Advanced metastatic breast cancer in pregnancy: the imperative of physical breast examination in pregnancy.
Breast cancer is the most frequent cancer diagnosed among women; its association with pregnancy is not encountered. As childbearing age is increasing, the diagnosis of breast cancer associated pregnancy tends to be more often than years ago. Here we report a case of a 37-year-old patient, gravida 7, para 7, diagnosed at 30 weeks gestation with metastatic breast cancer. The patient presented to hospital due to an altered performance status. Obstetrical evaluation was within normal range. A metastatic infiltrating breast cancer poorly differentiated (G3) with satellite skin lesions (T4b), ipsilateral axillary and supraclavicular lymph nodes (N3), lung metastasis bilateral with pleural effusion and hepatic metastasis (M1), were diagnosed. The tumor was positive for estrogen receptor (ER) and progesterone receptor (PR) status and negative for human epidermal receptor protein-2 (HER-2)÷neu immunostaining. Due to a significant worsening of the patient's dyspnea, a Caesarean section was performed under spinal anesthesia, at 30 + 2 days; and a newborn weighing 1700 g was delivered without malformations. The unsuccessful management of the cancer was inevitable and the patient died two weeks later. Despite her hospitalizations for six prior deliveries (last birth was one year ago), the presence of a palpable tumor was never observed. We aim to highlight the importance of the clinical examination at any given point in pregnancy in order to detect, investigate and treat any suspect tumor of the breast.


Phase imaging for absorptive phase objects using hybrid uniform and structured illumination transport of intensity equation.
Transport of intensity equation (TIE) has been a popular and convenient phase imaging method that retrieves phase profile from the measurement of intensity differentials. Conventional 2-shot uniform illumination TIE can give reliable inversion of the phase from intensity in many situations of practical interest; however, it has a null space consisting of fields with non-zero circulation of the Poynting vector. Here, we propose the hybrid illumination TIE method to disambiguate such objects. By comparing the diffraction signals using uniform and structured (sinusoidal) illumination patterns, we obtain a modulation-induced signal that depends solely on the phase gradient. In this way, we also increase signal sensitivity in the low spatial frequency region.


Electrochemical Dearomative 2,3-Difunctionalization of Indoles.
We report the use of electrochemistry to perform a direct oxidative dearomatization of indoles leading to 2,3-dialkoxy or 2,3-diazido indolines under undivided conditions at a constant current. This operationally simple electro-oxidative procedure avoids the use of an external oxidant and displays excellent functional group compatibility. The formation of the two C-O or C-N bonds is believed to arise from the oxidation of the indoles into radical cation intermediates.


Involvement of vitronectin and of a natural extracellular matrix in prostatic cell to cell contact and interaction with the substratum in culture.
The kinetics and regulation of attachment, the spreading and initial growth of canine prostatic epithelial cells in primary monolayers, as well as the ability of the cells to produce a natural extracellular matrix (nECM) have been studied. Within 1 day of culture, attachment without spreading occurred in uncoated dishes while spreading was observed in nECM-coated dishes. The attachment was stimulated by dialyzed fetal bovine serum (dFBS) and/or by the nECM and was not affected by the presence of cycloheximide at 10(-6) M. This effect of dFBS on attachment was maximal at a concentration of 10% and increased with cell density and was mainly attributed to vitronectin as demonstrated by gel filtration, selective adsorption of serum proteins to the substratum, and indirect immunofluorescence of prostatic epithelial cells incubated with a rabbit antiserum against bovine vitronectin. Dog serum reduced attachment while bovine serum albumin, phenol red, and steroids were inactive. The maximal effect of the nECM on attachment was observed with matrices produced by canine prostatic epithelial cells cultured in the presence of dog serum for more than 10 days. As revealed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, several proteins of relative mass (Mr) of 210, 113, 61, 56, 52, 49, 45, and 42 kDa remained in the dish following nECM denudation and could be responsible for its effect on attachment. Their deposition as well as intercell adhesion and cell-to-substratum interactions required an active protein synthesis plus non-steroidal serum components. Once attached and spread in primary monolayers, prostatic epithelial cells divided by the 3rd to 4th day; their growth, stimulated by dFBS at an optimal concentration of 20%, was inhibited by cycloheximide while the nECM was inactive. Thus, vitronectin in serum and the nECM synthesized by canine prostatic epithelial cells are responsible for the attachment and spreading of homologous cells to an in vitro substratum; nECM proteins also contribute to cell-to-cell contact and cell-to-substratum interaction in the monolayers.


Effect of alpha-methyldopa on lung microembolism in the rat.
The effect of chronic pretreatment with alpha-methyldopa on acute pulmonary hypertension induced by lung microembolization with Sephadex particles in the rat was studied. Alpha-methyldopa was administered twice a day for 10 days by oesophageal gavage (20 mg X kg-1 of body weight) prior to embolization. Rats were anaesthetized with urethane. A catheter was positioned in closed chest rats in the pulmonary artery and 50 microliter of Sephadex suspension in saline were injected. The control group was not pretreated with alpha-methyldopa. In a subgroup of control and pretreated rats, the cardiac output was measured by the dye dilution technique before and after lung microembolization. Rats pretreated with alpha-methyldopa had less pulmonary hypertension, higher cardiac output and more severe arterial hypoxaemia 15 min after lung microembolization than untreated animals. There was no difference in platelet counts prior and after embolization. We suggest that pulmonary hypertension after lung microembolization in the rat includes a vasoconstrictor component which can be suppressed by alpha-methyldopa, and that severe arterial hypoxaemia in pretreated rats is probably the result of a decrease of the ventilation/perfusion ratio in unobstructed areas, which in untreated rats may be prevented by active vasoconstriction.


Fungal malignant otitis externa.
An 89-year-old man presented to the outpatient clinic with a 2-month history of persistent unilateral left-sided otalgia, otorrhoea and reduced hearing despite oral and topical antibiotics. Treatment was protracted, requiring a 4-month hospital admission for intravenous antifungal medication as well as 3 further months of oral antifungal treatment. We describe the clinical presentation, complications and treatment of this potentially fatal condition in the context of an unusual, and easily missed, causative organism.


GIT1 regulates synaptic structural plasticity underlying learning.
The signaling scaffold protein GIT1 is expressed widely throughout the brain, but its function in vivo remains elusive. Mice lacking GIT1 have been proposed as a model for attention deficit-hyperactivity disorder, due to alterations in basal locomotor activity as well as paradoxical locomotor suppression by the psychostimulant amphetamine. Since we had previously shown that GIT1-knockout mice have normal locomotor activity, here we examined GIT1-deficient mice for ADHD-like behavior in more detail, and find neither hyperactivity nor amphetamine-induced locomotor suppression. Instead, GIT1-deficient mice exhibit profound learning and memory defects and reduced synaptic structural plasticity, consistent with an intellectual disability phenotype. We conclude that loss of GIT1 alone is insufficient to drive a robust ADHD phenotype in distinct strains of mice. In contrast, multiple learning and memory defects have been observed here and in other studies using distinct GIT1-knockout lines, consistent with a predominant intellectual disability phenotype related to altered synaptic structural plasticity.


Ergonomic determinants of back pain in physiotherapists involved in paediatric neurorehabilitation.
Work-related musculoskeletal disorders in physiotherapists working with children are due to the failure to apply the principles of ergonomics in their daily practice, which is often caused by the necessity of working in forced positions. Health hazards are even bigger because of the disproportion of body weight and height between the patient and the therapist. The aim of the study was to evaluate positions of the spine at work among physiotherapists involved in child neurorehabilitation and their impact on the occurrence of back pain. The study enrolled 84 physiotherapists between the ages of 28-55 years involved in child neurorehabilitation whose seniority in the profession ranged from 2 to 33 years. The physiotherapists were interviewed about their work and its negative consequences. The 6-degree Jackson and Moskowitz scale was used to determine the level of pain intensity. Three-dimensional positions of the spine were recorded under natural working conditions using a SonoSens Monitor 8 ultrasonic measuring system. The recorded data was compared with the so-called "profile for ergonomic operation of the spine". The idea behind the study was to find the relation between pain intensity, duration and location on the one hand, and working positions of the spine and other data from the interview on the other. The statistical analysis was based on Spearman's rank correlation coefficient, analysis of variance with single classification, post hoc analysis (Tukey test) and the chi-square test (%2). The level of statistical significance was established at p < 0.05. All subjects reported 1-4° pain. The intensity of pain increased with age, profession seniority, duration of the history of pain and duration of a sense of fatigue persisting after work. Pain intensity correlated with the length of time the spine was placed in unergonomic positions - especially in excessive lateral flexion in the thoracic segment and rotation in the cervical, thoracic and lumbar segments. 1. Positions of the spine in physiotherapists involved in neurorehabilitation of children are unergonomic and back pain is common in these therapists. 2 There is a correlation between working techniques and the prevalence of pain in physiotherapists.


Functional MRI to assess alterations of functional networks in response to pharmacological or genetic manipulations of the serotonergic system in mice.
Imaging methods that enable the investigation of functional networks both in human and animal brain provide important insights into mechanisms underlying pathologies including psychiatric disorders. Since the serotonergic receptor 1A (5-HT(1A)-R) has been strongly implicated in the pathophysiology of depressive and anxiety disorders, as well as in the action of antidepressant drugs, we investigated brain connectivity related to the 5-HT(1A)-R system by use of pharmacological functional magnetic resonance imaging in mice. We characterized functional connectivity elicited by activation of 5-HT(1A)-R and investigated how pharmacological and genetic manipulations of its function may modulate the evoked connectivity. Functional connectivity elicited by administration of the 5-HT(1A)-R agonist 8-OH-DPAT can be described by networks characterized by small-world attributes with nodes displaying highly concerted response patterns. Circuits identified comprised the brain structures known to be involved in stress-related disorders (e.g. prefrontal cortex, amygdala and hippocampus). The results also highlight the dorsomedial thalamus, a structure associated with fear processing, as a hub of the 5-HT(1A)-R functional network. Administration of a specific 5-HT(1A)-R antagonist or use of heterozygous 5-HT(1A)-R knockout mice significantly reduced functional connectivity elicited by 8-OH-DPAT. Whole brain functional connectivity analysis constitutes an attractive tool to characterize impairments in neurotransmission and the efficacy of pharmacological treatment in a comprehensive manner.


