Neighboring chromaticity influences how white a surface looks.
To identify surface properties independently of the illumination the visual system must make assumptions about the statistics of scenes and their illumination. Are assumptions about the intensity of the illumination independent of assumptions about its chromaticity? To find out, we asked participants to judge whether test patches within three different sets of surrounding surfaces were white or grey. Two sets were matched in terms of their maximal luminance, their mean luminance and chromaticity, and the variability in their luminance and chromaticity, but differed in how luminance and chromaticity were associated: the highest luminance was either associated with colorful surfaces or with achromatic ones. We found that test patches had to have a higher luminance to appear white when the highest luminance in the surrounding was associated with colorful surfaces. This makes sense if one considers that being colorful implies that a surface only reflects part of the light that falls on it, meaning that the illumination must have a higher luminance (a perfectly white surface reflects all of the light falling on it). In the third set, the colorful surfaces had the same luminance as in the set in which they were associated with the highest luminance, but the achromatic surfaces had a lower luminance so that the overall mean luminance was lower. Despite the constraints on the illumination being identical, test patches did not have to have as high luminance to appear white for the third set. Considering the layout of the surfaces in the surrounding revealed that test patches did have to have the same high luminance if the high luminance colorful surfaces were adjacent to the target patch. Thus, the assumptions about the possible illumination are applied locally. A possible mechanism is relying on the contrast within each type of cone: for a surface to appear white it must stimulate each of the three kinds of cones substantially more than do any neighboring surfaces.


Synthesis and evaluation of new 1,2,4-oxadiazole based trans- acrylic acid derivatives as potential PPAR-alpha/gamma dual agonist.
Diabetes is a ubiquitously a metabolic disorder and life-threatening disease. Peroxisome proliferator-activated receptors (PPARs) belong to the class of nuclear receptors which acts as transcription factors to regulate lipid and glucose metabolism. PPAR alpha/gamma dual agonists tend to corroborate the functions of both thiazolidinediones and fibrates and they hold substantial promise for ameliorating the type 2 diabetic treatments and providing potential therapeutic diabetic interventions. New 1,2,4-oxadiazole based trans- acrylic acid derivatives compounds possessing aryl/methylene linker in between pharmacophore head and lipophilic tail for dual PPAR-alpha/gamma agonists are studied. AutoDock Vina used for potential PPAR alpha/gamma dual agonists and 6 compounds 9a, 9g, 9 m, 9n, 9o, and 9r were identified comparable to PPAR gamma agonist Pioglitazone on the basis of their affinity scores and further their in-silico toxicity and in-silico ADME properties. The selected compounds showed better-calculated lipophilicity (iLogP) was found to be 0.92 to 3.19. Compound 9n and 9a were found to be most potent on both PPAR alpha and gamma receptors with EC50 of 0.07 ± 0.0006 µM, 0.06 ± 0.0005 µM and 0.781 ± 0.008 µM, 3.29 µM ± 0.03 respectively as better to pioglitazone having EC50 of 32.38 ± 0.2 and 38.03 ± 0.13 for both receptors. The in-vivo evaluation found to reduce the plasma glucose level and total cholesterol level significantly in diabetic rats compared to pioglitazone at 5 mg/kg/day dose for 7 days of treatment. Thus, trans- acrylic acid derivatives can be further developed as oral therapeutic agents for diabetic interventions as PPAR alpha/gamma dual agonists.


Push out bond strength of glass fiber post to radicular dentin irrigated with Nisin and MTAD compared to methylene blue photodynamic therapy.
Present lab-based study intended to appraise the effect of nisin, Mixture of Tetracycline, Acid and Detergent (MTAD), and photodynamic therapy (PDT) when used as a canal disinfectant on push-out bond strength (PBS) of fiber post to radicular dentin MATERIALS AND METHODS: Forty uni-radicular premolar teeth were extracted and disinfected in 0.5 % thymol solution. All specimens were decoronated to achieve standardize root length of 14 mm. Cleaning and shaping of the canal were done using protaper NiTi system. The canal space was dried and obturated. Post space was prepared using peso reamers up to 10 mm length and samples were randomly divided into 4 groups (n = 10). Group 1 irrigated with 10 % Nisin with MTAD, group 2: 1.3 % NaOCl and MTAD, Group 3 irrigated with 2.5 % NaOCl and 17 % EDTA and post space of samples in group 4 with PDT with MTAD. Fiber-reinforced composite post (FRCP) was fitted in canal space using self-etch resin cement. Each sample was cut into 1 mm from coronal, middle, and apical and subjected to PBS via a universal testing machine. For comparison of means, Analysis of variance (ANOVA) and Tukey multiple comparison test was used maintaining the level of significance at p < 0.05. Samples in group 3 post space irrigated with 2.5 % NaOCl and 17 % EDTA demonstrated the highest PBS at all root levels (cervical: 8.83 ± 0.14 MPa, middle: 7.63 ± 0.82 MPa and apical: 5.82 ± 0.32 MPa) in comparison to other tested groups. Whereas, group 1 in which Nisin 10 % with MTAD was used as a canal disinfectant displayed the lowest PBS at all levels (cervical: 6.91 ± 0.54 MPa, middle: 6.15 ± 0.31 MPa, and apical: 3.62 ± 0.68 MPa). Post space irrigated with 1.3 % NaOCl and MTAD shows PBS similar to control group 2.5 % NaOCl and 17 % EDTA. Both types of irrigation methods have potential and can be recommended in clinical scenarios. Whereas, 10 % Nisin and PDT with MTAD as chelator needs further inquiry.


Morphological abnormalities in African catfish (Clarias gariepinus) larvae exposed to malathion.
Newly hatched larvae of Clarias gariepinus were exposed to malathion concentrations ranging from 0.3 mg/l to 5.0 mg/l. Their development was observed through five days posthatch, i.e., the stage in which the vertebral elements are not yet present and the notochord is the only functional body axis. A significant higher proportion of C. gariepinus larvae with deformed notochord and pericardial edema was detected at 2.5 mg/l malathion and higher. The results suggested that (1) deformed notochord was the result of the uncontrolled contractions of the body musculature due to malathion toxicity and (2) the vertebral deformities observed in the fish which have been exposed to malathion from the notochord-stage onwards were the result of a deformed notochord instead of the deformation of the vertebral elements themselves.


Immunological consequences of three doses of heat-killed Mycobacterium vaccae in the immunotherapy of tuberculosis.
We report the first study of triple-dose immunotherapy with heat-killed Mycobacterium vaccae (SRL 172) combined with short-course, directly observed chemotherapy in newly diagnosed pulmonary tuberculosis patients. The study was carried out in Rosario, Argentina, where single-dose immunotherapy with M. vaccae has previously been shown effective. Twenty-two HIV seronegative patients, sputum-positive for tubercle bacilli, entered a randomised and partly blinded trial. Twelve patients received injections of SRL 172 and 10 patients received placebo on days 1, 30 and 60 of chemotherapy. All patients were followed up clinically, by sputum bacteriology, chest radiography and haematology. Patients receiving SRL 172 showed faster and more complete clinical improvement, accelerated disappearance of bacilli from sputum, better radiological clearance and a more rapid fall in ESR, than did those receiving placebo. Follow-up continued for a year after therapy and no patient failed treatment or relapsed. Special investigations included longitudinal assessments of respiratory bursts and expression of CD11b on separated polymorphonuclear and mononuclear leukocytes. Tumour necrosis factor alpha (TNF-alpha) was measured in the supernates of cultured cells and both TNF-alpha and interleukin-4 (IL-4) were measured in serum samples. Immunotherapy recipients showed a significantly faster return towards normal values in all the immunological parameters, than did placebo recipients. The results are consistent with a regulatory activity on cellular immunity, reducing the influence of Th2 and enhancing Th1 to the benefit of the patients. This could allow a reduced period of chemotherapy without loss of efficacy and help to prevent the development of multi-drug resistance.


Effect of lead on physiological and antioxidant responses in two Vigna unguiculata cultivars differing in Pb-accumulation.
Lead (Pb) is one of the most toxic anthropogenic pollutants, occurring widely in both terrestrial and aquatic ecosystems, where it impairs plant growth and development. In this work, the effect of 0.5 mM EDTA-Pb was evaluated in two Vigna unguiculata cultivars (SV and SET), with the aim of detecting genotype/cultivar dependent changes in the physiological and anti-oxidant responses (CAT and APX) of a leguminous plant. The data showed that SV accumulated more Pb in roots while SET accumulated more in leaves, indicating differential regulation in Pb-translocation/accumulation. Lead affected the growth of SV less severely than SET, mainly associated with reduced inhibition in photosynthetic parameters. Furthermore, CAT and APX activities increased or were sustained at elevated levels in both cultivars in response to lead. However, gene expression analyses revealed that CAT1 was the main lead responsive gene in SET while CAT2 was more responsive in SV. APX1 was higher expressed in tissues with higher Pb-accumulation while APX2 was ubiquitously responsive to lead in both cultivars. Taken together, these results reveal differential ability of V. unguiculata cultivars in Pb-accumulation in different tissues affecting distinctly physiological and anti-oxidant responses. In addition, the existence of cultivars with predominant Pb-accumulation in aerial tissues invokes a need for studies to identify pollution-safe cultivars of leguminous plants to ensure food safety.


Neurocysticercosis-related seizures: Imaging biomarkers.
Neurocysticercosis (NCC)-a parasitic CNS infection endemic to developing nations-has been called the leading global cause of acquired epilepsy yet remains understudied. It is currently unknown why a large proportion of patients develop recurrent seizures, often following the presentation of acute seizures. Furthermore, the presentation of NCC is heterogenous and the features that predispose to the development of an epileptogenic state remain uncertain. Perilesional factors (such as oedema and gliosis) have been implicated in NCC-related ictogenesis, but the effects of cystic factors, including lesion load and location, seem not to play a role in the development of habitual epilepsy. In addition, the cytotoxic consequences of the cyst's degenerative stages are varied and the majority of research, relying on retrospective data, lacks the necessary specificity to distinguish between acute symptomatic and unprovoked seizures. Previous research has established that epileptogenesis can be the consequence of abnormal network connectivity, and some imaging studies have suggested that a causative link may exist between NCC and aberrant network organisation. In wider epilepsy research, network approaches have been widely adopted; studies benefiting predominantly from the rich, multimodal data provided by advanced MRI methods are at the forefront of the field. Quantitative MRI approaches have the potential to elucidate the lesser-understood epileptogenic mechanisms of NCC. This review will summarise the current understanding of the relationship between NCC and epilepsy, with a focus on MRI methodologies. In addition, network neuroscience approaches with putative value will be highlighted, drawing from current imaging trends in epilepsy research.


