Determination of temozolomide in human plasma and urine by high-performance liquid chromatography after solid-phase extraction.
As a part of a pilot clinical study, a high-performance reversed-phase liquid chromatography analysis was developed to quantify temozolomide in plasma and urine of patients undergoing a chemotherapy cycle with temozolomide. All samples were immediately stabilized with 1 M HCl (1 + 10 of biological sample), frozen and stored at -20 degrees C prior to analysis. The clean-up procedure involved a solid-phase extraction (SPE) of clinical sample (100 microliters) on a 100-mg C18-endcapped cartridge. Matrix components were eliminated with 750 microliters of 0.5% acetic acid (AcOH). Temozolomide was subsequently eluted with 1250 microliters of methanol (MeOH). The resulting eluate was evaporated under nitrogen at RT and reconstituted in 200 microliters of 0.5% AcOH and subjected to HPLC analysis on an ODS-column (MeOH-0.5% AcOH, 10:90) with UV detection at 330 nm. The calibration curves were linear over the concentration range 0.4-20 micrograms/ml and 2-150 micrograms/ml for plasma and urine, respectively. The extraction recovery of temozolomide was 86-90% from plasma and 103-105% from urine over the range of concentrations considered. The stability of temozolomide was studied in vitro in buffered solutions at RT, and in plasma and urine at 37 degrees C. An acidic pH (< 5-6) should be maintained throughout the collection, the processing and the analysis of the sample to preserve the integrity of the drug. The method reported here was validated for use in a clinical study of temozolomide for the treatment of metastatic melanoma and high grade glioma.


A role for protein kinase C in long term potentiation of nicotinic transmission in the superior cervical ganglion of the rat.
The superior cervical ganglion of rats was perfused with Ringer solution containing hexamethonium to produce a steady, partial, nicotinic block. The compound action potential (CAP) evoked by supramaximal single shock stimulation of the cervical sympathetic trunk (CST) was recorded from the internal carotid nerve. Bolus injection of the protein kinase C (PKC) activators 4 beta-phorbol-12,13-dibutyrate (PDBu) or 4 beta-phorbol-12,13-diacetate (PDAc) produced a marked, prolonged, dose-dependent potentiation of the CAP amplitude (e.g. 90% decay 2 h). A non-PKC activating phorbol ester (PE), 4 alpha-phorbol-12,13-didecanoate, produced no potentiation. The PE-induced potentiation was antagonized by the PKC inhibitor H-7. In addition, after 1 h exposure to PDBu (3 microM) and recovery from the potentiation (e.g. 2-4 h), a second exposure to PDBu or PDAc produced no potentiation. A 5 s 40 Hz supramaximal train to the CST produced a long lasting potentiation of the CAP (long-term potentiation, LTP) as described previously. However, a similar train did not evoke LTP after perfusion for 1 h with PDBu. The train-evoked LTP was depressed by the PKC inhibitor H-7 at a concentration which antagonized the PE-evoked potentiation. These data suggest that (i) PKC activation potentiates nicotinic transmission, and (ii) a component of the train-evoked LTP is mediated by PKC.


[Acute type A aortic dissection with leg ischemia].
The incidence of lower extremity ischemia secondary to acute aortic dissection is relatively low, however, the presenting symptoms are variable in term of severity. We report here in two cases of such circumstances who were successively differently treated. Case one was a 60 years old male presented with severe left leg pain. Even after the initiation of cardiopulmonary bypass, the leg ischemia did not improve, therefore selective leg perfusion was additionally performed through direct left femoral artery cannulation. The surgery toward dissection was completed by mean of simultaneous graft replacement of ascending aorta and aortic arch. The leg ischemia after the aortic procedure however had persisted, femorofemoral bypass was created to relieve the mal-perfusion. Case two was a 37 years old male admitted with severe left leg pain associated with sensory-motor nerve dysfunction with muscle rigidity. In this particular patient, femoro-femoral bypass was firstly reconstructed as the mean of leg salvage procedure. After we learned there was no serious reperfusion symptom manifested, we performed radical surgery toward the aorta. We believe that the decision making of surgical treatment for acute type A dissection complicated with the presence of lower extremity ischemia is based on the severeness of mal-perfusion.


Atmospheric pressure, nonthermal plasma inactivation of MS2 bacteriophage: effect of oxygen concentration on virucidal activity.
The main aim of this study was to determine the virucidal inactivation efficacy of an in-house-designed atmospheric pressure, nonthermal plasma jet operated at varying helium/oxygen feed gas concentrations against MS2 bacteriophage, widely employed as a convenient surrogate for human norovirus. The effect of variation of percentage oxygen concentration in the helium (He) carrier gas was studied and found to positively correlate with MS2 inactivation rate, indicating a role for reactive oxygen species (ROS) in viral inactivation. The inactivation rate constant increased with increasing oxygen concentrations up to 0·75% O2 . 3 log10 (99·9%) reductions in MS2 viability were achieved after 3 min of exposure to the plasma source operated in a helium/oxygen (99·25% : 0·75%) gas mixture, with >7 log10 reduction after 9 min exposure. Atmospheric pressure, nonthermal plasmas may have utility in the rapid disinfection of virally contaminated surfaces for infection control applications. The atmospheric pressure, nonthermal plasma jet employed in this study exhibits rapid virucidal activity against a norovirus surrogate virus, the MS2 bacteriophage, which is superior to previously published inactivation rates for chemical disinfectants.


Epigenomics and chromatin dynamics.
A report of the 'Joint Keystone Symposium on Epigenomics and Chromatin Dynamics', Keystone, Colorado, 17-22 January 2012.


Classification of pediatric migraine: proposed revisions to the IHS criteria.
The International Headache Society classification lends itself to modification to significantly improve the diagnostic sensitivity of migraine in the pediatric population. Children and adolescents require special modifications relating to duration, location, quality of intensity, and symptoms related to photophobia and phonophobia. We propose specific criteria for pediatric migraine with and without aura which are more sensitive. Forty-five children and adolescents seen at a headache center were evaluated, retrospectively, comparing diagnostic criteria of the International Headache Society, Vahlquist, and the proposed revised IHS classification for clinical diagnosis by a single examiner (pediatric neurologist)--comparing diagnostic rates for migraine of the total sample: IHS (53%), Vahlquist (69%), and IHS-R (80%) and evaluating a subset of those patients less than 12 years (n = 22): IHS (50%), Vahlquist (68%), and IHS-R (73%). The proposed revisions to IHS for pediatric migraine were more sensitive than existing criteria. These revisions may help to form the basis for future research guidelines and for further modifications to improve the diagnostic sensitivity of pediatric migraine using the IHS model.


Hepatitis C antibody intraassay correlation: is retest in duplicate necessary?
The hepatitis C virus antibody (anti-HCV) can be identified with third-generation immunoassays. The purpose of this study was to define the correlation or agreement between first and second reactive results of anti-HCV microparticle-based enzyme immunoassay (MEIA) and of chemiluminescence assays (ChLIAs) in blood donors, to determine whether repeat testing is necessary. Commercially available assays, third-generation HCV MEIA (Abbott), third-generation HCV ChLIA (Ortho), and third-generation HCV ChLIA (Abbott), were used to evaluate anti-HCV repeatedly reactive blood obtained from donations made at 23 Mexican blood centers over a period of 1 year. The intraassay correlation between first and second reactive anti-HCV tests with the Pearson r test and the coefficient of variation (CV) were determined. The intraassay correlation of 565 anti-HCV repeatedly reactive samples was 0.996 for the Abbott third-generation HCV MEIA, 0.995 for the Ortho third-generation HCV ChLIA, and 0.993 for the Abbott third-generation HCV ChLIA. The CVs of these assay systems were 2.82, 5.33, and 5.69 percent, respectively. A highly significant intraassay correlation between anti-HCV duplicates was found. Specimens with a single reactive anti-HCV result with the Abbott third-generation HCV MEIA, Ortho third-generation HCV ChLIA, and Abbott third-generation HCV ChLIA assays should be considered as positive and need not be retested. Such a change in the algorithm for blood donor screening is feasible because of the availability of highly automated platforms.


Environmental cleaning and infection prevention and control: The role of Patient Service Assistants.
In Australia, Patient Service Assistants are an integral part of all health care settings, yet there is a paucity of studies considering their understandings and perceptions of their role about infection prevention and control. The aim in this study was to explore haematology Personal Service Assistants' experience, understanding and perceptions of their role in improving patient safety through environmental cleaning. A qualitative exploratory descriptive design was utilised to collect data from cleaning staff via focus groups. Three semi-structured focus groups were conducted. Seven Patient Service Assistants participated in the study out of 11 employed. Two key themes emerged from the thematic analysis: (1) Playing a major role in Infection Prevention and Control, and (2) prioritising good interpersonal relationships over promoting infection prevention and control. Patient Service Assistants emphasised the importance of their involvement in keeping the ward clean, including patients' rooms and surroundings, to prevent cross infection. Most participants underlined the dilemmas they faced when visitors and/or informal cleaning employees or casual ward staff did not adhere to ward infection prevention and control norms. Patient Service Assistants were employing key infection prevention and control principles in their ward cleaning routine, with the aim of achieving a safer patient environment although they were reluctant to challenge observed practice deviations. The role of Patient Service Assistants highlights the widely held misconception that patient safety is solely dependent on healthcare workers.


Copper-zinc imbalance induces kidney tubule damage and oxidative stress in a population exposed to chronic environmental cadmium.
This cross-sectional study aimed to assess the effect of environmental cadmium (Cd) exposure and essential metal imbalance on renal tubular damage and oxidative stress in 979 adults living in a Cd-polluted area near an abandoned copper (Cu) refinery. We analyzed urinary Cd concentrations, renal tubular damage and oxidative stress markers, such as beta-2 microglobulin (β2-MG) and N-acetyl-β-D-glucosaminidase (NAG) activity and urine malondialdehyde (MDA) levels. The serum copper-to-zinc ratio (CZR) was used as an essential metal imbalance indicator. We divided the subjects into two Cd exposure groups based on the reference level of urinary Cd for renal dysfunction (2 μg/g creatinine). The geometric mean concentration of urinary Cd in all subjects was 2.25 μg/g creatinine. In both low and high Cd exposure groups, urinary Cd levels were positively correlated with urinary NAG activity, but not with serum CZR. After multivariate adjustment, serum CZR was strongly associated with urinary β2-MG levels in the low Cd exposure group (β = 1.360, P = 0.019) and was significantly associated with urinary MDA levels, regardless of Cd exposure level. In addition, the risk of renal tubular damage was significantly associated with urinary Cd level, particularly in the lowest or highest CZR tertile groups. Essential metal imbalance may be a determinant of oxidative stress and renal tubular damage in a chronically Cd-exposed population, and proper zinc supplementation will be effective in preventing adverse health effects due to Cd exposure.