The Influence of Menstrual Cycle on Bioimpedance Vector Patterns, Performance, and Flexibility in Elite Soccer Players.
To examine whether menstrual cycle affects body composition and bioimpedance vector analysis (BIVA) patterns, jumping and sprinting ability, and flexibility in elite soccer players. A total of 20 elite female soccer players (age: 23.8 [3.4] y, height: 1.63 [0.04] m, body mass: 61.4 [5.9] kg, and body mass index: 22.5 [2.4] kg/m2) were monitored during the early follicular and ovulatory phase across 2 consecutive menstrual cycles. Bioimpedance analysis was performed using foot-to-hand technology, and total body water and fat mass were determined by specific equations developed for athletes. Bioelectrical resistance and reactance were adjusted according to the BIVA procedures and plotted as a vector within the resistance-reactance graph. In addition, countermovement jump, 20-m sprint, and sit and reach were assessed. A time effect (P < .05) was found for body mass, total body water, bioelectrical resistance and reactance, and flexibility. Specifically, body mass increased (P = .021) along with a gain in total body water (P = .001) from the ovulatory to the early follicular phase, while it decreased from the early follicular to the ovulatory phase during the second menstrual cycle. The BIVA vector shortened during the early follicular phases (P < .001). No change in jumping and sprinting capacity was observed (P > .05). Flexibility was impaired during the early follicular phases (P < .05). Specific bioelectrical impedance analysis and BIVA procedures are able to detect menstrual cycle-induced changes in body composition in elite soccer players. The early follicular phase resulted in fluid accumulations and BIVA vector shortening. In addition, while menstrual cycle did not affect performance, a fluctuation in flexibility was observed.


Klk1 as one of the genes contributing to hypertension in Dahl salt-sensitive rat.
A genome-wide quantitative trait loci analysis for blood pressure was performed using 107 male F2 rats derived from Dahl salt-sensitive and Lewis rats. Blood pressure was assessed by telemetry, and >400 microsatellite markers were used for genotyping. Two major quantitative trait loci for blood pressure were identified at chromosome 1 and chromosome 10. The expression levels of 366 transcripts around the chromosome 1 quantitative trait loci were assessed by RT-PCR, and we found that the Klk1 (kallikrein 1) and Ngfg (nerve growth factor gamma) mRNA levels were significantly reduced in the kidneys of Dahl salt-sensitive rats compared with those in Lewis rats. The expression levels of kallikrein 1 protein were also suppressed in Dahl salt-sensitive rats compared with those in Lewis rats. Because the kallikrein-kinin system has been shown to be involved in renal function, including salt homeostasis, it is likely that the reduced expression of Klk1 contributes to salt-sensitive hypertension in Dahl salt-sensitive rats.


Cognitive-communication disorders in children with traumatic brain injury.
Children with moderate to severe traumatic brain injury (TBI) are at risk of developing cognitive-communication disorders that have devastating effects on their school life, family life, and social life. These problems can be difficult for families to describe and may be overlooked by community-based providers who are unfamiliar with TBI sequelae. To support the identification and management of cognitive-communication disorders, we review the common signs and symptoms of these disorders in children with TBI and discuss principles of assessment and intervention.


Rotavirus vaccines.
Encouraging results have been reported from several large trials of tetravalent rhesus rotavirus vaccine, with efficacy of 70-80% against severe disease. A recent Venezuelan study showed similar results to trials in USA and Europe. The vaccine may soon be licensed in USA. It provides the exciting prospect of a strategy to prevent one of the world's major child killers. Other candidate vaccines are under development including human-bovine reassortants, neonatal strains, non-replicating rotaviruses, vector vaccines and other genetically engineered products. Second and third generation rotavirus vaccines are on the horizon. The need for a rotavirus vaccine is well accepted by paediatricians, but public health authorities need to be lobbied. Other issues which need to be addressed include relative importance of non-group A rotaviruses, possible administration with OPV, the influence of breast feeding, and most importantly, cost. It is essential that rotavirus vaccine is somehow made available to all of the world's children, not just those in developed countries.


Suppression of survivin expression in glioblastoma cells by the Ras inhibitor farnesylthiosalicylic acid promotes caspase-dependent apoptosis.
The Ras inhibitor farnesylthiosalicylic acid (FTS) has been shown to induce apoptosis in glioblastoma multiforme, but its mechanism of action was unknown. We show that FTS or dominant-negative Ras, by deregulating extracellular signal-regulated kinase and Akt signaling, decreases survivin gene transcripts in U87 glioblastoma multiforme, leading to disappearance of survivin protein and cell death. FTS affected both Ras-controlled regulators of survivin transcription and Ras-regulated survival signals. Thus, Ras inhibition by FTS resulted in release of the survivin "brake" on apoptosis and in activation of the mitochondrial apoptotic pathway: dephosphorylation of Bad, activation of Bax, release of cytochrome c, and caspase activation. FTS-induced apoptosis of U87 cells was strongly attenuated by forced expression of survivin or by caspase inhibitors. These results show that resistance to apoptosis in glioblastoma multiforme can be abolished by a single Ras inhibitor, which targets both survivin, a critical inhibitor of apoptosis, and the intrinsic mitochondrial apoptotic machinery.


Reporting on first sexual experience: The importance of interviewer-respondent interaction.
Survey methodologists typically seek to improve data on sensitive topics by standardizing surveys and avoiding the use of human interviewers. This study uses data collected from 90 never-married young adults in rural Malawi to compare reports on first sexual encounters between a standard survey and an in-depth interview. A significant fraction of young women who claimed in the survey to have never been sexually active affirmed sexual experience during the in-depth interview, fielded shortly thereafter. Two elements of the in-depth interview, flexibility and reciprocal exchange, foster trust and more truthful reporting. The findings contradict the long-standing presumption that face-to-face interviews are inherently threatening when the topic is sex.


Filter based phase distortions in extracellular spikes.
Extracellular recordings are the primary tool for extracting neuronal spike trains in-vivo. One of the crucial pre-processing stages of this signal is the high-pass filtration used to isolate neuronal spiking activity. Filters are characterized by changes in the magnitude and phase of different frequencies. While filters are typically chosen for their effect on magnitudes, little attention has been paid to the impact of these filters on the phase of each frequency. In this study we show that in the case of nonlinear phase shifts generated by most online and offline filters, the signal is severely distorted, resulting in an alteration of the spike waveform. This distortion leads to a shape that deviates from the original waveform as a function of its constituent frequencies, and a dramatic reduction in the SNR of the waveform that disrupts spike detectability. Currently, the vast majority of articles utilizing extracellular data are subject to these distortions since most commercial and academic hardware and software utilize nonlinear phase filters. We show that this severe problem can be avoided by recording wide-band signals followed by zero phase filtering, or alternatively corrected by reversed filtering of a narrow-band filtered, and in some cases even segmented signals. Implementation of either zero phase filtering or phase correction of the nonlinear phase filtering reproduces the original spike waveforms and increases the spike detection rates while reducing the number of false negative and positive errors. This process, in turn, helps eliminate subsequent errors in downstream analyses and misinterpretations of the results.


Oncologic Impact of Renal Tissue Adjacent to Renal Cell Carcinoma.
The aim of the study was to investigate the clinical impact of the surgical margin width after nephron-sparing surgery (NSS) on the oncological course of renal cell carcinoma (RCC). The study comprised of 126 RCC patients with NSS between 2002 and 2009. Inclusion criteria were negative resection margins and a tumor diameter of ≤100 mm with the possibility of a complete circumferential histopathological reevaluation. The minimal benign margin width was correlated to the patients' clinical course. Median safety margin width was revealed to be 1 mm. Nine of 126 patients (7.1%) developed recurrent disease (five local, four distant). All patients with local recurrence had safety margins ≤1 mm, whereas out of 49 patients with a margin >1 mm no one developed local recurrence (p=0.0245). Safety margin ≤1 mm showed associations with increased risk for overall recurrence in univariate and multivariate analysis (p=0.0531 and 0.0539, respectively). Tumor adjacent renal parenchyma may have oncological relevance, corroborating the need for further molecular investigation of tumor-adjacent tissue in RCC.


[Application of microcarrier technology in cartilage repairing: a review].
Cartilage has poor self-recovery because of its characteristics of no blood vessels and high extracellular matrix. In clinical treatment, physical therapy or drug therapy is usually used for mild cartilage defects, and surgical treatment is needed for severe ones. In recent years, cartilage tissue engineering technology provides a new way for the treatment of cartilage defects. Compared with the traditional surgical treatment, cartilage tissue engineering technology has the advantages of small wound and good recovery. The application of microcarrier technology in the design of tissue engineering scaffolds further expands the function of scaffolds and promotes cartilage regeneration. This review summarized the main preparation methods and development of microcarrier technology in recent years. Subsequently, the properties and specific application scenarios of microcarriers with different materials and functions were introduced according to the materials and functions of microcarriers used in cartilage repair. Based on our research on osteochondral integrated layered scaffolds, we proposed an idea of optimizing the performance of layered scaffolds through microcarriers, which is expected to prepare bionic scaffolds that are more suitable for the structural characteristics of natural cartilage.


FRET-based characterisation of surfactant bilayer protected core-shell carbon nanoparticles: advancement toward carbon nanotechnology.
Surfactant bilayer protected core-shell carbon nanoparticles (CNPs) have been synthesised. Förster resonance energy transfer (FRET) between the core-shell CNPs and two strategically chosen organic dyes has been exploited to characterise the protective surfactant bilayer.


[Cardiovascular Complications of Rheumatoid Arthritis: Prevalence and Pathogenesis].
Rheumatoid arthritis (RA) is a chronic inflammatory disease associated with high risk of cardiovascular events. Among main causes of death in RA are: myocardial infarction, cerebrovascular accident, sudden cardiac death, which are determined by the early development and rapid progression of atherosclerotic vascular lesions. According to studies high risk of cardiovascular events is not explained by only classical risk factors. It is assumed that there are additional mechanisms of development of adverse outcomes such as systemic inflammation, increased arterial stiffness, and endothelial dysfunction. In this literature review we present various risk factors of cardiovascular events in patients with RA and their relation to RA pathogenesis.


SUSP1 antagonizes formation of highly SUMO2/3-conjugated species.
Small ubiquitin-related modifier (SUMO) processing and deconjugation are mediated by sentrin-specific proteases/ubiquitin-like proteases (SENP/Ulps). We show that SUMO-specific protease 1 (SUSP1), a mammalian SENP/Ulp, localizes within the nucleoplasm. SUSP1 depletion within cell lines expressing enhanced green fluorescent protein (EGFP) fusions to individual SUMO paralogues caused redistribution of EGFP-SUMO2 and -SUMO3, particularly into promyelocytic leukemia (PML) bodies. Further analysis suggested that this change resulted primarily from a deficit of SUMO2/3-deconjugation activity. Under these circumstances, PML bodies became enlarged and increased in number. We did not observe a comparable redistribution of EGFP-SUMO1. We have investigated the specificity of SUSP1 using vinyl sulfone inhibitors and model substrates. We found that SUSP1 has a strong paralogue bias toward SUMO2/3 and that it acts preferentially on substrates containing three or more SUMO2/3 moieties. Together, our findings argue that SUSP1 may play a specialized role in dismantling highly conjugated SUMO2 and -3 species that is critical for PML body maintenance.


