The Geriatric Mental State Examination as a case-finding instrument in the community.
The Geriatric Mental State Examination (GMS), a standardised psychiatric interview, and its computerised diagnostic system, AGECAT, have been applied to a large (1070) sample of subjects aged over 65 in Liverpool. In a split-half study of this sample, diagnostic scales within the GMS and a diagnostic index derived from them were tested for efficacy in cases of organic and early organic illness (mostly various stages of dementia) and depressive illness. Results demonstrated high levels of sensitivity and specificity, and positive predictive values were within the expected range when applied to these disorders, given their low prevalence in the community. The GMS, when used in this way, is a flexible and effective case-finding instrument.


[Pathophysiology and therapeutic approach in inflammatory demyelinating polyneuropathy--recent advances].
Recent advances on pathogenetic mechanism and therapeutic approach for Guillain-Barré syndrome (GBS) and chronic inflammatory demyelinating polyneuropathy (CIPD) were briefly reviewed. As for GBS, an axonal form has been recognized as a clinicopathological variant, in which Campylobacter jejuni infection and elevated anti-GM1 antibody tires are frequently observed. Other anti-glycolipid antibodies to GQ1b, GD1b and GM2 would also be significant as a determinant factor for a clinical phenotype. Beneficial effects of IVIg therapy and plasmapheresis have been established. Although CIDP has also been considered to be demyelinating neuropathy, axonal pathology is frequently noted, and in such cases, a substantial motor neuron loss is present. Clinical recovery in the cases with high anti-MAG and anti-SGPG titers is not necessarily favorable. Corticosteroid therapy, plasmapheresis and IVIg have been all established as therapies beneficial for CIDP.


The "Beacon" Structural Model of Protein Folding: Application for Trp-Cage in Water.
Protein folding is a process in which a polypeptide must undergo folding process to obtain its three-dimensional structure. Thermodynamically, it is a process of enthalpy to overcome the loss of conformational entropy in folding. Folding is primarily related to hydrophobic interactions and intramolecular hydrogen bondings. During folding, hydrophobic interactions are regarded to be the driving forces, especially in the initial structural collapse of a protein. Additionally, folding is guided by the strong interactions within proteins, such as intramolecular hydrogen bondings related to the α-helices and β-sheets of proteins. Therefore, a protein is divided into the folding key (FK) regions related to intramolecular hydrogen bondings and the non-folding key (non-FK) regions. Various conformations are expected for FK and non-FK regions. Different from non-FK regions, it is necessary for FK regions to form the specific conformations in folding, which are regarded as the necessary folding pathways (or "beacons"). Additionally, sequential folding is expected for the FK regions, and the intermediate state is found during folding. They are reflected on the local basins in the free energy landscape (FEL) of folding. To demonstrate the structural model, molecular dynamics (MD) simulations are conducted on the folding pathway of the TRP-cage in water.


Immunohistochemical study of natural killer cells in tumor-infiltrating lymphocytes of primary intracranial germinomas.
A monoclonal antibody against the surface marker IOT-10 of natural killer (NK) cells was used to investigate the presence and distribution of these cells in a series of nine primary intracranial germinomas. In all of these tumors, IOT-10-positive NK cells were found in small numbers, mainly distributed among the tumor cells. The data obtained in the present study suggest that the presence of NK cells in primary intracranial germinomas can be influenced by factors other than the mere quantity of tumor-infiltrating lymphocytes.


A systematic literature review of prognostic factors in patients with HR+/HER2- advanced breast cancer in Japan.
Breast cancer is the most prevalent cancer in women in Japan and the fifth in mortality. This systematic review summarized the evidence for prognostic factors for patients with HR+/HER2- advanced and metastatic breast cancer in Japan. MEDLINE and EMBASE were searched with keywords 'breast neoplasms' AND 'Japan' AND 'advanced' or equivalent, and Japan Medical Abstract Society database with 'breast cancer' AND 'advanced/metastatic' for publications from January 2010 to October 2019. ASCO, ESMO, ABC4 abstracts and WHO website were hand searched. The endpoints of interest were overall survival, progression-free survival, tumour response and post-progression survival. Factors were evaluated based on the consistency in direction and the strength (hazard ratios) of association. Searches identified 4530 publications, of which 27 were eligible. All were observational studies. Among the endpoints, overall survival was the most commonly assessed (n = 22) and evaluated further. Ki-67 expression, progesterone receptor expression status, tumour grade and lymph node metastases were consistently associated with poor overall survival in univariate analysis but not in multivariate analysis. Short disease-free interval, the number of metastatic organs and liver metastasis were consistently associated with poor overall survival in both of univariate and multivariate analysis. The association was strong for liver metastasis (hazard ratio ≥2.8 in the majority of studies) and moderate for disease-free interval and the number of metastatic organs (hazard ratio 1.3-2.8 in the majority of studies). Disease-free interval, the number of metastatic organs and liver metastasis were identified as independent prognostic factors for overall survival. These findings may help clinical decision-making to improve outcomes in patients with HR+/HER2- advanced and metastatic breast cancer.


Splash basin contamination in orthopaedic surgery.
Samples of splash basin fluid were cultured at the end of 78 randomly selected orthopedic operations. Fifty-eight (74%) of the specimens were positive on culture. Staphylococcus epidermidis was the prevalent organism. Thirty-four (59%) of the positive cultures grew multiple organisms. Seven (12%) grew more than 100 colonies per 100 ml specimen. This study demonstrates that splash basin fluid is frequently contaminated and may be a source of wound contamination during orthopedic surgery. Implants should not be placed in the splash basin, and instruments placed in it should not be returned to the operative wound.


Association between Phase Angle and Subjective Perceptions of Health Variables in Cancer Patients.
The phase angle, an increasingly studied healthcare tool, was studied to explore its relationship with psychological factors in cancer patients. The aim of this study was to investigate the relationship between the phase angle (PhA), obtained by the bioimpedance analysis of body composition, and psychological factors measured by questionnaire in cancer patients. The study included 311 patients who underwent bioimpedance testing to determine their PhA value; their psychological profiles were assessed using SF-36, FACIT, QLQ-C30, and GHQ-12 questionnaires. Mixed linear regression models were used to analyze the relationship between PhA and the psychological tests. The results showed a statistical correlation between PhA and the GHQ-12, FACIT, and SF-36 questionnaires, with higher PhA values associated with better results on the questionnaires. In the QLQ-C30 questionnaire, a correlation was observed between PhA and the functioning scales (p < 0.001), except for emotional and cognitive functioning (p = 0.148 and p = 0.544, respectively), but not in most of the symptom scales. The PhA is a useful tool for assessing the subjective health perception of cancer patients, especially with regard to psychological factors. While there is a statistically significant correlation, further research is required before confidently applying it in clinical practice. The current predictive value of this predictor for certain psychological aspects is limited, underscoring the need for additional research.


Ash production by attrition in volcanic conduits and plumes.
Tephra deposits result from explosive volcanic eruption and serve as indirect probes into fragmentation processes operating in subsurface volcanic conduits. Primary magmatic fragmentation creates a population of pyroclasts through volatile-driven decompression during conduit ascent. In this study, we explore the role that secondary fragmentation, specifically attrition, has in transforming primary pyroclasts upon transport in volcanic conduits and plumes. We utilize total grain size distributions from a suite of natural and experimentally produced tephra to show that attrition is likely to occur in all explosive volcanic eruptions. Our experimental results indicate that fine ash production and surface area generation is fast (<15 min) thereby rapidly raising the fractal dimension of tephra deposits. Furthermore, a new metric, the Entropy of Information, is introduced to quantify the degree of attrition (secondary fragmentation) from grain size data. Attrition elevates fine ash production which, in turn, has consequences for eruption column stability, tephra dispersal, aggregation, volcanic lightening generation, and has concomitant effects on aviation safety and Earth's climate.


Outcomes of repeat endothelial keratoplasty in patients with failed Descemet stripping endothelial keratoplasty.
To report the outcomes of repeat endothelial keratoplasty (EK) in patients with failed Descemet stripping endothelial keratoplasty (DSEK). The clinical records of patients with failed DSEK who underwent repeat EK surgery at a single institution were reviewed. A total of 20 eyes of 20 patients (8 men and 12 women) were included. The mean age at initial DSEK surgery was 69.9 ± 11.9 years (range, 41-83 years). The causes of DSEK failure included progressive endothelial failure (8 eyes; 40%), primary graft failure (8 eyes; 40%), and endothelial rejection (4 eyes; 20%). The mean duration from primary DSEK to repeat EK was 13.1 ± 10.3 months (range, 2-33 months). Removal of the failed DSEK donor disc was performed in all eyes. Mean preoperative corrected distance visual acuity (logMAR) before repeat EK surgery was 1.76, and this improved to 0.5 (P < 0.001) at the final follow-up at 27 months. Three eyes had limited corrected distance visual acuity secondary to ocular comorbidities (age-related macular degeneration and advanced glaucomatous optic neuropathy). Repeat EK in patients with DSEK failure is an effective treatment modality. This is the preferred management option compared with penetrating keratoplasty because the advantages of EK surgery are maintained with repeat EK surgery.


Micro-Computed Tomography-Based Three-Dimensional Anatomical Structure of the Region Around the Pterygoid Hamulus.
Palatoplasty would involve the structures around the pterygoid hamulus. However, clinicians hold different opinions on the optimal approach for the muscles and palatine aponeurosis around the pterygoid hamulus. The absence of a consensus regarding this point can be attributed to the lack of investigations on the exact anatomy of this region. Therefore, we used micro-computed tomography to examine the anatomical structure of the region surrounding the pterygoid hamulus. Cadaveric specimens were stained with iodine-potassium iodide and scanned by micro-computed tomography to study the structures of the tissues, particularly the muscle fibers. We imported Digital Imaging and Communications in Medicine images to Mimics to reconstruct a 3-dimensional model and simplified the model. Three muscles were present around the pterygoid hamulus, namely the palatopharyngeus (PP), superior constrictor (SC), and tensor veli palatini (TVP). The hamulus connects these muscles as a key pivot. The TVP extended to the palatine aponeurosis, which bypassed the pterygoid hamulus, and linked the PP and SC. Some muscle fibers of the SC originated from the hamulus, the aponeurosis of which was wrapped around the hamulus. There was a distinct gap between the pterygoid hamulus and the palatine aponeurosis. This formed a pulley-like structure around the pterygoid hamulus. Transection or fracture of the palatine aponeurosis or pterygoid hamulus, respectively, may have detrimental effects on the muscles around the pterygoid hamulus, which play essential roles in the velopharyngeal function and middle ear ventilation. Currently, cleft palate repair has limited treatment options with proven successful outcomes.


