Time Course and Mechanisms Underlying Standing Balance Recovery Early After Stroke: Design of a Prospective Cohort Study With Repeated Measurements.
Although most stroke survivors show some spontaneous neurological recovery from motor impairments of the most-affected leg, the contribution of this leg to standing balance control remains often poor. Consequently, it is unclear how spontaneous processes of neurological recovery contributes to early improvements in standing balance. We aim to investigate (1) the time course of recovery of quiet stance balance control in the first 12 weeks poststroke and (2) how clinically observed improvements of lower limb motor impairments longitudinally relate to this limb's relative contribution to balance control. In this prospective longitudinal study, a cohort of 60 adults will be recruited within the first 3 weeks after a first-ever hemispheric stroke and mild-to-severe motor impairments. Individual recovery trajectories will be investigated by means of repeated measurements scheduled at 3, 5, 8, and 12 weeks poststroke. The Fugl-Meyer Motor Assessment and Motricity Index of the lower limb serve as clinical measures of motor impairments at the hemiplegic side. As soon as subjects are able to stand independently, bilateral posturography during quietly standing will be measured. First, the obtained center-of-pressure (COP) trajectories at each foot will be used for synchronization and contribution measures that establish (a-)symmetries between lower limbs. Second, the COP underneath both feet combined will be used to estimate overall stability. Random coefficient analyses will be used to model time-dependent changes in these measures and, subsequently, a hybrid model will be used to investigate longitudinal associations with improved motor impairments. The current study aims to investigate how stroke survivors "re-learn" to maintain standing balance as an integral part of daily life activities. The knowledge gained through this study may contribute to recommending treatment strategies for early stroke rehabilitation targeting behavioral restitution of the most-affected leg or learning to compensate with the less-affected leg.


Behavioral correlates of cheating: Environmental specificity and reward expectation.
Academic dishonesty has been and continues to be a major problem in America's schools and universities. Such dishonesty is especially important in high schools, where grades earned directly impact the academic careers of students for many years to come. The rising pressure to get the best grades in school, get into the best college, and land the best paying job is a cycle that has made academic dishonesty increase exponentially. Thus, finding the widespread roots of cheating is more important now than ever. In this study, we focus on how societal norms and interactions with peers influence lying about scores in order to obtain a benefit in a high school population. We show that (1) the societal norms that go hand in hand with test-taking in school, as administered by a teacher, significantly dampen small-scale dishonesty, perhaps suggesting that context-dependent rewards offset cheating; (2) providing reminders of societal norms via pre-reported average scores leads to more truthful self-reporting of honesty; (3) the matrix search task was shown to not depend on class difficulty, confirming its effectiveness as an appropriate method for this study; (4) males seem to cheat more than females; and (5) teenagers are more dishonest earlier in the day. We suggest that students understand that cheating is wrong, an idea backed up by the literature, and that an environment which clearly does not condone dishonesty helps dampen widespread cheating in certain instances. This dampening effect seems to be dependent on the reward that students thought they would get for exaggerating their performance.


Ethyl alcohol as a cocarcinogen with special reference to the aerodigestive tract: a cytogenetic study.
Although prior to its metabolic conversion alcohol has no mutagenic activity, an interaction of alcohol with tobacco in carcinogenesis of the head and neck region is well characterized. In a recent ecogenetic case control study of these cancers we documented an interaction between alcohol use and in vitro mutagen-induced chromosome damage in cancer risk. The present report evaluates the in vitro genotoxicity of five mutagens (including cigarette smoke condensate) tested in conjunction with 2% and 4% ethanol in human lymphoid cell lines. Ethanol alone did not exert a demonstrable clastogenic effect, as measured by the frequency of chromatid breaks per cell. However, the clastogenic potential of all mutagens increased when ethanol was added concurrently with the mutagens, and there was a dose-dependent potentiation of clastogenicity by ethanol, with a threshold dose between 0.5% and 1.0%. Preliminary experimental results strongly indicate that ethanol, at relatively high doses, inhibits DNA and chromosome repair systems. These data support the epidemiologic evidence of an interaction between alcohol and mutagens in carcinogenesis and suggest that alcohol may have co-carcinogenic properties.


Assessment and modulation of resting-state neural networks after stroke.
Stroke is a major cause of disability; however, most patients experience spontaneous partial recovery of functions in subacute to chronic phases. Poststroke loss and recovery of functions have been increasingly correlated with brain-wide alterations in the connectivity of neural networks, which is described in this review. Elucidation of the mechanisms of functional brain remodeling could reveal targets and strategies for more effective neurorehabilitation. Data from recent resting-state functional MRI, electroencephalography, magnetoencephalography, and optical imaging studies in patients and animal models have demonstrated that loss of function after stroke is closely associated with disrupted connectivity in large-scale networks beyond the lesion territory. Restoration of functional connectivity in the surviving networks appears to be critical for functional recovery, and this may be promoted with specific therapeutic strategies, such as robot-assisted training and noninvasive brain stimulation. The adaptability of functional networks relies on the structural integrity of neuronal pathways, but the relationship between the two remains incompletely understood. Furthermore, disturbed neurovascular coupling after stroke can confound hemodynamically based measurements of functional connectivity. Identification of key network processes in adaptive brain plasticity can aid in the prediction of functional outcome and the development of therapeutic interventions to support and promote recovery after stroke.


Structure of the vortex wake in hovering Anna's hummingbirds (Calypte anna).
Hummingbirds are specialized hoverers for which the vortex wake has been described as a series of single vortex rings shed primarily during the downstroke. Recent findings in bats and birds, as well as in a recent study on Anna's hummingbirds, suggest that each wing may shed a discrete vortex ring, yielding a bilaterally paired wake. Here, we describe the presence of two discrete rings in the wake of hovering Anna's hummingbirds, and also infer force production through a wingbeat with contributions to weight support. Using flow visualization, we found separate vortices at the tip and root of each wing, with 15% stronger circulation at the wingtip than at the root during the downstroke. The upstroke wake is more complex, with near-continuous shedding of vorticity, and circulation of approximately equal magnitude at tip and root. Force estimates suggest that the downstroke contributes 66% of required weight support, whereas the upstroke generates 35%. We also identified a secondary vortex structure yielding 8-26% of weight support. Lift production in Anna's hummingbirds is more evenly distributed between the stroke phases than previously estimated for Rufous hummingbirds, in accordance with the generally symmetric down- and upstrokes that characterize hovering in these birds.


Intravenous administration of 9-aminocamptothecin to dogs with lymphoma.
A colloidal dispersion formulation of 9-aminocamptothecin (9-AC) was administered intravenously to 10 dogs with previously untreated, spontaneously occurring, multicentric lymphoma. The dogs received a 72-h infusion of 9-AC at a rate of 46.5-51.25 microg m(-2) h(-1) (total dose range 3.35-3.69 mg m(-2)). This dose range was associated with myelosuppression, consisting principally of neutropenia with a nadir at 7 days following the start of infusion. Neutropenia and thrombocytopenia were the most common toxicoses and are most likely to be dose-limiting toxicities; low-grade gastrointestinal signs were rarely seen. Concentrations of 9-AC lactone, as well as clinical toxicities, compare favourably with those found in humans. Tumour responses were seen in all treated dogs. Response to other chemotherapy, following cessation of 9-AC treatment, was not obviously compromised even in dogs clinically resistant to 9-AC. 9-AC is a novel treatment drug for canine lymphoma, which appears to show great promise.


Carbon Dot Therapeutic Platforms: Administration, Distribution, Metabolism, Excretion, Toxicity, and Therapeutic Potential.
Ultrasmall nanoparticles are often grouped under the broad umbrella term of "nanoparticles" when reported in the literature. However, for biomedical applications, their small sizes give them intimate interactions with biological species and endow them with unique functional physiochemical properties. Carbon quantum dots (CQDs) are an emerging class of ultrasmall nanoparticles which have demonstrated considerable biocompatibility and have been employed as potent theragnostic platforms. These particles find application for increasing drug solubility and targeting, along with facilitating the passage of drugs across impermeable membranes (i.e., blood brain barrier). Further functionality can be triggered by various environmental conditions or external stimuli (i.e., pH, temperature, near Infrared (NIR) light, ultrasound), and their intrinsic fluorescence is valuable for diagnostic applications. The focus of this review is to shed light on the therapeutic potential of CQDs and identify how they travel through the body, reach their site of action, administer therapeutic effect, and are excreted. Investigation into their toxicity and compatibility with larger nanoparticle carriers is also examined. The future of CQDs for theragnostic applications is promising due to their multifunctional attributes and documented biocompatibility. As nanomaterial platforms become more commonplace in clinical treatments, the commercialization of CQD therapeutics is anticipated.


Myoepithelioma possibly originating from the accessory parotid gland.
Myoepithelioma originates almost exclusively from myoepithelial cells of the salivary, prostate and mammary glands. The skin is a very rare site where myoepithelioma occurs. We describe a patient with a myoepithelioma on the right cheek seen as a subcutaneous nodule that was separated from the parotid gland at surgical resection. Histopathological findings were consistent with those of a myoepithelioma that had originated from the parotid gland, suggesting that this tumor may have developed from the accessory parotid gland.


Is pronuclear scoring a really good predictor for ICSI cycles?
Since the assessments of the morphology of oocytes, zygotes and/or embryos are of crucial importance to select the best candidate for pregnancy, many morphological evaluation tools have been proposed. Although embryo scoring, particularly cleavage and blastocyst stages, is more convincing due to successful results, zygote scoring still have a bias as different outcomes. In the current study, we designed a prospective study to test the reliability of zygote scoring by focusing on zygote evaluation techniques and its relation with embryo development and embryo selection for transfer. A total of 1215 mature oocytes from 139 couples were evaluated for the study. There is no correlation between published zygote scoring technique and embryo development. We conclude that the inconsistency of data obtained from zygote scoring might be caused by the static nature of pronuclear stage embryos and thus pronuclear scoring seems to be unreliable evaluation technique for embryo selection.


Problems in the current psychiatry residency training program in Croatia: residents' perspective.
The aim of this study is to evaluate the quality of the current residency training in psychiatry in Croatia using parameters of professional achievements of residents and their subjective evaluations of the residency training that is being offered. 66 residents from 15 Croatian psychiatric hospitals, clinics and wards in general hospitals fulfilled the questionnaire constructed to obtain information about the profile of psychiatry residents in Croatia, parameters of educational quality and evaluation of offered residency training as seen by residents. We interviewed 89% of all residents that had a trainee status in September and October 2006 in Croatia (66 out of 74). Study results indicate that Croatian psychiatry residents are derived from a pool of very good medical students and the majority is engaged in postgraduate studies and research activities and shows high interest in specific psychiatric fields such as psychotherapy and clinical psychiatry. Most of participants are only partially satisfied with the residency training that is being offered and feel that most problems reside from the lack of practical psychotherapy, the inefficiency of the mentorship system and the lack of funding resources. The results of this study revealed the major problems of psychiatry residents in Croatia. Following those results, we will perform the study that would include mentors and supervisors from different Croatian psychiatric centers. That could enable the development of specific interventions with aim to improve current residency training in Croatia.


