History of childhood physical abuse is associated with gut microbiota diversity among adult psychiatric inpatients.
Traumatic life events are associated with the development of psychiatric and chronic medical illnesses. This exploratory study examined the relationship between traumatic life events and the gut microbiota among adult psychiatric inpatients. 105 adult psychiatric inpatients provided clinical data and a single fecal sample shortly after admission. A modified version of the Stressful Life Events Screening Questionnaire was used to quantify history of traumatic life events. 16S rRNA gene sequencing was used to analyze the gut microbial community. Gut microbiota diversity was not associated with overall trauma score or any of the three trauma factor scores. Upon item-level analysis, history of childhood physical abuse was uniquely associated with beta diversity. Linear Discriminant Analysis Effect Size (LefSe) analyses revealed that childhood physical abuse was associated with abundance of distinct bacterial taxa associated with inflammation. This study did not account for dietary differences, though diet was highly restricted as all participants were psychiatric inpatients. Absolute variance accounted for by the taxa was small though practically meaningful. The study was not powered for full subgroup analysis based on race and ethnicity. This study is among the first to demonstrate a relationship between childhood physical abuse and gut microbiota composition among adult psychiatric patients. These findings suggest that early childhood adverse events may have long-conferred systemic consequences. Future efforts may target the gut microbiota for the prevention and/or treatment of psychiatric and medical risk associated with traumatic life events.


The human synovial fluid proteome: A key factor in the pathology of joint disease.
This review aims to summarise our knowledge to date on the protein complement of the synovial fluid (SF). The tissues, structure and pathophysiology of the synovial joint are briefly described. The salient features of the SF proteome, how it is composed and the influence of arthritic disease are highlighted and discussed. The concentrations of proteins that have been detected and quantified in SF are drawn together from the literature on osteoarthritis, rheumatoid arthritis and juvenile idiopathic arthritis. The measurements are plotted to give a perspective on the dynamic range of protein levels within the SF. Approaches to proteomic analysis of SF to date are discussed along with their findings. From the recent literature reviewed within, it is becoming increasingly clear that analysis of the SF proteome as a whole, could deliver the most valuable differential diagnostic fingerprints of a number of arthritic disorders. Further development of proteomic platforms could characterise prognostic profiles to improve the clinician's ability to resolve unremitting disease by existing and novel therapeutics.


Reactions of Group 4 metallocene complexes with mono- and diphenylacetonitrile: formation of unusual four- and six-membered metallacycles.
Reactions of Group 4 metallocene alkyne complexes [Cp'2M(η(2)-Me3SiC2SiMe3)] (1: M = Zr, Cp' = Cp* = η(5)-pentamethylcyclopentadienyl; 2 a: M = Ti, Cp' = Cp*, and 2 b: M = Ti, Cp'2 = rac-(ebthi) = rac-1,2-ethylene-1,1'-bis(η(5)-tetrahydroindenyl)) with diphenylacetonitrile (Ph2CHCN) and of the seven-membered zirconacyclocumulene 3 with phenylacetonitrile (PhCH2CN) were investigated. Different compounds were obtained depending on the metal, the cyclopentadienyl ligand and the reaction temperature. In the first step, Ph2CHCN coordinated to 1 to form [Cp*2Zr(η(2)-Me3SiC2SiMe3)(NCCHPh2)] (4). Higher temperatures led to elimination of the alkyne, coordination of a second Ph2CHCN and transformation of the nitriles to a keteniminate and an imine ligand in [Cp*2Zr(NC2Ph2)(NCHCHPh2)] (5). The conversion of 4 to 5 was monitored by using (1)H NMR spectroscopy. The analogue titanocene complex 2 a eliminated the alkyne first, which led directly to [Cp*2Ti(NC2Ph2)2] (6) with two keteniminate ligands. In contrast, the reaction of 2 b with diphenylacetonitrile involved a formal coupling of the nitriles to obtain the unusual four-membered titanacycle 7. An unexpected six-membered fused zirconaheterocycle (8) resulted from the reaction of 3 with PhCH2CN. The molecular structures of complexes 4, 5, 6, 7 and 8 were determined by X-ray crystallography.


Cytogenetics and molecular genetics of carcinomas arising from thyroid epithelial follicular cells.
Cytogenetic and molecular analyses of thyroid tumors have indicated that these neoplasms represent a good model for analyzing human epithelial cell multistep carcinogenesis. They comprise, in fact, a broad spectrum of lesions with different phenotypes and variable biological and clinical behavior. Molecular analysis has detected specific genetic alterations in the different types of thyroid tumors. In particular, the well-differentiated carcinomas of the papillary type are characterized by activation of the receptor tyrosine kinases (RTKs), RET and NTRK1 proto-oncogenes. Cytogenetic analysis of these tumors has contributed to defining the chromosomal mechanisms leading to RTK oncogenic activation. In the majority of cases, intrachromosomal inversions of chromosome 10 and chromosome 1 led to the formation of RET-derived and NTRK1-derived oncogenes, respectively. Interestingly, molecular analysis of these oncogenes revealed their nature of chimeric fusion proteins all sharing the tyrosine kinase (TK) domains of the respective proto-oncogenes. Moreover, the sequencing of the oncogenic rearrangements led to the identification of a breakpoint cluster region in both RTK proto-oncogenes. Exposure to ionizing radiation is associated with papillary carcinomas and RET activation has been suggested to be related to this event. Conversely, RAS point mutations are frequently observed in tumors with follicular histology and have been associated with metastatic dissemination. Iodide-deficient areas seem to provide a higher frequency of RAS positive follicular carcinomas. Finally, a high prevalence of TPS3 point mutations has been detected only in undifferentiated or anaplastic carcinomas and found to correlate inversely with 8CL2 expression. All of these findings are contributing to the definition of genetic and environmental factors relevant for the pathogenesis of thyroid tumors. Moreover, the characterization of specific genetic lesions could provide significant molecular tools for a better differential diagnosis and for the development of novel therapeutic avenues for thyroid cancer.


Impaired neutrophil function in patients with AIDS or AIDS-related complex: a comprehensive evaluation.
We measured the neutrophil function of 6 patients with AIDS and Kaposi's sarcoma (KS); 22 patients with AIDS-related complex (ARC); and 28 healthy, heterosexual controls. Neutrophils from patients with ARC showed significantly less chemotaxis (P less than or equal to .025) than did those from patients with AIDS and KS or from controls. Serum from patients with AIDS and KS or with ARC significantly (P less than or equal to .05) inhibited chemotaxis of neutrophils from controls; heat treatment of the serum abolished this inhibitory effect. Bacterial killing by neutrophils from patients with AIDS and KS or with ARC was also significantly (P less than or equal to .05) less than for neutrophils from controls, as was neutrophil phagocytosis binding of Candida albicans (P less than or equal to .05). Expression of OKM1 antigen was increased in the patients studied. Enzyme degranulation, adherence, and aggregation were also examined. The defects found in neutrophil function are selective and may be important in the increased susceptibility of patients with human immunodeficiency virus infection to bacterial and fungal infections.


Markers for characterization of bone marrow multipotential stromal cells.
Given the observed efficacy of culture-expanded multipotential stromal cells, also termed mesenchymal stem cells (MSCs), in the treatment of graft-versus host and cardiac disease, it remains surprising that purity and potency characterization of manufactured cell batches remains rather basic. In this paper, we will initially discuss surface and molecular markers that were proposed to serve as the indicators of the MSC potency, in terms of their proliferative potential or the ability to differentiate into desired lineages. The second part of this paper will be dedicated to a critical discussion of surface markers of uncultured (i.e., native) bone marrow (BM) MSCs. Although no formal consensus has yet been reached on which markers may be best suited for prospective BM MSC isolation, markers that cross-react with MSCs of animal models (such as CD271 and W8-B2/MSCA-1) may have the strongest translational value. Whereas small animal models are needed to discover the in vivo function on these markers, large animal models are required for safety and efficacy testing of isolated MSCs, particularly in the field of bone and cartilage tissue engineering.


Commentary: a call for culture change in academic medicine.
Disappointed by the lack of progress in the advancement of women and underrepresented minority faculty to senior positions and leadership roles in academic medicine and concerned by the prospect that these valuable faculty resources were being lost, a group of five medical school deans agreed to embark on a multiyear project to change the culture of their medical schools for these underrepresented faculty. This commentary outlines the rationale and motivation for the project and sets the stage for future reports from and wider participation in this initiative.


Trypsin adsorption by Hymenolepis diminuta (Cestoda).
Significant amounts of radioactivity were associated with Hymenolepis diminuta following incubation in 3H-trypsin. Autoradiography of worms incubated in 3H-trypsin for 30 min demonstrated that all radioactivity was associated with the worm's surface (tegument). The amount of 3H-trypsin adsorbed by the worms was not sufficient to account for the inactivation of this enzyme in the presence of intact worms. Unlabeled trypsin and poly-L-glutamate (but not poly-L-lysine) inhibited adsorption of 3H-trypsin, but were without effect on trypsin inactivation by H. diminuta. Therefore, trypsin was adsorbed by intact H. diminuta, but the process of adsorption apparently did not play any role in inactivation of the enzyme.


Portable forced oscillation device for point-of-care pulmonary function testing.
The forced oscillation technique (FOT) provides a simple and accurate approach for pulmonary function testing. However, most current devices are large and high cost, hence the test remains sparingly used. To address this problem, we verified the feasibility of a smart and portable forced oscillation device based on a small subwoofer and ultrasonic sensor that is targeted at point-of-care pulmonary function testing. In this paper, we first develop and optimize the signal processing algorithm for impedance estimation. Then we characterize the signal quality of programmable oscillatory waveforms with varying frequency, amplitude and duration. Finally, we evaluate the performance of the device against both mechanical models and human subjects. The results show that the coherence function is above 0.9 for all frequencies and the measurement error is less than 10%. The device yields good repeatability and satisfies the clinical diagnostic requirements.