OPTICAL COHERENCE TOMOGRAPHY AND OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY EVALUATION OF COMBINED HAMARTOMA OF THE RETINA AND RETINAL PIGMENT EPITHELIUM.
To study multimodal imaging features of combined hamartoma of the retina and retinal pigment epithelium (CHRRPE). Six patients (3 males, mean age 11 years) and a healthy age-matched control group made up of 15 healthy subjects (8 males, mean age 12.6 years) were included in the analysis. Complete ophthalmologic examination was performed, including best-corrected visual acuity, anterior and posterior segment slit-lamp evaluation, and tonometry. The multimodal imaging protocol included fundus images, structural optical coherence tomography (OCT), and swept-source OCT angiography (OCTA). The main outcome measures included the qualitative evaluation of both OCT and OCTA features of CHRRPE, retinal and choroidal thickness measurements, and the quantitative analysis of superficial capillary plexus, deep capillary plexus, and choriocapillaris vessel densities. Optical coherence tomography features of CHRRPE were examined extensively. Multiple little hyperreflective triangular outer retinal alterations were found at the CHRRPE edges in all patients; these were dubbed the "shark-teeth" sign. Optical coherence tomography angiography showed rarefaction and morphologic alterations of all retinal plexa. Moreover, quantitative analysis revealed a statistically significant decrease in superficial capillary plexus, deep capillary plexus, and choriocapillaris vessel densities in patients affected by CHRRPE compared with the control group. Optical coherence tomography and OCTA analyses allowed the accurate qualitative and quantitative analyses of CHRRPE features. Further studies are needed to better define OCTA changes of CHRRPE better and to improve our understanding of the possible causes of the shark-teeth sign.


Ultrastructural observations on life cycle stages of Pneumocystis carinii.
An ultrastructural study of life cycle stages of Pneumocystis carinii in infected rat lungs in situ was undertaken utilizing 8 different modes of fixation. Three of the fixatives employed gave good fixation of cysts and intracystic bodies, but for the trophic forms fixation was only fair. Both the trophic forms and intracystic bodies have nuclear pores. The mitochondria of the organism have cristae that appear lamellar. One of the fixation modes revealed a thin, electron-dense layer on the outer surface of the cell wall, a "fuzzy coat" that had not been described previously. This material appears to mediate tight adhesion of trophic forms with other trophic forms, cysts, and with pneumocytes of the lung alveolus.


Plant physiology. Virtue on both sides.
Experiments with transgenic plants are beginning to unravel how the products of photosynthesis get into the phloem from transport throughout the living tissues of the plant.


Evaluating the efficiency of humic acid to remove micro-organisms from denture base material.
To evaluate the efficiency of humic acid substances on removing micro-organisms from denture base materials. Old denture wearer needs effective, easy-use and safe denture-cleaning material. Square-shaped, heat-polymerised acrylic resin specimens (n = 550) were prepared and divided into five groups (n = 110 for each) corresponding to the microbial contamination (Candida albicans, Staphylococcus aureus, Bacillus cereus, Enterococcus faecalis, Pseudomonas aeruginosa). Contaminated specimens were randomly assigned to the application of five different denture-cleaning agents as follows (n = 20 for each): Kloroben, Corsodyl, Steradent, Corega, experimental solution with humic acid. Ten specimens were assessed as an experimental control carried out simultaneously for the treatment groups for each micro-organism. It was divided into two groups: negative control and positive control (n = 5 for each). All acrylic specimens were incubated 37°C for 24 h (for bacterial strains) and 37°C for 48 h (for yeast strains). After incubation period, all brain-heart infusion broths (BHI) which contain disinfectant acrylic specimens were cultured on 5% sheep blood agar (for bacteria) and Sabouraud dextrose agar (SDA) for yeast using loop. The numbers of colony-forming units per millilitre (CFU/ml) were calculated. The results were analysed by Mann-Whitney U-test and Kruskal-Wallis tests (p = 0.05). Corsodyl and Kloroben completely eliminated the adherence of all investigated micro-organisms (100%) and showed the highest removal activity compared with other cleaning agents (p < 0.05). There was no statistically significant difference between Corsodyl and Kloroben (p ≥ 0.05), and there was no statistically significant difference between Corega, Steradent and experimental solution (p ≥ 0.05). Humic acid could be used as an alternative 'natural' solution for denture-cleaning agent.


Inhibition of mouse fibroblast interferon by gangliosides. Differential effects on biological activity and on induction of (2'--5')oligoadenylate synthetase.
Gangliosides are potent inhibitors of the antiviral activity of mouse fibroblasts and other beta-interferons. We have compared the effects of gangliosides on antiviral and antigrowth activities of mouse fibroblast interferon and on the induction of (2'--5')oligoadenylate synthetase, one of the enzymes implicated in the antiviral state induced by interferon. Whereas both biological effects appear to be inhibited by gangliosides in an analogous fashion, inhibition of induction of (2'--5')oligoadenylate synthetase does not correlate with inhibition of vesicular stomatitis virus replication. Ganglioside concentrations that inhibit the interferon-induced (2'--5')oligoadenylate synthetase to levels close to those of uninduced cells, still allow for a 100--1000-fold reduction of viral yield. Significantly higher ganglioside concentrations are required to prevent completely the antiviral effect. This biphasic relationship between (2'--5')oligoadenylate synthetase levels and inhibition of viral yield suggests that no or very small increases in synthetase levels are involved in inhibition of virus by between two and three orders of magnitude.


Acylphloroglucinols from Elaphoglossum crassipes: antidepressant-like activity of crassipin A.
Nine new terpenylated acylphloroglucinols, crassipins A-I, were isolated from the rhizomes and roots of the fern Elaphoglossum crassipes, and their structures were elucidated by analysis of spectroscopic data and chemical derivatization. The absolute configurations of some of the compounds were established by CD and VCD in combination with a quantum mechanical method. Crassipin A (1), the major acylphloroglucinol of the Et(2)O extract of E. crassipes, as well as its peracetylated derivative (8), displayed antidepressant-like activity in a mouse forced-swimming test when administered orally at a dose of 15 mg/kg.


Spatial-frequency characteristics of letter identification.
To investigate the spatial-frequency components that govern letter identification we compared contrast thresholds for three types of visual stimulus (1) standard Sloan letters, (2) Sloan letters that were spatially bandpass filtered by cosine log filters, and (3) D6 patterns (sixth spatial derivatives of Gaussians). Stimuli were presented on a gray-scale display screen of a Macintosh computer-based testing system at temporal frequencies primarily of 2 and 16 Hz. Contrast thresholds were measured in two subjects with normal visual acuity with use of forced-choice staircases. Contrast sensitivity functions for standard Sloan letters and D6 patterns were comparable at a temporal frequency of 16 Hz but differed systematically at a temporal frequency of 2 Hz. The measurement of contrast sensitivity for cosine log filtered letters presented at a temporal frequency of 2 Hz indicated that the object spatial frequency of maximum sensitivity shifted to lower frequencies as letter size decreased, whereas the retinal spatial frequency of maximum sensitivity remained relatively constant. When letters were spatially bandpass filtered at a peak object spatial frequency of 2.5 cycles/letter, then contrast sensitivity functions for letter identification were equivalent to those for D6 patterns at both temporal frequencies. These results suggest that spatially filtered letters may provide a more appropriate test of visual function than do standard letter optotypes.


Hereditary cataracts in Russian Blue cats.
The purpose of this study was to investigate the prevalence of cataracts in the Russian Blue breed of cats in Sweden, and to describe the clinical appearance of this presumed inherited form of cataract. A total of 66 Russian Blue cats were examined in Sweden, between March and October 2014, using standard examination techniques. The examined cats were between 3 months and 14 years of age. Pedigrees were collected from all examined cats for genetic studies. Mild-to-severe forms of mainly bilateral cataracts were observed in 22/66 examined Russian Blue cats of both sexes. Two affected cats were <1 year of age. The most frequently observed appearance of a cataract was a small triangular, Y-shaped or circular opacity at the border of the posterior nucleus and the anterior part of the posterior cortex, which caused no observable visual impairment. More extended forms were observed in 6/22 cats, with involvement of both the nucleus and either the entire cortex or parts of the posterior and/or anterior cortex. Visual impairment or blindness was observed in the latter six cases. Pedigree analyses indicated a simple autosomal recessive mode of inheritance for the defect, although a dominant mode with incomplete penetrance could not be excluded. This study indicates that the Russian Blue breed of cat is affected by hereditary cataracts. The high prevalence in young cats and the characteristic location of the most frequently observed defect in the study suggest an early onset type of cataract. The breeders should be aware of this defect and have their cats examined by a veterinary ophthalmologist before breeding of an individual Russian Blue cat is considered.


Time-resolved immunofluorometry of serum hTSH with enhanced sensitivity.
Sensitive TSH immunoassays offer a clear advance in discriminating the TSH concentrations in serum between hyperthyroid and euthyroid individuals; they have been proposed as the best single screening test for thyroid disorders. We have developed a highly sensitive serum TSH TRFIA based on DELFIA technology. Three monoclonal antibodies (McAbs) directed against different epitopes of the TSH molecule were involved in this assay, of which, one McAb was used to coat clear microwells, and the other two were biotinylated' for signal generation after being bound by the europium labeled streptavidin. The europium label captured on the well surface was quantified by a routine dissociation-enhancement procedure. The fluorescence intensity was directly proportional to the serum hTSH concentration. The assay required two steps and could be completed within 5 h. The analytical sensitivity reached 0.002 mIU/L with a sample volume of 100 microL, the function sensitivity was 0.017 mIU/L. Measurements by the present method correlated well with that obtained by the ACS-180 chemi-luminescence immunoassay (CLIA). The discrimination of hyperthyroid patients from clinically euthyroid patients by the present method was much better than that by the routine IRMA.


