that older women ascribe to their maternal role. In the future, this information may promote health and wellbeing of older women. A systematic search of peer reviewed articles, that included healthy, community-dwelling mothers, 60 years of age or older, was conducted. Maternal-role occupations and perceptions of older mothers were identified and classified according to the Occupational Therapy Practice Framework (OTPF). Fourteen articles, representing 3102 older mothers, were included. The identified occupations and activities within the maternal role were from two categories: Instrumental Activities of Daily Living (IADL) (such as assistance with daily chores) and social participation (such as sharing holiday rituals). Three themes reflecting maternal-role perceptions were identified: providing support; relationship with children; and motherhood as a never-ending role. Maternal occupations were identified in only a few articles and from only two categories, IADL and social participation. These findings together with the perception that motherhood is a 'never-ending' role suggests that further research is needed to better characterize the maternal role of older women from an occupational perspective.


Chromosomal loci influencing chronic alcohol withdrawal severity.
Ethanol (alcohol) withdrawal-induced convulsions are a key index of physical dependence on ethanol and a clinically important consequence of alcohol abuse in humans. In rodent models, severity of withdrawal is strongly influenced by genotype. For example, many studies have reported marked differences in withdrawal severity between the WSR (Withdrawal Seizure Resistant) and WSP (Withdrawal Seizure Prone) mouse strains selectively bred for over 25 generations to differ in chronic withdrawal severity. Therefore, we used an F(2) intercross between the inbred WSP and WSR strains for a genome-wide search for quantitative trait loci (QTLs), which are chromosomal sites containing genes influencing the magnitude of withdrawal. We also used the recently developed HW, RHW (high withdrawal) and LW, RLW (low withdrawal) lines selectively bred for the same trait and in the same manner as the WSP, WSR lines. QTL analysis was then used to dissect the continuous trait distribution of withdrawal severity into component loci, and to map them to broad chromosomal regions by using the Pseudomarker 0.9 and Map Manager QT29b programs. This genome-wide search identified five significant QTLs influencing chronic withdrawal severity on Chromosomes (Chrs) 1 (proximal), 4 (mid), 8 (mid), 11 (proximal), and 14 (mid), plus significant interactions (epistasis) between loci on Chr 11 with 13, 4 with 8, and 8 with 14.


Nigrostriatal Dopaminergic Dysfunction and Altered Functional Connectivity in REM Sleep Behavior Disorder With Mild Motor Impairment.
Rapid eye movement sleep behavior disorder is parasomnia characterized by symptoms of dream enactment and loss of muscle atonia during rapid eye movement sleep. Mild motor impairment is present in some patients with rapid eye movement sleep behavior disorder and presumed to be a risk factor for conversion to synucleinopathies. The purpose of this study is to identify patients with mild motor impairment by evaluating finger tapping and to investigate its pathophysiology. Twenty-three patients with rapid eye movement sleep behavior disorder and 20 healthy control subjects were recruited in the present study. We accurately evaluated finger tapping including amplitude, peak open, and close speed with a magnetic sensing device and identified patients with mild motor impairment. Moreover, we performed 123I-2β-carbomethoxy-3β-(4-iodophenyl) nortropane SPECT and resting state functional MRI. 123I-2β-carbomethoxy-3β-(4-iodophenyl) nortropane uptake for each bilateral caudate, anterior putamen, and posterior putamen was calculated and the resting state functional connectivity of sensorimotor network was analyzed. Using finger tapping parameters, we identified eight patients with mild motor impairment. In patients with mild motor impairment, all finger tapping parameters were significantly impaired when compared to patients with normal motor function, while they exhibited no significant differences in Unified Parkinson's Disease Rating Scale part III score. 123I-2β-carbomethoxy-3β-(4-iodophenyl) nortropane uptake in the right posterior putamen, bilateral anterior putamen, and caudate was significantly lower when compared to healthy controls or patients with rapid eye movement sleep behavior disorder with normal motor function. These patients also exhibited decreased cortico-striatal functional connectivity and increased cortico-cerebellar functional connectivity when compared to healthy controls or patients with normal motor function. Our results show that mild motor impairment in rapid eye movement sleep behavior disorder evaluated by finger tapping task presented mild nigrostriatal dopaminergic dysfunction as well as alterations in resting state sensorimotor network. Although longitudinal follow up is necessary, such patients may have higher risk of short-term conversion to synucleinopathies.


