Expression in cultured human neuroblastoma cells of epitopes associated with affected neurons in Alzheimer's disease.
Of three human neuroblastoma lines tested, IMR32K (and IMR32 parental line) was the only cell line that, after its exposure to a differentiation medium, consistently developed materials recognized immunocytochemically by a panel of antibodies against paired helical filaments (PHF). Ultrastructurally, these cells accumulated, at their perikarya and neuritic extensions, spatially discrete arrays of fibrils, which occasionally occurred in twisted pairs. When these fibrillar structures appeared as paired helices, they exhibited dimensions and configurations reminiscent of PHF found in affected Alzheimer neurons, although less compact. Immunoelectron microscope examinations of the fibrillar structures in these neuroblastoma cells with one of these anti-PHF immunoprobes revealed that only subsets of fibrillar structures that appeared thickened or aggregated to form bundles were selectively immunolabeled. Cultures of these immortal neuroblastoma lines may provide a convenient model for studying aspects of PHF formation that are hard to examine in Alzheimer brain obtained at autopsy.


Theory-driven classification of reading difficulties from fMRI data using Bayesian latent-mixture models.
Decades of research have led to several competing theories regarding the neural contributors to impaired reading. But how can we know which theory (or theories) identifies the types of markers that indeed differentiate between individuals with reading disabilities (RD) and their typically developing (TD) peers? To answer this question, we propose a new analytical tool for theory evaluation and comparison, grounded in the Bayesian latent-mixture modeling framework. We start by constructing a series of latent-mixture classification models, each reflecting one existing theoretical claim regarding the neurofunctional markers of RD (highlighting network-level differences in either mean activation, inter-subject heterogeneity, inter-region variability, or connectivity). Then, we run each model on fMRI data alone (i.e., while models are blind to participants' behavioral status), which enables us to interpret the fit between a model's classification of participants and their behavioral (known) RD/TD status as an estimate of its explanatory power. Results from n=127 adolescents and young adults (RD: n=59; TD: n=68) show that models based on network-level differences in mean activation and heterogeneity failed to differentiate between TD and RD individuals. In contrast, classifications based on variability and connectivity were significantly associated with participants' behavioral status. These findings suggest that differences in inter-region variability and connectivity may be better network-level markers of RD than mean activation or heterogeneity (at least in some populations and tasks). More broadly, the results demonstrate the promise of latent-mixture modeling as a theory-driven tool for evaluating different theoretical claims regarding neural contributors to language disorders and other cognitive traits.


Natural hot-ion modes in a rotating plasma.
In steady state, the fuel cycle of a fusion plasma requires inward particle fluxes of fuel ions. These particle flows are also accompanied by heating. In the case of classical transport in a rotating cylindrical plasma, this heating can proceed through several distinct channels depending on the physical mechanisms involved. Some channels directly heat the fuel ions themselves, whereas others heat electrons. Which channel dominates depends, in general, on the details of the temperature, density and rotation profiles of the plasma constituents. However, remarkably, under relatively few assumptions concerning these profiles, if the α particles, the by-products of the fusion reaction, can be removed directly by other means, then a hot-ion mode tends to emerge naturally.


Hypothalamic-pituitary-adrenal axis function: relative contributions of perceived stress and obesity in women.
A range of behavioral and psychosocial factors may contribute to a chronically stimulated hypothalamic-pituitary-adrenal (HPA) axis and subsequently altered diurnal patterns. The goal of this cross-sectional study was to examine associations among diurnal cortisol levels, perceived stress, and obesity patterns. Seventy-eight women (aged 24-72 years) employed in a rural public school system completed the perceived stress scale, collected diurnal saliva samples, and underwent anthropometric assessments. Reduced peak-to-nadir cortisol values across the day were considered a sign of impairment in HPA function. A series of linear regression models determined the best predictors of diurnal cortisol variation. There was a marginal linear trend in stress levels across body mass index (BMI) categories, with obese women reporting the highest levels of stress (p = 0.07). Perceived stress was the only significant predictor of the degree of flattening of the diurnal cortisol curve in the sample as a whole (beta = -0.042, R(2) = 0.11, F = 8.6, p = 0.005), indicating reduction in the normal diurnal pattern. Among overweight women (BMI = 25-29.9 kg/m(2)), stress and waist circumference combined predicted 35% of the variability in diurnal cortisol. In contrast, among obese women (BMI > or = 30 kg/m(2)), BMI predicted 31% of the variability in diurnal cortisol (F = 13.8, p = 0.001), but stress was no longer significantly related to diurnal cortisol. Psychological stress predicts a significant portion of HPA axis functioning. In overweight women, perceived stress and waist circumference were of approximately equal importance in predicting adrenal cortisol secretion. However, among obese women, a major portion of the diurnal cortisol variation was predicted by BMI alone, not stress or waist circumference. This may help elucidate the mechanisms linking obesity to increased risk of cardiovascular disease (CVD).


Diversity analysis of starch physicochemical properties in 95 proso millet (Panicum miliaceum L.) accessions.
In this study, 95 accessions of proso millet (Panicum miliaceum L.) were characterized for starch physicochemical properties, including apparent amylose content (AAC), gel textural properties, Rapid Visco Analyzer (RVA) pasting viscosity properties, thermal and retrogradation properties. Based on genotypic data, the genetic diversity and inter-relationship of these starch traits were analyzed. Diverse starch quality was found, for example, AAC ranged from 0 to 32.3%, gelatinization temperature (GT) varied from 71.5 to 79.0 ℃, and RVA profile showed distinct patterns among proso millet of different AAC types. Interestingly, high AAC proso millet usually had GT lower than that of low AAC proso millet, which is different from the findings in rice starch. Many starch traits were significantly correlated and most of the 18 tested traits could be classified as either AAC-related traits or GT-related traits. In summary, the information presented here will be useful for further development of proso millet products.


A paper/polymer hybrid CD-like microfluidic SpinChip integrated with DNA-functionalized graphene oxide nanosensors for multiplex qLAMP detection.
A paper/poly(methyl methacrylate) (PMMA) hybrid CD-like microfluidic SpinChip integrated with DNA probe-functionalized graphene oxide (GO) nanosensors was developed for multiplex quantitative LAMP detection (mqLAMP). This approach can simply and effectively address a major challenging problem of multiplexing in current LAMP methods.


Delayed cyst formation after radiosurgery for cerebral arteriovenous malformation: two case reports.
Two patients who underwent gamma knife radiosurgery for ruptured cerebral arteriovenous malformations (AVM) developed cystic lesions at 78 and 111 months after undergoing treatment. Both patients presented initially with intracerebral hemorrhage. In one patient, the cystic lesion was discovered during routine follow-up imaging and clinical examination revealed homonymous hemianopsia; the second patient presented with seizure and the lesion was identified more than 9 years after radiosurgery. One patient underwent resection of the nidus and histologic analysis of the resected specimen showed vessels in various stages of obliteration. The present paper discusses the possible mechanism for the delayed development of cystic lesions, and the possibility that radiation-induced vascular changes may continue in a nidus even when angiography shows complete obliteration of the nidus.


Prostaglandin I2 and the constricted maternal ovine placenta: effects of local infusion and placental age.
We have tested the hypotheses that systemic responses to the infusion of prostaglandin I2 may have masked the ability of this substance to dilate the maternal placenta and that the inability of prostaglandin I2 to dilate the maternal near-term placenta may be a function of placental age. Regional blood flows were measured with radioactive microspheres. In 8 near-term sheep the control flows were measured and angiotensin II (AII) infusion was begun at 5 micrograms/min and continued for the duration of the experiments. At t = 15 min, regional blood flows were again measured. Prostaglandin I2 was then infused via a retrograde uterine arterial catheter at 10 micrograms/min. At t = 30 min, the flows were again measured. At this time the infusion of prostaglandin I2 was stopped and at t = 45 min the blood flows were measured for the last time. AII increased the resistance of all tissues examined. The blood pressure increased with AII and did not change thereafter. The non-placental uterine tissue served by the retrograde catheter dilated with prostaglandin I2. The placental tissue had an initial resistance of 59 +/- 6 mmHg.ml-1.min.g which increased to 98 +/- 22 mmHg.ml-1.min.g with the infusion of AII (P less than 0.05). This resistance remained constant at 82 +/- 19 mmHg.ml-1.min.g with the administration of prostaglandin I2 and did not change after prostaglandin I2 was removed. The local application of prostaglandin I2 in the presence of AII induced vasoconstriction caused vasodilatation in the nonplacental vessels but could not change the AII induced constriction in the placental vasculature.(ABSTRACT TRUNCATED AT 250 WORDS)


Integrated multi-cohorts for characterizing the immunogenomic landscape and predicting drug response in triple-negative breast cancer.
Triple-negative breast cancer (TNBC) is the breast cancer subtype with the highest fatality rate, and it seriously threatens women's health. Recent studies found that the level of immune cell infiltration in TNBC was associated with tumor progression and prognosis. However, due to practical constraints, most of these TNBC immune infiltration studies only used a small number of patient samples and a few immune cell types. Therefore, it is necessary to integrate more TNBC patient samples and immune cell types to comprehensively study immune infiltration in TNBC to contribute to the prognosis and treatment of patients. In this study, 12 TNBC datasets were integrated and an extensive collection of 182 gene sets with immune-related signatures were included to comprehensively investigate tumor immune microenvironment of TNBC. A single sample gene set enrichment analysis was performed to calculate the infiltration score of each immune-related signature in each patient, and an immune-related risk scoring model for TNBC was constructed to accurately assess patient prognosis. Significant differences were found in immunogenomic landscape between different immune risk subtypes. In addition, the immunotherapy response and chemotherapy drug sensitivity of patients with different immune risk subtypes were also analyzed. The results showed that there were significant differences in these characteristics. Finally, a prediction model for immune risk subtypes of TNBC patients was constructed to accurately predict patients with unknown subtypes. Based on the aforementioned findings, we believed that the immune-related risk score constructed in this study can assist in providing personalized medicine to TNBC patients.


