Using whole-exome sequencing to investigate the genetic bases of lysosomal storage diseases of unknown etiology.
Lysosomes are membrane-bound, acidic eukaryotic cellular organelles that play important roles in the degradation of macromolecules. Mutations that cause the loss of lysosomal protein function can lead to a group of disorders categorized as the lysosomal storage diseases (LSDs). Suspicion of LSD is frequently based on clinical and pathologic findings, but in some cases, the underlying genetic and biochemical defects remain unknown. Here, we performed whole-exome sequencing (WES) on 14 suspected LSD cases to evaluate the feasibility of using WES for identifying causal mutations. By examining 2,157 candidate genes potentially associated with lysosomal function, we identified eight variants in five genes as candidate disease-causing variants in four individuals. These included both known and novel mutations. Variants were corroborated by targeted sequencing and, when possible, functional assays. In addition, we identified nonsense mutations in two individuals in genes that are not known to have lysosomal function. However, mutations in these genes could have resulted in phenotypes that were diagnosed as LSDs. This study demonstrates that WES can be used to identify causal mutations in suspected LSD cases. We also demonstrate cases where a confounding clinical phenotype may potentially reflect more than one lysosomal protein defect.


Phase III trials of toremifene vs tamoxifen.
Three pivotal phase III trials conducted in North America and Europe served as the basis for the application for approval of toremifene (Fareston) by the FDA. These trials demonstrated that 60 mg/d of toremifene is safe and effective in the treatment of advanced breast cancer in postmenopausal women. The studies also indicated that, on the basis of antitumor efficacy, as well as safety, toremifene is at least equivalent to tamoxifen and may have some long-term advantages.


A direct comparison of appetitive and aversive anticipation: Overlapping and distinct neural activation.
fMRI studies of reward find increased neural activity in ventral striatum and medial prefrontal cortex (mPFC), whereas other regions, including the dorsolateral prefrontal cortex (dlPFC), anterior cingulate cortex (ACC), and anterior insula, are activated when anticipating aversive exposure. Although these data suggest differential activation during anticipation of pleasant or of unpleasant exposure, they also arise in the context of different paradigms (e.g., preparation for reward vs. threat of shock) and participants. To determine overlapping and unique regions active during emotional anticipation, we compared neural activity during anticipation of pleasant or unpleasant exposure in the same participants. Cues signalled the upcoming presentation of erotic/romantic, violent, or everyday pictures while BOLD activity during the 9-s anticipatory period was measured using fMRI. Ventral striatum and a ventral mPFC subregion were activated when anticipating pleasant, but not unpleasant or neutral, pictures, whereas activation in other regions was enhanced when anticipating appetitive or aversive scenes.


Strategies of behavior, energetic and thermogenesis of striped hamsters in response to food deprivation.
The life history of many animals includes periods of food shortage. Two behavioral strategies are involved in small mammals in response to food shortage: an increase in activity behavior, representing the increased foraging or migratory behavior, and a decrease in activity level, serving as a mechanism for conserving energy. However, it is uncertain whether animals adopt both strategies in response to food shortage, and whether hormone and neuroendocrine mechanisms are involved in both strategies. In the present study, changes in behavior and metabolic rate were examined in food-deprived striped hamsters (Cricetulus barabensis). The effects of leptin supplement on activity behavior, metabolic rate and hypothalamic neuropeptide gene expression were also examined. The behavior of food-deprived hamsters significantly changed with photoperiod phases: with increasing activity during the dark phase compared to those fed ad libitum, whereas decreasing activity and simultaneously increasing resting behavior during the light phase. Resting metabolic rate, body mass, and masses of fat depots and digestive tracts significantly decreased in food-deprived hamsters compared with ad libitum controls. Leptin supplement tended to attenuate the increased activity in the dark phase. Gene expression of hypothalamic neuropeptide Y (NPY) was significantly upregulated in food-deprived hamsters, while was significantly attenuated by exogenous leptin. These findings suggest that both behavior strategies are important behavioral adjustments in free-living animals to cope with food shortage. Leptin and hypothalamic NPY gene expression may be involved in the adjustments of physiology and behavior in animals demonstrating a hyperactivity strategy in response to food shortage.


Epidemiologic features of cerebrovascular disease in Manitoba: incidence by age, sex and residence, with etiologic implications.
To determine the incidence of and risk factors in cerebrovascular disease in Manitoba, all 1367 new cases in defined areas (population, 660 391) in an 18-month period were studied. Pertinent data were collected from hospital records, death certificates and autopsy reports. The annual incidence of cerebrovascular disease in these areas was 138/100 000 and the incidence was generally higher in men than in women. The incidence of cerebral infarction (INF) and that of hemorrhage (HGE) were similar in men and women less than 50 years old; thereafter the incidence of INF increased faster with age than did that of HGE, the disparity being greater in men than in women, whereas the incidence of HGE increased at similar rates in the two sexes. The incidence of INF was significantly greater in men than in women in urban areas, and in men it was greater in urban than in rural areas. Elevated concentrations of serum lipids and smoking are implicated as risk factors in INF, and hypertension as a risk factor in HGE.


Periodontal tissue and serum concentration of clarithromycin after systemic administration in patients affected by chronic periodontitis.
During the past two decades, dentists and microbiologists have relied on periodontal antibiotic therapy in the management of periodontitis. This association has accumulated and strengthened exponentially. Macrolides attain high therapeutic concentrations in infected tissue, so they are potentially a good choice for inhibiting invasive periodontal pathogens. Clarithromycin accumulates in phagocytes, monocytes, fibroblasts, polymorphonuclear cells, macrophages, and lymphocytes. These cells are more numerous at inflamed sites, so it is reasonable to expect clarithromycin levels to be higher in periodontally diseased sites. This study determines the distribution profile of clarithromycin in the gingiva of patients with periodontitis compared to serum after systemic administration of clarithromycin. Twenty patients (14 males and six females, aged 25 to 45 years) with chronic periodontitis were enrolled in the study. Gingival index and plaque index were recorded at baseline and 3 days after administration of 500 mg clarithromycin, twice daily, for 3 days. Intravenous blood and biopsy of periodontal tissue samples were taken on the third day. These samples were analyzed for detection of clarithromycin concentration using high-performance liquid chromatography. Approximately 6 hours after the last dose of clarithromycin, mean clarithromycin concentrations in serum and periodontal tissue were 0.465 μg/mL and 2.61 μg/g, respectively, and the difference was statistically significant. Clarithromycin can attain higher levels in gingiva than serum of patients with periodontitis. This distribution profile of clarithromycin can thus be advantageous in the management of periodontal lesions.


Vancomycin-induced nephrotoxicity in rats: is enzyme elevation a consistent finding in tubular injury?
Measurement of urinary enzymes facilitates early detection of acute renal impairment. Since in the case of vancomycin-induced nephrotoxicity, there are different findings for the enzyme N-acetyl-beta-D-glucosaminidase (NAG) in various studies, we decided to measure 3 other important urinary enzymes -- gamma-glutamyl-transferase (GGT), alanine aminopeptidase (AAP) and lactate dehydrogenase (LDH) -- in nephrotoxic rats. Male rats were given intraperitoneal injections of vancomycin (VAN) in doses of 50, 100, 200 and 400 mg/kg or normal saline every 12 hours for 7 days. After the 14th injection, the animals were placed in metabolic cages to collect urine samples. All animals receiving 400 mg/kg VAN died before completion of treatment course. The nephrotoxicity was completely dose-dependent according to pathologic findings. The major insults were in tubules, resembling acute tubular necrosis. GGT, AAP and LDH activity was measured in urine and corrected by dividing it by urinary creatinine (Cr) concentration. LDH activity showed a dose-dependent increase, while GGT and AAP activity decreased in the 200 mg/kg treated group, but only GGT showed a significant difference with controls. Serum urea and Cr and kidney weights were increased and animals' weights were decreased significantly in the 200 mg/kg VAN group compared with other groups. It seems that pathologic assessment remains the most accurate way to diagnose VAN nephrotoxicity. Changes in urinary enzymes could be not detected in minor tubular injuries; however, LDH appears to be the most sensitive factor. In multiple-dose studies, activity of AAP and GGT seems not to be a reliable index of nephrotoxicity.


Use of Linear Ion Traps in Data-Independent Acquisition Methods Benefits Low-Input Proteomics.
The need for a better understanding of cellular heterogeneity has pushed mass spectrometry technologies to the analysis of single-cell and single-cell-type proteomes, although several challenges still limit their widespread implementation. Among the efforts toward single-cell and low-input analyses, there is the adoption of data-independent acquisition methods to increase analytical sensitivity. Here, we revisited the use of linear ion traps mass analyzers in data-independent acquisition methods and demonstrate their benefits to boost peptide and protein identifications in low-input proteomes.


68Ga-siderophores for PET imaging of invasive pulmonary aspergillosis: proof of principle.
The diagnosis of invasive pulmonary aspergillosis (IPA) is difficult and lacks specificity and sensitivity. In the pathophysiology of Aspergillus fumigatus, iron plays an essential role as a nutrient during infection. A. fumigatus uses a specific and highly efficient iron uptake mechanism based on iron-complexing ferric ion Fe(III) siderophores, which are a requirement for A. fumigatus virulence. We aimed to evaluate the potential of siderophores radiolabeled with (68)Ga, a positron emitter with complexing properties comparable to those of Fe(III), as a radiopharmaceutical for imaging IPA. (68)Ga radiolabeling of the A. fumigatus siderophores desferri-triacetylfusarinine C (TAFC) and desferri-ferricrocin (FC) was performed at high specific activity. Stability, protein binding, and log P values were determined. In vitro uptake in A. fumigatus cultures was tested under varying conditions. Biodistribution was studied in healthy noninfected BALB/c mice, and uptake was studied in a model of A. fumigatus infection using immunosuppressed Lewis rats. High-specific-activity (68)Ga labeling could be achieved, and resulting complexes were stable in serum, toward diethylenetriaminepentaacetic acid and Fe(III) challenge. Both siderophores showed hydrophilic properties ((68)Ga-TAFC, log P = -2.59; (68)Ga-FC, log P = -3.17) with low values of protein binding for (68)Ga-TAFC (<2%). Uptake of both siderophores was highly dependent on the mycelial iron load and could be blocked with an excess (10 microM) of siderophore or NaN(3), indicating specific, energy-dependent uptake. In noninfected mice, (68)Ga-TAFC showed rapid renal excretion and low blood values (1.6 +/- 0.37 percentage injected dose per gram [%ID/g] at 30 min); in urine only intact (68)Ga-TAFC was detected. In contrast, (68)Ga-FC revealed high retention in blood (16.1 +/- 1.07 %ID/g at 90 min) and rapid metabolism. In the rat IPA model, lung uptake of (68)Ga-TAFC was dependent on the severity of infection, with less than 0.04 %ID/g in control rats (n = 5) and 0.29 +/- 0.11 %ID/g in mildly infected (n = 3) and 0.95 +/- 0.37 %ID/g in severely infected (n = 4) rats. PET showed focal accumulation in infected lung tissue. Both siderophores bound (68)Ga with high affinity, and (68)Ga-TAFC, especially, showed high stability. (68)Ga-TAFC displayed highly selective accumulation by A. fumigatus subspecies in vitro and in vivo. The high and specific uptake by A. fumigatus proves the potential of (68)Ga-labeled siderophores for the specific detection of A. fumigatus during infection. They hold promise as new PET agents for IPA.