Investigation into the effect of infrastructure on fly-in fly-out mining workers.
To explore fly-in fly-out (FIFO) mining workers' attitudes towards the leisure time they spend in mining camps, the recreational and social aspects of mining camp culture, the camps' communal and recreational infrastructure and activities, and implications for health. In-depth semistructured interviews. Individual interviews at locations convenient for each participant. A total of seven participants, one female and six males. The age group varied within 20-59 years. Marital status varied across participants. A qualitative approach was used to interview participants, with responses thematically analysed. Findings highlight how the recreational infrastructure and activities at mining camps impact participants' enjoyment of the camps and their feelings of community and social inclusion. Three main areas of need were identified in the interviews, as follows: (i) on-site facilities and activities; (ii) the role of infrastructure in facilitating a sense of community; and (iii) barriers to social interaction. Recreational infrastructure and activities enhance the experience of FIFO workers at mining camps. The availability of quality recreational facilities helps promote social interaction, provides for greater social inclusion and improves the experience of mining camps for their temporary FIFO residents. The infrastructure also needs to allow for privacy and individual recreational activities, which participants identified as important emotional needs. Developing appropriate recreational infrastructure at mining camps would enhance social interactions among FIFO workers, improve their well-being and foster a sense of community. Introducing infrastructure to promote social and recreational activities could also reduce alcohol-related social exclusion.


Diurnal microstructural variations in healthy adult brain revealed by diffusion tensor imaging.
Biorhythm is a fundamental property of human physiology. Changes in the extracellular space induced by cell swelling in response to the neural activity enable the in vivo characterization of cerebral microstructure by measuring the water diffusivity using diffusion tensor imaging (DTI). To study the diurnal microstructural alterations of human brain, fifteen right-handed healthy adult subjects were recruited for DTI studies in two repeated sessions (8∶30 AM and 8∶30 PM) within a 24-hour interval. Fractional anisotropy (FA), apparent diffusion coefficient (ADC), axial (λ//) and radial diffusivity (λ⊥) were compared pixel by pixel between the sessions for each subject. Significant increased morning measurements in FA, ADC, λ// and λ⊥ were seen in a wide range of brain areas involving frontal, parietal, temporal and occipital lobes. Prominent evening dominant λ⊥ (18.58%) was detected in the right inferior temporal and ventral fusiform gyri. AM-PM variation of λ⊥ was substantially left side hemisphere dominant (p<0.05), while no hemispheric preference was observed for the same analysis for ADC (p = 0.77), λ// (p = 0.08) or FA (p = 0.25). The percentage change of ADC, λ//, λ⊥, and FA were 1.59%, 2.15%, 1.20% and 2.84%, respectively, for brain areas without diurnal diffusivity contrast. Microstructural variations may function as the substrates of the phasic neural activities in correspondence to the environment adaptation in a light-dark cycle. This research provided a baseline for researches in neuroscience, sleep medicine, psychological and psychiatric disorders, and necessitates that diurnal effect should be taken into account in following up studies using diffusion tensor quantities.


[Strontium-89 for bone metastases from prostate cancer: an update].
Strontium-89 (Sr-89) is a pure emitter with maximum beta energy of 1.46 MeV, average beta energy of 0.58 MeV, and a physical half-life of 50.5 days. It is rapidly taken up by bone and preferentially retained at the sites of osseous metastases. Its biological half-life is >50 days at the metastatic sites, but about 14 days only in the normal bone. The dose of its absorption in the tumor-bearing bone ranges from 21 +/- 4 to 231 +/- 56 cGy/MBq, 2-25 times higher than in the normal bone. Strontium-89 therapy is an effective palliative treatment of bone metastases from prostate cancer, with analgesic effectiveness in 80%.


Association Between Fibroblast Growth Factor Receptor 1 Gene Amplification and Human Papillomavirus Prevalence in Tonsillar Squamous Cell Carcinoma With Clinicopathologic Analysis.
Amplification of fibroblast growth factor receptor 1 ( FGFR1) has been reported in many squamous cell carcinomas, and human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma has been characterized as a distinct subset with favorable prognosis. Here, we investigated the FGFR1 amplification and HPV status in tonsillar squamous cell carcinoma (TSCC) and analyzed the clinical characteristics. HPV in situ hybridization (HPV ISH) and FGFR1 fluorescence in situ hybridization (FISH) were performed using tissue microarray from 89 cases of TSCC. Fourteen of 89 (15.7%) TSCC cases had FGFR1 amplification, and HPV was detected in 59 of 89 (66.3%) cases. FGFR1 amplification status was not associated with HPV positivity ( p=0.765). Outcomes were not significantly different between FGFR1 amplified and non-amplified patients. Although FGFR1 amplified patients ( n=4) in the HPV ISH-negative group ( n=30) had a tendency for poorer overall survival, no statistical significance was identified ( p=0.150, log-rank). FGFR1 protein overexpression showed better disease-free survival ( p=0.031, log-rank) in HPV-negative TSCC. This study suggests FGFR1 amplification may be important in the pathogenesis of TSCC regardless of HPV status.


Papillary thyroid carcinoma: demographics, treatment, and outcome in eleven pediatric patients treated at a single institution.
We describe 11 cases (8 females, 3 males) of papillary thyroid carcinoma in children treated at St. Jude Children's Research Hospital over a 33-year period, and review the literature. Ages ranged from 7-25 years (median, 16 years). Six patients had primary papillary thyroid carcinoma. Five patients had secondary papillary thyroid carcinoma after treatment of Hodgkin's disease (n = 2), acute lymphoblastic leukemia (n = 2), and neuroblastoma (n = 1) with chemotherapy and cervical radiation. The typical presentation was either cervical lymphadenopathy or a thyroid mass of short duration. Treatment consisted of thyroidectomy, cervical lymph node dissection, and postoperative thyroid hormone replacement (n = 1), parathyroid reimplantation (n = 1), 131I ablation (n = 4), external-beam irradiation (n = 1), and chemotherapy with doxorubicin (n = 1) or carboplatin and topotecan (n = 1). Nine patients are alive without evidence of disease 3.0-22.4 years from diagnosis. One patient has persistent but stable disease 17.3 years after diagnosis. One patient relapsed with metastatic lung disease 0.3 years after the initial diagnosis. He continues to do well after a brief but unsustained complete radiographic remission of disease to combination chemotherapy with carboplatin and topotecan. Our review supports excellent long-term outcome for primary or secondary papillary thyroid carcinoma in pediatric patients although complications may require close follow-up in a multidisciplinary setting.


Laser-driven localization of collective CO vibrations in metal-carbonyl complexes.
Using the example of a cobalt dicarbonyl complex it is shown that two perpendicular linearly polarized IR laser pulses can be used to trigger an excitation of the delocalized CO stretching modes, which corresponds to an alternating localization of the vibration within one CO bond. The switching time for localization in either of the two bonds is determined by the energy gap between the symmetric and asymmetric fundamental transition frequencies. The phase of the oscillation between the two local bond excitations can be tuned by the relative phase of the two pulses. The extend of control of bond localization is limited by the anharmonicity of the potential energy surfaces leading to wave packet dispersion. This prevents such a simple pulse scheme from being used for laser-driven bond breaking in the considered example.


Effectiveness of Mobile Emitter Location by Cooperative Swarm of Unmanned Aerial Vehicles in Various Environmental Conditions.
This paper focused on assessing the effectiveness of the signal Doppler frequency (SDF) method to locate a mobile emitter using a swarm of unmanned aerial vehicles (UAVs). Based on simulation results, we showed the impact of various factors such as the number of UAVs, the movement parameters of the emitter and the sensors on location effectiveness. The study results also showed the dependence of the accuracy and continuity of the emitter coordinate estimation on the type of propagation environment, which was determined by line-of-sight (LOS) or non-LOS (NLOS) conditions. The applied research methodology allowed the selection of parameters of the analyzed location system that would minimize the error and maximize the monitoring time of the emitter position.


Medical management of venous thromboembolism: what the interventional radiologist needs to know.
Deep vein thrombosis and pulmonary embolism are considered manifestations of the same pathophysiological process and are together referred to as venous thromboembolism (VTE). VTE is a common disorder with an incidence of 1 to 3 in 1000 in the general population. It is estimated that the incidence of VTE is likely to increase as the average life expectancy of the U.S. population increases. Treatment of VTE consists of anticoagulation; the duration of anticoagulation is largely determined by the circumstances surrounding development of the thrombotic event. Vitamin K antagonists, the only oral anticoagulants approved for treatment of VTE in the United States, have several drawbacks and therefore new oral anticoagulants are currently in various stages of development. This review focuses on the risk factors for VTE and the approach to determining the duration of anticoagulation in patients with VTE. Results of clinical trials on the new oral anticoagulants that may soon be licensed for the treatment of VTE are also discussed.


Hindlimb unloading decreases thioredoxin-related antioxidant proteins and increases thioredoxin-binding protein-2 in rat skeletal muscle.
To investigate role(s) of thioredoxin-related antioxidant proteins in disuse muscle atrophy, we examined the levels of thioredoxin-1 (Trx-1), peroxiredoxin-3/SP-22 (Prx-3) and thioredoxin-binding protein-2 (TBP-2) in rat soleus muscle subjected to hindlimb unloading (HU) for 2, 4, 7 or 14 days. The muscle weight loss was initially observed on day 4. The increases in aclorein- and malondialdehyde-modified proteins, and the decreases in the levels of Trx-1, Prx-3 and Mn-SOD were observed in the late phase of muscle atrophy, whereas, the increase in mRNA expression of TBP-2, a negative regulator of thioredoxin, preceded muscle atrophy. These findings suggest that the decrease of those antioxidant proteins, particularly a marked decrease of Trx-1, may be responsible for the enhanced oxidative damage during the late phase of disuse muscle atrophy. Furthermore, the increase in TBP-2 preceding the muscle atrophy may suppress the thioredoxin-mediated redox signaling, which can be an initial trigger leading to disuse muscle atrophy.


[Surgical treatment of patients with chronic critical ischemia of legs, caused by atherosclerosis].
208 patients with primary chronic critical ischemia of lower extremities (CCILE) were operated on from 1988 to 1995. The criteria of CCILE were the following: ischemia of an extremity in rest with specific ischemic pain for more than 2 weeks; existence of ulcernecrotic changes in distal parts of the extremity; brachiommalleous index (BMI) less than 0.35; malleous systolic pressure less than 50 mm Hg. Functional condition of the patients corresponded to class 3A, B and 4. The share of patients with CCILE among patients with lower extremities arterial lesions was 35%. In 150 (72%) of them there were lesions of aorto-illo-femoral-tibio-popliteal segment; in 58 (28%)-damage of a femoral-popliteal-tibial segment. The number of patients with trophic changes appear in early stage. 154 reconstructive operations have been performed in patients with multiple arterial lesions higher and lower of the Poupart's ligament, and only one primary amputation and sympathectomy. In 63 (42%) of the patients the "two-floor" reconstruction has been performed. In 142 (92%) of the cases positive results have been achieved. In 78.5% cases the grafts were competent a year after the surgery and the extremities were saved in 88% of the patients. 60 reconstructive operations, 3 primary amputations and 1 sympathectomy have been performed in patients with the lesions, located lower than Poupart's ligament. In 58 (96%) of the patients positive results were achieved. One year after surgery the grafts patency was 63.5%, and extremities were saved in 79% of the patients. The immediate and long-term follow-up results of femoral-politeal and femoral-tibial grafting did not differ significantly. Long-term follow-up results were better in case of less duration of CCILE before surgery. Adequate revascularisation of the extremity is an optimal method of treatment of patients with CCILE.