Climate change, air pollution, and allergic respiratory diseases: a call to action for health professionals.
Rising emissions of greenhouse gases in the atmosphere have warmed the planet substantially and are also accompanied by poor air quality. The increased prevalence of allergic airway disease worldwide can be partially attributed to those global environmental changes. Climate change and air pollution pose adverse impacts on respiratory allergies, and that the mechanisms are complex and interactive. Adverse weather conditions, such as extreme temperatures, can act directly on the respiratory tract to induce allergic respiratory illnesses. Thunderstorms and floods can alter the production and distribution of aeroallergens while wildfires and dust storms increase air pollution, and therefore indirectly enhance health risks. Concentrations of particulate matter and ozone in the air have been projected to increase with climate warming and air stagnation, and the rising temperatures and CO2 increase pollen, molds, and spores, which escalate the risk of allergic respiratory diseases. The synergistic effects of extreme heat and aeroallergens intensify the toxic effect of air pollutants, which in turn augment the allergenicity of aeroallergens. With the Earth's climate change, migration of humans and plants shift the living environments and allergens of susceptible people. Urban residents are exposed to multiple factors while children are sensitive to environmental exposure. Since climate change may pose many unexpected and persistent effects on allergic respiratory diseases, health professionals should advocate for effective mitigation and adaptation strategies to minimize its respiratory health effects.


Caution for simple sequence repeat number variation in the mitochondrial DNA D-loop to determine cancer-specific variants.
The mitochondrial DNA (mtDNA) displacement loop (D-loop) is often altered in various cancer types, including with regard to simple sequence repeat number variation (SSRNV), which includes the C-tract and CA-tract. However, because of mitochondrial heteroplasmy and slippage errors by the Taq DNA polymerase used in polymerase chain reaction (PCR) analysis, it is difficult to precisely evaluate mtDNA D-loop SSRNV experimentally. In this study, to precisely determine cancer-specific variants in mtDNA SSRNV, various microscopic portions of cancerous tissues and normal control tissues were obtained from a patient with breast cancer, followed by laser-capture microdissection of formalin-fixed paraffin-embedded specimens. Regions containing (CA)7 repeats (positions 514-523) and (C)8 repeats (positions 303-315) of the mitochondria DNA D-loop were amplified and sequenced. Variant signals of mtDNA SSRs of (CA)7 and (C)8 were observed in normal and cancerous tissues, with the content of minor alleles (CA)6 and (C)7/(C)9 differing among samples. These results were confirmed by PCR using various primers and proofreading DNA polymerases. PCR of genomic SSRs of (CA)7 in the NAALD2 gene and (C)8 in the BMP6 gene showed a simple repeat in all samples that was different from the observed mtDNA SSRNV. The present study suggests a reliable procedure for determining cancer-specific variants in mtDNA SSRNV: Using a proofreading DNA polymerase for PCR, the background of slippage by PCR is determined by PCR of the same genomic sequence as the target. Due to the varied heteroplasmy level of mtDNA SSRNV among normal tissues, the second background of polymorphic variations should be determined by several normal tissue DNA as PCR templates. Finally, the cancer-specific variant, including its variation frequency, is determined by subtracting the two background signals from the variant signals in cancer. However, care must be taken, as normal heteroplasmy drifts observed in mtDNA SSRNV may complicate such estimations.


Tracheal Diverticula.
Extraluminal paratracheal air bubbles are occasionally seen on computed tomography (CT) studies that include the thoracic inlet (ie, CT of the neck, of the cervical spine, and of the chest). In most cases, these paratracheal air bubbles are tracheal diverticula (TD), sometimes also referred to as tracheal pouch, tracheocele, and tracheogenic cyst. TD are most commonly seen at the right posterolateral aspect of the upper trachea at the level T1-T3. Because of their typical location and appearance, they are easily recognized and should not be confused with pneumomediastinum or other causes of air bubbles in the same region. This article describes the prevalence, possible pathophysiology, and associated complications of TD and illustrates the spectrum of their appearance on CT.


Abnormal p-wave delays in the geysers--clear lake geothermal area, california.
Large teleseismic delays, exceeding 1 second, are found near Mount Hannah in the Clear Lake volcanic field and in the steam-production area at The Geysers. The delays are superimposed on a general delay field of about 0.5 second extending over the volcanic rocks and the steam reservoir. It is postulated that a magma chamber under the surface volcanic rocks with a core of severely molten rock beneath Mount Hannah and a highly fractured steam reservoir probably underlain by partially molten rock at The Geysers are responsible for the observed delays. Both zones extend to depths of 20 kilometers or more.


Changes in population dynamics during long-term evolution of sabin type 1 poliovirus in an immunodeficient patient.
The evolution of the Sabin strain of type 1 poliovirus in a hypogammaglobulinemia patient for a period of 649 days is described. Twelve poliovirus isolates from sequential stool samples encompassing days 21 to 649 after vaccination with Sabin 1 were characterized in terms of their antigenic properties, virulence in transgenic mice, sensitivity for growth at high temperatures, and differences in nucleotide sequence from the Sabin 1 strain. Poliovirus isolates from the immunodeficient patient evolved gradually toward non-temperature-sensitive and neurovirulent phenotypes, accumulating mutations at key nucleotide positions that correlated with the observed reversion to biological properties typical of wild polioviruses. Analysis of plaque-purified viruses from stool samples revealed complex genetic and evolutionary relationships between the poliovirus strains. The generation of various coevolving genetic lineages incorporating different mutations was observed at early stages of virus excretion. The main driving force for genetic diversity appeared to be the selection of mutations at attenuation sites, particularly in the 5' noncoding region and the VP1 BC loop. Recombination between virus strains from the two main lineages was observed between days 63 and 88. Genetic heterogeneity among plaque-purified viruses at each time point seemed to decrease with time, and only viruses belonging to a unique genotypic lineage were seen from day 105 after vaccination. The relevance of vaccine-derived poliovirus strains for disease surveillance and future polio immunization policies is discussed in the context of the Global Polio Eradication Initiative.


Cholesterol emboli after cardiac catheterization. Eight cases and a review of the literature.
Cholesterol embolization is a puzzling event that may be increasingly iatrogenic in origin. Diagnosis is difficult and requires a high index of suspicion, an appropriate clinical picture, and usually, confirmation by biopsy. Certain laboratory abnormalities may be helpful; the elevated sedimentation rate and relative eosinophilia found in our patients concurs with other cases reported in the literature. Prognosis is related to the extent of systemic involvement, but renal disease is particularly threatening and gangrene and infection can be lethal. Multiple therapeutic regimens have been generally unsuccessful in altering the course of the disease process. The most significant impact on the disease can be made by its prevention. Cholesterol emboli occur spontaneously, but also after invasive aortic procedures such as diagnostic angiography or cardiovascular surgery. In addition, cardiac catheterization and percutaneous transluminal coronary angioplasty have the potential for arterial trauma and consequent cholesterol embolization. Although the apparent increasing numbers of cholesterol emboli may be a reflection of the increased use of arterial invasive procedures, they are being performed on an older, more severely ill population, with other risk factors for the development of embolic phenomena, i.e., age, smoking history, diabetes mellitus, hypertension, and peripheral vascular disease. Our observed cases and review of the literature do not furnish information concerning the comparative incidences of embolization as related to the suggested etiologies. Careful documentation of the clinical situation preceding the event, the type of procedure, the site of arterial entry, and the duration, difficulty, and extent of the intravascular invasion (i.e., above or below the left subclavian artery) are necessary for this purpose. Such data should help to develop guidelines for patient and procedure selection in order to minimize the possibility of cholesterol embolization.


Thermal tuning of terahertz metamaterial absorber properties based on VO2.
We present a novel, structurally simple, multifunctional broadband absorber. It consists of a patterned vanadium dioxide film and a metal plate spaced by a dielectric layer. Temperature control allows flexible adjustment of the absorption intensity from 0 to 0.999. The modulation mechanism of the absorber stems from the thermogenic phase change properties of the vanadium dioxide material. The absorber achieves total reflection properties in the terahertz band when the vanadium dioxide is in the insulated state. When the vanadium dioxide is in its metallic state, the absorber achieves near-perfect absorption in the ultra-broadband range of 3.7 THz-9.7 THz. Impedance matching theory and the analysis of electric field are also used to illustrate the mechanism of operation. Compared to previous reports, our structure utilizes just a single cell structure (3 layers only), and it is easy to process and manufacture. The absorption rate and operating bandwidth of the absorber are also optimised. In addition, the absorber is not only insensitive to polarization, but also very tolerant to the angle of incidence. Such a design would have great potential in wide-ranging applications, including photochemical energy harvesting, stealth devices, thermal emitters, etc.


Modulation of repopulation processes in oral mucosa: experimental results.
Repopulation processes, i.e. the tissue regeneration responses to radiotherapy with increasing overall treatment time, are the predominant factors defining the radiation tolerance of turnover tissues, such as squamous epithelia of the skin or gastrointestinal tract. The purpose was to assess experimental approaches for the modulation, i.e. stimulation of repopulation, in normal oral mucosa. Numerous studies have been performed to identify and quantify the efficacy of repopulation processes in oral mucosa in experimental animal models, mainly mouse lip and tongue mucosa, and in some clinical studies. However, only a few investigations focused on the stimulation of these processes, aiming at a reduction in oral mucosal side-effects of radiotherapy. The present review summarizes the biological mechanisms underlying effective repopulation, and delineates experimental approaches for effective stimulation of these processes, eventually resulting in an increase in oral mucosal radiation tolerance. Repopulation in oral mucosa is a complex process dominated by a substantial reorganization of the proliferative structure, including a loss of the stem cell division asymmetry and acceleration of stem cell proliferation, as well as abortive divisions of 'sterilized' cells. Repopulation in mouse oral mucosa is more effective if the initial dose intensity (weekly dose) during the first treatment week(s) is increased. Stem cell production occurs mainly during the treatment weeks, while during treatment breaks, including weekends, differentiating (transit) cells are preferentially produced. Stimulation of superficial cell loss, e.g. by topical administration of mild astringent agents, stimulates mucosal proliferation. This translates into increased radiation tolerance to fractionated irradiation in experimental systems, like mouse tongue mucosa. In clinical studies, a reduction of oral mucosal reactions using the same approach was found during an accelerated radiotherapy regimen, but not during conventionally fractionated protocols. Keratinocyte growth factor has been demonstrated to reduce oral mucosal reactions significantly to single dose and fractionated irradiation. This effect is presumably based on an interaction with repopulation processes. Repopulation in oral mucosa is a highly complex process, which includes a substantial reorganization of the proliferative structure. In experimental models, its efficacy can be modulated by changes in the fractionation protocol, but more effectively by intervention in the regulation processes, e.g. by stimulation of proliferation through enhancement of cell loss. An alternative promising approach is the administration of growth factors, like keratinocyte growth factor, for effective modulation of oral mucosal repopulation. However, selectivity for the normal tissue, as well as biological mechanisms, must be studied in detail in relevant animal models.


