VGLL4 Selectively Represses YAP-Dependent Gene Induction and Tumorigenic Phenotypes in Breast Cancer.
Members of the mammalian Vestigial-like (VGLL) family of transcriptional cofactors activate genes in response to a wide variety of environmental cues. Recently, VGLL proteins have been proposed to regulate key signaling networks involved in cancer development and progression. However, the biological and clinical significance of VGLL dysregulation in human breast cancer pathogenesis remains unknown. Here, we report that diminished VGLL4 expression, but not VGLL1-3, correlated with both shorter relapse-free survival and shorter disease-specific survival of cancer patients with different molecular subtypes of breast cancer. Additionally, we further demonstrate that overexpression of VGLL4 reduces breast cancer cell proliferation, migration, intravasation/extravasation potential, favors cell death, and suppresses tumor growth in vivo. Mechanistically, VGLL4 negatively regulates the TEAD1-YAP1 transcriptional complex and exerts its growth inhibitory control through its evolutionary conserved TDU2 domain at its C-terminus. The results suggest that VGLL4 is a candidate tumor suppressor gene which acts by selectively antagonizing YAP-dependent tumor growth. VGLL4 may be a promising therapeutic target in breast cancer.


Influence of age-related changes in rodent liver morphology and physiology on drug metabolism--a review.
Age-related changes in weight, morphology and physiology of the rodent liver influencing hepatic drug metabolism are reviewed. Next to the changes in liver weight/body weight ratio with age, the spontaneous occurrence of neoplastic and non-neoplastic lesions may be of particular importance. In addition, the decrease in liver blood blow with age diminishes the biotransformation capacity of the total liver. However, the albumin concentration in plasma and drug uptake do not play important roles, since they are unchanged or only slightly lower in old rats or mice. Drugs are generally metabolized by the liver in two phases: the so-called phase I and phase II metabolism. For most drugs, the phase I reaction is an oxidation. This reaction is catalyzed by cytochrome P-450, cytochrome b5 and NADPH-cytochrome c reductase. In microsomes, a decrease with age is generally observed in the cytochrome P-450 concentration and the NADPH-cytochrome c reductase activity, while there is no change in cytochrome b5. In addition, most microsomal drug-metabolizing enzymes decrease with age in male rats but not in females. The changes in enzyme activities in the male and female mouse are more complex. In fact, increases, decreases and no changes were found. Important phase II reactions are glutathione conjugation and glucuronidation; changes in both reactions with age seem to be of minor importance. Studies with hepatocytes isolated from male rats of different ages reveal that the monooxygenase system mediated metabolism of digitoxin and aflatoxin B1 decreases with age. It can be concluded that the observed decrease in the functional capacity of the monooxygenase system greatly determines the decrease in drug metabolism with age. However, it should always be kept in mind that, among others, the age-related changes in drug metabolism in rats are strongly sex dependent, which is not the case in man. Therefore, caution should be exercised in transferring these data to the human situation.


Methods to detect and characterize introgression.
Introgression, also known as introgressive hybridization, refers to the process that genetic components from the gene pool of one population transfer to the other via constant backcrossing. Introgression is widespread in nature, which plays important roles in increasing genetic diversity and improving adaptability to the environment, and in turn, influences the evolutionary progress of animals, plants and humans. Being as an important evolutionary event, researchers pay great attention to the detection of introgression, the introgression direction, the introgression timing, the pattern of introgression and so on. With the rapid development of high-throughput sequencing technologies, methods to detect and characterize introgression based on genome-wide data are continuously developed. In this review, we summarize a series of methods for introgression detection, and introduce the design principles and applications of these methods. We also discuss the maintenance and selection of gene segments after introgression. This review provides a relatively comprehensive reference for the studies on introgression.


Borrowing strength: a likelihood ratio test for related sparse signals.
Cancer biology is a field where the complexity of the phenomena battles against the availability of data. Often only a few observations per signal source, i.e. genes, are available. Such scenarios are becoming increasingly more relevant as modern sensing technologies generally have no trouble in measuring lots of channels, but where the number of subjects, such as patients or samples, is limited. In statistics, this problem falls under the heading 'large p, small n'. Moreover, in such situations the use of asymptotic analytical results should generally be mistrusted. We consider two cancer datasets, with the aim to mine the activity of functional groups of genes. We propose a hierarchical model with two layers in which the individual signals share a common variance component. A likelihood ratio test is defined for the difference between two collections of corresponding signals. The small number of observations requires a careful consideration of the bias of the statistic, which is corrected through an explicit Bartlett correction. The test is validated on Monte Carlo simulations, which show improved detection of differences compared with other methods. In a leukaemia study and a cancerous fibroblast cell line, we find that the method also works better in practice, i.e. it gives a richer picture of the underlying biology. The MATLAB code is available from the authors or on http://www.math.rug.nl/stat/Software. email@example.com email@example.com.


Ring-Enhancing Progressive Multifocal Leukoencephalopathy Mimicking Glioma in a Presumed Immunocompetent Patient With a History of Multiple Sclerosis: A Case Report and Review of the Literature.
The differential diagnoses of ring-enhancing lesions of the brain parenchyma is broad, but complete ring-enhancing lesions often indicate a neoplastic or infectious process. We present a case of a 70-year-old female with a history of multiple sclerosis (MS) who was not on current disease-modifying therapy (DMT) and was found to have a ring-enhancing lesion that mimicked a high-grade glioma. The patient underwent gross total resection, and histopathologic and molecular analysis revealed a diagnosis of progressive multifocal leukoencephalopathy (PML). A subsequent medical workup on the patient was unrevealing aside from mild lymphopenia. This is a unique case that highlights both an unusual clinical presentation and radiographic appearance of PML. There is a known associated increased risk of PML with the use of some DMTs for MS. However, this case raises the question of the possibility of developing PML years after interferon beta-1a therapy in a patient without overt immunosuppression.


Strength deficits in lower limb prosthesis users: A scoping review.
Strength deficits may play a central role in the severity of balance, mobility, and endurance impairments in lower limb prosthesis users. A body of literature detailing the scope and specifics of muscle weakness in lower limb prosthesis users is emerging, but has yet to be summarized. A synopsis of strength deficits, and their impact on functional abilities in lower limb prosthesis users, may inform rehabilitation and research needs. Synthesize reported strength deficits in lower limb prosthesis users, and discuss possible causes, consequences, and solutions. Scoping review. A search of biomedical databases was performed, and inclusion/exclusion criteria were applied to identify publications relevant to the purpose of the review. In all, 377 publications were identified, of which 12 met the inclusion/exclusion criteria. When compared with the controls and the intact limb, the primary strength outcome, peak torque, was lower in transtibial residual limb knee flexors and extensors, as well as transfemoral residual limb hip muscles. The reviewed studies provide evidence of strength deficits in lower limb prosthesis users. These deficits appear to be consequential, as they may contribute to balance, mobility, and endurance impairments. Additional research exploring alternative strength metrics, clinical tests, and causal links to functional impairments is required. Evidence of muscle weakness among lower limb prosthesis users, and its influence on balance, mobility, and endurance, suggests that greater clinical attention and scientific inquiry into physical conditioning of lower limb prosthesis users is merited and required.


In Vivo MRI Measurement of Spinal Cord Displacement in the Thoracolumbar Region of Asymptomatic Subjects with Unilateral and Sham Straight Leg Raise Tests.
Normal displacement of the conus medullaris with unilateral and bilateral SLR has been quantified and the "principle of linear dependence" has been described. Explore whether previously recorded movements of conus medullaris with SLRs are i) primarily due to transmission of tensile forces transmitted through the neural tissues during SLR or ii) the result of reciprocal movements between vertebrae and nerves. Controlled radiologic study. Ten asymptomatic volunteers were scanned with a 1.5T magnetic resonance (MR) scanner using T2 weighted spc 3D scanning sequences and a device that permits greater ranges of SLR. Displacement of the conus medullaris during the unilateral and sham SLR was quantified reliably with a randomized procedure. Conus displacement in response to unilateral and sham SLRs was quantified and the results compared. The conus displaced caudally in the spinal canal by 3.54±0.87 mm (mean±SD) with unilateral (p≤.001) and proximally by 0.32±1.6 mm with sham SLR (p≤.542). Pearson correlations were higher than 0.99 for both intra- and inter-observer reliability and the observed power was 1 for unilateral SLRs and 0.054 and 0.149 for left and right sham SLR respectively. Four relevant points emerge from the presented data: i) reciprocal movements between the spinal cord and the surrounding vertebrae are likely to occur during SLR in asymptomatic subjects, ii) conus medullaris displacement in the vertebral canal with SLR is primarily due to transmission of tensile forces through the neural tissues, iii) when tensile forces are transmitted through the neural system as in the clinical SLR, the magnitude of conus medullaris displacement prevails over the amount of bone adjustment.


Uncoupling of oxidative phosphorylation enables Candida albicans to resist killing by phagocytes and persist in tissue.
After five serial passages of Candida albicans SC5314 through murine spleens by intravenous inoculation, we recovered a respiratory mutant (strain P5) that exhibited reduced colony size, stunted growth in glucose-deficient media, increased oxygen consumption and defective carbohydrate assimilation. Strain P5 was indistinguishable from SC5314 by DNA typing methods, but had a greater concentration of mitochondria by SYTO18 staining. Treatment with various inhibitors demonstrated that strain P5's electron transport chain was intact and oxidative phosphorylation was uncoupled. During disseminated candidiasis, the mutant did not kill mice or cause extensive damage to kidneys. The burden of strain P5 within kidneys on the first 3 days of disseminated candidiasis was significantly reduced. By days 28 and 60, it was similar to that at the time of death among mice infected with SC5314, suggesting that the mutant persisted and proliferated without killing mice. Strain P5 was resistant to phagocytosis by neutrophils and macrophages. It was also significantly more resistant to paraquat, suggesting that it is able to neutralize reactive oxygen species. Our findings indicate that regulation of respiration influences the interaction between C. albicans and the host. Uncoupling of oxidative phosphorylation might be a mechanism by which the organism adapts to stressful host environments.


[Cultivation of aerobic granules by a method of alternative feed loading].
The formation process and morphological and physicochemical properties of aerobic granules were examined in a SBR system by a method of alternative feed loading. The results showed that the aerobic granules could be quickly and effectively cultivated using the alternative feeding COD 400, 800, 1200 mg/L [feed loading 0.96, 1.92 and 3.84 kg/(m3 x d)] when other conditions were fixed. The developed granules of the reactor were maintained in MLSS 20-22 g/L and SVI 14-16 mL/g. The average size of completely granular particles was 613.6 microm in diameter. The cocci occupied mainly in outer layer of granules, and both cocci and rods existed in inner layer of particles. The granules reached 95% COD removal and 97% NH4+ -N-removal simultaneously. The analysis of FISH showed AOB was distributed in outer surface of aerobic granules, and NOB existed in outer and inner layer small amounts of aerobic granules.