Co(II) Macrocyclic Complexes Appended with Fluorophores as paraCEST and cellCEST Agents.
Four high-spin macrocyclic Co(II) complexes with hydroxypropyl or amide pendants and appended coumarin or carbostyril fluorophores were prepared as CEST (chemical exchange saturation transfer) MRI probes. The complexes were studied in solution as paramagnetic CEST (paraCEST) agents and after loading into Saccharomyces cerevisiae yeast cells as cell-based CEST (cellCEST) agents. The fluorophores attached to the complexes through an amide linkage imparted an unusual pH dependence to the paraCEST properties of all four complexes through of ionization of a group that was attributed to the amide NH linker. The furthest shifted CEST peak for the hydroxypropyl-based complexes changed by ∼90 ppm upon increasing the pH from 5 to 7.5. At acidic pH, the Co(II) complexes exhibited three to four CEST peaks with the most highly shifted CEST peak at 200 ppm. The complexes demonstrated substantial paramagnetic water proton shifts which is a requirement for the development of cellCEST agents. The large shift in the proton resonance was attributed to an inner-sphere water at neutral pH, as shown by variable temperature 17O NMR spectroscopy studies. Labeling of yeast with one of these paraCEST agents was optimized with fluorescence microscopy and validated by using ICP mass spectrometry quantitation of cobalt. A weak asymmetry in the Z-spectra was observed in the yeast labeled with a Co(II) complex, toward a cellCEST effect, although the Co(II) complexes were toxic to the cells at the concentrations necessary for observation of cellCEST.


[Greater success by cooperation between claim review experts and the police].
The examination of claims settlement in life assurance usually begins when police investigation is finished. During the acute phase of police investigation there is very rarely contact between the police and the life insurance company concerned. The advantages of early cooperation are demonstrated by two case reports. Immediate communication during the first four days after death initially helps the police investigators; later the life insurance company profits from the accelerated examination of the insured event.


Correlation between structural and semiconductor-metal changes and extreme conditions materials chemistry in Ge-Sn.
High pressure and temperature experiments on Ge-Sn mixtures to 24 GPa and 2000 K reveal segregation of Sn from Ge below 10 GPa whereas Ge-Sn agglomerates persist above 10 GPa regardless of heat treatment. At 10 GPa Ge reacts with Sn to form a tetragonal P4(3)2(1)2 Ge(0.9)Sn(0.1) solid solution on recovery, of interest for optoelectronic applications. Using electron diffraction and scanning electron microscopy measurements in conjunction with a series of tailored experiments promoting equilibrium and kinetically hindered synthetic conditions, we provide a step by step correlation between the semiconductor-metal and structural changes of the solid and liquid states of the two elements, and whether they segregate, mix or react upon compression. We identify depletion zones as an effective monitor for whether the process is moving toward reaction or segregation. This work hence also serves as a reference for interpretation of complex agglomerates and for developing successful synthesis conditions for new materials using extremes of pressure and temperature.


Function of lymphocyte subpopulations in chronic lymphocytic leukemia. Activity in the allogeneic and autologous mixed lymphocyte reaction.
Lymphocyte subpopulations from patients with chronic lymphocytic leukemia (CLL) and from normal age-matched controls were evaluated for their ability to participate in allogeneic and autologous mixed lymphocyte reactions (MLR). Unfractionated and T enriched lymphocyte populations from normal age-matched controls responded well to allogeneic stimulation. T enriched lymphocytes from patients will CLL also responded to allogeneic lymphocytes. B enriched lymphocytes from normal age-matched individuals produced a stronger stimulus in the allogeneic MLR than did unfractionated mononuclear cell populations. Unfractionated and B enriched lymphocyte subpopulations from patients with CLL were poor stimulators in the allogeneic MLR. In normal age-matched controls T enriched lymphocyte subpopulations were able to respond to autologous B enriched lymphocytes. Autologous mixed lymphocyte cultures from patients with CLL failed to demonstrate any activity.


Changes in the Enzymes for Fatty Acid Synthesis and Desaturation during Acclimation of Developing Soybean Seeds to Altered Growth Temperature.
Temperature-induced changes in the enzymes for fatty acid synthesis and desaturation were studied in developing soybean seeds (Glycine max L. var Williams 82). Changes were induced by culture of the seed pods for 20 hours in liquid media at 20, 25, or 35 degrees C. Linoleoyl and oleoyl desaturases were 94 and 10 times as active, respectively, in seeds cultured at 20 degrees C as those cultured at 25 degrees C. Both desaturases had negligible activity in seeds cultured at 35 degrees C compared to seeds cultured at 20 degrees C. Though less dramatic, other enzymes also showed differences in activity after 20 hours in culture at 20, 25, or 35 degrees C. Stearoyl-acyl carrier protein (ACP) desaturase and CDP-choline:diacylglycerol phosphorylcholine transferase were most active in preparations from 20 degrees C cultures. Activities were twofold lower at 25 degrees C and a further threefold lower in 35 degrees C cultures. Cultures from 25 and 35 degrees C had 60 and 40%, respectively, of the phosphorylcholine:CTP cytidylyl transferase activity present in cultures grown at 20 degrees C. Fatty acid synthetase, malonyl-coenzyme A:ACP transacylase, palmitoyl-ACP elongation, and choline kinase were not significantly altered by culture temperature. These data suggest that the enzymes for fatty acid desaturation and phosphatidylcholine synthesis can be rapidly modulated in response to altered growth temperatures, while the enzymes for fatty acid synthesis and elongation are not.


[Significance of elemental diets in the therapy of Crohn disease in childhood].
Aminoacid and oligopeptide formulas of low molecular weight have frequently been used in the past on an empirical basis for nutritional support of patients with Crohn's disease. Improvement of intestinal symptoms and laboratory parameters reflecting the inflammatory process have been demonstrated. Only a few controlled therapeutic trials have compared elemental diets with conventional drug therapy. In small bowel involvement, therapeutic efficiency in active disease is as good as salazosulfapyridine combined with corticosteroids. Elemental diet is less effective in large bowel disease. In the therapeutic application of elemental diets in active disease these formulas should be the only nutritional source for the patient. Particularly in small bowel disease the growth retarding side effects of corticosteroids can markedly be reduced by elemental diets. Children with moderate disease and additional growth retardation may benefit from either supplemental elemental diet and/or high molecular weight formula or from parenteral hyperalimentation. --Crohn-specific fistulas seem to close rarely on elemental diets while favourable results are seen in postoperative fistulas.


Macrodactyly in tuberous sclerosis complex: Case report and review of the literature.
Macrodactyly in the context of tuberous sclerosis complex (TSC) is a known but rare manifestation. We report the case of a boy diagnosed with TSC at 2 years and 4 months of age, presenting with bilateral macrodactyly of the first three fingers of both hands, with underlying radiographic changes, in whom molecular analysis identified a frameshift mutation on the TSC1 gene (encoding hamartin), leading to a premature stop codon. We reviewed the literature for reported cases of TSC patients with the same manifestation. In four of 14 patients, including ours, macrodactyly caused some type of joint limitation or flexion deformity, thus contradicting the established idea that this is a finding without clinical significance. Our patient is, to our knowledge, the first reported to have clear bilateral involvement. We briefly discuss the underlying mechanism for this phenomenon, which has yet to be fully elucidated, although somatic mosaicism for loss of heterozygosity at TSC loci is a plausible explanation. © 2016 Wiley Periodicals, Inc.


Efficacy of cervicothoracic sympathectomy versus conservative management in patients suffering from incapacitating Raynaud's syndrome after frost bite.
Raynaud's syndrome is a known complication of cold injuries. Stress, smoking and metabolic diseases may further aggravate the disease course. The purpose of this study was to determine the efficacy of Cervico-thoracic sympathectomy as compared to conservative management in severe Raynaud's syndrome after frostbite. This non-randomized controlled trial was conducted at Railway Hospital, Rawalpindi and Islamic International Medical Complex, Islamabad between January 1999 and June 2006. All patients sustained severe cold trauma in the mountain ridges of Himalayas in Kashmir. In all cases, an informed consent was obtained from patients and families. All operations performed were free of charges. Out of the total 48 patients who developed incapacitating Raynaud's syndrome of the upper limbs after frost bite, 17 patients underwent thoracic sympathectomy through anterior supraclavicular route. Remaining 31 patients were treated conservatively and were placed in the control group. Data was collected on pre-designed proforma and assessed using SPSS (version 11). Chi-square test was applied to assess the effectiveness of the two treatment modalities. All operated cases initially showed improvement in symptoms and incapacitation. Among sympathectomised patients, 11 patients became symptom free and 3 patients showed mild but improved symptoms. Two patients after initial transient improvement developed incapacitating symptoms requiring further treatment, one patient developed gangrene ofdistal phalanx nine month after sympathectomy requiring amputation of the finger. Frequency of attacks and duration between the attacks reduced in all operated patients of cervical sympathectomy (p < 0.05) as compared to conservative management. Cervical sympathectomy is a very effective modality of treatment in patients having severe Raynaud's disease of upper limbs secondary to frost bite.


Disorders of coagulation misdiagnosed as nonaccidental bruising.
Two cases of idiopathic thrombocytopenia and one case of hemophilia with unexplained bruising are presented. The children were all initially thought to be victims of nonaccidental trauma until coagulation disorder screening tests were returned with abnormal values. A review of the literature of similar cases is presented. It is recommended that any child with unexplained or implausible bruising receive a screen for coagulation disorders consisting of a complete blood count with platelet count, prothrombin time, a partial thromboplastin time, and a bleeding times.


Genetic studies of the population of the Isle of Man.
A sample of the Isle of Man population was tested for the following red cell antigens, serum proteins and red cell enzymes: ABH; MNSs He; Cc CwD Du Ee Ce; K k Kpa Kpb; Lua; P1; Fya Fyb; haptoglobin; transferrin; Ag; acid phosphatase; phosphoglucomutase; adenylate kinase; esterase D; adenosine deaminase and 6-phosphogluconate dehydrogenase. The study comprised 219 blood donors, 338 secondary school children and 116 females attending the only antenatal clinic. The results were studied for intra-island variation and for their their relationship with other Irish Sea Basin populations. The total sample results were compared with data for England, Cumbria, Eire, Northern Ireland, S.W. Scotland and Wales using a genetic distance measure.


