Experimental demonstration of topological surface states protected by time-reversal symmetry.
We report direct imaging of standing waves of the nontrivial surface states of topological insulator Bi2Te3 using a scanning tunneling microscope. The interference fringes are caused by the scattering of the topological states off Ag impurities and step edges on the Bi2Te3(111) surface. By studying the voltage-dependent standing wave patterns, we determine the energy dispersion E(k), which confirms the Dirac cone structure of the topological states. We further show that, very different from the conventional surface states, backscattering of the topological states by nonmagnetic impurities is completely suppressed. The absence of backscattering is a spectacular manifestation of the time-reversal symmetry, which offers a direct proof of the topological nature of the surface states.


Cone-beam computed tomography evaluation on the changes in condylar long axis according to asymmetric setback in sagittal split ramus osteotomy patients.
To determine whether the condylar rotation is affected by asymmetric setback in patients undergoing sagittal split ramus osteotomy. Thirty patients who underwent bilateral sagittal split ramus osteotomy setback surgery were divided into the two groups, symmetric setback and asymmetric setback, according to the right/left difference of setback amount (<2.0, ≥2.0 mm). Condylar long axis changes were evaluated using the three-dimensional superimposition of before and immediately after surgery cone-beam computed tomography volume images. Evaluations were performed separately in lesser setback and greater setback side in patients undergoing asymmetric setback, whereas both side condyles were evaluated together in patients undergoing symmetric setback. Condylar axis changes on axial view were correlated with setback amount or right/left setback difference using Pearson correlation analysis. In general, the condylar axis change occurred in a pattern of inward rotation. The condyles in patients undergoing symmetric setback showed 3.4° rotation in average. In case of asymmetric setback, the lesser setback side showed larger value (4.3°) than the greater setback side (2.3°) with a statistical significance. In the correlation analysis, setback amount showed no significant correlation with the condylar axis changes in both groups. However, correlation with right/left setback difference showed a positive correlation in lesser setback side of patients undergoing asymmetric setback. The findings of this study indicate that large amount of setback alone does not contribute to the change in condylar long axis, but asymmetric setback might cause a change in condylar long axis, particularly on the lesser setback side.


A Rapid Method for Selecting Non-Saccharomyces Strains with a Low Ethanol Yield.
The alcohol content in wine has increased due to external factors in recent decades. In recent reports, some non-Saccharomyces yeast species have been confirmed to reduce ethanol during the alcoholic fermentation process. Thus, an efficient screening of non-Saccharomyces yeasts with low ethanol yield is required due to the broad diversity of these yeasts. In this study, we proposed a rapid method for selecting strains with a low ethanol yield from forty-five non-Saccharomyces yeasts belonging to eighteen species. Single fermentations were carried out for this rapid selection. Then, sequential fermentations in synthetic and natural must were conducted with the selected strains to confirm their capacity to reduce ethanol compared with that of Saccharomyces cerevisiae. The results showed that ten non-Saccharomyces strains were able to reduce the ethanol content, namely, Hanseniaspora uvarum (2), Issatchenkia terricola (1), Metschnikowia pulcherrima (2), Lachancea thermotolerans (1), Saccharomycodes ludwigii (1), Torulaspora delbrueckii (2), and Zygosaccharomyces bailii (1). Compared with S. cerevisiae, the ethanol reduction of the selected strains ranged from 0.29 to 1.39% (v/v). Sequential inoculations of M. pulcherrima (Mp51 and Mp FA) and S. cerevisiae reduced the highest concentration of ethanol by 1.17 to 1.39% (v/v) in synthetic or natural must. Second, sequential fermentations with Z. bailii (Zb43) and T. delbrueckii (Td Pt) performed in natural must yielded ethanol reductions of 1.02 and 0.84% (v/v), respectively.


Variance estimators for the Lempel-Ziv entropy rate estimator.
Lempel and Ziv's 1976 algorithm provides an easy-to-compute way to automatically estimate the entropy rate for symbolic time series, requiring no free parameters. Here we derive an analytical variance estimate for the Lempel-Ziv entropy rate estimator that is easily computable from observations with negligible extra effort beyond the entropy rate itself, and compare to another procedure, a time-series-based bootstrap method. These provide a justified "error bar" quantifying the size of expected fluctuations on the estimate itself, given by the single time series of symbols.


Herlyn-Werner-Wunderlich and Prader-Willi syndromes: more than a coincidence?
A neonate with a prenatal diagnosis of left renal agenesis was born at 33 weeks gestation. A postnatal abdominal ultrasound confirmed the absence of the left kidney and revealed two non-divergent hemiuteri, consistent with the diagnosis of Herlyn-Werner-Wunderlich syndrome. During admission, significant axial hypotonia was noted, warranting additional investigations. Brain ultrasounds and MRI were normal, as were a preliminary metabolic study and comparative genomic hybridisation array. DNA methylation testing confirmed the diagnosis of Prader-Willi syndrome. The baby was discharged after 70 days, breast feeding and with modest hypotonia improvement.


A crosstalk imbalance between p27(Kip1) and its interacting molecules enhances breast carcinogenesis.
p27(Kip1) (p27) is an inhibitor of cyclin/cyclin-dependent kinase complexes, the nuclear loss of which indicates poor prognoses in various solid tumors. In breast cancer cells, the p27 expression level usually decreases during tumor development and progression. In addition, p27 cytoplasmic mislocalization has been reported, but the exact molecular mechanisms remain unclear. Studies have indicated that its phosphorylation status is the key regulator and that several signal transduction pathways are involved in the regulation of both the expression and distribution of p27. To further understand the signals involved, the differences in the profiles of interacting proteins between tumor and normal cells should be elucidated. It is well known that p27 has various interacting partners, such as cyclin, cyclin-depend kinases, CRM1, Jab1, SKP2, and Spy1. Assays used to profile these proteins show differing intracellular p27 expression and localization depending on the cell-cycle phase. We hypothesize that the imbalance of crosstalk between p27 and the other molecules involved in the same signaling pathways plays an indispensable role in breast cancer carcinogenesis.


Voltammetric determination of sulfamethoxazole at a multiwalled carbon nanotube modified glassy carbon sensor and its application studies.
Sulfamethoxazole (SMX) is an anti-bacterial sulfonamide. It prevents the formation of dihydrofolic acid, a compound that bacteria need in order to survive. The present work details the voltammetric analysis of SMX at a multiwalled carbon nanotube (MWCNT)-Nafion modified glassy carbon electrode (GCE). Sulfamethoxazole gives a well defined oxidation peak at 0.74 V in 0.1 M phosphate buffer solution (PBS) of pH 8.0. The experimental parameters such as the amount of MWCNT-Nafion suspension, the pH of the supporting electrolyte and scan rate were optimized and a direct electrochemical method for the determination of SMX was developed. Under optimum conditions the oxidation peak current is linear to the concentration of SMX in the range 1 x 10(-2) - 5 x 10(-5) M with a detection limit of 1 x 10(-5) M. The MWCNT/GCE showed good stability, selectivity and was successfully used to quantify SMX in pharmaceutical formulations and urine sample.


Social Aspect of Functioning Deteriorates More Than Individual Aspect in Patients with Remitted Bipolar Disorder.
Many studies have demonstrated that patients with bipolar disorder (BD) suffer from significant functional impairment, even during remission periods. This study aimed to assess the levels of overall functioning and specific areas of functioning in remitted patients with BD compared with those in healthy controls. Eighty completely remitted patients with BD and 80 healthy controls were included in the study. The Bipolar Disorder Functioning Questionnaire (BDFQ), Young Mania Rating Scale, and Beck Depression Inventory were used. There were fewer married and employed cohorts in the BD group than in the control group. Compared with healthy controls, patients with BD exhibited a worse functioning in terms of intellectual and sexual functioning, feelings of stigmatization, social withdrawal, household relationships, relationships with friends, and participation in social activities. There was no difference between the groups in terms of emotional functioning, daily activities and hobbies, taking initiative and self-sufficiency, and occupation. The total BDFQ scores of patients were lower than those of healthy controls. A better functionality was observed in patients using only a mood stabilizer than in patients using three or more drugs. Remarkably, remitted patients with BD tended to perform daily activities well when these activities were not in a social context. Stigma-oriented interpersonal approaches can be particularly beneficial for these patients.


The Burkholderia cepacia bceA gene encodes a protein with phosphomannose isomerase and GDP-D-mannose pyrophosphorylase activities.
The bceA gene is part of the Burkholderia cepacia IST408 exopolysaccharide (EPS) biosynthetic cluster. It encodes a 55.3-kDa bifunctional protein (type II PMI family) with phosphomannose isomerase (PMI) and GDP-mannose pyrophosphorylase (GMP) activities. GMP activity is strongly dependent on the presence of Ca(2+) or Mn(2+), while PMI activity can use a broader variety of divalent cations (Ca(2+)>Mn(2+)>Mg(2+)>Co(2+)>Ni(2+)). The lack of a functional bceA gene does not affect EPS production yield in a non-polar insertion bceA mutant. The in silico search for putative bceA homologues revealed the presence of 2-5 bceA orthologues in the Burkholderia genomes available. This suggests that in B. cepacia IST408 putative bceA functional homologues may compensate the bceA mutation. However, the viscosity of aqueous solutions prepared with the EPS produced by the bceA mutant was significantly reduced compared with wild-type biopolymer and the mutant forms biofilms with a size reduced by 6-fold.


Age and Anatomical Location-Related Dermoscopic Patterns of 210 Acral Melanocytic Nevi in a Turkish Population.
Dermoscopy is a useful tool for earlier diagnosis and differentiating benign lesions from melanoma. We aim to investigate dermoscopic features of acral nevi, age, and localisation-related findings of these lesions. This was an observational, descriptive study. Patients were retrospectively collected from the Department of Dermatology. The patients with acral nevi were included in the study. Inclusion criteria were Turkish nationality and the presence of at least 1 acral nevus diagnosed both clinically and dermoscopically. Lesions in dorsal and subungual areas were excluded. All nevi were examined by the same dermatologist. The most common dermoscopic patterns were as follows: parallel furrow (87 patients; 41.4%), globular (24 patients; 11.4%), fibrillar (22 patients; 10.5%), combination patterns (19 patients; 9.1%), globulostreak-like (16 patients; 7.6%), lattice-like (15 patients; 7.1%), homogeneous (12 patients; 5.7%), nontypical (8 patients; 3.8%), parallel ridge (4 patients; 1.9%), reticular (2 patients; 1.0%), and crista dotted pattern (1 patient; 0.5%). The parallel furrow pattern was the most common pattern in all localisations. The number of parallel furrow patterns (5 lesions) was equal to the globulostreak-like pattern (5 lesions) on the thenar area. The number of parallel furrow patterns (4 lesions) was equal to the fibrillar pattern (4 lesions) on the heel. Parallel furrow (dotted variants) (11 lesions) and globulostreak-like patterns (5 lesions) were the most common patterns in the pediatric population (0-15 years old). The fibrillar pattern showed a tendency for soles (12 lesions), while a lattice-like pattern was seen more often in the plantar arch (3 lesions). Description of the dermoscopic features of acral nevi is important to improve management and reduce the number of unnecessary excisions. The most common patterns were parallel furrow, globular, and fibrillar in our study. Parallel furrow (dotted variants) and globulostreak-like patterns were the most common patterns in the pediatric population. The fibrillar pattern showed a tendency for soles, while a lattice-like pattern was seen more often on the plantar arch. Therefore, there may be a relation between anatomic localisation, age, and dermoscopic pattern.


