Incidence and outcome of Staphylococcus aureus endocarditis--a 10-year single-centre northern European experience.
Staphylococcus aureus is a leading cause of infective endocarditis. Little has been published on the outcome and epidemiology of S. aureus endocarditis (SAE) in the twenty-first century. Our aim was to evaluate the short-term and long-term outcome of SAE in Stockholm, Sweden, and assess its incidence over time. Patients treated for SAE from January 2004 through December 2013 were retrospectively identified at the Karolinska University Hospital. Clinical data were obtained from medical records and the diagnosis was verified according to the modified Duke criteria. Of 245 SAE cases, 152 (62%) were left-sided and 120 (49%) occurred in intravenous drug users. The calculated incidence in Stockholm County was 1.56/100 000 person-years, increasing from 1.28 in 2004-08 to 1.82/100 000 person-years in 2009-13 (p 0.002). In-hospital and 1-year mortality rates were 9.0% (22/245) and 19.5% (46/236), respectively. Age (OR 1.06 per year) and female sex (OR 3.0) were independently associated with in-hospital mortality in multivariate analysis. Involvement of the central nervous system (CNS) was observed in 30 (12%) patients, and valvular surgery was performed during hospitalization in 37 (15%). In left-sided endocarditis the strongest predictors for surgery were severe valvular insufficiency (OR 8.9), lower age (OR 1.07 per year) and no intravenous drug use (OR 10.7), and for CNS involvement lower age (OR 1.04 per year). In conclusion we noted low mortality, low CNS complication rate, and low valvular surgery frequency associated with SAE in our setting. The incidence was high and increased over time. The study provides an update on the outcome and epidemiology of SAE in the twenty-first century.


Assessment of health-related quality of life among patients with obesity, hypertension and type 2 diabetes mellitus and its relationship with multimorbidity.
Obesity, hypertension (HTN) and type 2 diabetes (T2D) are among the multifactorial disorders that occur at higher prevalence in a population. This study aims to assess the health-related quality of life (HRQoL) of patients with obesity, HTN and T2D individually and in the form of multimorbidity. A questionnaire-based cross-sectional study was conducted among the patients in 15 private clinics of Punjab, Pakistan. A stratified random sampling technique was used to collect the data from patients with obesity, HTN and T2D or their comorbidity. A total of 1350 patients responded by completing the questionnaire. The HRQoL of these patients was assessed using the EQ-5D-5L questionnaire (a standardized instrument for measuring generic health status). Statistical analysis was performed using chi-square test, Mann-Whitney U test, and Kruskal-Wallis test. Multivariate linear regression model was used to model the visual analogue scale (VAS) score. In total, 15% of patients had combined obesity, HTN and T2D; 16.5% had HTN and T2D; 13.5% had obesity and HTN and 12.8% had obesity and T2D. Only 15.8% of patients had obesity, 14.3% had HTN, and 12% had T2D. Mann Whitney-U test gave the statistically significant (p = <0.001) HRQoL VAS score55.1 (±23.2) of patients with the obesity. HRQoL VAS scores of patients with obesity were found to be higher when compared to patients with both T2D 49.8 (±15.4) and HTN 48.2 (±21). Diagnosis of one, two and three diseases showed significant results in VAS with all variables including gender (p = 0.004), educational level (p = <0.001), marital status (p<0.001), residence (p = <0.001), financial situation (p = <0.001) and monthly income (p = <0.001). The most frequently observed extremely problematic dimension was anxiety/ depression (47%) and the self-care (10%) was the least affected. Patient HRQoL is decreased by T2D, HTN, and obesity. The impact of these diseases coexisting is more detrimental to HRQoL.


Neighbor influences and seasonal growth patterns for Vallisneria americana in a mesotrophic lake.
Biomass of the submersed macrophyte Vallisneria americana rose steadily from early June to 50 g dry wt·m-2 in ealry August. Leaves dominated the biomass of this perennial from mid-June through August, after which plants senesced to leave only winter buds as perennating organs. Only 24% of plants sampled flowered during the 1978 growing season, yielding a population mean of less than 0.6% of dry weight allocated to sexual reproduction, with a maximum value of 7.8% for one plant. In contrast, allocation to winter buds accounted for 11% of total dry weight at the close of the growing season.Total dry weight, leaf length, stolon length, rosette number, and winter bud production of Vallisneria americana at the close of the growing season had significantly higher mean values for individual plants in a monospecific stand of Vallisneria than at sites dominated by Potamogeton amplifolius or Chara vulgaris. The basis of site differences in growth by V. americana is unknown, although we demonstrate significantly higher interstitial soluble reactive phosphorus concentration and organic content of sediment at a Vallisneria site.Removal of neighbors of some Vallisneria plants at the Vallisneria, Potamogeton, and Chara sites resulted in longer leaves, but fewer rosettes for plants with neighbors than plants without neighbors. It appears that this changing growth pattern permitted Vallisneria plants to compensate for the presence of neighbors, and thereby attain similar biomass and sustain similar winter bud production in the presence and absence of neighbors.


[Epidemiological, clinical and therapeutic features of pediatric ocular injuries in an eye emergency unit in Île-de-France].
Ocular and orbital trauma is a leading cause of acquired monocular blindness in childhood. These injuries differ from those in adults in some aspects of the management and prognosis, notably the risk of amblyopia. The goal of this study was to analyze the epidemiological, clinical and therapeutic features of ocular trauma in children who consulted in an eye emergency department in Île-de-France. This was a descriptive, prospective and longitudinal study. Over a period of 6 months, we included children aged 15 years old or less, who consulted during calls for ocular trauma. Each child received an ophthalmologic examination as complete as his or her condition and cooperation permitted. Mechanical injuries of the eyeball and chemical ocular burns were distributed respectively according to the Birmingham Eye Trauma Terminology and Dua's classification. The visual prognosis was defined as the best corrected visual acuity of the affected eye, measured at the conclusion of treatment. Among 586 children who consulted during the study period, 265 suffered from ocular trauma (45.22%). The male:female ratio was 1.6:1. The main places of occurrence of the injuries were home (64.15%) and school (18.11%). Injuries from finger nail scratch were the most frequent (12.45%). One hundred and fifty-seven patients consulted within 6 hours (59.19%). The cornea was the predominant site of the injury (44.40%). Mechanical injuries of the eyeball accounted for 75% of cases. The incidence of ocular chemical burns was 6.41%. Eyelid and orbital injuries were observed in 22.26% and 2.26% of cases respectively. Surgical treatment was required in 6.79% of cases. The incidence of hospitalization was 3.02% with a mean length of stay of 3 days. Four children developed sequelae, including 2 corneal scars and 2 cataracts. No case of blindness was recorded. The high frequency of traumatic ocular and orbital pathology in our study may be due to its sudden and accidental onset, leading parents to seek emergency care. Most injuries occurred at home and at school, which reflects the presence in these places of potential hazards, often unrealized or neglected. The low frequency of open-globe injury may be related to the ubiquitous recruitment. Indeed, in studies including only severe trauma, this rate may reach 73.4%. This clinical presentation is associated with a poor prognosis because of the risk of infection and sequelae causing decreased visual acuity and amblyopia. Few children were hospitalized. This could be explained by the predominance of mild to moderate trauma. Ocular trauma accounts for nearly half of pediatric conditions encountered in the eye emergency unit. Adequate emergency care improves the visual prognosis.


Pharmacological treatment with annexin A1-derived peptide protects against cisplatin-induced hearing loss.
Cisplatin is an antineoplastic agent widely used, and no effective treatments capable of preventing cisplatin-induced ototoxicity and neurotoxicity in humans have yet been identified. This study evaluated the effect of the anti-inflammatory annexin A1 (AnxA1)-derived peptide Ac2-26 in a cisplatin-induced ototoxicity model. Wistar rats received intraperitoneal injections of cisplatin (10 mg/kg/day) for 3 days to induce hearing loss, and Ac2-26 (1 mg/kg) was administered 15 min before cisplatin administration. Control animals received an equal volume of saline. Hearing thresholds were measured by distortion product otoacoustic emissions (DPOAE) before and after treatments. Pharmacological treatment with Ac2-26 protected against cisplatin-induced hearing loss, as evidenced by DPOAE results showing similar signal-noise ratios between the control and Ac2-26-treated groups. These otoprotective effects of Ac2-26 were associated with an increased number of ganglion neurons compared with the untreated cisplatin group. Additionally, Ac2-26 treatment produced reduced immunoreactivity on cleaved caspase 3 and phosphorylated ERK levels in the ganglion neurons, compared to the untreated group, supporting the neuroprotective effects of the Ac2-26. Our results suggest that Ac2-26 has a substantial otoprotective effect in this cisplatin-induced ototoxicity model mediated by neuroprotection and the regulation of the ERK pathway.


Management of Adnexal Torsion in the Pediatric and Adolescent Population at Western Australia's Single Tertiary Children's Hospital over the Last 10 Years: Retrospective Study.
To review our institutional data regarding the management of adnexal torsion (AT) and assess the ovarian conservation rates. Retrospective study. Tertiary children's hospital. Pediatric and adolescent patients with surgically diagnosed AT. Participants (n = 54, mean age 9.80 ± 3.95 years) were identified between June 2010 and May 2019. Surgical management of AT. The primary outcome was to determine the ovarian conservation rates in AT cases. The secondary outcomes were to determine the incidence of AT to total emergency department (ED) presentations, decision to operation theater (OT) time in AT cases, return to OT, histopathology, and follow-up with ultrasound to determine ovarian function. Data were collected on demographic and clinical characteristics. Continuous data were compared with t tests or Kruskal-Wallis tests; categoric data were compared with chi-square tests. A total of 52 (96.29%) patients had ovarian conservation, and 53 (98.14%) had laparoscopic management. The incidence rate for AT cases to total ED presentations for the last 10 years was 9.9 per 100 000, which was based on a Poisson distribution. Presentations to an ED for AT cases have trended upward since 2010. Decision to OT time was statistically significantly shorter in cases with preoperative suspicion of AT than those with intraoperative diagnosis of AT (p = .000). A total of 7 (12.96%) patients returned to OT for suspicion of recurrent torsion. Of these, 5 (9.26%) had confirmed repeat AT. The presence of fever, pain duration, severity of pain, and severity of torsion did not correlate with the follow-up ultrasound findings of ovarian activity. The findings from our study suggest that high ovarian conservation rates are achievable in AT cases. A high index of suspicion is required to prevent a delay in surgery.


Use of a chemically defined hypoallergenic diet (Vivonex in the management of patients with suspected food allergy/intolerance.
The use of a hypoallergenic diet was evaluated in patients suspected of food allergy/intolerance. Symptom scores for one week of regular diet were compared with symptom scores while taking Vivonex. Results indicate that patients had fewer symptoms while on Vivonex than during the preceding week of normal diet.