Personal and Contextual Factors Affecting the Functional Ability of Children and Adolescents with Chronic Pain: A Systematic Review.
Chronic pain can significantly impair functioning of children and adolescents; however, evidence suggests that current psychological approaches have limited effect on functioning post treatment. The objective of this review is to present the current evidence for the personal and contextual factors that affect functioning and disability of children and adolescents with chronic pain, to support the evolution of new treatments. Key word searches were conducted in PsycINFO, MEDLINE via Ovid, CINAHL, and PubMed from 1995 to October 2014. Studies were included if they (1) were written in English, (2) included children or adolescents with chronic pain (>3 mo), (3) had at least 1 personal attribute or 1 contextual factor, (4) had 1 measure of functional ability, and (5) had reported correlations between personal or contextual factors and functional measure. Thirty-three studies were identified which met all inclusion criteria. Several personal factors (depression, anxiety, pain intensity, and catastrophizing) and contextual/environmental factors (parenting characteristics) were consistently associated with higher levels of disability, whereas evidence for other factors was less consistent. Complex interactions between personal and contextual factors were reported. Child physical/cognitive capacities, teacher/peer behaviors, and broader cultural and environmental social systems, received little attention. Several parent and child factors were consistently linked with functional disability, whereas better family functioning was associated with functional ability. Applying an ecological framework, assisted identification of areas for further research, and provides direction for treatments that may be more effective in optimizing long-term functional outcomes, extending current psychological approaches.


[Disorder of copper homeostasis induced by lead exposure among mice and intervention effect of quercetin].
To investigate the effect of lead exposure on copper and copper metalloenzyme and the intervention effect of quercetin. Twenty-four specific pathogen-free male Sprague-Dawley rats of good health were randomly divided into control group (n = 8), lead acetate group (n = 8), and lead acetate + quercetin group (n = 8). The rats in lead acetate group were poisoned by drinking water with 1 g/L lead acetate for 8 weeks, while the rats in control group were fed by drinking water with sodium acetate of the same volume for 8 weeks; the rats in lead acetate+quercetin group were intraperitoneally injected with quercetin (30 mg × kg-1 × d-1) for 8 weeks while drinking water with lead acetate. The Morris water maze was used to test the learning and memory abilities of rats. The lead and copper levels in the serum, hippocampus, cortex, and bone were measured by graphite furnace atomic absorption spectrometry. The level of advanced glycation end products, activity of Cu/Zn superoxide dismutase (SOD), and content and activity of ceruloplasmin (CP) in the hippocampus and serum were measured using a test kit. HE staining was performed to observe the pathological changes in the hippocampus. The Morris water maze test showed that the latency in lead acetate group (52.50±12.04 s) was significantly longer than that in control group (28.08±7.31 s) (P<0.05), and the number of platform crossings was significantly lower in the lead acetate group than in the control group. Compared with those in the control group, the lead levels in the cortex and hippocampus in lead acetate group increased 2.72-fold and 3.79-fold, and the copper in the cortex and hippocampus, and serum free copper levels in lead acetate group increased 1.15-fold, 1.48-fold, and 6.44-fold. Compared with the control group, the lead acetate group had a lower content of CP in the hippocampus (1.23±0.40 U/mg provs0.78±0.08 U/mg pro) and 31.81%and 19.49%decreases in CP content and Cu/Zn SOD activity. Free copper level in serum was positively correlated with the latency and lead levels in the serum, cortex, and hippocampus. The escape latency of rats in lead acetate + quercetin group was decreased by 42.15% (P<0.05). The lead levels in the cortex and hippocampus in lead acetate + quercetin group (0.246 ± 0.58 µg/g and 0.202±0.049 µg/g) were significantly lower than those in lead acetate group (0.391±0.49 µg/g and 0.546±0.120 µg/g), but the free copper and copper levels in the hippocampus and cortex were not significantly reduced. The lead acetate + quercetin group had higher Cu/Zn SOD activity and CP content in the hippocampus than the lead acetate group (P < 0.05). The light microscope observation showed that the number of cells in the hippocampus was reduced with disordered arrangement in the lead acetate group; with quercetin intervention, the hippocampus damage was reduced. Lead exposure results in disorder of copper homeostasis, while quercetin may alleviate the damage induced by lead to some extent.


EphrinB1 is essential in T-cell-T-cell co-operation during T-cell activation.
Eph kinases are the largest family of receptor tyrosine kinases, and their ligands are ephrins (EFNs), which are also cell surface molecules. We have very limited knowledge about the expression and function of these kinases and their ligands in the immune system. In this study we investigated the effect of EFNB1 on mouse T-cells. EFNB1 and the Eph kinases it interacts with (collectively called EFNB1 receptors (EFNB1R)) were expressed on T-cells, B cells, and monocytes/macrophages. Some T-cells were double positive for EFNB1 and EFBB1R. Solid phase EFNB1 in the presence of suboptimal TCR ligation augmented T-cell responses in terms interferon-gamma secretion, proliferation, and cytotoxic T lymphocyte activity but not interleukin-2 production. After T-cell receptor (TCR) ligation, EFNB1R congregated to TCR caps, and then both of them translocated to raft caps. This provides a morphological basis for EFNB1R to enhance TCR signaling. Further downstream of the signaling pathway, EFNB1R stimulation led to increased LAT (linker for activation of T-cells) phosphorylation and p44/42 and p38 MAPK activation. Similar to CD28 costimulation, EFNB1R costimulation was insensitive to cyclosporin A inhibition. On the other hand, unlike the former, EFNB1R costimulation failed to activate Akt, which is essential in triggering interleukin-2 production. Our study suggests that EFNB1 is pivotal in T-cell-T-cell costimulation and in reducing T-cell response threshold to antigen stimulation.


Deconstructing current comorbidity: data from the Australian National Survey of Mental Health and Well-Being.
Comorbidity in epidemiological surveys of mental disorders is common and of uncertain importance. To explore the correlates of current comorbidity. Data from the Australian National Survey of Mental Health and Well-Being were used to evaluate the relationships between comorbidity, disability and service utilisation associated with particular mental disorders. The number of current comorbid disorders predicted disability, distress, neuroticism score and service utilisation. Comorbidity is more frequent than expected, which might be due to the effect of one disorder on the symptom level of another, or to the action of common causes on both. The combination of affective and anxiety disorders was more predictive of disability and service utilisation than any other two or three group combinations. When people nominated their principal disorder as the set of symptoms that troubled them the most, the affective and anxiety disorders together were associated with four-fifths of the disability and service utilisation. To make clinical interventions more practical, current comorbidity is best reduced to a principal disorder and subsidiary disorders.


Nasal Airway Function After Prophylactic Intranasal Surgery for Excessive Maxillary Superior Repositioning: A Retrospective Cohort Study Using the Nasal Obstruction Symptom Evaluation Scale.
The purpose of this study is to evaluate the degree of nasal airway function after simultaneous intranasal corrective surgery and bimaxillary surgery in patients with excessive superior maxillary repositioning. A retrospective cohort study was conducted on consecutive LeFort I superior repositioning patients who also underwent simultaneous intranasal surgery to prevent airway obstruction between 2015 and 2019. The Nasal Obstruction Symptom Evaluation (NOSE) scale was administered to all participants before the operation and after 1 year. Fifteen patients (n=12 females; n=3 males) among 440 bimaxillary orthognathic surgery patients were enrolled with inclusion criteria of maxillary impaction between 8 and 12 mm. All subjects underwent at least LeFort I osteotomy, septoplasty, bilateral inferior turbinectomy, and bilateral sagittal split osteotomy. Two patients received custom-made total joint prosthesis. The primary outcome variable investigated was nasal function. The mean preop Nasal Obstruction Symptom Evaluation score was 24.33 and the mean postop score was 5. Intranasal procedures performed simultaneously with 8 mm or more maxillary impaction improves postoperative functional outcome in terms of nasal airway patency and breathing. Partial inferior turbinectomies and septoplasty should be performed consistently to avoid nasal obstruction if the impaction of upper jaw exceeds 8 mm.


Expression of Angiogenic Factors in Patients With Sporadic Small Bowel Angiodysplasia.
To identify putative angiogenic factors associated with sporadic small bowel angiodysplasia (SBA). SBAs account for 50% of obscure gastrointestinal bleeding and due to delays in diagnosis and ineffective treatments, are associated with high levels of morbidity and mortality. Treatment development is impeded by a limited knowledge of the pathophysiology behind SBA formation. We identified patients with definite sporadic SBA, and fecal immunochemical-negative controls were recruited from our institution's colorectal cancer screening program. Serum levels of VEGF, endoglin, Angiopoietin-2 (Ang-2), PDGF, Angiopoietin-1 (Ang-1), and TNF-α were measured using commercially available enzyme-linked immunosorbent assay kits. On the basis of serum results, we measured gene expression of target angiogenic factors in small bowel biopsy samples from angiodysplasias and unaffected tissue by quantitative PCR assessment. Serum samples were analyzed from 40 SBA patients and 40 controls. Median serum levels of Ang-2 were significantly higher in patients than controls with levels of Ang-1 and TNF-α significantly lower. There were no differences in serum levels of VEGF, endoglin, or PDGF. Gene expression levels of Ang-1, Ang-2, and their receptor Tie2 were all significantly higher in biopsies from areas of angiodysplasia compared with normal small bowel. This study, the first to explore the role of angiogenic factors in SBA, has identified a positive association between SBA and the Angiopoietin pathway, with increased serum and mucosal expression of Ang-2, which could potentially be used as a serum biomarker and future therapeutic target to improve outcome in affected patients.


The axial load teardrop fracture. A biomechanical, clinical and roentgenographic analysis.
The anteroinferior cervical vertebral body corner fracture was originally described by Schneider and Cann as the "teardrop" fracture. This report analyzes the biomechanical, clinical, and roentgenographic features of 55 such fractures obtained from the National Football Head and Neck Injury Registry. Teardrop fractures resulting from tackle football characteristically occurred in players attempting to make a tackle in which initial contact was made with the top or crown of the helmet. There were two fracture patterns associated with the anteroinferior corner (teardrop) fracture fragment: 1) the isolated fracture, which is usually not associated with permanent neurologic sequelae; and 2) the three-part, two-plane fracture in which there is an associated sagittal vertebral body fracture as well as fracture of the posterior neural arch. This latter pattern was almost always associated with permanent neurologic sequelae, specifically quadriplegia. Axial loading of the cervical spine was clearly identified as a mechanism of injury for both fracture patterns. Roentgenographic examination must include both anteroposterior and lateral views with computed tomography or tomography as necessary to determine the presence of the sagittal vertebral body fracture and the integrity of the posterior neural arch.