Regulation of microbial immunity: the suppressor cell renaissance.
Regulatory/suppressor cells have become rehabilitated and respectable. They returned as regulators of autoimmunity, but are now acknowledged to critically influence immunity to foreign antigens, such as those found on microbes. This review describes the principal types of regulatory cells that influence immunity to microbes, focusing on viruses. We discuss both the merits and downside of the Treg response during infection. The mechanisms by which Treg are induced, recognize microbes, and exert their function is also discussed. Finally, we examine approaches that might prove useful to manipulate regulatory cell response against infections.


Fractional parentage analysis and a scale-free reproductive network of brown trout.
In this study, we developed a method of fractional parentage analysis using microsatellite markers. We propose a method for calculating parentage probability, which considers missing data and genotyping errors due to null alleles and other causes, by regarding observed alleles as realizations of random variables which take values in the set of alleles at the locus and developing a method for simultaneously estimating the true and null allele frequencies of all alleles at each locus. We then applied our proposed method to a large sample collected from a wild population of brown trout (Salmo trutta). On analyzing the data using our method, we found that the reproductive success of brown trout obeyed a power law, indicating that when the parent-offspring relationship is regarded as a link, the reproductive system of brown trout is a scale-free network. Characteristics of the reproductive network of brown trout include individuals with large bodies as hubs in the network and different power exponents of degree distributions between males and females.


Interactions of complementary PEGylated liposomes and characterization of the resulting aggregates.
The interaction of complementary liposomes bearing both recognizable and protective ligands at their external surface has been investigated. Aggregation of hydrogenated phosphatidyl choline/cholesterol (2:1 molar ratio) based liposomes was mediated by the molecular recognition of the complementary phosphate and guanidinium groups incorporated in separate unilamellar liposomes. The phosphate group was incorporated in the bilayer employing dihexadecyl phosphate, while the guanidinium moiety was introduced in the membrane through the incorporation of various guanidinium lipids. For the latter, anchoring ability and primarily introduction of a spacer group between their lipophilic part and the guanidinium group was found to affect the ability for molecular recognition. Also, poly(ethylene glycol) (PEG) introduced in both types of liposomes at various concentrations and up to 15% with respect to cholesterol modifies the interaction effectiveness and morphology of the obtained aggregates. Interaction of these complementary liposomes leads to large precipitating aggregates or fused liposomes, as shown by phase contrast microscopy and dynamic light scattering. Specifically, fusion of liposomes takes place under a nonleaking process involving lipid mixing, as demonstrated by calcein entrapment and resonance energy transfer experiments. Calorimetric parameters also correlate with the processes of aggregation and fusion. The interactions of non-PEGylated liposomes involve exothermic processes of higher enthalpic content than those of the PEGylated counterparts.


[A case of pheochromocytoma of the urinary bladder].
A case of pheochromocytoma of the urinary bladder is reported. A 17-year-old male was admitted to our hospital because of gross hematuria and urinary retention on Nov. 10, 1985. There was no history of hypertension. Intravenous pyelography and cystogram demonstrated a filling defect in the bladder. Transabdominal sonography disclosed a solid mass in the anterior wall and bladder neck. Cystoscopic examination revealed a non-papillary and broad based tumor in the anterior wall and bladder neck. Partial resection of the bladder wall was performed under the diagnosis of bladder tumor. The histological diagnosis was pheochromocytoma of the urinary bladder.


Disparities in receipt of 5As for smoking cessation in diverse primary care and HIV clinics.
Clinical practice guidelines recommend that clinicians implement the 5As (Ask, Advise, Assess, Assist, and Arrange) for smoking cessation at every clinical encounter. We sought to examine the prevalence of patient- and clinician-reported 5As in two primary care and one HIV care clinics in San Francisco, California between August 2013 and March 2014 (n = 462 patients and n = 61 clinicians). We used multivariable logistic regression analysis to identify factors associated with receipt of the 5As, adjusting for patient demographics, patient insurance, clinic site, patient tobacco use, and patient comorbidities. The patient-reported prevalence of 5As receipt was as follows: Ask, 49.9%; Advise, 47.2%; Assess, 40.6%; any Assist, 44.9%; and Arrange, 22.4%. In multivariable analysis, receipt of Advise, Assess, and Assist were associated with older patient age. Whereas patients with HIV had a lower odds of reporting being advised (AOR 0.5, 95% CI 0.3-0.8) or assessed for readiness to quit (AOR 0.6, 95% CI 0.4-0.9), patients with pulmonary diseases had higher odds of reporting being assisted (AOR 1.6, 95% 1.0-2.6) than patients without these diagnoses. Although the majority of clinicians reported asking (91.8%), advising (91.8%), and assessing (93.4%) tobacco use 'most of the time' or 'always' during a clinical encounter, fewer reported assisting (65.7%) or arranging (19.7%) follow-up. Only half of patients reported being screened for tobacco use and fewer reported receipt of the other 5As, with significant disparities in receipt of the 5As among patients with HIV. Our findings confirm the need for interventions to increase clinician-delivered cessation treatment in primary and HIV care.


Experimental demonstration of 50-m/5-Gbps underwater optical wireless communication with low-complexity chaotic encryption.
In this paper, a low-complexity two-level chaotic encryption scheme is introduced and experimentally demonstrated to improve the physical layer security of a 450-nm laser underwater optical wireless communication (UOWC) system using discrete Fourier transform spread discrete multi-tone (DFT-S DMT) modulation. In the first encryption stage, the original bit stream is encrypted with a chaotic sequence based on a one-dimensional Logistic map. In the second encryption stage, the real and imaginary components of the DFT-S symbols are further encrypted with a pair of separate chaotic sequences, which are generated from a two-dimensional Logistic iterative chaotic map with infinite collapse (2D-LICM). The experimental results indicate that the encryption operation has no negative effect on the performance of the proposed UOWC system. For chaotic encryption, the DFT-S DMT gives a better performance than the DMT scheme under different water turbidities. 55-m/4.5-Gbps and 50-m/5-Gbps underwater transmissions are successfully demonstrated by the chaotic encrypted DFT-S DMT scheme. To the best of our knowledge, this is the first time to verify the feasibility of chaotic encryption in a high-speed UOWC system.


Decoding the mechanisms of embryo development with spatial biology.
[Formula: see text] Spatial genomics first emerged in the 1990s to map biological function data onto multidimensional images of embryo specimens and has continued to be instrumental in studying embryogenesis and understanding early human development in the decades since.


Assay of urinary protein carbonyl content can predict the steroid dependence and resistance in children with idiopathic nephrotic syndrome.
Nephrotic syndrome in pediatric age is mostly idiopathic. Idiopathic nephrotic syndrome (INS) by default is treated with steroids from the very beginning. Some do not respond to steroids and are grouped later as either steroid-resistant (SR) or steroid-dependent (SD) cases. The protein selectivity index often fails to predict the SR and SD cases. The SD and SR cases of INS exhibit higher degrees of oxidative stress compared to steroid responders. Proteins get carbonylated when they are exposed to free radicals. The significance of excretion of these carbonylated proteins in urine is yet to be studied in detail. In this study, 70 cases of INS were enrolled, and urinary protein carbonyl content (UPCC) was estimated by Levine's method before starting the steroid therapy. All the cases were followed up and, based on the response to steroid therapy, were grouped as Group A (n = 47). Steroid sensitive and Group B (n = 23), SD + SR cases. UPCC was significantly higher in Group B compared to Group A. Receiver-operating curve showed at a cutoff limit of 5.10 nmoles/mg of protein, UPCC can predict SD or SR cases with 83.3% sensitivity and 85.2% specificity and area under the curve of 0.833, P<0.05. UPCC levels more than 5.10 nmoles/mg of protein, before starting the therapy can predict SD or SR in pediatric INS cases.


Dynamics of genomic innovation in the unicellular ancestry of animals.
Which genomic innovations underpinned the origin of multicellular animals is still an open debate. Here, we investigate this question by reconstructing the genome architecture and gene family diversity of ancestral premetazoans, aiming to date the emergence of animal-like traits. Our comparative analysis involves genomes from animals and their closest unicellular relatives (the Holozoa), including four new genomes: three Ichthyosporea and Corallochytrium limacisporum. Here, we show that the earliest animals were shaped by dynamic changes in genome architecture before the emergence of multicellularity: an early burst of gene diversity in the ancestor of Holozoa, enriched in transcription factors and cell adhesion machinery, was followed by multiple and differently-timed episodes of synteny disruption, intron gain and genome expansions. Thus, the foundations of animal genome architecture were laid before the origin of complex multicellularity - highlighting the necessity of a unicellular perspective to understand early animal evolution.


Reflections on a systematic nomenclature for antimicrobial peptides from the skins of frogs of the family Ranidae.
Frogs belonging to the extensive family Ranidae represent a valuable source of antimicrobial peptides with therapeutic potential but there is currently no consistent system of nomenclature to describe these peptides. Terminology based solely on species name does not reflect the evolutionary relationships existing between peptides encoded by orthologous and paralogous genes. On the basis of limited structural similarity, at least 14 well-established peptide families have been identified (brevinin-1, brevinin-2, esculentin-1, esculentin-2, japonicin-1, japonicin-2, nigrocin-2, palustrin-1, palustrin-2, ranacyclin, ranalexin, ranatuerin-1, ranatuerin-2, temporin). It is proposed that terms that are synonymous with these names should no longer be used. Orthologous peptides from different species may be characterized by the initial letter of that species, set in upper case, with paralogs belonging to the same peptide family being assigned letters set in lower case, e.g. brevinin-1Pa, brevinin-1Pb, etc. When two species begin with the same initial letter, two letters may be used, e.g. P for pipiens and PL for palustris. Species names and assignments to genera may be obtained from Amphibian Species of the World Electronic Database, accessible at http://research.amnh.org/herpetology/amphibia/index.php. American Museum of Natural History, New York, USA.


