Supramolecular Hydrogel Formation in a Series of Self-Assembling Lipopeptides with Varying Lipid Chain Length.
The self-assembly in aqueous solution of three lipopeptides comprising a bioactive motif conjugated at the N terminus to dodecyl, tetradecyl or hexadecyl lipid chains has been examined. The bioactive motif is the peptide block YEALRVANEVTLN; a C-terminal fragment of the lumican proteoglycan. This study was motivated by our previous studies on the hexadecyl homologue C16-YEALRVANEVTLN, which showed aggregation into β-sheet structures above a critical aggregation concentration (cac), but most remarkably, we found that these aggregates were stable to dilution below the cac.1 Here we find that the C12- and C14-homologues also self-assemble above a cac into β-sheet nanotapes based on bilayer packing. The cac decreases with increasing lipopeptide hydrophobicity. Unexpectedly, the β-sheet secondary structure is present upon dilution and the aggregates are thermally stable. These results indicate that the dilution trapping of β-sheet secondary structure is not associated with lipid chain melting behavior. Instead, we associate it with pH-dependent favorable intermolecular electrostatic interactions. Investigation of the pH-dependence of aggregation led to the discovery of conditions for formation of lipopeptide hydrogels (initial sample preparation at pH 10 in NaOH solution, followed by reduction to pH ∼ 1 by addition of HCl). The lipopeptide hydrogels comprise networks of bilayer-based peptide nanotape bundles and to our knowledge this type of hydrogel is unprecedented. These hydrogels may have future applications based on processes such as encapsulation and release that involve fast switches between solution and hydrogel nanostructures.


Concurrent chemoradiotherapy with vinorelbine plus split-dose cisplatin may be an option in inoperable stage III non-small cell lung cancer: a single-center experience.
Concurrent chemoradiotherapy is the current standard treatment for inoperable stage III non-small cell lung cancer (NSCLC). In this study we aimed to investigate the efficacy and toxicity of CCRT with split dose of cisplatin (30 mg/m2) and vinorelbine (20 mg/m2) in patients with inoperable stage III NSCLC followed in our oncology clinic. Medical records of 97 patients with inoperable stage III NSCLC treated with concurrent chemoradiotherapy with cisplatin-vinorelbine were retrospectively analyzed. Cisplatin (30 mg/m2) and vinorelbine (20 mg/m2) were administered on days 1, 8, 22, and 29 during radiotherapy. Two cycles of consolidation chemotherapy were given. All patient data, including pathological, clinical, radiological, biochemical, and hematological data, were assessed retrospectively using our database system. Our study included 97 unresectable stage III NSCLC patients who were treated with CCRT. Median age was 58 years old (range 39-75) and 87 (89.7%) of the patients were men. ECOG performance score was 0-1 in 93 patients (95.9%). Squamous histology, the most common histology, was diagnosed in 46 patients (47.4%). Median follow-up time was 23.8 months. Median progression-free survival (PFS) and median overall survival time (OS) were 10.3 months and 17.8 months, respectively. Objective response rate and clinical benefit rate were 75.3% and 83.5%, respectively. Distant and local relapse rate were 57.1% and 42.9%, respectively. Hematological and non-hematological grade 3-4 toxicities were seen in 13 (13.4%) and 16 (16.5%) patients, respectively. Six (6.1%) patients died due to toxicity. The results of this study suggest that split-dose cisplatin may offer fewer grade III-IV toxicities without sacrificing efficacy and could be an option in patients with inoperable stage III NSCLC during CCRT. Similar to past studies, despite high response rate during CCRT, distant relapse is the major parameter that influences patient survival in long-term in NSCLC.


[Structural and normative problems in recording medical facts in a structured social security system].
Medical expertising in the German structured social security system suffers from the fact that uniform standards and conditions have been worked out so far only very inadequately. The on-target accuracy of medical expertises is also hampered by the fact that experts are not sufficiently aware of the targets set by the various security systems. Sociomedical knowledge is hardly incorporated in the expertises. Due to the general lack of criteria and proportions the expert becomes the personal fate of the person to be expertised. This could be remedied in several ways: by improving the concepts laid down in section 96 of the German Social Code Book 10 as well as by a greater standardisation of medical services and last but by no means least by including "expertising" in the curriculum of the study of medicine at universities.


[Effects of rifamdin on pharmacokinetics of dexamethasone].
The rabbits of same sex and approximate weight, were randomly divided into following two groups: a group given all rifamdin for 12 days before dexamethasone injection and a control group without RFD. After a single IV injection of dexamethasone sodium phosphate, the concentrations of dexamethasone in rabbit plasma taken at 5, 15, 30 min, and 1, 2, 4, 8 h were analysed by reversed phase HPLC-UV. Linear regression analysis was made by LnC(t)-t. The pharmacokinetic parameters of dexamethasone in rabbits were calculated by methods of residuals. The results of main parameters, i.e. K10, beta, T1/2 beta, cls and AUD0-infinity kg-1 showed that rifamdin apparently promotes metabolic clearance of dexamethasone in plasma.


V2-Specific Antibodies in HIV-1 Vaccine Research and Natural Infection: Controllers or Surrogate Markers.
Most human immunodeficiency virus (HIV) vaccine trials have lacked efficacy and empirical vaccine lead targets are scarce. Thus far, the only independent correlate of reduced risk of HIV-1 acquisition in humans is elevated levels of V2-specific antibodies identified in the modestly protective RV144 vaccine trial. Ten years after RV144, human and non-human primate vaccine studies have reassessed the potential contribution of V2-specific antibodies to vaccine efficacy. In addition, studies of natural HIV-1 infection in humans have provided insight into the development of V1V2-directed antibody responses and their impact on clinical parameters and disease progression. Functionally diverse anti-V2 monoclonal antibodies were isolated and their structurally distinct V2 epitope regions characterized. After RV144, a plethora of research studies were performed using different model systems, immunogens, protocols, and challenge viruses. These diverse studies failed to provide a clear picture regarding the contribution of V2 antibodies to vaccine efficacy. Here, we summarize the biological functions and clinical findings associated with V2-specific antibodies and discuss their impact on HIV vaccine research.


