Recent advances and clinical implications of the micropapillary histological subtype in lung adenocarcinomas.
Micropapillary (MIP) histologic subtype included in the classification of lung adenocarcinomas (ADCs) is associated with both size- and stage-independent poor prognoses. MIP pattern in lung ADCs, even at small, early stages, correlates with high lymphovascular invasion, visceral pleural invasion and lymph node metastases. Recently, we reported that patients with a MIP component are at a higher risk of locoregional recurrence after limited resection. Identification of a MIP pattern is only possible with permanent pathologic sections; preoperative imaging, cytology or intraoperative frozen section specimens remain unreliable. The intermixed, heterogenous morphology of lung ADC presents a technical challenge in investigating the molecular biology of cells with MIP morphology. A comprehensive understanding of the biology of MIP morphology is vital for therapeutic interventions.


Epidemiology of methicillin-susceptible Staphylococcus aureus in a university medical center day care facility.
Few data are available on methicillin-susceptible Staphylococcus aureus (MSSA) colonization in day care. We performed a study in a child care center on a medical university campus to study the epidemiology of MSSA in this population. A cross-sectional study was done on 104 day care attendees and 32 adult employees of the child care center. Swab samples were taken from the nose, oropharynx, axilla, groin, and perirectal area of children, from the nose and oropharynx of employees, and from the environment. Parents and employees completed questionnaires. Swabs were placed in broth, then plated on agar and identified as MSSA by routine methods. Molecular typing was performed. The prevalence of MSSA was 21.15% in children and 28.13% in employees. MSSA was found in 8.72% of environmental samples. Univariate analysis identified 3 risk factors and 5 protective factors for MSSA colonization. In multivariable analysis, only 2 variables remained significantly related to MSSA colonization, with older age remaining as a risk factor and receipt of beta-lactams approaching significance as being protective. Many of the isolates were indistinguishable by molecular typing. The prevalence of MSSA colonization in children and care providers in a university medical center child care center is similar to that of the general population. Children colonized with MSSA tended to be older and to have received fewer courses of antibiotics than children who did not have MSSA. The relatedness of many of the isolates indicates that transmission of MSSA occurred at this child care center.


Ophthalmic Pyogenic Granulomas Treated With Topical Timolol-Clinical Features of 17 Cases.
Topical timolol has been increasingly demonstrated to be an effective treatment for pyogenic granulomas (PG). The authors review the treatment outcomes of 17 patients with ocular PG treated with topical timolol. Retrospective interventional study of 17 patients with ocular PGs treated with timolol 0.5% solution. Patient demographics, clinical features, treatment response, and recurrence were noted. Nine females and 8 males with a mean age of 23 years (range, 3-67 years) were included. Mean duration of disease prior to treatment was 3.81 months (range, 0.25-11 months). Etiologies included chalazia (12 cases, 71%), postsurgical (4, 24%) and trauma (1, 6%). Five patients (29%) had treatment with topical steroids prior to presentation. Fifteen patients (88%) had PG located on the palpebral conjunctiva and 2 (12%) involving the bulbar conjunctiva. Mean lesion size was 5.06 × 6.06 mm (range, 3-8 × 3-18 mm). Fifteen patients (88%) had complete lesion resolution with a mean treatment duration of 3.07 weeks (range, 2-5 weeks) and no adverse events or recurrences with a mean follow up of 9.47 months (range, 6-27 months). Two patients (12%) underwent lesion excision after 6 weeks of timolol failed to yield resolution. Topical timolol appears to be a well-tolerated nonsurgical treatment of ocular PG in both children and adults. Clinicians may wish to consider topical timolol to treat PG as opposed to topical steroids, given the inherent risk of steroid response ocular hypertension and the difficulty to measure intraocular pressure in younger children who require general anesthesia for excision.


ABCModeller: an automatic data mining tool based on a consistent voting method with a user-friendly graphical interface.
In order to extract useful information from a huge amount of biological data nowadays, simple and convenient tools are urgently needed for data analysis and modeling. In this paper, an automatic data mining tool, termed as ABCModeller (Automatic Binary Classification Modeller), with a user-friendly graphical interface was developed here, which includes automated functions as data preprocessing, significant feature extraction, classification modeling, model evaluation and prediction. In order to enhance the generalization ability of the final model, a consistent voting method was built here in this tool with the utilization of three popular machine-learning algorithms, as artificial neural network, support vector machine and random forest. Besides, Fibonacci search and orthogonal experimental design methods were also employed here to automatically select significant features in the data space and optimal hyperparameters of the three algorithms to achieve the best model. The reliability of this tool has been verified through multiple benchmark data sets. In addition, with the advantage of a user-friendly graphical interface of this tool, users without any programming skills can easily obtain reliable models directly from original data, which can reduce the complexity of modeling and data mining, and contribute to the development of related research including but not limited to biology. The excitable file of this tool can be downloaded from http://lishuyan.lzu.edu.cn/ABCModeller.rar.


Immune thrombocytopenia in adults: an update.
Immune thrombocytopenia (ITP) in adults is a chronic disease resulting from increased platelet destruction and impaired platelet production. Splenectomy remains the most effective and durable treatment in cases that are refractory to first-line therapy, but its use has declined because of the availability of alternate medical therapy, the associated risk of infection, and concern for surgery-related complications. Rituximab (Rituxan) may be an effective alternative but carries the risk of immunosuppression.


The duplicated deacetylases Sir2 and Hst1 subfunctionalized by acquiring complementary inactivating mutations.
Protein families are generated by successive rounds of gene duplication and subsequent diversification. However, the paths by which duplicated genes acquire distinct functions are not well characterized. We focused on a pair of duplicated deacetylases from Saccharomyces cerevisiae, Sir2 and Hst1, that subfunctionalized after duplication. As a proxy for the ancestral, nonduplicated deacetylase, we studied Sir2 from another yeast, Kluyveromyces lactis. We compared the interaction domains of these deacetylases for the Sir transcriptional silencing complex, which acts with ScSir2, and the Sum1 repressor, which acts with ScHst1, and found that these interaction domains have been retained over the course of evolution and can be disrupted by simple amino acid substitutions. Therefore, Sir2 and Hst1 subfunctionalized by acquiring complementary inactivating mutations in these interaction domains.


[Cardiovascular syndrome X and endothelial dysfunction].
Up to 30% of patients with chest pain who undergo coronary arteriography, have completely normal coronary angiograms. The subgroup with typical angina and a positive response to stress testing is generally included under the diagnosis of cardiovascular syndrome X. Several causes and mechanisms have been investigated in the past twenty years, to explain both chest pain and ischemic angina-like ST segment depression that are commonly observed in these patients. Clinical and pathogenic heterogeneity appears to be the main features of the syndrome. Among the suggested pathophysiological mechanisms, endothelial dysfunction of the coronary microcirculation features prominently. In this review, we present the available evidence regarding endothelial dysfunction in cardiovascular syndrome X.


Synthesis, crystal structure and some physical properties of RuZn3.
The crystal structure, phase relations and some physical properties of the binary zinc-rich phase RuZn3 are reported. The title compound is accessible via high-temperature reaction from the elements in the appropriate substance amount ratio. Its crystal structure was determined from a Rietveld profile fit to an X-ray diffractogram of pristine RuZn3 and confirmed by single-crystal X-ray structure analysis. The title compound adopts a tetragonal Al3Zr-type structure corresponding to an A2B2 anti-phase domain structure of the cubic AuCu3-type: a=376.82(3) pm, c=1554.78(13) pm, I4/mmm, Z=4, R(F)(all data)=0.0197, 153 unique reflections, 12 variables. The structure is discussed in the light of the Hume-Rothery concept. RuZn3 melts at 1373(2) K, is a moderate metallic conductor (rho(293 K)=6.2 mOmega cm) and exhibits basically temperature-independent paramagnetic properties. It coexists with Ru1-xZnx and RuZn6.


Expression of CD147 in advanced non-small cell lung cancer correlated with cisplatin-based chemotherapy resistance.
CD147, a widely expressed cell surface glycoprotein in cancer, is associated with tumor invasiveness and chemotherapy resistance. Recently, CD147 is also regarded as a potential therapeutic target for cancer therapy. The aim of the study was to investigate CD147 expression in non-small cell lung cancer (NSCLC), and evaluate its correlation with cisplatin-based chemotherapy resistance. In this study, we examined immunohistochemically the expression of CD147 in 118 advanced NSCLC cases treated with cisplatin-based chemotherapy, and then the association of CD147 expression with clinicopathological characteristics was analyzed. Furthermore, RNA interference approach was used to silence CD147 expression in a cisplatin-resistant human lung cancer cell line A549/DDP, and the inhibition effect of cisplatin on tumor cells was assayed by MTT. In the overall series, positive CD147 expression was observed in 101/118 (85.6%) cases. A membranous CD147 pattern was identified in 76/101 (75.2%) of CD147 positive tumors. CD147 membranous expression,but not the overall CD147 expression, was associated with poor response to cisplatin-based chemotherapies and a poor prognosis in advanced NSCLC patients. In vitro results showed that silencing CD147 increased the proliferation inhibitory effect of cisplatin to A549/DDP cells. In conclusion, our study indicated that membranous CD147 expression is a predictive factor of the response to cisplatin-based chemotherapies, and the use of CD147-targeted therapeutic adjuvants might be considered in the treatment of advanced NSCLC patients.


Blue-LED-Light Photobiomodulation of Inflammatory Responses and New Tissue Formation in Mouse-Skin Wounds.
Background: Recent studies evidence that blue-LED-light irradiation can modulate cell responses in the wound healing process within 24 h from treatment. This study aims to investigate blue-light (410-430 nm) photobiomodulation used in a murine wound model within six days post-treatment. Methods: A superficial wound was made in 30 CD1 male mice. The injuries were treated with a blue LED light (20.6 J/cm2), and biopsies were collected at 24, 72, and 144 h. Histology, fluorescence analysis, and advanced microscopy techniques were used. Results: We can observe an increase in the cellular infiltrate response, and in mast-cell density and their degranulation index correlated to the expression of the major histocompatibility complex after 24 h. Furthermore, after six days, the vessel density increases with the expression of the platelet-derived growth factor in the mast cells. Finally, collagen deposition and morphology in the treated wounds appear more similar to unwounded skin. Conclusions: Blue-light photobiomodulation stimulates several cellular processes that are finely coordinated by mast cells, leading to more rapid wound healing and a better-recovered skin morphology.


