Fracture incidence and characterization in patients on osteoporosis treatment: the ICARO study.
None of the available osteoporosis therapies have been shown to completely abolish the risk of fractures. In clinical practice, the outcome may be even poorer. In 880 patients prescribed with antiresorptives (alendronate, risedronate, and raloxifene) for >1 year, a fragility fracture was recorded in 8.9%/year of them. This incidence is considerably higher than that observed in randomized clinical trials, and it was significantly related to poor compliance and lack of supplementation with calcium and vitamin D. Osteoporotic fracture is one of the most important public health concerns among the elderly. Currently available therapies have been shown to significantly decrease the risk of fracture, although none of them completely abolishes this risk. In clinical practice, poor treatment response may also result from a number of other factors. The Incidence and ChAracterization of inadequate clinical Responders in Osteoporosis (ICARO) is a multicenter, observational study carried out in Italy. It aimed to analyze, in postmenopausal women with established osteoporosis, the risk factors for an "inadequate clinical response" to drug therapy, defined as the occurrence of new vertebral or nonvertebral fragility fractures in patients prescribed, for at least 1 year, alendronate, risedronate, or raloxifene, with a compliance >50%. In 880 patients treated with antiresorptive agents for a median of 2.0 years (95% CI: 1.0-4.5) years, the "inadequate clinical responder (ICR)" subjects over the observation period were 220 (25%), with an annual incidence of 8.9%. ICRs, compared with "adequate clinical responders (ACRs)," had more pretreatment fractures and were treated longer (2.8 versus 1.8 years; p < 0.001). After multiple adjustment for these confounding factors, significant determinants of inadequate clinical response were a poorer treatment compliance and a less frequent co-administration of calcium and vitamin D supplements. The incidence of fractures during treatment with antiresorptive agents in a clinical setting is considerably higher than that observed in randomized clinical trials. Inadequate compliance to treatment and lack of supplementation of calcium and vitamin D are major determinants of this poor response.


[Primary nasopharyngeal tuberculosis].
A 59-year-old female was complaining of sore throat, right otorrhea, and hearing impairment. There were no abnormal findings suggestive of pulmonary tuberculosis on her chest XP and CT. Nasopharyngoscopic examination detected a lesion coated with white mass on her nasopharynx, and a biopsy-specimen from this lesion revealed histopathological findings compatible with tuberculosis and the presence of acid-fast bacilli. PCR was positive for Mycobacterium tuberculosis complex. Therefore, we diagnosed the case as primary nasopharyngeal tuberculosis and treated her by 4-drug combination regimen with daily isoniazid, rifampicin, ethambutol and pyrazinamide. Later, low degree of resistance was noticed, isoniazid was replaced by levofloxacin. After the anti-tuberculosis chemotherapy, her symptoms almost completely diminished and the mass in her nasopharynx disappeared. As far as we can search, 23 Japanese cases of primary nasopharyngeal tuberculosis, including this case, have been reported in the literatures. We summarized the clinical features of these cases in Table. Nasopharyngeal tuberculosis is a rather rare disease. But, recently, due to the advances in diagnostic technology, the number of the case-reports has been increasing. Difficulties in detecting tubercle bacilli in nasopharyngeal lesion sometimes delayed definite diagnosis and treatment. If a patient complains the symptoms compatible with this disease, such as sore throat, pharyngeal pain and otorrhea, which are refractory to the general antibiotic therapy, we should be aware of the existence of this disease and repeat bacteriological and/or molecular examinations to prove tubercle bacilli to be able to start timely anti-tuberculosis chemotherapy.


Viral hepatitis with intracytoplasmic cholestasis and cholesterol crystals in a drug addict.
Electron-microscopical exammination of a liver biopsy from a young female drug addict with clinically relapsing serum hepatitis revealed virus-like particles free in the liver cell cytoplasm. In addition, there was intracellular cholestasis, and numerous clefts were found in the cytoplasm of hepatocytes, presumably caused by the presence of cholesterol crystals which were dissolved during the processing of the tissue. Such clefts have earlier been reported in liver cells in patients with cholestasis and hypercholesterolemia, but not in patients with viral hepatitis and a normal serum cholesterol concentration.


Transdural approach for calcified central disc herniations of the upper lumbar spine. Technical note.
Disc herniations of the upper lumbar spine (L1-2 and L2-3) have a frequency of 1 to 2% of all disc herniations. During posterior discectomy after laminectomy, significant manipulation of the exiting nerve root is unavoidable because of the narrow lamina and the difficulty in mobilizing the nerve root. The authors adopted a transdural approach in patients with calcified central disc herniation at the L1-2 level to reduce the risk of nerve root injury. Four patients suffering from radiating pain together with back pain were treated using the transdural approach. Preoperative neuroimaging studies revealed severe central disc herniation with calcification at the L1-2 level. After laminectomy or laminotomy, the incised dura mater was tacked, and the cauda equina rootlets were gently retracted. An intentional durotomy was performed over its maximal bulging of the ventral dura. After meticulous dissection of dense adhesions between the disc herniation and the dural sac, adequate decompression with removal of calcified disc fragments and osteophytes was accomplished. Clinical symptoms improved in all patients. Postoperative permanent cerebrospinal fluid leakage and pseudomeningocele were not observed, and no patient had a progressive lumbar deformity at an average follow-up of 53 months. Transient mild motor weakness and sensory change were observed in two patients postoperatively; however, these symptoms resolved completely within 1 week. The posterior transdural approach offers an alternative in central calcified upper lumbar disc herniation when root retraction is dangerous.


Tinea versicolor and body lotions.
A woman complained she had caught her "white spots" from an American sun lotion. The daughter also had them. The mother's spots showed malassezia furfur. The daughter, by a curious coincidence, had developed vitiligo at the same time. As a comfort it was agreed that the sun lotion should be examined for fungal contamination. Scrapings from lesions of patients with tinea versicolor show a typical appearance of malassezia furfur. Roberts (9) cultured specimens from 27 patients and isolated Pitysporum orbiculare in 25.


In Vivo Measurement of Rat Brain Water Content at 9.4 T MR Using Super-Resolution Reconstruction: Validation With Ex Vivo Experiments.
Given that changes in brain water content are often correlated with disease, investigating water content non-invasively and in vivo could lead to a better understanding of the pathogenesis of several neurologic diseases. To adapt a super-resolution-based technique, previously developed for humans, to the rat brain and report in vivo high-resolution (HR) water content maps in comparison with ex vivo wet/dry methods. Prospective. Eight healthy male Wistar rats. 9.4-T, multi-echo gradient-echo (mGRE) sequence. Using super-resolution reconstruction (SRR), a HR mGRE image (200 μm isotropic) was reconstructed from three low-resolution (LR) orthogonal whole-brain images in each animal, which was followed by water content mapping in vivo. The animals were subsequently sacrificed, the brains excised and divided into five regions (front left, front right, middle left, middle right, and cerebellum-brainstem regions), and the water content was measured ex vivo using wet/dry measurements as the reference standard. The water content values of the in vivo and ex vivo methods were then compared for the whole brain and also for the different regions separately. Friedman's non-parametric test was used to test difference between the five regions, and Pearson's correlation coefficient was used for correlation between in vivo and ex vivo measurements. A P-value <0.05 was considered statistically significant. Water content values derived from in vivo MR measurements showed strong correlations with water content measured ex vivo at a regional level (r = 0.902). Different brain regions showed significantly different water content values. Water content values were highest in the frontal brain, followed by the midbrain, and lowest in the cerebellum and brainstem regions. An in vivo technique to achieve HR isotropic water content maps in the rat brain using SRR was adopted in this study. The MRI-derived water content values obtained using the technique showed strong correlations with water content values obtained using ex vivo wet/dry methods. 1 TECHNICAL EFFICACY: Stage 1.


Refractory Dermatomyositis Complicated with Myelodysplastic Syndrome.
We herein describe a case of refractory dermatomyositis (DM) complicated with myelodysplastic syndrome (MDS). Despite intensive immunosuppressive therapies, the activity of myositis, skin ulcers, and interstitial pneumonia did not improve. The patient ultimately died following the progression of interstitial pneumonia. There are few reports of DM accompanying MDS to date, and any association in the pathogenesis between the two is still unclear. However, underlying MDS may have the potential to influence the therapeutic response of DM.


Laryngeal papillomatosis: clinical, histopathologic and molecular studies.
The clinical course and pathology of 57 patients with laryngeal papillomatosis were reviewed. Tissues from 26 patients were analyzed for human papillomavirus (HPV) DNA by Southern blot hybridization. Histopathologic evaluation of the papillomas showed no correlation with age of onset or clinical pattern of remission and recurrence. The pathology was characterized by abnormal squamous maturation with parakeratosis, retardation of superficial cell maturation, papillomatosis, and basal hyperplasia. HPV DNA was present in all lesions, with 92% containing either HPV-6 or 11. Latent HPV DNA was detected in clinically uninvolved tissues of 11 of 14 (78.5%) patients studied. There was no correlation between HPV type, histopathology and/or clinical pattern. Despite homogeneity of pathology, the clinical expression of laryngeal HPV infection varied widely. A mechanism for the pathogenesis of laryngeal papillomatosis, based on the concept of maturational arrest, is proposed.


Effects of Acanthocephalus lucii (Acanthocephala) on intermediate host survival and growth: implications for exploitation strategies.
Intermediate host exploitation by parasites is presumably constrained by the need to maintain host viability until transmission occurs. The relationship between parasitism and host survival, though, likely varies as the energetic requirements of parasites change during ontogeny. An experimental infection of an acanthocephalan (Acanthocephalus lucii) in its isopod intermediate host (Asellus aquaticus) was conducted to investigate host survival and growth throughout the course of parasite development. Individual isopods were infected by exposure to fish feces containing parasite eggs. Isopods exposed to A. lucii had reduced survival, but only early in the infection. Mean infection intensity was high relative to natural levels, but host mortality was not intensity dependent. Similarly, a group of naturally infected isopods harboring multiple cystacanths did not have lower survival than singly infected isopods. Isopods that were not exposed to the parasite exhibited sexual differences in survival and molting, but these patterns were reversed or absent in exposed isopods, possibly as a consequence of castration. Further, exposed isopods seemed to have accelerated molting relative to unexposed controls. Infection had no apparent effect on isopod growth. The effects of A. lucii on isopod survival and growth undermine common assumptions concerning parasite-induced host mortality and the resource constraints experienced by developing parasites.