[Fracture resistance of the all-ceramic posts in post-and-core system].
To make a comparative study on the fracture resistance of the all-ceramic posts in post-and-core system where the ceramic core was combined with the post by direct sintering and by two other methods. A total of 15 all-ceramic posts fabricated by alumina-zirconia nano-composite infiltrated ceramics were randomly divided into three groups. They were given the following treatments: Group A: forming and combining the ceramic core with the post by direct sintering; group B: combining the ceramic core with the post by use of 3M RelyX for adhesion; group C: forming composite resin core onto the post. Each specimen was placed into a special jig and subjected to a load perpendicular to the post axis on INSTRON 4302 universal testing instrument until failure. ANOVA was used for statistical analysis. There was no statistically significant difference between the groups (P>0.05). The findings indicate that the strength of the post remains uninfluenced during the combination of the core with the post by direct sintering.


Using Two-Step Cluster Analysis and Latent Class Cluster Analysis to Classify the Cognitive Heterogeneity of Cross-Diagnostic Psychiatric Inpatients.
The heterogeneity of cognitive profiles among psychiatric patients has been reported to carry significant clinical information. However, how to best characterize such cognitive heterogeneity is still a matter of debate. Despite being well suited for clinical data, cluster analysis techniques, like the Two-Step and the Latent Class, received little to no attention in the literature. The present study aimed to test the validity of the cluster solutions obtained with Two-Step and Latent Class cluster analysis on the cognitive profile of a cross-diagnostic sample of 387 psychiatric inpatients. Two-Step and Latent Class cluster analysis produced similar and reliable solutions. The overall results reported that it is possible to group all psychiatric inpatients into Low and High Cognitive Profiles, with a higher degree of cognitive heterogeneity in schizophrenia and bipolar disorder patients than in depressive disorders and personality disorder patients.


Borderline ovarian tumors and diagnostic dilemma of intraoperative diagnosis: could preoperative He4 assay and ROMA score assessment increase the frozen section accuracy? A multicenter case-control study.
The aim of our study was to assess the value of a preoperative He4-serum-assay and ROMA-score assessment in improving the accuracy of frozen section histology in the diagnosis of borderline ovarian tumors (BOT). 113 women presenting with a unilateral ovarian mass diagnosed as serous/mucinous BOT at frozen-section-histology (FS) and/or confirmed on final pathology were recruited. Pathologists were informed of the results of preoperative clinical/instrumental assessment of all patients. For Group_A patients, additional information regarding He4, CA125, and ROMA score was available (in Group_B only CA125 was known). The comparison between Group A and Group B in terms of FS accuracy, demonstrated a consensual diagnosis in 62.8% versus 58.6% (P: n.s.), underdiagnosis in 25.6% versus 41.4% (P<0.05), and overdiagnosis in 11.6% versus 0% (P<0.01). Low FS diagnostic accuracy was associated with menopausal status (OR: 2.13), laparoscopic approach (OR: 2.18), mucinous histotype (OR: 2.23), low grading (OR: 1.30), and FIGO stage I (OR: 2.53). Ultrasound detection of papillae (OR: 0.29), septa (OR: 0.39), atypical vascularization (OR: 0.34), serum He4 assay (OR: 0.39), and ROMA score assessment (OR: 0.44) decreased the probability of underdiagnosis. A combined preoperative assessment through serum markers and ultrasonographic features may potentially reduce the risk of underdiagnosis of BOTs on FS while likely increasing the concomitant incidence of false-positive events.


Immunogenicity and reactogenicity of four Haemophilus influenzae type b capsular polysaccharide vaccines in Finnish 24-month-old children.
Stimulated by questions raised on potential differences between the Haemophilus influenzae type b capsular polysaccharide (PRP) vaccines on the market and the applicability of the efficacy data of a similar PRP vaccine obtained in a large field study in 1974 in Finland, we wished to compare the immunogenicity of all these preparations in 24-month-old Finnish children. In our study 137 children received the now recommended 25-micrograms dose of 1 of 4 H. influenzae type b PRP vaccines currently available, and an additional 86 children received half this dose corresponding to the 12.7 micrograms used in 1974. Anti-PRP antibodies were measured in blood samples taken before and 4 weeks after vaccination by the same radioimmunoassay and in the same laboratory as in 1974. The vaccines were equally immunogenic. Furthermore the now recommended dose of 25 micrograms did not give results (geometric mean concentrations, 2.38 to 3.45 micrograms/ml) differing from those after a 12.5-micrograms (2.01- to 3.45-micrograms/ml) dose which was used in 1974. Antibody concentrations of 0.15 and 1.0 micrograms/ml were achieved in 91 to 95 and 66 to 84% of the children, respectively. The corresponding values after 1974 vaccinations were 3.53 micrograms/ml and 100 and 82% of children, respectively. The percentage of those responding with concentrations greater than or equal to 1 microgram/ml was somewhat higher in these Finnish children than reported for children of the same age receiving the same vaccine lots in the United States. Adverse reactions were mild or moderate and transient.


Sensitivity of Lagrangian coherent structure identification to flow field resolution and random errors.
The effect of spatial and temporal resolutions and random errors on identification of Lagrangian coherent structures (LCSs) from Eulerian velocity fields is evaluated using two canonical flows: a two-dimensional vortex pair and a vortex ring formed by transient ejection of a jet from a tube. The flow field for the vortex pair case was steady and obtained analytically while the transient vortex ring flow was simulated using computational fluid dynamics. To evaluate resolution and random error effects, the flow fields were degraded by locally smoothing the flow and sampling it on a sparser grid to reduce spatial resolution, adding Gaussian distributed random noise to provide random errors, and/or subsampling the time series of vector fields to reduce the temporal resolution (the latter applying only for the vortex ring case). The degradation methods were meant to emulate distortions and errors introduced in common flow measurement methods such as digital particle image velocimetry. Comparing the LCS corresponding to the vortex boundary (separatrix) obtained from the degraded velocity fields with the true separatrix (obtained analytically for the vortex pair case or from high resolution, noise-free velocity fields for the vortex ring case) showed that noise levels as low as 5%-10% of the vortex velocity can cause the separatrix to significantly deviate from its true location in a random fashion, but the "mean" location still remained close to the true location. Temporal and spatial resolution degradations were found to primarily affect transient portions of the flow with strong spatial gradients. Significant deviations in the location of the separatrix were observed even for spatial resolutions as high as 2% of the jet diameter for the vortex ring case.


Simple, Safe, and Cost-Effective Technique for Resected Stomach Extraction in Laparoscopic Sleeve Gastrectomy.
Background. Laparoscopic sleeve gastrectomy (LSG) has become a popular operation during the recent years. This procedure requires resection of 80-90% of the stomach. Extraction of gastric specimen is known to be a challenging and costly stage of the operation. In this paper, we report results of a simple and cost-effective specimen extraction technique which was applied to 137 consecutive LSG patients. Methods. Between October 2013 and October 2015, 137 laparoscopic sleeve gastrectomy surgeries were performed at Dokuz Eylul University General Surgery Department, Upper Gastrointestinal Surgery Unit. All specimens were extracted through a 15 mm trocar site without using any special device. Results. We noticed one superficial incisional surgical site infection and treated this patient with oral antibiotics. No cases of trocar site hernia were observed. Conclusion. Different techniques have been described for specimen extraction. This simple technique allows extraction of specimen safely in a short time and does not require any special device.


Grammatical aspect is a strength in the language comprehension of young children with autism spectrum disorder.
The comprehension of tense/aspect morphology by children with autism spectrum disorder (ASD) was assessed via Intermodal Preferential Looking (IPL) to determine whether this population's difficulties with producing these morphemes extended to their comprehension. Four-year-old participants were assessed twice, 4 months apart. They viewed a video that presented side-by-side ongoing and completed events paired with familiar verbs with past tense and progressive morphology. Their eye movements were recorded and coded offline; the IPL measures included percentage of looking time at, and latency of first look to, the matching scene. Spontaneous speech samples were also obtained and coded for number of words, past tense, and progressive inflections. Relative to their baseline preferences, these 4-year-old children with ASD looked more quickly to and longer at the matching scene for both morphemes. Children who produced more words, including progressive and past morphemes, and those who performed better on standardized language assessments demonstrated better comprehension of -ing. Overall, these children with ASD demonstrated consistent comprehension of grammatical aspect morphology; moreover, their degree of comprehension was found to correlate with spontaneous production and standardized test scores.


Dual Cross-Linked Biofunctional and Self-Healing Networks to Generate User-Defined Modular Gradient Hydrogel Constructs.
Gradient hydrogels have been developed to mimic the spatiotemporal differences of multiple gradient cues in tissues. Current approaches used to generate such hydrogels are restricted to a single gradient shape and distribution. Here, a hydrogel is designed that includes two chemical cross-linking networks, biofunctional, and self-healing networks, enabling the customizable formation of modular gradient hydrogel construct with various gradient distributions and flexible shapes. The biofunctional networks are formed via Michael addition between the acrylates of oxidized acrylated hyaluronic acid (OAHA) and the dithiol of matrix metalloproteinase (MMP)-sensitive cross-linker and RGD peptides. The self-healing networks are formed via dynamic Schiff base reaction between N-carboxyethyl chitosan (CEC) and OAHA, which drives the modular gradient units to self-heal into an integral modular gradient hydrogel. The CEC-OAHA-MMP hydrogel exhibits excellent flowability at 37 °C under shear stress, enabling its injection to generate gradient distributions and shapes. Furthermore, encapsulated sarcoma cells respond to the gradient cues of RGD peptides and MMP-sensitive cross-linkers in the hydrogel. With these superior properties, the dual cross-linked CEC-OAHA-MMP hydrogel holds significant potential for generating customizable gradient hydrogel constructs, to study and guide cellular responses to their microenvironment such as in tumor mimicking, tissue engineering, and stem cell differentiation and morphogenesis.