Spatiotemporal Patterns of Menin Localization in Developing Murine Brain: Co-Expression with the Elements of Cholinergic Synaptic Machinery.
Menin, a product of MEN1 (multiple endocrine neoplasia type 1) gene is an important regulator of tissue development and maintenance; its perturbation results in multiple tumors-primarily of the endocrine tissue. Despite its abundance in the developing central nervous system (CNS), our understanding of menin's role remains limited. Recently, we discovered menin to play an important role in cholinergic synaptogenesis in the CNS, whereas others have shown its involvement in learning, memory, depression and apoptosis. For menin to play these important roles in the CNS, its expression patterns must be corroborated with other components of the synaptic machinery imbedded in the learning and memory centers; this, however, remains to be established. Here, we report on the spatio-temporal expression patterns of menin, which we found to exhibit dynamic distribution in the murine brain from early development, postnatal period to a fully-grown adult mouse brain. We demonstrate here that menin expression is initially widespread in the brain during early embryonic stages, albeit with lower intensity, as determined by immunohistochemistry and gene expression. With the progression of development, however, menin expression became highly localized to learning, memory and cognition centers in the CNS. In addition to menin expression patterns throughout development, we provide the first direct evidence for its co-expression with nicotinic acetylcholine, glutamate and GABA (gamma aminobutyric acid) receptors-concomitant with the expression of both postsynaptic (postsynaptic density protein PSD-95) and presynaptic (synaptotagamin) proteins. This study is thus the first to provide detailed analysis of spatio-temporal patterns of menin expression from initial CNS development to adulthood. When taken together with previously published studies, our data underscore menin's importance in the cholinergic neuronal network assembly underlying learning, memory and cognition.


Altered expression of extracellular superoxide dismutase in mouse lung after bleomycin treatment.
The antioxidant enzyme extracellular superoxide dismutase (EC-SOD) is highly expressed in the extracellular matrix of lung tissue and is believed to protect the lung from oxidative damage that results in diseases such as pulmonary fibrosis. This study tests the hypothesis that proteolytic removal of the heparin-binding domain of EC-SOD results in clearance of the enzyme from the extracellular matrix of pulmonary tissues and leads to a loss of antioxidant protection. Using a polyclonal antibody to mouse EC-SOD, the immunodistribution of EC-SOD in normal and bleomycin-injured lungs was examined. EC-SOD labeling was strong in the matrix of vessels, airways, and alveolar surfaces and septa in control lungs. At 2 d post-treatment, a slight increase in EC-SOD staining was evident. In contrast, lungs examined 4 or 7 d post-treatment, showed an apparent loss of EC-SOD from the matrix and surface of alveolar septa. Notably, at 7 d post-treatment, the truncated form of EC-SOD was found in the bronchoalveolar lavage fluid of bleomycin-treated mice, suggesting that EC-SOD is being removed from the extracellular matrix through proteolysis. However, loss of EC-SOD through proteolysis did not correlate with a decrease in overall pulmonary EC-SOD activity. The negligible effect on EC-SOD activity may reflect the large influx of intensely staining inflammatory cells at day 7. These results indicate that injuries leading to pulmonary fibrosis have a significant effect on EC-SOD distribution due to proteolytic removal of the heparin-binding domain and may be important in enhancing pulmonary injuries by altering the oxidant/antioxidant balance in alveolar interstitial spaces.


Diversity of Intestinal Clostridium coccoides Group in the Japanese Population, as Demonstrated by Reverse Transcription-Quantitative PCR.
We used sensitive rRNA-targeted reverse transcription-quantitative PCR (RT-qPCR) to quantify the Clostridium coccoides group, which is a major anaerobic population in the human intestine. For this purpose, the C. coccoides group was classified into 3 subgroups and 19 species for expediency in accordance with the existing database, and specific primers were newly developed to evaluate them. Population levels of the C. coccoides group in human feces determined by RT-qPCR were equivalent to those determined by fluorescence in situ hybridization. RT-qPCR analysis of fecal samples from 96 volunteers (32 young children, 32 adults and 32 elderly) by using the 22 new primer sets together with the C. coccoides group-specific primer setm revealed that (i) total counts obtained as the sum of the 3 subgroups and 19 species were equivalent to the results obtained by using the C. coccoides group-specific primer set; (ii) total C. coccoides-group counts in the elderly were significantly lower than those in young children and adults; (iii) genus Blautia was the most common subgroup in the human intestinal C. coccoides-group populations at all age populations tested; (iv) the prevalences of Fusicatenibacter saccharivorans and genus Dorea were significantly higher in adults than in young children and the elderly; and (v) the prevalences of C. scindens and C. hylemonae, both of which produce secondary bile acid in the human intestine, were significantly higher in the elderly than in young children and adults. Hierarchical clustering and principal component analysis showed clear separation of the bacterial components between adult and elderly populations. Taken together, these data suggest that aging plays an important role in the diversity of C. coccoides-group populations in human intestinal microbiota; changes in this diversity likely influence the health of the host.


Criteria for the cytologic assessment of hyperplasias in endometrial samples obtained by the Endopap Endometrial Sampler.
The Endopap Endometrial Sampler was used in 1,465 women, either just before endometrial biopsy or curettage (in 760 symptomatic patients) or as an office procedure (in 705 women). The samples were inadequate for interpretation in only 8.7% of the cases. Although all malignant lesions were identified by this screening technique, about one-fourth were initially classified cytologically as hyperplasia. Endometrial hyperplasias presented the greatest difficulties in interpretation, with only slightly over half of the proven cases correctly assessed on the endometrial sample. In an attempt to improve the accuracy of the cytologic diagnosis of hyperplasias, ten morphologic features were examined retrospectively in 207 cases. Five of the criteria were shown to provide an increased probability of correctly diagnosing endometrial hyperplasias on the cytologic sample: (1) the overlapping of cells in the glandular clusters or sheets, (2) the presence of nucleoli, (3) anisokaryosis, (4) granularity of chromatin and (5) the presence of sheets of stromal cells. The more of these criteria observed in a given case, the better was the chance of cytologically identifying a hyperplasia in the Endopap sample.


Oestrous behaviour and timing of ovulation in relation to onset of oestrus and LH peak in Mithun (Bos frontalis) cows.
The objectives of the study were to evaluate the oestrus behaviour and to determine the timing of ovulation in relation to onset of oestrus and the pre-ovulatory LH surge in mithun (Bos frontalis). For this purpose, the blood samples collected at 15-min intervals for 9 h period following onset of oestrus and thereafter, at an interval of 2 h till 4 h post-ovulation for three consecutive cycles from 12 mithun cows were assayed for plasma LH and progesterone. Ovulation was confirmed by palpation of ovaries per rectum at hourly intervals. Various signs of behavioural oestrus were also recorded. The common signs of oestrus and their frequency of occurrence in mithuns were following and mounting by male mithuns (100%), standing to be mounted (100%), frequent urination (62.33%), raising of tail (65.23%), swelling of vulva (54.26%) and congestion of vulvar mucous membrane (69.87%). The pre-ovulatory LH surges consisted of several pulses (2.92 +/- 0.26 pulses/animal; range, 1-4). The mean (+/-SEM) peak level of LH for individual mithun varied from 6.99 +/- 0.44 to 12.69 +/- 2.10 ng/ml and the mean pooled LH peak concentration was 9.10 +/- 0.60 ng/ml. The highest peak (highest amplitude of LH during LH surge) was 10.83 +/- 0.76 ng/ml (range, 8.07-16.49 ng/ml). The duration of LH surge was 6.98 +/- 0.22 h (6-8 h). Onset of LH surge was at 1.23 +/- 0.17 h post-oestrus onset (range, 0.25-2.25 h). Mean plasma progesterone stayed low (<0.24 ng/ml) during the entire duration of sampling. Ovulation occurred at 26.92 +/- 0.31 (range, 26-29 h) after the onset of oestrus and 18.63 +/- 0.35 h (range, 17-20.75 h) after the end of LH surge. The occurrence of the highest LH peaks within a narrow time frame of 2- to 5-h post-oestrus onset in mithuns could have contributed to the animals ovulating within a narrow time interval. These results are very promising from a practical standpoint of potential success when AI program in this species is implemented in a big way. Furthermore, the results of the occurrence of LH pulses during pre-ovulatory LH surges, which are required for ovulation in this species of animals, is unique and species specific.


Effect of a magnetic field on the wake potential in a dusty plasma with streaming ions.
The wake potential of a test dust particulate due to an ion cyclotron wave in a dusty plasma with streaming ions is calculated. The role of the external magnetic field on the periodic attractive forces is clarified. The amplitude of wake potential is reduced because the overshielding by streaming ions is inhibited in the presence of the external magnetic field.


Exploring physical therapy clinical decision making for children with spastic diplegia: survey of pediatric practice.
The purpose of this special interest report is to describe the outcomes of a research round table discussion regarding the physical therapy management of mobility for children with spastic diplegia. Sixty-two pediatric physical therapists and physical therapists assistants participated in focus groups during the Research Round Table at the American Physical Therapy Association (APTA) 1999 Combined Sections Meeting. A case description of a child with spastic diplegia and guiding questions were used to facilitate discussion. Common practices in patient management across the child's life-span emerged from the discussion. Practices in examination, evaluation and prognosis, and intervention differed depending on the age and function of the child and the family's needs. In general, therapists reported that younger children receive examinations that include standardized tests of development and ongoing intervention with a frequency of one to five times per week. In contrast, older children receive therapy services on an episodic basis that address their specific needs. The elements of patient management served as a useful framework for exploring decision making. The information compiled from this project needs to be validated through systematic inquiry. Therapists may, however, use the practices reported here to reflect on their clinical decision making and to identify questions for further exploration. This descriptive document is the first step in the development of a guideline for evidence-based practice. The development of such a clinical guideline could serve as an education tool for novice therapists, a program evaluation tool to ensure quality care, and a foundation for future research to promote evidence-based practice.


Bilayer Wood Membrane with Aligned Ion Nanochannels for Spontaneous Moist-Electric Generation.
Water-enabled electricity generation (WEG) technologies are considered to be an attractive and renewable approach to meet energy crisis and environmental pollution globally. However, the existing WEG technologies still face tremendous challenges including high material cost, harmful components, and specific environmental requirements. Herein, a high-performance wood-based moisture-enabled electric generator (WMEG) is fabricated. Natural wood is cut perpendicular to the tree growth direction and engineered by simple chemical modification. The obtained bilayer wood membrane has robust mechanical framework with aligned ion nanochannels, abundant dissociated functional groups, and spontaneous water adsorption in the air. At the relative humidity of 85%, one WMEG can generate a voltage of 0.57 V. The device can also effectively sense biological water information as a self-powered sensor. The biophile design contributes a practical moist-electric generation strategy that offers clean energy, especially for undeveloped and disaster-relief regions where electricity is limited by high cost or crippled power facilities.


