Promoting independence in residential care: successful recruitment for a randomized controlled trial.
To describe the recruitment strategy and association between facility and staff characteristics and success of resident recruitment for the Promoting Independence in Residential Care (PIRC) trial. Cross-sectional study of staff and facility characteristics and recruitment rates within facilities with calculation of cluster effects of multiple measures. Staff of low-level dependency residential care facilities and residents able to engage in a physical activity program in 2 cities in New Zealand. A global impression of staff willingness to facilitate research was gauged by research nurses, facility characteristics were measured by staff interview. Relevant outcomes were measured by resident interview and included the following: (1) Function: Late Life FDI scale, timed-up-and-go, FICSIT balance scale and the Elderly Mobility Scale; (2) Quality of Life: EuroQol quality of life scale, Life Satisfaction Index; and (3) falls were assessed by audit of the medical record. Correlation between recruitment rates, facility characteristics and global impression of staff willingness to participate were investigated. Design effects were calculated on outcomes. Forty-one (85%) facilities and 682 (83%) residents participated, median age was 85 years (range 65-101), and 74% were women. Participants had complex health problems. Recruitment rates were associated (but did not increase linearly) with the perceived willingness of staff, and were not associated with facility size. Design effects from the cluster recruitment differed according to outcome. The recruitment strategy was successful in recruiting a large sample of people with complex comorbidities and high levels of functional disability despite perceptions of staff reluctance. Staff willingness was related to recruitment success.


Detailed analysis of the S-RESPDOR solid-state NMR method for inter-nuclear distance measurement between spin-1/2 and quadrupolar nuclei.
We present a detailed analysis of the Symmetry-based Resonance-Echo Saturation-Pulse DOuble-Resonance (S-RESPDOR) method in order to measure the inter-nuclear distances between spin-1/2 and quadrupolar nuclei. This recently introduced sequence employs a symmetry-based recoupling scheme on the observed spin-1/2 channel and a saturation pulse on the quadrupolar channel. This method requires a low radio-frequency (rf) field, is compatible with high MAS frequency and allows a rapid determination of inter-nuclear distances by fitting the experimental signal fraction to an analytical expression. Here, we analyze in detail the influence of the various experimental and spin-interaction parameters on the S-RESPDOR signal fraction and the measured distance. We show that the S-RESPDOR signal fraction only depends on the quadrupole interaction and the inter-nuclear distance. We demonstrate that the required rf-field on the quadrupolar channel is smaller than that required for an adiabatic-passage pulse in REAPDOR-type experiments. The only limitation of the method is the requirement of accurate rotor synchronization between the two parts of the dipolar recoupling sequences. Using S-RESPDOR, we have quantitatively measured a (31)P-(51)V distance of 357 pm in a mono-vanadium-substituted polyoxo-tungstate, K(4)PVW(11)O(40), from the Keggin family and a (13)C-(67)Zn distance of 286 pm in [80%-(67)Zn]zinc [1-(13)C]acetate. These results show that S-RESPDOR can be employed in the challenging cases of quadrupolar nuclei exhibiting a high spin number and either large chemical-shift anisotropy ((51)V) or low gyromagnetic ratio ((67)Zn).


Carotid Revascularization Improves Cognitive Function in Patients with Asymptomatic Carotid Artery Stenosis.
To investigate cognitive changes after carotid revascularization in elderly patients with asymptomatic carotid artery stenosis. We also compared cognitive outcomes of carotid endarterectomy CEA with stenting in asymptomatic patients. From April 2019 to December 2019, patients with ≥70% asymptomatic carotid stenosis who were treated with CEA or CAS, were recruited for this study. The Montreal cognitive assessment (MoCA) instrument was used to evaluate cognitive function preoperatively and postoperatively at 3, 6, and 12 months. The incidence of ipsilateral ischemic cerebrovascular events and restenosis were analyzed within 12 months. In 50 patients treated with CEA or carotid artery stenting CAS, baseline cognitive function was not different between CEA and CAS groups (P > 0.05). There was no difference in the incidence of ipsilateral ischemic cerebrovascular events and restenosis within the first 12 months between the two groups. There was a significant improvement in the total MoCA score, scores of attention, and delayed recall at 3, 6 and 12 months after revascularization compared with scores at baseline (all P < 0.001). At 12 months, scores of cube copying and clock drawing were significantly improved (P = 0.014, P = 0.020). The clock drawing score was improved at 12 months after CAS compared with CEA (P = 0.040). Carotid revascularization has a beneficial effect on cognition in asymptomatic patients within 12 months of the procedure. Compared with CEA, CAS show improved test scores of executive functioning by 1 year.


Restoring soil quality and carbon sequestration potential of waterlogged saline land using subsurface drainage technology to achieve land degradation neutrality in India.
Subsurface drainage (SSD) has been proved to be an effective technology to reclaim waterlogged saline soils. Three SSD projects were implemented in Haryana, India in 2009, 2012 and 2016 to study the long term effect of SSD (10, 7 and 3 years) operation on restoring productivity and carbon sequestration potential of degraded waterlogged saline soils under prevalent rice-wheat cropping system. These studies indicated that successful operation of SSD improved soil quality parameters such as bulk density, BD (from 1.58 to 1.52 Mg m-3), saturated hydraulic conductivity, SHC (from 3.19 to 5.07 cm day-1); electrical conductivity, ECe (from 9.72 to 2.18 dS m-1), soil organic carbon, OC (from 0.22 to 0.34 %), dehydrogenase activity, DHA (from 15.44 to 31.65 μg g-1 24 h-1), and alkaline phosphatase, ALPA (from 16.66 to 40.11 μg P-NP g-1 h-1) in upper soil surface (0-30 cm). The improved soil quality resulted in increased rice-wheat system yield (rice equivalent yield) by 328 %, 465 % and 665 % at Kahni, Siwana Mal and Jagsi sites, respectively. Studies also revealed that carbon sequestration potential of degraded land increased with the implementation of SSD projects. The principal component analysis (PCA) showed that % OC, ECe, ALPA, available N and K content were the most contributing factor for soil quality index (SQI). The overall result of the studies showed that SSD technology holds great potential to improve soil quality, increase crop productivity, farmers' income and ensure land degradation neutrality and food security in waterlogged saline areas of western Indo Gangetic Plain of India. Hence, it can be concluded that large scale adoption of SSD may fulfill the promise "No poverty, Zero hunger, and Life on land" sustainable development goals of United Nation in degraded waterlogged saline areas.


Effects of Monomer Composition of Urethane Methacrylate Based Resins on the C=C Degree of Conversion, Residual Monomer Content and Mechanical Properties.
(1) Background: This study investigated the influence of Bis-GMA, TEGDMA, UDMA, and two different polyethylene glycol (PEG)-containing, UDMO-based co-monomers on the Young's modulus and flexural strength, degree of methacrylate C=C double bond conversion and residual monomer elution of experimental dental resins. (2) Methods: Urethane methacrylate-based monomer was synthesised via a radical chain growth polymerization mechanism using PEG in order to improve the mechanical properties. Dental resins were formulated using Bis-GMA, UDMA, or UDMO as base monomers combined with TEGDMA as a dilution monomer and DMAEM + CQ as the photo-initiator system. Degree of conversion (DC), mechanical properties, and residual monomer content of light-activated methacrylate resin formulations were evaluated and statistically analysed by ANOVA and a Tukey's test. (3) Results: PEG-containing UDMO resins had lower Young's modulus and elastic strength than UDMA-derived resin for all irradiation times. The highest DC (67,418%) was observed for the PEG-containing UDMO-based resin formulation when light cured for 40 s. For all samples, DC increased with the photo-polymerization time. The amount of residual monomer decreased after increasing the light-curing period from 20 to 40 s, resin with UDMO content 0.01 mol of PEG having the smallest amount of free eluted monomer. (4) Conclusions: A strong structure-property relationship exists in photo-cured dimethacrylate-based dental resins. The time and quantity of the photochemical initiation system can influence the physical-mechanical properties of the resins but also the monomers in their composition.


Synthesis and characterization of a multi-sensitive polysaccharide hydrogel for drug delivery.
Salecan is a novel water soluble polysaccharide produced by a salt-tolerant strain Agrobacterium sp. ZX09. Poly(dimethylaminoethyl methacrylate) (PDMAEMA) is a pH, thermo, and ionic strength multi-sensitive polymer with anti-bacterial property. Here, we report a semi-interpenetrating polymer network (semi-IPN) hydrogel based on salecan and PDMAEMA. The obtained hydrogel is simultaneous sensitive to pH, ionic strength and temperature: the swelling ratio maximizes at pH 1.2 and shrinks at pH value greater than 3; besides, water content of the hydrogel decreases as the ionic strength increases; in terms of temperature, the hydrogel swells/deswells at temperatures below/above 40°C. Cytotoxicity test shows the hydrogel is non-cytotoxic to COS-7 cells. Protein drug insulin was selected as model drug to test the in vitro release behavior of the hydrogel. Results show the release rate increases with the swelling ratio of the hydrogel. In addition, when the temperature is higher than the lower critical solution temperature (LCST) of PDMAEMA, the hydrogel shrinks to extrude more drug molecules. Moreover, the release rate and release amount were higher in acid condition (pH 1.2) than at pH 7.4. In summary, this polysaccharide hydrogel is a promising material for drug delivery.


Lower serum 15-HETE level predicts nasal ILC2 accumulation during COX-1 inhibition in AERD.
Aspirin-exacerbated respiratory disease (AERD) is associated with high levels of cysteinyl leukotrienes, prostaglandin D2, and low levels of prostaglandin E2. Further, 15-hydroxyeicosatetraenoic acid (15-HETE) levels may have predictive value in therapeutic outcomes of aspirin desensitization. Accumulation of nasal group 2 innate lymphoid cells (ILC2s) has been demonstrated during COX-1 inhibition in AERD, although the relationships between tissue ILC2 accumulation, reaction symptom severity, and novel lipid biomarkers are unknown. We sought to determine whether novel lipid mediators are predictive of nasal ILC2 accumulation and symptom scores during COX-1 inhibitor challenge in patients with AERD. Blood and nasal scraping samples from patients with AERD were collected at baseline and COX-1 inhibitor reaction and then processed for flow cytometry for nasal ILC2s and serum for lipidomic analysis. Eight patients with AERD who were undergoing aspirin desensitization were recruited. Of the 161 eicosanoids tested, 42 serum mediators were detected. Baseline levels of 15-HETE were negatively correlated with the change in numbers of airway ILC2s (r = -0.6667; P = .0428). Docosahexaenoic acid epoxygenase metabolite 19,20-dihydroxy-4Z,7Z,10Z,13Z,16Z-docosapentaenoic acid (19,20-diHDPA) was positively correlated with both changes in airway ILC2s (r = 0.7143; P = .0305) and clinical symptom scores (r = 0.5000; P = .0081). Low levels of baseline 15-HETE predicted a greater accumulation of airway ILC2s in patients with AERD who were receiving COX-1 inhibition. Further, increases in the cytochrome P pathway metabolite 19,20-dihydroxy-4Z,7Z,10Z,13Z,16Z-docosapentaenoic acid (19,20-diHDPA) were associated with increased symptoms and nasal ILC2 accumulation. Future studies to assess how these mediators might control ILC2s may improve the understanding of AERD pathogenesis.