In vivo selection of KPC-94 and KPC-95 in Klebsiella pneumoniae isolates from patients treated with ceftazidime/avibactam.
Ceftazidime/avibactam (CZA) is used to treat infections caused by Klebsiella pneumoniae carbapenemase-producing K. pneumoniae (KPC-Kp). Resistance to CZA is commonly related to point mutations in the blaKPC gene. Here we describe the in vivo emergence of CZA resistance in clinical isolates of KPC-Kp from four patients treated with this combination therapy. Four pre-therapy and five post-therapy KPC-Kp isolates were examined. Antibiogram (microdilution and gradient strips) and whole-genome sequencing were performed. The role of KPC mutations was validated by cloning blaKPC genes into competent Escherichia coli. All KPC-Kp isolates recovered before treatment with CZA were susceptible to CZA and produced KPC-3. Five KPC-Kp isolates recovered after treatment were resistant to this combination. Three post-therapy isolates from two patients produced KPC-31 (D179Y mutation). Additionally, we identified the novel substitution LN169-170H (KPC-94) in one isolate, and the combination of two independently described mutations, D179Y and A172T (KPC-95), in another isolate. All KPC-Kp isolates belonged to sequence type 512 (ST512). All CZA-resistant isolates with blaKPC variants had restoration of carbapenem susceptibility. In conclusion, resistance to CZA was related to blaKPC mutations, including the new KPC-94 and KPC-95 alleles, which do not cause carbapenem resistance.


Role of natural killer activity in development of spontaneous metastases in murine renal cancer.
We have studied the role of natural killer activity during the growth and dissemination of a transplantable renal adenocarcinoma (Renca) of spontaneous origin in BALB/c mice. The pattern of growth of this tumor accurately mimics that of adult human renal cell carcinoma in terms of clinical stages I-IV, particularly with regard to spontaneous metastasis to lung and liver. Renca is moderately sensitive to lysis by natural killer cells from normal mice and is more efficiently lysed by natural killer cells from mice treated with the biological response modifier maleic anhydride divinyl ether, a pyran copolymer. Our studies demonstrate that selective depression of natural killer activity by administration of antiserum specific for the neutral glycosphingolipid asialo GM1 correlated with increased formation of spontaneous metastases in the lungs, liver, and lymph nodes. Conversely, augmentation of natural killer activity by the biological response modifier decreased the formation of spontaneous metastases in lungs, liver and lymph nodes. Further, the suppression of natural killer activity and subsequent increased formation of metastases were accompanied by a significantly reduced survival time, whereas the augmented natural killer activity and decreased incidence of metastases in biological response modifier-treated mice were accompanied by an increase in time of survival. These results demonstrate a significant role for natural killer cells in the control of spontaneous metastasis during growth of this murine renal cancer.


Tinnitus: the dark side of the auditory cortex plasticity.
Music has increasingly been used as a tool for investigation of human cognition and its underlying brain mechanisms. However, music can be used also for neurorehabilitation. Chronic tinnitus is a symptom with high prevalence, especially in industrialized countries. There is evidence that the tinnitus perception is related to unfavorable cortical plastic changes. Maladaptive auditory cortex reorganization may contribute to the generation and maintenance of tinnitus. Because cortical organization can be modified by behavioral training, potentially via reversing maladaptive auditory cortex reorganization, we attempted to reduce tinnitus loudness by exposing chronic tinnitus patients to self-chosen, enjoyable music that was modified ("notched") to contain no energy in the frequency range surrounding the individual tinnitus frequency and thus attracting lateral inhibition to the brain area generating tinnitus. On this basis, we have developed and evaluated a customized music training strategy that appears capable of both reducing cortical tinnitus-related neuronal activity and alleviating subjective tinnitus perception.


Design and evaluation of an oligonucleotide-microarray for the detection of different species of the genus Kitasatospora.
An oligonucleotide-microarray method was developed for the detection of Kitasatospora species in soil samples. The 16S-23S rDNA internal transcribed spacer (ITS) sequence of these antibiotics-producing actinomycetes was applied to design short oligonucleotide probes. Two different 26-mers were synthesized, specific to each species used. Additionally, four oligonucleotide probes were designed to evaluate the system. The oligonucleotides were spotted onto slides of the ArrayTube microarray system and examined with a new silver-labeling detection technique. Prior to hybridization analysis, the 16S-23S rDNA were amplified by polymerase chain reaction both from bacterial cells and environmental samples using two actinomycetes specific primers containing a 5' biotin labeling. The type strains of eight Kitasatospora species included in this study were K. phosalacinea DSM 43860, K. setae DSM 43861, K. cochleata DSM 41652, K. cystarginea DSM 41680, K. azatica DSM 41650, K. mediocidica DSM 43929, K. paracochleata DSM 41656, and K. griseola DSM 43859. The actinomycetes-specific primers were shown to amplify the entire 16S-23S rDNA ITS region from all tested strains. More importantly, the described technique allows the detection of Kitasatospora strains from soil samples by extracting metagenomic DNA followed by a PCR amplification step. This indicates that the oligonucleotide-microarray method developed in this study is a reliable tool for the detection of Kitasatospora species in environmental samples.


The safety and efficacy of different doses of bacillus Calmette Guérin in superficial bladder transitional cell carcinoma.
To conduct a trial using three different doses of bacillus Calmette-Guérin (BCG) to determine whether lowering the dose of BCG could reduce toxicity without compromising its efficacy in the treatment of superficial bladder cancer. From July 2002 to June 2005, 152 patients with superficial bladder cancer entered the trial. The patients were randomized to receive three different doses of BCG: 40, 80, and 120 mg. There were no significant differences in clinical and pathologic characteristics among the three groups. Twenty-four patients could not be followed to the end of the study because of poor compliance. At completion of the study, 40 patients could be evaluated in group A (40 mg), 48 in group B (80 mg), and 40 in group C (120 mg). After treatment patients were evaluated for a mean follow-up period of 36 months (range 18 to 52 months). No significant difference in recurrence rate (20% versus 25% versus 20% respectively; P >0.05) was observed among the groups, and no progression of the disease was seen. Significant differences were observed among groups A, B, and C in local toxicity (30% versus 41.7% versus 70%, respectively; P <0.01). Systemic toxicity was more common in group C compared with groups B and A (P <0.01). Reduction in the dose of intravesical BCG can reduce the toxicity associated with the treatment of superficial bladder cancer without affecting the efficacy of therapy.


Synthesis and characterization of silver nanoparticles using curcumin: cytotoxic, apoptotic, and necrotic effects on various cell lines.
Nanostructures have distinctive chemical and physical features owing to their surface area and nanoscale size. In this study, silver nanoparticles were synthesized using curcumin, a medicinally valuable natural product. The structure of curcumin-mediated silver nanoparticles (c-AgNPs) was identified by extensive spectroscopic techniques. The maximum absorption was observed at 430 nm in UV-Vis spectrum. The crystal structure of c-AgNPs was identified by XRD. The morphology of the structure was determined by SEM image. The particle size was found as 51.13 nm. The functional groups of curcumin and c-AgNPs were established by FTIR spectroscopy. Cytotoxic activity of c-AgNPs was carried out using A549, DLD-1, and L929 with MTT assay. c-AgNPs revealed excellent activity on DLD-1 cell lines and A549 cell lines at 1.0 mg/mL concentration with the lethal effect of 80%. However, nanoparticles did not show the considerable effect on L929. Moreover, they induced apoptosis. Consequently, c-AgNPs are a promising material for anticancer drugs candidate.


A potential for granulocyte-colony stimulating factor for use as a prophylactic agent for heatstroke in rats.
Heatstroke is a form of excessive hyperthermia associated with a systemic inflammatory response that leads to multi-organ dysfunction in which central nervous system disorders predominate. Herein we determined to ascertain whether heat-induced multi-organ dysfunction in rats could be attenuated by granulocyte-colony stimulating factor (G-CSF) preconditioning. Anesthetized rats were divided into 2 major groups and given vehicle solution (isotonic saline, 0.3 ml, subcutaneously) or G-CSF (50-200 μg/kg body weight in 0.3 ml normal saline, subcutaneously) daily and consecutively for 5 days before the start of thermal experiments. They were exposed to an ambient temperature of 43°C for 68 min to induce heatstroke. G-CSF preconditioning significantly prolonged the survival time in heatstroke rats in a dose-related way (82-98 min vs 127-243 min). The non-preconditioning heatstroke animals showed hyperthermia, arterial hypotension, increased serum levels of systemic inflammatory response molecules, increased hypothalamic apoptotic cell numbers as well as neuronal damage scores, and increased serum levels of renal and hepatic dysfunction indicators. These heatstroke syndromes could be significantly reduced by G-CSF preconditioning. Thus our results revealed a potential for G-CSF used as a prophylactic agent for heatstroke in rats.


Timing of Complication and Failure to Rescue after Hepatectomy: Single-Institution Analysis of 28 Years of Hepatic Surgery.
Morbidity after hepatectomy remains a significant, potentially preventable, outcome. Understanding the pattern of complications and rescue pathways is critical for the development of targeted initiatives intended to salvage patients after operative morbidity. Patients undergoing liver resection from 1991 to 2018 at a single institution were analyzed. Failure to rescue (FTR) was defined as percentage of deaths in patients with a complication within 30 days. Generalized estimating equations with log-link function assessed associations between clinical characteristics and major complications and between complications at fewer than 30 days and 30 to 90 days. Logistic regression assessed associations between complications and FTR. A total of 6,191 patients and 6,668 operations were identified, of which 55.6% were performed for management of metastatic colorectal cancer. Major complications (grade ≥3) occurred in 20.2% of operations (1,346 of 6,668). Ninety-day mortality was 2.2%. The most common complication was intra-abdominal abscess at 9.0% (95% CI, 8.3% to 9.7%). Ten percent of patients with a complication at 30 days had another complication between 30 and 90 days compared with 2% without an early complication (odds ratio [OR] 5.09; 95% CI, 3.97 to 6.54; p < 0.001). FTR for liver failure, cardiac arrest, abscess, and hemorrhage was 36%, 56%, 3%, and 6%, respectively. Risk of 90-day mortality was higher in patients with liver failure (53% vs 2%; OR 61.42; 95% CI, 37.47 to 100.67; p < 0.001), cardiac arrest (69% vs 2%; OR 96.95; 95% CI, 33.23 to 283.80; p < 0.001), hemorrhage (11% vs 2%; OR 5.51; 95% CI, 2.59 to 11.73; p < 0.001), and abscess (7% vs 2%; OR 4.05; 95% CI, 2.76 to 5.94; p < 0.001) compared with those without these complications. Morbidity after hepatectomy is frequent despite low mortality. This study identifies targets for improvement in morbidity and failure to rescue after hepatectomy. Efforts to improve recognition and intervention for infections and early complications are needed to improve outcomes.


