The tachykinin peptide neurokinin B binds copper forming an unusual [CuII(NKB)2] complex and inhibits copper uptake into 1321N1 astrocytoma cells.
Neurokinin B (NKB) is a member of the tachykinin family of neuropeptides that have neuroinflammatory, neuroimmunological, and neuroprotective functions. In a neuroprotective role, tachykinins can help protect cells against the neurotoxic processes observed in Alzheimer's disease. A change in copper homeostasis is a clear feature of Alzheimer's disease, and the dysregulation may be a contributory factor in toxicity. Copper has recently been shown to interact with neurokinin A and neuropeptide γ and can lead to generation of reactive oxygen species and peptide degradation, which suggests that copper may have a place in tachykinin function and potentially misfunction. To explore this, we have utilized a range of spectroscopic techniques to show that NKB, but not substance P, can bind Cu(II) in an unusual [Cu(II)(NKB)2] neutral complex that utilizes two N-terminal amine and two imidazole nitrogen ligands (from each molecule of NKB) and the binding substantially alters the structure of the peptide. Using 1321N1 astrocytoma cells, we show that copper can enter the cells and subsequently open plasma membrane calcium channels but when bound to neurokinin B copper ion uptake is inhibited. This data suggests a novel role for neurokinin B in protecting cells against copper-induced calcium changes and implicates the peptide in synaptic copper homeostasis.


Maryland Dental Hygienists' Association Rehabilitation Committee.
The Maryland Dental Hygienists' Association Rehabilitation Committee was formed in 1990 and is patterned after the Maryland State Dental Association (MSDA) Dentists' Well-Being Committee. The Rehabilitation Committee serves to assist dental hygienists who may be impaired by alcohol or drug abuse; chemical dependency; or other physical, emotional, or mental conditions.


Lactoferrin-lipopolysaccharide interactions. Effect on lactoferrin binding to monocyte/macrophage-differentiated HL-60 cells.
Lactoferrin (LF) has been implicated in a number of functions including the negative regulation of myelopoiesis in vitro and in vivo, an effect mediated by suppression of cytokine release from monocytes/macrophages. This suppression is abrogated by bacterial LPS. In the present study, HL-60 cells were induced to differentiate to monocytes/macrophages by 12-O-tetradecanoyl phorbol-13-acetate, and LF-binding assays were performed. After differentiation, HL-60 cells showed a twofold increase of LF-binding sites with no difference in the specificity or affinity of LF between pre- and post-differentiated cells. CD11a, CD11b, and CD11c Ag, which have been associated with specific binding sites for LPS on monocytes/macrophages, were also increased three- to fourfold after differentiation. With the use of this system, the effect of LPS on LF binding was studied. At 37 degrees C, LPS enhanced LF binding on HL-60 cells, especially after differentiation. Conversely, at 4 degrees C, LPS inhibited LF binding. There was little effect of temperature on LF binding in the absence of LPS. In the presence of polymyxin B sulfate, the enhanced LF binding by LPS was abrogated. Also, pretreatment with mAbCD11 and/or mAb5D3, which are associated with or directed against candidate LPS receptors, reduced LF binding. Cross-linking studies using an iodinated, photoactivatable LPS derivative ([125I]ASD-LPS) demonstrated directly the specific binding of LPS to LF. These data indicate a dichotomous nature of LF binding on monocyte/macrophage-differentiated HL-60 cells--one being mediated by specific LF receptors whereas the other is apparently mainly via LPS receptors after formation of an LF-LPS complex. These interactions, for which a model is proposed, help to explain the mechanism behind LPS abrogation of the myelopoietic suppressive effects of LF, and a situation that probably occurs during bacterial infection.


Absorption and screening in Phycomyces.
In vivo absorption measurements were made through the photosensitive zones of Phycomyces sporangiophores and absorption spectra are presented for various growth media and for wavelengths between 400 and 580 mmicro. As in mycelia, beta-carotene was the major pigment ordinarily found. The addition of diphenylamine to the growth media caused a decrease in beta-carotene and an increase in certain other carotenoids. Growth in the dark substantially reduced the amount of beta-carotene in the photosensitive zone; however, growth on a lactate medium failed to suppress beta-carotene in the growing zone although the mycelia appeared almost colorless. Also when diphenylamine was added to the medium the absorption in the growing zone at 460 mmicro was not diminished although the colored carotenoids in the bulk of the sporangiophore were drastically reduced. Absorption which is characteristic of the action spectra was not found. Sporangiophores immersed in fluids with a critical refractive index show neither positive nor negative tropism. Measurements were made of the critical refractive indices for light at 495 and 510 mmicro. The critical indices differed only slightly. Assuming primary photoreceptors at the cell wall, the change in screening due to absorption appears too large to be counterbalanced solely by a simple effect of the focusing change. The possibility is therefore advanced that the receptors are internal to most of the cytoplasm; i.e., near the vacuole.


Assessment of cortical bone fracture resistance curves by fusing artificial neural networks and linear regression.
Bone injures (BI) represents one of the major health problems, together with cancer and cardiovascular diseases. Assessment of the risks associated with BI is nontrivial since fragility of human cortical bone is varying with age. Due to restrictions for performing experiments on humans, only a limited number of fracture resistance curves (R-curves) for particular ages have been reported in the literature. This study proposes a novel decision support system for the assessment of bone fracture resistance by fusing various artificial intelligence algorithms. The aim was to estimate the R-curve slope, toughness threshold and stress intensity factor using the two input parameters commonly available during a routine clinical examination: patients age and crack length. Using the data from the literature, the evolutionary assembled Artificial Neural Network was developed and used for the derivation of Linear regression (LR) models of R-curves for arbitrary age. Finally, by using the patient (age)-specific LR models and diagnosed crack size one could estimate the risk of bone fracture under given physiological conditions. Compared to the literature, we demonstrated improved performances for estimating nonlinear changes of R-curve slope (R2 = 0.82 vs. R2 = 0.76) and Toughness threshold with ageing (R2 = 0.73 vs. R2 = 0.66).


A field study on the anthelmintic resistance of Parascaris spp. in Arab foals in the Riyadh region, Saudi Arabia.
In the last decade, Parascaris spp. resistance to anthelmintics has been recorded in many countries. In Saudi Arabia, there are limited data available on Parascaris spp. resistance to anthelmintics. To determine the current status of ivermectin, abamectin and praziquantel combined, and fenbendazole resistance to Parascaris spp. in horses in Saudi Arabia. Three hundred and forty-one foals from eleven different farms were examined by faecal egg count (FEC). The foals were all Arab horses aged 17.2 ± 4.5 (SD) months. Ivermectin (n = 46 foals), abamectin and praziquantel combined (n = 46), and fenbendazole (n = 46) were administered on day 0 and faeces were collected on day 14. The study comprised 41 untreated foals as controls. Animals that have FEC of ≥100 eggs per gram (EPG) were used to measure anthelmintic efficacy. Parascaris spp. populations were considered susceptible when faecal egg count reduction (FECR) was ≥95% associated with a lower 95% confidence limit (LCL) >90%, suspected resistant when FECR ≤90% or LCL <90% and resistant when FECR <90% and LCL <90%. Prevalence of Parascaris spp. infection was 53% (179/341 horses). Anthelmintic resistance to Parascaris spp. were highest following fenbendazole (55% of farms and 65% of foals) and to a lower extent following ivermectin or the combination of abamectin and praziquantel which comprised 27% of farms (and 46% of foals) and 18% of farms (and 10% of foals), respectively. These data indicate that anthelmintics-resistant Parascaris spp. populations are present on horse farms in Saudi Arabia.


Differences between gastric signet-ring cell carcinoma and poorly differentiated adenocarcinoma: A comparison of histopathologic features determined by mucin core protein and trefoil factor family peptide immunohistochemistry.
We investigated differences between the pathological features of gastric signet-ring cell carcinoma (sig) and poorly differentiated adenocarcinoma (por) by examining the expressions of the trefoil factor family peptides (TFFs) and mucin core proteins (MUCs). Ninety-seven tissues of 97 gastric cancer patients were selected for this study. After gastrectomy, the major histopathologic types were determined to be sig, solid-type poorly differentiated adenocarcinoma (por1), non-solid type poorly differentiated adenocarcinoma (por2), and well-differentiated tubular adenocarcinoma (tub1). We evaluated the prevalence of positive staining for MUCs (MUC5AC and MUC2) and TFFs (TFF1 and TFF3) and assessed the correlation between MUCs and TFFs in each histopathological type. The rate of MUC2 expression significantly differed between sig and por2 (50.0% vs 11.7%, P = 0.011). TFF3 expression in sig significantly differed from TFF3 expression in both por2 (100% vs 17.6%, P < 0.0001) and por1 (100% vs 33.3%, P = 0.0004). MUC5AC and TFF1 expressions were significantly correlated in por1 (r = 0.705, P = 0.002), por2 (r = 0.535, P = 0.0009), and tub1 (r = 0.470, P = 0.0034), while MUC2 and TFF3 expressions were significantly correlated only in sig (r = 0.593, P = 0.040). The expression and correlation patterns of the TFFs and MUCs suggest that the histopathologic features of gastric sig differ from those of por.


Mobile string-like thrombus on the calcified aortic valve in cardioembolic stroke--a case report.
The calcified aortic valve has been associated with being a possible source of emboli in cardioembolic stroke. However, thrombus on the calcified aortic valve has not been identified with two-dimensional echocardiography. A seventy-two-year-old woman with calcified aortic stenosis was admitted with brain embolism. She had not previously received any platelet antiaggregant or anticoagulant. At admission, two-dimensional echocardiography demonstrated a mobile string-like abnormal echo attached to the calcified aortic valve, which showed regression and enlargement repeatedly during admission. No symptoms or clinical data suggested infective endocarditis or nonbacterial thrombotic endocarditis. After commencement of antiplatelet therapy, the abnormal echo regressed and disappeared. She continued to take the medication for seven months and then discontinued. Three months later, she developed recurrence of stroke, and an abnormal echo on the calcified aortic valve was again detected by two-dimensional echocardiography. The authors believe that the abnormal echo on the calcified aortic valve was thrombus and that it was the embolic source. Calcified aortic valve may thus be a causative lesion for mobile string-like thrombus. Two-dimensional echocardiography should be performed repeatedly in patients with calcified aortic valve and brain embolism.


Pulmonary venoocclusive disease in pregnancy.
A 23-year-old woman in her 27th week of gestation presented with clinical findings of progressive pulmonary hypertension. After cardiac catheterization she went into labor and was delivered by cesarean section. She died shortly thereafter from right heart failure. Pulmonary venoocclusive disease was found at autopsy. Hemodynamic changes during pregnancy, labor, delivery, and the postpartum period may have contributed to her deterioration and death. This is the first description of pulmonary venoocclusive disease in pregnancy.