The complex formed between trypsin and alpha(2)-macroglobulin retains the whole hydrolytic activity for benzoylarginine-p-nitroanilide (DL BAPNA). We have observed that the inhibition of this activity is dependent on the inhibitor used. While soya bean inhibitor (MW = 20 000) is ineffective, the basic pancreatic inhibitor (MW = 6 500) progressively inhibits the complex. In this latter case, we have observed the formation of a very weakly active ternary compound by two methods: kinetic and fluorescence polarization.Such differences suggest either that the contact site of trypsin for binding is not the same for each inhibitor or that the steric hindrance by macroglobulin prevents large inhibitors from reaching the active site. The pancreatic inhibitor can reach this site but its affinity is lower for the complex than for free trypsin.


Synthesis and characterization of polysulfone/graphene oxide nano-composite membranes for removal of bisphenol A from water.
Bisphenol A (BPA) is an emerging contaminant of water resources that disrupts endocrine function. Attempts are continuing to develop cost-effective methods to remove BPA from water environments. The aim of this study was to prepare and characterize polysulfone/graphene oxide nano-composite membranes for removal of BPA from water. Three membranes were synthetized using phase inversion method: polysulfone membrane as PSF and two polysulfone/graphene oxide nano-composite membranes with graphene oxide (GO) weight ratios of 0.4 and 1.0% as PSF/GO 0.4% and PSF/GO 1.0%, respectively. The membrane characteristics including morphology, surface roughness, pore size, zeta potential and presence of functional groups were determined using field emission scanning electron microscopy, atomic force microscopy, streaming potential, and attenuated total reflectance Fourier transform infrared spectroscopy techniques. Inclusion of GO remarkably increased permeate flux of the membranes, so that pure water flux of PSF, PSF/GO 0.4% and PSF/GO 1.0% at operating pressure of 2 bar was determined 226, 449 and 512 L/m2 h, respectively. The membrane PSF/GO 0.4% with the most negative zeta potential (-10.46 mV) and the highest BPA removal efficiency was determined as the optimal membrane. The optimum conditions of input pressure, operating time, initial concentration of BPA, and pH for BPA removal efficiency by PSF/GO 0.4% were determined using surface response methodology to be 1.02 bar, 10.6 min, 7.5 mg/L, and 5.5, respectively. By optimizing the conditions of operating parameters, experimental BPA removal efficiency by PSF/GO 0.4% reached to as high as 93%.


Effect of the odour of female rat urine on plasma testosterone concentrations in male rats.
Testosterone levels were significantly higher in males, regardless of sexual experience, exposed to the odour of urine from females than in those exposed to saline or kept in ordinary groups.


Purification and characterization of thermostable beta-glucosidase from the brown-rot basidiomycete Fomitopsis palustris grown on microcrystalline cellulose.
An extracellular beta-glucosidase was purified 154-fold to electrophoretic homogeneity from the brown-rot basidiomycete Fomitopsis palustris grown on 2.0% microcrystalline cellulose. SDS-polyacrylamide gel electrophoresis gel gave a single protein band and the molecular mass of purified enzyme was estimated to be approximately 138 kDa. The amino acid sequences of the proteolytic fragments determined by nano-LC-MS/MS suggested that the protein has high homology with fungal beta-glucosidases that belong to glycosyl hydrolase family 3. The Kms for p-nitorophenyl-beta-D-glucoside (p-NPG) and cellobiose hydrolyses were 0.117 and 4.81 mM, and the Kcat values were 721 and 101.8 per sec, respectively. The enzyme was competitively inhibited by both glucose (Ki= 0.35 mM) and gluconolactone (Ki= 0.008 mM), when p-NPG was used as substrate. The optimal activity of the purified beta-glucosidase was observed at pH 4.5 and 70 degrees. The F. palustris protein exhibited half-lives of 97 h at 55 degrees and 15 h at 65 degrees, indicating some degree of thermostability. The enzyme has high activity against p-NPG and cellobiose but has very little or no activity against p-nitrophenyl-beta-lactoside, p-nitrophenyl-beta-xyloside, p-nitrophenyl-alpha-arabinofuranoside, xylan, and carboxymethyl cellulose. Thus, our results revealed that the beta-glucosidase from F. palustris can be classified as an aryl-beta-glucosidase with cellobiase activity.


A review of the readmissions of patients with tetraplegia to the Regional Spinal Injuries Centre, Southport, United Kingdom, between January 1994 and December 1995.
Patients with chronic tetraplegia are prone to develop unique clinical problems which require readmission to specialised centres where the health professionals are trained specifically to diagnose, and treat the diseases afflicting this group of patients. An appraisal of the readmission pattern of tetraplegic patients will provide the necessary data for planning allocation of beds for treatment of chronic tetraplegic patients. Hospital records of patients with tetraplegia readmitted to the Regional Spinal Injuries Centre, Southport, UK between 1 January 1994 and 31 December 1995 were analyzed to find out the number of tetraplegic patients who required readmission, reasons for readmission, duration of hospital stay, and mortality among patients readmitted. During the 2-year period, 155 tetraplegic patients were readmitted and 44 of them (28.4%) required more than one readmission (total readmission episodes: 221); these patients occupied 4.5 beds which is equivalent to 11.5% of the total bed capacity of the spinal unit. Among the reasons for the readmissions, evaluation and care of urinary tract disorders topped the list with 96 readmission episodes (43.43%) involving 70 patients; the median hospital stay was 3 days, and 18 patients (26%) required more than one readmission during this period. One hospital bed was occupied by the tetraplegic patients requiring treatment/evaluation of urinary tract disorders. Assessment and treatment of cardio-respiratory diseases was the second most common reason for readmission with 51 readmission episodes pertaining to 27 patients having a median hospital stay of 6 days; 13 patients (48%) were readmitted more than once within this 2-year period. Treatment of cardio-respiratory diseases in chronic tetraplegic patients required 1.2 hospital beds yearly. Only five tetraplegic patients were readmitted for treatment of pressure sore(s); however they had a prolonged hospital stay (median duration: 101 days). Social reasons accounted for 13 readmission episodes concerning nine patients who stayed in the hospital for varying periods (median: 6.5 days; mean: 35 days). Four tetraplegic patients readmitted with acute chest infection expired. An 81 year-old tetraplegic died of myocardial infarction. Urinary sepsis, renal insufficiency, respiratory failure and intra-cerebral haemorrhage accounted for the demise of a 41 year-old tetraplegic patient following surgical removal of a large, impacted stone at the pelviureteric junction. A tetraplegic patient who was admitted with haematuria subsequently underwent cystectomy for squamous cell carcinoma of the urinary bladder; he developed secondaries and expired 5 months later. As more patients with high cervical spinal cord injury survive the initial period of trauma, and as the life expectancy of tetraplegic patients increases, it is likely that greater numbers of tetraplegic patients will be requiring readmission to spinal injuries centre. Although it may be possible to prevent some of the complications of spinal cord injury and hence the need for a readmission, progress in medicine and rehabilitation technology will create additional demands for readmissions of chronic tetraplegic patients in order to implement the newer therapeutic strategies. Thus a change in the pattern of readmission of chronic tetraplegic patients is likely to be the future trend and this should be taken into account while making plans for providing the optimum care to chronic tetraplegic patients.


Adverse effects from the circadian fluctuations of carbamazepine plasma levels.
In children on carbamazepine therapy who were complaining of tiredness it was proposed that the considerable plasma drug level variation over the day could explain this side effect. In spite of a "normal" fasting level the plasma drug level 2-4 hours after drug intake was well above the upper recommended therapeutic level. It is recommended that the time of sampling should be taken into account in carbamazepine drug monitoring.


Performance Evaluation of Automated Immunohematology Analyzer IH-500 for Blood Bank Testing.
The automated immunohematology analyzer IH-500 (Bio-rad, Cressier FR, Switzerland) was developed recently for blood bank tests and this study evaluated performance of IH-500. 200 blood samples for ABO/Rh typing were collected. ABO/Rh typing results measured by IH-500 was compared with conventional manual methods. Antibody screening tests were performed with 100 samples using both IH-500 and the Ortho BioVue System, and results were compared. Antibody identification tests were conducted on 5 samples using both IH-500 and the Ortho BioVue System and results were compared. Crossmatching was performed with both IH-500 and conventional manual tube method using 4 patient serum samples and 10 blood cell donors, and 40 results were compared. Isoagglutinin titer of anti-A and anti-B was determined in 10 samples using both IH-500 and the automated analyzer Ortho AutoVue Innova and concordance rates were obtained. The concordance rates of ABO/Rh typing, antibody screening test, antibody identification test, and crossmatching between comparative manual methods and the IH-500 were all 100%. In the evaluation of isoagglutinin titer, 8 (80.0%) results out of 10 samples (80%) showed results within ± 1 titer between the IH-500 and the AutoVue Innova, which indicates the concordance rates of 80.0%. IH-500 reported results with two titers lower than Ortho AutoVue Innova in two samples. The IH-500 demonstrated good concordance rates and provided reliable results compared to comparative manual methods in the blood bank testing. IH-500 would be useful as a possible replacement for conventionally performed manual methods in blood bank testing.


A 32 key keyboard for the HP PDMS.
The keyboard remains the primary human interface device for existing patient data management systems. The standard bedside keyboard for the Hewlett-Packard PDMS has 16 keys which are used for both numeric data entry and multiple functions, accessed by shift key combinations. We have designed and constructed a 32 key keyboard which speeds single keystroke access to all PDMS functions. The new keyboard is backwards compatible and requires no PDMS software changes. A 32 key keyboard offers many advantages for use with the HP PDMS. The device presented is backwards compatible with the vendor's keyboard and requires no software changes. This keyboard could serve as an updated functional replacement for thousands of keyboards now in use.