Increasing Insulin Pump Use Among 12- to 26-Year-Olds With Type 1 Diabetes: Results From the T1D Exchange Quality Improvement Collaborative.
Insulin pump therapy in pediatric type 1 diabetes has been associated with better glycemic control than multiple daily injections. However, insulin pump use remains limited. This article describes an initiative from the T1D Exchange Quality Improvement Collaborative aimed at increasing insulin pump use in patients aged 12-26 years with type 1 diabetes from a baseline of 45% in May 2018 to >50% by February 2020. Interventions developed by participating centers included increasing in-person and telehealth education about insulin pump technology, creating and distributing tools to assist in informed decision-making, facilitating insulin pump insurance approval and onboarding processes, and improving clinic staff knowledge about insulin pumps. These efforts yielded a 13% improvement in pump use among the five participating centers, from 45 to 58% over 22 months.


Malnutrition and respiratory function.
Malnutrition has a tremendous impact on respiratory functions. It affects respiratory muscle performance, lung structure, defense mechanisms, and control of ventilation and predisposes to respiratory failure and prolonged mechanical ventilation. Calling clinicians' attention to this common clinical problem is the first step toward developing a systematic approach to patient care in which correction of malnutrition is an integral part of the therapy. The increased morbidity and mortality in malnourished patients can be better understood when they are superimposed on other disease conditions, such as chronic lung disease, sepsis, trauma, and cardiovascular dysfunction. Most important is the fact that many of the consequences of malnutrition can be partially reversible with appropriate refeeding.


Noise-driven neuroplasticity in self-organizing feature maps: a neurocomputational model of phantom limbs.
The term "phantom limb" denotes the sensation that an extremity is present although it has been lost. A number of clinical features and recent findings of cortical map plasticity after destruction of afferent pathways (deafferentation) suggest that phantom limbs are caused by large-scale cortical reorganization processes. However, in paraplegics, who also suffer from cortical deafferentation, phantom sensations rarely develop, and if they do, they are weak, lacking in detail, and delayed, occurring after months. This has been taken to suggest a non-cortical genesis of phantom limbs. This article proposes a biologically plausible minimal neural network model to solve this apparent puzzle. Deafferentation was simulated in trained self-organizing feature maps. Reorganization was found to be directed by input noise. According to the model, the production of input noise by the deafferented primary sensory neuron promotes cortical reorganization in amputees. No such noise is generated or conducted to the cortex in paraplegics.


Routine genetic testing of lung cancer specimens derived from surgery, bronchoscopy and fluid aspiration by next generation sequencing.
After the development of EGFR tyrosine kinase inhibitors (TKIs), genetic testing of EGFR became required for effective treatment of lung cancer. Initially, the testing was conducted separately for each mutated region. However, many EGFR mutations have since been identified that determine the efficacy of EGFR-TKIs. Therefore, genetic testing of EGFR by next generation sequencing (NGS) may be a suitable strategy for lung cancer. Here we examined the applicability of the NGS method in regard to sensitivity, time and cost. A total of 939 specimens were obtained from 686 lung cancer patients at our hospital. DNA and RNA were simultaneously extracted from specimens derived from surgery, bronchoscopy, and fluid aspiration. Specimens included cerebrospinal fluid, pleural effusion, abdominal fluid, and pericardial effusion. From RNA, target regions (EGFR, KRAS, ALK fusion and RET fusion) were enriched by RT-PCR and sequenced with MiSeq. From DNA, PCR or PCR-RFLP conventional methods were performed. NGS and conventional methods were carried out routinely per week. Among the total 939 specimens, 38 specimens could not be examined with NGS. Among these, 34 specimens were analyzed by conventional testing with simultaneously extracted DNA. The remaining four specimens could not be tested with either method. Compared with the conventional method, the concordance rate of mutations was 99% (892/901), excluding specimens with NGS failure. The time period required from processing of specimens to results was 4 days, and the cost per sample was sufficiently low. In conclusion, the genetic testing with NGS method was useful for lung cancer treatment. The cost, sensitivity and time were able to tolerate routine examinations.


[Risk factors in cerebrovascular disease. Do transient ischemic attacks lead to changes in lifestyle?].
A minor stroke does not cause sufficient alarm in patients to change their lifestyles. 46 patients who suffered strokes in the previous 2 years were contacted by telephone, recording rehabilitation programs, medical therapy and modification of dietary habits. It was discovered that only 50% of those requiring motor rehabilitation actually received such treatment; and only one of twenty carried on speech exercises. Subsequent ischemic events were reported by 22 patients: 12 of whom had strokes, 8 ischemic myocardial attacks and two patients suffered both conditions. The majority of patients followed the prescribed medical treatment and advice badly. Of the 46 patients reviewed, 31 were hypertensive and only 16 follow recommended diets. Out of 15 smokers only, 6 gave up, and from 21 with dislypemia only 10 modified their diets. Of all patients only the most severely affected complied satisfactorily to medical treatments; a possible explanation for this would be that the contact between patients and physician (neurologist and family doctors) was discontinued immediately after the patients discharge from hospital. It is recommended therefore that steps be taken to insure better communication between neurologist, general practitioner and patient; thereby improving prognosis.


Sulforhodamine B (SRB) Assay in Cell Culture to Investigate Cell Proliferation.
The SRB assay has been used since its development in 1990 (Skehan et al., 1990) to inexpensively conduct various screening assays to investigate cytotoxicity in cell based studies (Vichai and Kirtikara, 2006). This method relies on the property of SRB, which binds stoichiometrically to proteins under mild acidic conditions and then can be extracted using basic conditions; thus, the amount of bound dye can be used as a proxy for cell mass, which can then be extrapolated to measure cell proliferation. The protocol can be divided into four main steps: preparation of treatment, incubation of cells with treatment of choice, cell fixation and SRB staining, and absorbance measurement. This assay is limited to manual or semiautomatic screening, and can be used in an efficient and sensitive manner to test chemotherapeutic drugs or small molecules in adherent cells. It also has applications in evaluating the effects of gene expression modulation (knockdown, gene expression upregulation), as well as to study the effects of miRNA replacement on cell proliferation (Kasinski et al., 2015).


Surgery for multiple endocrine neoplasia type 1-related insulinoma: long-term outcomes in a large international cohort.
Insulinomas are found in 10-15 per cent of patients with multiple endocrine neoplasia type 1 (MEN1) and lead to life-threatening hypoglycaemia. Surgical outcome and the optimal surgical strategy for MEN1-related insulinoma are unknown. Patients with MEN1-related insulinomas were identified in 46 centres in Europe and North America between 1990 and 2016. Insulinomas were considered localized if the lesion was in the pancreatic head or body/tail. Patients with pancreatic neuroendocrine tumours throughout the pancreas were suspected of having multifocal insulinoma. The primary outcome was postoperative hypoglycaemia, defined as persistent hypoglycaemia, or recurrent hypoglycaemia caused by a new insulinoma or insulin-producing liver metastases. Hypoglycaemia-free survival was estimated by the Kaplan-Meier method. Ninety-six patients underwent resection for MEN1-related insulinoma. Sixty-three and 33 patients had localized and multifocal insulinomas respectively. After a median follow-up of 8 (range 1-22) years, one patient (1 per cent) had persistent disease and six (6 per cent) had developed recurrent disease, of whom four had a new insulinoma. The 10-year hypoglycaemia-free survival rate was 91 (95 per cent c.i. 80 to 96) per cent. Of those with localized disease, 46 patients underwent pancreatic resection and 17 enucleation. One of these patients had persistent disease and one developed recurrent insulinoma. Among patients with multifocal disease, three developed new insulinomas and two developed insulin-producing liver metastases. Surgery for MEN1-related insulinoma is more successful than previously thought.


Upregulation of TLR1, TLR2, TLR4, and IRAK-2 Expression During ML-1 Cell Differentiation to Macrophages: Role in the Potentiation of Cellular Responses to LPS and LTA.
12-O-tetradecanoylphorbol 13-acetate (TPA) induces the differentiation of human myeloid ML-1 cells to macrophages. In the current study, the expression, responsiveness, and regulation of toll-like receptors (TLRs) in TPA-induced ML-1-derived macrophages were investigated. We have found that TPA-induced differentiation of ML-1 cells was accompanied by the upregulation of TLR1, TLR2, TLR4, and CD14 expression at both the mRNA and protein levels. Interestingly, TLR1 and TLR4 protein expression on ML-1 cells could be blocked by pretreatment with U0126, suggesting the role of an Erk1/2-induced differentiation signal in this process. In addition, the expression of IRAK-2, a key member of the TLR/IRAK-2/NF-κB-dependent signaling cascade was also induced in response to TPA. Accordingly, we demonstrated an increased cellular release of inflammatory cytokines (TNF-α and various interleukins) upon stimulation with LPS and LTA ligands for TLR4 and TLR2, respectively. Furthermore, using luminol-dependent chemiluminescence, addition of LPS and LTA induces a sustained DPI-inhibitable generation of reactive oxygen species (ROS) by the differentiated ML-1 cells. Together, these data suggest that the increase in the responsiveness of TPA-treated ML-1 cells to LPS and LTA occurs in response to the upregulation of their respective receptors as well as an induction of the IRAK-2 gene expression.


Lower Body Lymphedema in Patients with Gynecologic Cancer.
Lower body lymphedema is a chronic condition and a significant cause of morbidity following treatment of gynecologic cancer that strongly impacts patients' quality of life (QoL). Most studies on secondary lymphedema have been performed on the upper limb after breast cancer treatment and much less is known about lower body lymphedema after gynecologic malignancies. This review focuses on secondary lymphedema due to gynecologic cancer treatment, analyzing its incidence in the different types of gynecologic cancer, diagnosis, risk factors, impact on QoL and treatment. A systematic search of Medline has been performed to track the studies evaluating lower body lymphedema after treatment for endometrial, ovarian, cervical and vulvar cancer. Unfortunately, there is no consensus about a uniform evaluation and, as a consequence, the reported incidence is broadly different among the studies. Standardization in lymphedema evaluation is required to better compare the outcome of different types of treatment.


Ecology and economic impact of two plant bugs (Hemiptera: Miridae) in commercial vineyards.
The current study investigated the seasonal phenology, spatial distribution, feeding damage and economic impact of two plant bugs, Lygocoris inconspicuous Knight and Taedia scrupeus Say, in commercial vineyards. For both plant bugs, densities of nymphs were higher on vines located near the edge of woodlots rather than in the interior of vineyards, which may be attributed to the presence of wild vines and other alternate host-plants in wooded areas. Nymphs of both species fed on apical leaves and developing fruit clusters of vine shoots, initiating development after swelling of buds in the spring and reaching the adult stage when vines were in bloom. Confining high densities of L. inconspicuous (10 nymphs) on individual shoots early in the season resulted in significant reduction of the number of fruit clusters per shoot, even when feeding was restricted to short (7 d) duration; the average weight of fruit clusters, in contrast, was not affected to a large extent by feeding activity of nymphs. An experiment evaluating the impact of low density of L. inconspicuous (0-0.3 nymphs per shoot) indicated a marginally significant negative relationship between density of nymphs and average weight of fruit clusters. Control measures may be economically justified when population density exceeds a combined threshold of one nymph of either L. inconspicuous or T. scrupeus per 10 shoots of vines.