Comparison of female rat reproductive effects of pubertal versus adult exposure to known endocrine disruptors.
A prevailing challenge when testing chemicals for their potential to cause female reproductive toxicity is the lack of appropriate toxicological test methods. We hypothesized that starting a 28-day in vivo toxicity study already at weaning, instead of in adulthood, would increase the sensitivity to detect endocrine disruptors due to the possibility of including assessment of pubertal onset. We compared the sensitivity of two rat studies using pubertal or adult exposure. We exposed the rats to two well-known human endocrine disruptors, the estrogen diethylstilbestrol (DES; 0.003, 0.012, 0.048 mg/kg bw/day) and the steroid synthesis inhibitor ketoconazole (KTZ; 3, 12, 48 mg/kg bw/day). Specifically, we addressed the impact on established endocrine-sensitive endpoints including day of vaginal opening (VO), estrous cyclicity, weights of reproductive organs and ovarian histology. After 28 days of exposure, starting either at weaning or at 9 weeks of age, DES exposure altered estrous cyclicity, reduced ovary weight as well as number of antral follicles and corpora lutea. By starting exposure at weaning, we could detect advanced day of VO in DES-exposed animals despite a lower body weight. Some endpoints were affected mainly with adult exposure, as DES increased liver weights in adulthood only. For KTZ, no effects were seen on time of VO, but adrenal and liver weights were increased in both exposure scenarios, and adult KTZ exposure also stimulated ovarian follicle growth. At first glance, this would indicate that a pubertal exposure scenario would be preferrable as timing of VO may serve as sensitive indicator of endocrine disruption by estrogenic mode of action. However, a higher sensitivity for other endocrine targets may be seen starting exposure in adulthood. Overall, starting a 28-day study at weaning with inclusion of VO assessment would mainly be recommended for substances showing estrogenic potential e.g., in vitro, whereas for other substances an adult exposure scenario may be recommended.


Treatment advances in small cell lung cancer (SCLC).
Small cell lung cancer (SCLC) is an aggressive tumor characterized by rapid doubling time and high propensity for early development of disseminated disease. Although most patients respond to initial therapy with a platinum doublet, the majority of those with limited stage and virtually all patients with metastatic disease eventually develop tumor progression for which there are limited treatment options. There have been no recent changes in the treatment of SCLC, with platinum plus etoposide and topotecan as the standard first-line and second-line respectively, neither showing survival benefit over the combination of cyclophosphamide, doxorubicin and vincristine, which was developed in the 1970s. More recently, a new understanding of the biology of SCLC has led to the development of novel drugs, of which the most promising are the immune checkpoint inhibitors and the antibody drug conjugate rovalpituzumab tesirine.


Inhaled corticosteroid use in asthma and the prevention of myocardial infarction.
Asthma patients may be at increased risk of cardiovascular outcomes due to hypoxemia from asthma exacerbations and bronchodilator-induced tachycardia. We investigated whether inhaled corticosteroids, which are known to improve asthma control and reduce exacerbations, are associated with a lower rate of myocardial infarction. We used the Saskatchewan Health databases to form a population-based cohort of subjects aged 5 to 44 years who were using antiasthma drugs between 1975 and 1991. Subjects were followed until 1997, the age of 55 years, or death. A nested case-control approach was used where each subject with a first myocardial infarction was matched on calendar time, age, and sex with up to 10 controls randomly selected from the cohort. The cohort consisted of 30,569 subjects, including 105 patients with myocardial infarction who were matched with 933 controls. The adjusted rate ratio of myocardial infarction for inhaled corticosteroid use during the year before the index date was 0.56 (95% confidence interval [CI]: 0.32 to 0.99) as compared with no use. Myocardial infarction decreased by 12% (95% CI: 0% to 23%) with each additional canister used during this 1-year period. The rate ratio of myocardial infarction for inhaled corticosteroid use was 0.78 (95% CI: 0.41 to 1.51) among patients with milder asthma and 0.19 (95% CI: 0.04 to 0.97) among those with more severe asthma. Inhaled corticosteroid use may reduce the risk of myocardial infarction in asthma patients, particularly those with more severe disease.


High-dose cytarabine neurotoxicity: MR findings during the acute phase.
The authors report an acute cerebral and cerebellar syndrome in a patient treated with high-dose cytarabine. Diffuse high-intensity lesions in the central white matter on T2-weighted MR completely reversed with resolution of the clinical syndrome. Although the autopsy revealed cerebellar injury, the cerebral cortex was grossly and microscopically normal, consistent with a reversible process.


Targeted delivery of microRNA 146b mimic to hepatocytes by lactosylated PDMAEMA nanoparticles for the treatment of NAFLD.
Non-alcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases worldwide, and precision therapeutic will be a benefit for the NAFLD regression. In this study, we observed low microRNA 146 b (miR-146 b) expression in NAFLD mice model induced by methionine-choline-deficient diet (MCD) compared with control group. Furthermore, miR-146b-/- mice induced MCD exhibited severe liver steatosis and hepatitis. A bio-distribution study showed that novel Lactosylated PDMAEMA nanoparticles effectively targeted hepatocytes Lac-PDMAEMA. We coupled miR-146b mimic with Lac-PDMAEMA and then were administrated to NAFLD mice model, which could obviously alleviate the hepatic steatosis. Lac-PDMAEMA effectively delivered miR-146b mimic to hepatocytes with a ∼8-fold upregulation of miR-146b mimic targeting MyD88 and IRAK1, and in turn suppressed the expression of PPARγ. Meanwhile, TNF-α and IL-6 mRNA levels were decreased after administration of Lac-PDMAEMA/miR-146b mimic. So, we made a conclusion that targeted delivering miR-146b mimic to the hepatocytes by, coupling Lac-PDMAEMA nanoparticles could effectively alleviate the hepatic steatosis in NAFLD mice, which maybe bring a new and effective way to intervene and therapy the NAFLD.


Physical mapping and RFLP analysis of mtDNAs from the ascosporogenous yeasts: Saccharomyces exiguus, S. kluyveri and Hansenula wingei.
Mitochondrial DNAs from the ascosporogenous yeasts S. exiguus, S. kluyveri and H. wingei were prepared by a new rapid method without CsCl isopycnic centrifugation. The mtDNA RFLPs were identified and clearly distinguished each species from the other. The physical maps were constructed by single and double digestion with nine restriction endonucleases. The location of rRNA genes was assigned to the maps by Southern hybridization with synthetic consensus probes. The genome sizes of these mtDNAs were estimated to be 45 kb for S. exiguus, 54 kb for S. kluyveri and 27 kb for H. wingei. The mtDNA RFLP analysis indicates a phylogenetic relationship among these yeasts. This indicates that S. cerevisiae is closer to H. wingei than S. kluyveri. However, the derived phylogenetic tree is completely consistent with that which was previously constructed on amino acid replacement in mating pheromones and electrophoretic karyotypes (Yoshida et al., 1989).


Novel Approach to Endoscopic Foreign Body Retrieval From the Gastric Body.
Foreign body (FB) ingestion is a common occurrence in the United States with a reported incidence of 120 per 1 million people, accounting for up to 1500 fatalities annually. The majority of FB ingestions will pass through the gastrointestinal tract spontaneously, while in 10% to 20% of patients, intervention will be necessary. A variety of endoscopic devices can be utilized to facilitate FB removal from the gastrointestinal tract, including snares, retrieval nets, and grasping forceps. We report the case of a 58-year-old female who required utilization of endoscopic scissors for FB removal in the setting of multiple failed attempts with traditional methods. This case highlights a novel approach to gastric FB removal utilizing endoscopic scissor forceps, which should be considered in select cases to further improve the efficacy of endoscopic FB removal and reduce the need for surgical intervention.


Detection of RET (rearranged during transfection) variants and their downstream signal molecules in RET rearranged lung adenocarcinoma patients.
We screened resected tumor tissues from patients with lung cancer for EGFR mutations, ALK rearrangements, and rearranged during transfection (RET) gene variants (including RET rearrangements and the Kinesin Family Member 5B (KIF5B)-RET fusion gene) using various methods including reverse transcription polymerase chain reaction (RT-PCR), transcript assays, fluorescence in situ hybridization (FISH), and immunohistochemistry (IHC). We also examined the protein expression of associated downstream signaling molecules to assess the effect of these variants on patient outcome. We constructed a tissue microarray (TMA) comprising 581 resected tumor tissues from patients with lung adenocarcinoma and analyzed the microarray by both FISH (using RET break-apart and KIF5B-RET SY translocation probes) and a commercial RET transcript assay. We evaluated the expression of RET and RET-related signaling molecules, including p-AKT and p-ERK, by TMA -based IHC staining. Among the 581 specimens, 51 (8.8%) specimens harbored RET rearrangements, including 12 cases (2.1%) carrying a KIF5B-RET fusion gene. Surprisingly, RET expression was lower in KIF5B-RET fusion gene-positive than in RET wild-type specimens. We detected activating EGFR mutations in 11 (21.6%) of the 51 RET variant-positive specimens. Among the KIF5B-RET fusion gene-positive specimens, p-ERK expression was significantly lower in the EGFR mutation subgroup showing RET expression than in the EGFR mutation subgroup that did not express RET. Similarly, the RET rearrangement group showed significant variation in the expression level of p-AKT (P = 0.028) and p-ERK, whose expression remarkably increased in specimens not expressing RET. The expression of p-ERK markedly increased in the RET rearrangement group regardless of RET expression. This result suggests that a combination of RET and ERK inhibitors may be an effective treatment strategy for lung adenocarcinoma patients harboring RET variants.


Screening of Peruvian Medicinal Plants for Tyrosinase Inhibitory Properties: Identification of Tyrosinase Inhibitors in Hypericum laricifolium Juss.
Tyrosinase inhibitors are of far-ranging importance in cosmetics, medicinal products, and food industries. Peru is a diverse country with a wide variety of plants that may contain excellent anti-tyrosinase inhibitors. In the present study, the tyrosinase inhibitory properties of 50 medicinal plant extracts from Peru were investigated using tyrosinase assay. Among plant extracts, those that showed an inhibition rate >50% were Hypericum laricifolium Juss., Taraxacum officinaleF.H.Wigg., and Muehlenbeckia vulcanicaMeisn., with H. laricifolium Juss. showing the greatest anti-tyrosinase activity. Although H. laricifolium Juss. has been widely used as a medicinal plant by Peruvians, little is known regarding its bioactive components and effects on tyrosinase activity. For this reason, we attempted to discover tyrosinase inhibitors in H. laricifolium Juss. for the first time. The bioactive components were separated by Sephadex LH-20 chromatography and eluted with 100% methanol. Eight compounds were discovered and characterized by high-performance liquid chromatography coupled with diode array detection (HPLC-DAD): protocatechuic acid, p-hydroxybenzoic acid, chlorogenic acid, vanilic acid, caffeic acid, kaempferol 3-O-glucuronide, quercetin, and kaempferol. In addition, the concentration of these compounds required for 50% inhibition (IC50) of tyrosinase activity were evaluated. Quercetin exhibited the strongest tyrosinase inhibition (IC50 14.29 ± 0.3 μM). Therefore, the Peruvian plant H. laricifolium Juss. could be a novel source for anti-tyrosinase activity.