Ruptura hepática espontánea en paciente con síndrome HELLP.
Hemorrhagic liver rupture is a rare and deadly complication. The pathogenesis is unknown. This situation forces the multidisciplinary team, the immediate termination of pregnancy, the treatment and management of the patient in an intensive care unit (ICU). We report the results of two patients with spontaneous rupture of the liver during pregnancy and HELLP (hemolysis, elevated liver enzymes, low platelet count) syndrome, asymptomatic, during cesarean section, with management in ICU, poor evolution without adequate response; one died and the other leaves hospital. Liver rupture requires high suspicion and timely, aggressive multidisciplinary management in all cases and surgical intervention in those who develop liver ruptura, to improve survival.


Assessment of Lymphovascular Invasion in Breast Cancer Using a Combined MRI Morphological Features, Radiomics, and Deep Learning Approach Based on Dynamic Contrast-Enhanced MRI.
Assessment of lymphovascular invasion (LVI) in breast cancer (BC) primarily relies on preoperative needle biopsy. There is an urgent need to develop a non-invasive assessment method. To develop an effective model to assess the LVI status in patients with BC using magnetic resonance imaging morphological features (MRI-MF), Radiomics, and deep learning (DL) approaches based on dynamic contrast-enhanced MRI (DCE-MRI). Cross-sectional retrospective cohort study. The study included 206 BC patients, with 136 in the training set [97 LVI(-) and 39 LVI(+) cases; median age: 51.5 years] and 70 in the test set [52 LVI(-) and 18 LVI(+) cases; median age: 48 years]. 1.5 T/T1-weighted images, fat-suppressed T2-weighted images, diffusion-weighted imaging (DWI), and DCE-MRI. The MRI-MF model was developed with conventional MR features using logistic analyses. The Radiomic feature extraction process involved collecting data from categorized DCE-MRI datasets, specifically the first and second post-contrast images (A1 and A2). Next, a DL model was implemented to determine LVI. Finally, we established a joint diagnosis model by combining the MRI-MF, Radiomics, and DL approaches. Diagnostic performance was compared using receiver operating characteristic curve analysis, confusion matrix, and decision curve analysis. Rim sign and peritumoral edema features were used to develop the MRI-MF model, while six Radiomics signature from the A1 and A2 images were used for the Radiomics model. The joint model (MRI-MF + Radiomics + DL models) achieved the highest accuracy (area under the curve [AUC] = 0.857), being significantly superior to the MRI-MF (AUC = 0.724), Radiomics (AUC = 0.736), or DL (AUC = 0.740) model. Furthermore, it also outperformed the pairwise combination models: Radiomics + MRI-MF (AUC = 0.796), DL + MRI-MF (AUC = 0.796), or DL + Radiomics (AUC = 0.826). The joint model incorporating MRI-MF, Radiomics, and DL approaches can effectively determine the LVI status in patients with BC before surgery. 4 TECHNICAL EFFICACY: Stage 2.


Learning a Prototype Discriminator With RBF for Multimodal Image Synthesis.
Multimodal image synthesis has emerged as a viable solution to the modality missing challenge. Most existing approaches employ softmax-based classifiers to provide modal constraints for the generated models. These methods, however, focus on learning to distinguish inter-domain differences while failing to build intra-domain compactness, resulting in inferior synthetic results. To provide sufficient domain-specific constraint, we hereby introduce a novel prototype discriminator for generative adversarial network (PT-GAN) to effectively estimate the missing or noisy modalities. Different from most previous works, we introduce the Radial Basis Function (RBF) network, endowing the discriminator with domain-specific prototypes, to improve the optimization of generative model. Since the prototype learning extracts more discriminative representation of each domain, and emphasizes intra-domain compactness, it reduces the sensitivity of discriminator to pixel changes in generated images. To address this dilemma, we further propose a reconstructive regularization term which connects the discriminator with the generator, thus enhancing its pixel detectability. To this end, the proposed PT-GAN provides not only consistent domain-specific constraints, but also reasonable uncertainty estimation of generated images with the RBF distance. Experimental results show that our method outperforms the state-of-the-art techniques. The source code will be available at: https://github.com/zhiweibi/PT-GAN.


Topical application of Rosa multiflora root extract improves atopic dermatitis-like skin lesions induced by mite antigen in NC/Nga mice.
The roots of Rosa multiflora THUNB. (RM) has been used in oriental traditional medicines as remedies for scabies, rheumatic arthralgia and stomatitis which were practicably related with today's inflammatory and allergic diseases. In the present study, we evaluated whether RM root extract (RME) and its major constituent, 2-(3,4-dihydroxyphenyl)-6-(4-hydroxyphenyl)-8-(2,4-dihydroxyphenyl)-2,3-trans-6,7-cis-7,8-trans-3,4,7,8-tetrahydro-2H,6H-pyrano[2,3-f] chromene-3,7,9-triol (RM-3) belongs to condensed tannins, improve atopic dermatitis (AD)-like skin lesions in NC/Nga mice induced by mite antigen. Topical application of RME as well as RM-3 improved skin severity and suppressed mRNA levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) on skin tissues, in addition, significantly reduced T helper 2 (Th2) immune responses via interleukin 10 (IL-10) up-regulation. Thus, RME, contains lots of condensed tannins such as RM-3 which possesses potent anti-inflammtory and immune-modulatory effects, may be useful for treatment of skin allergies and can be developed as new alternative herbal therapy against AD.


Identification and characterization of permissive cells to dengue virus infection in human hematopoietic stem and progenitor cells.
Dengue virus (DENV) is a significant threat to public health in tropical and subtropical regions, where the frequency of human migration is increasing. Transmission of DENV from donors to recipients after hematopoietic stem cell transplantation has been steadily described. However, the underlying mechanisms remain unclear. Freshly isolated bone marrow (BM) was subjected to DENV infection, followed by multicolor fluorescence-activated cell sorting (FACS) analysis. Virus in supernatants was collected and analyzed by plaque assay. DENV-1 to DENV-4 could effectively infect freshly obtained BM and produced infectious virus. DENV infection did not change the quantitative population of hematopoietic stem and progenitor cells (HSPCs), megakaryocytic progenitor cells (MkPs) and megakaryocytes. Additionally, DENV antigen, nonstructural protein 1, was enriched in HSPCs and MkPs of DENV infected marrow cells. CD34+, CD133+, or CD61+ cells sorted out from BM were not only the major contributing targets facilitating the DENV infection directly but also facilitated the spread of DENV into other cells when cocultured. Results suggest that DENV can efficiently infect HSPCs, which might jeopardize the recipients if DENV-infected cells were subsequently used. We therefore raise the need for DENV screening for both the donors and recipients of hematopoietic stem cell transplantation, especially for donors exposed to endemic areas, to mitigate DENV infection in immunocompromised recipients.


Role of fetal and infant growth in programming metabolism in later life.
Fetal growth and development is dependent upon the nutritional, hormonal and metabolic environment provided by the mother. Any disturbance in this environment can modify early fetal development with possible long-term outcomes as demonstrated by extensive work on 'programming'. Growth restriction resulting from a deficit in tissue/organ cell number (as measured by tissue DNA content) is irrecoverable. However, when the cell size (or cell protein content) is reduced, the effects on growth may not be permanent. Recent epidemiological studies using archival records of anthropometric measurements related to early growth in humans have shown strong statistical associations between these indices of early development and diseases in later life. It has been hypothesised that the processes explaining these associations involve adaptive changes in fetal organ development in response to maternal and fetal malnutrition. These adaptations may permanently alter adult metabolism in a way which is beneficial to survival under continued conditions of malnutrition but detrimental when nutrition is abundant. This hypothesis is being tested in a rat model which involves studying the growth and metabolism in the offspring of rat dams fed a low-protein diet during pregnancy and/or lactation. Using this rat model, it has been demonstrated that there is: (i) Permanent growth retardation in offspring nursed by dams fed a low-protein diet. (ii) Permanent and selective changes in organ growth. Essential organs like the brain and lungs are relatively protected from reduction in growth at the expense of visceral organs such as the liver, pancreas, muscle and spleen. (iii) Programming of liver metabolism as reflected by permanent changes in activities of key hepatic enzymes of glycolysis and gluconeogenesis (glucokinase and phosphoenolpyruvate carboxykinase) in a direction which would potentially bias the liver towards a 'starved' setting. We have speculated that these changes could be a result of altered periportal and perivenous regions of the liver which may also affect other aspects of hepatic function. (iv) Deterioration in glucose tolerance with age. (v) An increase in the life span of offspring exposed to maternal protein restriction only during the lactation period, and a decrease in life span when exposed to maternal protein restriction only during gestation. These studies show that hepatic metabolism and even longevity can be programmed by events during early life.


Antitubercular Bis-Substituted Cyclam Derivatives: Structure-Activity Relationships and in Vivo Studies.
We recently reported the discovery of nontoxic cyclam-derived compounds that are active against drug-resistant Mycobacterium tuberculosis. In this paper we report exploration of the structure-activity relationship for this class of compounds, identifying several simpler compounds with comparable activity. The most promising compound identified, possessing significantly improved water solubility, displayed high levels of bacterial clearance in an in vivo zebrafish embryo model, suggesting this compound series has promise for in vivo treatment of tuberculosis.


Fine-needle aspiration cytology of pilomatrixoma: A short series of three cases.
Pilomatrixoma (PMX) (pilomatricoma, calcifying epithelioma of Malherbe) is a benign tumor with differentiation toward the hair matrix cells and is common in head and neck region. It is most commonly seen in the first two decades of life and presents as a subcutaneous, small, asymptomatic firm solitary nodule. Fine-needle aspiration cytology (FNAC) has been described as an important preoperative diagnostic investigation though on cytology the diagnosis of PMX is sometimes difficult and misdiagnosed. We describe two patients with gradually increasing asymptomatic swelling on pinna and middle finger. FNAC was done and a diagnosis of PMX was given, further confirmed by histopathological examination. The present cases highlight the importance of FNAC in considering PMX as differential diagnosis of dermal or subcutaneous nodules in locations other than head and neck. Cytopathologists who play an important role in the preliminary diagnosis should keep in mind the variability of the cellular composition of these types of lesions to avoid misdiagnosis.