Reconstruction and analysis of nutrient-induced phosphorylation networks in Arabidopsis thaliana.
Elucidating the dynamics of molecular processes in living organisms in response to external perturbations is a central goal in modern systems biology. We investigated the dynamics of protein phosphorylation events in Arabidopsis thaliana exposed to changing nutrient conditions. Phosphopeptide expression levels were detected at five consecutive time points over a time interval of 30 min after nutrient resupply following prior starvation. The three tested inorganic, ionic nutrients NH(+) 4, NO(-) 3, PO(3-) 4 elicited similar phosphosignaling responses that were distinguishable from those invoked by the sugars mannitol, sucrose. When embedded in the protein-protein interaction network of Arabidopsis thaliana, phosphoproteins were found to exhibit a higher degree compared to average proteins. Based on the time-series data, we reconstructed a network of regulatory interactions mediated by phosphorylation. The performance of different network inference methods was evaluated by the observed likelihood of physical interactions within and across different subcellular compartments and based on gene ontology semantic similarity. The dynamic phosphorylation network was then reconstructed using a Pearson correlation method with added directionality based on partial variance differences. The topology of the inferred integrated network corresponds to an information dissemination architecture, in which the phosphorylation signal is passed on to an increasing number of phosphoproteins stratified into an initiation, processing, and effector layer. Specific phosphorylation peptide motifs associated with the distinct layers were identified indicating the action of layer-specific kinases. Despite the limited temporal resolution, combined with information on subcellular location, the available time-series data proved useful for reconstructing the dynamics of the molecular signaling cascade in response to nutrient stress conditions in the plant Arabidopsis thaliana.


Single vital-capacity and successive tidal-volume breathing of sevoflurane in induction of anesthesia for tracheal intubation in gynecologic patients.
The optimal end-tidal concentrations of sevoflurane in induction of anesthesia for tracheal intubation have been widely studied and discussed. Single vital-capacity breathing of a high concentration of inspiratory sevoflurane rapidly elevates the end-tidal concentration to cause loss of consciousness, although it does not bear relation to proportional body or brain uptake. This study was designed to investigate the time effect of fast wash-in of alveolar sevoflurane in induction of anesthesia for tracheal intubation with single vital-capacity and ensuing tidal-volume breathing in gynecologic patients. Thirty-six ASA I-II patients undergoing gynecologic surgeries under general anesthesia were included in the study. Prior to anesthesia, they were instructed on the vital capacity technique for induction with prior primed 7.2% inspiratory sevoflurane in 6 L/min oxygen in the breathing circuit. Immediately after loss of consciousness, assisted ventilation with fixed 3.5% sevoflurane in oxygen was applied to patients in groups 1 and 2 for 3 minutes, and for 4.5 minutes in group 3. Patients in group 2 received fentanyl 1.5 mug/kg before induction. In all patients, tracheal intubation was performed following succinylcholine 1.5 mg/kg. Inspiratory and end-tidal concentrations of sevoflurane, blood pressure and heart rate were recorded. All patients achieved vital capacity induction uneventfully, of whom two-thirds needed a second or third breath. The induction time was 60.6 +/- 19.2 seconds and could be reduced to 48.3 +/- 17.9 seconds with fentanyl pretreatment. The end-tidal concentration of sevoflurane was 2.68 +/- 0.20% after 4.5 minutes of ventilation with 3.5% sevoflurane, at which concentration the intubation-induced hemodynamic responses could not be suppressed. This study demonstrated that vital-capacity induction with a high concentration of sevoflurane is a safe and feasible technique for our female patients. The end-tidal 1.5 minimum alveolar concentration sevoflurane following 4.5 minutes of tidal-volume ventilation did not suppress intubation-induced hemodynamic responses. Pretreatment with fentanyl helped to shorten the induction time and provide better hemodynamic control for tracheal intubation.


Tips for making the job search productive and enjoyable.
Tips for making the search for a new job productive and enjoyable are presented. Identifying job opportunities requires a network of individuals who might assist in the job search. Traditional sources of job information can also be helpful. The most important element in following up on job leads is determining in advance that qualifications meet the established requirements. In preparing for a job interview, the applicant should learn as much as possible about the potential employer, the job, and the interviewer. General points to follow during and after the interview are outlined. Accepting a new job is a major life decision. Advance preparation, including a clear understanding of personal goals, motivations, and expectations, combined with strong interviewing skills can ensure that each job-specific short-range decision will contribute to the achievement of a life-long career path.


Growth-factor independence of a new differentiated hepatitis B virus DNA-negative human hepatoma cell line.
The establishment of a new, differentiated, hepatitis B virus DNA-negative, human hepatoma cell line (named PLC/AN/2) is described. Neoplastic liver tissue was obtained during hepatectomy in an HBsAg-negative man. The established cell line is negative for alpha-fetoprotein and carcinoembryonic antigen; it has retained in vitro some of the differentiated functions of normal hepatocytes. Additionally, it presents a distinctive rearrangement (translocation) at the long arm of chromosome 4. The high degree of independence from serum growth factor requirements appears to be a major in vitro characteristic of PLC/AN/2 cells, making them a suitable model system for the more precise definition of the human hepatocellular carcinoma phenotype, including mechanisms of growth control.


History of spine surgery in the ancient and medieval worlds.
There is a paucity of surviving texts from ancient and medieval times that can shed light on the early development of spine surgery. Nevertheless, the author reviews many of the available books and fragments and discusses early developments in the field of spine surgery from the point of view of physicians' personalities, general themes, and actual surgical practices. For purposes of an overview and to highlight changing trends in spine surgery, he divides the paper into four eras of medicine: 1) Egyptian and Babylonian; 2) Greek and early Byzantine; 3) Arabic; and 4) medieval.


Screening adult tuberculosis patients for diabetes mellitus in Ebeye, Republic of the Marshall Islands.
A retrospective cohort study was conducted to evaluate the screening of adult TB patients for diabetes (DM) using glycated haemoglobin (HbA1C) in Ebeye, Republic of the Marshall Islands. Of 62 patients registered between July 2010 and December 2012, 28 (45%) had DM. The only significant difference in baseline characteristics between those with and those without DM was higher age in those with DM. Two-month sputum smears and cultures were also not different between the two groups. Despite the limited sample size, this study shows that screening TB patients for DM in Ebeye is feasible and worthwhile and that it should be continued.


Murine gammaherpesvirus M2 protein induction of IRF4 via the NFAT pathway leads to IL-10 expression in B cells.
Reactivation of the gammaherpesviruses Epstein-Barr virus (EBV), Kaposi's sarcoma-associated herpesvirus (KSHV) and murine gammaherpesvirus 68 (MHV68) from latently infected B cells has been linked to plasma cell differentiation. We have previously shown that the MHV68 M2 protein is important for virus reactivation from B cells and, when expressed alone in primary murine B cells, can drive B cell differentiation towards a pre-plasma cell phenotype. In addition, expression of M2 in primary murine B cells leads to secretion of high levels of IL-10 along with enhanced proliferation and survival. Furthermore, the absence of M2 in vivo leads to a defect in the appearance of MHV68 infected plasma cells in the spleen at the peak of MHV68 latency. Here, employing an inducible B cell expression system, we have determined that M2 activates the NFAT pathway in a Src kinase-dependent manner--leading to induction of the plasma cell-associated transcription factor, Interferon Regulatory Factor-4 (IRF4). Furthermore, we show that expression of IRF4 alone in a B cell line up-regulates IL-10 expression in culture supernatants, revealing a novel role for IRF4 in B cell induced IL-10. Consistent with the latter observation, we show that IRF4 can regulate the IL-10 promoter in B cells. In primary murine B cells, addition of cyclosporine (CsA) resulted in a significant decrease in M2-induced IL-10 levels as well as IRF4 expression, emphasizing the importance of the NFAT pathway in M2- -mediated induction of IL-10. Together, these studies argue in favor of a model wherein M2 activation of the NFAT pathway initiates events leading to increased levels of IRF4--a key player in plasma cell differentiation--which in turn triggers IL-10 expression. In the context of previous findings, the data presented here provides insights into how M2 facilitates plasma cell differentiation and subsequent virus reactivation.


Association of the functional serotonin transporter haplotype with familial form of obsessive compulsive disorder in Iranian patients.
Several polymorphisms have been reported in the 5-HTTLPR of the serotonin transporter gene (SLC6A4). Family-based evidences for the association of 5-HTTLPR polymorphisms with OCD were previously reported but results were controversial. The present study investigated the possible correlation of SLC6A4 polymorphisms (5-HTTLPR, rs25532, rs25531) in Iranian OCD patients considering gender, age of onset, family history of psychiatric disorders, obsessive and compulsive subtypes and severities. The included OCD patients fulfilled the criteria for DSM-IV-TR whom Y-BOCS score was more than 9. Blood samples (184 cases and 192 controls) were genotyped by means of PCR-RFLP. Mean of Y-BOCS scores of included patients was 20.1 ± 0.69. Rs25532 CC genotype showed significant association with OCD in men and were detected more in the patients reported positive family history of psychiatric disorders but the other single loci (5-HTTLPR and rs25531) did not associate with OCD. Haplotype analysis showed significant association of 14-A variant with OCD and revealed the association of 14-A/14-A genotype with familial form of OCD. The findings of this study showed the association of SLC6A4 variants with familial form of OCD and proposed stratified analyses in the genetic studies facilitate identification of genetic risk factors for this heterogeneous disorder.