A Bayesian Scoring Technique for Mining Predictive and Non-Spurious Rules.
Rule mining is an important class of data mining methods for discovering interesting patterns in data. The success of a rule mining method heavily depends on the evaluation function that is used to assess the quality of the rules. In this work, we propose a new rule evaluation score - the Predictive and Non-Spurious Rules (PNSR) score. This score relies on Bayesian inference to evaluate the quality of the rules and considers the structure of the rules to filter out spurious rules. We present an efficient algorithm for finding rules with high PNSR scores. The experiments demonstrate that our method is able to cover and explain the data with a much smaller rule set than existing methods.


Understanding reactions and pore-forming mechanisms between waste cotton woven and FeCl3 during the synthesis of magnetic activated carbon.
FeCl3 is a valuable iron salt used in the synthesis of magnetic waste cotton woven-based activated carbon. Although it has received extensive research attention, more information is required regarding its interactions with the carbon matrix. This systematic study describes the potential reactions of FeCl3 and waste cotton woven. First, the textural properties of waste cotton woven-based activated carbon synthesized under various conditions were investigated via element analysis, N2 sorption/desorption isotherms, and scanning electron microscopy. Then, the possible reaction mechanisms were deduced through various characterization methods. The results demonstrate that FeCl3 can lower the initial decomposition temperature of WCW to 135 °C and catalyze decarboxylation and decarbonylation at 100-330 °C to elevate the formation of microporous structures. Moreover, FeCl3 can also form Lewis acid sites at 330-700 °C and promote the cross-linking reaction to develop intricate microporous structures and carbonaceous materials with the synergistic effect of Fe3+ and Cl-. FeCl3 could be used as a template-like agent to form mesoporous structures. Meanwhile, it can also act as a magnetizer that Fe3O4 derived from the decomposition of FeCl3 would insert into the carbon matrix and combine with C-Cl to tailor the magnetic controllable activated carbon. Finally, we confirmed that extending the activation time could convert the structure of waste cotton woven-based activated carbon and increase the number of active sites, thereby further improving the catalytic properties of FeCl3 in pore formation.


Dental implant-based oral rehabilitation in patients reconstructed with free fibula flaps: Clinical study with a follow-up 3 to 6 years.
Oral rehabilitation of patients after maxillofacial reconstructive surgery represents a challenge and stable prosthetic retention can be achieved with the use of dental implants. This retrospective report aimed to evaluate implant-based oral rehabilitation following maxillofacial reconstruction with free fibula flaps. A total of 14 patients who had reconstruction with fibula flaps either by CAD/CAM or conventional surgery were included in this study. A total of 56 implants (40 in flaps, 16 in native bone) were evaluated. Follow-up after reconstructive surgery ranged between 3.25 and 6.3 years. Follow-up after implant surgery ranged between 1.5 and 3.8 years. Overall survival rate was 85.7% in free fibula flaps and 85.6% in dental implants. Eight implants were lost in three patients and all of these failures were in dental implants inserted in free flaps. According to the results on patient basis, the implant survival was not influenced by any variable. The maxillofacial reconstruction with free fibula flap and oral rehabilitation with implant-supported prostheses after ablative surgery can be considered as an effective and safe procedure with successful aesthetic and functional outcomes.


Development of cell-to-cell relationships in the thyroid gland of the chick embryo.
Thyroid glands of 7 to 21 day-old chick embryos were examined by electron microscopy using freeze-fracture and thin-section preparations. The primitive follicle lumen first appears between two adjacent epithelial cells in 8 day-old embryos, and is formed in the region of a focal tight junction (macula occludens). The focal tight junction develops into the zonula occludens when the primitive follicle lumen first forms. The zonula occludens is, at first, composed of 4.6 +/- 2.45 strands, but with increasing embryonic age the number of strands increases to 5.9 +/- 1.41 in 13 day-old, and 8.0 +/- 1.75 in 19 day-old embryos. Thyroglobulin stored within the embryonic gland lumina is isolated from the mesenchymal tissue even at the first appearance of these follicle cavities. Well developed gap junctions already occur in the thyroid gland of the 7 day-old embryo, so that an intimate relationship and communication between these cells already exists at the time of their functional differentiation.


Physiological analysis and transcriptome profiling reveals the impact of microplastic on melon (Cucumis melo L.) seed germination and seedling growth.
The wide application of agricultural plastics leads to microplastic (MP) accumulation in the soil and inevitably result in MP pollution. Melon is an economically important horticultural crop that is widely cultivated with plastic film mulching. However, the impact of MP pollution on plant growth remains largely unclear. Here we reported the morphological, physiological, biochemical responses and transcriptome re-programing of melon responses to MP on seed germination and seedling growth. Polyvinyl chloride particles were added to potting mix to simulate MP exposure environment (MEE). The results showed that low and medium concentrations (1-4 g kg-1) of MEE had a significant adverse effect on seed germination and seedling growth. In both cases, the germination potential was decreased, young root forks increased, and tips decreased; and the dry weight of seedlings, the total length, surface area, forks and tips of root were also decreased. However, the root activity was increased. The concentration of MEE to give the best parameters was at 2 g kg-1. Catalase enzymatic activity and reactive oxygen species (ROS) in roots were decreased continuously with increased MEE concentrations. The peak values of peroxidase activity, O2.- content and generation rate, ROS enrichment and malondialdehyde content all reached the highest at 2 g kg-1. MEE also increased the proline content and decreased the contents of ascorbic acid, soluble sugar and soluble protein in these seedlings. Medium and high concentrations of MEE (4-8 g kg-1) also increased the chlorophyll b content. Low concentrations MEE (1-2 g kg-1) inhibited actual photochemical efficiency of photosystem II and photochemical quenching, two key chlorophyll fluorescence parameters. Transcriptome analysis showed that the differentially expressed genes caused by the MEE were mainly belonged to defense response, signal transduction, hormone metabolism, plant-pathogen interaction, and phenylpropanoid biosynthesis. The results of this study will help to understand the ecotoxicological effects of MEE on melons and provide data for ecological risk assessment of Cucurbitaceae vegetable cultivation.


Opioid rotation from morphine to fentanyl in delirious cancer patients: an open-label trial.
Although recent studies suggest that opioid rotation could be an effective treatment strategy for morphine-induced delirium, there have been no prospective studies to investigate the treatment effects of opioid rotation using fentanyl. The primary aim of this study was to clarify the efficacy of opioid rotation from morphine to fentanyl in symptom palliation of morphine-induced delirium. Twenty-one consecutive cancer patients with morphine-induced delirium underwent opioid rotation to fentanyl. Physicians recorded the symptom severity of delirium (the Memorial Delirium Assessment Scale, MDAS), pain, and other symptoms (categorical verbal scale from 0: none to 3: severe) and the Schedule for Team Assessment Scale (STAS) (from 0: none to 4: extreme); and performance status at the time of study enrollment and three and seven days after. Of 21 patients recruited, one patient did not complete the study. In the remaining 20 patients, morphine was substituted with transdermal fentanyl in 9 patients and parenteral fentanyl in 11 patients. Total opioid dose increased from 64 mg oral morphine equivalent/day (Day 0) to 98 mg/day (Day 7), and the median increase in total opioid dose was 42%. Treatment success, defined as an MDAS score below 10 and pain score of 2 or less, was obtained in 13 patients on Day 3 and 18 patients on Day 7. The mean MDAS score significantly decreased from 14 (Day 0) to 6.4 and 3.6 (Days 3 and 7, respectively, P < 0.001). Pain scores significantly decreased from 2.2 (Day 0) to 1.3 and 1.1 on the categorical verbal scale (Days 3 and 7, respectively, P < 0.001); from 2.6 (Day 0) to 1.6 and 1.3 on the STAS (Days 3 and 7, respectively, P < 0.001). Symptom scores of dry mouth, nausea, and vomiting significantly decreased, and performance status significantly improved. Opioid rotation from morphine to fentanyl may be effective in alleviating delirium and pain in cancer patients with morphine-induced delirium.


Early life nutrition and brain development: breakthroughs, challenges and new horizons.
The role of early life nutrition's impact on relevant health outcomes across the lifespan laid the foundation for the field titled the developmental origins of health and disease. Studies in this area initially concentrated on nutrition and the risk of adverse cardio-metabolic and cancer outcomes. More recently the role of nutrition in early brain development and the subsequent influence of later mental health has become more evident. Scientific breakthroughs have elucidated two mechanisms behind long-term nutrient effects on the brain, including the existence of critical periods for certain nutrients during brain development and nutrient-driven epigenetic modifications of chromatin. While multiple nutrients and nutritional conditions have the potential to modify brain development, iron can serve as a paradigm to understand both mechanisms. New horizons in nutritional medicine include leveraging the mechanistic knowledge of nutrient-brain interactions to propose novel nutritional approaches that protect the developing brain through better timing of nutrient delivery and potential reversal of negative epigenetic marks. The main challenge in the field is detecting whether a change in nutritional status truly affects the brain's development and performance in human subjects. To that end, a strong case can be made to develop and utilise bioindicators of a nutrient's effect on the developing brain instead of relying exclusively on biomarkers of the nutrient's status.


The relationship between 25-hydroxyvitamin D levels and ambulatory arterial stiffness index in newly diagnosed and never-treated hypertensive patients.
Vitamin D insufficiency has been shown to be associated with cardiac dysfunctions, such as cardiac hypertrophy and hypertension, in animal studies. Arterial stiffness is a prognostic marker for cardiovascular disease. Previous studies have demonstrated that 25-hydroxyvitamin D [25(OH)D] levels were negatively correlated with arterial stiffness index. The aim of this study was to investigate the relationship between 25(OH)D levels and arterial stiffness, which is evaluated using an ambulatory arterial stiffness index (AASI), in patients who have untreated and newly diagnosed essential hypertension. A total of 123 consecutive patients with newly diagnosed and untreated essential hypertension were included. Patients were divided into two groups according to their 25(OH)D levels. Vitamin D insufficiency was defined by 25(OH)D levels less than 20 ng/ml. All patients were referred for ambulatory blood pressure monitoring. The regression slope of diastolic and systolic blood pressure was computed for each individual on the basis of ambulatory blood pressure readings. AASI was described as one minus the respective regression slope. The mean AASI was significantly higher in patients with 25(OH)D levels less than 20 as compared with patients with 25(OH)D levels greater than or equal to 20 (0.50±0.20 vs. 0.34±0.17, P<0.001). In Pearson's correlation analysis, AASI had a significantly strong negative correlation with vitamin D levels (r=-0.385, P<0.001). In multivariate linear regression analysis, vitamin D levels were found to be significantly and independently associated with AASI (β=-0.317, P=0.035). Arterial stiffness measured by AASI in newly diagnosed and untreated patients with essential hypertension were significantly related to vitamin D levels.


