[Diagnosis and intervention of disability-causing neonatological risk factors].
Early care attempts to offer children with, or at risk of suffering from, development disorders a series of optimising compensatory actions that help them to mature properly in all spheres, thus allowing them to reach a maximum level of personal development and social integration. In this study we review the main instruments used for the diagnosis and prevention of neurological disabilities during the pre-and post-natal period. In this field, neuropaediatrics intervenes in a joint, coordinated fashion with neonatology in the detection, diagnosis and therapeutic care of the new-born. The progress made in diagnostic techniques allows the early detection of anomalies that are associated with disability. Neuroimaging (transfontanellar echography, computerised tomography (CAT), magnetic resonance imaging, brain SPECT), genetic and molecular genetics studies, metabolic neonatal and infection screening, neurophysiological techniques and so on will enable earlier and more sensitive diagnoses to be made. In addition, throughout the neonatal period the obstetrician has the enormous responsibility of diagnosing many processes that can be subsidiary to a future disability. We believe that close collaboration between the obstetrician, neonatologist and neuropaediatrician will enable the detection and prevention of risk factors that can lead to a neurological disability. It is also the neuropaediatrician's duty to take part in programmes to monitor the development of children with a biopsychosocial risk, as well as participating in the detection of warning signs and in the diagnosis of neurological disorders.


Assessment of renal artery stenosis severity by pressure gradient measurements.
The purpose of this study was to define "significant" renal artery stenosis (i.e., a stenosis able to induce arterial hypertension). The degree of renal artery stenosis that justifies an attempt at revascularization is unknown. In 15 patients, transstenotic pressure measurements were obtained before and after unilateral stenting. After stenting, graded stenoses were created in the stented segment by progressive inflation of a balloon catheter. Stenosis severity was expressed as the ratio of distal pressure (P(d)) corrected for aortic pressure (P(a)). Balloon inflation pressure was adjusted to create 6 degrees of stenosis (P(d)/P(a) from 1.0 to 0.5, each step during 10 min). Plasma renin concentration was measured at the end of each step in the aorta and in both renal veins. For a P(d)/P(a) ratio >0.90, no significant change in plasma renin concentration was observed. However, when P(d)/P(a) became <0.90, a significant increase in renin was observed in the renal vein of the stenotic kidney, finally reaching a maximal increase of 346 +/- 145% for P(d)/P(a) of 0.50 (p = 0.006). These values returned to baseline when the stenosis was relieved. In addition, plasma renin concentration increased significantly in the vein from the non-stenotic kidney (p = 0.02). In renal artery stenoses, a P(d)/P(a) ratio of 0.90 can be considered a threshold value below which the stenosis is likely responsible for an up-regulation of renin production and, thus, for renovascular hypertension. These findings might contribute to better patient selection for renal angioplasty.


Calibrating violence risk assessments for uncertainty.
Psychiatrists and other mental health clinicians are often tasked with assessing patients' risk of violence. Approaches to this vary and include both unstructured (based on individual clinicians' judgement) and structured methods (based on formalised scoring and algorithms with varying scope for clinicians' judgement). The end result is usually a categorisation of risk, which may, in turn, reference a probability estimate of violence over a certain time period. Research over recent decades has made considerable improvements in refining structured approaches and categorising patients' risk classifications at a group level. The ability, however, to apply these findings clinically to predict the outcomes of individual patients remains contested. In this article, we review methods of assessing violence risk and empirical findings on their predictive validity. We note, in particular, limitations in calibration (accuracy at predicting absolute risk) as distinct from discrimination (accuracy at separating patients by outcome). We also consider clinical applications of these findings, including challenges applying statistics to individual patients, and broader conceptual issues in distinguishing risk and uncertainty. Based on this, we argue that there remain significant limits to assessing violence risk for individuals and that this requires careful consideration in clinical and legal contexts.


Reaction for the synthesis of benzimidazol-2-ones, imidazo[5,4-b]-, and imidazo[4,5-c]pyridin-2-ones via the rearrangement of quinoxalin-2-ones and their aza analogues when exposed to enamines.
A synthetically useful protocol has been developed for the preparation of highly functionalized N-pyrrolylbenzimidazol-2-ones. The reaction of variously substituted 3-aroyl- and 3-alkanoylquinoxalin-2(1H)-ones with commercially available enamines in acetic acid results in a rapid rearrangement and formation of N-pyrrolylbenzimidazol-2-ones in modest to excellent yields. The key step of the rearrangement involves the novel ring contraction of 3-aroyl- and 3-alkanoylquinoxalin-2(1H)-ones with enamines. In this case, the atom of carbon which is displaced from the pyrazine ring of quinoxalin-2(1H)-one becomes the fourth carbon atom of the newly formed pyrrole ring. The method is applicable for the aza analogues of quinoxalin-2(1H)-ones.


Time-dependent photobiomodulation management of neuropathic pain induced by spinal cord injury in male rats.
Neuropathic pain (NP) following spinal cord injury (SCI) often lasts for a long time and causes a range of problems that reduce the quality of life. Current treatments are not generally effective; however, photobiomodulation therapy (PBMT) has made some progress in this area. Due to the novelty of this treatment, standard therapeutic protocols have not yet been agreed upon. In the present study, we compare the analgesic effect of two PBMT protocols (2 and 4 weeks of radiation). A total of thirty-two adult male Wistar rats were divided into four groups: control, SCI, 2 W PBMT, and 4 W PBMT. SCI was induced by an aneurism clip and PBMT used a 660-nm, initiated 30 min post-SCI, and continued daily for 2 or 4 weeks. Functional recovery, hyperalgesia, and allodynia were measured weekly. At the end of the study, the Gad65, interleukin 1-alpha (IL1α), interleukin 10 (IL10), IL4, and purinergic receptor (P2xR and P2yR) expressions were measured. Data were analyzed by Prism6. The results showed PBM irradiation for 2 and 4 weeks had the same effects in improving hyperalgesia. In the case of allodynia and functional recovery, 4 W PBMT was more effective (p<0.01). 4 W PBMT increased the Gad65 expression (p <0.001) and reduced P2Y4R (p <0.05) compared to SCI animals. The effects of 2 and 4 W PBMT were the same for IL1α, IL10, and P2X3 receptors. 4 W PBMT was more effective in reducing the complications of SCI such as pain and disability. PBMT therapy is an effective method aimed at immune system function modulation to reduce NP and motor dysfunction.


Video-assisted sacral nerve stimulation.
Sacral nerve simulation (SNS) is an accepted therapy for patients with urinary or bowel dysfunction. However, infection rates are as high as 20% and can result in removal of the expensive device. We present a new video-assisted technique minimizing the risk of infection. Between April and July 2005, six consecutive women of median age 68 years (range, 60-74), with faecal incontinence (4 patients) and idiopathic constipation (2 patients) underwent video-assisted electrode implantation for SNS. The motor response of the pelvic floor during percutaneous nerve evaluation and implantation of the permanent lead was monitored by a video optic (same as that normally used for laparoscopic or endoscopic procedures) placed between the legs of the patients. The video optic and the perianal area were completely covered with drapes, separating them from the operating field. All but one screening was successful, and no wound infections at the electrode or at the pocket of the stimulator were noted (mean postoperative follow-up, 8 weeks). With the use of a video optic, the anus and the implantation site can be completely separated and contamination during the operation becomes unlikely. Furthermore, the response of the pelvic floor to the stimulation is better visualized. We routinely recommend the use of video equipment for SNS electrode implantation.


Foamability and foam stability of molecular reconstituted model sparkling wines.
The present work aims at identifying the contribution of the different wine components to the foaming properties of wines. Twelve fractions were isolated from wine, and foam aptitude of each fraction was measured individually at the concentration at which it was recovered, using wine model solutions. For these concentrations, the maximum foam height (HM) was 8.4-11.7 cm, foam height on stability was 6.9-7.5 cm, and foam stability (TS) was 3.0-6.5 s. Moreover, foam measurements were also performed using 2-, 5-, and 10-fold concentrations of these compounds in wine. The HM increased linearly with the concentration of mannoproteins having low content of protein (MP1), and TS increased exponentially. The fractions that individually showed higher foaming properties were mixed in binary and ternary combinations, demonstrating that MP1 when mixed with low molecular weight hydrophobic compounds strengthens the air/water interface of these solutions, a characteristic that is on the basis of sparkling wines' foamability and foam stability.


Metabolic depression: a historical perspective.
An extended period of inactivity and reduced metabolic rate of many animals and plants, as well as unicellular organisms, has long been recognized by natural historians, e.g., Aristotle and Pliny. Biologists have studied this phenomenon since the 1550s (Gessner) and 1700s (Van Leeuwenhoek, Buffon). The period of inactivity can be less than a day, a few consecutive days or weeks, an entire season, or even many years. It can involve very different physiological states in response to a variety of environmental stimuli, such as extreme temperatures or unavailability of food or water. These periods of inactivity have been described and classified according to the group of organisms in question, extent and duration of the metabolic depression, ambient and body temperatures, state of body water (frozen or hyperosmotic), or availability of oxygen. Cryptobiosis, or "hidden life," is an extreme form of inactivity, with often complete cessation of metabolism. It was first described in the 1700s, was further characterized in the 1800s, and in the 1900s physiological studies delineated the extent of metabolic depression. Molecular mechanisms for cryptobiosis have been sought since the late 1900s. Cryptobiosis includes three physiological states, anhydrobiosis (desiccation), osmobiosis (high osmotic concentration), and cryobiosis (freezing), where metabolic depression is associated with an altered physical state of cell water and often involves accumulation of compatible solutes, and one physiological state, anoxybiosis (anoxia), where metabolic depression occurs at the normal cellular hydration state. Dormancy (torpor) is a less extreme form of inactivity, associated with a moderate reduction in metabolic rate (hypometabolism). Although first described by Aristotle and Pliny, studies in the 1900s delineated the basic physiological changes that accompany dormancy. Dormancy allows avoidance of unfavorable short- or long-term climatic conditions and conservation of energy and water. Hibernation is long-term multiday torpor during winter, whereas aestivation is dormancy during summer. In ectotherms, the metabolic depression that accompanies dormancy is intrinsic, with metabolic rate declining to about 10 to 20% of resting metabolic rate at the same body temperature. The molecular mechanisms for intrinsic metabolic depression are poorly understood. In endotherms, torpor involves a fundamental physiological change in body temperature regulation that markedly reduces metabolic rate and water loss, often to <10% of the normothermic resting metabolic rate at the same ambient temperature. Most of this reduction in metabolic rate reflects the decreased setpoint for thermoregulation resulting in reduced metabolic heat production and a Q(10) effect; there may be some intrinsic molecular-based metabolic depression in some hibernators. Dormancy allows species to exploit ephemeral environments and colonise habitats that would otherwise be unsuitable for growth or survival at certain times of the year. There are costs to dormancy, but for many species, the energetic and hygric advantages outweigh these costs.