Role of side chains in collagen triple helix stabilization and partner recognition.
Collagen is a widespread protein family involved in a variety of biological processes. The complexity of collagen and its fibrous nature prevent detailed investigations on the full-length protein. Reductionist approaches conducted by dissecting the protein complexity through the use of model peptides have proved to be quite effective. There are, however, several issues regarding structure-stability relationships, aggregation in higher-order assemblies, and partner recognition that are still extensively investigated. In this review, we discuss the role that side chains play in triple helix stabilization and in partner recognition. On the basis of recent literature data, we show that collagen triple helix stability is the result of the interplay of different factors. As a general trend, interactions established by amino/imino acid side chains within the triple helix scaffold effectively modulate the intrinsic residue propensity for this common structural motif. The use of peptide models has also highlighted the role that side chains play in collagen self-association and in its interactions with receptors. Valuable examples in these fields are illustrated. Finally, future actions required to obtain more detailed information on the structure and the function of this complex protein are also delineated.


Biomechanical properties of canine cortical bone allografts: effects of preparation and storage.
The effects of various preparation and storage procedures and of different storage times on structural properties of canine cortical bone allografts were determined by evaluation of the compressive load to failure of a whole diaphyseal segment, the ability of a screw to resist being pulled from a cortical segment, and the torque required to strip the threads of a screw hole in a cortical segment. Preparation and storage procedures evaluated were sterile collection and storage at -20 C; ethylene oxide sterilization and storage at room temperature (22 C); chemical sterilization (methanol and chloroform, then iodoacetic acid) and storage at -20 C; and chemical sterilization, partial decalcification, and storage at -20 C. Storage times were 1, 16, and 32 weeks for each procedure. After 1 week of storage, aseptically collected frozen bone and ethylene oxide-sterilized bone had an increase, compared with matched controls, in load to failure in compression, but pullout load or screw-stripping torque did not change. Chemically sterilized bone had not changed after 1 week of storage, whereas chemically sterilized and partially decalcified bone had a 40% to 60% decrease in compressive load to failure, pullout load, and screw-stripping torque. Chemically sterilized and partially decalcified bone remained weak after 16 and 32 weeks of storage. Significant structural alterations were not detected in aseptically collected bone after 16 or 32 weeks of storage. Ethylene oxide-sterilized bone had a reduced pullout load after 32 weeks of storage. Chemically sterilized bone had significantly reduced compressive load to failure and pullout load after 16 and 32 weeks of storage.(ABSTRACT TRUNCATED AT 250 WORDS)


A treatment-specific marginal structural Cox model for the effect of treatment discontinuation.
Patients taking a prescribed medication often discontinue their treatment; however, this may negatively impact their health outcomes. If doctors had statistical evidence that discontinuing some prescribed medication shortened, on average, the time to a clinical event (e.g., death), they could use that knowledge to encourage their patients to stay on the prescribed treatment. We describe a treatment-specific marginal structural Cox model for estimation of the causal effect of treatment discontinuation on a survival endpoint. The effect of treatment discontinuation is quantified by the hazard ratio of the event hazard rate had the population followed the regime "take treatment a until it is discontinued at some time ν ," versus the event hazard rate had the population never discontinued treatment a . Valid causal analysis requires control for treatment confounding, regime confounding, and censoring due to regime violation. We propose new inverse probability of regime compliance weights to address the three issues simultaneously. We apply the framework to data from the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) study. Patients from this study are treated with one of two types of oral anticoagulants (OACs). We test whether the causal effect of treatment discontinuation differs by type of OAC, and we also estimate the size and direction of the effect. We find evidence that OAC discontinuation increases the hazard for certain events, but we do not find evidence that this effect differs by treatment.


Bismuth-doped-glass optical fibers--a new active medium for lasers and amplifiers.
Optical fibers with bismuth-doped silicate and germanate glass cores were fabricated by the modified chemical vapor deposition technique (solution and vapor-phase Bi incorporation). The fibers revealed an efficient luminescence with a maximum in the 1050-1200 nm spectral range, FWHM up to 200 nm, and a lifetime of the order of 1 ms.


Secondary radiation-induced bone tumours demonstrate a high degree of genomic instability predictive of a poor prognosis.
Secondary bone tumours arising in the field of a preceding radiotherapy are a serious late effect, in particular considering the increasing survival times in patients treated for paediatric malignancies. In general, therapy associated tumours are known to show a more aggressive behaviour and a limited response to chemotherapy compared with their primary counterparts. It is not clear however whether this less favourable outcome is caused by inherent genetic factors of the tumour cells or by a general systemic condition of the patient. To elucidate this we analysed a series of bone sarcomas with a history of prior irradiation for the presence of genomic alterations and compared them with the alterations identified earlier in primary osteosarcomas. We analysed seven radiation induced bone sarcomas for genome-wide losses of heterozygosity (LOH) using Affymetrix 10K2 high-density single nucleotide polymorphism (SNP) arrays. Additionally, copy number changes were analysed at two distinct loci on 10q that were recently found to be of major prognostic significance in primary osteosarcomas. All the investigated tumours showed a LOH at 10q21.1 with 86% of cases (6/7) revealing a total genome-wide LOH score above 2400 and more than 24% of the genome being affected. Our results indicate similar genetic alterations in radiation induced sarcomas of bone and primary osteosarcomas with a poor prognosis. We speculate that the high degree of genomic instability found in these tumours causes the poor prognosis irrespective of the initiating event.


A service evaluation comparing home-based testing to clinic-based testing for HIV, syphilis and hepatitis B in Birmingham and Solihull.
The sexual health services in the Birmingham and Solihull area of the United Kingdom, called Umbrella, has been offering home-based testing for sexually transmitted infections to patients since August 2015. The aim of this service evaluation was to evaluate the uptake, return rate and new diagnosis rates of home-based testing in comparison with clinic-based testing for human immunodeficiency virus (HIV), syphilis (STS) and hepatitis B. Home-based testing, although popular, had low uptake amongst high-risk groups such as men who have sex with men (MSM), compared to the clinic-based group (1% versus 11%, p < 0.001). This resulted in low positivity rates for HIV (0.02%) and STS (0.17%) and no new cases of hepatitis B in the home-based group. Therefore, our results show that home-based testing is not a cost-effective method of testing for HIV and likely this is also the case for hepatitis B and STS. Our recommendation would be to encourage uptake of home-based testing in high-risk groups such as MSM and Black Africans to improve the diagnosis rates of HIV, STS and hepatitis B. Alternatively, the continuation of home-based blood testing in the Birmingham and Solihull area will need to be reviewed by Umbrella as a cost-saving strategy for the service in the future.


Clinical outcomes and etiology of acquired sixth cranial nerve palsy.
The objective of this study was to investigate the difference in clinical features according to age and factors affecting recovery of acquired sixth cranial nerve (CN6) palsy.A total of 156 patients with acute CN6 palsy between March 2016 and August 2021 who were followed up for at least 3 months were included in this study. Etiology, rate of recovery, and factors associated with recovery were retrospectively investigated.The average age of patients with CN6 palsy was about 60years and the mean duration of recovery was about 2.5 months. Of 156 patients, 72 (46.15%) had a microvascular etiology and 25 (16.03%) patients had a brain vascular lesions. Brain neoplasm, trauma, and "others" were found in 10 (6.41%), 11 (7.05%), and 15 (9.62%) patients, respectively. Among the total of 156 patients, 28 (17.95%) failed to completely recover. Non-isolated CN6 palsy with other cranial nerve palsies were recorded in 29 (18.59%) cases. Comparison of age (<50years vs ≥50years), between recovery and non-recovery groups showed that etiology was significantly different.The recovery rate of acquired CN6 palsy was about 82% and about 27% of patients had brain lesions. Also, varying rates and duration of recovery were found according to etiology, so we should be pay attention to diagnosis of causative disease in CN6 palsy patients.


[Malignant angiosarcoma of the right atrium in pregnancy. Diagnostic and therapeutic problems].
Primary tumors of the heart, in contrast to secondary metastatic tumors show a very rare occurrence. About 25% of all primary cardiac tumors are malignant with angiosarcomas being the most frequent type of tumor. The clinical presentation include pericardial tamponade by hemorrhagic pericardial effusion, right heart failure, lung embolism and thoracal pain. Diagnostic procedures include echocardiography, magnetic resonance imaging, CT scan, angiography, pericardioscopy and finally surgical exploration. We report on a 27-year old pregnant woman (23rd week) with a malignant primary angiosarcoma of the right atrium. The patient was admitted to the hospital with progressive shortening of breath due to pericardial tamponade from pericardial effusion. A tumor of the right atrium was detected by echocardiography. Diagnostic procedures had to consider the pregnancy of the patient. Transesophageal echocardiography, magnetic resonance imaging and finally angiography of the right heart with tumor biopsy were performed. Histological examination did not show any signs of malignancy. After corticosteroids pericardial effusion disappeared. Surgical exploration of the tumor was not performed because of the pregnancy. Two weeks later the patient underwent emergency surgery because of progressive heart failure due to obstruction of the tricuspidal valve by the tumor. Thereby intrauterine death of the fetus occurred. The tumor was removed and the right atrium was reconstructed using a Dacron patch. Adjuvant chemotherapy was performed. Eight months later the tumor recurred and heart transplantation was performed. two months later pulmonary metastases were found. the patient died 20 months after onset of symptoms. This is a rare case of the very unusual coincidence of pregnancy and a primary malignant heart tumor.


The lncRNA SNHG16 affects prognosis in hepatocellular carcinoma by regulating p62 expression.
Long noncoding RNAs (lncRNAs) regulate tumor development and progression by promoting proliferation, invasion, and metastasis. The oncogenic role of lncRNA SNHG16 in hepatocellular carcinoma (HCC) has not been revealed. LncRNA SNHG16 is upregulated in HCC and correlates with poorer prognosis. Patients with high SNHG16 expression showed lower rates of overall and disease-free survival than patients with low SNHG16 expression. Multivariate Cox regression revealed that SNHG16 expression was an independent predictor of poor overall and disease-free survival. In vitro, SNHG16 promoted HCC cell proliferation, migration, and invasion while inhibiting apoptosis; in vivo, it accelerated tumor development. Altering SNHG16 expression altered levels of miR-17-5p, which in turn modified expression of p62, which has been shown to regulate the mTOR and NF-κB pathways. Indeed, altering SNHG16 expression in HCC cells activated mTOR and NF-κB signaling. These results reveal a potential mechanism for the oncogenic role of SNHG16 in HCC. SNHG16 may therefore be a promising diagnostic marker as well as therapeutic target in HCC.