Differences in the diagnosis and management of type 2 diabetes in 3 countries (US, UK, and Germany): results from a factorial experiment.
This article examines the diagnosis and management of type-2 diabetes when exactly the same "patient" is encountered by 192 randomly selected primary care doctors in 3 different health care systems--the United States, United Kingdom, and Germany. We conducted a factorial experiment, employing 2 clinically authentic filmed scenarios, to examine country differences in the treatment of diabetes, while controlling the effects of selected characteristics of patients and physicians. The patient in the first scenario presented with (undiagnosed) signs and symptoms strongly suggestive of diabetes, while the second scenario presented an already diagnosed patient with an emerging foot neuropathy. Physicians were asked how they would diagnose and manage the patients after watching the video vignettes using a questionnaire with standardized and open-ended questions. Regarding the first (undiagnosed) case, US doctors would ask significantly more questions than physicians from the UK and Germany (P < 0.001). German physicians would give less advice but would want to see the patient again much sooner (P < 0.001). Regarding the diagnosed case with an emerging foot neuropathy, US physicians would be most active in terms of questioning, testing, prescribing, and advice giving. Again, physicians from Germany would be less active in terms of therapeutic strategies but they would like to see the patient again sooner (P = 0.005). Although physicians in the 3 countries encountered exactly the same patient, differences in diagnostic and management decisions were evident. The experimental design provides unconfounded estimates of health system differences while simultaneously controlling for the effects of selected patient attributes and physician characteristics.


Continuous positive airway pressure-associated cutaneous amoebiasis in an immunosuppressed patient.
Organisms of the genus Acanthamoeba are environmentally ubiquitous and colonizers of the oral mucosa in humans. While largely asymptomatic in healthy persons, Acanthamoeba infection can cause disseminated disease with poor prognosis in immunosuppressed populations. Here we report a unique case of cutaneous amoebiasis associated with continuous positive airway pressure use in an immunosuppressed patient.


Intramedullary nailing of proximal quarter tibial fractures.
To report the results of intramedullary nailing of proximal quarter tibial fractures with special emphasis on techniques of reduction. Retrospective clinical study. Level 1 trauma center. During a 36-month period, 456 patients with fractures of the tibial shaft (OTA type 42) or proximal tibial metaphysis (OTA type 41A2, 41A3, and 41C2) were treated operatively at a level 1 trauma center. Thirty-five patients with 37 fractures were treated primarily with intramedullary nailing of their proximal quarter tibial fractures and formed the study group. Thirteen fractures (35.1%) were open and 22 fractures (59.5%) had segmental comminution. Three fractures had proximal intraarticular extensions. Alignment and reduction postoperatively and at healing. An angular malreduction was defined as greater than 5 degrees in any plane. Fractures extended proximally to an average of 17% of the tibial length (range, 4% to 25%). The average distance from the proximal articular surface to the fracture was 67.8 mm (range, 17 mm to 102 mm, not corrected for distance magnification, included for preoperative planning purposes only). Postoperative angulation was satisfactory (average coronal and sagittal plane deformity of less than 1 degree) as was the final angulation. Acceptable alignment was obtained in 34 of 37 fractures (91.9%). Two patients had 5-degree coronal plane deformities (one varus and one valgus), and 1 patient had a 7-degree varus deformity. Two patients with open fractures with associated bone loss underwent a planned, staged iliac crest autograft procedure postoperatively. Four patients were lost to follow-up. In the remaining 31 patients with 33 fractures, the proximal tibial fractures united without additional procedures. No patient had any change in alignment at final radiographic evaluation. Secondary procedures to obtain union at the distal fracture in segmental injuries included dynamizations (n = 3) and exchange nailing (n = 1). Complications included deep infections in 2 patients that were successfully treated. Multiple techniques were required to obtain and maintain reduction prior to nailing and included attention to the proper starting point, the use of unicortical plates, and the use of a femoral distractor applied to the tibia. Simple articular fractures and extensions were not a contraindication to intramedullary fixation. The proximal tibial fracture healed despite open manipulations. Short plate fixations to maintain this difficult reduction, either temporary or permanent, were effective.


Attenuating microwave radiation by absorption through controlled nanoparticle localization in PC/PVDF blends.
Nanoscale ordering in a polymer blend structure is indispensable to obtain materials with tailored properties. It was established here that controlling the arrangement of nanoparticles, with different characteristics, in co-continuous PC/PVDF (polycarbonate/poly(vinylidene fluoride)) blends can result in outstanding microwave absorption (ca. 90%). An excellent reflection loss (RL) of ca. -71 dB was obtained for a model blend structure wherein the conducting (multiwall carbon nanotubes, MWNTs) and the magnetic inclusions (Fe3O4) are localized in PVDF and the dielectric inclusion (barium titanate, BT) is in PC. The MWNTs were modified using polyaniline, which facilitates better charge transport in the blends. Furthermore, by introducing surface active groups on BT nanoparticles and changing the macroscopic processing conditions, the localization of BT nanoparticles can be tailored, otherwise BT nanoparticles would localize in the preferred phase (PVDF). In this study, we have shown that by ordered arrangement of nanoparticles, the incoming EM radiation can be attenuated. For instance, when PANI-MWNTs were localized in PVDF, the shielding was mainly through reflection. Now by localizing the conducting inclusion and the magnetic lossy materials in PVDF and the dielectric materials in PC, an outstanding shielding effectiveness of ca. -37 dB was achieved where shielding was mainly through absorption (ca. 90%). Thus, this study clearly demonstrates that lightweight microwave absorbers can be designed using polymer blends as a tool.


Assessing managerial information needs: Modification and evaluation of the Hospital Shift Leaders' Information Needs Questionnaire.
The aims were (1) to evaluate the modified version of the Intensive Care Unit Information Need Questionnaire for the broader hospital setting, and (2) to describe the differences in respondents' managerial activities and information needs according to the position held by the respondent and the type of hospital unit. Information systems do not support managerial decision-making sufficiently and information needed in the day-to-day operations management in hospital units is unknown. An existing questionnaire was modified and evaluated. Shift leaders, that is, the nurses and physicians responsible for the day-to-day operations management in hospital units were reached using purposive sampling (n = 258). The questionnaire ascertained the importance of information. Cronbach's α ranged from .85-.96 for the subscales. Item - total correlations showed good explanatory power. Managerial activities and information needs differed between respondents in different positions, although all shared about one-third of important information needs. The response rate was 26% (n = 67). The validity and reliability of the questionnaire were good. Attention should be paid to the positions of shift leaders when developing information systems. The questionnaire can be used to determine important information when developing information systems to support day-to-day operations management in hospitals.


CyHV-3: the third cyprinid herpesvirus.
Common carp (including ornamental koi carp) Cyprinus carpio L. are ecologically and economically important freshwater fish in Europe and Asia. C. carpio have recently been endangered by a third cyprinid herpesvirus, known as cyprinid herpesvirus-3 (CyHV-3), the etiological agent of koi herpesvirus disease (KHVD), which causes significant morbidity and mortality in koi and common carp. Clinical and pathological signs include epidermal abrasions, excess mucus production, necrosis of gill and internal organs, and lethargy. KHVD has decimated major carp populations in Israel, Indonesia, Taiwan, Japan, Germany, Canada, and the USA, and has been listed as a notifiable disease in Germany since 2005, and by the World Organisation for Animal Health since 2007. KHVD is exacerbated in aquaculture because of the relatively high host stocking density, and CyHV-3 may be concentrated by filter-feeding aquatic organisms. CyHV-3 is taxonomically grouped within the family Alloherpesviridae, can be propagated in a number of cell lines, and is active at a temperature range of 15 to 28°C. Three isolates originating from Japan (KHV-J), USA (KHV-U), and Israel (KHV-I) have been sequenced. CyHV-3 has a 295 kb genome with 156 unique open reading frames and replicates in the cell nucleus, and mature viral particles are 170 to 200 nm in diameter. CyHV-3 can be detected by multiple PCR-based methods and by enzyme-linked immunosorbent assay. Several modes of immunization have been developed for KHVD; however, fish immunized with either vaccine or wild-type virus may become carriers for CyHV-3. There is no current treatment for KHVD.


Effects of Mini-Basketball Training Program on Executive Functions and Core Symptoms among Preschool Children with Autism Spectrum Disorders.
This study examined the effects of a 12-week mini-basketball training program (MBTP) on executive functions and core symptoms among preschoolers with autism spectrum disorder (ASD). In this quasi-experimental pilot study, 33 ASD preschoolers who received their conventional rehabilitation program were assigned to either a MBTP group (n = 18) or control group (n = 15). Specifically, the experimental group was required to take an additional 12-week MBTP (five days per week, one session per day, and forty minutes per session), while the control group was instructed to maintain their daily activities. Executive functions and core symptoms (social communication impairment and repetitive behavior) were evaluated by the Childhood Executive Functioning Inventory (CHEXI), the Social Responsiveness Scale-Second Edition (SRS-2), and the Repetitive Behavior Scale-Revised (RBS-R), respectively. After the 12-week intervention period, the MBTP group exhibited significantly better performances in working memory (F = 7.51, p < 0.01, partial η2 = 0.195) and regulation (F = 4.23, p < 0.05, partial η2 = 0.12) as compared to the control group. Moreover, the MBTP significantly improved core symptoms of ASD preschoolers, including the social communication impairment (F = 6.02, p < 0.05, partial η2 = 0.020) and repetitive behavior (F = 5.79, p < 0.05, partial η2 = 0.016). Based on our findings, we concluded that the 12-week MBTP may improve executive functions and core symptoms in preschoolers with ASD, and we provide new evidence that regular physical exercise in the form of a MBTP is a promising alternative to treat ASD.


Predictors of post-hospitalization recovery of renal function among patients with acute kidney injury requiring dialysis.
Acute kidney injury (AKI) requiring dialysis complicates 1% of all hospital admissions, and up to 30% of survivors will still require dialysis at hospital discharge. There is a paucity of data to describe the postdischarge outcomes or to guide evidence-based dialysis management of this vulnerable population. Single-center, retrospective analysis of 100 consecutive patients with AKI who survived to hospital discharge and required outpatient dialysis. Data collection included baseline characteristics, hospitalization characteristics, and outpatient dialysis treatment variables. Primary outcome was dialysis independence 90 days after discharge. Overall, 43% of patients recovered adequate renal function to discontinue dialysis, with the majority recovering within 30 days post discharge. Worse baseline renal function was associated with lower likelihood of renal recovery. In the first week postdischarge, patients with subsequent nonrecovery of renal function had greater net fluid removal (5.3 vs. 4.1 L, P = 0.037), higher ultrafiltration rates (6.0 vs. 4.7 mL/kg/h, P = 0.041) and more frequent intradialytic hypotension (24.6% vs. 9.3% with 3 or more episodes, P = 0.049) compared to patients that later recovered. A significant proportion of AKI survivors will recover renal function following discharge. Outpatient intradialytic factors may influence subsequent renal function recovery.