Imaging of male breast disease: the good, the bad and the ugly - A pictorial review.
The male breast is affected by a broad spectrum of conditions, ranging from benign to malignant, many of which are similar to those occurring in its female counterpart. Despite the challenge motivated by different imaging characteristic features, correct imaging interpretation in male breast disease may aid at differentiation between benign and suspected conditions, narrow the differential diagnosis and guide subsequent management. The purpose of this review is to showcase a wide array of male breast diseases, discuss their imaging presentations and key features for diagnosis.


Enumeration of rat allospecific antibody-producing cells by a solid-phase antibody-forming cell focus (AFCF) assay.
Individual rat cells producing antibody to rat MHC class I alloantigens ( RT1A ) and other erythrocyte (E)-associated alloantigens can be enumerated by a solid-phase antibody-forming cell focus ( AFCF ) assay. Cells are incubated in solid agarose medium in petri dishes coated with affinity-purified anti-immunoglobulin antibodies and antibody produced by any cell is captured by these anti-immunoglobulin antibodies. Foci of antibody to E alloantigens produced by single cells become visible upon subsequent addition of the appropriate target E. Execution of the assay in solid agarose medium facilitates handling of the petri dishes and reduces target background binding compared to performance of the assay in liquid medium.


[Bleeding as a complication of resuscitation in a case of thromboembolism of the pulmonary artery].
Massive blood shed (1700 ml) from the punction wound in the left ventricle was observed in a patient on 65,000 U heparin. Comatose condition was accompanied by a pronounced lactacidemia of liquor (10 mmol/l) developed due to adrenaline administration with an extremely high glucose level (33 mmol/l--in blood; 11 mmol/l--in liquor). High efficacy of hyperbaric oxygenation in hypoxemic coma has been established.


TRAIL enhances thymidine kinase/ganciclovir gene therapy of neuroblastoma cells.
The clinical benefit of suicide gene therapy of tumors has been marginal, mostly due to the low gene transfer efficiency in vivo. The death-inducing ligand, TRAIL, effectively kills many tumor cell types, while sparing most normal tissues. We hypothesized that TRAIL may enhance HSV thymidine kinase/ganciclovir (TK/GCV) gene therapy of tumor cells by augmenting both target and bystander cell kill. Human SH-EP neuroblastoma cells expressing TK as well as bystander cells were effectively killed by apoptosis, and their clonogenicity was ablated following GCV. Human TRAIL enhanced TK/GCV-induced cell death and decreased clonogenicity of TK-expressing cells and also of bystander cells. Cooperation between TRAIL and TK/GCV depended both on caspase activation and on mitochondrial apoptogenic function because both the broad-spectrum caspase inhibitor zVAD.fmk and overexpression of Bcl-2 decreased enhancement of cell kill by TRAIL. Facilitation of TRAIL signalling by up-regulation of TRAIL receptors did not contribute to enhancement because cell surface expression of the agonistic TRAIL receptors 1 and 2 was not increased by TK/GCV. In conclusion, the concerted activation of caspases and the mitochondrial amplification of caspase activation by TK/GCV may explain the cooperative effect of TK/GCV and TRAIL on the kill of neuroblastoma cells. Because combined treatment also augmented the bystander cell kill, the addition of TRAIL may increase the efficacy of TK/GCV gene therapy of neuroblastoma.


Rapid and sensitive phenotypic marker detection on breast cancer cells using surface-enhanced Raman scattering (SERS) imaging.
We report a surface-enhanced Raman scattering (SERS)-based cellular imaging technique to detect and quantify breast cancer phenotypic markers expressed on cell surfaces. This technique involves the synthesis of SERS nano tags consisting of silica-encapsulated hollow gold nanospheres (SEHGNs) conjugated with specific antibodies. Hollow gold nanospheres (HGNs) enhance SERS signal intensity of individual particles by localizing surface electromagnetic fields through pinholes in the hollow particle structures. This capacity to enhance imaging at the level of single molecules permits the use of HGNs to detect specific biological markers expressed in living cancer cells. In addition, silica encapsulation greatly enhances the stability of nanoparticles. Here we applied a SERS-based imaging technique using SEHGNs in the multiplex imaging of three breast cancer cell phenotypes. Expression of epidermal growth factor (EGF), ErbB2, and insulin-like growth factor-1 (IGF-1) receptors were assessed in the MDA-MB-468, KPL4 and SK-BR-3 human breast cancer cell lines. SERS imaging technology described here can be used to test the phenotype of a cancer cell and quantify proteins expressed on the cell surface simultaneously. Based on results, this technique may enable an earlier diagnosis of breast cancer than is currently possible and offer guidance in treatment.


CircSCAF8 promotes growth and metastasis of prostate cancer through the circSCAF8-miR-140-3p/miR-335-LIF pathway.
Circular RNAs (circRNAs) have been increasingly linked to cancer progression. However, the detailed biological functions of circRNAs in prostate cancer (PCa) remain unclear. Using high-throughput circRNA sequencing, we previously identified 18 urine extracellular vesicle circRNAs that were increased in patients with PCa compared with those with benign prostatic hyperplasia. Spearman correlation analysis of the expression levels of the 18 circRNAs between the tumor tissue and matched urine extracellular vesicles in 30 PCa patients showed that circSCAF8 had the highest R2 (R2 = 0.635, P < 0.001). The Cox proportional hazards regression model was used to estimate the effect of circSCAF8 on progression-free survival. The in vitro and in vivo functional experiments were implemented to investigate the effects of circSCAF8 on the phenotype of PCa. We found that the knockdown of circSCAF8 in PCa cells suppressed the proliferation, migration, and invasion ability, while overexpression of circSCAF8 had the opposite effects. Similar results were observed in vivo. In a cohort of 85 patients who had undergone radical prostatectomy, circSCAF8 expression in PCa tissues was a powerful predictor of progression-free survival (HR = 2.14, P = 0.022). Mechanistically, circSCAF8 can function by binding to both miR-140-3p and miR-335 to regulate LIF expression and activate the LIF-STAT3 pathway that leads to the growth and metastasis of PCa. Collectively, our findings demonstrate that circSCAF8 contributes to PCa progression through the circSCAF8-miR-140-3p/miR-335-LIF pathway.


Association between resistance to cerebrospinal fluid flow and cardiac-induced brain tissue motion for Chiari malformation type I.
Chiari malformation type I (CMI) patients have been independently shown to have both increased resistance to cerebrospinal fluid (CSF) flow in the cervical spinal canal and greater cardiac-induced neural tissue motion compared to healthy controls. The goal of this paper is to determine if a relationship exists between CSF flow resistance and brain tissue motion in CMI subjects. Computational fluid dynamics (CFD) techniques were employed to compute integrated longitudinal impedance (ILI) as a measure of unsteady resistance to CSF flow in the cervical spinal canal in thirty-two CMI subjects and eighteen healthy controls. Neural tissue motion during the cardiac cycle was assessed using displacement encoding with stimulated echoes (DENSE) magnetic resonance imaging (MRI) technique. The results demonstrate a positive correlation between resistance to CSF flow and the maximum displacement of the cerebellum for CMI subjects (r = 0.75, p = 6.77 × 10-10) but not for healthy controls. No correlation was found between CSF flow resistance and maximum displacement in the brainstem for CMI or healthy subjects. The magnitude of resistance to CSF flow and maximum cardiac-induced brain tissue motion were not statistically different for CMI subjects with and without the presence of five CMI symptoms: imbalance, vertigo, swallowing difficulties, nausea or vomiting, and hoarseness. This study establishes a relationship between CSF flow resistance in the cervical spinal canal and cardiac-induced brain tissue motion in the cerebellum for CMI subjects. Further research is necessary to understand the importance of resistance and brain tissue motion in the symptomatology of CMI.


Acute gastric volvulus: diagnosis and management over 10 years.
Gastric volvulus is a rare, potentially life-threatening condition, which is difficult to diagnose. This study represents a series of patients with acute gastric volvulus. All patients presenting with acute gastric volvulus over a 10-year period were reviewed. Twenty-one patients with a median age of 66 years were identified. Acute gastric volvulus was secondary to a paraesophageal hiatus hernia in 16 patients. The major symptoms were abdominal pain, vomiting and upper gastrointestinal bleeding/anemia. The most useful investigations were barium studies and upper gastrointestinal endoscopy. Treatment was open surgery in all patients. There were no major complications and no deaths. Median hospitalization was 8 days. Acute gastric volvulus is a rare condition which requires a high index of suspicion for diagnosis, which is usually based on imaging studies. The treatment is immediate surgery. Volvulus can be treated successfully by open surgery with minimal morbidity and short hospitalization.


Controlled release behaviour and antibacterial effects of antibiotic-loaded titania nanotubes.
Bacterial infections have been identified as the main cause of orthopaedic implant failure. Owing to their high antibiotic delivery efficiency, titania nanotubes loaded with antibiotics constitute one of the most promising strategies for suppressing bacterial infections. However, it is difficult to control the drug-release behaviour of such nanotubes. Although sealing the nanotubes with a polymer solution provides sustained release effects to a certain extent, it inevitably influences their initial antibacterial activity. This study reports on the controlled release of gentamicin sulphate (GS) from titania nanotube surfaces whereby their initial antibacterial activity remains unaffected. Titania nanotubes were fabricated via electrochemical anodization and loaded with GS through physical adsorption. Experimental results showed that this loading method is feasible and efficient. The GS-loaded titania nanotubes were further covered by a thin film comprising a mixture of GS and chitosan (GSCH). The release kinetics confirmed that the drug release could be controlled by this thin film. Moreover, such a film was shown to not only inhibit initial bacterial adherence owing to its strong antibacterial properties but also enhance cell viability. Thus, GS-loaded titania nanotubes coated with GSCH have considerable potential as biomaterials for preventing initial release and peri-implant infection in the field of orthopaedics.