Immunorelated gene polymorphisms associated with acute myeloid leukemia.
Although the pathogenesis of acute myeloid leukemia (AML) is still unknown, accumulating evidence has revealed that immune response plays a vital part in the pathogenesis. Here, we investigated the involvement of 21 single nucleotide polymorphisms (SNPs) of immunorelated genes, including cytokines [interleukin (IL)-2, IL-4, IL-9, IL-12A, IL-22, interferon (IFN-α) and transforming growth factor (TGF)-β1], transcriptional regulatory genes (TBX21, STAT1, STAT3, STAT5B, STAT6, GATA3, FOXP3 and IRF4) and others (IL2RA, IL6R, NFKBIA) in 269 AML in-patients and 200 healthy controls. Furthermore, we analyzed the relationship between the SNPs and clinical characteristics. Immunorelated SNP genotyping was performed on the Sequenom MassARRAY iPLEX platform. All the SNPs in healthy controls were consistent with Hardy-Weinberg equilibrium. All final P-values were adjusted by Bonferroni multiple testing. Our results showed that IL-22 (rs2227491) was significantly associated with the white blood cell (WBC) counts. Signal transducer and activator of transcription 5B (STAT-5B) (rs6503691) showed a close relationship with the recurrent genetic abnormalities in patients with AML. We verified the negatively independent effect of age and risk of cytogenetics on overall survival (OS). More importantly, the GG genotype of IL-12A (rs6887695) showed a negative impact on AML prognosis independently. Furthermore, the relative expression of IL-12 was decreased in GG genotype, no matter under a co-dominant or recessive model. However, no correlation was observed between the SNPs mentioned above and disease susceptibility, risk stratification and survival. Our findings suggest that immunorelated gene polymorphisms are associated with prognosis in AML, which may perform as novel inspection targets for AML patients.


The value of HPV DNA typing in the distinction between adenocarcinoma of endocervical and endometrial origin.
Distinguishing between adenocarcinomas of endocervical and endometrial origin histologically can be difficult, particularly in small biopsies. Most endocervical adenocarcinomas contain human papillomavirus (HPV) deoxyribonucleic acid (DNA) of 'high-risk' (HR) types, whereas this has not been consistently demonstrated in endometrial adenocarcinomas. The aim of this study was to determine whether HPV DNA testing could aid in this differential diagnosis. The frequency of HPV DNA in paraffin-embedded tissue samples from 50 endocervical and 50 endometrial adenocarcinomas was investigated using polymerase chain reaction (PCR) amplification techniques involving (i) a screening HPV test followed by HPV DNA sequencing, and (ii) a test designed to detect HR genotypes 16, 18, 31, 33, 35, 45 and 58. Control specimens included cervical intraepithelial neoplasia (CIN) III lesions, squamous cell carcinomas (SCCs) of the cervix and lung, and colonic adenocarcinomas. Measures to minimise cross-contamination were implemented. The screening test followed by HPV DNA sequencing had the highest sensitivity. By this test HR HPV DNA was detected in 11 of 11 (100%) cervical intraepithelial neoplasia (CIN III) lesions, nine of 10 (90%) cervical SCCs, none of 10 (0%) colorectal adenocarcinomas and none of 10 (0%) SCCs of the lung. Thirty-nine (78%) endocervical adenocarcinomas contained HR HPV DNA, compared to one (2.0%) endometrial adenocarcinoma. The results suggest that HPV DNA testing could be a useful adjunct in distinguishing between endocervical and endometrial adenocarcinomas in curettings or small biopsy specimens.


Plasma membrane fluidity affects transient immobilization of oxidized phospholipids in endocytotic sites for subsequent uptake.
Oxidized phospholipids in serum initiate severe pathophysiological responses during the process of atherogenesis. On the cellular level it is known that these lipids induce apoptosis; however, the uptake mechanism remains enigmatic. We investigated here the behavior of the fluorescent oxidized phospholipid 1-palmitoyl-2-glutaroyl-sn-glycero-3-phospho-N-Alexa647-ethanolamine (PGPE-Alexa647) in the plasma membrane of various cell lines. The probe was taken up by the cells unspecifically via caveolae or clathrin-coated pits. Interestingly, we found the uptake to be facilitated by the overexpression of the scavenger receptor class B type I. Ultra-sensitive microscopy allowed us to follow the uptake process at the single molecule level; we observed rapid diffusion of PGPE-Alexa647 in the plasma membrane, interrupted by transient halts with duration of approximately 0.9 s at endocytotic sites. Scavenger receptor class B type I overexpression yielded a pronounced increase in the single molecule mobility, and in consequence an increased frequency of immobilization. Alternatively, the plasma membrane fluidity could also be increased by treating cells with high levels of the unlabeled oxidized phospholipid 1-palmitoyl-2-glutaroyl-sn-glycero-3-phosphocholine; also in this case, the immobilization frequency of PGPE-Alexa647 was concomitantly increased. The data demonstrate the relevance of plasma membrane properties for uptake of oxidized phospholipids, and indicate a novel indirect mechanism for the control of endocytosis.


Adoption and correlates of the Dundee Ready Educational Environment Measure (DREEM) in the evaluation of undergraduate learning environments - a systematic review.
The Dundee Ready Educational Environment Measure (DREEM) was specifically designed to measure the undergraduate medical educational environment. This study seeks to review the adoption of DREEM internationally, and its association with different learning contexts and learner factors in order to better support our learners and facilitate future applications and research. A systematic literature review was conducted on all articles that adopted and reported data using the DREEM from 1997 to April 2017. Overall, the majority of 106 included studies from over 30 countries were conducted in Asia and Europe (76.4% of studies) within medical, dental, and nursing programs (86.8% of studies). Seventy-nine out of 98 studies (80.6%) which reported DREEM scores observed a mean total DREEM score within the range of "more positive than negative" (101-150 out of maximum 200 points). Higher DREEM scores were associated with better past academic achievement, quality of life, resilience, positive attitudes towards course, mindfulness, preparedness for practice, less psychological distress, and greater peer support. Future studies may want to examine other correlates of DREEM such as coping styles, personality profiles, burnout level, and DREEM scores can be incorporated into reviews of learning environments to ascertain longitudinal changes following educational interventions.


Decorin-mediated regulation of fibrillin-1 in the kidney involves the insulin-like growth factor-I receptor and Mammalian target of rapamycin.
Decorin, a small leucine-rich proteoglycan, affects the synthesis of the elastic fiber component fibrillin-1 in the kidney via hitherto unknown mechanisms. Here, we show that decorin binds to and induces phosphorylation of insulin-like growth factor-I (IGF-I) receptor in renal fibroblasts. Inhibition of the IGF-I receptor tyrosine kinase and its downstream target phosphoinositide-3 kinase prevented decorin-mediated synthesis of fibrillin-1. Furthermore, decorin induced phosphorylation of phosphoinositide-dependent kinase 1, protein kinase B/Akt, mammalian target of rapamycin (mTOR), and p70 S6 kinase. Accordingly, the enhanced synthesis of fibrillin-1 was blocked by rapamycin, an inhibitor of mTOR. Notably, IGF-I, which signals through the same pathway, also stimulated fibrillin-1 synthesis. Systemic administration of rapamycin to mice subjected to unilateral ureteral obstruction, a model of renal fibrosis and increased fibrillin-1 synthesis, markedly reduced the number of interstitial fibroblasts and fibrillin-1 deposition. In streptozotocin-induced diabetes, IGF-I receptor was up-regulated in the kidneys from decorin-null mice. However, this could not compensate for the decorin deficiency, resulting ultimately in decreased fibrillin-1 content. This study provides evidence for the involvement of decorin and the IGF-I receptor/mTOR/p70 S6 kinase signaling pathway in the translational regulation of fibrillin-1.


Aldehyde-appended distyrylbenzenes: amine recognition in water.
Change in water: Aqueous solutions of aldehyde-substituted, water-soluble distyrylbenzenes reacted with amines to give imines or aminals with dramatically changed fluorescence. This approach allowed the detection and recognition of amines in water (see figure).


Regulation of the Escherichia coli uvrD gene in vivo.
The roles of two putative promoter sequences, P1 and P2, and a potential antiterminator sequence found in the uvrD control region were examined in vivo. Constitutive and SOS-induced levels of uvrD mRNA were determined by S1 mapping, and it was shown that the majority of uvrD transcripts are from P1, while P2 plays only a minor role. A series of increasing deletions from the 5' end of the uvrD gene was used to assay transcription in the promoterless vector pKO-1. Loss of just the -35 region of P1 was sufficient to switch off detectable transcription from both P1 and P2. Disruption of the antiterminator by site-specific mutagenesis had no effect on constitutive levels of transcription, but led to a significant increase over wild-type levels following SOS induction. This suggests that the attenuator comes into play following DNA damage to moderate the increase in UvrD protein synthesis.


Shaping vulnerability to addiction - the contribution of behavior, neural circuits and molecular mechanisms.
Substance use disorders continue to impose increasing medical, financial and emotional burdens on society in the form of morbidity and overdose, family disintegration, loss of employment and crime, while advances in prevention and treatment options remain limited. Importantly, not all individuals exposed to abused substances effectively develop the disease. Genetic factors play a significant role in determining addiction vulnerability and interactions between innate predisposition, environmental factors and personal experiences are also critical. Thus, understanding individual differences that contribute to the initiation of substance use as well as on long-term maladaptations driving compulsive drug use and relapse propensity is of critical importance to reduce this devastating disorder. In this paper, we discuss current topics in the field of addiction regarding individual vulnerability related to behavioral endophenotypes, neural circuits, as well as genetics and epigenetic mechanisms. Expanded knowledge of these factors is of importance to improve and personalize prevention and treatment interventions in the future.