Poor Attendance for bone densitometry in patients at high risk of subsequent fragility fractures.
Fracture Liaison Services (FLS) are considered the most effective model for the prevention of subsequent fractures however, the uptake of these services has shown to be suboptimal. 6,528 patients were identified and referred on for bone densitometry assessment over a 6 yr period, however, 21% of these patients did not attend, with a trend towards a higher re-fracture rate in those that did not attend compared to those that did. The presence of a fragility fracture increases the risk of further fractures. Fracture Liaison Services (FLS) are considered the most effective model for the prevention of subsequent fractures, although the uptake amongst patients invited for bone densitometry assessment has shown to be suboptimal. The UK has one of the most comprehensive numbers of FLS, however the proportion and characteristics of patients identified through the FLS that do not respond to bone densitometry invitation, in the UK, remains unclear. We report the 6 yr. findings from the Nottingham FLS. The Nottingham Fracture Liaison Service (N-FLS) systematically identifies those adults aged 50 yr. and older with fragility fractures presenting to the fracture clinic and where appropriate, arranges referral for bone densitometry assessment. Routine clinical data is collected onto the N-FLS database. Patient characteristics, between January 2012 and December 2017, were examined of those referred for bone densitometry examination, comparing those that attended to those that did not attend (DNA). Deprivation scores for each patient were calculated using the English indices of deprivation 2015 (1-Most deprived; 5- Least deprived). Follow up data was available for those attending from 2016 onwards, which allowed an assessment of re-fracture. Over the 6 yr period, 6,528 patients as identified by the N-FLS were referred on for bone densitometry assessment. 1,386 patients (21%) did not attend (DNA) for bone densitometry assessment. The proportion was similar for each of the years. High prevalence of non-attendance was in females [1032 patients (74%)] and the most deprived individuals [398 patients (29%), which were significant when compared to those that did attend, p=0.042]. 826 patients were referred in 2016. Median follow-up time was 2.46 yr. (IQR 0.16-3.00 yr.). 52 (7%) patients, in this group, sustained a subsequent fracture (35 patients in the group that did not attend for bone density assessment and 17 in those that attend, p=0.092). Nottingham FLS have identified patients with fragility fractures that are at high-risk of further fractures. Despite a dedicated FLS, 21% of those invited for bone densitometry assessment, did not attend for their appointment, over the 6 yr. period, similar proportion each year. There was a significantly higher proportion of those identified as 'most deprived' not attending for a bone densitometry, compared to those who attended. Sub-analysis in those aged 75 yr. and over, showed a high non-attendance in this group. Further qualitative studies are necessary to explore this patient group in detail, who remain at high risk of re-fracture.


The effect of corticotrophin (ACTH) administration on the pressor action of angiotensin II, noradrenaline and tyramine in sheep.
1. Pressor responses to angiotensin II, noradrenaline and tyramine were examined in sheep prior to and during the development of corticotrophin-induced hypertension. 2. Pressor responses to angiotensin II amide did not change with corticotrophin (ACTH) administration. Small significant increases in pressor responses to noradrenaline occurred at low doses only (0.27 and 1.06 mumol/h). Significant increases in response to tyramine occurred after 24h of ACTH administration, but were not maintained after 6 days of ACTH. These changes are quantitatively small and do not suggest that changes in pressor sensitivity contribute significantly to the rise in blood pressure following ACTH administration. 3. Sodium depletion significantly reduced the pressor responses to angiotensin II amide at all doses and to tyramine in the middle range only, but did not affect the responses to noradrenaline.


Safety assessment of Superba™ krill powder: Subchronic toxicity study in rats.
The safety of krill powder was assessed in a subchronic 13-week toxicity study where rats were fed krill powder or control diets. The krill powder inclusion in the test diet was 9.67% (w/w). There were no differences noted in body weight or food consumption in either gender. Differences in clinical chemistry values were noted in the krill powder-treated animals, but these findings were of no toxicological significance. A significant decrease in absolute heart weight, but not relative heart weight, was observed in both sexes given krill powder, although no corresponding histological changes were observed. Hepatocyte vacuolation was noted histologically in males fed krill powder. This finding was not associated with other indications of hepatic dysfunction. The no observed adverse effect level (NOAEL) for the conditions of this study was considered to be 9.67% krill powder.


Molecular mechanisms underlying RB protein function.
Inactivation of the RB protein is one of the most fundamental events in cancer. Coming to a molecular understanding of its function in normal cells and how it impedes cancer development has been challenging. Historically, the ability of RB to regulate the cell cycle placed it in a central role in proliferative control, and research focused on RB regulation of the E2F family of transcription factors. Remarkably, several recent studies have found additional tumour-suppressor functions of RB, including alternative roles in the cell cycle, maintenance of genome stability and apoptosis. These advances and new structural studies are combining to define the multifunctionality of RB.


The influence of acoustic radiation force beam shape and location on wave spectral content for arterial dispersion ultrasound vibrometry.
Objective. Arterial dispersion ultrasound vibrometry (ADUV) relies on the use of guided waves in arterial geometries for shear wave elastography measurements. Both the generation of waves through the use of acoustic radiation force (ARF) and the techniques employed to infer the speed of the resulting wave motion affect the spectral content and accuracy of the measurement. In particular, the effects of the shape and location of the ARF beam in ADUV have not been widely studied. In this work, we investigated how such variations of the ARF beam affect the induced motion and the measurements in the dispersive modes that are excited.Approach.The study includes an experimental evaluation on an arterial phantom and anin vivovalidation of the observed trends, observing the two walls of the waveguide, simultaneously, when subjected to variations in the ARF beam extension (F/N) and focus location.Main results.Relying on the theory of guided waves in cylindrical shells, the shape of the beam controls the selection and nature of the induced modes, while the location affects the measured dispersion curves (i.e. variation of phase velocity with frequency or wavenumber, multiple modes) across the waveguide walls.Significance.This investigation is important to understand the spectral content variations in ADUV measurements and to maximize inversion accuracy by tuning the ARF beam settings in clinical applications.


Increase in glial fibrillary acidic protein following neural trauma.
Immunohistochemical staining and quantitative evaluation of glial fibrillary acidic protein (GFAP) were carried out in a stab wound model of neural trauma in the rat. Increased GFAP staining was detected in reactive cortical astrocytes in the vicinity of the wound at 3, 7, and 30 d following injury. Western blots immunostained for GFAP also demonstrated an increase in GFAP in homogenates from the lesioned cortex, compared to the contralateral control side, on days 3, 7, and 30. Specific activity of GFAP expressed as a ratio of lesion/control values showed a fivefold increase from day 0 to day 7, with no further change on day 30. We conclude that neural trauma elicits a quantitative increase in GFAP in the rat cortex during the first week following injury. This increase correlates with both astrocyte hyperthrophy and proliferation. Thus, specific activity of GFAP is a reliable indicator of the onset and progression of astrogliosis in neural trauma.


MicroRNA-142-5p contributes to Hashimoto's thyroiditis by targeting CLDN1.
MicroRNAs have the potential as diagnostic biomarkers and therapeutic targets in autoimmune diseases. However, very limited studies have evaluated the expression of microRNA profile in thyroid gland related to Hashimoto's thyroiditis (HT). MicroRNA microarray expression profiling was performed and validated by quantitative RT-PCR. The expression pattern of miR-142-5p was detected using locked nucleic acid-in situ hybridization. The target gene was predicted and validated using miRNA targets prediction database, gene expression analysis, quantitative RT-PCR, western blot, and luciferase assay. The potential mechanisms of miR-142-5p were studied using immunohistochemistry, immunofluorescence, and quantitative assay of thyrocyte permeability. Thirty-nine microRNAs were differentially expressed in HT (Fold change ≥2, P < 0.05) and miR-142-5p, miR-142-3p, and miR-146a were only high expression in HT thyroid gland (P < 0.001). miR-142-5p, which was expressed at high levels in injured follicular epithelial cells, was also detected in HT patient serum and positively correlated with thyroglobulin antibody (r ≥ 0.6, P < 0.05). Furthermore, luciferase assay demonstrated CLDN1 was the direct target gene of miR-142-5p (P < 0.05), and Immunohistochemical staining showed a reverse expression patterns with miR-142-5p and CLDN1. Overexpression of miR-142-5p in thyrocytes resulted in reducing of the expression of claudin-1 both in mRNA and protein level (P = 0.032 and P = 0.009 respectively) and increasing the permeability of thyrocytes monolayer (P < 0.01). Our findings indicate a previously unrecognized mechanism that miR-142-5p, targeting CLDN1, plays an important role in HT pathogenesis.


[PRETAGREF study: Prevalence of tobacco use and factors associated with smoking cessation in kidney transplant recipients].
Tobacco use increases the risk of mortality, cancers and cardiovascular diseases in transplanted patients. Transplanted patients are encouraged to quit tobacco use before and after renal transplantation. This study was carried out to evaluate the prevalence of tobacco consumption in transplanted patients in one French region. This survey was also conducted to identify factors associated with failure in smoking cessation. A questionnaire was sent by mail to transplanted patients followed in our center between the 1/01/95 and the 31/12/10. A second mail was sent to increase the response rate. During the study period, 544 questionnaires were sent to kidney transplant recipients. Among these 544 patients, there were 362 responders. Of these 362 patients, 121 patients (33.4%) were past smokers, and 21 (5.8%) were active smokers. Among the smokers, 20% were exposed to second-hand smoke, 48% had criteria for tobacco moderate to high dependency, and 13.4% were addicted to alcohol. In the multivariate analysis, exposure to second-hand smoke and living alone at home were associated with failure in smoking cessation. This study shows that the prevalence of tobacco use is not high in transplanted patients. Only 6% of our patients report tobacco use at the study time. Environmental factors are associated with failure in tobacco cessation. Living alone and exposure to second-hand smoke are associated with smoking. Therefore, in transplantation centers, programs devoted to tobacco cessation should be implemented and should take care of patients' lifestyle.


Summary Report Panel 4: Communication and Interpretation: Presenting Information to the General Public.
Complex scientific information is often difficult to communicate to nonscience audiences who may not have the foundational knowledge to understand the content. Scientists are called on with increasing frequency to share the results of their research for the purposes of education, outreach, and popular media stories. These three spheres of activity, represented in Fig. 1, are geared toward different but complementary goals.