Endocrine mucin-producing sweat gland carcinoma: a study of three cases and CK8, CK18 and CD5/6 immunoexpression.
Endocrine mucin-producing sweat gland carcinoma is a cutaneous adnexal tumor that is rarely reported in the literature. We identified only 29 previously reported cases. All these cases share some clinical morphologic and immunohistochemical features. Among the immunohistochemical markers, cytokeratins 5/6, 8 and 18 (CK5/6, CK8 and CK18) had not been previously studied in this tumor. Although studies with cytokeratin Cam5.2 exist, we know at present that this marker does not correspond to antibodies CK8/18, but rather to CK7 and CK8. We studied three examples of endocrine mucin-producing sweat gland carcinoma with 18 immunostains. Our cases showed an immunoprofile CK8+, CK18+, CK5/6- (or only focally positive), CK7+, GCDFP-15+ (2 cases), estrogen receptor+, progesterone receptor+, HER2-, neuron-specific enolase + (2 cases), anti-synaptophysin+, chromogranin A +, CD56 variable (1 case +, 1 case-), CD57-, anti-human D2-40- (two cases), p63- or focally positive, smooth muscle actin + with variable pattern of expression and smooth muscle myosin heavy chain expressed in a peripheral discontinuous layer in some nodules, but absent in most.


Integrated dynamic probabilistic material flow analysis of engineered materials in all European countries.
Uncertainties remain regarding the potential environmental risks of engineered nanomaterials, reflecting missing information on both the exposure and the hazard sides. Probabilistic material flow analysis (PMFA) is a useful exposure assessment tool that maps the flows of a substance through its lifecycle towards the environment, taking into account the uncertainties associated with the input data. In the last years, several refinements have been made to the original PMFA method, increasing its complexity with respect to systems dynamics, fate during recycling and reprocessing and forms of release. In this work, an integrated dynamic probabilistic material flow analysis (IDPMFA) was developed that combines all separate advancements of the method in one overarching software code. The new method was used to assess the forms in which nano-Ag, nano-TiO2 and nano-ZnO are released into air, soils and surface water. Each European country (EU28, Norway and Switzerland) was studied from the year 2000 to the year 2020. The present model includes new assessments of the forms in which nano-ZnO is released into the environment and of the flows out of reprocessing (last step of recycling) of nano-Ag, nano-TiO2 and nano-ZnO towards both technical and environmental compartments. The forms of ZnO released to different compartments vary greatly with different proportions between pristine, dissolved, matrix-embedded and transformed forms. The same applies for the forms of the other ENMs released after reprocessing, where different processes result in very different distributions between the various forms. The country-specific assessment showed that it is mainly the different solid waste treatment schemes that influence the distribution to final environmental sinks. Overall, the results of IDPMFA show the great importance of considering the full life cycle of nanoproducts including the different stages of recycling, the differences between countries, and the forms of the released materials. The results from the integrated model will provide useful input information for environmental fate models and for environmental risk assessments.


Cutaneous malignant melanoma in women. Phenotypic characteristics, sun exposure, and hormonal factors: a case-control study from Italy.
We examined the role of personal host characteristics in relation to cutaneous malignant melanoma (CMM) among women, with a particular focus on hormonal and reproductive factors. A case-control study conducted in Italy between 1992 and 1994, including 316 women with incident, histologically confirmed CMM and 308 controls, admitted to the same network of hospitals as cases for acute, non-dermatological, and non-neoplastic conditions. CMM was significantly associated with body mass index (kg/m(2)) (odds ratio [OR]=1.96 for > or =27 compared with < 23) and body surface area (m(2)) (OR=1.68 for > or =1.71 compared with < 1.59), eye color (OR=1.74 for green/hazel compared with brown), solar lentigines (OR=1.47), and number of melanocytic nevi (OR=3.39 for total number of nevi > or =16 compared with < 5). Age at first (OR=2.69 for > or =27 compared with < 23 years) and last birth (OR=2.13 for > or =31 compared with < 27 years) were associated with the risk of CMM, whereas other reproductive, menstrual, and hormonal factors, including menopause, number of live-births and abortions, use of oral contraceptives, and hormone replacement therapy were not significantly associated. Our results confirm findings from previous studies on the role of major recognized risk factors for CMM, and add further evidence of an absence of a consistent association between hormonal and reproductive factors and CMM risk.


The role of the Th-1 to Th-2 shift of the cytokine profiles of CD4 helper cells in the pathogenesis of autoimmune and hypercatabolic diseases.
The task of the immune system is the continuous elimination of endogenous cellular debris and the elimination, when necessary, of exogenous structures. It therefore seems useful and practical to add to the paradigms 'self' and 'not self' the term 'altered self'. The concept of stress, introduced by W. B. Cannon and H. Selye in the 1930s, covers the wide range of aggressive environmental influences which for their part result in a uniform shift of the metabolism in the direction of catabolism. This results from the activation of the neuroendocrine stress axis, hypothalamus-pituitary-adrenals, and causes an increased release of catecholamines and glucocorticoids. These latter substances limit life-threatening acute-phase reactions by endogenous inflammation mediators. The purpose of the shift of the cytokine profiles of the CD4 lymphocytes from Th-1 to Th-2 is, with the return of a raised cortisol level to normal values, to temporarily take over the anti-inflammatory functions of the cortisol. A sustained Th-2 shift is an expression of a persistent hypercortisolism in autoimmune states. The suppression of the anti-inflammatory effects of cortisol as a result of states of excessive stress leads to hypercatabolic diseases such as AIDS, sepsis and toxic shock syndrome and protein calorie malnutrition (NAIDS). In the prevention and treatment of AIDS and NAIDS, besides the elimination of the causes of stress, the prophylactic and therapeutic efforts are based mainly on the activation of the mesenchymal production of anabolic matrix components, mainly glycosaminoglycans, and the neutralization of O2 and NO radicals and inflammation mediators from macrophages by polyanions and polyphenols. In our opinion, in sepsis and toxic shock syndromes, lasting reduction of the mortality rates for these diseases is best achieved through the early administration of high intravenous doses of gammaglobulins.


Beyond Traditional RN-BSN Programs: Partnerships for Dual Admission Progression Programs.
Seamless academic programs are essential to support key national recommendations to increase the number of baccalaureate-prepared nurses (BSN). Associate degree nursing programs graduate approximately 50 percent of the registered nurse workforce. Graduates need a quality RN-BSN in nursing pathway to advance their education. This article discusses a seamless dual admission program in northeast Ohio, a cost-effective partnership between one associate degree nursing program and one BSN program that reduced barriers for students and had positive student outcomes.


The epithelium in the female urethra: a quantitative study.
Histological sections were prepared from 8 regions along the length of the urethra in 16 women 19 to 82 years old. The epithelium was examined under the light microscope at 4 points in each region and the type of epithelium was classified. Our results indicate that the human female urethra is lined by stratified squamous, pseudostratified columnar and, occasionally, transitional epithelium. There is a gradual change from squamous to columnar epithelium with advancing age. More squamous epithelium is present at the distal end of the urethra.


Biasing effect of the electromyogram on BIS: a controlled study during high-dose fentanyl induction.
A biasing effect of the electromyogram (EMG) on the Bispectral Index (BIS) may explain discrepancies in previous studies assessing BIS in the presence of neuromuscular activity. Our aims were: to evaluate variations of BIS in the presence of high EMG activity associated with muscular rigidity after administration of high-dose fentanyl; to compare muscular rigidity, as measured by the EMG variable of the BIS monitor, in patients who were administered two different dosages of fentanyl at induction of cardiac anaesthesia. 26 patients undergoing CABG surgery, after premedication with morphine 0.15 mg/kg, were randomized to receive either fentanyl 50 mcg/kg (group F) or fentanyl 10 mcg/kg plus etomidate 0.2 mg/kg (group EF). The induction dose was administered over 2 minutes. Patients were manually ventilated with O2 via face mask. Five minutes after induction was complete, patients were clinically assessed using the Responsiveness portion of the Observer's Assessment of Alertness/Sedation scale (OAAS). Haemodynamic data were recorded and arterial blood samples obtained at the time of OAAS observation. Patients were administered a neuromuscular blocking agent only after the OAAS assessment. BIS (3.4) was recorded from an A-2000 EEG monitor (Aspect Medical Systems) using disposable sensors (BIS Sensor, Aspect Medical Systems) applied per manufacturer's instructions. Data were recorded on a PC for off-line analysis. At the time of OAAS observation, mean (95% CI) BIS in group F was 85 (77-92) compared to 67 (56-79) in group EF (p = 0.01). Similarly, mean (95% CI) EMG was 50 dB (45-56) in F and 41 dB (35-47) in EF (p = 0.01). Correlation between BIS and EMG was very high (r2 = 0.88). OAAS scores were significantly higher in group F (p = 0.03). Non significant correlation was observed between BIS and OAAS scores (r2 = 0.32, p = 0.1). Backward stepwise multiple regression analysis including EMG, pH, CO2, O2 and OASS scores showed EMG as strong predictor of BIS (p < 0.0001, r2 = 0.7). Regression of EMG against BIS yielded the equation: BIS = 3.7 + (1.6 x EMG). During fentanyl-induced muscular rigidity BIS recordings reflect EMG variations. When assessing BIS in the absence of neuromuscular blockade, it is necessary to evaluate the effect of EMG on BIS before making conclusions about depth of sedation. Fentanyl-induced rigidity appears to be a dose-related phenomenon which the EMG variable of BIS 3.4 is able to quantify.


Dissecting the Pol II transcription cycle and derailing cancer with CDK inhibitors.
Largely non-overlapping sets of cyclin-dependent kinases (CDKs) regulate cell division and RNA polymerase II (Pol II)-dependent transcription. Here we review the molecular mechanisms by which specific CDKs are thought to act at discrete steps in the transcription cycle and describe the recent emergence of transcriptional CDKs as promising drug targets in cancer. We emphasize recent advances in understanding the transcriptional CDK network that were facilitated by development and deployment of small-molecule inhibitors with increased selectivity for individual CDKs. Unexpectedly, several of these compounds have also shown selectivity in killing cancer cells, despite the seemingly universal involvement of their target CDKs during transcription in all cells. Finally, we describe remaining and emerging challenges in defining functions of individual CDKs in transcription and co-transcriptional processes and in leveraging CDK inhibition for therapeutic purposes.


Use of purified lyophilized human lactate dehydrogenase isoenzyme 5 in a study of measuring lactate dehydrogenase activity.
We examined the stability of human lactate dehydrogenase (EC 18.104.22.168) isoenzyme 5--purified to a specific activity of about 400 kU/g--when lyophilized in a buffered, stabilized matrix of bovine albumin. This isoenzyme was prepared with a final activity of about 500 U/L and stored at -20, 4, 20, 37, and 56 degrees C for as long as six months. This isoenzyme decayed with approximate first-order kinetics, with an estimated half-life at -20 degrees C of about 475 years. Stability of reconstituted samples stored at 20 or 4 degrees C was poor, suggesting that the reconstituted material should be used without delay; material stored at -20 degrees C showed excellent stability for 15 days. We propose that such preparations might be further investigated as standards for use in electrophoresis of lactate dehydrogenase isoenzymes.