[Advantages of biomatrices in chondrogenesis of pluripotent mesenchymal stem].
The autologous in vitro expansion of chondrocytes is a new method for the treatment of localized cartilage defect zones in humans. In the past several investigators have shown the occurrence of mesenchymal stem cells (MSC) in human bone marrow, periosteum and somite mesoderm. Moreover it has been shown that these progenitor cells are able to differentiate into chondral tissue under special in vitro conditions. The following study shows current possibilities and borders of a chondrogenetic stem cell therapy. Furthermore advantages and disadvantages of different cellular biomatrix carriers are described, cartilage tissue engineering-related problems are discussed and possible solutions were pointed out. A literature investigation served for evaluation of the present clinical and experimental data. Furthermore our own cell culture experiences were considered. Until now there exists no clinical concept using the potential of MSC for cartilage tissue engineering. Reasons are the lack of biomechanical and histological stability and handling problems of the cultivated cartilage tissue, especially the difficulties to fix and secure the transplant in the cartilage defect zones in situ. The systematic investigation of biomatrices by chondrogenic progenitor cell culture systems may lead to important data for the evaluation of the chondrogenic potency biomatrices.


Incidence of loss of heterozygosity at p53 and BRCA1 loci in serous surface carcinoma.
Serous surface carcinoma (SSC) is a neoplasm histologically indistinguishable from typical serous carcinomas that arise from the ovary but has a distinct clinical presentation. It is characterized by widespread peritoneal dissemination at presentation, but the ovaries are grossly normal in size and shape. If the carcinoma involves the ovaries microscopically, the tumor is confined to the surface or is minimally invasive. The recognition of this entity is important, because in some studies it appears to have a poorer prognosis than stage-matched serous cancers of the ovary. Loss of heterozygosity (LOH) of the p53 (17p) and BRCA1 (17q) tumor suppressor genes has been frequently identified in sporadic ovarian carcinomas. Although 17p LOH is correlated with common p53 gene mutations, inactivating mutations of the BRCA1 gene are uncommon in sporadic ovarian cases. In contrast, germline BRCA1 mutations are responsible for some hereditary forms of ovarian cancer, where it has been suggested that germline BRCA1 mutations confer a more favorable prognosis. In this study, 12 sporadic SSC were assessed for the presence of allelic deletions on the p53 and BRCA1 gene loci. DNA from both tumor and normal cells was obtained for LOH studies using tissue microdissection. Polymerase chain reaction (PCR) amplification was performed with the polymorphic DNA markers TP53 (17p13.1/p53 gene) and D17S579 (17q/BRCA1 gene). LOH in the p53 and BRCA1 loci was detected in 62.5% and 66.6% of the cases, respectively. In 50% of tumors informative for both markers, it is possible that an entire chromosome may be lost. In conclusion, we have shown that LOH of the p53 and BRCA1 loci is a frequent event in sporadic SSC, similar to what has been described in the usual form of serous ovarian carcinoma. Mutational analysis will be necessary to determine the exact role of these genes in this group of tumors.


Role of Molecular Weight in Polymer Wrapping and Dispersion of MWNT in a PVDF Matrix.
The thermal and electrical properties of a polymer nanocomposite are highly dependent on the dispersion of the CNT filler in the polymer matrix. Non-covalent functionalisation with a PVP polymer is an excellent driving force towards an effective dispersion of MWNTs in the polymer matrix. It is shown that the PVP molecular weight plays a key role in the non-covalent functionalisation of MWNT and its effect on the thermal and electrical properties of the polymer nanocomposite is reported herein. The dispersion and crystallisation behaviour of the composite are also evaluated by a combination of scanning electron microscopy (SEM) and differential scanning calorimetry (DSC).


Ascending Aortic Endoballoon Occlusion Feasible Despite Moderately Enlarged Aorta to Facilitate Robotic Mitral Valve Surgery.
Aortic occlusion with an endoballoon is a well-established technique to facilitate robotic and minimally invasive mitral valve surgery. Use of the endoballoon has several relative contraindications including ascending aortic dilatation greater than 38 mm in size. We sought to review our experience using the endoballoon in cases of totally endoscopic mitral valve surgery with aortic diameters greater than 38 mm. A retrospective review of our single-site database was conducted to identify patients undergoing totally endoscopic mitral valve surgery by a single surgeon using an endoballoon and who had ascending aortic dilation. We defined aortic dilation as greater than 38 mm. Computed tomography was done preoperatively on all patients to evaluate the aortic anatomy as well as iliofemoral access vessels. Femoral artery cannulation was done in a standardized fashion to advance and position the endoballoon, to occlude the ascending aorta, and to deliver cardioplegia. From October 2011 through June 2015, 196 patients underwent totally endoscopic mitral valve surgery using an endoballoon at our institution. Twenty-two patients (11.2%) had ascending aortic diameters greater than 38 mm (range, 38.1-46.6 mm; mean, 40.5 ± 2.5 mm). In these cases, there were no instances of aortic dissection or other injury due to balloon rupture, balloon migration, device movement leading to loss of occlusion, or inability to complete planned surgery due to occlusion failure. Our experience suggests that it is possible to successfully use endoaortic balloon occlusion in patients with ascending aortic dilation with proper preoperative imaging and planning.


Esophageal squamous cell carcinoma with marked eosinophil infiltration.
We report a case of esophageal squamous cell carcinoma (SCC) with marked eosinophil infiltration which was identified postoperatively in the esophageal wall in areas not surrounding the SCC. The eosinophil infiltration was seen in the submucosa, muscle and adventitia, but not in the mucosa. Eosinophilic esophagitis (EoE) is a pathological condition defined as eosinophil infiltration within the esophageal mucosa. Eosinophil infiltration at the invasion front of esophageal SCC is termed tumor-associated tissue eosinophilia (TATE). However, the eosinophil infiltration in this case may be pathologically different from both EoE and TATE. To our knowledge, this is the first report of esophageal SCC with eosinophil infiltration.


[Mechanisms of molecular development of human glioma].
Malignant gliomas present a difficult therapeutic problem. Within the last ten years, however, some of the molecular mechanisms have been disclosed that are involved in brain tumour development. According to these results the occurrence of a malignant tumour cell is the result of a multistage process, which involves mutations in several genes. These mutations affect genes regulating cellular proliferation and differentiation, which are called protooncogenes and tumour-suppressor genes (anti-oncogenes). Critical alterations in the proteins encoded by these genes may lead to uncontrolled cell proliferation. In astrocytic gliomas mutations of the tumour suppressor gene p53 are common; mutations of the c-erbB gene, encoding the Epidermal Growth Factor receptor (EGF-receptor), frequently affect glioblastomas. The vast majority of glioblastomas show deletions or loss of a copy of chromosome 10. Anaplastic astrocytomas, glioblastomas and oligodendrogliomas frequently carry deletions in one copy of the chromosome 9q and 19q region, respectively. Allelic loss of these regions suggest the presence of a tumour-suppressor gene on these chromosomal loci and a pathogenetic role of anti-oncogene allelic loss in brain tumour development. Molecular studies provide insight into the pathogenesis of brain tumour development. However, they may also have an impact on developing new forms of tumour-specific therapy. The efficacy of such therapeutic strategies is currently being evaluated in clinical studies.


Asymmetrical [Ni(dmit)2]- arrangements induced by (1R,2R)-cyclohexanediammonium-crown ether supramolecules.
Structurally flexible (1R,2R)-cyclohexanediammonium (CHDA(2+)) dication formed hydrogen-bonding supramolecules with [18]crown-6, benzo[18]crown-6 (B[18]crown-6), dibenzo[18]crown-6 (DB[18]crown-6), and dicyclohexano[18]crown-6 (DCH[18]crown-6) in [Ni(dmit)(2)](-) salts (dmit(2-) = 2-thioxo-1,3-dithiole-4,5-dithiolate). The two ammonium moieties of CHDA(2+) interacted with the crown ethers to form open-mouth-shaped sandwich-type cationic structures of (CHDA(2+))(crown ethers)(2), that is, (CHDA(2+))([18]crown-6)(2)[Ni(dmit)(2)](2)(-)() (1), (CHDA(2+))(B[18]crown-6)(2)[Ni(dmit)(2)](2)(-)() (2), (CHDA(2+))(DB[18]crown-6)(2)[Ni(dmit)(2)](2)(-)() (3), and (CHDA(2+))(DCH[18]crown-6)(2)[Ni(dmit)(2)](2)(-)() (4). The chiral structure of CHDA(2+) induced asymmetrical [Ni(dmit)(2)](-) arrangements in the crystals. A large frequency and temperature dependence of the dielectric response was observed in (CHDA(2+))(B[18]crown-6)(2), due to the pendulum motion of the cyclohexane ring along the nitrogen-nitrogen direction of CHDA(2+). Since the inversion center of the [Ni(dmit)(2)](-) arrangements was lost in the unit cell due to the chiral space group, the salts 1-4 showed rather complicated magnetic behaviors. The temperature-dependent magnetic properties of salts 3 and 4 were explained by the sum of the Curie-Weiss and singlet-triplet thermal excitation models, with positive (ferromagnetic) and negative (antiferromagnetic) magnetic exchange energies, respectively.