Distribution and related factors of corneal regularity and posterior corneal astigmatism in cataract patients.
To study the distribution of posterior corneal astigmatism (PCA) and its influencing factors in Chinese patients before cataract surgery. A retrospective study was conducted in the First Affiliated Hospital of Soochow University, Suzhou, China. In all, this study enrolled 121 eligible eyes of 121 cataract patients. The astigmatism, aberrations and Q value of anterior, posterior and total cornea and anterior segment parameters (ACD, CCT, WTW, ATA) were measured by the Sirius System, and AL was measured by Lenstar LS 900. Cataract was diagnosed using slit-lamp examination. The mean age of patients was 67.44±10.66 years old. Mean PCA was 0.31±0.17 (range 0.05-1.09) D and 85.9% eyes had PCA values <0.5 D. With-the-rule (WTR) astigmatism predominated the anterior cornea astigmatism (ACA) (48.8%) and total corneal astigmatism (TCA) (61.2%), while against-the-rule (ATR) astigmatism predominated posterior (86.0%). Significant positive correlation was found between the astigmatic power vector (APV) of ACA and PCA (Pearson correlation=0.318, P<0.001); TCA and PCA (Pearson correlation=0.204, P=0.025); keratometric astigmatism and PCA (Pearson correlation=0.356, P<0.001); this study also found a positive correlation between primary spherical aberration (Z4°) of the total cornea and PCA (Pearson correlation=0.266, P=0.003); primary spherical aberration (Z4°) of the corneal front surface and PCA (Pearson correlation=0.260, P=0.004); total corneal aberrations (Total cornea root mean square [RMS]) and PCA (Pearson correlation=0.327, P<0.001); total corneal higher-order aberrations (Total HOA RMS) (Pearson correlation=0.232, P=0.011); total corneal lower-order aberrations (Total LOA RMS) (Pearson correlation=0.250, P=0.006). A positive linear correlation between Q value of corneal front surface and PCA, either 6 mm pupil diameter (Pearson correlation=0.264, P=0.003) or 8 mm pupil diameter (Pearson correlation=0.184, P=0.043) was found in this study. Corneal aberration, Q value (front surface specifically) was essential that we need to take into consideration when we conduct PCA and intraocular lens measurement in clinics.


Seeing yourself helps you see others.
It has been proposed that self-face representations are involved in interpreting facial emotions of others. We experimentally primed participants' self-face representations. In Study 1, we assessed eye tracking patterns and performance on a facial emotion discrimination task, and in Study 2, we assessed emotion ratings between self and nonself groups. Results show that experimental priming of self-face representations increases visual exploration of faces, facilitates the speed of facial expression processing, and increases the emotional distance between expressions. These findings suggest that the ability to interpret facial expressions of others is intimately associated with the representations we have of our own faces.


Serum vitamin D, parathyroid hormone levels, and carotid atherosclerosis.
Evidence suggests low vitamin D and elevated parathyroid hormone (PTH) concentrations may increase risk for cardiovascular disease. However, little is known about the association between vitamin D or PTH and subclinical atherosclerosis. This cross-sectional study included 654 community-dwelling older adults aged 55-96 years (mean age, 75.5 years) without a history of coronary heart disease, revascularization, or stroke enrolled in the Rancho Bernardo Study who completed a clinic examination in 1997-1999 and provided a blood sample for determination of serum 25-hydroxyvitamin D [25(OH)D], 1,25-dihydroxyvitamin D [1,25(OH)(2)D], and PTH concentrations. Carotid artery intima-media wall thickness (IMT) was measured as an indicator of atherosclerosis at two sites with B-mode ultrasound. After adjusting for age, sex, smoking, alcohol intake, waist-to-hip ratio, exercise, season of blood draw, diabetes, and hypertension, geometric mean internal carotid IMT (p(trend) 0.022), but not common carotid IMT (p(trend) 0.834) decreased in a dose-dependent fashion with increasing concentration of 25(OH)D. There was no association of 1,25(OH)(2)D or PTH with either measure of carotid IMT. In subgroup analyses, 1,25(OH)(2)D was inversely associated with internal carotid IMT among those with hypertension (p for interaction 0.036). These findings from a population-based cohort of older adults suggest a potential role for vitamin D in the development of subclinical atherosclerosis. Additional research is needed to determine whether vitamin D may influence the progression of atherosclerosis, including the effects of supplementation on the atherosclerotic process.


Design of high-temperature f-block molecular nanomagnets through the control of vibration-induced spin relaxation.
One of the main roadblocks that still hamper the practical use of molecular nanomagnets is their cryogenic working temperature. In the pursuit of rational strategies to design new molecular nanomagnets with increasing blocking temperature, ab initio methodologies play an important role by guiding synthetic efforts at the lab stage. Nevertheless, when evaluating vibration-induced spin relaxation, these methodologies are still far from being computationally fast enough to provide a useful predictive framework. Herein, we present an inexpensive first-principles method devoted to evaluating vibration-induced spin relaxation in molecular f-block single-ion magnets, with the important advantage of requiring only one CASSCF calculation. The method is illustrated using two case studies based on uranium as the magnetic centre. Finally, we propose chemical modifications in the ligand environment with the aim of suppressing spin relaxation.