Participation of small GTPases Rac1 and Cdc42Hs in myoblast transformation.
We have previously shown that expression of active Rac1 and Cdc4Hs inhibits skeletal muscle cell differentiation. We show here, by bromodeoxyuridine incorporation and cyclin D1 expression, that the expression of active Rac1 and Cdc42Hs but not RhoA impairs cell cycle exit of L6 myoblasts cultured in differentiation medium. Furthermore, expression of activated forms of Rac1 and Cdc42Hs elicits the loss of cell contact inhibition and anchorage-dependent growth as measured by focus forming activity and growth in soft agar. RhoA was once again not found to have this effect. We found a constitutive Rac1 and Cdc42Hs activation in three human rhabdomyosarcoma-derived cell lines, one of the most common causes of solid tumours arising from muscle precursors during childhood. Finally, dominant negative forms of Rac1 and Cdc42Hs inhibit cell proliferation of the RD rhabdomyosarcoma cell line. These data suggest an important role for the small GTPases Rac1 and Cdc42Hs in the generation of skeletal muscle tumours.


Visual control of straight flight in Drosophila melanogaster.
The optomotor system of Drosophila is investigated in a flight simulator in which the fly's yaw torque controls the angular velocity of the panorama (striped drum, negative feedback). Flies in the flight simulator maintain a stable orientation even in a homogeneously textured panorama without landmarks. During 'straight' flight, torque is not zero. It consists of small pulses mostly alternating in polarity. The course is controlled by the duration (and possibly amplitude) of the pulses. The system operates under reafference control. By comparing the pulses with the visual input the system continuously measures and adjusts the efficacy of the torque output. The comparison, however, is not between angular velocity and yaw torque but, instead, between visual acceleration and pretorque, the first time derivative of torque. For comparison, the system first computes a cross-correlation. If the correlation coefficient is above a certain threshold the system calculates the external gain and adjusts its internal gain so as to keep the total gain constant. With the correlation coefficient below threshold, however, the system keeps the internal gain low despite the infinitely small external gain. We propose that for a reafferent optomotor system the coupling coefficient and the correlation coefficient of pretorque and visual acceleration are more relevant than the distinction between exafference and reafference.


Spinal cord injury: a study protocol for a systematic review and meta-analysis of microRNA alterations.
Spinal cord injury (SCI) is a devastating condition with no current neurorestorative treatments. Clinical trials have been hampered by a lack of meaningful diagnostic and prognostic markers of injury severity and neurologic recovery. Objective biomarkers and novel therapies for SCI represent urgent unmet clinical needs. Biomarkers of SCI that objectively stratify the severity of cord damage could expand the depth and scope of clinical trials and represent targets for the development of novel therapies for acute SCI. MicroRNAs (miRNAs) represent promising candidates both as informative molecules of injury severity and recovery, and as therapeutic targets. miRNAs are small, regulatory RNA molecules that are tissue-specific and evolutionarily conserved across species. miRNAs have been shown to represent powerful predictors of pathology, particularly with respect to neurologic disorders. Studies investigating miRNA alterations in all species of animal models and human studies of acute, traumatic SCI will be identified from PubMed, Embase, and Scopus. We aim to identify whether SCI is associated with a specific pattern of miRNA expression that is conserved across species, and whether SCI is associated with a tissue- or cell type-specific pattern of miRNA expression. The inclusion criteria for this study will include (1) studies published anytime, (2) including all species, and sexes with acute, traumatic SCI, (3) relating to the alteration of miRNA after SCI, using molecular-based detection platforms including qRT-PCR, microarray, and RNA-sequencing, (4) including statistically significant miRNA alterations in tissues, such as spinal cord, serum/plasma, and/or CSF, and (5) studies with a SHAM surgery group. Articles included in the review will have their titles, abstracts, and full texts reviewed by two independent authors. Random effects meta-regression will be performed, which allows for within-study and between-study variability, on the miRNA expression after SCI or SHAM surgery. We will analyze both the cumulative pooled dataset, as well as datasets stratified by species, tissue type, and timepoint to identify miRNA alterations that are specifically related to the injured spinal cord. We aim to identify SCI-related miRNA that are specifically altered both within a species, and those that are evolutionarily conserved across species, including humans. The analyses will provide a description of the evolutionarily conserved miRNA signature of the pathophysiological response to SCI. Here, we present a protocol to perform a systematic review and meta-analysis to investigate the conserved inter- and intra-species miRNA changes that occur due to acute, traumatic SCI. This review seeks to serve as a valuable resource for the SCI community by establishing a rigorous and unbiased description of miRNA changes after SCI for the next generation of SCI biomarkers and therapeutic interventions. The protocol for the systematic review and meta-analysis has been registered through PROSPERO: CRD42021222552 .


25-Hydroxyvitamin D levels in African-American and Caucasian/Hispanic subjects with cutaneous lupus erythematosus.
Because exposure to ultraviolet radiation accounts for a significant portion of endogenous vitamin D production, subjects with cutaneous lupus (CLE) who practise sun-protective measures are at risk for vitamin D insufficiency. Previous studies have shown light-skinned subjects with CLE to have lower serum 25-hydroxy (25-OH) vitamin D levels than normal controls. To assess the status of vitamin D insufficiency in dark-skinned individuals with CLE. We performed a cross-sectional study comparing serum 25-OH vitamin D levels in 25 African-American (AA) subjects with CLE and 26 normal AA subjects matched by age, sex and season in Dallas, Texas. A questionnaire on demographics, medical history and lifestyle habits was administered to determine factors potentially affecting vitamin D levels. Findings were contrasted to a similar comparison in 26 Caucasian and Hispanic (C/H) subjects with CLE and 24 normal C/H subjects matched by age, sex and season. We found similar mean±SD 25-OH vitamin D levels in AA subjects with CLE (52·0±18·5nmolL(-1) ) and normal AA subjects (54·8±21·2 nmolL(-1) ) (P=0·62). Almost half of AA subjects in both groups were vitamin D insufficient. A larger difference in 25-OH vitamin D levels was found between C/H subjects with CLE (59·4±21·0nmolL(-1) ) and normal C/H subjects (70·5±27·4nmolL(-1) ) (P=0·12). Two-way anova demonstrated that skin colour (AA vs. C/H) had a significant effect on 25-OH vitamin D levels (P=0·008), although CLE status (CLE vs. normal) did not (P=0·13). Providers are encouraged to address vitamin D insufficiency concerns in all dark-skinned individuals. Future studies should stratify subjects by skin colour in determining differences between subjects with CLE and normal controls.


Development and characterization of a monoclonal antibody reactive with a 28 kDa protease of Fasciola gigantica.
A monoclonal antibody that was reactive with a 28-kDa protease of Fasciola gigantica was produced after hyperimmunizing BALB/c mice with a partially purified extract and a purified 28-kDa protease obtained from the fluke. Isotype analysis showed that the immunoglobulin is IgG3. Seven other monoclonals of isotypes IgG1, IgG2 and IgG3 which reacted with the protease and one to three other protein bands were also produced. In addition, four other clones of hybridoma produced antibodies which recognised a 27/28-kDa protein doublet but the 28-kDa component of this doublet was different from the 28-kDa protease. The reactivities and characteristics of the monoclonal antibodies were studied by enzyme-linked immunosorbent assay (ELISA), immunoblotting and immunoprecipitation tests.


The release and percutaneous permeation of anthralin products, using clinically involved and uninvolved psoriatic skin.
The release and permeation of 1% Westragel and 1% Westrastick and three commercial 1% anthralin products were investigated in vitro with the use of a Franz diffusion cell unit. An inert Teflon membrane with a mesh opening of 74 mu was used for measuring the rate of release. Involved psoriatic and uninvolved human skin collected from the same subjects were used for the permeation study. The permeation of danthron and dianthrone, the major degradation products of anthralin, was also studied with the use of microemulsion gels of 1% danthron and 1% dianthrone, which were prepared in the same way as 1% Westragel. The penetrating anthralin, danthron, and dianthrone were stabilized by a modified receptor fluid, and sample solutions were analyzed by a high-power liquid chromatography method. Involved psoriatic skin was found to be much more permeable to anthralin than was uninvolved psoriatic skin. The slow permeation rate of anthralin, danthron, and dianthrone through normal skin and uninvolved skin indicates that the stratum corneum is the rate-limiting barrier. In involved psoriatic skin, the release rate of anthralin from the topical product becomes the rate-determining step. Large individual variations were found in the permeation of anthralin through involved psoriatic skin, suggesting that the permeation rate of anthralin also may depend on the disease state of psoriatic patients. The anthralin molecule, possessing both hydrophilic and lipophilic centers, diffused significantly faster than did danthron and dianthrone. Westragel, 1%, showed the highest diffusion rate as well as the highest driving force when compared to other commercial 1% anthralin products. This suggests that 1% Westragel may be an optimal design, especially for short-contact anthralin therapy.


Alteration of thromboxane and prostacyclin levels in experimental spinal cord injury.
We measured levels of thromboxane B2 and 6-keto-PGF1 alpha in rabbit spinal cord and cat CSF after impact injury to spinal cord. Rabbit tissue thromboxane B2 levels increased more than 6-keto-PGF1 alpha. In cat, CSF thromboxane B2 was higher the first hour postinjury; CSF 6-keto-PGF1 alpha also increased, but less so. These results imply activation of arachidonic acid metabolism. The relatively greater increase of thromboxane B2 suggests that thromboxane-prostacyclin imbalance may contribute to post-traumatic ischemia.


Hippocampal interneuron transplants reverse aberrant dopamine system function and behavior in a rodent model of schizophrenia.
Schizophrenia patients exhibit increased hippocampal activity that is correlated with positive symptoms. Although the cause of this hippocampal hyperactivity has not been demonstrated, it likely involves a decrease in GABAergic signaling. Thus, we posit that restoring GABAergic function may provide a novel therapeutic approach for the treatment of schizophrenia. It has been demonstrated that transplanted GABAergic precursor cells from the medial ganglionic eminence (MGE) can migrate and differentiate into mature interneurons. Here, we demonstrate that ventral hippocampal MGE transplants can restore hippocampal function and normalize downstream dopamine neuron activity in a rodent model of schizophrenia. Furthermore, MGE transplants also reverse the hyper-responsive locomotor response to amphetamine. Taken together, these data demonstrate that restoring interneuron function reverses neurophysiological and behavioral deficits in a rodent model of schizophrenia and moreover, demonstrate the feasibility of a neuronal transplant procedure as a potential novel therapeutic approach for the treatment of schizophrenia.