Acute respiratory distress syndrome during the third infusion of rituximab in a patient with follicular lymphoma.
We present the case of a 66-year-old man with follicular lymphoma who developed acute respiratory distress syndrome (ARDS) during a third infusion of rituximab. High fever, tachypnea, and progressive hypoxemia accompanied by massive bilateral pleural effusions appeared suddenly approximately 3 hours after the third infusion was started, although the 2 prior infusions of rituximab had produced only mild adverse effects. The patient was treated successfully with high-dose methylprednisolone and 3 days of mechanical ventilatory support. No evidence was obtained to indicate that the ARDS had been caused by either cytokine release or tumor lysis, and serum human antichimeric antibody was not detected. Although the cause of ARDS was not confirmed, our experience in this case suggested that an anaphylactic reaction induced by repeated infusion of rituximab was involved in the onset of pulmonary disease. Although ARDS is rarely seen with rituximab infusion, careful management is required for safe administration of the newly developed rituximab therapy. This management includes monitoring biological reactions not only during the initial infusion but also during subsequent infusions of the antibody.


The response of human anulus fibrosus cells to cyclic tensile strain is frequency-dependent and altered with disc degeneration.
Mechanical loads are important for homeostasis of the intervertebral disc (IVD) cell matrix, with physiologic and nonphysiologic loads leading to matrix anabolism and catabolism, respectively. Previous investigations into the effects of load on disc cells have predominantly used animal models, with the limited number of human studies focusing primarily on nucleus pulposus cells. The aim of this study was to examine the effect of cyclic tensile strain (CTS) on human anulus fibrosus (AF) cells to ascertain whether the response was frequency-dependent and to compare AF cells derived from nondegenerated and degenerated tissue samples. AF cells were isolated from nondegenerated and degenerated human IVDs, expanded in monolayer, and cyclically strained for 20 minutes, applying 10% strain at a frequency of 1.0 Hz or 0.33 Hz with the use of a Flexcell strain device. Total RNA was extracted from the cells at baseline (control) and at 1, 3, and 24 hours following application of CTS. Real-time quantitative polymerase chain reaction was used to analyze gene expression of matrix proteins (aggrecan, type I collagen, and type II collagen) and enzymes (matrix metalloproteinases [MMPs] 3, 9, 13, and ADAMTS-4). The expression of catabolic genes (MMP-3 and ADAMTS-4) in AF cells derived from nondegenerated tissue decreased in response to 1.0 Hz of CTS, whereas changing the frequency to 0.33 Hz resulted in a shift toward matrix catabolism. Application of 1.0 Hz of CTS reduced anabolic gene expression (aggrecan and type I collagen) in AF cells derived from degenerated tissue, with 0.33 Hz of CTS resulting in increased catabolic gene expression. The response of human AF cells to CTS is frequency-dependent and is altered by degeneration.


Nanoprobes visualizing gliomas by crossing the blood brain tumor barrier.
The difficulty in delineating the glioma margins in brain is a major obstacle for its completed resection, which leads to the disproportionately high recurrence and mortality. Besides the fast exertion rate, inadequate sensitivity and non-targeting specificity, the main reason leading to failure of small molecular probes to define gliomas is their incapability to efficiently cross the blood brain tumor barrier (BBTB). Nanoprobes (NPs) show promise to precisely delineate the geographically irregular tumor margins due to their tunable size/circulation lifetime that maximize their passive intratumoral accumulation and their convenience for surface modification that increases the BBTB transcytosis efficacy, imaging sensitivity and receptor targeting specificity. In this work, the characteristics of the BBTB are addressed from biological and physiological perspectives, strategies are presented to deliver NPs across the BBTB, recent developments of NPs are reviewed for glioma visualization and finally the difficulty and promise for clinical translation of NPs are described. Overall, NPs hold great potential for glioma imaging and treatment by pre-surgically delineating tumor margins and intra-operatively guiding tumor excision.


Neurologic aspects of mitral valve prolapse.
Mitral valve prolapse (MVP), the most frequently encountered valvular condition in the population, has been reported in an increasing variety of neurologic, muscular, and psychiatric disorders during the last twelve years. Extensive review of reports indicates this has resulted from observations of either (1) inordinate incidence of MVP in well-defined neurologic entities or (2) development of neurologic or ophthalmologic complications attributed to MVP. In the review presented, basis is found for categorizing MVP by its association with (1) well-defined, genetically determined neurologic disorders; (2) disorders characterized by structural abnormalities, many genetically determined, or inflammatory processes of connective tissues; (3) "mechanical" prolapse resulting from disproportion of mitral valve annulus and left ventricular size, which is, at times, reversible; and (4) a generally asymptomatic state that, at times, is associated with ischemic, thrombotic, embolic, and infectious disorders of the brain and eye. The paradox between the large number of persons with MVP in the general population who remain healthy and a subpopulation of patients with complications of MVP (eg, stroke) or other entities has been identified. A second paradox is found between the well-known increased incidence of MVP, especially in young patients with stroke, and the apparent rarity of stroke among patients with both common (eg, migraine) and unusual (eg, myotonic dystrophy) neurologic entities in which an extraordinary high prevalence of MVP is known to exist.