Uncertainty and anxiety during the diagnostic period for women with suspected breast cancer.
A possible diagnosis of breast cancer imposes a huge psychological impact on most women, but few studies have addressed uncertainty and anxiety changes at different diagnostic stages in women with suspected breast cancer. Thus, this longitudinal study examined uncertainty and anxiety and predictive factors for uncertainty in women with suspected breast cancer. Data were collected on uncertainty (Uncertainty in Illness Scale) and anxiety (State Anxiety Inventory) from 127 women at 3 times: upon notice of a breast biopsy, before biopsy, and after diagnosis. The results showed that uncertainty and anxiety levels were significantly higher before than after diagnosis. At the 3 data collection times, uncertainty and anxiety were significantly lower for participants diagnosed with benign tumors than for those with malignant diagnoses. Uncertainty and anxiety were positively, moderately correlated. Uncertainty was predicted by age, marital status, education level, religious status, family history of benign breast tumor, regular breast self-examination, self-perceived probability of receiving a breast cancer diagnosis, and biopsy result. Therefore, nursing professionals should be aware of the uncertainty and anxiety changes and impact of personal attributes on women with suspected breast cancer during the diagnostic period and provide care programs to alleviate their psychological distress.


Screening for atrial fibrillation in primary care.
To investigate a population of elderly people for atrial fibrillation and to determine how many of the cases identified might benefit from treatment with anticoagulants. From a practice of four primary care physicians, 1422 patients aged 65 years and over were identified, of whom 1207 (85% of the total population) underwent electrocardiographic screening to detect the presence of atrial fibrillation. Patients with the arrhythmia were further evaluated by echocardiography and interview, to stratify their risk of stroke based on echocardiographic and clinical risk factors, their perceived risk from anticoagulation, and their attitude towards this treatment. Their primary care physician was also interviewed to determine the factors influencing the prescription of anticoagulants. The arrhythmia occurred in 65 patients (5.4% overall), its prevalence increasing markedly with age (2.3% in 65 to 69 years age group; 8.1% in those over 85). Warfarin was being prescribed to 21.4% of these patients, although the findings of the study indicate that a further 20% were eligible for this treatment. Symptoms suggestive of cardiac failure were common (32.1%) and coexisting pathology was often identified by cardiac ultrasound in these patients (left ventricular hypertrophy, 32.1%; impaired left ventricular contractility, 21.4%; left atrial dilation, 80.4%; mitral annular calcification, 42.9%; mitral stenosis, 7.1%; mitral regurgitation, 48.2%; aortic stenosis, 8.9%). In all but one case, the decision to anticoagulate was based on the clinical rather than the echocardiographic findings. Individual risk-benefit assessment in elderly patients with atrial fibrillation suggests that almost half (41.4%) are eligible for full anticoagulation with warfarin, whereas presently only one fifth are receiving this treatment. The decision to anticoagulate can be made on clinical grounds in most cases. If these results are confirmed, a doubling of the current number of patients taking anticoagulants can be anticipated.


Selective breeding for diet-induced obesity and resistance in Sprague-Dawley rats.
In outbred Sprague-Dawley rats, about one-half develop diet-induced obesity (DIO) on a diet relatively high in fat and energy (HE diet). The rest are diet resistant (DR), gaining weight and fat at the same rate as chow-fed controls. Here we selectively bred for high (DIO) and low (DR) weight gainers after 2 wk on HE diet. By the F5 generation, both male and female inbred DIO rats gained > 90% more weight than inbred DR rats on HE diets. Even on low-fat chow diet, DIO males were 31% and females were 22% heavier than their respective DR rats. Full metabolic characterization in male rats showed that weight-matched, chow-fed DIO-prone rats had similar energy intakes and feed efficiency [body weight (kg0.75)/energy intake (kcal)] but 44% more carcass fat than comparable DR-prone rats. Their basal plasma insulin and glucose levels in the fed state were 70 and 14% higher, respectively. But, when fasted, DIO-prone oral glucose tolerance results were comparable to DR-prone rats. Chow-fed DIO-prone males also had 42% greater 24-h urine norepinephrine levels than DR-prone males. During 2 wk on HE diet, DIO rats ate 25% more, gained 115% more weight, had 36% more carcass fat, and were 42% more feed efficient than comparable DR rats. Fasted HE diet-fed DIO rats developed frank glucose intolerance during a glucose tolerance test with 55 and 158% greater insulin and glucose areas under the curve, respectively. Thus the DIO and DR traits in the outbred Sprague-Dawley population appear to be due to a polygenic pattern of inheritance.