Dexamethasone treatment prior to reperfusion improves the survival of skin flaps subjected to secondary venous ischaemia.
The potential use of the anti-inflammatory glucocorticoid, dexamethasone, to treat ischaemic skin flaps prior to reperfusion was investigated. Island flaps were raised in rats, subjected to arteriovenous ischaemia for 2 h, normal blood flow for 24 h, secondary venous ischaemia for 4 h and secondary reperfusion for 7 days. This sequence mimics the clinical sequence of free flap transfer followed by a subsequent venous thrombosis. Groups of 10 rats were administered with an intraperitoneal dose of either saline (controls) or dexamethasone (2.5 mg/kg) 30 min before the end of the venous ischaemia. Compared with viability of 70.0% in controls, dexamethasone treatment increased viability significantly to 92.0% (P < 0.01). In skin flap tissue harvested at 24 h reperfusion, dexamethasone treatment resulted in significant attenuation of tissue water content, tissue myeloperoxidase activity and tissue hydroperoxide levels. Thus the protective effect of this agent may be explained by the combined reduction of oedema formation, neutrophil infiltration and free radical production, respectively. We conclude that a single systemic dose of dexamethasone prior to reperfusion may be beneficial in treating skin flaps that have undergone secondary venous ischaemia.


The SBP-Box Gene VpSBP11 from Chinese Wild Vitis Is Involved in Floral Transition and Affects Leaf Development.
Flowering occurs in angiosperms during a major developmental transition from vegetative growth to the reproductive phase. Squamosa promoter binding protein (SBP)-box genes have been found to play critical roles in regulating flower and fruit development, but their roles in grapevine have remained unclear. To better understand the functions of the grape SBP-box genes in both vegetative and reproductive growth phases, a full-length complementary DNA (cDNA) sequence of the putative SBP-box transcription factor gene, VpSBP11, was obtained from Chinese wild grapevine Vitis pseudoreticulata Wen Tsai Wang (W. T. Wang) clone 'Baihe-35-1'. VpSBP11 encoded a putative polypeptide of 170 amino acids with a highly conserved SBP-domain with two zinc-binding sites of the Cx2C-x3-H-x11-C-x6-H (C2HCH) type and a nuclear localization signal. We confirmed that the VpSBP11 protein was targeted to the nucleus and possessed transcriptional activation activity by subcellular localization and trans-activation assay. Over-expression of VpSBP11 in Arabidopsis thaliana was shown to activate the FUL gene, and subsequently the AP1 and LFY genes, all of which were floral meristem identity genes, and to cause earlier flowering than in wild type (WT) plants. The pattern of vegetative growth was also different between the transgenic and WT plants. For example, in the VpSBP11 over-expressing transgenic plants, the number of rosette leaves was less than that of WT; the petiole was significantly elongated; and the rosette and cauline leaves curled upwards or downwards. These results were consistent with VpSBP11 acting as a transcription factor during the transition from the vegetative stage to the reproductive stage.


Junctional Rhythm: A Rare Sign in Leptospirosis.
Leptospirosis is an important re-emerging infectious disease. Leptospirosis has been estimated to affect tens of millions of humans annually with a case fatality rate ranging from 5% to 25%; however, it is underreported due to the lack of clinical suspicion and barriers to diagnostic capacity. A 33-year-old healthy male presented with a history of fever of 2-day duration. His examination revealed icterus. His workup did not show any significant findings except for a mild transaminitis and a rise in serum creatinine by 0.5 mg/dl. Later, the patient developed bradycardia. An ELISA test for Leptospira antibodies was positive. The patient recovered after a course of intravenous antibiotics. Leptospirosis should be considered early in the diagnosis of any patient who presents with acute, nonspecific febrile illness with multiorgan involvement. Our case had an atypical presentation with involvement of the cardiovascular system in the form of junctional rhythm.


Successful unrelated cord blood transplantation for homozygous α-thalassemia.
A now 10-year-old Laotian female was delivered at 30-week gestation by cesarean section because of severe hydrops. Fetal blood sampling revealed homozygous α-thalassemia. After immediate resuscitation, the infant was supported with frequent red cell transfusions. At 44 months of age, she received a 5 of 6 human leukocyte antigen-matched unrelated cord blood transplantation. She was treated with phlebotomy and chelation therapy with Deferasirox for correction of hemosiderosis and has been transfusion-independent since 41 days after transplant. She is currently 6 years after transplantation with stable, 100% donor engraftment, resolved iron overload, and normal growth and development.


Mutants altering coordinate synthesis of specific myosins during nematode muscle development.
Mutations in the unc-52 gene on linkage group II retard the construction of body-wall muscle sarcomeres during larval development in the nematode Caenorhabditis elegans. Unc-52 mutants show decreased accumulation of myosin heavy chains relative to other polypeptides during larval development, correlating with the structural retardation. Pulse radiolabeling experiments show that decreased synthesis of specific body-wall myosin heavy chains that are encoded by the unc-54 gene on linkage group I is responsible for the defective myosin accumulation. In the wild type, a constant ratio of the synthesis of the unc-54-coded myosin B to myosin A, about 2:1, is maintained during the larval stages in which the synthesis of both myosins increases exponentially and rapid sarcomere growth and addition ensues. During the first 26 hr of larval development, before any structural or behavioral effects of unc-52 mutations are apparent, the synthesis of myosin heavy chains is also normal. By 38 hr, decreased synthesis of myosin B is detected in the unc-52 mutant SU200, when sarcomere growth slows considerably. The effects of mutation in the unc-52 locus are trans acting upon the synthesis of unc-54-coded myosin in a specific set of muscle cells during a defined period of larval development.


[A Case of Postoperative Paraplegia Caused by Idiopathic Spinal Cord Infarction following Hepatectomy under Both General and Epidural Anesthesia].
A 73-year-old woman (height : 155 cm, weight : 55 kg) was scheduled to undergo a laparotomic hepatectomy and radiofrequency ablation for hepatocellular carcinoma. Her medical history did not include any relevant conditions such as cardiovascular or neurological disorders. A thoracic epidural catheter was introduced at T8-9 before the induction of anesthesia with intravenous propofol. General anesthesia was maintained with the inhalation of oxygen, air, and desflurane, and the continuous infusion of remifentanil. Several intraoperative episodes of mild hypotension occurred, each of which was successfully treated with intravenous ephedrine, but otherwise her anesthetic course was uneventful, and she recovered from the anesthesia smoothly. Her postoperative pain was well controlled with continuous epidural infusion of levobupivacaine and fentanyl, and she could walk by herself on postoperative day (POD) 1. However, she suffered weakness in her lower extremities on POD2 and subsequently fell into complete paraplegia with sensory loss below the T4 level on POD3. A magnetic resonance imaging scan taken on POD4 showed an idiopathic spinal cord infarction (SCI) involving levels T1 through T4, although no epidural abnormalities, e.g., hematomas, were detected. Immediate treatment with methylprednisolone, ozagrel, and edaravone failed to resolve her symptoms. We suggest that it is of great importance to consider SCI as a differential diagnosis as soon as possible in cases of unanticipated postoperative paraplegia.


Differential effectiveness of an elementary school social and emotional learning program during middle school transition in Portugal.
This study analyzed the effectiveness of an elementary school Social and Emotional Learning (SEL) program during middle school transition in Portugal, and the influence of gender, classroom size and student's perception of two school climate dimensions (student-student relationships and teacher-student relationships) upon its effectiveness. One-thousand-sixty-three students (M age = 9.14; SD = 0.64; 51.2% were boys) participated: 702 in the intervention group and 361 in the control group, assessed at pretest, post-test, and follow-up 10 months later (after middle school transition). Multilevel analyses identified that the program was effective in enhancing social awareness, self-control, and self-esteem, even after middle school transition. Results also showed that there no differential gains by gender, and that intervention group students who had more positive perceptions of student-student relationships and teacher-student relationships displayed more positive trajectories in self-esteem. Students from smaller fourth-grade classrooms displayed lower social awareness than students from larger fourth-grade classrooms, but a more positive trajectory in that competence than students from medium and larger fourth-grade classrooms. This study highlights the importance of analyzing the differential effectiveness of SEL programs. (PsycInfo Database Record (c) 2021 APA, all rights reserved).


Localization of the fertilized germinal disc in the chicken egg before incubation.
At the time of oviposition, the embryo in the fertilized chicken egg has developed the germinal disc on top of the yolk and contains thousands of blastodermal cells. The germinal disc escapes exact localization because it is surrounded by albumen and shell membranes under a calcified shell. This study investigated whether or not ultrasonography or nuclear magnetic resonance imaging (MRI) are suited to localize the germinal disc and, if so, to estimate the accuracy of localization. Hatchability of treated eggs was also recorded. The ultrasound waves were reflected by the shell. The germinal disc could be seen only after removal of the eggshell and the outer shell membrane. In all, 39 intact eggs, MRI localized the germinal disc within 2 mm thick image slices. The mean position of the germinal disc deviated 3.0+/-2.1 mm from the maximum vertical plane of the egg with a mean distance to the inner surface of the shell of 2.7+/-1.1 mm. Incubation resulted in 84.2 and 77.5% hatched chicks for imaged eggs and controls, respectively. The localization results of MRI were verified manually in 38 open shell cultures. Correlation coefficients for the position of the germinal disc were r = 0.86 to 0.99 for the x-axis, r = 0.75 to 0.89 for the y-axis, and r = 0.63 to 0.76 for the z-axis. The study thus shows that MRI is a reliable tool to localize the germinal disc within the intact freshly laid egg.


The differential effects of medication on mood, sleep disturbance, and work ability in outpatient alcohol detoxification.
A double-blind, randomized controlled trial of patients (n = 136) meeting DSM-IV criteria for alcohol withdrawal and stratified based on detoxification history were treated with carbamazepine or lorazepam for 5 days on a fixed dose tapering schedule. Mood symptoms improved for all subjects regardless of medication or detoxification history. There was a significant main effect favoring carbamazepine in reducing anxiety (p = 0.0007). Anxiety was highest in those individuals who had multiple previous detoxifications (p = 0.02). Visual analog measures of sleep quality indicated a statistically significant main effect of medication on sleep that again favored carbamazepine (p = 0.0186). Visual analog rating of perceived ability to return to work was decreased in individuals who had multiple previous detoxifications (p = 0.025). In this study of outpatients with mild to moderate alcohol withdrawal, carbamazepine was superior to lorazepam in reducing anxiety and improving sleep.