Refined protocols of tamoxifen injection for inducible DNA recombination in mouse astroglia.
Inducible DNA recombination of floxed alleles in vivo by liver metabolites of tamoxifen (TAM) is an important tool to study gene functions. Here, we describe protocols for optimal DNA recombination in astrocytes, based on the GLAST-CreERT2/loxP system. In addition, we demonstrate that quantification of genomic recombination allows to determine the proportion of cell types in various brain regions. We analyzed the presence and clearance of TAM and its metabolites (N-desmethyl-tamoxifen, 4-hydroxytamoxifen and endoxifen) in brain and serum of mice by liquid chromatographic-high resolution-tandem mass spectrometry (LC-HR-MS/MS) and assessed optimal injection protocols by quantitative RT-PCR of several floxed target genes (p2ry1, gria1, gabbr1 and Rosa26-tdTomato locus). Maximal recombination could be achieved in cortex and cerebellum by single daily injections for five and three consecutive days, respectively. Furthermore, quantifying the loss of floxed alleles predicted the percentage of GLAST-positive cells (astroglia) per brain region. We found that astrocytes contributed 20 to 30% of the total cell number in cortex, hippocampus, brainstem and optic nerve, while in the cerebellum Bergmann glia, velate astrocytes and white matter astrocytes accounted only for 8% of all cells.


[Destabilizing effect of chicken selection using the functional adrenal reserves criteria].
Chicken lines produced by divergent selection for the functional adrenal reserves showed significant between-line differences in the content of corticosterone and other hormones (thyroxin, progesterone), as well as in body weight, early maturation, and egg yield. DNA fingerprinting with the pGB725 probe revealed molecular changes in genomic DNA of the chicken lines subjected to plus and minus selection. The genetic distances between the original population and the selected chicken lines, which were estimated from the molecular hybridization patterns, reflected the history of breeding. Analysis of mixed DNA from several individuals of each line revealed specific hybridization bands that could serve as DNA markers during selection for the high and low corticosterone levels in blood.


Water quality assessment of coastal Caloosahatchee River watershed, Florida.
Caloosahatchee River watershed and estuary has experienced a general decline in the water quality over the last several decades due to agriculture practices, development, and other human activities. The objective of this study is to assess the water quality condition in coastal Caloosahatchee River watershed by analyzing the data collected by South Florida Water Management District and Lee County. Results indicated that during 1995 to 2006, averaged annually, Lake Okeechobee released 1124 million m3 of freshwater into the Caloosahatchee River, whereas the average annual freshwater discharge out of the Caloosahatchee River was approximately 2277 million m3. Lake Okeechobee might have more impacts on the water quality condition of Caloosahatchee River in dry season than wet season. The loads ratios of Lake Okeechobee to those out of Caloosahatchee River were much higher in dry season than wet season for flow (72% to 36%), total phosphorus (63% to 20%), total nitrogen (72% to 41%), organic nitrogen (85% to 47%), and NH3 (78% to 39%). In the coastal watershed area where the urban area is concentrated, of the total 5453 water samples, 74% of them have dissolved oxygen concentration less than 5 mg L(-1), the United States Environmental Protection Agency and Florida Department of Environmental Protection water quality standard. Only in January is the average monthly dissolved oxygen concentration higher than 5 mg L(-1).


Intrinsic Blue Fluorescence of 2.0G PAMAM-DCM Polymer Dots and Its Applications for Fe3+ Sensing.
A typical and environment-friendly fluorescent polyamine-amine (PAMAM) features good compatibility and unique surface modification, while it is restricted by a low fluorescence property performance and an unclear fluorescence mechanism. In this work, we prepared blue fluorescent PAMAM polymer dots (PDs) via a simple hydrothermal method based on dichloromethane (DCM) and 2.0G PAMAM. The quantum yield achieved was 32.1%, which was 25 times stronger than that of 2.0G PAMAM due to the lone-pair electron leap of the amine groups, the aggregation of carbonyl groups, as well as the crosslinking induced by DCM inside the PAMAM. In addition, the fluorescent 2.0G PAMAM-DCM PDs show a great Fe3+ sensing property with the detection limit of 56.6 nM, which is much lower than the safety limits (5.36 μM) in drinking water, indicating its great potential for Fe3+ detection in aqueous media.


Clinical advantages of papaverine cardioplegia.
To determine the efficacy of papaverine in improving myocardial protection by causing a uniform distribution of the cardioplegic solution, a prospective study was carried out in 200 consecutive patients undergoing various open heart procedures. Several parameters (creatine kinase MB, electron microscopy of myocardium, perioperative myocardial infarction rate, frequency of postoperative arrhythmias) were monitored and compared with those of a control group which consisted of the previous 200 consecutive patients in whom the same cardioplegic solution was used, but without papaverine. In the papaverine group the operative mortality due to low cardiac output was 0.5% compared to 3%, and the spontaneous recovery of the heart after release of the aortic cross-clamp was 89% compared to 47% in the control group (P less than 0.01). The perioperative myocardial infarction rate was 5% and the incidence of postoperative temporary arrhythmias was also 5% in the papaverine group, while in the control group the perioperative myocardial infarction rate was 10% and the postoperative arrhythmia incidence was 13% (P less than 0.01).


A Systematic Review and Meta-Analysis Examining Whether Changing Ovarian Sex Steroid Hormone Levels Influence Cerebrovascular Function.
Sex differences in cerebrovascular disease rates indicate a possible role for ovarian sex steroid hormones in cerebrovascular function. To synthesise and identify knowledge gaps, a systematic review and meta-analysis was conducted to assess how ovarian sex steroid hormone changes across the lifespan affect cerebrovascular function in women. Three databases (EMBASE, MEDLINE and Web of Science) were systematically searched for studies on adult cerebrovascular function and ovarian sex steroid hormones. Forty-five studies met pre-defined inclusion criteria. Studied hormone groups included hormone replacement therapy (HRT; n = 17), pregnancy (n = 12), menstrual cycle (n = 7), menopause (n = 5), oral contraception (n = 2), and ovarian hyperstimulation (n = 2). Outcome measures included pulsatility index (PI), cerebral blood flow/velocity (CBF), resistance index (RI), cerebral autoregulation, and cerebrovascular reactivity. Meta-analysis was carried out on HRT studies. PI significantly decreased [-0.05, 95% CI: (-0.10, -0.01); p = 0.01] in post-menopausal women undergoing HRT compared to post-menopausal women who were not, though there was considerable heterogeneity (I 2 = 96.8%). No effects of HRT were seen in CBF (p = 0.24) or RI (p = 0.77). This review indicates that HRT improves PI in post-menopausal women. However, there remains insufficient evidence to determine how changing ovarian sex steroid hormone levels affects cerebrovascular function in women during other hormonal phases (e.g., pregnancy, oral contraception).


Common procedures in reptiles and amphibians.
Reptiles and amphibians continue to be popular as pets in the United States and throughout the world. It therefore behooves veterinarians interested in caring for these exotic species to continually gather knowledge concerning both their proper husbandry and the conditions that require medical and/or surgical intervention. This article covers husbandry, physical examination, and clinical and diagnostic techniques in an effort to present guidelines for the evaluation of the reptile or amphibian patient. Gathering clinical data will aid veterinarians in arriving at the proper diagnosis,increasing the chances of success with treatment protocols, and educating the clients in proper nutrition and husbandry for their pets.


Bilateral carpometacarpal joint dislocations of the thumb.
A traumatic carpometacarpal joint dislocation of the thumb accounts for less than 1% of all hand injuries. Optimal treatment strategies for this injury are still a subject of debate. In this article, we report a case of bilateral thumb carpometacarpal joint dislocations: a unique combination of injuries. We believe our case is the second report of bilateral carpometacarpal joint dislocation regarding the thumb in English literature. It was successfully treated with closed reduction and percutaneous K-wires fixation on one side, and an open reduction and reconstruction of the ligament on the other side.


Modulation of LH-RH stimulated gonadotropin release by progestagens and 17 beta-estradiol in primary pituitary cell culture.
Simple trypsination procedure for rat anterior pituitary gland which permits a high yield of viable cells was described. Primary cell cultures set up by this method was characterized for their ability to release gonadotropic hormones into the culture medium with or without stimulation by hypothalamic extracts and a synthetic LH-RH, maximal sensitivity to the latter being found at 3--4 days after plating. Gonadotropin secretion was maximal after 4 hr of incubation with LH-RH, its maximal effective dose (ED50) being between 10(-11) and 10(-10) mol 1(-1). Such a dose stimulated rLH release into the medium by a factor of about 6 and rFSH secretion by a factor of 3 over controls. The preincubation of cultures wih progesterone, D-norgestrel and delta 15-D-norgestrel resulted in a progestagen dose-dependent desensitization of the cell cultures against LH-RH for both gonadotropic hormones. This effect of progestagens was found to be time-dependent and maximal inhibition was found after 12-20 h. However, more effective inhibition of LH-RH stimulated rLH release was caused by preincubation with cycloheximide suggesting the importance of protein synthesis in the course of LH-RH augmented gonadotropin release. A dissociation of sensitivity of cultured cells against LH-RH concerning their rLH and rFSH release was also found after preincubation with a mixture of progesterone and estradiol. Present data and previous observations strongly suggest the modulatory influence of steroid hormones on LH-RH provoked gonadotropin release at the pituitary level.