[Risk factors of retinopathy of prematurity in extremely low birth weight infants by strictly controlling oxygen inhalation after birth].
Objective: To observe the incidence and severity of retinopathy of prematurity (ROP) in extremely low birth weight (ELBW) infants by strictly controlling the risk factors of ROP, such as oxygen inhalation after birth, to explore the related factors of ROP in ELBW infants. Methods: This was a cross-sectional study. 166 ELBW infants underwent neonatal screening were enrolled in this study, whose birth weight was less than 1 000 g. There were 79 males and 87 females infants, whose average gestational age was (27.99±1.73)weeks, and average birth weight was (904.45±80.23)g. According to the final screening results, the ELBW infants were grouped as follows: (1)ROP group and non-ROP group; (2)severe ROP group and mild or no ROP group. Risk factors included gestational age, birth weight, test-tube infants, fetuses number, complications during pregnancy, delivery mode and Apgar scores in 1 to 10 minutes, weight and weight gain proportion at 1-6 weeks after birth, postnatal feeding mode, history of oxygen inhalation, anemia and blood transfusion, and other systemic diseases were recorded. And their correlation with severe ROP was analyzed by SPSS 20.0 statistical software. Results: Ninty-four (56.63%) ELBW infants developed ROP, 16 (9.64%) were severe ROP and 14(8.43%) received treatment. Average birth weight between ROP group (911.95±72.80)g and non-ROP group (894.67±88.58)g had no difference(t=1.379, P=0.170). Average gestational age between ROP group (27.49±1.53) weeks and non-ROP group (28.64±1.76) weeks had significant difference(t=-4.491,P<0.001).And pregnancy-induced hypertension during pregnancy (χ(2)=4.479, P=0.034), Apgar score in 5 minutes (t=-2.760, P=0.006) and 10 minutes (t=-2.099, P=0.043), pneumonia (χ(2)=6.233, P=0.013), neonatal pneumonia (χ(2)=18.026, P<0.001) had significant difference between ROP group and non-ROP group. There was no effect on weight (F=0.009,P=0.753) or weight gain proportion (F=2.394,P=0.124) at 1-6 weeks after birth in ELBW infants with or without ROP. Average birth weight between severe ROP group(875.63±74.85)g and mild or no ROP group(907.53±80.41)g had no difference(t=-1.518, P=0.131).Average gestational age between severe ROP group(26.88±1.31)weeks and mild or no ROP group (28.11±1.73)weeks had significant difference(t=-2.766,P=0.006).And only fundus hemorrhage (χ(2)=4.507,P=0.034) had significant difference between severe ROP group and mild or no ROP group. There was no effect on weight (F=2.683,P=0.103) or weight gain proportion (F=0.431,P=0.513) at 1-6 weeks after birth in ELBW infants with or without ROP. Logistic regression analysis revealed that only gestational age was correlated to the incidence (β=-0.437,P<0.001) and severity (β=-0.616,P=0.007) of ROP significantly. Conclusion: By strictly controlling the risk factors of ROP, such as oxygen inhalation after birth, the severe rate of ROP in ELBW infants is low. However, gestational age is still the inevitable independent high risk factor for the incidence of ROP in ELBW infants. (Chin J Ophthalmol, 2019, 55:280-288).


[Clinicopathologic features and prognosis of 28 cases of pleuralpulmonary blastoma in children].
Objective: To explore the clinical characteristics, therapeutic methods and prognosis of pleuropulmonary blastoma in children. Methods: The clinical data of 28 patients with pleuropulmonary blastoma diagnosed in Guangzhou Women and Children's Medical Centre from November 2008 to May 2018 were collected and retrospectively analyzed. Results: Of the 28 patients, 18 were male and 10 were female, aged from 22 days to 5 years 10 month, the average age was 2 years 6 months. One patient underwent biopsy and other 27 underwent operation, 14 patients with type Ⅱ/Ⅲ pleuropulmonary blastoma received postoperative chemotherapy. Five patients were pathologically diagnosed as typeⅠpleuropulmonary blastoma, 5 were type Ⅱ pleuropulmonary blastoma and 18 were type Ⅲ pleuropulmonary blastoma. During the follow-up period of 24 patients, 15 patients were disease free survival, 3 patients relapsed within 6 months, 10 months and 18 months after chemotherapy, respectively. One patient who received postoperative chemotherapy suffered a bone metastasis within 11 months, 2 patient without chemotherapy relapsed within 2 months and suffered bone or renal metastasis within 3 months, respectively. Three patients who left hospital voluntarily died within 1 month. Conclusions: Pleuropulmonary blastoma is a highly malignant and rapidly progressed neoplasm. Patients with type Ⅰ pleuropulmonary blastoma have good prognoses while the prognoses of Ⅱ/Ⅲ pleuropulmonary blastoma are poor. Postoperative chemotherapy seems to improve the survival of patients withⅡ/Ⅲ pleuropulmonary blastoma.


The antifungal activity of human parotid secretion is species-specific.
Candida albicans is the major fungal colonizer of the oral cavity and causes oral candidiasis in immunocompromised patient populations. While antifungal proteins in saliva have been identified and the virulence factors of C. albicans have been well studied, little is known about the role saliva plays in the preferential colonization of the oral cavity by C. albicans. We report that the fungistatic activity of human parotid secretion toward six C. albicans strains is considerably lower than towards nine non-C. albicans fungal species (average IC₅₀ values >1000 mg/l and <70 mg/l, respectively). The species-specific activity of parotid secretion suggests that saliva may play a determining role in oral fungal colonization patterns.


Attenuation of transcriptional bursting in mRNA transport.
Because of the stochastic nature of biochemical processes, the copy number of any given type of molecule inside a living cell often exhibits large temporal fluctuations. Here, we develop analytic methods to investigate how the noise arising from a bursting input is reshaped by a transport reaction which is either linear or of the Michaelis-Menten type. A slow transport rate smoothes out fluctuations at the output end and minimizes the impact of bursting on the downstream cellular activities. In the context of gene expression in eukaryotic cells, our results indicate that transcriptional bursting can be substantially attenuated by the transport of mRNA from nucleus to cytoplasm. Saturation of the transport mediators or nuclear pores contributes further to the noise reduction. We suggest that the mRNA transport should be taken into account in the interpretation of relevant experimental data on transcriptional bursting.


Electric susceptibility of unsolvated glycine-based peptides.
The DC electric susceptibilities of unsolvated glycine-based peptides, WGn (W = tryptophan and G = glycine) with n = 1-5, have been measured by deflection of a molecular beam in an electric field. These are the first electric deflection measurements performed on peptides. At 300 K the susceptibilities are in the range of 200-400 A(3). By far the largest contribution to the susceptibilities is from the permanent dipole moment of the peptides. The results indicate that the peptides do not have rigid conformations with fixed dipoles. Instead the dipole is averaged as the peptides explore their energy landscape. For a given WGn peptide, all molecules have almost the same average dipole, which suggests that they all explore a similar energy landscape on the microsecond time scale of the measurement. The measured susceptibilities are in good overall agreement with values calculated from the average dipole moment deduced from Monte Carlo simulations.


Software for selecting the most informative sets of genomic loci for multi-target microbial typing.
High-throughput sequencing can identify numerous potential genomic targets for microbial strain typing, but identification of the most informative combinations requires the use of computational screening tools. This paper describes novel software-- Automated Selection of Typing Target Subsets (AuSeTTS)--that allows intelligent selection of optimal targets for pathogen strain typing. The objective of this software is to maximise both discriminatory power, using Simpson's index of diversity (D), and concordance with existing typing methods, using the adjusted Wallace coefficient (AW). The program interrogates molecular typing results for panels of isolates, based on large target sets, and iteratively examines each target, one-by-one, to determine the most informative subset. AuSeTTS was evaluated using three target sets: 51 binary targets (13 toxin genes, 16 phage-related loci and 22 SCCmec elements), used for multilocus typing of 153 methicillin-resistant Staphylococcus aureus (MRSA) isolates; 17 MLVA loci in 502 Streptococcus pneumoniae isolates from the MLVA database (http://www.mlva.eu) and 12 MLST loci for 98 Cryptococcus spp. isolates.The maximum D for MRSA, 0.984, was achieved with a subset of 20 targets and a D value of 0.954 with 7 targets. Twelve targets predicted MLST with a maximum AW of 0.9994. All 17 S. pneumoniae MLVA targets were required to achieve maximum D of 0.997, but 4 targets reached D of 0.990. Twelve targets predicted pneumococcal serotype with a maximum AW of 0.899 and 9 predicted MLST with maximum AW of 0.963. Eight of the 12 MLST loci were sufficient to achieve the maximum D of 0.963 for Cryptococcus spp. Computerised analysis with AuSeTTS allows rapid selection of the most discriminatory targets for incorporation into typing schemes. Output of the program is presented in both tabular and graphical formats and the software is available for free download from http://www.cidmpublichealth.org/pages/ausetts.html.


Cultural estrangement: the role of personal and societal value discrepancies.
Study 1 examined whether cultural estrangement arises from discrepancies between personal and societal values (e.g., freedom) rather than from discrepancies in attitudes toward political (e.g., censorship) or mundane (e.g., pizza) objects. The relations between different types of value discrepancies, estrangement, subjective well-being, and need for uniqueness also were examined. Results indicated that personal-societal discrepancies in values and political attitudes predicted estrangement, whereas mundane attitude discrepancies were not related to estrangement. As expected, value discrepancies were the most powerful predictor of estrangement. Value discrepancies were not related to subjective well-being but fulfilled a need for uniqueness. Study 2 replicated the relations between value discrepancies, subjective well-being, and need for uniqueness while showing that a self-report measure of participants' values and a peer-report measure of the participants' values yielded the same pattern of value discrepancies. Together, the studies reveal theoretical and empirical benefits of conceptualizing cultural estrangement in terms of value discrepancies.


A physician's guide to disability insurance.
Many physicians purchase disability insurance to protect their families and financial resources against unforeseen illness or injury. This article discusses various issues frequently encountered in disability claims and suggests ways of maximizing coverage and avoiding pitfalls that may negatively impact benefit claims.


Molecular cloning, nucleotide sequencing, and affinity labeling of bovine liver UDP-glucose pyrophosphorylase.
A bovine liver cDNA encoding UDP-glucose pyrophosphorylase [EC 220.127.116.11], which catalyzes the reversible uridylyl transfer between glucose 1-phosphate and MgUTP, has been cloned by the use of oligonucleotide probes synthesized on the basis of partial amino acid sequences of the enzyme. The cDNA clone contained a 1,689 base-pair insert including the complete message for the subunit polypeptide (508 amino acid residues) of the octameric enzyme. The bovine liver enzyme shows significant sequence similarities with the enzymes from potato tuber and a slime mold, Dictyostelium discoideum, but not with the enzyme from Escherichia coli, or ADP-glucose pyrophosphorylases from rice seed and E. coli. To probe the substrate-binding site in the bovine liver enzyme, the purified enzyme was incubated with an affinity labeling reagent, uridine triphosphopyridoxal, and then reduced with sodium borohydride. The enzyme was inactivated rapidly and irreversibly by the reagent at low concentrations. The inactivation was almost completely retarded by UDP-glucose and MgUTP. Structural analysis of the labeled enzyme revealed that three lysyl residues, Lys291, Lys357, and Lys396, were modified by the reagent. The three lysyl residues are conserved at the corresponding positions in the sequence of the potato tuber enzyme, in which they have catalytically important functions. These results show that the active-site structure of bovine liver UDP-glucose pyrophosphorylase is very similar to that of the potato tuber enzyme.


Intranuclear inclusions in oculopharyngeal muscular dystrophy among Bukhara Jews.
We studied, by electron microscopy, muscle biopsies from seven patients with autosomal dominant oculopharyngeal muscular dystrophy (OPMD) belonging to the recently described Bukhara-Jewish cluster. Typical tubulofilamentous intranuclear inclusions (INI) of 8.5 nm outer diameter were present in all cases. The INI were observed in 4.5 +/- 1.8% of the nuclei in five patients. In the other two, they occurred in 9.5 +/- 0.5% of the nuclei and often occupied a larger nuclear area. These two patients, offspring of intermarriage between affected cousins, had an unusually severe form of OPMD beginning in their early 30s, suggesting homozygote state. Our results confirm that INI are pathognomonic for OPMD and suggest that their frequency may be quantitatively related to the number of abnormal DNA copies.