Hypoxic conditioning and the central nervous system: A new therapeutic opportunity for brain and spinal cord injuries?
Central nervous system diseases are among the most disabling in the world. Neuroprotection and brain recovery from either acute or chronic neurodegeneration still represent a challenge in neurology and neurorehabilitation as pharmacology treatments are often insufficiently effective. Conditioning the central nervous system has been proposed as a potential non-pharmacological neuro-therapeutic. Conditioning refers to a procedure by which a potentially deleterious stimulus is applied near to but below the threshold of damage to the organism to increase resistance to the same or even different noxious stimuli given above the threshold of damage. Hypoxic conditioning has been investigated in several cellular and preclinical models and is now recognized as inducing endogenous mechanisms of neuroprotection. Ischemic, traumatic, or chronic neurodegenerative diseases can benefit from hypoxic conditioning strategies aiming at preventing the deleterious consequences or reducing the severity of the pathological condition (preconditioning) or aiming at inducing neuroplasticity and recovery (postconditioning) following central nervous system injury. Hypoxic conditioning can consist in single (sustained) or cyclical (intermittent, interspersed by short period of normoxia) hypoxia stimuli which duration range from few minutes to several hours and that can be repeated over several days or weeks. This mini-review addresses the existing evidence regarding the use of hypoxic conditioning as a potential innovating neuro-therapeutic modality to induce neuroprotection, neuroplasticity and brain recovery. This mini-review also emphasizes issues which remain to be clarified and future researches to be performed in the field. Impact statement Neuroprotection and brain recovery from either acute or chronic neurodegeneration still represent a challenge in neurology and neurorehabilitation. Hypoxic conditioning may represent a harmless and efficient non-pharmacological new therapeutic modality in the field of neuroprotection and neuroplasticity, as supported by many preclinical data. Animal studies provide clear evidence for neuroprotection and neuroplasticity induced by hypoxic conditioning in several models of neurological disorders. These studies show improved functional outcomes when hypoxic conditioning is applied and provides important information to translate this intervention to clinical practice. Some studies in humans provide encouraging data regarding the tolerance and therapeutic effects of hypoxic conditioning strategies. The main issues to address in future research include the definition of the appropriate hypoxic dose and pattern of exposure, the determination of relevant physiological biomarkers to assess the effects of the treatment and the evaluation of combined strategies involving hypoxic conditioning and other pharmacological or non-pharmacological treatments.


Intracranial venous thrombosis in the parturient.
Intracranial venous thrombosis is a rare but potentially fatal complication of pregnancy and the postpartum period. The presenting symptoms can mimic those of a postdural puncture headache and are easily misdiagnosed, especially in a parturient who has undergone regional anesthesia. The incidence of 10-20 per 100,000 is likely higher than reported. The etiology, clinical presentation and course, risk factors, management, and relation of intracranial venous thrombosis to pregnancy are presented. Published case reports and series of intracranial venous thrombosis that have either occurred during the puerperium or involved women of childbearing age after dural puncture are summarized. Finally, the diagnosis and management of intracranial venous thrombosis in parturients, focusing on parturients who have undergone regional anesthesia, is discussed. When intracranial venous thrombosis occurs in a parturient after regional anesthesia, it is often treated as a post-dural puncture headache.


Antiepileptic drug combinations not involving valproate and the risk of fetal malformations.
To investigate the relationship between antiepileptic drug (AED) polytherapy in pregnant women and the risk of fetal malformations as prescribing practice changed, with valproate being used less often and at lower doses. Specifically, the risks associated with two of the most common AEDs included in polytherapy over recent years, levetiracetam and topiramate, were examined. An observational cohort study in which malformation rates were analyzed in 1,461 pregnancies exposed to AED monotherapy, and in 484 exposed to antiepileptic drug combinations, from the Australian Register of Antiepileptic Drugs in Pregnancy over a 15-year period (1999-2014). Fetal malformation rates had fallen over time in monotherapy pregnancies, but increased in polytherapy pregnancies, despite decreasing use and lower dosages of valproate. The rise in polytherapy malformation rates began around 2005 when levetiracetam and topiramate use began to increase. Excluding pregnancies involving valproate exposure, malformation rates were higher in the remaining polytherapy pregnancies as compared with the monotherapy ones (6.90% vs. 3.64%; odds ratio [OR] 1.96, 95% confidence interval [CI] 1.14-3.39). Malformation rates were similar in polytherapy pregnancies whether or not levetiracetam was included (7.14% vs. 8.38%), but were higher in polytherapy pregnancies involving topiramate (14.94% vs. 6.55%: OR 2.507, 95% CI 1.23-5.10). Logistic regression showed that topiramate in polytherapy had a positive dose relationship with teratogenicity risk (p = 0.025). The malformation risk associated with AED polytherapy depends on the specific drugs involved. Topiramate, when used as part of AED polytherapy that did not include valproate, was associated with a dose-related increased risk of fetal malformations.


The impact of pedigree structure on heritability estimates for pulse pressure in three studies.
Pulse pressure (PP) is a measure of large artery stiffness and has been shown to be an important predictor of cardiovascular morbidity and mortality. The aims of the present study were to investigate the heritability of PP in three studies, the Diabetes Heart Study (DHS), the Insulin Resistance Atherosclerosis Family Study (IRAS FS), and the NHLBI Family Heart Study (FHS), to estimate the residual heritability after inclusion of a common set of covariates, and to investigate the impact of pedigree structure on estimating heritability. DHS is primarily a sibling pair nuclear family study design, while both IRAS FS and FHS have large pedigrees. Heritability estimates of log-transformed PP were obtained using variance component models. After adjusting for age, gender, ethnicity/center, height, diabetes status, and mean arterial pressure (MAP), heritability estimates of PP were 0.40 +/- 0.08 , 0.22 +/- 0.05, and 0.19 +/- 0.03 in DHS, IRAS FS, and FHS, respectively. The heritability estimate from DHS was significantly different from both IRAS FS and FHS (both p values <0.05). A random re-sampling technique (modified bootstrap) was used to explore the heritability in the IRAS FS and FHS data when these pedigrees were trimmed to mimic the DHS pedigree structure. The re-sampling method (mimicking a sibling pair nuclear family design in all studies) yielded PP heritability estimates of 0.37, 0.34, and 0.27 in DHS, IRAS FS, and FHS, respectively. There was no significant difference among the heritability estimates from the three studies based on the re-sampling method. We have shown that PP has a moderately heritable component in three different studies. These data illustrate the influence of pedigree structure can have on estimating heritability. Thoughtful comparisons of heritability estimates must consider study design factors such as pedigree structure.


Northern range expansion of the Asian tiger mosquito (Aedes albopictus): Analysis of mosquito data from Connecticut, USA.
The Asian tiger mosquito (Aedes albopictus) is an invasive species and important arbovirus vector that was introduced into the U.S. in the 1980's where it continues to expand its range. Winter temperature is an important constraint to its northward expansion, with potential range limits located between the 0° and -5°C mean cold month isotherm. Connecticut is located within this climatic zone and therefore, Ae. albopictus was monitored statewide to assess its northern range expansion and to delineate where populations can stably persist. Ae. albopictus females were monitored at fixed trapping sites throughout Connecticut from June-October over a 20-year period, 1997-2016. In addition, Ae. albopictus larvae and pupae were collected from tire habitats and tires were retrieved from the field in the spring and flooded to evaluate overwintering success of hatching larvae. Ae. albopictus was first detected during statewide surveillance when a single adult female was collected in 2006. This species was not collected again until 2010 and was subsequently detected each successive year with increasing abundance and distribution except following the unusually cold winters of 2014 and 2015. Ae. albopictus mosquitoes were most abundant in urban and suburban locations along the southwestern shoreline of Connecticut; however, single specimens were occasionally detected in central parts of the state. Field-collected females were also screened for arbovirus infection yielding two isolations of Cache Valley virus and one isolation of West Nile virus, highlighting the threat posed by this mosquito. Ae. albopictus overwintered in Connecticut under mild winter conditions as shown by recovery of hatched larvae from field collected tires in spring and by early season detection of larvae and pupae. This study documents the establishment and expansion of Ae. albopictus at the northern boundary of its range in the northeastern U.S. and provides a baseline for monitoring the future spread of this species anticipated under climate change.


Sox9 inhibits Wnt signaling by promoting beta-catenin phosphorylation in the nucleus.
Chondrocyte fate determination and maintenance requires Sox9, an intrinsic transcription factor, but is inhibited by Wnt/beta-catenin signaling activated by extrinsic Wnt ligands. Here we explored the underlying molecular mechanism by which Sox9 antagonizes the Wnt/beta-catenin signaling in chondrocyte differentiation. We found that Sox9 employed two distinct mechanisms to inhibit Wnt/beta-catenin signaling: the Sox9 N terminus is necessary and sufficient to promote beta-catenin degradation, whereas the C terminus is required to inhibit beta-catenin transcriptional activity without affecting its stability. Sox9 binds to beta-catenin and components of the beta-catenin "destruction complex," glycogen synthase kinase 3 and beta-transducin repeat containing protein, to promote their nuclear localization. Independent of its DNA binding ability, nuclear localization of Sox9 is both necessary and sufficient to enhance beta-catenin phosphorylation and its subsequent degradation. Thus, one mechanism whereby Sox9 regulates chondrogenesis is to promote efficient beta-catenin phosphorylation in the nucleus. This mechanism may be broadly employed by other intrinsic cell fate determining transcription factors to promptly turn off extrinsic inhibitory Wnt signaling mediated by beta-catenin.


Tackling surgical infection prevention takes teamwork.
Even though infection control practices have improved dramatically in the United States, surgical infections still are a problem for many hospitals, ranking as the second most common cause of nosocomial infections. But hospitals are finding ways to fight back by implementing best practices, redesigning systems, and using hospital-wide teams--which include administrators, surgeons, nurses, anesthesiologists, pharmacists, and environmental services staff--that cut across many departments.