1H NMR chemical shifts of cyclopropane and cyclobutane: a theoretical study.
This study was undertaken in order to rationalize the peculiar (1)H NMR chemical shifts of cyclopropane (δ 0.22) and cyclobutane (δ 1.98) which are shifted upfield and downfield with respect to larger cycloalkanes (δ 1.44-1.54). This is conventionally accounted for by shielding contributions arising from an aromatic-like ring current in cyclopropane, involving six electrons in the three C-C bonds, and deshielding coming from the σ antiaromatic CC framework of cyclobutane. The shielding pattern arising from the cyclopropane and cyclobutane CC framework response to a perpendicular magnetic field was visualized as two-dimensional grid distribution of NICS values. Further insight into the origin of chemical shift values was obtained by the NCS-NBO analysis of proton shielding tensor. In the case of cyclopropane, the CC framework shielding pattern implies the existence of both delocalized and localized currents that have a dominant shielding effect on protons. The magnitude of C-H bonds shielding effect is significant, too. Unlike the conventional interpretation, the CC framework shields cyclobutane hydrogens, and its response to a perpendicular magnetic field is quite similar to responses of other planar σ CC frameworks.


Different methods to select the best extraction system for solid-phase extraction.
The optimization methods for planning a solid-phase extraction experiment are presented. These methods are based on a study of interactions between different parts of an extraction system. Determination of the type and strength of interaction depends on the physicochemical properties of the individual components of the system. The main parameters that determine the extraction properties are described in this work. The influence of sorbents' and solvents' polarity on extraction efficiency, Hansen solubility parameters and breakthrough volume determination on sorption and desorption extraction step are discussed.


A randomized controlled clinical trial of topical insulin-like growth factor-1 therapy for sudden deafness refractory to systemic corticosteroid treatment.
To date, no therapeutic option has been established for sudden deafness refractory to systemic corticosteroids. This study aimed to examine the efficacy and safety of topical insulin-like growth factor-1 (IGF-1) therapy in comparison to intratympanic corticosteroid therapy. We randomly assigned patients with sudden deafness refractory to systemic corticosteroids to receive either gelatin hydrogels impregnated with IGF-1 in the middle ear (62 patients) or four intratympanic injections with dexamethasone (Dex; 58 patients). The primary outcome was the proportion of patients showing hearing improvement (10 decibels or greater in pure-tone average hearing thresholds) 8 weeks after treatment. The secondary outcomes included the change in pure-tone average hearing thresholds over time and the incidence of adverse events. In the IGF-1 group, 66.7% (95% confidence interval [CI], 52.9-78.6%) of the patients showed hearing improvement compared to 53.6% (95% CI, 39.7-67.0%) of the patients in the Dex group (P = 0.109). The difference in changes in pure-tone average hearing thresholds over time between the two treatments was statistically significant (P = 0.003). No serious adverse events were observed in either treatment group. Tympanic membrane perforation did not persist in any patient in the IGF-1 group, but did persist in 15.5% (95% CI, 7.3-27.4%) of the patients in the Dex group (P = 0.001). The positive effect of topical IGF-1 application on hearing levels and its favorable safety profile suggest utility for topical IGF-1 therapy in patients with sudden deafness. UMIN Clinical Trials Registry Number UMIN000004366, October 30th, 2010.


Ketanserin in essential hypertension. Effects of blood pressure on renal hemodynamics.
Essential hypertension is a multifactorial disorder mediated by multiple mechanisms. Serotonin may cause vasoconstriction either directly or indirectly by amplifying the actions of vasoconstrictor substances. Clinical trials indicate that ketanserin, a serotonin antagonist, is effective in treating hypertension. It is desirable for an antihypertensive agent to enhance or preserve renal hemodynamic function. In this study, we evaluated the acute (1 week) and chronic (8 weeks) effects of ketanserin (20-40 mg twice a day) on glomerular filtration rate, renal plasma flow, and sodium excretion in patients with uncomplicated hypertension. Patients with untreated diastolic blood pressure (greater than 90 mm Hg) received either ketanserin or a placebo during an 8-week double-blind trial. Findings demonstrated that patients treated with ketanserin showed an increase in renal plasma flow compared with those who received placebo. Sodium excretion remained unchanged, indicating the absence of sodium retention during therapy. These results show that ketanserin lowers blood pressure in essential hypertension while preserving renal hemodynamics and function.


[Open antireflux surgery].
In over 80% of patients with gastroesophageal reflux disease, the Nissen antireflux fundoplication gives good long-term results. Dysphagia, inability to belch or vomit as well as the gas bloat syndrome are possible sequelae after fundoplication. The frequency of these symptoms could be reduced by modification of the original Nissen-Rossetti fundoplication into the so-called "floppy" Nissen fundoplication, a short and loose wrap of mobilized gastric fundus. Failures of the antireflux procedure are mainly due to disruption or displacement of the wrap with the telescope phenomenon. Here, reoperation with refashioning of the original wrap may lead to same functional results like a primary fundoplication. Technical alternatives may selectively be chosen, when gastroesophageal reflux disease is complicated by fixated hiatal hernia, esophageal shortening, or serious esophageal motility disorders. Such specific anatomic or functional abnormalities are detected by preoperative endoscopy, barium swallow, 24-h pH monitoring, and manometry. Alternative techniques are mainly transthoracic repairs, including the Nissen fundoplication, Collis gastroplasty, and the Belsey Mark IV. Modifications of the 360 degrees Nissen operation are partial fundoplications like the Hill repair and the Toupet dorsal fundoplication. Because of a high failure rate in the long-term follow-up, application of the ligamentum teres cardiopexy and of the Angelchik prosthesis is not recommended.


Patient versus health care provider perspectives on spirituality and spiritual care: the potential to miss the moment.
Spirituality and spiritual care are well recognized as important facets of patient care, particularly in the palliative care population. Challenges remain, however, in the provision of such care. This study sought to compare patient and health care professional (HCP) views on spirituality/spiritual care, originally with a view to exploring a simple question(s) HCP's could use to identify spiritual distress, but evolved further to a comparison of how patients and HCPs were both concordant and discordant in their thoughts, and how this could lead to HCP's 'missing' opportunities to both identify spirituality/spiritual distress and to providing meaningful spiritual care. Patients (n=16) with advanced illnesses and HCP's (n=21) with experience providing care to those with advanced disease were interviewed using a semi-structured interview guide. Qualitative analysis distress and spiritual care, and screening for spiritual distress). Within each category there were areas of both concordance and discordance. Most notably, HCP's struggled to articulate definitions of spirituality whereas patients generally spoke with much more ease, giving rich examples. Equally, HCP's had difficulty relating stories of patients who had experienced spiritual distress while patients gave ready responses. Key areas where HCP's and patients differed were identified and set up the strong possibility for an HCP to 'miss the moment' in providing spiritual care. These key misses include the perception that spiritual care is simply not something they can provide, the challenge in defining/ recognizing spirituality (as HCP and patient definitions were often very different), and the focus on spiritual care, even for those interested in providing, as 'task oriented' often with emphasis on meaning making or finding purpose, whereas patients much more commonly described spiritual care as listening deeply, being present and helping them live in the moment. Several discrepancies in perception of spirituality, spiritual distress and spiritual care may hinder the ability of HCP's to effectively offer meaningful spiritual care. A focus on active listening, being led by the patient, and by providing presence may help limit the risk of a disconnect, or a 'miss', in the provision of spiritual care.


In vivo production of A-protein, lipopolysaccharide, iron-regulated outer membrane proteins and 70-kDa serine protease by Aeromonas salmonicida subsp. salmonicida.
Using specific immunostaining of Western blots, the in vivo expression of several putative virulence factors of Aeromonas salmonicida subsp. salmonicida was demonstrated in infected muscle tissue of Atlantic salmon and rainbow trout. Three virulent isolates of A. salmonicida were used. One isolate was chosen because in vitro it was apparently a non-producer of the 70-kDa serine protease. Infected furuncle tissue was centrifuged and samples of the pellet and supernatant probed for evidence that the components of interest were bacterial cell-associated or secreted. The A-protein was detected in pelleted furuncle material but not in the supernatant. Lipopolysaccharide, both high and low molecular mass, was present in the pellet but only high molecular mass lipopolysaccharide was detected in the furuncle supernatant. Iron-regulated outer membrane proteins were detected in the furuncle pellet. The 70-kDa serine protease was detected in the furuncle supernatant of both protease-producing strains. However, whilst the protease-deficient isolate was demonstrated to produce low levels of the 70-kDa protease when grown in vitro under iron restricted conditions, none could be detected in vivo.


Contribution of the mGluR7 receptor to antiparkinsonian-like effects in rats: a behavioral study with the selective agonist AMN082.
Metabotropic glutamate receptors (mGluRs) have been shown to be potential targets for numerous neurological diseases, including Parkinson's disease (PD). We previously reported that ACPT-1, a non-selective group III mGluRs agonist, injected locally into the globus pallidus, striatum or substantia nigra pars reticulata (SNr), significantly attenuated the haloperidol-induced catalepsy in rats. N,N'-dibenzhydryl-ethane-1,2-diamine dihydrochloride (AMN082) is a potent, brain penetrating mGluR7 agonist, selective over other mGluRs. The aim of the present study was to determine whether (1) activation of mGluR7 by systemic administration of AMN082 may produce antiparkinsonian-like effects in the haloperidol-induced catalepsy and reserpine-induced akinesia models in rats; (2) striatal and nigral mGluR7 is likely to contribute to such an effect. We found that AMN082 (1 and 3 mg/kg) decreased the haloperidol (0.25 mg/kg)-induced catalepsy, but was not efficient in attenuating the reserpine (2.5 mg/kg)-induced akinesia. When given locally, AMN082 also significantly diminished catalepsy in rats; however, its effective striatal doses were 10-fold lower than those used in the SNr (2.5 and 7.5 pmol/0.5 μl/ side vs. 25 and 75 pmol/0.5 μl/side, respectively). The above findings support the idea that the activation of mGluR7 can produce antiparkinsonian-like effects in rats. Furthermore, our results indicate contribution of both striatal and nigral mGluR7 to the anticataleptic effects of AMN082.