Truncation of the C-terminal region of Toscana Virus NSs protein is critical for interferon-β antagonism and protein stability.
Toscana Virus (TOSV) is a Phlebovirus responsible for central nervous system (CNS) injury in humans. The TOSV non-structural protein (NSs), which interacting with RIG-I leads to its degradation, was analysed in the C terminus fragment in order to identify its functional domains. To this aim, two C-terminal truncated NSs proteins, Δ1C-NSs (aa 1-284) and Δ2C-NSs (aa 1-287) were tested. Only Δ1C-NSs did not present any inhibitory effect on RIG-I and it showed a greater stability than the whole NSs protein. Moreover, the deletion of the TLQ aa sequence interposed between the two ΔC constructs caused a greater accumulation of the protein with a weak inhibitory effect on RIG-I, indicating some involvement of these amino acids in the NSs activity. Nevertheless, all the truncated proteins were still able to interact with RIG-I, suggesting that the domains responsible for RIG-I signaling and RIG-I interaction are mapped on different regions of the protein.


Morphological effects of an anabolic steroid on muscle fibres of the diaphragm in mice.
Until recently, rats have been used for studies on the effects of anabolic steroids (AS) for improving physical performance. However, no consistent results on the changes in muscle fibre volume have ever been obtained. In this study we investigated the morphological effects of nandrolone phenylpropionate, an AS, on the muscle fibres of the diaphragm in adult male mice. AS (5 mg kg(-1) week(-1)) was injected intramuscularly in the experimental group (AS-administration group), and peanut oil (0.08 ml week(-1)) was injected in the control group. The cross-sectional areas of Type I (red) and Type II (white and intermediate) muscle fibres after 4 weeks of AS administration were 135% and 139% larger than those in the control group, respectively. The mean cross-sectional areas of mitochondria in the subsarcolemmal (SS) region and interfibrillar (IF) region in Type I fibres and the SS region of the Type II muscle fibres in the AS-administration group were 139%, 135% and 124% larger than those in the control group, respectively. No significant differences in the cross-sectional area of mitochondria were noted between the group of mice administered with AS for 8 weeks and the control group, showing that the effect of the AS administration attained a peak at 4 weeks, but that the effect of the 8 weeks of AS administration declined. We concluded from these results that the response of Type I muscle fibres to AS is stronger than that of Type II muscle fibres, as is the response of SS mitochondria compared to IF mitochondria. We also suggested that the two types of mitochondria may have different roles and that administration of AS may cause a different response in the two types of mitochondria.


Time-dependent Jahn-Teller problem: phonon-induced relaxation through conical intersection.
A theoretical study of time-dependent dynamical Jahn-Teller effect in an impurity center in a solid is presented. We are considering the relaxation of excited states in the E⊗e-problem through the conical intersection of the potential energy. A strict quantum-mechanical treatment of vibronic interactions with both the main Jahn-Teller active vibration and the nontotally symmetric phonons causing the energy loss is given. The applied method enables us to calculate the time-dependence of the distribution function of the basic configurational coordinate. We have performed a series of numerical calculations allowing us, among other relaxation features, to visualise the details of the relaxation through the conical intersection. In particular, we elucidate how the Slonczewski quantization of the states in the conical intersection affects the relaxation.


Notch signaling regulates growth and differentiation in the mammalian lens.
The Notch signal transduction pathway regulates the decision to proliferate versus differentiate. Although there are a myriad of mouse models for the Notch pathway, surprisingly little is known about how these genes regulate early eye development, particularly in the anterior lens. We employed both gain-of-function and loss-of-function approaches to determine the role of Notch signaling in lens development. Here we analyzed mice containing conditional deletion of the Notch effector Rbpj or overexpression of the activated Notch1 intracellular domain during lens formation. We demonstrate distinct functions for Notch signaling in progenitor cell growth, fiber cell differentiation and maintenance of the transition zone. In particular, Notch signaling controls the timing of primary fiber cell differentiation and is essential for secondary fiber cell differentiation. Either gain or loss of Notch signaling leads to formation of a dysgenic lens, which in loss-of-function mice undergoes a profound postnatal degeneration. Our data suggest both Cyclin D1 and Cyclin D2, and the p27(Kip1) cyclin-dependent kinase inhibitor act downstream of Notch signaling, and define multiple critical functions for this pathway during lens development.


A Looming Spatial Localization Neural Network Inspired by MLG1 Neurons in the Crab Neohelice.
Similar to most visual animals, the crab Neohelice granulata relies predominantly on visual information to escape from predators, to track prey and for selecting mates. It, therefore, needs specialized neurons to process visual information and determine the spatial location of looming objects. In the crab Neohelice granulata, the Monostratified Lobula Giant type1 (MLG1) neurons have been found to manifest looming sensitivity with finely tuned capabilities of encoding spatial location information. MLG1s neuronal ensemble can not only perceive the location of a looming stimulus, but are also thought to be able to influence the direction of movement continuously, for example, escaping from a threatening, looming target in relation to its position. Such specific characteristics make the MLG1s unique compared to normal looming detection neurons in invertebrates which can not localize spatial looming. Modeling the MLG1s ensemble is not only critical for elucidating the mechanisms underlying the functionality of such neural circuits, but also important for developing new autonomous, efficient, directionally reactive collision avoidance systems for robots and vehicles. However, little computational modeling has been done for implementing looming spatial localization analogous to the specific functionality of MLG1s ensemble. To bridge this gap, we propose a model of MLG1s and their pre-synaptic visual neural network to detect the spatial location of looming objects. The model consists of 16 homogeneous sectors arranged in a circular field inspired by the natural arrangement of 16 MLG1s' receptive fields to encode and convey spatial information concerning looming objects with dynamic expanding edges in different locations of the visual field. Responses of the proposed model to systematic real-world visual stimuli match many of the biological characteristics of MLG1 neurons. The systematic experiments demonstrate that our proposed MLG1s model works effectively and robustly to perceive and localize looming information, which could be a promising candidate for intelligent machines interacting within dynamic environments free of collision. This study also sheds light upon a new type of neuromorphic visual sensor strategy that can extract looming objects with locational information in a quick and reliable manner.


Stereochemistry and neuropharmacology of a 'bath salt' cathinone: S-enantiomer of mephedrone reduces cocaine-induced reward and withdrawal in invertebrates.
Knowledge about the neuropharmacology of mephedrone (MEPH) applies primarily to the racemate, or street form of the drug, but not to its individual enantiomers. Here, through chemical isolation of MEPH enantiomers and subsequent behavioral characterization in established invertebrate (planarian) assays, we began separating adverse effects of MEPH from potential therapeutic actions. We first compared stereotypical and environmental place conditioning (EPC) effects of racemic MEPH, S-MEPH, and R-MEPH. Stereotypy was enhanced by acute treatment (100-1000 μM) with each compound; however, S-MEPH was less potent and efficacious than racemate and R-MEPH. Both R-MEPH (10, 100, 250 μM) and racemate (100 μM) produced EPC, but S-MEPH was ineffective at all concentrations (10-100 μM). After showing that S-MEPH lacked rewarding efficacy, we investigated its ability to alter three of cocaine's behavioral effects (EPC, withdrawal, and stereotypy). Cocaine (1 μM) produced EPC that was abolished when S-MEPH (100 μM) was administered after cocaine conditioning. Spontaneous withdrawal from chronic cocaine exposure caused a reduction in motility that was not evident during acute or continuous cocaine treatment but was attenuated by S-MEPH (100 μM) treatment during the cocaine abstinence interval. Acute stereotypy produced by 1 mM cocaine, nicotine or racemic MEPH was not affected by S-MEPH (10-250 μM). The present results obtained using planarian assays suggest that the R-enantiomer of MEPH is predominantly responsible for its stimulant and rewarding effects and the S-enantiomer is capable of antagonizing cocaine's addictive-like behaviors without producing rewarding effects of its own.


Rearrangement of 3-Hydroxyazetidines into 2-Oxazolines.
A novel rearrangement sequence of 3-hydroxyazetidines via a Ritter initiated cascade provides highly substituted 2-oxazolines in high yields. The reaction conditions and substrate scope of the transformation have been studied demonstrating the generality of the process. The derived products can also be functionalized in order to undergo further intramolecular cyclization leading to a new class of macrocycle. The final cyclization step was shown to be a transformation amenable to continuous flow processing allowing for a dramatic reduction in the reaction time and simple scale-up.


Indirect Competitive Determination of Tetracycline Residue in Honey Using an Ultrasensitive Gold-Nanoparticle-Linked Aptamer Assay.
Tetracycline residue in honey has become an increasingly important food safety problem. In this work, an ultrasensitive gold nanoparticles (AuNPs)-linked aptamer assay was developed to determine the tetracycline residue in honey. First, a tetracycline-bovine serum albumin conjugate coating was applied to a microplate. Then, with the incubation of AuNPs-linked aptamer, the fixed tetracycline in the microplate competed for the limited aptamer with the free tetracycline in the sample. Higher amounts of free tetracycline in the sample were associated with more competitive binding of aptamer-AuNPs, and the aptamer-AuNPs binding with tetracycline-BSA was lower. Finally, as a kind of nanozyme, AuNPs exhibited peroxidase activity and oxidized 3,3',5,5'-tetramethylbenzidine, transforming it from colorless to blue, and achieving the measurement at 652 nm. The analytical performance-including linearity, limit of detection, selectivity, precision, repeatability, and accuracy-has been investigated. It was successfully applied to the determination of tetracycline in honey samples with high accuracy and sensitivity.


Characterization of single vs. recurrent spontaneous coronary artery dissection.
Background Spontaneous coronary artery dissection is a rare non-atherosclerotic cause of acute coronary syndromes, often underdiagnosed based on standard coronary angiography. Moreover, features, presentation, and intravascular imaging of recurrent spontaneous dissections have not been assessed. Methods Patients with recurrent spontaneous coronary artery dissection, who were admitted to our catheterization laboratory over a 10-year period, were identified. Demographic, clinical, angiographic, and intravascular imaging data were reviewed and analyzed, comparing patients with a single event with those who had a recurrence. Results Over the study period, 31 (0.2%, mean age 48.1 ± 8.8 years, 24 females) of 10,954 patients who underwent coronary angiography experienced a single spontaneous coronary artery dissection, and 6 (0.05%, mean age 49.3 ± 10.1 years, 4 females) experienced recurrent spontaneous coronary artery dissection. No patient suffered more than 2 dissections. Arterial hypertension ( p = 0.004), a string sign measuring >15 mm on angiography, and hematoma on intravascular ultrasound imaging were more frequently observed in patients with recurrent spontaneous coronary artery dissection. Conclusions Hypertension, length of the string sign on angiography, and hematoma on intravascular ultrasound imaging might identify patients at higher risk of recurrent spontaneous coronary artery dissection despite a lifelong dual antiplatelet regimen.