A fucoidan fraction purified from Chnoospora minima; a potential inhibitor of LPS-induced inflammatory responses.
Fucoidans are an interesting group of bioactive sulfated polysaccharides abundant in brown seaweeds. The current study highlights the enrichment and extraction of fucoidan from Chnoospora minima by means of enzyme-assistant extraction using Celluclast and evaluation of its anti-inflammatory potential through in vitro and in vivo studies. The purified C. minima fucoidan (F2,4) inhibited the nitrous oxide (NO) production (IC50=27.82±0.88μg/ml) and expression of PGE2 through the subsequent downregulation of iNOS and COX-2 expression in lipopolysaccharide (LPS) stimulated RAW 264.7 macrophages. F2,4 downregulated TNF-α, IL1-β, and IL-6 in RAW 264.7 macrophages in a dose-dependent manner and suppressed NO and ROS production in LPS stimulated zebrafish embryos while exerting a protective effect against the cell damage caused by LPS. Polysaccharide structural characterization was performed using FTIR, HPAE-PAD analysis of the monosaccharide content and NMR spectroscopy. Current findings confirm the potential anti-inflammatory activity of fucoidan purified from C. minima and elaborate its potential application as a functional ingredient in consumer products.


Technical Aspects of Orthotopic Liver Transplantation-a Survey-Based Study Within the Eurotransplant, Swisstransplant, Scandiatransplant, and British Transplantation Society Networks.
Orthotopic liver transplantation (OLT) has emerged as the mainstay of treatment for end-stage liver disease. However, technical aspects of OLT are still subject of ongoing debate and are widely based on personal experience and local institutional protocols. An international online survey was sent out to all liver transplant centers (n = 52) within the Eurotransplant, Swisstransplant, Scandiatransplant, and British Transplant Society networks. The survey sought information on center-specific OLT caseload, vascular and biliary reconstruction, graft reperfusion, intraoperative control of hemodynamics, and drain policies. Forty-two centers gave a valid response (81%). Out of these, 50% reported piggy-back and 40.5% total caval replacement as their standard technique. While 48% of all centers generally do not apply veno-venous bypass (vvBP) or temporary portocaval shunt (PCS) during OLT, vvBP/PCS are routinely used in six centers (14%). Portal vein first reperfusion is used in 64%, followed by simultaneous (17%), and retrograde reperfusion (12%). End-to-end duct-to-duct anastomosis without biliary drain (67%) is the most frequently performed method of biliary reconstruction. No significant associations were found between the center caseload and the surgical approach used. The predominant part of the centers (88%) stated that techniques of OLT are not evidence-based and 98% would participate in multicenter clinical trials on these topics. Technical aspects of OLT vary widely among European centers. The extent to which center-specific variation of techniques affect transplant outcomes in Europe should be elucidated further in prospective multicenter trials.


Nanoparticle-based bioactive agent release systems for bone and cartilage tissue engineering.
The inability to deliver bioactive agents locally in a transient but sustained manner is one of the challenges on the development of bio-functionalized scaffolds for tissue engineering (TE) and regenerative medicine. The mode of release is especially relevant when the bioactive agent is a growth factor (GF), because the dose and the spatiotemporal release of such agents at the site of injury are crucial to achieve a successful outcome. Strategies that combine scaffolds and drug delivery systems have the potential to provide more effective tissue regeneration relative to current therapies. Nanoparticles (NPs) can protect the bioactive agents, control its profile, decrease the occurrence and severity of side effects and deliver the bioactive agent to the target cells maximizing its effect. Scaffolds containing NPs loaded with bioactive agents can be used for their local delivery, enabling site-specific pharmacological effects such as the induction of cell proliferation and differentiation, and, consequently, neo-tissue formation. This review aims to describe the concept of combining NPs with scaffolds, and the current efforts aiming to develop highly multi-functional bioactive agent release systems, with the emphasis on their application in TE of connective tissues.


Histone Acetyltransferase GCN5 Regulates Osteogenic Differentiation of Mesenchymal Stem Cells by Inhibiting NF-κB.
As the most well-studied histone acetyltransferase (HAT) in yeast and mammals, general control nonderepressible 5 (GCN5) was documented to play essential roles in various developmental processes. However, little is known about its role in osteogenic differentiation of mesenchymal stem cells (MSCs). Here, we detected the critical function of GCN5 in osteogenic commitment of MSCs. In this role, the HAT activity of GCN5 was not required. Mechanistically, GCN5 repressed nuclear factor kappa B (NF-κB)-dependent transcription and inhibited the NF-κB signaling pathway. The impaired osteogenic differentiation by GCN5 knockdown was blocked by inhibition of NF-κB. Most importantly, the expression of GCN5 was decreased significantly in the bone tissue sections of ovariectomized mice or aged mice. Collectively, these results may point to the GCN5-NF-κB pathway as a novel potential molecular target for stem cell mediated regenerative medicine and the treatment of metabolic bone diseases such as osteoporosis.


Laparoscopic removal of an artery forceps.
Numerous foreign bodies, such as surgical gauze, pads and instruments, and other items, have been left behind in the abdominal cavity during open surgeries. These have been traditionally removed at redo open surgeries. Here we describe a case of an artery forceps left behind at a previous surgery (open cholecystectomy and appendicectomy) performed 5 years earlier that was removed by laparoscopy.


Ruanjian Sanjie decoction exhibits antitumor activity by inducing cell apoptosis in breast cancer.
Traditional Chinese medicine, based on theories developed and practiced for >2,000 years, is one of the most common complementary and alternative types of medicine currently used in the treatment of patients with breast cancer. Ruanjian Sanjie (RJSJ) decoction, is composed of four herbs, including Ban xia (Pinellia ternata), Xia ku cao (Prunella vulgaris), Shan ci gu (Cremastra appendiculata) and Hai zao (Sargassum pallidum), and has traditionally been used for softening hard lumps and resolving hard tissue masses. However, the active compounds and mechanisms of action of RJSJ remain unknown. The present study demonstrated the antitumor activity of RJSJ against Ehrlich ascites carcinoma in Swiss albino mice and breast cancer xenografts in nude mice. Notably, RJSJ does not induce body weight loss, immune function toxicity or myelosuppression in mice, indicating that it is safe and well tolerated. In addition, RJSJ shows potent cytotoxicity against breast cancer cells in vitro by the suppression of the anti-apoptotic proteins B-cell lymphoma 2 and survivin, leading to the activation of caspase-3/7 and caspase-9, and the apoptotic cascade. These findings provide a clear rationale to explore the therapeutic strategy of using RJSJ alone or in combination with chemotherapeutic agents for breast cancer patients and the characterization of its active principles.


Additional records of the pagurid hermit crab genus Trichopagurus de Saint Laurent, 1968 (Crustacea: Decapoda: Anomura), with description of a new species from the Philippines.
The pagurid hermit crab genus Trichopagurus de Saint Laurent, 1968 is currently represented by three shallow water spe- cies from the tropical Indo-West Pacific region. In this paper, three species of the genus, including one new species, are reported. Trichopagurus tenuidactylus n. sp. is described on the basis of a single ovigerous female from the Bohol Sea, the Philippines, and compared with two close relatives, T. asper Komai & Poupin, 2012 and T. macrochela Komai & Os- awa, 2005. New locality records are provided for T. macrochela (the Philippines) and T. trichophthalinus (Forest, 1954) (Taiwan and Marianas). An identification key to the four species of the genus is presented.


NK cells promote islet allograft tolerance via a perforin-dependent mechanism.
Although major histocompatibility complex (MHC) class II-restricted CD4 T cells are well appreciated for their contribution to peripheral tolerance to tissue allografts, little is known regarding MHC class I-dependent reactivity in this process. Here we show a crucial role for host MHC class I-dependent NK cell reactivity for allograft tolerance in mice induced through either costimulation blockade using CD154-specific antibody therapy or by targeting LFA-1 (also known as CD11a). Tolerance induction absolutely required host expression of MHC class I, but was independent of CD8 T cell-dependent immunity. Rather, tolerance required innate immunity involving NK1.1(+) cells, but was independent of CD1d-restricted NKT cells. Therefore, NK cells seem to be generally required for induction of tolerance to islet allografts. Additional studies indicate that CD154-specific antibody-induced allograft tolerance is perforin dependent. Notably, NK cells that are perforin competent are sufficient to restore allograft tolerance in perforin-deficient recipients. Together, these results show an obligatory role for NK cells, through perforin, for induction of tolerance to islet allografts.


Role of medication therapy management in preexposure prophylaxis therapy for HIV prevention.
Patient medication adherence is a long-standing problem and is one that raises serious issues for patient health, public health, and health care quality. Medication nonadherence costs the US economy an estimated US$290 billion in avoidable medical spending every year. One of the most costly health conditions is HIV disease, which continues to be a serious health issue for parts of the world. About 34 million people are living with HIV around the world. With the emerging preventative treatment against HIV, known as preexposure prophylaxis (PrEP), come concerns surrounding the potential impact of nonadherence to this newly approved medication therapy. Nonadherence to antiretroviral treatments are commonly the root cause for patients not reaching their treatment goals, putting them at risk of progression and worsening of their disease and complications, such as increased risk of opportunistic infections. Therefore, it is essential to improve antiretroviral medication adherence. By identifying members who are nonadherent to their prescribed antiretroviral medications and working collaboratively with patients, physicians, and pharmacists, Medication Therapy Management (MTM) can potentially increase medication adherence by helping patients identify, resolve, and prevent issues that may affect their decision not to take a medication as intended.


Chronic-stage deep vein thrombosis of the lower extremities: indirect CT venographic findings.
To describe the computed tomographic (CT) findings of chronic deep vein thrombosis (DVT) and its evolution from acute DVT. Fifty-one consecutive patients with 52 legs confirmed as acute DVT by CT venography underwent follow-up computed tomography more than 2 months later. Follow-up CT findings were assessed retrospectively by consensus between 2 radiologists. The frequencies of CT findings were analyzed for affected venous segments: common iliac, external iliac, femoral, popliteal, and calf veins. Twelve legs (23%) were completely normalized on follow-up computed tomography, but 40 legs (77%) showed abnormal findings as follows: luminal obliteration (n = 16), decreased caliber (n = 30), residual thrombi (n = 3), fibrotic bands (n = 28), ipsilateral muscle enlargement (n = 28), ipsilateral subcutaneous edema (n = 11), and superficial collateral vein development (n = 23). The external iliac vein (26/40, 65%) was the most commonly affected site followed in decreasing order by femoral (29/50, 58%), common iliac (9/18, 50%), popliteal (22/47, 47%), and calf veins (9/43, 21%). Trends were observed whereby luminal obliteration affected iliac veins and fibrotic bands affected femoropopliteal veins. Luminal obliteration, decreased caliber, fibrotic bands, ipsilateral muscle enlargement, and superficial collateral vein development are common CT findings in chronic DVT of the lower extremity.