Treatment of chronic hepatitis C in patients with HIV/HCV coinfection.
Hepatitis C virus (HCV) infection is one of the most frequent causes of comorbidity and mortality in the human immunodeficiency virus (HIV) population, and liver-related mortality is now the second highest cause of death in HIV-positive patients, so HCV infection should be countered with adequate antiviral therapy. In 2011 began the era of directly acting antivirals (DAAs) and the HCV NS3/4A protease inhibitors telaprevir and boceprevir were approved to treat HCV-genotype-1 infection, each one in combination with pegylated interferon alfa (Peg-IFN) + ribavirin (RBV). The addition of the first generation DAAs, strongly improved the efficacy of antiviral therapy in patients with HCV-genotype 1, both for the HCV-monoinfected and HIV/HCV coinfected, and the poor response to Peg-IFN + RBV in HCV/HIV coinfection was enhanced. These treatments showed higher rates of sustained virological response than Peg-IFN + RBV but reduced tolerability and adherence due to the high pill burden and the several pharmacokinetic interactions between HCV NS3/4A protease inhibitors and antiretroviral drugs. Then in 2013 a new wave of DAAs arrived, characterized by high efficacy, good tolerability, a low pill burden and shortened treatment duration. The second and third generation DAAs also comprised IFN-free regimens, which in small recent trials on HIV-positive patients have shown comforting preliminary results in terms of efficacy, tolerability and adherence.


Improving the realism of deterministic multi-strain models: implications for modelling influenza A.
Understanding the interaction between epidemiological and evolutionary dynamics for antigenically variable pathogens remains a challenge, particularly if analytical insight is wanted. In particular, while a variety of relatively complex simulation models have reproduced the evolutionary dynamics of influenza, simpler models have given less satisfying descriptions of the patterns seen in data. Here, we develop a set of relatively simple deterministic models of the transmission dynamics of multi-strain pathogens which give increased biological realism compared with past work. We allow the intensity of cross-immunity generated against one strain given exposure to a different strain to depend on the extent of genetic difference between the strains. We show that the dynamics of this model are determined by the interplay of parameters defining the cross-immune response function and can include fully symmetric equilibria, self-organized strain structures, regular periodic and chaotic regimes. We then extend the model by incorporating transient strain-transcending immunity that acts as a density-dependent mechanism to lower overall infection prevalence and thus pathogen diversity. We conclude that while some aspects of the evolution of influenza can be captured by deterministic models, overall, the description obtainable using a purely deterministic framework is unsatisfactory, implying that stochasticity of strain generation (via mutation) and extinction needs to be captured to appropriately capture influenza dynamics.


Interaction between non-classical beta-lactam compounds and the Zn2+-containing G and serine R61 and R39 D-alanyl-D-alanine peptidases.
Streptomyces albus G secretes a Zn2+-containing D-alanyl-D-alanine peptidase. Streptomyces R61 and Actinomadura R39 secrete D-alanyl-D-alanine-cleaving serine peptidases. The effect of non-classical beta-lactam antibiotics on these three model enzymes has been studied. Mecillinam, cefoxitin, quinacillin, quinacillin sulphone, clavulanate and N-formimidoylthienamycin have no effect on the Zn2+-containing enzyme. 6-Amino-penicillanic acid slowly inactivates this enzyme and 7-aminocephalosporanic acid behaves as a reversible inhibitor. Cefoxitin and N-formimidoylthienamycin are potent anti-bacterial agents; they effectively inactivate the serine R39 enzyme and, to a lesser extent, the serine R61 enzyme. All the other beta-lactam compounds tested, including mecillinam, are slow inactivators of these serine enzymes. The intermediates formed between 6-aminopenicillanic acid and the R61 and R39 enzymes are long- and short-lived respectively, whereas those formed between 7-aminocephalosporanic acid and the same R61 and R39 enzymes are short- and long-lived respectively. Breakdown of the short-lived intermediates thus obtained gives rise to several ninhydrin-positive degradation products. The intermediates formed between clavulanate and the serine enzymes are long-lived. With the R39 enzyme, the inactivated complex formed in a first step undergoes subsequent monomolecular rearrangement to give rise to a second species exhibiting a high absorbance at 273 nm.


Ileocecal endometriosis and a diagnosis dilemma: a case report and literature review.
Bowel endometriosis affects between 3.8% and 37% of women with endometriosis. The evaluation of symptoms and clinical examination are inadequate for an accurate diagnosis of intestinal endometriosis. We describe the case of a 41-year-old woman who presented to our hospital because of six months of recurrent abdominal pain, vomiting and diarrhea, without previous history of bowel disease. Physical examination revealed a palpable 3 cm × 5 cm mass in the right lower quadrant abdomen. Laboratory tests showed slightly elevated levels of CA19-9 and CA125. Small bowel computer tomography scanning revealed an ileocecal mass with bowel wall thickening and luminal narrowing. Small bowel endoscopy identified a deep longitudinal ulcer and mucosal edema in the distal ileum. All these findings supported the diagnosis of Crohn's disease. The patient underwent a laparotomy, which identified a 5 cm × 5 cm ileocecal mass with severe mucosal edema and luminal stricture in the distal ileum. Histopathological examination confirmed a diagnosis of ileocecal endometriosis without other areas involved. After one-year follow-up, there was no recurrence of the symptoms.


Donor-recipient gender difference affects severity of dry eye after hematopoietic stem cell transplantation.
To determine whether the incidence rate and severity of dry eye after hematopoietic stem cell transplantation varies with donor vs recipient gender. We limited this study to patients received bone marrow transplantation (BMT). In all, 172 patients received BMT at Keio University School of Medicine between January 2000 and May 2007. Of them, 136 recipients who survived at least 70 days were studied prospectively. We classified the 136 patients according to the gender of the donor and the recipient (group I: female to female; group II: male to male; group III: male to female; group IV: female to male). The incidence and severity of chronic graft-vs-host disease-associated dry eye were determined for each group. The donor gender was masked when we assessed dry eye and calculate the incidence. The incidence of dry eye was 47.4% for group I, 37.5% for group II, 58.6% for group III, and 42.9% for group IV. The percentage of patients with severe dry eye was 44.4, 50.0, 35.3, and 77.8% respectively. There was a significant difference between the percent severe dry eye/total dry eye incidences in groups III and IV (P=0.0375) (odds ratio, 7.6; 95% confidence interval, 1.00-101.01). Close attention must be paid to the development of dry eye in cases of female to male BMTs, because the ratio of severe/total dry eye is more common in cases of female to male BMTs than in other gender combination.