Inhibitors of the kinin system as an alternative method of prevention or reduction reperfusive damages within thrombolytic therapy in patients with acute myocardium infarction.
The aim is to show the effectiveness of inhibitors of the kallikrein-kinin system (KKS) to avoid early microcirculation impairment and low reperfusion damages in the ischemic area during systemic thrombolysis (T) in order to achieve optimal results of thrombolytic therapy (TLT) in patients with acute myocardium infarction. Patients (n=104) with acute myocardium infarction were divided into 4 groups: treatment with early TLT infusing Contrycal (Aprotinin) and Heparin (CH) during the first 2 hrs from the onset of disease (Gr. 1); treatment for isolated T at an early stage (Gr. 2); TLT with late T (in 3-6 hrs) (Gr. 3); and conventional therapy (Gr. 4). The dynamics of clinical and ECG data were evaluated for each of the groups. Before the clinical study was fully evaluated, an experimental-morphological, controlled study was carried out on dogs. These results showed improved retrograde blood flow of the acute ischemized myocardium and decrease in ischemia level, together with reduction of frequency and area of reperfused intramiocardial haemorrhages (RPIMH) in infarction areas under the TLT and CH infusion. When CH was infused a significant advantage was revealed in early T that showed high antianginal and antiarrhythmic effect, while no Q wave was observed or it was deepened non-significantly. More clinical dynamic problems with extrasystols and significant deepening of Q wave were seen in the earlier isolated T (Gr. 2) that were worse than those seen in Gr. 1 conditions, but the problems were more negative in the patients from Gr. 3 and 4. CH optimizes the situation causing suppression of the pathological activation of KKS, decreasing vessel permeability, and reducing reperfusion damage. The latest thrombolytic drugs ensure faster thromb lysing but do not prevent the reperfusion damage, as higher fibrinolytic activity at the moment of T causes enhanced activation of KKS and RPIMH development and prevents peroxide oxidation of the lipids but this may result in higher affectivity of antioxidant use. Earlier administration of KKS inhibitors optimizes the affectivity of TLT and widens the indication to the systemic and intracoronary T, minimizes complications, and may cause higher affectivity of coronary angioplasty (CAP) and aorta-coronary shunting in patients with acute myocardium infarction.


Bacterial enteric infections in children: etiology, clinical manifestations and antimicrobial therapy.
Bacterial enteric infections have a huge impact on human health, particularly among the pediatric population. Despite the explosion of knowledge of the pathogenesis of bacterial enteric infections experienced in the past decade, the number of diarrheal episodes and childhood deaths reported continues to increase in many areas of the world. Specific antimicrobial therapy is indicated for certain confirmed infections, notably shigellosis, enterotoxigenic and enteroinvasive Escherichia coli infections, typhoid fever and cholera. Antimicrobial therapy may have a role in severe and prolonged gastrointestinal illness caused by nontyphoid Salmonella and Campylobacter. However, the use of antimicrobial agents may increase the risk of hemolytic uremic syndrome in children with E. coli O157:H7 infection. Bacterial genome sequencing and better understanding of the pathogenic mechanisms involved in the onset of diarrhea are leading to new preventive interventions, such as enteric vaccines, which may have a significant impact on the magnitude of this human plague.


Development of highly potent and selective dynorphin A analogues as new medicines.
Dynorphin A (Dyn A), a 17 amino acid peptide H-Tyr-Gly-Gly-Phe-Leu-Arg-Arg-Ile-Arg-Pro-Lys-Leu-Lys-Trp-Asp-Asn-Gln-OH, is a potent opioid peptide which interacts preferentially with kappa-opioid receptors. Research in the development of selective and potent opioid peptide ligands for the kappa-receptor is important in mediating analgesia. Several cyclic disulphide bridge-containing peptide analogues of Dyn A, which were conformationally constrained in the putative message or address segment of the opioid ligand, were designed, synthesized and assayed. To further investigate the conformational and topographical requirements for the residues in positions 5 and 11 of these analogues, a systematic series of Dyn A(1-11)-NH2 cyclic analogues incorporating the sulphydryl-containing amino acids L- and D-Cys and L- and D-Pen in positions 5 and 11 were synthesized and assayed. Cyclic lactam peptide analogues were also synthesized and assayed. Several of these cyclic analogues, retained the same affinity and selectivity (vs. the mu- and delta-receptors) as the parent Dyn A(1-11)-NH2 peptide in the guinea-pig brain (GPB), but exhibited a much lower activity in the guinea-pig ileum (GPI), thus leading to centrally vs. peripherally selective peptides. Studies of the structure-activity relationship of Dyn A peptide provide new insights into the importance of each amino acid residue (and their configurations) in Dyn A analogues for high potency and good selectivity at kappa-opioid receptors. We report herein the progress towards the development of Dyn A peptide ligands, which can act as agonists or antagonists at cell surface receptors that modulate cell function and animal behaviour using various approaches to rational peptide ligand-based drug design.


The role of energy intake and energy misreporting in the associations between eating patterns and adiposity.
Research examining associations between eating occasion (EO) frequency and adiposity is inconclusive; studies examining the impact of energy misreporting are rare. This study examined associations between eating patterns and adiposity, with adjustment for energy misreporting, in a nationally representative sample of Australian adults. Dietary intake was assessed via two 24-h recalls collected during the 2011-12 National Nutrition and Physical Activity Survey (n=4050 adults, aged ⩾19 years). Frequencies of all EOs, meals and snacks were calculated. Height, weight and waist circumference (WC) were measured. Energy misreporting was assessed as the ratio of energy intake to predicted energy expenditure (EI:EE). Energy misreporters were identified by EI:EE ratios, <0.68 or >1.32. Multivariate regression models assessed associations between eating patterns and body mass index (BMI), WC, overweight/obesity (BMI ⩾25 kg m-2) and central overweight/obesity (WC ⩾94 cm in men and ⩾80 cm in women). After adjustment for covariates and EI:EE, frequency of all EOs, meals (women only) and snacks was positively associated with WC and BMI (all P<0.01). Snack, but not meal frequency, was also associated with overweight/obesity (men: OR=1.22, 95% CI 1.07-1.39; women: OR=1.26, 95% CI 1.10-1.43) and central overweight/obesity (men: OR=1.17, 95% CI 1.04-1.32; women: OR=1.21, 95% CI 1.06-1.37). Multivariate analysis that excluded energy misreporters and adjusted for EI yielded either null or inverse associations (P<0.05). These findings suggest that the associations between eating patterns and adiposity are complicated by the role of EI and energy misreporting. Longitudinal research that considers the impact of EI and energy misreporting is needed to better understand the relationship between eating patterns and obesity.


Contribution to the Uropodina mites of Peru (Acari: Mesostigmata).
Soil dwelling Uropodina mites were collected from a primary lowland rainforest in Amazonian Peru. The species found belong to three different families. A new diagnosis and the type genus of Tetrasejaspidae fam. nov. are given, and the family is recorded from Peru for the first time on the basis of Tetrasejaspis sellnicki Hirschmann, 1973. Two rotundabaloghid mites were collected (Rotundabaloghia (Circobaloghia) magna Hirschmann, 1992 and Rotundabaloghia (Circobaloghia) iquitosensis Hirschmann, 1992), both already reported from Peru. A new species (Origmatrachys peruensis sp. nov.) from the family Trachyuropodidae was collected in large numbers from soil, and is described on the basis of females, males, nymphs and larvae. This is the first description of the protonymphs and larvae of Origmatrachys. The new species differs from the previously described ones in the basis of sculptural pattern of dorsal, ventral, sternal shields and the length of the setae in the central part of the dorsal shield. A new key to the known adults and deutonymphs of Origmatrachys is given.


Expression of Tetrahymena snRNA gene variants including a U1 gene with mutations in the 5' splice site recognition sequence.
The expression of U1, U2 and U5 snRNA gene variants has been studied under different physiological states of Tetrahymena. Variants of all three snRNA genes are expressed. Among the snRNAs detected is U1-3, a variant with 66 mutations compared to the normal U1 snRNA. Three of these mutations affect the 5' splice site recognition sequence. The U1-3 snRNA is present in a few hundred copies per cell. The expression of Tetrahymena snRNA genes is independent of the physiological state of the cell.


Differentiation of renal cell carcinoma subtypes with different iodine quantification methods using single-phase contrast-enhanced dual-energy CT: areal vs. volumetric analyses.
To investigate the possibility of iodine quantification during a single nephrographic phase in characterizing renal cell carcinoma (RCC) subtypes and if there is a difference between areal and volumetric iodine quantification methods. This retrospective study included 110 patients with 113 histopathologically confirmed RCCs scanned by dual-energy CT at the nephrographic phase before surgeries. For each lesion, an areal measurement of the iodine concentration with maximum enhancement (I max enhan) and the iodine concentration with maximum area among slices (I max area), as well as a volumetric iodine concentration of the whole-tumor (I volume), were evaluated by two independent radiologists. The diagnostic performances in a single nephrographic phase for characterizing RCC subtypes were evaluated, and three iodine quantification methods were compared with each other. There were significant differences (clear cell vs. papillary and clear cell vs. chromophobe RCC) and no significant differences (papillary vs. chromophobe RCC) at the nephrographic phase in all three methods. The area under the receiver operating characteristic (ROC) curve (AUC) derived from the I max enhan for discriminating clear cell from papillary RCC was significantly higher than that derived from the I max area (P = 0.0357) and the I volume (P = 0.0206), and no significant differences existed among the three methods in distinguishing clear cell RCC from chromophobe RCC. The reliability of all three parameters was very high with an interclass correlation coefficient (ICC) exceeding 0.8. Iodine quantification in a single nephrographic phase can be used to differentiate RCC subtypes preoperatively, and the areal maximum enhancement iodine quantification would probably be the most appropriate approach.


Mesothelin as a biomarker for ovarian carcinoma: a meta-analysis.
The objective of this work was to estimate the accuracy of mesothelin as a biomarker for ovarian cancer. A quantitative systematic review was performed. A comprehensive search of the Medline, LILACS, SCOPUS, Embase, Cochrane Central Register of Controlled Trials, Biomed Central, and ISI Web of Science databases was conducted from January 1990 to June 2015. For inclusion in this systematic review, the papers must have measured mesothelin levels in at least two histological diagnoses; ovarian cancer (borderline or ovarian tumor) vs. benign or normal ovarian tissue. For each study, 2 x 2 contingency tables were constructed. We calculated the sensitivity, specificity and diagnostic odds ratio. The verification bias was performed according to QUADAS-2. Statistical analysis was performed with the software Stata 11, Meta-DiSc(r) and RevMan 5.2. Twelve studies were analyzed, which included 1,561 women. The pooled sensitivity was 0.62 (CI 95% 0.58 - 0.66) and specificity was 0.94 (CI 95% 0.92 - 0.95). The DOR was 38.92 (CI 95% 17.82 - 84.99). Our systematic review shows that mesothelin cannot serve alone as a biomarker for the detection of ovarian cancer.