Differential regulation of brain aromatase by androgen in adult and fetal ferrets.
The contribution of androgens to the regulation of aromatase activity (AA), measured by quantifying the in vitro formation of [3H]estrone from 19-[3H]hydroxyandrostenedione precursor, was studied in equivalent microdissected brain regions of adult and fetal ferrets. In adulthood, AA was similar in the bed nucleus of the stria terminalis, medial (M) and lateral (L) preoptic area (POA), medial (MA) and lateral amygdala (LA), ventromedial hypothalamus (VMH), and parietal cortex of gonadectomized males and females given no concurrent steroid treatment. Daily sc injections of the androgen dihydrotestosterone propionate significantly stimulated AA in MPOA, MA, and VMH of adult males and in MA of females; a similar trend was seen in MPOA and VMH of females. By contrast, no evidence of androgenic regulation of AA was obtained in these three brain regions microdissected from fetuses killed on embryonic day 35 (E35; 41-day gestation). Transplacental administration of the antiandrogen flutamide beginning on day E24 failed to affect AA in MPOA, LPOA, MA, LA, or parietal cortex, although this treatment significantly reduced AA in bed nucleus of the stria terminalis of fetal males. The results suggest that the responsiveness of aromatizing enzymes to androgenic induction is similar in several subcortical brain regions of adult ferrets of both sexes. In breeding males such an action of androgen may augment the neural production of estrogen, which has previously been implicated in the control of sexual behavior and the feedback regulation of LH secretion. By contrast, androgen apparently contributes minimally to the regulation of AA in brain regions of fetal ferrets, particularly in the MPOA, in which a sexually dimorphic nucleus differentiates in males around E37 in response to estrogen produced locally.


Technique for obtaining high-energy ultrashort pulses from an additive-pulse mode-locked erbium-doped fiber ring laser.
We report a self-starting stretched-pulse polarization additive-pulse mode-locked erbium-doped fiber ring laser with high output power. By using the light normally absorbed by the intracavity polarizer as the output, we obtained pulses with energies greater than 0.5 nJ at a repetition rate of 48 MHz. External chirp compensation was used to shorten the highly chirped output pulses to durations of less than 100 fs. The power levels suggest that erbium-doped fiber lasers may replace bulk solid-state lasers, such as the color-center laser, for some applications.


Transcriptome analyses and virus-induced gene silencing identify HuWRKY40 acting as a hub transcription factor in the preservation of Hylocereus undatus by trypsin.
Trypsin can significantly improve the storage quality of Hylocereus undatus (H. undatus). To verify the hub WRKY gene of H. undatus in trypsin preservation, joint analysis of transcriptome and protein-protein interaction (PPI) network was carried out, and virus-induced gene silencing (VIGS) was conducted. In the transcriptome of H. undatus, GO directed acyclic graph (DAG) showed that the GO terms of 55 WRKY genes were mainly enriched in sequence-specific DNA binding, DNA binding transcription factor activity, and so on. The GO enrichment chord diagram showed that HuWRKY40 was significantly up-regulated in the enriched top10 GO terms. KEGG enrichment analysis showed that 55 WRKY genes were mainly enriched in plant-pathogen interaction and MAPK pathway. The results of PPI network showed that HuWRKY40 was a hub protein of WRKY transcription factors (TFs) family regulated by trypsin, which was consistent with the results of transcriptome analysis. Bioinformatics analysis showed that HuWRKY40 of H. undatus had the highest homology with Beta vulgaris L. and Spinacia oleracea L. The function of the core regulatory protein HuWRKY40 was further clarified by VIGS technology. The results of VIGS showed that there was a big difference between the phenotype of the pTRV2-HuWRKY40 group and that of the control group. Finally, it was confirmed that HuWRKY40 accelerated the synthesis of flavonoids and improved the fruit quality during the storage of H. undatus. This study found that trypsin may regulate HuWRKY40 activity through the MAPK cascade pathway, affect the participation of flavonoid synthesis, and then delay fruit corruption. PRACTICAL APPLICATIONS: With attention of people to the safety and freshness of fruits and vegetables, biological preservation technology has become one of the hotspots in the field of preservation in recent years. Trypsin can significantly improve the antioxidant capacity of fruits and vegetables. As a new biological preservative, it is convenient to operate and economical. In the current work, the mechanism of trypsin on the WRKY TFs during H. undatus storage was investigated. The application of trypsin would provide a new strategy for the storage quality control of fruits and vegetables.


Determination of optimal fiducial marker across image-guided radiation therapy (IGRT) modalities: visibility and artifact analysis of gold, carbon, and polymer fiducial markers.
The purpose of this study was to evaluate the visibility and artifact created by gold, carbon, and polymer fiducial markers in a simple phantom across computed tomography (CT), kilovoltage (kV), and megavoltage (MV) linear accelerator imaging and MV tomotherapy imaging. Three types of fiducial markers (gold, carbon, and polymer) were investigated for their visibility and artifacts in images acquired with various modalities and with different imaging parameters (kV, mAs, slice thickness). The imaging modalities include kV CT, 2D linac-based kilovoltage and megavoltage X-ray imaging systems, kV cone-beam CT, and normal and fine tomotherapy imaging. The images were acquired on a phantom constructed using Superflab bolus in which markers of each type were inserted into the center layer. The visibility and artifacts produced by each marker were assessed qualitatively and quantitatively. All tested markers could be identified clearly on the acquired CT and linac-based kV images; gold markers demonstrated the highest contrast. On the CT images, gold markers produced a significant artifact, while no artifacts were observed with polymer markers. Only gold markers were visible when using linac-based MV and tomotherapy imaging. For linac-based kV images, the contrast increased with kV and mAs values for all the markers, with the gold being the most pronounced. On CT images, the contrast increased with kV for the gold markers, while decreasing for the polymer and carbon marker. With the bolus phantom used, we found that when kV imaging-based treatment verification equipment is available, polymer and carbon markers may be the preferred choice for target localization and patient treatment positioning verification due to less image artifacts. If MV imaging will be the sole modality for positioning verification, it may be necessary to use gold markers despite the artifacts they create on the simulation CT images.


High fluid-low calcium intake: not all renal stone formers adhere to this simple treatment.
FActors predisposing to renal stone formation have been studied in 309 patients. Dehydration before diagnosis of urolithiasis was due in 12% of the cases to frequent diarrhea and in 36% to bad working conditions. Daily fluid intake was less than 1 liter in 25% of the patients before stone formation and was persistently low in 11% after stone discovery. 41% of the patients drank irregularly over the day, before stone formation, and 11% continued to do so after its detection. Immobilization was present in the patient's history in over 20% of the cases. Normocalcemic hypercalciuria was found in 26% of the patients. 24% of the patients drank water with a calcium concentration of 100--500 mg/l before the lithiasis was diagnosed; 21% continued to do so after stone discovery or paradoxically even drank harder water than before stone detection.


The effect of dilation of immature pedicles on pullout strength of the screws: Part 2: In vivo study.
Experimental study. To evaluate the biomechanical stability of screws placed in expanded pedicles, and to compare those with the screws placed in the nonexpanded pedicles in an in vivo model. Pullout strength of a pedicle screw increases as the diameter of the screw gets larger. Small pedicles of pediatric patients prevent the use of large size pedicle screws in this age group. As shown in an in vitro study one option to overcome this problem is to dilate and use larger screw in immature spine. But dilation reduces the pullout strength of pedicle screws in in vitro model. Six-week-old 3 pigs were used. One of them was lost in the postoperative period. After posterior subperiosteal exposure of lumbar segments (L1-L5), 4.0 mm diameter and 20 mm long pedicle screws were placed on the left. The right pedicles were dilated with stainless steel dilators and instrumented with screws of same dimension. At the end of 3 months the pigs were killed and the pull out strength of each screw were measured. The average pull out strength of the expanded and nonexpanded screws was 378.7 +/- 73 (542-308) Newton and 397 +/- 80 (535-289) Newton, respectively. There was no statistically significant difference between the 2 groups. The biomechanical stability of the same size screws inserted at the expanded and nonexpanded pedicles are the same after 3 months. Even dilation of the pedicle decreases the pullout strength of the screw at the beginning, and the pull out strength of both sides became equal after 3 months. The remodeling capacity of pedicles and overgrowth of bone on screws may have an effect on this result.


Selective down-regulation of aquaporin-1 in salivary glands in primary Sjögren's syndrome.
Salivary and lacrimal gland secretions are reduced in primary Sjögren's syndrome (pSS). Aquaporins (AQPs) are involved in transmembrane water transport, and different isoforms show specific cellular and subcellular distributions in salivary and lacrimal glands. Changes in expression of AQP molecules have therefore been suggested to contribute to the glandular dysfunction in pSS. AQP-5 is present in the apical membrane of acinar cells, where it mediates fluid outflow; however, we have recently shown that its expression is not altered in pSS. We therefore studied whether expression of other isoforms of AQP would be altered in pSS. Using high-resolution confocal microscopy, we determined the distribution of AQP-1 and AQP-3 in labial salivary gland biopsies from 11 patients with pSS and 9 healthy controls. AQP-1 is present in myoepithelial cells surrounding acini, and its expression in these cells was decreased by 38% in pSS glands. By contrast, expression of AQP-1 in endothelial cells of nonfenestrated capillaries was not altered in pSS. AQP-3 was expressed in the basolateral membrane of acinar epithelial cells, and its expression was not altered in disease. We therefore conclude that AQP-1 expression in myoepithelial cells is selectively down-regulated in pSS and that myoepithelial cell dysfunction may play a crucial role in the pathology of this disease.


Cerebral Amyloid Angiopathy and Atrial Fibrillation: An up to Date Case Report.
Concurrent Cerebral Amyloid Angiopathy (CAA) and Atrial Fibrillation are becoming an increasingly common dilemma in clinical practice due to the aging population and the comorbidities associated with it. In such patients, the physician must appreciate and strike the difficult balance between the risk of ischemic strokes from atrial fibrillation on one hand, and that of intracerebral hemorrhage from coexisting CAA on the other. Anticoagulation is necessary for the former but potentially deleterious for the latter. In this case report, we present the case of a 67-year-old woman with a long history of atrial fibrillation on rivaroxaban who recently began to experience recurrent transient neurological deficits that were later diagnosed as amyloid spells related to concomitant CAA. While there is no clear-cut consensus in published literature on how to best manage these patients regarding the use of anticoagulation, it is recommended to involve a multidisciplinary team for optimal management of these patients.


Family routines and parental monitoring as protective factors among early and middle adolescents affected by maternal HIV/AIDS.
The influence of parenting skills on adolescent outcomes among children affected by maternal HIV/AIDS (N = 118, M age = 13) was investigated. Among families with more frequent family routines, over time adolescents showed lower rates of aggression, anxiety, worry, depression, conduct disorder, binge drinking, and increased self-concept. Among families with higher levels of parental monitoring, adolescents showed significant declines in anxiety and depression, conduct disorder, and binge drinking, along with increased self-concept. Mothers' level of illness was associated with parenting. Greater variability in parental monitoring resulted in higher levels of problem behaviors.