Faster PET reconstruction with non-smooth priors by randomization and preconditioning.
Uncompressed clinical data from modern positron emission tomography (PET) scanners are very large, exceeding 350 million data points (projection bins). The last decades have seen tremendous advancements in mathematical imaging tools many of which lead to non-smooth (i.e. non-differentiable) optimization problems which are much harder to solve than smooth optimization problems. Most of these tools have not been translated to clinical PET data, as the state-of-the-art algorithms for non-smooth problems do not scale well to large data. In this work, inspired by big data machine learning applications, we use advanced randomized optimization algorithms to solve the PET reconstruction problem for a very large class of non-smooth priors which includes for example total variation, total generalized variation, directional total variation and various different physical constraints. The proposed algorithm randomly uses subsets of the data and only updates the variables associated with these. While this idea often leads to divergent algorithms, we show that the proposed algorithm does indeed converge for any proper subset selection. Numerically, we show on real PET data (FDG and florbetapir) from a Siemens Biograph mMR that about ten projections and backprojections are sufficient to solve the MAP optimisation problem related to many popular non-smooth priors; thus showing that the proposed algorithm is fast enough to bring these models into routine clinical practice.


A comparative study of variables differentiating false labor from early labor.
False labor is a common and frustrating problem for women and health-care providers. The purpose of this study was to compare characteristics of true and false labor. A convenience sample of 65 women compared data for three groups who were observed for labor including: false labor, women who were dismissed and returned in true labor more than 48 hours later, impending labor, women who were dismissed but returned in true labor 48 hours or less later, and early labor, women who were admitted for true labor directly following an observation period. Psychosocial differences among the groups were measured by the Maternal Adjustment and Maternal Attitudes (MAMA) scale and a semistructured interview schedule. Chart reviews were conducted to measure physiologic differences and perinatal outcomes. Descriptive and inferential statistics were computed using the SPSSX program. The following variables were statistically significant at P less than .05 for false labor: somatic scores on the MAMA scale, contraction frequency, cervical Bishop scores, gestational age, and Apgar scores. Increased frequency of abnormal labor patterns, intervention with amniotomy, and oxytocin augmentation were observed in false labor subjects. The negative emotional responses of women who were interviewed suggest a need for further investigation of interventions to promote both physical comfort and psychological support.


New Alkaloids From a Hawaiian Fungal Strain Aspergillus felis FM324.
Two new alkaloids tryptoquivaline Y (1) and pseurotin I (2), together with eight known compounds (3-10), were purified from a fungal strain Aspergillus felis FM324, which was isolated from a Hawaiian beach soil sample. The absolute configuration and physicochemical data of tryptoquivaline Z (3) were reported for the first time here in this paper. Compound 1 is an uncommon tryptoquivaline analog containing a 3-O-isobutanoyl group. The structures of the new compounds 1-2 and known compound 3 were elucidated through HRESIMS, NMR spectroscopy and ECD analysis. All the compounds were evaluated for their antiproliferative, antibacterial and NF-κB inhibitory activities. Compound 4 showed weak antibacterial activity against Staphylococcus aureus, methicillin resistant Staphylococcus aureus and Bacillus subtilis with the same MIC value of 59.2 µM. Compounds 3 and 2 inhibited NF-κB with IC50 values of 26.7 and 30.9 μM, respectively.


INSM1 Demonstrates Superior Performance to the Individual and Combined Use of Synaptophysin, Chromogranin and CD56 for Diagnosing Neuroendocrine Tumors of the Thoracic Cavity.
Despite the importance of recognizing neuroendocrine differentiation when diagnosing tumors of the thoracic cavity, the sensitivity of traditional neuroendocrine markers is suboptimal, particularly for high-grade neuroendocrine carcinomas such as small cell lung carcinoma and large cell neuroendocrine carcinoma. To increase sensitivity, neuroendocrine markers are routinely ordered as panels of multiple immunostains where any single positive marker is regarded as sufficient evidence of neuroendocrine differentiation. Insulinoma-associated protein 1 (INSM1) is a well-validated transcription factor of neuroendocrine differentiation that has only recently been evaluated for diagnostic use. We performed INSM1 immunohistochemistry on a large series of thoracic neuroendocrine and non-neuroendocrine tumors and compared its performance to synaptophysin, chromogranin, and CD56. INSM1 was positive in 94.9% of small cell lung carcinomas and 91.3% of large cell neuroendocrine carcinomas, compared with 74.4% and 78.3% with the combined panel of traditional markers. INSM1 also stained all (100%) of the atypical carcinoids, typical carcinoids and mediastinal paragangliomas, but only 3.3% of adenocarcinomas and 4.2% of squamous cell carcinomas. Overall, INSM1 demonstrated a sensitivity of 96.4% across all grades of thoracic neuroendocrine tumors, significantly more than the 87.4% using the panel of traditional markers (P=0.02). INSM1 is sufficiently sensitive and specific to serve as a standalone first-line marker of neuroendocrine differentiation. A more restrained approach to immunohistochemical analysis of small thoracic biopsies is appropriate given the expanding demand on this limited material for therapeutic biomarker analysis.