Sexual lifestyles and HIV risk.
Britain's first large, national survey of sexual attitudes and lifestyles will allow improved estimates of the magnitude of the HIV epidemic in Britain and should lead to better strategies for prevention.


The elevated risk of sight-threatening cataract in diabetes with retinopathy: a retrospective population-based cohort study.
The effect of diabetic retinopathy (DR) on the development of sight-threatening cataracts was assessed using the National Health Insurance Research Database of Taiwan. Patients diagnosed with diabetes mellitus (DM) and DR were enrolled in the study group. Age- and sex-matched DM individuals without DR and patients without DM served as the DM control group and non-DM control group, respectively, both with 1:4 ratios. The outcome was set as the performance of cataract surgery. Cox proportional hazard regression was used to calculate the adjusted hazard ratio (aHR) of DR considering multiple factors underlying cataract formation. A total of 3297 DR patients, 13,188 DM control patients and 13,188 non-DM control subjects were enrolled. The study group included 919 events of sight-threatening cataracts (27.87%), the DM control group included 1108 events (8.40%), and the non-DM control group included 957 events (7.26%). A multivariable analysis indicated that the study group presented a higher aHR of cataract surgery (2.93, 95% CI: 2.60-3.30) and a higher cumulative probability of cataract surgery than both the DM control and non-DM control groups (both log rank P < 0.001). In addition, both the proliferative DR (3.90, 95% CI: 3.42-4.45) and nonproliferative DR (2.35, 95% CI: 2.08-2.65) subgroups showed a higher aHR of cataract surgery than the DM control group. The presence of DR increases the risk of sight-threatening cataracts that warrant surgery, and the effect is prominent among patients with both proliferative DR and nonproliferative DR.


Perceived parental monitoring and adolescent internet addiction: A moderated mediation model.
Bronfenbrenner's (1979) ecological model focuses on the interrelation between different contexts and the interaction between individuals and their proximal contexts. Based on this theory, the present study tested a moderated mediation model of family, peer, and individual characteristics to investigate how they impact adolescent Internet addiction. Specifically, we examined whether deviant peer affiliation partially mediated the relation between perceived parental monitoring and adolescent Internet addiction, and whether this indirect relation was moderated by effortful control. A total of 747 Chinese middle school students filled out anonymous questionnaires concerning perceived parental monitoring, deviant peer affiliation, effortful control, and Internet addiction. The findings indicated that while the impact of parental monitoring on Internet addiction was partially mediated by deviant peer affiliation, effortful control moderated the first stage of the indirect relationship. For low effortful control adolescents, perceived parental monitoring negatively predicted deviant peer affiliation. Conversely, the indirect path was not significant for high effortful control adolescents. These findings highlight the need to consider family, peer and individual factors simultaneously when evaluating risks associated with adolescent Internet addiction and have important implications for the prevention and intervention of adolescent Internet addiction.


A crystallographic investigation on NADPH-adrenodoxin oxidoreductase.
Single crystals of NADPH-adrenodoxin oxidoreductase were grown in 50 mM potassium phosphate (pH 7.4) containing 5% glycerol and ammonium sulfate. The crystals are monoclinic, belong to space group P21 and have dimensions of a= 83.4 A, b = 62.6 A, c = 59.3 A, alpha = gamma = 90 degrees, and beta = 107.1 degrees. There is one molecule per asymmetric unit.


Digital endpoints for self-administered home-based functional assessment in pediatric Friedreich's ataxia.
Friedreich's ataxia is an inherited, progressive, neurodegenerative disease that typically begins in childhood. Disease severity is commonly assessed with rating scales, such as the modified Friedreich's Ataxia Rating Scale, which are usually administered in the clinic by a neurology specialist. This study evaluated the utility of home-based, self-administered digital endpoints in children with Friedreich's ataxia and unaffected controls and their relationship to standard clinical rating scales. In a cross-sectional study with 25 participants (13 with Friedreich's ataxia and 12 unaffected controls, aged 6-15 years), home-based digital endpoints that reflect activities of daily living were recorded over 1 week. Domains analyzed were hand motor function with a digitized drawing, automated analysis of speech with a recorded oral diadochokinesis test, and gait and balance with wearable sensors. Hand-drawing and speech tests were easy to conduct and generated high-quality data. The sensor-based gait and balance tests suffered from technical limitations in this study setup. Several parameters discriminated between groups or correlated strongly with modified Friedreich's Ataxia Rating Scale total score and activities of daily living total score in the Friedreich's ataxia group. Hand-drawing parameters also strongly correlated with standard 9-hole peg test scores. Deploying digital endpoints in home settings is feasible in this population, results in meaningful and robust data collection, and may allow for frequent sampling over longer periods of time to track disease progression. Care must be taken when training participants, and investigators should consider the complexity of the tasks and equipment used.


Clinical usefulness of extraction-free PCR assay to detect SARS-CoV-2.
Due to the coronavirus disease 2019 pandemic, the demand for an easily accessible high-throughput screening test is increasing. We aimed to evaluate the usefulness of the extrac-tion-free polymerase chain reaction (PCR) as a screening test to detect severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Real-time reverse transcription PCR was performed in 300 samples (260 SARS-CoV-2 positives and 40 negatives), using both the conventional nucleic acid extraction method (standard method) and the direct method without nucleic acid extraction (direct method). The overall agreement between the standard and direct methods was 86.8 % (kappa 0.60), and the sensitivity of the direct method compared to the standard method was 85.4 %. When the cycle threshold (Ct) value was less than 35, the sensitivity was approximately 90 %-98 %, and when Ct exceeded 35, it decreased to approximately 60 %-65 %. The extraction-free PCR could be useful as a screening test that processes many samples in a short time.


Hemophagocytic syndrome complicating T-cell acute lymphoblastic leukemia with a novel t(11;14)(p15;q11) chromosome translocation.
A case of hemophagocytic syndrome that developed in a patient with T-cell acute lymphoblastic leukemia (ALL) with a novel chromosome translocation involving 14q11 is reported. A 15-year-old boy with T-cell ALL in relapse showed leukemic cells with an abnormal karyotype of 46,XY,-15,t(11;14)(p15;q11), +der(15)t(15;?)(p11;?). Pancytopenia and extensive hemophagocytosis by macrophages in the bone marrow were observed after reinduction chemotherapy and again at the terminal stage. At autopsy, infiltration of such cells was also found in other organs. The findings suggested occurrence of hemophagocytic syndrome probably associated with cytomegalovirus (CMV) infection. The t(11;14)(p15;q11) may be a novel translocation specific for T-cell ALL, and conceivably, the association of T-cell ALL with the histiocytosis in this patient may not have been coincidental.


Effects of gender role on personal resources and coping with stress.
This current study investigates the relationship between the endorsement of masculine and feminine gender role orientation in accordance with Bem's indices and both personal resources and coping with stress. The Bem Sex Role Inventory, the Coping Inventory for Stressful Situations, the Satisfaction with Life Scale, the Life Orientation Scale-Revised, the General Self-Efficacy Scale and the Personal Competence Scale were completed by 308 employees of a city transport company (123 females and 185 males). Results reveal that androgynous individuals, masculine women and masculine men, possess stronger psychological resources compared with undifferentiated and feminine individuals. and feminine individuals. Moreover, satisfaction with life, femininity, the sense of personal competence and optimism are significant predictors of coping (in descending order of influence). significant predictors of coping (in descending order of influence). Masculinity is a significant positive predictor only in problem-oriented coping. These findings may have implications for the conservation of personal resources as well as for stress management interventions.


The engineered CRISPR-Mb2Cas12a variant enables sensitive and fast nucleic acid-based pathogens diagnostics in the field.
Existing CRISPR/Cas12a-based diagnostic platforms offer accurate and vigorous monitoring of nucleic acid targets, but have the potential to be further optimized for more efficient detection. Here, we profiled 16 Cas12a orthologs, focusing on their trans-cleavage activity and their potential as diagnostic enzymes. We observed the Mb2Cas12a has more robust trans-cleavage activity than other orthologs, especially at lower temperatures. An engineered Mb2Cas12a-RRVRR variant presented robust trans-cleavage activity and looser PAM constraints. Moreover, we found the existing one-pot assay, which simultaneously performed Recombinase Polymerase Amplification (RPA) and Cas12a reaction in one system, resulted in the loss of single-base discrimination during diagnosis. Therefore, we designed a reaction vessel that physically separated the RPA and Cas12a steps while maintaining a closed system. This isolated but closed system made diagnostics more sensitive and specific and effectively prevented contamination. This shelved Mb2Cas12a-RRVRR variant-mediated assay detected various targets in less than 15 min and exhibited equal or greater sensitivity than qPCR when detecting bacterial pathogens, plant RNA viruses and genetically modified crops. Overall, our findings further improved the efficiency of the current CRISPR-based diagnostic system and undoubtedly have great potential for highly sensitive and specific detection of multiple sample types.


Genomic profiling of intestinal/mixed-type superficial non-ampullary duodenal epithelial tumors.
The mechanism underlying carcinogenesis and the genomic features of superficial non-ampullary duodenal epithelial tumors (SNADETs) have not been elucidated in detail. In this study, we examined the genomic features of incipient SNADETs, such as small lesions resected via endoscopic treatment, using next-generation sequencing (NGS). Twenty consecutive patients who underwent endoscopic treatment for SNADETs of less than 20 mm between January and December 2017 were enrolled. Targeted genomic sequencing was performed through NGS using a panel of 160 cancer-related genes. Furthermore, the alteration/mutation frequencies in SNADETs were examined. The maximum size of the SNADETs examined in this study was 12 mm in diameter. Five SNADETs were classified as low-grade dysplasia (LGD) tumors, while 14 SNADETs were classified as high-grade dysplasia tumors. Only one carcinoma in situ was detected. NGS data for 16 samples were obtained. APC alterations were detected in 81% of samples (13/16). KRAS, BRAF, and TP53 alterations were detected in 25% (4/16), 18.8% (3/16), and 6.3% (1/16) of cases, respectively. We detected APC alterations in most small SNADETs resected via endoscopic treatment, from LGD to carcinoma samples. Even in SNADETs classified as small LGD exhibited KRAS and BRAF alterations.