Intestinal anastomosis with the biofragmentable anastomosis ring.
The fear of anastomotic complications prevents the spread of the use of the biofragmentable anastomosis ring (BAR) in intestinal surgery. A total of 453 patients underwent intestinal resection and anastomosis with the BAR. In all, 514 anastomoses have been carried out, 424 (83%) in elective settings, and 90 (18%) in emergency. Fifty-one patients had multiple anastomoses. Reoperation was performed in 4 patients (1%) who had a complete anastomotic leakage. In 13 patients (3%), anastomotic leakage was partial, and only 1 patient required reoperation. No postoperative intestinal obstruction occurred. Four patients (1%) developed late anastomotic strictures, which have been treated by endoscopic dilation. The results of our experience and those of other large clinical series definitely confirm the effectiveness of the BAR method, which seems to be a standard, easy, rapid, and safe technique either in elective or emergency surgery.


Validation of a food frequency questionnaire for nutritional calcium intake assessment in Italian women.
To evaluate a food frequency questionnaire assessing calcium intake in women. : Estimates of calcium intake from the food frequency questionnaire were compared with those from 14 day records from 206 Caucasian women aged 25-75 y in Siena, Italy. Subjects were randomly recruited from the residents list of the city of Siena, Italy. Of the 250 initially recruited, 39 did not meet the inclusion criteria or failed to complete the diet record and five outliers were excluded before the statistical analysis on the basis that their diet record was unlikely to represent habitual intake. Mean dietary calcium intakes were 829+/-255 (s.d.) mg/day from the questionnaire and 818+/-260 (s.d.) mg/day from the diet record. The mean difference in intake by the two methods (-11.3+/-116.4 mg/day) did not differ significantly from zero. Specificity in classifying women consuming less than 800 mg/day calcium was 86.6%, and sensibility in classifying women consuming more than 800 mg/day calcium was 89.4%. The food frequency questionnaire could be used in epidemiological studies to assess calcium intake in young to elderly women. The specificity in identifying low calcium intake subjects makes it useful also as an educational tool in diet counselling and for prescribing calcium supplementation.


Selection and use of vegetable parenting practices did not vary by parent feeding styles: Mixed methods investigation.
Parents influence their child's vegetable intake through their feeding style, i.e. the emotional tone established around feeding, and vegetable parenting practices (VPPs), i.e. the specific behaviors employed to influence their child's vegetable intake. A model of precision food parenting proposes that child healthy dietary intake could be optimized by the selection and implementation of effective food parenting practices. Parents use and learn from these complex interactions with their child, which are reflective of feeding style. Intervention research has targeted VPPs in general without a delineation of which practices were selected, which were used, or why they were selected. It is not clear how these users were influenced by feeding style, nor what the parent learned from the interaction. The current study used mixed methods wherein middle socioeconomic status parents of 3-5 year old children were categorized within feeding style groups (n = 122), asked to select two VPPs, implemented them for a week (n = 63), and qualitatively interviewed about their experience. Responsiveness VPPs were most commonly selected, primarily due to their perceived ease of implementation. Parents believed there would be long term positive outcomes, e.g. more vegetable intake from using the practices selected. Frequency of use depended in part on opportunity, e.g. food purchase parenting practices could only be employed during intermittent shopping events. Few differences were detected by parent feeding styles in the types of VPPs selected, frequency of use, or effectiveness. Food parenting interventions can encourage selection of specific VPPs to employ and do not appear to have to tailor the types of VPPs offered to parent feeding style. Research is needed with larger, socioeconomically diverse samples to assess optimal categorization into feeding styles and confirm the present results.


[Treatment of sudden deafness of vascular etiology with venoruton].
The sudden deafness of vascular origin was treated by Venoruton. 4 patients were observed with positive results as improvement of hearing acuity and disappearance of tinnitus.


The use of chondrogenic differentiation drugs to induce stem cell differentiation using double bead microsphere structure.
A double bead microsphere device that functions as a 3D scaffold and also delivers bioactive molecules to cells has been developed. The system we developed consists of large polymeric microspheres that were loaded with dexamethasone (DEXA) and coated with DHEA, which were physically immobilized using a layer-by-layer (LbL) system. The initial step in this strategy involves the creation of microparticles that contain DHEA, which were simply produced using a water-in-oil-in-water (W/O/W) emulsion method. In the second step, small sized microparticles containing DHEA were coated onto positively-charged poly(d,l-lactic-co-glycolic acid) (PLGA) microspheres that contained DEXA pretreated with poly(ethyleneimmine) (PEI). Microsphere constructs that contain DEXA and DHEA showed a significantly higher number of specific lacuna phenotypes at the end of a 4-week study in vitro and at the end of a 6-week study in vivo, irrespective of the presence of DEXA and DHEA. Therefore, the dual delivery of DEXA and DHEA can be used to engineer inflammation-free tissue in the vicinity of the implant. These double beaded PLGA microsphere constructs containing DEXA and DHEA show promise as coatings for implantable biomedical devices to improve biocompatibility and ensure in vivo performance.


Pulmonary gas exchange in the morbidly obese.
The literature on pulmonary gas exchange at rest, during exercise, and with weight loss in the morbidly obese (body mass index or BMI > or = 40 kg m(-2)) is reviewed. Forty-one studies were found (768 subjects weighted mean = 40 years old, BMI = 48 kg m(-2)). The alveolar-to-arterial oxygen partial pressure difference (AaDO2) was large at rest in upright subjects at sea level (23, range 5-38 mmHg) while the arterial pressure of oxygen (PaO2) was low (81, range 50-95 mmHg). Arterial pressure of carbon dioxide (PaCO2) was normal. At peak exercise (162 W), gas exchange improves. Weight loss of 45 kg (BMI = -13 kg m(-2)) over 18 months is associated with an improvement in PaO2 (by 10 mmHg, range 1-23 mmHg), a reduction in AaDO2 (by 8 mmHg, range -3 to -16 mmHg), and PaCO2 (by -3 mmHg, range 3 to -14 mmHg) at rest. Every 5-6 kg reduction in weight increases PaO2 by 1 and reduces AaDO2 by 1 mmHg, respectively. Morbidly obese women have better gas exchange at rest compared with morbidly obese men which is likely due to lower waist-to-hip ratios in women than from differences in weight or BMI.


Implantable cardioverter-defibrillator: patient selection and implantation protocol.
The experience obtained from the clinical trials with the automatic implantable cardioverter-defibrillator have reemphasized the need for a detailed pathophysiologic evaluation of the patient preoperatively. This evaluation requires careful documentation of the probable cause of the ventricular tachyarrhythmia and evaluation of other surgical needs of the patient, as well as consideration of the interactive effects of pacemakers and concurrent pharmacologic therapy postoperatively.


A chaotic cosmology.
An anisotropic, inhomogeneous cosmological model is proposed in which the inhomogeneity is generated by shear fluctuations. This is a sufficient condition for dissipative heating by collisional neutrinos to explain the present large heat content of the universe, S(b o) approximately 10(8), together with its isotropy and comparative homogeneity on large scales when the photons were last scattered. The model does not require the chaotic motions to be arbitrarily truncated on large scales and isotropises early enough with high entropy to ensure the synthesis of light elements with the observed abundancies. A population of black holes which arises in a natural way can also provide the necessary ingredients for a theory of galaxy formation and morphology. The 10(15)-g black holes, predicted by some authors, are not necessarily expected to be a feature of chaotic cosmologies.


Peptide mapping on HIV polypeptides expressed in Escherichia coli. Quality control of different batches and identification of tryptic fragments containing residues of aromatic amino acids or cysteine.
Peptide mapping was used for the quality control of different batches of the recombinant HIV proteins p24 core and p24-gp41, expressed in Escherichia coli. These proteins comprise gag and env region polypeptides of the virus and may serve as suitable components in the diagnosis of HIV infections. The proteins were digested with trypsin and the mixtures were subjected to peptide mapping to prove batch equivalence of p24-gp41 and to isolate fragments of the p24-gp41 digest that differ from those of the p24 core digest. The proteins were reduced with dithiothreitol and the cysteine residues were derivatized by addition of 4-vinylpyridine. Peptide mapping was performed by means of reversed-phase high-performance liquid chromatography. Batch equivalence was proved by comparison of the maps. Peaks present in one map but not in the other were considered to be due to sequence differences or variability in digestion.


Ameliorative and Neuroprotective Effect of Core-Shell Type Se@Au Conjugated Hesperidin Nanoparticles in Diabetes-Induced Cognitive Impairment.
Diabetes mellitus is the most chronic metabolic ailment characterized by insulin deficiency leading to aberrant cognitive dysfunction in later stages. Hesperidin is a bioflavonoid, having different pharmacological activities, but its poor water solubility and short plasma half-life restrict its applications in the clinical field. So, the hesperidin was conjugated with gold, selenium, and core-shell bimetallic nanoparticles of gold and selenium. Different spectroscopic methods characterized the synthesized monometallic and bimetallic nanoparticles. The rats were injected with streptozotocin to induce cognitive dysfunction, followed by administering HSP, HSP-Au NPs, HSP-Se NPs, and Se@Au-HSP NPs daily for 21 days. Then, the neurobehavioral studies, oxidative stress parameters, AChE and nitrite levels, the content of amyloid-β42, and inflammatory mediators were accessed to evaluate the effect of the nanoparticles against the STZ rat model. The results showed a significant increase in oxidative stress, AChE activity, amyloid-β42, nitrite levels, and neuroinflammation by upregulating the inflammatory cytokines in the streptozotocin-administered rat brain. The HSP, HSP-Au NPs, HSP-Se NPs, and Se@Au-HSP NPs effectively reversed all these effects of streptozotocin. However, the bimetallic nanoparticle Se@Au-HSP NPs revealed better neuroprotective action than HSP-Au NPs and HSP-Se NPs. Hesperidin-conjugated bimetallic nanoparticles improved learning and memory in the STZ rat model and may be an alternative approach for neurodegenerative diseases, including Alzheimer's disease.