Still a place for the classical systematic sextant technique? Cancer detection rates and complications in 1025 consecutive prostatic biopsies.
To verify if there might still be an indication to the sextant biopsy technique we reviewed the cancer detection rate obtained and the complications encountered during a five years interval, at our hospital. From January 1997 to December 2002 we have submitted to prostatic biopsy a total of 1025 consecutive patients with a clinical suspect of prostate cancer. A total of six cores were obtained in all the patients with an additional core at suspect lesions. Overall, prostate cancer was present in the biopsies of 444 of 1025 patients giving a detection rate of 43.3%. In patients with serum PSA levels between 4.1 and 10 ng/ml., 169 of 466 biopsies were positive, for a detection rate of 36.3%. An increase in percentage of positivity was observed with increasing decades of age. Overall complication rate was 1.4%. In patients older than 70 years, and with PSA levels higher than 10 ng/ml, the sextant technique may offer cancer detection rates comparable with techniques using an increased number of cores, and with lower complication rates.


Isoflavones and gamma irradiation inhibit cell growth in human salivary gland cells.
We studied the effects of isoflavones and irradiation on cell cycle in a human salivary gland cell line (HSG). Genistein and a soy isoflavone conjugate (NS) inhibited DNA synthesis. Cells deconjugated the glucoside form of isoflavones in NS to the aglycones genistein and daidzein. NS, genistein and IR increased phosphorylation of p53 and p21 CIP1 at serine 15 (phos-p53). Irradiation and NS also increased levels of p21 CIP1. In a cologenic survival assay, cells in log phase growth had high radio-sensitivity with 2 Gy causing a reduction in survival (SF2=0.45). isoflavones and radiation may interact to sensitize cancer cells to radiation.


Long-term sequelae of simple dislocation of the elbow.
Fifty-two patients with a radiographically verified dislocation of the elbow were re-examined at an average of twenty-four years after injury. Half of the patients had no residual symptoms or signs whatsoever and more than one-third had a slight or moderate decrease in the range of extension, which was associated with slight degenerative change in the joint or with periarticular calcification. No reduction in joint space was evident. Even when the examination revealed some instability in a few patients they did not register complaints. Among the patients who had sustained the injury when they were less than sixteen years old, there were few with residual symptoms, signs, or radiographic changes.


Beta blocker treatment for infantile hemangiomas.
Infantile hemangiomas (IH) are common childhood vascular tumors. Treatment of IH has undergone rapid change in recent years. Since 2008, oral propranolol has been used to treat complicated IH and has proven superior to previously used therapies. More recently, the efficacy of other systemic beta blockers, specifically atenolol and nadolol, has been reported. In addition, topical timolol solution has been effective for treatment of smaller, more superficial IH. The purpose of this article is to review the current literature of beta-blocker therapy for IH.


Senescence Alters PPARγ (Peroxisome Proliferator-Activated Receptor Gamma)-Dependent Fatty Acid Handling in Human Adipose Tissue Microvascular Endothelial Cells and Favors Inflammation.
Adipose tissue (AT) dysfunction associated with obesity or aging is a major cause for lipid redistribution and the progression of cardiometabolic disorders. Our goal is to decipher the contribution of human AT microvascular endothelial cells (ECs) in the maintenance of fatty acid (FA) fluxes and the impact of senescence on their function. We used freshly isolated primary microvascular ECs from human AT. Our data identified the endothelial FA handling machinery including FATPs (FA transport proteins) FATP1, FATP3, FATP4, and CD36 as well as FABP4 (FA binding protein 4). We showed that PPARγ (peroxisome proliferator-activated receptor gamma) regulates the expression of FATP1, CD36, and FABP4 and is a major regulator of FA uptake in human AT EC (hATEC). We provided evidence that endothelial PPARγ activity is modulated by senescence. Indeed, the positive regulation of FA transport by PPARγ agonist was abolished, whereas the emergence of an inflammatory response was favored in senescent hATEC. This was associated with the retention of nuclear FOXO1 (forkhead box protein O1), whereas nuclear PPARγ translocation was impaired. These data support the notion that PPARγ is a key regulator of primary hATEC function including FA handling and inflammatory response. However, the outcome of PPARγ activation is modulated by senescence, a phenomenon that may impact the ability of hATEC to properly respond to and handle lipid fluxes. Finally, our work highlights the role of hATEC in the regulation of FA fluxes and reveals that dysfunction of these cells with accelerated aging is likely to participate to AT dysfunction and the redistribution of lipids.


Toxic Dimethylarginines: Asymmetric Dimethylarginine (ADMA) and Symmetric Dimethylarginine (SDMA).
Asymmetric and symmetric dimethylarginine (ADMA and SDMA, respectively) are toxic, non-proteinogenic amino acids formed by post-translational modification and are uremic toxins that inhibit nitric oxide (NO) production and play multifunctional roles in many human diseases. Both ADMA and SDMA have emerged as strong predictors of cardiovascular events and death in a range of illnesses. Major progress has been made in research on ADMA-lowering therapies in animal studies; however, further studies are required to fill the translational gap between animal models and clinical trials in order to treat human diseases related to elevated ADMA/SDMA levels. Here, we review the reported impacts of ADMA and SDMA on human health and disease, focusing on the synthesis and metabolism of ADMA and SDMA; the pathophysiological roles of these dimethylarginines; clinical conditions and animal models associated with elevated ADMA and SDMA levels; and potential therapies against ADMA and SDMA. There is currently no specific pharmacological therapy for lowering the levels and counteracting the deleterious effects of ADMA and SDMA. A better understanding of the mechanisms underlying the impact of ADMA and SDMA on a wide range of human diseases is essential to the development of specific therapies against diseases related to ADMA and SDMA.


Case Report: Exceptional response to nivolumab plus cabozantinib in a patient with extrarenal clear cell renal cell carcinoma.
Extrarenal clear cell renal cell carcinoma (eccRCC) is a rare type of RCC that arises in areas other than the kidney. Given its rarity, consensus guidelines for optimal treatment of eccRCC have not been established, and the literature is lacking any reports of patient response to systemic therapy and any reports of administration of immunotherapy to patients with ecRCC. Here, we present the case of a patient in their 60s with eccRCC arising in the spleen. The patient underwent splenic resection and then received systemic therapy, due to disease recurrence, with a combination of immunotherapy (IO) and tyrosine kinase inhibitor targeted therapy (VEGF-TKI). The patient had an excellent and durable response to this therapeutic regimen with minimal adverse effects, completing 2 years of therapy of nivolumab and cabozantinib. At the time of this report, the disease remains stable. This case demonstrates that combination therapy with IO+VEGF-TKI represents a reasonable and well-tolerated treatment option with activity in eccRCC and reveals interesting correlative data, including nests of stem-like CD8+T-cell infiltration in tumor tissue, which provide important biological context to this patient's exceptional therapeutic response.


Importance of D1 and D2 receptor stimulation for the induction and expression of cocaine-induced behavioral sensitization in preweanling rats.
The behavioral manifestations of psychostimulant-induced sensitization vary markedly between young and adult rats, suggesting that the neural mechanisms mediating this phenomenon differ across ontogeny. In this project we examined the importance of D1 and D2 receptors for the induction and expression of cocaine-induced behavioral sensitization during the preweanling period. In the behavioral experiments, rats were injected with reversible D1 and/or D2 antagonists (SCH23390 and/or raclopride) or an irreversible receptor antagonist (EEDQ) either before cocaine administration on the pretreatment day (induction) or before cocaine challenge on the test day (expression). In the EEDQ experiments, receptor specificity was assessed by using selective dopamine antagonists to protect D1 and/or D2 receptors from inactivation. Receptor binding assays showed that EEDQ caused substantial reductions in dorsal striatal D1 and D2 binding sites, while SCH23390 and raclopride fully protected D1 and D2 receptors from EEDQ-induced alkylation. Behavioral results showed that neither D1 nor D2 receptor stimulation was necessary for the induction of cocaine sensitization in preweanling rats. EEDQ disrupted the sensitization process, suggesting that another receptor type sensitive to EEDQ alkylation was necessary for the induction process. Expression of the sensitized response was prevented by an acute injection of a D1 receptor antagonist. The pattern of DA antagonist-induced effects described for preweanling rats is, with few exceptions, similar to what is observed when the same drugs are administered to adult rats. Thus, it appears that maturational changes in D1 and D2 receptor systems are not responsible for ontogenetic differences in the behavioral manifestation of cocaine sensitization.


Surgical nuances in the separation of craniopagus twins - Our experience and a follow up of 15 years.
Craniopagus twins are conjoined twins fused at the cranium. This is the rarest anomaly seen in conjoined twins and craniopagus twins account for 2- 6% of conjoined twins. Conjoined twins are also extremely rare, with the anomaly seen in about 10-20 subjects per billion births. A female preponderance has been noted. Craniopagus twins can be classified into complete or partial, depending on whether or not they have shared dural venous sinuses. They can be further classified into angular or total depending on the alignment of the inter-twin longitudinal axis. Surgical separation of these cases can be an elective procedure or an emergency, mandated by the death of one of the twins. Surgical separation of craniopagus twins is a complex exercise needing detailed evaluation and planning. For the successful management of these twins, a multi-disciplinary approach involving neurosurgeons, plastic surgeons, anesthetists, radiologists, pediatric critical care specialists and ancillary staff is mandatory. We present a case of partially successful elective separation of partial angular craniopagus twins performed in 2002.The surviving twin was managed conservatively for a cerebrospinal fluid leak. The patient subsequently developed a pseudomeningocele, necessitating re-exploration, excision of the gliotic tissue, and repair of the dura and the overlying scalp flap. The patient has a skull defect for which cranioplasty has been deferred. The child is neurologically intact. The post-operative evaluation and the detailed periodic neurological assessment till date (with a follow up of 15 years) have been presented in this study.