Diagnostic, Prognostic, and Recurrence Monitoring Value of Plasma CYFRA21-1 and NSE Levels in Patients With Esophageal Squamous Cell Carcinoma.
This study was aimed to evaluate the clinical values of single markers and combination in the diagnosis, short-term efficacy and recurrence risk assessment of esophageal squamous cell carcinoma (ESCC). Totally 50 patients with I-IVa stage ESCC, 50 healthy controls and 11 patients with recurrent esophageal cancer after comprehensive treatment were enrolled. Serum biomarkers were collected and evaluated. Serum concentrations of carcinoembryonic antigen (CEA), cytokeratin 19 fragment antigen 21-1 (CYFRA21-1) and neuron specific enolase (NSE) were measured by enzyme-linked immunosorbent assay before and after treatment. The diagnostic efficacy ROC curve area of CEA, CYFRA21-1 and NSE in esophageal cancer was 0.70, 0.71 and 0.64(all P <0.05), respectively, the sensitivity was 80%, 88.89% and 60% respectively, and the specificity was 53%, 58.5% and 58% respectively. The sensitivity and specificity of the combined detection were 68% and 78% respectively. The area under ROC curve was 0.75. CEA, CYFRA21-1 and NSE were significantly higher than the healthy control group and thus can be used as diagnostic markers of esophageal cancer (all P <0.05). After standard treatment, the clinical CR and PR rate of patients with positive CYFRA21-1 or NSE before treatment was significantly lower than that of patients with negative CYFRA21-1 or NSE (X2 = 4.52,P =0.03). A significant negative correlation was found between N stage and clinical efficacy (HR 2.48, 95%CI 1.07-5.73). After comprehensive treatment, the serum CYFRA21-1 and NSE levels in recurrent patients also increased significantly(all P<0.05), indicating these two markers play obvious roles in recurrence monitoring. CYFRA21-1 and NSE may help to predict the response of ESCC to CRT, and play important roles in the diagnosis and recurrence monitoring of esophageal cancer. These markers have a diagnostic value of esophageal cancer when combined with CEA.


Genomic DNA sequence, promoter expression, and chromosomal mapping of rat muscle carnitine palmitoyltransferase I.
Carnitine palmitoyltransferase I (CPT-I) is a key enzyme involved in the regulation of fatty acid oxidation. CPT-IA and CPT-IB are isoforms of carnitine palmitoyltransferase I, of which CPT-IA is expressed in liver, kidney, fibroblasts, and heart and CPT-IB is expressed in skeletal muscle, heart, brown and white adipocytes, and testes. Although the genomic DNA sequence of human CPT-IB is available, the transcription start site and upstream regulatory sequences are not known. For rat CPT-IB, only the cDNA sequence has been published. We have cloned the entire rat CPT-IB gene from a Lambda fix II rat kidney genomic library. The genomic structure contains 19 exons, with the transcription start site for CPT-IB located in a short first exon, which is a 13-bp extension to the previously published cDNA 5' sequence. The coding sequence is identical with the rat muscle cDNA. The rat CPT-IB gene contains 18 introns and 19 exons, the latter 18 exons showing 85% homology to the human CPT-IB cDNA. CPT-IB maps to rat chromosome 7 at band q34. A putative promoter region was identified to within 391 bp of the transcription start site. The muscle specificity of the 5' flanking region was verified by comparison of luciferase expression to that of beta-galactosidase in cardiac myocytes and in HepG2 cells.


Redescription of Tintinnopsis cylindrica Daday, 1887 (Ciliophora: Spirotricha) and Unification of Tintinnid Terminology.
Although Tintinnopsis cylindrica Daday, 1887 is apparently widely distributed in the plankton of marine and brackish coastal waters, its ciliary pattern remained unknown. Without detailed knowledge of the cell morphology, however, the proposed synonymies cannot be proved. Hence, the cell and lorica features of T. cylindrica are redescribed from live and protargol-impregnated specimens collected in mixo-polyhaline basins at the German North Sea coast. An improved species diagnosis and a comprehensive unified terminology are provided. The somatic ciliary pattern of T. cylindrica is complex, comprising a ventral, dorsal, and posterior kinety as well as a right, left, and lateral ciliary field. Accordingly, the species differs from its congener T. cylindrata that has merely a right and left ciliary field and ventral organelles. On the other hand, the genera Codonella, Codonellopsis, Cymatocylis, Helicostomella, Leprotintinnus, and Stenosemella share this pattern. The oral primordium of T. cylindrica develops hypoapokinetally posterior to the lateral ciliary field as in Codonella cratera and Cymatocylis convallaria.


Suppression of nitric oxide production in lipopolysaccharide-stimulated macrophage cells by omega 3 polyunsaturated fatty acids.
Although nitric oxide (NO) is an important biological mediator, its excessive production in inflammation is thought to be a causative factor for cellular injury and, over the long term, cancer. In the present study, the effects of several fatty acids on NO production in murine macrophage cell line RAW264 cells stimulated with lipopolysaccharide were examined. Suppression of NO production was observed with the omega 3 polyunsaturated fatty acids (PUFAs), docosahexaenoic acid, eicosapentaenoic acid and alpha-linolenic acid, in a dose-dependent fashion. In contrast, no inhibition was observed with omega 6 PUFA (linoleic acid), omega 9 PUFA (oleic acid) or a saturated fatty acid (stearic acid). Western and northern blot analyses suggested that suppression of the induction of inducible NO synthase gene expression is responsible for the inhibition of NO production by omega 3 PUFAs. The inhibitory effect of omega 3 PUFA on NO production in activated macrophages could contribute to their cancer chemopreventive influence.


Giant Breast Lipoma: A Case Report.
Lipomas are slow-growing, benign mesenchymal masses. Most lipomas are small, weighing only a few grams; however, if their size becomes exceptionally large, they are called giant lipomas. Giant lipoma of the breast is infrequently observed due to the rarity of size and location, with very few case reports available in the literature. Here, we report the case of a 48-year-old female patient who presented with a painless, huge lump in her right breast. The patient underwent surgical removal of the mass with a histologic examination confirming the diagnosis of a giant breast lipoma.


Effects of epinephrine and norepinephrine on lipid mobilization from coho salmon liver incubated in vitro.
The direct effects of epinephrine and norepinephrine (NE) on lipid mobilization were studied in coho salmon liver slices incubated in vitro. Fatty acid (FA) release from liver slices was measured continuously by pH-stat titration. The pH-stat assay system was validated by simultaneous colorimetric measurement of FA and glycerol release. Liver slices incubated in a glucose-free, low buffering capacity medium and stimulated with NE (10(-6) M) exhibited a one proton (titrimetric) to one FA (colorimetric) release profile. Under similar conditions, NE administration also stimulated glycerol release, in the expected three FA (colorimetric) to one glycerol (colorimetric) ratio. NE stimulated FA release from liver slices in a dose-dependent manner; epinephrine did not have a lipolytic effect. The beta-agonist isoproterenol stimulated FA release, whereas alpha-agonists had no effect. Furthermore, the beta-antagonist propranolol inhibited both NE- and beta-agonist-stimulated FA release. Liver triacylglycerol lipase activity was also stimulated by NE. Propranolol inhibited NE-stimulated lipase activity. These results establish the presence of hormone-sensitive lipase in salmon liver and suggest that NE-stimulated lipid mobilization in salmon liver is mediated through beta-adrenergic pathways.


Prolonged irradiation of enhanced cyan fluorescent protein or Cerulean can invalidate Forster resonance energy transfer measurements.
Since its discovery, green fluorescent protein (GFP) and its variants have proven to be a good and convenient fluorescent label for proteins: GFP and other visible fluorescent proteins (VFPs) can be fused selectively to the protein of interest by simple cloning techniques and develop fluorescence without additional cofactors. Among the steadily growing collection of VFPs, several pairs can be chosen that can serve as donor and acceptor fluorophores in Forster resonance energy transfer (FRET) experiments. Among them, the cyan fluorescent proteins (ECFP/Cerulean) and the enhanced yellow fluorescent protein (EYFP) are most commonly used. We show that ECFP and Cerulean have some disadvantages despite their common use: Upon irradiation with light intensities that are commonly used for intensity- and lifetime-based FRET measurements, both the fluorescence intensity and the fluorescence lifetime of ECFP and Cerulean decrease. This can hamper both intensity- and lifetime-based FRET measurements and emphasizes the need for control measurements to exclude these artifacts.


Discrete Spectral Hashing for Efficient Similarity Retrieval.
To meet the required huge data analysis, organization, and storage demand, the hashing technique has got a lot of attention as it aims to learn an efficient binary representation from the original high-dimensional data. In this paper, we focus on the unsupervised spectral hashing due to its effective manifold embedding. Existing spectral hashing methods mainly suffer from two problems, i.e., the inefficient spectral candidate and intractable binary constraint for spectral analysis. To overcome these two problems, we propose to employ spectral rotation to seek a better spectral solution and adopt the alternating projection algorithm to settle the complex code constraints, which are therefore named as Spectral Hashing with Spectral Rotation and Alternating Discrete Spectral Hashing, respectively. To enjoy the merits of both methods, the spectral rotation technique is finally combined with the original spectral objective, which aims to simultaneously learn better spectral solution and more efficient discrete codes and is called as Discrete Spectral Hashing. Furthermore, the efficient optimization algorithms are also provided, which just take comparable time complexity to existing hashing methods. To evaluate the proposed three methods, extensive comparison experiments and studies are conducted on four large-scale data sets for the image retrieval task, and the noticeable performance beats several state-of-the-art spectral hashing methods on different evaluation metrics.


A placental extract inhibits breathing induced by umbilical cord occlusion in fetal sheep.
Umbilical cord occlusion in the presence of adequate oxygenation induces continuous breathing and arousal in the chronic unanesthetized fetal sheep preparation. The mechanism responsible for this is unknown. We hypothesized that if a placental factor is responsible for the inhibition of breathing in the fetus, the administration of a placental extract while the fetus is breathing continuously after cord occlusion should reverse these changes. Thus, at about 10 min after the induction of continuous breathing by cord occlusion, we administered a placental extract and three subfractions separated by ultrafiltration to 14 chronically instrumented fetal sheep at 133 +/- 1 day gestation. The Krebs solution in which the placental extract was prepared was used as control. Within two minutes of the infusion of the whole placental extract in the carotid artery of the fetus, breathing output (integral of EMGdi x f) diminished in all experiments and was completely abolished in 15/17 (88%). Krebs solution had no effect on breathing. The infusion of subfractions of different molecular weight showed that the inhibition was primarily related to the subfraction between 3.5 and 10 kD. There were no significant changes in blood gas tensions, pH, blood pressure, and heart rate associated with the infusions of the extracts. The ECoG switched from low to high voltage in the majority of the experiments using whole extract and the subfraction 3.5 to 10 kD. These findings suggest that a placental factor, probably a peptide with a molecular weight between 3.5 and 10 kD, inhibits breathing in fetal life.