Efficacy of measuring procalcitonin levels in determination of prognosis and early diagnosis of bacterial resistance in sepsis.
Rapid and proper diagnosis of sepsis is one of the daily challenges of emergency department (ED) and intensive care units. The general aim of the present study was to determine the efficacy of measuring procalcitonin levels in the early diagnosis of bacterial resistance to antibiotics administered empirically in patients with sepsis. The present cross-sectional study consisted of patients with clinical evidence of sepsis or systemic inflammatory response syndrome (SIRS), referring to the ED of a third-level hospital in Tehran, Iran in 2012. After collection of basic and clinical data of patients, venous blood samples were taken for routine laboratory tests and determination of procalcitonin serum levels at baseline and 6 and 24 hours after administration of the first dose of an empirical antibiotic. The subjects were divided into two groups of discharged and expired and then comparisons were made using t-test, Chi-squared test and Fisher's test. Specificity and sensitivity of procalcitonin were evaluated along with ROC curve. In the present study, 170 patients with sepsis were included. Evaluation of serum levels of procalcitonin 24 hours after administration of antibiotics exhibited the best sensitivity and specificity for each patient's response to antibiotics. Use of the cutoff point of 6.5 mg/mL for procalcitonin can predict the disease outcome with sensitivity and specificity of 67% and 80%, respectively. It is suggested that procalcitonin be used for the diagnosis of sepsis or SIRS resulting from an infectious disease, for follow-up of treatment and for evaluation of response to treatment.


Statistical shape analysis of hand and wrist in paediatric population on radiographs
The goal of this study was to compare differences in hand and wrist shapes and to evaluate these according to growth and allometry in children on radiographs related to bone age. The study included 263 males and 189 females. A total of 452 left hand and wrist radiographs were retrospectively collected. Standard anatomical landmarks marked on radiographs. There were seen to be significant differences in comparisons of hand and wrist shapes according to sex (P = 0.009). The most suitable model in the growth models was seen as the Gompertz growth model for both females and males (model P < 0.001). For the relationship between shape and size to evaluate allometry, significant models were obtained in females (model P = 0.017, MSE = 0.0002) and in males (model P < 0.001, MSE = 0.0002). In our study, the difference between the sexes was found mostly in the radiocarpal region. It was observed that the deformation of the carpal bones started in the distal row carpal bones. Significant differences were found in hand and wrist shapes according to sex. Models for growth and allometry of hand and wrist shapes were found to be significant in children.


[The effect of taurine on the carbohydrate metabolism of diabetic animals].
A study was made of a new antidiabetic preparation--taurin in various methods of its administration to rats and rabbits with alloxan and ditisone model of diabetes. A short-term restoration of carbohydrate metabolism was seen after intraperitoneal and intravenous injection in a dose of 200 mg/kg. Oral use of aqueous taurin solution in the same dose failed to produce the desirable result. Microcapsulated taurin with acetylcellulose in the capacity of a filler given per os in a dose of 300 mg/kg restored to the normal glycogen content in the liver and leukocytes, blood and urine sugar level, and the insulin-like activity of blood plasma. Taurin (in a concentration of 3 mg/ml) possessed an insulinogenic action in experiments on fragments of the pancreas isolated from diabetia animals.


A feasibility study using radiochromic films for fast neutron 2D passive dosimetry.
The objective of this paper is threefold: (1) to establish sensitivity of XRQA and EBT radiochromic films to fast neutron exposure; (2) to develop a film response to radiation dose calibration curve and (3) to investigate a two-dimensional (2D) film dosimetry technique for use in establishing an experimental setup for a radiobiological irradiation of mice and to assess the dose to the mice in this setup. The films were exposed to a 10 MeV neutron beam via the (2)H(d,n)(3)He reaction. The XRQA film response was a factor of 1.39 greater than EBT film response to the 10 MeV neutron beam when exposed to a neutron dose of 165 cGy. A film response-to-soft tissue dose calibration function was established over a range of 0-10 Gy and had a goodness of fit of 0.9926 with the calibration data. The 2D film dosimetry technique estimated the neutron dose to the mice by measuring the dose using a mouse phantom and by placing a piece of film on the exterior of the experimental mouse setup. The film results were benchmarked using Monte Carlo and aluminum (Al) foil activation measurements. The radiochromic film, Monte Carlo and Al foil dose measurements were strongly correlated, and the film within the mouse phantom agreed to better than 7% of the externally mounted films. These results demonstrated the potential application of radiochromic films for passive 2D neutron dosimetry.