Postdependent state in rats as a model for medication development in alcoholism.
Rational development of novel therapeutic strategies for alcoholism requires understanding of its underlying neurobiology and pathophysiology. Obtaining this knowledge largely relies on animal studies. Thus, choosing the appropriate animal model is one of the most critical steps in pre-clinical medication development. Among the range of animal models that have been used to investigate excessive alcohol consumption in rodents, the postdependent model stands out. It was specifically developed to test the role of negative affect as a key driving force in a perpetuating addiction cycle for alcoholism. Here, we will describe our approach to make rats dependent via chronic intermittent exposure to alcohol, discuss the validity of this model, and compare it with other commonly used animal models of alcoholism. We will summarize evidence that postdependent rats fulfill several criteria of a 'Diagnostic and Statistical Manual of Mental Disorders IV/V-like' diagnostic system. Importantly, these animals show long-lasting excessive consumption of and increased motivation for alcohol, and evidence for loss of control over alcohol intake. Our conclusion that postdependent rats are an excellent model for medication development for alcoholism is underscored by a summary of more than two dozen pharmacological tests aimed at reversing these abnormal alcohol responses. We will end with open questions on the use of this model. In the tradition of the Sanchis-Segura and Spanagel review, we provide comic strips that illustrate the postdependent procedure and relevant phenotypes in this review.


[Application of digital technique in shaping of emergence profile for prostheses supported by dental implant].
In the field of dental implantology, the design of interface esthetics not only affects the esthetic coutcome, but also affects the health and long-term stability of the tissue around dental implant. Dental implant, bone tissue, soft tissue, and prostheses' morphology are the four critical elements of interface esthetics. The emergence profile located at the junction of these four components is an important form of oral esthetics. With the wide application of digital technique in the field of dentistry, the shaping of emergence profile also involves the application of many kinds of digital approaches. This article intends to make a review of the application of digital technique in rehabilitation of interface esthetics to provide a reference for clinical practic.


Improving timely sepsis care using the surviving sepsis campaign one-hour bundle in a rural emergency department.
Sepsis is deadly when not recognized and treated in a timely manner and leads to 270,000 deaths each year in America. Mortality increases eight percent for each hour treatment is delayed. Sepsis-related admission is the most expensive condition in the United States with a median cost per patient of $32,421. Baseline data for patients with sepsis revealed that only 30% were recognized in triage, only 20% received correct amounts of fluids, and only 45% received antibiotics within one hour. The aim of this project was to improve timely sepsis care to 75% for patients in a rural emergency department within 90 days. A rapid cycle quality improvement project was completed, consisting of four plan-do-study-act cycles over 90 days. Each cycle included tests of change related to team and patient engagement, screening, and the use of timely sepsis orders. Data were collected three times weekly and analyzed using run charts. Interventions included screening in triage with positively screened patients receiving participatory education, team handoff communication, a sepsis checklist for nurse-driven orders, and Power Hour for timely care. Team communication improved to 83%. Patient education exceeded goal, with 100% of patients taking an active role in care. Sepsis screening improved to 100%. The recommended One-Hour Bundle for timely sepsis treatment improved to 83%. The project was successful in improving patient and team engagement, screening, and sepsis care within 1 hour for emergency department patients.


Distribution of Clostridium botulinum in Japan and in Shinkiang district of China.
Soil specimens obtained from several areas of Japan, which are closely located to or facing the Continental land of China, were examined for the distribution of Clostridium botulinum, especially pertaining to types A and B. A total of 266 specimens of Japan, when cultured, showed no type A or B toxicity, although 30 (11.3%), 4 (1.5%), and 10 (3.8%) of the specimens showed C1, C2, and type E toxicities, respectively. On the contrary, types A and/or B toxicities were shown, by the same method, in 14 of 20 specimens of Shinkiang district, China. The highest number of C. botulinum cells found in one gram of soil specimen was 25 for type A and 10 for type B.


Genetic analyses of the fusion protein genes in human parainfluenza virus types 1 and 3 among patients with acute respiratory infections in Eastern Japan from 2011 to 2015.
To genetically explore the fusion protein gene (F) in human parainfluenza virus type 1 (HPIV1) and type 3 (HPIV3) strains, we analysed them in patients with acute respiratory infections in Eastern Japan from 2011 to 2015. We constructed phylogenetic trees based on the HPIV and HPIV3 F gene using the maximum likelihood method and conducted P-distance and selective pressure analyses. We also predicted the linear epitopes of the protein in the prototype strains. Furthermore, we mapped the amino acid substitutions of the proteins. Nineteen strains of HPIV1 and 53 strains of HPIV3 were detected among the clinical acute respiratory infection cases. The phylogenetic trees indicated that the HPIV1 and HPIV3 strains were classified into clusters II and III and cluster C, respectively. The P-distance values of the HPIV1 and HPIV3 F genes were <0.03. Two positive selection sites were inferred in the HPIV1 (aa 8 and aa 10), and one positive selection site was inferred in the HPIV3 (aa 108), but over 10 negative selection sites were inferred. Four epitopes were predicted for the HPIV1 prototype strains, while five epitopes were predicted for the HPIV3 prototype strain. A positive selection site (aa 108) or the HPIV3 F protein was involved in the predicted epitope. Additionally, we found that an amino acid substitution (R73K) in the LC76627 HPIV3 strain presumably may affect the resistance to neutralization by antibodies. The F gene of HPIV1 and HPIV3 was relatively well conserved in the eastern part of Japan during the investigation period.


Exploiting plant virus-derived components to achieve in planta expression and for templates for synthetic biology applications.
This review discusses the varying roles that have been played by many plant-viral regulatory sequences and proteins in the creation of plant-based expression systems and virus particles for use in nanotechnology. Essentially, there are two ways of expressing an exogenous protein: the creation of transgenic plants possessing a stably integrated gene construction, or the transient expression of the desired gene following the infiltration of the gene construct. Both depend on disarmed strains of Agrobacterium tumefaciens to deliver the created gene construction into cell nuclei, usually through the deployment of virus-derived components. The importance of efficient mRNA translation in the latter process is highlighted. Plant viruses replicate to sustain an infection to promote their survival. The major product of this, the virus particle, is finding increasing roles in the emerging field of bionanotechnology. One of the major products of plant-viral expression is the virus-like particle (VLP). These are increasingly playing a role in vaccine development. Similarly, many VLPs are suitable for the investigation of the many facets of the emerging field of synthetic biology, which encompasses the design and construction of new biological functions and systems not found in nature. Genetic and chemical modifications to plant-generated VLPs serve as ideal starter templates for many downstream synthetic biology applications.


Specific Raman signatures of a dimetallofullerene peapod.
We report on the Raman spectroscopy of a dimetallofullerene peapod, (La(2)@C(80))(m)@SWNT. Drastic changes are observed with respect to pristine nanotubes. A sharp intense line at 142 cm(-1) is interpreted as a signature of polymerization of the encapsulated metallofullerenes. Additional strong signatures appear at about 400, 520, and 640 cm(-1), respectively. Their intensity suggests the existence of an enhancement effect. The stiffening and the up-shift of the G-band modes appear to imply that a charge transfer process between the nanotube and the peas occurs.


Lysosomal accumulation of SCMAS (subunit c of mitochondrial ATP synthase) in neurons of the mouse model of mucopolysaccharidosis III B.
The neurodegenerative disease MPS III B (Sanfilippo syndrome type B) is caused by mutations in the gene encoding the lysosomal enzyme alpha-N-acetylglucosaminidase, with a resulting block in heparan sulfate degradation. A mouse model with disruption of the Naglu gene allows detailed study of brain pathology. In contrast to somatic cells, which accumulate primarily heparan sulfate, neurons accumulate a number of apparently unrelated metabolites, including subunit c of mitochondrial ATP synthase (SCMAS). SCMAS accumulated from 1 month of age, primarily in the medial entorhinal cortex and layer V of the somatosensory cortex. Its accumulation was not due to the absence of specific proteases. Light microscopy of brain sections of 6-months-old mice showed SCMAS to accumulate in the same areas as glycosaminoglycan and unesterified cholesterol, in the same cells as ubiquitin and GM3 ganglioside, and in the same organelles as Lamp 1 and Lamp 2. Cryo-immuno electron microscopy showed SCMAS to be present in Lamp positive vesicles bounded by a single membrane (lysosomes), in fingerprint-like layered arrays. GM3 ganglioside was found in the same lysosomes, but was not associated with the SCMAS arrays. GM3 ganglioside was also seen in lysosomes of microglia, suggesting phagocytosis of neuronal membranes. Samples used for cryo-EM and further processed by standard EM procedures (osmium tetroxide fixation and plastic embedding) showed the disappearance of the SCMAS fingerprint arrays and appearance in the same location of "zebra bodies", well known but little understood inclusions in the brain of patients with mucopolysaccharidoses.


Predictive value of 1H MR spectroscopy and 18F-FDG PET/CT for local control of advanced oropharyngeal and hypopharyngeal squamous cell carcinoma receiving chemoradiotherapy: a prospective study.
To determine whether pretreatment in vivo 1H magnetic resonance (MR) spectroscopy at 3 Tesla (T) and 18F-FDG PET/CT can offer predictive power regarding the local control of oropharyngeal or hypopharyngeal squamous cell carcinoma (OHSCC) patients. 1H MR spectroscopy was performed in addition to conventional MR imaging before definitive chemoradiotherapy in 58 patients with advanced OHSCC. The relationship of local control with the 1H MR spectroscopy and 18F-FDG PET/CT parameters was analyzed. With a median follow-up of 17.6 months, 13 (22.4%) patients exhibited local failure; whereas the remaining 45 achieved local control. Kaplan-Meier analysis identified age > 60 years, creatine level on MRS ≦ 6.02 mM, glutamine and glutamate (Glx) level on MRS > 3.31 mM, and total lesion glycolysis (TLG) on 18F-FDG PET/CT > 217.18 g/mL × mL as significant adverse predictors for 2-year local control. Multivariate Cox regression analysis showed that age (p=0.017), Glx level on MRS (p=0.021), and TLG on 18F-FDG PET/CT (p=0.028) retained their independent prognostic significance. A scoring system was constructed based on the sum of these three factors. We found that patients with scores of 2-3 had significantly poorer local control rates than patients with scores of 0-1 (33.3% versus 86.8%, p=0.003). We conclude that Glx on 1H MR spectroscopy at 3 T was the independent prognostic factor for local control of OHSCC patients treated with chemoradiotherapy, and its combination with age and TLG may help identify a subgroup of patients at high risk for developing local failure.