[Therapeutic approach to pulmonary hamartoma patients].
Hamartoma is one of the most common benign tumour of the lung. The authors report their results of the surgical treatment of 17 patients with lung hamartoma. Twelve of them underwent open thoracotomy and 5 video-assisted thoracoscopy. Lobectomy was performed in 6 patients, segmentectomy in 3 and patients atypical lung resection in 8. All of the patients did not have complications.


[The formation of an artificial bladder from the intestines].
Basing on the long-term experience in radical surgery of 252 patients with invasive bladder cancer, the authors come to the conclusion that the establishment of intestinal bladder with postcystectomy recovery of physiological uresis is the most proper therapeutic approach. Extra- or intraperitoneal position of the transplant was decided upon regarding the type and stage of cystectomy and prior methods of derivation. The techniques of one- and multistage operations are presented. Clinical practice evidences that more rapid recovery of urethral uresis can be obtained with application of primary continuous suture of artificial intestinal bladder (ideal enterocystoplasty) at the end of the surgery. Urodynamic low urinary tract findings are provided. The technique developed by the authors offers new surgical opportunity for bladder cancer patients following cystectomy.


Surface Electromyographic Examination of Poststroke Neuromuscular Changes in Proximal and Distal Muscles Using Clustering Index Analysis.
Whether stroke-induced paretic muscle changes vary across different distal and proximal muscles remains unclear. The objective of this study was to compare paretic muscle changes between a relatively proximal muscle (the biceps brachii muscle) and two distal muscles (the first dorsal interosseous muscle and the abductor pollicis brevis muscle) following hemisphere stroke using clustering index (CI) analysis of surface electromyograms (EMGs). For each muscle, surface EMG signals were recorded from the paretic and contralateral sides of 12 stroke subjects versus the dominant side of eight control subjects during isometric muscle contractions to measure the consequence of graded levels of contraction (from a mild level to the maximal voluntary contraction). Across all examined muscles, it was found that partial paretic muscles had abnormally higher or lower CI values than those of the healthy control muscles, which exhibited a significantly larger variance in the CI via a series of homogeneity of variance tests (p < 0.05). This finding indicated that both neurogenic and myopathic changes were likely to take place in paretic muscles. When examining two distal muscles of individual stroke subjects, relatively consistent CI abnormalities (toward neuropathy or myopathy) were observed. By contrast, consistency in CI abnormalities were not found when comparing proximal and distal muscles, indicating differences in motor unit alternation between the proximal and distal muscles on the paretic sides of stroke survivors. Furthermore, CI abnormalities were also observed for all three muscles on the contralateral side. Our findings help elucidate the pathological mechanisms underlying stroke sequels, which might prove useful in developing improved stroke rehabilitation protocols.


The evolution of duplicate gene expression in mammalian organs.
Gene duplications generate genomic raw material that allows the emergence of novel functions, likely facilitating adaptive evolutionary innovations. However, global assessments of the functional and evolutionary relevance of duplicate genes in mammals were until recently limited by the lack of appropriate comparative data. Here, we report a large-scale study of the expression evolution of DNA-based functional gene duplicates in three major mammalian lineages (placental mammals, marsupials, egg-laying monotremes) and birds, on the basis of RNA sequencing (RNA-seq) data from nine species and eight organs. We observe dynamic changes in tissue expression preference of paralogs with different duplication ages, suggesting differential contribution of paralogs to specific organ functions during vertebrate evolution. Specifically, we show that paralogs that emerged in the common ancestor of bony vertebrates are enriched for genes with brain-specific expression and provide evidence for differential forces underlying the preferential emergence of young testis- and liver-specific expressed genes. Further analyses uncovered that the overall spatial expression profiles of gene families tend to be conserved, with several exceptions of pronounced tissue specificity shifts among lineage-specific gene family expansions. Finally, we trace new lineage-specific genes that may have contributed to the specific biology of mammalian organs, including the little-studied placenta. Overall, our study provides novel and taxonomically broad evidence for the differential contribution of duplicate genes to tissue-specific transcriptomes and for their importance for the phenotypic evolution of vertebrates.


Severe allergic conjunctivitis and chemosis caused by disodium cromoglycate.
A 63-year-old man with chronic, nonallergic rhinoconjunctivitis presented immediate adverse reactions, such as intense itching, burning, redness and severe swelling of both conjunctivae after using disodium cromoglycate eye drops. Skin prick tests and conjunctival provocation tests were positive with pure disodium cromoglycate. Circulating IgE-specific antibodies to disodium cromoglycate in serum were demonstrated by RAST. We suggest that the acute ocular reaction was caused by disodium cromoglycate and that the underlying mechanism was probably an IgE-mediated immunological reaction.


Asymmetric Catalytic Synthesis of Hexahydropyrrolo-isoquinolines via Three-Component 1,3-Dipolar-Cycloaddition.
An asymmetric three-component 1,3-dipolar cycloaddition of 3,4-dihydroisoquinolines, bromoacetates and α,β-unsaturated pyrazole amide is realized by using a chiral N,N'-dioxide-Y(OTf)3 complex as the catalyst. The process includes a base-promoted formation of dihydroisoquinolium ylides in situ, and a chiral Lewis acid-catalyzed asymmetric [3+2] cycloaddition with α,β-unsaturated pyrazole amides. A series of hexahydropyrrolo-isoquinolines are obtained in moderate to good yields with excellent diastereo- and enantioselectivities.


Obstetric management following traumatic tetraplegia: case series and literature review.
Pregnancy in tetraplegia is a rare event, with only sporadic cases reported. This case series describes seven pregnancies in five tetraplegic women, all with spinal cord injuries in the region of C6. Retrospective case series. Sydney, Australia. All tetraplegic women presenting to the obstetric service of a university teaching hospital, which also provides a regional spinal injury service, between 1981 and 2006. Hospital records of all patients were examined and information extracted regarding demographics, pregnancies and their complications, labour and delivery and neonatal data. Course, complications, management and outcomes of pregnancy in tetraplegic women. Mean age at the time of injury was 22 years, and, at the time of pregnancy, 33 years. All patients suffered recurrent, and sometimes severe, urinary tract infections and episodes of autonomic dysreflexia during pregnancy. Frequent and sometimes lengthy hospital admissions were required for these and other reasons. Only two pregnancies required caesarean section and all entered labour spontaneously, at a mean of 37.9 weeks of gestation. Episodes of autonomic dysreflexia were aggressively managed using pre-emptive epidural anaesthesia and sublingual nifedipine. All pregnancies resulted in normal, near-term babies with no serious perinatal problems. Pregnancy and childbirth in tetraplegic women can be undertaken safely, usually with spontaneous onset of labour and vaginal delivery. However, hospitalisation for intercurrent problems is common. Management requires a multidisciplinary approach and is best undertaken in major centres with both obstetric and spinal cord injuries medical expertise.


Idiopathic granulomatous mastitis: time to avoid unnecessary mastectomies.
Idiopathic granulomatous mastitis is a rare disease of the breast. Clinically and radiologically it may mimic breast carcinoma. Awareness of surgeons, pathologists, and radiologists is essential to avoid unnecessary mastectomies. Data regarding 24 patients with histologically confirmed idiopathic granulomatous mastitis treated at our center over 8 years were analyzed. The mean age of patients was 34.3 years. Breast lump was the most common presentation. The right breast was affected in 16 cases. Four patients were pregnant at the time of presentation. Lactation within 6 months of presentation was documented in four patients. Two patients used contraceptives pills. A clinical suspicion of malignancy was present in 17 cases. Mammography was performed in 16 patients and showed focal asymmetrical dense lesions in 9, well-circumscribed opacity in 4, spiculated lesion in 1, and was normal in 2. Fine-needle aspiration was performed in 17 patients, of which 2 were reported as malignant. Wide local excision was the mainstay of treatment. One patient underwent mastectomy upon clinical, mammographic, and repeated cytologic findings consistent with malignancy, and the final histology confirmed idiopathic granulomatous mastitis with no evidence of malignancy. Four patients developed recurrence after a mean follow-up of 31.2 months. A greater awareness of the rare entity of idiopathic granulomatous mastitis is mandatory to avoid unnecessary mastectomies. Clinical, radiologic, and even cytologic findings are sometimes confused with malignancy. To the best of our knowledge, our patient who developed the disease at the age of 11 years is the youngest reported case.


Mothers' Grief Experiences of Losing Their Only Child in the 2008 Sichuan Earthquake: A Qualitative Longitudinal Study.
The purpose of this study is to explore bereaved mothers' 2-year experiences of losing their only child in the 2008 Sichuan earthquake. Taking an interpretative phenomenological approach, this study interviewed six bereaved mothers four times (6 months, 12 months, 18 months, and 24 months) in Dujiangyan area in Sichuan Province. The findings suggest that these mothers' personal grief experiences evolved: initially, anger toward the cause of their children's deaths, following despair of meaningless life, guilt and regret, and finally yearning. Although their yearning and missing ebbed after 2 years, these mothers still had unresolved grief. These mothers also faced strained marital relationships and additional pressure from social interactions. This study illuminates that these mothers' personal grief experiences and their coping strategies corresponded to Chinese family and sociocultural context.


Trophic transfer of microbeads to jellyfish and the importance of aging microbeads for microplastic experiments.
Concepts in microplastics studies are not well established due to the emerging nature of microplastic research, especially in jellyfish. We conducted experiments to test whether ephyrae would ingest more microbeads via trophic transfer than direct ingestion and whether medusae would ingest more aged microbeads than virgin microbeads. We exposed ephyrae of Aurelia coerulea to two treatments, aged microbeads and Artemia nauplii that had ingested microbeads. We found that the ephyrae ingested 35 times more microbeads via trophic transfer than by direct ingestion. In the second experiment, medusae of A. coerulea were exposed to virgin microbeads and microbeads in seawater under a 12/12 light/dark cycle or constant darkness. Ingestion rates of microbeads from the light incubation were greater than those from the dark incubation or virgin microbeads, suggesting the likely presence of photosynthetic organisms in biofilms from the light incubation increased the palatability of the microbeads and promoted their ingestion.