Translational Research in the Nonhuman Primate Model of Tuberculosis.
Infection with Mycobacterium tuberculosis predominantly establishes subclinical latent infection over the lifetime of an individual, with a fraction of infected individuals rapidly progressing to active disease. The immune control in latent infection can be perturbed by comorbidities such as diabetes mellitus, obesity, smoking, and coinfection with helminthes or HIV. Modeling the varying aspects of natural infection remains incomplete when using zebrafish and mice. However, the nonhuman primate model of tuberculosis offers a unique and accurate model to investigate host responses to infection, test novel therapeutics, and thoroughly assess preclinical vaccine candidates. Rhesus macaques and cynomolgus macaques manifest the full gamut of clinical and pathological findings in human Mycobacterium tuberculosis infection, including the ability to co-infect macaques with Simian Immunodeficiency Virus to model HIV co-infection. Here we discuss advanced techniques to assay various clinical outcomes of the natural progression of infection as well as therapeutics in development and novel preclinical vaccines. Finally, we survey the translational aspects of nonhuman primate research and argue the urgent need to thoroughly examine preclinical therapeutics and vaccines using this model prior to clinical implementation.


Microscopic and Molecular Detection of Camel Piroplasmosis in Gadarif State, Sudan.
The socioeconomic importance of camels (Camelus dromedarius) could not be neglected in the Sudan. The present study was planned to confirm the presence of piroplasmosis in camels from the Eastern region of the Sudan (Gedarif State) using microscopical (blood film) and molecular technique (PCR). A total of 55 camels of different sexes (34 females and 21 males) were sampled from four localities of the state between January 2011 and January 2012. The prevalence rates using parasitological and molecular examinations were 43.6% and 74.5%, respectively. The prevalence rates significantly vary between the localities (p = 0.011) but not between the different sexes (p = 0.515). PCR technique showed higher sensitivity than microscopy. The present paper was to be the first report investigating camel piroplasmosis using both parasitological and molecular methods in the Eastern region of the Sudan. Further studies in the phylogenetic sequencing are to be continued for parasite speciation. Moreover, studies on the clinical and economic consequences of camel piroplasmosis are recommended.


Belatacept As an Alternative to Calcineurin Inhibitors in Patients with Solid Organ Transplants.
The goal of immunosuppression in transplantation has shifted to improving long-term outcomes, reducing drug-induced toxicities while preserving the already excellent short-term outcomes. Long-term gains in solid organ transplantation have been limited at least partly due to the nephrotoxicity and metabolic side effects of calcineurin inhibitors (CNIs). The alloimmune response requires activation of the costimulatory pathway for T cell proliferation and amplification. Belatacept is a molecule that selectively blocks T cell costimulation. In June 2011, the U.S. Food and Drug Administration approved it for maintenance immunosuppression in kidney transplantation based on two open-label, randomized, phase III trials. Since its introduction, belatacept has shown promise in both short- and long-term renal transplant outcomes in several other trials. It exhibits a superior side effect profile compared to CNIs with a comparable efficacy. Across all solid organ transplants, the burden of chronic kidney disease, its associated cardiovascular morbidity, mortality, and inferior patient/allograft survival is a well-documented problem. In this review, we aim to discuss the evidence behind the use of belatacept in solid organ transplants as an effective alternative to CNIs for renal rescue in patients with acute and/or chronic kidney injury.


Tyrosinase modulation by five Rwandese herbal medicines traditionally used for skin treatment.
Traditional herbal medicines provide an interesting, largely unexplored source for the development of potential new drugs and skin-care cosmetics. Some herbal extracts are known to be inhibitors of melanin formation, sometimes more potent than the classical inhibitors, hydroquinone/arbutin or kojic acid, and are not associated with melanocytes cytotoxicity or mutagenicity. Such plants are used in traditional medicine in many countries, particularly in Africa, for skin lightening. To evaluate in vitro the ability of Rwandese medicinal plants, traditionally used for the treatment of skin (discoloration and attenuation of discolored spots), to modulate pigmentation and tyrosinase activity. Based on an ethnopharmacological survey, five herbs [Brillantaisia cicatricosa Lindau (Acanthaceae), Chenopodium ugandae (Aellen) Aellen (Chenopodiaceae), Dolichopentas longiflora Oliv. (Rubiaceae), Protea madiensis Oliv. (Proteaceae) and Sesamum angolense Welw. (Pedaliaceae)] were selected. Twenty-seven extracts, obtained by treating the herbs with increasing polarities solvents, were investigated for their effects on cell viability (MTT test) and on pigmentation: inhibition of the enzyme tyrosinase (colorimetry of reaction products, measurement of enzyme activity, TLC-autography; studies on crude cellular extracts obtained from normal melanocytes and on a mushroom tyrosinase) and measurement of melanogenesis by human melanoma cells. None of the tested plant extracts were cytotoxic on tested human melanoma cell lines, except for Dolichopentas longiflora (IC50 of leaves n-hexane extract, 4μg/ml for MM028 and 4.5μg/ml for MM001; IC50 of roots ethyl acetate extract, 0.8μg/ml for MM028 and 3.9μg/ml for MM001). Almost all extracts inhibited melanogenesis in a melanoma whole cells overall pigmentation assay, a model reflecting the entire cycle of melanogenesis. All the Protea madiensis extracts quite strongly inhibited melanogenesis and, surprisingly, one of the Dolichopentas longiflora leaves extracts was found to increase melanogenesis. These results were confirmed by the modulation of pigmentation reactions by crude cellular extracts obtained from normal melanocytes; interestingly, one of the extracts (Dolichopentas longiflora ethyl acetate extract) is even more active (61% at 500μg/ml) than kojic acid (<3% at 142μg/ml and 68% at 1421μg/ml). In a mushroom tyrosinase inhibition assay, data obtained on some extracts fairly agree with pigmentation inhibition measured on melanocytes proteins as, for example, the methanol extract of Protea madiensis. While a few others extract display discording data, this probably reflects either differences between human and mushroom tyrosinase, interference with melanocytes enzymes at later steps than tyrosinase or the simultaneous presence of compounds with conflicting activities in a given extract. Ethnopharmacological data represent an efficient approach to discover active herbs. Some of the selected medicinal plants clearly show potent tyrosinase inhibitions while one extract significantly increases cell pigmentation; one extract contains potent growth melanocytes inhibitors.


Master slave en-face OCT/SLO.
Master Slave optical coherence tomography (MS-OCT) is an OCT method that does not require resampling of data and can be used to deliver en-face images from several depths simultaneously. As the MS-OCT method requires important computational resources, the number of multiple depth en-face images that can be produced in real-time is limited. Here, we demonstrate progress in taking advantage of the parallel processing feature of the MS-OCT technology. Harnessing the capabilities of graphics processing units (GPU)s, information from 384 depth positions is acquired in one raster with real time display of up to 40 en-face OCT images. These exhibit comparable resolution and sensitivity to the images produced using the conventional Fourier domain based method. The GPU facilitates versatile real time selection of parameters, such as the depth positions of the 40 images out of the set of 384 depth locations, as well as their axial resolution. In each updated displayed frame, in parallel with the 40 en-face OCT images, a scanning laser ophthalmoscopy (SLO) lookalike image is presented together with two B-scan OCT images oriented along rectangular directions. The thickness of the SLO lookalike image is dynamically determined by the choice of number of en-face OCT images displayed in the frame and the choice of differential axial distance between them.


Changes in structural characteristics and metal speciation for biochar exposure in typic udic ferrisols.
Recent studies on biochars confirmed their potential benefits in improving soil fertility and sequestrating contaminants. However, little information on the changes in structural characteristics and metal speciation of biochars after exposure to soils is currently available. The aim of this study was to use double experimental bags to study the transformation of ozonized biochars derived from poultry manure and drying sludge (denoted PB and SB, respectively) in typic udic ferrisols. The carbon and sulfur functional groups and chemical characteristics of the biochars were determined using spectroscopic techniques, such as Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy, and near-edge X-ray absorption fine structure spectroscopy spectroscopy, combined with chemical extractions. Metal species were characterized using Cu K-edge X-ray absorption near-edge structure and chemical sequential fractionation schemes. The results showed that the potential changes in structural characteristics and metal species of biochars in soil were highly dependent on the composition of the biochars. PB comprised highly aromatic and chemically stable C, whereas SB contained a substantial amount of easily degradable C. Oxygen-containing groups slightly increased after incubation in the soil with either 60% water holding capacity (WHC) or flooding for 3 months. Sulfur in the biochars was predominantly inorganic S. Minerals such as K, Na, Mg, and S were mobilized from the biochars, accounting for 5-55% depending on the properties and sources of the element. Both PB and SB contained high concentrations of Cu and Zn. CuO in PB dissolved within 3 months, whereas CuS in both PB and SB was partly oxidized in the soil with 60% WHC for 9 months and adsorbed to the organic phase. Zn had relatively high mobility in both biochars, resulting in its vertical migration into soils.


[Reflections on Occupational Health Nursing in Taiwan: Challenges and Perspectives].
The development of the occupational health nursing profession has promoted stable and healthy human resources in Taiwan. In order to improve the occupational safety, health, and healthcare of workers, the professional core competencies and role functions of occupational health nursing is of utmost importance. This article investigated the current status of occupational health nursing education, role functions, practice scope, and the development and responsibilities of professional associations and proposed the challenges to and the future prospects of the development of occupational health nursing in Taiwan. The key findings include: (1) the role functions and practice scope of occupational health nursing; (2) occupational health nursing courses should be included in the required credits of Department of Nursing and master and doctor programs in occupational health nursing should be established; (3) a certification system of occupational health nursing should be established as soon as possible; (4) the professional associations for occupational health nursing should take responsibility for continuing education and training; and (5) interdisciplinary collaborations among relevant occupational health professionals should be strengthened.


Identifying miRNA-mRNA Pairs and Novel miRNAs from Hepatocelluar Carcinoma miRNomes and TCGA Database.
Increasing evidence shows microRNAs (miRNAs) are engaged in hepatocelluar carcinoma (HCC). To identify novel feasible miRNA/mRNA pairs involved in hepatocarcinogenesis, an in-depth analysis of miRNomes in human non-tumor liver and HCC samples was carried out in this study. Firstly, differentially expressed miRNAs were obtained from deep sequencing of 15 liver samples, and verified in an independent data from The Cancer Genome Atlas (TCGA) database. Then, differentially expressed mRNA targets were selected from TCGA, and the differential miRNA/mRNA pairs with negative correlations were screened out. Finally, functional enrichment analysis was used to predict the functions of miRNA/mRNA pairs in HCC. In our study, 81 miRNA/mRNA pairs and 7 novel miRNAs were found. We constructed a hub interaction model with 9 miRNA/mRNA pairs to further investigate molecular mechanism of HCC. Survival analysis identified nine genes (hsa-miR-137, hsa-miR-490, BIRC5, TOP2A, CDC25C, IGF2BP1, IQGAP3, NCAPG and VIPR1) with significant influence on prognosis of HCC patients. In conclusion, the miRNA/mRNA pairs identified in our study may have some potential values to be further studied in progression, diagnosis and prognosis of HCC.