Heme oxygenase activity modulates vascular endothelial growth factor synthesis in vascular smooth muscle cells.
Hypoxia, cytokines, and nitric oxide (NO) stimulate the generation of vascular endothelial growth factor (VEGF) and induce heme oxygenase-1 (HO-1) expression in vascular tissue. HO-1 degrades heme to carbon monoxide (CO), iron, and biliverdin, the latter being reduced to bilirubin by biliverdin reductase. In the present study, we investigated the role of HO-1 in the modulation of VEGF synthesis in rat vascular smooth muscle cells (VSMC). In VSMC stimulated with cytokines, inhibition of NO production significantly, but not completely, reduced VEGF release. In contrast, inhibition of HO activity by tin protoporphyrin IX (SnPPIX) totally prevented cytokine-induced increase in VEGF, despite an augmented synthesis of intracellular NO. Stimulation of HO-1 activity by hemin enhanced VEGF production; this effect was abrogated by blockade of the HO pathway. Similarly, VEGF synthesis induced by hypoxia was down-regulated by SnPPIX, but not by inhibitors of NO synthase. To elucidate further a direct involvement of HO-1 in the observed effects, we generated transfected cells that overexpressed the HO-1 gene. Notably, these cells synthesized significantly more VEGF protein than cells transfected with a control gene. Among the products of HO-1, biliverdin and bilirubin showed no effect, whereas iron ions inhibited VEGF synthesis. Exposure of cells to 1% CO resulted in a marked accumulation of VEGF (20-fold increase) over the basal level. Our data indicate that HO-1 activity influences the generation of VEGF in VSMC in both normoxic and hypoxic conditions. As CO and iron, respectively the inducer and the inhibitor of VEGF synthesis, are concomitantly produced during the degradation of heme, these data indicate that HO by-products may differentially modulate VEGF production.


CT coronary angiography and COVID-19: inpatient use in acute chest pain service.
CT coronary angiography (CTCA) is a well-validated clinical tool in the evaluation of chest pain. In our institution, CTCA availability was increased in January 2020, and subsequently, expanded further to replace all exercise testing during the COVID-19 pandemic. Our objective was to assess the impact of increased utilisation of CTCA on length of stay in patients presenting with chest pain in the prepandemic era and during the COVID-19 pandemic. Study design was retrospective. Patients referred for cardiology review between October 2019 and May 2020 with chest pain and/or dyspnoea were broken into three cohorts: a baseline cohort, a cohort with increased CTCA availability and a cohort with increased CTCA availability, but after the national lockdown due to COVID-19. Coronary angiography and revascularisation, length of stay and 30-day adverse outcomes were assessed. 513 patients (35.3% female) presented over cohorts 1 (n=179), 2 (n=182), and 3 (n=153). CTCA use increased from 7.8% overall in cohort 1% to 20.4% in cohort 3. Overall length of stay for the patients undergoing CTCA decreased from a median of 4.2 days in cohort 1 to 2.5 days in cohort 3, with no increase in 30 days adverse outcomes. Invasive coronary angiogram rates were 45.8%, 39% and 34.2% across the cohorts. 29.6% underwent revascularisation in cohort 1, 15.9% in cohort 2 and to 16.4% in cohort 3. Increased CTCA availability was associated with a significantly reduced length of stay both pre-COVID-19 and post-COVID-19 lockdown, without any increase in 30-day adverse outcomes.


Electrochemical oxidation of N-p-toluenesulfinamides.
[reaction: see text] Contrasting and interesting electrochemical behavior is observed in anodic oxidation of N-substituted p-toluenesulfinamides under controlled current conditions. For sulfinamides derived from secondary alkylamines and primary arylamines, the N-sulfinyl group is removed and the corresponding amines are formed; for sulfinamides derived from primary alkylamines, sulfur oxidation yields the corresponding sulfonamides in good yields.


Pancreas transcription factor 1alpha expression is regulated in pancreatitis.
Expression of acinar cell-specific genes requires the pancreas transcription factor 1alpha (Ptf1alpha). p48 is the only component of Ptf1alpha that is involved in both acinar gene regulation and pancreatic ontogenesis. To determine whether Ptf1alpha/p48 expression is regulated during pancreatitis, acute pancreatitis was induced in rats by repeated caerulein injections; early chronic pancreatitis by the combined administration of caerulein and cyclosporin A; and focal pancreas fibrosis by trinitrobenzene sulfonic acid infusion into the pancreatic duct. AR42J cells were used to examine caerulein effects on acinar cells. Ptf1alpha/p48 expression was examined using immunohistochemistry, Western blotting, and qRT-PCR methods. In acute pancreatitis, Ptf1alpha/p48 decreased markedly within 6 h as determined by Western blotting and immunohistochemistry. After 24 h, Ptf1alpha/p48 increased continuously and normalized at day six. In contrast, pancreas amylase reached a nadir at 48 h, when Ptf1alpha/p48 had largely recovered. In the early chronic pancreatitis model Ptf1alpha/p48 levels did not completely recover even at day 14, and this was associated with a failure to restore normal histology and amylase content. qRT-PCR showed that p48 mRNA were reduced after pancreatitis induction and were followed by a decrease in elastase mRNA. In the focal pancreas fibrosis model, Ptf1alpha/p48 expression was undetectable in areas with substantial acinar cell loss and tubular complexes. Caerulein did not affect Ptf1alpha/p48 expression in AR42J cells. Ptf1alpha/p48 protein and mRNA levels are regulated in acute and chronic experimental pancreatitis. Inability to re-express Ptf1alpha/p48 after injury may preclude acinar cell differentiation and appropriate pancreatic regeneration.


Targets for human encoded microRNAs in HIV genes.
MicroRNAs (miRNAs) are increasingly being shown to play vital roles in development, apoptosis, and oncogenesis by interfering with gene expression at the post-transcriptional level. miRNAs, in principle, can contribute to the repertoire of host pathogen interactions during HIV-1 infection. Using a consensus scoring approach, high scoring miRNA-target pairs were selected which were identified by four well-established target prediction softwares. While hsa-mir-29a and 29b target the nef gene, hsa-mir-149 targets the vpr gene, hsa-mir-378 targets env, and hsa-mir-324-5p targets the vif gene. Not only were the minimum free energy values lowest for the bound complex, but also, the rules so far observed for microRNA-target pairing, viz., a continuous stretch of 6-7 base pairing towards the 5' end of the miRNA and incomplete complementarity with the target sequence, were found to be valid. The target regions were highly conserved across the various clades of HIV-1. microRNA expression profiles from previously reported microarray based experiments show that the five human miRNAs are expressed in T-cells, the normal site of infection of HIV-1 virus. This is the first report of human microRNAs which can target crucial HIV-1 genes including the nef gene, which plays an important role in delayed disease progression.


Factor analysis linking functions for simultaneously modeling neural and behavioral data.
A growing number of researchers have advocated for the advancement of cognitive neuroscience by blending cognitive models with neurophysiology. The recently proposed joint modeling framework is one way to bridge the gap between the abstractions assumed by cognitive models and the neurophysiology obtained by modern methods in neuroscience. Despite this advancement, the current method for linking the two domains is hindered by the dimensionality of the neural data. In this article, we present a new linking function based on factor analysis that allows joint models to grow linearly in complexity with increases in the number of neural features. The new linking function is then evaluated in two simulation studies. The first simulation study shows how the model parameters can be accurately recovered when there are many neural features, that mimics real-world applications. The second simulation shows how the new linking function can (1) properly recover a representation of the data generating model, even in the case of model misspecification, and (2) outperform the previous linking function in a cross-validation test. We close by applying a model equipped with the new linking function to real-world data from a perceptual decision making task. The model allows us to understand how differences in the model parameters emerge as a function of differences in brain function across speed and accuracy instruction.


Self-assembled hyaluronic acid nanoparticles for controlled release of agrochemicals and diosgenin.
Commercial sodium hyaluronate (HA) and synthetic hydrazide-modified HA were functionalized with diosgenin and two agrochemicals (brassinosteroids DI31 and S7) with degree of substitution ranging from 5.6 to 13.1%. The HA-steroid conjugates were studied with FTIR, 1H NMR and differential scanning calorimetry. Dynamic light scattering revealed self-assembly of the HA-steroid conjugates into stable negatively charged nanoparticles of around 159nm-441nm in water, which after drying appeared as 140nm-370nm spherically shaped nanoparticles according to transmission electron microscopy. These nanoparticles exhibited almost constant release rates of steroids for the first 8h, demonstrating sustained steroids delivery for 72h in acidic medium. The nanoparticles formed from HA-steroid conjugates were not cytotoxic to human microvascular endothelial cells (HMVEC), while the HA- brassinosteroid nanoparticles showed in vitro agrochemical activity that was superior to the activity observed for the parent brassinosteroids DI31 and S7 at 10-5 to 10-7mgmL-1.


Advances in transcorneal electrical stimulation: From the eye to the brain.
The mammalian brain is reported to contain about 106-109 neurons linked together to form complex networks. Physiologically, the neuronal networks interact in a rhythmic oscillatory pattern to coordinate the brain's functions. Neuromodulation covers a broad range of techniques that can alter neuronal network activity through the targeted delivery of electrical or chemical stimuli. Neuromodulation can be used to potentially treat medical conditions and can serve as a research tool for studying neural functions. Typically, the main method of neuromodulation is to electrically stimulate specific structures in both the central and peripheral nervous systems via surgically implanted electrodes. Therefore, it is imperative to explore novel and safer methods for altering neuronal network activity. Transcorneal electrical stimulation (TES) has rapidly emerged as a non-invasive neuromodulatory technique that can exert beneficial effects on the brain through the eyes. There is substantial evidence to show that TES can change the brain oscillations in rodents. Moreover, the molecular data clearly shows that TES can also activate non-visual brain regions. In this review, we first summarize the use of TES in the retina and then discuss its effects in the brain through the eye-brain connection. We then comprehensively review the substantial evidence from electrophysiological, behavioral, and molecular studies on the role of TES on modulating neurons in the brain. Lastly, we discuss the implications and possible future directions of the research on TES as a non-invasive tool for neuromodulation of the brain via directly stimulating the mammalian eye.