Effect of pulsed electromagnetic field on growth and structure properties of ZnO nanorod arrays.
Well-aligned ZnO nanorod arrays had been prepared by hydrothermal methods assisted with pulsed electromagnetic field (PEMF). The effects of pulsed electromagnetic field on growth and structure properties of ZnO nanorod arrays were studied in detail. XRD and SEM analysis showed ZnO nanorod arrays had bigger length to diameter ratio and better verticality on the substrate. And the Raman analysis showed well-aligned ZnO nanorod arrays have highly crystallized wurtzite structure with much fewer defects after a pulsed electromagnetic field was introduced. At last, a possible mechanism of pulsed electromagnetic field acted on nanorod arrays was proposed.


[Surgical management of extracranial internal carotid aneurysms].
Extracranial internal carotid artery (EICA) aneurysms are rare and their causes are variable. Our main goal was to evaluate the results of the surgical treatment of the EICA aneurysms. Between January 1993 and January 2008, 1028 carotid surgeries were performed by the senior author. Of these, 11 patients (1,07%), been nine men (mean age, 61,89 +/- 8,58 years) were submitted to surgical treatment of the EICA aneurysms. The causes were: atherosclerosis (n=8); fibromuscular dysplasia (n=2); and dissection (n=1). Eight patients (72 %) were symptomatic before the surgery, and the symptoms were transient ischemic attack (n=3); painful pulsatile mass in neck (n=3); and amaurosis fugax (n=2(. Demographic and surgical data and long term results were evaluated. There were no deaths, none neurologic complications (stroke and transient ischemic attacks) after the surgery. Furthermore, there were two transient cranial nerve dysfunction (18,2%) in the perioperative period. The median follow up time was 36 months (1 a 180 meses). During the follow up, one patient died after a trauma by gunshot after 36 months of the carotid surgery. There was a reoperation in a female patient with fibromuscular dysplasia that presented a critical stenosis in the distal anastomosis of her first operation (18 months before(. After surgery, she developed a transient dysfagia that resolved in four weeks. In the remain patients that were submitted to carotid revascularization, there was no vascular problem (stenosis, occlusion, pseudoaneurysm) diagnosed by duplex ultrasonography during the follow up. Surgical treatment of the EICA aneurysms can be performed with very good short and long term results with very low neurologic complications and mortality. The follow up of the operated patients is very important and permit to identify vascular problems which can be corrected, when necessary.


Phase II evaluation of dianhydrogalactitol in the treatment of advanced non-squamous cervical carcinoma. A Gynecologic Oncology Group study.
In an on-going Phase II evaluation, dianhydrogalactitol (NSC 132313) was administered intravenously to 28 patients with advanced or recurrent non-squamous cell carcinoma of the cervix. The initial dosage was 60 mg/m2/wk with escalation to 75 mg/m2/wk if there were no adverse effects. Twenty-seven patients were evaluable for toxicity and response. There was one complete response and one partial response. Adverse effects were not infrequent but tolerable.


Protein mediated cholesterol absorption in locusts Schistocerca gregaria (Forskal) and Locusta migratoria (Linn).
Absorption and transport of 3H cholesterol from the midgut to hemolymph and other tissues was studied in the locusts Schistocerca gregaria and Locusta migratoria. S. gregaria are able to absorb dietary cholesterol in the midgut and release into the hemolymph in vivo and into the incubation medium in virto. Certain proteins of midgut origin are involved in the absorption and release of cholesterol. The proteins designated as cholesterol binding proteins (CBP's) were fractionated by gel filtration chromatography using Sepharose CL-6B-200 column. Presence of a protein and its binding with cholesterol is confirmed by TCA precipitation after subsequent incubation of midgut in the incubation medium. Cholesterol binding with the proteins was also confirmed in native polyacrylamide gel electrophoresis. Biosynthesis of this protein takes place in the midgut which is inhibited by a protein synthesis inhibitor, cycloheximide. It also inhibits absorption and release of cholesterol from the midgut. The cholesterol binding activity was associated with a peak containing proteins ranging from molecular weights of 17-32 kDa in SDS-PAGE gels. Treatment of midgut with cycloheximide resulted in reduced cholesterol binding activity. Dilipidation of mucin and transport in presence of bile salts yielded a higher cholesterol binding activity. Although the absorption and release of cholesterol was observed in the hemolymph of both sexes, the ovary exhibited higher cholesterol binding as compared to testis.


[Investigation of the neck swelling due to accumulation of irrigation fluid during shoulder arthroscopy in the beach-chair position].
The primary purpose of this study was to investigate the degree of neck swelling by accumulation of irrigation fluid during shoulder arthroscopy in the beach-chair position. Twenty-one patients undergoing shoulder arthroscopy in the beach-chair position were included in this study. There were 16 male and 5 female patients, with a mean age of 58.7 +/- 16.1 years. All patients' weight and neck circumference were compared pre- and postoperatively and correlated to each other. There was a strong correlation between the increase rate of weight and the increase rate of neck circumference (r = 0.69, P < 0.05). Pre- and postoperative measurement of the neck circumference might be an easy and useful measure for prediction of postoperative airway obstruction.


Basic science for the clinician 38: B cells, factories, and immunomodulators.
In a previous article in this series, we explored how developing pre-T cells learn how to be well-behaved T cells that recognize and honor the "self versus nonself" dichotomy of the universe. B cells do much of the same sort of thing, with multipotent stem cells becoming committed to ultimately becoming B cells within the bone marrow and then, after judicious culling of the flock, going off to the spleen to learn the final lessons needed to become "well-behaved" B cells. Like with T cells, there are a large number of things that can, and do, go wrong. If there is a failure of the system and B cells do not develop properly, hypogammaglobulinemia may develop as a result of a number of immune deficiency syndromes that can be quite devastating. If autoreactive cells survive to emerge into the periphery, autoimmunity, either organ-specific or more global, may occur. If B cells in the periphery proliferate in an uncontrolled fashion, a variety of B cell lymphoproliferative syndromes may develop, recognizable by the phenotypic markers of their originating B cell lineage level of differentiation. The full details of how autoreactive B cells survive and thrive, only to cause disease, are not yet clear, but identification of many of the phenotypic surface markers and circulating growth factors identified to this point have borne therapeutic fruit.


Polymer Coatings in 3D-Printed Fluidic Device Channels for Improved Cellular Adherence Prior to Electrical Lysis.
This paper describes the design and fabrication of a polyjet-based three-dimensional (3D)-printed fluidic device where poly(dimethylsiloxane) (PDMS) or polystyrene (PS) were used to coat the sides of a fluidic channel within the device to promote adhesion of an immobilized cell layer. The device was designed using computer-aided design software and converted into an .STL file prior to printing. The rigid, transparent material used in the printing process provides an optically transparent path to visualize endothelial cell adherence and supports integration of removable electrodes for electrical cell lysis in a specified portion of the channel (1 mm width × 0.8 mm height × 2 mm length). Through manipulation of channel geometry, a low-voltage power source (500 V max) was used to selectively lyse adhered endothelial cells in a tapered region of the channel. Cell viability was maintained on the device over a 5 day period (98% viable), though cell coverage decreased after day 4 with static media delivery. Optimal lysis potentials were obtained for the two fabricated device geometries, and selective cell clearance was achieved with cell lysis efficiencies of 94 and 96%. The bottleneck of unknown surface properties from proprietary resin use in fabricating 3D-printed materials is overcome through techniques to incorporate PDMS and PS.


Epitaxial growth and surface properties of half-metal NiMnSb films.
We present, herein, an extended study of the half-Heusler alloy NiMnSb, starting with the deposition technique, continuing with the basic structural and magnetic properties of the thin films, and finishing with the electronic and compositional properties of their surfaces. The experimental methods we apply combine magnetization and magnetoresistivity measurements, atomic force microscopy, ferromagnetic resonance, x-ray and neutron diffraction, low energy electron diffraction, angle resolved x-ray photoemission, extended x-ray absorption fine structure spectroscopy, soft x-ray magnetic circular dichroism and spin polarized inverse photoemission spectroscopy. We find that stoichiometric surfaces exhibit close to 100% spin polarization at the centre of the surface Brillouin zone at the Fermi edge at ambient temperatures. There is strong evidence for a moment reordering transition at around 80 K which marks the crossover from a high polarization state (T<80 K) to a more representative metallic ferromagnetic state (T>80 K). The results from the different experimental techniques are successively reviewed, with special emphasis on the interplay between composition and electronic structure of the NiMnSb film surfaces. Surface segregation, consistent with a difference in free enthalpy between the surface and the bulk, is induced by annealing treatments. This surface segregation greatly reduces the surface polarization.


The risk of fetal death in nonanomalous pregnancies affected by polyhydramnios.
The objective of the study was to evaluate the ongoing risk of intrauterine fetal demise (IUFD) in nonanomalous pregnancies affected by polyhydramnios. We analyzed a retrospective cohort of all singleton, nonanomalous births in California between 2005 and 2008 as recorded in a statewide birth certificate registry. We included all births between 24+0 and 41+6 weeks' gestational age, excluding multiple gestations, major congenital anomalies, and pregnancies affected by oligohydramnios. Polyhydramnios was identified by International Classification of Diseases, ninth revision, codes. χ(2) tests were used to compare the dichotomous outcomes, and multivariable logistic regression analyses were then performed to control for potential confounders. We analyzed the data for pregnancies affected and unaffected by polyhydramnios. The IUFD risk was expressed as a rate per 10,000. The risk of IUFD in pregnancies affected by polyhydramnios was greater at every gestational age compared with unaffected pregnancies. The IUFD risk in pregnancies affected by polyhydramnios was more than 7 times higher than unaffected pregnancies at 37 weeks at a rate of 18.0 (95% confidence interval [CI], 9.0-32.6) vs 2.4 (95% CI, 2.0-2.5) and was 11-fold higher by 40 weeks' gestational age at a rate of 66.3 (95% CI, 10.8-68.6) vs 6.0 (95% CI, 5.1-6.3) in unaffected pregnancies. When adjusted for multiple confounding variables, the presence of polyhydramnios remained associated with an increased odds of IUFD in nonanomalous singleton pregnancies, with an adjusted odds ratio of 5.5 (95% CI, 4.1-7.6). Ongoing risk of IUFD is greater in low-risk pregnancies affected by polyhydramnios at all gestational ages compared with unaffected pregnancies with the greatest increase in risk at term. Although further study is needed to explore the underlying etiology of polyhydramnios in these cases, the identification of polyhydramnios alone may warrant increased antenatal surveillance.