Different susceptibilities of Staphylococcus and Gram-negative rods to epigallocatechin gallate.
We examined the antibacterial effects of epigallocatechin gallate (EGCg, the main constituent of tea catechins) against various strains of Staphylococcus and Gram-negative rods. Compared to the minimum inhibitory concentrations (MICs) of EGCg against S. aureus, S. epidermidis, S. hominis, and S. haemolyticus (50-100 micro g/ml), higher MICs (>or=800 micro g/ml) were observed against Gram-negative rods, including Escherichia coli, Klebsiella pneumoniae, Salmonella typhi, Proteus mirabilis, Pseudomonas aeruginosa, and Serratia marcescens. And difference was observed between the binding abilities of EGCg with viable S. aureus and with E. coli. The bactericidal activity of EGCg for S. aureus was blocked dose-dependently by purified peptidoglycan but not by lipopolysaccharide or dextran. It was also found that peptone and protein, but not amino acids, in the culture medium greatly affected the antibacterial activity of EGCg. These results indicate that the structure of the bacterial cell wall and the different affinities of EGCg with the various cell wall components are responsible for the different susceptibilities of Staphylococcus and Gram-negative rods to EGCg.


Determination of binding constant of transcription factor myc-max/max-max and E-box DNA: the effect of inhibitors on the binding.
The truncated myc and max proteins, only containing basic regions and helix-loop-helix/zipper (b/HLH/Zip) regions were over-expressed in E. coli and used for the determination of the binding constant and of the inhibitory mechanism on myc-max (or max-max)-DNA complex formation. The association kinetic constants (k(1) and k(-1)) of truncated max-max or myc-max dimer and DNA were determined as k(1)=(1.7+/-0.6)x10(5) M(-1) s(-1), k(-1)=(3.4+/-1.2)x10(-2) s(-1) for max-max and DNA or k(1)=(2.1+/-0.7)x10(5) M(-1) s(-1), k(-1)=(3.2+/-1.4)x10(-2) s(-1) for myc-max and DNA. The equilibrium binding constant (K(1)) was determined using these kinetic parameters [K(XXD)=(7.8+/-2.6)x10(6) M(-1) for max-max and DNA or K(XYD)=(6.9+/-2.2)x10(6) M(-1) for myc-max and DNA]. The binding constants of myc-max or max-max dimer formation were K(XX)=(2.6+/-0.9)x10(5) M(-1) or K(XY)=(1.3+/-0.4)x10(4) M(-1), respectively. When truncated proteins were used, the max-max dimer formation was easier than the myc-max dimer formation, contrary to the physiologically determined case. This leads us to deduce that domains other than b/HLH/Zip are very important for the transcriptional regulatory activity in physiological conditions. The truncated myc and max proteins, which were expressed in E. coli and contained only b/HLH/Zip regions were also used for the screening of inhibitors of myc-max-DNA complex formation. A synthesized curcuminoid, 1,7-bis(4-methyl-3-nitrophenyl)-1,6-heptadiene-3,5-dione (curcuminoid 004), showed the most potent inhibition out of the synthesized curcuminoids, in competition with DNA. The dissociation constant of max-max dimer and the inhibitor was 9 microM, when investigated using in vitro expressed b/HLH/Zip dimer proteins. The curcuminoid 004 showed an inhibitory effect on the binding of myc-max protein to the E-box element in SNU16 cells, and suppressed the expression of myc target genes including ornithine decarboxylase (ODC), cdc25a and c-myc in myc over-expressed human stomach cancer cell line SNU16.


Magnetic mesoporous silica nanoparticles modified by phosphonate functionalized ionic liquid for selective enrichment of phosphopeptides.
In this study, new magnetic nanoparticles (denotated as Fe3O4@mSiO2-PFIL-Ti4+) have been prepared by immobilizing titanium ions with phosphonate functionalized ionic liquid (PFIL) on the wall of core-shell structured mesoporous nanomaterials. The resulting nanoparticles possess large specific surface area, strong hydrophilicity and fast magnetic response. The composites can capture traces of phosphopeptides from the tryptic β-casein digest (0.08 fmol), a digest mixture of β-casein and BSA (1 : 10 000, molar ratio) as well as a blend of β-casein digest and a great quantity of phosphorylated protein (β-casein) and non-phosphorylated protein (BSA) (1 : 2000 : 2000, mass ratio), respectively, showing excellent sensitivity, selectivity and size exclusion ability. Additionally, Fe3O4@mSiO2-PFIL-Ti4+ shows excellent steadiness and can be reused at least 12 times. Moreover, this material was successfully applied to enrich endogenous phosphopeptides from complex bio-samples, including human saliva and serum.


Alternating L4 loop architecture of the bacterial polysaccharide co-polymerase WzzE.
Lipopolysaccharides such as the enterobacterial common antigen are important components of the enterobacterial cell envelope that act as a protective barrier against the environment and are often polymerized by the inner membrane bound Wzy-dependent pathway. By employing cryo-electron microscopy we show that WzzE, the co-polymerase component of this pathway that is responsible for the length modulation of the enterobacterial common antigen, is octameric with alternating up-down conformations of its L4 loops. The alternating up-down nature of these essential loops, located at the top of the periplasmic bell, are modulated by clashing helical faces between adjacent protomers that flank the L4 loops around the octameric periplasmic bell. This alternating arrangement and a highly negatively charged binding face create a dynamic environment in which the polysaccharide chain is extended, and suggest a ratchet-type mechanism for polysaccharide elongation.


Development of an EvaGreen based real-time RT-PCR assay for rapid detection, quantitation and diagnosis of goose calicivirus.
An unclassified calicivirus (CV) detected in geese was recently reported and proposed as a new member of the family Caliciviridae. There is limited information about the epidemiology, etiology and detection method of goose-origin CV (GCV) to date. In this study, an EvaGreen based fluorescence quantitative real-time RT-PCR assay was developed and optimized for the detection of GCVs. The assay sensitively detected GCV RNA template with a good linear standard curve. We also demonstrated the specificity and reproducibility of the detection method for GCVs. Thus, the method developed in this study will benefit the investigation of possible sporadic outbreaks of CV infections in geese, as well as epidemiological and etiological studies of GCVs.


Accuracy of the Demirjian and Willems methods of dental age estimation for children from central southern China.
The aim of this study was to compare the accuracy of the Demirjian method and the Demirjian method as revised by Willems for age estimation based on orthopantomograms from central southern Chinese Han population aged 8-16 years. Discrepancies between chronological and estimated ages were statistically evaluated by analyzing 1249 orthopantomograms from 603 girls and 646 boys. Using the Demirjian method, the mean age estimates underestimated chronological age by 0.03 years (p = 0.48) for girls and overestimated it by 0.03 years (p = 0.59) for boys; these differences with respect to chronological age were not statistically significant. In contrast, the Willems method underestimated chronological age by 0.54 years (p < 0.01) for girls and 0.44 years (p < 0.01) for boys; these differences with respect to chronological age were statistically significant. Compared to the Demirjian method, the overall mean absolute error generated using the Willems method was slightly higher (0.85 and 0.86 years, respectively). Since the Demirjian method was more accurate, we highly recommend that it should be applied when estimating dental age in the Chinese Han population. Further modifications of these two methods for populations from other regions and additional studies of other age groups are warranted.


Angiotensin II AT2 receptor stimulation extends the upper limit of cerebral blood flow autoregulation: agonist effects of CGP 42112 and PD 123319.
The effects of the angiotensin II AT2 receptor ligands CGP 42112 and PD 123319, the AT1 antagonist losartan, and the nonselective angiotensin II antagonist Sar1,Ile8-angiotensin II on the upper limit of CBF autoregulation were studied in pentobarbital-anesthetized rats. Blood pressure was increased by intravenous phenylephrine infusion, while CBF was measured continuously from the parietal cortex by laser-Doppler flowmetry. Intravenous infusions of CGP 42112 (0.1 and 1 mg kg-1 min-1) and PD 123319 (0.36 and 1 mg kg-1 min-1) shifted the upper limit of CBF autoregulation toward higher blood pressures without affecting baseline CBF. Sar1,Ile8-angiotensin II (4 micrograms kg-1 min-1) had no effect on baseline CBF or CBF autoregulation but antagonized the effect of CGP 42112 and PD 123319. Losartan (10 mg/kg i.v. bolus) reduced baseline blood pressure and CBF and shifted the autoregulation curve toward higher blood pressures. Sar1,Ile8-angiotensin II blocked the effect of losartan on baseline CBF but not on CBF autoregulation. These results suggest that both CGP 42112 and PD 123319 exert their effects on CBF autoregulation through stimulation of angiotensin II AT2 receptors. The mechanism by which losartan affects CBF remains unclear.


Carbon Nanotube Template-Assisted Synthesis of Conjugated Microporous Polytriphenylamine with High Porosity for Efficient Supercapacitive Energy Storage.
Engineering of conjugated microporous polymers (CMPs) with high porosity, redox activity, and electronic conductivity is of significant importance for their practical applications in electrochemical energy storage. Aminated-multiwall carbon nanotubes (NH2 -MWNT) are utilized to modulate the porosity and electronic conductivity of polytriphenylamine (PTPA), which is synthesized via Buchwald-Hartwig coupling reaction of tri(4-bromophenyl)amine and phenylenediamine as constitutional units in a one-step in situ polymerization process. Compared to PTPA, the specific surface area of core-shell PTPA@MWNTs has been greatly improved from 32 to 484 m2 g-1 . The PTPA@MWNTs exhibites an improved specific capacitance, with the highest value 410 F g-1 in 0.5 M H2 SO4 at a current of 10 A g-1 achieve for PTPA@MWNT-4 due to the hierarchical meso-micro pores, high redox-activity and electronic conductivity. Symmetric supercapacitor assemble by PTPA@MWNT-4 has a capacitance of 216 F g-1 of total electrode materials and retains 71% of initial capacitance after 6000 cycles. This study gives new insights into the role of CNT templates in the adjustment of molecular structure, porosity, and electronic property of CMPs for the high-performance electrochemical energy storage.


Transglutaminase 2 transamidation activity during first-phase insulin secretion: natural substrates in INS-1E.
Transglutaminase 2 (TG2) is a multifunctional protein with Ca(2+)-dependent transamidating and G protein activity. Previously, we reported that tgm2 -/- mice have an impaired insulin secretion and that naturally occurring TG2 mutations associated with familial, early-onset type 2 diabetes, show a defective transamidating activity. Aim of this study was to get a better insight into the role of TG2 in insulin secretion by identifying substrates of TG2 transamidating activity in the pancreatic beta cell line INS-1E. To this end, we labeled INS-1E that are capable of secreting insulin upon glucose stimulation in the physiologic range, with an artificial acyl acceptor (biotinamido-pentylamine) or donor (biotinylated peptide), in basal condition and after stimulus with glucose for 2, 5, and 8 min. Biotinylated proteins were analyzed by two-dimensional electrophoresis and mass spectrometry. In addition, subcellular localization of TG2 in human endocrine pancreas was studied by electron microscopy. Among several TG2's transamidating substrates in INS-1E, mass spectrometry identified cytoplasmic actin (a result confirmed in human pancreatic islet), tropomyosin, and molecules that participate in insulin granule structure (e.g., GAPDH), glucose metabolism, or [Ca(2+)] sensing (e.g., calreticulin). Physical interaction between TG2 and cytoplasmic actin during glucose-stimulated first-phase insulin secretion was confirmed by co-immunoprecipitation. Electron microscopy revealed that TG2 is localized close to insulin and glucagon granules in human pancreatic islet. We propose that TG2's role in insulin secretion may involve cytoplasmic actin remodeling and may have a regulative action on other proteins during granule movement. A similar role of TG2 in glucagon secretion is also suggested.