6 DOF synchronized control for spacecraft formation flying with input constraint and parameter uncertainties.
This paper treats the problem of synchronized control of spacecraft formation flying (SFF) in the presence of input constraint and parameter uncertainties. More specifically, backstepping based robust control is first developed for the total 6 DOF dynamic model of SFF with parameter uncertainties, in which the model consists of relative translation and attitude rotation. Then this controller is redesigned to deal with the input constraint problem by incorporating a command filter such that the generated control could be implementable even under physical or operating constraints on the control input. The convergence of the proposed control algorithms is proved by the Lyapunov stability theorem. Compared with conventional methods, illustrative simulations of spacecraft formation flying are conducted to verify the effectiveness of the proposed approach to achieve the spacecraft track the desired attitude and position trajectories in a synchronized fashion even in the presence of uncertainties, external disturbances and control saturation constraint.


Communicating junctions of the human sensory retina. A freeze-fracture study.
Using the freeze-fracture technique communicating junctions could be identified between the cells of the adult human sensory retina. Communicating junctions with particles arranged in linear or circular rows as well as in small aggregates were found between adjacent photoreceptor endings. Communicating junctions with particles forming plaques were localized in the inner plexiform layer. They were isolated between unidentified cell processes or lay close to active sites of chemical synapses, thus suggesting the occurrence of "mixed" (chemical and electrical) synapses in this layer. Furthermore, communicating junctions were detected between portions of Müller's cells.


Wide-range wavelength and angle resolved light scattering measurement setup.
We present a new version of a light scattering measurement setup, using a high-power supercontinuum laser source, two volume hologram filters, and two low-noise scientific grade cameras. This configuration enables spectral and angle resolved characterization of the light scattered by complex thin-film filters from 400 to 1650 nm. Measurements carried out on specific filters illustrate the performances of the setup.


Mercury distribution in the rat brain after mercury vapor exposure.
Brown Norwegian rats were exposed to mercury vapor at a concentration of approximately 1 mg/m3 for 5 weeks 24 hr/day 7 days a week and 6 hr/day 3 days a week, respectively. The total mercury absorption was calculated to 264 and 35 micrograms per week and 100 g body weight. The mean blood mercury concentration was 0.25 +/- 0.03 and 0.09 +/- 0.01 microgram/g, and the total concentration in the brain was 5.03 +/- 0.73 and 0.71 +/- 0.10 microgram/g tissue, respectively. The mercury distribution in the brains was examined using a method based on chemographic principles. Mercury was found primarily in the neocortex, in the basal nuclei, and in the cerebellar Purkinje cells. This distribution pattern corresponded to the pattern of inorganic mercury described after exposure to methyl mercury. Distribution of mercury after administration of different mercury compounds is discussed.


Role of the Kock pouch in adolescent urology.
Although cutaneous urinary diversion will continue to have a place in some urological diseases, some patients may benefit from an undiversion. The Kock pouch with a continent reservoir is an alternative where conventional undiversion to the bladder is impossible. Indications, pre-operative preparation, operative technique, results and complications are outlined in detail. In the adolescent patient requiring urinary diversion the Kock pouch should be considered as the last resort. Where reconstruction of the urinary tract is impossible, a continent urinary reservoir by means of the Kock pouch may be indicated.


[Type I Salter-Harris lesion of the distal humeral epiphysis in children under one year of age. Case report and literature review].
The pure physeal lesion of the distal humeral epiphysis is an uncommon and difficult-to-diagnose condition due to the absence of calcified ossification centers during the first three months of life, which usually leads to delaying the diagnosis or to misdiagnosis. However, the prognosis is good and complications are few. We report the case of a 3-month-old female patient who was admitted for open reduction and fixation with Kirschner nails.


Target identification for small-molecule discovery in the FOXO3a tumor-suppressor pathway using a biodiverse peptide library.
Genetic screening technologies to identify and validate macromolecular interactions (MMIs) essential for complex pathways remain an important unmet need for systems biology and therapeutics development. Here, we use a library of peptides from diverse prokaryal genomes to screen MMIs promoting the nuclear relocalization of Forkhead Box O3 (FOXO3a), a tumor suppressor more frequently inactivated by post-translational modification than mutation. A hit peptide engages the 14-3-3 family of signal regulators through a phosphorylation-dependent interaction, modulates FOXO3a-mediated transcription, and suppresses cancer cell growth. In a crystal structure, the hit peptide occupies the phosphopeptide-binding groove of 14-3-3ε in a conformation distinct from its natural peptide substrates. A biophysical screen identifies drug-like small molecules that displace the hit peptide from 14-3-3ε, providing starting points for structure-guided development. Our findings exemplify "protein interference," an approach using evolutionarily diverse, natural peptides to rapidly identify, validate, and develop chemical probes against MMIs essential for complex cellular phenotypes.


40 S subunits from rat liver ribosomes contain two codon-dependent sites for transfer RNA.
40 S subunits from rat liver ribosomes are able to bind, after heat activation, two molecules of either Phe-tRNAPhe, Ac-Phe-tRNAPhe or deacylated tRNAPhe. Addition of 60 S subunits to the quaternary complex 40 S.poly(U).(Phe-tRNAPhe)2 results in quantitative formation of (Phe)2-tRNAPhe. This indicates that the two binding sites for tRNA on 40 S subunits should be considered as the constituent of P and A sites of 80 S ribosomes.


Studying Behaviors Among Neurosurgery Residents Using Web 2.0 Analytic Tools.
Web 2.0 technologies (e.g., blogs, social networks, and wikis) are increasingly being used by medical schools and postgraduate training programs as tools for information dissemination. These technologies offer the unique opportunity to track metrics of user engagement and interaction. Here, we employ Web 2.0 tools to assess academic behaviors among neurosurgery residents. We performed a retrospective review of all educational lectures, part of the core Neurosurgery Residency curriculum at the University of Toronto, posted on our teaching website (www.TheBrainSchool.net). Our website was developed using publicly available Web 2.0 platforms. Lecture usage was assessed by the number of clicks, and associations were explored with lecturer academic position, timing of examinations, and lecture/subspecialty topic. The overall number of clicks on 77 lectures was 1079. Most of these clicks were occurring during the in-training examination month (43%). Click numbers were significantly higher on lectures presented by faculty (mean = 18.6, standard deviation ± 4.1) compared to those delivered by residents (mean = 8.4, standard deviation ± 2.1) (p = 0.031). Lectures covering topics in functional neurosurgery received the most clicks (47%), followed by pediatric neurosurgery (22%). This study demonstrates the value of Web 2.0 analytic tools in examining resident study behavior. Residents tend to "cram" by downloading lectures in the same month of training examinations and display a preference for faculty-delivered lectures.


Identification of two novel synaptic γ-secretase associated proteins that affect amyloid β-peptide levels without altering Notch processing.
Synaptic degeneration is one of the earliest hallmarks of Alzheimer disease (AD) and results in loss of cognitive function. One of the causative agents for the synaptic degeneration is the amyloid β-peptide (Aβ), which is formed from its precursor protein by two sequential cleavages mediated by β- and γ-secretase. We have earlier shown that γ-secretase activity is enriched in synaptic compartments, suggesting that the synaptotoxic Aβ is produced locally. Proteins that interact with γ-secretase at the synapse and regulate the production of Aβ can therefore be potential therapeutic targets. We used a recently developed affinity purification approach to identify γ-secretase associated proteins (GSAPs) in synaptic membranes and synaptic vesicles prepared from rat brain. Liquid chromatography-tandem mass spectrometry analysis of the affinity purified samples revealed the known γ-secretase components presenilin-1, nicastrin and Aph-1b along with a number of novel potential GSAPs. To investigate the effect of these GSAPs on APP processing, we performed siRNA experiments to knock down the expression of the GSAPs and measured the Aβ levels. Silencing of NADH dehydrogenase [ubiquinone] iron-sulfur protein 7 (NDUFS7) resulted in a decrease in Aβ levels whereas silencing of tubulin polymerization promoting protein (TPPP) resulted in an increase in Aβ levels. Treatment with γ-secretase inhibitors often results in Notch-related side effects and therefore we also studied the effect of the siRNAs on Notch processing. Interestingly, silencing of TPPP or NDUFS7 did not affect cleavage of Notch. We also studied the expression of TPPP and NDUFS7 in control and AD brain and found NDUFS7 to be highly expressed in vulnerable neurons such as pyramidal neurons in the hippocampus, whereas TPPP was found to accumulate in intraneuronal granules and fibrous structures in hippocampus from AD cases. In summary, we here report on two proteins, TPPP and NDUFS7, which interact with γ-secretase and alter the Aβ levels without affecting Notch cleavage.


Immunocytochemical localization of vitamin D-dependent calcium-binding protein in the yolk sac of the rat.
The yolk sac from normal pregnant rats contains a vitamin D-dependent calcium-binding protein (CaBP). To localize CaBP within the yolk sac, a rabbit antiserum specifically directed against purified rat CaBP, in indirect immunofluorescence and immunoperoxidase, has been used. Using yolk sac sections, positive reactions indicative of the presence of CaBP were found only in the endodermal cell layer. A method for isolation of pure endodermal cells, using EDTA treatment, was developed. On smears of isolated endodermal cells exposed to anti-CaBP antiserum, CaBP was distributed throughout the endodermal cytoplasm; no CaBP was detected in the nucleus. Our results suggest that the endodermal cells, which are functional absorptive cells of the yolk sac, may play a role in vitamin D-mediated processes.


Population Thinking Instruction in High Schools: a Public Health Intervention with Triple Benefits.
America faces a series of intersecting problems that relate to health inequities, failing schools, and an inadequate science, technology, engineering, and math (STEM) workforce, particularly in cities and among low-income Black and Latino youth. Here, we propose a solution, namely reforming secondary school education to include mandatory exposure to population thinking instruction to address these overlapping issues. Public health education has expanded in recent decades in undergraduate education, though it has yet to become an integral component of high school curricula. In this paper, we make the case that all youth should gain exposure to the skills of population thinking through public health education initiated in high school. We further provide a rationale for this approach drawn from multiple youth development frameworks and the community schools movement for honing youth critical thinking skills and problem solving relating to individual and community health, policy, and activism.