Root caries and some related factors in 88-year-old carriers and non-carriers of Streptococcus sobrinus in saliva.
The prevalence of caries on exposed root surfaces in 88-year-old subjects with and without salivary levels of Streptococcus sobrinus was studied. Ninety-two individuals were examined with regard to root caries lesions and fillings. The root caries index (RCI) was calculated and related to salivary flow rate and buffer capacity, plaque score and salivary counts of Streptococcus mutans, S. sobrinus and lactobacilli. In 89 subjects with exposed root surfaces, all but 2 harbored mutans streptococci; 51 subjects carried S. mutans only, 35 both S. sobrinus and S. mutans, and 1 S. sobrinus only. The RCI was significantly higher in persons with than those without S. sobrinus (p < 0.05). Subjects with both S. sobrinus and S. mutans had higher counts of total mutans streptococci and lactobacilli than subjects with only S. mutans (p < 0.05). The RCI was significantly correlated to S. sobrinus and S. mutans (p < 0.05). The positive correlation between the RCI and S. sobrinus was still significant when the other tested variables were kept constant, whereas the correlation between the RCI and S. mutans was weaker when S. sobrinus and lactobacilli were kept constant. The D-component of the RCI (DSr%) was significantly correlated to S. sobrinus, S. mutans and lactobacilli, whereas the F-component of the RCI showed no significant correlation to any of the tested variables. A stepwise multiple correlation showed that the variance of DSr% was best explained in the S. sobrinus carriers by S. sobrinus and the salivary buffer effect, and in the non-carriers by S. mutans.


The 50-kDa glucose 6-phosphate-sensitive hexokinase of Schistosoma mansoni.
Hexokinase has been purified from adult Schistosoma mansoni worms and the activity shown to be associated with a single protein species having an M(r) about 50,000. This protein is recognized on Western blots probed with antisera against rat Type I hexokinase or against a recombinant S. mansoni hexokinase that had been expressed in Escherichia coli using a previously cloned cDNA. An 18-residue N-terminal sequence determined for the purified S. mansoni hexokinase is identical to that deduced from the nucleotide sequence of the cDNA, consistent with the view that the cloned cDNA encodes the hexokinase characterized in the present study. The S. mansoni enzyme has a relatively low Km (approximately 60 microM) for glucose and is sensitive to inhibition (competitive versus ATP, Ki approximately 50 microM) by its product, glucose 6-phosphate (Glc-6-P). With these kinetic properties and 50 kDa molecular mass, S. mansoni hexokinase resembles the ancestral hexokinase predicted to have given rise, by gene duplication and fusion, to the present day 100-kDa Glc-6-P-sensitive mammalian hexokinases. The schistosomal hexokinase represents the first 50-kDa Glc-6-P-sensitive hexokinase whose sequence has been obtained. The schistosomal hexokinase does not bind to mitochondria, consistent with its lack of a hydrophobic segment at the N terminus which is required for binding of the mammalian Type I and II isoenzymes to mitochondria. The marked Crabtree effect exhibited by S. mansoni cercariae may be at least partly attributed to the expression of rather high levels of a hexokinase having a high affinity for glucose but only a moderate sensitivity to product inhibition by Glc-6-P.


Buerger's disease (Thromboangiitis obliterans): a diagnostic challenge.
Buerger's disease or Thromboangiitis obliterans is a segmental inflammatory disease that affects the vessels and nerves of the extremities. It usually affects men below 45 years old and correlates with tobacco, as a predisposing factor. The authors present the case of a 34-year-old male, with ulcers in the fingertips with progressive worsening: acrocyanosis, slow healing, necrosis and finally loss of substance. Dorsalis pedis and posterior tibial pulses were not palpable. Personal history of heavy smoking was (20 pack-years). The angiography revealed proximal occlusion of the left posterior tibial and interosseal arteries, with distal circulation by the anterior tibial artery. He was submitted to disarticulation of the second left toe and therapy with pentoxifyline and iloprost infusion, calcium antagonist, antiplatelet drugs, statin and low molecular weight heparin (later replaced by oral anticoagulation). Improvement was seen of active vascular lesions and pain symptoms.


[Membranous glomerulonephritis].
Membranous nephropathy remains the most common cause of nephrotic syndrome in adults. The common variant is idiopathic membranous nephropathy with no evidence of any known precipitating factors. Membranous nephropathy also occurs as a secondary form in association with inflammatory or neoplastic diseases. Prognosis is mostly favorable as shown by the frequency of spontaneous remissions which averages 30%, although about one-third of patients progress to end-stage renal failure. Risk factors for a poor prognosis include severe proteinuria, hypertension, older age, male gender and impaired renal function. Therapy should include an ACE-Inhibitor and/or angiotensin-II receptor blocker to lower proteinuria (blood pressure < or =130/80 mmHg). The majority of patients should be observed for six months whilst receiving conservative treatment before deciding about an immunosuppressive approach. The debate over its management continues today. Steroids alone are ineffective. Evidence-based medicine supports the use of cyclosporine or the Ponticelli regimen (monthly cycling routine of chlorambucil or cyclophosphamide alternating with prednisone).


Pancreatic ductal adenocarcinomas from Mexican patients present a distinct genomic mutational pattern.
Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers in humans, with less than 5% 5-year survival rate. PDAC is characterized by a small number of recurrent mutations, including KRAS, CDKN2A, TP53, and SMAD4 and a long "tail" of infrequent mutated genes. Most of the studies have been performed in US and European populations, so new studies are needed to describe the mutational landscape of these tumors in other cohorts. The present study analyzed the exome and transcriptome of four PDAC tumors from Mexican patients. We found a paucity of the previously described recurrent mutations, with mutations in only three genes (HERC2, CNTNAP2 and HMCN1) previously reported in PDAC with a frequency > 1%. In addition, we discovered several recurrent putative copy number aberrations in SKP2, BRAF, CSSF1R, FOXE1, JAK2 and MET genes and in genes previously reported as putative drivers in PDAC, including KRAS, SF3B1, BRAF, MYC and MET. Although a larger cohort is needed to validate these findings, our results could be pointing toward potential differences in contributing factors for PDAC in Latin-American populations.


Role of autophagy in prion protein-induced neurodegenerative diseases.
Prion diseases, characterized by spongiform degeneration and the accumulation of misfolded and aggregated PrP(Sc) in the central nervous system, are one of fatal neurodegenerative and infectious disorders of humans and animals. In earlier studies, autophagy vacuoles in neurons were frequently observed in neurodegenerative diseases such as Alzheimer's, Parkinson's, and Huntington's diseases as well as prion diseases. Autophagy is a highly conserved homeostatic process by which several cytoplasmic components (proteins or organelles) are sequestered in a double-membrane-bound vesicle termed 'autophagosome' and degraded upon their fusion with lysosome. The pathway of intercellular self-digestion at basal physiological levels is indispensable for maintaining the healthy status of tissues and organs. In case of prion infection, increasing evidence indicates that autophagy has a crucial ability of eliminating pathological PrP(Sc) accumulated within neurons. In contrast, autophagy dysfunction in affected neurons may contribute to the formation of spongiform changes. In this review, we summarized recent findings about the effect of mammalian autophagy in neurodegenerative disorders, particularly in prion diseases. We also summarized the therapeutic potential of some small molecules (such as lithium, rapamycin, Sirtuin 1 and resveratrol) targets to mitigate such diseases on brain function. Furthermore, we discussed the controversial role of autophagy, whether it mediates neuronal toxicity or serves a protective function in neurodegenerative disorders.


Benefits of procyanidins on gut microbiota in Bama minipigs and implications in replacing antibiotics.
Several studies have reported the effect of absorption of procyanidins and their contribution to the small intestine. However, differences between dietary interventions of procyanidins and interventions via antibiotic feeding in pigs are rarely reported. Following 16S rRNA gene Illumina MiSeq sequencing, we observed that both procyanidin administration for 2 months (procyanidin-1 group) and continuous antibiotic feeding for 1 month followed by procyanidin for 1 month (procyanidin-2 group) increased the number of operational taxonomic units, as well as the Chao 1 and ACE indices, compared to those in pigs undergoing antibiotic administration for 2 months (antibiotic group). The genera Fibrobacter and Spirochaete were more abundant in the antibiotic group than in the procyanidin-1 and procyanidin-2 groups. Principal component analysis revealed clear separations among the three groups. Additionally, using the online Molecular Ecological Network Analyses pipeline, three co-occurrence networks were constructed; Lactobacillus was in a co-occurrence relationship with Trichococcus and Desulfovibrio and a co-exclusion relationship with Bacillus and Spharerochaeta. Furthermore, metabolic function analysis by phylogenetic investigation of communities by reconstruction of unobserved states demonstrated modulation of pathways involved in the metabolism of carbohydrates, amino acids, energy, and nucleotides. These data suggest that procyanidin influences the gut microbiota and the intestinal metabolic function to produce beneficial effects on metabolic homeostasis.


FSHB -211 G>T Polymorphism as Predictor for TESE Success in Patients With Unexplained Azoospermia.
Testicular sperm extraction (TESE) followed by assisted reproductive techniques often remains the only therapeutic option for men with azoospermia due to spermatogenic failure. Reproductive parameters, such as gonadotropin levels and testicular volume or histopathology, contribute to the prediction of sperm retrieval rate (SRR) in TESE. However, there is an eminent lack of noninvasive predictive factors for TESE outcome. To clarify the impact of three common genetic variants affecting FSH and its cognate receptor on testicular histopathology patterns and SRR in TESE. We evaluated the association of the single-nucleotide polymorphisms (SNP) FSHB -211G>T (rs10835638), FSHR -29G>A (rs1394205), and FSHR c.2039A>G (rs6166) with testicular histopathology and SRR in patients with azoospermia. Tertiary referral center for andrology. Men (n = 1075) with azoospermia who underwent TESE (grouped by clinical pathologies). All participants underwent TESE. Testicular histopathology, SRR, and reproductive hormone levels. FSHB -211G>T was significantly associated with reduced chances of sperm retrieval in patients with unexplained azoospermia. Indicating an additional mechanism, the association of the SNP with SSR could not be solely attributed to decreased FSH levels. A common genetic factor was significantly associated with SRR in TESE. In perspective, a calculator or score including the noninvasive parameters FSH level, testicular volume, and FSHB haplotype should be considered to estimate the chances for sperm retrieval in men with azoospermia.