[Cochlear implantation - Adverse effects on the cochlea and the vestibular organ].
Cochlear implantation is the treatment of choice for patients with profound hearing loss and deafness. At the same time, inserting a cochlear implant (CI) leaves damage to the inner ear. The preservation of inner ear structure and function has become a central issue in CI surgery. The reasons for this are i) electroacoustic stimulation (EAS), i.e., the option of joint stimulation by a hearing aid and a CI; ii) an improved audiologic outcome in electric-only stimulation; iii) the preservation of structures and residual hearing for potential future therapy options; and iv) the avoidance of side effects, such as vertigo. The exact mechanisms that determine the extent of damage to the inner ear and which factors contribute to preservation of residual hearing are not yet fully understood. In addition to the surgical technique, electrode selection may play a role. This article provides an overview of what is known about the direct and indirect adverse effects of cochlear implantation on the inner ear, of the methods available to monitor inner ear function during cochlear implantation, and of the focus of future research on preservation of inner ear structure and function.


A Quality Measurement Framework for Emergency Department Care of Psychiatric Emergencies.
As a primary access point for crisis psychiatric care, the emergency department (ED) is uniquely positioned to improve the quality of care and outcomes for patients with psychiatric emergencies. Quality measurement is the first key step in understanding the gaps and variations in emergency psychiatric care to guide quality improvement initiatives. Our objective was to develop a quality measurement framework informed by a comprehensive review and gap analysis of quality measures for ED psychiatric care. We conducted a systematic literature review and convened an expert panel in emergency medicine, psychiatry, and quality improvement to consider if and how existing quality measures evaluate the delivery of emergency psychiatric care in the ED setting. The expert panel reviewed 48 measures, of which 5 were standardized, and 3 had active National Quality Forum endorsement. Drawing from the measure appraisal, we developed a quality measurement framework with specific structural, process, and outcome measures across the ED care continuum. This framework can help shape an emergency medicine roadmap for future clinical quality improvement initiatives, research, and advocacy work designed to improve outcomes for patients presenting with psychiatric emergencies.


Prescription practices for malaria in Mozambique: poor adherence to the national protocols for malaria treatment in 22 public health facilities.
Current World Health Organization and national protocols recommend the 'test and treat' strategy for the management of uncomplicated malaria, to reduce over prescription of artemisinin-based combination treatment (ACT). Therefore, adherence to these protocols varies in different sub-Saharan African countries and no information is available for Mozambique. This study was conducted with the aim to evaluate the prescription practices of ACT in Mozambique. Retrospective audit of medical records corresponding to the period between July and December 2011 was conducted in 22 health units across 11 provinces in Mozambique. Two health units were selected per province according to availability of laboratory data (performing microscopy and rapid diagnostics testing-RDT or RDT only) and geographic setting (rural versus urban). At each facility, demographic data, laboratory results (blood smear or RDT), and prescription of ACT were all collected from the existing records. Between July and December 2011, a total of 61,730 cases were tested for malaria, of which 42.7 % (26,369/61,730) were positive. A total of 35.361 patients were malaria negative, and ACT was prescribed to 72.0 % (25.448/35.361) of them. Prescription of ACT to malaria negative patients was higher in the central region of the country as compared to the northern and southern (81.1 % in the central region versus 72.4 and 63.7 % in the northern and southern, respectively, p = 0.000) and in urban settings (88.7 % in rural versus 58.0 % in urban settings, p = 0.000). Stock out of RDT was observed in six (27.3 %) of the health facilities. When no RDT was available, patients were empirically treated with ACT. Findings from this study demonstrate that health care worker's adherence to the new guidelines for malaria treatment is poor in Mozambique and prescription of ACT to malaria negative patients remains very high. Enhanced training and supervision activities, community education and external quality assurance might lead to significant improvements in the clinician's adherence to the new guideline for malaria treatment in Mozambique.


Taxodione and Extracts from Salvia austriaca Roots as Human Cholinesterase Inhibitors.
Taxodione, an abietane diterpenoid, was isolated from Salvia austriaca transformed roots grown in in vitro conditions. The compound is known to have antibacterial, cytotoxic and anti-tumour properties. This study evaluates the ability of pure taxodione and extracts obtained from the S. austriaca hairy roots and roots from field-grown plants to inhibit human acetylcholinesterase and butyrylcholinesterase. Both extracts were found to have similar actions against acetylcholinesterase. The IC50 for extracts from transformed and untransformed roots were 142.5 and 139.5 µg ml(-1), respectively. The highest activity towards human acetylcholinesterase was demonstrated by taxodione (IC50 = 54.84 µg ml(-1)). With respect to BChE inhibition, the root extracts demonstrated stronger activity (IC50 = 23.6 µg ml(-1): field-grown plants and 41.6 µg ml(-1): transformed roots) than taxodione (IC50 = 195.9 µg ml(-1)). Taxodione showed significant cytotoxicity against A549 cell line (IC50 = 9.1 µg ml(-1)), whereas the activities for the extracts from S. austriaca roots of field-grown plants (IC50 = 75.7 µg ml(-1)) and hairy roots (IC50 = 86.2 µg ml(-1)) were lower. Computer modelling suggests that taxodione should not demonstrate cardiotoxic or genotoxic activity. It also indicates that taxodione should demonstrate very rapid transport from the body with very good blood-brain barrier penetration, but with no cumulative effect on the human body. The obtained results indicate that taxodione is a safe compound and may be used for further investigations in pharmacological activities.


A part of the upstream promoter region of SHN2 gene directs trichome specific expression in Arabidopsis thaliana and heterologous plants.
A promoter trap mutant line of Arabidopsis carrying a promoterless β-glucuronidase (uidA) gene exhibited GUS expression predominantly in all the trichomes. In this mutant, the T-DNA insertion was localized at 147bp upstream of the putative start codon, ATG, of the At5g11190 (SHN2) gene. Transcript profiling of the SHN2 suggested a constitutive expression of the gene in all the tissues. Deletion analysis of the upstream sequences established that a 565bp (-594/-30) region confers trichome-specific gene expression. The trichomes isolated from young, mature and senesced leaf tissues also showed the presence of SHN2 transcript. The occurrence of multiple TSSs on the SHN2 gene sequence, presence of the SHN2 transcript in the homozygous trip mutant, despite an insertional mutation event, and diverse reporter gene expression pattern driven by 5' and 3' promoter deletion fragments, suggest a complex transcriptional regulation of SHN2 gene in Arabidopsis. The promoter sequence -594/-30 showed a conserved functional role in conferring non-glandular trichome-specific expression in other heterologous systems like Brassica juncea and Solanum lycopersicon. Thus, in the present study T-DNA tagging has led to the identification of a trichome-specific regulatory sequence in the upstream region of a constitutively expressed SHN2 gene. The study also suggests a complex regulation of SHN2 gene. Isolated trichome specific region retains its functions in other systems like Brassica and tomato, hence could be effectively exploited in engineering trichome cells in heterologous crop plants to manipulate traits like biopharming and insect herbivory.


In vitro and in vivo pharmacodynamic properties of metoprolol in fructose-fed hypertensive rats.
This study of metoprolol pharmacokinetic and pharmacodynamic properties investigates cardiac beta1-adrenoceptors activity and its involvement in the hypertensive stage in 6-week-old fructose-fed male Sprague-Dawley rats. A microdialysis probe was inserted in the carotid artery to monitor metoprolol levels, blood pressure, and heart rate after drug administration (3-10 mg/kg intravenously). The relationship between levels and cardiovascular effects was studied using a pharmacokinetic-pharmacodynamic model with effect compartment. Dissociation constant and inverse agonism were evaluated in isolated atria. Metoprolol pharmacokinetics were similar in both groups. Metoprolol induced a greater hypotensive effect in fructose-fed animals (Emax: -24 +/- 1 mm Hg, n = 6, P < 0.05 vs. control) than in control rats (Emax: -14 +/- 1 mm Hg, n = 6). Bradycardic response was similar in both groups; metoprolol chronotropic potency was greater in fructose-fed rats (IC50: 123 +/- 15 ng/mL, P < 0.05 vs. control) compared to control animals (IC50: 216 +/- 36 ng/mL) after administration of 3 mg/kg. Metoprolol constants of dissociation for beta1-adrenoceptors and inverse agonism were similar in both groups. Results demonstrate the beta1-adrenoceptors involvement in the fructose hypertension. A greater potency to metoprolol in vivo chronotropic effect was found in fructose-fed rats. This greater potency was not caused by alteration in the activity of beta1-adrenoceptors.


Babywalkers: prevalence of use and relationship with other safety practices.
To examine the prevalence of walker use, and to compare sociodemographic factors, perceptions of the risk of injury and of household hazards, and safety practices in families by walker use. 36 Primary care practices across Nottingham, UK. Postal questionnaire to all parents of children aged 3-12 months registered at each practice (n = 2152) to assess safety practices, perceptions of risk of injury, and of the risk associated with household hazards and sociodemographic factors. Data were analysed using chi 2 tests for categorical data, Mann-Whitney U tests for ordinal data, and logistic regression analysis. The response rate was 74%. Fifty per cent of parents used babywalkers. Receipt of means tested benefits (odds ratio (OR) 1.42, 95% confidence interval (CI) 1.02 to 1.99), non-owner occupation (OR 1.46, 95% CI 1.04 to 2.04), residence in a deprived area (OR 1.42, 95% CI 1.06 to 1.91), and unemployment (OR 0.64, 95% CI 0.41 to 0.99) were independently associated with use of walkers. Families using babywalkers were less likely to use stair gates (chi 2 = 4.36, 1 df, p = 0.037), fireguards (chi 2 = 6.80, 1 df, p = 0.009), and had a higher total number of unsafe practices (Mann-Whitney U test, Z = -2.90, p = 0.004). Perceptions of risk of injury and of the risk associated with household hazards however, did not differ by walker use. Babywalker use is common across all social groups and is associated with other unsafe practices such as not using stair gates or fireguards. Health professionals should support campaigns to limit the sale of babywalkers, but, in addition, they should ascertain each family's reasons for walker use and try to find acceptable alternatives. They should also make the family aware of the importance of properly fitted stair gates and fireguards and help the family to obtain and use such items of safety equipment.