Discordant patient pain level reporting between questionnaires and physician encounters of the same day.
We examined the consistency of pain reporting by patients in a community pain management practice in Michigan. We compared pain levels (range 0-10) entered by patients in questionnaires versus those provided during their face-to-face physician encounter on the same day. Both of these values were available for approximately 10,000 encounters during the study period (2010-2014). Two subpopulations of patients were identifiable. One was consistent in reporting worst or least pain levels on the questionnaire and during the provider encounter. The other was discordant. Factor analysis had previously identified severity scales for patient biopsychosocial characteristics derived from the full questionnaire. The two subpopulations differed in their factor profiles even though they had similar demographics. In general, pain reported directly to physicians was more correlated to biopsychosocial indicators. Pain self-reporting using questionnaires has often been assumed to be ground truth, but those obtained during the physician encounter may be more reliable.


Effects of dietary leucine on antioxidant activity and expression of antioxidant and mitochondrial-related genes in longissimus dorsi muscle and liver of piglets.
The study was conducted to investigate the effects of dietary leucine on antioxidant activity and expression of antioxidant- and mitochondrial-related genes in longissimus dorsi muscle and liver of piglets. Three diets were formulated with different levels of supplemented leucine (0%, 0.25%, 0.5%). Results showed that supplementation of 0.25% leucine significantly increased antisuperoxide anion (ASA) and antihydroxyl radical (AHR) levels and activities of total superoxide dismutade (T-SOD), glutathione peroxidase (GPx), glutathione S-transferase (GST), and total antioxidant capacity (T-AOC) in serum, longissimus dorsi muscle and liver of piglets as compared with the control group. The SOD2, catalase (CAT), GPx, GST, glutathione reductase (GR), and nuclear factor erythroid 2-related factor 2 (Nrf2) mRNA levels in longissimus dorsi muscle and liver were significantly increased by 0.25% leucine supplementation. However, the malondialdehyde (MDA) content and the mRNA level of Kelch-like ECH-associated protein 1 (Keap1) exhibited an opposite tendency. Additionally, supplementation of 0.25% leucine significantly increased the mRNA levels of mitochondrial-related genes in longissimus dorsi muscle and liver of piglets. Results suggested that supplementation of 0.25% leucine improved antioxidant activity and mitochondrial biogenesis and function of piglets, which was related to the increase in antioxidant enzymes activities and upregulation of expression of antioxidant- and mitochondrial-related genes.


Barcoding ciliates: a comprehensive study of 75 isolates of the genus Tetrahymena.
The mitochondrial cytochrome-c oxidase subunit 1 (cox1) gene has been proposed as a DNA barcode to identify animal species. To test the applicability of the cox1 gene in identifying ciliates, 75 isolates of the genus Tetrahymena and three non-Tetrahymena ciliates that are close relatives of Tetrahymena, Colpidium campylum, Colpidium colpoda and Glaucoma chattoni, were selected. All tetrahymenines of unproblematic species could be identified to the species level using 689 bp of the cox1 sequence, with about 11 % interspecific sequence divergence. Intraspecific isolates of Tetrahymena borealis, Tetrahymena lwoffi, Tetrahymena patula and Tetrahymena thermophila could be identified by their cox1 sequences, showing <0.65 % intraspecific sequence divergence. In addition, isolates of these species were clustered together on a cox1 neighbour-joining (NJ) tree. However, strains identified as Tetrahymena pyriformis and Tetrahymena tropicalis showed high intraspecific sequence divergence values of 5.01 and 9.07 %, respectively, and did not cluster together on a cox1 NJ tree. This may indicate the presence of cryptic species. The mean interspecific sequence divergence of Tetrahymena was about 11 times greater than the mean intraspecific sequence divergence, and this increased to 58 times when all isolates of species with high intraspecific sequence divergence were excluded. This result is similar to DNA barcoding studies on animals, indicating that congeneric sequence divergences are an order of magnitude greater than conspecific sequence divergences. Our analysis also demonstrated low sequence divergences of <1.0 % between some isolates of T. pyriformis and Tetrahymena setosa on the one hand and some isolates of Tetrahymena furgasoni and T. lwoffi on the other, suggesting that the latter species in each pair is a junior synonym of the former. Overall, our study demonstrates the feasibility of using the mitochondrial cox1 gene as a taxonomic marker for 'barcoding' and identifying Tetrahymena species and some other ciliated protists.


Prevalence of chronic pain with neuropathic characteristics in the general population.
We conducted a large nationwide postal survey to estimate the prevalence of chronic pain with or without neuropathic characteristics in the French general population. A questionnaire aimed at identifying chronic pain (defined as daily pain for at least 3 months), evaluating its intensity, duration and body locations, was sent to a representative sample of 30,155 subjects. The DN4 questionnaire was used to identify neuropathic characteristics. Of the questionnaires, 24,497 (81.2%) were returned and 23,712 (96.8%) could be assessed. Seven thousand five hundred and twenty-two respondents reported chronic pain (prevalence=31.7%; [95%CI: 31.1-32.3]) and 4709 said the pain intensity was moderate to severe (prevalence=19.9%; [95%CI: 19.5-20.4]). Neuropathic characteristics were reported by 1631 respondents with chronic pain (prevalence=6.9%; [95%CI: 6.6-7.2]), which was moderate to severe in 1209 (prevalence=5.1% [95%CI: 4.8-5.4]). A higher prevalence of chronic pain with neuropathic characteristics was associated with middle age (50-64 years), manual professions and those living in rural areas. It was more frequently located in the lower limbs and its intensity and duration were higher in comparison with chronic pain without neuropathic characteristics. This large national population-based study indicates that a significant proportion of chronic pain patients report neuropathic characteristics. We identified distinctive socio-demographic profile and clinical features indicating that chronic pain with neuropathic characteristics is a specific health problem.


Yttrium-90 -- current status, expected availability and applications of a high beta energy emitter.
Yttrium-90 ((90)Y, T(1/2) 64.14 h) is a key example of a high beta energy-emitting radionuclide which is available from the strontium-90 ((90)Sr)/(90)Y radionuclide generator system. Clinical uses of (90)Y-labeled radiopharmaceutical agents have been pursued for many years and many applications have proven to be clinical effective. These most notably include the application of 90Y-labeled antibodies for a variety of applications such as for effective treatment of non-Hodgkin's lymphoma. One of the major advantages for use of (90)Y is ready availability from the very long-lived (90)Sr parent (T(1/2) 28.78 y). Because of the importance of maintaining generator performance and minimizing parent breakthrough, this paper describes development, use and quality control of both high capacity cation adsorption-type and electrochemical generator systems. In addition, the preparation and targeting to tumors in mice of DOTA-conjugated Nimotuzamab (h-R3) antibody which recognizes the external domain of the EPFR antibody radiolabeled with (90)Y obtained from the electrochemical generator is also described. As a key example for clinical applications of (90)Y, the use of (90)Y-labeled biotin for intra-operative pre-targeting for radionuclide therapy (IART®) of breast cancer is also described.


Dysregulation of miR-223 constitutes a promising biomarker that informs about clinical outcomes of acute liver failure.
In this issue of Clinical Science, Schueller et al. [Clin. Sci. (2017) 131, 1971-1987] evaluated the role of miR-223 across multiple etiologies of acute and chronic liver insults in murine models and clinical samples. The authors find that while miR-223 is not mechanistically involved in liver injury, its intracellular levels in hepatocytes are increased upon hepatic damage in a broad panel of mechanistically distinct injury models. Furthermore, the authors provide evidence that circulating miR-223 levels provide a promising minimally invasive biomarker for acute liver failure (ALF) that defines a distinct subset of ALF cases and correlates with clinical outcomes. Combined, the highlighted study suggests that miR-223 constitutes a promising biomarker whose clinical validity and utility warrant further investigations.


A two-disease model of female breast cancer: mortality in 1969 among white females in the United States.
A mathematical model of the age distribution of breast cancer mortality was developed on the basis of the two-disease theory of breast cancer incidence. The model included representations of the time from tumor initiation to death, the competing risk effects of other disease, and differential susceptibility to each of the disease components. This model successfully predicted the single year of age frequency of breast canceomponents of this model was consistent with several epidemiologic findings. Most significantly, the age distribution of breast cancer deaths from premenopausal disease was consistent with incidence patterns in non-Western countries, where the incidence of the postmenopausal disease component was hypothesized to be lower because of nutritional differences.


Detection and molecular typing of Streptococcus suis in tonsils from live pigs in France.
Streptococcus suis is an important pathogen of swine, causing meningitis, arthritis, polyserositis, septicemia, and sudden death in weaning piglets as well as fattening pigs. Recently, 3 molecular tests have been developed in our laboratory: a multiplex polymerase chain reaction (m-PCR) assay for the detection of S. suis species and serotypes 2 and 1/2, and 2 molecular typing methods, pulsed-field gel electrophoresis and an approach based on PCR amplification of a fragment of rRNA genes, including a part of the 16S and 23S genes and the 16S-23S rDNA intergenic spacer region (ISR), followed by restriction fragment length polymorphism (RFLP) analysis (ISR-RFLP). In the present study, we used these tests to analyze tonsil samples from clinically healthy pigs and to identify individual isolates of S. suis during epidemiologic investigations of 8 related herds with a history of septicemia caused by S. suis serotype 2. Capsular typing showed that 58% of the strains were nontypable. Of the 17 serotypes present, serotype 22 was the most prevalent. In the 7 farms without clinical signs on the day of sampling, we detected S. suis serotype 2 or 1/2, or both, in less than 5% of the pigs by m-PCR or by bacteriologic culture. In the 8th farm, on which 2 pigs had clinical signs of septicemia on the day of sampling, we detected S. suis serotype 2 or 1/2, or both, by m-PCR in the tonsils of 40% of fattening pigs (21 wk old) that lacked symptoms. Molecular typing of the serotype 2 strains showed a common origin of contamination in these herds, given that 1 pattern (C1) was detected in the isolates from 6 of the 8 herds. However, up to 4 patterns were associated with septicemia and sudden death. Several patterns of S. suis serotype 2 can be responsible for disease in the same herd. These molecular tools may be useful for confident studies of the transmission of S. suis, thereby contributing to the control of S. suis infection.