A comparative study of ceramic nanoparticles synthesized for antibiotic removal: catalysis characterization and photocatalytic performance modeling.
The heterogeneous photocatalysis process has been known to provide significant levels of degradation and mineralization of emerging contaminants including antibiotics. For that, nanoparticle CuCr2O4 (CCO) ceramics were successfully prepared via sol-gel (SG) and co-precipitation (CP) methods to obtain spinel with desired structural features and properties and also to improve the photocatalytic performances. The CCO crystallite phase was produced at 750 °C all ceramics, disregarding the synthesis route. CCO physical and chemical properties were checked by X-ray diffraction (XRD) with Rietveld refinement, Brunauer-Emmett-Teller (BET), Fourier transform infrared spectroscopy (FT-IR), scanning electron microscope (SEM), transmission electron microscope (TEM), and diffuse reflectance solid (DRS). The XRD patterns demonstrated that the synthesized catalysts displayed a small crystallite size between 17.45 and 26.24 nm for SG and 20.97 and 36.86 nm for the CCOCP samples. The observation by SEM and TEM of the nanopowders showed a typical morphology with comparable particle sizes for both synthesized routes (20-30 nm). SG agglomeration rates were higher, and particles stick together more efficiently considering the CP method, while the CCOCP method led to a more significant porosity. Their photocatalytic and adsorption performances were examined for cefaclor (CFC) removal chosen as a target pharmaceutical contaminant in water. The results obtained by the methods differed since nanoparticles prepared by SG led to high photocatalytic activity. In contrast, a high CFC adsorption was observed for those prepared via the CP method, and that agreed with the findings of the characterization analysis. The kinetics of the adsorption process was found to follow the pseudo-second-order rate law. In contrast, the data of the photodegradation process were further found to comply with the Lagergren kinetic law. Nevertheless, the global reaction rate is probably controlled by the intra-particular diffusion of CFC, regardless of the elimination process.


Diagnosis and surgical treatment of a nasolabial cyst.
Nasolabial cysts are uncommonly diagnosed nonodontogenic soft tissue lesions located close to the nasal alar region of the face, presenting as extraosseous swelling in the region of the nasolabial fold. Nasolabial cysts are likely to remain undetected unless and until they become infected or are associated with facial deformity. Histologically, it is lined with nonkeratinized squamous epithelium or, more frequently, with respiratory-type cylindrical epithelium with goblet cells. The aim of this article was to present and discuss the surgical management of a case of nasolabial cyst and to briefly review the literature.


TIA-1 and TIAR interact with 5'-UTR of enterovirus 71 genome and facilitate viral replication.
Enterovirus 71 is one of the major causative pathogens of HFMD in children. Upon infection, the viral RNA is translated in an IRES-dependent manner and requires several host factors for effective replication. Here, we found that T-cell-restricted intracellular antigen 1 (TIA-1), and TIA-1 related protein (TIAR) were translocated from nucleus to cytoplasm after EV71 infection and localized to the sites of viral replication. We found that TIA-1 and TIAR can facilitate EV71 replication by enhancing the viral genome synthesis in host cells. We demonstrated that both proteins bound to the stem-loop I of 5'-UTR of viral genome and improved the stability of viral genomic RNA. Our results suggest that TIA-1 and TIAR are two new host factors that interact with 5-UTR of EV71 genome and positively regulate viral replication.


A New DREADD Facilitates the Multiplexed Chemogenetic Interrogation of Behavior.
DREADDs are chemogenetic tools widely used to remotely control cellular signaling, neuronal activity, and behavior. Here we used a structure-based approach to develop a new Gi-coupled DREADD using the kappa-opioid receptor as a template (KORD) that is activated by the pharmacologically inert ligand salvinorin B (SALB). Activation of virally expressed KORD in several neuronal contexts robustly attenuated neuronal activity and modified behaviors. Additionally, co-expression of the KORD and the Gq-coupled M3-DREADD within the same neuronal population facilitated the sequential and bidirectional remote control of behavior. The availability of DREADDs activated by different ligands provides enhanced opportunities for investigating diverse physiological systems using multiplexed chemogenetic actuators.


Selection of normalization factors for quantitative real time RT-PCR studies in Japanese flounder (Paralichthys olivaceus) and turbot (Scophthalmus maximus) under conditions of viral infection.
Disease outbreaks caused by iridoviruses are known to affect farmed flounder (Paralichthys olivaceus) and turbot (Scophthalmus maximus). To facilitate quantitative real time RT-PCR (qRT-PCR) analysis of gene expression in flounder and turbot during viral infection, we in this study examined the potentials of 9 housekeeping genes of flounder and turbot as internal references for qRT-PCR under conditions of experimental infection with megalocytivirus, a member of the Iridoviridae family. The mRNA levels of the 9 housekeeping genes in the brain, gill, heart, intestine, kidney, liver, muscle, and spleen of flounder and turbot were determined by qRT-PCR at 24h and 72h post-viral infection, and the expression stabilities of the genes were determined with geNorm and NormFinder algorithms. The results showed that (i) viral infection induced significant changes in the mRNA levels of the all the examined genes in a manner that was dependent on both tissue type and infection stage; (ii) for a given time point of infection, stability predictions made by the two algorisms were highly consistent for most tissues; (iii) the optimum reference genes differed at different infection time points at least in some tissues; (iv) at both examined time points, no common reference genes were identified across all tissue types. These results indicate that when studying gene expression in flounder and turbot in relation to viral infection, different internal references may have to be used not only for different tissues but also for different infection stages.


Public's perceptions of marine bioinvasive risks and responsible parties - Implications for social acceptability and better-informed communication in the marine biosecurity context.
Using the survey data on a representative sample of the New Zealand population, our study presents a process of understanding citizens' perceptions, identifying patterns in the perceptions, and recognising the knowledge gaps existing in the citizenry in the marine biosecurity context. While our findings show a healthy sign of the public accepting their own responsibility and the devolved responsibility of business/industry, there are considerable gaps between the general public's perceptions and (marine) biosecurity current practices and expectations. There is a moderately strong signal from survey respondents that suggest the need of significantly more effort and improved transparency in marine biosecurity communication. Our outcomes indicate an anthropocentric tendency, with influences of gender, age, education, income, frequency of beach visitation upon societal perceptions in terms of awareness, concern, perceived non-indigenous marine species impacts, and accountability in marine biosecurity management. The recognised socio-demographic patterns in societal perceptions would inform marine biosecurity communication strategies.


Attention is required for the perceptual integration of action object pairs.
Previous studies have demonstrated that functionally related objects are perceptually grouped during visual identification if they are depicted as if interacting with each other (Green and Hummel in J Exp Psychol Hum Percept Perform 32(5):1107-1119, 2006). However, it is unclear whether this integration requires attention or occurs pre-attentively. Here, we used a divided-attention task with variable attentional load to address this question. Participants matched a word label to a target object that was immediately preceded by a briefly presented, task-irrelevant tool that was either functionally related or unrelated to the word label (e.g., axe | "log" or hammer | "log"). The tool was either positioned to interact with the target object or faced away from it. The amount of attention available to process the tool was manipulated by asking participants to make a concurrent perceptual discrimination of varying difficulty on a surrounding frame stimulus. The previously demonstrated advantage for the related-and-interacting condition was replicated under conditions of no or low attentional load. This benefit disappeared under high competing attentional load, indicating that attention is required to integrate functionally related objects together into a single perceptual unit.


Conservation of intron position indicates separation of major and variant H2As is an early event in the evolution of eukaryotes.
Genomic clones of Drosophila and Tetrahymena histone H2A variants were isolated using the corresponding cDNA clones (van Daal et al. 1988; White et al. 1988). The site corresponding to the initiation of transcription was defined by primer extension for both Drosophila and Tetrahymena genomic sequences. The sequences of the genomic clones revealed the presence of introns in each of the genes. The Drosophila gene has three introns: one immediately following the initiation codon, one between amino acids 26 and 27 (gln and phe), and one between amino acids 64 and 65 (glu and val). The Tetrahymena gene has two introns, the positions of which are identical to the first two introns of the Drosophila gene. The chicken H2A.F variant gene has been recently sequenced and it contains four introns (Dalton et al. 1989). The first three of these are in the same positions as the introns in the Drosophila gene. The fourth intron interrupts amino acid 108 (gly). In all cases the sizes and the sequences of the introns are divergent. However, the fact that they are in conserved positions suggests that at least two of the introns were present in the ancestral gene. A phylogenetic tree constructed from the sequences of the variant and major cell cycle-regulated histone H2A proteins from several species indicates that the H2A variant proteins are evolutionarily separate and distinct from the major cell cycle-regulated histone H2A proteins. The ancestral H2A gene must have duplicated and diverged before fungi and ciliates diverged from the rest of the eukaryote lineage. In addition, it appears that the variant histone H2A proteins analyzed here are more conserved than the major histone H2A proteins.


Differential cytokine regulation of type I and type VII collagen gene expression in cultured human dermal fibroblasts.
Type VII collagen is the major component of anchoring fibrils in the cutaneous basement membrane zone. In this study, we have examined the effects of various cytokines on the expression of types I and VII collagen genes in dermal fibroblasts in culture. The pro-inflammatory cytokines, interleukin-1 alpha (IL-1 alpha), interleukin-1 beta (IL-1 beta), tumor necrosis factor-alpha (TNF-alpha), and leukoregulin (LR) strongly elevated (approximately 5-9-fold) type VII collagen mRNA levels, as measured by Northern blot hybridizations. These effects were also observed at the protein level by indirect immunofluorescence using a monoclonal antibody specific for type VII collagen. By contrast, IL-1 beta had only a slight stimulatory effect (approximately 2-fold) on type I collagen gene expression, while TNF-alpha and LR markedly reduced type I collagen mRNA steady-state levels. Interestingly, IL-1, TNF-alpha and LR had additive effects with transforming growth factor-beta (TGF-beta) on type VII collagen gene expression, whereas they counteracted the up-regulatory effect of TGF-beta on type I collagen gene expression. Thus, our data indicate that the modulation of type I and type VII collagen gene expression by cytokines involves different regulatory pathways.