Signal transduction mechanisms mediating rapid, nongenomic effects of cortisol on prolactin release.
While the mechanisms governing genomically mediated glucocorticoid actions are becoming increasingly understood, relatively little is known with regard to the cell signaling pathways that transduce rapid glucocorticoid actions. Studies of the cultured tilapia rostral pars distalis (RPD), a naturally segregated region of the fish pituitary gland that contains a 95-99% pure population of prolactin (PRL) cells and is easily dissected and maintained in a completely defined, serum-free media, indicate that physiological concentrations of cortisol rapidly inhibit PRL release. The attenuative action of cortisol on PRL release occurs within 10-20 min, is insensitive to the protein synthesis inhibitor, cycloheximide, and mimicked by its membrane impermeable analog, cortisol-21 hemisuccinate-conjugated bovine serum albumin (BSA). Cortisol and somatostatin, a peptide known to work through membrane receptors to inhibit PRL release, rapidly and reversibly reduces intracellular free Ca(2+) (Ca(i)(2+)), and inhibits 45Ca(2+) influx and BAYK-8644 induced PRL release. Preliminary investigations show cortisol, but not somatostatin, suppresses phospholipase C (PLC) activity in PRL cell membrane preparations. In addition, cortisol and somatostatin reduce intracellular cAMP and membrane adenylyl cyclase activity. These findings indicate that the acute inhibitory effects of cortisol on PRL release occur through a nongenomic mechanism involving interactions with the plasma membrane and inhibition of both the Ca(2+) and cAMP signal transduction pathways. Cortisol may reduce Ca(i)(2+) by inhibiting influx through L-type voltage-gated channels and possibly release through a PLC/inositol triphosphate sensitive intracellular Ca(2+) pool. In addition, it is also likely the steroid inhibits adenylyl cyclase activity in events leading to reduced cAMP production and the subsequent release of PRL.


The behaviour of bioadhesive betamethasone tablets in the mouth.
Disk-shaped adhesive tablets, for treatment of mouth lesions, were prepared by direct compression of a mix of high viscosity sodium carboxymethyl-cellulose and 0.061% betamethasone valerate. They were evaluated in six healthy volunteers. The tablets hydrated rapidly, increased their wet weight fourfold in 15 min and maintained contact with the oral mucosa for at least 4 h. Erosion of the tablets was variable with only minor losses in one subject at all times tested, whereas over 80% tablet weight loss occurred in two subjects after 2.5 h. These differences were not solely related to differences in salivary flow. Loss of betamethasone occurred in parallel with the loss of weight from the tablet suggesting that drug release was mainly by erosion of the gelled polymer and not by diffusion from the matrix. The tablets provided prolonged contact with the mucosa but the intersubject variability and drug loss should be addressed to improve the formulation.


Intraoperative electron beam radiotherapy for previously irradiated advanced head and neck malignancies.
This is a retrospective review to evaluate the role of surgery and intraoperative electron beam radiotherapy (IOERT) in the treatment of patients with previously irradiated advanced head and neck cancers. Between January 1992 and March 1997, 38 patients (31 males, 7 females; median age of 62 years) with recurrent head and neck cancer were treated with maximal resection and IOERT at the Ohio State University (OSU). All had been previously treated with full-course radiotherapy (median 65.1 Gy, range 50-74.4 Gy). Twenty-nine patients (76%) had previously undergone one or more surgical procedures. After maximal surgery the tumor bed was treated with IOERT (single field in 36 patients and 2 fields in 2 patients), most commonly with 6 MeV electrons (87%). The dose administered (at 90% isodose line) was 15 Gy for close or microscopically positive margins in 34 patients and 20 Gy for gross disease in 1 patient. Further external beam radiation therapy (EBRT) was not given. After a median follow-up of 30 months (range 8-39 months), 24 of the 38 patients (66%) recurred within the IOERT field. Median time to IOERT failure was 6 months (95% CI: 4.3-7.7). The 6-month, 1-, and 2-year control rates within the IOERT volume were 41%, 19%, and 13%, respectively. Thirty of the 38 patients (79%) recurred in locoregional areas. Median time to locoregional failure was 4 months (95% CI: 3.3-4.7). The 6-month, 1-, and 2-year locoregional control rates were 33%, 11%, and 4%, respectively. Distant metastases occurred in 7 patients, 5 in association with IOERT failure and 2 with locoregional failure. Median overall survival was 7 months (95% CI: 4.7-9.3). The 6-month, 1-, 2-, and 3-year actuarial survival rates were 51%, 21%, 21%, and 8%, respectively. Major treatment-related complications occurred in 6 patients (16%). IOERT alone, at the dose used, is not sufficient for control of recurrent, previously irradiated head and neck cancers. Since higher IOERT doses are associated with high morbidity, we are currently evaluating the addition of limited EBRT dose and/or brachytherapy to improve the local control of these poor prognostic recurrent tumors, with acceptable morbidity.


Functional mitral regurgitation: a 30-year unresolved surgical journey from valve replacement to complex valve repairs.
Functional mitral regurgitation remains one of the most complex and controversial aspect--for both clinicians and surgeons--in the management of mitral valve disease in the context of left ventricular dysfunction. Given the current absence of clear guidelines, as well as of results from randomized trials comparing the outcome of different surgical strategies potentially available for this complex scenario, surgical decision making for these high-risk patients poses a real dilemma in the daily practice. The resulting surgical choices often represent a questionable combination of surgeons' personal feeling, local supplies, patients' life expectancy and risk/benefit ratios, opinions and statements of the experts, and so on. This review provides an overview of the present knowledge about the complex pathophysiology underlying functional mitral regurgitation, the different pathophysiology-guided surgical techniques suggested in the last decades, as well as the current results following these different surgical techniques.


Highlights in basic autonomic neuroscience: contribution of the urothelium to sensory mechanisms in the urinary bladder.
Urothelial cells in the urinary bladder express neural properties including: (1) release of neurotransmitters and neurotrophic factors, (2) expression of neurotransmitter receptors and ion channels, and (3) sensitivity to mechanical and chemical stimuli. These properties have focused attention on the possible contribution of the urothelium to the storage and emptying functions of the bladder. In addition chemicals released from urothelial cells can affect the excitability of adjacent afferent nerves and this interaction can be affected by pathological conditions. This raises the possibility that abnormal urothelial-afferent interactions may contribute to bladder dysfunctions and therefore be a target for drug therapy.


[Lyme disease, an infectious cause of facial paralysis. Apropos of a case].
A case of facial palsy first unilateral then bilateral, due to Lyme disease, is reported. This disease, transmitted by ticks, is caused by a spirochete (Borrelia burgdorferi) known as the etiologic agent since 1982.


Dissociation of pp70 ribosomal protein S6 kinase from insulin-stimulated glucose transport in 3T3-L1 adipocytes.
The metabolic and mitogenic actions of insulin have been proposed to be mediated by cellular serine/threonine kinases such as the ribosomal protein S6 kinases pp70-S6 (pp70-S6 kinase) and pp90rsk and the erk-encoded mitogen-activated protein kinases (pp42mapk and pp44mapk). Rapamycin completely blocked activation of pp70-S6 kinase by insulin in 3T3-L1 adipocytes, but did not inhibit insulin-stimulated glucose transport, translocation of GLUT4 to the cell surface, or activation of pp90rsk or pp44mapk by insulin. Concordant with the inhibition of kinase activity, rapamycin prevented the insulin-induced decrease in mobility of pp70-S6 kinase visualized by SDS-polyacrylamide gel electrophoresis, reflecting a reduction in the hormone-stimulated phosphorylation of the enzyme. The structurally related macrolide, FK506, had no effect on pp70-S6 kinase or hexose uptake. These data demonstrate that rapamycin blocks insulin activation of pp70-S6 kinase in 3T3-L1 adipocytes and that pp70-S6 kinase is not required in the signaling pathway leading to insulin-stimulated glucose transport.


Determination of acyclovir by ultrafiltration and high-performance liquid chromatography.
A simple, sensitive and rapid high-performance liquid chromatographic (HPLC) procedure to determine total serum acyclovir concentrations is described. The assay involves a heat inactivation step at 56 degrees C to prevent risk of infection, ultrafiltration as a pretreatment step prior to ion-pair reversed-phase liquid chromatography using guanosine as internal standard, and ultraviolet detection at 254 nm. This method has excellent recovery (97-100%), linearity (0.5-100 mg/l) and precision (1.2-8.0% coefficient of variation). The detection limit is 50 micrograms/l. The assay proved to be suitable for therapeutic drug monitoring of acyclovir.


Persistent idiopathic facial pain exists independent of somatosensory input from the painful region: findings from quantitative sensory functions and somatotopy of the primary somatosensory cortex.
In 14 patients with unilateral persistent idiopathic facial pain (PIFP), classified according to the criteria of the International Headache Society, and 16 age-matched control subjects sensory functions were examined on the face by quantitative sensory testing (QST). Additionally, the somatotopy of the primary somatosensory cortex (SI) to tactile input from the pain area was evaluated by means of magnetoencephalography. Previously reported abnormalities in PIFP as a dishabituation of the R2 component of the blink reflex and psychiatric disturbances were co-evaluated. Psychiatric evaluation included a Structured Clinical Interview for axis-I DSM IV disorders (SCID-I) and employment of the SCL-90-R and a depression scale (ADS). Thresholds to touch, pin prick, warm, cold, heat and pressure pain as well as the pain ratings to single and repetitive (perceptual wind up) painful pin prick stimuli did not indicate a significant sensory deficit or hyperactivity in the pain area when compared with the asymptomatic side nor when compared with the values of healthy control subjects. QST results were not significantly altered in patients (n=4) that showed an abnormal dishabituation of the R2 component of the blink reflex. The interhemispheric difference in distance between the cortical representation of the lip and the index finger did not differ between patients and control subjects. Psychiatric evaluation did not disclose significant abnormalities at a group level. It is concluded that PIFP is maintained by mechanisms which do not involve somatosensory processing of stimuli from the pain area.


Peculiarities of a novel bioenzymatic reactor using carbon nanotubes as enzyme activity enhancers: application to arginase.
Multiwalled carbon nanotubes have been entrapped in a porous monolithic chromatographic support. This support was used for the covalent immobilization of the arginase enzyme a novel target in hypertension. The effect of the nanotube (NT) amount into the monolith was analyzed. The obtained results demonstrated the ability of carbon nanotubes to increase significantly the performance of this novel bioactive support.