Inhibition of Nitric Oxide Production in LPS-Stimulated RAW 264.7 Macrophages and 15-LOX Activity by Anthraquinones from Pentas schimperi.
The anti-inflammatory activity of a coumarin and nine anthraquinone derivatives, 3-hydroxy-1-methoxy-2-methylanthraquinone (1), 2-hydroxymethyl anthraquinone (2), schimperiquinone B (3), cleomiscosin A (4), damnacanthal (5), 1,2-dihydroxy anthraquinone (6), damnacanthol (7), 3-hydroxy-2-hydroxymethyl anthraquinone (8), 1-hydroxy-2-methoxyanthraquinone (9), and 2-hydroxymethyl-3-O-prenylanthraquinone (10), isolated from the roots of Pentas schimperi were determined. The anti-15-lipoxygenase activity and nitric oxide production inhibition on lipopolysaccharide-activated macrophages RAW 264.7 cells were determined as indicators of anti-inflammatory activity. The Griess assay was used to measure nitric oxide production and the ferrous oxidation-xylenol orange assay was used to determine the 15-lipoxygenase inhibitory activity. All the compounds significantly decreased nitrite + nitrate accumulation in lipopolysaccharide-stimulated RAW 264.7 cells in a concentration-dependent manner with 85.67 % to 119.75 % inhibition of nitrite + nitrate production at 20 µg/mL. Most of the compounds had a moderate inhibitory effect on 15-lipoxygenase activity. Compounds 8 and 10 were the most potent inhibitor both in nitrite + nitrate production with respective IC50 values of 1.56 µM and 6.80 µM. Compounds 2, 7, and 8 had good anti-15-lipoxygenase activity with respective IC50 values of 13.80 µM, 14.80 µM, and 15.80 µM compared to quercetin, which was used as a standard lipoxygenase inhibitor (IC50 of 16.80 µM). Our study revealed 3-hydroxy-2-hydroxymethyl anthraquinone and damnacanthol as potent inhibitors of both 15-lipoxygenase activity and nitric oxide production. Further studies are needed in order to envisage its possible future use as a therapeutic alternative against inflammatory diseases.


[Minimally invasive surgery of abscesses of the retroperitoneal space].
The article presents an experience with treatment of abscesses of the retroperitoneal space in 28 patients using interventions under ultrasonic control. All the patients underwent draining operations. Determination was made of optimal terms of operative treatment under the ultrasonic control depending on the character of pathological fluid accumulation; of rational approaches to the abscess cavity to support the safest passing the needle through the retroperitoneal space tissues. An algorithm of management of the patients at the stages of both stationary and ambulatory treatment was developed. An analysis of causes of the approach conversion after minimally invasive draining operations was made. Draining operations under USI control in most cases of retroperitoneal abscesses allowed sanitation of purulent cavities without open operations.


Effect of upper limb botulinum toxin injections on impairment, activity, participation, and quality of life among stroke patients.
The purpose of this study was to study the effect of Botulinum toxin type A (BoNT-A) injections in spastic upper limb muscles on impairment, activity, participation and quality of life in chronic stroke patients. BoNT-A (Dysport) was injected into several upper limb spastic muscles in a group of 20 patients. Neurological impairment (muscle tone and strength, dexterity, SIAS), activity (ABILHAND), participation (SATIS-Stroke), and quality of life (SF36) were assessed before and 2 months after the injections. BoNT-A injections improved muscle tone, but had no impact on dexterity, manual ability, social participation, and quality of life. In this study, BoNT-A injections in spastic upper limbs significantly reduced neurological impairments, but had no functional impact.


Cognitive impairment and employment status in systemic lupus erythematosus: a prospective longitudinal study.
To determine the relationship between cognitive impairment and employment in patients with systemic lupus erythematosus (SLE). A total of 167 consecutive patients with SLE were prospectively evaluated, and underwent standardized neuropsychological tests. Multivariate logistic regression was used to determine the likelihood of being unemployed, adjusting for sociodemographic characteristics, employment status at study entry, disease activity, disease duration, damage scores, and depression. At study entry, 118 (70.7%) of 167 patients were employed. In the multivariate analysis, after adjusting for confounders, unemployment was predicted by the number of cognitive domains impaired (odds ratio [OR] 1.76, 95% confidence interval [95% CI] 1.58-6.72), depression (OR 1.3, 95% CI 1.1-3.1), fewer years of education (OR 0.12, 95% CI 0.02-0.34), and the presence of anticardiolipin antibodies (OR 1.43, 95% CI 1.2-6.1). Complex attention (OR 1.7, 95% CI 1.2-3.6), memory (OR 3.1, 95% CI 1.5-6.2), and executive functions (OR 2.4, 95% CI 1.9-6.1) were predictors of unemployment at study entry. After 3 years, 61 (51.7%) of 118 patients were employed (OR 2.25, 95% CI 1.38-3.68; P = 0.001). The likelihood of being unemployed after 3 years was predicted by the number of cognitive domains impaired (OR 3.8, 95% CI 2.5-7.71), depression (OR 2.31, 95% CI 1.01-5.21), fewer years of education (OR 0.09, 95% CI 0.01-0.42), and the presence of anticardiolipin antibodies (OR 2.1, 95% CI 1.2-4.9). Complex attention (OR 2.2, 95% CI 1.1-3.8), memory (OR 3.6, 95% CI 2.1-6.4), executive functions (OR 1.8, 95% CI 1.2-7.3), and reasoning/problem solving (OR 1.9, 95% CI 1.4-7.2) were associated with unemployment after 3 years. The number of cognitive spheres, and especially attention, memory, and executive functions, are important factors associated with unemployment in patients with SLE.


Eimeria tenella: experimental development of resistance to monensin in the chicken.
The development of resistance by the Houghton strain of Eimeria tenella (H) to monensin has been studied by serially passaging the strain in groups of 30 birds, each inoculated with 10(6) oocysts and given 100 p.p.m. of drug in the food. After 16 passages a line partially resistant to this concentration of monensin was produced. Passage of the line in birds medicated with 200 or 300 p.p.m. of monensin did not result in the acquisition of a greater degree of resistance. A further reduction in sensitivity to 100 p.p.m. monensin was obtained, however, when the line was serially passaged in 15 groups of 6 birds each given 3 X 10(6) oocysts. Five passages in the absence of monensin resulted in restoration of sensitivity, suggesting that the resistance developed was not stable. The pathogenic effects of the line that had been passaged in chickens given 300 p.p.m. of monensin were less than those of the parent line.


Sex-Dependent Pathology in the HPA Axis at a Sub-acute Period After Experimental Traumatic Brain Injury.
Over 2.8 million traumatic brain injuries (TBIs) are reported in the United States annually, of which, over 75% are mild TBIs with diffuse axonal injury (DAI) as the primary pathology. TBI instigates a stress response that stimulates the hypothalamic-pituitary-adrenal (HPA) axis concurrently with DAI in brain regions responsible for feedback regulation. While the incidence of affective symptoms is high in both men and women, presentation is more prevalent and severe in women. Few studies have longitudinally evaluated the etiology underlying late-onset affective symptoms after mild TBI and even fewer have included females in the experimental design. In the experimental TBI model employed in this study, evidence of chronic HPA dysregulation has been reported at 2 months post-injury in male rats, with peak neuropathology in other regions of the brain at 7 days post-injury (DPI). We predicted that mechanisms leading to dysregulation of the HPA axis in male and female rats would be most evident at 7 DPI, the sub-acute time point. Young adult age-matched male and naturally cycling female Sprague Dawley rats were subjected to midline fluid percussion injury (mFPI) or sham surgery. Corticotropin releasing hormone, gliosis, and glucocorticoid receptor (GR) levels were evaluated in the hypothalamus and hippocampus, along with baseline plasma adrenocorticotropic hormone (ACTH) and adrenal gland weights. Microglial response in the paraventricular nucleus of the hypothalamus indicated mild neuroinflammation in males compared to sex-matched shams, but not females. Evidence of microglia activation in the dentate gyrus of the hippocampus was robust in both sexes compared with uninjured shams and there was evidence of a significant interaction between sex and injury regarding microglial cell count. GFAP intensity and astrocyte numbers increased as a function of injury, indicative of astrocytosis. GR protein levels were elevated 30% in the hippocampus of females in comparison to sex-matched shams. These data indicate sex-differences in sub-acute pathophysiology following DAI that precede late-onset HPA axis dysregulation. Further understanding of the etiology leading up to late-onset HPA axis dysregulation following DAI could identify targets to stabilize feedback, attenuate symptoms, and improve efficacy of rehabilitation and overall recovery.


[Dental enamel hypoplasia apropos of a case].
The developmental anomalies of dental hard tissues are relatively common in children. These anomalies can involve separately the enamel and they are due to many factors acting during odontogenesis. The paper deals with the main ethological factors and describes a case of idiopathic hypercalcemia. It is normally accompanied by aortic stenosis, mental retardation and a characteristic elfin face. This is called Williams syndrome. In this case we only found enamel hypoplasia on the cusps of the first molars.


Interaction between External and Internal Conditions in the Development of Photosynthetic Features in a Grass Leaf: II. REVERSIBILITY OF LIGHT-INDUCED RESPONSES AS A FUNCTION OF DEVELOPMENTAL STAGES.
Lolium multiflorum plants were grown under a low- or high-light regime until third leaves had emerged to one-third their final length and then were transferred to a contrasting light regime. At this stage, the leaf possesses a tissue-age gradient from tip to base; thus, the reversibility of light-acclimated responses as a function of the degree of differentiation was analyzed in individual leaves.Regional responses in the apical, medial, and basal zones of leaves of transferred plants were analyzed before and after light transfer and compared to leaves from plants kept in constant light. Leaves transferred from low to high light showed rapid recovery and attained light-saturated rates and ribulose bisphosphate carboxylase activities equivalent to those of high-light controls. However, fresh or dry weight and chlorophyll content were intermediate between those for the two irradiances. In the reciprocal experiment, the apical leaf zone retained high-light characteristics for maximum photosynthesis, whereas all the other functional parameters adapted rapidly to values characteristic of their low-light counterparts (equivalent foliar zones).On the ultrastructural level, chloroplasts in the apical zone of transferred leaves surpassed their respective constant light controls in absolute membrane content and size. However, a shift to high light induced an increase in plastid volume and, in relative terms, the plastid membrane content was diluted. A shift to low-light treatment led to smaller membrane-dense plastids. The ultrastructural readaptation is realized through differential rates of increase in plastid volume and lamellar content. Proplastids (leaf base), or juvenile plastids having reached an intermediate developmental stage (leaf middle zone) at the time of transfer, took on characteristics of the latter light regime (equivalent to controls).These results provide evidence for rapid reacclimation processes under changing light regimes and suggest a capacity for regional light responses along the leaf.