Revealing mechanism and influence of microalgae cells' periodical auto-agglomeration induced by high concentration of carbon dioxide.
The efficient cultivation of microalgae using CO2 from flue gas can be a win-win situation for both environmental protection and energy accessibility. In general, 10-20% of CO2 in flue gas would decrease pH and inhibit microalgae growth. However, Chlorella sorokiniana MB-1 under 15% CO2 showed a periodical auto-agglomeration, which promoted microalgae growth on the contrary in this study. The maximum biomass concentration of 3.27 g L-1 was higher than that cultivated with an optimal CO2 concentration. The pH decreased to 6.04 after the mixed gas with 15% CO2 (v/v) was bubbled into medium for 0.5 h, which resulted in auto-agglomeration to protect microalgae from acidification and keep a high specific growth rate of 0.03 h-1. Then the pH recovered to 7 during stabilization phase, auto-agglomeration ratio was up to 100% because of lamellar extracellular polymeric substances. Therefore, the interesting periodical agglomeration both enhanced growth and simplified harvesting.


Continuous wavelet transform analysis of ERG in patients with diabetic retinopathy.
Diabetic retinopathy (DR) is one of the leading causes of blindness worldwide. Non-proliferative diabetic retinopathy (NPDR) is a stage of the disease that contains morphological and functional disruption of the retinal vasculature and dysfunction of retinal neurons. This study aimed to compare time and time-frequency-domain analysis in the evaluation of electroretinograms (ERGs) in subjects with NPDR. The ERG responses were recorded in 16 eyes from 12 patients with NPDR and 24 eyes from 12 healthy subjects as the control group. The implicit time, amplitude, and time-frequency-domain parameters of photopic and scotopic ERGs were analyzed. The implicit times of b-waves in the dark-adapted 10.0 (P = 0.0513) and light-adapted 3.0 (P = 0.0414) were significantly increased in the NPDR group. The amplitudes of a- and b-wave showed a significantly decreased dark-adapted 10.0 (P = 0.0212; P = 0.0133) and light-adapted 3.0 (P = 0.0517; P = 0.0021) ERG of the NPDR group. The Cohen's d effect size had higher values in the amplitude of dark-adapted 10.0 b-wave (|d|= 1.8058) and amplitude of light-adapted 3.0 b-wave (|d|= 1.9662). The CWT results showed that the frequency ranges of the dominant components in dark-adapted 10.0 and light-adapted 3.0 ERG were decreased in the NPDR group compared to the healthy group (P < 0.05). The times associated with the NDPR group's dominant components were increased compared to normal eyes in both dark-adapted 10.0 and light-adapted 3.0 ERG (P < 0.05). All Cohen's d effect sizes of the implicit times and dominant frequency components were on a large scale (|d|> 1). These findings suggest that the time and time-frequency parameters of both photopic and scotopic ERGs can be good indicators for DR. However, time-frequency-domain analysis could present more information might be helpful in the assessment of the DR severity.


Crystal structures of (1E,4E)-1,5-bis-(5-bromo-thio-phen-2-yl)-2,4-di-methyl-penta-1,4-dien-3-one and (E)-4-(5-bromo-thio-phen-2-yl)-1,3-di-phenyl-but-3-en-2-one.
The title compounds, C15H12Br2OS2, (I), and C20H15BrOS, (II), were synthesized by employing Claisen-Schmidt condensation of pentan-3-one and di-benzyl-acetone with 5-bromo-thio-phene-2-carbaldehyde in the presence of methano-lic KOH. Even though 1:2 products were expected in both of the reactions, 1:2 and 1:1 products were obtained as (I) and (II), respectively. In (I), the two methyl groups are trans to each other, 29.5 (7) and 28.7 (7)° away from the central carbonyl bond between them, whereas the two phenyl rings of di-benzyl-acetone subtend a dihedral angle of 53.09 (18)°. In the crystal of (I), C-H⋯O hydrogen bonds define mol-ecular chains along c. A second type of mol-ecular chain is formed along b by means of C-Br⋯π inter-actions. These two families of mol-ecular chains are stacked by π-π inter-actions, forming a three-dimensional supra-molecular architecture. In (II), similar C-H⋯O hydrogen bonds as in (I) define inversion dimers, whilst C-H⋯.π inter-actions build a staircase structure along the a axis.


Lower-adherence direct oral anticoagulant use is associated with increased risk of thromboembolic events than warfarin.
Real-world data have suggested inconsistent adherence to oral anticoagulation for thromboembolic event (TE) prevention in patients with Non valvular atrial fibrillation (NVAF), yet it remains unclear if event risk is elevated during gaps of non-adherence. To compare difference in outcomes between direct oral anticoagulant (DOAC) and warfarin based on adherence to the therapy in patients with NVAF. Using the MarketScan claims data, patients receiving prescription of warfarin or a DOAC for NVAF from January 2015 to June 2016 were included. Outcomes included hospitalization for TE (ischemic stroke or systemic embolism), hemorrhagic stroke, stroke of any kind, and major bleeding. Event rates were reported for warfarin and DOACs at a higher-adherence proportion of days covered (PDC > 80%) and lower-adherence (PDC 40-80%). The cohort included 83,168 patients prescribed warfarin (51% [n = 42,639]) or DOAC (49% [n = 40,529]). Lower adherence occurred in 36% (n = 15,330) of patients prescribed warfarin and 26% (n = 10,956) prescribed DOAC. As compared to higher-adherence warfarin after multivariable adjustment, the risk of TE was highest in lower-adherence DOAC (HR 1.26; 95% CI, 1.14-1.33), and lowest in higher-adherence DOAC (HR, 0.93; 95% CI, 0.88-0.99). There was a significantly higher risk of hemorrhagic stroke and stroke of any kind in the lower-adherence groups. Major bleeding was more common with lower-adherence DOAC (HR, 1.43, 95% CI, 1.35-1.52) and lower-adherence warfarin (HR, 1.32, 95% CI, 1.26-1.39). In this large real-world study, low adherence DOAC was associated with higher risk of TE events as compared to high and low adherence warfarin.


Generation of higher-order optical vortices by a dielectric wedge.
Diffraction of a Gaussian beam with a system of successively located optical wedges is considered. It is shown that the system is able to form higher-order optical vortices.


A cosmid-based system for inserting mutations and foreign genes into the simian varicella virus genome.
Simian varicella is a natural varicella-like disease of nonhuman primates. The etiologic agent, simian varicella virus (SVV), is genetically related to varicella-zoster virus (VZV) and SVV infection of nonhuman primates is a useful model to investigate VZV pathogenesis and latency. In this study, we report development of a cosmid-based genetic system to generate SVV mutant viruses. SVV subgenomic DNA fragments (32-38kb) that span the viral genome were cloned into cosmid vectors. Co-transfection of Vero cells with four overlapping cosmid clones representing the entire SVV genome resulted in recombination and generation of infectious virus. SVV mutants were produced by manipulation of one cosmid and substitution into the genetic system. This genetic approach was used to insert a site-specific mutation within the SVV open reading frame 14 which encodes the nonessential glycoprotein C gene. In a subsequent experiment, the green fluorescent protein (GFP) gene was inserted into the SVV genome within ORF 14. These SVV mutants replicate as efficiently as wild-type SVV in cell culture. This cosmid-based genetic system will be useful to investigate the effect of viral mutations on SVV pathogenesis and latency and also to develop and evaluate recombinant varicella vaccines that express foreign antigens.


Inhibition of Salmonella typhimurium on radish sprouts using nitrogen-cold plasma.
This study investigated the effects of cold plasma treatment (CPT) on the inhibition of Salmonella typhimurium on radish sprouts and the quality attributes of the sprouts. Radish sprouts were treated with nitrogen (N2)-cold plasma at 900W and 667Pa for 0, 2, 5, 10, and 20min using a microwave-powered CPT system. The sensory attributes of the radish sprouts, appearance and odor, were evaluated before and after the treatment. The effects of N2-CPT for 10min on microbial growth and the quality attributes of the radish sprouts were evaluated during storage for 12days at 4 and 10°C. N2-CPT at 900W and 667Pa for 20min reduced the number of S. typhimurium by 2.6±0.4logCFU/g. The moisture content of the radish sprouts decreased with treatment time. The appearance and odor of the radish sprouts were not altered by CPT (p>0.05) and this treatment did not affect the quality attributes of the sprouts in terms of color, ascorbic acid concentration, or antioxidant activity during storage at both 4 and 10°C. These findings suggest that CPT has the potential to improve the microbiological safety of radish sprouts with reference to S. typhimurium during cold storage without significant detriment to its quality properties.


Quantitative histology of bone: a computerized method of measuring the total mineral content of bone.
A comparatively simple quantitative method for assessing bone morphology has been evolved. Microradiographs of thin sections of mandible have been scanned with a Joyce-Loebl double beam recording microdensitometer with a scanning autodensidater attachment, using a white beam. For each image the optical densities for all the pixels (picture elements) were divided into 10 groups. The limits of the division were fixed by the maximum and minimum densities occurring within the image. A computer generated map was produced which indicated the spatial distribution of the pixels within each group to which an arbitrarily chosen shading was attached. The number of pixels within each group is also shown on the map. The computer map was compared with the photomicrograph and, where necessary, the original section. The fractional area of hard tissue was then readily determined using the numerical values of each group of pixels.


Levels of circulating follicular helper T cells, T helper 1 cells, and the prognostic significance of soluble form of CD40 ligand on survival in patients with alcoholic cirrhosis.
Excessive drinkers (ED) and patients with alcoholic liver disease (ALD) are several times more susceptible to bacterial and viral infections and have a decrease in antibody responses to vaccinations. Follicular helper T (TFH) cells are essential to select B cells in the germinal center and to produce antibodies. TFH cells express both a membrane-associated and a soluble form of CD40 ligand (sCD40L); in which the latter form is released to circulation upon T cell activation. The effect of alcohol on TFH cells has not been studied. The goals of this study are to determine the levels of TFH and T helper 1 (Th1) cells in ED and those with alcoholic cirrhosis (AC) when compared to healthy controls and to determine the prognostic significance of sCD40L in a cohort of patients with AC. Controls, ED, and those with AC were enrolled. Baseline demographic, laboratory tests, and peripheral blood mononuclear cells (PBMCs) were isolated and assessed via flow cytometry for TFH cells. In vitro study was performed to determine the ability of PBMCs to secrete interferon (IFN)-γ upon stimulation. Serum sCD40L were also determined and its prognostic significance was tested in a cohort of AC patients. The levels of circulating TFH (cTFH) cells were significantly lower in peripheral blood of subjects with ED and AC compared to controls (P<0.05). IFN-γ secretion from PBMCs upon stimulation was also lower in ED and those with cirrhosis. Serum sCD40L was significantly lower in ED and AC when compared to that in controls (P<0.0005). Its level was an independent predictor of mortality. Patients with AC had significantly lower level of cTFH and sCD40L. The level of sCD40L was an independent predictor of mortality in these patients.