Confocal microscopic observations of the human cornea following overnight contact lens wear.
Striae and folds are observed with a slitlamp biomicroscope in the cornea following overnight contact lens wear. These phenomena are poorly understood. The aim of this study is to employ confocal microscopy to observe and document these and other morphological changes in the human cornea following overnight contact lens wear. Slitlamp biomicroscopy, slit-scanning confocal microscopy and ultrasonic pachometry were performed on both eyes of 13 subjects (3M, 10F, age 24 +/- 3 years) before and after eight hours overnight wear of a -3.00 D Bausch & Lomb one day disposable soft contact lens (Dk/t = 15.1 x 10(-9) [cm/sec] x [ml O2/ml x mmHg]) in one eye; the other non-lens-wearing eye acted as a control. Following sleep, both corneas were swollen (lens-wearing eye 11.8 +/- 3.8 per cent; control eye 2.1 +/- 1.9 per cent) and the stroma of both corneas displayed an apparent reduction in keratocyte density (lens-wearing eye 21 per cent; control eye 10 per cent). Folds were observed with the slitlamp biomicroscope and long, straight, dark, orthogonal lines were observed with the confocal microscope, in the posterior stroma of the oedematous lens-wearing eyes. Such features were not observed in the control eyes. The keratocytes appeared less distinct with greater levels of corneal oedema. The apparent loss of keratocytes following overnight lens wear is an optical artefact that can be explained in terms of corneal oedema causing volumetric tissue expansion and a loss of optical clarity, which hampers keratocyte detection. These findings place the onus on researchers postulating a loss of stromal keratocytes following clinical interventions, such as contact lens wear, to account for the effects of oedema.


Rapid-freeze-quench magnetic circular dichroism of intermediate X in ribonucleotide reductase: new structural insight.
To elucidate the electronic structure of intermediate X in the oxygen activation reaction of the R2 subunit of ribonucleotide reductase, a protocol has been developed to perform magnetic circular dichroism (MCD) on a rapid-freeze-quench, strain free optical sample. RFQ-MCD data have been collected on intermediate X in the double mutant of R2, Y122/Y356F. While X has been reported to exhibit a broad absorption band at 365 nm, there are at least 10 electronic transitions observed at low-temperature MCD. From C0/D0 ratios, the transitions of X can be divided into three regions: 16 000-22 000 cm-1 region involving spin-allowed ligand field transitions of the Fe(IV), 23 000-24 000 cm-1 region of spin-forbidden, spin-flip transitions on the Fe(IV), and the charge transfer (CT) region from 26 000 to 32 000 cm-1. The C0/D0 ratios from d --> d and CT transitions strongly support significant Fe(IV) character coupled into the paramagnetic center. Ligand field (spin-allowed d --> d region) analysis allows the bis-mu-oxo and mu-oxo plus other monoanionic bridge possibilities for the structure of intermediate X to be distinguished, providing new insight into the molecular mechanism of the cluster formation in R2.


Protein focusing in a conductivity gradient.
Conductivity gradient focusing (CGF) is one member of a family of gradient focusing techniques, characterized by two opposing forces which produce a dynamic equilibrium and which are able to simultaneously separate and concentrate proteins. In CGF, the two counteracting forces result from a constant convective flow of buffer opposed by an electric field gradient. This gradient in the electric field is formed by gradually decreasing buffer conductivity, i.e., when a slow-moving, relatively high conductivity buffer is dialyzed against a low conductivity purge buffer. This paper presents the design of an analytical-scale CGF device and the results of several experiments with colored proteins, both in free solution and with the use of a 45 micron size-exclusion (SEC) packing to decrease dispersion. Experimental results with hemoglobin suggest that CGF may one day be capable of resolving proteins with small charge differences. A linear computer model of conductivity gradient focusing is derived, and some suggestions are made for further development of this new electrophoretic method.


Nanocrystals of PbSe core, PbSe/PbS, and PbSe/PbSxS(1-x) core/shell as saturable absorbers in passively Q-switched near-infrared lasers.
The saturable optical absorption properties of PbSe core nanocrystals (NCs), and their corresponding PbSe/PbScore/shell and PbSe/PbSexS(1-x) core/alloyed-shell NCs, were examined at lambda = 1.54 microm. Saturation intensities of approximately 100 MW/cm2 were obtained. The NCs act as passive Q switches in near-infrared pulsed lasers. Q-switched output pulse energies up to 3 mJ, with a pulse duration of 40-55 ns were demonstrated. Analysis of the optical transmission versus pulse light intensity was carried out according to a model that includes ground-state as well as excited-state absorption. For pulses approximately 10 ns long, the NCs act as fast saturable absorbers. The theoretical fits yield a ground-state absorption cross section of 10-16-10-15 cm2, an excited-state absorption cross section of sigma(es) is congruent to 10(-16) cm2, and an effective lifetime of tau(eff) is congruent to 5 x 10(-12) s.


Influence of fat-free mass and functional status on resting energy expenditure in underweight elders.
In underweight elders, resting energy expenditure (REE) and its relationship with fat-free mass (FFM) could be modified by sarcopenia, physical activity, and functional limitation. The aims of this study were to investigate REE and its relationship with quantity and metabolic activity of FFM and to evaluate the influence of functional status on REE in underweight elderly subjects. Forty-eight underweight elders (BMI < 20) and 54 normal weight elderly subjects (BMI 20-30) as a control group were selected. Body composition was determined by dual energy x-ray absorptiometry (DEXA). REE was measured by indirect calorimetry. Ability in activities of daily living (ADLs) was assessed by the Katz index. Underweight elders had significantly lower FFM, FFM index (FFM/height(2)), and REE than healthy subjects. REE adjusted for FFM with analysis of covariance remained significantly lower in the underweight group (1287 +/- 85 vs 1715 +/- 139 kcal/day in men, and 1124 +/- 63 vs 1366 +/- 91 kcal/day in women). Katz index in the underweight group was inversely correlated with REE (r = -0.68; p <.001) even after removal of FFM, FM, and gender, by multiple regression analysis. In this model, FFM and Katz index together explained approximately 54% of REE variability. Underweight elderly subjects show a hypometabolism due to a reduction of both FFM quantity and its metabolic activity. Functional status in ADLs comes out as an important predictor of REE independently from FFM. The limited physical activity might be the underlying determinant of this hypometabolism, but further investigations are necessary to confirm this issue.


Slither Into the Heart: Salmonella Endocarditis Following Rattlesnake Meat Ingestion.
Salmonellae foodborne infections are a well described and documented entity, however cardiac complications of Salmonellae foodborne infections including infective endocarditis (IE) are rare. Here we present a case of infective endocarditis as a result of bacteremia caused by multiple species of Salmonella. The patient initially presented with chest pain, fever and altered mental status. Troponin and ECG were unremarkable. The patient was started on empiric antibiotics. Blood cultures grew Salmonella species serotype O&H. Transesophageal echocardiogram (TEE) confirmed aortic valve vegetation. Regional cultural practices suggested possible contamination attributed to ingestion of rattlesnake meat, a practice that has been previously described and well-established in various Hispanic folk practices. Upon further history taking, the patient was found to be regularly consuming dried rattlesnake meat preparations, a rather common practice in Chihuahua desert region. Surgery was not indicated, and the patient was treated with six weeks of antibiotics. This case presents an opportunity to gain insight into such a unique manifestation of Salmonellae, offering a potential facet of information for clinicians to better understand its presentation, susceptibility, and potential adverse outcomes.


Magnetofection Enhances Adenoviral Vector-based Gene Delivery in Skeletal Muscle Cells.
The goal of magnetic field-assisted gene transfer is to enhance internalization of exogenous nucleic acids by association with magnetic nanoparticles (MNPs). This technique named magnetofection is particularly useful in difficult-to-transfect cells. It is well known that human, mouse, and rat skeletal muscle cells suffer a maturation-dependent loss of susceptibility to Recombinant Adenoviral vector (RAd) uptake. In postnatal, fully differentiated myofibers, the expression of the primary Coxsackie and Adenoviral membrane receptor (CAR) is severely downregulated representing a main hurdle for the use of these vectors in gene transfer/therapy. Here we demonstrate that assembling of Recombinant Adenoviral vectors with suitable iron oxide MNPs into magneto-adenovectors (RAd-MNP) and further exposure to a gradient magnetic field enables to efficiently overcome transduction resistance in skeletal muscle cells. Expression of Green Fluorescent Protein and Insulin-like Growth Factor 1 was significantly enhanced after magnetofection with RAd-MNPs complexes in C2C12 myotubes in vitro and mouse skeletal muscle in vivo when compared to transduction with naked virus. These results provide evidence that magnetofection, mainly due to its membrane-receptor independent mechanism, constitutes a simple and effective alternative to current methods for gene transfer into traditionally hard-to-transfect biological models.


Osteogenic ability of Cu-bearing stainless steel.
A newly developed copper-bearing stainless steel (Cu-SS) by directly immobilizing proper amount of Cu into a medical stainless steel (317L SS) during the metallurgical process could enable continuous release of trace amount of Cu(2+) ions, which play the key role to offer the multi-biofunctions of the stainless steel, including the osteogenic ability in the present study. The results of in vitro experiments clearly demonstrated that Cu(2+) ions from Cu-SS could promote the osteogenic differentiation by stimulating the Alkaline phosphatase enzyme activity and the osteogenic gene expressions (Col1a1, Opn, and Runx2), and enhancing the adhesion and proliferation of osteoblasts cultured on its surface. The in vivo test further proved that more new bone tissue formed around the Cu-SS implant with more stable bone-to-implant contact in comparison with the 317L SS. In addition, Cu-SS showed satisfied biocompatibility according to the results of in vitro cytotoxicity and in vivo histocompatibility, and its daily released amount of Cu(2+) ions in physiological saline solution was at trace level of ppb order (1.4 ppb/cm(2) ), which is rather safe to human health. Apart from these results, it was also found that Cu-SS could inhibit the happening of inflammation with lower TNF-α expression in the bone tissue post implantation compared with 317L SS. In addition to good biocompatibility, the overall findings demonstrated that the Cu-SS possessed obvious ability of promoting osteogenesis, indicating a unique application advantage in orthopedics.