Stimulation of glycine catabolism in isolated perfused rat liver by calcium mobilizing hormones and in isolated rat liver mitochondria by submicromolar concentrations of calcium.
Glucagon stimulates flux through the glycine cleavage system (GCS) in isolated rat hepatocytes (Jois, M., Hall, B., Fewer, K., and Brosnan, J. T. (1989) J. Biol. Chem. 264, 3347-3351. In the present study, flux through GCS was measured in isolated rat liver perfused with 100 nM glucagon, 1 microM epinephrine, 1 microM norepinephrine, 10 microM phenylephrine, or 100 nM vasopressin. These hormones increased flux through GCS in perfused rat liver by 100-200% above the basal rate. The possibility that the stimulation of flux by adrenergic agonists and vasopressin is mediated by increases in cytoplasmic Ca2+ which in turn could regulate mitochondrial glycine catabolism was examined by measuring flux through GCS in isolated mitochondria in the presence of 0.04-2.88 microM free Ca2+. Flux through GCS in isolated mitochondria was exquisitely sensitive to free Ca2+ in the medium; half-maximal stimulation occurred at about 0.4 microM free Ca2+ and maximal stimulation (7-fold) was reached when the free Ca2+ in the medium was 1 microM. The Vmax (nanomoles/mg protein/min) and Km (millimolar) values for the flux through GCS in intact mitochondria were 0.67 +/- 0.16 and 20.66 +/- 4.82 in the presence of 1 mM [ethylenebis(oxyethylenenitrilo)]tetraacetic acid and 3.28 +/- 0.76 and 10.98 +/- 1.91 in presence of 0.5 microM free Ca2+, respectively. The results show that the flux through GCS is sensitive to concentrations of calcium which would be achieved in the cytoplasm of hepatocytes stimulated by calcium-mobilizing hormones.


Prevalence and determinants of anticholinergic medication use in elderly dementia patients.
People with dementia are sensitive to cognitive side effects of anticholinergic drugs. However, little is known about the prevalence of anticholinergic medications and its predictors in a nationally representative sample of community-based elderly dementia patients in the USA. The objectives of the study were to determine the prevalence and predictors of anticholinergic drugs use in elderly dementia patients. The study involved retrospective analysis of the 2005-2009 Medical Expenditure Panel Surveys (MEPS), a nationally representative sample of the non-institutionalized US population. The study evaluated annual prevalence of anticholinergic drug use during the study period and factors associated with the use of anticholinergics among community-dwelling persons aged 65 and older with dementia. The anticholinergic drugs were identified using the Anticholinergic Drug Scale (ADS). Multiple logistic regression within the conceptual framework of the Anderson Behavioral Model was performed to identify predictors associated with clinically significant anticholinergic drug (ADS level 2 or 3) use. According to the MEPS, there were a total of 1.56 [95 % confidence interval (CI) 1.34, 1.73] million elderly dementia patients annually during the study period. Approximately, 23.3 % (95 % CI 19.2, 27.5) of elderly dementia patients used clinically significant anticholinergic agents (ADS level 2 or 3). Among the need factors, elderly dementia patients having mood disorders [odds ratio (OR) 2.19; 95 % CI 1.19, 4.06] and urinary incontinence (OR 6.58; 95 % CI 2.84, 15.29) were more likely to use drugs with clinically significant anticholinergic activities. Of the enabling factors, the odds of receiving higher-level anticholinergic drugs were significantly lower for patients who resided in the West region (OR 0.41; 95 % CI 0.17, 0.95) compared to the reference group, Northeast. Over one in five elderly dementia patients used drugs with clinically significant anticholinergic effects. Mood disorder, urinary incontinence, and region were significantly associated with use of these drugs. Concerted efforts are needed to improve the quality of medication use by focusing on clinically significant anticholinergic agents.


Tunnel enlargement after anterior cruciate ligament reconstruction in patients with post-operative septic arthritis.
Tunnel enlargement is a frequent issue after ACL reconstruction and the "synovial bathing effect" is thought to be among the biological factors contributing to this phenomenon. Since the amount and the pressure of the synovial fluid inside the knee joint are higher and the length of its presence is longer in patients with post-operative septic arthritis after ACL reconstruction, we reviewed the tunnel enlargement in these cases in order to better evaluate this phenomenon in such a hostile environment. The null hypothesis of this study was that the highly represented phenomenon of the "synovial bathing effect" that occurs in an infected ACL reconstruction would not affect the amount of post-operative tunnel widening. A case-control study was done. At a mean follow up of 10 months (range 9-11 months) eight patients with septic arthritis following ACL reconstruction (group A) were radiologically reviewed using a CT scan and the diameters of femoral and tibial tunnels were measured. The results were compared with a control group (B) of uncomplicated ACL reconstruction cases operated by the same surgeon using the same technique. Although patients of Group A experienced a bigger amount of tunnel enlargement than patients of group B both on femoral (9.53 +/- 1.07 vs. 9.35 +/- 1.52 mm) and tibial side (10.07 +/- 1.3 vs. 9.92 +/- 0.74 mm), no clinical or statistically significant differences were detected between the groups (P > 0.05). No significant tunnel enlargement could be detected in patients of group A when compared with patients of group B. This seems to minimize the role of biological factors contributing to tunnel widening.


Compact single-panel LCD projector with high uniformity.
In this study, we introduce a single-panel LCD projector that employs a direct-lit LED array as its illumination system. Each LED in the array is coupled to a Fresnel lens to ensure light collimation. To create a uniform light distribution on the LCD panel, the LED array is arranged in a hexagonal pattern. To eliminate the hotspot effects caused by individual LED units, the optical distance between each unit and the LCD panel is extended to allow sufficient light mixing. Köhler illumination is adopted to generate adequate and homogeneous illumination on the screen. With these design enhancements, we managed to shrink the system by 29% of the traditional designs and increase uniformity to 90.1%.


Aspects of common marmoset basic biology and life history important for biomedical research.
While common marmosets are increasingly used as alternative primate models in biomedical research, their life history, specialized behavior and unique physiology are not well known. This paper describes important marmoset attributes that are particularly relevant for biomedical research, including reproduction, neurobiology, immunology, endocrine signaling, obesity and aging, in addition to fetal and postnatal development. While common marmosets exhibit characteristic anthropoid primate traits, they clearly differ from Old World primates and humans in a variety of functions, including reproduction, endocrine signaling and immunology. These differences, however, permit the use of common marmosets in unconventional research strategies targeted on human pathology.


Atorvastatin reduces β-Adrenergic dysfunction in rats with diabetic cardiomyopathy.
In the diabetic heart the β-adrenergic response is altered partly by down-regulation of the β1-adrenoceptor, reducing its positive inotropic effect and up-regulation of the β3-adrenoceptor, increasing its negative inotropic effect. Statins have clinical benefits on morbidity and mortality in diabetic patients which are attributed to their "pleiotropic" effects. The objective of our study was to investigate the role of statin treatment on β-adrenergic dysfunction in diabetic rat cardiomyocytes. β-adrenergic responses were investigated in vivo (echocardiography) and ex vivo (left ventricular papillary muscles) in healthy and streptozotocin-induced diabetic rats, who were pre-treated or not by oral atorvastatin over 15 days (50 mg.kg-1.day-1). Micro-array analysis and immunoblotting were performed in left ventricular homogenates. Data are presented as mean percentage of baseline ± SD. Atorvastatin restored the impaired positive inotropic effect of β-adrenergic stimulation in diabetic hearts compared with healthy hearts both in vivo and ex vivo but did not suppress the diastolic dysfunction of diabetes. Atorvastatin changed the RNA expression of 9 genes in the β-adrenergic pathway and corrected the protein expression of β1-adrenoceptor and β1/β3-adrenoceptor ratio, and multidrug resistance protein 4 (MRP4). Nitric oxide synthase (NOS) inhibition abolished the beneficial effects of atorvastatin on the β-adrenoceptor response. Atorvastatin restored the positive inotropic effect of the β-adrenoceptor stimulation in diabetic cardiomyopathy. This effect is mediated by multiple modifications in expression of proteins in the β-adrenergic signaling pathway, particularly through the NOS pathway.


Computational Prediction of DrugTarget Interactions Using Chemical, Biological, and Network Features.
Drugtarget interactions (DTIs) are central to current drug discovery processes. Efforts have been devoted to the development of methodology for predicting DTIs and drugtarget interaction networks. Most existing methods mainly focus on the application of information about drug or protein structure features. In the present work, we proposed a computational method for DTI prediction by combining the information from chemical, biological and network properties. The method was developed based on a learning algorithm-random forest (RF) combined with integrated features for predicting DTIs. Four classes of drugtarget interaction networks in humans involving enzymes, ion channels, G-protein-coupled receptors (GPCRs) and nuclear receptors, are independently used for establishing predictive models. The RF models gave prediction accuracy of 93.52 %, 94.84 %, 89.68 % and 84.72 % for four pharmaceutically useful datasets, respectively. The prediction ability of our approach is comparative to or even better than that of other DTI prediction methods. These comparative results demonstrated the relevance of the network topology as source of information for predicting DTIs. Further analysis confirmed that among our top ranked predictions of DTIs, several DTIs are supported by databases, while the others represent novel potential DTIs. We believe that our proposed approach can help to limit the search space of DTIs and provide a new way towards repositioning old drugs and identifying targets.


n-3 Polyunsaturated fatty acid-enriched diet does not protect from liver injury but attenuates mortality rate in a rat model of systemic endotoxemia.
We investigated the potential of dietary fish oil containing n-3 polyunsaturated fatty acids to attenuate hepatic injury and mortality rate of rats in response to systemic endotoxemia. Prospective, randomized, controlled animal study. University laboratory. A total of 43 male Sprague Dawley rats. Rats were fed either fish oil supplement or regular standard lab chow. After 8 wks of feeding, each diet group was subjected to a single exposure of lipopolysaccharide (Escherichia coli, 10 mg/kg intravenously) or saline. Hepatic microvascular response and liver injury were assessed by in vivo analysis of Kupffer cell phagocytic activity, leukocyte-endothelial cell interaction, nutritive sinusoidal perfusion failure, and parenchymal cell apoptosis (intravital fluorescence epi-illumination technique) as well as bile flow, serum liver enzyme activities, and tissue histomorphology. In animals fed a standard diet, livers at 16 hrs after lipopolysaccharide-exposure exhibited depressed Kupffer cell phagocytic activity, enhanced hepatic microvascular leukocyte activation, leukocytic tissue infiltration, sinusoidal perfusion failure, and parenchymal cell apoptosis. Hepatic microvascular injury was further accompanied by reduced bile flow and enhanced liver enzyme release. The fish oil enriched diet did not significantly change the multiple features of endotoxemia-associated liver injury; however, it maintained arterial blood pressure, systemic leukocyte count, and acid base balance and showed a tendency toward improved survival on lipopolysaccharide exposure with a 16 hr-survival rate of 80% (p =.06 vs. survival rate of 40% in animals fed a regular diet). Moreover, slightly increased serum concentrations of interleukin-10 coincided with enhanced concentrations of interleukin-6 in fish oil fed endotoxemic animals. Healthy, non-lipopolysaccharide-exposed, fish oil fed animals did not differ from those fed with the regular diet, except for dampened Kupffer cell phagocytic activity. Fish oil feeding does not protect from local endotoxemia-induced hepatic microvascular dysfunction. However, dietary modulation of inflammatory mediator response by macrophages, constituting an appropriate immune response, could add to the survival advantage seen in fish oil-fed animals on exposure to lipopolysaccharide.