The polysialic acid mimetics idarubicin and irinotecan stimulate neuronal survival and neurite outgrowth and signal via protein kinase C.
Polysialic acid (PSA) is a large, negatively charged, linear homopolymer of alpha2-8-linked sialic acid residues. It is generated by two polysialyltransferases and attached to N- and/or O-linked glycans, and its main carrier is the neural cell adhesion molecule (NCAM). PSA controls the development and regeneration of the nervous system by enhancing cell migration, axon pathfinding, synaptic targeting, synaptic plasticity, by regulating the differentiation of progenitor cells and by modulating cell-cell and cell-matrix adhesions. In the adult, PSA plays a role in the immune system, and PSA mimetics promote functional recovery after nervous system injury. In search for novel small molecule mimetics of PSA that are applicable for therapy, we identified idarubicin, an antineoplastic anthracycline, and irinotecan, an antineoplastic agent of the topoisomerase I inhibitor class, as PSA mimetics using a competition enzyme-linked immunosorbent assay. Idarubicin and irinotecan compete with the PSA-mimicking peptide and colominic acid, the bacterial analog of PSA, for binding to the PSA-specific monoclonal antibody 735. Idarubicin and irinotecan stimulate neurite outgrowth and survival of cultured cerebellar neurons after oxidative stress via protein kinase C and Erk1/2 in a similar manner as colominic acid, whereas Fyn, casein kinase II and the phosphatase and tensin homolog are only involved in idarubicin and irinotecan-stimulated neurite outgrowth. These novel results show that the structure and function of PSA can be mimicked by the small organic compounds irinotecan and idarubicin which trigger the same signaling cascades as PSA, thus introducing the possibility of retargeting these drugs to treat nervous system injuries.


Sorting nexin 27 (SNX27) regulates the trafficking and activity of the glutamine transporter ASCT2.
Alanine-, serine-, cysteine-preferring transporter 2 (ASCT2, SLC1A5) is responsible for the uptake of glutamine into cells, a major source of cellular energy and a key regulator of mammalian target of rapamycin (mTOR) activation. Furthermore, ASCT2 expression has been reported in several human cancers, making it a potential target for both diagnostic and therapeutic purposes. Here we identify ASCT2 as a membrane-trafficked cargo molecule, sorted through a direct interaction with the PDZ domain of sorting nexin 27 (SNX27). Using both membrane fractionation and subcellular localization approaches, we demonstrate that the majority of ASCT2 resides at the plasma membrane. This is significantly reduced within CrispR-mediated SNX27 knockout (KO) cell lines, as it is missorted into the lysosomal degradation pathway. The reduction of ASCT2 levels in SNX27 KO cells leads to decreased glutamine uptake, which, in turn, inhibits cellular proliferation. SNX27 KO cells also present impaired activation of the mTOR complex 1 (mTORC1) pathway and enhanced autophagy. Taken together, our data reveal a role for SNX27 in glutamine uptake and amino acid-stimulated mTORC1 activation via modulation of ASCT2 intracellular trafficking.


Two-Photon Na+ Imaging Reports Somatically Evoked Action Potentials in Rat Olfactory Bulb Mitral and Granule Cell Neurites.
Dendrodendritic synaptic interactions are a hallmark of neuronal processing in the vertebrate olfactory bulb. Many classes of olfactory bulb neurons including the principal mitral cells (MCs) and the axonless granule cells (GCs) dispose of highly efficient propagation of action potentials (AP) within their dendrites, from where they can release transmitter onto each other. So far, backpropagation in GC dendrites has been investigated indirectly via Ca2+ imaging. Here, we used two-photon Na+ imaging to directly report opening of voltage-gated sodium channels due to AP propagation in both cell types. To this end, neurons in acute slices from juvenile rat bulbs were filled with 1 mM SBFI via whole-cell patch-clamp. Calibration of SBFI signals revealed that a change in fluorescence ΔF/F by 10% corresponded to a Δ[Na+]i of ∼22 mM. We then imaged proximal axon segments of MCs during somatically evoked APs (sAP). While single sAPs were detectable in ∼50% of axons, trains of 20 sAPs at 50 Hz always resulted in substantial ΔF/F of ∼15% (∼33 mM Δ[Na+]i). ΔF/F was significantly larger for 80 Hz vs. 50 Hz trains, and decayed with half-durations τ1/2 ∼0.6 s for both frequencies. In MC lateral dendrites, AP trains yielded small ΔF/F of ∼3% (∼7 mM Δ[Na+]i). In GC apical dendrites and adjacent spines, single sAPs were not detectable. Trains resulted in an average dendritic ΔF/F of 7% (16 mM Δ[Na+]i) with τ1/2 ∼1 s, similar for 50 and 80 Hz. Na+ transients were indistinguishable between large GC spines and their adjacent dendrites. Cell-wise analysis revealed two classes of GCs with the first showing a decrease in ΔF/F along the dendrite with distance from the soma and the second an increase. These classes clustered with morphological parameters. Simulations of Δ[Na+]i replicated these behaviors via negative and positive gradients in Na+ current density, assuming faithful AP backpropagation. Such specializations of dendritic excitability might confer specific temporal processing capabilities to bulbar principal cell-GC subnetworks. In conclusion, we show that Na+ imaging provides a valuable tool for characterizing AP invasion of MC axons and GC dendrites and spines.


Joint engagement and the emergence of language in children with autism and Down syndrome.
Systematic longitudinal observations were made as typically developing toddlers and young children with autism and with Down syndrome interacted with their caregivers in order to document how joint engagement developed over a year-long period and how variations in joint engagement experiences predicted language outcome. Children with autism displayed a persistent deficit in coordinated joint attention; children with Down syndrome were significantly less able to infuse symbols into joint engagement. For all groups, variations in amount of symbol-infused supported joint engagement, a state in which the child attended to a shared object and to language but not actively to the partner, contributed to differences in expressive and receptive language outcome, over and above initial language capacity.


The atrial natriuretic peptide as a regulator of Kupffer cell functions.
Kupffer cells (KCs), the resident macrophages of the liver, contribute prominently to liver injury by inflammatory mediators. Pre-conditioning with the atrial natriuretic peptide (ANP), known also as a regulator of macrophage functions, attenuates hepatic ischemia-reperfusion injury. Therefore, the aim of this study was to determine the presence of functional ANP receptors on isolated KCs and to investigate whether this hepatoprotective hormone influences the activation of KCs. KCs were isolated by collagenase/pronase digestion followed by elutrial centrifugation and cultured for 1 to 3 days. Intracellular cyclic guanosine 3'5'-monophosphate (cGMP) concentrations were measured by radioimmunoassay after treating the cells with sodium nitroprusside or ANP. KCs were stimulated with bacterial lipopolysaccharide in the presence or absence of ANP, and inflammatory mediators were determined. Phagocytosis was assayed using Coumarin-labeled latex particles and flow cytometric analysis. Treatment of KCs with ANP but not with sodium nitroprusside resulted in a significant elevation of intracellular cGMP levels indicating functional type A natriuretic peptide receptors (NPR-As). ANP significantly reduced lipopolysaccharide (LPS)-induced tumor necrosis factor alpha (TNFalpha) secretion, paralleled by an increased cell-associated TNFalpha. LPS-induced TNFalpha mRNA expression was not affected. ANP significantly increased phagocytotic activity of KCs via NPR-A. No effect of ANP on LPS-activated inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 protein levels, iNOS mRNA expression, nitric oxide, and PGE2-production was observed. We demonstrated functional cGMP-dependent ANP receptors in isolated rat KCs. ANP reduced TNFalpha release possibly by influencing post-translational processing of TNFalpha in LPS-activated KCs. In addition, we demonstrated that ANP enhances phagocytosis in KCs. These effects may contribute to the hepatoprotective actions of ANP.


Incorporation of (E)-5-(2-iodovinyl)-2'-deoxyuridine into deoxyribonucleic acids of varicella-zoster virus (TK+ and TK- strains)-infected cells.
The incorporation of (E)-5-(2-iodovinyl)-2'-deoxyuridine (IVDU) into DNA of varicella-zoster virus (VZV)-infected human embryo fibroblasts was studied, using thymidine kinase-positive (TK+) and thymidine kinase-negative (TK-) VZV strains. [125I]IVDU was taken up by cells infected with TK+ VZV-, but not by TK- VZV- or mock-infected cells. [125I]IVDU was incorporated into both VZV DNA and cellular DNA of TK+ VZV-infected cells. When the cells were exposed to 0.3 microM IVDU, a more marked shift was noted in the buoyant density of viral DNA than of host DNA. In contrast, the DNAs isolated from TK- VZV- or mock-infected cells did not exhibit a detectable incorporation of [125I]IVDU. [125I] IVDU-labeled VZV DNA was purified from the viral nucleocapsids of TK+ VZV-infected cells. Substitution of no more than 0.1-1% of the thymidine residues in the VZV DNA by IVDU seemed to suffice to inhibit the replication of VZV.


Potential lessons from public health and health promotion for the prevention of child abuse.
Two successful public health efforts of the last third of the twentieth century-tobacco control and automobile injury control-are reviewed for relevance to the problem of child abuse. Potential lessons for child abuse prevention are identified and the following approaches are suggested: Investigate varied logic models or conceptual frameworks to identify new opportunities for effective intervention. Use a multidisciplinary, multi-sector approach. Normalize desired behaviors and denormalize undesirable behaviors. Balance efficacy, feasibility, and cultural appropriateness. Develop strategies for effective policy advocacy based upon who benefits and who shoulders most of the burden.


A Comparison of Bilateral and Unilateral Drop Jumping Tasks in the Assessment of Vertical Stiffness.
This study sought to compare vertical stiffness during bilateral and unilateral drop jumping. Specifically, the intersession reliabilities and force-deformation profiles associated with each task were to be examined. On 3 occasions, following familiarization, 14 healthy males (age: 22 [2] y; height: 1.77 [0.08] m; and body mass: 73.5 [8.0] kg) performed 3 bilateral, left leg and right leg drop jumps. All jumps were performed from a drop height of 0.18 m on to a dual force plate system. Vertical stiffness was calculated as the ratio of peak ground reaction force (GRF) to the peak center of mass (COM) displacement. Unilateral drop jumping was associated with higher GRF and greater COM displacement (both Ps < .001), but vertical stiffness was not different between tasks when considering individual limbs (P = .98). A coefficient of variation of 14.6% was observed for bilateral vertical stiffness during bilateral drop jumping; values of 6.7% and 7.6% were observed for left and right limb vertical stiffness during unilateral drop jumping. These findings suggest that unilateral drop jumps may exhibit greater reliability than bilateral drop jumps while eliciting similar vertical stiffness. It is also apparent that higher GRFs during unilateral drop jumping are mitigated by increased COM displacement.