Material-related complications in implant-supported fixed dental restorations. A systematic review.
A large variety of dental materials are available for the production of implant-supported fixed restorations. Materials with different properties are likely to behave differently during clinical function, which may result in different prevalence and types of complications. The aim of the present review was to summarise, analyse and discuss the prevalence and types of complications or failures related to dental materials in implant-supported restorations. A strategy was set up using the PICO format and the search was performed using the PubMed database, including a hand search of reference lists. Two independent reviewers selected papers based on a set of criteria. The number of events of complications was summarised. The initial search produced 2764 titles. After application of criteria, 47 publications were selected for analysis. Seventeen studies reported on 1447 single crowns and 30 studies reported on 2190 fixed dental prostheses. The most common complications were fracture or chipping of the veneer material, loss of retention and lost access hole fillings. Due to the heterogeneity of studies, and large variation in number of restorations per material group, no conclusive correlation between type of material and type of technical complication and/or failure could be established. The review did not succeed in providing convincing evidence to answer the question concerning a possible relationship between restoration materials and prevalence of technical complications in implant-supported restorations.


Elevated vascular endothelial growth factor is correlated with elevated erythropoietin in stable, young cystic fibrosis patients.
Angiogenesis is an important mechanism of airway remodeling in lung disease. We previously demonstrated that serum vascular endothelial growth factor (VEGF) is elevated in cystic fibrosis (CF) patients and declines with therapy for pulmonary exacerbation. We hypothesized that VEGF is elevated early in the course of CF and is associated with markers of tissue hypoxia. A prospective, single-visit evaluation of thirty stable infants and children with CF was performed. Serum was analyzed for VEGF and for other markers of tissue hypoxia (erythropoietin (EPO), insulin-like growth factor binding protein-1 (IGFBP-1)) and for inflammatory mediators (IL-1 beta, IL-6, IL-8, and tumor necrosis factor alpha (TNFα)) using Meso Scale multi-spot serum immunoassays. Measurements were correlated between assay groups; and with age in months and pulmonary function (FEV0.5 or FEV1). VEGF, EPO, TNFα and IL-8 were elevated compared to published normative values. VEGF levels were not significantly correlated with any inflammatory mediators. However, VEGF correlated with EPO (r=0.505; P<0.05). There was no correlation between lung function and markers of inflammation or tissue hypoxia. VEGF is elevated in young, stable infants and children suggesting angiogenesis as a contributing mechanism for early lung disease in CF. VEGF elevation does not show significant correlation with inflammatory mediators known to be increased in CF, but is significantly correlated with EPO levels. We propose that VEGF elevation and angiogenesis contribute to early lung disease and may result from a direct tissue hypoxia pathway in CF.


[A large-scale epidemic of diphtheria in Moscow in recent years: patterns of development].
Data on the dynamics of diphtheria morbidity in Moscow in 1958-1999 are presented. The last epidemic which started at the end of the 1980s and reached its peak in 1994, giving a 59-fold rise in morbidity in comparison with the pre-epidemic period, is characterized in detail. During the epidemic 12,267 persons fell ill, 454 of them died (mortality rate was 4%). Having started in Moscow, the epidemic gradually spread not only over the territory of Russia, but also over some other republics of the former Soviet Union (Ukraine, Belarus, etc.). Possible causes of this epidemic emergency are considered. The ever increasing share of adult population among persons affected by the epidemic (75%) is noted. The infection adults is characterized by severity of clinical manifestations and increased morbidity among adults, is shown. Under complicated social and economic conditions (crisis situation) the increase of groups of high risk which included unemployed adults of working age, retirees as well as socially non-adapted persons, was registered. Mainly these groups determined tense epidemiological situation in diphtheria in Moscow.