Stimulus-evoked changes in cerebral vessel diameter: A study in healthy humans.
The high metabolic demand of neuronal tissue, coupled with its relatively low energy storage capacity, requires that increases in neuronal activation are quickly matched with increased blood flow to ensure efficient supply of oxygen and nutrients to the tissue. For this to occur, dilation of nearby arterioles must be coordinated with the dilation of larger upstream feeding arteries. As it stands, the exact spatial extent of such dilation in humans is unknown. Using non-invasive time-of-flight magnetic resonance angiography in healthy participants, we developed an automatic methodology for reconstructing cerebral arterial vessels and quantifying their diameter on a voxel-by-voxel basis. Specifically, we isolated the posterior cerebral artery (PCA) supplying each occipital lobe and quantified its vasodilation induced by visual stimulation. Stimulus-induced changes were strongest (∼30%) near primary visual cortex and progressively decreased in a non-linear fashion as a function of distance. Surprisingly, weak - albeit significant - changes (∼2%) were observed ∼70 mm from the visual cortex. This demonstrates that visual stimulation modulates vascular tone along the bulk of the PCA segment, and thus may have important implications for our understanding of functional hyperemia in healthy and diseased states.


Colloid osmotic pressure as a prognostic indicator of pulmonary edema and mortality in the critically ill.
The relationship of colloid osmotic pressure (COP) to pulmonary edema and mortality in 128 critically ill patients was investigated in our critical care unit, and confirms previously reported observations. The COP in the 86 survivors was 22.0 (+/- 0.4 SEM) mm Hg versus 17.2 (+/- 0.6 SEM) mm Hg in the 42 who died (P less than 0.001). The patients were divided into three groups: 71 with no pulmonary edema, COP of 21.5 (+/- 0.5 SEM) mm Hg; 40 with cardiogenic pulmonary edema, COP of 21.4 (+/- 0.4 SEM) mm Hg; and 17 with noncardiogenic pulmonary edema, COP OF 13.6 (+/- 0.8 SEM) mm Hg. Colloid osmotic pressure was significantly lower in patients with noncardiogenic pulmonary edema (P less than 0.001). In 36 patients in whom pulmonary artery wedge pressures (PWP) were available, a COP-PWP gradient of 4.0 mm Hg or less was always associated with pulmonary edema, while a COP-PWP gradient greater than 4.0 mm Hg was never associated with pulmonary edema. Colloid osmotic pressure is a useful prognostic indicator of pulmonary edema and mortality in the critically ill.


Use of emergency transport by patients with cardiopathies: a focus group study.
The importance of emergency systems accessible by telephone for the early attention of patients with ischemic cardiopathy is well known. In Andalusia, this service is provided by calling 061. However, studies show an insufficient use of the existing emergency system in this type of patient. To identify explanations related to the decision regarding the method of transport to health-care systems, by private means of transport or 061 services, for people with ischemic cardiopathy from the onset of symptoms until their arrival at the Emergency Department. Eleven focal groups were held with subjects diagnosed with ischemic cardiopathy. The discussions were related to the method of transport (using 061 or their own means of transport to a major hospital or to a nearby health facility for onward transfer), depending on the existence of previous experience and distance to the hospital. The method of transport is related to the degree of ignorance about what is happening, perceptions regarding the fastest way to reach the hospital, people available around the patient when the event takes place, vehicle availability and possible stressful situations. This study provides information about the reasons for using or not using the emergency transport systems for these patients and understanding how decisions were made. The study's importance lies in the possibility of improving individuals' access to health care systems through education-based actions and a strategic information and training plan that targets patients, families and health professionals.


Microcystin-LR Detected in a Low Molecular Weight Fraction from a Crude Extract of Zoanthus sociatus.
Cnidarian constitutes a great source of bioactive compounds. However, research involving peptides from organisms belonging to the order Zoanthidea has received very little attention, contrasting to the numerous studies of the order Actiniaria, from which hundreds of toxic peptides and proteins have been reported. In this work, we performed a mass spectrometry analysis of a low molecular weight (LMW) fraction previously reported as lethal to mice. The low molecular weight (LMW) fraction was obtained by gel filtration of a Zoanthus sociatus (order Zoanthidea) crude extract with a Sephadex G-50, and then analyzed by matrix-assisted laser desorption/ionization time-of-flight/time-of-flight (MALDI-TOF/TOF) mass spectrometry (MS) in positive ion reflector mode from m/z 700 to m/z 4000. Afterwards, some of the most intense and representative MS ions were fragmented by MS/MS with no significant results obtained by Protein Pilot protein identification software and the Mascot algorithm search. However, microcystin masses were detected by mass-matching against libraries of non-ribosomal peptide database (NORINE). Subsequent reversed-phase C18 HPLC (in isocratic elution mode) and mass spectrometry analyses corroborated the presence of the cyanotoxin Microcystin-LR (MC-LR). To the best of our knowledge, this finding constitutes the first report of MC-LR in Z. sociatus, and one of the few evidences of such cyanotoxin in cnidarians.


Draft Genome Sequence of the Symbiotic Frankia Sp. Strain KB5 Isolated from Root Nodules of Casuarina equisetifolia.
Frankia sp. strain KB5 was isolated from Casuarina equisetifolia and previous studies have shown both nitrogenase and uptake hydrogenase activities under free-living conditions. Here, we report 5.5-Mbp draft genome sequence with a G+C content of 70.03 %, 4,958 candidate protein-encoding genes, and 2 rRNA operons.


[Comparison of Preferential Hyperacuity Perimeter (PHP) test and Amsler grid test in the diagnosis of different stages of age-related macular degeneration].
Age-related macular degeneration (ARMD) is the leading cause of blindness in people over 65 years of age. A rapid loss of vision occurs especially in cases with choroidal neovascularisation. Early detection of ARMD and timely treatment are mandatory. We have prospectively studied the results of two diagnostic self tests for the early detection of metamorphopsia and scotoma, the PHP test and the Amsler grid test, in different stages of ARMD. Patients with ARMD and best corrected visual acuity of 6/30 or better (Snellen charts) were examined with a standardised protocol, including supervised Amsler grid examination and PHP, a new device for metamorphopsia or scotoma measurement, based on the hyperacuity phenomenon in the central 14 degrees of the visual field. The stages of ARMD were independently graded in a masked fashion by stereoscopic ophthalmoscopy, stereoscopic fundus colour photographs, fluorescein angiography, and OCT. The patients were subdivided into 3 non-neovascular groups [early, late (RPE atrophy > 175 microm) and geographic atrophy], a neovascular group (classic and occult CNV) and an age-matched control group (healthy volunteers). 140 patients, with ages ranging from 50 to 90 years (median 68 years), were included in the study. Best corrected visual acuity ranged from 6/30 to 6/6 with a median of 6/12. 95 patients were diagnosed as non-neovascular ARMD. Thirty eyes had early ARMD (9 were tested positive by the PHP test and 9 by the Amsler grid test), and 50 late ARMD (positive: PHP test 23, Amsler grid test 26). The group with geographic atrophy consisted of 15 eyes (positive: PHP test 13, Amsler grid test 10). Forty-five patients presented with neovascular ARMD (positive: PHP test 38, Amsler grid test 36), 34 volunteers served as control group (positive: PHP test 1, Amsler grid test 5). The PHP and Amsler grid tests revealed comparable results detecting metamorphopsia and scotoma in early ARMD (30 vs. 30 %) and late ARMD (46 vs. 52 %). However, the PHP test more often revealed disease-related functional changes in the groups of geographic atrophy (87 vs. 67 %) and neovascular ARMD (84 vs. 80 %). This implies that the PHP and Amsler grid self tests are useful tools for detection of ARMD and that the PHP test has a greater sensitivity in the groups of geographic atrophy and neovascular AMD.


Management of oil of citronella poisoning.
The management for ingestion of oil of citronella, an essential oil, has traditionally been rigorous, including dilution with milk or oil, and gastric lavage or emesis, taking care to prevent aspiration. Recently our Centre handled five oil of citronella poisonings and their outcomes led us to review our management protocol which had been based on information from standard poisoning texts. The source data used to determine the human toxicity of oil of citronella and the appropriate management of poisoning included a case report of a fatal ingestion of oil of citronella in a child. On scrutiny, however, the management of this poisoning included now out-moded techniques, giving rise to uncertainties in establishing the true cause of the child's death. Our own experiences indicate that advice given in standard texts based on poisoning cases managed with out-moded techniques should be carefully evaluated.


Genetic analysis of a new subgroup of human and simian T-lymphotropic retroviruses: HTLV-IV, LAV-2, SBL-6669, and STLV-IIIAGM.
A new primate retrovirus, STLV-IIIAGM, has been recently isolated from healthy African green monkeys and is apparently nonpathogenic in its natural host. However, spontaneous infection as well as inoculation of STLV-IIIAGM into macaques induces a disease with clinical features that resemble human AIDS. Independent isolates of human retroviruses, serologically closely related to STLV-IIIAGM, have been obtained from healthy individuals (HTLV-IV) and patients with immunodeficiency (LAV-2FG and SBL 6669) from West Africa. The latter have also been referred to as HIV-2 because, like HTLV-III/HIV-1, they may be associated with immune deficiency, or as West African human retroviruses because of their prevalence and probable origin from that region. We have molecularly cloned the STLV-IIIAGM genome and have generated probes from the gag-pol and envelope genes to analyze the genetic relatedness of these simian and human retroviruses. Our results indicate that all these retroviruses are genetically closely related to each other, HTLV-IV and STLV-IIIAGM differing only by a few restriction enzyme sites while LAV-2FG and SBL 6669 exhibit greater polymorphism from HTLV-IV/STLV-IIIAGM. These data mirror the variable degree of relatedness among members of the first subgroup of human retroviruses, HTLV-III/HIV.