The activity of the intrinsically water-soluble enzyme ADAMTS13 correlates with the membrane state when bound to a phospholipid bilayer.
Membrane-associated enzymes have been found to behave differently qualitatively and quantitatively in terms of activity. These findings were highly debated in the 1970s and many general correlations and reaction specific models have been proposed, reviewed, and discarded. However, new biological applications brought up the need for clarification and elucidation. To address literature shortcomings, we chose the intrinsically water-soluble enzyme a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13) and large unilamellar vesicles with a relative broad phase transition. We here present activity measurements of ADAMTS13 in the freely dissolved state and the membrane associated state for phosphocholine lipids with different acyl-chain lengths (13:0, 14:0 and 15:0) and thus main phase transition temperatures. While the freely dissolved enzyme shows a simple Arrhenius behavior, the activity of membrane associated ADAMTS13 in addition shows a peak. This peak temperature correlates with the main phase transition temperature of the used lipids. These findings support an alternative theory of catalysis. This theory predicts a correlation of the membrane associated activity and the heat capacity, as both are susceptibilities of the same surface Gibb's free energy, since the enzyme is attached to the membrane.


Tyrosine kinase mediated phosphorylation of the hexamerin receptor in the rice moth Corcyra cephalonica by ecdysteroids.
Hexamerins are multifunctional insect storage proteins utilized during metamorphosis of holometabolous insects. These proteins are stage specifically taken up by the fat body cells from the haemolymph due to receptor-mediated endocytosis. The hexamerin receptor and the concomitant hexamerin sequestration in the rice moth Corcyra cephalonica is controlled by the steroid hormone 20-hydroxy-ecdysone (20E). However, the mechanism of receptor activation for hexamerin uptake is not yet clear. We report here that 20E stimulates the phosphorylation of 120 kDa hexamerin binding protein which has been demonstrated to represent the receptor. Phosphorylation of the receptor is suggested to be essential for receptor activation and occurs prior to the hexamerin uptake. The 20E stimulated phosphorylation is mediated partly by a tyrosine kinase as phosphotyrosine antibodies cross-react with the receptor and its phosphorylation is blocked partly by genistein. Back phosphorylation study provides additional evidence for 20E regulation of hexamerin receptor phosphorylation in intact fat body. The receptor phosphorylation is developmentally regulated. This is the first report demonstrating that (i) the uptake of hexamerin is dependent on the phosphorylation of hexamerin receptor and (ii) the phosphorylation is catalyzed partly by a tyrosine kinase which is activated by 20E through a non-genomic action.


An update on the unfolded protein response in brain ischemia: Experimental evidence and therapeutic opportunities.
After ischemic stroke or cardiac arrest, brain ischemia occurs. Currently, no pharmacologic intervention that targets cellular processes has proven effective in improving neurologic outcome in patients after brain ischemia. Recent experimental research has identified the crucial role of proteostasis in survival and recovery of cells after ischemia. In particular, the unfolded protein response (UPR), a key signaling pathway that safeguards cellular proteostasis, is emerging as a promising therapeutic target for brain ischemia. For some time, the UPR has been known to play a critical role in the pathophysiology of brain ischemia; however, only in the recent years has the field grown substantially, largely due to the extensive use of UPR-specific mouse genetic models and the rapidly expanding availability of pharmacologic tools that target the UPR. In this review, we provide a timely update on the progress in our understanding of the UPR in experimental brain ischemia, and discuss the therapeutic implications of targeting the UPR in ischemic stroke and cardiac arrest.


Effect of membrane-associated f1 bacteriophage coat protein upon the activity of Escherichia coli phosphatidylserine synthetase.
The effects of insertion of the major coat protein of f1 bacteriophage into Escherichia coli membranes were investigated under conditions allowing in vivo analysis of phosphatidylserine synthesis. An E. coli strain possessing a temperature-sensitive phosphatidylserine decarboxylase was utilized under conditions in which the decarboxylase activity was reduced but nonlethal. The presence of the coat protein in the host membranes inhibits the activity of the phosphatidylserine synthetase and perhaps affects the activity of the phosphatidylserine decarboxylase.


Exophytic Atheroma Mimicking Papillary Fibroelastoma Adjacent to the Aortic Valve.
Follow-up echocardiography in a 69-year-old man with alcoholic cardiomyopathy showed a mass above the aortic valve near the left coronary ostium. Transesophageal echocardiography and computed tomography suggested a papillary fibroelastoma with a high risk of embolism. At operation we found an exophytic atheroma adjacent to the left coronary artery orifice. The atheroma was removed, and the patient made an uneventful recovery. We describe this very rare case of an exophytic atheroma mimicking a papillary fibroelastoma situated at the left coronary orifice.


In silico study of substrate chemistry effect on the tethering of engineered antibodies for SARS-CoV-2 detection: Amorphous silica vs gold.
The influence of the properties of different solid substrates on the tethering of two antibodies, IgG1-CR3022 and IgG1-S309, which were specifically engineered for the detection of SARS-CoV-2, has been examined at the molecular level using conventional and accelerated Molecular Dynamics (cMD and aMD, respectively). Two surfaces with very different properties and widely used in immunosensors for diagnosis, amorphous silica and the most stable facet of the face-centered cubic gold structure, have been considered. The effects of such surfaces on the structure and orientation of the immobilized antibodies have been determined by quantifying the tilt and hinge angles that describe the orientation and shape of the antibody, respectively, and the dihedrals that measure the relative position of the antibody arms with respect to the surface. Results show that the interactions with amorphous silica, which are mainly electrostatic due to the charged nature of the surface, help to preserve the orientation and structure of the antibodies, especially of the IgG1-CR3022, indicating that the primary sequence of those antibodies also plays some role. Instead, short-range van der Waals interactions with the inert gold surface cause a higher degree tilting and fraying of the antibodies with respect to amorphous silica. The interactions between the antibodies and the surface also affect the correlation among the different angles and dihedrals, which increases with their strength. Overall, results explain why amorphous silica substrates are frequently used to immobilize antibodies in immunosensors.


Addition of S-1 to radiotherapy for treatment of T2N0 glottic cancer: Results of the multiple-center retrospective cohort study in Japan with a propensity score analysis.
This multicenter retrospective cohort study aimed to evaluate the significance of adding S-1 to radiotherapy (RT) for the treatment of T2N0 glottic cancer using a propensity score matched analysis in Japan. This study was conducted on 287 patients with T2N0 glottic cancer who were treated with definitive RT or chemoradiotherapy with S-1 (S-1 RT) between April 2007 and March 2017. Propensity score matched analysis was performed to ensure the well-balanced characteristics of the groups of patients who received RT alone and S-1 RT. Overall, progression-free and laryngectomy-free survivals and local control and laryngeal preservation rates were compared. Fifty-four pairs of patients were selected after performing propensity score matched analysis. Clinical characteristics were well-balanced between the two groups. The overall survival of patients in the S-1 RT group was significantly better than those in the RT alone group (P = 0.008). The progression-free and laryngectomy-free survivals of patients in the S-1 RT group were also better than those in the RT alone group; however, the differences were not significant. In contrast, patients in the S-1 RT group had slightly lower local control and laryngeal preservation rates compared with those in the RT alone group. The incidence of dermatitis in the S-1 RT group was significantly higher than that in the RT alone group in the matched population (P = 0.013). The addition of S-1 to RT for the treatment of T2N0 glottic cancer was not associated with better local control and laryngeal preservation rates in this study.


Ultrasound screening for structural defects in early pregnancy.
Since 1975, the primary method of antenatal diagnosis of structural defects has been by ultrasound visualisation. Improvements in equipment and operator experience have progressively increased the confidence and reliability of this technique which in 1982 provided a 100% detection rate. (Alternative methods are relatively costly and in our opinion, unsatisfactory). Total population screening for structural defects is entirely feasible by ultrasound and acceptable to the patient. Serum alpha feto-protein screening techniques are less reliable- generate unnecessary anxieties, and have given no supplementary assistance to detection rates in our experience. Ultrasound is considered to be the best screening technique available to the obstetrician for the detection of structural defects in early pregnancy and obviates the use of amniocentesis as a confirmatory procedure.


Elevated cell-free mitochondria DNA level of patients with premature ovarian insufficiency.
Premature ovarian insufficiency (POI) patients present with a chronic inflammatory state. Cell-free mitochondria DNA (cf-mtDNA) has been explored as a reliable biomarker for estimating the inflammation-related disorders, however, the cf-mtDNA levels in POI patients have never been measured. Therefore, in the presenting study, we aimed to evaluate the levels of cf-mtDNA in plasma and follicular fluid (FF) of POI patients and to determine a potential role of cf-mtDNA in predicting the disease progress and pregnancy outcomes. We collected plasma and FF samples from POI patients, biochemical POI (bPOI) patients and control women. Quantitative real-time PCR was used to measure the ratio of mitochondrial genome to nuclear genome of cf-DNAs extracted from the plasma and FF samples. The plasma cf-mtDNA levels, including COX3, CYB, ND1 and mtDNA79, were significantly higher in overt POI patients than those in bPOI patients or control women. The plasma cf-mtDNA levels were weakly correlated with ovarian reserve, and could not be improved by regular hormone replacement therapy. The levels of cf-mtDNA in FF, rather than those in plasma, exhibited the potential to predict the pregnancy outcomes, although they were comparable among overt POI, bPOI and control groups. The increased plasma cf-mtDNA levels in overt POI patients indicated its role in the progress of POI and the FF cf-mtDNA content may hold the value in predicting pregnancy outcomes of POI patients.


Tumour-mediated disruption of dendritic cell function: inhibiting the MEK1/2-p44/42 axis restores IL-12 production and Th1-generation.
Dysfunctional dendritic cells (DC) are common in cancer patients; however, the underlying molecular targets are poorly understood. Nevertheless, adoptive-transfer and in situ vaccination protocols continue, largely without addressing immune-suppression. Understanding tumour-mediated DC suppression would assist rational design of next generation immunotherapy. This study used a tumour-lysate loaded DC model of adoptive immunotherapy and also necrotic cells common in many tumours. Patient-derived and healthy-donor monocyte-derived DC were examined for disruptions in mitogen-activated protein kinase (MAPK) signalling pathways associated with their capacity to generate Type-1 helper-T cell populations (Th1). Melanoma-lysate markedly suppressed TLR4-dependent IL-12p40 and p70 production. Suppression of IL-12p70 occurred independently of maturation markers (e.g., CD40, CD80, CD83) and correlated with depressed p35 and p40 transcription. Decreased IL-12 secretion was not associated with IL-10, TGFbeta, VEGF, PGE(2) or ganglioside in tumour lysates or attributable to endogenous PGE(2) release from DC. In contrast to HUVEC lysate, melanoma-lysate-treated DC were less able to generate Th1-responses from naïve T-cells. The p44/42 MAPK was hyper-activated by melanoma lysate, but not that of HUVEC. Blockade of MEK1/2, the upstream kinase for p44/42, with U0126 prevented p44/42 activation, restored IL-12p70, and permitted effective generation of Th1-responses. Therefore the p44/42 MAPK is a target for tumour-mediated immune suppression of DC resulting in transcriptional down-regulation of IL-12 p35 and p40 genes, reduced IL-12 secretion and suppressed Th1-responses. Pharmacological intervention in the MEK-p44/42 axis may be applicable to render DC resistant to the suppressive effects of tumour lysates and may form part of a combination immunotherapy.