Results of distraction callus osteogenesis in hand and foot in Iran: A 15-year experience.
Distraction osteogenesis (DS) is currently an important technique for lengthening shortened bones of the hand and foot. Authors report their experience in applying DS for various conditions of the hand and foot using a distractor that the senior author has designed. Records of patients who underwent DS for hand and foot conditions in a private clinic were retrieved between January 2001 and January 2015. Data concerning distraction, outcome, and complications were recorded. There were 17 patients, 7 males, and 10 females with a total 24 distractions. The mean length gained was 21.2 mm (1.69) and the mean total treatment time was 198.58 (15.88) days. Overall, complications occurred in 9 (37.5%) distractions. Major complications occurred in 2 (8.33%) of distractions. Minor complications occurred in 7 (29.2%) distractions. DS is an effective modality for lengthening bones of the hand and feet for both traumatic and congenital conditions. Joint stiffness/contracture is an important complication following DS of the metatarsals.


Induction of promiscuous G protein coupling of the follicle-stimulating hormone (FSH) receptor: a novel mechanism for transducing pleiotropic actions of FSH isoforms.
Under physiological conditions, FSH is secreted into the circulation as a complex mixture of several isoforms that vary in the degree of glycosylation. Although it is well established that the glycosylation of FSH is important for the serum half-life of the hormone and coupling of the receptor to adenylate cyclase, little is known concerning how physiologically occurring glycosylation patterns of this hormone affect receptor signaling. In this study, we have examined the biological activity of deglycosylated human FSH (DeGly-phFSH), recombinant mammalian-expressed hFSH (CHO-hFSH), and insect cell-expressed hFSH (BV-hFSH, alternatively glycosylated) as compared with that of purified human pituitary FSH (phFSH) using a Chinese hamster ovarian cell line stably expressing the hFSH receptor (3D2 cells). Differentially glycosylated forms of FSH did not bind to the FSH receptor in the same manner as phFSH. Although all hormones showed similar potency in competing for [125I]phFSH binding to the hFSH receptor, competition curves for deglycosylated and insect cell-produced FSH were steeper. Similarly, glycosylation of FSH had a profound effect on bioactivity of the hormone. Purified hFSH produced a sigmoidal dose-dependent stimulation in cAMP production, whereas DeGly-phFSH and BV-hFSH induced biphasic (bell-shaped) dose-response curves. BV-hFSH also elicited biphasic effects on steroidogenesis in primary cultures of rat granulosa cells. The cellular response to BV-hFSH was dependent on the degree of receptor-transducer activation. BV-hFSH bioactivity was strictly inhibitory when combined with the ED80 of phFSH. Lower concentrations of phFSH resulted in a gradual shift from inhibition to a biphasic activity in the presence of the ED20 of phFSH. Biphasic responses to BV-hFSH were attributed to activation of different G protein subtypes, since treatment of 3D2 cells with cholera toxin or pertussis toxin differentially blocked the two phases of BV-hFSH bioactivity. These data suggest that alternative glycosylation of FSH leads to a functionally altered form of the hormone. Functionally different hormones appear to convey distinct signals that are transduced by the receptor-transduction system as either stimulatory or inhibitory intracellular events via promiscuous, glycosylation-dependent G protein coupling. Promiscuity in signaling of the FSH receptor, in turn, may represent a potentially novel mechanism for FSH action, whereby the gonad may respond in diverse ways to complex hormonal signals such as those presented by circulating FSH isoforms.


Inside out: a neuro-behavioral signature of free recall dynamics.
Free recall (FR) is a ubiquitous internally-driven retrieval operation that crucially affects our day-to-day life. The neural correlates of FR, however, are not sufficiently understood, partly due to the methodological challenges presented by its emerging property and endogenic nature. Using fMRI and performance measures, the neuro-behavioral correlates of FR were studied in 33 healthy participants who repeatedly encoded and retrieved word-lists. Retrieval was determined either overtly via verbal output (Experiment 1) or covertly via motor responses (Experiment 2). Brain activation during FR was characterized by two types of performance-based parametric analyses of retrieval changes over time. First was the elongation in inter response time (IRT) assumed to represent the prolongation of memory search over time, as increased effort was needed. Using a derivative of this parameter in whole brain analysis revealed the default mode network (DMN): longer IRT within FR blocks correlated with less deactivation of the DMN, representing its greater recruitment. Second was the increased number of words retrieved in repeated encoding-recall cycles, assumed to represent the learning process. Using this parameter in whole brain analysis revealed increased deactivation in the DMN (i.e., less recruitment). Together our results demonstrate the naturally occurring dynamics in the recruitment of the DMN during utilization of internally generated processes during FR. The contrasting effects of increased and decreased recruitment of the DMN following dynamics in memory search and learning, respectively, supports the idea that with learning FR is less dependent on neural operations of internally-generated processes such as those initially needed for memory search.


Utility of a multiplex PCR assay for detecting herpesvirus DNA in clinical samples.
A multiplex PCR was designed to amplify herpes simplex virus types 1 and 2, cytomegalovirus, and varicella-zoster virus DNA present in a diverse range of clinical material. The susceptibility of these viruses to in vivo inhibition by at least one antiviral drug was an important consideration in their inclusion in the multiplex detection system. An aliquot of equine herpesvirus was introduced into each specimen prior to extraction and served as an indicator of potential inhibitors of the PCR and a detector of suboptimal PCR conditions. Compared to virus isolation and immunofluorescence-based antigen detection, the multiplex assay yielded higher detection rates for all viruses represented in the assay. The turnaround time for performance of the assay was markedly reduced compared to those for the other techniques used to identify these viruses. More than 21,000 tests have been performed using the assay. Overall, the multiplex PCR enabled the detection of substantially increased numbers of herpesviruses, in some cases in specimens or anatomical sites where previously they were rarely if ever identified using traditional detection methods.


T4216C mutation in NADH dehydrogenase I gene is associated with recurrent pregnancy loss.
Several genetic factors are involved with recurrent pregnancy loss (RPL). However, few attempts have been made to associate mitochondrial DNA (mtDNA) variations with RPL. Therefore, we investigated the possible effect of the T4216C mutation in the mitochondrial NADH dehydrogenase I (ND1) gene of 33 women with RPL and 100 controls, using polymerase chain reaction amplification and DNA sequence analysis. Our results showed a statistically significant association of the T4216C mutation (p < 0.05) between patients and controls, which are 30% and 11%, respectively. In conclusion, more research is essentially needed to understand the effect and role of the T4216C mutation in the progress of RPL, which may vary among individuals and different ethnic groups.


The effect of binders on the bioavailability of ofloxacin tablets in animal model.
Present study was undertaken to evaluate the effect of binders on the bioavailability of the drug. Two formulations of ofloxacin were manufactured with two different binders, i.e. gelatin and starch, which were analyzed by different in vitro tests such as dissolution test using USP apparatus II (paddle method) by using 0.1 M HCl solution. For in vivo studies, blood samples were collected through the heparinized syringe at zero time (before dosing) and at 0.5, 1.0, 2.0, 4.0, 6.0, 8.0, 10.0, 12.0, 24.0 hours after the dosing of ofloxacin tablets to 24 rabbits and analyzed by high performance liquid chromatography. Mobile phase consisted of distilled water, acetonitrile and triethylamine (700 : 300 : 1.4, v/v/v). The pH of the mobile phase was adjusted at 2.4 with orthophosphoric acid. The maximum plasma concentration attained after the administration of formulation 1 (containing gelatin) was 7.56 +/- 0.835 microg/mL (the mean +/- SEM) and of formulation 2 (containing starch) was 3.4417 +/- 1.16 microg/mL (the mean +/- SEM). There is also statistically significant difference between the volume of distribution and total body clearance of both formulations. Therefore, formulation 1 is more bioavailable than formulation 2. Thus it can be concluded that binder can affect the bioavailability and pharmacokinetics of a drug.


Odd, outsized, and obscure: Sarcophaga (Hadroxena) karakoncolos sp. n. (Diptera: Sarcophagidae) from Turkey.
A new species of flesh fly, Sarcophaga karakoncolos sp. n., is described based on a single adult male from Turkey (Isparta Province, Anatolia), characterised by its very large size (almost 22mm in body length) and by a unique combination of morphological features. These, together with available molecular data, do not support inclusion of the new species in any of the currently recognised subgenera of Sarcophaga, and it is placed in a new subgenus, Hadroxena subg. n.


Isoflavone diet ameliorates experimental autoimmune encephalomyelitis through modulation of gut bacteria depleted in patients with multiple sclerosis.
The gut microbiota is a potential environmental factor that influences the development of multiple sclerosis (MS). We and others have demonstrated that patients with MS and healthy individuals have distinct gut microbiomes. However, the pathogenic relevance of these differences remains unclear. Previously, we showed that bacteria that metabolize isoflavones are less abundant in patients with MS, suggesting that isoflavone-metabolizing bacteria might provide protection against MS. Here, using a mouse model of MS, we report that an isoflavone diet provides protection against disease, which is dependent on the presence of isoflavone-metabolizing bacteria and their metabolite equol. Notably, the composition of the gut microbiome in mice fed an isoflavone diet exhibited parallels to healthy human donors, whereas the composition in those fed an isoflavone-free diet exhibited parallels to patients with MS. Collectively, our study provides evidence that dietary-induced gut microbial changes alleviate disease severity and may contribute to MS pathogenesis.


Association between fetal exposure to phthalate endocrine disruptor and genome-wide DNA methylation at birth.
Phthalic acid esters are ubiquitous and antiandrogenic, and may cause systemic effects in humans, particularly with in utero exposure. Epigenetic modification, such as DNA methylation, has been hypothesized to be an important mechanism that mediates certain biological processes and pathogenic effects of in utero phthalate exposure. The aim of this study was to examine the association between genome-wide DNA methylation at birth and prenatal exposure to phthalate. We studied 64 infant-mother pairs included in TMICS (Taiwan Maternal and Infant Cohort Study), a long-term follow-up birth cohort from the general population. DNA methylation levels at more than 450,000 CpG sites were measured in cord blood samples using Illumina Infinium HumanMethylation450 BeadChips. The concentrations of three metabolites of di-(2-ethylhexyl) phthalate (DEHP) were measured using liquid chromatography tandem-mass spectrometry (LC-MS/MS) in urine samples collected from the pregnant women during 28-36 weeks gestation. We identified 25 CpG sites whose methylation levels in cord blood were significantly correlated with prenatal DEHP exposure using a false discovery rate (FDR) of 5% (q-value < 0.05). Via gene-set enrichment analysis (GSEA), we also found that there was significant enrichment of genes involved in the androgen response, estrogen response, and spermatogenesis within those genes showing DNA methylation changes in response to exposure. Specifically, PA2G4, HMGCR, and XRCC6 genes were involved in genes in response to androgen. Phthalate exposure in utero may cause significant alterations in the DNA methylation in cord blood. These changes in DNA methylation might serve as biomarkers of maternal exposure to phthalate in infancy and potential candidates for studying mechanisms via which phthalate may impact on health in later life. Future investigations are warranted.