Oral Monosodium Glutamate Administration Causes Early Onset of Alzheimer's Disease-Like Pathophysiology in APP/PS1 Mice.
Glutamate excitotoxicity has long been related to Alzheimer's disease (AD) pathophysiology, and it has been shown to affect the major AD-related hallmarks, amyloid-β peptide (Aβ) accumulation and tau phosphorylation (p-tau). We investigated whether oral administration of monosodium glutamate (MSG) has effects in a murine model of AD, the double transgenic mice APP/PS1. We found that AD pathogenic factors appear earlier in APP/PS1 when supplemented with MSG, while wildtype mice were essentially not affected. Aβ and p-tau levels were increased in the hippocampus in young APP/PS1 animals upon MSG administration. This was correlated with increased Cdk5-p25 levels. Furthermore, in these mice, we observed a decrease in the AMPA receptor subunit GluA1 and they had impaired long-term potentiation. The Hebb-Williams Maze revealed that they had memory deficits. We show here for the first time that oral MSG supplementation can accelerate AD-like pathophysiology in a mouse model of AD.


Multi-factorial approach associated with a new 'on/off' Orlistat® use in a weight loss maintenance programme: 4 years follow-up.
To assess the efficacy of a specific long-term programme for weight loss maintenance using a new 'on/off' Orlistat approach in obese subjects who previously lost more than 10% of their body weight. 50 patients were followed up during 4 years; 34 completed the study. Subjects were followed up by physicians trained in obesity management. Anthropometrical, biological and psychological parameters were measured. Insulin sensitivity was evaluated by euglycaemic insulin clamp. Orlistat was given in case of weight relapse more than 2.5%. Subjects could take Orlistat on a voluntary basis for special occasions. The BMI of completers remained stable (29.5 ± 0.9 vs. 30.6 ± 1.0 kg/m(2)). 73% of completers maintained 10% or more of their weight loss. Subjects from the no-regain group improved most of their parameters while the regain group did not. Insulin sensitivity was negatively linked to body weight during the follow up (p < 0.01, r(2) = 0.20). A negative relationship has been found between extent of the previous weight loss and the evolution of body weight during the 4 years follow-up (p < 0.01, r(2) = 0.26). Orlistat intake showed a body fat lowering effect (p < 0.05). 73% of subjects maintained more than 10% of their weight loss. Subject with a large weight loss amount are at high risk for weight regain. The Orlistat 'on/off' intake regarding his lowering body fat mass effect seems to be efficient.


A new perspective of the hippocampus in the origin of exercise-brain interactions.
Exercising regularly is a highly effective strategy for maintaining cognitive health throughout the lifespan. Over the last 20 years, many molecular, physiological and structural changes have been documented in response to aerobic exercise training in humans and animals, particularly in the hippocampus. However, how exercise produces such neurological changes remains elusive. A recent line of investigation has suggested that muscle-derived circulating factors cross into the brain and may be the key agents driving enhancement in synaptic plasticity and hippocampal neurogenesis from aerobic exercise. Alternatively, or concurrently, the signals might originate from within the brain itself. Physical activity also produces instantaneous and robust neuronal activation of the hippocampal formation and the generation of theta oscillations which are closely correlated with the force of movements. The repeated acute activation of the hippocampus during physical movement is likely critical for inducing the long-term neuroadaptations from exercise. Here we review the evidence which establishes the association between physical movement and hippocampal neuronal activation and discuss implications for long-term benefits of physical activity on brain function.


[Effect of deltamethrin on production of free radical and transcription factor Nrf2 in rats' brain tissue].
To explore the effect of deltamethrin (DM) on production of free radical and transcription factor Nrf2 in rats' brain tissue. 8 male rats were randomly assigned to four groups and administered with 1% W/W tertiary butylhydroquinone (tBHQ) or olive oil for 3 days, prior to exposure to DM and then with 12.50 mg or 0mg DM/Kg BW for 5 days. The level of free radical in rats' hippocampus tissue was detected by electron spin resonance (ESR) spectroscopy. 18 male rats were randomly assigned to three groups and administered with i.p. (daily dose was respectively 0, 3.13, 12.50 mg/kg DM) for five days. After treatment, Nrf2 protein levels in the cytoplasmic and nuclear fractions of both cerebral cortex and hippocampus tissue were measured by western blot. The level of free radical in hippocampus tissue of rats administered by DM and pretreatment with tBHQ prior to DM were increased to a 2.45-fold and 2.97-fold of values of control group, respectively (P < 0.05). Nrf2 protein levels in the cytoplasmic fractions of cerebral cortex of both low and high dose group were significantly increased, 1.68- fold and 1.34- fold of values of control group, respectively. Nrf2 protein levels in the nuclear fractions of cerebral cortex of both low and high dose group were increased in a dose- dependent model, 1.51-fold and 2.29-fold of values of control group, respectively (P < 0.01). Nrf2 protein levels in the cytoplasmic fractions of hippocampus tissue of both low and high dose group were increased in a dose- dependent model, 2.26-fold and 3.58-fold of values of control group, respectively. Nrf2 protein levels in the nuclear fractions of hippocampus tissue of both low and high dose group were increased, 2.42-fold and 2.45-fold of values of control group, respectively (P < 0.01). The studies in vivo demonstrate that DM treatment could induce free radical production and expression of Nrf2 protein in both cerebral cortex and hippocampus tissue and activate Nrf2.


Regulation of neurite extension by expression of LECT2 and neurotrophins based on findings in LECT2-knockout mice.
Leukocyte cell-derived chemotaxin 2 (LECT2) was first isolated as a chemotactic factor from phytohemagglutinin-activated human T-cell leukemia SKW-3 cells. LECT2 is expressed in various tissues, including in the brain, stomach and liver, but the functions of LECT2 in the brain remains unclear. To elucidate these functions, we investigated the influence of a deficiency of LECT2 on the morphology of cultured hippocampal neurons during neuronal development, and examined the expression of neurotrophins (NGF, BDNF, and NT-3) and their receptors (TrkA, TrkB, TrkC, and p75NTR) in these neurons. The extension of axons and dendrites in neurons from LECT2-knockout (LECT2-KO) mice was shorter than that in neurons from wild-type mice during culture and significantly less than that in wild-type mice after 4 days in culture. Moreover, neurons from LECT2-KO mice showed different expression of NGF, BDNF and NT-3 during culture compared to wild-type mice. Our results show that LECT2 regulates the extension of axons and dendrites and the expressions of NGF, BDNF and NT-3 during neuronal development.


Characterization of full-length HIV type 1 subtype C sequences from South Africa.
Four full-length genome subtype C sequences from South Africa, three of which are being used for vaccine development, were characterized. Three isolates were obtained from recently infected individuals in KwaZulu/Natal: Du151, Du422, and Du179. A fourth isolate, CTSc2, was obtained from an individual residing in Cape Town. All four strains used the CCR5 coreceptor, although Du179 also used CXCR4. The four isolates clustered within subtype C, but the three Du isolates formed a subcluster with a bootstrap value of 100%, with CTSc2 outside the subcluster. None of the strains showed evidence of intersubtype recombination, as expected from the predominance of subtype C in South Africa. All 4 isolates had a 16-amino acid truncation on the 3' end of the Rev protein, identified in other subtype C isolates. Like many other subtype C strains, Du151, Du422, and Du179 had three NF-kappa B-binding sites in the LTR; however, CTSc2 had only two.


Influence of the new immunosuppressive combinations on arterial hypertension after renal transplantation.
Arterial hypertension is highly prevalent after renal transplantation and may contribute to the risk of cardiovascular disease. Also, arterial hypertension has been reported to be an independent risk factor for graft failure. Immunosuppressive drugs such as corticosteroids, cyclosporine and tacrolimus may be important contributing factors to post-transplant hypertension. Recent data from multicenter trials and from conversion studies (cyclosporine to tacrolimus) suggest that renal transplant patients under tacrolimus-based therapy showed less arterial hypertension compared with cyclosporine treated patients. New immunosuppressive drugs, including mycophenolate mofetil and rapamycin, are not nephrotoxic and they do not have any hypertensive effect. New immunosuppressive combinations including mycophenolate mofetil in a triple therapy regimen (associated with corticosteroids and cyclosporine) can reduce blood pressure so that corticosteroids can be stopped or cyclosporine reduced or even eliminated. Non-nephrotoxic regimens using rapamycin (sirolimus) as basic immunosuppression, associated with azathioprine or mycophenolate mofetil, could reduce the incidence of post-transplant arterial hypertension. Also, in renal transplant patients initially immunosuppressed with rapamycin, cyclosporine and corticosteroids, after the elimination of CSA, a lower blood pressure is achieved. In summary, new protocols with mycophenolate mofetil and/or rapamycin may permit several combinations that offer important alternatives to classical immunosuppressive regimens to reduce the incidence and clinical impact of arterial hypertension after renal transplantation.


[More equity in Lazio region health care: results from the Regional Outcome Evaluation Program (PReValE), 2012-2017].
to evaluate equity in the Lazio regional Health System, both in terms of unequal access to health care among individuals with different educational levels and of heterogeneity in hospital performance, between 2012 and 2017. retrospective cohort study. all patients living in Lazio region and discharged from a regional facility between 2012 and 2017 were enrolled. Three cohorts of hospitalizations were selected: acute myocardial infarctions with ST segment elevation (STEMI), hip fractures, and deliveries. the proportions of STEMIs with PCI within 90 minutes, of patients with a hip fracture who underwent surgery within 2 days, and of deliveries with primary caesarean section were evaluated, accounting for patient demographic characteristics and comorbidities that could affect the outcome under study. These proportions were calculated by education and by hospital of admission. The heterogeneity among facilities was assessed through the median odds ratio (MOR). in Lazio region, between 2012 and 2017, an improvement of the quality of care was observed: in 2017, 50.4% of STEMI patients underwent to a PCI within 90 minutes, 54.4% of patients with a hip fracture underwent surgery within 2 days, and 26.2% of women had a C-section. In 2012, when comparing the adjusted proportions of outcomes by educational level, the probability of being treated with a PCI within 90 minutes for STEMIs and with surgery within 2 days for hip fractures was higher for graduated patients than for those with the lowest education. In contrast, graduated women had the highest risk of having a C-section. In 2017, there was no difference anymore between classes of education in STEMIs and C-sections, while in patients with hip fracture the difference was decreased, but still present. For hip fractures, a reduction of heterogeneity of hospital performances was also detected. in Lazio region, a reduction in inequalities in access to health care was observed for different clinical areas. The "public disclosure" of the PReValE results and the management strategy applied in mid-2013 could have driven the overall improvement of the health system for the conditions under study, helping to achieve a fairer access to health.