Filling in the helper-gap: the intentions of frail older widows.
Despite marked interest in continuity of care and transitions experienced by older persons, there is little information available about the intentions of older women regarding changes that occur in their support networks. This article reports the findings of a descriptive phenomenological study of older widows' experience of home care and describes the experiences of 10 women who lost a key helper during the 3-year study. Compared with theories of continuity of care or transition, the findings are in keeping with the focus of nonequilibrium systems theory: bringing order out of disorder. Findings imply the need for holistic nursing interventions with older women who hope to continue living alone for as long as possible.


Effects of edrophonium on saccadic velocity in normal subjects and myasthenic and nonmyasthenic ocular palsies.
We measured saccadic peak velocities in 8 patients with myasthenia gravis, 9 patients with proven nonmyasthenic ocular palsies, and 3 controls. Patients followed a target moving to and from primary position at 1-second intervals for 8 minutes. We measured the amplitudes and velocities of centrifugal saccades at the start of the task, after 3 minutes of the task (fatigue) and 1 minute after receiving IV edrophonium. The effects of fatigue, though prominent in some myasthenic patients, did not distinguish between the groups. However, edrophonium increased saccadic peak velocities in myasthenic patients but decreased them in both controls and nonmyasthenic patients. Analysis of saccades by amplitude bins showed that these changes in peak velocity reflected shifts in the velocity-amplitude relationship.


Effect of oral glucose administration on ghrelin levels in obese children.
Coexpression of GH secretagogue receptor and ghrelin in the pancreas suggests that this peptide is involved in glucose metabolism. Previous reports in adult humans have demonstrated that plasma ghrelin levels decrease after oral glucose administration. However, no data are available in children. Therefore, the aim of this study was to analyze the response of plasma ghrelin levels in obese children after oral glucose administration. Twenty-eight obese children ranging from Tanner I to Tanner V were studied. All subjects were given 0.75 g/kg (maximum 75 g) glucose solution after overnight fasting. Ghrelin, insulin, glucose and IGF-binding-protein-1 were determined at 0, 30, 60 and 120 min of the oral glucose tolerance test (OGTT). Basal plasma ghrelin levels were significantly lower than in the respective control groups. These levels decreased significantly during OGTT in obese children, reaching a nadir of 28+/-9% at 60 min in parallel with the maximum increase in glucose levels and previous to maximum insulin levels. The rapid fall in plasma ghrelin concentration in obese children after glucose load suggests a mechanism for the control of appetite after food intake.


Suntanning: differences in perceptions throughout history.
In ancient times, the sun was venerated as a source of life in some cultures. Scientifically, the relationship between vitamin D and sunlight and the deficiency of vitamin D in patients with rickets were ultimately discovered. In 1903, Niels Finsen was awarded the Nobel Prize in medicine or physiology for his "Finsen light therapy" for infectious diseases, especially lupus vulgaris. In the 1930s and 1940s, the medical profession promoted sunbathing as beneficial for children. From these bases, the popularity of suntanning emerged, promoted by the availability of more leisure time and, eventually, the development of sunlamps and commercial tanning salons. Although the precise role of ultraviolet light in the pathogenesis of melanoma is uncertain, a melanoma epidemic began to be noticed in the 1970s. During the past 15 years, campaigns have attempted to educate the public about the potential dangers of suntanning and exposure to ultraviolet light. Whether the melanoma epidemic can be reversed remains to be seen.


Effects of oxidizing and reducing agents on ovine pulmonary artery responses to nitric oxide donors, sodium nitroprusside and 3-morpholino-sydnonimine.
Nitrovasodilators-sodium nitroprusside (SNP; 10(-9)-10(-4) M) and 3-morpholino-sydnonimine (SIN-1; 10(-9)-10(-4) M) produced concentration-dependent relaxation of the fourth generation sheep pulmonary artery, preconstricted with 5-hydroxytryptamine (1 microM). Oxidizing agents [oxidized glutathione (GSSG, 1 mM) and CuSO4 (5 and 20 microM)] and reducing agents [dithiothreitol (DTT, 0.1 mM), ascorbic acid (1 mM) and reduced glutathione (GSH, 1 mM)] caused opposite effects on nitric oxide (NO)-induced vasodilation in the artery. Ascorbic acid and GSH potentiated the NO responses, while GSSG and CuSO4 inhibited relaxation caused by the nitrovasodilators. DTT, however, reduced the relaxant potency and efficacy of SNP and SIN-1. Pretreatment of the pulmonary artery strips with DTT (0.1 mM) inhibited SNP (10 microM)-induced Na(+)-K(+)-ATPase activity, while ascorbic acid (1 mM) and GSH (1 mM) had no effect either on basal or SNP (10 microM)-stimulated 86Rb uptake, an index of Na(+)-K(+)-ATPase activity, in ovine pulmonary artery. The results suggest that reducing agents like ascorbic acid may have beneficial effect in improving the vascular function under oxidative stress.


Death Due to Complications of Bowel Obstruction Following Raw Poppy Seed Ingestion.
Eating poppy seeds can cause a positive urine drug screen, but it is unknown whether ingesting large quantities can result in opiate intoxication or toxicity. A 54-year-old woman with intractable vomiting was found unresponsive at home and later pronounced dead. At autopsy, a cast-like large bowel obstruction composed of poppy seeds was identified. Postmortem blood morphine level was < 10 ng/mL. Cause of death was determined to be complications of a bowel obstruction secondary to poppy seed ingestion. Deaths related to eating poppy seeds have not been described in the literature. This case illustrates that consuming raw poppy seeds in large quantities did not cause lethal opiate toxicity. However, overdose deaths associated with ingesting poppy seed tea (PST) have been described. Poppy seed derivatives should be considered a potential source in cases of opiate toxicity without evidence of prescription or street drug abuse.


Multiphasic encephalomyelitis in a patient with recurrent herpes simplex type 2 meningitis.
We here describe a patient with a history of recurrent HSV-2 meningitis who had been free from symptoms for almost 20 y when he developed an acute encephalomyelitis. The clinical course laboratory and radiological findings support an acute multiphasic disseminated encephalomyelitis induced by a recurrent HSV-2 infection.


Quantified water intake in laboratory cats from still, free-falling and circulating water bowls, and its effects on selected urinary parameters.
The study objectives were to determine if the method of water presentation (still [S], circulating [C] or free-falling [FF] bowl systems) influences daily water consumption in cats in a controlled environment, and whether differences in water intake affect urine relative super saturation (RSS) for calcium oxalate and struvite, urine specific gravity (USG), urine osmolality (Uosmol) and urine volume. Sixteen healthy laboratory cats fed a dry diet were individually housed with urine collection systems. Each cat underwent a randomized 2 week crossover period with all bowl systems, allowing a 1 week acclimation period between each crossover. Water intake was measured daily by bowl weight, accounting for spillage and evaporation. USG and urine volume were measured daily, whereas other urinary parameters were measured at various time points throughout each 14 day crossover period. Fourteen cats completed the study. Average daily water intake (ml/kg/day), urine volume, USG and urine RSS for struvite and calcium oxalate were not significantly different between water bowls. Uosmol was significantly higher in C compared with S and FF bowl systems (P = 0.009 for both). Three individual cats demonstrated a significant water bowl preference (Cat 4: C >S, P = 0.039; Cat 10: FF >C, P = 0.005; Cat 11: S >C, P = 0.037). Overall, water bowl type had no appreciable effect on water intake. Uosmol was the only urinary parameter found to be significantly different, and was higher for the C bowl. The implication of this is unknown, considering water intake did not differ significantly between bowls. Alternative methods to increase water intake should be implemented beyond providing unique water bowls in patients where augmented water intake would be beneficial for disease management.


Multispot HIV-1/HIV-2 Rapid Test: advantages over other rapid HIV tests.
The Multispot HIV-1/HIV-2 Rapid Test is sensitive and specific for the detection and differentiation of HIV-1 and HIV-2. These attributes, along with best-in-class specificity among HIV-1 rapid tests, make its use attractive in a confirmatory capacity, especially in settings where HIV-2 is prevalent. Widespread use as a primary screening test is largely thwarted by moderate complexity and high cost.


The Xe shielding surfaces for Xe interacting with linear molecules and spherical tops.
The 129Xe nuclear magnetic resonance spectrum of xenon in gas mixtures of Xe with other molecules provides a test of the ab initio surfaces for the intermolecular shielding of Xe in the presence of the other molecule. We examine the electron correlation contributions to the Xe-CO2, Xe-N2, Xe-CO, Xe-CH4, and Xe-CF4 shielding surfaces and test the calculations against the experimental temperature dependence of the density coefficients of the Xe chemical shift in the gas mixtures at infinite dilution in Xe. Comparisons with the gas phase data permit the refinement of site-site potential functions for Xe-N2, Xe-CO, and Xe-CF4 especially for atom-Xe distances in the range 3.5-6 A. With the atom-atom shielding surfaces and potential parameters obtained in the present work, construction of shielding surfaces and potentials for applications such as molecular dynamics averaging of Xe chemical shifts in liquid solvents containing CH3, CH2, CF3, and CF2 groups is possible.


Generation and characterization of a collection of knock-down lines for the chloroplast Clp protease complex in tobacco.
Protein degradation in chloroplasts is carried out by a set of proteases that eliminate misfolded, damaged, or superfluous proteins. The ATP-dependent caseinolytic protease (Clp) is the most complex protease in plastids and has been implicated mainly in stromal protein degradation. In contrast, FtsH, a thylakoid membrane-associated metalloprotease, is believed to participate mainly in the degradation of thylakoidal proteins. To determine the role of specific Clp and FtsH subunits in plant growth and development, RNAi lines targeting at least one subunit of each Clp ring and FtsH were generated in tobacco. In addition, mutation of the translation initiation codon was employed to down-regulate expression of the plastid-encoded ClpP1 subunit. These protease lines cover a broad range of reductions at the transcript and protein levels of the targeted genes. A wide spectrum of phenotypes was obtained, including pigment deficiency, alterations in leaf development, leaf variegations, and impaired photosynthesis. When knock-down lines for the different protease subunits were compared, both common and specific phenotypes were observed, suggesting distinct functions of at least some subunits. Our work provides a well-characterized collection of knock-down lines for plastid proteases in tobacco and reveals the importance of the Clp protease in physiology and plant development.