Antibodies to actin in autoimmune haemolytic anaemia.
In autoimmune haemolytic anaemia (AIHA), autoreactive antibodies directed against red blood cells are up-regulated, leading to erythrocyte death. Mycoplasma suis infections in pigs induce AIHA of both the warm and cold types. The aim of this study was to identify the target autoantigens of warm autoreactive IgG antibodies. Sera from experimentally M. suis-infected pigs were screened for autoreactivity. Actin-reactive antibodies were found in the sera of 95% of all animals tested. The reactivity was species-specific, i.e. reactivity with porcine actin was significantly higher than with rabbit actin. Sera of animals previously immunised with the M. suis adhesion protein MSG1 showed reactivity with actin prior to infection with M. suis indicating that molecular mimicry is involved in the specific autoreactive mechanism. A potentially cross-reactive epitope was detected. This is the first report of autoreactive anti-actin antibodies involved in the pathogenesis of autoimmune haemolytic anaemia.


Impact of Xuezhikang on coronary events in hypertensive patients with previous myocardial infarction from the China Coronary Secondary Prevention Study (CCSPS).
The lowering of cholesterol concentrations in individuals at high risk for cardiovascular disease improves clinical outcome. Xuezhikang has a marked impact on lipids. In this randomized, double-blinded, placebo-controlled, parallel-group clinical trial, a total of 2704 hypertensive patients with previous myocardial infarction (MI) were assigned either to placebo (n = 1341) or to Xuezhikang (0.6 g twice daily, n = 1363) for an average of 4.5 years. The primary end-point was recurrent coronary events; the secondary end-point was all-cause mortality and other clinical events, including adverse effects. There were no differences between the Xuezhikang and placebo group in base-line characteristics. However, Xuezhikang treatment reduced the incidence of coronary events by 43.0% (P = 0.02), deaths from coronary heart disease (CHD) by 30.0% (P < 0.01), and all-cause mortality by 35.8% (P = 0.001). This study, for the first time, demonstrated that long-term Xuezhikang therapy resulted in significant reduction in cardiovascular events and death in Chinese hypertensive patients with previous MI in a safe manner.


VDAC1, mitochondrial dysfunction, and Alzheimer's disease.
Alzheimer's disease (AD) is an age-related neurodegenerative disorder. Although an accumulation of brain amyloid-β (Aβ) peptide and hyperphosphorylated tau protein have been implicated in the pathogenesis of AD, the etiology of the disease remains unclear. Mitochondrial dysfunction has been identified as an early event in AD pathogenesis and is reflected by reduced metabolism, disruption of Ca2+ homeostasis, and increased levels of reactive oxygen species, lipid peroxidation, and apoptosis. The focus of this review is the involvement of mitochondrial dysfunction in AD, and specifically, the role of the voltage-dependent anion channel 1 (VDAC1), which has been linked to AD pathogenesis. VDAC1 is a multi-functional protein, expressed in the mitochondria and other cell compartments, including the plasma membrane. The protein regulates the main metabolic and energetic functions of the cell, including Ca2+ homeostasis, oxidative stress, and mitochondria-mediated apoptosis. VDAC1 represents a hub protein that interacts with over 150 other proteins including phosphorylated tau, Aβ, and γ-secretase, and participates in their toxicity. The high levels of VDAC1 demonstrated post-mortem in the brains of AD patients and in amyloid precursor protein (APP) transgenic mice prompted the hypothesis that the protein may be associated with neuronal cell destruction since over-expression of VDAC1 triggers cell death. Thus, targeting mitochondrial dysfunction via VDAC1, to prevent this pro-apoptotic activity, could represent a novel strategy for inhibiting cell death. In addition, the review also discusses possible VDAC1 involvement in the link between AD and diabetes and the inverse association between cancer and AD.


Association of gastroesophageal reflux disease with increased risk of chronic otitis media with effusion in adults: A nationwide population-based cohort study.
This study aimed to evaluate the risk of developing chronic otitis media with effusion (OME) in individuals with gastroesophageal reflux disease (GERD).A retrospective propensity score-matched cohort study was performed using data from the Korea National Health Insurance Service. The GERD group (n = 3532) included certain individuals who had been diagnosed with GERD between January 2002 and December 2005. A comparison control group (n = 14,128) was calculated by 1:4 Propensity Score (PS) matching considering age, sex, and comorbidities and year of enrolment. Each patient was monitored until 2013. Survival analysis, the log-rank test, and Cox proportional hazard regression models were used to calculate the incidence, survival rate, and hazard ratio (HR) of chronic OME for each group.Among the 17,660 individuals included in the study population (53.2% male), the overall incidence of chronic OME during the 11-year follow-up was 1.84-fold higher in the GERD group than in the non-GERD group (1.8 vs 3.0 per 1000 person-year; adjusted HR 1.84; 95% confidence interval [CI], 1.46-2.31). Moreover, the adjusted HRs of developing chronic OME (allergic rhinitis, 1.69 [95% CI, 1.37-2.10]; asthma, 1.29 [95% CI, 1.02-1.64]; chronic rhinosinusitis, 1.61 [95% CI, 1.26-2.05]) were greater in study population with comorbidities.From long-term follow-up, the prevalence of chronic OME in adults was 1.84 times higher in the GERD group compared with the non-GERD group. Specifically, it found that allergic rhinitis, asthma, or chronic rhinosinusitis showed increase the risk of developing chronic OME than those without these conditions.


KRAS and BRAF mutations in circulating tumour DNA from locally advanced rectal cancer.
There are limited data on circulating, cell-free, tumour (ct)DNA analysis in locally advanced rectal cancer (LARC). Digital droplet (dd)PCR was used to investigate KRAS/BRAF mutations in ctDNA from baseline blood samples of 97 LARC patients who were treated with CAPOX followed by chemoradiotherapy, surgery and adjuvant CAPOX ± cetuximab in a randomised phase II trial. KRAS mutation in G12D, G12V or G13D was detected in the ctDNA of 43% and 35% of patients with tumours that were mutant and wild-type for these hotspot mutations, respectively, according to standard PCR-based analyses on tissue. The detection rate in the ctDNA of 10 patients with less common mutations was 50%. In 26 cases ctDNA analysis revealed KRAS mutations that were not previously found in tissue. Twenty-two of these (84.6%) were detected following repeat tissue testing by ddPCR. Overall, the ctDNA detection rate in the KRAS mutant population was 66%. Detection of KRAS mutation in ctDNA failed to predict prognosis or refine patient selection for cetuximab. While this study confirms the feasibility of ctDNA analysis in LARC and the high sensitivity of ddPCR, larger series are needed to better address the role of ctDNA as a prognostic or predictive tool in this setting.


Microbial transformation of maridomycin III by Serratia marcescens.
Two transformation products of maridomycin (MDM) III, MDM-S1 and MDM-S2 named after Serratia marcescens, were isolated by silica gel chromatography. NMR and IR analysis revealed that MDM-S1 and -S2 had no aldehyde group at C-18 on the macrolactone ring, and that the hydroxyl group at C-9 seemed to disappear. Although MDM-S1 and -S2 are less active against Gram-positive bacteria than starting MDM III they are interesting materials in view of the introduction of nitrogen into each molecule, and that the transformation products are produced by Gram-negative bacteria which are thought to be insensitive to macrolide antibiotics.


HER-2÷neu expression in different histological subtypes of papillary thyroid carcinoma.
The identification and validation of new, complementary prognostic factors represents a challenging issue in thyroid pathology, opening the perspective of papillary thyroid carcinoma (PTC) stratification based on differences of aggressiveness at molecular level. Our study aims to analyze the HER-2÷neu expression in different subtypes of PTC and its relationship with the classical clinicopathological factors. We investigated 120 cases of sporadic PTC. The cases were selected based on the histological criteria reported to clinical course and prognosis and distributed in two different subgroups, namely low- and high-risk. HER-2÷neu expression was assessed using an adapted semiquantitative score proposed for thyroid carcinomas. The correlations between HER-2÷neu expression and clinicopathological prognostic factors were statistically analyzed. HER-2÷neu positivity was found in 25 (20.8%) cases, from which 20 cases were classified as subtypes with low-risk and five with high-risk; 95 (79.2%) cases were HER-2÷neu negative, 53 cases being included in low- and 42 cases, respectively, in high-risk group. HER-2÷neu expression was significantly associated with histological subtypes, extrathyroidal extension, and tumor focality. Our results highlight the potential of HER-2÷neu as supplementary marker useful for the stratification of PTC in low-risk and high-risk histological groups, along with the well-known clinicopathological prognostic factors. Our data could be considered as new evidences that indicate different involvement of HER-2÷neu in tumor development and behavior, possible due to its connection with other factors present in the molecular environment.


Households' willingness to pay for water for the environment in an urban setting.
Continued population growth, and climate change are placing stress on many of the world's water sources and this often manifests in environmental damage to rivers and wetlands. Most of the published literature around allocating more water to the environment considers trade-offs with agriculture. In contrast this study focusses on scenarios for different potable water supplies in cities and thus adds a novel perspective on the value of riverine restoration. This study sheds light on urban households' willingness to pay for more water to be allocated to the environment where it directly competes with their own water demands. The study uses two stated preference techniques (choice modelling and best-worst scaling) to establish the value of environmental water and the motivations for households paying for an increase in environmental water reserves. The study is set in Australia's fastest growing city, Melbourne, although the approach and method have implications for other developed-world settings. The paper also offers practical advice on the management of water allocated for different uses. Overall, the results indicate a positive and significant willingness to pay by households for additional water entitlements. Importantly, this provides a benchmark for contemplating the costs and benefits of activating alternative water supplies, such as desalination, to free up rainwater for environmental purposes.