Sensitivity of FEV1 and Clinical Parameters in Children With a Suspected Asthma Diagnosis.
Asthma is the most common chronic disease in children and a robust diagnosis is crucial to optimize patient care and reduce its burden. To diagnose asthma in children, the Global Initiative for Asthma (GINA) recommendations propose a 12% improvement in forced expiratory volume in 1 second (FEV1) after a bronchodilation test. Nevertheless, such a criterion is rarely confirmed in these patients in clinical practice. The objective of this study was to evaluate the sensitivity of spirometric and clinical parameters in identifying children with possible asthma. The VERI-VEMS Study is a multicenter international retrospective cohort study. Data were collected, from January 2008 until January 2019, for all consecutive children (aged 5-18 years), with a diagnosis of asthma, who performed a spirometry at the time of the diagnosis. We compared the sensitivity of the reversibility criterion proposed by GINA guidelines, with other spirometric and clinical variables, using physician-diagnosed asthma and response to treatment as the standard. The study included 871 children. The reversibility criterion of 12% of FEV1 showed a sensitivity of 30.4%. The 3 best spirometric or clinical criteria were the presence of dry cough, or wheezing or atopy and dry cough, or wheezing or exercise-induced dyspnea, with a sensitivity reaching 99.5%, with no added value of the spirometric parameters in the calculation of the cumulated sensitivity for the diagnosis of pediatric asthma. Postbronchodilator reversibility of 12%, although essential for patients' follow-up, has an insufficient low sensitivity in reaching a diagnosis of asthma in pediatric patients, compared with a combination of clinical symptoms, that show a better sensitivity. Further studies on specificity will help clarify the role of this change in the diagnostic paradigm in formally diagnosing children with asthma.


Current challenges for doctors in India: Deprofessionalisation, reprofessionalisation or fragmentation?
Western-trained doctors in India struggled to establish themselves as a medical 'profession' in the 1920s and 1930s and these struggles continued into the post-colonial period. The direction of travel is, however, no longer clear. Increasing evidence of a crisis in doctors' collective ability to provide a form of self-regulation since 2000 is highlighted. India's Supreme Court suspended the operations of their country's medical councils in the face of a proliferation of poorly regulated private medical colleges. Practitioners of alternative systems of medicine and unqualified medical practice continue, while new 'short-course' doctors take over tasks previously restricted to fully fledged MBBS doctors. The diversification of the social origins of medical students, with rising numbers of doctors from a wider range of social backgrounds, threatens their aspirations to high status. There is little diminution of the earnings of elite doctors, yet their conditions of work are increasingly constrained by financial targets. Young doctors face uncertain futures. This article analyses the increasingly diverse occupational positions of doctors in India using a Bourdieusian lens and asks whether an alternative, stable form of institutional arrangements is emerging, as some have claimed, or if fragmentation is a more apt description.


Expression levels of serine/glycine metabolism-related proteins in triple negative breast cancer tissues.
To evaluate the expression levels of serine/glycine metabolism-related proteins (PHGDH, PSAT, PSPH, SHMT, and GLDC) in six different subtypes of triple negative breast cancer (TNBC) patients and gain insight into their implications. Formalin-fixed, paraffin-embedded tissues from 129 TNBC patients were assembled into tissue microarrays. Immunohistochemical staining was performed for serine/glycine metabolism-related proteins (PHGDH, PSAT, PSPH, SHMT, and GLDC) and surrogate immunohistochemical markers (CK5/6, EGFR, claudin 3, claudin 4, claudin 7, E-cadherin, STAT1, interleukin-8 [IL-8], AR, and GGT-1) for identifying the molecular subtype of TNBC. TNBC subtype classifications included the following: basal-like (CK5/6-positive and/or EGFR-positive), molecular apocrine (AR-positive and/or GGT-1-positive), claudin-low (claudin 3-, claudin 4-, claudin 7-negative and/or E-cadherin-negative), immune-related (IL-8-negative and stromal STAT1-positive), mixed (features from two or more of the four subtypes), and null (no features from any of the four subtypes). Tissues from basal marker-positive patients showed increased expression levels of tumoral PHGDH compared with those from basal marker-negative patients (p = 0.029); lack of stromal SHMT1 expression was significantly correlated with T stage (p = 0.016). Multivariate Cox analysis revealed that a lack of stromal SHMT1 expression was an independent prognostic factor for predicting a shorter disease-free survival period (hazard ratio 4.002, 95 % confidence interval [CI] 1.077-14.83, p = 0.038); furthermore, a lack of tumoral PHGDH expression was predictive of a shorter overall survival rate (hazard ratio 3.053, 95 % CI 1.002-9.305, p = 0.050). In conclusion, the most abundantly expressed serine/glycine metabolism-related protein in basal-like TNBC tissues was tumoral PHGDH, and expression levels of stromal SHMT1 and tumoral PHGDH were inversely correlated with clinical prognostic factors. Also, this study is the first to assess serine/glycine relationships at the protein level in regards to clinical outcomes.


[Characterization of bacteriophages of Clostridium novyi type A (author's transl)].
Four bacteriophages of Clostridum novyi type A (PFö, P5771, PA1350e and P19402) were examined. The phages were spontaneously released to the culture medium in titers of 10(6) to 10(8) pfu/ml at the end of the bacterial growth of the donor strain. The phage titer could be increased to 10(9) to 10(12) pfu/ml by growing the phages in the culture of the indicator strain C. novyi 5771/HS 10. These high titered phage suspensions were used for morphological studies and for the production of anti-phage-sera. The phages of C. novyi were unstable and lost most of their infectivity within 24 h. Lyophilizing the phages in glutamate medium seemed to be one possible way of partially stabilizing these phages. Phages PFö, P5771, PA1350e and P19402 were similar in morphology and size, in antigenic pattern and in plaque morphology. Phage PA1350e was stabile only at pH 7 and below 40 degrees C for a short time. It was inactivated at 50 degrees C within 20 min, at 55 degrees C and at 60 degrees C in 4 min.


Hyaluronic acid binding capacity of malignant glioma cells.
The mechanisms underlying the rapid invasive growth of malignant gliomas are poorly understood. Adhesion to extracellular hyaluronic acid (HA) has been implicated in the invasive properties of tumor cells. We investigated the HA binding capacity of human (T98G, A172, U87MG, 86HG39, 85HG66) and rat (C6, 9L) glioma cell lines by means of HA coated, bovine serum albumin (BSA)-blocked (HA/BSA) and only BSA-blocked culture plates. Results were compared with adhesion to native wells (100% adhesion). Adhesion to HA/BSA was high for T98G (84.4%), medium for 86HG39 (36%), 9L (33.1%), A172 (35.5%) and low for 85HG66 (21.3%) and U87MG (26.8%). Adhesion to only BSA-coated wells was significantly lower in all these cell lines, suggesting a specific HA-adhesion. Only C6 showed similar adhesion to HA/BSA and BSA alone, therefore, C6 failed to bind HA specifically. These results suggest that adhesion to extracellular HA might be involved in the invasion of some gliomas.


PE12 interaction with TLR4 promotes intracellular survival of Mycobacterium tuberculosis by suppressing inflammatory response.
Macrophages serve as the primary immune cells responsible for the innate immune defense against Mycobacterium tuberculosis (MTB) infection within the host. Specifically, NLRP3, a member of the NLRs family, plays a significant role in conferring resistance against MTB infection. Conversely, MTB evades innate immune killing by impeding the activation of the NLRP3 inflammasome, although the precise mechanism remains uncertain. In this study, we have identified PE12 (Rv1172c), a member of the PE/PPE family proteins, as an extracellular protein of MTB. PE12 interacts with Toll like receptor 4 (TLR4) in macrophages, forming the PE12-TLR4 complex which subsequently inhibits the transcription and expression of NLRP3. As a result, the transcription and secretion of IL-1β are reduced through the PE12-TLR4-NLRP3-IL-1β immune pathway. In vitro and in vivo experiments using a PE12-deficient strain (H37RvΔPE12) demonstrate a weakening of the suppression of the inflammatory response to MTB infection. Our findings highlight the role of the PE12 protein in not only inhibiting the transcription and release of inflammatory cytokines but also mediating the killing of MTB escape macrophages through TLR4 and inducing lung injury in MTB-infected mice. These results provide evidence that PE12 plays a significant role in the inhibition of the host immune response by MTB.


Increased male fertility using fertility-related biomarkers.
Conventional semen analyses are used to evaluate male factor fertility/infertility in humans and other animals. However, their clinical value remains controversial. Therefore, new tools that more accurately assess male fertility based on sperm function and fertilization mechanism are of interest worldwide. While protein markers in spermatozoa that might help differentiate fertile and infertile sperm have been identified, studies are in their infancy, and the markers require validation in field trials. In the present study, to discover more sensitive biomarkers in spermatozoa for predicting male fertility, we assessed protein expression in capacitated spermatozoa. The results demonstrated that cytochrome b-c1 complex subunit 2 (UQCRC2) was abundantly expressed in high-litter size spermatozoa (>3-fold). On the other hand, equatorin, beta-tubulin, cytochrome b-c1 complex subunit 1 (UQCRC1), speriolin, Ras-related protein Rab-2A (RAB2A), spermadhesin AQN-3, and seminal plasma sperm motility inhibitor were abundantly expressed in low-litter size spermatozoa (>3-fold). Moreover, RAB2A and UQCRC1 expression negatively correlated with litter size, while UQCRC2 expression positively correlated with litter size. Finally, the putative biomarkers predicted litter size in field trials. Our study suggests that biomarkers present in spermatozoa after capacitation can help differentiate superior male fertility from below-average fertility with high sensitivity.