Metformin Alters Locomotor and Cognitive Function and Brain Metabolism in Normoglycemic Mice.
Metformin is currently the most effective treatment for type-2 diabetes. The beneficial actions of metformin have been found even beyond diabetes management and it has been considered as one of the most promising drugs that could potentially slow down aging. Surprisingly, the effect of metformin on brain function and metabolism has been less explored given that brain almost exclusively uses glucose as substrate for energy metabolism. We determined the effect of metformin on locomotor and cognitive function in normoglycemic mice. Metformin enhanced locomotor and balance performance, while induced anxiolytic effect and impaired cognitive function upon chronic treatment. We conducted in vitro assays and metabolomics analysis in mice to evaluate metformin's action on the brain metabolism. Metformin decreased ATP level and activated AMPK pathway in mouse hippocampus. Metformin inhibited oxidative phosphorylation and elevated glycolysis by inhibiting mitochondrial glycerol-3-phosphate dehydrogenase (mGPDH) in vitro at therapeutic doses. In summary, our study demonstrated that chronic metformin treatment affects brain bioenergetics with compound effects on locomotor and cognitive brain function in non-diabetic mice.


Prenatal diagnosis of partial trisomy 3p(3p23-->pter) and monosomy 7q(7q36-->qter) in a fetus with microcephaly alobar holoprosencephaly and cyclopia.
We report the prenatal diagnosis of partial trisomy 3p(3p23-->pter) and monosomy 7q(7q36-->qter) in a fetus with microcephaly, alobar holoprosencephaly and cyclopia. A 26-year-old primigravida woman was referred for genetic counselling at 23 gestational weeks due to sonographic findings of intra-uterine growth retardation and cranio-facial abnormalities. Level II ultrasonograms further demonstrated alobar holoprosencephaly, a proboscis above the eye and a single median orbit consistent with cyclopia. Genetic analysis and fluorescence in situ hybridization on cells obtained from amniocentesis showed distal 3p trisomy (3p23-->pter) and 7q36 deletion, 46,XX,der(7)t(3;7)(p23;q36), resulting from a paternal t(3;7) reciprocal translocation. The pregnancy was terminated. Autopsy further confirmed the presence of arrhinencephaly, agenesis of the corpus callosum and a single ventricle of the brain. The phenotype of this antenatally diagnosed case is compared with those observed in 10 previously reported cases with simultaneous occurrence of partial trisomy 3p and terminal deletion 7q. All cases are associated with severe forms of holoprosencephaly and facial dysmorphism. This delineates an autosomal imbalance syndrome or a dosage effect involving duplication of distal 3p/deficiency of terminal 7q and dysmorphogenesis of the forebrain and mid-face.


[Cytokines of bone turnover in postmenopause and old age].
The aim of the study was the assessment of the influence of cytokines on bone ageing by measuring their level in serum and their secretion in vitro by monocytes from women of different age. The levels of cytokines in 34 postmenopausal subjects and 14 old subjects were compared to those measured in 13 cycling subjects who were considered as control group. Subjects suffering from diseases inducing secondary osteoporosis, subjects taking medications that affect bone metabolism and alcohol- or tobacco-consumers were excluded from the study. The levels in serum of (i) the bone stimulating peptide insulin-like growth factor-I (IGF-I), (ii) the inhibitor of bone resorption interferon-gamma (IFN gamma), (iii) the stimulators of bone resorption interleukin-1 beta (IL-1 beta) tumor necrosis factor alpha (TNF alpha) and interleukin 6 (IL-6) were evaluated by immunoassay. IL-1 beta, TNF alpha and IL-6 secreted by monocytes (MO) cultured in vitro from peripheral blood of the same subjects were measured, too. Bacterial endotoxin (LPS) was used as stimulator for cytokine secretion by monocytes. Unlike IFN gamma, which was unaltered, circulating IGF-I level was found significantly diminished in postmenopausal and old subjects compared to control group. Among stimulators of bone resorption, IL-6 was greatly increased in postmenopausal and old subjects, while TNF alpha was reduced in postmenopausal group. In the supernatants of unstimulated monocytes the level of IL-1 beta was consistently decreased in old subjects; TNF alpha was found to be decreased in postmenopausal and old subjects. The stimulation index (SI), calculated as the ratio between the level of cytokines secreted by LPS-stimulated MO and the level of cytokines secreted by unstimulated MO, was found to be significantly increased for IL-1 beta and TNF alpha in postmenopausal subjects vs control group. In the old subjects the SI for IL-6 was enhanced. The data collected suggest that the measurement of cytokines in serum and supernatants from monocytes may give a picture of the mechanisms regulating bone aging.


Surgical anatomy and dissection techniques for laparoscopic surgery.
All anatomically important pelvic structures lie embedded in the fatty-fibrous connective tissue of the retroperitoneum from which they may be freed by blunt dissection in the correct tissue planes. By relying on fixed laparoscopic landmarks, the correct surgical planes of dissection can be found, and all vital structures freed and identified by a systematic dissection consisting of a precise sequence of operative steps. Once the retroperitoneal dissection has been completed and all vital structures identified, most gynecologic operations can be carried out safely and without much difficulty laparoscopically. A nonanatomical approach to laparoscopic pelvic surgery may be easier to learn, but it is neither very versatile nor very safe except in the simplest of cases.