Efficacy of Saccharomyces cerevisiae fermentation product on intestinal health and productivity of coccidian-challenged laying hens.
A 37-d laying hen experiment was performed to determine the effect of Diamond V XPC(LS) (XPC(LS), Diamond V Mills, Cedar Rapids, IA) during a subclinical Eimeria maxima infection on intestinal health and productivity. Two hundred and sixteen 18-wk-old Brown Nick laying hens were allocated to 24 litter pens based on a weight class system (9 hens/pen). The trial was carried out as a 2 × 2 factorial design with XPC(LS) and E. maxima challenge as main factors. Birds were fed a corn/wheat-based mash prelayer diet from wk 18 to 20 (10.9 MJ/kg of AME and 13.7% CP) and a standard phase I layer diet from wk 20 to 24 (11.7 MJ/kg of AME and 15.3% CP) that were supplemented with XPC(LS) at the rate of 0 or 0.75 g/kg. Hens were orally inoculated on d 23 (22 wk of age) with either 1 mL of saline (not infected) or 10,000 sporulated E. maxima oocysts/bird in 1 mL of saline (infected). Effects of XPC(LS) on intestinal health were determined by E. maxima lesion scoring. Results of E. maxima lesions were analyzed by Fisher exact, whereas severity of lesions and production parameters were analyzed by ANOVA. Supplementation of XPC(LS) significantly reduced severity of E. maxima lesions (P < 0.05) from 1.1 to 0.8 in challenged hens. An overall significant effect of XPC(LS) supplementation was demonstrated on d 34 by decreasing the severity of lesions from 0.3 to 0.1. The E. maxima challenge decreased (P < 0.05) production performance between 7 and 14 d postchallenge by lowering egg weight from 50 to 47 g/egg and laying rate from 84 to 70% and increasing feed per dozen eggs (P < 0.01) from 1.60 to 2.06 kg. Results indicate that Diamond V XPC(LS) supplementation reduced intestinal damage caused by an E. maxima infection in laying hens.


Potentiometric detection in UPLC as an easy alternative to determine cocaine in biological samples.
The analytical methods which are often used for the determination of cocaine in complex biological matrices are a prescreening immunoassay and confirmation by chromatography combined with mass spectrometry. We suggest an ultra-high-pressure liquid chromatography combined with a potentiometric detector, as a fast and practical method to detect and quantify cocaine in biological samples. An adsorption/desorption model was used to investigate the usefulness of the potentiometric detector to determine cocaine in complex matrices. Detection limits of 6.3 ng mL(-1) were obtained in plasma and urine, which is below the maximum residue limit (MRL) of 25 ng mL(-1). A set of seven plasma samples and 10 urine samples were classified identically by both methods as exceeding the MRL or being inferior to it. The results obtained with the UPLC/potentiometric detection method were compared with the results obtained with the UPLC/MS method for samples spiked with varying cocaine concentrations. The intraclass correlation coefficient was 0.997 for serum (n =7) and 0.977 for urine (n =8). As liquid chromatography is an established technique, and as potentiometry is very simple and cost-effective in terms of equipment, we believe that this method is potentially easy, inexpensive, fast and reliable.


Alveolar macrophages from septic mice promote polymorphonuclear leukocyte transendothelial migration via an endothelial cell Src kinase/NADPH oxidase pathway.
Alveolar macrophages (AMphi) have been implicated in the polymorphonuclear leukocyte (PMN) recruitment to the lungs during sepsis. Using an in vivo murine model of sepsis (feces in the peritoneum), we show that peritonitis leads to increased activation of AMphi and PMN migration into pulmonary alveoli. To assess cellular mechanisms, an in vitro construct of the pulmonary vascular-interstitial interface (murine AMphi, pulmonary endothelial cells, and PMN) and a chimera approach were used. Using immunologic (Abs) and genetic blockade (CXCR2-deficient AMphi), we show that CXC chemokines in septic plasma are responsible for the activation of AMphi. The activated AMphi can promote PMN transendothelial migration, even against a concentration gradient of septic plasma, by generating platelet-activating factor and H(2)O(2). Platelet-activating factor/H(2)O(2) induce an oxidant stress in the adjacent endothelial cells, an event that appears to be a prerequisite for PMN transendothelial migration, since PMN migration is abrogated across Cu/Zn-superoxide dismutase overexpressing endothelial cells. Using gp91-deficient endothelial cells, we show that NADPH oxidase plays an important role in the AMphi-induced PMN transendothelial migration. Pharmacologic/small interfering RNA blockade of Src kinase inhibits AMphi-induced endothelial NADPH oxidase activation and PMN migration. Collectively, our findings indicate that the PMN transendothelial migration induced by septic AMphi is dependent on the generation of superoxide in endothelial cells via the Src kinase/NADPH oxidase signaling pathway.


An unique n-propyl sesquiterpene from Eryngium creticum L. (Apiaceae).
The unique 1-n-propyl-perhydronaphthaline 1,2,4a,5,6,7,8,8a-octahydro-4-methyl-1-propyl-naphthalene-7-carbaldehyde, a compound which possesses an unusual sesquiterpene carbon skeleton, was isolated and identified, together with the new natural methyl ketone eicos-8,11 -dien-18-ol-2-one, from the hexane: ether extract of the aerial parts of Eryngium creticum growing in Sinai, Egypt. The structures were established by conventional methods of analysis and confirmed by DEPT, COSY, HMQC and HMBC.


Wnt and Nodal signaling simultaneously induces definitive endoderm differentiation of mouse embryonic stem cells.
Induced differentiation of definitive endoderm (DE) from embryonic stem cells (ESCs) has been the recent focus of studies investigating regeneration and transplantation of organs of the digestive system. Poor cell survival is the most important challenge to DE differentiation from ESCs. This study aimed to optimize culture conditions to promote the differentiation of mouse ESCs into DE, and to investigate the roles of the Wnt and Nodal signaling pathways in the DE differentiation. The mouse ESCs were treated with or without leukemia inhibitory factor, Wnt3a and Activin A alone or together, and examined the DE differentiation by the DE marker CXCR4 and the ESC marker Oct4. The result showed the optimal induction of differentiation was achieved in cells simultaneously treated with Wnt3a and Activin A. Induction of CXCR4 was also earlier when there was simultaneous activation of Wnt and Nodal signaling compared to the groups treated with only Wnt3a or Activin A alone. These findings provide the basis for the induced differentiation of ESCs for the generation of functional, mature cells of gastrointestinal lineage, which can be potentially used for cell replacement therapy, disease modeling, as well as drug discovery studies.


Autonomous Motivation as a Mediator Between an Empowering Climate and Enjoyment in Male Volleyball Players.
The objective of this work was to analyze a mediation model concerning the perception of an empowering climate generated by a coach and enjoyment through the autonomous motivation of athletes. The sample consisted of 71 elite male volleyball players from six countries. The age range was 14 to 18 years (M = 16.5, SD = 0.96). The relationships between the perception of an empowering climate, autonomous motivation, and enjoyment were positive and significant. The mediation model showed that autonomous motivation acts as a mediator in the relationship between the perception of an empowering climate generated by the coach and the enjoyment reported by the athletes.


Expressing and storing colostrum antenatally for use in the newborn period.
Colostrum is universally acknowledged as the perfect first food for infants. Oxytocin is the hormone of both labour and lactation but the literature shows that it does not always induce labour. A review of the custom of expressing antenatally by all women is followed by the maternal and infant medical reasons for expressing and storing colostrum. A suggested regime for expressing and storage of colostrum during pregnancy is included with advice about skin-to-skin contact in the first twenty-four hours to maximise breastmilk output in the long term.


Light-Triggered Nitric Oxide Nanogenerator with High l-Arginine Loading for Synergistic Photodynamic/Gas/Photothermal Therapy.
The development of nanomedicines that combine photothermal therapy (PTT) with photodynamic therapy (PDT) is considered promising for cancer treatment, but still faces the challenge of enhancing tumoricidal efficiency. Fortunately, apart from the well-acknowledged effect on direct tumor cell-killing, nitric oxide (NO) is also considered to be effective for the enhancement of both PTT and PDT. However, both the low loading efficiency of NO precursor and the short half-life time and diffusion distance of NO hamper the synergistic therapeutic efficacy of NO. Taking the aforementioned factors into account, a mitochondria-targeted nitric oxide nanogenerator, EArgFe@Ce6, is constructed to achieve high loading of the NO donor l-Arginine (l-Arg) for synergistic photodynamic/gas/photothermal therapy upon single 660 nm light irradiation. The coordination of epigallocatechin gallate (EGCG) and ferric ions (Fe3+ ) provides EArgFe@Ce6 supreme photothermal capability to perform low-temperature PTT (mPTT). EGCG endows EArgFe@Ce6 with mitochondria-targeting capability and meanwhile favors hypoxia alleviation for enhanced PDT. The PDT-produced massive reactive oxygen species (ROS) further catalyzes l-Arg to generate a considerable amount of NO to perform gas therapy and sensitize both mPTT and PDT. In vitro and in vivo studies demonstrate that the synergistic photodynamic/gas/photothermal therapy triggered by single 660 nm light irradiation is highly effective for tumor treatments.


Corporate and philanthropic models of hospital governance: a taxonomic evaluation.
We assess the theoretical integrity and practical utility of the corporate-philanthropic governance typology frequently invoked in debates about the appropriate form of governance for nonprofit hospitals operating in increasingly competitive health care environments. Data were obtained from a 1985 national mailed survey of nonprofit hospitals conducted by the American Hospital Association (AHA) and the Hospital Research and Educational Trust (HRET). A sample 1,577 nonprofit community hospitals were selected for study. Representativeness was assessed by comparing the sample with the population of non-profit community hospitals on the dimensions of bed size, ownership type, urban-rural location, multihospital system membership, and census region. Measurement of governance types was based on hospital governance attributes conforming to those cited in the literature as distinguishing corporate from philanthropic models and classified into six central dimensions of governance: (1) size, (2) committee structure and activity, (3) board member selection, (4) board composition, (5) CEO power and influence, and (6) bylaws and activities. Cluster analysis and ANCOVA indicated that hospital board forms adhered only partially to corporate and philanthropic governance models. Further, board forms varied systematically by specific organizational and environmental conditions. Boards exhibiting more corporate governance forms were more likely to be large, privately owned, urban, and operating in competitive markets than were hospitals showing more philanthropic governance forms. Findings suggest that the corporate-philanthropic governance distinction must be seen as an ideal rather than an actual depiction of hospital governance forms. Implications for health care governance are discussed.


Community and interpersonal functioning in the course of schizophrenic disorders.
The purpose of this article is to evaluate the role of community and interpersonal functioning in the developmental course and outcome of schizophrenic disorders. Based on a review of the research literature, it appears that certain patterns of poor functioning may be characteristic of at least a subgroup of schizophrenic individuals, predate the onset of the disorder, and predict the outcome of the disorder. Thus, some patterns of poor community and interpersonal functioning may be seen as potential indicators of vulnerability to the development of schizophrenic episodes rather than solely as consequences of schizophrenic psychotic symptoms.