The role of the social worker in the in-vitro fertilization program.
The role of the clinical social worker in the In-Vitro fertilization Program is to help provide patients with an environment that includes realistic expectation and emphasizes the emotional spectrum of euphoria, anxiety and dysphoria that can accompany the demanding protocol. The literature supports the need for counseling and supportive psychotherapy in the infertility clinic but has not dealt specifically with the psychological demands of In-Vitro fertilization. This paper addresses the emotional stress of in-vitro fertilization and emphasizes the role of social worker as counselor, educator and guide.


Formulation of Solid Lipid Nanoparticles Loaded with Nociceptin/Orphanin FQ (N/OFQ) and Characterization in a Murine Model of Airway Hyperresponsiveness.
Asthma is characterized by chronic inflammation and a variable degree of airway hyperresponsiveness (AHR). Our previous papers documented a role for Nociceptin/Orphanin FQ (N/OFQ) and its receptor N/OFQ peptide (NOP) in AHR. Therefore, the aim of this study was to improve the bioavailability of N/OFQ by developing solid lipid nanoparticles (SLNs). N/OFQ-loaded SLNs were prepared by the Quasi Emulsion Solvent Diffusion (QESD) technique and then characterized. Brown Norway rats were sensitized to ovalbumin (OVA) and treated with an intratracheal administration of saline solution or N/OFQ-SLN. Then, 24 h after the last challenge, functional histological and molecular evaluations were performed. SLNs showed a mean diameter of 233 ± 0.03 nm, a polydispersity index (PDI) value around 0.28 ± 0.02 and a drug release percentage of 84.3. The in vitro release of N/OFQ from SLNs showed that the release of the peptide starts already after two hours of incubation. Animals receiving N/OFQ-SLN showed a significative decrease in allergen-induced AHR compared to the control group. These results showed the positive effects of N/OFQ-SLNs on the inflammatory process and on the mechanical properties of the airways, suggesting that the innovative nanotechnological approach may be therapeutically beneficial for asthmatic patients.


The immunomodulatory effect of IL-4 accelerates bone substitute material-mediated osteogenesis in aged rats via NLRP3 inflammasome inhibition.
Bone defect repair by implanting bone substitute materials has been a common clinical treatment. With the understanding of substance-immune system interactions and increasing evidence indicating that the post-implantation immune response determines the fate of bone substitute materials, active modulation of host macrophage polarization is considered a promising strategy. However, whether the same regulatory effects exist when an individual immune system is altered with aging is unclear. In this study, we mechanistically investigated the effect of immunosenescence on the active regulation of macrophage polarization by establishing a cranial bone defect model in young and aged rats implanted with Bio-Oss®. Forty-eight young and 48 aged specific pathogen-free (SPF) male SD rats were randomly divided into two groups. In the experimental group, 20 μL of IL-4 (0.5 μg/mL) was injected locally on the third to seventh postoperative days, while an equal volume of PBS was injected in the control group. Specimens were collected at 1, 2, 6, and 12 weeks postoperatively, and bone regeneration at the defect site was evaluated by micro-CT, histomorphometry, immunohistochemistry, double-labeling immunofluorescence, and RT-qPCR. The application of exogenous IL-4 reduced activation of NLRP3 inflammasomes by promoting the polarization of M1 macrophages to M2 macrophages, thus promoting bone regeneration at the site of bone defects in aged rats. However, this effect was gradually weakened after the IL-4 intervention was discontinued. Our data confirmed that a strategy to regulate macrophage polarization is also feasible under conditions of immunosenescence, i.e., the local inflammatory microenvironment can be regulated by reducing M1-type macrophages. However, further experiments are needed to determine an exogenous IL-4 intervention that can maintain a more sustained effect.


Low apoptotic index & bak expression in EBV-associated childhood classical Hodgkin lymphoma.
Association of Epstein-Barr virus (EBV) with Hodgkin lymphoma (HL) is particularly high in low-income countries, and resistance to apoptosis might play a role in pathogenesis and survival. Data from previous studies are not consistent, and none is available in children. Thus this study was undertaken on Indian children with classical Hodgkin lymphoma to assess the significance of bcl-2, bak and p53 expression, and apoptotic index in relation with EBV status and treatment outcome with chemotherapy alone. Children (age<15 yr) with classical HL (n=143) were included in the study. Bcl-2, bak, p53, Ki67 and latent membrane protein-1 (LMP1) were detected by immunohistochemistry in pre-treatment lymph node biopsies. Apoptotic index was assessed by TdT-dUTP nick-end labelling (TUNEL). Bcl-2, bak, p53 were expressed above positivity threshold in 83.3, 94.0 and 7.1 per cent of the cases respectively. More than 10 per cent of apoptotic tumour cells were seen in 60.4 per cent of the cases. 131 (91.6%) cases were EBV associated. EBV-positive cases had a significantly lower mean bak expression (p=0.001) and a lower apoptotic index, without higher proliferation index. Advanced stage showed a borderline association with bcl-2 expression in >25 per cent of tumour cells and p53 negative tumours. In univariate analysis, p53 positive cases, which were significantly associated with B symptoms, had a poorer overall survival (P=0.03) while low proliferation index was associated with poorer failure-free survival. Neither EBV status nor any of the apoptotic parameters studied showed independent association with survival. EBV detection in children with classical Hodgkin lymphoma was associated with significant lower bak expression and with lower spontaneous apoptosis of H-RS cells suggesting that EBV-LMP1 might downregulate bak pro-apoptotic protein. this needs to be substantiated further.


Simultaneous pathological findings in biopsy specimens of patients with surgically resected lung carcinoids and their role in survival.
Pulmonary carcinoid tumors are rare, low-grade malignant tumors that constitute 1-2% of all lung tumors. The present study aimed to describe the simultaneous pathological findings in biopsy specimens of patients with surgically resected lung carcinoids and determine their association with survival rates. For this purpose, 108 patients with resected carcinoid lung tumors were followed-up for 96 months and analyzed for simultaneous pathological findings in biopsy specimens. Among these, simultaneous pathological findings were found in 82 patients. The association between these findings and patient survival rates was evaluated. Atelectasis was a simultaneous finding in 52.4% of the patients, desquamative interstitial pneumonia (DIP) in 13.4%, emphysema in 24.4% and bronchiectasis in 9.8%. The survival rate was 100% for the patients with atelectasis, 81.8% for the patients with DIP, 90% for the patients with emphysema and 75% for the patients with bronchiectasis (P<0.05). According to the univariate analysis, the type of carcinoid was associated with patient survival with better survival rates for patients with typical carcinoids, while age, sex, stage and simultaneous pathological findings were not associated with patient survival. On the whole, there was a statistically significant difference in the survival rates of patients with resected lung carcinoids with different simultaneous pathological findings. However, further studies are warranted to assess the role of these findings in the survival of these patients.


Effects of combined traditional processing methods on the nutritional quality of beans.
Consumption of dry beans is limited by long cooking times thus high fuel requirement. The bioavailability of nutrients in beans is also limited due to presence of antinutrients such as phytates and tannins. Little research has been done on combined processing methods for production of nutritious fast cooking bean flour and the effect of combined treatments on nutritional quality of beans has not previously determined. The aim of this study was to reduce cooking time and enhance the nutritional value of dry beans. Specifically to: develop protocols for production of fast cooking bean flours and assess the effect of processing on the nutritional characteristics of the flours. Dry beans (K131 variety) were soaked for 12 h; sprouted for 48 h; dehulled and steamed for 25 and 15 min for whole and dehulled beans respectively or roasted at 170°C for 45 and 15 min for whole and dehulled beans respectively. Dehulling eliminated phytates and tannins and increased protein digestibility. In vitro protein digestibility and mineral (iron and zinc) extractability were negatively correlated with tannin and phytate content. Total available carbohydrates were highest in moist heat-treated bean flours. Overall, combined processing of beans improved the nutritional quality of dry beans and the resulting precooked flours need less cooking time compared to whole dry beans.


Effect of Child Overweight/Obesity Didactic Session on Resident Confidence and Detection.
Objective. To evaluate the impact of an obesity didactic session for pediatric physicians on confidence in counseling and identified overweight/obesity and follow-up recommendations. Methods. Pediatric residents underwent training and completed pre/post online surveys evaluating confidence in obesity prevention and identification. A booster training occurred 1 year later. Pre-/post-training scores were compared using χ2 or Fisher's exact tests. Electronic medical records data for patients ≥3 years with BMI-for-age percentile ≥85 during 3 months prior/following the training/booster compared frequency of overweight/obesity identification and follow-up recommendations (≤3 months recommended vs longer) using logistic regression adjusting for age and overweight/obese status. Results. Post trainings, improvements in confidence to define/screen for obesity were observed, with a decline between trainings. Overweight/obese identification and follow-up time recommendations improved post-training (identification: 14.2% to 27.4%, adjusted odds ratio [aOR] = 3.16, 95% confidence interval [CI] = 1.54-6.51; follow-up: 48.9% to 58.9%, aOR = 1.63, 95% CI = 1.01-2.64), aOR = 1.77, 95% CI = 1.10-2.85, and identification remained stable/above pre-training rates both pre-/post-booster (25.8%, aOR = 3.14, 95% CI = 1.53-6.45; and 22.1%, aOR = 2.57, 95% CI = 1.25-5.30, respectively). Recommended follow-up time rates continued to rise when measured pre-booster (60.6%, aOR = 1.77, 95% CI = 1.10-2.85), then declined (46.0%, aOR = 0.95, 95% CI = 0.60-1.52). Conclusion. This didactic session improved resident confidence in defining/screening, identification of overweight/obesity and follow-up recommendations; however, rates of identification remained low. The successes of this intervention support similar didactic sessions in residency programs and identifies opportunities for improved resident/attending education.


Updated CDC Recommendations for Using Artemether-Lumefantrine for the Treatment of Uncomplicated Malaria in Pregnant Women in the United States.
Malaria infection during pregnancy is associated with an increased risk for maternal and fetal complications. In the United States, treatment options for uncomplicated, chloroquine-resistant Plasmodium falciparum and P. vivax malaria in pregnant women are limited to mefloquine or quinine plus clindamycin (1). However, limited availability of quinine and increasing resistance to mefloquine restrict these options. Strong evidence now demonstrates that artemether-lumefantrine (AL) (Coartem) is effective and safe in the treatment of malaria in pregnancy. The World Health Organization (WHO) has endorsed artemisinin-based combination therapies (ACTs), such as AL, for treatment of uncomplicated malaria during the second and third trimesters of pregnancy and is currently considering whether to add ACTs, including AL, as an option for malaria treatment during the first trimester (2,3). This policy note reviews the evidence and updates CDC recommendations to include AL as a treatment option for uncomplicated malaria during the second and third trimesters of pregnancy and during the first trimester of pregnancy when other treatment options are unavailable. These updated recommendations reflect current evidence and are consistent with WHO treatment guidelines.