Initial Analysis of the Arylomycin D Antibiotics.
The arylomycins are a class of natural product antibiotics that inhibit bacterial type I signal peptidase and are under development as therapeutics. Four classes of arylomycins are known, arylomycins A-D. Previously, we reported the synthesis and analysis of representatives of the A, B, and C classes and showed that their spectrum of activity has the potential to be much broader than originally assumed. Along with a comparison of the mechanism of acquired and innate resistance, this led us to suggest that the arylomycins are latent antibiotics, antibiotics that once possessed broad-spectrum activity, but which upon examination today, have only narrow spectrum activity due to prior selection for resistance in the course of the competition with other microorganisms that drove their evolution in the first place. Interestingly, actinocarbasin, the only identified member of the arylomycin D class, has been reported to have activity against MRSA. To confirm and understand this activity, several actinocarbasin derivatives were synthesized. We demonstrate that the previously reported structure of actinocarbasin is incorrect, identify what is likely the correct scaffold, confirm that scaffold has activity against MRSA, and determine the origin of this activity.


Extrafollicular adenomatoid odontogenic tumour.
Adenomatoid odontogenic tumour (AOT) is an uncommon, benign tumour that represents 3-7% of all odontogenic tumours. It is slow growing, occurs twice as common in females and usually in the second decade of life. There are three subclinical types of this tumour with identical histology: follicular type (73%), extrafollicular variant (24%) and peripheral form (3%). Here, the authors have presented two rare cases of extrafollicular varieties of AOT in 25-year-old female patients, of which one was situated in the maxillary canine area and the other one situated in an unusual location of mandibular premolar area. Such lesions may be confused as an odontogenic cyst and should be carefully differentiated from other benign and malignant lesions arising in this region.


Posterior canal wall reconstruction tympanoplasty for operated ears with open mastoid.
We investigated the postoperative conditions of ears and the hearing acuity of patients who underwent posterior canal wall reconstruction tympanoplasty for operated ears with open mastoid. The study included 118 ears of 105 patients (57 males, 48 females; age range 5-75 years) and the patients were followed for > 1 year after the final operation. Although 114 ears (97%) were dry after the final operation, retraction pockets and eardrums in a lateral position were observed in 5 ears and in 1 ear, respectively. Ossicular reconstruction was performed in 83 ears and in these the mean air conduction hearing levels were significantly improved after the final operation in those that were subjected to type III and IV tympanoplasty. These results indicate that posterior canal wall reconstruction tympanoplasty can be considered to be an effective procedure.


Inhibition of thyroid hormone uptake by calcium antagonists of the dihydropyridine class.
A series of substituted 4-phenyl-1,4-dihydropyridines 2a-m was tested for their inhibitory effects on L-triiodothyronine (L-T3) uptake by human HepG2 hepatoma cells. The most potent compounds were the nitro-substituted derivatives 2,6-dimethyl-4-(4'-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylic acid 3-ethyl ester 5-methyl ester (2m) and the well-known calcium antagonists nitrendipine (2k) and nifedipine (2j) with an uptake inhibition between 80.5 and 85.8% at an application dose of 10(-5) M. On the basis of a theoretical conformational analysis (ab initio MO theory, molecular mechanics, molecular dynamics) of the dihydropyridine derivatives, a unifying stereochemical concept was derived postulating an angular arrangement of the two rings where the phenyl ring of the calcium antagonists, which corresponds to the outer phenyl ring of the thyroid hormones, is bisecting the dihydropyridine ring as a prerequisite for inhibitory potency. This model includes also inhibitors of the N-phenylanthranilic acid type. The interaction of the calcium antagonists with transthyretin (TTR) is discussed in relation to thyroid hormones. The influence of hydrophobicity was estimated by the experimental determination of the 1-octanol/water partition coefficients.


Utility and safety of procalcitonin in an antimicrobial stewardship program (ASP) in patients with malignancies.
As data on procalcitonin utility in antibiotics discontinuation [under an antimicrobial stewardship program (ASP)] in patients with malignancies are lacking, we aimed to evaluate the utility of procalcitonin in an ASP in patients with malignancies. We conducted a retrospective review of the ASP database of all patients with malignancies in whom at least one procalcitonin level was taken and our ASP had recommended changes in carbapenem regimen, from January to December 2011. We compared clinical outcomes between two groups of patients: patients whose physicians accepted and those whose physicians rejected ASP interventions. There were 749 carbapenem cases reviewed. Ninety-nine were suggested to either de-escalate, discontinue antibiotics, or narrow the spectrum of empiric treatment, based on procalcitonin trends. While there was no statistical difference in the mortality within 30 days post-ASP intervention (accepted: 8/65 patients vs. rejected: 9/34 patients; p = 0.076), the median duration of carbapenem therapy was significantly shorter (5 vs. 7 days; p = 0.002). Procalcitonin use safely facilitates decisions on antibiotics discontinuation and de-escalation in patients with malignancies in the ASP.


[Struma ovarii, a rare form of ovarian tumor].
Struma ovarii, a rare form of ovarian tumor, represents less than 3% of ovarian teratomas. The peak frequency occurs during the fifth decade of life. Diagnosis is usually a surprise of pelvic ultrasound or histological analysis. Surgery is the main mode of treatment and prognosis is excellent. Struma ovarii can be associated with thyroid biology abnormalities, or exceptionally become malignant, and thus managed as a thyroid cancer.


Management of oral health in patients irradiated for head and neck cancer: a review.
Management of oral health plays an integral role in the treatment of Head & Neck Cancers. Radiation therapy is a significant treatment modality in the management of Head and Neck Cancers. However, high dose of radiation is also associated with side effects. Oral health management plays an important role in preventing these complications. Therefore it is mandatory to initiate prompt oral health care that can prevent the associated orodental complications. This article is a review on oral complications associated with radiation therapy, their prevention and management.


[Case of Behcet's disease diagnosed by bilateral epididymitis].
A 24-year-old man visited our emergency room with testicular pain and left shoulder pain, and was admitted to our hospital for diagnosis of bilateral epididymitis. Antibiotics and anti-inflammatory medication were started, but the symptoms did not improve. During hospitalization, ulcerous lesions, erythema nodosum, folliculitis-like exanthema and multiple oral aphtha appeared. Then, we consulted the department of dermatology. As he had a combination of arthritis and epididymitis, he was diagnosed with the abortive form of Behcet's disease. After diagnosis, we began administering colchicine. Then, all symptoms improved in a few days, and he has remained free of the disease after the discontinuation of colchicine.


Can intraoperative cholangiography be avoided during laparoscopic cholecystectomy?
Controversy exists as to whether intraoperative cholangiography should be performed routinely or selectively during laparoscopic cholecystectomy. The aim of the present study was to assess in which circumstances intraoperative cholangiography can be avoided during laparoscopic cholecystectomy. From January 1999 to June 2002, 168 patients undergoing laparoscopic cholecystectomy for cholelithiasis without intraoperative cholangiography were prospectively evaluated at our Department. Inclusion criteria were established according to a preoperative diagnostic protocol, considering only those patients with normal liver function tests and ultrasound common bile duct diameters < or = 5 mm or > 5 mm, but with normal magnetic resonance cholangiopancreatography findings. Laparoscopic cholecystectomy was carried out without intraoperative cholangiography and postoperative results and follow-up data were recorded and analysed. No major biliary injuries were encountered and no patients had residual bile duct stones after at least a one-year postoperative follow-up. A complete preoperative diagnostic work-up proved to be of fundamental importance for decreasing the incidence of residual bile duct stones. When protocol criteria are satisfied, intraoperative cholangiography may be safely omitted during laparoscopic cholecystectomy and meticulous laparoscopic technique is the main way to reduce the incidence of iatrogenic biliary lesions to a minimum.


Physicochemical characterization of porcine pararotavirus and detection of virus and viral antibodies using cell culture immunofluorescence.
A cell culture immunofluorescence (CCIF) assay was optimized for detection of porcine pararotavirus (group C rotavirus) in intestinal contents. The greatest viral infectivity was observed when MA104 cells (5 days after subculturing) were rinsed and refed in serum-free medium before inoculation, pancreatin was added to the inocula, and the inocula were centrifuged onto the cells. Gentamicin treatment of pararotavirus samples to reduce bacterial contamination also reduced the viral infectivity of these samples for MA104 cells. An indirect CCIF assay was used to determine the prevalence of pararotavirus and rotavirus antibodies in pig sera. In pigs from four herds, pararotavirus antibodies were detected in 100% (68 of 68) of adults and 59% (24 of 41) of weanling pigs, while 86% (24 of 28) of nursing pigs from 12 herds had pararotavirus antibodies. The physicochemical properties of pararotavirus were examined and compared with those of group A rotaviruses by using the CCIF assay to quantitate in vitro changes in viral infectivity. Pararotavirus was inactivated (greater than or equal to 99% reduction in titer) by heating to 56 degrees C for 30 min, was slightly labile at pH 3 (16 to 34% reduction in titer), and was stable at pH 5 (0 to 17% reduction in titer) and in either (3 to 19% reduction in titer). One group A rotavirus (Gottfried strain) was stable at 56 degrees C (0% reduction in titer), whereas the OSU strain of group A rotavirus was inactivated at this temperature (99% reduction in titer).


Chiral metal-organic frameworks for high-resolution gas chromatographic separations.
Chiral metal-organic framework coated open tubular columns are used in the high-resolution gas chromatographic separation of chiral compounds. The columns have excellent selectivity and also possess good recognition ability toward a wide range of organic compounds such as alkanes, alcohols, and isomers.


Girl child marriage as a risk factor for early childhood development and stunting.
This paper quantitatively examines the intergenerational effects of girl child marriage, or the developmental and health outcomes of children born to women who marry before age 18. The overall objective is to understand the mechanisms through which girl child marriage affects the health and well-being of children in sub-Saharan Africa, as well as the relative magnitude and impact of these mechanisms. We used data from 37,558 mother-child pairs identified through 16 national and sub-national cross-sectional surveys across sub-Saharan Africa conducted between 2010 and 2014 by the UNICEF Multiple Indicator Clusters Survey program. The Early Childhood Development Index was used to measure child development, and stunting was used to measure health. Using logistic regression, we found that the odds of being off-track for development and being stunted were 25% and 29% higher, respectively, for children born to women who married before age 18 compared to those whose mothers married later (p < 0.001). Geographic location and primary education, which were conceptualized as contextual factors, explained most of this relationship, controlling for country fixed-effects. In adjusted models, we found that early childbearing was not the sole pathway through which girl child marriage affected child development and health. Our final models revealed that disparities in advanced maternal education and wealth explained child development and stunting. We conclude that there are intergenerational consequences of girl child marriage on her child's well-being, and that through association with other contextual, socioeconomic, and biological factors, marrying early does matter for child development and health. Our findings resonate with existing literature and point toward important policy considerations for improving early childhood outcomes.