Association of Toll-like receptor 4 gene polymorphisms with normal tension glaucoma.
Toll-like receptor 4 (TLR4) is a transmembrane receptor that mediates immune responses to exogenous and endogenous ligands and interacts with heat shock proteins, which are reportedly involved in normal tension glaucoma (NTG). This study was undertaken to investigate whether TLR4 polymorphisms are associated with NTG. Two hundred fifty Japanese patients with NTG and 318 Japanese healthy control subjects were recruited. Eight single-nucleotide polymorphisms (SNPs) in the TLR4 gene were genotyped, and allelic and phenotypic diversity was assessed between cases and control subjects. Strong linkage disequilibrium was observed among all SNPs (D' >or= 0.85), which were located in one haplotype block. With respect to allelic diversity, the minor allele of three SNPs (rs10759930, rs1927914, and rs7037117) carried a significantly increased risk of NTG. With regard to genotypic diversity, individuals with the minor allele of six SNPs (rs10759930, rs1927914, rs1927911, rs12377632, rs2149356, and rs7037117) had a 1.47- to 1.65-fold increased risk of NTG. rs7037117, located in the 3'-untranslated region of TLR4, was most strongly associated with NTG, and when incorporated into a haplotype with rs10759930, the strongest association was detected (P = 0.0038, P(c) = 0.0095). Multiple SNPs in the TLR4 gene are associated with the risk of NTG. This finding suggests that the ligands and/or cytokines involved in the TLR4 signaling network may be risk factors for the development of NTG.


The Role of Multistakeholder Platforms in Environmental Governance: Analyzing Stakeholder Perceptions in Kalomo District, Zambia, Using Q-Method.
Multistakeholder platforms (MSPs) are increasingly applied in environmental governance as institutions to collectively negotiate challenges, opportunities, and policy options in contested landscapes. However, their contributions and effectiveness depend on how stakeholders perceive and frame the role of MSPs in addressing social and environmental challenges. Despite this dependence, stakeholder perceptions of MSPs are currently under-researched. Hence this empirical study carried out in Zambia's Kalomo District asks: how do stakeholder groups perceive the role of MSPs in addressing landscape challenges, given the context of the dual land tenure system, and what does this imply for the implementation of integrated landscape approaches? This study uses Q-methodology to analyze the perceptions of purposefully selected stakeholders from state institutions, civil society organizations, land users, and others familiar with existing MSPs at the district and village levels. The findings reveal three narratives. The first one presents MSPs as institutions that foster dialogue. The second narrative foregrounds the role of the government and private sector, despite acknowledging the diversity of stakeholders in MSPs. In this narrative, MSPs should focus on supporting market-driven solutions to resolve landscape challenges. The third narrative recognizes power imbalances and considers MSPs as institutions to identify policy gaps and needs. The first two narratives are positioned in Dryzek's discourse classification as environmental problem-solving, while the third inclines toward green radicalism. Despite this divergence, there was consensus that MSPs have the potential to harmonize policies in a dual governance system and encourage dialogue between stakeholders to reconcile landscape challenges.


Advantage of monoclonal vs. polyclonal antisera in a beta 2-microglobulin radioimmunoassay.
Unassociated human beta 2-microglobulin (beta 2m) and histocompatibility peptide associated beta 2-microglobulin produce significantly different inhibition curves in a competitive binding assay with rabbit anti-beta 2-microglobulin. This difference disallows the use of the rabbit antisera for measuring MHC-beta 2-microglobulin complex concentration using free beta 2m as a standard. Presumably the close amino acid sequence homology between human and rabbit beta 2-microglobulin results in rabbit antisera against a small number of epitopes, some of which are covered or conformationally altered in the MHC-beta 2-microglobulin complex. A monoclonal anti-beta 2-microglobulin antibody, LG1 reacted equally well with both forms of beta 2-microglobulin and is used to measure the concentration of beta 2-microglobulin in the histocompatibility peptide complex.


Ibuprofen in needle procedures in children with cancer-A feasibility and pilot study.
To investigate the feasibility, and perform a pilot study, of a randomised clinical trial, investigating whether children experience less pain, fear and/or distress when they receive oral ibuprofen vs placebo before a needle is inserted in a subcutaneously implanted intravenous port. Twenty-three children were included consecutively and randomised to either oral ibuprofen (n = 12) 7.5 mg/kg body weight or placebo (n = 11). The child's pain, fear and distress were reported by parents, nurses and the children (if ≥7 years of age). Feasibility criteria were defined as (a) ≥4 children included/month, (b) ≥80% of eligible patients agreed to participate, (c) >90% treated according to protocol, (d) <5% missing data, (e) s-cortisol samples analysed in ≥90% of the children. All feasibility criteria were met except recruitment and consent. Parents, nurses and children reported no trend of benefit of oral ibuprofen with regard to pain, fear and distress compared with placebo. The study failed to meet important feasibility criteria and was closed due to low recruitment rate and absence of trend of effect. From this data, we cannot state that ibuprofen is not helpful in needle procedures but that it seems unlikely.


Long-term Effects of Remote Ischemic Preconditioning on Kidney Function in High-risk Cardiac Surgery Patients: Follow-up Results from the RenalRIP Trial.
In a multicenter, randomized trial, the authors enrolled patients at high-risk for acute kidney injury as identified by a Cleveland Clinic Foundation score of 6 or more. The authors enrolled 240 patients at four hospitals and randomized them to remote ischemic preconditioning or control. The authors found that remote ischemic preconditioning reduced acute kidney injury in high-risk patients undergoing cardiac surgery. The authors now report on the effects of remote ischemic preconditioning on 90-day outcomes. In this follow-up study of the RenalRIP trial, the authors examined the effect of remote ischemic preconditioning on the composite endpoint major adverse kidney events consisting of mortality, need for renal replacement therapy, and persistent renal dysfunction at 90 days. Secondary outcomes were persistent renal dysfunction and dialysis dependence in patients with acute kidney injury. Remote ischemic preconditioning significantly reduced the occurrence of major adverse kidney events at 90 days (17 of 120 [14.2%]) versus control (30 of 120 [25.0%]; absolute risk reduction, 10.8%; 95% CI, 0.9 to 20.8%; P = 0.034). In those patients who developed acute kidney injury after cardiac surgery, 2 of 38 subjects in the remote ischemic preconditioning group (5.3%) and 13 of 56 subjects in the control group (23.2%) failed to recover renal function at 90 days (absolute risk reduction, 17.9%; 95% CI, 4.8 to 31.1%; P = 0.020). Acute kidney injury biomarkers were also increased in patients reaching the major adverse kidney event endpoint compared to patients who did not. Remote ischemic preconditioning significantly reduced the 3-month incidence of a composite endpoint major adverse kidney events consisting of mortality, need for renal replacement therapy, and persistent renal dysfunction in high-risk patients undergoing cardiac surgery. Furthermore, remote ischemic preconditioning enhanced renal recovery in patients with acute kidney injury.


Transcranial direct current stimulation of the unaffected hemisphere in stroke patients.
Recovery of function after a stroke is determined by a balance of activity in the neural network involving both the affected and the unaffected brain hemispheres. Increased activity in the affected hemisphere can promote recovery, while excessive activity in the unaffected hemisphere may represent a maladaptive strategy. We therefore investigated whether reduction of the excitability in the unaffected hemisphere by cathodal transcranial direct current stimulation could result in motor performance improvement in stroke patients. We compared these results with excitability-enhancing anodal transcranial direct current stimulation of the affected hemisphere and sham transcranial direct current stimulation. Both cathodal stimulation of the unaffected hemisphere and anodal stimulation of the affected hemisphere (but not sham transcranial direct current stimulation) improved motor performance significantly. These results suggest that the appropriate modulation of bihemispheric brain structures can promote motor function recovery.


How acute total sleep loss affects the attending brain: a meta-analysis of neuroimaging studies.
Attention is a cognitive domain that can be severely affected by sleep deprivation. Previous neuroimaging studies have used different attention paradigms and reported both increased and reduced brain activation after sleep deprivation. However, due to large variability in sleep deprivation protocols, task paradigms, experimental designs, characteristics of subject populations, and imaging techniques, there is no consensus regarding the effects of sleep loss on the attending brain. The aim of this meta-analysis was to identify brain activations that are commonly altered by acute total sleep deprivation across different attention tasks. Coordinate-based meta-analysis of neuroimaging studies of performance on attention tasks during experimental sleep deprivation. The current version of the activation likelihood estimation (ALE) approach was used for meta-analysis. The authors searched published articles and identified 11 sleep deprivation neuroimaging studies using different attention tasks with a total of 185 participants, equaling 81 foci for ALE analysis. The meta-analysis revealed significantly reduced brain activation in multiple regions following sleep deprivation compared to rested wakefulness, including bilateral intraparietal sulcus, bilateral insula, right prefrontal cortex, medial frontal cortex, and right parahippocampal gyrus. Increased activation was found only in bilateral thalamus after sleep deprivation compared to rested wakefulness. Acute total sleep deprivation decreases brain activation in the fronto-parietal attention network (prefrontal cortex and intraparietal sulcus) and in the salience network (insula and medial frontal cortex). Increased thalamic activation after sleep deprivation may reflect a complex interaction between the de-arousing effects of sleep loss and the arousing effects of task performance on thalamic activity.


Role of reactive metabolites in the circulation in extrahepatic toxicity.
Reactive metabolite-mediated toxicity is frequently limited to the organ where the electrophilic metabolites are generated. Some reactive metabolites, however, might have the ability to translocate from their site of formation. This suggests that for these reactive metabolites, investigations into the role of organs other than the one directly affected could be relevant to understanding the mechanism of toxicity. The authors discuss the physiological and biochemical factors that can enable reactive metabolites to cause toxicity in an organ distal from the site of generation. Furthermore, the authors present a case study which describes studies that demonstrate that S-(1,2-dichlorovinyl)-L-cysteine sulfoxide (DCVCS) and N-acetyl-S-(1,2-dichlorovinyl-L-cysteine sulfoxide (N-AcDCVCS), reactive metabolites of the known trichloroethylene metabolites S-(1,2-dichlorovinyl)-L-cysteine (DCVC), and N-acetyl-S-(1,2-dichlorovinyl)-L-cysteine (N-AcDCVC), are generated in the liver and translocate through the circulation to the kidney to cause nephrotoxicity. The ability of reactive metabolites to translocate could be important to consider when investigating mechanisms of toxicity. A mechanistic approach, similar to the one described for DCVCS and N-AcDCVCS, could be useful in determining the role of circulating reactive metabolites in extrahepatic toxicity of drugs and other chemicals. If this is the case, intervention strategies that would not otherwise be feasible might be effective for reducing extrahepatic toxicity.