Facile fabrication of long alpha-Fe(2)O(3), alpha-Fe and gamma-Fe(2)O(3) hollow fibers using sol-gel combined co-electrospinning technology.
Long alpha-Fe(2)O(3) hollow fibers have been prepared through a facile sol-gel combined co-electrospinning technique using ferric citrate as precursor, and alpha-Fe and gamma-Fe(2)O(3) hollow fibers have been obtained by reduction and reoxidation at different conditions. The outer diameter of the as-prepared hollow fibers is 0.5-5 microm with wall thickness of 200-800 nm. The obtained tubular fibers were characterized by thermal gravimetric (TG), FT-IR spectra, X-ray diffraction (XRD), transmission electron microscopy (TEM), scanning electron microscopy (SEM) and Raman techniques. In addition, magnetic properties of alpha-Fe and gamma-Fe(2)O(3) hollow fibers have also been investigated.


Is there an association between acromegaly and thyroid carcinoma? A critical review of the literature.
Patients with acromegaly may have higher rates of cancer, possibly due to increased plasma levels of IGF-I, which is known to promote cellular growth. While simple and multinodular goiters are more common among acromegalics, reports of thyroid carcinoma are rare, and its true incidence is unclear. Here, we review the relevant literature in the context of a case of a patient with acromegaly with persistently elevated IGF-I levels who was subsequently diagnosed with thyroid carcinoma. The incidence and potential pathophysiologic mechanisms of benign and malignant thyroid disease in acromegaly are discussed. We conclude that in acromegalic patients with persistently elevated IGF-I levels, one should ensure careful monitoring of goiter and thyroid nodules, including fine-needle aspiration of nodules that are 1 cm or larger.


Anisotropy of electrostatic interaction in free-standing smectic-C^{*} films.
The correlation function of the director fluctuations in a free-standing smectic ferroelectric film is calculated theoretically. In the functional of free energy, the anisotropy of the Coulomb interaction of polarization charges is taken into account. The results of calculations were used to obtain the angular dependences of scattered light intensity. It has been shown that for relatively thick films, the anisotropy of the Coulomb interaction of polarization charges can change significantly the scattered light intensity.


Going against the flow: the impact of PHARMAC not funding COX-2 inhibitors for chronic arthritis.
COX-2 inhibitors have come under a lot of scrutiny lately, with questions raised regarding class effects and the risk-benefit of these pharmaceuticals. From 1999 to 2003 the New Zealand Pharmaceutical Management Agency (PHARMAC) evaluated the evidence on COX-2 inhibitors, including their efficacy, cost-effectiveness and budgetary impact. In September 2003 PHARMAC decided not to list celecoxib, rofecoxib and meloxicam on the Pharmaceutical Schedule. This decision meant that at least 18 other pharmaceuticals were able to be funded or have access extended, resulting in 437 'statistical lives' saved per year, with net health gains, and savings for District Health Boards. Had PHARMAC funded COX-2 inhibitors at the same time as Australia, it is estimated that this may have resulted in approximately 740 to 4220 excess myocardial infarctions (MIs) and approximately 330 to 1900 excess deaths from MI.


Accurate Matching of a Secondary Amino-Functionality Metal-Organic Cage for Selective Recognition and Supramolecular Binding during Photoinduced Hydrogen Evolution.
Accurate matching of the active sites between the host and guest molecules has a great effect on the selective recognition of different but similar guest molecules or different binding abilities toward the same molecule. Herein, a pseudotetrahedral metal-organic cage (MOC, Co-TAP) that contains secondary amino groups designed as guest-interacting sites was achieved. Co-TAP exhibits the selective recognition of uridine over other similar natural molecules via a fluorescent response. However, a reference structure (Co-TOP) with the same configuration was also synthesized by replacing the secondary amine group with an oxygen atom of the ligand, and it reveals the selective recognition of guanosine. In addition, the accurate matching also enables Co-TAP to strongly bind the organic dye as a guest molecule via host-guest interactions, thus facilitating photoinduced electron transfer between the redox catalytic sites in MOC and the excited guest via a pseudointramolecular pathway.


Body composition as an indicator of metabolic changes in mice obtained by in vitro fertilization.
To identify body systems subject to epigenetic transformation during in vitro fertilization (IVF), comparative morphological and functional studies were performed on sexually mature offspring of outbred CD1 mice, specific-pathogen-free (SPF), obtained by IVF (experiment) and natural conception (control). The studies included assessment of age-related changes in body weight and composition, energy intake and expenditure, and glucose homeostasis. To level the effects caused by the different number of newborns in the control and in the experiment, the size of the fed litters was halved in the control females. Males obtained using the IVF procedure were superior in body weight compared to control males in all age groups. As was shown by analysis of variance with experiment/control factors, gender, age (7, 10 and 20 weeks), the IVF procedure had a statistically significant and unidirectional effect on body composition. At the same time, IVF offspring outperformed control individuals in relative fat content, but were behind in terms of lean mass. The effect of the interaction of factors was not statistically significant. IVF offspring of both sexes had higher fat to lean mass ratios (FLR). Since adipose tissue contributes significantly less to total energy intake compared to muscle, the main component of lean mass, it is not surprising that at the same level of IVF locomotor activity offspring consumed less food than controls. When converted to one gram of body weight, this difference reached 19 %. One of the consequences of reduced utilization of IVF energy substrates by offspring is a decrease in their tolerance to glucose loading. The integral criterion for the effectiveness of restoring the initial glucose level is the area under the curve (AUC), the value of which was 2.5 (males) and 3.2 (females) times higher in IVF offspring compared to the corresponding control. Thus, the totality of our original and literature data shows an increase in the risk of metabolic disorders in IVF offspring, which is confirmed by epidemiological studies of a relatively young cohort of people born using assisted reproductive technologies.


[Chemotherapy for human gastric cancer: a review].
The authors review the actual position of medical treatment for human gastric cancer. Chemotherapy has been evaluated first in palliative situation, then as adjuvant post-surgical approach either through systemic or intraperitoneal route. Now chemotherapy may also be proposed as neoadjuvant (before surgery) treatment as part of an integrated global pluridisciplinary approach. New hopes to improve the prognosis come then from both neoadjuvant and adjuvant chemotherapy (+/- radiotherapy) and further from less toxic infusional therapies (chronomodulation), new schedules with proved active molecules (docetaxel, oxaliplatin, irinotecan, pemetrexed) as well as from new targeted treatments (against ie, EGF-receptor and angiogenesis).


The link between nursing discourses and nurses' silence: implications for a knowledge-based discourse for nursing practice.
Much emphasis has been placed on the importance of nurses' articulating what they do to counteract the invisibility of nursing practice. Yet there has been minimal focus on why nurses are silent. This article explores the link between technical and caring discourses and nurses' silence and suggests an alternative discourse that conceptualizes nursing as a knowledge-driven enterprise that shifts the focus from what nurses do to what nurses know by promoting nurses' practice knowledge as a language for articulating their practice.


Robustness of Bio-Inspired Visual Systems for Collision Prediction in Critical Robot Traffic.
Collision prevention sets a major research and development obstacle for intelligent robots and vehicles. This paper investigates the robustness of two state-of-the-art neural network models inspired by the locust's LGMD-1 and LGMD-2 visual pathways as fast and low-energy collision alert systems in critical scenarios. Although both the neural circuits have been studied and modelled intensively, their capability and robustness against real-time critical traffic scenarios where real-physical crashes will happen have never been systematically investigated due to difficulty and high price in replicating risky traffic with many crash occurrences. To close this gap, we apply a recently published robotic platform to test the LGMDs inspired visual systems in physical implementation of critical traffic scenarios at low cost and high flexibility. The proposed visual systems are applied as the only collision sensing modality in each micro-mobile robot to conduct avoidance by abrupt braking. The simulated traffic resembles on-road sections including the intersection and highway scenes wherein the roadmaps are rendered by coloured, artificial pheromones upon a wide LCD screen acting as the ground of an arena. The robots with light sensors at bottom can recognise the lanes and signals, tightly follow paths. The emphasis herein is laid on corroborating the robustness of LGMDs neural systems model in different dynamic robot scenes to timely alert potential crashes. This study well complements previous experimentation on such bio-inspired computations for collision prediction in more critical physical scenarios, and for the first time demonstrates the robustness of LGMDs inspired visual systems in critical traffic towards a reliable collision alert system under constrained computation power. This paper also exhibits a novel, tractable, and affordable robotic approach to evaluate online visual systems in dynamic scenes.


Blocking the maturation of OncomiRNAs using pri-miRNA-17∼92 aptamer in retinoblastoma.
The miR-17∼92. or oncomiR-1, cluster encodes oncogenic microRNAs (miRNAs), and it also promotes retinoblastoma (RB) tumor formation. Antagomir and miRNA mimics based approaches are widely tried against oncogenic and tumor suppressive miRNAs. Other methods for targeting cancer related miRNAs are still under development. In the current study, we focused on the pri-miRNA-17∼92 aptamer (pri-apt), which can potentially replace the mix of five antagomirs by one aptamer that function to abrogate the maturation of miR-17, miR-18a, and miR-19b (P<0.05) for targeting RB. We used RB cell lines WERI-Rb1 and Y79 as an in vitro model. Cellular changes upon transfecting the pri-apt led to S-phase arrest in WERI-Rb1 cells and onset of apoptosis in both Y79 and WERI-Rb1 cell lines. There was increased cytotoxicity as measured by lactate dehydrogenase activity in pri-apt treated Y79 cells (P<0.05), and significant inhibition of cell proliferation was observed in both of the cell lines. Thus we showed the antiproliferative property of pri-apt in RB cell lines, which can be readily modified by developing appropriate vectors for the delivery of the aptamer specifically to cancer cells.


Brain-computer interfaces: a neuroscience paradigm of social interaction? A matter of perspective.
A number of recent studies have put human subjects in true social interactions, with the aim of better identifying the psychophysiological processes underlying social cognition. Interestingly, this emerging Neuroscience of Social Interactions (NSI) field brings up challenges which resemble important ones in the field of Brain-Computer Interfaces (BCI). Importantly, these challenges go beyond common objectives such as the eventual use of BCI and NSI protocols in the clinical domain or common interests pertaining to the use of online neurophysiological techniques and algorithms. Common fundamental challenges are now apparent and one can argue that a crucial one is to develop computational models of brain processes relevant to human interactions with an adaptive agent, whether human or artificial. Coupled with neuroimaging data, such models have proved promising in revealing the neural basis and mental processes behind social interactions. Similar models could help BCI to move from well-performing but offline static machines to reliable online adaptive agents. This emphasizes a social perspective to BCI, which is not limited to a computational challenge but extends to all questions that arise when studying the brain in interaction with its environment.