Remote Management of Spinal Cord Stimulation Devices for Chronic Pain: Expert Recommendations on Best Practices for Proper Utilization and Future Considerations.
Emerging spinal cord stimulation (SCS) remote monitoring and programming technologies provide a unique opportunity to address challenges of in-person visits and improve patient care, although clinical guidance on implementation is needed. The goal of this document is to establish best clinical practices for integration of remote device management into the care of patients with SCS, including remote monitoring and remote programming. A panel of experts in SCS met in July 2022, and additional experts contributed to the development of recommendations after the meeting via survey responses and correspondence. Major goals of remote SCS device management were identified, including prompt identification and resolution of SCS-related issues. The panel identified metrics for remote monitoring and classified them into three categories: device-related (eg, stimulation usage); measurable physiologic or disease-related (eg, patient physical activity or pedometry); and patient-reported (eg, sleep quality and pain intensity). Recommendations were made for frequency of reviewing remote monitoring metrics, although providers should tailor follow-up to individual patient needs. Such periodic reviews of remote monitoring metrics would occur separately from automatic monitoring system notifications (if key metrics fall outside an acceptable range). The guidelines were developed in consideration of reimbursement processes, privacy concerns, and the responsibilities of the care team, industry professionals, manufacturers, patients, and caregivers. Both existing and needed clinical evidence were covered, including outcomes of interest for future studies. Given the expansion of SCS device capabilities, this document provides critical guidance on best practices for using remote device management, although medical necessity should drive all remote monitoring decisions, with individualized patient care. The authors also describe the potential of these emerging technologies to improve outcomes for patients with SCS, although more clinical evidence is needed.


Serum-free culture of rabbit meniscal fibrochondrocytes: proliferative response.
We have formulated a serum-free medium capable of supporting DNA synthesis in rabbit meniscal fibrochondrocytes at a level equivalent to 10% fetal bovine serum (FBS). The medium consists of a 1:1 mixture of Dulbecco's Modified Eagle's Medium and Ham's F-12 medium supplemented with transferrin (1 microgram/ml), selenium (1 pg/ml), trace metal mix (1:100), dexamethasone (100 ng/ml), insulin-like growth factors I and II (50 ng/ml each), pituitary fibroblast growth factor (100 ng/ml), and lactalbumin hydrolysate (2 micrograms/ml). Endothelial cell growth supplement could be substituted for lactalbumin hydrolysate to obtain similar results. Ventrex PC-1, a commercially available, low-protein, serum-free medium, was found to support proliferation of fibrochondrocytes but not as well as 10% FBS or our medium formulation. Lipid supplements, which are known to support the serum-free growth of hyaline chondrocytes, were found to be either of no value or antagonistic for the culture of fibrochondrocytes. Likewise, vitamin E alone, progesterone, putrescine, and hydrocortisone were also without benefit in our culture system. The cells had a more chondrocytic morphology when grown in defined medium as opposed to 10% FBS. The results of this study should now make it possible to identify and quantitate those factors necessary to affect meniscal repair by utilizing further techniques in vitro.


Theoretical Study of Monolayer and Double-Layer Waveguide Love Wave Sensors for Achieving High Sensitivity.
Love wave sensors have been widely used for sensing applications. In this work, we introduce the theoretical analysis of the monolayer and double-layer waveguide Love wave sensors. The velocity, particle displacement and energy distribution of Love waves were analyzed. Using the variations of the energy repartition, the sensitivity coefficients of Love wave sensors were calculated. To achieve a higher sensitivity coefficient, a thin gold layer was added as the second waveguide on top of the silicon dioxide (SiO₂) waveguide-based, 36 degree-rotated, Y-cut, X-propagating lithium tantalate (36° YX LiTaO₃) Love wave sensor. The Love wave velocity was significantly reduced by the added gold layer, and the flow of wave energy into the waveguide layer from the substrate was enhanced. By using the double-layer structure, almost a 72-fold enhancement in the sensitivity coefficient was achieved compared to the monolayer structure. Additionally, the thickness of the SiO₂ layer was also reduced with the application of the gold layer, resulting in easier device fabrication. This study allows for the possibility of designing and realizing robust Love wave sensors with high sensitivity and a low limit of detection.


L-[3H]Carnosine binding in the olfactory bulb. II. Biochemical and biological studies.
During the first 10 days after peripheral deafferentation of the mouse olfactory bulb stereoselective binding of L-[3H]carnosine declines markedly. The initial phase of this decline is due to a decrease in binding site stereoselectivity, which is then followed by a loss of assayable binding sites. The specificity of inhibition of L-[3H]carnosine binding by various peptides is also altered after denervation. Competitive inhibitors of carnosine binding become less potent after denervation, while analogues which are not competitive inhibitors remain equipotent before and after denervation. Several carnosine analogues that are normally poor inhibitors become more potent after denervation. Treatment of bulb membranes with trypsin, RNase and hyaluronidase, but not DNase or collagenase, resulted in significant alterations in carnosine binding. L-, but not D-carnosine, protected the binding site from trypsin digestion, and induced additional binding in bulb membranes in a dose-and temperature-dependent fashion. Preincubation of membranes with L-carnosine also led to the induction of additional carnosine binding in membranes from cerebral cortex, cerebellum and deafferentated bulbs but not from muscle. Bulbs from newborn mice contain about one-half of the adult levels of binding and no significant sex differences in carnosine binding were detected in bulbs from adult rats. L-[3H]carnosine binding was two-fold higher in the anterior compared to the posterior portion of the bulb, but there were no significant differences in binding of opiate, GABA, alpha-adrenergic, muscarinic cholinergic, benzodiazepine of glutamic acid receptor ligands.


Detection of reversible and irreversible changes of erythrocyte osmotic fragility induced by Yoshida tumor cells in rats.
A coil planet centrifuge (CPC) is an apparatus for the dynamic measurement of erythrocyte osmotic fragility, and it was applied to the observation of altered erythrocyte osmotic fragility induced by Yoshida tumor cells. The osmotic fragility of erythrocytes directly collected from the vein passing through the site of tumor inoculation began to increase from day 4 post-inoculation, whereas the osmotic fragility of the erythrocytes collected from the vein through the tumor-free (normal) region of the same animal remained normal until day 8 post-inoculation. This discrepancy in osmotic fragility suggests the presence of a plasma factor which recovers the altered erythrocyte membrane, the hypothesis being strongly supported by the results of our in vitro experiments. On day 10 post-inoculation, osmotically fragile erythrocytes failed to respond to the plasma treatment in vitro, suggesting that an irreversible change had occurred on the erythrocyte membranes.


Polysaccharides in contact lenses: From additives to bulk materials.
As the number of applications has increased, so has the demand for contact lenses comfort. Adding polysaccharides to lenses is a popular way to enhance comfort for wearers. However, this may also compromise some lens properties. It is still unclear how to balance the variation of individual lens parameters in the design of contact lenses containing polysaccharides. This review provides a comprehensive overview of how polysaccharide addition impacts lens wear parameters, such as water content, oxygen permeability, surface wettability, protein deposition, and light transmittance. It also examines how various factors, such as polysaccharide type, molecular weight, amount, and mode of incorporation into lenses modulate these effects. Polysaccharide addition can improve some wear parameters while reducing others depending on the specific conditions. The optimal method, type, and amount of added polysaccharides depend on the trade-off between various lens parameters and wear requirements. Simultaneously, polysaccharide-based contact lenses may be a promising option for biodegradable contact lenses as concerns regarding environmental risks associated with contact lens degradation continue to increase. It is hoped that this review will shed light on the rational use of polysaccharides in contact lenses to make personalized lenses more accessible.


Convolutional neural network assistance significantly improves dermatologists' diagnosis of cutaneous tumours using clinical images.
Convolutional neural networks (CNNs) have demonstrated expert-level performance in cutaneous tumour classification using clinical images, but most previous studies have focused on dermatologist-versus-CNN comparisons rather than their combination. The objective of our study was to evaluate the potential impact of CNN assistance on dermatologists for clinical image interpretation. A multi-class CNN was trained and validated using a dataset of 25,773 clinical images comprising 10 categories of cutaneous tumours. The CNN's performance was tested on an independent dataset of 2107 images. A total of 400 images (40 per category) were randomly selected from the test dataset. A fully crossed, self-control, multi-reader multi-case (MRMC) study was conducted to compare the performance of 18 board-certified dermatologists (experience: 13/18 ≤ 10 years; 5/18>10 years) in interpreting the 400 clinical images with or without CNN assistance. The CNN achieved an overall accuracy of 78.45% and kappa of 0.73 in the classification of 10 types of cutaneous tumours on 2107 images. CNN-assisted dermatologists achieved a higher accuracy (76.60% vs. 62.78%, P < 0.001) and kappa (0.74 vs. 0.59, P < 0.001) than unassisted dermatologists in interpreting the 400 clinical images. Dermatologists with less experience benefited more from CNN assistance. At the binary classification level (malignant or benign), the sensitivity (89.56% vs. 83.21%, P < 0.001) and specificity (87.90% vs. 80.92%, P < 0.001) of dermatologists with CNN assistance were also significantly improved than those without. CNN assistance improved dermatologist accuracy in interpreting cutaneous tumours and could further boost the acceptance of this new technique.


A semi-automatic method of measuring leucocyte movement.
A semi-automatic system has been developed for measuring the migration of leucocytes within a micropore filter. The distance in micrometers is displayed digitally or analysed on-line by a digital computer. These improvements have resulted in considerable saving in time, permitting the full potential of the micropore method to be utilised. To illustrate this technique we report results from experiments to measure dose-response relationships of leucocytes to casein and the variation in response to Staphylococcus aureus and casein of cells from normal human subjects.


Effect of prolonged treatment with adrenergic neuron blocking drugs on sympathoadrenal reactivity in rats.
The effects of repeated high doses of the adrenergic neuron blocking drug guanethidine or a hexahydropyrazinoindole compound (2-guanyl-1,2,3,10,10a, hexahydro-1,2,a-pyrazinoindole, EMD 21192) (30 mg/kg i.p., 21.5 mg/kg i.p. respectively, equimolar doses) on sympathoadrenal activity were investigated in normotensive adult rats. During treatment for 5 weeks with either guanethidine or EMD 21192 the systemic blood pressure fell steadily. Noradrenaline content in the heart and vas deferens were decreased markedly by guanethidine and to a much less degree by EMD 21192. EMD 21192 markedly lowers the catecholamine content of the adrenal medulla, presumably as a result of inhibition of dopamine-beta-hydroxylase. The plasma catecholamine concentrations reflected the different sites of action of the drugs in the sympathoadrenal system, i.e. guanethidine mainly reduced circulating norepinephrine and dopamine-beta-hydroxylase by more than 50%, whereas EMD 21192 decreased considerably by the total catecholamines (mainly epinephrine) without altering significantly in the plasma norepinephrine. Disappearance or reduction of fluorescent nerve endings in the iris and the heart and a decrease of the intensity of fluorescence in chromaffin cells of the adrenal gland caused by the drugs were consistent with the biochemical alteration. Whereas the repeated doses of guanethidine caused degeneration of sympathetic nerves, destruction of adrenergic neurons was not found after prolonged treatment with EMD 21192.