Quantification of Multiple Mitral Regurgitant Jets: An In Vitro Validation Study Comparing Two- and Three-Dimensional Proximal Isovelocity Surface Area Methods.
The accuracy of the proximal isovelocity surface area (PISA) method for the quantification of mitral regurgitation (MR), in the case of multiple jets, is unknown. The aim of this study was to evaluate different two-dimensional (2D) and three-dimensional (3D) PISA methods using 3D color Doppler data sets. Several regurgitant volumes (Rvols) were simulated using a pulsatile pump connected to a phantom equipped with single and double regurgitant orifices of different sizes and interspaces. A flowmeter served as the reference method. Transthoracic (TTE) and transoesophageal echocardiography (TEE) were used to acquire the 3D data sets. Offline, Rvols were calculated by 2D PISA methods based on hemispheric and hemicylindric assumptions and by 3D integrated PISA. A fusion of the PISA was observed in the setting of narrow-spaced regurgitant orifices; compared with flowmeter, Rvol was underestimated using the single hemispheric PISA model (TTE: Bland-Altman bias ± limit of agreement, -17.5 ± 8.9 mL; TEE: -15.9 ± 7.3 mL) and overestimated using the double hemispheric PISA model (TTE: +7.1 ± 14.6 mL; TEE: +10.4 ± 11.9 mL). The combined approach (hemisphere for single orifice, hemicylinder with two bases for nonfused PISAs, and hemicylinder with one base for fused PISAs) was more precise (TTE: -3.4 ± 6.3 mL; TEE: -1.9 ± 5.6 mL). Three-dimensional integrated PISA was the most accurate method to quantify Rvol (TTE: -2.1 ± 6.5 mL; TEE -3.2 ± 4.8 mL). In the setting of double MR orifices, the 2D combined approach and integrated 3D PISA appear to be superior as compared with the conventional hemispheric method, thus providing tools for the challenging quantification of MR with multiple jets.


Endoscopic Fenestration of Cavum Septum Pellucidum Cysts to the Third Ventricle: Technical Note.
Cavum septum pellucidum (CSP) and cavum vergae (CV) cysts are common incidental findings on imaging studies. However, they may rarely present with symptoms related to the obstruction of the foramen of Monro by the cyst leaflets. There is no consensus regarding the management of symptomatic CSP and CV cysts. We present an original transcavum interforniceal endoscopic fenestration technique. The step-by-step surgical procedure and two illustrative cases are presented. A 31-yr-old male and a 24-yr-old woman presented with symptomatic CSP and CV cysts. For both patients, neuronavigation was used to plan the procedure. An endoscope was introduced into the cyst through a right frontal burr-hole. After an examination of the endoscopic anatomy, a communication between the cyst and the third ventricle was performed using an endoscopic forceps. In both cases, directly after the fenestration, cerebrospinal fluid (CSF) passed through the communication, and the collapse of the cyst was appreciated. Symptoms were relieved in both patients, and neuropsychological assessment improved. Postoperative imaging showed a reduction in the cyst bulge, and patent foramen of Monro. Endoscopic fenestration of CSP and CV cysts to the third ventricle through an interforniceal navigated approach is a feasible and efficient surgical procedure. Theoretical advantages include a single tract through noneloquent brain, a perpendicular trajectory to the membrane for fenestration, and a large CSF space beyond the fenestration point.


Dose dependence of covalent binding of acrylonitrile to tissue protein and globin in rats.
The dose dependence of acrylonitrile (AN) covalent binding to tissue protein, following a single acute exposure over a 100-fold range in dose, was measured. Covalent binding was a linear function of AN dose in the lower dose range (0.02-0.95 mmol AN/kg). The slopes of the dose-response curves indicated that tissues varied by nearly 10-fold in their reactivity with AN. The relative order of covalent binding was as follows: blood > > kidney = liver > forestomach = brain > glandular stomach > > muscle. Similar dose-response behavior was observed for globin total covalent binding and for globin N-(2-cyanoethyl) valine (CEValine) adduct formation. The latter adduct was found to represent only 0.2% of the total AN adduction to globin. Regression of tissue protein binding versus globin total covalent binding or globin CEValine adduct indicated that both globin biomarkers could be used as surrogates to estimate the amount of AN bound to tissue protein. At higher AN doses, above approximately 1 mmol/kg, a sharp break in the covalent binding dose-response curve was observed. This knot value is explained by the nearly complete depletion of liver glutathione and the resultant termination of AN detoxification. The toxicity of AN is known to increase sharply above this dose. The data suggest that a comparison of specific tissue proteins labeled by AN above and below this threshold dose may provide some insight into the mechanism of AN-induced toxicity.


Effects of membrane cation transport on pH and microbial fuel cell performance.
Due to the excellent proton conductivity of Nafion membranes in polymer electrolyte membrane fuel cells (PEMFCs), Nafion has been applied also in microbial fuel cells (MFCs). In literature, however, application of Nafion in MFCs has been associated with operational problems. Nafion transports cation species other than protons as well, and in MFCs concentrations of other cation species (Na+, K+, NH4+, Ca2+, and Mg2+) are typically 10(5) times higher than the proton concentration. The objective of this study, therefore, was to quantify membrane cation transport in an operating MFC and to evaluate the consequences of this transport for MFC application on wastewaters. We observed that during operation of an MFC mainly cation species other than protons were responsible for the transport of positive charge through the membrane, which resulted in accumulation of these cations and in increased conductivity in the cathode chamber. Furthermore, protons are consumed in the cathode reaction and, consequently, transport of cation species other than protons resulted in an increased pH in the cathode chamber and a decreased MFC performance. Membrane cation transport, therefore, needs to be considered in the development of future MFC systems.


Clinical Application of Cultured Stratified Epithelial Sheets Grown Under Feeder or Feeder-Free Conditions for Stable Vitiligo.
Autologous cultured therapy has emerged as an effective treatment for stable vitiligo. However, culture methods may include harmful agents and be unsuitable for therapeutic use in humans. To investigate the safety and efficacy of autologous cultured epithelial sheets propagated under serum-free and feeder-free conditions for the treatment of stable vitiligo. Twenty-eight patients with stable vitiligo were included in this study. Keratinocytes and melanocytes from 14 patients were cultured under serum-free, feeder-free conditions (Group A). Epithelial cells from the remaining 14 patients were cultured according to Rheinward and Green's technique (Group B). Patients were followed up at 1, 3, 6, and 12 months after transplantation. The epithelial sheets cultured in Group A were thinner and more fragile than Group B, but there were no significant differences in repigmentation between the 2 groups. At 12-month follow-up, in Group A, repigmentation at graft sites was classified as excellent in 9 patients and good in 2 patients. In Group B, repigmentation was excellent in 8 patients and good in 4 patients. Scars at the donor sites were the most frequent adverse events associated with the procedure. Autologous epithelial sheet cultured in serum-free, feeder-free conditions is a safe and efficacious approach to cure stable vitiligo.


Stretchable and Ambient Stable Perovskite/Polymer Luminous Hybrid Nanofibers of Multicolor Fiber Mats and Their White LED Applications.
We report the fabrication and optical/mechanical properties of perovskite/thermoplastic polyurethane (TPU)-based multicolor luminescent core-shell nanofibers and their large-scale fiber mats. One-step coaxial perovskite/TPU nanofibers had a high photoluminescence quantum yield value exceeding 23.3%, surpassing that of its uniaxial counterpart, due to the homogeneous distribution of perovskite nanoparticles (NPs) by the confinement of the TPU shell. The fabricated core-shell nanofibers exhibited a high mechanical endurance owing to the well elastic properties of TPU and maintained the luminescence intensity even under a 100% stretched state after 1000 stretching-relaxing cycles. By taking advantage of the hydrophobic nature of TPU, the ambient and moisture stability of the fabricated fibers were enhanced up to 1 month. Besides, large-area stretchable nanofibers with a dimension of 15 cm × 30 cm exhibiting various visible-light emission peaks were fabricated by changing the composition of perovskite NPs. Moreover, a large-scale luminescent and stretchable fiber mat was successfully fabricated by electrospinning. Furthermore, the white-light emission from the fabricated fibers and mats was achieved by incorporating orange-light-emitting poly[2-methoxy-5-(2-ethylhexyloxy)-1,4-phenylenevinylene] into the TPU shell and coupling the turquoise blue-light-emitting perovskite NPs in the core site. Finally, the integrity of the perovskite-based TPU fibers was realized by fabricating a light-emitting diode (LED) device containing the orange-light-emitting fibers embedded in the polyfluorene emissive layer. This work demonstrated an effective way to prepare stable and stretchable luminous nanofibers and the integration of such nanofibers into LED devices, which could facilitate the future development of wearable electronic devices.


Evidence for prehistoric origins of the G2019S mutation in the North African Berber population.
The most common cause of the monogenic form of Parkinson's disease known so far is the G2019S mutation of the leucine-rich repeat kinase 2 (LRRK2) gene. Its frequency varies greatly among ethnic groups and geographic regions ranging from less than 0.1% in Asia to 40% in North Africa. This mutation has three distinct haplotypes; haplotype 1 being the oldest and most common. Recent studies have dated haplotype 1 of the G2019S mutation to about 4000 years ago, but it remains controversial whether the mutation has a Near-Eastern or Moroccan-Berber ancestral origin. To decipher this evolutionary history, we genotyped 10 microsatellite markers spanning a region of 11.27 Mb in a total of 57 unrelated Moroccan PD patients carrying the G2019S mutation for which the Berber or Arab origin was established over 3 generations based on spoken language. We estimated the age of the most recent common ancestor for the 36 Arab-speaking and the 15 Berber-speaking G2019S carriers using the likelihood-based method with a mutation rate of 10-4. Data analysis suggests that the shortest haplotype originated in a patient of Berber ethnicity. The common founder was estimated to have lived 159 generations ago (95% CI 116-224) for Arab patients, and 200 generations ago (95% CI 123-348) for Berber patients. Then, 29 native North African males carrying the mutation were assessed for specific uniparental markers by sequencing the Y-chromosome (E-M81, E-M78, and M-267) and mitochondrial DNA (mtDNA) hypervariable regions (HV1 and HV2) to examine paternal and maternal contributions, respectively. Results showed that the autochthonous genetic component reached 76% for mtDNA (Eurasian and north African haplogroups) and 59% for the Y-chromosome (E-M81 and E-M78), suggesting that the G2019S mutation may have arisen in an autochthonous DNA pool. Therefore, we conclude that LRRK2 G2019S mutation most likely originated in a Berber founder who lived at least 5000 years ago (95% CI 3075-8700).