Total synthesis of ustiloxin D and considerations on the origin of selectivity of the asymmetric allylic alkylation.
As part of investigations into cell cycle checkpoint inhibitors, an asymmetric synthesis of the antimitotic natural product, ustiloxin D, has been completed. A salen-Al-catalyzed aldol reaction was employed to construct a chiral oxazoline 9 (99% yield, 98% ee) that served the dual purpose of installing the necessary 1,2-amino alcohol functionality as well as providing an efficient synthon for the requisite methylamino group at C9. The chiral aryl-alkyl ether was assembled using a Pd-catalyzed asymmetric allylic alkylation that notably delivered a product with stereochemistry opposite to that predicted by precedent. The linear tetrapeptide was subsequently cyclized to produce ustiloxin D. The mechanistic origin of the allylic alkylation selectivity was further investigated, and a working hypothesis for the origin of the observed stereoselectivity has been proposed.


Copy number and loss of heterozygosity detected by SNP array of formalin-fixed tissues using whole-genome amplification.
The requirement for large amounts of good quality DNA for whole-genome applications prohibits their use for small, laser capture micro-dissected (LCM), and/or rare clinical samples, which are also often formalin-fixed and paraffin-embedded (FFPE). Whole-genome amplification of DNA from these samples could, potentially, overcome these limitations. However, little is known about the artefacts introduced by amplification of FFPE-derived DNA with regard to genotyping, and subsequent copy number and loss of heterozygosity (LOH) analyses. Using a ligation adaptor amplification method, we present data from a total of 22 Affymetrix SNP 6.0 experiments, using matched paired amplified and non-amplified DNA from 10 LCM FFPE normal and dysplastic oral epithelial tissues, and an internal method control. An average of 76.5% of SNPs were called in both matched amplified and non-amplified DNA samples, and concordance was a promising 82.4%. Paired analysis for copy number, LOH, and both combined, showed that copy number changes were reduced in amplified DNA, but were 99.5% concordant when detected, amplifications were the changes most likely to be 'missed', only 30% of non-amplified LOH changes were identified in amplified pairs, and when copy number and LOH are combined ∼50% of gene changes detected in the unamplified DNA were also detected in the amplified DNA and within these changes, 86.5% were concordant for both copy number and LOH status. However, there are also changes introduced as ∼20% of changes in the amplified DNA are not detected in the non-amplified DNA. An integrative network biology approach revealed that changes in amplified DNA of dysplastic oral epithelium localize to topologically critical regions of the human protein-protein interaction network, suggesting their functional implication in the pathobiology of this disease. Taken together, our results support the use of amplification of FFPE-derived DNA, provided sufficient samples are used to increase power and compensate for increased error rates.


Microfluidic immobilized metal affinity chromatography based on Ti(IV)-decorated silica microspheres for purification of phosphoproteins.
A silica-based immobilized metal affinity chromatography (IMAC) sorbent with the morphological properties suitable for purification of large phosphorylated biomolecules was synthesized. The sorbent was designed in the form of monodisperse-porous silica microspheres, 5.3 μm in size, having bimodal pore size distribution with a large median pore size (40 nm) and high surface area (163 m2/g) decorated with Ti(IV) cations (i.e. Ti(IV)@THSPMP@SiO2 microspheres). The decoration of silica microspheres with Ti(IV) cations was made by using 3-(trihydroxysilyl)propyl methylphosphonate (THSPMP) as a bifunctiontional linker, by preserving their bimodal pore size distribution. The mesopores provided a large surface area for parking of adsorbed phosphoproteins as large phosphorylated biomolecules while the intraparticular transport of phosphoproteins was facilitated by the macropores providing a large median pore size. High equilibrium adsorption capacity and high desorption yield in the purification of phosphoproteins were obtained using Ti(IV)@THSPMP@SiO2 microspheres as the sorbent in batch- and microfluidic-IMAC systems. The phosphoproteins, α-casein and β-casein were isolated from milk and human serum with almost quantitative yields and high purity in the batch IMAC system. The appropriate microcolumn permeability (3.66 × 10-14 m2) originating from its appropriate average diameter (5.3 μm), high porosity (0.948 cm3/g) and high surface area (163 m2/g) of Ti(IV)@THSPMP@SiO2 microspheres makes the synthesized sorbent a promising stationary phase for dynamic chromatography. Hence, a new phosphoprotein enrichment format, a microfluidic IMAC system was constructed and successfully operated for highly selective purification of phosphoproteins from non-fat milk as a complex sample. The microfluidic-IMAC system is a promising tool particularly for phosphoproteomic applications performed using samples in microliter or nanoliter scale, also involving an on-line connection of purification unit to LC-MS for the identification of large phosphorylated biomolecules enriched.


Downregulation of Matrix Metalloproteinases 2 and 9 is Involved in the Protective Effect of Trehalose on Spinal Cord Injury.
Upregulation of matrix metalloproteinases (MMPs), in particular MMP-2 and MMP-9 contributes to secondary pathogenesis of spinal cord injury (SCI) via promoting inflammation. Recently, we have reported that trehalose suppresses inflammatory responses following SCI. Therefore, we investigated the effect of trehalose on MMP-2 and MMP-9 expression in SCI. A weight-drop contusion SCI was induced in male rats. Then, the animals received trehalose at three doses of 10 (T10), 100 (T100) and 1000 (T1000) mM intrathecally. MMP-2 and MMP-9 transcripts were then measured in damaged spinal cord at 1, 3 and 7 days after trauma, and compared with vehicle and sham groups. Additionally, behavioral analysis was conducted for 1 week using Basso-Beattie-Bresnahan (BBB) locomotor rating scale. Our data showed an early upregulation of MMP-9 at 1 day post-SCI. However, MMP-2 expression was increased at 3 days after trauma. Treatment with 10 mM trehalose significantly reduced MMP-2 expression in 3 and 7 days (P< 0.01) and MMP-9 expression in 1, 3, and 7 days (P< 0.05) post-damage compared with vehicle. Nonetheless, downregulation of both MMPs was not observed in T100 and T1000 groups. In addition, T10 group showed more rapid recovery of hind limb strength compared with T100 and T1000 groups. We propose that the neuroprotective effect of low dose trehalose is mediated by attenuation of MMP-2 and MMP-9 expression.


Post tonsillectomy haemorrhage: "is day care surgery safe"?
To compare the frequency of haemorrhage after tonsillectomy as a day care procedure versus tonsillectomy as a one day procedure. A comparative study was conducted at the Department of ENT and Head and Neck Surgery, Shifa International Hospital, Islamabad from January 2003 to December 2007. The sample consisted of 400 patients, divided into two groups, One group was kept in the hospital for eight hours and was labeled as the daycare group while other group was kept admitted for 23 hours stay (overnight) and was labeled as the one day group. Patients with nasal pathology, bleeding diathesis and less than 4 years of age were excluded. Patients were followed up post operatively on 7th and 14th day and were inquired about any bleeding episode from the mouth during stay at home. The data was analysed at SPSS 13. Post tonsillectomy haemorrhage was seen in 10 patients (2.5%), 4 (2%) occurred in day care group while 6 (3%) in one day group. All were secondary haemorrhages. Chi square test showed no significant difference in haemorrhages between the two groups. Tonsillectomy can safely be done as a daycare procedure as there is no significant difference of post operative haemorrhage between daycare and one day admission.


Risk of a second malignant neoplasm among 5-year survivors of cancer in childhood and adolescence in British Columbia, Canada.
We examined second malignancies, a recognized late effect of therapy among survivors of childhood and adolescent cancer, among a recent, population-based cohort of 2,322 5-year survivors diagnosed before 20 years of age in British Columbia (BC), Canada between 1970 and 1995. Survivors and second malignancies were identified from the BC Cancer Registry. Risk of second malignancy was evaluated using standardized incidence ratios (SIRs), absolute excess risk (AER), and cumulative risk. The effect of demographic, temporal, and disease-related characteristics on risk was assessed. Fifty-five second malignancies were observed after 26,071 person-years of follow-up. Relative rate of developing a second malignancy among survivors was 5 times higher than expected (SIR = 5.0, 95% CI, 3.8-6.5), and absolute excess risk was 1.7 deaths per 1,000 person-years. Cumulative incidence of a second malignancy was 5.1% at 25 years after diagnosis of the first cancer. SIRs and absolute excess risk of subsequent cancer was higher among females (SIR = 5.9, 95% CI, 4.5-8.3 and AER = 2.66). While relative risk of second cancer was higher for those diagnosed before 10 years of age (SIR = 10.6, 95% CI, 7.1-16.0), absolute excess risk was slightly higher for those diagnosed after 10 years of age. SIRs were significantly elevated for all follow-up periods, but absolute excess risk of a second cancer was highest among patients surviving more than 15 years. Increased risk of a subsequent neoplasm is evident among childhood cancer survivors diagnosed in more recent periods than has been previously reported, continues years after diagnosis, and varies according to several risk factors. Continued surveillance is essential to quantify and characterize long-term and changing risks for appropriate follow-up.


[Bladder pain syndrome--an urological-gynecological problem].
Bladder Pain Syndrome remains a great challenge for urologists, both in diagnostics and treatment. Etiopathogenesis of the disease is unknown. It is reported that the reason for Bladder Pain Syndrome is the urothelium dysfunction resulting in the destruction of the protective glycosaminoglycan layer/barrier protecting the urothelium from bacteria adhesion and penetration of toxic substances/by bacteria. It is considered to be a syndrome of dysuria and diuresis. Urine analysis usually is normal. It is diagnosed after exclusion of other causes leading to painful symptoms. It is estimated that 90% of the cases of the disease concern women. Treatment with glycocorticosteroids, antihistaminic drugs and antiallergic drugs was not successful. The attempts to find the right method of treatment led to the introduction of hyaluronic acid, which alleviated Bladder Pain Syndrome and its symptoms. Hyaluronic acid reacting with glycosaminoglycans on the bladder decreases penetrability of irritant substances. The patients were treated with 4-8 weekly instillations--40 mg of hyaluronic acid in 50 ml NaCl solution for 1-2 months. After the last instillation, therapy is repeated for the next 6-8 months with one instillation monthly. This method is for patients a chance for getting rid of painful symptoms from the bladder


Path length dependence of optical homodyne signal strength.
A theoretical analysis has been performed in order to determine optical homodyne signal strength as a function of path length difference between coherent spherical reference and signal waves. Signal strength is found to decrease with increasing path length mismatch. Experimental verification of the results are also given, along with methods for minimizing the detrimental effect of wavefront curvature.