In vitro study of potential prebiotic properties of monovarietal extra virgin olive oils.
Olive oil, essential ingredient of the Mediterranean diet, is attracting a growing interest due to increasing evidence on its beneficial effects on human health. This study investigated whether extra virgin olive oil (EVOO) possess prebiotic properties. Twenty different monovarietal EVOO samples from 5 Marche region cultivars (Italy) were studied. The prebiotic activity of EVOOs was assessed monitoring the selective stimulation of gut bacterial species and the short chain fatty acids (SCFAs) production, using an in vitro fermentation system. All EVOOs selectively stimulated Lactobacillus spp., with a stronger activity than that observed in the inulin fermentation (positive control). Also, the bifidobacteria population increased; this bifidogenic stimulation was of EVOOs from Raggia cultivar. SCFAs appeared significantly higher after 24 h in all EVOO fermentations than in the control. Acetic and propionic acids production was particularly stimulated. Overall, most of the investigated EVOOs had a potential prebiotic activity, similar or stronger than inulin.


The poisoned gift: AIDS and blood.
The moral and communal ends served by a system of gifts of blood have been threatened by the fear of AIDS transmission. Blood banks and those at risk for HIV infection have made changes in their practices to reduce the risk to recipients, and physicians and patients now understand better that blood carries risks and should never be used unless necessary. The deeper importance of gifts of blood, nevertheless, has not significantly changed; millions still need blood each year, and millions are personally willing to meet that need. Embodied in the system of blood gifts is an affirmation of the value of community with the strangers among whom we live.


Advances in Orthopaedic Oncology.
Advances in MR imaging, allograft tissue use, and the design of prosthetic implants have dramatically improved survival rates and clinical results in patients with tumours. In younger patients with high-grade sarcomas, adjuvant chemotherapy has increased the chance of survival from 25 per cent to 75 per cent, and tumorous limbs now have a 90 per cent chance of being salvaged.


Urinary Concentrations of Parabens and Other Antimicrobial Chemicals and Their Association with Couples' Fecundity.
Human exposure to parabens and other antimicrobial chemicals is continual and pervasive. The hormone-disrupting properties of these environmental chemicals may adversely affect human reproduction. We aimed to prospectively assess couples' urinary concentrations of antimicrobial chemicals in the context of fecundity, measured as time to pregnancy (TTP). In a prospective cohort of 501 couples, we examined preconception urinary chemical concentrations of parabens, triclosan and triclorcarban in relation to TTP; chemical concentrations were modeled both continuously and in quartiles. Cox's proportional odds models for discrete survival time were used to estimate fecundability odds ratios (FORs) and 95% confidence intervals (CIs) adjusting for a priori-defined confounders. In light of TTP being a couple-dependent outcome, both partner and couple-based exposure models were analyzed. In all models, FOR estimates < 1.0 denote diminished fecundity (longer TTP). Overall, 347 (69%) couples became pregnant. The highest quartile of female urinary methyl paraben (MP) concentrations relative to the lowest reflected a 34% reduction in fecundity (aFOR = 0.66; 95% CI: 0.45, 0.97) and remained so when accounting for couples' concentrations (aFOR = 0.63; 95% CI: 0.41, 0.96). Similar associations were observed between ethyl paraben (EP) and couple fecundity for both partner and couple-based models (p-trend = 0.02 and p-trend = 0.05, respectively). No associations were observed with couple fecundity when chemicals were modeled continuously. Higher quartiles of preconception urinary concentrations of MP and EP among female partners were associated with reduced couple fecundity in partner-specific and couple-based exposure models.


Malignant teratoid medulloepithelioma in a dog.
A malignant teratoid medulloepithelioma that arose from the ciliary body was found in an adult Beagle. The anterior part contained relatively well-differentiated tumor cells, cartilage, and ganglion cells. These structures were interpreted as teratoid formations derived from the embryonic anlage of the medullary epithelium. The more posterior part was highly anaplastic and invasive. A transitional area contained neural rosettes of the Flexner-Wintersteiner type. This tumor is rare in both man and animals.


Neuropathy-causing mutations in HSPB1 impair autophagy by disturbing the formation of SQSTM1/p62 bodies.
HSPB1 (heat shock protein family B [small] member 1) is a ubiquitously expressed molecular chaperone. Most mutations in HSPB1 cause axonal Charcot-Marie-Tooth neuropathy and/or distal hereditary motor neuropathy. In this study we show that mutations in HSPB1 lead to impairment of macroautophagic/autophagic flux. In HSPB1 knockout cells, we demonstrate that HSPB1 is necessary for autophagosome formation, which was rescued upon re-expression of HSPB1. Employing a label-free LC-MS/MS analysis on the various HSPB1 variants (wild type and mutants), we identified autophagy-specific interactors. We reveal that the wild-type HSPB1 protein binds to the autophagy receptor SQSTM1/p62 and that the PB1 domain of SQSTM1 is essential for this interaction. Mutations in HSPB1 lead to a decrease in the formation of SQSTM1/p62 bodies, and subsequent impairment of phagophore formation, suggesting a regulatory role for HSPB1 in autophagy via interaction with SQSTM1. Remarkably, autophagy deficits could also be confirmed in patient-derived motor neurons thereby indicating that the impairment of autophagy might be one of the pathomechanisms by which mutations in HSPB1 lead to peripheral neuropathy. Abbreviations: ACD: alpha-crystallin domain; ALS: amyotrophic lateral sclerosis; ATG14: autophagy related 14; BAG1/3: BCL2 associated athanogene 1/3; CMT: Charcot-Marie-Tooth; dHMN: distal hereditary motor neuropathy; GFP: green fluorescent protein; HSPA8: heat shock protein family A (Hsp70) member 8; HSPB1/6/8: heat shock protein family B (small) member 1/6/8; LIR: LC3-interacting region; LC3B: microtubule associated protein 1 light chain 3 beta; PB1: Phox and Bem1; SQSTM1: sequestosome 1; STUB1/CHIP: STIP1 homology and U-box containing protein 1; UBA: ubiquitin-associated; WIPI1: WD repeat domain, phosphoinositide interacting 1; WT: wild-type.


Endocrine responses to resistance exercise.
The purpose of this brief review is to examine resistance training responses of selected hormones related to acute stress and growth promoting actions. Hormonal mechanisms appear to be involved with both short-term homeostatic control and long-term cellular adaptations. Few studies have modeled the exercise stimulus in resistance training to determine the role of different exercise variables to the hormonal response. A variety of resistance exercise protocols result in increases in peripheral hormonal concentrations. It appears that single factor variables such as the intensity (% of RM) of exercise and amount of muscle mass utilized in the exercise protocol are important determinants of hormonal responses. The volume (sets x repetitions x intensity) of exercise also appears to be an important determinant of hormonal response. Still, little is known with regard to other single and multiple factor variables (e.g., rest period length) and their relationships to peripheral hormonal alterations. Collectively, such information will allow greater understanding concerning the nature of the exercise stimulus and its relationship to training adaptations resulting from heavy resistance exercise.


Hydrogen sulfide suicide: a new trend and threat to healthcare providers.
First popularized in Japan, hydrogen sulfide (H2S) gas suicide is an underreported form of suicide with known risk for secondary disaster. Mortality rate commonly exceeds 90% because of the gas's lethal, noncontained nature. Instances in the United States are increasing, up from 2 cases in 2008 to 18 in 2010. Because H2S poisonings remain rare, there exists a lack of knowledge regarding the residual effects of gas venting after victim extrication. Identifying instances of the efficacious use of personal protection equipment (PPE) is critical in the effort to alleviate risks faced by hospital and rescue personnel. The current case demonstrates the effective use of PPEs after prolonged H2S exposure. In 2011, a 20-year-old man threatened suicide using H2S gas inside a vehicle on a remote rural highway. First responders identified a "rotten egg smell" and subsequently experienced low poisoning symptoms. After prolonged Hazmat-assisted extrication (4 hours) the patient was unconscious and experiencing seizures. He was decontaminated on-scene (20 minutes) and transported to the closest hospital (22 minutes). Ambulance personnel who wore PPE and used the ambulance's reverse ventilation system (RVS)reported no adverse effects. The patient was transferred to the authors' burn facility by helicopter (38 minutes). Life-flight personnel, who did not wear PPE (no ventilatory system available), complained of watery eyes, headache, and dizziness. Hospital personnel, who did not use PPE (or RVS), complained of watery eyes or headache. Exposed personnel demonstrated no deficits or residual effects. In spite of spontaneous movement, the patient began to seize and died. This case is unique given the multiple primary and secondary H2S gas exposures involved. Exposed personnel without RVS and not using PPE demonstrated moderate H2S symptoms. PPE (self-contained breathing apparatuses) and RVS were shown to be effective during an H2S emergency; however, there are currently limited data supporting their appropriate use. Until data demonstrating duration of H2S venting for small enclosed spaces are made available, PPEs should be required.


[Diabetes mellitus and heart failure].
Chronic heart failure (CHF) in patients with diabetes mellitus (DM) is a condition that is frequent and has a poor prognosis. Diabetes mellitus is an independent risk factor for CHF and vice versa. CHF is found in 10-15% of the patients with DM compared to 3% in individuals without DM. Apart from CHD and hypertension, hyperglycaemia and insulin resistance are directly linked to the development of diastolic dysfunction and to CHF. According to the stepwise diagnostic procedure recommended by the ESC in its guidelines from 2005, if heart failure is suspected, the disease should first be diagnosed by ECG, X-ray, or testing for natriuretic peptide and followed by echocardiography when test results are abnormal. Treatment of CHF in patients with diabetes mellitus is the same as that for nondiabetic patients and includes the use of ACEIs, ARBSs (as an alternative to or in combination with ACEIs), BBs, diuretics (in particular loop diuretics), aldosterone inhibitors and digitalis. Most importantly, meticulous glucose control is a must in patients with diabetes mellitus and CHF to improve prognosis. Contraindications for antidiabetic drugs such as glitazones for CHF-NYHA classes I-IV and metformin for NYHA classes III-IV need to be considered in patients with CHF and diabetes mellitus.


Erratum: Critical properties of a two-dimensional Ising magnet with quasiperiodic interactions [Phys. Rev. E 93, 042111 (2016)].
This corrects the article DOI: 10.1103/PhysRevE.93.042111.