Properties and self-assembled packing morphology of long alkyl-chained substituted polyhedral oligomeric silsesquioxanes (POSS) cages.
Polyhedral oligomeric silsesquioxane (POSS) cubic cage systems (octa-n-octadecyloctasilsesquioxane, (T8C18) and octakis(n-octadecyldimethylsiloxy)octasilsesquioxane, (Q8C18)) were synthesised with eight long n-alkyl chain (R = C18H37) substituent arms, as model nano-functionalized compounds. The crystalline packing morphology of the cages was studied using time-resolved Small- and Wide-angle X-ray scattering (SAXS/WAXS), thermal and optical techniques. From thermal analysis the melting and crystallization temperatures of the Q8 cage were significantly less than those for the T8 cage. X-ray scattering showed that both cage systems have long-range crystalline ordering where the alkyl chains align in a parallel axial disposition from the POSS core giving a 'rod-like' self-assembled packing morphology. The packing length-scale can be directly related to the overall dimensions of the POSS molecules. Compared to the T8 cages, the Q8 cages pack more efficiently allowing the interdigitation of the alkyl chain arms. Different packing modes and thermal behaviour observed for the T8 and Q8 cages is directly attributed to their structural chemistry. For the Q8 cage, the presence of the OSiMe2 spacer groups which tether the alkyl chain arms to the cage (absent in the T8 cages) allows greater flexibility of the arms letting them interdigitate with each other when packing which is not observed for the analogous T8 cages.


Pivotal Roles of Interleukin-17 as the Epicenter of Bone Loss Diseases.
Bone remodelling is a strictly regulated dynamic process between bone resorption and bone formation. Many factors are involved in the process and affect the dynamic balance. Inflammation-mediated bone loss is a major feature of various bone diseases, including periodontitis, rheumatoid arthritis (RA) and spondyloarthritis (SpA). Interleukin-17 (IL-17) plays an important role in inflammatory bone disease and could be an attractive therapeutic target. This review focuses on the osteoclastic effects of IL-17 in different cell types and summarizes the current knowledge of IL-17 signalling pathways. Typical IL-17-mediated bone destruction disorders are examined. The review also provides an overview of possible strategies for therapeutic intervention for inflammatory loss of bone targeting IL-17.


A prospective investigation of elevated lipoprotein (a) detected by electrophoresis and cardiovascular disease in women. The Framingham Heart Study.
Sinking prebeta lipoprotein is a putative marker for elevated levels of lipoprotein (a). Although prospective data suggest that increased plasma lipoprotein (a) is an independent risk factor for coronary heart disease in men, no prospective studies are available in women. From 1968 through 1975, sinking prebeta lipoprotein was determined by paper electrophoresis in 3103 women Framingham Heart Study participants who were free of prevalent cardiovascular disease. A sinking prebeta lipoprotein band was detectable in 434 of the women (14%) studied. The median follow-up interval was approximately 12 years. Incident cardiovascular disease was associated with band presence using a proportional hazards model that included age, smoking, body mass index, systolic blood pressure, glucose intolerance, low- and high-density lipoprotein cholesterol, and ECG left ventricular hypertrophy. Multivariable adjusted relative risk estimates (with 95% confidence intervals) for outcomes in the band present versus absent groups were as follows: myocardial infarction (82 events), 2.37 (1.48 to 3.81); intermittent claudication (62 events), 1.94 (1.07 to 3.50); cerebrovascular disease (83 events), 1.88 (1.12 to 3.15); total coronary heart disease (174 events), 1.61 (1.13 to 2.29); and total cardiovascular disease (305 events), 1.44 (1.09 to 1.91). A subset analysis indicated that band presence was 50.9% sensitive and 95.4% specific for detecting plasma lipoprotein (a) levels of > 30 mg/dL, the threshold value linked to increased cardiovascular disease risk in men. Sinking prebeta lipoprotein was a valid surrogate for elevated lipoprotein (a) levels in Framingham Heart Study women. Band presence and, equivalently, elevated plasma lipoprotein (a), was a strong, independent predictor of myocardial infarction, intermittent claudication, and cerebrovascular disease. Confirmation of these findings in other longitudinal studies of women is needed.


Siege of Leningrad Survivors Phenotyping and Biospecimen Collection.
Poor nutrition during the early stages of human development can lead to rare pathological conditions in adult life. The best-known and most severe historical cases of famine include the Dutch 'Hunger Winter,' the Finnish famine, the Chinese Great famine, and the siege of Leningrad. The siege of Leningrad (now Saint Petersburg) was one of the longest in history, lasting 872 days, from September 8, 1941 to January 27, 1944. There were 670,000 registered deaths of the civil population, in which 97% died due to starvation. The aim of the present study is to create a collection of biospecimens from extensively phenotyped siege of Leningrad survivors, who underwent starvation during the early periods of their lives, and from a matched control group. A total 305 siege survivors and 51 age- and sex- matched control subjects were investigated in of an observational retroprospective cohort study in 2009-2011 at a baseline visit. After 3 years of follow-up, 252 siege survivors (182 females and 70 males; mean age 74.7 ± 2.6 years) and 45 controls (32 females and 13 males; mean age 75.5 ± 2.8 years) were examined. All siege survivors were exposed to the extreme dietary restriction and stress associated with the siege in their early childhood. All participants signed informed consent and were subject to questionnaires and physical examination, as well as various laboratory and instrumental tests. Anthropometry, blood measurement, cognitive and physiological testing, and vascular damage assessment were performed. Blood specimens of the extensively phenotyped siege survivors were collected and processed (blood plasma, blood serum, and flash-frozen PBMC); serum and urine were used for laboratory tests. We believe that data obtained from this unique collection of biospecimens can elucidate the mechanisms of healthy aging and emphasize the importance of reproductive health, counseling, and monitoring among people with eating disorders.


Sequence analysis of the bovine coronavirus nucleocapsid and matrix protein genes.
The 3' end of the 20-kb genome of the Mebus strain of bovine enteric coronavirus (BCV) was copied into cDNA and cloned into the PstI site of the pUC9 vector. Four clones from the 3' end of the genome were sequenced either completely or in part to determine the sequence of the first 2451 bases. Within this sequence were identified, in order, a 3'-noncoding region of 291 bases, the gene for a 448-amino acid nucleocapsid protein (N) having a molecular weight of 49,379, and the gene for a 230-amino acid matrix protein (M) having a molecular weight of 26,376. A third large open reading frame is contained entirely within the N gene sequence but is positioned in a different reading frame; it potentially encodes a polypeptide of 207 amino acids having a molecular weight of 23,057. A higher degree of amino acid sequence homology was found between the M proteins of BCV and MHV (87%) than between the N proteins (70%). For the M proteins of BCV and MHV, notable differences were found at the amino terminus, the most probable site of O-glycosylation, where the sequence is N-Met-Ser-Ser-Val-Thr-Thr for BCV and N-Met-Ser-Ser-Thr-Thr for MHV. BCV apparently uses two of its six potential O-glycosylation sites.


An origin of transfer (oriT) on the conjugative element pRS01 from Lactococcus lactis subsp. lactis ML3.
Previous analysis of the Tra1 region of the conjugative element pRS01 from Lactococcus lactis subsp. lactis ML3 suggested that an origin of transfer (oriT) was present. Deletion derivatives of this cloned Tra1 region were assayed for mobilization in the presence of the wild-type pRS01 element in trans. The pRS01 oriT was localized to a 446-nucleotide segment in the intergenic region between open reading frames ltrD and ltrE. Sequence analysis of this region revealed a cluster of direct and inverted repeat structures characteristic of oriT regions associated with other conjugative systems.


Nanoscale Transient Magnetization Gratings Created and Probed by Femtosecond Extreme Ultraviolet Pulses.
We utilize coherent femtosecond extreme ultraviolet (EUV) pulses from a free electron laser (FEL) to generate transient periodic magnetization patterns with periods as short as 44 nm. Combining spatially periodic excitation with resonant probing at the M-edge of cobalt allows us to create and probe transient gratings of electronic and magnetic excitations in a CoGd alloy. In a demagnetized sample, we observe an electronic excitation with a rise time close to the FEL pulse duration and ∼0.5 ps decay time indicative of electron-phonon relaxation. When the sample is magnetized to saturation in an external field, we observe a magnetization grating, which appears on a subpicosecond time scale as the sample is demagnetized at the maxima of the EUV intensity and then decays on the time scale of tens of picoseconds via thermal diffusion. The described approach opens multiple avenues for studying dynamics of ultrafast magnetic phenomena on nanometer length scales.


Screening for cytotoxic chemical constituents from Justicia procumbens by HPLC-DAD-ESI-MS and NMR.
The Acanthaceae family is an important source of therapeutic drugs and ethno medicines. There are many famous medicinal plants from this family, such as Andrographis paniculata, Baphicacanthus cusia, and Dicliptera chinensis. Justicia procumbens (J. procumbens) is widely distributed in tropical and sub-tropical of the world. It has long been used in traditional Chinese medicine for cancer. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay showed the ethyl acetate extract of J. procumbens had a cytotoxic activity. Therefore, qualitative and quantitative analysis of the chemical constituents in the ethyl acetate extract was important for understanding its pharmacological mechanism. A high-performance liquid chromatography with diode array detection coupled to electrospray ionisation quadrupole time-of-flight tandem mass spectrometry procedure was established. Eleven dibenzylbutanes and four arylnaphthalenes were confirmed by HPLC-DAD-ESI-QTOF-MS analysis. A novel dibenzylbutane (5-methoxy-4,4'-di-O-methylsecolariciresinol-9'-monoacetate) and seven isomers of arylnaphthalene were isolated and characterized by NMR and QTOF-MS. Compounds 1, 2, and 13 were detected for the first time. The content of six lignans were determinated in the ethyl acetate extract. This study showed that the cytotoxic activity assay of J. procumbens could be mainly attributed to the constituents of lignans. The bioactivity of the ethyl acetate extract and determined compounds support the traditional use of this plant in cancer. These chemical constituents may be developed as novel therapeutics.