The role of medicinal plants in the treatment of diabetes: a systematic review.
Diabetes is a serious metabolic disorder and plenty of medical plants are used in traditional medicines to treat diabetes. These plants have no side effects and many existing medicines are derived from the plants. The purpose of this systematic review is to study diabetes and to summarize the available treatments for this disease, focusing especially on herbal medicine. Required papers about diabetes and effective plants were searched from the databases, including Science direct, PubMed, Wiley, Scopus, and Springer. Keywords in this study are "medicinal plants", "diabetes", "symptom", "herbal", and "treatment". Out of the 490 collected articles (published in the period between 1995 and 2015), 450 were excluded due to non-relevance or lack of access to the original article. Diabetes is mainly due to oxidative stress and an increase in reactive oxygen species that can have major effects. Many plants contain different natural antioxidants, in particular tannins, flavonoids, C and E vitamins that have the ability to maintain β-cells performance and decrease glucose levels in the blood. According to published results, it can be said that medical plants are more affordable and have less side effects compared synthetic drugs, and are more effective in treatment of diabetes mellitus.


In vitro protein splicing of purified precursor and the identification of a branched intermediate.
Protein splicing is a posttranslational processing event in which an internal polypeptide is excised from a protein precursor and the terminal polypeptides are then ligated together, resulting in the production of two proteins. This report presents direct evidence for protein splicing by demonstrating in vitro splicing of purified precursor that accumulated when the protein splicing element from Pyrococcus DNA polymerase was cloned into a foreign gene. In vitro splicing was temperature and pH dependent. A slowly migrating species exhibited kinetic properties of a splicing intermediate and was shown to be a branched molecule by N-terminal sequencing. The precursor and slowly migrating species were interconvertible in response to pH shifts.


A retrospective service audit of a mobile physiotherapy unit on the PGA European Golf Tour.
A 2-year retrospective audit was conducted to evaluate injury diagnosis and treatment provision from a mobile physiotherapy unit serving the Professional Golf Association (PGA) European Tour. Across two competitive seasons (2005/06), service data was collected at 36 tournaments (18 in 2005 and 18 in 2006). Service at each tournament was from Tuesday to Sunday, and equated to 216 days in total. Each approach made to the unit throughout this time was anonymously recorded as either i) a 'contact' where an injury diagnosis and/or treatment was provided, or ii) a 'non-contact' where no service was administered and players used the on-board fitness suite. Across the audit period a total of 7430 approaches were made to the unit, equating to 206 per event or 34 per service day. From all approaches 6705 'contacts' were documented with 2328 injuries recorded. A total of 9933 separate treatments were administered equating to 276 per event or 46 per day. Non-contacts equated to 725, representing only 9.8% of all approaches. Of the 2328 reported injuries, 66.6% (1551) were back-related, with 16.6% (385) and 16.8% (392), being related to upper and lower limbs, respectively. Of the 9933 treatments, 71.3% (7087) related to massage (40.7%), manipulation (15.6%) and stretching therapies (15.0%). As an overall trend, the total number of injury diagnoses and treatments increased across the 2-year period. The number of reported injuries rose by 25.6% (2005 = 1032; 2006 = 1296), whilst treatments rose by 17.2% (2005 = 4575; 2006 = 5359). This retrospective audit provides a valuable insight into a servicing mobile physiotherapy unit on a professional sporting tour. Findings reveal the specific type and location of injuries encountered by PGA European Tour players as well as the range of treatments administered. In developing effective support services to the professional player on tour, data presented will allow for a more structured injury management system based of typical injury occurrence and treatment provision.


Ultrasound-induced gelation of a giant macrocycle.
A 68-membered macrocycle undergoes ultrasound-induced supramolecular gelation in acetonitrile. The sonogel shows a remarkable thermostability, indicating that self-assembly is mediated by exceptionally robust non-covalent interactions. Model compounds indicate that the macrocyclic topology is essential for gelation to occur.


Diep Flap Volume Augmentation: Literature Review and "Calzone" Flap Shaping Technique.
Breast reconstruction with DIEP flap is a well-accepted and well-established technique for autologous breast reconstruction. In the past, this reconstructive option was typically offered to a limited group of patients as previous surgeries or low BMI were considered to be an obstacle to the success of the procedure or for the achievement of a satisfactory cosmetic outcome due to the lack of available tissue. Nowadays, this does not correspond to truth anymore and DIEP flaps are performed routinely on slender patients and on women who have undergone previous liposuction or abdominal surgeries. This paper analyzes current surgical options for volume recruitment in patients with scanty abdominal tissue or with abdominal scars and presents our standardized approach for DIEP volume augmentation with the "Calzone style" bipedicled DIEP flap.


Evidence for synergism between copper and prostaglandin E2 in stimulating the release of gonadotropin-releasing hormone from median eminence explants: Na+/Cl- requirements.
Copper (Cu) and PGE2 are known to stimulate LHRH release from explants of the median eminence area (MEA) by two mechanisms distinguishable by their Ca2+ dependence. Moreover, exposure to Cu and PGE2 results in an amplified release of LHRH which is partially Ca2+ dependent, thus, resembling the release process stimulated by PGE2 alone. We have shown that LHRH release stimulated by Cu alone is Na+/Cl- dependent. By defining the Na+/Cl- dependence of PGE2- and Cu/PGE2-stimulated release of LHRH, we wished to ascertain if there is synergism between Cu and PGE2 actions. MEA of adult male rats were incubated for 5 min with 150 microM Cu and then for 15 min with 10 microM PGE2 (Cu/PGE2). Controls were incubated with Cu or PGE2. LHRH release into the medium was evaluated by RIA. Substituting Cl- in the incubation buffer with the non-permeant anion, isethionate, did not alter PGE2 stimulation of LHRH release, but it drastically inhibited Cu/PGE2 stimulation of LHRH release, indicating that this process requires a permeant monovalent anion. PGE2 and Cu/PGE2 stimulation of LHRH release were both inhibited when Na+ was substituted with Li+, or when 0.5 mM ouabain was included in the Na+-containing buffer; neither 10 microM tetrodotoxin (TTX) nor 100 microM amiloride were inhibitory. To ascertain if Na+ is required for Cu uptake, we evaluated the uptake of 67Cu by MEA explants and found that neither ouabain nor Li+ inhibited uptake, indicating that the extracellular Na+ and the activity of Na+/K+ ATPase are required for the process of LHRH release.(ABSTRACT TRUNCATED AT 250 WORDS)


Demonstration of substances immunologically related to the identified arthropod neuropeptides AKH/RPCH in the CNS of several invertebrate species.
The occurrence of adipokinetic hormone (AKH) and red pigment concentrating hormone (RPCH)-like neuropeptides in the central nervous system of different invertebrate species other than insects was investigated immunocytochemically with polyclonal antisera to N- and C-terminal regions of the AKH molecule. Substances reacting with the C-terminal specific antiserum code 241 were present in neurons of the pond snail, Lymnaea stagnalis, the sowbug Porcellio scaber, the centiped Lithobius forficatus and the crayfish Astacus leptodactylus. Substances revealed by the N-terminal specific antiserum code 433 were demonstrated in the latter two species. The distribution of immunoreactive substances in neuropile areas of several ganglia suggests that these substances act as neurotransmitter/neuromodulator. Their presence in neurohemal organs such as the periphery of the pedal and visceral nerves in the pond snail and in the sinus gland of the crayfish suggests a neurohormonal role in these species.


Intravitreal aflibercept for myopic choroidal neovascularization.
To assess the use of aflibercept for the treatment of subfoveal myopic choroidal neovascularization (CNV). Thirty-two patients (33 eyes) with myopic subfoveal CNV were consecutively enrolled in this prospective open-label case series. All patients were treated with an off-label 2-mg intravitreal injection of aflibercept. After the first injection, administration of aflibercept followed an "on demand" pro re nata (PRN) regimen. The primary outcome was change in best-corrected visual acuity (BCVA) score after 12 months. Mean follow-up was 12 months, and the median number of aflibercept injections was 2.0 (range 1-4). Overall, mean BCVA improved from 0.59 ± 0.37 logMAR at baseline to 0.38 ± 0.33 logMAR at 12 months, a change of -0.21 ± 0.23 logMAR (p < 0.0001), and from 70.5 ± 18.5 to 81.1 ± 16.4 letters, a change of 10.6 ± 11.4 (p < 0.0001). Improvements were similar among patients irrespective of previous PDT. The Increase in BCVA was greater in younger patients (aged < 50 years) and those with baseline BCVA of ≤ 75 letters. Intravitreal aflibercept in a PRN regimen is effective for the treatment of myopic CNV, with no apparent short-term safety effects. Treated eyes had BCVA gains after 12 months, with a median of two injections.


[Phenotype structure and its dynamics at different stages of the reproductive period of Proteocephalus osculatus (Cestoda: Proteocephalidae)--a parasite of catfish (Silurus glanis L.)].
Discrete variability of four P. osculatus characteristics descriptive of cestodes' major functional complexes: attachment and trophic-reproduction, was determined. Phenotypic diversity of P. osculatus from 2 samples collected at different stages of the population reproductive period was analysed. Unequal adaptation of phenotypes to the ambient conditions was hypothesised.


Force measurements of Myosin II waves at the yolk surface during Drosophila dorsal closure.
The mechanical properties and the forces involved during tissue morphogenesis have been the focus of much research in the last years. Absolute values of forces during tissue closure events have not yet been measured. This is also true for a common force-producing mechanism involving Myosin II waves that results in pulsed cell surface contractions. Our patented magnetic tweezer, CAARMA, integrated into a spinning disk confocal microscope, provides a powerful explorative tool for quantitatively measuring forces during tissue morphogenesis. Here, we used this tool to quantify the in vivo force production of Myosin II waves that we observed at the dorsal surface of the yolk cell in stage 13 Drosophila melanogaster embryos. In addition to providing for the first time to our knowledge quantitative values on an active Myosin-driven force, we elucidated the dynamics of the Myosin II waves by measuring their periodicity in both absence and presence of external perturbations, and we characterized the mechanical properties of the dorsal yolk cell surface.


Microbial epoxide hydrolases for preparative biotransformations.
Epoxide hydrolases from microbial sources are highly versatile biocatalysts for the asymmetric hydrolysis of epoxides on a preparative scale. Besides kinetic resolution, which furnishes the corresponding vicinal diol and remaining non-hydrolysed epoxide in nonracemic form, enantioconvergent processes are possible: these are highly attractive as they lead to the formation of a single enantiomeric diol from a racemic oxirane. The data accumulated over recent years reveal a common picture of the substrate structure selectivity pattern of microbial epoxide hydrolases and indicate that substrates of various structural types can be selectively hydrolysed with enzymes from certain microbial sources.