Partition coefficients of selected pyridine carbamates and comparisons with their acetylcholinesterase and butyrylcholinesterase inhibitory potencies.
Partition coefficients of a series of 2-substituted 3-(N,N-dimethyl)carbamyloxypyridines were determined in an octanol-buffer (pH 7.4) system. The values obtained were compared with the ihnibitory potencies of acetylcholinesterase and butyrylcholinesterase. No significant difference was found for the role of hydrophobicity in the two enzyme systems.


Bayesian Network analysis of piglet scours.
Diarrhoeal disease (scours) in piglets, often associated with enterotoxigenic Escherichia coli (ETEC), is a substantial financial burden to the pig industry worldwide. Previous research has not explicitly examined the relationships between farm, pen and microbiological factors. Here we present a state of the art analysis to reveal empirical indirect - as well as direct - associations between management factors as putative risks for scours in pre- and post-weaned piglets. A Bayesian Network is constructed to identify the optimal structural model describing the relationships between risk factors. An additive model is then built to estimate more epidemiologically familiar odds ratios. Farm-level variance dominates the model, making many pen-level associations null. However, there is evidence that pre-weaning scours are less likely on farms with <400 sows (0.14, 0.03-0.50). Our results strongly suggest that smaller production units (piglets/pen) could reduce the incidence of scours in piglets. There is also some evidence that ownership of other livestock is a potential risk factor for pre-weaning scours, although this was observed only at one farm. Future research should be directed at better understanding the role of herd size and investigating the relationship between managing other livestock and the occurrence of scours in pig herds.


Environmental constraints on the compositional and phylogenetic beta-diversity of tropical forest snake assemblages.
The ongoing biodiversity crisis increases the importance and urgency of studies addressing the role of environmental variation on the composition and evolutionary history of species assemblages, but especially the tropics and ectotherms remain understudied. In regions with rainy summers, coexistence of tropical ectothermic species may be determined by the partitioning of the climatic niche, as ectotherms can rely on water availability and thermoregulatory behaviour to buffer constraints along their climatic niche. Conversely, tropical ectotherms facing dry summers would have fewer opportunities to climatic niche partitioning and other processes rather than environmental filtering would mediate species coexistence. We used 218 snake assemblages to quantify the compositional (CBD) and phylogenetic (PBD) beta-diversity of snakes in the Atlantic Forest (AF) hotspot, South America. We identify two AF regions with distinct climatological regimes: dry summers in the northern-AF and rainy summers in the southern-AF. While accounting for the influence of multiscale spatial processes, we disentangle the relative contribution of thermal, water-related and topographic conditions in structuring the CBD and PBD of snake assemblages, and determine the extent in which snake assemblages under distinct climatological regimes are affected by environmental filtering. Thermal conditions best explain CBD and PBD of snakes for the whole AF, whereas water-related factors best explain the structure of snake assemblages within a same climatological regime. CBD and PBD patterns are similarly explained by spatial factors but snake assemblages facing dry summers are more affected by spatial processes operating at fine to intermediate spatial scale, whereas those assemblages in regions with rainy summers have a stronger signature of coarse-scale processes. As expected, environmental filtering plays a stronger role in southern-AF than northern-AF, and the synergism between thermal and water-related conditions is the key cause behind this difference. Differences in climatological regimes within the tropics affect processes mediating species coexistence. The influence of broad-scale gradients (e.g. temperature and precipitation) in structuring tropical ectothermic assemblages is greater in regions with rainy summers where climatic niche partitioning is more likely. Our findings highlight the potential stronger role of biotic interactions and neutral processes in structuring ectothermic assemblages facing changes towards warmer and dryer climates.


[Cerebral hemisphere dominance].
There is a functional asymmetry of the human brain. This division of labour is brought about by the enormous complexity of the cerebral performances and the fundamental incompatibility between the analytical functions on the one hand and the synthetic functions on the other.


Difficulties and challenges in reviewing ethical aspects of research in Brazil.
Objective To reflect on the problems faced by researchers from different areas, especially of Humanities and Social Sciences, when submitting research projects for evaluation by the research ethics committees in Brazil. Method A theoretical and reflective study based on international literature and the critical analysis of the authors. Results Although Resolution 466/2012, which addresses human research, contains some innovations, issues related to the research participants remain obscure and the project evaluation process is time-consuming. Conclusion The difficulties faced by researchers, especially in the fields of Humanities and Social Sciences, must be transposed to ensure that the ethical guidelines are applicable, in terms of principles and procedures, to the different research traditions. Appropriate human research standards must be managed by a system with a satisfactory operational capacity, according to the specificities of the different areas of knowledge.


High-contrast coherent terahertz imaging of porcine tissue via swept-frequency feedback interferometry.
There is considerable interest in the interrogation of biological tissue at terahertz (THz) frequencies, largely due to the contrast in the optical properties of different biological tissues which occur in this electro-magnetic radiation band. Of particular interest are THz biomedical images, which have the potential to highlight different information than those acquired in other frequency bands, thereby providing an augmented picture of biological structures. In this work, we demonstrate the feasibility of an interferometric biological imaging technique using a THz quantum cascade laser (QCL) operating at 2.59 THz to perform coherent imaging of porcine tissue samples. We show the potential of this new THz biomedical imaging technique for in vivo studies, by virtue of its reflection geometry and useful tissue penetration depth enabled by the large THz powers emitted by the quantum cascade laser used in this work. The observed clustering of interferometric tissue signatures opens a pathway towards automatic techniques for the discrimination of healthy tissue types for the study of normal physiology and possible therapeutic approaches.


dlk1/FA1 regulates the function of human bone marrow mesenchymal stem cells by modulating gene expression of pro-inflammatory cytokines and immune response-related factors.
dlk1/FA1 (delta-like 1/fetal antigen-1) is a member of the epidermal growth factor-like homeotic protein family whose expression is known to modulate the differentiation signals of mesenchymal and hematopoietic stem cells in bone marrow. We have demonstrated previously that Dlk1 can maintain the human bone marrow mesenchymal stem cells (hMSC) in an undifferentiated state. To identify the molecular mechanisms underlying these effects, we compared the basal gene expression pattern in Dlk1-overexpressing hMSC cells (hMSC-dlk1) versus control hMSC (negative for Dlk1 expression) by using Affymetrix HG-U133A microarrays. In response to Dlk1 expression, 128 genes were significantly up-regulated (with >2-fold; p < 0.001), and 24% of these genes were annotated as immune response-related factors, including pro-inflammatory cytokines, in addition to factors involved in the complement system, apoptosis, and cell adhesion. Also, addition of purified FA1 to hMSC up-regulated the same factors in a dose-dependent manner. As biological consequences of up-regulating these immune response-related factors, we showed that the inhibitory effects of dlk1 on osteoblast and adipocyte differentiation of hMSC are associated with Dlk1-induced cytokine expression. Furthermore, Dlk1 promoted B cell proliferation, synergized the immune response effects of the bacterial endotoxin lipopolysaccharide on hMSC, and led to marked transactivation of the NF-kappaB. Our data suggest a new role for Dlk1 in regulating the multiple biological functions of hMSC by influencing the composition of their microenvironment "niche." Our findings also demonstrate a role for Dlk1 in mediating the immune response.


A fluorous, Pummerer cyclative-capture strategy for the synthesis of N-heterocycles.
A fluorous, cyclative-capture strategy based on a new Pummerer cyclization process allows rapid access to tagged, heterocyclic frameworks. Convenient modification of the fluorous, heterocyclic scaffolds by using a variety of approaches including Pd-catalyzed cross-couplings is possible. Traceless, reductive cleavage of the fluorous-phase tag or oxidative cleavage and further elaboration, completes a strategy for the high-throughput, fluorous-phase synthesis of a diverse range of N-heterocycles.


Setiferous structures of male coleoptera.
A scanning electron microscopy study was made of the male setiferous sex patches and analogous structures in 11 families of Coleoptera (Anthribidae, Bruchidae, Ciidae, Cleridae, Coccinellidae, Dermestidae, Leiodidae, Ptinidae, Staphylinidae, Tenebrionidae, and Ostomatidae). These secondary sexual characters appear to have several features in common including relatively long, often ridged, setae, cuticular ducts (frequently cribriform pore plates), and the production of a secretion. It is suggested that these structures may all be concerned with the production, release, and dissemination of pheromones.


[Use of biochemical markers of bone metabolism in veterinary medicine].
Effective, non-invasive bone assessment methods for screening, diagnosis and follow-up of the skeleton are more and more requested in veterinary medicine. In contrast to clinical parameters, invasive methods and imaging techniques, indices of bone turnover is a tool for bone metabolism evaluation of the whole skeleton. Biochemical bone markers therefore provide a more real-time assessment of the bone status with simple blood- or urine-analysis. This article surveys currently available biochemical marker of bone metabolism used in veterinary medicine. Additionally, information is provided about physiological and pathological, as well as therapeutic variations of biochemical bone marker concentrations in various species.


Aroma character impact compounds in Kinokuni mandarin orange (Citrus kinokuni) compared with Satsuma mandarin orange (Citrus unshiu).
The odor-active volatiles of Kinokuni mandarin (Citrus kinokuni Hort. ex Tanaka), an original mandarin orange in Japan, were characterized by a combination of instrumental and sensory analyses and compared with those of Satsuma mandarin (Citrus unshiu Marcovitch). An aroma extract dilution analysis (AEDA) of the polar fractions of Kinokuni and Satsuma mandarin peel oils identified five odorants in common as the most odor-active volatiles: (Z)-hex-3-enal, decanal, linalool, yuzuol, and (2E)-trans-4,5-epoxydec-2-enal. In addition, seven odorants were identified solely in Kinokuni mandarin as significant contributors: octanal, dodecanal, (2E,4E)-deca-2,4-dienal, geraniol, yuzunone, (2E,7Z)-trans-4,5-epoxydeca-2,7-dienal, and thymol. The odor-active volatiles in both the non-polar components of the peel oil and an extract of the juice prepared from Kinokuni mandarin were also identified. The (S)-isomer of linalool in Kinokuni mandarin peel oil was dominant in the enantiomeric distribution (92%), whereas the (R)-isomer was dominant in Satsuma mandarin peel oil (90%).