[The "wake-up correction" for preventing spinal cord injury in scoliosis surgery].
To observe the effects of "wake-up correction" technique for preventing iatrogenic spinal cord injury in scoliosis surgery. Twenty-one patients who had scoliosis with Cobb's angle 92 degrees - 145 degrees received operation of pedicle screw insertion in all or important vertebral bodies, release of stiff segments, decompression and osteotomy. All the patients were trained how to wake up before anesthesia. Maintenance of anesthesia was achieved with infusion of propofol at target-controlled concentration 3-4 mg/L and remifentanil at 0.15 microg/(kg.min). Fresh gas 2 L/min of N(2)O:O(2) 1:1 was inhaled during mechanical ventilation. Wake-up methods:the muscle relaxant was stopped injection 30 min before wake-up, decreasing propofol's target-controlled concentration to 1-2 mg/L and remifentanil to 0.05 - 0.10 microg/(kg x min). Once the spontaneous respiration returned, woke up the patients and asked them move both toes following our orders (the first wake-up). Then patients inhaled 6% sevoflurane in fresh gas 6 L/min (N(2)O:O(2) 1:1). When the end-tidal anesthetic gas concentration was arrived 1.3 - 1.5 MAC, all of the anesthetics were stopped. The correction operation was completed and the patient was woke up again (the second wake-up). Recorded data included time used to wake up, directive action returning time, whether the patient had memory of wake-up during operation when following up. All patients woke up with satisfaction. The time taken the first wake-up was (10.3 + or - 4.5) min, and for the second was (4.3 + or - 2.3) min. There were two patients who had slightly agitation during correction. There was no one who had neurological injury. There was no memory of wake-up and no pain in all patients during operation. Cobb' angle was corrected to 22 degrees - 38 degrees (average 29 degrees ), and the correction rate was 74%. The "wake-up correction" is effective and satisfactory by detecting the cord function in time.


Increased expression of the adult stem cell marker Musashi-1 in endometriosis and endometrial carcinoma.
Adult stem cells are thought to be responsible for the high regenerative capacity of the human endometrium, and have been implicated in the pathology of endometriosis and endometrial carcinoma. The RNA-binding protein Musashi-1 is associated with maintenance and asymmetric cell division of neural and epithelial progenitor cells. We investigated expression and localization of Musashi-1 in endometrial, endometriotic and endometrial carcinoma tissue specimens of 46 patients. qPCR revealed significantly increased Musashi-1 mRNA expression in the endometrium compared to the myometrium. Musashi-1 protein expression presented as nuclear or cytoplasmic immunohistochemical staining of single cells in endometrial glands, and of single cells and cell groups in the endometrial stroma. Immunofluorescence microscopy revealed colocalization of Musashi-1 with its molecular target Notch-1 and telomerase. In proliferative endometrium, the proportion of Musashi-1-positive cells in the basalis layer was significantly increased 1.5-fold in the stroma, and three-fold in endometrial glands compared to the functionalis. The number of Musashi-1 expressing cell groups was significantly increased (four-fold) in proliferative compared to secretory endometrium. Musashi-1 expressing stromal cell and cell group numbers were significantly increased (five-fold) in both endometriotic and endometrial carcinoma tissue compared to secretory endometrium. A weak to moderate, diffuse cytoplasmic glandular staining was observed in 50% of the endometriosis cases and in 75% of the endometrioid carcinomas compared to complete absence in normal endometrial samples. Our results emphasize the role of Musashi-1-expressing endometrial progenitor cells in proliferating endometrium, endometriosis and endometrioid uterine carcinoma, and support the concept of a stem cell origin of endometriosis and endometrial carcinoma.


Effect of age on leucine-induced insulin secretion by the beta-cell.
We have previously shown that aging is associated with a marked decrease in glucose-stimulated insulin release by the beta-cell. To determine whether this age-related defect occurs with other insulin secretagogues, we have investigated leucine-stimulated insulin release. Islets of Langerhans were isolated from 2- and 12-month-old rats, and incubated with 5-20 mM 5-20 mM leucine or with 16.7 mM glucose. Islets from 12-month-old rats showed a decline in rate of leucine-induced secretion as compared to islets of 2-month-old donors (i.e., mean (+/- SEM) insulin secretion at 20 mM leucine was 0.79 (+/- 0.06) and 1.17 (+/- 0.09) microU/min/islet), respectively for 12- and 2-month-old rats. beta-cell number is increased in islets from 12-month-old donors, and when this increase is taken into account, the average beta-cell from 12-month-old donors secretes only one-half the rate of beta-cells from 2-month-old donors. These findings are comparable to those seen after glucose-stimulation, and emphasize the potential global nature of the age-related defect in beta-cell function.


Novel Extracellular Electron Transfer Channels in a Gram-Positive Thermophilic Bacterium.
Biogenic transformation of Fe minerals, associated with extracellular electron transfer (EET), allows microorganisms to exploit high-potential refractory electron acceptors for energy generation. EET-capable thermophiles are dominated by hyperthermophilic archaea and Gram-positive bacteria. Information on their EET pathways is sparse. Here, we describe EET channels in the thermophilic Gram-positive bacterium Carboxydothermus ferrireducens that drive exoelectrogenesis and rapid conversion of amorphous mineral ferrihydrite to large magnetite crystals. Microscopic studies indicated biocontrolled formation of unusual formicary-like ultrastructure of the magnetite crystals and revealed active colonization of anodes in bioelectrochemical systems (BESs) by C. ferrireducens. The internal structure of micron-scale biogenic magnetite crystals is reported for the first time. Genome analysis and expression profiling revealed three constitutive c-type multiheme cytochromes involved in electron exchange with ferrihydrite or an anode, sharing insignificant homology with previously described EET-related cytochromes thus representing novel determinants of EET. Our studies identify these cytochromes as extracellular and reveal potentially novel mechanisms of cell-to-mineral interactions in thermal environments.