A novel nonsense mutation in RSPO4 gene underlies autosomal recessive congenital anonychia in a Pakistani family.
Congenital anonychia is an inherited autosomal recessive disorder characterized by complete absence of fingernails or toenails, or both. In the present study, we have described a consanguineous Pakistani family having a family member affected with congenital anonychia. Genotyping using polymorphic microsatellite markers showed linkage of the family to gene RSPO4 encoding R-spondin and mapped on human chromosome 20p13. Deoxyribonucleic acid sequence analysis of the gene identified a novel nonsense mutation (c.18C>A; p.Cys6X) in the affected family member.


Prognostic factors for overall survival in patients with metastatic renal cell carcinoma treated with vascular endothelial growth factor-targeted agents: results from a large, multicenter study.
There are no robust data on prognostic factors for overall survival (OS) in patients with metastatic renal cell carcinoma (RCC) treated with vascular endothelial growth factor (VEGF) -targeted therapy. Baseline characteristics and outcomes on 645 patients with anti-VEGF therapy-naïve metastatic RCC were collected from three US and four Canadian cancer centers. Cox proportional hazards regression, followed by bootstrap validation, was used to identify independent prognostic factors for OS. The median OS for the whole cohort was 22 months (95% CI, 20.2 to 26.5 months), and the median follow-up was 24.5 months. Overall, 396, 200, and 49 patients were treated with sunitinib, sorafenib, and bevacizumab, respectively. Four of the five adverse prognostic factors according to the Memorial Sloan-Kettering Cancer Center (MSKCC) were independent predictors of short survival: hemoglobin less than the lower limit of normal (P < .0001), corrected calcium greater than the upper limit of normal (ULN; P = .0006), Karnofsky performance status less than 80% (P < .0001), and time from diagnosis to treatment of less than 1 year (P = .01). In addition, neutrophils greater than the ULN (P < .0001) and platelets greater than the ULN (P = .01) were independent adverse prognostic factors. Patients were segregated into three risk categories: the favorable-risk group (no prognostic factors; n = 133), in which median OS (mOS) was not reached and 2-year OS (2y OS) was 75%; the intermediate-risk group (one or two prognostic factors; n = 301), in which mOS was 27 months and 2y OS was 53%; and the poor-risk group (three to six prognostic factors; n = 152), in which mOS was 8.8 months and 2y OS was 7% (log-rank P < .0001). The C-index was 0.73. This model validates components of the MSKCC model with the addition of platelet and neutrophil counts and can be incorporated into patient care and into clinical trials that use VEGF-targeted agents.


GALT protein database, a bioinformatics resource for the management and analysis of structural features of a galactosemia-related protein and its mutants.
We describe the GALT-Prot database and its related web-based application that have been developed to collect information about the structural and functional effects of mutations on the human enzyme galactose-1-phosphate uridyltransferase (GALT) involved in the genetic disease named galactosemia type I. Besides a list of missense mutations at gene and protein sequence levels, GALT-Prot reports the analysis results of mutant GALT structures. In addition to the structural information about the wild-type enzyme, the database also includes structures of over 100 single point mutants simulated by means of a computational procedure, and the analysis to each mutant was made with several bioinformatics programs in order to investigate the effect of the mutations. The web-based interface allows querying of the database, and several links are also provided in order to guarantee a high integration with other resources already present on the web. Moreover, the architecture of the database and the web application is flexible and can be easily adapted to store data related to other proteins with point mutations. GALT-Prot is freely available at http://bioinformatica.isa.cnr.it/GALT/.


Eating behaviors and attitudes in women with infertility: a controlled study.
Infertility arises from a complex pathogenic process in which it is often difficult to identify etiology. Psychological and behavioral factors may play a role in some cases of infertility. The extent to which eating behaviors and attitudes contribute to infertility is unknown. In this study, 120 subjects with infertility, 80 fertile women, and 90 patients suffering from anorexia nervosa, restricting subtype (AN-R), were assessed with the Eating Disorder Inventory (EDI-2). The EDI-2 highlights differences among patients with AN-R and fertile and infertile subjects. Infertile patients had higher scores on the Interpersonal Distrust, Interoceptive Awareness, and Maturity Fears EDI-2 subscales than fertile subjects. Logistic regression identifies the independent variables of interpersonal distrust, interoceptive awareness, maturity fears, and asceticism as predictors of infertility. Infertile patients without eating disorders share some psychological features of women with AN. These features do not include disturbed eating attitudes and behaviors, but rather feelings of inadequacy, insecurity, and maturity fears.


Micro-angiography for neuro-vascular imaging. II. Cascade model analysis.
A micro-angiographic detector was designed and its performance was previously tested to evaluate its feasibility as an improvement over current x-ray detectors for neuro-interventional imaging. The detector was shown to have a modulation transfer function value of about 2% at the Nyquist frequency of 10 cycles/mm and a zero frequency detective quantum efficiency [DQE(0)] value of about 55%. An assessment of the system was required to evaluate whether the current system was performing at its full potential and to determine if any of its components could be optimized to further improve the output. For the purpose, in this study, the parallel cascade theory was used to analyze the performance of the detector under neuro-angiographic conditions by studying the output at the various stages in the imaging chain. A simple model for the spread of light in the CsI(Tl) entrance phosphor was developed and the resolution degradation due to K-fluorescence absorption was calculated. The total gain of the system was found to result in 21 e(-) (rms) detected at the charge coupled device per absorbed x-ray photon. The gain and the spread of quanta in the imaging chain were used to calculate theoretically the DQE using the parallel cascade model. The results of the model-based calculations matched fairly well with the experimental data previously obtained. This model was then used to optimize the phosphor thickness for the detector. The results showed that the area under the DQE curve had a maximum value at 150 microm of CsI(Tl), though when weighted by the squared signal in frequency space of a 100-microm-diam iodinated vessel, the integral DQE reached a maximum at 250 microm of CsI(Tl). Further, possible locations for gain increase in the imaging chain were determined, and the output of the improved system was simulated. Thus a theoretical analysis for the micro-angiographic detector was performed to better assess its potential.


[Clinicopathological features and prognosis of hormone receptor-positive/human epidermal growth factor receptor 2-negative breast cancer].
To investigate the clinicopathological features and prognosis of hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2 -) breast cancer. In the study, 3 035 consecutive breast cancer patients diagnosed in Breast Disease Center, Peking University First Hospital from January 2008 to December 2017 were collected. The prognostic signi-ficance of important pathological factors in HR +/HER2 - patients with complete clinicopathological information was analyzed. Within the 1 920 (63.26%) cases of HR +/HER2 - breast cancer, there were 1 624 cases with complete clinicopathological data, of which, 124 cases (7.64%) recurred and/or metastasized and 63 cases died of the disease, and the 5-year overall survival (OS) rate and disease-free survival (DFS) rate was 93.0% and 92.6% respectively. The stage of pT1-2 was 92.80%, while pN0 was 69.03%. 89.66% cases belonged to histologically non-specific type and 30.11%, 55.60%, 14.29% were credited to Grade 1, 2 and 3 respectively. The distribution of ER negative, low or high expression groups were 1.60%, 2.09% and 96.31%, while PR were 6.83%, 10.47%, 82.70%, respectively. The group of Ki67 index < 10% was 19.52%, ≥10% & < 20% for 32.02%, ≥20% for 48.46%. Survival analysis showed that cases with pT1 stage had lower risk of recurrence than those with pT3, while cases with pT2 and pT3 had shorter DFS than those with pT1, with higher risk of recurrence and metastasis. Analysis proved that both pN stage and histological grade were negatively correlated with DFS. The cases with pN0, pN1 and pN2 were lower risk of recurrence than those with pN3, while cases with Grade 1 and 2 had lower risk of recurrence than cases with Grade 3. And the group of Ki67 index ≥20% showed higher risk of recurrence and metastasis. The prognostic significance of ER expression in HR+/HER2- breast cancer was not significant. However, the negative/low PR expression groups showed higher risk of recurrence and metastasis, of which PR < 10% group had shortest DFS and OS, followed by 10%-60% group and then > 60% group. The most common site of metastasis was bone (55 cases, 44.35%), while cases with liver metastasis (30 cases, 24.20%) had the worst outcome. Our study revealed that pT, pN, Grade, HR expression level and Ki67 index were important prognostic factors for HR +/HER2 - breast cancer, although there are variables in prognostic value. Factors of pN and Grade showed independent prognostic significance. PR expression level had prognostic significance for the risk of recurrence and metastasis. The stratified level of PR expression (< 10%, 10%-60%, >60%) had independent prognostic value, showing successively longer DFS and OS, lower risk of recurrence. PR>60% group had the longest DFS and OS as well as the lowest risk of recurrence.


Quantification of ischaemia induced vulnerability by precordial T wave alternans analysis in dog and human.
The aim was to examine the regional specificity of T wave alternans and the value of precordial ECG monitoring for non-invasive tracking of cardiac vulnerability during acute coronary artery occlusion and reperfusion in animals and humans. The left ventricular ECG was monitored during two acute occlusions of the left anterior descending coronary artery and subsequent reperfusion in each of 61 chloralose anaesthetised dogs, and over 150,000 beats were analysed. In subgroups of these animals, lead II and precordial lead V5 were monitored or epicardial electrograms were recorded. In seven patients, lead II and precordial leads V1-6 were monitored during angioplasty. T wave alternans magnitude was quantified by complex demodulation. The same recording equipment and analytical methods were used in the clinical and experimental studies. A close temporal correspondence and linear correlation was found between T wave alternans magnitude--but not ST segment depression or ventricular premature beat incidence--and the incidence of spontaneous ventricular tachycardia and fibrillation during acute coronary artery occlusion and reperfusion. Epicardial electrograms showed alternans to be regionally specific, occurring in the ischaemic but not in the normal zones, and to predict spontaneous ventricular fibrillation and ventricular tachycardia (sensitivity = 79%, specificity = 86%). A significant linear relationship (r2 = 0.86, p < 0.01) between alternans magnitude detected in V5 and the left ventricular intracavitary lead indicates that the precordial leads could be used to assess cardiac vulnerability from the body surface. Lead V5 showed greater resolution than lead II. In humans, the precordial leads overlying the ischaemic zone were superior to lead II or Frank leads for alternans detection during both the occlusion and the reperfusion phases. In both animals and humans, alternation invariably occurred during the first half of the T wave, coinciding with the vulnerable period of the cardiac cycle and suggesting an important electrophysiological link to cardiac vulnerability. Alternans is regionally specific and is linearly projected to the precordium. Quantification of its magnitude in the precordial ECG may provide a non-invasive means for tracking cardiac vulnerability during acute myocardial ischaemia and reperfusion in both animals and humans.