Sympathetic and sensory innervation of small intensely fluorescent (SIF) cells in rat superior cervical ganglion.
The sympathetic ganglion contains small intensely fluorescent (SIF) cells derived from the neural crest. We morphologically characterize SIF cells and focus on their relationship with ganglionic cells, preganglionic nerve fibers and sensory nerve endings. SIF cells stained intensely for tyrosine hydroxylase (TH), with a few cells also being immunoreactive for dopamine β-hydroxylase (DBH). Vesicular acetylcholine transporter (VAChT)-immunoreactive puncta were distributed around some clusters of SIF cells, whereas some SIF cells closely abutted DBH-immunoreactive ganglionic cells. SIF cells contained bassoon-immunoreactive products beneath the cell membrane at the attachments and on opposite sites to the ganglionic cells. Ganglion neurons and SIF cells were immunoreactive to dopamine D2 receptors. Immunohistochemistry for P2X3 revealed ramified nerve endings with P2X3 immunoreactivity around SIF cells. Triple-labeling for P2X3, TH and VAChT allowed the classification of SIF cells into three types based on their innervation: (1) with only VAChT-immunoreactive puncta, (2) with only P2X3-immunoreactive nerve endings, (3) with both P2X3-immunoreactive nerve endings and VAChT-immunoreactive puncta. The results of retrograde tracing with fast blue dye indicated that most of these nerve endings originated from the petrosal ganglion. Thus, SIF cells in the superior cervical ganglion are innervated by preganglionic fibers and glossopharyngeal sensory nerve endings and can be classified into three types. SIF cells might modulate sympathetic activity in the superior cervical ganglion.


Molecular modelling and docking studies on heat shock protein 90 (Hsp90) inhibitors.
An adenosine tri-phosphate (ATP)-dependent molecular chaperone heat shock protein (Hsp90) is of current interest as a potential anticancer drug target. It has several oncogenic client proteins involved in signal transduction, cell cycle regulation and apoptosis. In order to identify essential chemical functional features for Hsp90 inhibition, a pharmacophore model consisting of one hydrogen bond donor, two hydrogen bond acceptor lipid and one hydrophobic feature has been developed using Hypogen (Catalyst 2.0 software) on a total set of 103 inhibitors consisting of 16 and 87 compounds in the training and the test set, respectively. The model shows good correlation for the training (r(2)= 0.887) and the test set ( [image omitted] = 0.692). In view of the X-ray data structure of Hsp90, GOLD 3.2 docking software was used to dock the 16 training set compounds. A good correlation (r(2)= 0.699) was observed between the experimental biological activity and the top-ranked Goldscore. The analysis of conserved patterns across the Hsp90 family, using the human Hsp90 X-ray structure as an alignment template, led to the identification of important amino acids involved in the ligand-binding interactions, which were found to be similar to those observed in docking studies. Hence, the best-generated pharmacophore model can be used for designing new Hsp90 inhibitors.


Familial aggregation of urinary kallikrein concentration in childhood: relation to blood pressure, race and urinary electrolytes.
Biochemical alterations that have been correlated with elevated blood pressure have not received extensive epidemiologic study because of the technical difficulties involved. Because the excretion of urinary kallikrein is reduced significantly in adult hypertensives, we have studied urinary kallikrein in a cohort of children in whom familial aggregation of blood pressure has been demonstrated. Casual specimens of urine were obtained in household surveys, and urinary concentration of kallikrein was determined in 601 children aged 5-18 years. The children were from 163 families, whose members also had their blood pressures measured. Familial aggregation of urinary kallikrein concentration was found by analysis of variance (F=3.45, p less than 0.001) even in these casual specimens and was demonstrable for black and white children analyzed separately. Urinary kallikrein concentration was significantly lower in black children than in white children (p less than 0.001) and was positively correlated with urinary creatinine and urinary potassium and inversely related to urinary sodium concentrations. Urinary kallikrein concentration also was being altered by season (being lowest in the summer) and by time of day (being highest in the morning). Families with the lowest mean kallikrein concentrations tended to have higher blood pressures than did families with the highest mean kallikrein concentrations, although the effect is small and subject to many variables.


Regenerative activity in acute hepatitis A virus. Autoradiographic study after in vitro incorporation of 3H-thymidine.
The in vitro incorporation of 3H-thymidine by liver tissue obtained using needle biopsy from 14 patients with acute hepatitis A virus (AHAV) in the fully developed and recovery stage of disease was studied by the autoradiographic technique. Marked incorporation in hepatocyte nuclei was observed in the biopsies of patients in the fully developed stage, while incorporation was absent in the recovery stage of the disease. Results show that hepatocyte regeneration begins early in the course of AHAV disease, during which signs of cellular suffering and necrosis are still present.


[Advances in the study of stem cell niche].
A stem cell niche is defined as the microenvironment surrounding stem cells, and it is generally composed of adjacent cells, adhensive molecules, extracellular matrix, and so on. Stem cells in different tissues differ in their niches. Stem cell niches regulate stem cell self-renewal and differentiation. According to the recent studies in stem cell niches, this review summarizes on the constitution and function of germ-line stem cells niche in fruit, hematopoietic stem cell niche, intestinal stem cell niche, hair follicle epidermal stem cell niche and neural stem cell niche in mammals, and discusses the internal mechanism of niches'action on stem cells.


Are the faithful becoming less fruitful? The decline of conservative protestant fertility and the growing importance of religious practice and belief in childbearing in the US.
Studies of religion and fertility argue that American childbearing has become less predicated on religious tradition and more on religious commitment and belief. Yet studies have not documented this transition over time or considered whether the growing importance of religious commitment and belief in childbearing applies across Christian traditions equally. Using data from the 1972-2016 General Social Surveys, we analyze childbearing trends across time and birth cohort focusing on the independent and interrelated effects of religious tradition, religious practice, and theological fundamentalism. We also utilize zero-inflated negative binomial regression models to better account for the increasing number of Americans who forego childbearing. Conservative Protestant affiliation is associated with faster than average declines in fertility, while monthly church attendance and biblical literalism are associated with slower than average declines in fertility, ceteris paribus. Examining moderating relationships, monthly worship attendance slightly increases the childbearing of mainline Protestants and Catholics over time, while conservative Protestant childbearing declines regardless of attendance. Unless offset by switching, our findings portend future population declines for conservative Protestants, notably, ones that are not attenuated by greater religious commitment.


[Effects of ultrapure water on the levels of oxidative stress and inflammation parameters in maintenance hemodialysis patients].
To evaluate the effects of ultrapure water on the levels of oxidative stress and inflammation parameters in maintenance hemodialysis patients. Thirty-six stable maintenance hemodialysis patients were involved in this study, who were free of acute infection, vasculitis or disease activity and on hemodialysis therapy for at least 3 months before using ultrapure water. The parameters including serum advanced oxidation protein products (AOPP), malondialdehyde (MDA), glutathione peroxidase (GSH-Px), myeloperoxidase (MPO), albumin (Alb), C-reactive protein (CRP), neopterin , tumor necrosis factor (TNF)-alpha, and interleukin (IL)-6 were measured before and 6, 12 months after use of ultrapure water, respectively. After modification of the water management system, the microbial counts and endotoxin concentration decreased significantly (P<0.01). During the study period, the levels of the measured parameters gradually improved, showing significant difference between the time points of measurement (P<0.05). Use of ultrapure water for 6 months significantly improved serum AOPP, MDA, GSH-Px, MPO, Alb, CRP, neopterin, and TNF-alpha levels (P<0.05), and the level of IL-6 was further reduced after 12 months (P<0.05). Serum MPO activity was closely correlated with AOPP (r=0.335, P<0.05) and CRP (r=0.369 or 0.347, P<0.05) before or after use of ultrapure water. Ultrapure water can improve the status of oxidative stress and inflammation in maintenance hemodialysis patients. Serum MPO activity may help estimate the levels of oxidative stress and inflammation.


Tuning supramolecular rigidity of peptide fibers through molecular structure.
We synthesized a series of peptide amphiphiles (PAs) with systematically modified amino acid sequences to control the mechanical properties of the nanofiber gels they form by self-assembly. By manipulating the number and position of valines and alanines in the peptide sequence, we found that valines increase the stiffness of the gel, while additional alanines decrease the mechanical properties. Vitreous ice cryo-transmission electron microscopy shows that all PA molecules investigated here form nanofibers 8-10 nm in diameter and several micrometers in length. We found through Fourier transform IR experiments a strong correlation between gel stiffness and hydrogen bond alignment along the long axis of the fiber. Molecules that form supramolecular structures with the highest mechanical stiffness were found by circular dichroism to self-assemble into beta-sheets with the least amount of twisting and disorder, a result that is consistent with IR experiments. Molecular control of mechanical stiffness in three-dimensional artificial peptide amphiphile matrices offers a chemical strategy to control biological phenomena such as stem cell differentiation and cell morphology.


Haplo-Cord transplantation compared to haploidentical transplantation with post-transplant cyclophosphamide in patients with AML.
For patients with AML, the best alternative donor remains to be defined. We analyze outcomes of patients who underwent myeloablative umbilical cord blood or haploidentical hemopoietic stem cell transplantation (HSCT) in Spain. Fifty-one patients underwent single umbilical cord blood transplantation supported by a third party donor (Haplo-Cord) between 1999 and 2012, and 36 patients received an haploidentical HSCT with post-transplant cyclophosphamide (PTCY-haplo) between 2012 and 2014 in GETH centers. The Haplo-Cord cohort included a higher proportion of patients with high disease risk index and use of TBI in the conditioning regimen, and hematopoietic cell transplantation-age Comorbidity Age Index was higher in PTCY-haplo patients. Cumulative incidence of neutrophil engraftment was 97% in the Haplo-Cord and 100% in the PTCY-haplo group, achieved in a median of 12 and 17 days, respectively (P=0.01). Grade II-IV acute GvHD rate was significantly higher in the PTCY-haplo group (9.8% vs 29%, P=0.02) as well as chronic GvHD rates (20% vs 38%, P=0.03). With a median follow-up of 61 months for the Haplo-Cord group and 26 months for the PTCY-haplo cohort, overall survival at 2 years was 55% and 59% (P=0.66), event-free survival was 45% vs 56% (P=0.46), relapse rate was 27% vs 21% (P=0.79), and non-relapse mortality was 17% vs 23% (P=0.54), respectively. In this multicenter experience, Haplo-Cord and PTCY-haplo HSCT offer valid alternatives for patients with AML. Neutrophil engraftment was faster in the Haplo-Cord cohort, with similar survival rates, with higher GvHD rates after haploidentical HSCT.