Separation of binaphthol enantiomers through achiral chromatography.
Chromatography is a key technique for the analytical, preparative, and production scale separation of enantiomers, particularly in the pharmaceutical and fine chemicals industries. Although it is common belief that this separation can be accomplished only using a chiral stationary phase, it has been recently shown that under certain circumstances a non-racemic mixture of specific chiral compounds can be separated in two fractions which differ in enantiomeric excess (e.e.) also on an achiral stationary phase. In this work we show that in the case of the enantiomers of binaphthol in chloroform achiral chromatography on LiChrospher 100 NH2 furnishes two fractions constituted of the pure enantiomer present in excess and of the racemic mixture, respectively. This is demonstrated by on-line monitoring the concentration of both enantiomers at the outlet of a chromatographic column fed with a non-racemic pulse of the two enantiomers by using a UV detector and a polarimeter in series. Furthermore, we provide experimental evidence of the presence of homo- and hetero-dimers in solution through NMR experiments and develop a consistent physico-chemical model of the solution itself and of the competitive achiral adsorption equilibria. When combined with a standard rate model of the chromatographic column this not only confirms the possibility of achieving 100% e.e. through achiral chromatography, but also allows for a qualitative and quantitative description of all the experimentally observed phenomena. Among these, the effect of the enantiomeric excess and of the overall concentration of the injected pulse on the chromatographic behaviour are worth mentioning.


Occurrence of thyroid autoimmunity in relapsing remitting multiple sclerosis patients undergoing interferon-beta treatment.
We analyzed the titer of antithyroid autoantibodies (Abs) and thyroid function in 17 multiple sclerosis (MS) patients undergoing interferon-beta (IFN-beta) treatment and in 40 MS control patients. Basal evaluation revealed normal thyroid function in all patients. Abs were detected in 5 IFN-beta-treated patients (29%) and in 4 MS control patients (10%). Our results indicate that IFN-beta treatment may lead to thyroid autoimmunity. We therefore recommend periodic evaluations of antithyroid Abs and thyroid functionality in IFN-beta-treated MS patients.


Idiopathic intracranial hypertrophic pachymeningitis: two case reports and review of the literature.
In 1949, Naffziger et al. first described idiopathic intracranial hypertrophic pachymeningitis (IIHP) as an aseptic, diffuse inflammatory disease that causes thickening of the dura mater and often headache and progressive multiple nerve palsies due to fibrous entrapment or ischemic damage of neurovascular structures. Pachymeningeal thickening can be diffuse or nodular. We report two cases of IIHP; one was affected by diffuse IIHP, while the other presented focal IIHP mimicking a convexity meningioma. We examine the differential diagnosis between IIHP and other known causes of hypertrophic pachymeningitis. We also discuss the clinical bases of treatment.


The role of tryptophan residues and hydrophobic interaction in the binding of riboflavin in egg-yolk flavoprotein.
Egg-yolk flavoprotein has 7.2 tryptophan residues exposed, while the apoprotein shows an apparent exposure of 80 percent of these (5.7 residues) with dimethylsulphoxide as the perturbant. In the apoprotein at pH 6.9 only 4 groups are perturbed to ethylene glycol, 3.2 to glycerol and 1.4 to sucrose. Diminishing estimates of exposure obtained with increasing molecular diameter of the perturbant suggests that part of indole chromophores of apoprotein are located in "crevices" of the protein molecule. The apoprotein was treated with 2-hydroxy-5-nitrobenzyl bromide, H2O2 and N-bromosuccinimide under conditions designed to accomplish modification of tryptophan residues. Five to six of the eight tryptophans present in the protein were modified. Under these conditions the apoprotein completely looses its capacity for binding riboflavin and the fluorescent intensity of the protein at 360 nm is quenched at the same time to about 80 percent of its initial value. The presence of nonpolar amino acid residues on the surface of the apoprotein suggested the importance of hydrophobic interactions as the dominant factor controlling the binding of riboflavin. The hydrophobic probes Indocyanine green and 4-benzoylamide-4-aminostilbene-2,2-disulphonic acid bound to the apoprotein giving equimolar complexes with dissocation constants, KD 6.5-10(-7) M and 1.8-10(-6) M, respectively, Addition of an equimolar amount of riboflavin quantitatively displaced these dyes from their complexes with apoprotein as shown by spectrophotometric and spectrofluorometric studies.


Prognostic Value of 68Ga-NOTA-RGD PET/CT for Predicting Disease-Free Survival for Patients With Breast Cancer Undergoing Neoadjuvant Chemotherapy and Surgery: A Comparison Study With Dynamic Contrast Enhanced MRI.
We performed pretreatment angiogenesis imaging (Ga-NOTA-arginyl-glycyl-aspartic acid [RGD] PET/CT) to compare its prognostic value to dynamic contrast-enhanced (DCE) MRI in breast cancer patients. Forty-four female patients with stage II or III breast cancer (aged 47.3 ± 8.1 years) were prospectively enrolled and underwent Ga-NOTA-RGD PET/CT and DCE-MRI imaging. All patients received neoadjuvant chemotherapy and underwent surgery. With pretreatment Ga-NOTA-RGD PET/CT, SUVmax of the tumor in the torso (-T) and regional (-R) images were measured. With pretreatment DCE-MRI, the largest diameter of the tumor and maximum enhancement index (EImax; EImax = [highest signal / baseline signal] - 1) of the tumor were assessed. Ten patients (22.7%) were found to have breast cancer recurrence after 17.9 ± 11.2 months. The SUVmax-R (P = 0.017, cutoff >2.79) of Ga-NOTA-RGD PET/CT, the largest diameter of tumor (P = 0.017, cutoff >6.3 cm), and the EImax (P = 0.008, cutoff >5.38) of DCE-MRI showed significant results by univariate analysis. The 3-year disease-free survival of SUVmax-R was 91.7% versus 59.1% by Kaplan-Meier analysis (hazard ratio, 5.379). Multivariable analysis demonstrated that SUVmax-R with tumor diameter or EImax were the significant parameters. In addition, the combined parameters of SUVmax-R and EImax revealed better predictive value for prediction of breast cancer recurrence (75.0%) than each parameter of SUVmax-R (64.2%) and EImax (68.7%). Increased angiogenic activity of regional Ga-NOTA-RGD PET/CT (SUVmax-R) can be an early prognostic marker for the prediction of breast cancer recurrence.


Vitamin D status is a determinant of skeletal muscle mass in obesity according to body fat percentage.
Vitamin D deficiency is now being recognized as an emerging problem worldwide. Obesity has been found to be associated with lower serum 25-hydroxyvitamin D [25(OH)D] concentrations due to various mechanisms. There is increasing evidence showing the extraskeletal health benefit of vitamin D. Previous studies demonstrated the relationship between vitamin D and adiposity. However, the association between vitamin D status and skeletal muscle mass has not been established in healthy obese individuals in tropical countries. The aim of this cross-sectional study was to assess vitamin D status and its relationship to serum 25(OH)D concentrations and body composition, including skeletal muscle mass (SMM) and adiposity in healthy obese individuals without diabetes who live in Thailand, which is located near the equator. We enrolled 163 obese Thai individuals (59.5% women) from the obesity clinic at the Ramathibodi Hospital, Mahidol University, in Bangkok, Thailand. The prevalence of vitamin D deficiency (<20 ng/mL) and vitamin D inadequacy (<30 ng/mL) were 49 (30.1%) and 148 (90.8%), respectively. In all, 98% of the individuals with body mass index >35 kg/m(2) had vitamin D inadequacy. Serum 25(OH)D concentrations were negatively associated with percent body fat (%BF) (r = -0.23; P = 0.003). Moreover, vitamin D status was positively associated with SMM (r = 0.18; P = 0.03) and the association remained after controlling for body fat mass and age (P = 0.003). Interestingly, in the individuals with lowest tertile of %BF, multiple linear regression analysis revealed that the significant positive predictors of %SMM were vitamin D status and male sex; the negative predictor was the body mass index after adjusting for age and exercise duration. Our study demonstrated the high prevalence of vitamin D deficiency in obese, Thai populations without diabetes. Vitamin D status was an independent predictor of %SMM of patients with lowest tertile of %BF. We speculated that adiposity might play a role in the relationship of vitamin D and SMM.


Streptococcus mutans isolated from a 4-year-old girl diagnosed with infective endocarditis.
Infective endocarditis (IE) has an extremely high fatality rate. In this study, we isolated a strain of Streptococcus mutans, which we called HM, from the blood drawn from a 4-year-old girl diagnosed with IE. We aimed to fully type the HM strain and investigate its biological properties, including its virulence with respect to IE. A 16S rRNA phylogenetic tree and glucosyltransferase gene sequences were used to type HM. Serotyping was performed using the Ouchterlony method. Morphological observations were made using phase contrast and electron microscopy. Fibrinogen adhesion and biofilm formation were investigated to examine the tissue colonization properties of HM, whereas its bodily origin was determined from its fingerprinting pattern. The isolated strain was S. mutans serotype e. However, its morphology was observed to be short chains, unlike that of the NCTC 10449 reference strain. Fibrinogen adhesion and biofilm formation were more apparent than in NCTC 10449. The fingerprinting pattern showed that HM came from the patient's saliva. HM differs from NCTC 10449 in its higher fibrinogen affinity. HM was also found to be derived from the oral cavity. These results highlight the importance of good oral hygiene for the prevention of IE in children.


Directly observed therapy of tuberculosis in Brazil: associated determinants and impact on treatment outcome.
All Brazilian states. To assess the determinants of tuberculosis (TB) in patients undergoing directly observed therapy (DOT) and the impact of DOT on treatment outcomes. This is a cross-sectional study among TB patients aged ⩾18 years conducted in 2011. The primary outcome was the status of DOT received, while the secondary was the outcome of anti-tuberculosis treatment. In 2011, 35 775 (38.3%) subjects received DOT. The odds of receiving DOT were higher in patients with the following characteristics: brown/mestizo patients (OR 1.18, 95%CI 1.14-1.22) and those of other ethnic groups (OR 2.01, 95%CI 1.79-2.27) compared to Whites, alcohol users (OR 1.37, 95%CI 1.28-1.47) and those with mental disorders (OR 1.88, 95%CI 1.54-2.29). The odds of receiving DOT were lower in human immunodeficiency virus positive patients (OR 0.64, 95%CI 0.60-0.68). Patients who did not receive DOT were more likely to default from anti-tuberculosis treatment (OR 0.62, 95%CI 0.57-0.66), die due to TB (OR 0.68, 95%CI 0.61-0.77) and to have unknown treatment outcomes (OR 0.71, 95%CI 0.66-0.76). The adjusted preventable fraction of DOT in the reduction of unfavorable outcomes was 25%. Sociodemographic and clinical characteristics are determinants of anti-tuberculosis treatment outcomes in patients undergoing DOT; DOT use led to a 25% reduction in unfavorable outcomes.