The neurotrophin receptor p75NTR mediates early anti-inflammatory effects of estrogen in the forebrain of young adult rats.
Estrogen suppresses microglial activation and extravasation of circulating monocytes in young animals, supporting an anti-inflammatory role for this hormone. However, the mechanisms underlying estrogen's anti-inflammatory effects, especially in vivo, are not well understood. The present study tests the hypothesis that anti-inflammatory effects of estrogen are mediated by the pan-neurotrophin receptor p75NTR. Previously, we reported that estrogen attenuated local increases of interleukin(IL)-1beta in the NMDA-lesioned olfactory bulb, while further increasing NGF expression. The present studies show that this lesion enhances expression of the neurotrophin receptor p75NTR at the lesion site, and p75NTR expression is further enhanced by estrogen treatment to lesioned animals. Specifically, estrogen stimulates p75NTR expression in cells of microvessels adjacent to the lesion site. To determine the role of this receptor in mediating estrogen's anti-inflammatory effects, a p75NTR neutralizing antibody was administered at the same time the lesion was created (by stereotaxic injections of NMDA) and specific markers of the inflammatory cascade were measured. Olfactory bulb injections of NMDA+vehicle (preimmune serum) increased IL-1beta and activated the signaling molecule c-jun terminal kinase (JNK)-2 at 6 h. At 24 h, the lesion significantly increased matrix metalloproteinase (MMP)-9 and prostaglandin (PG)E2, a COX-2 mediated metabolite of arachadonic acid. All of these markers were significantly attenuated by estrogen in a time-dependent manner. However, estrogen's effects on all these markers were abolished in animals that received anti-p75NTR. These data support the hypothesis that estrogen's anti-inflammatory effects may be, in part, mediated by this neurotrophin receptor. In view of the novel estrogen-dependent expression of p75NTR in cells associated with microvessels, these data also suggest that the blood brain barrier is a critical locus of estrogen's neuro-immune effects.


Differences in the therapeutic functioning of paraprofessionals with varying lengths of experience.
Measured differences in the ability of paraprofessionals to discriminate and communicate facilitative conditions in psychotherapy as a function of length of experience. Hypothesis tested were that discrimination and communication abilities would be greater in Ss with longer experience and that these abilities would be correlated positively within individuals. Thirty-six mental health workers were categorized into three levels of experience and initial competency. Ss were administered the Carkhuff Discrimination Rating Scale; the level of conditions communicated to patients was assessed through replies to taped patient interviewers. Results failed to support the hypothesized relationships between functioning and experience. However, several interactions were found. Initially more competent Ss tended to improve over time and less competent Ss declined. A positive correlation between abilities within individuals was found. Results were compared with studies that measured the functioning of professional psychology trainees over time, are relevant to issues of therapist selection, and support the use of experiential training programs.


Chloroquine and Hydroxychloroquine Use During Pregnancy and the Risk of Adverse Pregnancy Outcomes Using Real-World Evidence.
Introduction: Chloroquine (CQ) and hydroxychloroquine (HCQ) are currently used for the prevention/treatment of malaria, and treatment of systemic lupus erythematosus (SLE), and rheumatoid arthritis (RA). Although present data do not show their efficacy to treat COVID-19, they have been used as potential treatments for COVID-19. Given that pregnant women are excluded from randomized controlled trials, and present evidence are inconsistent and inconclusive, we aimed to investigate the safety of CQ or HCQ use in a large pregnancy cohort using real-world evidence. Methods: Using Quebec Pregnancy Cohort, we identified women who delivered a singleton liveborn, 1998-2015, (n = 233,748). The exposure time window for analyses on prematurity and low birth weight (LBW) was the second/third trimesters; was any time during pregnancy; only first trimester exposure was considered for analyses on major congenital malformations (MCM). The risk of prematurity, LBW, and MCM (overall and organ-specific) were quantified using generalized estimation equations. Results: We identified 288 pregnancies (0.12%) exposed to CQ (183, 63.5%) or HCQ (105, 36.5%) that resulted in liveborn singletons; CQ/HCQ was used for RA (17.4%), SLE (16.3%) or malaria (0.7%). CQ/HCQ was used for 71.8 days on average [standard-deviation (SD) 70.5], at a dose of 204.3 mg/d (SD, 155.6). We did not observe any increased risk related to CQ/HCQ exposure for prematurity (adjusted odds ratio [aOR] 1.39, 95%CI 0.84-2.30), LBW (aOR 1.11, 95%CI 0.59-2.06), or MCM (aOR 1.01, 95%CI 0.67-1.52). Conclusion: in this large CQ/HCQ exposed pregnancy cohort, we saw no clear increased risk of prematurity, LBW, or MCM, although number of exposed cases remained low.


Chemical synthesis of tea polyphenols and related compounds.
Tea polyphenol "catechin", which is a major constituent of green tea extract, has received special attention for its important bioactivities. In this article, we review the recent various syntheses of catechins by classifying the mode of of flavan ring-construction. Additionally, we also take notice of the application of the modified catechins that were created to uncover the mechanism of bioactivities and discover new activities.


Genetic predisposition in nonalcoholic fatty liver disease.
Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease whose prevalence has reached global epidemic proportions. Although the disease is relatively benign in the early stages, when severe clinical forms, including nonalcoholic steatohepatitis (NASH), cirrhosis and even hepatocellular carcinoma, occur, they result in worsening the long-term prognosis. A growing body of evidence indicates that NAFLD develops from a complex process in which many factors, including genetic susceptibility and environmental insults, are involved. In this review, we focused on the genetic component of NAFLD, with special emphasis on the role of genetics in the disease pathogenesis and natural history. Insights into the topic of the genetic susceptibility in lean individuals with NAFLD and the potential use of genetic tests in identifying individuals at risk are also discussed.


Open Displaced Fracture of Acromion with Associated Complete Supraspinatus Tear: A Rare Case Report.
Isolated acromion fractures are rare and in that too, orthopaedicians rarely come across open acromial fractures. Hence literature regarding their management, outcome and any associated complications is obscure. In an extensive search for literature related to our case we found very few articles. We hereby report a case of Gustilo IIIA open acromial fracture with associated supraspinatus, deltoid and capsular injury managed with tension band wiring (TBW) and soft tissue repair with 6 month follow up. A 21-year-old male was admitted in our hospital for wound of right shoulder with pain and inability to move this arm with a history of direct trauma with sharp object 3 days back. On examination, a wound 15 cm in length on the superior aspect of the right shoulder with its depth extending up to the glenohumeral joint was noted. The glenohumeral joint was exposed with a Gustilo Anderson type IIIA acromion fracture and injury of supraspinatus and capsule with no associated vascular or neurological injury. Wound was thoroughly irrigated and was used to approach the fracture site for repair. Capsule of shoulder was carefully closed with absorbable suture followed by suturing of supraspinatus with non-absorbable suture. Our initial plan to fix the acromial fracture to spinous process of scapula with 2 4 mm cannulated cancellous screw placed orthogonal to fracture site was modified intraoperative due to screw cut out and we went ahead with TBW with 1 screw and 1 Kirschner wire to prevent further fragmentation of the fragment. Wound was healing and healthy. Patient was started on a passive pendular exercises after 4 weeks and active exercises at 6 weeks. Six months postoperatively patient had complete range of shoulder rotation with forward flexion of 80° and abduction possible till 45°. Patient was able to do most of his activities of daily living barring overhead activities. As there are very limited cases of this sort of injury, this case report will cast a light on management options and outcomes of such injuries. We received fair results in our study with good healing and painless functional shoulder joint. However, long term and multi centric studies are required for further information pertaining to such scenarios.


Effects of cigarette smoking on maternal nutrition and the fetus.
Available evidence supports the importance of including facts about smoking and pregnancy in all teaching to women in the childbearing years. The incidence of low birthweight infants is possibly almost twice as high among smoking mothers, and these low birthweight babies are known to be at risk on several counts. Compromised utilization of vitamins and minerals is presented as a causative factor: calcium, vitamin B12, and vitamin C levels are lower in smokers. Other vitamin levels may be affected. Poor nutrition and other factors connected with smoking may result also in stillbirths, spontaneous abortions, congenital anomalies, and cancer in the offspring. Nurses have a unique opportunity to contribute to maternal-child health by teaching and counseling about smoking in pregnancy.


The Hildebrand solubility parameters of ionic liquids-part 2.
The Hildebrand solubility parameters have been calculated for eight ionic liquids. Retention data from the inverse gas chromatography measurements of the activity coefficients at infinite dilution were used for the calculation. From the solubility parameters, the enthalpies of vaporization of ionic liquids were estimated. Results are compared with solubility parameters estimated by different methods.


Prophylactic effects of alpha-blockers, Tamsulosin and Alfuzosin, on postoperative urinary retention in male patients undergoing urologic surgery under spinal anaesthesia.
Postoperative urinary retention (POUR) is one of the most common complications after surgical procedures under spinal anaesthesia. Recent studies have shown the beneficial effects of alpha-adrenergic blockers in preventing POUR. The aim of this prospective study was to investigate and compare the prophylactic effects of tamsulosin and alfuzosin on POUR after urologic surgical procedures under spinal anaesthesia. A total of 180 males who underwent elective urologic surgery were included in this study. The patients were randomly allocated into three Groups. The Group I received placebo. Patients in Group II were given 0.4mg of tamsulosin orally 14 and 2 hours before surgery. Patients in Group III were given 10mg of alfuzosin ER orally 10 and 2 hours before surgery. All patients were closely followed for 24 hours postoperatively and their episodes of urinary retentions were recorded. There were 60 patients in each Group. Their mean age was 35.95±15.16 years. Fifteen patients in Group I (25%), 3 patients in Group II (5%) and 4 patients in Group III (6.7%) required catheterization because of urinary retention. In tamsulosin group and alfuzosin group, there were a significantly lower proportion of patients with POUR compared with the placebo Group (p=0.002 and p=0.006). The beneficial effects of tamsulosin and alfuzosin on POUR were similar between both Groups (p=0.697). This study suggests that the use of prophylactic tamsulosin or alfuzosin can reduce the incidence of urinary retention and the need for catheterization after urologic surgical procedures under spinal anaesthesia.


Ultrastructure of substance P- and CGRP-immunoreactive nerve fibers in the nasal epithelium of rodents.
The respiratory and olfactory mucosae of rats and mice were examined at ultrastructural levels for the presence of intraepithelial nerve endings. Immunocytochemical studies utilizing antisera directed against substance P and calcitonin gene-related peptide (CGRP) revealed numerous intraepithelial peptide-immunoreactive fibers near the basal region of the epithelium. Occasional transepithelial fibers were observed to extend outward to nearly reach the epithelial surface. In no cases, however, did the transepithelial fibers reach the surface, but instead, stopped at the line of tight junctions approximately 1 micron from the surface. No specialized contacts between the nerve fibers and the epithelial cells were observed. The transepithelial fibers provide a possible anatomical substrate for the sensitivity of the trigeminal nerve to many air-borne chemical stimuli. That potential chemical stimuli must traverse the tight-junctional barrier may explain why lipid solubility is related to effectiveness for trigeminal stimuli.