Efficiency of standardized ileal digestible lysine utilization for whole body protein deposition in pregnant gilts and sows during early-, mid-, and late-gestation.
The efficiency of SID Lys utilization (kSID Lys) in gilts and sows during early (days 48 to 52), mid (days 75 to 79), and late gestation (days 103 to 107) was investigated using 88 pregnant females (PIC 1050; 27 gilts, 27 parity 1 sows, 34 parity 2+ sows; 192.96 ± 22.84 kg at days 42 ±1 of gestation) and whole body nitrogen (N) retention balance studies. Females were assigned to 1 of 4 SID Lys levels ranging from 40% to 70% of the daily SID Lys requirements above maintenance for a parity 1 sow according to the NRC (2012) gestating sow model in each gestation period. Experimental diets were isocaloric (3,335 kcal ME/kg) and isoproteic (11.75 % CP) and dietary indispensable AA were set to meet or exceed 100% of AA:Lys ratios. The slope of the linear response to graded SID Lys intake was defined as kSID Lys. With the aim of increasing the accuracy of kSID Lys estimates, gilt data from the current study was combined with gilt data from a previous study conducted at the same facility using 4 SID Lys levels ranging from 60% to 90% of the daily SID Lys requirements above maintenance for gilts according to the NRC (2012) gestating sow model. Whole body Lys retention of the combined gilt data set was assessed with different broken-line and nonlinear models. The kSID Lys was 0.65, 0.38, and 0.52 for early-, mid-, and late-gestation, respectively, in gilts. A linear response to graded SID Lys intake was found in late gestation only in parity 1 and 2+ sows; kSID Lys was determined as 0.44 and 0.52 in late gestation for parity 1 and parity 2+ sows, respectively. There were no differences in kSID Lys in late gestation between parities. For the combined gilt data, the model of best performance (reduced error and greater goodness of fit) was the Hoerl model. Maximum kSID Lys (i.e., g SID Lys retention/g SID Lys intake) in gilts was 0.67, 0.54, and 0.53 in early, mid, and late gestation predicted at 7.2, 9.1, and 13.5 g of SID Lys intake/d, respectively, based on the Hoerl model. Maximum SID Lys retention in gilts was similarly predicted at 8.5, 10.5, and 20.9 g of SID Lys intake per day in early, mid, and late gestation and resultant kSID Lys of 0.61, 0.51, and 0.44, respectively. The findings of this study demonstrate that kSID Lys varies by stage of gestation and SID Lys intake level and that, at least in gilts, a dynamic kSID adjusted for daily intake more adequately reflects biological response and hence allows more precise feeding of pregnant females.


Evidence for electrical synapses between neurons of the nucleus reticularis thalami in the adult brain in vitro.
It has been conclusively demonstrated in juvenile rodents that the inhibitory neurons of the nucleus reticularis thalami (NRT) communicate with each other via connexin 36 (Cx36)-based electrical synapses. However, whether functional electrical synapses persist into adulthood is not fully known. Here we show that in the presence of the metabotropic glutamate receptor (mGluR) agonists, trans-ACPD (100 muM) or DHPG (100 muM), 15% of neurons in slices of the adult cat NRT maintained in vitro exhibit stereotypical spikelets with several properties that indicate that they reflect action potentials that have been communicated through an electrical synapse. In particular, these spikelets, i) display a conserved all-or-nothing waveform with a pronounced after-hyperpolarization (AHP), ii) exhibit an amplitude and time to peak that are unaffected by changes in membrane potential, iii) always occur rhythmically with the precise frequency increasing with depolarization, and iv) are resistant to blockers of conventional, fast chemical synaptic transmission. Thus, these results indicate that functional electrical synapses in the NRT persist into adulthood where they are likely to serve as an effective synchronizing mechanism for the wide variety of physiological and pathological rhythmic activities displayed by this nucleus.


Patterns and correlates of alcohol consumption among African-American women.
The purpose of the present study was to assess patterns and correlates of alcohol consumption among African-American women. We used postal questionnaires to collect data in 1995 on alcohol consumption and on demographic, medical, and behavioral factors from 64,500 African-American women aged 21-69 years from across the United States enrolled in the Black Women's Health Study. We used logistic regression analysis to assess the association of consumption with potential correlates. The prevalence of current drinking was highest (37.1%) among women 40-49 years of age, and lowest (23.1%) among women aged 21-29. In every region, heavy drinking (at least 14 drinks a week), reported by about 8% of current drinkers, was associated with current smoking, lower educational attainment, commencement of drinking at younger ages and, particularly, consumption of greater amounts of alcohol in the early years of drinking. Alcoholic beverage consumption in later life is strongly related to early patterns. Heavy consumption is associated with smoking and lower levels of education.


Role of interleukin-17 in chondrocytes of herniated intervertebral lumbar discs.
Lumbar disc herniation (LDH) is a common cause of lumbosacral radiculopathy. An autoimmune response to a herniated nucleus pulposus (NP) has been suggested to play an important role in the initiation of radiculopathy. Interleukin-17 (IL-17) is a cytokine associated with inflammation and autoimmunity. The presence of IL-17 has been studied in patients with LDH; however, extensive investigation into the expression of IL-17 in different disc pathologies of LDH has not yet been conducted. The aim of the present study was to investigate the role of neovascularization and hypertrophic chondrocytes in herniated intervertebral lumbar discs. Fifty-two intervertebral lumbar disc specimens were extracted from 46 patients with LDH and were subsequently classified as either contained or non-contained disc herniation (CDH and NCDH, respectively). The specimens were stained with hematoxylin and eosin or toluidine blue, or were immunostained with polyclonal antibodies to IL-17 using the streptavidin-peroxidase method. The neovascular tissue and staining results were graded to establish the histological differences between the two herniation types. The intervertebral discs (IVDs) obtained from patients with NCDH showed significantly more neovascularization and granulation tissue than the discs obtained from patients with CDH (P<0.05). Furthermore, hypertrophic chondrocytes were more abundant in the NCDH specimens than in the CDH specimens (P<0.05). Similarly, the number of IL-17-immunoreactive cells was significantly higher in the NCDH specimens than that in the CDH specimens (P<0.01). In conclusion, local inflammation and autoreactive immune activation may play an important role in the pathogenesis of LDH. These results also suggest a role of chondrocytes in the repair of herniated IVDs.


Pituitary adenylate cyclase-activating polypeptide-immunoreactive (PACAP-IR) nerve fibers in the pig pineal gland.
The present study demonstrates the occurrence of PACAP-immunoreactive (PACAP-IR) nerve fibers in different compartments of the pig pineal gland, including glandular capsule (where they form a very dense network) and subependymal tissue close to the pineal recess (moderate to dense meshwork of varicose fibers). Furthermore, several varicose fibers penetrate from the capsule into the connective tissue septa and then into the parenchyma, where they form unequally distributed, fine network and, in some cases, basket-like structures around pinealocytes. Some of the PACAP-IR nerve fibers, observed both in the habenular and posterior epithalamic areas, extend to the pineal gland. PACAP-IR cells could be demonstrated neither in the pineal gland, nor in epithalamic areas.


Acrolein inhalation acutely affects the regulation of mitochondrial metabolism in rat lung.
Exposure of the airways to cigarette smoke (CS) is the primary risk factor for developing several lung diseases such as Chronic Obstructive Pulmonary Disease (COPD). CS consists of a complex mixture of over 6000 chemicals including the highly reactive α,β-unsaturated aldehyde acrolein. Acrolein is thought to be responsible for a large proportion of the non-cancer disease risk associated with smoking. Emerging evidence suggest a key role for CS-induced abnormalities in mitochondrial morphology and function in airway epithelial cells in COPD pathogenesis. Although in vitro studies suggest acrolein-induced mitochondrial dysfunction in airway epithelial cells, it is unknown if in vivo inhalation of acrolein affects mitochondrial content or the pathways controlling this. In this study, rats were acutely exposed to acrolein by inhalation (nose-only; 0-4 ppm), 4 h/day for 1 or 2 consecutive days (n = 6/group). Subsequently, the activity and abundance of key constituents of mitochondrial metabolic pathways as well as expression of critical proteins and genes controlling mitochondrial biogenesis and mitophagy were investigated in lung homogenates. A transient decreasing response in protein and transcript abundance of subunits of the electron transport chain complexes was observed following acrolein inhalation. Moreover, acrolein inhalation caused a decreased abundance of key regulators associated with mitochondrial biogenesis, respectively a differential response on day 1 versus day 2. Abundance of components of the mitophagy machinery was in general unaltered in response to acrolein exposure in rat lung. Collectively, this study demonstrates that acrolein inhalation acutely and dose-dependently disrupts the molecular regulation of mitochondrial metabolism in rat lung. Hence, understanding the effect of acrolein on mitochondrial function will provide a scientifically supported reasoning to shortlist aldehydes regulation in tobacco smoke.


Software for population pharmacokinetics and pharmacodynamics.
Pharmacokinetic-pharmacodynamic modelling is being used increasingly as a tool in drug development because often in phase III clinical trials only sparse data are available for analysis and so a nonlinear mixed effects modelling approach has to be adopted. Specialist data analytical techniques and software are required to analyse such data. This article reviews some of the software currently available for performing nonlinear mixed effects modelling. A questionnaire was devised and sent to a number of software producers and the findings are presented and discussed in this paper. The programs could be grouped into 3 main categories: parametric and nonparametric maximum likelihood and Bayesian. It was apparent from the questionnaire that software development for population data analysis is a very active area of investigation. The implementation of methodologies varied widely between the packages: some were self-contained programs, whereas others were written within another application, usually a statistical package. They also varied with respect to their ease of use and level of support offered by the software producers. Although robustness and reliability are important concerns, they were not addressed in the present review. Most of the programs surveyed are in continual development.