[What is new in pediatric neurology?].
Some significant advances in the field of pediatric neurology are reviewed. For many constitutional disorders, concepts and diagnostic procedures have progressed from various genetic techniques or from protein labeling in situ. Many neurodegenerative disorders, some poorly-defined metabolic diseases, and several syndromes associating mental retardation with neurologic or extraneurologic malformations have been characterized. In addition, for many disorders viewed as 'poorly specific' (mental retardation, epilepsy, migraine), familial forms have permitted us to define the first genes involved. In 'acquired' disorders, new data come from clinical trials (antiepileptic, anti-inflammatory drugs) rather than definite conceptual advances. Finally, clinics and biology are no longer the only approaches to brain functions, and clinical neurophysiology could encounter a second wind thanks to the techniques of functional imaging, especially in the fields of developmental neuropsychology.


Charge Transfer in Nanowire-Embedded PEDOT:PSS and Planar Heterojunction Solar Cells.
Hybrid metallic nanowire-embedded, highly conductive poly(3,4-ethylenedioxy thiophene):polystyrenesulfonate (PEDOT:PSS) with synergetic properties is indispensable for enhancing the performances of conductive polymer-based electronic devices. Here, we report embedment of silver nanowires (AgNWs), with diameter ∼100 nm and a high concentration (500 mg/mL) of nanowires dispersed in either ethanol or isopropanol, in PEDOT:PSS and compare the effects of the nanowire-dispersing solvents as well as its thicker diameter and high concentration on the overall properties and particularly its charge transfer characteristics and planar heterojunction solar cell (HSC) properties. Furthermore, electrostatic force microscopy is applied to elucidate the direct charge transfer from AgNWs to the PEDOT:PSS matrix. The AgNW-embedded PEDOT:PSS-based planar HSCs show a very high open-circuit voltage of over 638 mV and a high power conversion efficiency greater than 15.3% and without any significant influence from the AgNW dispersing solvents. While charge transfer in PEDOT:PSS without AgNWs occurs through the conducting PEDOT grains, enhanced charge transfer is realized in AgNW-embedded PEDOT:PSS with charge transport from PEDOT grains to AgNWs and then to PEDOT grains before reaching the top electrode in the HSC. The AgNW-embedded PEDOT:PSS hybrid materials pave a simple way to enhance the charge transfer performance in not only HSCs but also other hybrid or heterojunction electronics.


Murine high-fat diet and laser photochemical model of basal deposits in Bruch membrane.
To examine the histologic, histochemical, and ultrastructural changes in Bruch membrane in mice on a high-fat diet with and without laser photochemical injury. Five groups of C57BL/6 mice were studied. Group 1 included 2-month-old mice on a normal diet; group 2 included 8-month-old mice on a normal diet; group 3 included 8-month-old mice on a high-fat diet; groups 4 and 5 included 8-month-old mice on a normal diet or high-fat diet, respectively, that underwent laser application of one eye with argon blue laser (488 nm). The mice were killed and plasma lipid levels were measured. The eyes were examined by standard electron microscopy, filipin histochemistry for unesterified cholesterol (UC) and esterified cholesterol (EC), and the osmium-tannic acid-phenylenediamine method for preserving extracellular lipid particles. The plasma cholesterol level was significantly higher in the mice on the high-fat diet than the controls (P<.001). Bruch membrane was thicker in group 2 than group 1 (P =.04) and group 3 had a thicker Bruch membrane than group 2 (P =.003). All eyes in group 3 exhibited accumulation of electron-lucent debris. There was no histochemical and ultrastructural evidence that this material represented accumulated UC or EC. Seven of 9 laser-injured eyes in group 5 accumulated basal laminar deposit (BlamD)-like material in Bruch membrane (P =.02). Electron-lucent debris accumulates in murine Bruch membrane, and the amount correlates with age and high-fat diet. This debris has some similarities with basal linear deposits, although the debris does not form a discrete layer external to the basement membrane of the retinal pigment epithelium as occurs in basal linear deposits. These deposits do not appear to be UC or EC. Laser photochemical injury of the retinal pigment epithelium may result in the appearance of BlamD-like deposits in eyes with electron-lucent debris. The BlamD-like deposits in this model are similar to the basal laminar deposits that occur in age-related macular degeneration. This is an animal model of ultrastructural BlamD-like material in Bruch membrane that is very similar to the deposits that occur in age-related macular degeneration.


Recent advances of aminoazanium salts as amination reagents in organic synthesis.
Nitrogen-containing organic compounds are widely distributed in natural products, pharmaceuticals, and functional materials. Several methods have been reported for the construction of the C-N bond including the Curtius rearrangement, the Schmidt rearrangement, the Ullmann reaction, etc. Various sources of amines have been developed, among which the aminoazanium salt is a unique amine precursor because of its high operability, diversity of structures and diverse reaction modes. This review describes the synthesis of aminoazanium salts and discusses the relationship between their structure and reaction mode, in addition to highlighting the amination reactions using aminoazanium salts.


Biochemical properties of N-methylamides of sialic acids in gangliosides.
A simple and rapid method for the preparation of N-methylamides ( - CONHCH3) of sialic acids in gangliosides and biochemical properties of the modified gangliosides are described. The sialic acid carboxyl groups of gangliosides were esterified with CH3I-dimethylsulfoxide, followed by heating with monomethylamine. The modified gangliosides were chemically identified by TLC, IR spectroscopy, GLC-mass spectrometry and NMR spectroscopy. The N-methylamide derivative of GM1 produced a high titer IgG antibody. The antibody weakly cross-reacted with the methylester of GM1 and its reductive derivative but did not react with the intact GM1. A monoclonal antibody (M2590) specific for GM3 did not react with carboxyl-modified GM3 (methylester, N-methylamide, and reduced GM3), but it reacted with modified GM3 which contains the C7-analog of the sialic acid. Clostridium perfringens and Arthrobacter ureafaciens sialidases did not hydrolyze the N-methylamide derivatives, methylesters or reductive derivatives of the gangliosides and, furthermore, these derivatives did not inhibit the actions of these sialidases.


Nanoparticle-Based Magnetorheological Elastomers with Enhanced Mechanical Deflection for Haptic Displays.
Haptics allows tactile interactions between humans and digital interfaces. Magnetorheological elastomers (MREs) constitute a promising candidate material for creating the tactile interface of the future─one able to recreate 3D shapes that can be sensed with touch. Furthermore, an MRE formed by using nanoparticles, as opposed to previously used microparticles, is necessary to generate a variety of shapes involving sharp curvatures over small, micrometer-scale horizontal distances to pave the way for haptic displays with microtexture resolution. Here we fabricated both isotropic and anisotropic MREs with different concentrations (2-8 vol % nanoparticles) of soft, low-remanence ferromagnetic nanoparticles. When placed in a magnetic field gradient, isotropic MREs, nonintuitively, show higher deflection than anisotropic MREs, with the former achieving displacement on the order of a millimeter at just 100 mT. This enhanced performance in the isotropic case is explained based on the soft magnetic nature of the nanoparticles. We show that performance improves with magnetic content up to a composition of 6 vol %, where it plateaus. This behavior is attributed to the stiffness of the composite material increasing at a faster rate than the magnetization as the rigid magnetic nanoparticles are added to the elastomeric matrix. Moreover, 6 vol % microparticle-based isotropic and anisotropic MREs were fabricated and compared with the nanoparticle-based MREs. Anisotropic nanoparticle-based films show higher deflection when compared with their microparticle-based counterparts. The latter is only able to match the nanoparticle film deflection at higher applied fields of almost 300 mT. This performance difference between nanoparticle and microparticle-based films is attributed to the increased anisotropic film stiffness resulting from the larger micrometer-size particles. Finally, the optimally designed nanoparticle-based isotropic film was utilized to create a programmable and real-time reconfigurable braille-inspired interface.


Functional Analysis of Brain Imaging Suggests Changes in the Availability of mGluR5 and Altered Connectivity in the Cerebral Cortex of Long-Term Abstaining Males with Alcohol Dependence: A Preliminary Study.
Direct in vivo evidence of altered metabotropic glutamate receptor-5 (mGluR5) availability in alcohol-related disorders is lacking. We performed [11C]ABP688 positron emission tomography (PET) and resting-state functional magnetic resonance imaging (rs-fMRI) in prolonged abstinent subjects with alcohol dependence to examine alterations of mGluR5 availability, and to investigate their functional significance relating to neural systems-level changes. Twelve prolonged abstinent male subjects with alcohol dependence (median abstinence duration: six months) and ten healthy male controls underwent [11C]ABP688 PET imaging and 3-Tesla MRI. For mGluR5 availability, binding potential (BPND) was calculated using the simplified reference tissue model with cerebellar gray matter as the reference region. The initial region-of-interest (ROI)-based analysis yielded no significant group differences in mGluR5 availability. The voxel-based analysis revealed significantly lower [11C]ABP688 BPND in the middle temporal and inferior parietal cortices, and higher BPND in the superior temporal cortex in the alcohol dependence group compared with controls. Functional connectivity analysis of the rs-fMRI data employed seed regions identified from the quantitative [11C]ABP688 PET analysis, which revealed significantly altered functional connectivity from the inferior parietal cortex seed to the occipital pole and dorsal visual cortex in the alcohol dependence group compared with the control group. To our knowledge, this is the first report on the combined analysis of mGluR5 PET imaging and rs-fMRI in subjects with alcohol dependence. These preliminary results suggest the possibility of region-specific alterations of mGluR5 availability in vivo and related functional connectivity perturbations in prolonged abstinent subjects.


Exercise training improves neurovascular control and functional capacity in heart failure patients regardless of age.
Exercise training is a non-pharmacological strategy for treatment of heart failure. Exercise training improves functional capacity and quality of life in patients. Moreover, exercise training reduces muscle sympathetic nerve activity (MSNA) and peripheral vasoconstriction. However, most of these studies have been conducted in middle-aged patients. Thus, the effects of exercise training in older patients are much less understood. The present study was undertaken to investigate whether exercise training improves functional capacity, muscular sympathetic activation and muscular blood flow in older heart failure patients, as it does in middle-aged heart failure patients. Fifty-two consecutive outpatients with heart failure from the database of the Unit of Cardiovascular Rehabilitation and Physiology Exercise were divided by age (middle-aged, defined as 45-59 years, and older, defined as 60-75 years) and exercise status (trained and untrained). MSNA was recorded directly from the peroneal nerve using the microneurography technique. Forearm blood flow (FBF) was measured by venous occlusion plethysmography. Functional capacity was evaluated by cardiopulmonary exercise test. Exercise training significantly and similarly increased FBF and peak VO(2) in middle-aged and older heart failure patients. In addition, exercise training significantly and similarly reduced MSNA and forearm vascular resistance in these patients. No significant changes were found in untrained patients. Exercise training improves neurovascular control and functional capacity in heart failure patients regardless of age.