Deconvolution by omission libraries.
Omission libraries, synthesized by omitting one amino acid in all coupling positions, are very efficient tools for the rapid identification of the amino acid components of bioactive peptides. Based on the determined amino acids, an occurrence library can be defined and prepared which is much less complex than the full one while still comprising the bioactive peptide.


The effects of thyroxine on metabolism and water balance in a desert-dwelling rodent, Merriam's kangaroo rat (Dipodomys merriami).
Desert-dwelling mammals such as Merriam's kangaroo rat (Dipodomys merriani) need to conserve both energy and water to survive desert conditions characterized by aridity and low productivity. The thyroid hormone thyroxine increases both basal metabolic rate and urinary water loss in mammals. Increases in basal metabolism and urinary water loss are likely to be detrimental to D. merriami, therefore the regulation of this hormone may be important. To examine the effects of thyroxine in this species, we implanted adult kangaroo rats with pellets designed to release specific doses of thyroxine at a constant rate for 90 days or a placebo pellet. We measured plasma thyroxine concentration, basal metabolic rate, food consumption, urine concentration and water loss in all implanted animals. Thyroxine implants significantly increased both plasma thyroxine and basal metabolic rate in a relatively dose-dependent manner. In response to thyroxine. kangaroo rats increased food consumption only slightly, but this small increase was sufficient to compensate for their elevated metabolic rates. Neither urine concentration nor water loss varied among treatment groups. Thyroxine increased energy expenditure but not water loss in this species.


Revising the radiobiological model of synchronous chemotherapy in head-and-neck cancer: a new analysis examining reduced weighting of accelerated repopulation.
Previous studies of synchronous chemoradiation therapy have modeled the additional effect of chemotherapy as additional radiation therapy biologically effective dose (BED). Recent trials of accelerated versus conventional fractionation chemoradiation have cast doubt on such modeling. The purpose of this study was to identify alternative models. Nine trials of platinum-based chemoradiation were identified. In radiation therapy-alone arms, the radiation therapy BED for tumor was calculated using standard parameters. In chemoradiation arms, 3 methods were used to calculate tumor BED (tBED): additional BED, addition of 9.3 Gy BED for tumor to the radiation therapy BED; zero repopulation, BED with no correction for repopulation; variable t(p) (the average doubling time during accelerated repopulation), values of t(p) 3-10 were used to examine a partial suppression of repopulation. The correlations between the calculated percentage change in tBED for each method and observed percentage change in local control were assessed using the Pearson product moment correlation. Significant correlations were obtained for all 3 methods but were stronger with zero repopulation (P=.0002) and variable tp (t(p) = 10) (P=.0005) than additional BED (P=.02). Radiobiological models using modified parameters for accelerated repopulation seem to correlate strongly with outcome in chemoradiation studies. The variable tp method shows strong correlation for outcome in local control and is potentially a more suitable model in the chemoradiation setting. However, a lack of trials with an overall treatment time of more than 46 days inhibits further differentiation of the optimal model.


Can we quantify the aquatic environmental plastic load from aquaculture?
Aquaculture provides livelihoods for hundreds of millions of people, but it also forms a significant source of plastic litter that poses a serious hazard to aquatic ecosystems. How to assess and subsequently manage plastic loads from aquaculture is a pending and pressing issue for aquaculture sustainability, and an important concern for water environment monitoring and management. In this study, we developed the first framework for estimating plastic litter from aquaculture by combining data from satellite remote sensing, drones, questionnaires, and in situ measurements. By acquiring multidimensional (human and nature) and multiscale (centimeter to basin scale) data, this framework helped us understand the aquaculture farming patterns and its spatial and temporal evolution, and thus estimate the plastic load it generates and suggest effective management approaches. Applying this framework, we assessed the marine plastic load from oyster floating raft farming in the Maowei Sea, a typical mariculture bay in China, with an increasing farming area. Approximately 3840 tons of plastic waste is expected to be discharged into the sea in the next four years (the average service life of a floating raft) without improvements in aquaculture waste management. Strengthening governance, timely plastic removal, innovative replacement, and transforming farmers' behavior patterns are recommended as the subsequent measures for plastic management. This framework can be extended to other regions and other aquaculture patterns, and is applicable to local, regional, and global aquaculture plastic litter assessments. It is a source-based method for evaluating plastic pollution that is more conducive to subsequent plastic management than traditional post-contamination environmental monitoring. In the context of the global expansion of mariculture and the global commitment to action to combat plastic pollution, this approach could play a critical role in the investigation and management of plastic waste in aquatic environments.


Voltage-gated optics and plasmonics enabled by solid-state proton pumping.
Devices with locally-addressable and dynamically tunable optical properties underpin emerging technologies such as high-resolution reflective displays and dynamic holography. The optical properties of metals such as Y and Mg can be reversibly switched by hydrogen loading, and hydrogen-switched mirrors and plasmonic devices have been realized, but challenges remain to achieve electrical, localized and reversible control. Here we report a nanoscale solid-state proton switch that allows for electrical control of optical properties through electrochemical hydrogen gating. We demonstrate the generality and versatility of this approach by realizing tunability of a range of device characteristics including transmittance, interference color, and plasmonic resonance. We further discover and exploit a giant modulation of the effective refractive index of the gate dielectric. The simple gate structure permits device thickness down to ~20 nanometers, which can enable device scaling into the deep subwavelength regime, and has potential applications in addressable plasmonic devices and reconfigurable metamaterials.


Simple sonochemical synthesis and characterization of HgSe nanoparticles.
Mercury selenide (HgSe) nanostructures were synthesized via a sonochemical method based on the reaction between HgCl(2), SeCl(4) and hydrazine hydrate (N(2)H(4)·H(2)O) in water, in presence of various capping agents. The effects of preparation parameters such as: the kind of capping agent and its amount, ultrasonic power, reaction time and temperature were investigated. It was found that morphology, particle size and phase of the products could be greatly affected by these parameters. HgSe nanostructures were characterized by X-ray powder diffraction (XRD), transmission electron microscopy (TEM), scanning electron microscopy (SEM), photoluminescence spectroscopy (PL) and X-ray energy dispersive spectroscopy (EDS).


The impact of physical and psychological comorbid conditions on the quality of life of patients with acute myocardial infarction: a multi-center, cross-sectional observational study from Turkey.
Acute myocardial infarction (MI) has significant and detrimental effects on the lifestyles of the patients. It has been shown that quality of life (QoL) in patients with MI is impaired in every aspect. This study aims to evaluate the impact of depression and physical comorbidity on QoL in Turkish patients with acute first MI. This multi-center cross-sectional study was carried out in 15 centers with 998 patients hospitalized for acute first MI. For detection of depression, Beck Depression Inventory (BDI) was used. For evaluation of QoL, World Health Organization Quality of Life Questionnaire (WHOQOL) was applied. The mean age of the patients was 57.5 +/- 10.1 years and 79.2 % (n = 792) of the patients were men. Patients with comorbid depression (BDI > or = 10) and comorbid medical conditions, and female patients had significantly lower scores in every domain of WHOQOL. In the regression analysis model, female gender, low education, comorbid medical conditions, especially comorbid hypertension, and BDI score were found to have a significant effect on the domains of WHOQOL. Female patients are more prone to impairment in quality of life after myocardial infarction. Both comorbid medical conditions and depression have a significant impact on the impairment of QoL in Turkish patients with acute MI. In order to improve the subjective wellbeing of post MI patients, both psychiatric and physical comorbidities must be detected and managed even in the short-term.


Preparation and characterization of nanostructured lipid carriers as drug delivery system: Influence of liquid lipid types on loading and cytotoxicity.
In this study, we aimed to investigate the influence of liquid lipid types on different features of NLC. Four variations of liquid lipids such as coconut oil, fish oil, black seed oil and linseed oil were used, while for all variations, cetyl palmitate was used as the solid lipid. Different NLC were characterized and compared in terms of particle size, zeta potential, polydispersity index (PDI), drug entrapment percentage and drug loading capacity. The results indicated that NLC containing black seed oil has the smallest size. Other features like PDI, zeta potential and entrapment efficiency were the same for all the liquid lipids. By close margins, the NLC containing black seed oil had the highest percent of drug release and antioxidant activity compared to the rest. Diffusion was the major mechanism of the drug release according to the drug release kinetic fitted by Higuchi's model. Differential scanning calorimetry (DSC) and fourier transform infrared spectroscopy (FT-IR) confirmed no strong interaction between NLC constituents. The particles showed spherical shape morphology under atomic force microscopy (AFM). According to the cell viability assay on MCF-7 cell line, the curcumin loaded NLC composed of linseed oil showed better cytotoxic activity compared to the free curcumin.


Short implants versus bone grafting and standard-length implants placement: a systematic review.
The aim of this study was to conduct a systematic review to compare the survival rates between short implants (length < 10 mm) versus standard-length implants (≥ 10 mm) inserted in grafted bone. As secondary outcomes, marginal bone loss and survival rates of the implant supported prostheses were also analysed. Randomised controlled trials (RCT) that compared both techniques were searched on three electronic databases till June 2016, a manual search was performed on the bibliography of the collected articles, and the authors were contacted for additional references. The estimates of the interventions were expressed in relative risk (RR), mean implant survival rates and mean differences in marginal bone. Eight RCTs were included in this study. From a total of 458 short implants, 15 failed (mean survival rates = 96.7%), While from 488 regular implants, 13 failed (mean survival rates = 97.3%). The technique did not significantly affect: the implant failure rate (P > 0.05), with RR of 1.34 (95% CI 0.67-2.87), the mean differences of marginal bone loss (P = 0.18; MD - 0.04 mm [- 0.10; 0.02] 95% CI), at loading or prosthesis failures rates (RR:0.98; 95% CI 0.40-2.41). The mean differences of marginal bone at 1 year follow-up (post loading) presented significant marginal changes in the short implant group (P = 0.002; MD - 0.10 mm [- 0.16; - 0.03] 95% CI) although a significant high heterogeneity was found between groups. This systematic review suggests no difference between both techniques in the treatment of atrophic arches. However, more long-term RCTs are needed to evaluate the predictability at the long run. The use of short implants might be considered an alternative treatment, since it usually requires fewer surgical phases and tends to be a more affordable option.