Rapid aneuploidy diagnosis by multiplex ligation-dependent probe amplification and array comparative genomic hybridization in pregnancy with major congenital malformations.
To report five cases of major congenital malformations associated with common aneuploidies detected by rapid aneuploidy diagnosis. The fetus in the first case presented cebocephaly, semilobar holoprosencephaly, and tetralogy of Fallot on ultrasound at 25 gestational weeks. Cordocentesis using multiplex ligation-dependent probe amplification to detect aneuploidies of chromosomes X, Y, 13, 18, and 21 in uncultured cord blood revealed three copies of all targets on chromosome 13 consistent with the diagnosis of trisomy 13. The fetus in the second case presented bilateral choroid plexus cysts, congenital diaphragmatic hernia, and club foot on ultrasound at 18 gestational weeks. Amniocentesis using array-based comparative genomic hybridization (aCGH) in uncultured amniocytes revealed a gain in the DNA dosage of chromosome 18 consistent with the diagnosis of trisomy 18. The fetus in the third case presented aortic stenosis and nuchal edema on ultrasound at 22 gestational weeks. Amniocentesis using aCGH in uncultured amniocytes revealed a result of monosomy X and Turner syndrome. The fetus in the fourth case presented nuchal cystic hygroma and ventriculomegaly on ultrasound at 17 gestational weeks. Amniocentesis using aCGH in uncultured amniocytes revealed a gain in the DNA dosage of chromosome 21 consistent with the diagnosis of trisomy 21. The fetus in the fifth case presented holoprosencephaly, omphalocele, and hydronephrosis on ultrasound at 17 gestational weeks. Amniocentesis using aCGH in uncultured amniocytes revealed a gain in the DNA dosage of chromosome 13 consistent with the diagnosis of trisomy 13. Prenatal diagnosis of major congenital malformations should alert one to the possibility of chromosomal abnormalities. Multiplex ligation-dependent probe amplification and aCGH have the advantage of rapid aneuploidy diagnosis of common aneuploidies in cases with major congenital malformations.


Effect of Iron-Carbon Micro-Electrolysis-Fenton on the Dewatering Performance of Sludge.
In this paper, combined with iron-carbon micro-electrolysis-Fenton method, the sludge was adjusted, and the cracking performance and dewatering performance of the sludge were studied. Single factor experiments show that when the amount of iron powder is 1.2 g/L, the reaction time is 45 min, H2 O 2When the dosage was 4.2 g/L, the protein and polysaccharide content in the sludge decreased by 46.8 and 20.6, respectively. Compared with the original sludge %. Compared with the original sludge, the COD of the supernatant of the solution increased by 10.1%. The minimum moisture content of the treated sludge cake was 69%, and the SRF value was significantly reduced.The lowest value is 2.687×10 12 m/kg. During the micro-electric dust removal sludge, the Fe 2+can form a Fenton reagent with H2 O 2, thereby reducing the amount of additional iron powder that needs to be added in the conventional Fenton reaction. Three-dimensional fluorescence spectroscopy analysis showed that the humic acid and fulvic acid in the supernatant of the iron-carbon micro-electrolysis-Fenton conditioning solution increased more than after single electrolysis, indicating that the dehydration performance of the sludge was better.The Fenton reagent is formed , thereby reducing the amount of iron powder that needs to be added extra in the conventional Fenton reaction.


Rat models of human diseases and related phenotypes: a systematic inventory of the causative genes.
The laboratory rat has been used for a long time as the model of choice in several biomedical disciplines. Numerous inbred strains have been isolated, displaying a wide range of phenotypes and providing many models of human traits and diseases. Rat genome mapping and genomics was considerably developed in the last decades. The availability of these resources has stimulated numerous studies aimed at discovering causal disease genes by positional identification. Numerous rat genes have now been identified that underlie monogenic or complex diseases and remarkably, these results have been translated to the human in a significant proportion of cases, leading to the identification of novel human disease susceptibility genes, helping in studying the mechanisms underlying the pathological abnormalities and also suggesting new therapeutic approaches. In addition, reverse genetic tools have been developed. Several genome-editing methods were introduced to generate targeted mutations in genes the function of which could be clarified in this manner [generally these are knockout mutations]. Furthermore, even when the human gene causing a disease had been identified without resorting to a rat model, mutated rat strains (in particular KO strains) were created to analyze the gene function and the disease pathogenesis. Today, over 350 rat genes have been identified as underlying diseases or playing a key role in critical biological processes that are altered in diseases, thereby providing a rich resource of disease models. This article is an update of the progress made in this research and provides the reader with an inventory of these disease genes, a significant number of which have similar effects in rat and humans.


The methyl-CpG binding protein MeCP2 is essential for embryonic development in the mouse.
Vertebrate genomes are heavily methylated at cytosines in the sequence CpG. The biological role of this modification is probably mediated by DNA binding proteins that are either attracted to or repelled by methyl-CpG. MeCP2 is an abundant chromosomal protein that binds specifically to methylated DNA in vitro, and depends upon methyl-CpG for its chromosomal distribution in vivo. To assess the functional significance of MeCP2, the X-linked gene was mutated in male mouse embryonic stem (ES) cells using a promoterless gene-targeting construct containing a lacZ reporter gene. Mutant ES cells lacking MeCP2 grew with the same vigour as the parental line and were capable of considerable differentiation. Chimaeric embryos derived from several independent mutant lines, however, exhibited developmental defects whose severity was positively correlated with the contribution of mutant cells. The results demonstrate that MeCP2, like DNA methyltransferase, is dispensable in stem cells, but essential for embryonic development.


A literature review of the language needs of nursing students who have English as a second/other language and the effectiveness of English language support programmes.
Australia is increasingly becoming a culturally diverse country, with this trend being reflected in nursing education as significant numbers of students enrol from backgrounds where English is a second/other language (ESL). These students will enable the provision of culturally competent care that a culturally diverse health system requires (Ohr et al., 2010), however they require significant levels of support to not only achieve academically in their nursing programme, but also to perform at the expected level during clinical placements (Boughton et al., 2010). Difficulties communicating with colleagues, patients and their families in the clinical setting have been identified among the challenges that ESL nurses face (Boughton et al., 2010; Jeong et al., 2011). A review of the literature indicates sporadic research into the education of nurses from ESL backgrounds. This paper discusses and raises awareness of common themes such as the challenges of adjusting to Western culture and using the advanced and technical English required by higher education and healthcare. This paper also discusses mixed results reported from a number of English language support programmes. This indicates a need for further research in this area to strengthen support for these nurses who can assist in the provision of culturally competent care.


Computation of surface slant from optic flow: orthogonal components of speed gradient can be combined.
In previous work [Meese et al. (1995). Vision Research, 35, 2879-2888)] we showed that one-dimensional (1D) speed gradients are sufficient to produce a compelling impression of surface slant. Summing a 1D vertical shearing gradient or, less intuitively, a 1D horizontal shearing gradient with a random field of horizontally translating dots produces perceived slant about a horizontal axis. Similarly, a 1D vertical or horizontal compression gradient produces perceived slant about a vertical axis. Appropriately combining orthogonal 1D shears or compressions produces a purely deforming flow pattern. Here we asked whether both the vertical and horizontal components in such a stimulus contribute to perceived slant. Using a matching technique we found that for surfaces inclined about a vertical axis, this was indeed the case and that horizontal and vertical compression gradients contributed roughly equally to perceived slant. Similarly, for surfaces inclined about a horizontal axis, both vertical and horizontal shearing gradients contributed to the perceived slant, though here the horizontal gradient was given less weight than the vertical. We conclude that under appropriate conditions, the human visual system combines orthogonal speed gradients prior to the computation of slant from retinal flow.


An ecotoxicological approach for the Boka Kotorska Bay (south-eastern Adriatic Sea): first evaluation of lysosomal responses and metallothionein induction in mussels.
Mytilus galloprovincialis was used as a biomonitoring organism in Boka Kotorska Bay, a coastal transitional ecosystem in south-western Montenegro. Native mussels were collected in June 2008 at four sites thought to be differently impacted. Biological effects were investigated analysing both generic and specific biomarkers at cellular level (metallothionein content, lysosomal membrane stability, lipofuscin and neutral lipid accumulation, lysosomal structural changes). Trace element levels in mussels were quite low, only Cu and Zn exhibiting slight increases in the two sampling sites of Tivat Bay, the first one in front of a small working dockyard and the other in the water area of a former Naval dockyard. Mussels collected from these sites exhibited the highest values in neutral lipid and lysosomal volume density and the lowest neutral red retention times. Metallothionein content was always low, reflecting the minor body burden of the trace elements and suggesting a non-relevant environmental induction.


New combinations, synonymy and emendations can only be proposed based on names that were previously validly published.
Recently, articles were published in this journal in which new combinations were published based on basonyms that were not validly published at the time of submission, or a name not yet validly published was proposed as a later heterotypic synonym of another name. We here wish to remind authors and editors of the relevant rules of the International Code of Nomenclature of Prokaryotes that regulate the procedure for valid publication of names and specifically, of the fact that names in online pre-publication articles in the journal's website are not validly published.


The trypanolytic factor of human serum.
African trypanosomes (the prototype of which is Trypanosoma brucei brucei) are protozoan parasites that infect a wide range of mammals. Human blood, unlike the blood of other mammals, has efficient trypanolytic activity, and this needs to be counteracted by these parasites. Resistance to this activity has arisen in two subspecies of Trypanosoma brucei - Trypanosoma brucei rhodesiense and Trypanosoma brucei gambiense - allowing these parasites to infect humans, and this results in sleeping sickness in East Africa and West Africa, respectively. Study of the mechanism by which T. b. rhodesiense escapes lysis by human serum led to the identification of an ionic-pore-forming apolipoprotein - known as apolipoprotein L1 - that is associated with high-density-lipoprotein particles in human blood. In this Opinion article, we argue that apolipoprotein L1 is the factor that is responsible for the trypanolytic activity of human serum.


Providing dental care to patients with developmental disabilities. An introduction for the private practitioner.
During the past 20 to 25 years, in New York State, most individuals with developmental disabilities who had previously been housed in large institutions have been mainstreamed into community-based residences. This shift has created a need for dental services in the community. The article presented here provides information and tips to assist the general practitioner with integrating these patients into a private practice setting.


New species, phylogeny, host-associations and geographic distribution of genus Cryptosporella (Gnomoniaceae, Diaporthales).
The phylogeny of Cryptosporella is revised to include recently discovered species. Eight species new to science are described and two new combinations are proposed, raising the total number of species accepted in Cryptosporella to 19. The species delimitation and phylogeny for Cryptosporella are determined based on analyses of DNA sequences from three genes (β-tubulin, ITS and tef1-α), comparative morphology of sexual structures on their host substrate, and host associations. The inferred phylogeny suggests that Cryptosporella has speciated primarily on Betulaceae with 16 species occurring on hosts in that plant family. The host range of most species seems to be narrow with nine species reported from a single host species or subspecies and seven species occurring on plants within a single host genus. A key to species is provided. The known distribution of Cryptosporella is expanded to mountain cloud forests of the provinces of Chiriquí in Panama and Tucumán in Argentina.