Arginine vasopressin V1a receptor-deficient mice have reduced brain edema and secondary brain damage following traumatic brain injury.
The formation of brain edema and subsequent intracranial hypertension are major predictors of unfavorable outcome following traumatic brain injury (TBI). Previously, we reported that arginine vasopressin (AVP) receptor antagonists reduce post-traumatic and post-ischemic brain edema in mice. The aim of the current study was to investigate further the contribution of arginine vasopressin V1a receptors to TBI-induced secondary brain damage in V1a receptor knock-out mice. V1a receptor knock-out (V1a -/-) and wild-type mice were subjected to controlled cortical impact (CCI), and edema (brain water content measured before and 24 h after CCI), primary and secondary contusion volume (15 min and 24 h after CCI), neurological function (one day before and seven days after CCI), body weight (before and seven days after CCI) and mortality were measured. Twenty-four h after CCI, V1a receptor knock-out mice had significantly less brain water content than wild-type mice (mean±standard error of the mean: 79.8%±0.3 vs. 80.6%±0.2, respectively), and secondary contusion volume was significantly smaller (38.2±1.7 mm(3) vs. 45.1±1.5 mm(3) in wild-type mice). Furthermore, the V1a receptor knock-out mice had less neurological dysfunction (3.2±0.8 vs. 7.0±1.4 in wild-type mice) and weight loss (1.0±1.0% vs. 4.9±1.8% in wild-type mice) seven days after CCI. Our data show that mice lacking V1a receptors have less secondary brain damage following experimental traumatic brain injury. We therefore conclude that V1a receptors may represent a novel drug target for preventing post-traumatic brain edema.


"You Have to Keep Yourself Hidden": Perspectives From Malaysian Malay-Muslim Men Who Have Sex With Men on Policy, Network, Community, and Individual Influences on HIV Risk.
Malay-Muslim men who have sex with men (MSM) are marginalized and hidden in Malaysia, a predominantly Muslim country in southeast Asia. We explored the policy, network, community, and individual factors related to HIV infection among Malay-Muslim MSM through 26 in-depth interviews and one focus group discussion (n = 5) conducted in Kuala Lumpur and Kota Bharu between October 2013 and January 2014. As religion plays an important role in their lives, participants viewed homosexuality as a sin. Low risk perception and misconceptions about HIV/AIDS were common, and most participants expressed reluctance to consult a doctor unless they had symptoms. Additionally, buying condoms was embarrassing and anxiety-producing. Fear of discrimination by health care providers and community hindered participants from disclosing sexual behaviors and accessing health services. Homophobic comments and policies by the government and religious leaders were concerns of participants. A safe and enabling environment is needed to reduce HIV risks among Malay-Muslim MSM.


How to guide stent-graft implantation in type B aortic dissection? Comparison of angiography, transesophageal echocardiography, and intravascular ultrasound.
Despite growing interest in stent-graft implantation for type-B aortic dissection, there are no established recommendations to prepare and perform an implantation procedure. We directly compared angiography (ANGIO), transesophageal echocardiography (TEE), and intravascular ultrasound (IVUS) intraprocedually before and after placement of 48 stent grafts in 42 consecutive patients (12 women, 61+/-11 years of age) with acute and chronic type-B aortic dissection for both usefulness and capability to guide aortic stent-graft implantation. Both IVUS and TEE are superior to ANGIO to identify multiple entries (52 and 43 versus 34; P<0.005 each), to diagnose false-lumen slow flow after stent-graft implantation (32 and 31 versus 24; P<0.005 each) and to detect incomplete stent apposition (18 and 16 versus 8; P<0.005 each). In comparison with ANGIO, guide wire position over the entire length of the aorta was documented more frequently by TEE and IVUS (40 and 42 versus 25; P<0.001 each). In 4 patients with abdominal extension of the dissection, only IVUS was able to accurately identify the false lumen over the entire length of the diseased aorta. TEE was superior to IVUS and ANGIO in the detection of endoleaks (5 versus 0 and 1; P<0.05 each). Intraprocedural ANGIO, TEE, and IVUS had been performed without complications in all patients. TEE in conjunction with ANGIO appears to be advantageous and adds incremental information to safely guide stent-graft placement in type-B aortic dissection. Additional use of IVUS was found to be helpful in patients with complex anatomy and abdominal extension of the dissection.


Asymmetric deterioration of spatial awareness with diminishing levels of alertness in normal children and children with ADHD.
There is growing literature suggesting that some children diagnosed with attention deficit hyperactivity disorder (ADHD) can show a significant bias in attention away from left space. Here we examine mechanisms that may underpin these effects in both clinical and non-clinical child populations. Unilateral spatial inattention (unilateral neglect) is a commonly reported consequence of stroke in adults. Although for most patients the problem is relatively transient, persistent forms of neglect are almost exclusively associated with right hemisphere lesions. It has been suggested that this chronicity may result from co-existing disruption to right hemisphere dominant systems that mediate alertness. Here we present two studies examining the relationship between sustained attention and left spatial awareness in childhood. In the first, normal children without the ADHD diagnosis were administered a non-spatial test of sustained attention/alertness. Children who performed poorly at this task, relative to their more attentive peers, showed a modest but reliable delay in awareness of left-sided visual information. Furthermore, attention towards the left declined for both groups as a function of time-on-task, suggesting a significant within-subject modulatory effect of alertness on spatial awareness. The second study examines this relationship in children referred to clinical services for attention problems. Irrespective of their final diagnosis, children were divided into two groups according to their performance in sustained attention/alertness tasks. The results suggest that, regardless of the children's clinical diagnosis, diminished sustained attention/alertness levels formed the strongest predictor of relatively delayed awareness of information presented within left visual space. Two children within this group exhibited signs of hitherto undetected spatial neglect as severe as that observed in some brain-injured adults. Clinical and theoretical implications are discussed.


Detomidine-butorphanol sedation in equine clinical practice.
Combinations of detomidine (mean dose rate 13 micrograms/kg) and butorphanol (mean dose rate 26 micrograms/kg) were used to sedate 61 horses for a variety of surgical or diagnostic procedures in general equine practice. Three horses were sedated on more than one occasion. The degree of sedation was graded from 3 to 0 (deep sedation to no effect) and any side effects were recorded. Forty-three per cent of the horses were graded 3, 46 per cent were graded 2, 8 per cent were graded 1 and 3 per cent were graded 0. Bradycardia and ataxia were the major side effects. The combination was judged to be effective and safe for use in general practice. In 56 horses (92 per cent) the necessary procedure was carried out under excellent conditions and in only one horse was the degree of sedation considered to be totally unsatisfactory.


A review on photo-mediated ultrasound therapy.
Photo-mediated ultrasound therapy (PUT) is a novel therapeutic technique based on the combination of ultrasound and laser. The underlying mechanism of PUT is the enhanced cavitation effect inside blood vessels. The enhanced cavitation activity can result in bio-effects such as reduced perfusion in microvessels. The reduced perfusion effect in microvessels in the eye has the potential to control the progression of eye diseases such as diabetic retinopathy and age-related macular degeneration. Several in vivo studies have demonstrated the feasibility of PUT in removing microvasculature in the eye using rabbit eye model and vasculature in the skin using rabbit ear model. Numerical studies using a bubble dynamics model found that cavitation is enhanced during PUT due to the dramatic increase in size of air/vapor nuclei in blood. In addition, the study conducted to model cavitation dynamics inside a blood vessel during PUT found stresses induced on the vessel wall during PUT are higher than that at normal physiological levels, which may be responsible for bio-effects. The concentration of vasodilators such as nitric oxide and prostacyclin were also found to be affected during PUT in an in vitro study, which may limit blood perfusion in vessels. The main advantage of PUT over conventional techniques is non-invasive, precise, and selective removal of microvessels with high efficiency at relatively low energy levels of ultrasound and laser, without affecting the nearby structures. However, the main limitation of vessel rupture/hemorrhage needs to be overcome through the development of real-time monitoring of treatment effects during PUT. In addition to the application in removing microvessels, PUT-based techniques were also explored in treating other diseases. Studies have found a combination of ultrasound and laser to be effective in removing blood clots inside veins, which has the potential to treat deep-vein thrombosis. The disruption of atherosclerotic plaque using combined ultrasound and laser was also tested, and the feasibility was demonstrated.


The environmental fate of hexachlorobenzene.
The relative importance of different environmental fate processes for hexachlorobenzene (HCB) can be estimated from measured and estimated values of several physical properties and chemical kinetic and equilibrium constants. Photolysis of HCB in water and hexane is slow, while hydrolysis, oxidation and biotransformation appear to be unimportant. HCB will sorb strongly to soil and sediment but will be rapidly volatilized from water into the atmosphere, where slow photolysis is the dominant loss process.


In vitro evaluation of multiobjective hemodynamic control of a heart-assist pump.
Ventricular assist devices now clinically used for treatment of end-stage heart failure require responsive and reliable hemodynamic control to accommodate the continually changing demands of the body. This is an essential ingredient to maintaining a high quality of life. To satisfy this need, a control algorithm involving a trade-off between optimal perfusion and avoidance of ventricular collapse has been developed. An optimal control strategy has been implemented in vitro that combines two competing indices: representing venous return and prevalence of suction. The former is derived from the first derivative of diastolic flow with speed, and the latter derived from the harmonic spectra of the flow signal. The responsiveness of the controller to change in preload and afterload were evaluated in a mock circulatory simulator using a HeartQuest centrifugal blood pump (CF4b, MedQuest Products, Salt Lake City, UT). To avoid the need for flow sensors, a state estimator was used, based on the back-EMF of the actuator. The multiobjective algorithm has demonstrated more robust performance as compared with controllers relying on individual indices.


Planning Spatial Layout of a Typical Salt Tolerant Forage of Sweet Sorghum in the Yellow River Delta via Considering Resource Constraints, Nitrogen Use Efficiency, and Economic Benefits.
In order to effectively address the issue of severe soil salinization in the coastal area of the Yellow River Delta, which has led to a significant number of medium and low-yield fields in this region, and to satisfy the rising demand for feed grain in China in recent years, a highly effective solution is to replace conventional crops by cultivating a specialized type of forage grass that can withstand high salinity levels and is well adapted to the local climate. This study proposed a spatial layout scheme for planting salt-tolerant forages, with the aim of providing a foundation for enhancing saline-alkali land and increasing resource utilization efficiency. The results showed that the climate conditions in the Yellow River Delta were suitable for planting sweet sorghum. With respect to soil salt content, the suitable planting regions for sweet sorghum can be classified into four categories: Suitable, moderately suitable, less suitable, and unsuitable, with soil salt concentrations of 2.62-5.25‱, 5.25-7.88‱, respectively. Concerning economic benefits, sweet sorghum's input-output ratio (74.4%) surpasses that of cotton in high saline-alkali zones, providing a significant advantage in comparison with traditional crops. In non-saline-alkali and light saline-alkali areas, the traditional winter wheat-summer maize planting system offers higher economic benefits and nitrogen use efficiency, so it is recommended to maintain this system as the dominant agricultural model. In moderately and severe saline-alkali zones, although one-season maize exhibits greater nitrogen efficiency, its economic benefits are lower than those of sweet sorghum. Hence, it is advisable to promote one-season maize in suitable regions and introduce salt-tolerant forage, such as sweet sorghum in other areas. This approach offers novel ideas and methods for crop spatial layout planning and addresses potential feed grain shortages in the region.