Transarterial Chemoembolization of Hepatocellular Carcinoma Using Radiopaque Drug-Eluting Embolics: How to Pursue Periprocedural Cross-Sectional Imaging?
To compare different imaging techniques (volume perfusion CT, cone-beam CT, and dynamic gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid-enhanced dynamic contrast-enhanced MR imaging with golden-angle radial sparse parallel MR imaging) in evaluation of transarterial chemoembolization of hepatocellular carcinoma (HCC) using radiopaque drug-eluting embolics (DEE). MR imaging and CT phantom investigation of radiopaque DEE was performed. In the clinical portion of the study, 13 patients (22 HCCs) were prospectively enrolled. All patients underwent cross-sectional imaging before and after transarterial chemoembolization using 100-300 μm radiopaque DEE. Qualitative assessment of images using a Likert scale was performed. In the phantom study, CT-related beam-hardening artifacts were markedly visible at a concentration of 12% (v/v) radiopaque DEE; MR imaging demonstrated no significant detectable signal intensity changes. Imaging obtained before transarterial chemoembolization showed no significant difference regarding tumor depiction. Visualization of tumor feeding arteries was significantly improved with volume perfusion CT (P < .001) and cone-beam CT (P = .002) compared with MR imaging. Radiopaque DEE led to significant decrease in tumor depiction (P = .001) and significant increase of beam-hardening artifacts (P = .012) using volume perfusion CT before versus after transarterial chemoembolization. Greater residual arterial tumor enhancement was detected with MR imaging (10 HCCs) compared with volume perfusion CT (8 HCCs) and cone-beam CT (6 HCCs). Using radiopaque DEE, the imaging modalities provided comparable early treatment assessment. In HCCs with dense accumulation of radiopaque DEE, treatment assessment using volume perfusion CT or cone-beam CT may be impaired owing to resulting beam-hardening artifacts and contrast stasis. Dynamic contrast-enhanced MR imaging may add value in detection of residual arterial tumor enhancement.


Modulation of motion aftereffect by surround motion and its dependence on stimulus size and eccentricity.
As a mechanism to detect differential motion, we have proposed a model of 'a motion contrast detector' and have shown that it can explain the perceptual change from motion capture to induced motion with increasing stimulus size and decreasing eccentricity. To further test the feasibility of the model, we examined the effect of surround motion on the motion aftereffect (MAE) elicited in the center. Using a drifting grating surrounded by another drifting grating, the duration of MAE in the center after adaptation was measured for various surround velocities (Expt 1). MAE was stronger when the surround moved oppositely to, than together with, the center. This finding was consistent with some previous reports. Using similar stimuli, MAE was measured at various stimulus sizes and eccentricities by the cancellation technique (Expt 2). The effect of surround modulation turned out to vary with both size and eccentricity. We examined if the apparent dependence on eccentricity could reflect a simpler effect of cortical size when the data were rescaled according to a linear scaling factor. We interpret our results in terms of motion contrast detectors, possibly located in the area MT.


Toll-Like Receptor Signaling in Depression.
Depression is one of the most prevalent, disabling, and costly mental illnesses currently affecting over 300 million people worldwide. A subset of depressed patients display inflammation as indicated by increased levels of proinflammatory mediators in the blood and cerebrospinal fluid. Longitudinal and experimental studies suggest that this inflammatory profile may causally contribute to the initiation, maintenance, or recurrence of depressive episodes in the context of major depressive disorder (MDD). While the mechanistic pathways that mediate these depressogenic effects have not yet been fully elucidated, toll-like receptor (TLR) signaling is one potential common inflammatory pathway. In this review, we focus on the role that inflammation plays in depression, TLR signaling and its plasticity as a candidate pathway, its regulation by micro ribonucleic acids (miRNAs), and their potential as diagnostic biomarkers for identification of inflammatory subtypes of depression. Pre-clinical and clinical studies have demonstrated that TLR expression and TLR signaling regulators are associated with MDD. Further, TLR expression and signaling is in-turn, regulated in part by miRNAs and some TLR-responsive miRNAs indirectly modulate pathways that are implicated in MDD pathophysiology. These data suggest an intersection between TLR signaling regulation and MDD-linked pathways. While these studies suggest that miRNAs play a role in the pathophysiology of MDD via their regulatory effects on TLR pathways, the utility of miRNAs as biomarkers and potential treatment targets remains to be determined. Developing new and innovative techniques or adapting established immunological approaches to mental health, should be at the forefront in moving the field forward, especially in terms of categorization of inflammatory subtypes in MDD.


Comparative evaluation of bioactive phytochemicals in Spinacia oleracea cultivated under greenhouse and open field conditions.
Various factors related to growing conditions can influence the nutritional quality of plants, including vegetable crops, especially the contents of health-promoting phytochemicals. In this study, the phytochemical contents of spinach (Spinacia oleracea) cultivated under greenhouse and open field conditions were comparatively analyzed using a metabolomic approach with Mass Profiler Professional (MPP) software. S. oleracea, which is one of the well-known leafy vegetables belonging to the family Chenopodiaceae, is cultivated worldwide. Although the nutritional value of spinach is high, the phytochemical contents of spinach cultivated under greenhouse and open field conditions have not been comparatively analyzed. Metabolomic analysis of the methanol (MeOH) extracts of greenhouse-cultivated spinach (GS) and open field-cultivated spinach (OFS) using ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS), followed by principal component analysis (PCA) with MPP demonstrated the differential metabolite profiles of GS and OFS. The active compounds 1-3 were isolated and identified using LC-Q-TOF-MS-guided fractionation. Among these, 5,3',4'-trihydroxy-3-methoxy-6,7-methylenedioxyflavone 4'-glucuronide (2) exhibited growth-inhibitory activities against Helicobacter pylori 51. Distribution analysis of compound 2 revealed that the anti-H. pylori compound 2 is an OFS-specific bioactive phytochemical. This indicates that the phytochemical quality of OFS is better than that of GS. These findings will aid in providing vital data for vegetable processors, dieticians, nutritionists, and consumers to select optimal green leafy vegetables.


Different effects of oxytetracycline and doxycycline on mitochondrial protein synthesis in rat liver after long-term treatment.
The tetracyclines inhibit specifically mitochondrial (mt) and bacterial protein synthesis when they are present in low concentrations (2-10 micrograms/ml). There is no difference between the various members of this group of antibiotics in this respect. In the present study, however, it is shown that the inhibitory effect of doxycycline on mt-protein synthesis in rat liver is partially lost after continuous treatment for more than 1 week, whereas oxytetracycline continues to inhibit mt-protein synthesis effectively after 1 week of treatment. To find an explanation for this difference between doxycycline and oxytetracycline, a detailed study was made of the distribution and the effects on mt-protein synthesis of both tetracyclines under various conditions in rat liver. The results of the studies lead to the hypothesis that doxycycline treatment induces the formation of a doxycycline complex, and thus to a reduced amount of free doxycycline. This may explain the loss of effective inhibition of mt-protein synthesis.


Interaction of methotrexate and betamethasone with experimental phototoxic inflammation to PUVA (Psoralen and UVA) in mice.
The influence of methotrexate and of betamethasone on a following phototoxic reaction to 8-methoxypsoralen and long-wave ultraviolet light (PUVA) was studied in the mouse. High PUVA doses were not influenced by the two drugs tested. Both methotrexate and betamethasone tended to diminish the PUVA response when psoralen was given in a medium dose.


Role of the PI3K and Hippo pathways in follicle activation after grafting of human ovarian tissue.
Our aim was to elucidate the mechanisms involved in follicle activation of the ovarian reserve after human ovarian tissue transplantation, with specific focus on the role of the effectors of the PI3K (mTOR and FOXO1) and Hippo (YAP) signaling pathways and whether they are somehow altered. Frozen-thawed ovarian tissue was collected from six women (age 25-35 years) undergoing surgery for non-ovarian pathologies and divided into 4 fragments in each case: one for non-grafted controls and three for grafting to immunodeficient mice for 3, 7 and 21 days. The tissue was processed for hematoxylin and eosin staining, immunohistochemistry and immunofluorescence at different timepoints before and after grafting. Activation of the PI3K and Hippo signaling pathways was investigated by analysis of mTOR phosphorylation, FOXO1 cytoplasmic localization and YAP nuclear localization. No change in mTOR levels was observed in primordial follicles post-transplantation, but a significant upturn was recorded in growing follicles compared with primordial follicles, irrespective of grafting time. A higher percentage of primordial follicles was also found with FOXO1 in the cytoplasm after 3 days of transplantation than in non-grafted controls. Finally, a greater proportion of primordial follicles was detected with YAP in the nucleus at all timepoints after grafting. This study supports the hypothesis that follicle activation may occur as an early event after transplantation, with follicle growth and death both contributing to the burnout phenomenon. This is the first time that the effectors of the PI3K and Hippo pathways have been investigated in grafted human ovarian tissue and their role in burnout documented.


Prehospital hemoglobin-based oxygen carrier resuscitation attenuates postinjury acute lung injury.
Crystalloid infusion has been the standard prehospital fluid resuscitation in the United States for the past 35 years, but the emergence of a safe and effective hemoglobin-based oxygen carrier (HBOC) may change that practice. The purpose of this in vivo study is to simulate an existing multicenter prehospital trial of HBOC versus crystalloid to determine the effects in a controlled 2-event construct of postinjury multiple organ failure. Rats underwent hemorrhagic shock (30 mm Hg x 45 min) and were resuscitated over 2 hours in a clinically relevant design: 2 x volume of shed blood (SB) using normal saline (NS) in the first 30 minutes; 1/2 volume of SB in the next 30 minutes; another 2 x SB volume with NS over the remaining 60 minutes. Study groups represented alternative fluid strategies during the first hour of resuscitation: (1) Inhospital SB (standard resuscitation), (2) Inhospital HBOC, (3) Prehospital SB, and (4) Prehospital HBOC. Global physiologic response was assessed via tissue oxygenation (near infrared spectroscopy) and arterial base deficit, and pulmonary response, via lung polymorphonuclear neutrophil accumulation and vascular permeability. Prehospital HBOC resuscitation provided the most efficient recovery of tissue oxygenation and correction of base deficit, had the greatest reduction in pulmonary polymorphonuclear neutrophil accumulation, and abrogated acute lung injury. Prehospital SB and Inhospital HBOC regimens afforded intermediate lung protection, compared with standard resuscitation. The findings in this controlled in vivo study suggest prehospital HBOC resuscitation improves the recovery from postshock oxygen debt and reduces postinjury organ dysfunction.