Using high throughput screens to predict miscarriages with placental stem cells and long-term stress effects with embryonic stem cells.
A problem in developmental toxicology is the massive loss of life from fertilization through gastrulation, and the surprising lack of knowledge of causes of miscarriage. Half to two-thirds of embryos are lost, and environmental and genetic causes are nearly equal. Simply put, it can be inferred that this is a difficult period for normal embryos, but that environmental stresses may cause homeostatic responses that move from adaptive to maladaptive with increasing exposures. At the lower 50% estimate, miscarriage causes greater loss-of-life than all cancers combined or of all cardio- and cerebral-vascular accidents combined. Surprisingly, we do not know if miscarriage rates are increasing or decreasing. Overshadowed by the magnitude of miscarriages, are insufficient data on teratogenic or epigenetic imbalances in surviving embryos and their stem cells. Superimposed on the difficult normal trajectory for peri-gastrulation embryos are added malnutrition, hormonal, and environmental stresses. An overarching hypothesis is that high throughput screens (HTS) using cultured viable reporter embryonic and placental stem cells (e.g., embryonic stem cells [ESC] and trophoblast stem cells [TSC] that report status using fluorescent reporters in living cells) from the pre-gastrulation embryo will most rapidly test a range of hormonal, environmental, nutritional, drug, and diet supplement stresses that decrease stem cell proliferation and imbalance stemness/differentiation. A second hypothesis is that TSC respond with greater sensitivity in magnitude to stress that would cause miscarriage, but ESC are stress-resistant to irreversible stemness loss and are best used to predict long-term health defects. DevTox testing needs more ESC and TSC HTS to model environmental stresses leading to miscarriage or teratogenesis and more research on epidemiology of stress and miscarriage. This endeavor also requires a shift in emphasis on pre- and early gastrulation events during the difficult period of maximum loss by miscarriage.


Long-term sleep apnea as a pathogenic factor for cell-mediated autoimmune disease.
Previous medical literature has shown that cell injury from hypoxia, such as that induced by sleep apnea, leads to hyperuricemia. Furthermore, a recent study has shown that when hyperuricemia reaches sufficient concentration to precipitate as monosodium urate, a T-cell immune response is triggered. The frequent repetition of this cell injury and immune response over a prolonged time, as would occur with long-term sleep apnea, may lead to the development, continuation, or aggravation of autoimmune disease. Long-term sleep apnea is hypothesized to be a pathogenic factor in the development of cell-mediated autoimmune disease. Several corollaries are presented along with this general hypothesis. First, some of the diseases associated with sleep apnea may have an autoimmune etiology. Second, some autoimmune diseases not usually recognized to be associated with sleep apnea may indeed have that association. Third, resolving sleep apnea in some patients with autoimmune disease to remove that autoimmune stimulus may aid in deceleration, halt, or even reversal of the progress of the autoimmune disease. Fourth, because monosodium urate also causes gouty arthritis in some individuals, diagnosis of gout may allow for resolution of sleep apnea early enough to prevent autoimmune development. Fifth, allopurinol, which suppresses uric acid generation, may be an effective therapy for the remission or prevention of a number of autoimmune diseases. This hypothesis strengthens the evidence pointing to the danger of unresolved sleep apnea by a mechanism previously unrecognized, namely the risk of developing an autoimmune disease. As a result of this realization, new therapies may be adopted for the treatment and prevention of autoimmune disease, specifically, resolving sleep apnea and the use of allopurinol.


Tandem mass spectrometry of trimethylsilyl-terminated poly(dimethylsiloxane) ammonium adducts generated by electrospray ionization.
Ammonium adducts of trimethylsilyl-terminated poly(dimethylsiloxane) (CH(3)-PDMS) produced by electrospray ionization were submitted to collision induced dissociation and revealed a particular MS/MS behavior: the same three main product ions at m/z 221, 295, and 369 were always generated in very similar relative abundances regardless of the size of the precursor ion. Combining accurate mass measurements and ab initio calculation allowed very stable cyclic geometries to be obtained for these ionic species. Dissociation mechanisms were proposed to account for the three targeted ions to be readily generated in a two-step or a three-step reaction from any CH(3)-PDMS ammonium adducts. A second set of three product ions was also observed with low abundance at m/z 207, 281, and 355, which were shown in MS(3) experiments to be formed in secondary reactions. An alternative dissociation process was shown to consist of a concerted elimination of ammonia and methane and the need for a methyl of an end-group to be involved in the released methane molecule would account for this reaction to mainly proceed from the smallest precursor ions.


Overexpression of the ZmSUS1 gene alters the content and composition of endosperm starch in maize (Zea mays L.).
ZmSUS1 increases the amylose content of maize by regulating the expression of Shrunken2 (Sh2) and Brittle2 (Bt2) which encode the size subunits of endosperm ADP-glucose pyrophosphorylase, and Granule bound starchsynthase1 (GBSS1) and Starch synthase1 (SS1). Cereal crops accumulate starch in seeds as an energy reserve. Sucrose Synthase (SuSy) plays an important role in grain starch synthesis. In this study, ZmSUS1 was transformed into maize inbred line KN5585, and transgenic plants were obtained. Compared with the non-transgenic negative control, the content and activity of SuSy were significantly increased, the amylose content in mature seeds of transgenic maize increased by 41.1-69.2%, the total starch content increased by 5.0-13.5%, the 100-grain weight increased by 19.0-26.2% and the average diameter of starch granules increased by 10.8-17.2%. These results indicated that overexpression of ZmSUS1 can significantly improve the traits of maize seeds and obtain new lines with high amylose content. It was also found that the overexpression of ZmSUS1 may increase the amylose content by altering the expression of endosperm ADP-glucose pyrophosphorylase (AGPase) subunits Shrunken2 (Sh2) and Brittle2 (Bt2). Moreover, the ectopic expression of ZmSUS1 also affected the expression of Granule bound starch synthase1 (GBSS1) and Starch synthase1 (SS1) which encode starch synthase. This study proved the important role of ZmSUS1 in maize starch synthesis and provided a new technology strategy for improving maize starch content and yield.


Comparison of Autologous Osteoperiosteal and Osteochondral Transplantation for the Treatment of Large, Medial Cystic Osteochondral Lesions of the Talus.
Autologous osteoperiosteal transplantation (AOPT) using graft harvested from the iliac crest is used to treat large cystic osteochondral lesions of the talus (OLTs). However, no studies have compared clinical and radiologic outcomes between AOPT and autologous osteochondral transplantation (AOCT) using graft harvested from the nonweightbearing zone of the femoral condyle of the ipsilateral knee in patients with large cystic OLTs. To compare clinical and radiologic outcomes between patients undergoing AOPT and those undergoing AOCT for large cystic OLTs. Cohort study; Level of evidence, 3. Between March 2015 and March 2018, patients who underwent AOCT and AOPT to treat medial large cystic OLTs (>10 mm) were retrospectively evaluated. For comparability, the 2 groups were matched 1:1 based on their characteristics, including sex, age, body mass index, side of injury, follow-up period, and the preoperative cyst volume. After propensity score matching, 23 patients were enrolled in each group for the analysis. Clinical outcomes were assessed using the visual analog scale (VAS), the American Orthopaedic Foot & Ankle Society (AOFAS) score, and the Tegner score. Donor-site morbidity was recorded according to the symptoms, including pain, stiffness, swelling, and discomfort. In addition, the Lysholm score was used to assess the most common knee donor-site morbidity. Radiologic outcomes were evaluated using the magnetic resonance observation of cartilage repair tissue (MOCART) score, and the International Cartilage Regeneration & Joint Preservation Society (ICRS) score was obtained during second-look surgery. The mean follow-up period was about 48 months. There were no significant differences in patient characteristics and lesion volumes between groups. Postoperative ankle pain VAS score, AOFAS score, and Tegner score were not significantly different between groups at final follow-up. Total donor-site morbidity (P = .004) and discomfort morbidity (P = .009) were significantly lower in the AOPT group than in the AOCT group. However, the Lysholm score showed no significant difference between the donor knee and the opposite knee (P = .503) in the AOCT group. The MOCART and ICRS scores were not significantly different between groups. Clinical and radiologic outcomes of patients who underwent AOPT from the iliac crest were found to be comparable with those of patients who underwent AOCT from the ipsilateral knee for the treatment of medial large cystic OLTs. These results may be helpful for orthopaedic surgeons to decide appropriate treatments for patients with large cystic OLTs.


Farmers' assessment of the social and ecological values of land uses in central highland Ethiopia.
Often in land use evaluations, especially those in developing countries, only the financial aspect receives serious attention, while the social and ecological values are overlooked. This study compared the social and ecological values of four land use types (small-scale woodlot [SSW], boundary tree and shrub planting [BTP], homestead tree and shrub growing [HTG] and cereal farming [CF]) by a criteria-based scoring approach using a bao game. The impacts of local wealth status and proximity to a forest on the value the community renders to the land use types were also assessed. The value comparison, assessed by relative scoring, was accompanied by farmer's explanations to reveal the existing local knowledge about land use values. It was found that HTG ≥ SSW > BTP > CF for both social and ecological values. Though this trend applies for the medium and rich households, the poor ones chose SSW as the most valuable. With increasing distance from a forest, the social and ecological values of land uses increased. The accompanying scoring justifications indicated the existence of in-depth ecological knowledge, which conform to contemporary scientific reports. Generally, this study showed that social and ecological values, besides financial values, strongly influence farmer's decision in implementing various practices related to the land use types. Thus, such values are worth considering for a holistic understanding of the diverse benefits of land uses. Finally, the strong preference for tree and shrub-based land use types is a good opportunity for enhancing tree and shrub growing to minimize the major environmental problems (e.g., soil degradation, wood shortage and deforestation) in the central highlands of Ethiopia.