Vorinostat and Mithramycin A in combination therapy as an interesting strategy for the treatment of Sézary T lymphoma: a transcriptomic approach.
SAHA (vorinostat) is a histone deacetylase inhibitor approved by the USA Food and Drug Administration (FDA) for treating advanced refractory cutaneous T cell lymphomas. As SAHA alters the expression of many genes under control of the Sp1 transcription factor, we examined the effect of its association with the FDA-approved anticancer antibiotic Mithramycin A (MTR, plicamycin), a competitive inhibitor of Sp1 binding to DNA. Sézary syndrome (SS) cells, expanded ex vivo from peripheral blood mononuclear cells of 4 patients, were tested for their sensitivity to the drugs regarding cytotoxicity and differential responsive gene expression. Multivariate statistical methods were used to identify genes whose expression is altered by SAHA, MTR, and the synergist effect of the two drugs. MTR, like SAHA, induced the apoptosis of SS cells, while the two drugs in combination showed clear synergy or potentiation. Expression data stressed a likely important role of additive or synergistic epigenetic modifications in the combined effect of the two drugs, while direct inhibition of Sp1-dependent transcription seemed to have only limited impact. Ontological analysis of modified gene expression suggested that the two drugs, either independently or synergistically, counteracted many intertwined pro-survival pathways deregulated in SS cells, resistance of these tumors to intrinsic and extrinsic apoptosis, abnormal adhesion migration, and invasive properties, as well as immunosuppressive behavior. Our findings provide preliminary clues on the individual and combined effects of SAHA and MTR in SS cells and highlight a potential therapeutic interest of this novel pair of drugs for treatment of SS patients.


Plasmonic- and dielectric-based structural coloring: from fundamentals to practical applications.
Structural coloring is production of color by surfaces that have microstructure fine enough to interfere with visible light; this phenomenon provides a novel paradigm for color printing. Plasmonic color is an emergent property of the interaction between light and metallic surfaces. This phenomenon can surpass the diffraction limit and achieve near unlimited lifetime. We categorize plasmonic color filters according to their designs (hole, rod, metal-insulator-metal, grating), and also describe structures supported by Mie resonance. We discuss the principles, and the merits and demerits of each color filter. We also discuss a new concept of color filters with tunability and reconfigurability, which enable printing of structural color to yield dynamic coloring at will. Approaches for dynamic coloring are classified as liquid crystal, chemical transition and mechanical deformation. At the end of review, we highlight a scale-up of fabrication methods, including nanoimprinting, self-assembly and laser-induced process that may enable real-world application of structural coloring.


Improving hand hygiene in a low-resource setting: A nurse-led quality improvement project.
Hand hygiene is a simple but often ignored practice in health care systems worldwide, but it is integral for nosocomial infection prevention, with many hospital-acquired infections being linked to inadequate hand hygiene practice. At the burns unit in Kamuzu Central Hospital, 50% of patients were found to have acquired pseudomonas infections: one of the contributing factors being inadequate hand hygiene. This quality improvement project was part of a course for nurses to introduce change for patient benefit, with the aim of increasing the baseline figures for hand hygiene practices and hand hygiene facilities from 37% and 22%, respectively (baseline collected in November 2019). Using robust, standard quality improvement processes, measures were put in place such as checklists to observe hand hygiene compliance and facilities, appointment of a hand hygiene committee who monitored and sustained activities of the project, procurement and distribution of handrub and placement of hand-washing buckets and soap at strategic points. The project saw an increase in availability of hand-washing facilities to 95.6% and hand hygiene practices increase to >80% within 6 months. The project demonstrates that low cost interventions, led by nurses, can make a real difference to practice in resource poor countries.


[Effects of long-term tillage measurements on soil aggregate characteristic and microbial diversity].
Soil aggregate stability and microbial diversity play important roles in nutrient recycling in soil-crop systems. This study investigated the impacts of different soil tillage systems on soil aggregation and soil microbial diversity based on a 15-year long-term experiment on loess soil in Henan Province of China. Treatments included reduced tillage (RT), no-tillage (NT), sub-soiling with mulch (SM), wheat-peanut two crops (TC), and conventional tillage (CT). Soil aggregates were separated by wet sieving method, and soil microbial (bacterial, archaeal and fungal) diversity was examined by using the techniques of denaturing gradient gel electrophoresis (PCR-DGGE) analysis. The results showed that water-stable macroaggregates concent (R0.25) and the mean mass diameter (MWD) in the surface soil significantly increased under NT, SM and TC, R0.25 increased by 21.5%, 29.5% and 69.2%, and MWD increased by 18.0%, 12.2% and 50.4%, respectively, as compared with CT. Tillage practices caused changes in bacterial, archaeal and fungal community compositions. With NT, SM and TC, the bacterial, archaeal and fungal Shannon indices increased by 0.3%, 0.3%, and 0.6%, and 20.2%, 40.5%, and 49.1%, and 23.7%, 19.5%, and 25.8%, respectively, as compared with CT. Both bacterial and archaeal Shannon indices were significantly correlated with the indices of R0.25 and MWD, while the fungal Shannon index was not significantly correlated with these two indices. In conclusion, conservation tillage, including NT and SM, and crop rotation, including TC, improved soil aggregation and soil microbial diversity.


Stable method for the calculation of partition functions in the superconfiguration approach.
A general method for the calculation of the partition function of a canonical ensemble of noninteracting bound electrons is presented. It consists in a doubly recursive procedure with respect to the number of electrons and the number of orbitals. Contrary to existing approaches, this recursion relation contains no alternate summation of positive and negative numbers, which was the main source of numerical uncertainties. It is accompanied with a normalization of partition function through the determination of a free parameter consistent with the zeroth-order saddle-point approximation. The recursion relation allows one to calculate accurately partition functions for ions with a large number of orbitals, and is therefore important for calculations relying on the superconfiguration approximation.


Uncovering Spatiotemporal Dynamics of the Corticothalamic Network during Seizures.
Although the clinical efficacy of deep brain stimulation targeting the anterior nucleus (AN) and centromedian nucleus (CM) of the thalamus has been actively investigated for the treatment of medication-resistant epilepsy, few studies have investigated dynamic ictal changes in corticothalamic connectivity in human EEG recording. This study aims to establish the complex spatiotemporal dynamics of the ictal corticothalamic network associated with various seizure foci. We analyzed ten patients (aged 2.7-28.1) with medication-resistant focal epilepsy who underwent stereotactic EEG evaluation with thalamic coverage. We examined both undirected and directed connectivity, incorporating coherence and spectral Granger causality analysis (GCA) between the diverse seizure foci and thalamic nuclei (AN and CM). In our analysis of 36 seizures, coherence between seizure onset and thalamic nuclei increased across all frequencies, especially in slower bands (delta, theta, alpha). GCA showed increased information flow from seizure onset to the thalamus across all frequency bands, but outflows from the thalamus were mainly in slower frequencies, particularly delta. In the subgroup analysis based on various seizure foci, the delta coherence showed a more pronounced increase at CM than at AN during frontal lobe seizures. Conversely, in limbic seizures, the delta coherence increase was greater at AN compared to CM. It appears that the delta frequency plays a pivotal role in modulating the corticothalamic network during seizures. Our results underscore the significance of comprehending the spatiotemporal dynamics of the corticothalamic network during seizures, and this knowledge could guide personalized neuromodulation treatment strategies.


THE EFFECTS OF NEOSTIGMINE UPON GANGLION RESPONSES AFTER ADMINISTRATION OF BLOCKING DRUGS.
The effects of block of autonomic ganglia by chlorisondamine and by hexamethonium, the administration of neostigmine and of atropine upon blood pressure, nervous transmission through the superior cervical ganglion, stimulation of autonomic ganglia by dimethylphenylpiperazinium, and the carotid occlusion reflex, have been studied in the dog anaesthetized with sodium pentobarbitone. The results of these studies have shown: (1) A ganglion blocking agent blocks synaptic transmission in the superior cervical ganglion at the same time as it lowers blood pressure. Neostigmine administered after ganglion-block raises the blood pressure without much change in the response to stimulation of the preganglionic cervical sympathetic nerve. (2) If the effects of preganglionic nerve stimulation are recorded as a contraction of the nictitating membrane, a ganglion-blocking agent also abolishes this response at the same time as it blocks the reflex rise in blood pressure produced by occlusion of both common carotid arteries. Neostigmine administered under these conditions does not affect the responses of the nictitating membrane, but restores the carotid occlusion reflex. This restoration of reflex activity is sensitive to atropine, as is the blood pressure rise. (3) At the same time that neostigmine restores the carotid occlusion reflex, there is no restoration of sensitivity of autonomic ganglia to chemical stimulation by dimethylphenylpiperazinium. In these animals atropine not only blocked the restored carotid occlusion reflex, but produced a further inhibition of the pressor response to dimethylphenylpiperazinium. It is concluded that neostigmine may raise blood pressure by partially restoring autonomic ganglionic transmission, but that total ganglionic function is not restored.


Analysis of introgression of Aegilops ventricosa Tausch. genetic material in a common wheat background using C-banding.
Seven Triticum aestivum (cv. Moisson)-Aegilops ventricosa addition lines and four VPM-1 lines were studied by C-banding, and compared with the parental common wheat cultivars Marne-Desprez (hereafter Marne), Moisson, and A. ventricosa lines 10 and 11. All of the VPM-1 lines had similar C-banding patterns and carried the same major 5B:7B translocation as the parental Marne cultivar. According to the C-banding analysis, the VPM-1 lines carry a complete 7D(7D(v)) chromosome substitution and a translocation involving the 5D and 5D(v) chromosomes. However, the translocation of the 2N(v)/6N(v) chromosome of A. ventricosa to the short arm of the 2A chromosome of wheat that had been identified in an earlier study using molecular analysis (Bonhomme A, Gale MD, Koebner RMD, Nicolas P, Jahier J, Bernard M in Theor Appl Genet 90:1042-1048, 1995; Jahier J, Abelard P, Tanguy AM, Dedryver F, Rivoal R, Khatkar S, Bariana HS Plant Breed 120:125-128, 2001) was not detected in our study. However, the appearance of a small pAs1 site at the tip of the chromosome 2A short arm in VPM-1 could be indicative of a minor translocation of the A. ventricosa chromosome. The 5B:7B translocation was also found in all seven T. aestivum-A. ventricosa addition lines, although it was not present in the parental common wheat cultivar Moisson. These lines showed different introgression patterns; besides the addition of the five N(v)-genome chromosomes, they also possessed different D(D(v)) genome substitutions or translocations. A whole arm translocation between chromosome 1N(v) and 3D(v) was identified in lines v86 and v137, and also in the A. ventricosa line 10. This observation lends further support to the idea that A. ventricosa line 10, rather than line 11, was used to develop a set of wheat A. ventricosa addition lines.