Cardiac and pulmonary anaphylaxis in guinea pigs and rabbits induced by glycoprotein isolated from tobacco leaves and cigarette smoke condensate.
Cigarette smoking is a major risk factor for heart attack. The pathologic mechanisms responsible for this association are obscure. It has been reported that approximately one-third of human volunteers, smokers and nonsmokers, exhibit immediate cutaneous hypersensitivity to a glycoprotein antigen (TGP) purified from cured tobacco leaves and present in cigarette smoke. It is also known that the heart is a primary target organ for anaphylactic reaction in many animals, including primates. In experiments described herein anaphylaxis was induced in the isolated hearts and lungs of rabbits and guinea pigs previously sensitized by immunization with TGP and challenged with TGP isolated from either tobacco leaf or cigarette smoke condensate. Cardiac anaphylaxis was characterized by sinus tachycardia, decreased contractility, decreased coronary perfusion accompanied by hypoxic electrocardiographic changes, and a variety of rhythm disturbances, including idioventricular tachyarrhythmias. These observations suggest that allergic reactions to tobacco constituents may initiate cardiac arrhythmia and sudden death in some smokers and may, in part, underly the association between cigarette smoking and heart attack.


Evidence for a complex risk profile in obese postmenopausal Turkish women with hypertriglyceridaemia and elevated apolipoprotein B.
The aim of the present study was to examine possible pathophysiological relationships among a wide array of proatherogenic risk factors in postmenopausal women. Fasting lipids, apoB (apolipoprotein B), BMI (body mass index) and waist circumference were measured in 178 women (59.4+/-7.2 years) from the Turkish Adult Risk Factor Study. Fasting levels of complement C3, insulin, SHBG (sex hormone-binding globulin), cortisol, oestradiol, testosterone and DHEA-S (dehydroepiandrosterone sulphate) were also determined. This is the first study to examine the relationships of all these variables with apoB. In the first of two different approaches, three groups of obese women were compared. Group 1 comprised women who were normolipidaemic with normal apoB; group 2, women who were hypertriglyceridaemic, but with normal apoB; and group 3, women who were hypertriglyceridaemic with elevated apoB. Complement C3, fasting insulin and glucose were significantly higher and HDL-C (high-density lipoprotein-cholesterol) and SHBG levels were significantly lower in group 3 than in group 1. In the former group, the testosterone/SHBG ratio tended to be higher, indicating more free testosterone, than in group 1. The mean risk score in group 3 and the odds ratio for coronary disease by logistic regression analysis were significantly higher, 2.56 (confidence intervals, 1.12-5.85; P=0.026), compared with the two other groups combined. In examining the whole group, apoB levels correlated significantly with a wider array of pro-atherogenic risk factors than did LDL-C (low-density lipoprotein-cholesterol), particularly being linked to complement C3 and glucose, as well as the risk score. Complement C3 demonstrated the widest associations and was significantly linked with BMI, waist circumference, insulin, glucose, fibrinogen, triacylglycerols (triglycerides) and apoB and was inversely correlated with HDL-C and SHBG. SHBG was also correlated inversely with a wide spectrum of risk variables. In summary, in Turkish women, apoB was linked with a complex array of proatherogenic risk factors, and hypertriglyceridaemia with elevated apoB was associated with a higher risk of coronary disease.


Endocytosis of Intestinal Tight Junction Proteins: In Time and Space.
Eukaryotic cells take up macromolecules and particles from the surrounding milieu and also internalize membrane proteins via a precise process of endocytosis. The role of endocytosis in diverse physiological processes such as cell adhesion, cell signaling, tissue remodeling, and healing is well recognized. The epithelial tight junctions (TJs), present at the apical lateral membrane, play a key role in cell adhesion and regulation of paracellular pathway. These vital functions of the TJ are achieved through the dynamic regulation of the presence of pore and barrier-forming proteins within the TJ complex on the plasma membrane. In response to various intracellular and extracellular clues, the TJ complexes are actively regulated by intracellular trafficking. The intracellular trafficking consists of endocytosis and recycling cargos to the plasma membrane or targeting them to the lysosomes for degradation. Increased intestinal TJ permeability is a pathological factor in inflammatory bowel disease (IBD), and the TJ permeability could be increased due to the altered endocytosis or recycling of TJ proteins. This review discusses the current information on endocytosis of intestinal epithelial TJ proteins. The knowledge of the endocytic regulation of the epithelial TJ barrier will provide further understanding of pathogenesis and potential targets for IBD and a wide variety of human disease conditions.