A Rhizobacterium, Streptomyces albulus Z1-04-02, Displays Antifungal Activity against Sclerotium Rot in Mungbean.
Sclerotium rot causes damping-off and stem rot in seedlings and mature mungbeans, which negatively impacts cultivation. The use of a rhizobacterium to control soil-borne diseases is an alternative method to the excess use of synthetic fungicides; therefore, this study aims to screen rhizosphere actinobacteria with fungicidal activities against Sclerotium rolfsii, the pathogen that causes sclerotium rot in mungbeans. Primary screening showed that the Streptomyces sp. isolate Z1-04-02 displayed the highest effectiveness against S. rolfsii in dual culture plates, with a percentage inhibition of 74.28%. An assay containing enzymes that degrade cell walls, of the cell-free culture filtrate (CF) of Z1-04-02, showed that the activities of chitinase and β-1,3-glucanase were 0.0209 and 1.0210 U/mL, respectively, which was significantly higher than that of the control (media alone). The cell-free CF of Z1-04-02, incubated at 37 °C and 100 °C, using agar well diffusion, effectively inhibited the growth of S. rolfsii with inhibition percentages of 37.78% and 27.78%, respectively. Solid-phase microextraction (SPME) was applied to trap volatiles released from Z1-04-02 and gas chromatography-mass spectrometry (GC/MS); volatile antifungal compounds were tentatively identified as bicyclic monoterpene (1R)-(-)-myrtenal. The application of the cell-free CF, and the spore suspension of Z1-04-02, showed disease severity indexes (DSIs) of 12.5% and 8.25%, respectively, which were significantly lower than those showing inoculation by S. rolfsii alone. The identification of this strain by morphology, biochemistry tests, and 16s rDNA sequences revealed that Z1-04-02 was Streptomyces albulus. This finding revealed that S. albulus Z1-04-02 displayed diverse fungicidal activities against S. rolfsii, and it has the potential to act as a biological control agent in terms of inhibiting sclerotium rot in mungbeans.


The canine homeobox gene MSX2: sequence, chromosome assignment and genetic analysis in dogs of different breeds.
The MSX2 gene encodes a homeodomain transcription factor important for normal head and face morphogenesis. MSX2 is expressed in key craniofacial structures during development and mutations in the human gene give rise to various craniofacial abnormalities. We are interested in the genetic basis of non-pathogenic variation in skull and face shape. As part of this study we have analysed DNA from a panel of different dog breeds, selected for the differences they show in these traits and investigated MSX2 as a candidate gene. In this paper we describe the cloning of the canine homologue of MSX2, the determination of its structure, sequence and localization of the gene to dog chromosome 4q23. The DNAs from 11 individual domestic dogs belonging to 10 different breeds were sequenced in a search for genetic variation. Our studies show that variation in MSX2 does not contribute to the diversity of face shape observed in these domestic dogs and that the MSX2 sequence is strongly conserved between different dog breeds. The proximal promoter shows a high level of interspecies sequence conservation and several conserved transcription factor binding motifs have been identified and their significance discussed.


Polygenic risk score: use in migraine research.
The latest Genome-Wide Association Study identified 38 genetic variants associated with migraine. In this type of studies the significance level is very difficult to achieve (5 × 10- 8) due to multiple testing. Thus, the identified variants only explain a small fraction of the genetic risk. It is expected that hundreds of thousands of variants also confer an increased risk but do not reach significance levels. One way to capture this information is by constructing a Polygenic Risk Score. Polygenic Risk Score has been widely used with success in genetics studies within neuropsychiatric disorders. The use of polygenic scores is highly relevant as data from a large migraine Genome-Wide Association Study are now available, which will form an excellent basis for Polygenic Risk Score in migraine studies. Polygenic Risk Score has been used in studies of neuropsychiatric disorders to assess prediction of disease status in case-control studies, shared genetic correlation between co-morbid diseases, and shared genetic correlation between a disease and specific endophenotypes. Polygenic Risk Score provides an opportunity to investigate the shared genetic risk between known and previously unestablished co-morbidities in migraine research, and may lead to better and personalized treatment of migraine if used as a clinical assistant when identifying responders to specific drugs. Polygenic Risk Score can be used to analyze the genetic relationship between different headache types and migraine endophenotypes. Finally, Polygenic Risk Score can be used to assess pharmacogenetic effects, and perhaps help to predict efficacy of the Calcitonin Gene-Related Peptide monoclonal antibodies that soon become available as migraine treatment.


Innovative approach to teaching communication skills to nursing students.
This study assessed the effectiveness of a learner-centered simulation intervention designed to improve the communication skills of preprofessional sophomore nursing students. An innovative teaching strategy in which communication skills are taught to nursing students by using trained actors who served as standardized family members in a clinical learning laboratory setting was evaluated using a two-group posttest design. In addition to current standard education, the intervention group received a formal training session presenting a framework for communication and a 60-minute practice session with the standardized family members. Four domains of communication-introduction, gathering of information, imparting information, and clarifying goals and expectations-were evaluated in the control and intervention groups in individual testing sessions with a standardized family member. The intervention group performed better than the control group in all four tested domains related to communication skills, and the difference was statistically significant in the domain of gathering information (p = 0.0257).


Intravesical tension-free vaginal tape removal: is there a single solution?
Stress urinary incontinence (SUI) affects 10-20% of women in the general population. Surgery for stress incontinence has been performed on women for over a century, but with the advent of new urogynaecological sling procedures for its management, urological surgeons are having to deal with an increasing number of patients presenting with associated complications. With no clarity on the full range of possible complications or certain consensus on their optimal management, the ideal treatment remains a decision for the individual surgeon. In view of this, we felt it of common interest to review the literature for the history of sling procedures, present commonly arising complications, and seek to answer the question in the title.


Formation of Long-Lived Dark States during Electronic Relaxation of Pyrimidine Nucleobases Studied Using Extreme Ultraviolet Time-Resolved Photoelectron Spectroscopy.
Ultrafast electronic relaxation of nucleobases from 1ππ* states to the ground state (S0) is considered essential for the photostability of DNA. However, transient absorption spectroscopy (TAS) has indicated that some nucleobases in aqueous solutions create long-lived 1nπ*/3ππ* dark states from the 1ππ* states with a high quantum yield of 0.4-0.5. We investigated electronic relaxation in pyrimidine nucleobases in both aqueous solutions and the gas phase using extreme ultraviolet (EUV) time-resolved photoelectron spectroscopy. Femtosecond EUV probe pulses cause ionization from all electronic states involved in the relaxation process, providing a clear overview of the electronic dynamics. The 1nπ* quantum yields for aqueous cytidine and uracil (Ura) derivatives were found to be considerably lower (<0.07) than previous estimates reported by TAS. On the other hand, aqueous thymine (Thy) and thymidine exhibited a longer 1ππ* lifetime and a higher quantum yield (0.12-0.22) for the 1nπ* state. A similar trend was found for isolated Thy and Ura in the gas phase: the 1ππ* lifetimes are 39 and 17 fs and the quantum yield for 1nπ* are 1.0 and 0.45 for Thy and Ura, respectively. The result indicates that single methylation to the C5 position hinders the out-of-plane deformation that drives the system to the conical intersection region between 1ππ* and S0, providing a large impact on the photophysics/photochemistry of a pyrimidine nucleobase. The significant reduction of 1nπ* yield in aqueous solution is ascribed to the destabilization of the 1nπ* state induced by hydrogen bonding.


The number of breeders explains genetic connectivity in an endangered bird.
Connectivity is central to ecology and evolution as it focuses on the movement of individuals or genes across landscapes. Genetic connectivity approaches aim to understand gene flow but often estimate it indirectly based on metrics of genetic differentiation, which can also be affected by other evolutionary forces such as genetic drift. Gene flow and genetic drift are driven by separate ecological mechanisms with potentially differing effects on genetic differentiation and interpretations of genetic connectivity. The ecological mechanisms contributing to gene flow and genetic drift are primarily effective dispersal, or movement followed by successful reproduction, and the number of breeders in a local population, Nb , respectively. Yet, rarely are these ecological mechanisms and genetic connectivity measured simultaneously across landscapes. We examine the roles of effective dispersal and Nb on genetic connectivity across the entire range of the endangered snail kite (Rostrhamus sociabilis plumbeus), between 2006-2015. We find that both Nb and effective dispersal are important predictors of genetic connectivity across this landscape, but that Nb has a 3 × stronger effect on genetic connectivity. Furthermore, Nb is positively correlated with heterozygosity and allelic richness within patches, suggesting a potentially important role of genetic drift, in addition to gene flow, on genetic connectivity. These results emphasize that conservation efforts should focus on not only between-patch processes of movement but also within-patch processes regarding habitat quality and local population size for increasing genetic connectivity.


Detection of candidaemia in high risk patients: can yield of blood cultures be improved by blind subculture?
Rapid detection of candidaemia is crucial for timely antifungal chemotherapy. However, the sensitivity of automated blood culture (BC) systems has been questioned. Blind subculture might increase detection rate and possibly also reduce time to detection of candidaemia. This retrospective study aimed to evaluate the efficacy of blind subcultures in patients deemed at high risk of candidaemia. BCs were processed by the BacT/Alert BC system, and during a 5-y period (1998-2003) subculture on the third d of incubation was performed for patients selected by clinical and microbiological assessment. A total of 79,165 BCs were drawn during the study period. 2154 BCs from 285 patients were selected for subculture. 103 (4.8%) BCs from 52 patients were yeast positive; 71 were detected positive prior to the planned subculture, 25 were positive on subculture, and 7 were negative on subculture, but became positive during further incubation. The 25 BCs positive on subculture originated from 14 patients, 11 of whom had already been diagnosed with candidaemia during the previous 14 d. Thus, a primary diagnosis of candidaemia was obtained by subculture in only 3 (1.1%) of the 285 patients selected. In conclusion, in our clinical setting blind subculture did not materially increase the detection of candidaemia, but helped to document persistent infection in a subset of cases.