Electrochemical oxidation of polyethylene glycol in electroplating solution using paraffin composite copper hexacyanoferrate modified (PCCHM) anode.
Electrochemical oxidation of polyethylene glycol (PEG) in an acidic (pH 0.18 to 0.42) and high ionic strength electroplating solution was investigated. The electroplating solution is a major source of wastewater in the printing wiring board industry. A paraffin composite copper hexacyanoferrate modified (PCCHM) electrode was used as the anode and a bare graphite electrode was used as the cathode. The changes in PEG and total organic carbon (TOC) concentrations during the course of the reaction were monitored. The efficiency of the PCCHM anode was compared with bare graphite anode and it was found that the former showed significant electrocatalytic property for PEG and TOC removal. Chlorides present in the solution were found to contribute significantly in the overall organic removal process. Short chain organic compounds like acetic acid, oxalic acid, formic acid and ethylene glycol formed during electrolysis were identified by HPLC method. Anode surface area and applied current density were found to influence the electro-oxidation process, in which the former was found to be dominating. Investigations of the kinetics for the present electrochemical reaction suggested that the two stage first-order kinetic model provides a much better representation of the overall mechanism of the process if compared to the generalized kinetic model.


The supraclavicular artery island flap (SCAIF) in head and neck reconstruction: an Italian multi-institutional experience.
The supraclavicular artery island flap (SCAIF) is a thin and pliable pedicled flap that is easy and quick to harvest. Thanks to its particular features and high reliability, it is best indicated for the elderly or most fragile patients. SCAIF is very versatile, as it can be used for reconstruction of oral cavity, oropharynx, hypopharynx, facial and cervical skin and tracheostomal defects. We began using this flap in four Italian tertiary referral centres, with several indications, both as first treatment and as salvage surgery. The aim of the study was to demonstrate the easy reproducibility of the flap among four different centres. A series of 28 patients underwent head and neck reconstructions with SCAIF with no recorded complications during flap harvesting. After the very first cases, harvesting time was approximately 45 minutes; 24 patients had successful flap integration at the recipient site, while the remaining 4 suffered from partial flap necrosis, two of whom needed revision surgery. Other minor complications were reported at the recipient site, always at the most distal and most delicate portion of the flap. Donor site was always closed primarily, with only three cases of partial suture dehiscence. We only selected the most fragile patients for SCAIF reconstruction, such as the elderly or those with one or more comorbidities; for this reason, we reported some serious systemic complications and one intraoperative death. SCAIF is an easy reproducible flap, with multiple possible indications. Its use as an alternative to free flaps in the head and neck region is nowadays under discussion. Its use should be encouraged among head and neck surgeons thanks to its various advantages.


Turkish nurses' perceptions of professional values.
This study aimed to examine the professional values of nurses in Turkey. This descriptive cross-sectional study was conducted with 310 nurses employed at public, university, and private hospitals between May-June 2015. Data were collected using a data collection form and the Nurses' Professional Values Scale-Revised, and they were analysed using descriptive statistics. Associations between socio-demographic variables and mean scores were analysed using the Kruskal-Wallis test. Nurses had higher scores on perception of professional values, and education level and years of professional experience were associated with higher scores. Results indicated that trust and justice were the most prominent professional values, whereas altruism and obedience were less favoured values. Overall, results indicated that participants' had a strong professional value orientation, and education level and professional experience influenced nurses' scores on professional values. Nurses' professional values reflect their understanding of how care should be provided, which health care policy makers and nurse managers who make decisions on providing more humanistic health care should consider. Further studies using the Nurses' Professional Values Scale-Revised, and other reliable and culture-specific instruments are recommended.


Evoked responses in the diagnosis of thoracic outlet syndrome.
The lack of an objective method for diagnosing thoracic outlet syndrome and monitoring the results of treatment has prevented a clear understanding of its natural history and the indications for surgery. Although one can detect vascular compression, the majority of patients have symptoms that are primarily neurogenic; and neither electromyograms nor studies of nerve conduction velocity has proved consistently helpful in their evaluation. We have studied evoked responses in 22 patients and believe that this technique allows selection of patients with significant neural compression for operative treatment. In this procedure, a bipolar stimulating electrode is placed on the median and ulnar nerves at the wrist; and bipolar recording is performed from active electrodes placed at Erb's point, over the spines of C6 and C2, and over the contralateral parietal scalp, all referenced to a midfrontal electrode. A minicomputer temporally summates the low-amplitude potentials elicited by repetitive electrical stimulation to increase the signal to noise ratio and therefore distinguish the potentials of interest from the background bioelectric activity. Normative values have been determined, allowing detection of changes in conduction of the electrical activity that occur between the sites of stimulation and the sites of recording. Of 19 new patients, 13 had abnormal evoked responses. Nine of these underwent surgical treatment; eight obtained good or excellent results. Abnormalities in evoked responses disappeared after operation in seven of the eight in whom it was measured. Four patients with abnormal responses but no surgery are being evaluated. Two of three long-term patients with recurrent symptoms had abnormal evoked responses that changed after treatment. Longer follow-up is needed to determine if this method is helpful in selecting patients for operative treatment or in monitoring its results.