High-frequency subharmonic pulsed-wave Doppler and color flow imaging of microbubble contrast agents.
A recent study has shown the feasibility of subharmonic (SH) flow imaging at a transmit frequency of 20 MHz. This paper builds on these results by examining the performance of SH flow imaging as a function of transmit pressure. Further, we also investigate the feasibility of SH pulsed-wave Doppler (PWD) imaging. In vitro flow experiments were performed with a 1-mm-diameter wall-less vessel cryogel phantom using the ultrasound contrast agent Definity and an imaging frequency of 20 MHz. The phantom results show that there is an identifiable pressure range where accurate flow velocity and power estimates can be made with SH imaging at 10 MHz (SH10), above which velocity estimates are biased by radiation force effects and unstable bubble behavior, and below which velocity and power estimates are degraded by poor SNR. In vivo validation of SH PWD was performed in an arteriole of a rabbit ear, and blood velocity estimates compared well with fundamental (F20) mode PWD. The ability to suppress tissue signals using SH signals may enable the use of higher frame rates and improve sensitivity to microvascular flow or slow velocities near large vessel walls by reducing or eliminating the need for clutter filters.


Personal Determinants of Burden Among Indonesian Female Caregivers of Older Adults in Taiwan.
Families increasingly employ foreign domestic workers (FDWs) to care for older loved ones. Caregiver burden reflects FDWs' difficulty adapting to work demands. We test hypothesized associations between burden and six personal characteristics: children, marriage, education, Chinese proficiency, eldercare experience, and non-eldercare experience. In total, 299 Indonesian FDWs in Taiwan completed the Zarit Burden Interview. Exploratory factor analysis identified the dimensions of burden. Multiple and multinomial regressions related the variables to overall burden, burden dimensions, and burden severity. Four dimensions were found: personal strain, role strain, dependency, and guilt. Children were negatively associated with burden, role strain, dependency, and guilt. Chinese proficiency was negatively associated with severity and guilt. Eldercare experience was positively associated with severity and personal strain. Marriage was non-monotonically related to severity. Caregivers whose earnings benefit their children may be more likely to thrive in Taiwan. Language training may boost caregiver performance and host family satisfaction.


Inflammation, Fibrosis and Cancer: Mechanisms, Therapeutic Options and Challenges.
Uncontrolled inflammation is a salient factor in multiple chronic inflammatory diseases and cancers. In this review, we provided an in-depth analysis of the relationships and distinctions between uncontrolled inflammation, fibrosis and cancers, while emphasizing the challenges and opportunities of developing novel therapies for the treatment and/or management of these diseases. We described how drug delivery systems, combination therapy and the integration of tissue-targeted and/or pathways selective strategies could overcome the challenges of current agents for managing and/or treating chronic inflammatory diseases and cancers. We also recognized the value of the re-evaluation of the disease-specific roles of multiple pathways implicated in the pathophysiology of chronic inflammatory diseases and cancers-as well as the application of data from single-cell RNA sequencing in the success of future drug discovery endeavors.


Molecular cloning, sequence and regulation of expression of the recA gene of the phototrophic bacterium Rhodobacter sphaeroides.
The recA gene of Rhodobacter sphaeroides 2.4.1 has been isolated by complementation of a UV-sensitive RecA- mutant of Pseudomonas aeruginosa. Its complete nucleotide sequence consists of 1032 bp, encoding a polypeptide of 343 amino acids. The deduced amino acid sequence displayed highest identity to the RecA proteins from Rhizobium meliloti, Rhizobium phaseoli, and Agrobacterium tumefaciens. An Escherichia coli-like SOS consensus region, which functions as a binding site for the LexA repressor molecule was not present in the 215 bp upstream region of the R. sphaeroides recA gene. Nevertheless, by using a recA-lacZ fusion, we have shown that expression of the recA gene of R. sphaeroides is inducible by DNA damage. A recA-defective strain of R. sphaeroides was obtained by replacement of the active recA gene by a gene copy inactivated in vitro. The resulting recA mutant exhibited increased sensitivity to UV irradiation, and was impaired in its ability to perform homologous recombination as well as to trigger DNA damage-mediated expression. This is the first recA gene from a Gram-negative bacterium that lacks an E. coli-like SOS box but whose expression has been shown to be DNA damage-inducible and auto-regulated.


Norwegian speech-language pathologists treatment practices for preschool children who stutter: An explorative study.
This study investigated the treatment practices of speech-language pathologists (SLPs) with preschool children who stutter to explore variations in service delivery and, consequently to better inform and support evidence-based practice. 121 Norwegian SLPs completed an online survey about stuttering treatment for preschool children aged up to six years. They reported on treatment training, choices, setting, dosage, and outcomes. Data was analysed descriptively. Correlation analyses between years of clinical experience and clinician perceived outcomes were conducted. Sixty-eight percent of SLPs were trained in one or more stuttering treatment programs. The majority of SLPs (83 %) provided treatment in person in preschool centers; 59 % reported providing treatment once a week. Thirty-four percent of SLPs reported that they often or always delivered the whole treatment program. Treatment practice addressed various elements, including advising parents about language and communication strategies, supporting the child's self-image, and perceived outcomes. The SLPs reported their clinician perceived outcomes as 'always' or 'often' reduction of audible stuttering (70 %), reduced cognitive and emotional reactions (55 %), and improved communication skills (58 %). Factors influencing treatment choices were identified at the systemic level (e.g., work place regulations) and individual level (e.g., SLPs competency, child's best). Stuttering treatment services in Norway differ from those reported in existing literature as treatment is given in preschool settings, only 34 % of SLPs deliver programs as intended whilst the majority use treatment elements only, and still experience positive changes. Provision is variable, and seems influenced by SLP training and competence.


Correction of implant malalignment by segmental osteotomy: a case report.
This case report demonstrates that the position of malaligned osseointegrated implants can be corrected by a segmental osteotomy procedure with no loss of implants or bone support. The patient was a healthy teenage girl who sustained facial trauma with loss of teeth and alveolar bone. The defect was initially bone grafted. Brånemark implants were simultaneously placed in the graft. Their initial unfavorable positions and inclinations were later corrected by a segmental osteotomy.


Clinical features of small contraction wave recorded by an external tocodynamometer.
Clinical features of the small contraction wave recorded by a guardring tocodynamometer were examined retrospectively. This study included 578 patients and 6363 cardiotocographs ranging from 20 to 42 weeks of gestation. The small wave was observed in 7.5% of the cardiotocographs examined, and the rate of small-wave appearance in each gestational week tended to decrease gradually as the pregnancy progressed. This was not observed after 41 weeks of gestation. The small wave-positive group had relatively poor obstetric parameters and fetal outcome, and the small wave was frequently observed in cases of effective beta 2-stimulant intravenous infusion for the treatment of preterm labor. These results suggest that the small wave represents some degree of contractility and is ominous in general; however, the appearance of the wave does not lead to a poor prognosis in preterm labor if large phasic contractions can be abolished by beta 2-stimulant treatment.


Results of radiation therapy performed after unplanned surgery (without re-excision) for soft tissue sarcomas.
For soft tissue sarcomas (STS), some patients undergo an "unplanned surgery," non-oncologic resection for presumed benign tumor. The treatment of choice, in such cases, is re-excision combined (if indicated) with radiation. However, there are clinical situations when treatment by radiation alone is recommended. Here results of such an approach are assessed. Seventy-eight patients irradiated after unplanned surgery between 1970 and 1997 were identified from the MGH institutional database. Surgical margins were inevaluable in 50 (64%) and 28 (36%) had positive margins. Tumor characteristics: location, lower extremity (63%), upper extremity (27%), other (10%); median tumor size, 5 cm; grade-G1 (19%), G2 (49%), G3 (32%); AJCC stage (2002)-I (19%), II (54%), III (27%). Median radiation dose given was 66 Gy (range: 51-88). With a median follow-up of 10 years, estimated local control rate was 88% and 86% at 5 and 10 years, respectively. Distant control rate was 80% at 5 and 10 years. Depth in the relation to the fascia, tumor size, and AJCC stage significantly influenced local recurrence- and distant metastasis-free survival. Ten major radiotherapy complications occurred from 1 to 21 years after treatment. Despite convincing data about the necessity for re-excision after unplanned surgery for STS, these results demonstrate that radiation therapy alone can be an effective alternate for those patients in whom functional or medical considerations preclude further surgery. The risk for potential radiation therapy complications, however, must also be considered in the treatment decision.


Is preoperative CT-guided biopsy a valuable tool in the diagnostic workup of patients with visceral and retroperitoneal sarcoma?
We aimed to analyze the diagnostic accuracy of preoperative CT-guided biopsy to identify patients that might profit from neoadjuvant chemotherapy in a specialized high-volume sarcoma center. We retrospectively reviewed all patients with suspected soft tissue tumors of the abdomen cavity including the retroperitoneum, who received CT-guided biopsy followed by surgical tumor resection. Sensitivity, specificity, PPV and NPV were calculated in all patients with abdominal sarcomas at our hospital. A subgroup analysis was performed for patients with liposarcoma. A total of 82 patients (35 female, 47 male, age: 62.0 ± 14.7) received preoperative CT-guided biopsy followed by surgical resection. Overall accordance of CT-guided biopsy to identify final histology was 77 %. CT-guided biopsy revealed the diagnosis of liposarcoma in 23 patients whereas final analysis of the surgical specimen identified liposarcoma in 29 patients. Here, sensitivity, specificity, PPV and NPV was 79.3 %, 100.0 %, 100.0 % and 89.8 % respectively. Subgroup analysis revealed a better accuracy for correctly identifying patients with well-differentiated liposarcoma than patients with dedifferentiated liposarcoma (75.0 % vs 62.5 %). In patients with other sarcoma, sensitivity, specificity, PPV, NPV and diagnostic accuracy was 87.5 %, 95.5 %, 82.4 % and 96.9 %, respectively. CT-guided biopsy in a specialized high-volume sarcoma center is an accurate and effective method to assess patients with abdominal sarcoma and especially abdominal liposarcoma. Therefore, it is an indispensable tool in the pretherapeutic workup process. Nevertheless, our study underlines the previously reported difficulties in dedifferentiated liposarcoma diagnostics, whereby these patient cohort would profit the most from a neoadjuvant therapy regime.