Study design and ethical considerations related to using direct observation to evaluate physician behavior: reflections after a recent study.
In a recent study using direct observation of physicians, we demonstrated that physician-generated clinical documentation is vulnerable to error. In fact, we found that physicians consistently overrepresented their actions in certain areas of the medical record, such as the physical examination. Because of our experiences carrying out this study, we believe that certain investigations, particularly those evaluating physician behavior, should not rely on documentation alone. Investigators seeking to evaluate physician behavior should instead consider using observation to obtain objective information about occurrences in the patient-physician encounter. In this article, we describe our experiences using observation, and we offer investigators our perspectives related to study design and ethical questions to consider when performing similar work.


Predictors of Early Community Involvement: Advancing the Self and Caring for Others.
Recent research on community involvement points to the importance of both agentic (advancing the self) and communal motives (serving others) as key predictors, though few studies have examined both simultaneously. At the same time, research has identified generativity, defined as concern for future generations as a legacy of the self, as particularly relevant for community involvement. Moreover, generativity involves both agentic and communal motives, meaning that advancing personal goals and caring for others are integrated in this construct. Therefore, the purpose of this study was to examine how individual differences in attributes pertaining to self and to others-specifically, self-esteem, initiative, and empathy-related to both generativity and community involvement. A sample of adolescents (N = 160; 64% female, Mage = 17) and a sample of young adults (N = 237; 84% female, Mage = 20) completed a survey including measures of community involvement and generativity. Generative concern fully mediated the associations between individual differences (self-esteem, initiative, and empathy) and community involvement, suggesting that the early generativity has a role in fostering capacities and contribution in youth. These developmental indicators pertaining to self and others link to actions that benefit the community through a desire to benefit future generations.


The influence of poly(phenyleneethynylene) side chain structure on single-walled carbon nanotubes hybrid photovoltaic cells.
A novel poly(phenyleneethynylene)/single walled carbon nanotubes (SWNTs) donor-acceptor nanohybrid system was constructed based on the bulk heterojunction concept, and their photovoltaic (PV) properties were studied. Comparing with that of the pristine polymer poly(phenyleneethynylene) (PPE) device, the PV performance of the SWNTs/PPE hybrid is dramatically improved. The origin of open-circuit voltage (V(oc)) of the pristine polymer PPE device and SWNTs/PPE device was explained by metal-insulator-metal (MIM) diode model and pinning mechanism, respectively. Furthermore, incorporation of sensitizing groups to the side chain of PPE has great effect on the photovoltaic cell performance based on these hybrid materials and both the short-circuit current density (I(sc)) and power conversion efficiency are significantly enhanced. It is proposed that the main reason for the increase of short circuit current is due to efficient transfer of holes by sensitizer to PPE backbone and the transfer of electrons to the SWNTs. The power conversion efficiency is enhanced by approximately 1 order magnitude to 0.031% for the device based on the PPE3 with anthracene sensitizer group on the side chain compared with that (4.2 x 10(-3)% for SWNTs/PPE1 and 6.2 x 10(-3)% for SWNTs/PPE2) of the device without anthracene sensitizer on the side chain.


Application of pH-Responsive Fucoidan/Chitosan Nanoparticles to Improve Oral Quercetin Delivery.
Polymeric nanoparticles based on fucoidan and chitosan were developed to deliver quercetin as a novel functional food. Through the polyelectrolyte self-assembly method, fucoidan/chitosan (F/C) nanoparticles were obtained with three different weight ratios (1/1, 3/1, and 5/1). The content of quercetin in the fucoidan/chitosan nanoparticles was in the range 110 ± 3 to 335 ± 4 mg·mL-1, with the increase of weight ratio of fucoidan to chitosan in the nanoparticle. Physicochemically stable nanoparticles were obtained with a particle size within the 300⁻400 nm range and surface potential higher than +30 mV for the 1F/1C ratio nanoparticle and around -30 mV for the 3F/1C and 5F/1C ratios nanoparticles. The 1F/1C ratio nanoparticle became larger and more unstable as the pH increased from 2.5 to 7.4, while the 3F/1C and 5F/1C nanoparticles retained their initial characteristics. This result indicates that the latter nanoparticles were stable along the gastrointestinal tract. The quercetin-loaded fucoidan/chitosan nanoparticles showed strong antioxidant activity and controlled release under simulated gastrointestinal environments (in particular for the 3F/1C and 5F/1C ratios), preventing quercetin degradation and increasing its oral bioavailability.


Locally Weighted Ensemble Clustering.
Due to its ability to combine multiple base clusterings into a probably better and more robust clustering, the ensemble clustering technique has been attracting increasing attention in recent years. Despite the significant success, one limitation to most of the existing ensemble clustering methods is that they generally treat all base clusterings equally regardless of their reliability, which makes them vulnerable to low-quality base clusterings. Although some efforts have been made to (globally) evaluate and weight the base clusterings, yet these methods tend to view each base clustering as an individual and neglect the local diversity of clusters inside the same base clustering. It remains an open problem how to evaluate the reliability of clusters and exploit the local diversity in the ensemble to enhance the consensus performance, especially, in the case when there is no access to data features or specific assumptions on data distribution. To address this, in this paper, we propose a novel ensemble clustering approach based on ensemble-driven cluster uncertainty estimation and local weighting strategy. In particular, the uncertainty of each cluster is estimated by considering the cluster labels in the entire ensemble via an entropic criterion. A novel ensemble-driven cluster validity measure is introduced, and a locally weighted co-association matrix is presented to serve as a summary for the ensemble of diverse clusters. With the local diversity in ensembles exploited, two novel consensus functions are further proposed. Extensive experiments on a variety of real-world datasets demonstrate the superiority of the proposed approach over the state-of-the-art.


High liver fibrosis index FIB-4 is highly predictive of hepatocellular carcinoma in chronic hepatitis B carriers.
Screening for hepatocellular carcinoma (HCC) is clinically important given that its early detection has remarkable survival benefits. We investigated the possible role of FIB-4, a recently developed noninvasive marker for liver fibrosis based on routine laboratory tests, as a clinical indicator for predicting future HCC among hepatitis B surface antigen (HBsAg) carriers. Our retrospective cohort study involved 986 Korean HBsAg carriers 40 years of age or older who visited Seoul National University Hospital for a health checkup. National medical service claims data were used to determine HCC incidence. Median follow-up time was 5.4 years (interquartile range: 4.4 years). Adjusted for age, sex, body mass index, smoking, alcohol, and antiviral medication for hepatitis B, compared to subjects with FIB-4 <1.25, subjects with 1.7≤ FIB-4 <2.4 showed an adjusted hazard ratio (aHR) of 4.57 (95% confidence interval [CI]: 1.50-13.92) and subjects with FIB-4 ≥2.4 showed an aHR of 21.34 (95% CI: 7.73-58.92) for HCC incidence. FIB-4 was shown to have incremental predictive value to ultrasonographic liver cirrhosis for HCC incidence (C-index: 0.701 vs. 0.831; P = 0.001). FIB-4 was also better predictive of HCC incidence, compared to that of ultrasonographic liver cirrhosis (C-index: 0.775 vs. 0.701; P = 0.040). High FIB-4 is a highly predictive risk factor for HCC incidence among Korean HBsAg carriers. FIB-4 is a promising, easily applicable, and cost-effective clinical tool in identifying a subpopulation of HBsAg carriers who are at heightened risk. Our study needs to be replicated in larger future studies on various ethnic groups; nonetheless, our study suggests that FIB-4 may play a valuable role in HCC screening among HBsAg carriers.


Gold(I)-Assisted α-Allylation of Enals and Enones with Alcohols.
The intermolecular α-allylation of enals and enones occurs by the condensation of variously substituted allenamides with allylic alcohols. Cooperative catalysis by [Au(ItBu)NTf2] and AgNTf2 enables the synthesis of a range of densely functionalized α-allylated enals, enones, and acyl silanes in good yield under mild reaction conditions. DFT calculations support the role of an α-gold(I) enal/enone as the active nucleophilic species.


Corrosion test for dental amalgam.
A corrosion test for dental amalgam, based on controlled potential coulometry, provides an index of corrosion susceptibility. A special cell was designed, and optimum test conditions were determined. The test can be used for the rating of amalgams, and in studies of the effect of variables on the corrosion resistance.


Medication-overuse headache in China: clinical profile, and an evaluation of the ICHD-3 beta diagnostic criteria.
Although medication-overuse headache (MOH) is common in China, its clinical profile is not yet fully established. Meanwhile, ICHD-3 beta has been published, but its diagnostic criteria require further validation. We retrospectively classified the clinical features of 240 consecutive patients with MOH (55 males, 185 females), whose demographic data, headache features, overused medications (type, quantity, frequency and duration of use), headache-attributed burden, and outcomes were reviewed. We then applied the criteria of the several versions of ICHD (II, IIR and 3-beta) to these patients. Compared with those with other headaches, patients with MOH were more likely to be less well educated (64.6% vs 42.0% for secondary school or lower, p < 0.0001), and on lower annual incomes (72.3% vs 56.0% for an income of Chinese yuan (CNY) 30,000 or less, p < 0.0001). Combination analgesics were the most commonly overused medications, and, caffeine (89.9%), aminopyrine (70.0%), phenacetin (53.9%) and phenobarbital (48.8%) were the most commonly used specific components of these. Only two patients (0.8%) had previously been given the diagnosis of MOH; accordingly, the median time to diagnosis after the estimated onset of the disorder was 4.0 years. The majority of patients (83.7%) improved with treatment. All 240 patients fulfilled the diagnostic criteria for MOH according to ICHD-3 beta; only 134 (55.8%) satisfied the diagnostic criteria for definite MOH according to ICHD-II, while 195 (81.2%) met those of ICHD-IIR. MOH in China is associated with lower educational level and annual income. MOH has rarely been diagnosed and correctly treated in China. ICHD-3 beta appears to be more appropriate for the diagnosis of MOH than previous versions.