Development of a unified oil droplet size distribution model with application to surface breaking waves and subsea blowout releases considering dispersant effects.
An oil droplet size model was developed for a variety of turbulent conditions based on non-dimensional analysis of disruptive and restorative forces, which is applicable to oil droplet formation under both surface breaking-wave and subsurface-blowout conditions, with or without dispersant application. This new model was calibrated and successfully validated with droplet size data obtained from controlled laboratory studies of dispersant-treated and non-treated oil in subsea dispersant tank tests and field surveys, including the Deep Spill experimental release and the Deepwater Horizon blowout oil spill. This model is an advancement over prior models, as it explicitly addresses the effects of the dispersed phase viscosity, resulting from dispersant application and constrains the maximum stable droplet size based on Rayleigh-Taylor instability that is invoked for a release from a large aperture.


Experimental validation of Ankrd17 and Anapc10, two novel meiotic genes predicted by computational models in mice.
Prophase is a critical stage of meiosis, during which recombination-the landmark event of meiosis-exchanges information between homologous chromosomes. The intractability of mammalian gonads has limited our knowledge on genes or interactions between genes during this key stage. Microarray profiling of gonads in both sexes has generated genome-scale information. However, the asynchronous development of germ cells and the mixed germ/somatic cell population complicate the use of this resource. To elucidate functional networks of meiotic prophase, we have integrated global gene expression with other genome-scale datasets either within or across species. Our computational approaches provide a comprehensive understanding of interactions between genes and can prioritize candidates for targeted experiments. Here, we examined two novel prophase genes predicted by computational models: Ankrd17 and Anapc10. Their expression and localization were characterized in the developing mouse testis using in situ hybridization and immunofluorescence. We found ANKRD17 expression was predominantly restricted to pachytene spermatocytes and round spermatids. ANKRD17 was diffusely distributed throughout the nucleus of pachytene cells but excluded from the XY body and other heterochromatic regions. ANAPC10 was mainly expressed in the cytoplasm of spermatogonia and leptotene and pachytene spermatocytes. These experiments support our computational predictions of Ankrd17 and Anapc10 as potential prophase genes. More importantly, they serve as a proof of concept of our integrative computational and experimental approach, which has delivered a larger candidate gene set to the broader reproductive community.


The role of phase synchronisation between low frequency amplitude modulations in child phonology and morphology speech tasks.
Recent models of the neural encoding of speech suggest a core role for amplitude modulation (AM) structure, particularly regarding AM phase alignment. Accordingly, speech tasks that measure linguistic development in children may exhibit systematic properties regarding AM structure. Here, the acoustic structure of spoken items in child phonological and morphological tasks, phoneme deletion and plural elicitation, was investigated. The phase synchronisation index (PSI), reflecting the degree of phase alignment between pairs of AMs, was computed for 3 AM bands (delta, theta, beta/low gamma; 0.9-2.5 Hz, 2.5-12 Hz, 12-40 Hz, respectively), for five spectral bands covering 100-7250 Hz. For phoneme deletion, data from 94 child participants with and without dyslexia was used to relate AM structure to behavioural performance. Results revealed that a significant change in magnitude of the phase synchronisation index (ΔPSI) of slower AMs (delta-theta) systematically accompanied both phoneme deletion and plural elicitation. Further, children with dyslexia made more linguistic errors as the delta-theta ΔPSI increased. Accordingly, ΔPSI between slower temporal modulations in the speech signal systematically distinguished test items from accurate responses and predicted task performance. This may suggest that sensitivity to slower AM information in speech is a core aspect of phonological and morphological development.


Definition of Success after Surgery for Female Stress Incontinence or Voiding Dysfunction: An Attempt at Standardization.
There is currently no standardized definition of success for surgery for stress urinary incontinence (SUI) and voiding dysfunction (VD) in women. To review the use of outcome measures (OMs) and definitions of success in the literature on SUI and VD surgery in women in an attempt to provide recommendations for future publications. A PubMed search of all English language full-text articles on SUI and VD surgery in women published between 2010 and 2015 was performed. A list of randomized trials and prospective and retrospective studies was obtained. Specific objective and subjective OMs used to define success were reviewed. Some 95 articles met the inclusion criteria for SUI surgery outcomes. Most trials reported outcomes at 12 mo after surgery. The majority (n=48) reported their primary outcomes using both objective and subjective success measures, 24 defined success using subjective OMs alone, and 23 using objective OMs alone. The OMs most frequently used for objective success were a negative cough stress test (CST), a negative pad test, and the absence of retreatment for SUI. The definition of subjective success most often involved questionnaires. The questionnaires most frequently used were Patient Global Impression of Improvement (PGI-I), Urinary Distress Inventory (UDI)/UDI-6, International Consultation on Incontinence Questionnaire Short Form (ICIQ-SF) and Medical Epidemiologic and Social Aspects of Aging (MESA). Only 11 studies on OMs used for VD surgery were published between 2010 and 2015. The two most common criteria used for success were measurement of postvoid residual urine (PVR) and subjective resolution of VD symptoms. There is great heterogeneity in the definition of success used after surgery for SUI or VD in women. For SUI surgery, we recommend use of the CST and a 1-h pad test for the definition of objective success, and of the UDI/UDI-6, Incontinence Impact Questionnaire (IIQ), King's Health Questionnaire (KHQ), ICIQ-SF, or PGI-I questionnaire for subjective success. For VD surgery, cure should include measurement of PVR and self-reported resolution of VD symptoms. We looked at the definition of success used for surgery for stress urinary incontinence (SUI) and voiding dysfunction (VD) in women. We found that there is great heterogeneity among studies, making study comparison extremely difficult. According to the outcome measures used most frequently, we make recommendations regarding the definition of cure for SUI and VD in women to be used in future publications.