Comparison of cardiac sympathetic nervous function with left ventricular function and perfusion in cardiomyopathies by (123)I-MIBG SPECT and (99m)Tc-tetrofosmin electrocardiographically gated SPECT.
The objective of this study was to clarify the relationship between cardiac sympathetic nervous function (CSNF) and left ventricular (LV) function and perfusion in hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM). Thirty-eight cases (32 males, 6 females; mean age, 56 +/- 15 y), consisting of 5 healthy control subjects, 15 patients with DCM, and 18 patients with HCM, were studied with (123)I-metaiodobenzylguanidine (MIBG) and (99m)Tc-tetrofosmin SPECT. CSNF was evaluated from cardiac uptake and washout of MIBG, whereas LV perfusion and function were evaluated from tetrofosmin uptake and wall thickening on electrocardiographically gated SPECT. As quantitative parameters of global cardiac MIBG uptake and washout, the heart-to-mediastinum ratio (H/M) and percentage washout were calculated from early and delayed planar images. As quantitative regional parameters, the regional uptake and percentage washout of MIBG were calculated from SPECT images dividing the left ventricle into 12 segments. In the tetrofosmin study, the H/M and LV ejection fraction were calculated as the parameters of global LV perfusion and function. As quantitative regional parameters, the regional uptake and wall thickening were also calculated for the 12 myocardial segments using the quantitative gated SPECT software. Multiple linear regression analysis was performed to investigate the correlations between the parameters from the 2 studies. In DCM and HCM, multiple linear regression analysis of the regional parameters showed significant correlations between LV function and CSNF (P < 0.0001) and between LV perfusion and CSNF (P < 0.0001). According to the partial correlation coefficients, washout and early uptake of MIBG were the most significant factors for predicting LV function and LV perfusion, respectively. In cardiomyopathies, CSNF was closely related to LV function. The quantitative parameters of MIBG washout could reflect cardiac functional impairment. Early MIBG uptake might be determined by myocardial perfusion in cardiomyopathies.


Feeding and temperature responses to intravenous leptin infusion are differential predictors of obesity in rats.
Obesity is frequently associated with leptin resistance. The present study investigated whether leptin resistance in rats is present before obesity develops, and thus could underlie obesity induced by 16 wk exposure to a liquid, palatable, high-energy diet (HED). Before HED exposure, male Wistar rats (weighing between 330 and 360 g) received intravenous infusions of 20 microg leptin 2 h before dark (approximately 57 microg/kg rat). Relative to saline infusion, this caused a highly variable effect on food intake (ranging between -94 and +129%), with food intake suppression that appeared negatively correlated with HED-induced increases in body weight gain, caloric intake, adiposity, and plasma leptin levels. In contrast, leptin's thermogenic response was positively correlated to body weight gain linked to weights of viscera, but not to adiposity. Before HED exposure, leptin unexpectedly increased food intake in some rats (fi+, n = 8), whereas others displayed the normal reduction in food intake (fi-, n = 7). HED-exposed fi+ rats had higher plasma leptin levels, retroperitoneal fat pad weight, HED intake, and body weight gain than fi- and chow-fed rats. These parameters were also higher in HED-exposed fi-rats relative to chow rats, except for plasma leptin concentrations. It is concluded that leptin's reduced efficacy to suppress food intake could predict obesity on an HED. An unexpected orexigenic effect of leptin might potentially contribute to this as well.


Fabrication and electrical conductivity of poly(methyl methacrylate) (PMMA)/carbon black (CB) composites: comparison between an ordered carbon black nanowire-like segregated structure and a randomly dispersed carbon black nanostructure.
Poly(methyl methacrylate) (PMMA)/carbon black (CB) composites were fabricated using two different mixing methods: (1) mechanical mixing and (2) solution mixing of the precursors, followed by compression molding. The microstructures obtained were examined by optical and scanning electron microscopy. Electrical properties were measured using impedance spectroscopy over a wide frequency range (10(-3) to +10(9) Hz). With the mechanical mixing method, a segregated structure is produced with PMMA particles forming faceted grains with carbon black particles aligning to form a network of 3D-interconnected nanowires. This microstructure allows percolation to occur at a low volume fraction of 0.26 vol % CB. In contrast, specimens made by the solution method have a microstructure where carbon black is distributed more randomly throughout the bulk, and thus, the percolation threshold is higher (2.7 vol % CB). The electrical properties of the PMMA/CB composites fabricated by the mechanical mixing method are comparable to those obtained with single-wall nanotubes as fillers.


Initial Results of Tests Using GSR Biofeedback as a New Neurorehabilitation Technology Complementing Pharmacological Treatment of Patients with Schizophrenia.
Galvanic skin response (GSR) Biofeedback uses training to reduce tension and anxiety and improve concentration and self-regulation. The study was aimed to evaluate this method as a form of rehabilitation and quantify the outcomes achieved by patients undergoing training using this technique. Six schizophrenic patients were enrolled in the study and underwent training based on the relaxation training module (CENTER), concentration training module (BALANCE), and self-regulation training module (INSECTS). Training sessions were held twice a week for 6 weeks. From the total group of subjects involved in the study, two patients had a statistically significant increase in measured values after the CENTER exercise, indicating that relaxation was achieved. Four patients showed a statistically significant decrease in measured values after the BALANCE exercise, which was reflective of an improvement in concentration. Three patients had a statistically significant decrease in measured values after the INSECTS exercise, which indicated an improvement in self-regulation. GSR Biofeedback may be used to complement the pharmacological treatment of patients diagnosed with schizophrenia.


Efficacy and Tolerability of a New Formulation in Rectal Ointment Based on Zn-L-Carnosine (Proctilor®) in the Treatment of Haemorrhoidal Disease.
Haemorrhoidal disease (HD) shows high prevalence in western countries, reaching 4.4% per year in the US. Topical preparations are the first-line treatments, which are readily available as "over-the-counter" (OTC) products, often containing a nonstandardised mixture of "natural" remedies, or anaesthetics or cortisol;those latter are not free from undesirable effects. The Zinc-L-Carnosine is a cytoprotective compound, promoting mucosal repair in the gastrointestinal tract and also in mucosal repair, following radiation injuries to the rectum as well as in ulcerative colitis. Our aim was to study the efficacy of Zinc-L-Carnosine in relieving acute symptoms of HD, testing a preparation in the rectal ointment, Proctilor®, in patients complaining of bleeding or thrombosed piles. In a multicentre open trial, 21 patients older than 18 years of age were enrolled. The symptoms of HD were graded according to the Haemorrhoidal Disease Symptoms Score (HDSS) in association with the Short Health Scale (SHS) to assess the influence of HD on quality of life. The pain was assessed with the VAS score, bowel habit by means of the Bristol scale. The patients were evaluated at enrolment (T0) and 2 (T1) and 4 (T2) weeks of treatment with Proctilor® rectal ointment. There were 10 men and 11 women; mean age, 49 years. Pain, bleeding, and thrombosis were all significantly reduced after treatment; the mean VAS score decreased from 4.71 ± 3.05 at T0 to.52 ± 0.87 and.05 ± 0.22 at T1 and T2, respectively; (mean ± SD; p < 0.001 in both cases). Similarly, the HDSS score showed to be significantly reduced between T0, T1 (8.05 ± 4.55 vs. 1.14 ± 1.01), and T2 (8.05 ± 4.55 vs. 24 ± 0.44) (mean ± SD; p < 0.001 in both cases). Quality of life showed to be improved as the SHS score decreased significantly with treatment (7.90 ± 4.17 at T0 vs. 4.24 ± 0.44 at T1 vs. 4.05 ± 0.22 at T2; mean ± SD; p < 0.001 in both cases). The Bristol score of defecation remained substantially unchanged. No side effects or discontinuation of treatment were reported. Results of our investigation suggest a role of Proctilor® rectal ointment in treating symptomatic HD with good results and an excellent safety profile. However, our preliminary results encourage further studies on a larger number of patients to confirm the role of Zinc-L-Carnosine in the rectal ointment for the topical treatment of HD.


Biochemical analysis of interactions between outer membrane proteins that contribute to starch utilization by Bacteroides thetaiotaomicron.
An early step in the utilization of starch by Bacteroides thetaiotaomicron is the binding of starch to the bacterial surface. Four starch-associated outer membrane proteins of B. thetaiotaomicron that have no starch-degrading activity have been identified. Two of these, SusC and SusD, have been shown by genetic analysis to be required for starch binding. In this study, we provide the first biochemical evidence that these two proteins interact physically with each other. Both formaldehyde cross-linking and nondenaturing gel electrophoresis experiments showed that SusC and SusD interact to form a complex. Two other proteins encoded by genes in the same operon, SusE and SusF, proved not to be essential for starch utilization and actually decreased starch binding when they were present along with SusC and SusD. Consistent with this, nondenaturing gel analysis revealed that in a strain producing SusC, SusD, and SusE, the SusCD complex was partially destabilized. The strain producing SusC, SusD, and SusE also grew more slowly on starch than a strain producing SusC, SusD, SusE, and SusF (mu(max), 0.29 and 0.37/h, respectively). Thus, SusE appears to interact with the SusCD complex. SusE also interacts with SusF, because SusE was less susceptible to proteinase K digestion when SusF was present, and nondenaturing gel analysis detected a complex formed by these two proteins. Our results indicate that SusC, SusD, SusE, and SusF form a protein complex in the outer membrane but that SusE and SusF are dispensable members of this complex.


Intelligent Fault Diagnosis of Diesel Engines via Extreme Gradient Boosting and High-Accuracy Time-Frequency Information of Vibration Signals.
Accurate and timely misfire fault diagnosis is of vital significance for diesel engines. However, existing algorithms are prone to fall into model over-fitting and adopt low energy-concentrated features. This paper presents a novel extreme gradient boosting-based misfire fault diagnosis approach utilizing the high-accuracy time-frequency information of vibration signals. First, diesel engine misfire tests were conducted under different spindle speeds, and the corresponding vibration signals were acquired via a triaxial accelerometer. The time-domain features of signals were extracted by using a time-domain statistics method, while the high-accuracy time-frequency domain features were obtained via the high-resolution multisynchrosqueezing transform. Thereafter, considering the nonlinearity and high dimensionality of the original characteristic data sets, the locally linear embedding method was employed for feature dimensionality reduction. Eventually, to avoid model overfitting, the extreme gradient boosting algorithm was utilized for diesel engine misfire fault diagnosis. Experiments under different spindle speeds and comprehensive comparisons with other evaluation methods were conducted to demonstrate the effectiveness of the proposed extreme gradient boosting-based misfire diagnosis method. The results verify that the highest classification accuracy of the proposed extreme gradient boosting-based algorithm is up to 99.93%. Simultaneously, the classification accuracy of the presented approach is approximately 24.63% higher on average than those of algorithms that use wavelet packet-based features. Moreover, it is shown that it obtains the minimum root mean squared error and can effectively prevent the model from falling into overfitting.