The value of post-operative radiographs in clinical management of AO type A distal radius fractures.
The value of post-operative radiographs following stabilization of Arbeitsgemeinschaft für Osteosynthesefragen (AO) type A distal radius fractures with volar locking plates is unclear. We examined the value of post-operative radiographs of type A fractures treated with volar locking plates. A retrospective review was performed on all AO type A distal radius fractures treated with volar locking plates between 2007 and 2010 at two institutions. A total of 158 patients receiving 446 sets of post-operative radiographs were included. Reviewing all clinic, emergency, and operative notes, we found that 94% of radiographs were performed as routine follow-up, with no set of post-operative radiographs demonstrating findings of hardware/fracture site complications. All cases requiring further workup or interventions were heralded by patient complaints. Routine post-operative radiographs following volar locking plates for extra-articular distal radius fractures did not demonstrably alter clinical decision making; this is an area where a reduction in resource utilization would not seem to alter clinical quality care, but further studies with larger populations are needed to establish the incidence of radiographic problems prior to symptom occurrence. Level of evidence: Diagnostic III.


Multilineage Differentiating Stress Enduring (Muse) Cells: A New Era of Stem Cell-Based Therapy.
Stem cell transplantation has recently demonstrated a significant therapeutic efficacy in various diseases. Multilineage-differentiating stress-enduring (Muse) cells are stress-tolerant endogenous pluripotent stem cells that were first reported in 2010. Muse cells can be found in the peripheral blood, bone marrow and connective tissue of nearly all body organs. Under basal conditions, they constantly move from the bone marrow to peripheral blood to supply various body organs. However, this rate greatly changes even within the same individual based on physical status and the presence of injury or illness. Muse cells can differentiate into all three-germ-layers, producing tissue-compatible cells with few errors, minimal immune rejection and without forming teratomas. They can also endure hostile environments, supporting their survival in damaged/injured tissues. Additionally, Muse cells express receptors for sphingosine-1-phosphate (S1P), which is a protein produced by damaged/injured tissues. Through the S1P-S1PR2 axis, circulating Muse cells can preferentially migrate to damaged sites following transplantation. In addition, Muse cells possess a unique immune privilege system, facilitating their use without the need for long-term immunosuppressant treatment or human leucocyte antigen matching. Moreover, they exhibit anti-inflammatory, anti-apoptotic and tissue-protective effects. These characteristics circumvent all challenges experienced with mesenchymal stem cells and induced pluripotent stem cells and encourage the wide application of Muse cells in clinical practice. Indeed, Muse cells have the potential to break through the limitations of current cell-based therapies, and many clinical trials have been conducted, applying intravenously administered Muse cells in stroke, myocardial infarction, neurological disorders and acute respiratory distress syndrome (ARDS) related to novel coronavirus (SARS-CoV-2) infection. Herein, we aim to highlight the unique biological properties of Muse cells and to elucidate the advantageous difference between Muse cells and other types of stem cells. Finally, we shed light on their current therapeutic applications and the major obstacles to their clinical implementation from laboratory to clinic.


Acute myelomonocytic leukemia following a chemotherapeutic regimen for metastatic sarcoma.
Acute myelomonocytic leukemia developed in a patient 18 months after treatment with cyclophosphamide, vincristine, adriamycin, and DTIC, a chemotherapeutic regimen used for the treatment of metastatic sarcoma. The patient had had no prior history of radiation. More than 400 patients received this treatment and none of them developed leukemia. The occurrence of leukemia in this relatively short period of time may have been caused by the combined chemotherapeutic agents. However, confirmation of this will require long-term followup studies in cancer patients receiving chemotherapy to determine the true risk of second malignancies.


[The prognosis and clinicopathological characteristics of 70 gastric cancer patients with elevated serum AFP].
Objective: This study aimed to review the clinicopathological characteristics and prognosis of advanced gastric cancer patients with elevated serum Alpha-fetoprotein (AFP). Methods: From August 2006 to May 2016, 70patients with advanced gastric cancer were enrolled retrospectively. All these patients had pathologically confirmed gastric adenocarcinoma, had a serum AFP level of more than 20 ng/ml, and received at least first-line treatment. The clinicopathological data and follow-up data were collected for analysis. Results: Liver metastasis was more common in patients with AFP≥1 000 ng/ml, compared with AFP<1 000 ng/ml patients (78.6% vs 57.1%, P=0.064). In patients whose AFP level decreased ≥50% after first-line chemotherapy, the disease control rate and overall survival were both better than those in patients with AFP decreased <50%(96.3% vs 56.7%, P=0.001; 17.2 m vs 8.8 m P=0.007). The overall survival of all these 70 patients ranged from 0.5-50.0 months. 31 patients received chemotherapy only, and 39 patients received combined therapy modality. The overall survival of these two groups were similar(11.0 m and 15.6 m, respectively, P=0.070). Conclusions: Serum AFP-elevated gastric cancer is a special subtype of gastric cancer. It's a heterogeneous cancer with different clinical outcomes. The extent of decrease of serum AFP level during follow-up may be a sensitive prognostic and predictive biomarker. Liver metastasis were more common in these patients, and combined treatment may improve survival.


School-based early intervention and child well-being in the Chicago Longitudinal Study.
Chicago Child-Parent Centers provide comprehensive education and family support services to young, low-income children. Using data from 1,539 children in the Chicago Longitudinal Study, preschool participation was associated with significantly higher levels of school readiness, achievement, and educational attainment, and with lower rates of child maltreatment, juvenile delinquency, special education placement, and grade retention. Every dollar invested in the preschool program returned 7.14 dollars to society at large. School-age intervention also provided economic returns that exceeded costs. Findings provided strong evidence that large-scale, public, early interventions can enhance children's well-being. The authors recommend greater investments in programs with elements similar to the Child-Parent Centers.


Video Monitoring Application of CMOS 4T-PPD-APS Under γ-ray Radiation.
In this paper, we discuss the potential use of four transistor active pixel sensor (4T-APS) as a video monitor at a nuclear accident site with a high level of γ radiation. The resistance and radiation responses to γ radiation were investigated by radiation experiments using 137Cs and 60Co γ-ray sources. The radiation resistance of 4T-APS was studied by testing the mean and the maximum dark current of the sensors after irradiation. A random spatial distribution of radiation response events was observed upon analyzing these events on the video images in a given time during irradiation. The background dependence of the 4T-APS was also studied by comparing the grayscale incremental value of the images with different color and grayscale backgrounds: the radiation response events were obvious on the images with a background having a smaller grayscale value or a deeper color. Finally, the color saturation and resolution of the images were tested using a vector oscilloscope and a test card. When the total ionizing dose was less than or equal to the damage threshold, no significant performance deterioration of 4T-APS was observed in an environment with sufficient light.


Ultrasonic demonstration of ectopic urethral ureter in duplex kidney: report of two cases.
Two cases of duplex kidney with ectopic urethral ureter are reported. Using abdominal ultrasound, the poorly functioning upper pole pelvis of the involved kidney was found to be sonolucent which may have been misinterpreted for a simple renal cyst. The corresponding ureter was dilated and drained into the proximal urethra. Ultrasound is an ideal imaging modality in the assessment of children with a duplicated renal system and may provide detailed information about this structural anomaly, such as the exact insertion of the ectopic ureter.


[Lipoprotein(a) as a risk factor for cardiovascular disease in elderly patients with diabetes].
Lipoprotein(a) (Lp(a)) is an independent risk factor for cardiovascular diseases in non-diabetic people, but few studies have been done in diabetic patients. To investigate whether Lp(a) is a risk factor for cardiovascular disease in elderly people with diabetes, we examined the association of Lp(a) and serum lipid levels (total cholesterol: TC; triglycerides: TG; and high-density lipoprotein cholesterol: HDL-c) with the incidence of coronary artery disease and cerebrovascular disease. We studied 354 outpatients(131 men and 223 women, 60-97 years of age) with non-insulin-dependent diabetes mellitus. The mean concentration of Lp(a) was 21.1 +/- 19.6 mg/dl and the median was 14.0 mg/dl. The Lp(a) concentration did not correlate significantly with age or with sex, but it did correlate significantly with TC (r = 0.152, p < 0.05) and with the level of apoprotein B (r = 0.168, p < 0.05). The incidence of cerebrovascular disease was significantly higher in patients with high concentrations of Lp(a) (> or = 30 mg/ dl) than in those with low concentrations (< 30 mg/ dl). Multivariate logistic regression analysis revealed that male sex, hypertension, a high level of HbA1c, a low level of HDL, and a high level of Lp(a) were independent risk factors for cerebrovascular disease. The incidence of coronary artery disease tended to the higher in those with high concentrations of Lp(a) (> or = 30 mg/dl). However, multivariate logistic regression analysis revealed no significant correlation between Lp(a) concentration and the incidence of coronary artery disease. We conclude that a high concentration of Lp(a) is an independent risk factor for cerebrovascular disease in elderly patients with diabetes.


Production method affects the pharmacokinetic and ex vivo biological properties of low molecular weight heparins.
Low molecular weight (LMW) heparins have prolonged circulating half-lives relative to unfractionated heparin, but the rates of plasma clearance differ between different LMW preparations. To determine the impact of method of production on their pharmacokinetic and ex vivo biological properties, two LMW heparins of similar molecular weight distribution, Logiparin and Fragmin, were radiolabelled with 125I, administered intravenously with 4 mg/kg of carrier drug into rabbits, and the circulating radiolabelled material and anti-Xa activity were analysed by size exclusion chromatography and affinity for antithrombin and Polybrene. Following administration of Logiparin, the anti-Xa amidolytic activity was eliminated with the same half-life as the anti-thrombin-binding radiolabel and was not neutralised by antibody against tissue factor pathway inhibitor (TFPI). Larger molecules were cleared preferentially and were no longer detectable 8 h post injection. These findings resemble those we have previously described for Enoxaparin. After Fragmin administration the antithrombin binding radiolabel was cleared more rapidly than the anti-Xa activity, and at late times after injection a significant amount of this activity was neutralised by antibody against TFPI. Sulphated radiolabel was eliminated with a similar half-life to the anti-Xa activity and sulphated molecules > 6000 Da remained in the circulation 8 h after administration. Fragmin, unlike Logiparin and Enoxaparin, has no negatively charged sulphamino group at the reducing end of the molecule. We suggest that this minimises cellular interaction and protects the larger molecules from elimination. They remain in the circulation, contributing to anti-Xa activity by binding TFPI. Thus the method of production of LMW heparins may significantly influence their pharmacokinetic properties and circulating anticoagulant activities.