Relationship between histologic features, DNA flow cytometry, and clinical behavior of squamous cell carcinomas of the larynx.
Flow cytometric analysis of DNA content was done on 133 primary squamous cell carcinomas of the larynx. Overall, 76 tumors (57.1%) were not diploid (aneuploid or tetraploid). The DNA index (DI) was calculated and grouped into three levels. Fifty-seven cases had a DI in a range of 1.85 to 2.15 (44 diploid and 13 tetraploid). The cases were grouped in relation to ploidy, proliferative index, and the tumor-node-metastasis (TNM) system. Every group was analyzed with respect to survival rate. Ploidy was related to histocytologic grade. In well-differentiated tumors (G1) survival rates at 48 months were 41.7% in diploid cases and 27.7% in nondiploid ones (relative risk [RR], 2.01; 95% confidence interval [CI], 0.89, 4.52). In NO cases that underwent surgery, survival rates at 48 months were, respectively, 81.8% and 49.2% (RR, 5.07; 95% CI, 0.76, 33.93). These results suggest that ploidy may be a new independent parameter of prognosis in squamous cell carcinoma of the larynx. This is useful in clinical practice because it allows the clinician to recognize those cases with poorer prognosis among the early tumors at a stage where other prognostic parameters are not yet available.


Novel expansion/shrinkage modulation of 2D layered MOF triggered by clathrate formation with CO(2) molecules.
Crystal-to-crystal transformation from a 3D interpenetrated-type MOF {[Cu(BF(4))(2)(bpy)(H(2)O)(2)] (bpy)} (1) to a 2D square-grid-type [Cu(BF(4))(2)(bpy)(2)] (2) (bpy = 4,4'-bipyridine) was observed. It was derived from dehydration and confirmed by in situ FT-IR, TG, and elemental analysis. Moreover, we elucidate the novel expansion/shrinkage dynamic modulation of 2 triggered by clathrate formation with gas molecules.


Platelet-Rich Plasma Gel-Loaded Collagen/Chitosan Composite Film Accelerated Rat Sciatic Nerve Injury Repair.
Peripheral nerve injury (PNI) is a common clinical disease caused by severe limb trauma, congenital malformations, and tumor resection, which may lead to significant functional impairment and permanent disability. Nerve conduit as a method for treating peripheral nerve injury shows good application prospects. In this work, the COL/CS composite films with different mass ratios of 1:0, 1:1, and 1:3 were fabricated by combining physical doping. Physicochemical characterization results showed that the COL/CS composite films possessed good swelling properties, ideal mechanical properties, degradability and suitable hydrophilicity, which could meet the requirements of nerve tissue engineering. In vitro cell experiments showed that the loading of platelet-rich plasma (PRP) gel on the surface of COL/CS composite films could significantly improve the biocompatibility of films and promote the proliferation of Schwann cells. In addition, a rat model of sciatic nerve defect was constructed to evaluate the effect of COL/CS composite films on peripheral nerve repair and the results showed that COL/CS composite films loaded with PRP gel could promote nerve regeneration and functional recovery in rats with sciatic nerve injury, indicating that the combination of PRP gel with the COL/CS composite film would be a potential approach for the treatment of peripheral nerve injury.


The genotype CC of IL-28B SNP rs12979860 is significantly associated with a sustained virological response in chronic HCV-infected Pakistani patients.
To evaluate the association of genetic variation in interleukin 28B (IL-28B) gene and viral factors with treatment outcome in chronic hepatitis C virus (HCV)-infected patients in Pakistan. Patients with chronic HCV infection who received interferon plus ribavirin combination therapy were enrolled in the study. The viral loads were checked at the third and sixth month of treatment and 6 months after the completion of the treatment. Genotyping of single-nucleotide polymorphism (SNP) rs12979860 of IL-28B gene was performed by the restriction fragment length polymorphism method and direct sequence analysis. A total of 111 patients successfully completed antiviral therapy and the follow-up period. Early virological response (EVR) and a sustained virological response (SVR) were achieved in 92 and 91 patients, respectively. Patients infected with HCV genotype 3a had a higher SVR rate compared with other HCV genotypes. A higher C allele frequency (81.9%) was observed in patients with SVR than those with non-SVR (P = 0.00001). The odds ratio of achieving SVR was more than 10-fold greater for the CC genotype than the CT/TT genotypes of SNP rs12979860 (OR 10.351, 95% CI 1.925-55.653, P = 0.006). Other positive predictors observed for SVR were female gender and EVR. The CC genotype of IL-28B SNP rs12979860 is an independent predictive factor for SVR in chronic HCV-infected patients in Pakistan.


Case reports. Transient colonization with Scedosporium prolificans. Report of four cases in Madrid.
Four cases of transient colonization of the respiratory tract by Scedosporium prolificans are presented, two in patients with cystic fibrosis, one in a liver transplant patient and one in a patient with AIDS. Colonization versus infection by S. prolificans is discussed.


Skin test reactivity in infancy.
Skin tests represent a major tool in the diagnosis of reaginic allergy; however, their interpretation does not appear to be without difficulty in children under the age of 3 yr. Seventy-eight infants from birth to 24 mo were prick tested and compared with 30 nonallergic adult subjects. Skin tests were performed without bleeding by use of two strengths of histamine hydrochloride (1 and 10 mg/ml), a mast cell degranulating agent (codeine phosphate, 50 mg/ml), and allergenic extracts. Negative control solution elicited a small wheal (less than 1.5 mm) in two infants who were excluded from further results. A clear and significant (p less than 0.001) hyporeactivity to both histamine and codeine phosphate was observed in infancy, especially before the age of 6 mo. Six infants were allergic and presented positive prick tests to either food or inhalant allergens. These tests were confirmed by serum specific IgE and a suggestive clinical history. The size of the allergen-induced prick test wheal ranged from 2 to 5 mm in diameter, suggesting that prick test wheals may be smaller in infants. This study confirms that prick tests can be performed and interpreted without difficulty in infants, keeping in mind the small wheal size induced by both positive control solutions and allergen-induced prick tests.


The amniotic fluid as a source of neural stem cells in the setting of experimental neural tube defects.
We sought to determine whether neural stem cells (NSCs) can be isolated from the amniotic fluid in the setting of neural tube defects (NTDs), as a prerequisite for eventual autologous perinatal therapies. Pregnant Sprague-Dawley dams (n=62) were divided into experimental (n=42) and control (n=20) groups, depending on prenatal exposure to retinoic acid for the induction of fetal NTDs. Animals were killed before term for analysis (n=685 fetuses). Amniotic fluid samples from both groups underwent epigenetic selection for NSCs, followed by exposure to neural differentiation media. Representative cell samples underwent multiple morphological and phenotypical analyses at different time points. No control fetus (n=267) had any structural abnormality, whereas at least one type of NTD developed in 52% (217/418) of the experimental fetuses (namely, isolated spina bifida, n=144; isolated exencephaly, n=24; or a combination of the two, n=49). Only amniotic samples from fetuses with a NTD yielded cells with typical neural progenitor morphology and robust expression of both Nestin and Sox-2, primary markers of NSCs. These cells responded to differentiation media by displaying typical morphological changes, along with expression of beta-tubulin III, glial fibrillary acidic protein, and/or O4, markers for immature neurons, astrocytes, and oligodendrocytes, respectively. This was concurrent with downregulation of Nestin and Sox-2. We conclude that the amniotic fluid can harbor disease-specific stem cells, for example, NSCs in the setting of experimental NTDs. The amniotic fluid may be a practical source of autologous NSCs applicable to novel forms of therapies for spina bifida.


PALEONTOLOGY: Biggest Extinction Hit Land and Sea.
Two hundred and fifty million years ago, at the end of the Permian period and the opening of the Triassic, 85% of the species in the sea vanished in a geologic moment of less than half a million years. Now from South Africa comes evidence that the Permian-Triassic extinction of land plants was equally brutal and swift. In a paper on page 1740 of this issue of Science, researchers report that rocks that started as sediments laid down in South Africa's Karoo Basin 250 million years ago tell of an abrupt switch in style of sedimentation, as if the land had been permanently stripped of the rooted plants that held it in place. But in the absence of any trace of an impact, researchers are groping for an equally far-reaching explanation.


Identification and functional analysis of the doublesex gene in the sexual development of a hemimetabolous insect, the brown planthopper.
In the sex determination cascade, the genes dsx (doublesex) in insects, mab-3 (male abnormal 3) in nematodes, and Dmrt1 (dsx/mab-3 related transcription factor-1) in vertebrates act as the base molecular switches and play important roles. Moreover, these genes share the same conserved feature domain-DNA-binding oligomerization domain (OD1), and female-specific dsx also has a conserved oligomerization domain 2 (OD2). Although sex determination and the functions of dsx in several holometabolous insects have been well documented, sex determination and the function of dsx in hemimetabolous insects remain a mystery. In this study, four dsx homologs were unexpectedly found in the Nilaparvata lugens (brown planthopper, BPH, order Hemiptera), which also showed a different evolutionary status. We found that only one of the four homologs, Nldsx, which has three alternative splicing variants (female-specific NldsxF, male-specific NldsxM, non-sex-specific NldsxC), was required in the sexual development of N. lugens. Compared with that of holometabolous species, the dsx of N. lugens contains a less conserved OD1, while the OD2 domain of BPH was not identifiable because the common region is poorly conserved, and the female-specific region is short. RNAi-mediated knockdown of Nldsx in female BPH resulted in a larger body size with a normal abdomen and reproductive system, while no changes in fertility were noted. However, adult males with RNA interference knockdown of NldsxM in nymphs became pseudofemales, were infertile, had abnormal copulatory organs, and had impassable deferent ducts with hyperplastic walls; additionally, the pseudofemales could not produce the normal courtship signals. Our results suggest that dsx plays a critical role in male BPH somatic development and mating behavior. This is the first study to show that dsx is essential for sexual development in a hemipteran species.