Fatty acid amide hydrolase binding is inversely correlated with amygdalar functional connectivity: a combined positron emission tomography and magnetic resonance imaging study in healthy individuals.
Upregulation of the endocannabinoid enzyme fatty acid amide hydrolase (FAAH) has been linked to abnormal activity in frontoamygdalar circuits, a hallmark of posttraumatic stress disorder. We tested the hypothesis that FAAH levels in the amygdala were negatively correlated with functional connectivity between the amygdala and prefrontal cortex, subserving stress and affect control. Thirty-one healthy participants completed positron emission tomography (PET) imaging with the FAAH probe [C-11]CURB, and resting-state functional MRI scans. Participants were genotyped for the FAAH polymorphism rs324420, and trait neuroticism was assessed. We calculated amygdala functional connectivity using predetermined regions of interest (including the subgenual ventromedial prefrontal cortex [sgvmPFC] and the dorsal anterior cingulate cortex [dACC]) and a seed-to-voxel approach. We conducted correlation analyses on functional connectivity, with amygdala [C-11]CURB binding as a variable of interest. The strength of amygdala functional connectivity with the sgvmPFC and dACC was negatively correlated with [C-11]CURB binding in the amygdala (sgvmPFC: r = -0.38, q = 0.04; dACC: r = -0.44; q = 0.03). Findings were partly replicated using the seed-to-voxel approach, which showed a cluster in the ventromedial prefrontal cortex, including voxels in the dACC but not the sgvmPFC (cluster-level, family-wise error rate corrected p < 0.05). We did not replicate earlier findings of a relationship between an FAAH polymorphism (rs324420) and amygdala functional connectivity. Our data provide preliminary evidence that lower levels of FAAH in the amygdala relate to increased frontoamygdalar functional coupling. Our findings were consistent with the role of FAAH in regulating brain circuits that underlie fear and emotion processing in humans.


Folate serum levels in Italian women entering an in vitro fertilization program.
Italian public health authorities recommend women of childbearing age to assume a daily dose of 0.4 mg of folic acid (FA) from at least one month before conception in order to reduce the risk of having children affected by neural tube defects (NTDs). In this study, folate, homocysteine and vitamin B12 serum levels were determined in 77 women entering an in vitro fertilization program. About 75% of patients had serum folate values compatible with the intake of the recommended dose of FA for at least three months, whereas only the 61% of them reached or exceeded the serum folate concentration regarded as the optimal concentration during the periconceptional period. Mean vitamin B12 serum levels and mean homocysteine plasma levels resulted in normal range in all the women with mean values of 381.2 ± 2.2 pg/ml and 8.48 ± 2.2 μmol/l, respectively. In conclusion, only a portion of women entering an IVF program presents proper folate levels.


Regulation of the nucleolar DNA-dependent RNA polymerase by amino acids in Ehrlich ascites tumor cells.
Experiments were performed to ascertain the degree to which the amount of amino acids might be one of the regulatory factors that control the activity of the nucleolar RNA polymerase. Assays of the enzymatic activity were done with isolated nuclei from cells incubated with low and high concentrations of amino acids. Soon after the cells were exposed to a medium enriched in amino acids, a rapid increase of nucleolar RNA polymerase activity occurred. A similar result was obtained in cells incubated with lower concentrations of amino acids. However, the rate of ribosomal RNA synthesized was regularly much higher in cells incubated in a medium enriched with amino acids than in a medium low in amino acids. Apparently, the amino acids only controlled ribosomal RNA synthesis. Thus, neither maturation, processing, and transport of nuclear precursors into cytoplasmic ribosomal RNA, nor the synthesis of rapidly labeled RNA was affected.


Lin28 gene and mammalian puberty.
Lin28a and Lin28b, homologs of the Caenorhabditis elegans Lin28 gene, play important roles in cell pluripotency, reprogramming, and tumorigenicity. Recently, genome-wide association and transgenic studies showed that Lin28a and/or Lin28b gene were involved in the onset of mammalian puberty, the stage representing the attainment of reproduction capacity; however, the detailed mechanism of these genes in mammalian puberty remains largely unknown. The present paper reviews the research progress on the roles of Lin28a/b genes in the onset of mammalian puberty by analyzing the results coming from gene expression patterns, mutations, and transgenic studies, and put forward possible pathways for further studies on their roles in animal reproduction.


Evaluation of a simple technique for rapid access to left main bronchus.
A suction catheter with dual curvature at its tip was evaluated for its successful rapid access to left main bronchus. The catheter with dual curvature was passed through endotracheal tube in neutral position of head in 58 adult patients of both sexes in need of mechanical ventilation. Bedside x-ray (AP view) chest was taken to confirm its location. It is observed that this suction catheter had very high success rate of 95% in first attempt and 100% after repositioning endothracheal tube. It did not require any position alteration of head or body and easily allowed aspiration from left lung.


A computer-designed macrocyclic zinc receptor.
A macrocycle containing a pair of bipyridine moieties with a linker designed using the computer program CAVEAT exhibits unique selectivity in the binding of zinc ion relative to other metals.


The recovery model in chronic mental health: A community-based investigation of social identity processes.
The recovery model has been enormously influential in shaping mental health services globally over the last two decades. However, empirical research on its outcomes and psychological mechanisms is sparse. This community-based case study utilised both semi-structured qualitative interviews and quantitative survey methods to investigate perceptions of recovery, identity, and wellbeing among people with chronic and severe mental illness attending recovery-oriented support groups. Consistent with a social identity approach and the recovery model, to the extent that people identified as "in recovery", they reported better recovery outcomes (e.g., sense of purpose) and reduced psychological distress. Furthermore, recovery identity more strongly predicted recovery outcomes than it did psychological distress. Both the quantitative and qualitative data pointed to collective efficacy (i.e., group-based empowerment) as a key mediator of these outcomes. These findings are consistent with the recovery model and speak to the utility of a social identity approach for conceptualizing its efficacy. However, these findings also speak to the need for further evaluation of how and when recovery-oriented mental health services achieve their intended goal of improving quality of life for people with chronic and severe mental illness.


[Methods for the superselective radioembolization of liver tumors with 90yttrium-resin particles].
An improved technique for radioembolization of non-resectable liver tumours is described. 90yttrium-labelled Bio-Rex-70 particles which show high stability and good tissue tolerance are applied superselectively via the tumour-feeding artery using a microcatheter. The procedure includes both diagnostic and therapeutic angiography. Angiography is complemented by angioscintigraphy (99mTc-MAP) and an i.v. 99mTc-colloid scan of the liver. Thus it is possible pretherapeutically to evaluate tumour volume and dose distribution both in and outside of the liver, and in the lung due to shunt. These estimates were re-evaluated posttherapeutically. Radioembolization can thus be quantified and the doses absorbed by the tumour as well as the liver and lung can be calculated.


Electron beam lithography with negative tone resist for highly integrated silicon quantum bits.
Process technologies have been developed for electron-beam (EB) lithography aimed at silicon quantum devices and their large-scale integration. It is necessary to understand the proximity effect and construct a method for its correction to perform EB lithography of fine and complicated structures. In this study, we investigate the lithography of Si quantum devices with a point-beam EB system and a maN 2401 negative tone resist, in order to correspond to various types of device structures. We optimize temperatures for specialized pre- and post-exposure bakes for forming ∼20 nm fine patterns with small line-edge roughness. Further, we demonstrated the fabrication of Si-on-insulator device patterns that have some tiny dots connected with many large wires/pads in the layout, with the careful tuning of the dose assignment. In this tuning, we used the EB process simulation to estimate the cumulative dose distribution effectively. In addition, we reproduced the experimentally obtained resist patterns via the EB process simulation after considering the mid-range effect, which is a factors in the proximity effect but is not yet deeply understood. The results of this study are expected to provide useful process technologies for EB lithography, which will help drastically accelerate the research on Si quantum devices with a high degree of freedom.


Transapical beating-heart septal myectomy for recurrent left ventricular outflow tract obstruction after septal reduction therapy in hypertrophic obstructive cardiomyopathy.
We present a case of a 58-year-old man for surgical myectomy due to recurrent left ventricular outflow tract (LVOT) obstruction, who had prior transaortic septal myectomy and embolization of the septal branch. On admission, transthoracic echocardiography showed a typical hypertrophic obstructive cardiomyopathy (HOCM) with asymmetric septal hypertrophy, significant LVOT obstruction and severe mitral regurgitation due to the systolic anterior movement of the anterior mitral valve leaflet. We performed a novel procedure of the transapical beating-heart septal myectomy, following which the LVOT obstruction was resolved. And a decreased grade of systolic anterior movement and a reduction in the severity of mitral regurgitation were observed.


Role of Oxidative Stress in Retinal Disease and the Early Intervention Strategies: A Review.
The retina, owing to its cellular anatomy and physical location, is susceptible to generating reactive oxygen species (ROS), which are associated with several major retinal diseases. When ROS exceeds the body's natural antioxidants, the retina is in a state of oxidative stress, which is recognized as the pathogenesis of retinal diseases. The early stage of the pathogenic process is an adaptive change in which oxidative stress and endogenous defense mechanisms occur. If no treatment is applied, the retinal diseases will progress to the pathological stage with neuronal and vascular dysfunction or damage and even blindness. This review summarizes the role of oxidative stress in several common retinal diseases, including retinitis pigmentosa, age-related macular degeneration, diabetic retinopathy, glaucoma, and retinopathy of prematurity. In addition, we discuss the early intervention strategies for these diseases. An outline is provided to identify potential intervention targets for further research. Early intervention for retinal diseases is necessary and urgent and may offer hope to improve patients' quality of life through functional vision.


Enhanced Pb Absorption by Hordeum vulgare L. and Helianthus annuus L. Plants Inoculated with an Arbuscular Mycorrhizal Fungi Consortium.
The effect of an arbuscular mycorrhizal fungi (AMF) consortium conformed by (Glomus intraradices, Glomus albidum, Glomus diaphanum, and Glomus claroideum) on plant growth and absorption of Pb, Fe, Na, Ca, and (32)P in barley (Hordeum vulgare L.) and sunflower (Helianthus annuus L.) plants was evaluated. AMF-plants and controls were grown in a substrate amended with powdered Pb slag at proportions of 0, 10, 20, and 30% v/v equivalent to total Pb contents of 117; 5,337; 13,659, and 19,913 mg Pb kg(-1) substrate, respectively. Mycorrhizal root colonization values were 70, 94, 98, and 90%, for barley and 91, 97, 95, and 97%, for sunflower. AMF inoculum had positive repercussions on plant development of both crops. Mycorrhizal barley absorbed more Pb (40.4 mg Pb kg(-1)) shoot dry weight than non-colonized controls (26.5 mg Pb kg(-1)) when treated with a high Pb slag dosage. This increase was higher in roots than shoots (650.0 and 511.5 mg Pb kg(-1) root dry weight, respectively). A similar pattern was found in sunflower. Plants with AMF absorbed equal or lower amounts of Fe, Na and Ca than controls. H. vulgare absorbed more total P (1.0%) than H. annuus (0.9%). The arbuscular mycorrizal consortium enhanced Pb extraction by plants.