Quantitative morphological analysis reveals ultrastructural diversity of amyloid fibrils from alpha-synuclein mutants.
High resolution atomic force microscopy is a powerful tool to characterize nanoscale morphological features of protein amyloid fibrils. Comparison of fibril morphological properties between studies has been hampered by differences in analysis procedures and measurement error determination used by various authors. We describe a fibril morphology analysis method that allows for quantitative comparison of features of amyloid fibrils of any amyloidogenic protein measured by atomic force microscopy. We have used tapping mode atomic force microscopy in liquid to measure the morphology of fibrillar aggregates of human wild-type alpha-synuclein and the disease-related mutants A30P, E46K, and A53T. Analysis of the images shows that fibrillar aggregates formed by E46K alpha-synuclein have a smaller diameter (9.0 +/- 0.8 nm) and periodicity (mode at 55 nm) than fibrils of wild-type alpha-synuclein (height 10.0 +/- 1.1 nm; periodicity has a mode at 65 nm). Fibrils of A30P have smaller diameter still (8.1 +/- 1.2 nm) and show a variety of periodicities. This quantitative analysis procedure enables comparison of the results with existing models for assembly of amyloid fibrils.


Engineered Resistant-Starch (ERS) Diet Shapes Colon Microbiota Profile in Parallel with the Retardation of Tumor Growth in In Vitro and In Vivo Pancreatic Cancer Models.
Pancreatic cancer (PC) is ranked as the fourth leading cause of cancer-related deaths worldwide. Despite recent advances in treatment options, a modest impact on the outcome of the disease is observed so far. We have previously demonstrated that short-term fasting cycles have the potential to improve the efficacy of chemotherapy against PC. The aim of this study was to assess the effect of an engineered resistant-starch (ERS) mimicking diet on the growth of cancer cell lines in vitro, on the composition of fecal microbiota, and on tumor growth in an in vivo pancreatic cancer mouse xenograft model. BxPC-3, MIA PaCa-2 and PANC-1 cells were cultured in the control, and in the ERS-mimicking diet culturing condition, to evaluate tumor growth and proliferation pathways. Pancreatic cancer xenograft mice were subjected to an ERS diet to assess tumor volume and weight as compared to mice fed with a control diet. The composition and activity of fecal microbiota were further analyzed in growth experiments by isothermal microcalorimetry. Pancreatic cancer cells cultured in an ERS diet-mimicking medium showed decreased levels of phospho-ERK1/2 (extracellular signal-regulated kinase proteins) and phospho-mTOR (mammalian target of rapamycin) levels, as compared to those cultured in standard medium. Consistently, xenograft pancreatic cancer mice subjected to an ERS diet displayed significant retardation in tumor growth. In in vitro growth experiments, the fecal microbial cultures from mice fed with an ERS diet showed enhanced growth on residual substrates, higher production of formate and lactate, and decreased amounts of propionate, compared to fecal microbiota from mice fed with the control diet. A positive effect of the ERS diet on composition and metabolism of mouse fecal microbiota shown in vitro is associated with the decrease of tumor progression in the in vivo PC xenograft mouse model. These results suggest that engineered dietary interventions could be supportive as a synergistic approach to enhance the efficacy of existing cancer treatments in pancreatic cancer patients.


The nature and evolution of interstellar ices.
The evolution of icy grain mantles is governed by the environment in which they exist. This review presents an overview of the study of the molecules that make up the mantles and discusses their relevance to the origin of life. Models predict two phases of mantle growth during cloud collapse: simple polar and nonpolar molecules dominate the mantle layers at early and late times, respectively (Section 1). The effect of processing on grain mantle composition and the connection between organics in grain mantles and prebiotic chemistry is introduced. Section 2 describes how infrared spectroscopy of dense cloud sources, combined with theoretical models and laboratory data, gives us information on the composition and abundance of the ices in varying regions. The observed features and how they are used as diagnostics of mantle evolution are discussed in Section 3. This section also discusses the importance of these molecules to prebiotic chemistry. Section 4 compares grain mantle composition in different low-mass star forming regions, which best represent the solar birthplace. The final section (Section 5) summarizes the information presented, emphasizing the link between the study of interstellar dust and the origin of life.


An efficient optimized method for isolation of villous trophoblast cells from human early pregnancy placenta suitable for functional and molecular studies.
The uniqueness of the human placenta cannot be replaced by animal models. In vitro studies are compulsory to elucidate the biology of human placenta and require isolation and purification of villous trophoblasts, which can be used in molecular and functional studies. Constant improvement in the isolation technique is required to obtain a high yield of pure trophoblast cells with high viability and well preserved morphology. Optimized isolation procedure for human villous trophoblasts based on mild enzymatic treatment, Percoll gradient centrifugation and additional purification step involving positive or negative immunoselection on magnetic beads is described. A simple and effective isolation protocol gave a reasonably high yield of villous trophoblast cells with high purity and viability, and excellent morphology as assessed by flow cytometry and electron microscopy. This protocol provides an efficient, optimized method for isolation and enrichment of villous trophoblast cells, suitable for phenotypic, ultrastructural, molecular and functional analyses and for establishment of primary cultures.


Ectopia vasa deferentia inguinal hernia, vesicourteric reflux, imperforate anus, and recto-vesical fistula: a case report.
Urologic congenital anomalies are frequently associated with anorectal abnormalities. Vas deferens anomalies in the general population are estimated to be less than 0.05%. Many of the abnormalities can be explained by events in early fetal life. Urosepsis and epididymitis are the usual presenting signs and symptoms in such patients. We describe an infant who was discovered after birth to have an association of high imperforate anus with recto-vesical fistula, right inguinal hernia, left vesicoureteral reflux, and bilateral dilated vasa deferentia ectopically terminating in the posterior urethra, which caused recurrent epididymo-orchitis.


Short- and long-term redox regulation of photosynthetic light energy distribution and photosystem stoichiometry by acetate metabolism in the green alga, Chlamydobotrys stellata.
The effect of acetate metabolism on the light energy distribution between the two photosystems, on the PS II/PS I stoichiometry and on the expression of psbA and psbB and psaA genes was investigated in the green alga, Chlamydobotrys stellata during autotrophic (CO(2)), mixotrophic (CO(2) plus acetate) and photoheterotrophic (only acetate) cultivation. It was observed that acetate assimilation in the glyoxylate cycle resulted in a large drop in the ATP content and a concomitant increase in the NADPH content of the cells. The combined effect of high NADPH concentration and linear electron transport brought about an over-reduction of the inter-photosystem electron transport components. The reduced state of the inter-photosystem components initiated a state 1/state 2 transition of LHC II and a decrease in the PS II/PS I ratio. The PS II/ PS I ratio was reduced because the synthesis of PS II reaction centers was repressed and that of the PS I reaction centers was slightly enhanced by acetate cultivation. The amount of PsbA and PsbB proteins of PS II and the abundance of psbA mRNA decreased. The abundance of PS I PsaA protein and psaAmRNA were only slightly increased. All of the acetate-induced effects were reversible when the cells were transferred back to an acetate-free medium. Our observations demonstrate that the expression of the PS II psbA and psbB and PS I psaA genes is regulated by the redox state of the inter-photosystem components at the transcriptional level. Experiments carried out in the presence of DBMIB which facilitates the reduction of plastoquinone pool indicate that the expression of genes encoding the components of PS II and PS I are controlled by the redox state of a component (cytochrome b/f complex) located behind the plastoquinone pool.


Circulating programmed death-1 as a marker for sustained high hepatitis B viral load and risk of hepatocellular carcinoma.
Recent evidence indicates a crucial role of the immunoinhibitory receptor programmed death-1 (PD-1) in enforcing T-cell dysfunction during chronic viral infection and cancer. We assessed the impact of circulating soluble PD-1 (sPD-1) levels on long-term dynamics of hepatitis B virus (HBV) load and hepatocellular carcinoma (HCC) risk. In a case-cohort study on longitudinal analysis of viral load within a cohort of 2903 men chronically infected with HBV, followed up from baseline (1989-1992) through 2010, we determined sPD-1 levels in baseline plasma with enzyme-linked immunosorbent assay from 126 men who subsequently developed HCC and 1155 men who did not develop HCC. To evaluate whether patients' characteristics involved the use of sPD-1 as a biomarker, sPD-1 was also tested in 614 newly-diagnosed patients with HBV-related HCC recruited from a multicenter study for comparison with the 1155 noncases in the case-cohort study. Plasma quartile levels of sPD-1 were positively associated with HCC risk for men in the case-cohort analysis (vs. quartile 1: adjusted odds ratios [95% confidence intervals] for quartile 2-quartile 4 were 1.51 [0.75-3.03], 2.15 [1.12-4.13], and 2.29 [1.20-4.38], respectively), and in the case-control study regardless of age-of-onset and clinical stage. Furthermore, we found longitudinal effect of elevated sPD-1 levels to maintain higher viral load for 4 or more years, with greater and more prolonged effect among HBV genotype C- vs. non-C-infected participants. High levels of viral load and sPD-1 (vs. absence of both) was associated with a 6.29-fold increase in risk of HCC, and combining both conditions with HBV genotype C yielded an odds ratio of 30.47 with significant additive interaction (relative excess risk due to interaction: 27.08 [95% confidence interval = 8.76-45.41]). Our data suggest plasma sPD-1 as an important immune-related marker for assessment of HBV activity and HCC risk.


Queensland public sector nurse executives: professional development needs.
In a time of health care reform and rapid change, nurse executives need effective leadership skills to be able to respond to a challenging environment, provide quality cost-effective care and promote the professional development of nursing. This research aimed to provide an understanding of nursing executives' roles and professional development needs and obtain concise information for the development of strategies and professional development programs to enhance the effectiveness of the present and future roles of nursing executives. A descriptive cross-sectional postal survey was sent to all public sector Level 4 and 5 nursing executives in Queensland (n = 281), with a response rate of 52.3% (n = 147). Financial management, human resource management and information technologies were identified as the areas where professional development was most needed. Structured educational activities such as short courses or seminars covering information technology, financial and budget management and general business management were identified as the type of activities best suited to nurse executives' needs. The most frequently reported barriers to professional development were difficulties obtaining relief staff, inadequate time, financial cost and inadequate district manager and regional support to enable access to professional development programs.