Seasonality of reproduction in sheep and its control by photoperiod.
Seasonality of the reproductive cycle in sheep is a general phenomenon for mid-latitude breeds. The proximal part (breeding season) and also partially distal part (end of gestation and beginning of lactation) of this cycle is controlled by photoperiod, whatever the form of light regimens. Data are presented which indicate that male and female do not necessarily have the same photoperiodic sensitivity. Gonadal stimulation in the ram starts 1.5-2 months earlier than in the ewe under annual variations. Photoperiod controls the reproductive cycle by the intermediary of the hypothalamo-pituitary axis. There are both a steroid-independent and a steroid-dependent effect of light, depending on both decreasing and increasing daylength in mid-latitudes. Data are also presented which support Bunning's hypothesis on photoperiodic time measurement in mammals. Sheep measure photoperiodic time by using a circadian rhythm of photosensitivity. Daylength is not measured by the total duration of exposure to light but by the illumination of two special set points during the day, one of them entraining the circadian rhythm of photosensitivity and the other inducing or not inducing a physiological response if it is coincident, or not coincident, with photoinducible phase of that rhythm. A photoinducible phase has been found for prolactin secretion, and perhaps also for LH secretion. Melatonin secretion is used by sheep for measuring daylength. However, that secretion disappears during two set points during the day, thus raising the possibility of using alternatively melatonin and light pulse for controlling the reproductive cycle in sheep.


Improved outcomes of large B-cell lymphoma patients treated with CD19 CAR T in the UK over time.
The success of CD19 Chimeric antigen receptor (CAR) T-cell therapy in large B-cell lymphoma (LBCL) has been partially offset by toxicity and logistical challenges, which off-the-shelf agents like CD20xCD3 bispecific antibodies might potentially overcome. However, when using CAR T outcomes as the 'standard-of-care comparator̕ for relapsed/refractory (r/r) LBCL, a potential learning curve with implementing a novel, complex therapy like CAR T needs to be considered. To address this, we analysed 726 UK patients intended to be treated with CD19 CAR T for r/r LBCL and compared outcomes between the first year of the national CAR T programme (Era 1; 2019) and the more recent treatment era (Era 2; 2020-2022). We identified significant improvements for Era 2 versus Era 1 in dropout rate (17% vs. 27%, p = 0.001), progression-free survival (1-year PFS 50% vs. 32%, p < 0.001) and overall survival (1-year OS 60% vs. 40%, p < 0.001). We also observed increased use of bridging therapy, improvement in bridging outcomes, more tocilizumab/corticosteroid use, reduced high-grade cytokine release syndrome (4% vs. 9%, p = 0.01) and intensive care unit admissions (20% vs. 32%, p = 0.001). Our results demonstrate significant improvement in CAR T outcomes over time, highlighting the importance of using up-to-date clinical data when comparing CAR T against new treatment options for r/r LBCL.


Neonatal maternal separation induces sex-specific augmentation of the hypercapnic ventilatory response in awake rat.
Neonatal maternal separation (NMS) is a form of stress that exerts persistent, sex-specific effects on the hypoxic ventilatory response. Adult male rats previously subjected to NMS show a 25% increase in the response, whereas NMS females show a response 30% lower than controls (8). To assess the extent to which NMS affects ventilatory control development, we tested the hypothesis that NMS alters the ventilatory response to hypercapnia in awake, unrestrained rats. Pups subjected to NMS were placed in a temperature- and humidity-controlled incubator 3 h/day for 10 consecutive days (P3 to P12). Control pups were undisturbed. At adulthood (8 to 10 wk old), rats were placed in a plethysmography chamber for measurement of ventilatory parameters under baseline and hypercapnic conditions (inspired CO(2) fraction = 0.05). After 20 min of hypercapnia, the minute ventilation response measured in NMS males was 47% less than controls, owing to a lower tidal volume response (22%). Conversely, females previously subjected to NMS showed minute ventilation and tidal volume responses 63 and 18% larger than controls respectively. Although a lower baseline minute ventilation contributes to this effect, the higher minute ventilation/CO(2) production response observed in NMS females suggests a greater responsiveness to CO(2)/H(+) in this group. We conclude that NMS exerts sex-specific effects on the hypercapnic ventilatory response and that the neural mechanisms affected by NMS likely differ from those involved in the hypoxic chemoreflex.


Experimental studies on the treatment of unilateral vocal cord paralysis.
After the injection of Teflon and Silicon behind the vocal cords of sheeps we noticed that these materials are quite well supported. The little particles of Teflon are surrounded by conjective tissue wheras the Silicon is enclosed in an unic membrane. We could not see a migration of the materials in the depth.


Sorting functions of the individual cytoplasmic domains of the G protein-coupled vasopressin V(2) receptor in Madin Darby canine kidney epithelial cells.
Previous studies have shown that the G protein-coupled human vasopressin V(2) receptor (V(2) receptor) is expressed predominantly in the basolateral membrane of Madin Darby canine kidney type II (MDCKII) epithelial cells at steady state. Here we have assessed the influence of the individual cytoplasmic domains of the V(2) receptor on polarized sorting in MDCKII cells. The second (ICL2) and third (ICL3) intracellular loops and the C-terminal tail were fused separately to a green fluorescent protein-tagged receptor fragment comprising the first transmembrane domain and flanking regions. We show that the ICL2 domain of the V(2) receptor alone promotes basolateral cell surface expression and thus seems to contain the basolateral sorting signal of the V(2) receptor. Fusion of the other cytoplasmic domains, however, does not lead to a randomized cell surface expression. The C-terminal tail of the V(2) receptor promotes apical targeting. Fusion of ICL3 leads to a receptor fragment that is retained in the endoplasmic reticulum (ER). The results are consistent with a model in which the V(2) receptor contains signals for both apical and basolateral cell surface expression, the latter being dominant. Furthermore, ICL3 may contain a RXR [corrected] ER retention signal, which is not accessible in the correctly folded full-length receptor but which is unmasked when ICL3 is fused alone.


NATURAL RADIOACTIVITY AND ASSESSMENT OF HAZARD INDICES OF THE SOIL FOUND AT SUNG VALLEY, MEGHALAYA.
In this work, the variation of the radioactivity at different depth of the soil found at the Sung Valley in West Jaiñtia Hills District of Meghalaya in India is estimated by using the gamma-ray spectroscopy. The average activity concentration of 226Ra, 232Th and 40K for soil samples at different depths are measured to be 57, 156 and 352 Bq kg-1, respectively. The radiological hazard indices for the soil samples are calculated using standard models in order to determine the safe utility of these materials that are being used to manufacture domestic products by the locals. Values of all the radiological hazard indices are observed to be within the internationally recommended values as proposed by the European Commission and the United Nations Scientific Committee on the Effects of Atomic Radiation. The present study ensures that the soil analysed presents a negligible radiation hazard, and produced poetries and artefacts radiological incidence will stay within the allowed natural limit.


Lacrimal sac empyema incision and drainage followed by early external dacryocystorhinostomy.
To evaluate the success of lacrimal sac empyema incision and drainage followed by early external dacryocystorhinostomy. Interventional consecutive case series conducted in Farabi Eye Hospital between August 2007 and November 2010. Patients with acute dacyocystitis and lacrimal sac empyema underwent incision and drainage, followed by early (less than 4 weeks) external DCR. Data collection included patient demographics, past medical history, procedure technique, culture results, and formation of a persistent cutaneous fistula. A total of 32 patients were included: 87.5% had a positive history of chronic epiphora before dacryocystitis. Of these 32 cases, 55.6% had positive culture. Staphylococcus aureus was the most common organism with 8 isolates (38%). The average number of days between empyema drainage and DCR was 11.44 days. All patients had complete resolution of dacryocystitis, with no recurrence during the follow-up period. Neither of 32 patients treated with early DCR after primary empyema drainage, developed a persistent lacrimal-cutaneous fistula. Incision and drainage of the lacrimal sac empyema followed by early external dacryocystorhinostomy can be an appropriate treatment strategy for acute dacryocystitis.


Characterization and bioactivities of the exopolysaccharide from a probiotic strain of Lactobacillus plantarum WLPL04.
Exopolysaccharide (EPS) was extracted and purified from Lactobacillus plantarum WLPL04, which has been confirmed previously as a potential probiotic for its antagonistic and immune-modulating activity. It has a molecular weight of 6.61 × 104 Da, consisting of xylose, glucose, and galactose in an approximate molar ratio of 3.4:1.8:1. Microstructural studies demonstrated that the EPS appeared as a smooth sheet structure with many homogeneous rod-shaped lumps. The preliminary in vitro assays indicated that the EPS could significantly inhibit the adhesion of Escherichia coli O157:H7 to HT-29 cells in competition, replacement, and inhibition assays at a dose of 1.0 mg/mL, with an inhibition rate of 20.24 ± 2.23, 29.71 ± 1.21, and 30.57 ± 1.73%, respectively. Additionally, the EPS exhibited strong inhibition against biofilm formation by pathogenic bacteria, including Pseudomonas aeruginosa CMCC10104, E. coli O157:H7, Salmonella Typhimurium ATCC13311, and Staphylococcus aureus CMCC26003. Furthermore, the EPS showed good inhibitory activity against the proliferation of HT-29 cells. The characteristics and bioactivities of this EPS may make it a promising candidate in developing functional food.


Transcriptional regulation of retinoic acid responsive genes by cellular retinoic acid binding protein-II modulates RA mediated tumor cell proliferation and invasion.
The chemotherapeutic agent retinoic acid (RA) inhibits the proliferation and invasion of many tumor types. RA chemotherapy in head and neck squamous cell carcinoma (SCC) patients reduces recurrence and induces regression of premalignant lesions. The effects of RA are mediated by both cytoplasmic and nuclear proteins. In the nucleus, a family of ligand-dependent transcription factors, the retinoic acid receptors (RAR) and the retinoid X receptors (RXR), regulate target gene response to RA. In the cytoplasm, the cellular retinoic acid binding proteins I and II (CRABP) regulate intracellular RA concentration, transport, and metabolism. Alterations in CRABP expression have been shown to affect target gene response and the phenotype of cancer cells. To elucidate the role of these proteins in mediating the RA response, we examined target gene expression and malignant phenotype in SCC25 cells expressing an antisense CRABP II construct. RA induced CRABP II mRNA levels 2 fold in SCC25 cells by transcriptional upregulation. Expression of the antisense construct reduced CRABP II expression to undetectable levels. Inhibition of CRABP II expression resulted in significant downregulation of RA responsive genes. These reductions were the result of decreased transcription from RA responsive promoters. Surprisingly, clones expressing the antisense CRABP construct were less sensitive to RA mediated inhibition of proliferation. These clones were also less invasive in an in vitro invasion assay, likely due to downregulation of matrix metalloproteinase activity. We conclude that CRABP II affects the transcription of RA responsive genes which regulate proliferation and invasion of head and neck SCCs.