Effects of ultra-high pressure homogenization on the cheese-making properties of milk.
The effects of single- or 2-stage ultra-high pressure homogenization (UHPH; 100 to 330 MPa) at an inlet temperature of 30 degrees C on the cheese-making properties of bovine milk were investigated. Effects were compared with those from raw, heat-pasteurized (72 degrees C for 15 s), and conventional homogenized-pasteurized (15 + 3 MPa, 72 degrees C for 15 s) treatments. Rennet coagulation time, rate of curd firming, curd firmness, wet yield, and moisture content of curds were assessed. Results of particle size and distribution of milk, whey composition, and gel microstructure observed by confocal laser scanning microscopy were analyzed to understand the effect of UHPH. Single-stage UHPH at 200 and 300 MPa enhanced rennet coagulation properties. However, these properties were negatively affected by the use of the UHPH secondary stage. Increasing the pressure led to higher yields and moisture content of curds. The improvement in the cheese-making properties of milk by UHPH could be explained by changes to the protein-fat structures due to the combined effect of heat and homogenization.


Changes in small intestinal digestive enzyme activity and bile acids with dietary cellulose in rats.
Rats were fed semipurified diets which contained either 20% cellulose, Solka Floc, (HF) or no fiber (C) for 10 days. In the intestinal contents, the HF group had lower activity per milligram contents of trypsin, chymotrypsin, amylase, lipase and total proteolytic activity. Total activity of enzymes in the intestinal contents was also lower, except for chymotrypsin and leucine amino peptidase. Bile acid levels per milligram were lower in the HF group but the total amount was greater. The total weight of intestinal contents was greater in the HF group and total amount of protein present was elevated. The results indicate that a source of dietary fiber, cellulose, can affect the availability of enzymes and bile acids in the small intestine.


Regulation of HIPK Proteins by MicroRNAs.
The homeodomain-interacting protein kinase (HIPK) family consists of four evolutionarily conserved and highly related nuclear serine/threonine kinases of recent discovery. They interact with homeobox proteins and other transcription factors, as well as transcriptional coactivators or corepressors depending on the cellular context. HIPK proteins are sensors for various extracellular stimuli, which control key cellular functions such as signal transduction to downstream effectors that regulate apoptosis, embryonic development, DNA-damage response, and cellular proliferation. Thus, HIPKs are involved in proliferative diseases such as cancer and fibrosis. mRNA levels and protein stability tightly regulate expression levels of HIPKs. Here, we review recent works investigating the regulation of HIPKs expression by microRNAs (miRNAs) that are involved in the control of cell proliferation, sensitivity to chemotherapeutic drugs, epithelial-mesenchymal transition, and glucose-stimulated insulin secretion. It appears that HIPK family members, and their related miRNAs, may be considered as novel therapeutic targets for treating cancer, renal fibrosis and type 2 diabetes.


Double immunocytochemical staining for in vivo detection of epitope specificity and isotype of antibody-forming cells against synthetic peptides homologous to human immunodeficiency virus-1.
Many infections evoke a strong humoral immune response. Some (e.g., HIV-1, EBV, CMV) also lead to disorders of the B-cell system. Data concerning cell dysfunction are largely derived from in vitro studies, which necessarily exclude all microenvironmental influences. The aim of this study was to develop a tool for the investigation of epitope specific humoral immune responses in vivo. Mice were immunized with one of two synthetic peptides, both 21 amino acids long and homologous to regions of the HIV-1 gp160. Cryostat sections of spleen and lymph nodes were incubated with the corresponding peptide coupled to alkaline phosphatase and simultaneously incubated with peroxidase-conjugated rabbit antisera specific for mouse immunoglobulin isotypes. We were able to show simultaneous detection of epitope specificity, isotype, and localization of antibody-forming cells and immune complexes in tissue sections. It should prove useful for in vivo investigation of the development of specific (e.g., anti-HIV-1) humoral immune response, the determination of B-cell specificity in lymph node infiltrates, and the role of immune complexes in lymph node pathology.


Components Analyses of a School-Based Cognitive Behavioral Treatment for Youth Depression.
The current study sought to build upon research on cognitive behavioral therapy (CBT) as the first-line treatment for depressed youth by investigating the effects of the various components of a CBT treatment on changes in depressive symptoms in young female participants. Female participants 9-14 years of age (n = 40; M age = 10.58 years) with a diagnosis of a depressive disorder from the CBT-only treatment condition of a larger randomized clinical trial were included in the current study. Participants engaged in a 20-session, 11-week, school-based CBT group intervention (ACTION Treatment; Stark et al., 2006). Depressive symptoms were assessed pre- and posttreatment, and intervention components were coded based on review of audio recordings of treatment sessions. Data were examined using two-level mixed-effects models using hierarchical linear modeling with full maximum likelihood estimation. Results indicated that higher quality behavioral intervention components were associated with greater improvement in posttreatment depression scores, higher quality cognitive intervention components were marginally associated with worsening posttreatment depression scores, and relational intervention components were not associated with depression outcome. Age significantly moderated the relationships between intervention components and depression outcome, with younger female participants benefiting most from higher quality behavioral and relational intervention components. These findings provide preliminary evidence about the differential impact of CBT components on depression treatment outcome for young female participants, with consideration of age as a moderator. This study highlights the importance of continuing to dismantle CBT treatment components for youth depression, as such findings can be used to design more potent, developmentally tailored interventions.


Adherence to iron and folic acid supplementation and prevalence of anemia among pregnant women attending antenatal care clinic at Tikur Anbessa Specialized Hospital, Ethiopia.
Anemia during pregnancy has a significant adverse effect on both the mother and fetus. Iron and folic acid supplementation (IFAS) is the feasible and cost effective strategy to control and prevent anemia in pregnancy. However, the success of this strategy is suboptimal due to poor maternal adherences to the regimen. The aim of this study was to assess prevalence of anemia, rate of adherence to IFAS and associated factors among pregnant women at Tikur Anbessa Specialized Hospital (TASH), Ethiopia. Institution based cross sectional study was conducted among 250 pregnant women who were selected using systematic random sampling from antenatal care clinic (ANC) attendants of TASH. Data was collected through interview and medical chart review by using structured questionnaire. The data was analyzed by SPSS v.24. Binary logistic regression was used to identify the associated factors for IFAS and P < 0.05 was used to declare the association. The prevalence of anemia was 4.8% and half of the study participants were knowledgeable about anemia. The rate of adherence to IFAS was 63.6%. Forgetfulness and fear of side effect were the commonest reasons for poor adherence to IFAS. Gestational age at first ANC visit and educational level were significantly associated with adherence to IFAS. Thus, pregnant women who started their ANC follow up at first trimester (AOR = 1.87, 95% CI (1.18-3.36)) and education level of college and above (AOR = 4.236, 95% CI (1.35-13.25)) and completed secondary education (AOR = 4.09, 95% CI (1.39-12.02)) were more likely to be adherent to IFAS compared with their comparators. Even though anemia prevalence was very low among the study participants, adherence to IFAS was still a challenge during pregnancy. Therefore, counseling about IFAS and anemia prevention and promoting the benefits of early ANC visit are recommended to improve adherence to IFAS.


Global diversity and phylogeny of pelagic shrimps of the former genera Sergestes and Sergia (Crustacea, Dendrobranchiata, Sergestidae), with definition of eight new genera.
We revise the global diversity of the former genera Sergia and Sergestes which include 71 valid species. The revision is based on examination of more than 37,000 specimens from collections in the Natural History Museum of Denmark and the Museum of Natural History, Paris. We used 72 morphological characters (61 binary, 11 multistate) and Sicyonella antennata as an outgroup for cladistic analysis. There is no support for the genera Sergia and Sergestes as they have been defined until now. We define and diagnose eight genera of the former genus Sergia (Sergia and new genera Gardinerosergia, Phorcosergia, Prehensilosergia, Robustosergia, Scintillosergia, Challengerosergia, and Lucensosergia) and seven genera of the former genus Sergestes (Sergestes, Deosergestes, Eusergestes, Allosergestes, Parasergestes, Neosergestes, and a new genus Cornutosergestes). An identification key is presented for all genera of the family Sergestidae. The phylogeny of Sergestidae is mainly based on three categories of characters related to: (1) general decapod morphology, (2) male copulatory organs, and (3) photophores. Only simultaneous use of all three character types resulted in a resolved tree with minimal Bootstrap support 75 for each clade. Most genera are interzonal mesopelagic migrants, some are benthopelagic (Scintillosergia, Lucensosergia), bathypelagic (Sergia), or epipelagic (Cornutosergestes). Within each of meso- and benthopelagic genera there is one species with panoceanic distribution, while most species ranges are restricted to a single ocean. The genera demonstrate two different strategies expressed both in morphology and behavior: protective (Eusergestes, Sergestes, Cornutosergestes, Prehensilosergia, Scintillosergia, Lucensosergia, Challengerosergia, Gardinerosergia, Robustosergia, Phorcosergia, Sergia) and offensive (Neosergestes, Parasergestes, Allosergestes, Deosergestes).


Effect of proline rich domain of an RNA-binding protein Sam68 in cell growth process, death and B cell signal transduction.
Sam68 plays an important role as a multiple functional RNA binding nuclear protein in cell cycle progress, RNA usage, signal transduction, and tyrosine phosphorylation by Src during mitosis. However, its precise impact on these essential cellular functions remains unclear. The purpose of this study is to further elucidate Sam68 functions in RNA metabolism, signal transduction regulation of cell growth and cell proliferation in DT40 cell line. By using gene targeting method, we isolated a mutation form of Sam68 in DT40 cells and described its effect on cell growth process and signal transduction. Southern, Northern, and Western blot, phosphorylation and flow-cytometric analyses were performed to investigate the Sam68 functions. A slower growth rate (2.1 hours growth elongation) and longer S phase (1.7 hours elongation) was observed in the Sam68 mutant cells. Serum depletion resulted in increased amounts of dead cells, and expansion of S phase in mutant cells. Upon B cell cross-linking, the maximal level of tyrosine phosphorylation on BLNK was observed to be significantly lower in mutant cells. The proline rich domain of Sam68 is involved in cell growth control by modulating the function of mRNAs in S phase or earlier and the functions as an adaptor molecule in B cell signal transduction pathways.