Femoral stem failure and ectopic bone formation in total hip arthropalsty: four case reports.
In 4 cases of fracture of the femoral stem in total hip arthroplasty (THA), 3 were preceded by clinical and radiographic evidence of loosening and the last was not. Each developed a significant amount of ectopic bone. Stem failure in THA is a continuum progressing in some cases from ectopic bone formation and calcar resorption to stem loosening. An association between ectopic ossification and stem loosening is determined by grading the quantity of new bone not only by the amount but also by its spatial relationship with the implant. Observation on a large number of cases by the method of DeLee, Ferrari, and Charnley is required to prove or disprove the effect of ectopic bone on stem failure. In any case, patients who develop ectopic bone should be restricted in their activities.


Male fertility study on N,N-dimethylacetamide administered by the inhalation route to Sprague-Dawley rats.
Male Sprague-Dawley rats were exposed to N,N-dimethylacetamide (DMAC) and mated to untreated virgin females. Mean analytical exposure concentrations were 40, 116, and 386 ppm, respectively. A control group was exposed to air containing no DMAC. A total of 69 d of exposure to DMAC at these levels produced treatment-related effects of increased liver weights and liver/body weight ratios in the high- and medium-exposure groups of male rats. Reproductive data indicated no treatment-related effects on copulation efficiency or efficiency in effecting pregnancy, and there were no detectable treatment-related effects on preimplantation loss, postimplantation loss, embryotoxicity, or fetotoxicity in litters of females mated to males exposed to DMAC at the levels used in this study. The significance of these findings is discussed.


Appropriate use of indwelling urethra catheters in hospitalized patients: results of a multicentre prevalence study.
Although indwelling urethra catheterization is a medical intervention with well-defined risks, studies show that approximately 14-38% of the indwelling urethra catheters (IUCs) are placed without a specific medical indication. In this paper we describe the prevalence of IUCs, including their inappropriate use in the Netherlands. We also determine factors associated with inappropriate use of IUCs in hospitalized patients. In 28 Dutch hospitals, prevalence surveys were performed biannually in 2009 and 2010 within the PREZIES-network. All patients admitted to a participating hospital and who had an IUC in place at the day of the survey were included. Pre-determined criteria were used to categorize the indication for catheterization as appropriate or inappropriate. A total of 14,252 patients was included and 3020 (21.2%) of them had an IUC (range hospitals 13.4-27.3). Initial catheter placement was inappropriate in 5.2% of patients and 7.5% patients had an inappropriate indication at the day of the survey. In multivariate analyses inappropriate catheter use at the time of placement was associated with female sex, older age, admission on a non-intensive care ward, and not having had surgery. Inappropriate catheter use at the time of survey showed comparable associated factors. Although lower than in many other countries, inappropriate use of IUC is present in Dutch hospitals. To reduce the inappropriate use of IUCs, recommended components of care (bundle for UTI), including daily revision and registration of the indication for catheterization, should be introduced for all patients with an IUC. Additionally, an education and awareness campaign about appropriate indications for IUC should be available.


Emphysematous Pyelonephritis in Type 2 Diabetes - Clinical Profile and Management.
Emphysematous pyelonephritis (EPN) is a rare but life-threatening acute suppurative infection of the kidney among diabetics. There is no current consensus on the management of EPN. A prospective observational study was conducted at the Department of General Surgery, RML Institute of Medical Sciences, Lucknow, as well as at Eras Lucknow Medical College, Lucknow, from 2015 to 2018 to look for clinical, microbial profile and treatment outcome of diabetic patients with EPN. A total of 76 diabetic patients diagnosed with pyelonephritis were identified, of which 15 patients were diagnosed with EPN (26.3%). The mean age of the patients was 58.4 ± 6.5 years. The mean duration of diabetes was 5.3 ± 3.3 years. 12 (82%) of the 15 patients with diabetes mellitus had a glycosylated hemoglobin level higher than 7.5. Renal dysfunction at presentation was seen in 11 (73.3%) patients. Among the unilateral involvement, the left kidney was more affected. Escherichia coli in 11 (73.3%), Klebsiella sp. in one (6.6%), Pseudomonas in one (6.6%), and one each with polymicrobial and fungal urinary tract infection, respectively. Of 15 EPN patients, 13 (86.6 %) survived, and one (6.6 %) expired. Two of them underwent nephrectomy both survived. All patients with Stage I, II, and IIIa EPN (n = 12) were managed with antibiotics with or without percutaneous catheter drainage (PCD). In EPN Stage IIIb/IV (n = 3), all the three (20%) patients were managed with antibiotics and PCD, and later two (13.3%) needed nephrectomy. Only time to diagnosis, altered sensorium, shock at presentation, and thrombocytopenia were associated with poor outcome in EPN patients (P <0.05) Multiple logistic regression tests showed shock (P = 0.04) and disturbance of consciousness (P = 0.05) on (hospital admission as being the independent factors for poor outcome. EPN in diabetics needs a high index of suspicion, timely diagnosis, and good multidisciplinary approach with adequate antibiotics and surgical management for better patient outcomes.


How bilingualism modulates selective attention in children.
There is substantial evidence that learning and using multiple languages modulates selective attention in children. The current study investigated the mechanisms that drive this modification. Specifically, we asked whether the need for constant management of competing languages in bilinguals increases attentional capacity, or draws on the available resources such that they need to be economised to support optimal task performance. Monolingual and bilingual children aged 7-12 attended to a narrative presented in one ear, while ignoring different types of interference in the other ear. We used EEG to capture the neural encoding of attended and unattended speech envelopes, and assess how well they can be reconstructed from the responses of the neuronal populations that encode them. Despite equivalent behavioral performance, monolingual and bilingual children encoded attended speech differently, with the pattern of encoding across conditions in bilinguals suggesting a redistribution of the available attentional capacity, rather than its enhancement.


In vitro susceptibilities of the Bacteroides fragilis group species: change in isolation rates significantly affects overall susceptibility data.
A comparison of antimicrobial susceptibility data of species of the Bacteroides fragilis group for 1989-1990 and 1998-1999 studies showed statistically significant increases or decreases in in vitro activity. Overall significant increases in resistance were noted for ampicillin-sulbactam and clindamycin, while significant decreases in resistance were noted for ertapenem and cefoxitin. Susceptibilities to piperacillin-tazobactam, imipenem, meropenem, and trovafloxacin remained virtually the same for the two studies. Importantly, a change in the rates of isolation of the various species showed the B. fragilis species comprised 58% of the isolates in 1989 to 1990 and 45% of the isolates in 1998 to 1999. This change in rates of isolation of B. fragilis versus non-B. fragilis species had an overall effect on susceptibility data.


The chromatographic assay of 4-hydroxynonenal as a biomarker of diseases by means of MEPS and HPLC technique.
The aim of this study was to develop and validate a new analytical method for the determination of 4-hydroxy-2-nonenal (4-HNE) in biological samples while applying microextraction by packed sorbent as a sample preparation method and HPLC with UV-vis detection. Various microextraction by packed sorbent (MEPS) sorbents like C2 , C8 , C18 , M1 (80% C8 and 20% SCX) and silica were used to separate 4-HNE from biological samples. The highest affinity of 4-HNE was observed for sorbents like C18 . The extraction efficiency was in the range from 47.4 to 89.2% dependent on the concentration of 4-HNE. Lower efficiency of 4-HNE extraction was obtained with use of MEPS packings such as C8 and M1. The extraction efficiency was in the range from 35.2 to 66.3% for packing C8 and from 34.2 to 64.3% for packing M1, respectively. The limit of detection and lower limit of quantitation for UV-vis detection were respectively 4.5 and 9.0 nmol/mL. The proposed method can be used for the evaluation of extraction efficiency of 4-HNE in biological sample because the values of lower limit of quantitation are lower than the determined amounts of the analyte in samples. The method yields excellent performance of quantification and identification in analysis of inflammation biomarkers.


Added therapeutic value of new drugs approved in Brazil from 2004 to 2016.
This study aimed to assess the level of therapeutic innovation of new drugs approved in Brazil over 13 years and whether they met public health needs. Comparative descriptive analysis of therapeutic value assessments performed by the Brazilian Chamber of Drug Market Regulation (CMED) and the French drug bulletin Prescrire for new drugs licensed in Brazil, from January 1st 2004 to December 31st 2016. The extent to which new drugs met public health needs was examined by: checking inclusions into government-funded drug lists and/or clinical guidelines; comparing Anatomical Therapeutic Chemical Classification (ATC) codes and drug indications with the list of conditions contributing the most to the national disease burden; and assessing new medicines aimed to treat neglected diseases. 253 new drugs were approved. Antineoplastics, immunossupressants, antidiabetics and antivirals were the most frequent. Thirty-three (14%) out of 236 drugs assessed by the Brazilian chamber and sixteen (8.2%) out of 195 assessed by the French bulletin Prescrire were considered innovative. Thirty-six drugs (14.2%) were selected for coverage by the Brazilian Unified National Health System (SUS), seven of which were therapeutically innovative, and none were aimed to treat neglected disease. About 1/3 of the drugs approved aimed to treat conditions among the top contributors to Brazil's disease burden. Few therapeutically innovative drugs entered the Brazilian market, from which only a small proportion was approved to be covered by the SUS. Our findings suggest a divergence between public health needs, research & development (R&D) and drug licensing procedures.


Biotransformation of Dehydroabietic, Abietic, and Isopimaric Acids by Mortierella isabellina Immobilized in Polyurethane Foam.
Polyurethane foam supports immobilization of Mortierella isabellina ATCC 38063, a zygomycete that hydroxylates and thereby detoxifies resin acids found in certain pulp mill effluents. The fungus becomes entrapped as it threads growing mycelia through the open foam matrix. The tenacity of binding and the amount of biomass bound depend on initial spore numbers and nutrient concentration. Optimal dehydroabietic acid transformation occurs with early-stationary-phase foam-bound mycelia suspended in buffer at pH 6.5 to 8.5 with aeration >0.1 liter liter min and near a temperature maximum of 33 degrees C. Neither a greater number of similarly loaded foam cubes nor a greater surface area for similar amounts of biomass increased transformation rates. Compared to free mycelial cultures, foam presence retards growth and decreases the rate of precursor transformation but does not alter the nature of the metabolites formed from dehydroabietic acid, abietic acid, or isopimaric acid. Diffusional barriers or binding of substrates in an inaccessible manner may cause the observed inhibitions. Overall, foam immobilization stabilizes enzymic activity and is a facile laboratory process with scaleup potential.