Influence of Human Cytomegalovirus Glycoprotein O Polymorphism on the Inhibitory Effect of Soluble Forms of Trimer- and Pentamer-Specific Entry Receptors.
Human cytomegalovirus (HCMV) envelope glycoprotein complexes, gH/gL/gO trimer and gH/gL/UL128-131 pentamer, are important for cell-free HCMV entry. While soluble NRP2-Fc (sNRP2-Fc) interferes with epithelial/endothelial cell entry through UL128, soluble platelet-derived growth factor receptor α-Fc (sPDGFRα-Fc) interacts with gO, thereby inhibiting infection of all cell types. Since gO is the most variable subunit, we investigated the influence of gO polymorphism on the inhibitory capacities of sPDGFRα-Fc and sNRP2-Fc. Accordingly, gO genotype 1c (GT1c) sequence was fully or partially replaced by gO GT2b, GT3, and GT5 sequences in the bacterial artificial chromosome (BAC) TB40-BAC4-luc background (where luc is luciferase). All mutants were tested for fibroblast and epithelial cell infectivity, for virion content of gB, gH, and gO, and for infection inhibition by sPDGFRα-Fc and sNRP2-Fc. Full-length and partial gO GT swapping may increase epithelial-to-fibroblast ratios due to subtle alterations in fibroblast and/or epithelial infectivity but without substantial changes in gB and gH levels in mutant virions. All gO GT mutants except recombinant gO GT1c/3 displayed a nearly complete inhibition at 1.25 μg/ml sPDGFRα-Fc on epithelial cells (98% versus 91%), and all experienced complete inhibition on fibroblasts (≥99%). While gO GT replacement did not influence sNRP2-Fc inhibition at 1.25 μg/ml on epithelial cells (97% to 99%), it rendered recombinant mutant GT1c/3 moderately accessible to fibroblast inhibition (40%). In contrast to the steep sPDGFRα-Fc inhibition curves (slope of >1.0), sNRP2-Fc dose-response curves on epithelial cells displayed slopes of ∼1.0, suggesting functional differences between these entry inhibitors. Our findings demonstrate that artificially generated gO recombinants rather than the major gO genotypic forms may affect the inhibitory capacities of sPDGFRα and sNRP2 in a cell type-dependent manner.IMPORTANCE Human cytomegalovirus (HCMV) is known for its broad cell tropism, as reflected by the different organs and tissues affected by HCMV infection. Hence, inhibition of HCMV entry into distinct cell types could be considered a promising therapeutic option to limit cell-free HCMV infection. Soluble forms of cellular entry receptor PDGFRα rather than those of entry receptor neuropilin-2 inhibit infection of multiple cell types. sPDGFRα specifically interacts with gO of the trimeric gH/gL/gO envelope glycoprotein complex. HCMV strains may differ with respect to the amounts of trimer in virions and the highly polymorphic gO sequence. In this study, we show that the major gO genotypes of HCMV that are also found in vivo are similarly well inhibited by sPDGFRα. Novel gO genotypic forms potentially emerging through recombination, however, may evade sPDGFRα inhibition on epithelial cells. These findings provide useful additional information for the future development of anti-HCMV therapeutic compounds based on sPDGFRα.


[Simple kinetic analysis of 99mTc-GSA by direct integral linear least square regression method: calculation of hepatic blood flow and receptor index based on three-compartment model].
To obtain both hepatic blood flow and an index of asialoglycoprotein receptor amount by simple calculation in the asialoglycoprotein receptor imaging with 99mTc-DTPA-Galactosyl Human Serum Albumin (99mTc-GSA), we have tested the applicability of the direct integral linear least square regression (DILS) method based on a linear 3-compartment model (Bronqvist, 1984) to the kinetic analysis of 99mTc-GSA scintigraphy. DILS method can provide hepatic blood flow (k1) and the product of receptor amount and forward binding rate constant (k1k3/k2) as a receptor index, without requiring iterative calculation and initial estimates of the parameters. To compare DILS method with nonlinear least square regression (NLS) method as a standard, data from 35 patients with liver dysfunction were analyzed by both methods. The effect of the data noise to parameter estimate were simulated, and both DILS and NLS method could provide reliable parameter estimate which is relatively insensitive to the data noise. In estimated model parameters, both hepatic blood flow (k1) and the receptor index (k1k3/k2) showed significant correlation between 2 methods (r2 = 0.96, p < 0.0001; r2 = 0.99, p < 0.0001, respectively). We concluded that DILS method was comparable to NLS method in determination of the model parameters and could be useful in the asialoglycoprotein receptor imaging.


Unenhanced CT texture analysis with machine learning for differentiating between nasopharyngeal cancer and nasopharyngeal malignant lymphoma.
Differentiating between nasopharyngeal cancer and nasopharyngeal malignant lymphoma (ML) remains challenging on cross-sectional images. The aim of this study is to investigate the usefulness of texture features on unenhanced CT for differentiating between nasopharyngeal cancer and nasopharyngeal ML. Thirty patients with nasopharyngeal tumors, including 17 nasopharyngeal cancers and 13 nasopharyngeal MLs, were underwent 18F-FDG PET/CT. All nasopharyngeal cancers and 7 of 13 nasopharyngeal MLs were confirmed by endoscopic biopsy. On unenhanced CT, 34 texture features were analyzed following lesion segmentation in the maximum area of the target lesion. The Mann-Whitney U test and areas under the curve (AUCs) were used for analysis and to compare the maximum standardized uptake values (SUV)max, SUVmean, and 34 texture features. A support vector machine (SVM) was constructed to evaluate the diagnostic accuracy and AUCs of combinations of texture features, with 50 repetitions of 5-fold cross-validation. Differences between the SUVmax and SUVmean for nasopharyngeal cancers and nasopharyngeal MLs were not significant. Significant differences of texture features were seen, as follows: 1 histogram feature (p = 0.038), 3 gray-level co-occurrence matrix features (p < 0.05), and 1 neighborhood gray-level different matrix feature (NGLDM) (p = 0.003). Coarseness in NGLDM provided the highest diagnostic accuracy and largest AUC of 76.7% and 0.82, respectively. SVM evaluation of the combined texture features obtained the highest accuracy of 81.3%, with an AUC of 0.80. Combined texture features can provide useful information for discriminating between nasopharyngeal cancer and nasopharyngeal ML on unenhanced CT.


Esophageal carcinoma. A six-year review of the Cleveland Veterans Administration Hospital experience.
The records of 51 patients with esophageal carcinoma were reviewed. Twenty-two patients underwent attempted curative resection with a mean survival of 7.7 months. Twenty patients underwent primary radiotherapy (mean survival, 4.3 months). Nine patients received palliative therapy alone (mean survival, 2.8 months). Surgical mortality was 27%, but symptomatic palliation was complete in 59% of the surgical patients. Only 5% of the radiotherapy group, and 11% of the palliative group were completely palliated. There is only one long-term survivor (21 + months). Lesions in the middle third of the esophagus, and the presence of clinical evidence of metastatic disease were predictive of a shorter survival. Patients with metastatic disease at presentation had a mean survival of only 2.5 months from diagnosis. It is concluded that surgery should be considered a palliative, not curative procedure, and that it should be attempted only in those patients without clinical evidence of metastatic disease.


Characterization of the morphonuclear features and DNA ploidy of typical and atypical carcinoids and small cell carcinomas of the lung.
The authors analyzed several cytomorphonuclear parameters related to chromatin distribution and DNA ploidy in typical and atypical carcinoids and in small cell lung cancers. Nuclear measurements and analysis were performed with a SAMBA 200 (TITN, Grenoble, France) cell image processor with software allowing the discrimination of parameters computed on cytospin preparations of Feulgen-stained nuclei extracted from deparaffinized tumor tissues. The authors' results indicate a significant increase in DNA content--assessed by integrated optical density (IOD)--from typical carcinoids to small cell lung carcinomas, with atypical carcinoids showing an intermediate value. Parameters related to hyperchromatism (short and long run length and variance of optical density) also characterize the atypical carcinoids as being intermediate between typical carcinoids and small cell lung cancers. The systematic measurement of these cytomorphonuclear parameters seems to define an objective, reproducible "scale" of differentiation that helps to define the atypical carcinoid and may be of value in establishing cytologic criteria for differential diagnosis.


Spontaneous membrane formation and self-encapsulation of active rods in an inhomogeneous motility field.
We study the collective dynamics of self-propelled rods in an inhomogeneous motility field. At the interface between two regions of constant but different motility, a smectic rod layer is spontaneously created through aligning interactions between the active rods, reminiscent of an artificial, semipermeable membrane. This "active membrane" engulfes rods which are locally trapped in low-motility regions and thereby further enhances the trapping efficiency by self-organization, an effect which we call "self-encapsulation." Our results are gained by computer simulations of self-propelled rod models confined on a two-dimensional planar or spherical surface with a stepwise constant motility field, but the phenomenon should be observable in any geometry with sufficiently large spatial inhomogeneity. We also discuss possibilities to verify our predictions of active-membrane formation in experiments of self-propelled colloidal rods and vibrated granular matter.


Continuous positive airway pressure and adherence in patients with different endotypes of obstructive sleep apnea.
Determining the endotypes of obstructive sleep apnea (OSA) has potential implications for precision interventions. Here we assessed whether continuous positive airway pressure (CPAP) treatment outcomes differ across endotypic subgroups. We conducted a retrospective analysis of data obtained from 225 patients with moderate-to-severe OSA from a single sleep centre. Polysomnographic and CPAP titration study data were collected between May 2020 and January 2022. One-month CPAP treatment adherence was followed. Obstructive sleep apnea endotypes, namely arousal threshold, collapsibility, loop gain, and upper airway gain were estimated from polysomnography and dichotomised as high versus low. We examined associations between endotypic subgroups and (1) optimal CPAP titration pressure, (2) CPAP-related improvements in sleep architecture (proportions of slow-wave and rapid eye movement (REM) sleep), and (3) CPAP adherence. We observed that patients with high collapsibility required a higher CPAP pressure than those with low collapsibility (∆ = 0.4 cmH2 O, 95% confidence interval [CI] = 0.3-1.7). A larger increase in slow-wave sleep and in REM sleep proportions after CPAP treatment were observed in patients with a high arousal threshold, high collapsibility, high loop gain, or high upper airway gain than in those with low levels of endotypes. High loop gain and high collapsibility were independently associated with longer CPAP use hours per night (∆ = 0.6 h, 95% CI = 0.2-1.5 and ∆ = 0.3 h, 95% CI = 0.03-1.5, respectively). In conclusion, different endotypic subgroups of OSA exhibit a difference in outcomes of CPAP treatment. Knowledge of endotypes may help clinicians to understand which patients are expected to benefit most from CPAP therapy prior to its administration.


Clinically amyopathic dermatomyositis during the COVID-19 pandemic.
An 84-year-old Japanese woman presented to our hospital with a month-long dry cough during the coronavirus disease 2019 (COVID-19) pandemic. She also had skin lesions on her fingers from 3 months prior. A chest computed tomography (CT) scan showed bilateral ground- glass opacities with a subpleural distribution, similar to the findings of COVID-19. The results of COVID-19 tests were negative. The titer of the anti-melanoma differentiation-associated gene 5 (MDA5) antibody was elevated. Consequently, we confirmed the diagnosis of clinically amyopathic dermatomyositis (CADM) and then administered oral prednisolone combined with tacrolimus. After the treatment, her symptoms, skin lesions and CT findings were gradually resolved.