Recombinant production of human microsomal cytochrome P450 2D6 in the methylotrophic yeast Pichia pastoris.
Microsomal cytochrome P450 monooxygenases of groups 1-3 are mainly expressed in the liver and play a crucial role in phase 1 reactions of xenobiotic metabolism. The cDNAs encoding human CYP2D6 and human NADPH-P450 oxidoreductase (CPR) were transformed into the methylotrophic yeast Pichia pastoris and expressed with control of the methanol-inducible AOX1 promoter. The determined molecular weights of the recombinant CYP2D6 and CPR closely matched the calculated values of 55.8 and 76.6 kDa. CPR activity was detected by conversion of cytochrome c by using isolated microsomes. Nearly all of the recombinant CYP was composed of the active holoenzyme, as confirmed by reduced CO difference spectra, which showed a single peak at 450 nm. Only by coexpression of human CPR and CYP was CYP2D6 activity obtained. Microsomes containing human CPR and CYP2D6 converted different substrates, such as 3-cyano-7-ethoxycoumarin, parathion and dextrometorphan. The kinetic parameters of dextrometorphan conversion closely matched those of CYP2D6 from other recombinant expression systems and human microsomes. The endogenous NADPH-P450 oxidoreductase of Pichia pastoris seems to be incompatible with human CYP2D6, as expression of CYP2D6 without human CPR did not result in any CYP activity. These recombinant strains provide a novel, easy-to-handle and cheap source for the biochemical characterisation of single microsomal cytochromes, as well as their allelic variants.


Mechanism of nitric oxide production induced by H2O2 in cultured endothelial cells.
This study examined the mechanism of stimulation of nitric oxide (NO) synthesis induced by hydrogen peroxide (H2O2). To determine the role of Ca2+ on H2O2-induced NO synthesis in bovine aortic endothelial cells, the increases in intracellular Ca2+ and NO production induced by H2O2 were compared with the effects of the Ca2+ ionophore ionomycin in the same batches of endothelial cells. NO production was assessed by formation of [3H]citrulline from [3H]arginine, and changes in intracellular Ca2+ were measured using fluorescent indicator fluo-3 with a confocal laser scanning system. Both H2O2 (1-10 mM) and ionomycin (10(-7)-10(-5) M) increased intracellular Ca2+ and stimulated the synthesis of L-citrulline from L-arginine. Although H2O2 induced only a small increase in intracellular Ca2+, it markedly increased L-citrulline formation compared with ionomycin. Thus, stimulation of NO synthesis induced by H2O2 may involve the mechanisms other than the increases in intracellular Ca2+ in endothelial cells. In the particulate fraction from cultured endothelial cells, addition of exogenous H2O2 (1 mM) or catalase (100 U/ml) did not affect L-citrulline formation. However, co-administration of H2O2 and catalase stimulated L-citrulline formation. These findings suggested that not only the increases in intracellular Ca2+ but also the products by the reaction with H2O2 and catalase are likely to be involved in the stimulation of NO synthesis induced by H2O2.


[Pulmonary aspergillosis: variable appearances (pictorial essay)].
Pulmonary aspergillosis can present in different clinical, pathological and radiological forms depending on the patient's immunological status and underlying pulmonary disease. Allergic bronchopulmonary aspergillosis, aspergilloma, invasive and semi-invasive forms can be recognized. In this article, we review the radiological findings of different forms of pulmonary aspergillosis.


MR imaging signal response to sustained stimulation in human visual cortex.
The response of signal intensity to transient (on-off) motor and sensory stimulation has been well studied; however, the dependence of signal response on the duration of stimulus requires further characterization. The objective of this study was to determine the time course of signal response in the human visual cortex to prolonged, sustained stimulation and to examine possible contributory physiologic mechanisms. Nine healthy volunteers underwent magnetic resonance (MR) imaging during sustained visual stimulation with light-proof binocular goggles. With photic stimulation, activation was observed in all subjects as an increase in signal intensity of the visual cortex. With sustained stimulation, a gradual decrease in signal intensity was subsequently observed, with progression toward an apparent steady state. Correlation with positron emission tomographic, MR spectroscopic, and visual evoked-potential data suggests that the initial uncoupling of cerebral blood flow and oxidative metabolism with a neuronal activation burst may represent a transient phenomenon. This quick-response phase may proceed to an equilibrium coupling of flow and oxidative metabolism, with a gradual normalization of venous deoxyhemoglobin levels and signal intensity.


Understanding the effects of surface chemistry on Q: mechanical energy dissipation in alkyl-terminated (C1-C18) micromechanical silicon resonators.
The rate of mechanical energy dissipation in 300-nm-thick, megahertz-range micromechanical silicon resonators is sensitive to single monolayer changes in surface chemistry. Resonators terminated with a single monolayer of methyl groups have significantly higher quality factors (Q's), and thus lower mechanical energy dissipation, than comparable resonators terminated with either long-chain alkyl monolayers (C2H2n+1, n = 2-18) or monolayers of hydrogen atoms. This effect cannot be attributed to mechanical energy dissipation within the alkyl monolayer, as a 9-fold increase in alkyl chain length does not lead to an observable increase in dissipation. Similarly, this effect is not correlated with the chemical structure of the silicon-monolayer interface (e.g., the density of Si-H vs Si-C bonds.) Instead, the chemical trends in resonator quality and stability are consistent with a dissipation mechanism involving the coupling of long-range strain fields to localized, electronically active defects in the monolayer coatings.


A computational method for semi-automatic measurement of pressure ulcers.
Pressure ulcers are skin lesions caused by the excessive compression of soft tissues between bones and hard surfaces that may increase treatment risks and costs. Manual techniques to evaluate the area of the affected region include the use of adhesive labels and rulers in direct contact with the ulcer. In this article, a semi-automatic method is proposed to estimate the lesion area through computerized techniques in different color spaces using filters and morphological operators. Experiments with a set of 110 images of pressure ulcers resulted in a statistically significant increase in effectiveness, when compared with other published results, reaching 90.8% of precision, 81.6% of sensitivity, and 81.3% of accuracy.


Catalyst-assisted solution-liquid-solid synthesis of CdS/CdSe nanorod heterostructures.
We report the synthesis and characterization of axial nanorod heterostructures composed of cadmium selenide (CdSe) and cadmium sulfide (CdS). The synthesis employs a solution-liquid-solid (SLS) mechanism with the assistance of bismuth nanocrystals adhered to a substrate (silicon or a III-V semiconductor). Transmission electron microscopy (TEM) and diffraction studies show that CdSe and CdS segments exhibit the wurtzite (hexagonal) crystal structure with <5% stacking faults. Both of these segments grow along the [002] direction with an epitaxial interface between them. Energy-dispersive X-ray (EDX) spectrometry using a high-resolution TEM operating in scanning mode confirms the alloy-free composition modulation in the nanorod heterostructures, showing that Se and S are localized in the CdSe and CdS portions of the nanorod heterostructures, respectively. This study demonstrates that SLS synthesis provides an alternate route to prepare axial nanorod heterostructures that have been difficult to generate using either vapor-liquid-solid growth or catalyst-free solution-phase synthesis.


[Consequences of a bipolar disorder and use of mood stabilizers for its management during pregnancy].
For patients with a bipolar disorder who are pregnant or consider pregnancy, the following issues are of importance: Genetic counselling: genetic vulnerability is virtually certainly the basis of the occurrence of a bipolar disorder. discontinuation of the medication may lead to recurrence; continuation may cause intoxications in the woman and her child and congenital anomalies in the child. Alternatives to mood stabilizers can be applied; electroconvulsive therapy is a possibility as is medication with antidepressants, antipsychotics and benzodiazepines during acute episodes of mood disorder. Precautions for mother and child if mood-stabilizing treatment is continued: use sustained-release preparations, regularly check blood levels and thyroid function, administer vitamin K if necessary, perform ultrasonoscopy/examination of amniotic fluid, have the child delivered in hospital. Management of the newborn child: observation, determination of blood levels, regular checks of thyroid function, if necessary administration of vitamin K.


Rapid, sensitive and inexpensive detection of SCN5A genetic variations by high resolution melting analysis.
SCN5A mutations lead to a wide spectrum of cardiovascular disorders. Due to large cohorts to investigate and the large gene size, mutational screening must be performed using an extremely sensitive and specific scanning method. High Resolution Melting (HRM) analysis was developed for SCN5A mutation detection using control DNAs and DNAs carrying previously identified gene variants. A cohort of 40 patients was further screened. To evaluate HRM sensitivity, this cohort was also screened using an optimized DHPLC methodology. All gene variants detected by DHPLC were also readily identified as abnormal by HRM analysis. Mutations were identified for 5 patients. Complete molecular SCN5A investigation was completed two times faster and cheaper than using DHPLC strategy. HRM analysis represents an inexpensive, highly sensitive and high-throughput method to allow identification of SCN5A gene variants. Identification of more SCN5A mutations could provide new insights into the pathophysiology of SCN5A-linked diseases syndromes.


Stable expression of the neuronal BI (class A) calcium channel in baby hamster kidney cells.
Plasmids containing the BI (alpha 1) cDNA with the dihydrofolate reductase (DHFR) gene, skeletal muscle alpha 2-subunit cDNA with the neo marker gene, and beta-subunit cDNA were co-transfected into baby hamster kidney (BHK) cells. BHK cells lack endogenous calcium channel activity. Twenty percent of the methotrexate (MTX) and G418 resistant clones were found to express calcium channel activity using the patch-clamp technique. A single clone, BHKBI147, demonstrated stable electrophysiological characteristics over 20 passages. Ca2+ currents of the BI channel in BHKBI147 cells were largely blocked by a specific P-type blocker, omega-AgaIVA, with an IC50 of 150 nM. Unlike the BI channel, Ca2+ currents of cardiac L-type channels expressed in BHK cells were completely blocked by the L-type antagonist, nifedipine, with an IC50 of 56 nM.


Modelling of dissolving microneedles for transdermal drug delivery: theoretical and experimental aspects.
A mathematical model was developed to predict the amount of drug delivered into the skin via the dissolution of a microneedle (MN). This approach differs markedly from previous research which focused on similar phenomena but failed to include a biological membrane. Dimensionless governing equations were derived to help predict the needle height and fate of the active ingredient in the skin layer after application of the device. Simulation studies with fentanyl revealed that the drug concentration was proportional to its mass fraction in the MN. The effect of the pitch on skin permeation was mildly nonlinear. A larger amount of fentanyl was delivered from microneedle arrays with smaller pitch size. The dissolution process was independent of changes in the elimination rate constant. An optimization algorithm was applied to show how to recover this parameter from needle height--time data.