Seroprevalence of Epstein-Barr virus antibody among children in various age groups in Bangkok, Thailand.
There are no current data on previous Epstein-Barr virus (EBV) infections in different age groups of Thai children. This study was conducted to determine the prevalence of anti-EBV IgG antibody in healthy children of various age ranges in Bangkok, Thailand. Between June and December 1998, blood samples were collected from 425 volunteers aged 6 months to 15 years who attended a well baby clinic in the northern suburban part of Bangkok, Thailand. Serum samples were assayed for specific anti-EBV IgG antibodies using a commercial enzyme-linked immunosorbent assay kit. The percentage of children with positive anti-EBV IgG antibody increased with advancing age. The overall seropositivity rate was 72.7%. Children with anti-EBV IgG antibody were significantly older than those without the antibody. Seronegative children were reared at home significantly more frequently than seropositive children. These seroopidemiologic data will guide calculation of the appropriate age for administration of an EBV vaccine to children, when it becomes available.


A double-blind comparison of clomipramine and desipramine in the treatment of trichotillomania (hair pulling)
Trichotillomania, an irresistible impulse to pull out one's own hair, is a chronic psychiatric illness that causes severe discomfort, interferes with daily activities, and leads to social isolation. Treatment is usually unsatisfactory. Thirteen women with severe trichotillomania completed a 10-week double-blind, crossover trial of clomipramine, a new tricyclic antidepressant agent with selective antiobsessional effects, and desipramine, a standard tricyclic antidepressant. Treatment with clomipramine resulted in significantly greater improvement in symptoms than desipramine, as indicated by physicians' ratings of the women's clinical progress on a scale in which lower scores indicate improvement (mean [+/- SD] scores: at base line, 10.0; after desipramine treatment, 8.7 +/- 2.4; after clomipramine treatment, 4.7 +/- 3.1; P = 0.006) and by scores on a trichotillomania-impairment scale, in which higher scores indicate greater impairment (at base line, 6.8 +/- 1.7; after desipramine treatment, 6.2 +/- 1.7; after clomipramine treatment, 4.2 +/- 2.7; P = 0.03). The severity of symptoms (mean base-line score, 15.9 +/- 3.8) was reduced more by clomipramine (10.6 +/- 6.4) than by desipramine (14.4 +/- 3.9). The patients reported that the compulsion decreased in intensity and that they were more able to resist the urge to pull out their hair during treatment with clomipramine. We conclude that clomipramine appears to be effective in the short-term treatment of trichotillomania.


Stable radical trianions from reversibly formed sigma-dimers of selenadiazoloquinolones studied by in situ EPR/UV-vis spectroelectrochemistry and quantum chemical calculations.
The redox behavior of the series of 7-substituted 6-oxo-6,9-dihydro[1,2,5]selenadiazolo[3,4-h]quinolines and 8-substituted 9-oxo-6,9-dihydro[1,2,5]selenadiazolo[3,4-f]quinolines with R(7), R(8) = H, COOC(2)H(5), COOCH(3), COOH, COCH(3), and CN has been studied by in situ EPR and EPR/UV-vis spectroelectrochemistry in dimethylsulfoxide. All selenadiazoloquinolones undergo a one-electron reduction process to form the corresponding radical anions. Their stability strongly depends on substitution at the nitrogen atom of the 4-pyridone ring. The primary generated radical anions from N-ethyl-substituted quinolones are stable, whereas for the quinolones with imino hydrogen, the initial radical anions rapidly dimerize to produce unusually stable sigma-dimer (σ-dimer) dianions. These are reversibly oxidized to the initial compounds at potentials considerably less negative than the original reduction process in the back voltammetric scan. The dimer dianion can be further reduced to the stable paramagnetic dimer radical trianion in the region of the second reversible reduction step. The proposed complex reaction mechanism was confirmed by in situ EPR/UV-vis cyclovoltammetric experiments. The site of the dimerization in the σ-dimer and the mapping of the unpaired spin density both for radical anions and σ-dimer radical trianions with unusual unpaired spin distribution have been assigned by means of density functional theory calculations.


Low oxygen tension suppresses the death of chondrocyte-like ATDC5 cells induced by interleukin-1ß.
The articular cartilage is an avascular tissue, and oxygen tensions in its superficial and deeper zones are estimated to be 6% and 1%. Degeneration of the articular cartilage begins from the surface zone in osteoarthritis. We previously reported that monocarboxylate transporter-1, a transmembrane transporter for monocarboxylates, played an essential role in the interleukin-1β-induced expression of NADPH oxidase-2, a reactive oxygen species-producing enzyme, and reactive oxygen species-dependent death of mouse chondrogenic ATDC5 cells cultured in a normal condition (20% oxygen). Here, we investigated the effect of oxygen tension on interleukin-1β-induced events described above in ATDC5 cells. Interleukin-1β induced the death of ATDC5 cells under 20% and 6% oxygen but did not under 2% and 1% oxygen. Interleukin-1β induced Mct1 (monocarboxylate transporter-1 gene) and Nox2 (NADPH oxidase-2 gene) mRNAs' expression under 20% oxygen in 24 h, respectively, but not under 2% oxygen. On the other hand, a 24-h incubation with interleukin-1β upregulated the expression of Nos2 (inducible nitric oxide synthase gene) mRNA irrespective of oxygen tension. Furthermore, inhibition of I-κB kinase suppressed the interleukin-1β-induced expression of Mct1 mRNA in the cells cultured under 20% and 2% oxygen, indicating NF-κB plays an essential role in the induction of the Mct1 gene expression. The results suggest that interleukin-1β induces monocarboxylate transporter-1 in an oxygen tension-dependent manner required for cell death in ATDC5 cells. These results might explain some part of the degenerative process of the articular cartilage, which begins from its superficial zone in the pathogenesis of osteoarthritis.


Fluorescence Resonance Energy Transfer Aptasensor of Ochratoxin A Constructed Based on Gold Nanorods and DNA Tetrahedrons.
Ochratoxin A (OTA) contamination of corn has received significant attention due to the wide distribution and high toxicity of OTA. The maximum residue limit standard of OTA in corn has been established by the Chinese Government and other unions. Nanoparticle-based fluorescence resonance energy transfer (FRET) assays are promising methods for the sensitive and fast detection of OTA. However, satisfactory detection sensitivity is commonly achieved with complicated signal amplification processes or specific nanoparticle morphologies, which means that these assays are not conducive to fast detection. This study proposes a simple and novel strategy to improve the sensitivity of FRET aptasensors. In this strategy, a DNA tetrahedron was first used in gold nanorod-based FRET aptasensors. DNA tetrahedron-modified gold nanorods are used as fluorescent acceptors, and Cy5-modified complementary sequences of the OTA aptamer are used as fluorescent donors. The aptamers of OTA are embedded in the DNA tetrahedrons, and FRET occurs when the aptamers hybridize with the Cy5-modified complementary sequences. The aptamer-integrated DNA tetrahedron modified on the surface of gold nanorods acts as an anchor, thus avoiding the crowding and entanglement of aptamers. Due to the competitive combination between the OTA aptamers and complementary sequences, the greater the amount of OTA, the less the amount of Cy5-modified complementary sequences that bind with the aptamers and the less the amount of Cy5 that is quenched. Thus, the fluorescence intensity is positively related to the OTA concentration. In this study, in the concentration range of 0.01-10 ng/mL, the fluorescence intensity was found to be linearly related to the logarithmic concentration of OTA. The limit of detection was calculated to be 0.005 ng/mL. The specificity of the developed biosensor was demonstrated to be efficient. The accuracy and stability of the developed aptasensor were also tested, and the method exhibited good performance in real samples.


A20 and ABIN-1 synergistically preserve intestinal epithelial cell survival.
A20 (TNFAIP3) and ABIN-1 (TNIP1) are candidate susceptibility genes for inflammatory bowel disease and other autoimmune or inflammatory diseases, but it is unclear how these proteins interact in vivo to prevent disease. Here we show that intestinal epithelial cell (IEC)-specific deletion of either A20 or ABIN-1 alone leads to negligible IEC loss, whereas simultaneous deletion of both A20 and ABIN-1 leads to rapid IEC death and mouse lethality. Deletion of both A20 and ABIN-1 from enteroids causes spontaneous cell death in the absence of microbes or hematopoietic cells. Studies with enteroids reveal that A20 and ABIN-1 synergistically restrict death by inhibiting TNF-induced caspase 8 activation and RIPK1 kinase activity. Inhibition of RIPK1 kinase activity alone, or caspase inhibition combined with RIPK3 deletion, abrogates IEC death by blocking both apoptosis and necroptosis in A20 and ABIN-1 double-deficient cells. These data show that the disease susceptibility proteins A20 and ABIN-1 synergistically prevent intestinal inflammation by restricting IEC death and preserving tissue integrity.


Experimentally induced toxic-haemolytic anaemia in laboratory rats following phenacetin administration.
In an attempt to give assistance in the search for a simple haematological system for the detection of toxic-haemolytic effects of chemical substances, we used a battery of simple tests and phenacetin as a reference substance. The drug was administered in a single dose or repeatedly for two or four weeks. Higher plasma haemoglobin levels and symptoms of anaemia (decreased blood haemoglobin levels, erythrocytic counts, haematocrit) and activated erythropoiesis (increased reticulocyte counts, MCV, marrow and splenic E:M ratios) were found to be best marked following administration of phenacetin in the very high dose of 1.0 g/kg per orally for two weeks. Our results suggest that plasma haemoglobin levels could provide information on the haemolytic potential of phenacetin if the experimental schedule included the optimal combination of suitable phenacetin dosage and duration of loading.


[Does non-quantum secretion of acetylcholine from motor neuron endings participate in the neurotrophic control of the membrane potential of muscle fibers in the rat?].
The resting membrane potential of synaptic zone of muscle fibres within 2-3 mm (near) and 9-11 mm (far) of the nerve section of the rat diaphragm muscle was measured after 3 hours or on the 5th day after the motor nerve section. The membrane potential of "near" fibres was lower than that of "far" fibres. The presence of carbamylcholine or cGMP in the culture medium maintained the membrane potential of "near" fibres close to that of "far" fibres. Ouabain prevented these effects. On the 5th day after the nerve section the presence of carbamylcholine or cGMP had no effect on the membrane potential. In the in vitro experiments the nonquantal acetycholine release was equal in "near" and "far" fibres and just the same as in the control preparations. A conclusion is made that synaptic acetylcholine from motor nerve endings in nonquantal form does not play a significant role in neurotrophic control of the resting membrane potential of muscle fibres membrane in mammals.