Understanding cross-data dynamics of individual and social/environmental factors through a public health lens: explainable machine learning approaches.
The rising prevalence of obesity has become a public health concern, requiring efficient and comprehensive prevention strategies. This study innovatively investigated the combined influence of individual and social/environmental factors on obesity within the urban landscape of Seoul, by employing advanced machine learning approaches. We collected 'Community Health Surveys' and credit card usage data to represent individual factors. In parallel, we utilized 'Seoul Open Data' to encapsulate social/environmental factors contributing to obesity. A Random Forest model was used to predict obesity based on individual factors. The model was further subjected to Shapley Additive Explanations (SHAP) algorithms to determine each factor's relative importance in obesity prediction. For social/environmental factors, we used the Geographically Weighted Least Absolute Shrinkage and Selection Operator (GWLASSO) to calculate the regression coefficients. The Random Forest model predicted obesity with an accuracy of >90%. The SHAP revealed diverse influential individual obesity-related factors in each Gu district, although 'self-awareness of obesity', 'weight control experience', and 'high blood pressure experience' were among the top five influential factors across all Gu districts. The GWLASSO indicated variations in regression coefficients between social/environmental factors across different districts. Our findings provide valuable insights for designing targeted obesity prevention programs that integrate different individual and social/environmental factors within the context of urban design, even within the same city. This study enhances the efficient development and application of explainable machine learning in devising urban health strategies. We recommend that each autonomous district consider these differential influential factors in designing their budget plans to tackle obesity effectively.


Leadership and management in the undergraduate medical curriculum: a qualitative study of students' attitudes and opinions at one UK medical school.
To explore undergraduate medical students' attitudes towards and opinions about leadership and management education. Between 2009 and 2012 we conducted a qualitative study comprising five focus group discussions, each devoted to one of the five domains in the Medical Leadership Competency Framework, (Personal Qualities, Working with Others, Managing Services, Improving Services and Setting Direction). Each discussion examined what should be learnt, when should learning occur, what methods should be used, how should learning be assessed, what are the barriers to such education. 28 students from all three clinical years (4-6) of whom 10 were women. 2 inter-related themes emerged: understanding the broad perspective of patients and other stakeholders involved in healthcare provision and the need to make leadership and management education relevant in the clinical context. Topics suggested by students included structure of the National Health Service (NHS), team working skills, decision-making and negotiating skills. Patient safety was seen as particularly important. Students preferred experiential learning, with placements seen as providing teaching opportunities. Structured observation, reflection, critical appraisal and analysis of mistakes at all levels were mentioned as existing opportunities for integrating leadership and management education. Students' views about assessment and timing of such education were mixed. Student feedback figured prominently as a method of delivery and a means of assessment, while attitudes of medical professionals, students and of society in general were seen as barriers. Medical students may be more open to leadership and management education than thought hitherto. These findings offer insights into how students view possible developments in leadership and management education and stress the importance of developing broad perspectives and clinical relevance in this context.


The polyclonal B cell activator dextran-sulphate induces formation of colony stimulating activity.
The effect of dextran-sulphate (DS), a polyclonal activator known to stimulate immature murine B-cells, was assayed in a culture system allowing the growth of myeloid cells. It was known that DS induced the production of a myeloid colony stimulating factor (CSF) by cells from both spleen and bone marrow. Nylonwool purified mouse spleen cells, enriched for T cells, showed a dimished CSF production in response to DS, while CSF production in response to Con A was increased. Furthermore, DS induced CSF in both spleen and bone marrow cells from nude mice. Removal of macrophages did not affect CSF production. The CSF induced was non-dialysable and no small molecular weight or lipoprotein inhibitors could be demonstrated. The results suggest that DS activates cells other than T cells or macrophages (possibly B cells or null cells) to produce a myeloid stem cell stimulating substance. These results indicate that interactions between lymphoid and myeloid cells can take place during differentiation.


Population parameters for birth and ewe fleece weight at different parities in Baluchi sheep.
ZUSAMMENFASSUNG: Populationsparameter für Geburts- und Vließgewicht von Baluchi Schafen Das Datenmarterial stammt von zwei Herden einer Schafzuchtstation in NO Iran aus den Jahren 1966-1989. Die Tiere waren unselektiert und stammten aus zufällig verteilten Paarungen. Es wurden Geburtsgewicht und Vließgewicht bei verschiedenen Altersstufen erhoben und Varianzkomponenten mittels Restringierter Maximaler Likelihood mit einem bivariaten Tiermodell mit fixen Wirkungen von Jahr, Geschlecht, Geburtstyp und Parität sowie Zufallswirkungen für additiven Genotyp des Lammes (direkt) und des Mutterschafes (maternal), gemeinsamer Umwelt (ausgenommen Vließgewicht) und Resteinfluß geschätzt. Direkte und maternale genetische Korrelationen zwischen Leistungen verschiedener Paritäten wurden berechnet. In Herde 1 scheinen Varianzen und Heritabilitätswerte für Lammgewicht bis Parität 5 zuzunehmen, kaum aber in Herde 2. Die durchschnittlichen Heritabilitätswerte, direkt, maternal und gesamt waren 0.12, 0.11 und 0.26, die genetische Korrelation zwischen direkten und maternalen Wirkungen 0.42. Bei Vließgewicht waren in Herde 1 keine Veränderungen der Varianzen und Heritabilitätswerte mit Alter zu erkennen, aber bei Herde 2 nahmen phänotypische und Umweltvarianz mit Alter leicht zu. Durchschnittliche direkte, maternale und Gesamtheritabilität waren 0.19, 0.04 und 0.22, die genetische Korrelation zwischen direkten und maternalen Wirkungen geringgradig positiv in Herde 1, aber mit Alter zunehmend negativ in Herde 2. Die genetischen Korrelationen für direkte Wirkungen auf Geburtsgewicht waren hoch zwischen Paritäten 1 bis 5, aber niedriger bei Parität 6 und jene zwischen maternal bedingten Wirkungen zeigten ähnliche Trends. In Herde 2 waren Werte mit Parität 6 ähnlich wie die zwischen den übrigen Paritäten. Die die Vließgewichte betreffenden direkt genetischen Korrelationen zwischen Paritäten waren in beiden Herden ähnlich (0.73-0.92), jene, die maternale Wirkungen betreffen, deutlich geringer, besonders soweit sie Paritäten 5 und 6 betroffen haben und zeigten besonders bei Herde 2 starke Schwankungen (-0.54 bis 0.74). Direct and maternal performance of ewes at different parities were examined in Baluchi sheep. The data set was collected during the period 1966-1989 from two flocks at a sheep breeding station in the north-east of Iran. The animals included in the data set were unselected and randomly mated. The traits analysed were birth weight of lamb and fleece weight at different parities of the ewe. Variance components were estimated using Restricted Maximum Likelihood with a bivariate animal model including fixed effects of year, sex, type of birth and parity, and random effects of additive genotype of lamb (direct genetic effect), additive genotype of ewe (maternal genetic effect) and common environment (excluded for ewe fleece weight), and random residual effect. Direct and maternal genetic correlations between different parities were estimated. There was evidence of increasing phenotypic and genetic variances and heritabilities from parity 5 for birth weight of lamb in flock 1, but only evidence of a slightly increasing age trend for the environmental and phenotypic variance in flock 2. The average heritabilities over flocks and parities were 0.12, 0.11 and 0.26 for the direct, maternal and total heritability, respectively, while the average genetic correlation between direct and maternal effects for this trait was 0.42. There were no indications of any age changes in variances or heritabilities for ewe fleece weight in flock 1, but indications of slightly increasing age trends for the environmental and phenotypic variance. The average heritabilities over flocks and parities were 0.19, 0.04 and 0.22 for the direct, maternal and total heritability, respectively, while the average genetic correlation between direct and maternal effects was slightly positive in flock 1 but increasingly negative with age of the ewe in flock 2. Direct genetic correlations between parities 1-5 were very high for birth weight of lambs (on average 0.96) in contrast to the markedly lower correlations of parities 1-5 with parity 6 (on average 0.67) in flock 1 with a similar pattern for the maternal genetic correlations. In flock 2, these correlations were also high but without the marked decrease between parities 1-5 with parity 6 that was found in flock 1. Direct genetic correlations between the various parities for ewe fleece weight were similar for the two flocks, ranging from 0.73 to 0.92 and without any obvious differences between the various combinations of parities. However, the maternal were markedly lower than the direct genetic correlations, especially for the combinations of parity 5 and 6 with the earlier parities, and most pronounced in flock 2 fluctuating from -0.54 to 0.79. To obtain reliable estimates of breeding values for birth weight of lamb, it is recommended that the prediction should include not only earlier but also later parities (ages) of the ewe.


Out-of-pocket costs for childhood stroke: the impact of chronic illness on parents' pocketbooks.
Direct costs for children who had stroke are similar to those for adults. There is no information regarding the out-of-pocket costs families encounter. We described the out-of-pocket costs families encountered in the first year after a child's ischemic stroke. Twenty-two subjects were prospectively recruited at four centers in the United States and Canada in 2008 and 2009 as part of the "Validation of the Pediatric NIH Stroke Scale" study; families' indirect costs were tracked for 1 year. Every 3 months, parents reported hours they did not work, nonreimbursed costs for medical visits or other health care, and mileage. They provided estimates of annual income. We calculated total out-of-pocket costs in US dollars and reported costs as a proportion of annual income. Total median out-of-pocket cost for the year after an ischemic stroke was $4354 (range, $0-$28,666; interquartile range, $1008-$8245). Out-of-pocket costs were greatest in the first 3 months after the incident stroke, with the largest proportion because of lost wages, followed by transportation, and nonreimbursed health care. For the entire year, median costs represented 6.8% (range, 0%-81.9%; interquartile range, 2.7%-17.2%) of annual income. Out-of-pocket expenses are significant after a child's ischemic stroke. The median costs are noteworthy provided that the median American household had cash savings of $3650 at the time of the study. These results with previous reports of direct costs provide a more complete view of the overall costs to families and society. Childhood stroke creates an under-recognized cost to society because of decreased parental productivity.


The comet assay to determine the mode of cell death for the ultrasonic delivery of doxorubicin to human leukemia (HL-60 Cells) from Pluronic P105 micelles.
This notes examines the mode of cell death of HL-60 cells exposed to 70 kHz and 1.3 W/cm(2) ultrasound in the presence of 1% Pluronic P105 and 1.67 microg/ml doxorubicin (Dox). The cells were ultrasonicated for 30, 60, and 120 minutes. They were then lysed, electrophorised, stained using propidium iodide, and their DNA profile captured using a fluorescent microscope. The gradual DNA damage observed and the comet tails captured after one and two hours of insonation suggest that the mode of cell killing is apoptosis.