Investigation into Early Steps of Actin Recognition by the Intrinsically Disordered N-WASP Domain V.
Cellular regulation or signaling processes are mediated by many proteins which often have one or several intrinsically disordered regions (IDRs). These IDRs generally serve as binders to different proteins with high specificity. In many cases, IDRs undergo a disorder-to-order transition upon binding, following a mechanism between two possible pathways, the induced fit or the conformational selection. Since these mechanisms contribute differently to the kinetics of IDR associations, it is important to investigate them in order to gain insight into the physical factors that determine the biomolecular recognition process. The verprolin homology domain (V) of the Neural Wiskott-Aldrich Syndrome Protein (N-WASP), involved in the regulation of actin polymerization, is a typical example of IDR. It is composed of two WH2 motifs, each being able to bind one actin molecule. In this study, we investigated the early steps of the recognition process of actin by the WH2 motifs of N-WASP domain V. Using docking calculations and molecular dynamics simulations, our study shows that actin is first recognized by the N-WASP domain V regions which have the highest propensity to form transient α -helices. The WH2 motif consensus sequences "LKKV" subsequently bind to actin through large conformational changes of the disordered domain V.


A fast and scalable radiation hybrid map construction and integration strategy.
This paper describes a fast and scalable strategy for constructing a radiation hybrid (RH) map from data on different RH panels. The maps on each panel are then integrated to produce a single RH map for the genome. Recurring problems in using maps from several sources are that the maps use different markers, the maps do not place the overlapping markers in same order, and the objective functions for map quality are incomparable. We use methods from combinatorial optimization to develop a strategy that addresses these issues. We show that by the standard objective functions of obligate chromosome breaks and maximum likelihood, software for the traveling salesman problem produces RH maps with better quality much more quickly than using software specifically tailored for RH mapping. We use known algorithms for the longest common subsequence problem as part of our map integration strategy. We demonstrate our methods by reconstructing and integrating maps for markers typed on the Genebridge 4 (GB4) and the Stanford G3 panels publicly available from the RH database. We compare map quality of our integrated map with published maps for GB4 panel and G3 panel by considering whether markers occur in the same order on a map and in DNA sequence contigs submitted to GenBank. We find that all of the maps are inconsistent with the sequence data for at least 50% of the contigs, but our integrated maps are more consistent. The map integration strategy not only scales to multiple RH maps but also to any maps that have comparable criteria for measuring map quality. Our software improves on current technology for doing RH mapping in areas of computation time and algorithms for considering a large number of markers for mapping. The essential impediments to producing dense high-quality RH maps are data quality and panel size, not computation.


A novel role for the chemokine receptor Cxcr4 in kidney morphogenesis: an in vitro study.
The CXCR4 chemokine receptor is involved in hematopoietic stem cell homing, neuronal development, and angiogenesis. We show a significant new role for this receptor in epithelial patterning and renal morphogenesis. This receptor is expressed in the ureteric bud (UB) and the metanephric mesenchyme (MM). Stimulation of Cxcr4 in renal tubular cells leads to activation of multiple signaling pathways and tubulogenesis and cell migration. Knocking down of this receptor in tubular cells leads to cyst formation. Inactivation of this receptor in embryonic kidney explants results in impaired UB branching and mesenchymal tubulogenesis. The data presented here point to its importance in the process of mesenchymal-to-epithelial transitioning (MET), a crucial developmental process in the embryonic kidney. A number of genes important for normal tubulogenesis and MET are decreased upon CXCR4 inactivation.


Nontypeable Haemophilus influenzae meningitis complicated by hearing loss in a 9-year-old HIV-infected boy.
A 9-year old boy with perinatal HIV infection developed meningitis due to nontypeable Haemophilus influenzae. His course was complicated by progressive hearing loss due to labyrinthitis ossificans. Placement of cochlear implant improved hearing thresholds. Nontypeable H. influenzae meningitis and use of cochlear implants have not previously been in HIV-infected children.


Necrotizing lymphadenitis--a clinico-pathologic study of 36 cases with immunohistochemical analysis.
Thirty-six cases of necrotizing lymphadenitis--including 33 cases of unknown etiology, 1 typhoid lymphadenopathy, and 2 cases of suspicious lupus lymphadenopathy--were clinico-pathologically reviewed and analyzed with immunostaining for s-100 and lysozyme. All cases histologically showed architectural effacement by paracortical lesions composed of nuclear karyorrhexis and mononuclear cell proliferation. Immunohistochemical study revealed proliferation of lysozyme-positive macrophages in the necrotizing areas and an increase in the number of s-100-positive cells in the uninvolved paracortical areas. This observation suggests that necrotizing lymphadenitis may be a common morphologic expression of a T cell-mediated hyperimmune condition induced by diverse etiologies.


Effects of chronic exposure to haloperidol, olanzapine or lithium on SV2A and NLGN synaptic puncta in the rat frontal cortex.
Positron emission tomography studies using the synaptic vesicle glycoprotein 2A (SV2A) radioligand [11C]-UCB-J provide in vivo evidence for synaptic dysfunction and/or loss in the cingulate and frontal cortex of patients with schizophrenia. In exploring potential confounding effects of antipsychotic medication, we previously demonstrated that chronic (28-day) exposure to clinically relevant doses of haloperidol does not affect [3H]-UCB-J radioligand binding in the cingulate and frontal cortex of male rats. Furthermore, neither chronic haloperidol nor olanzapine exposure had any effect on SV2A protein levels in these brain regions. These data do not exclude the possibility, however, that more subtle changes in SV2A may occur at pre-synaptic terminals, or the post-synaptic density, following chronic antipsychotic drug exposure. Moreover, relatively little is known about the potential effects of psychotropic drugs other than antipsychotics on SV2A. To address these questions directly, we herein used immunostaining and confocal microscopy to explore the effect of chronic (28-day) exposure to clinically relevant doses of haloperidol, olanzapine or the mood stabilizer lithium on presynaptic SV2A, postsynaptic Neuroligin (NLGN) puncta and their overlap as a measure of total synaptic density in the rat prefrontal and anterior cingulate cortex. We found that, under the conditions tested here, exposure to antipsychotics had no effect on SV2A, NLGN, or overall synaptic puncta count. In contrast, chronic lithium exposure significantly increased NLGN puncta density relative to vehicle, with no effect on either SV2A or total synaptic puncta. Future studies are required to understand the functional consequences of these changes.


One-Pot Dual Catalysis of a Photoactive Coordination Polymer and Palladium Acetate for the Highly Efficient Cross-Coupling Reaction via Interfacial Electron Transfer.
We report herein an exploration of the straightforward one-pot dual-catalysis strategy, i.e., direct combination of a photoactive coordination polymer (CP) with another metal catalyst, for carrying out the desirable photoinduced organic transformation. The strategy overcomes the necessity of the presynthesis of the metal/CP composite that has been demonstrated to be invalid in our case. A new two-dimensional CP showing the desirable properties of wide-range visible-light absorption and efficient photoinduced charge generation was synthesized via a solvothermal reaction. The synthesized CP was successfully applied to the photocatalytic C-C cross-coupling reaction via the one-pot dual-catalysis method, in combination with the simple and ligand-free palladium salt of Pd(OAc)2 as a metal catalyst. The reaction features a short reaction time, mild reaction conditions, good recyclability, and a high yield of Heck products from a broad variety of substrates. A comparative experiment showed the presynthesized Pd/CP composite was invalid for the reaction, demonstrating the significance of the one-pot dual-catalysis strategy. Mechanistic studies suggest the one-pot reaction depends on the synergy between the photocatalysis of a synthesized CP to generate reactive aryl radicals and Pd catalysis to generate target products, in which the interfacial electron transfer has been demonstrated to be vital for producing the transient and catalytically active Pd(0) species near the surface of the CP. The study shows the direct combination of a CP photocatalyst and a metal catalyst is a highly feasible method for the photochemical reaction and enhances the prospects of application of photoactive CPs.


Molecule-Confined Engineering toward Superconductivity and Ferromagnetism in Two-Dimensional Superlattice.
Superconductivity is mutually exclusive with ferromagnetism, because the ferromagnetic exchange field is often destructive to superconducting pairing correlation. Well-designed chemical and physical methods have been devoted to realize their coexistence only by structural integrity of inherent superconducting and ferromagnetic ingredients. However, such coexistence in freestanding structure with nonsuperconducting and nonferromagnetic components still remains a great challenge up to now. Here, we demonstrate a molecule-confined engineering in two-dimensional organic-inorganic superlattice using a chemical building-block approach, successfully realizing first freestanding coexistence of superconductivity and ferromagnetism originated from electronic interactions of nonsuperconducting and nonferromagnetic building blocks. We unravel totally different electronic behavior of molecules depending on spatial confinement: flatly lying Co(Cp)2 molecules in strongly confined SnSe2 interlayers weaken the coordination field, leading to spin transition to form ferromagnetism; meanwhile, electron transfer from cyclopentadienyls to the Se-Sn-Se lattice induces superconducting state. This entirely new class of coexisting superconductivity and ferromagnetism generates a unique correlated state of Kondo effect between the molecular ferromagnetic layers and inorganic superconducting layers. We anticipate that confined molecular chemistry provides a newly powerful tool to trigger exotic chemical and physical properties in two-dimensional matrixes.


Bergenin as a Novel Urate-Lowering Therapeutic Strategy for Hyperuricemia.
Bergenin is a C-glucoside of 4-O-methyl gallic acid isolated from several medicinal plants and has multiple biological activities. The aim of this study was to assess the potential usefulness of bergenin in hyperuricemia. We found that bergenin reduced serum urate levels in hyperuricemia mice by promoting renal and gut uric acid excretion. Bergenin treatment increased Abcg2 expression both in the kidneys and intestine, while the expression of Slc2a9 was suppressed in the kidney and increased in the intestine. Moreover, bergenin induced ABCG2 expression in HK-2 and Caco-2 cells, as well as SLC2A9 in Caco-2 cells, via the activation of PPARγ. Nevertheless, bergenin suppressed SLC2A9 expression in HK-2 cells by inhibiting the nuclear translocation of p53. Furthermore, bergenin decreased the serum levels of IL-6, IL-1β, and TNF-α in hyperuricemia mice, and promoted a polarization shift from the M1 to M2 phenotype in RAW264.7 cells. In conclusion, these findings provide evidence supporting the further development of bergenin as a novel therapeutic strategy for hyperuricemia.


Mind-refreshing acupuncture therapy for facial spasm, trigeminal neuralgia and stubborn facial paralysis.
It has been proved by clinical experiment that needling at Fengchi (GB 20), Wangu (GB 12) and Tianzhu (BL 10) can markedly improve the blood supply to the vertebral basilar artery, increase the cerebral blood flow, and relax the spasm of the vascular smooth muscles. The combined use of Shangxing (GV 23) and Yintang (EX-HN3) can give the effects of resuscitating and tranquilizing the mind, dispelling wind, dredging the channels, and relieving spasm and pain. In short, the above therapy may turn the pathological state into a normal physiological state, and bring a quicker recovery for patients with facial spasm, trigeminal neuralgia and stubborn facial paralysis.