Life-threatening orolingual angioedema during thrombolysis in acute ischemic stroke.
Orolingual angioedema can occur during thrombolysis with alteplase in stroke patients. However, data about its frequency, severity and the significance of concurrent use of angiotensin-converting-enzyme inhibitors (ACEi) are sparse. (1), to alert to the potentially life-threatening complication of orolingual angioedema. (2), to present CT-scans of the tongue which exclude lingual hematoma. (3), to estimate the frequency of orolingual angioedema. (4), to evaluate the risk associated with the concurrent use of ACEi. Single center, databank-based observational study on 120 consecutive patients with i. v. alteplase for acute stroke. Meta-analysis of all stroke studies on alteplase-associated angioedema, which provided detailed information about the use of ACE-inhibitors. Across studies, the Peto odds ratio of orolingual angioedema for "concurrent use of ACEi" was calculated. Orolingual angioedema occurred in 2 of 120 patients (1.7%, 95% CI 0.2-5.9 %). Angioedema was mild in one, but rapidly progressive in another patient. Impending asphyxia prompted immediate intubation. CT showed orolingual swelling but no bleeding. One of 19 (5%) patients taking ACEi had orolingual angioedema, compared to 1 of 101 (1%) patients without ACEi. Medline search identified one further study about the occurrence of alteplase-associated angioedema in stroke patients stratified to the use of ACEi. Peto odds ratio of 37 (95 % CI 8-171) indicated an increased risk of alteplasetriggered angioedema for patients with ACEi (p <0.001). Orolingual angioedema is a potentially life-threatening complication of alteplase treatment in stroke patients, especially in those with ACEi. Orolingual hematoma as differential diagnosis can be excluded by CT-scan.


Economics of psychosocial factors in patients with cardiovascular disease.
Growing evidence supports a causal relationship between cardiovascular disease and psychosocial factors such as mental health and behavioral disorders, acute and chronic stress, and low socioeconomic status. While this has enriched our understanding of the interaction between cardiovascular risk factors, much less is known about its economic implications. In this review, we evaluate the economic impact of psychosocial factors in persons at risk for or diagnosed with cardiovascular disease. Most studies have focused on depression and almost uniformly conclude that patients with cardiovascular disease and comorbid depression use a greater number of ambulatory and hospital services and incur higher overall costs. Additionally, comorbid depression may also reduce employment productivity in patients with cardiovascular disease, further magnifying its economic impact. Recent randomized trials have demonstrated that innovative care delivery models that target depression may reduce costs or at least be cost neutral while improving quality of life. The growing population burden and overlap of cardiovascular disease, comorbid mental illness, and other psychosocial factors suggest that future research identifying cost-effective or cost-saving treatment models may have significant health and economic implications.


Analysis of the dentoalveolar effects of slow and rapid maxillary expansion in complete bilateral cleft lip and palate patients: a randomized clinical trial.
The purpose of this study was to compare the dentoalveolar effects of slow (SME) and rapid (RME) maxillary expansions in patients with complete bilateral cleft lip and palate (BCLP). A sample of 50 patients with BCLP and maxillary arch constriction was randomly and equally allocated into two groups. Group SME comprised patients (mean age of 8.8 years) treated with quad-helix appliance. Group RME comprised individuals (mean age of 8.9 years) treated with Hyrax expander. Digital dental models obtained immediately pre-expansion (T1) and 6 months after the active expansion period (T2) were used for measuring maxillary dental arch widths, arch perimeter, arch length, palatal depth, buccolingual inclination of posterior teeth and differential amount of expansion accomplished at the canine and molar regions. Inter-phase and intergroup comparisons were performed using paired t tests and t tests, respectively (p < 0.05). SME and RME caused significant increase of arch widths and arch perimeter. Arch length and palatal depth decreased nonsignificantly with SME but significantly with RME. Buccal tooth inclination was significant only for maxillary deciduous canines in both groups. The quad-helix appliance showed a significant differential expansion between anterior and posterior regions. No differences were observed between SME and RME for all variables. Differences were not found between the dentoalveolar effects of SME and RME in patients with BCLP. SME demanded a greater therapy time compared to RME. Both expansion procedures can be similarly indicated to correct maxillary arch constriction in patients with BCLP in the mixed dentition.


Preparation and characterisation of envelope proteins from Haemophilus pleuropneumoniae.
Envelope proteins of Haemophilus pleuropneumoniae were extracted by 3 methods and analysed by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE). Three major envelope proteins (45,000 Mr, 41,000 Mr, 31,500 Mr) were distinguished in sonicated cell envelopes together with minor proteins. Using selective solubilisation with sodium lauryl sarcosinate or Triton X-100, outer membrane proteins were distinguished from those of the cytoplasmic membrane. Extraction into LiCl produced a similar profile, but the 41,000 Mr and 31,500 Mr bands were present in reduced amounts. Extraction into saline at 60 degrees C produced a grossly different pattern, with a major band at 20,000 Mr. All 3 major envelope proteins were shown to be heat-modifiable, and the 31,500 Mr band was found to be the non-heat-modified form of a 43,000 Mr protein, which showed similar properties to the Protein d of H. influenzae which is related to the OmpA protein of E. coli K-12. The 45,000 Mr major protein was also weakly associated with the peptidoglycan in SDS/Triton at low temperature.


Isolation of bluetongue virus serotype 21 from Culicoides spp. in Indonesia.
The isolation of a bluetongue (BLU) virus from Culicoides spp. in Indonesia is reported. BLU serotype 21 was isolated from a mixed pool of C. fulvus and C. orientalis of the Avaritia subgenus.


Pituitary site of action of endothelin: selective inhibition of prolactin release in vitro.
Endothelin-3 (ET-3) inhibited in a dose-dependent, significant fashion prolactin release from cultured anterior pituitary cells (ovariectomized female and intact male rat donors, ED50 = 5 X 10(-9) M). ET-3 in log doses ranging from 10(-11) to 10(-6) M did not alter significantly the release of luteinizing hormone, growth hormone or thyroid stimulating hormone. The inhibitory effect of ET-3 (rat, human) was specific for that molecule since ET-1 (porcine, human) was ineffective and was not due to an action on the dopamine receptor since the inhibitory action was still expressed in the presence of 100 nM domperidone. These data further suggest a role for neuropeptides of the posterior lobe in the control of lactotroph function.


[Type IV Ehlers-Danlos syndrome disclosed by acute obstructive renal insufficiency].
A 64 year-old man was admitted for congestive heart failure induced by an acute renal failure due to obstruction. Retroperitoneal periaortic-aneurysmal fibrosis was the etiology of the obstruction. Type IV Ehlers-Danlos syndrome was diagnosed based upon clinical and histological cutaneous signs.


A Crosstalk Between K ras (Kirsten Rat Sarcoma Viral Oncogene Homologue) and Adherence Molecular Complex Leads to Disassociation of Cells-A Possible Contribution Towards Metastasis in Colorectal Cancer.
Constitutive activation of mutant K ras (Kirsten rat sarcoma viral oncogene homologue) and disassembly of E-cadherin-catenin complex (E-cadherin, α-catenin, β-catenin, and γ-catenin) play an important role in apoptosis, differentiation, and cell proliferation. In this study, the expression pattern of K ras and E-cadherin-catenin complex has been evaluated in normal and mutant colorectal cancer cell lines with an object to determine its impact on disassociation of cells from one another. We addressed the expression analysis of K ras with reference to its association with adherence molecules in two colorectal cancer cell lines, that is, Caco-2 (wild type K ras served as a control) and DLD1 (heterozygous mutation at codon 13) at message level by qRT-PCR and translational level by western blotting. Compared to the control Caco-2 cell lines, the K ras in DLD1 cell lines showed slightly higher values while α-catenin showed a slight lower (1.3-folds), β-catenin and E-cadherin showed significantly lower expression (4.2-fold decrease). It can be inferred that a possible cross talk exists between K ras and adherent junction mediated signalling. Mutation at codon 13 (G to D) leads to the overexpression of K ras and reduced expression of adherent junction complex resulting in metastasis. J. Cell. Biochem. 117: 2340-2345, 2016. © 2016 Wiley Periodicals, Inc.


Molecular bases for the stronger plastic response to high nitrate in the invasive plant Xanthium strumarium compared with its native congener.
High expressions of nitrate use and photosynthesis-related transcripts contribute to the stronger plasticity to high nitrate for the invader relative to its native congener, which may be driven by hormones. Strong phenotypic plasticity is often considered as one of the main mechanisms underlying exotic plant invasions. However, few studies have been conducted to investigate the related molecular mechanisms. Here, we determined the differences in the plastic responses to high nitrate between the invasive plant X. strumarium and its native congener, and the molecular bases by transcriptome analysis and quantitative real-time PCR validation. Our results showed that the invader had higher plasticity of growth, nitrogen accumulation and photosynthesis in responses to high nitrate than its native congener. Compared with its congener, more N utilization-related transcripts, including nitrate transporter 1/peptide transporter family 6.2 and nitrate reductase 1, were induced by high nitrate in the root of X. strumarium, improving its N utilization ability. More transcripts coding for photosynthetic antenna proteins were also induced by high nitrate in the shoot of X. strumarium, enhancing its photosynthesis. Hormones may be involved in the regulation of the plastic responses to high nitrate in the two species. Our study contributes to understanding the molecular mechanisms underlying the stronger plasticity of the invader in responses to high nitrate, and the potential function of plant hormones in these processes, providing bases for precise control of invasive plants using modern molecular techniques.


Managing Waldenström's macroglobulinemia with BTK inhibitors.
Bruton's tyrosine kinase (BTK) inhibition is one of the treatment standards for patients with relapsed/refractory Waldenström's macroglobulinemia (WM) and for patients with WM who are unsuitable for immunochemotherapy (ICT). It offers deep and durable responses with a manageable safety profile that is generally favorable compared with ICT regimens. However, the limitations of the first approved BTK inhibitor (BTKi), ibrutinib, include reduced efficacy in patients lacking the characteristic WM mutation (MYD88L265P) and toxicities related to off-target activity. The risk of atrial fibrillation (AF) and other cardiovascular side effects are a notable feature of ibrutinib therapy. Several next-generation covalent BTKis with greater selectivity for BTK are at various stages of development. In November 2021, zanubrutinib became the first of these agents to be approved by the European Medicines Agency for the treatment of WM. Head-to-head trial data indicate that it has comparable efficacy to ibrutinib for patients with WM overall, although it may be more effective in patients with CXCR4 mutations or wild-type MYD88. In the clinical trial setting, its greater selectivity translates into a reduced risk of cardiovascular side effects, including AF. Acalabrutinib, which is pre-approval in WM, appears to offer similar advantages over ibrutinib in terms of its safety profile. Beyond the next-generation covalent BTKis, non-covalent BTKis are an emerging class with the potential to provide a therapeutic option for patients who relapse on covalent BTKis. In the future, BTKis may be increasingly utilized within combination regimens. Several ongoing trials in WM are investigating the potential for BTKi use in combination with established and novel targeted agents.