NanoMonitor: a miniature electronic biosensor for glycan biomarker detection.
The goal of our research is to develop an ultrasensitive diagnostic platform called 'NanoMonitor' to enable rapid label-free analysis of a highly promising class of biomarkers called glycans (oligosaccharide chains attached to proteins) with high sensitivity and selectivity. The glycosylation of fetuin - a serum protein - and extracts from a human pancreatic cancer line was analyzed to demonstrate the capabilities of the NanoMonitor. The NanoMonitor device consists of a silicon chip with an array of gold electrodes forming multiple sensor sites and works on the principle of electrochemical impedance spectroscopy. Each sensor site is overlaid with a nanoporous alumina membrane that forms a high density of nanowells on top of each electrode. Lectins (proteins that bind to and recognize specific glycan structures) are conjugated to the surface of the electrode. When specific glycans from a test sample bind to lectins at the base of each nanowell, a perturbation of electrical double-layer occurs, which results in a change in the impedance. Using the lectins Sambucs nigra agglutinin (SNA) and Maackia amurensis agglutinin (MAA), subtle variations to the glycan chains of fetuin were investigated. Protein extracts from BXPC-3, a cultured human pancreatic cancer cell line were also analyzed for binding to SNA and MAA lectins. The performance of the NanoMonitor was compared to a conventional laboratory technique: lectin-based enzyme linked immunosorbent assay (ELISA). The NanoMonitor was used to identify glycoform variants of fetuin and global differences in glycosylation of protein extracts from cultured human pancreatic cancerous versus normal cells. While results from NanoMonitor correlate very well with results from lectin-based ELISA, the NanoMonitor is rapid, completely label free, requires just 10 microl of sample, is approximately five orders of magnitude more sensitive and highly selective over a broad dynamic range of glycoprotein concentrations. Based on its performance metrics, the NanoMonitor has excellent potential for development as a point-of-care handheld electronic biosensor device for routine detection of glycan biomarkers from clinical samples.


Brain blood flow pulse analysis may help to recognize individuals who suffer from hydrocephalus.
Normal pressure hydrocephalus (NPH) is often associated with altered cerebral blood flow. Recent research with the use of the ultrasonic method suggests specific changes in the shape of cardiac-related cerebral arterial blood volume (CaBV) pulses in NPH patients. Our study aims to provide a quantitative analysis of the shape of CaBV pulses, estimated based on transcranial Doppler ultrasonography (TCD) in NPH patients and healthy individuals. The CaBV pulses were estimated using TCD cerebral blood flow velocity signals recorded from probable NPH adults and age-matched healthy individuals at rest. The shape of the CaBV pulses was compared to a triangular shape with 27 similarity parameters calculated for every reliable CaBV pulse and compared between patients and volunteers. The diagnostic accuracy of the most prominent parameter for NPH classification was evaluated using the area under the receiver operating characteristic curve (AUC). The similarity parameters were calculated for 31 probable NPH patients (age: 59 years (IQR: 47, 67 years), 14 females) and 23 healthy volunteers (age: 54 years (IQR: 43, 61 years), 18 females). Eighteen of 27 parameters were different between healthy individuals and NPH patients (p < 0.05). The most prominent differences were found for the ascending slope of the CaBV pulse with the AUC equal to 0.87 (95% confidence interval: 0.77, 0.97, p < 0.001). The findings suggest that in NPH, the ascending slope of the CaBV pulse had a slower rise, was more like a straight line, and generally was less convex than in volunteers. Prospective research is required to verify the clinical utility of these findings.


Holistic self care: strategies for initiating a personal assessment.
To be fully present for clients, occupational health nurses must assume responsibility for meeting their own self care needs. To promote holistic health care, occupational health nurses must assess personal values, priorities, and responsibilities. This can be accomplished by completing a personal assessment focusing on current use of holistic modalities. To implement a plan for holistic self care, nurses can write goals, set intentions, be open to holistic modalities, begin with small changes, recognize feelings, pay attention to breathing and self talk, simplify their lives, build support systems, and apply self care at work.


Membrane interactions of non-membrane targeting antibiotics: The case of aminoglycosides, macrolides, and fluoroquinolones.
Numerous antibiotics are known to target intracellular pathways, such as protein translation or DNA replication. Membrane transporters typically regulate drug uptake; however, little is known about direct interactions between these antibiotics and the cell membranes. Here, we studied the interactions between different aminoglycosides (kanamycin, gentamicin, streptomycin, neomycin), macrolides (azithromycin, clarithromycin, erythromycin), and fluoroquinolones (ciprofloxacin, levofloxacin) with bacterial membrane mimics to determine drug partitioning and potential drug-induced membrane disruption. The antibiotics' exact location in the bilayers and their effect on membrane thickness and fluidity were determined from high-resolution X-ray diffraction. While the antibiotics did not change membrane thickness at low (1:100 drug/lipid) or high (1:10 drug/lipid) concentrations, they were found to increase membrane disorder in a dose-dependent manner. However, no membrane damage, such as membrane disruption or pore formation, was observed for any of the antibiotics. To note, all antibiotics partitioned into the lipid head groups, while macrolides and fluoroquinolones also partitioned into the bilayer core. The results suggest that the bacterial membrane is relatively inert in the direct mechanisms of actions of these antibiotics.


Changes in neutrophil surface protein composition accompany phagocytosis.
Phagocytosis is a critical host defense mechanism of neutrophils. In this study, membrane protein changes occurring during phagocytosis were studied in human neutrophils using surface radiolabeling before or after phagocytosis of various target particles. Cells were labeled at the cell surface using lactoperoxidase-catalyzed iodination or neuraminidase-galactose oxidase-NaB3H4, galactose oxidase-NaB3H4, or periodate-NaB3H4 techniques. Such studies are complicated by the fact that these techniques identify many surface proteins on the phagocyte, and labeling after phagocytosis occurs often results in radiolabeling proteins of the target particle, thus making changes in cell-surface proteins more difficult to detect. Immunoprecipitation with monoclonal antibody AHN-1, which reacts with a carbohydrate present on several human neutrophil surface proteins and inhibits phagocytosis, eliminated interference caused by radiolabeled proteins of the target particle and simplified analysis by restricting the study to a limited number of proteins. AHN-1 immunoprecipitated less radiolabeled protein from neutrophils labeled after phagocytosis of particles opsonized with IgG or complement than from cells labeled before phagocytosis. Isolation of phagocytic vesicles containing opsonized emulsified paraffin oil demonstrated that three proteins of mol wt 105,000, 140,000, and 170,000 recognized by AHN-1 were internalized in the phagocytic vesicle during phagocytosis.