Absolute Lymphocyte Count Thresholds: A Simple, Readily Available Tool to Predict the Risk of Cytomegalovirus Infection After Transplantation.
This study of 64 solid organ and hematopoietic stem cell transplant recipients found that peripheral blood absolute lymphocyte count of <610 and <830/µL, respectively, correlated with cytomegalovirus infection. In an era when sophisticated measures of CMV-specific T cells are emerging, we emphasize the utility of the inexpensive and readily-available absolute lymphocyte count.


PHKG2 mutation spectrum in glycogen storage disease type IXc: a case report and review of the literature.
PHKG2 gene mutation can lead to liver phosphorylase kinase (PhK) deficiency, which is related to glycogen storage disease type IX (GSD IX). GSD IXc due to PHKG2 mutation is the second most common GSD IX. We identified a novel mutation (c.553C>T, p.Arg185X) in PHKG2 in a Chinese family and verified it by next-generation and Sanger sequencing. The mutation spectrum of the PHKG2 gene was summarized based on 25 GSD IXc patients with PHKG2 mutations. We found that missense mutation (39%) was the most common type of mutation, followed by nonsense mutation (23%). Mutations were more prevalent in Asian (12/25) and European (9/25) populations than in populations from elsewhere. The exons had more sites of mutation than the introns, and exons 3 and 6 were the most frequent sites of mutations. This study expands our knowledge of the PHKG2 gene mutation spectrum, providing a molecular basis for GSD IXc.


The effect of antinuclear antibody titre and its variation on outcomes in children with primary immune thrombocytopenia.
Antinuclear antibody (ANA) can be positive in children with primary immune thrombocytopenia (ITP), but the effect of ANA titre and its variation on outcomes of children with primary ITP remains unclear. Here, we conducted a single-centre retrospective cohort study of children with primary ITP at the Peking Union Medical College Hospital in China. A total of 324 children with primary ITP included in this study were followed for a median time of 25 months. In this cohort, 39.2% had an ANA titre of 1:160 or higher. Results from a generalized estimating equation model revealed that patients with higher ANA titres had lower platelet counts at onset but a higher recovery rate of subsequent platelet counts. Results from Cox regression models adjusted for potential confounders revealed that patients with ANA titres of 1:160 or more were more likely to develop to autoimmune disease (AID) than those without, and the risk of AID development increased with the rise of ANA titres (p value for trend less than 0.001). These data highlight the predictive value of ANA titre for platelet counts and the risk of AID development in children with primary ITP.


Association of early caffeine administration and neonatal outcomes in very preterm neonates.
Advantages of caffeine for apnea of prematurity have prompted clinicians to use it prophylactically even before apnea. To determine the effect of early initiation of caffeine therapy on neonatal outcomes in very preterm infants born in Canada. A retrospective cohort study was conducted. Patients included preterm neonates born at less than 31 weeks' gestation admitted to 29 participating Canadian Neonatal Network neonatal intensive care units between January 1, 2010, and December 31, 2012. Neonates who received caffeine were divided into 2 groups based on the following timing of caffeine initiation: within the first 2 days after birth (early) and on or after the third day following birth (late). A composite of death or bronchopulmonary dysplasia. Of 5517 eligible neonates, 5101 (92.5%) received caffeine (early: 3806 [74.6%]; late: 1295 [25.4%]). There was no difference in weight or gestational age at birth between the groups. Neonates in the early group had decreased odds of a composite outcome of death or bronchopulmonary dysplasia (adjusted odds ratio [AOR], 0.81; 95% CI, 0.67-0.98) and patent ductus arteriosus (AOR, 0.74; 95% CI, 0.62-0.89). There was no difference between the groups in mortality (AOR, 0.98; 95% CI, 0.70-1.37), necrotizing enterocolitis (AOR, 0.88; 95% CI, 0.65-1.20), severe neurological injury (AOR, 0.80; 95% CI, 0.63-1.01), or severe retinopathy of prematurity (AOR, 0.78; 95% CI, 0.56-1.10). In very preterm neonates, early (prophylactic) caffeine use was associated with a reduction in the rates of death or bronchopulmonary dysplasia and patent ductus arteriosus. No adverse impact on any other outcomes was observed.


Aberrations of the perfect grating rhomb.
The aberrations caused by a perfect grating rhomb beam sampler are calculated for a diverging beam. In the geometric optics limit a tilt does not appear, whereas astigmatism and higher-order aberrations are introduced by a perfect grating rhomb.


Myocarditis in systemic lupus erythematosus diagnosed by 18F-fluorodeoxyglucose positron emission tomography.
Cardiovascular diseaseand heart failure (CHF) are leading causes of death in systemic lupus erythematosus (SLE). The underlying mechanisms for increased CHF in SLE are unclear but myocardial inflammation and lupus myocarditis (LM) may play a role. We propose that 18F-fluorodeoxyglucose-positron emission tomography (18F-FDG-PET)/CT can help diagnose LM. This report describes eight patients with presumed LM; five patients were evaluated due to active cardiorespiratory symptoms and three patients were participating in a pilot study to determine the prevalence of subclinical myocarditis in SLE. Clinical characteristics, laboratory and cardiac testing including electrocardiography (ECG), transthoracic echocardiogram (TTE), coronary artery evaluation as well as 18F-FDG-PET/CT imaging are discussed. Four patients were African American and the others were Hispanic. Half presented with chest pain; 37% had dyspnoea and 25% were asymptomatic. The median SLE Disease Activity Index (SLEDAI-2K) was 5 (2-18) and SLICC Damage Index (SDI) 0.5 (0-5). The median troponin level was 0.08 ng/mL (0-0.9). The most common ECG findings were non-specific ST-T wave abnormalities (n=5). Fifty per cent of the patients had a decreased ejection fraction on TTE and all patients had diffuse myocardial FDG uptake on 18F-FDG-PET/CT consistent with myocardial inflammation. This case series is the first to describe the use of 18F-FDG-PET/CT in the diagnosis of LM and discuss the clinical characteristics and cardiac findings of eight patients with LM supporting the role for cardiac 18F-FDG-PET/CT in its diagnosis.


Systemic hemodynamic and hormonal responses during angiotensin II blockade with saralasin.
The effect of saralasin infusion on systemic hemodynamics, plasma renin activity (PRA), and aldosterone levels was studied under various conditions of sodium balance in 25 patients with essential hypertension. The results of 66 paired observations were statistically analyzed, to elucidate some controversial aspects of the mechanisms of saralasin action. The total peripheral resistance index (TPRI) increased when saralasin had an agonistic effect on blood pressure (BP) and decreased when it acted as an antagonist. The TPRI changed more than the BP by an inversely directed change in the cardiac index (CI). In addition, the changes in the CI were only weakly correlated with the changes in MAP; CI decreased consistently when BP increased but showed no distinct pattern when saralasin acted as an antagonist. The pulse rate did not change under any of the conditions applied. The present findings suggest that in addition to its antagonistic effects on peripheral circulation, saralasin has some action on the heart and autonomic nervous system. The observed changes in the plasma aldosterone level were in accordance with the changes in TPRI and did not point to a difference between adrenal and vascular sensitivity to saralasin or angiotensin II. The overall hemodynamic responses were related to the existing level of PRA. No correlation was found between the degree of volume depletion and the blood pressure response during saralasin after elimination of the effect of PRA by partial regression analysis. These findings do not support the concept that more information about the renin dependency of the BP is provided by the BP reaction to saralasin than by determination of the PRA.


FocalCall: An R Package for the Annotation of Focal Copy Number Aberrations.
In order to identify somatic focal copy number aberrations (CNAs) in cancer specimens and to distinguish them from germ-line copy number variations (CNVs), we developed the software package FocalCall. FocalCall enables user-defined size cutoffs to recognize focal aberrations and builds on established array comparative genomic hybridization segmentation and calling algorithms. To distinguish CNAs from CNVs, the algorithm uses matched patient normal signals as references or, if this is not available, a list with known CNVs in a population. Furthermore, FocalCall differentiates between homozygous and heterozygous deletions as well as between gains and amplifications and is applicable to high-resolution array and sequencing data.


[Points of view: the role of quality measurement from the Federal Joint Committee's perspective].
The Federal Joint Committee (G-BA) is a central decision-making body that issues binding directives to ensure the quality of both inpatient and outpatient health care services within the German Statutory Health Insurance system. Quality measurement on the basis of quality indicators has proceeded furthest in the field of external quality assurance (QA) of inpatient services. Originally designed for quality development in a "protected environment" through learning from better practices, it has been faced with new expectations since competitive elements have been introduced into the health care system. The economisation of medicine is de facto the driving force of the development of QA measures. In terms of health policy, the 2013 coalition agreement includes "a renaissance of the concept of quality competition". In particular, this is meant to strengthen the decision-making options of insured persons by creating more transparency into the quality of not only inpatient but also outpatient care and, if necessary, to support the possibility of selective agreements with individual health insurance funds. The campaign planned to improve the quality of hospitals also provides for a quality-oriented advancement of hospital planning and funding; and the Federal Joint Committee, supported by the new Institute for Quality Assurance and Transparency in the Healthcare System in accordance with Section 137a of Book V of the Social Code (SGB V) in the GKV-FQWG version will be assigned new tasks within this context, too. On the whole, the measures already agreed upon in the Act to Improve the Financial Structure and Quality of the Statutory Health Insurance System (GKV-FQWG) and—as far as can now be anticipated—the proceedings of the working group set up between the German government and the German federal states indicate that there is a high need to improve the methods and tools of external quality assurance available, starting with questions about the validity of the quality indicators used and their relevance to patient care. Special issues and tasks require the development of new methods and tools. The need for paying more attention to the patient perspective will pose a particular challenge to future quality measurement. Additional information about the QA documentation of health care providers and the basis of social data that should be used preferentially can be gained from patient surveys. Despite the high political expectations (for example, concerning the development of online charts comparing the quality of inpatient care delivery), the Federal Joint Committee should not overlook the necessity of embedding quality measurement and public reporting into a comprehensive quality framework which can be used to promote continuous quality improvement through a structured feedback of the results to health care providers. In addition, we need a consistent patient orientation and a systematic evaluation of the QA measures employed. By networking more closely with evidence-based medicine and health services research, quality assurance may give rise to a systematic quality research from which genuine quality and care objectives can be derived and which, as an integral part of a "learning care", supports a patient-oriented advancement of care structures.