Multiple Past Concussions in High School Football Players: Are There Differences in Cognitive Functioning and Symptom Reporting?
There is increasing concern about the possible long-term effects of multiple concussions, particularly on the developing adolescent brain. Whether the effect of multiple concussions is detectable in high school football players has not been well studied, although the public health implications are great in this population. To determine if there are measureable differences in cognitive functioning or symptom reporting in high school football players with a history of multiple concussions. Cross-sectional study; Level of evidence, 3. Participants included 5232 male adolescent football players (mean [±SD] age, 15.5 ± 1.2 years) who completed baseline testing between 2009 and 2014. On the basis of injury history, athletes were grouped into 0 (n = 4183), 1 (n = 733), 2 (n = 216), 3 (n = 67), or ≥4 (n = 33) prior concussions. Cognitive functioning was measured by the Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT) battery, and symptom ratings were obtained from the Post-Concussion Symptom Scale. There were no statistically significant differences between groups (based on the number of reported concussions) regarding cognitive functioning. Athletes with ≥3 prior concussions reported more symptoms than did athletes with 0 or 1 prior injury. In multivariate analyses, concussion history was independently related to symptom reporting but less so than developmental problems (eg, attention or learning problems) or other health problems (eg, past treatment for psychiatric problems, headaches, or migraines). In the largest study to date, high school football players with multiple past concussions performed the same on cognitive testing as those with no prior concussions. Concussion history was one of several factors that were independently related to symptom reporting.


Sedation during voiding cystourethrography: comparison of the efficacy and safety of using oral midazolam and continuous flow nitrous oxide.
We compare the efficacy and safety profile of oral midazolam and continuous flow 50% nitrous oxide (N(2)O) for alleviating anxiety and pain during voiding cystourethrography (VCU) in children. This prospective, randomized clinical trial study was conducted in the radiology unit of a tertiary care center. Children older than 3 years scheduled for VCU were given either 0.5 mg/kg midazolam orally or continuous flow 50% N(2)O. Main outcomes were degree of anxiety and pain as assessed by the attending nurse and radiologist performing the test using a behavioral anxiety score, a distress score and an overall satisfaction score, side effects and recovery profile. The study included 47 children (89% girls) with a mean age of 6 years (range 3 to 15). There were 24 subjects in the midazolam group and 23 in the N(2)O group. Midazolam and N(2)O provided adequate anxiety and pain relief to perform the examination, yet children given N(2)O required less restraining and experienced a significantly shorter recovery time (29 +/- 10 vs 63 +/- 25 minutes, p <0.001). Continuous flow 50% nitrous oxide and oral midazolam are comparably safe and effective in reducing anxiety and distress during VCU in children older than 3 years. However, N(2)O provides a more rapid onset of sedating effect and has a shorter recovery time.


The extent of co-metabolism of glucose and galactose by Lactococcus lactis changes with the expression of the lacSZ operon from Streptococcus thermophilus.
The lactose transporter and beta-galactosidase from Streptococcus thermophilus, encoded by the lacSZ operon, were introduced into the lactose-negative strain Lactococcus lactis MG1363 and the expression of the lacSZ operon was modulated by substitution of the native promoter with randomized synthetic promoters. A series of strains with various expression levels of lacSZ were examined for their fermentation of lactose. Strains with a high expression level were found to metabolize lactose in a similar manner to S. thermophilus, i.e. the galactose moiety of lactose was excreted to the growth medium and only glucose was metabolized in glycolysis. Interestingly, strains with low expression of the operon showed a mixed acid metabolism and co-metabolism of galactose and glucose. The lactose flux increased gradually with increasing expression of the lacSZ operon until an optimum was observed at intermediate beta-galactosidase activities of 2000-3000 Miller units. At higher expression levels, the flux decreased. These strains had a glycolytic flux comparable with those of reference strains with the standard lactococcal PTS(lac) (lactose phosphotransferase transport system) lactose transporter, which indicates that lactose transport is not rate-limiting for glycolysis in Lactococcus. Finally, an additional ATP drain was introduced into the fastest growing strain, CS2004, to test whether the ATP demand controlled glycolysis under these conditions, but in fact no increase in glycolytic flux was observed.


[Study on the distribution and correlation of trace elements in whole blood of children in Beijing].
To study the distribution and correlation of trace elements in peripheral blood of children in Beijing so as to offer scientific evidence for the supplementation of trace elements and to prevent lead intoxication. Contents of trace elements in whole blood of 13 929 children in Beijing region were detected by Atomic Absorption Spectrometer. According to developmental condition, children were divided into young infancy group, infancy group, toddler's age group, preschool age group, school age group and adolescence group. Every group was divided into males and females. Distribution and correlation of trace elements in different age groups and in different sex sets were then analyzed and compared. The level of copper, calcium and magnesium were stable in different age groups and in different sex sets. There were no obvious significant differences in age groups and sex sets and there were no deficiency of copper, calcium and magnesium discovered. The level of zinc increased gradually following the growth of age and the level of zinc was (81.71 +/- 15.91) micromol/L. There were significant differences in different age groups noticed as well in sex sets of infancy group, toddler's age group and preschool age group. The rate of deficiency of zinc decreased gradually following the growth of age. The rate of zinc deficiency was 13.7% and there were obvious differences noticed in sex sets of toddler, preschool and school age groups. The level of iron increased gradually following the growth of age with the level of iron as (8.28 +/- 0.78) mmol/L. There were significant differences noticed in different age groups, after infancy stage. There was significant difference noticed also in sex sets after school age group. The rate of iron deficiency decreased obviously following the growth of age. The iron deficiency rate was 12.9%, and significantly different in sex sets of young infancy, school age and adolescence groups. The level of lead increased gradually following the growth of age, with the overall level as (59.97 +/- 26.52) microg/L; There was an obvious significant differences noticed in different age groups with significant differences noticed in sex sets after toddler's age group. The rate of lead intoxication increased gradually following the growth of age. The rate of lead intoxication was 8.2%. There were significant differences noticed in sex sets after toddler's age group. However, there were negative correlations noticed among the levels of lead and copper, zinc, calcium, magnesium and iron. There were no correlations between the level of calcium and iron found but showed positive correlation among other trace elements. The deficiency of calcium was basically corrected but the deficiency of zinc and iron were still obvious. There was a high level of lead noticed in these children. It is important to advocate on healthy feeding program, on culture good hygienic habit and on away from the lead pollution sites.


Laparoscopic heminephrectomy of a horseshoe kidney with giant renal cell carcinoma: A case report.
A 72-year-old male was diagnosed incidentally with a 7-cm renal tumor in the right moiety of a horseshoe kidney during a routine physical examination, and was treated with laparoscopic radical heminephrectomy. The surgical time was 153 min and the estimated blood loss was 150 ml. The patient was discharged on post-operative day eight with no complications. Computed tomography angiography is desirable prior to surgery for the evaluation of the anatomical variations of horseshoe kidneys, and a pre-operative understanding is necessary for achieving reliable vascular control. In conclusion, the present technique is safe and effective for this complex clinical condition.


Does diabetes mellitus affect the development of fetal brain structures and spaces including corpus callosum, subarachnoid space, insula, and parieto-occipital fissure?
We investigated the impact of pregestational and gestational diabetes mellitus (PGDM and GDM) on the development of fetal intracranial structures and spaces. This prospective cross-sectional study involved singleton pregnancies between 20 and 32 weeks of gestation. The study comprised a control group (n = 65) of healthy pregnant women without diabetes mellitus (DM); a PGDM group (n = 43) of pregnant women having type 2 DM in a controlled diabetic state; and a GDM group (n = 26) of pregnant women with GDM diagnosed with 2-h 75-g oral glucose tolerance test and received intervention to reduce the diabetic impact on fetus. During neurosonographic evaluation, the simultaneous measurements of corpus callosum (CC) width and depth in the midsagittal image; and lateral craniocortical and posterior craniocortical widths of the subarachnoid space and insular and parieto-occipital fissure depths in the axial image were performed. Before statistical analysis, these values were carefully adjusted for the occipitofrontal diameter. The DM groups displayed substantially higher frequencies of family history of DM and obstetric history of GDM compared to the control group (p < 0.05). Regarding the neurosonographic parameters, the CC length and insular and parieto-occipital fissure depths were significantly increased in the GDM group but not in the PGDM group (p < 0.05). No significant difference was found among the study groups regarding other neurosonographic parameters (p > 0.05). The results of neurosonographical evaluation of fetal brain structures and spaces reveal that diabetic impact may not be seen in the presence of PGDM, especially in pregnant women receiving prenatal interventions to reduce or avoid diabetic adverse effects on fetal brain development. The effect of GDM on neurosonographically assessed fetal brain development should be evaluated in further studies with subjects matched for gestational weeks and antenatal care conditions.


Staged surgical palliation in hypoplastic left heart syndrome and its variants.
Surgical options for infants with hypoplastic left heart syndrome (HLHS) and/or its variants are cardiac transplantation or the heart-preserving staged palliation with Norwood operation,followed by a two-staged Fontan procedure. We describe our 17-year experience with staged palliation of HLHS and/or its variants. Between December 1989 and December 2006, 64 patients with HLHS and/or its variants underwent a Norwood procedure (mean age/weight, 11.8+/-2.5 days/3.4 kg). Forty-four patients had classical HLHS. Twenty-eight percent had associated congenital cardiac, structural, and genetic anomalies. Subsequently, 25 patients underwent a bidirectional Glenn procedure (stage II) and 11 patients a modified Fontan procedure (stage III). Others await stage II and/or stage III. The follow-up was 143.2 patient-years. Including the learning curve, overall early mortality from 1989 to 1999 after the Norwood procedure was 39.06%. This decreased tremendously for the last seven years, and reduced to 12.8% in 2000 to 2003 until 0% in 2004 to 2006 (p < 0.005). The causes of mortality were sepsis, capillary leak,or heart failure. Three patients died between stages II and III. One patient underwent heart transplantation after the second stage because of heart failure. Among 34 Norwood survivors, four are slightly tachypneic from a mild pulmonary hyperperfusion; one presents symptoms of minimal brain disease. This report identified an outcome improvement after staged palliation of HLHS, attributed to an increase in experience and expertise gained over time. Lower operative weight, ascending aortic size, prolonged duration of cardiopulmonary bypass, and hypothermic circulatory arrest were identified to significantly influence early mortality after the Norwood procedure.