Source localization in the deep ocean using a convolutional neural network.
In deep-sea source localization, some of the existing methods only estimate the source range, while the others produce large errors in distance estimation when estimating both the range and depth. Here, a convolutional neural network-based method with high accuracy is introduced, in which the source localization problem is solved as a regression problem. The proposed neural network is trained by a normalized acoustic matrix and used to predict the source position. Experimental data from the western Pacific indicate that this method performs satisfactorily: the mean absolute percentage error of the range is 2.10%, while that of the depth is 3.08%.


Phase-dependent selectivity control over TiO2 in the photocatalytic oxidation of bio-polyols.
Photocatalytic oxidation shows great potential in the valorization of biomass under mild conditions, while the selectivity control is particularly challenging for the complex and reactive bio-polyols. Herein, we report a selective photocatalytic process to convert bio-polyols into formic acid (FA) or carbon monoxide (CO) by controlling the phase of TiO2. The bio-polyols are facially oxidized to formic acid (FA) which is stable over rutile and could be dehydrated to CO over anatase TiO2. Through controlling the phase, FA or CO could be obtained from a wide range of bio-polyols with selectivity up to 63% or 52%. Our studies elucidate that the phase-dependent selectivity is essentially derived from the difference in the adsorption configuration of FA. In situ Fourier transform infrared spectroscopy (FTIR) and density functional (DFT) calculations were used to study the FA decomposition process on the surface of TiO2. The phase-dependent FA decomposition is mainly derived from the different surface geometry, which affects the configuration of FA adsorption. Molecular adsorbed FA on anatase favors the dehydration of FA to CO while bidentate dissociated adsorption of FA on the rutile phase is inert to be further converted. This work provides a new horizon to the design of photocatalytic systems for biomass conversion.


Maisonneuve fracture.
Maisonneuve fracture (MF) is a generally known entity in ankle trauma. However, details about this type of injury can be found only rarely in the literature. For these reasons we have decided to perform a study on MF epidemiology and pathoanatomy. The group comprised 70 patients (47 men, 23 women), with the mean age of 48 years, who sustained an ankle fracture-dislocation involving the proximal quarter of the fibula. Ankle radiographs in three views and lower leg radiographs in two views were performed in all patients. A total of 59 patients underwent CT examination in three views, including 3D CT reconstruction in 49 of these patients. MRI was performed in 4 patients. Operative treatment was used in 67 patients; open reduction of the distal fibula into the fibular notch was opted for in 54 of them. The highest MF incidence rate was recorded in the 5th decade in the whole group and in men, while in women the peak incidence was in the 6th decade. After the age of 50, the share of women significantly increased. In 64 cases, the fibular fracture was subcapital, and in 6 cases it involved the fibular head. In 24% of the patients, the fibular fracture was seen only in the lateral radiograph of the lower leg. Widening of the tibiofibular clear space was shown by radiographs in 40 cases. Posterior dislocation of the fibula (Bosworth fracture) and tibiofibular diastasis were recorded in 2 cases each. An injury to the anterior and posterior tibiofibular ligaments was found in all 54 patients with open reduction of the distal fibula. A fracture of the medial malleolus was identified in 27 cases (39%) and a complete lesion of the deltoid ligament in 36 cases (51%); in 7 cases (10%) the medial structures were intact. A fracture of the posterior malleolus occurred in 54 (77%) patients. Osteochondral fracture of the talar dome was diagnosed in 2 patients and compression of the articular surface of the distal tibia in the region of the fibular notch in 1 patient. Maisonneuve fracture includes a wide range of injuries both to bone and ligamentous structures of the ankle. Therefore, CT examination is an indispensable part of assessment of this type of fracture.


Environmental Variables Including Heavy Metals Significantly Shape the Soil Bacterial Community Structure in the Tatun Volcano Group, Northern Taiwan.
Recent studies suggested the presence of magma chambers from the Tatun volcano group under northern Taiwan's surface, the result of episodic volcanism for 0.2-2.8 million years. However, the microbial community in volcanic soil has not yet been characterized. Therefore, the present study investigated the spatial distribution of microbial communities and their relationships with environmental variables, including heavy metals. Next-generation sequencing was used to analyze the microbial community structures in three areas with different land uses: Lengshuikeng (recreational area), Zhuzihu (agricultural area), and Huangzuishan (conservation area). High contents of environmental factors, such as nitrogen (0.46-1.14%) and phosphorus (2.01-13.88 ppm), were detected. Large concentrations of heavy metals, such as copper (55.90-127.60 ppm) and zinc (36.13-147.73 ppm), were found among the three sites, whereas those of lead (83.13 ppm) and chromium (48.33 ppm) were higher in the Zhuzihu area. The most prevalent phylum across all sites was Proteobacteria, followed by Actinobacteria, Acidobacteria, and Chloroflexi, while the most abundant bacterial species was Koribacteraceae: NA_01, followed by Cyanobacteria: NA. A network ana-lysis showed that Koribacteracea: NA_01 positively correlated with bacterial groups, including Flavisolibacter sp., Oxalobacteraceae: NA, and Actinomycetales: NA_01. Based on Shannon and Simpson's diversity indices, the diversity of bacteria was significantly less in the Huangzuishan area than in the Lengshuikeng and Zhuzihu areas. Bacterial assemblages also significantly differed (P<0.05) among the three sites. The present results provide clear evidence to show that environmental variables, including heavy metals, are key factors affecting the bacterial community structure in volcanic soil.


Studies on the biosynthesis of extracellular proteases by bacteria. I. Serratia marcescens, synthetic and gelatin media.
Apparently the extracellular protease of S. marcescens is present in protein- or protein derivative-free media only when the conditions favor an abundant growth and bacterial conglomerates are formed, which possibly could be explained by assuming that the proteins of dead bacteria or proteic metabolic products act as inducers of protease formation. Dilute solutions of gelatin induce the production of proteolytic activity after a short period of time and its rapid increase before the initial number of bacteria has been duplicated. Calcium is necessary to preserve the activity of the enzyme formed in synthetic media but not that produced in gelatin.


Effect of exercise of the lower limbs on the non-exercised biceps brachii muscle.
The electrophysiological pattern of fatigue of the biceps brachii (BB) muscle before and after bicycle leg exercise (LE), was evaluated in 12 healthy volunteers. In healthy people, the onset of isometric contraction is initiated by smaller motor units with briefer durations and higher spike frequencies. With the progression of contraction and muscular fatigue, electromyographic decrease in frequency and an increased spike duration occur. In our study, these findings were presented in subjects at the Final Value (FV) of electromyography before and after LE. In 8 subjects, the Initial Value (IV) of spike duration was longer after LE and a decrease in the frequency of electromyography was found in 9 of the 12 subjects. The changes in these two parameters at the onset of the BB contraction after LE may be due to the existence of an electrophysiological transfer effect. Eight subjects sustained the isometric BB contraction longer after LE than before LE. This may be explained by a diverting activity or other factors. Venous lactic acid was measured in 7 subjects and showed an increase after LE. No definite correlation between electromyographic changes and lactic acid was found.


Characterization of the Dioscorin Gene Family in Dioscorea alata Reveals a Role in Tuber Development and Environmental Response.
Dioscorin is one of the major soluble proteins in yam tubers. Unlike other well-known plant storage proteins, such as patatin and sporamin, dioscorin is argued for its function as storage proteins, and the molecular mechanisms underlying its expressional complexity are little understood. In this study, we isolated five dioscorin genes from Dioscorea alata L., comprising three class A (Da-dio1, -3 and -4) and two class B (Da-dio2 and -5) isoforms. Expressions of all dioscorin genes gradually decreased in mother tubers during yam sprouting and regrowth. On the other hand, all dioscorin genes accumulated transcripts progressively with tuber development in new tubers, with Da-dio5 being the most prominent isoform. In yam leaves, the expressions of Da-dio5 were up-regulated by the treatments of five phytohormones (gibberellic acid, salicylic acid, indole-3-acetic acid, abscisic acid, and ethylene), and three abiotic stresses (high-temperature, low-temperature and drought). To further elucidate the regulatory mechanisms of Da-dio5 expressions, transgenic Arabidopsis plants harboring the Da-dio5 promoter-β-glucuronidase (GUS) fusion were generated. GUS staining showed that expressions of the Da-dio5 promoter were detected mainly in the shoot apical meristem (SAM) and hypocotyls, and enhanced by the treatments of the five hormones, and the three abiotic stresses mentioned above. These results suggest diverse roles of Da-dio5 in yam sprouting, regrowth, and tuberization, as well as in response to enviromental cues.


Pre-cometary ice composition from hot core chemistry.
Pre-cometary ice located around star-forming regions contains molecules that are pre-biotic compounds or pre-biotic precursors. Molecular line surveys of hot cores provide information on the composition of the ice since it sublimates near these sites. We have combined a hydrostatic hot core model with a complex network of chemical reactions to calculate the time-dependent abundances of molecules, ions, and radicals. The model considers the interaction between the ice and gas phase. It is applied to the Orion hot core where high-mass star formation occurs, and to the solar-mass binary protostar system IRAS 16293-2422. Our calculations show that at the end of the hot core phase both star-forming sites produce the same prebiotic CN-bearing molecules. However, in the Orion hot core these molecules are formed in larger abundances. A comparison of the calculated values with the abundances derived from the observed line data requires a chemically unprocessed molecular cloud as the initial state of hot core evolution. Thus, it appears that these objects are formed at a much younger cloud stage than previously thought. This implies that the ice phase of the young clouds does not contain CN-bearing molecules in large abundances before the hot core has been formed. The pre-biotic molecules synthesized in hot cores cause a chemical enrichment in the gas phase and in the pre-cometary ice. This enrichment is thought to be an important extraterrestrial aspect of the formation of life on Earth and elsewhere.


Two Cases of Primary Sclerosing Cholangitis Overlapping with Autoimmune Hepatitis in Adults.
Overlap syndrome between primary sclerosing cholangitis (PSC) and autoimmune hepatitis (AIH) is extremely rare in Japan. We herein report two adult patients with PSC-AIH overlap syndrome. They were diagnosed with PSC-AIH overlap syndrome based on the findings of endoscopic retrograde cholangiography and liver biopsy, and using the International Autoimmune Hepatitis Group scoring system. In both cases, PSC preceded AIH, and combination therapy with steroid and ursodeoxycholic acid was effective. Because there are few reported cases in Japan, it is important to study more cases to shed light on the clinical and pathological features of PSC-AIH overlap syndrome.