Activity of Multidrug Resistance-Associated Proteins 1-5 (MRP1-5) in the RPMI 2650 Cell Line and Explants of Human Nasal Turbinate.
The profound influence of ATP-binding cassette (ABC) transporters on the disposition of numerous drugs has led to increased interest in characterizing their expression profiles in various epithelial and endothelial barriers. The present work examined the presence and functional activity of five ABC efflux proteins, i.e., MRP 1-5, in freshly isolated human nasal epithelial cells and two in vitro models based on the human RPMI 2650 cell line. To evaluate the expression patterns of MRP1, MRP2, MRP3, MRP4, and MRP5 at the mRNA and protein levels in the ex vivo model and the differently cultured RPMI 2650 cells, reverse transcriptase polymerase chain reaction (RT-PCR), Western blot analysis, and indirect immunofluorescence staining were used. The functionality of the MRP transporters in the three models was assessed using efflux experiments and accumulation assays with the respective substrates and inhibitors. The mRNA and protein expression of all selected ABC transporters was detected in excised human nasal mucosa as well as in the corresponding cell culture models. Moreover, the functional expression of the MRP transport proteins was demonstrated in the three models for the first time. Therefore, the potential impact of multidrug resistance-associated proteins 1-5 on drug disposition after intranasal administration may be taken into consideration for future developments. The specimens of human nasal turbinate exhibited slightly lower efflux capacities of MRP1, MRP3, and MRP5 in relation to the submerged and ALI-cultured RPMI 2650 cells, but showed a promising comparability to both in vitro models concerning the activity of MRP2 and MRP4. In this regard, the different RPMI 2650 cell culture models will be able to provide useful experimental data in the preclinical phase to estimate the interaction of particular efflux transporters with drug candidates for nasal application.


[HIV/AIDS spread and influence on other health-related Millennium Development Goals].
HIV/AIDS is threatening the development of countries with high HIV prevalence. This article analyses the impact of HIV/AIDS on the Millennium Development Goals for Health. The analysis is based on a literature survey on the impact of HIV on child health, maternal mortality, tuberculosis and malaria. We find a strong correlation between HIV and child mortality and HIV and TB. We conclude that, in order to reach the Millennium Development Goals, health strategies must include a comprehensive and coordinated approach to fight major health problems including improved resource allocation.


An American Crisis: the Lack of Black Men in Medicine.
The current state of diversity within the US medical workforce does not reflect representative numbers of the Black male population. Research data continues to reveal continuing trends in the areas of discrimination, incarceration, health disparities, and mortality with respect to Black males. The lack of increase in Black male medical school applications and matriculation contrasted by the continuing trends mentioned above illustrates that there is in fact an American crisis. We present here a call to arms, to address the need of African-American men in medicine. The absence of Black males in medical school represents an American crisis that threatens efforts to effectively address health disparities and excellence in clinical care. This disturbing trend is in need of more empirical examination of medical school data specifically in the areas of qualification barriers, race/ethnic classification, and the impact of diversity on quality of healthcare in the USA.


Osteoplastic frontal sinusotomy: an analysis of 250 operations.
The operative approach and findings of 250 osteoplastic frontal sinusotomy operations performed from 1956 through 1972 at the Massachusetts Eye and Ear Infirmary are reviewed. Indications for surgery were symptomatic and/or complicated disease of the frontal sinus, including primary chronic sinusitis and osteoma or trauma with or without associated infection. Immediate postoperative complications were minor. Follow-up of at least three years was obtained in 83% of the patients, and 93% of these have no significant symptoms to date. A distressing problem of persistent postoperative frontal pain is discussed in detail. Revision surgery has been performed in 6% of patients due to recurrent frontal sinus infection. The reasons for failure are anlyzed, and recommendations are made to minimize the possibility of recurrence.


alpha-L-arabinofuranosidase from Ruminococcus albus 8: purification and possible role in hydrolysis of alfalfa cell wall.
An alpha-L- arabinofuranosidase has been purified from the extracellular broth of cultures of Ruminococcus albus 8. The purification procedure utilized gel filtration, (NH4)2SO4 precipitation, and isoelectric focusing. The purified enzyme appeared to be homogeneous when chromatographed on disc and analytical isoelectric focusing gels. The estimated molecular weight of the native protein was 305,000 to 310,000. Sodium dodecyl sulfate-gel electrophoresis analysis suggested that the native protein is a tetramer composed of 75,000-molecular-weight subunits. The enzyme appeared to have no metal cofactor requirement but was sensitive to several sulfhydryl reagents. The pH optimum with p-nitrophenyl-alpha-L-arabinofuranoside as the substrate was 6.9 and the Km was 1.3 mM. Several lines of evidence indicated that the enzyme is a glycoprotein. When assayed against alfalfa cell wall material, the enzyme hydrolyzed only small amounts of arabinose from the substrate. When assayed together with hemicellulolytic or pectinolytic enzymes against the same substrate, the arabinosidase significantly enhanced the hydrolytic action of the glycanases .


The role of choroidal optical coherence tomography for follow-up of carotid cavernous fistula with anterior drainage.
To evaluate the role of the choroidal vascularity index (CVI) and the tortuosity index (TI), along with choroidal thickness measurements, in follow-up for anteriorly draining carotid cavernous fistulas (CCF) that would otherwise necessitate an invasive carotid angiogram. In this longitudinal observational study, analysis of enhanced depth imaging spectral domain optical coherence tomography (SD-EDI-OCT) images of 22 patients with angiographically proven unilateral CCF with anterior drainage was performed for subfoveal choroidal thickness (SFCT), central foveal thickness (CFT), CVI and TI. Baseline measurements were compared with those taken at the last visit after occlusion of the fistula. Both in the clinically affected and unaffected eyes, there was a significant decrease in CFT (p = 0.015 and p = 0.005, respectively), SFCT (p = 0.000 for both eyes), CVI (p = 0.002 and 0.001, respectively) and all three TI parameters, including inferior (p < 0.001 and p = 0.01, respectively) and superior temporal vein tortuosity index (p = 0.005 and p = 0.02, respectively) as well as total venular tortuosity index (p < 0.001 and p = 0.002, respectively) after successful closure of the fistula compared to first presentation. Changes in all parameters were similar between the D-CCF and I-CCF groups except for CVI. In this first study concerning follow-up of anteriorly draining unilateral CCFs by SD-EDI-OCT, we not only demonstrated involvement of the clinically unaffected eye but also showed that, this modality, utilizing CVI and TI together with choroidal thickness measurements, can be used as a readily available, noninvasive first-line followup method for evaluating occlusion of fistulas by endovascular treatment or spontaneous resolution.


Universal relations in the self-assembly of proteins and RNA.
Concepts rooted in physics are becoming increasingly important in biology as we transition to an era in which quantitative descriptions of all processes from molecular to cellular level are needed. In this perspective I discuss two unexpected findings of universal behavior, uncommon in biology, in the self-assembly of proteins and RNA. These findings, which are surprising, reveal that physics ideas applied to biological problems, ranging from folding to gene expression to cellular movement and communication between cells, might lead to discovery of universal principles operating in adoptable living systems.


Demographics and Clinical Features of Postresuscitation Comorbidities in Long-Term Survivors of Out-of-Hospital Cardiac Arrest: A National Follow-Up Study.
The outcome of patients suffering from out-of-hospital cardiac arrest (OHCA) is very poor, and postresuscitation comorbidities increase long-term mortality. This study aims to analyze new-onset postresuscitation comorbidities in patients who survived from OHCA for over one year. The Taiwan National Health Insurance (NHI) Database was used in this study. Study and comparison groups were created to analyze the risk of suffering from new-onset postresuscitation comorbidities from 2011 to 2012 (until December 31, 2013). The study group included 1,346 long-term OHCA survivors; the comparison group consisted of 4,038 matched non-OHCA patients. Demographics, patient characteristics, and risk of suffering comorbidities (using Cox proportional hazards models) were analyzed. We found that urinary tract infections (n = 225, 16.72%), pneumonia (n = 206, 15.30%), septicemia (n = 184, 13.67%), heart failure (n = 111, 8.25%) gastrointestinal hemorrhage (n = 108, 8.02%), epilepsy or recurrent seizures (n = 98, 7.28%), and chronic kidney disease (n = 62, 4.61%) were the most common comorbidities. Furthermore, OHCA survivors were at much higher risk (than comparison patients) of experiencing epilepsy or recurrent seizures (HR = 20.83; 95% CI: 12.24-35.43), septicemia (HR = 8.98; 95% CI: 6.84-11.79), pneumonia (HR = 5.82; 95% CI: 4.66-7.26), and heart failure (HR = 4.88; 95% CI: 3.65-6.53). Most importantly, most comorbidities occurred within the first half year after OHCA.


The discrete syndromes of transvestism and transsexualism.
The literature concerning the relationship between transvestism and transsexualism is briefly reviewed. Some workers consider the two conditions to be on a continuum, whereas others feel that they are independent clinical entities. To clarify the relationship between the two syndromes, biographical data were collected and penile volume changes recorded in 29 subjects who identified themselves as transsexuals and 35 who identified themselves as transvestites. In comparison to the transvestite subjects, significantly more transsexuals were younger, were single, cross-dressed fully, and reported homosexual interest, a feminine gender identity, and a desire for a sex-change surgery. In comparison to the transsexual subjects, significantly more transvestites reported heterosexual interest, cross-dressed partially, and had shown fetishistic arousal. It is concluded that transvestism and transsexualism are separate clinical entities.


Global Tn-seq analysis of carbohydrate utilization and vertebrate infectivity of Borrelia burgdorferi.
Borrelia burgdorferi maintains a complex life cycle between tick and vertebrate hosts. Although some genes have been identified as contributing to bacterial adaptation in the different hosts, the list is incomplete. In this manuscript, we report the first use of transposon mutagenesis combined with high-throughput sequencing (Tn-seq) in B. burgdorferi. We utilize the technique to investigate mechanisms of carbohydrate utilization in B. burgdorferi and the role of carbohydrate metabolism during mouse infection. We performed genetic fitness analyses to identify genes encoding factors contributing to growth on glucose, maltose, mannose, trehalose and N-acetyl-glucosamine. We obtained insight into the potential functions of proteins predicted to be involved in carbohydrate utilization and identified additional factors previously unrecognized as contributing to the metabolism of the tested carbohydrates. Strong phenotypes were observed for the putative carbohydrate phosphotransferase transporters BB0408 and BBB29 as well as the response regulator Rrp1. We further validated Tn-seq for use in mouse studies and were able to correctly identify known infectivity factors as well as additional transporters and genes on lp54 that may contribute to optimal mouse infection. As such, this study establishes Tn-seq as a powerful method for both in vitro and in vivo studies of B. burgdorferi.