Importance of reactive oxygen species in the peritoneal fluid of women with endometriosis or idiopathic infertility.
To determine whether reactive oxygen species in peritoneal fluid might be a factor in infertility. Prospective study. Andrology laboratory and gynecology clinic at a tertiary care facility. Women with endometriosis (n = 15) or idiopathic infertility (n = 11) who underwent laparoscopy for infertility. Patients undergoing tubal ligation served as controls (n = 13). Aspiration of peritoneal fluid. Reactive oxygen species levels, presence of polymorphonuclear granulocytes, and leukocyte distribution in peritoneal fluid. Reactive oxygen species were present in the peritoneal fluid of patients with endometriosis, idiopathic infertility, and tubal ligation. Levels of reactive oxygen species did not show a statistically significant difference between patients with endometriosis and the control group in either unprocessed or processed (cell-free) peritoneal fluid, but did differ significantly between patients with idiopathic infertility and controls in processed peritoneal fluid. Polymorphonuclear granulocytes (> 1 x 10(6)/mL) were not present in the peritoneal fluid of any patient. Macrophage concentrations of peritoneal fluid did not differ significantly between controls and patients with endometriosis or idiopathic infertility. Reactive oxygen species in the peritoneal fluid may not affect fertility directly in women with endometriosis; however, they may have a role in patients with idiopathic infertility.


A design concept of planar conjugated ladder oligomers of perylene bisimides and efficient synthetic strategy via regioselective photocyclization.
By photocyclization, benzene, thieno[3,2-b]thiophene, and fluorene units were embedded between the two perylene units. Symmetric oligomeric perylene bisimide 6 displays broad absorption and strong electron-accepting ability.


IBPred: A sequence-based predictor for identifying ion binding protein in phage.
Ion binding proteins (IBPs) can selectively and non-covalently interact with ions. IBPs in phages also play an important role in biological processes. Therefore, accurate identification of IBPs is necessary for understanding their biological functions and molecular mechanisms that involve binding to ions. Since molecular biology experimental methods are still labor-intensive and cost-ineffective in identifying IBPs, it is helpful to develop computational methods to identify IBPs quickly and efficiently. In this work, a random forest (RF)-based model was constructed to quickly identify IBPs. Based on the protein sequence information and residues' physicochemical properties, the dipeptide composition combined with the physicochemical correlation between two residues were proposed for the extraction of features. A feature selection technique called analysis of variance (ANOVA) was used to exclude redundant information. By comparing with other classified methods, we demonstrated that our method could identify IBPs accurately. Based on the model, a Python package named IBPred was built with the source code which can be accessed at https://github.com/ShishiYuan/IBPred.


Hepatitis C transmission on the north coast of New South Wales: explaining the unexplained.
To determine the routes of hepatitis C virus (HCV) transmission in an Australian community. Questionnaire-based, cross-sectional survey of notified HCV cases. All cases notified to the New South Wales North Coast Public Health Unit between 1 January 1993 and 30 September 1994. Frequency of potential transmission exposures (parenteral and sexual); most likely primary exposure; HCV infection rates in sexual partners and offspring. 467 subjects responded (47% of resident cases). Of these, all but one reported actual or potential blood exposures (injecting drug user [IDU], 85%; IDU with sharing of injection equipment, 76%; pre-1990 blood transfusions, 6%; other blood exposures, 8%). Most subjects reported multiple exposures and none reported sexual contact as the only potential exposure. Of 233 sexual partners tested for HCV, 83 were positive; 54 of these were questioned and all had other parenteral exposures. Only three children out of 91 children tested were positive for HCV (two expressing maternal antibodies). In contrast with previous studies, possible HCV transmission modes were identified for almost all respondents. Most respondents in this community were IDUs. Non-parenteral transmission appeared minimal. Novel approaches to preventing HCV transmission in IDUs are needed.


Efficient Biosynthesis of Low-Molecular-Weight Poly-γ-glutamic Acid Based on Stereochemistry Regulation in Bacillus amyloliquefaciens.
Low-molecular-weight poly-γ-glutamic acid (LMW-γ-PGA) has attracted much attention because of its many potential applications in food, agriculture, medicine, and cosmetics. Enzymatic degradation is an efficient way for the synthesis of LMW-γ-PGA. However, the stereochemistry of γ-PGA limits the degradation of γ-PGA. This study identifies the role of γ-PGA synthase (pgsA) and glutamate racemase (racE) in the regulation of γ-PGA stereochemistry and demonstrates their combinational use for LMW-γ-PGA synthesis. First, the expression of pgsA and racE was enhanced, leading to improvements both in the molecular weight (Mw) and the d-glutamate proportion of γ-PGA. Then, an optimal combination of pgsA, racE, and γ-PGA hydrolase pgdS was constructed by exchanging the gene origins for the synthesis of LMW-γ-PGA. Finally, the Mw of γ-PGA was decreased to 6-8 kDa, which was much lower compared with the case without stereochemistry switching (20-30 kDa). This study provides a novel strategy to control the Mw of γ-PGA based on stereochemistry regulation and lays a solid foundation for synthesis of LMW-γ-PGA.


Release of florfenicol in seawater using chitosan-based molecularly imprinted microspheres as drug carriers.
Novel molecularly imprinted polymer (MIP) microspheres using functionalized chitosan as eco-friendly substrates were prepared by surface imprinting method and applied as drug delivery carriers to provide extended-release of florfenicol (FF) in seawater. The chitosan-based composites were characterized by scanning electron microscopy and Fourier transforms infrared spectroscopy analyses. The swelling behavior, adsorption capability, and selectivity for FF were investigated. The results show that the MIPs possessed high drug loading saturation capacity and specific recognition affinity for FF. The release studies of MIPs as drug delivery carriers were evaluated in natural seawater. The microspheres exhibited slow sustained release profiles of FF and the release behavior conformed to the first-order kinetic equation. The imprinted microspheres as drug delivery devices would be a promising application for improving the efficacy of the antibiotic without exposing the ecological system to excess FF in aquaculture.


Antibacterial and antibiofilm efficacy of repurposing drug hexestrol against methicillin-resistant Staphylococcus aureus.
There has been an explosion in the prevalence of methicillin-resistant Staphylococcus aureus (MRSA) because of the indiscriminate use of antibiotics. In this study, we repurposed hexestrol (HXS) as an antibacterial agent to fight planktonic and biofilm-related MRSA infections. HXS is a nonsteroidal synthetic estrogen that targets estrogen receptors (ERα and ERβ) and has been used as a hormonal antineoplastic agent. In our work, the minimum inhibitory concentrations (MICs) were determined using the antimicrobial susceptibility of MSSA and MRSA strains. Anti-biofilm activity was evaluated using biofilm inhibition and eradication assays. Biofilm-related genes were analyzed with or without HXS treatment using RTqPCR analysis of S. aureus. HXS was tested using the checkerboard dilution assay to identify antibiotics that may have synergistic effects. Measurement of ATP and detection of ATPase allowed the determination of bacterial energy metabolism. As shown in the results, HXS showed effective antimicrobial activity against S. aureus, including both type strains and clinical isolations, with MICs of 16 µg/mL. Sub-HXS strongly inhibited the adhesion of S. aureus. The content of extracellular polymeric substances (EPS) and the relative transcription levels of eno, sacC, clfA, pls and fnbpB were reduced after HXS treatment. HXS showed antibacterial effects against S. aureus and synergistic activity with aminoglycosides by directly interfering with cellular energy metabolism. HXS inhibits adhesion and biofilm formation and eradicates biofilms formed by MRSA by reducing the expression of related genes. Furthermore, HXS increases the susceptibility of aminoglycosides against MRSA. In conclusion, HXS is a repurposed drug that may be a promising therapeutic option for MRSA infection.


Efficient use of clinical EEG data for deep learning in epilepsy.
Automating detection of Interictal Epileptiform Discharges (IEDs) in electroencephalogram (EEG) recordings can reduce the time spent on visual analysis for the diagnosis of epilepsy. Deep learning has shown potential for this purpose, but the scarceness of expert annotated data creates a bottleneck in the process. We used EEGs from 50 patients with focal epilepsy, 49 patients with generalized epilepsy (IEDs were visually labeled by experts) and 67 controls. The data was filtered, downsampled and cut into two second epochs. We increased the number of input samples containing IEDs through temporal shifting and using different montages. A VGG C convolutional neural network was trained to detect IEDs. Using the dataset with more samples, we reduced the false positive rate from 2.11 to 0.73 detections per minute at the intersection of sensitivity and specificity. Sensitivity increased from 63% to 96% at 99% specificity. The model became less sensitive to the position of the IED in the epoch and montage. Temporal shifting and use of different EEG montages improves performance of deep neural networks in IED detection. Dataset augmentation can reduce the need for expert annotation, facilitating the training of neural networks, potentially leading to a fundamental shift in EEG analysis.


Determinants of response in a longitudinal health study following the firework-disaster in Enschede, The Netherlands.
Very few longitudinal health studies after disasters published data on the determinants of loss to follow up. However, these determinants provide important information for future disaster studies to improve their response and reduce selection bias. For this purpose we analyzed the data of a longitudinal health survey which was performed among residents and emergency workers, at 3 weeks (n = 3662) and at 18 months (n = 2769) after a major firework disaster in The Netherlands (Enschede, May 13, 2000). The response was lower among immigrants (54%) than among native Dutch (81%). Severe damage to the house due to the disaster (OR: 1.8; 95% CI: 1.1-3.0) and being involved as an emergency workers (OR: 2.1; 95% CI: 1.2-3.4) were associated with higher response among native Dutch, while this was not the case among immigrants. Non-western immigrants with health problems in the first study were more likely to participate in the second study (for example physical symptoms OR: 2.5: 95% CI: 1.4-4.4), while the native Dutch with these symptoms were less likely to participate (OR: 0.7; 95% CI: 0.5-0.9). In conclusion, disaster-related characteristics were associated with higher response in native Dutch. Health problems were associated with higher response among non-western immigrants and with lower response among the native Dutch.


Complete mitochondrial genome of Iksookimia hugowolfeldi and its phylogenetic position within genus Iksookimia.
In this study, the complete mitochondrial genome sequences of Iksookimia hugowolfeldi, Korean loach species, was determined using next-generation sequencing analysis. The complete mitogenome of I. hugowolfeldi has 16,634 bp in length and consists of 13 protein-coding genes (PCGs), 22 tRNAs, two rRNAs, and one control region (D-loop). Both gene orders and characteristics were exactly accord with mitochondrial genome of other species those belong to the family Cobitidae. Phylogenetic analysis revealed that the establishment of taxonomic relationship between Iksookimia and Cobitis has still uncompleted because of the not distinguished as monophyletic status.