Clinical Outcomes of Permanent Left Bundle Branch Area Pacing in Patients With Left Bundle Branch Block and Left Ventricular Ejection Fraction >35 vs. ≤35.
The present study aimed to compare the effects of left bundle branch area pacing (LBBAP) on cardiac function and clinical outcomes in patients with left bundle branch block (LBBB) and left ventricular ejection fraction (LVEF) >35 vs. ≤35%. Thirty-six consecutive patients with LBBB and LVEF <50% were enrolled. All patients were followed up for a mean of 6 months. The successful LBBAP was defined as a paced QRS complex presented as right bundle branch block (RBBB) morphology and QRSd < 130 ms. Echocardiography parameters, pacing parameters and clinical outcomes were collected. The successful LBBAP was achieved in 77.8% of all cases (28/36). In LVEF > 35% group (70 ± 8 years, 9 male), the success rate was 81.0% (17/21). QRSd significantly decreased from 174 ± 23 ms to 108 ± 13 ms (P < 0.001). The pacing threshold and R-wave amplitude were 0.6 ± 0.2 V @ 0.5 ms and 12 ± 7 mV, respectively. In LVEF ≤ 35% group (69 ± 5 years, 9 male), the success rate was 73.3% (11/15) with QRSd decreasing from 188 ± 25 ms to 107 ± 11 ms (P < 0.001). The hyperresponders to LBBAP (functional recovery and LVEF ≥ 50%) in LVEF > 35% group was 52.9%, which were almost twice of that in LVEF ≤ 35% group (33.3%). Whether patients had LBBAP or left ventricular septal pacing (LVSP), patients in the LVEF > 35% group showed significantly lower incidence of heart failure hospitalizations or death from any cause (hazard ratio in LVEF > 35% group, 0.22; 95%CI, 0.06 to 0.75, P = 0.011). LBBAP can significantly shorten the QRSd and improve cardiac function in LBBB patients with either LVEF > 35 or ≤ 35%. LBBAP should be considered as an effective therapy for preventing the deterioration of cardiac function in early-stage heart failure patients with LBBB and LVEF > 35%.


Case-only analysis of treatment-covariate interactions in clinical trials.
Differential effectiveness of treatments across subgroups defined by pretreatment variables are of increasing interest, particularly in the expanding research field of pharmacogenomics. When the pretreatment variable is difficult to obtain or expensive to measure, but can be assessed at the end of the study using stored samples, nested case-control and case-cohort methods can be used to reduce costs in large efficacy trials with rare outcomes. Case-only methods are even more efficient, and reliable under a range of circumstances.


Paraoxonase-1 deficiency is associated with severe liver steatosis in mice fed a high-fat high-cholesterol diet: a metabolomic approach.
Oxidative stress is a determinant of liver steatosis and the progression to more severe forms of disease. The present study investigated the effect of paraoxonase-1 (PON1) deficiency on histological alterations and hepatic metabolism in mice fed a high-fat high-cholesterol diet. We performed nontargeted metabolomics on liver tissues from 8 male PON1-deficient mice and 8 wild-type animals fed a high-fat, high-cholesterol diet for 22 weeks. We also measured 8-oxo-20-deoxyguanosine, reduced and oxidized glutathione, malondialdehyde, 8-isoprostanes and protein carbonyl concentrations. Results indicated lipid droplets in 14.5% of the hepatocytes of wild-type mice and in 83.3% of the PON1-deficient animals (P < 0.001). The metabolomic assay included 322 biochemical compounds, 169 of which were significantly decreased and 16 increased in PON1-deficient mice. There were significant increases in lipid peroxide concentrations and oxidative stress markers. We also found decreased glycolysis and the Krebs cycle. The urea cycle was decreased, and the pyrimidine cycle had a significant increase in orotate. The pathways of triglyceride and phospholipid synthesis were significantly increased. We conclude that PON1 deficiency is associated with oxidative stress and metabolic alterations leading to steatosis in the livers of mice receiving a high-fat high-cholesterol diet.


Some health problems of the Maldives.
It is difficult to quantify the major health scourges from which the Maldivians suffer because of the scattered nature of their settlements and their conservative attitudes to health and hygiene-related matters. Projects to improve the quality of the health and disease data have been instituted by the World Health Organization (WHO) and the Maldivian Ministry of Health. The paper analyses information that has since become available on three major ill-health conditions in the Maldives, namely infant deaths, malaria and leprosy.


[Out of phase magnetic resonance imaging and liver applications].
The increasing indications for MRI evaluation of diseases of the abdomen, especially liver tumors, has promoted the development of sequences allowing further histological characterization. Out of phase sequences provide suppression of lipids and water signal at the cellular level. Available on all MR imagers, it is the most sensitive sequence to depict small amounts of lipids in the liver. Best applications of this sequence include liver steatosis, tumoral characterization with regards to lipid content (adenoma, hepatocellular carcinoma...) and depiction of tumors in abnormal liver. Performed without contrast injection, and using fast imaging acquisition, we believe that out of phase imaging should be performed for magnetic resonance imaging of the liver.


Recurrent urinary tract infections and bladder dysfunction in systemic lupus erythematosus.
To assess bladder function in systemic lupus erythematosus (SLE) patients with recurrent urinary tract infections (UTIs). A convenience sample of consecutive patients with SLE (American College of Rheumatology criteria), with recurrent UTIs (>/=3 events in the preceding 12 months), without history of central nervous system involvement, urolithiasis or preceding tuberculosis were studied. Disease activity (SLEDAI-2K), damage (SDI), lower urinary tract symptoms [Pelvic pain and Urgency/Frequency (PUF) and the Interstitial Cystitis Symptom and Problem Index (ICSPI) scales] and Autonomic Symptom Profile (ASP) were assessed. All patients underwent urological examination and urodynamic assessment with cystometry, uroflow, micturition and urethral pressure profile. Ten patients (nine women) were included. The majority of the patients reported urinary symptoms: urgency (n = 8), frequency (n = 8), nocturia (n = 9) and pain (n = 10). The patients had a mean (SD) ICSPI score of 18.4 (9.8), PUF score of 17.4 (5.3) and ASP weighted score of 31.7 (16.1). Abnormal urodynamics findings were identified in seven of the 10 patients, including small bladder capacity (two patients), reduced bladder sensation (four patients), subnormal urinary flow rate (one patient) and a significant amount of residual urine (two patients). The urodynamics findings suggest that bladder dysfunction could be one of the mechanisms involved on the occurrence of recurrent UTIs in patients with SLE. These findings have potential implications for the proper assessment and management of SLE patients with recurrent UTIs. Further studies are needed to corroborate our results.


Drivers of Live Cattle Price in the Livestock Trading System of Central Cameroon.
Livestock production and trade are critical for the food security and welfare of rural households in sub-Saharan Africa. In Cameroon, animal trade consists mainly of live cattle commercialized through livestock markets. Identifying the factors contributing to cattle price formation is critical for designing effective policies for sustainable production and for increasing food availability. In this study, we evaluated the influence of a range of individual- and market-level factors on the price of cattle that were sold in all transactions (n = 118,017) recorded over a 12-month period from 31 livestock markets in the main cattle production area of the country. An information-theoretic approach using a generalized additive mixed-effect model was implemented to select the best explanatory model as well as evaluate the robustness of the identified drivers and the predictive ability of the model. The age and gender of the cattle traded were consistently found to be important drivers of the price (p < 0.01). Also, strong, but complex, relationships were found between cattle prices and both local human and bovine population densities. Finally, the model highlighted a positive association between the number of incoming trading connections of a livestock market and the price of the traded live cattle (p < 0.01). Although our analysis did not account for factors informing on specific phenotypic traits nor breed characteristics of cattle traded, nearly 50% of the observed variation in live cattle prices was explained by the final model. Ultimately, our model gives a large scale overview of drivers of cattle price formation in Cameroon and to our knowledge is the first study of this scale in Central Africa. Our findings represent an important milestone in designing efficient and sustainable animal health management programme in Cameroon and ensure livelihood sustainability for rural households.


[Milk of calcium renal stone: echographic diagnosis].
"Milk of calcium renal stone" (liquid renal calculosis) is a quite uncommon lithiasis distinguished by the presence of a semiliquid suspension of calcium salts or a "seed-like" sediment in a caliceal diverticulum or an ectasia segment of the collecting system. We reviewed 5 patients (1 male and 4 females, mean age 48.6 years), with a history of urinary tract infection, renal pain or haematuria. All patients underwent renal ultrasonographic assessment in both clinostatic and orthostatic position. Three patients underwent intravenous pyelography before ultrasound. Ultrasonography showed a sonolucent "levelled" image with a posterior acoustic shadow inside a hydro-caliceal dilation (2 pts.) or caliceal diverticulum (3 pts.); the persistence of the "level" in both clinostatic and orthostatic position allowed an immediate diagnosis in all patients. Intravenous pyelography performed before renal ultrasound showed no abnormality in 1 patient and was misleading in two; it otherwise confirmed the diagnosis when performed after renal ultrasonography. Three patients underwent surgery, two patients refused therapy; sonographic follow-up showed no evolution of the morphologic picture. Once considered as exceptional, liquid renal calculosis still remains rare pathology and accounts for 0.6% of all the urinary lithiasis diagnosed by ultrasound in our series. An accurate sonographic assessment allows a reliable diagnosis of this particular lithiasis and an easy discrimination from solid lithiasis, nephrocalcinosis, medullary sponge kidney and hydropyonephrosis. Hence, a correct diagnosis of this rare condition lets uneffective and improper treatments be avoided.


Self-avoiding walks and connective constants in small-world networks.
Long-distance characteristics of small-world networks have been studied by means of self-avoiding walks (SAW's). We consider networks generated by rewiring links in one- and two-dimensional regular lattices. The number of SAW's u(n) was obtained from numerical simulations as a function of the number of steps n on the considered networks. The so-called connective constant, mu=lim(n-->infinity)u(n)/u(n-1), which characterizes the long-distance behavior of the walks, increases continuously with disorder strength (or rewiring probability p). For small p, one has a linear relation mu=mu(0)+ap, mu(0) and a being constants dependent on the underlying lattice. Close to p=1 one finds the behavior expected for random graphs. An analytical approach is given to account for the results derived from numerical simulations. Both methods yield results agreeing with each other for small p, and differ for p close to 1, because of the different connectivity distributions resulting in both cases.