Anatomy of the normal left atrial appendage: a quantitative study of age-related changes in 500 autopsy hearts: implications for echocardiographic examination.
Transesophageal echocardiography (TEE) is the diagnostic modality of choice for visualizing the left atrial appendage (LAA). This study defined the morphology of the LAA in normal autopsy specimen hearts and considered the implications of these findings for TEE studies. Five hundred normal autopsy hearts were reviewed (25 male and 25 female subjects from each decade for 10 decades). LAA length, width, orifice size, and number of lobes were recorded. Number of lobes was compared between sexes with the rank sum test and regressed against age. Mean length, width, and orifice size increased with age, up to age 20 years, in both sexes. Rates were significantly different between sexes for LAA size (P=.011) and width (P=.006). After age 20, statistically significant but clinically insignificant age-related changes were observed. Fifty-four percent of LAAs had two lobes (range, 1 to 4), with no age or sex differences. Lobes exist in different planes of the heart. Most pectinate muscles were > or = 1 mm in width. Pectinate muscles < 1 mm (2.6% of cases) were seen in only the first and last decades. Age- and sex-related differences in LAA dimensions exist. These differences and the existence of multilobed appendages are important in the accurate TEE evaluation of LAA. Because lobes exist in different planes, imaging must be done in multiple planes to visualize the entire LAA.


Eag1, Eag2, and SK3 potassium channel expression in the rat hippocampus after global transient brain ischemia.
Transient global brain ischemia causes delayed neuronal death in the hippocampus that has been associated with impairments in hippocampus-dependent brain function, such as mood, learning, and memory. We investigated the expression of voltage-dependent Kcnh1 and Kcnh5, ether à go-go-related Eag1 and Eag2 (K(V) 10.1 and K(V) 10.2), and small-conductance calcium-activated SK3 (K(Ca) 2.3, Kcnn3) K(+) channels in the hippocampus in rats after transient global brain ischemia. We tested whether the expression of these channels is associated with behavioral changes by evaluating the animals in the elevated plus maze and step-down inhibitory avoidance task. Seven or tweny-eight days after transient global brain ischemia, one group of rats had the hippocampus bilaterally dissected, and mRNA levels were determined. Seven days after transient global brain ischemia, the rats exhibited a decrease in anxiety-like behavior and memory impairments. An increase in anxiety levels was detected 28 days after ischemia. Eag2 mRNA downregulation was observed in the hippocampus 7 days after transient global brain ischemia, whereas Eag1 and SK3 mRNA expression remained unaltered. This is the first experimental evidence that transient global brain ischemia temporarily alters Eag2. The number of intact-appearing pyramidal neurons was substantially decreased in CA1 and statistically measurable in CA2, CA3, and CA4 hippocampal subfields compared with sham control animals 7 or 28 days after ischemia. mRNA expression in the rat hippocampus. The present results provide further information for the characterization of the physiological role of Eag2 channels in the central nervous system.


Optimal medical management before lower extremity bypass for claudication in the veteran population.
Optimizing medical management through glucose control, smoking cessation, and drug therapy (ie, antiplatelet and statin agents) is recommended as first-line therapy for patients with claudication. The aims of this study were to determine how frequently veterans with claudication received optimal medical management (OMM) before undergoing elective open lower extremity bypass procedures nationwide and whether preoperative OMM was associated with improved surgical outcomes. We reviewed all patients within the Veterans Affairs (VA) Surgical Quality Improvement Program database who underwent elective open lower extremity bypass procedures for claudication at nationwide VA medical centers from 2005 until 2015. We defined OMM as a claudicant's having documentation of receiving all of the following within 12 months before surgery: prescriptions for antiplatelet, statin, and smoking cessation therapy (if a smoker) and monitoring of hemoglobin A1c (if diabetic). Outcome measures included occurrence of any 30-day VA Surgical Quality Improvement Program complication, amputation-free survival, and 30-day and 1-year mortality. We used multivariate regression and Cox proportional hazards models incorporating inverse probability treatment weighting to analyze the effect of OMM on outcome measures after adjusting for patient-level confounding. Among 10,271 lower extremity bypass procedures performed, 2265 (22%) were undertaken in claudicants with a median age of 63 years (interquartile range, 58-68 years). Of claudicants, 839 (37%) were diabetic, and 1333 (59%) patients smoked within 12 months before surgery. OMM was achieved in only 581 (26%) claudicants before they underwent surgery, although adherence to individual components was variable: antiplatelet, 55%; statin, 63%; smoking cessation, 58%; and hemoglobin A1c monitoring, 92%. In risk-adjusted analyses, there were no statistically significant differences in complication rates, amputation-free survival, or mortality outcomes among patients who received OMM compared with non-OMM patients. Only a quarter of veterans with claudication were documented as receiving OMM within the year before undergoing open lower extremity bypass across nationwide VA medical centers, highlighting the need for strategies to ensure that medical therapy is intensified before surgical revascularization. Nevertheless, our data showed that documentation of preoperative OMM did not lead to improved short- or long-term postoperative outcomes in these patients, suggesting that more objective measures of medical management are needed to ensure that peripheral arterial disease goals are achieved.