HIV testing among youth in a high-risk city: prevalence, predictors, and gender differences.
While HIV is prevalent among adolescents and young adults, testing levels remain low and little is known about gender differences in HIV testing. The objectives of this study were to describe the prevalence of past-year HIV testing and evaluate associations between HIV testing and individual- and partner-level factors by gender among heterosexually experienced youth (15-24 years) in Baltimore, Maryland (N = 352). Past-year HIV testing was prevalent (60.1%) and differed by gender (69.4% among women vs. 49.6% among men, p = 0.005). For women, African-American race (AOR 3.09) and recent older partner by ≤2 years (AOR 4.04) were significantly associated with testing. Among men, only African-American race was associated with testing (OR 4.23), with no patterns identified based on risk behavior or perceived partner risk. HIV testing among adolescent and young adults was prevalent in this highly affected urban area. Findings emphasize the value of a gender lens, and provide direction for optimizing engagement in HIV testing.


Gynaecomastia: is one cause enough?
Gynaecomastia can be detected in between one-third and two-thirds of men. A wide variety of causes of gynaecomastia, some physiological, some very serious, have been identified. We present a case in which the cause of the gynaecomastia seemed obvious after history taking and physical examination but we finally ended up with a more complex combination of diagnoses. This case stresses the importance of combining history taking and physical examination with additional laboratory testing for the assessment of gynaecomastia.


Modern imaging techniques in GH secretory disorders.
Magnetic resonance images of the pituitary-hypothalamic area in patients with GH secretory disorders, divided into two groups (hypersecretory and hyposecretory), were studied. In the first group there were 42 patients with pituitary adenoma; size, signal characteristics, direction of growth, and type of enhancement were analyzed and compared with similar studies in 40 age and sex matched control patients with non-GH secreting pituitary adenomas. No significant differences were found except for a higher frequency of chiasm involvement and a more pronounced contrast enhancement in the control group. The hyposecretory group was composed of 101 patients with congenital idiopathic growth hormone deficiency (CIGHD). MR revealed morphological abnormalities consisting of hypoplastic anterior pituitary and ectopic posterior pituitary (PPE) in 59 patients, without evidence of a complete pituitary stalk; in 42 patients the posterior pituitary was in normal position and the pituitary stalk visible. The group with PPE showed a greater frequency of multiple pituitary hormone deficiency (51% vs 12%), breech delivery (30% vs 7%) and associated congenital brain anomalies (12% vs 7%). These data suggest that CIGHD could be the result of a congenital midline brain anomaly in a significant proportion of patients.


Iron-catalyzed β-hydroxymethylative carbonylation of styrene under photo-irradiation.
This study describes an iron-catalyzed divergent oxidation of styrene into β-hydroxylmethylketone and ketone under photo-irradiation. This divergence is ascribed to the use of styrene with various substituents. More importantly, methanol is oxidized into formaldehyde in the reaction and serves as a C1 synthon. Mechanism investigations show that the reaction is initiated by oxidative SET to transfer styrene into the cation radical. The reaction pathway undergoes HAT and β-hydride elimination as well as a concerted cyclization. Particularly, several drug-like molecules, such as melperone analogue, lenperone analogue, and haloperidol analogue, are synthesized. In addition, this method is also applicable to the synthesis of natural product (R)-atomoxetine.


Living Gerontology: Providing Long-Distance, Long-term Care.
My own living and working through normative family transitions of parent care (as both a professional gerontologist and an intergenerational family member) facilitated five important kinds of growth: (a) providing parent care with optimal integrity; (b) understanding, elaborating, and teaching life-cycle theory with increasing depth; (c) using this theory to enrich practice approaches to long-term care; (d) identifying valuable new research directions; and (e) creating a multidimensional professional life that furthers theoretical development and identifies practice principles that promote individual, familial, and societal experiences of a "good old age." This reflective essay addresses these different kinds of growth, as they emerged from and contribute to the ever-developing gerontological domains of theory and practice.


Effects of porcine reproductive and respiratory syndrome virus on pig growth, diet utilization efficiency, and gas release from stored manure.
The objectives of this study were to examine the effects of porcine reproductive and respiratory syndrome virus (PRRSV) infection and vaccination on pig growth, dietary nutrient efficiency of utilization, manure output, and emissions of CO, CH, HS, NO, and NH gases from stored manure. Forty-eight pigs, aged 21 d at the start of the study, were subjected to 1 of 4 treatment combinations arranged in a 2 × 2 factorial design with main factors of PRRSV vaccination and PRRSV infection. Body weight, ADFI, manure output, and nutrient efficiency of utilization were assessed and gas emissions from stored manure were determined daily from 50 to 78 d of age and for 24 d after completion of the animal phase. Infection with PRRSV markedly reduced final BW, ADG, and ADFI ( < 0.01) and reduced efficiencies of ADF and ether extract utilization ( = 0.05 and = 0.02, respectively) regardless of vaccination status. No significant treatment effects were found on manure output, manure pH, efficiencies of lignin utilization, and N retention. Infecting pigs with PRRSV increased daily manure CO emission per pig ( = 0.01). There was an interaction between immunization and infection for NO per pig with manure from uninfected, vaccinated pigs producing as much as the manure from infected, vaccinated pigs whereas there was a difference by PRRSV infection state for nonvaccinated pigs. There were also interactions between treatments for HS and NO emissions per kilogram of manure volatile solids excreted ( = 0.01 and = 0.0001, respectively) with the same pattern as for NO per pig; that is, the vaccinated pigs had similar rates of emission regardless of infection state. Pigs infected with PRRSV increased NO nitrogen per kilogram of total N excreted compared with noninfected groups ( = 0.03). Collectively, these results indicated that PRRSV infection caused decreased growth rates and nutrient utilization efficiency and increased gas emissions from stored manure.


Development of fibrous PLGA/fibrin scaffolds as a potential skin substitute.
The aim of this study has been to fabricate a hybrid electrospun nanofibrous scaffold composed of poly(lactic-co-glycolic) acid (PLGA)/fibrin polymers to be used as a skin substitute and analyze its physical and biological properties. Fibrin was obtained from rat blood plasma, characterized and solubilized in formic acid. The final electrospinning solution concentration was 40% PLGA (w/v) and 1% fibrin (w/v). To improve spinnability, 3% PEG (w/v) was added. The scaffolds were characterized by scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FTIR). Water contact angle, maximum elongation, thermal stability, degree of swelling, blood compatibility, cytotoxicity and cell viability were analyzed. The characterization by SEM showed randomly oriented nanofibers with a mean diameter of 639.8 ± 241.8 nm for the PLGA/fibrin and 1051.0 ± 290.2 nm for the PLGA. FTIR spectra confirmed the presence of fibrin in the mats. Fibrin incorporation reduced the water contact angle from 118.9 ± 2.9 to 111.1 ± 2.8. The fibrin increased tensile strength and decreased elongation at break. The scaffolds demonstrated blood compatibility and fibrin incorporation improved cell adhesion and viability when direct and indirect MTT analyses were carried out. Thus, it can be concluded that the PLGA/fibrin mat is a promising material for use as a skin substitute.


Left main coronary artery atresia with concomitant mitral regurgitation in an adult: A case report.
Left main coronary artery (LMCA) atresia is a quite rare congenital malformation, which may present with various symptoms. Past literatures were sporadic without recent summary of world-wide cases. We hereby report an adult case of LMCA atresia with concomitant mitral regurgitation and also summarize all cases found in published literatures. A 48-year old female presented with sudden dyspnea. Preliminary impression was acute heart failure caused by mitral regurgitation. Preoperative coronary angiography demonstrated that there was no left coronary ostium and multiple collateral vessels arising from right coronary artery. The diagnosis of left main coronary atresia was made and the patient received successful valvuloplasty and coronary artery bypass grafting with left internal mammary artery anastomosed to the left anterior descending (LAD) artery. She recovered well and 3-month follow-up showed the graft was patent. This case highlights the importance of angiography for diagnosis of LMCA and performance of CABG once diagnosed.


Ion Channel Dysfunctions in Dilated Cardiomyopathy in Limb-Girdle Muscular Dystrophy.
Limb-Girdle muscular dystrophies (LGMD) are a heritable group of genetically determined disorders with a primary involvement of the pelvic or shoulder girdle musculature with partially cardiac manifestation, such as dilated cardiomyopathy (DCM) and life-threatening tachyarrhythmia. We report here that human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes from a patient with LGMD2I and DCM associated with recurrent ventricular tachycardia displayed ion channel dysfunction and abnormality of calcium homeostasis. Dermal fibroblasts obtained from a patient with LGMD2I harboring a fukutin-related protein gene mutation (826C>A; Leu276Ile) and 3 healthy donors were reprogrammed to hiPSCs. The hiPSCs were differentiated into cardiomyocytes and used for biological and electrophysiological studies. Compared with hiPSC cardiomyocytes from the healthy donors, the hiPSC cardiomyocytes from the patient exhibited abnormal action potentials characterized by reduced amplitude and upstroke velocity. The peak and late Na channel currents (INa) as well as the peak L-type calcium channel currents were significantly reduced. The expression of SCN5A and CACNA1C was reduced in DCM cardiomyocytes, consistent with reduction of INa and L-type calcium channel currents. In addition, the rapidly activating delayed rectifier potassium current (IKr) was reduced, whereas the transient outward current (Ito) and slowly activating delayed rectifier potassium current (IKs) were similar in DCM and control cardiomyocytes. Finally, a significant reduction of systolic and diastolic intracellular Ca2+ concentrations was detected in DCM cardiomyocytes. This study demonstrates that patient-specific hiPSC cardiomyocytes can recapitulate some phenotypic properties of LGMD2I with DCM and provide a platform for studies on the cardiac events in LGMD.