Silicon (Si): Review and future prospects on the action mechanisms in alleviating biotic and abiotic stresses in plants.
In the era present, due to increasing incidences of a large number of different biotic and abiotic stresses all over the world, the growth of plants (principal crops) may be restrained by these stresses. In addition to beneficial microorganisms, use of silicon (Si)-fertilizer is known as an ecologically compatible and environmentally friendly technique to stimulate plant growth, alleviate various biotic and abiotic stresses in plants, and enhance the plant resistance to multiple stresses, because Si is not harmful, corrosive, and polluting to plants when presents in excess. Here, we reviewed the action mechanisms by which Si alleviates abiotic and biotic stresses in plants. The use of Si (mostly as industrial slags and rice straw) is predicted to become a sustainable strategy and an emerging trend in agriculture to enhance crop growth and alleviate abiotic and biotic stresses in the not too distant future. In this review article, the future research needs on the use of Si under the conditions of abiotic and biotic stresses are also highlighted.


Inhibition of K-ras-transformed rodent and human cancer cell growth via induction of apoptosis by irreversible inhibitors of Ras endoprotease.
Proteolytic removal of the carboxyl terminal tripeptide of Ras oncoproteins is important in the Ras function. Two chloromethyl ketones, BFCCMK and UM96001, designed to be the Ras C-terminal sequence-specific endoprotease inhibitors, at low micromolar concentrations (5.0 microM), potently inhibit the growth of ras-transformed rodent and human cancer cells, whereas untransformed NIH/3T3 cells are not affected under the same conditions. Furthermore, BFCCMK and UM96001 block more than 98% of the anchorage-independent clonogenic growth of ras-transformed rat and human cancer cells at low micromolar concentrations. The blocking of cancer cell growth may be due to the selective induction of apoptosis of ras-transformed cells by these inhibitors. These results provide the first experimental evidence that the endoproteolysis of Ras oncoproteins is important for the growth and apoptosis of ras-transformed cancer cells. Therefore, the Ras C-terminal sequence-specific endoprotease may be a potential new target for the treatment of human cancers induced by ras mutations.


Stable room-temperature ferromagnetic phase at the FeRh(100) surface.
Interfaces and low dimensionality are sources of strong modifications of electronic, structural, and magnetic properties of materials. FeRh alloys are an excellent example because of the first-order phase transition taking place at ~400 K from an antiferromagnetic phase at room temperature to a high temperature ferromagnetic one. It is accompanied by a resistance change and volume expansion of about 1%. We have investigated the electronic and magnetic properties of FeRh(100) epitaxially grown on MgO by combining spectroscopies characterized by different probing depths, namely X-ray magnetic circular dichroism and photoelectron spectroscopy. We find that the symmetry breaking induced at the Rh-terminated surface stabilizes a surface ferromagnetic layer involving five planes of Fe and Rh atoms in the nominally antiferromagnetic phase at room temperature. First-principles calculations provide a microscopic description of the structural relaxation and the electron spin-density distribution that support the experimental findings.


Intelligibility of spontaneous conversational speech produced by children with cochlear implants: a review.
The emergence of cochlear implant technology has raised hopes about improved outcomes for children with severe and profound hearing impairments. This study sought to examine the current literature to help evaluate whether the new technology is living up to its promise specifically relative to the intelligibility of conversational speech produced by these children. At least 20 studies to date have reported findings for the intelligibility of speech produced by children fitted with cochlear implants. The current review involved a descriptive, summary examination of 10 of these studies that analyzed spontaneous conversational speech. The review suggested that intelligibility outcomes for these children appear to be considerably better than we have historically seen in this population (i.e., prior to the development of cochlear implant technology). For children implanted very early it appears that progress toward intelligible speech is more rapid, and the development of fully intelligible speech may be a reasonable goal for many such children. Even for children implanted somewhat later, progress on speech intelligibility appears to continue for at least 10 years post-implantation. It would appear that cochlear implants are providing much better outcomes compared to older intervention approaches, at least relative to the intelligibility of spontaneous conversation.


P-Mediated Cu-N4 Sites in Carbon Nitride Realizing CO2 Photoreduction to C2 H4 with Selectivity Modulation.
Photocatalytic CO2 reduction to high value-added C2 products (e.g., C2 H4 ) is of considerable interest but challenging. The C2 H4 product selectivity strongly hinges on the intermediate energy levels in the CO2 reduction pathway. Herein, Cu-N4 sites anchored phosphorus-modulated carbon nitride (CuACs/PCN) is designed as a photocatalyst to tailor the intermediate energy levels in the the C2 H4 formation reaction pathway for realizing its high production with tunable selectivity. Theoretical calculations combined with experimental data demonstrate that the formation of the C-C coupling intermediates can be realized on Cu-N4 sites and the surrounding doped P facilitates the production of C2 H4 . Thus, CuACs/PCN exhibits a high C2 H4 selectivity of 53.2% with a yielding rate of 30.51 µmol g-1 . The findings reveal the significant role of the coordination environment and surrounding microenvironment of Cu single atoms in C2 H4 formation and offer an effective approach for highly selective CO2 photoreduction to produce C2 H4 .


Antibody-dependent cellular cytotoxicity against Epstein-Barr virus-associated antigens in African patients with nasopharyngeal carcinoma.
Antibody-dependent cellular cytotoxicity (ADCC) was performed on serum samples from African patients with nasopharyngeal carcinoma (NPC) to determine whether antibody titers determined by this assay might be of prognostic value in this disease. The serum donors were divided into two groups: (1) those individuals who died within 2 years following diagnosis of NPC; and (2) individuals who responded well to therapy and surivived for more than 2 years following diagnosis. The ADCC GMT for the survivor group was significantly higher than the GMT for non-survivors (%5,410 versus 615). Interestingly, there were a number of discordant sera in the non-survivor group that had very low ADCC titers (less than 240) at diagnosis in the presence of high VCA titers. When ADCC titers were compared with anti-EA or IgA antibody titers to VCA, a statistically significant inverse correlation was noted. These data suggest that ADCC titers might be of prognostic importance in African NPC.


Repeat adrenocortical-sparing adrenalectomy for recurrent hereditary pheochromocytoma.
Many endocrine surgeons advocate subtotal adrenalectomy for patients with bilateral hereditary pheochromocytoma despite the risk of recurrence. However, as the effectiveness of this procedure for locally recurrent pheochromocytoma is not well known, we investigated two patients who underwent this operation. We performed repeat subtotal adrenalectomy for recurrent hereditary pheochromocytoma in two patients who had undergone primary subtotal adrenalectomy. Patient 1 was a 23-year-old woman with multiple endocrine neoplasia type 2A, in whom about 25% of the right adrenal gland was left in situ. Patient 2 was a 22-year-old man with von-Hippel-Lindau syndrome, in whom about 25% of both normal adrenal glands was left in situ. No steroid replacement was required postoperatively, and adrenocorticotropic hormone stimulation revealed sufficient adrenocortical function in both patients. No sign of recurrent pheochromocytoma has been found in 96 months and 11 months of follow-up, respectively. Recurrent hereditary benign pheochromocytoma after subtotal adrenalectomy may be treated successfully by repeated subtotal adrenalectomy. However, the risk of recurrence and malignancy must be weighed carefully against the risk of lifelong steroid replacement and potential Addisonian crisis. Thus, repeated subtotal adrenalectomy should be considered for selective patients who want to avoid steroid replacement.


Genetic differentiation between sandfly populations of Phlebotomus chinensis and Phlebotomus sichuanensis (Diptera: Psychodidae) in China inferred by microsatellites.
Phlebotomus chinensis is a primary vector of visceral leishmaniasis; it occurs in various biotopes with a large geographical distribution, ranging from Yangtze River to northeast China. Phlebotomus sichuanensis, a species closely related to P. chinensis in high altitude regions, has a long term disputation on its taxonomic status. Both species occur in the current epidemic regions and are responsible for the transmission of leishmaniasis. Population genetic analysis will help to understand the population structure and infer the relationship for morphologically indistinguishable cryptic species. In this study, microsatellite markers were used for studying the genetic differentiation between P. chinensis and P. sichuanensis. Sandflies were collected in 6 representative localities in China in 2005-2009. Ten microsatellite loci were used to estimate population genetic diversity. The intra-population genetic diversity, genetic differentiation and effective population size were estimated. All 10 microsatellite loci were highly polymorphic across populations, with high allelic richness and heterozygosity. Hardy-Weinberg disequilibrium was found in 23 out of 60 (38.33%) comparisons associated with heterozygote deficits, which was likely caused by the presence of null allele and the Wahlund effect. Bayesian clustering analysis revealed three clusters. The cluster I included almost all specimens in the sample SCD collected at high altitude habitats in Sichuan. The other two clusters were shared by the remaining 5 populations, SCJ in Sichuan, GSZ in Gansu, SXL and SXX in Shaanxi and HNS in Henan. The diversity among these 5 populations was low (FST = -0.003-0.090) and no isolation by distance was detected. AMOVA analysis suggested that the variations were largely derived from individuals within populations and among individuals. Consistently, the analysis of ribosomal DNA second internal transcribed spacer (ITS2) sequence uncovered three types of variants, which corresponded with the three gene pools revealed by microsatellites. The data suggested that the SCD population carried a distinct gene pool, which was differentiated from the other populations. The high altitude ecological habitats, distinctive ITS2 and herein divergence inferred by microsatellite loci support the species status of P. sichuanensis. The P. chinensis populations did not have a significant divergence from each another.


Chick connexin-56, a novel lens gap junction protein. Molecular cloning and functional expression.
We used primers corresponding to the amino-terminal sequence shared by rat connexin-46 and ovine MP70 and a consensus sequence of the second extracellular loop conserved in all connexins to amplify and subsequently clone from chick genomic DNA a new member of the connexin family of gap junction proteins, chick connexin-56. The derived chick connexin-56 polypeptide contains 510 amino acids with a predicted molecular mass of 55,857 daltons. Although identical in the first 70 amino acids to rat connexin-46, chick connexin-56 diverges significantly in length and composition in predicted cytoplasmic regions, which have previously been inferred to determine functional and regulatory specificity. We were able to detect hybridization of connexin-56 probes only to RNA derived from lens. Connexin-56 was functionally expressed by the stable transfection of communication-deficient Neuro2A cells. The connexin-56-transfected cells demonstrated intercellular coupling by transfer of microinjected 6-carboxyfluorescein. Double whole-cell patch clamp recordings demonstrated electrical coupling. The induced intercellular conductances were insensitive to uncoupling by heptanol, octanol, or acidification. This behavior of chick connexin-56 may explain previous observations of the unusual physiology of lens fiber gap junctions.