Morphological and immunocytochemical identification of periacinar fibroblast-like cells derived from human pancreatic acini.
Fibroblast-like cells in the periacinar region may play an important role in periacinar fibrosis. In the present study, we isolated and cultured periacinar fibroblast-like cells (PFCs) derived from human pancreatic acini and examined the characteristics of human PFCs morphologically and immunocytochemically. Immunocytochemical study of human PFCs showed that they were positively stained with antibodies against type I collagen/procollagen, type III collagen/procollagen, fibronectin, prolyl hydroxylase beta sub-unit, type IV collagen, laminin, alpha-smooth muscle actin, vimentin, and nonmuscle myosin. Electron microscopic study showed that human PFCs contained a number of microfilaments, forming dense bodies in the cytoplasm. These results indicated that human PFCs possess characteristics of myofibroblasts. Expression of alpha-smooth muscle actin, a marker of the myofibroblast-like phenotype, was increased with time in culture and was enhanced by treatment with transforming growth factor (TGF)-beta 1. Collagen synthesis in human PFCs was stimulated by TGF-beta 1 and the proliferation of human PFCs was stimulated by platelet-derived growth factor. These findings suggest that PFCs from human pancreas seem to be involved in periacinar fibrosis.


Rad18 and Rnf8 facilitate homologous recombination by two distinct mechanisms, promoting Rad51 focus formation and suppressing the toxic effect of nonhomologous end joining.
The E2 ubiquitin conjugating enzyme Ubc13 and the E3 ubiquitin ligases Rad18 and Rnf8 promote homologous recombination (HR)-mediated double-strand break (DSB) repair by enhancing polymerization of the Rad51 recombinase at γ-ray-induced DSB sites. To analyze functional interactions between the three enzymes, we created RAD18(-/-), RNF8(-/-), RAD18(-/-)/RNF8(-/-) and UBC13(-/-)clones in chicken DT40 cells. To assess the capability of HR, we measured the cellular sensitivity to camptothecin (topoisomerase I poison) and olaparib (poly(ADP ribose)polymerase inhibitor) because these chemotherapeutic agents induce DSBs during DNA replication, which are repaired exclusively by HR. RAD18(-/-), RNF8(-/-) and RAD18(-/-)/RNF8(-/-) clones showed very similar levels of hypersensitivity, indicating that Rad18 and Rnf8 operate in the same pathway in the promotion of HR. Although these three mutants show less prominent defects in the formation of Rad51 foci than UBC13(-/-)cells, they are more sensitive to camptothecin and olaparib than UBC13(-/-)cells. Thus, Rad18 and Rnf8 promote HR-dependent repair in a manner distinct from Ubc13. Remarkably, deletion of Ku70, a protein essential for nonhomologous end joining (NHEJ) significantly restored tolerance of RAD18(-/-) and RNF8(-/-) cells to camptothecin and olaparib without affecting Rad51 focus formation. Thus, in cellular tolerance to the chemotherapeutic agents, the two enzymes collaboratively promote DSB repair by HR by suppressing the toxic effect of NHEJ on HR rather than enhancing Rad51 focus formation. In contrast, following exposure to γ-rays, RAD18(-/-), RNF8(-/-), RAD18(-/-)/RNF8(-/-) and UBC13(-/-)cells showed close correlation between cellular survival and Rad51 focus formation at DSB sites. In summary, the current study reveals that Rad18 and Rnf8 facilitate HR by two distinct mechanisms: suppression of the toxic effect of NHEJ on HR during DNA replication and the promotion of Rad51 focus formation at radiotherapy-induced DSB sites.


Neurodevelopment in seizure-prone and seizure-resistant rat strains: recognizing conflicts in management.
Cytoarchitectural alterations during central nervous system (CNS) development are believed to underlie aberrations in brain morphology that lead to epilepsy. We have recently reported marked reductions in hippocampal and white matter volumes along with relative ventriculomegaly in a rat strain bred to be seizure-prone (FAST) compared to a strain bred to be seizure-resistant (SLOW) (Gilby et al., 2002, American Epilepsy Society 56th Annual Meeting). This study was designed to investigate deviations in gene expression during late-phase embryogenesis within the brains of FAST and SLOW rats. In this way, we hoped to identify molecular mechanisms operating differentially during neurodevelopment that might ultimately create the observed differences in brain morphology and/or seizure susceptibility. Using Superarray technology, we compared the expression level of 112 genes, known to play a role in neurodevelopment, within whole brains of embryonic day 21 (E21) FAST and SLOW rats. Results revealed that while most genes investigated showed near equivalent expression levels, both Apolipoprotein E (APOE) and the beta2 subunit of the voltage-gated sodium channel (SCN2beta) were significantly underexpressed in brains of the seizure-prone embryos. Currently, these transcripts have no known interactions during embryogenesis; however, they have both been independently linked to seizure disposition and/or neurodevelopmental aberrations leading to epilepsy. Thus, alterations in the timing and/or degree of expression for APOE and SCN2beta may be important to developmental cascades that ultimately give rise to the differing brain morphologies, behaviors, and/or seizure vulnerabilities that characterize these strains.


Cross-sectional study of patients with type 2 diabetes in OR Tambo district, South Africa.
South Africa has pledged to the sustainable development goal of promoting good health and well-being to all residents. While this is laudable, paucity of reliable epidemiological data for different regions on diabetes and treatment outcomes may further widen the inequalities of access and quality of healthcare services across the country. This study examines the sociodemographic and clinical determinants of uncontrolled type 2 diabetes mellitus (T2DM) in individuals attending primary healthcare in OR Tambo district, South Africa. A cross-sectional analytical study. Primary healthcare setting in OR Tambo district, South Africa. Patients treated for T2DM for 1 or more years (n=327). Prevalence of uncontrolled T2DM. Determinants of uncontrolled T2DM (glycosylated haemoglobin (HbA1c) ≥7%). Out of the 327 participants, 274 had HbA1c≥7% (83.8%). Female sex (95% CI 1.3 to 4.2), overweight/obesity (95% CI 1.9 to 261.2), elevated low-density lipoprotein cholesterol (95% CI 4.4 to 23.8), sedentary habits (95% CI 7.2 to 61.3), lower monthly income (95% CI 1.3 to 6.5), longer duration of T2DM (95% CI 4.4 to 294.2) and diabetes information from non-health workers (95% CI 1.4 to 7.0) were the significant determinants of uncontrolled T2DM. There was a significant positive correlation of uncontrolled T2DM with increasing duration of T2DM, estimated glomerular filtration rate and body mass index. However, a significant negative correlation exists between monthly income and increasing HbA1c. We found a significantly high prevalence (83.8%) of uncontrolled T2DM among the patients, possibly attributable to overweight/obesity, sedentary living, lower income and lack of information on diabetes. Addressing these determinants will require re-engineering of primary healthcare in the district.


Polyamine Metabolism and Gene Methylation in Conjunction with One-Carbon Metabolism.
Recent investigations have revealed that changes in DNA methylation status play an important role in aging-associated pathologies and lifespan. The methylation of DNA is regulated by DNA methyltransferases (DNMT1, DNMT3a, and DNMT3b) in the presence of S-adenosylmethionine (SAM), which serves as a methyl group donor. Increased availability of SAM enhances DNMT activity, while its metabolites, S-adenosyl-l-homocysteine (SAH) and decarboxylated S-adenosylmethionine (dcSAM), act to inhibit DNMT activity. SAH, which is converted from SAM by adding a methyl group to cytosine residues in DNA, is an intermediate precursor of homocysteine. dcSAM, converted from SAM by the enzymatic activity of adenosylmethionine decarboxylase, provides an aminopropyl group to synthesize the polyamines spermine and spermidine. Increased homocysteine levels are a significant risk factor for the development of a wide range of conditions, including cardiovascular diseases. However, successful homocysteine-lowering treatment by vitamins (B6, B12, and folate) failed to improve these conditions. Long-term increased polyamine intake elevated blood spermine levels and inhibited aging-associated pathologies in mice and humans. Spermine reversed changes (increased dcSAM, decreased DNMT activity, aberrant DNA methylation, and proinflammatory status) induced by the inhibition of ornithine decarboxylase. The relation between polyamine metabolism, one-carbon metabolism, DNA methylation, and the biological mechanism of spermine-induced lifespan extension is discussed.


Rapid synthesis of core/shell ZnS:Mn/Si nanotetrapods by a catalyst-free thermal evaporation route.
We report the fabrication of a hybrid all semiconductor core/shell nanotetrapod structure consisting of crystalline ZnS:Mn core and amorphous Si shell for the first time. The nanostructures were produced via a catalyst-free rapid thermal evaporation technique. Core/shell nanotetrapods were formed in two steps: (i) formation of the crystalline ZnS:Mn tetrapods and (ii) simultaneous surface adsorption of the in situ formed Si vapor species providing the amorphous shell. Crystalline tetrapod formation was guided by the formation of cubic structured ZnS octahedrons with four active (111) polar growth planes, which served as the favored growth site for the four wurtzite structured legs of the tetrapods. Choice of chloride salt as the source of dopant ion was crucial for the in situ generation of Si vapor. At elevated temperature, chloride salt reacted with the sulfur vapor to produce S2Cl2 gas that etched the Si wafers, generating Si vapor. Suppression of the surface-state-related blue emission was observed in the core/shell structures that clearly supported the formation of a shell layer. Elimination of the surface states ensured efficient energy transfer to the dopant Mn ionic state, resulting in the strong orange emission via (4)T(1)-(6)A(1) electronic transition.


Donor-to-host transmitted Candida endophthalmitis after penetrating keratoplasty.
To report the first case of Candida albicans endophthalmitis following penetrating keratoplasty after warm preservation. Observational case report. We reviewed the patient's chart and the available literature on fungal endophthalmitis after keratoplasty. After keratoplasty, a 45-year-old man developed an endophthalmitis on the first postoperative day. The same day, results of the culture of the transportation medium were available and revealed Candida albicans. Despite therapy with topical and subtenon amphotericin B, there was no clinical improvement, and a regraft was performed 4 days after the initial corneal transplant. A best corrected visual acuity of 20/32 was achieved. The majority of reported cases of postkeratoplasty candidal endophthalmitis are associated with cold storage preservation and a poor prognosis of the affected eye. We describe a case of postkeratoplasty candidal endophthalmitis after organ-cultured preservation, with a final visual acuity above expectations. In our opinion, early diagnosis based on routine culturing of the transportation medium and early removal of the infected corneal graft when local antifungal therapy failed are important factors contributing to the good clinical outcome.