Peroxiredoxin 1 is required for efficient transcription and replication of measles virus.
Measles is a highly contagious human disease caused by the measles virus (MeV). In this study, by proteomic analysis, we identified peroxiredoxin 1 (Prdx1) as a host factor that binds to the C-terminal region of the nucleoprotein (N; N(TAIL)) of MeV. Glutathione S-transferase (GST) pulldown experiments showed that the Prdx1-binding site overlapped with the MeV phosphoprotein (P)-binding site on N(TAIL) and that Prdx1 competed for the binding to N(TAIL) with the P protein, which is a component of RNA-dependent RNA polymerase (RdRp). Furthermore, RNA interference for Prdx1 resulted in a significant reduction in MeV growth in HEK293-SLAM cells. A minigenome assay indicated that Prdx1 suppression affected the viral RNA transcription and/or replication step. Relative quantification of viral RNA by real-time PCR (RT-PCR) showed that Prdx1 suppression not only reduced viral RNA transcription and replication but also enhanced polar attenuation in viral mRNA transcription. Surface plasmon resonance analysis showed that the binding affinity of Prdx1 to MeV-N was 40-fold lower than that of MeV-P to MeV-N, which suggested that Prdx1 might be involved in the early stage of MeV infection, when the expression level of Prdx1 was much higher than that of MeV-P. Since Prdx1 was expressed abundantly and constitutively in various cells, the results in this study indicate that Prdx1 is one of the inherent host factors implicated in MeV RNA synthesis.


Targeting the receptor-Gq interface to inhibit in vivo pressure overload myocardial hypertrophy.
Hormones and neurotransmitters may mediate common responses through receptors that couple to the same class of heterotrimeric guanine nucleotide-binding (G) protein. For example, several receptors that couple to Gq class proteins can induce cardiomyocyte hypertrophy. Class-specific inhibition of Gq-mediated signaling was produced in the hearts of transgenic mice by targeted expression of a carboxyl-terminal peptide of the alpha subunit Galphaq. When pressure overload was surgically induced, the transgenic mice developed significantly less ventricular hypertrophy than control animals. The data demonstrate the role of myocardial Gq in the initiation of myocardial hypertrophy and indicate a possible strategy for preventing pathophysiological signaling by simultaneously blocking multiple receptors coupled to Gq.


Scanning electron microscopy of experimentally induced hepatocellular carcinoma.
Hepatocellular carcinomas (HCC) induced in rats by diethylnitrosamine were observed by light microscopy (LM) and scanning electron microscopy (SEM). Liver cirrhosis did not develop. The tumors were of 4 types; trabecular, glandular, adenoid and hyperplastic nodular (HN). SEM demonstrated that trabecular lesions were packed with many layers of HCC cells which had in some places bile canaliculi on the intercellular surfaces with sparse microvilli. Glandular lesions were composed of gland-like structures having columnar or cuboidal cells with numerous microvilli on the hemispherical apex. Glandular lumens were bordered from intercellular spaces by the zona occludens. The glandular structures were derived from the exterior of the trabecular lesions and were closed at both ends, as confirmed by reconstruction of serial sections. Adenoid lesions, which had gland-like structures in the trabecula, were often observed between purely trabecular and purely glandular lesions. HN-type lesions composed of two-cell-thick plates were mostly located at the peripheral parts of the HCC tumor and were continuous with other lesions. HN-type lesions had markedly dilated bile canaliculi and well-developed microvillous projections on the intercellular surfaces. The HN-type lesions had structures similar to those of late HN. The existence of lesions indistinguishable from late HN in the periphery of HCC tumors indicates the HCC develop from HN. In summary, the rat HCC were of 4 types of lesions which had characteristic histological and cytological structures, but which were connected with each other, changing gradually from one to the other.


Parental illness, family functioning, and adolescent well-being: a family ecology framework to guide research.
A family ecology model for understanding adolescents' reactions to parental illness is presented and used to (a) critically evaluate existing research that examines direct effects of parental illness on family functioning and youth well-being and (b) provide a blueprint for future research in the area. Theoretical, clinical, and empirical literature is reviewed for each mediational and moderational pathway in the model, and limitations of the existing research are discussed. The blueprint for future research emphasizes a greater understanding of the mediational pathways in the model, which is essential for developing effective interventions for families experiencing parental illness. In addition, greater elucidation of moderator variables, such as the youth's developmental stage, social support, and cultural norms will provide critical information on contextual factors that enhance or impede adolescents' adaptation to serious parental illness.


Arthroscopic Reduction and Fixation of Transverse Intra-articular Glenoid Fractures With Scapular Extension.
The most common procedure to address transverse glenoid fractures that are characterized by intra-articular step-off or gapping is open reduction and internal fixation. Disadvantages of open surgery are delay in regaining full range of motion, increased approach morbidity, neurovascular complications, and the need for capsulotomy, which delays healing and increases the risk of stiffness. An arthroscopically assisted fracture fixation, as described in this article, is characterized by better visualization of the glenoid articular surface and reduction of the intra-articular fragments under direct vision, which diminishes the chances of residual step-off after fixation. Furthermore, arthroscopic fixation provides the advantages of minimal surgical trauma, which speeds up the recovery time, decreased morbidity as there is less blood loss compared with the open technique, lower chance of neurologic injury as there is less dissection around the spinoglenoid or suprascapular notch, less trauma to the joint capsule, and lower chances of stiffness and capsulorrhaphy arthropathy.


Memory colours affect colour appearance.
Memory colour effects show that colour perception is affected by memory and prior knowledge and hence by cognition. None of Firestone & Scholl's (F&S's) potential pitfalls apply to our work on memory colours. We present a Bayesian model of colour appearance to illustrate that an interaction between perception and memory is plausible from the perspective of vision science.


First-glance diagnosis of Strongyloides stercoralis autoinfection by stool microscopy.
We report a case of autoinfection due to Strongyloides stercoralis in a 27-year-old Ethiopian AIDS patient living in Germany for nearly 3 years. This case was diagnosed on the basis of a single-view field in microscopy of a freshly obtained formalin-fixed stool specimen showing both rhabditiform and filariform larvae. The diagnosis of autoinfection by microscopy is discussed in detail.


Translating biased signaling in the ghrelin receptor system into differential in vivo functions.
Biased signaling has been suggested as a means of selectively modulating a limited fraction of the signaling pathways for G-protein-coupled receptor family members. Hence, biased ligands may allow modulation of only the desired physiological functions and not elicit undesired effects associated with pharmacological treatments. The ghrelin receptor is a highly sought antiobesity target, since the gut hormone ghrelin in humans has been shown to increase both food intake and fat accumulation. However, it also modulates mood, behavior, growth hormone secretion, and gastric motility. Thus, blocking all pathways of this receptor may give rise to potential side effects. In the present study, we describe a highly promiscuous signaling capacity for the ghrelin receptor. We tested selected ligands for their ability to regulate the various pathways engaged by the receptor. Among those, a biased ligand, YIL781, was found to activate the Gαq/11 and Gα12 pathways selectively without affecting the engagement of β-arrestin or other G proteins. YIL781 was further characterized for its in vivo physiological functions. In combination with the use of mice in which Gαq/11 was selectively deleted in the appetite-regulating AgRP neurons, this biased ligand allowed us to demonstrate that selective blockade of Gαq/11, without antagonism at β-arrestin or other G-protein coupling is sufficient to decrease food intake.


Constitutive glucose transport in rat Leydig cells and pyruvate support of steroidogenesis.
To facilitate the interpretation of in vitro experiments that use pharmacological agents, such as cytochalasin B, which inhibits glucose transport, an alternative to glucose as an energy source for rat Leydig cells was sought. Pyruvate was superior to glucose as an energy source for the support of steroidogenesis. The concentration of pyruvate required to support half-maximum androgen production was lower than that for glucose (60 +/- 8 versus 478 +/- 87 microM, respectively), and pyruvate supported a higher rate of maximum LH-stimulated androgen production. The latter result suggested that glucose availability can be rate limiting for steroidogenesis in in vitro experiments. The acute regulation of glucose transport was therefore investigated using 2-Deoxy-D-[2,6(3)H]glucose. Uptake of 2-Deoxy-D-[2,6(3)H]glucose by Leydig cells was not affected by insulin, LH, or glucose deprivation, suggesting that it is a constitutive process in these cells.


Suppressive Effects of Docosahexaenoic Acid Intake on Increased Seizure Susceptibility after Growth Due to Febrile Seizures in Infancy.
Febrile seizures are seizures accompanied by a fever and frequently occur in children six months to five years of age. Febrile seizures are classified as simple or complex, and complex febrile seizures increase the risk of temporal lobe epilepsy after growth. Therefore, it is important to interfere with epileptogenesis after febrile seizures to prevent post-growth epilepsy. The present study challenged nutritional intervention using docosahexaenoic acid (DHA). Febrile seizures were induced in mice at the age of 10 d using a heat chamber, and seizure sensitivity was examined using pentylenetetrazol (PTZ) administration after growth. PTZ increased the seizure score and shortened the latency in the complex febrile seizure group compared to the control, hyperthermia and simple febrile seizure groups. Mice in the complex febrile seizure group showed abnormal electroencephalograms pre- and post-PTZ administration. Therefore, seizure susceptibility increases the episodes of complex febrile seizures. DHA supplementation after febrile seizures clearly suppressed the increased seizure susceptibility due to complex febrile seizures experienced in infancy. DHA also attenuated microglial activation after complex febrile seizures. Taken together, DHA suppressed microglial activation following complex febrile seizures, which may contribute to protecting the brain from post-growth seizures. The intake of DHA in infancy may protect children from high fever-induced developmental abnormalities.


Analysis of Dickkopf3 interactions with Wnt signaling receptors.
Wnt signaling regulates essential biological processes ranging from embryogenesis to neurodegeneration. Recently, we demonstrated that Dickkopf3 (Dkk3) is a pro-survival glycoprotein that positively modulates Wnt signaling. An important step in understanding the mechanism of action of Dkk3 is identifying its interacting proteins in the Wnt pathway. In this study, we used a series of biochemical and functional assays to investigate the interaction between Dkk3 and the Wnt pathway receptors Kremen1 (Krm1), Kremen 2 (Krm2) and low-density lipoprotein receptor-related protein 6 (LRP6). Here, we report that, contrary to previous studies, Dkk3 interacts with Krm1 and Krm2. However, Dkk3 did not interact with, or alter expression of, LRP6. Blocking protein glycosylation did not alter the interaction between Dkk3 and Krm proteins. Additionally, Krm2 abolished Dkk3-mediated potentiation of Wnt signaling. Therefore, our data establish that Krm proteins are novel binding partners of Dkk3 and suggest a mechanism by which Dkk3 potentiates Wnt signaling.