Asymptomatic aggressive angiomyxoma with a two-year follow up in a middle-aged healthy male: A case report and brief review of literature.
A 48-year old male found to have an asymptomatic perineal mass during hospital evaluation for urolithiasis presented two years later for follow up. He underwent imaging which showed slow growth. He subsequently underwent surgical excision of the mass. Histopathology showed it to be an aggressive angiomyxoma. He is currently being followed up on and will continue to do so due to the recurrent nature of the tumor. This case highlights the asymptomatic presentation of aggressive angiomyxomas, consideration for the differential diagnosis in males with a pelvic mass, need for research to potentially prevent recurrence, and importance of follow-up.


Efficacy of methotrexate in reducing the risk of bone erosion in patients with rheumatoid arthritis: a systematic review of randomized controlled trials.
Even though new drugs for the treatment of rheumatoid arthritis (RA) have been developed, methotrexate (MTX) remains a commonly used drug for RA management. In addition to monitoring disease activity during RA treatment, bone erosion should be closely assessed throughout long-term RA management. In this review article, we present a systematic review of MTX effectiveness in reducing the risk of bone erosion. We reviewed randomized controlled trial studies that involved MTX monotherapy or MTX in combination with placebo. Evaluation of the progression of bone erosion was examined by radiographic assessment such as total Sharp score (TSS) or van der Heijde score (SvdH or vdH TSS), joint space narrowing (JSN), erosion score (ERO), and proportion of radiographic nonprogressors. Several key factors were found to influence the response to MTX treatment, such as gene polymorphism. The exact mechanism of the prevention of bone erosion by MTX remains unclear, which warrants future investigations. The variability of RA disease activity in study subjects resulted in variations in the results reported by individual studies. Collective analysis suggests that MTX could slow down the progression of bone erosion based on a radiographic score of less than 0.5-1/year.


Effects of high fat diet-induced obesity on pathophysiology, immune cells, and therapeutic efficacy in systemic lupus erythematosus.
Prior studies have suggested a strong link between obesity and autoimmune diseases. This study aimed to evaluate the effects of high fat diet (HFD)-induced obesity on the disease pathogenesis, immune cell infiltration, and therapeutic efficacy in systemic lupus erythematosus (SLE). Treatment with methylprednisolone significantly increased the survival in the control diet group, but not in the HFD group. An HFD significantly increased the incidence of severe proteinuria and glucose intolerance. Regardless of the diet, treatment with methylprednisolone significantly decreased the serum levels of anti-dsDNA antibodies, IL-2, IL-10, and interferon γ-induced protein 10 (IP-10), and improved the renal pathology scores. Treatment with methylprednisolone significantly lowered the serum levels of IL-6, MCP-1, and TNF-α in the control diet group, but not in the HFD group. HFD significantly increased the proportions of CD45+ and M1 cells and significantly decreased the proportion of M2 cells in white adipose tissue; methylprednisolone treatment significantly rescued this effect. In the HFD group, methylprednisolone treatment significantly decreased the M1:M2 and increased the Foxp3+:RORγt+ cell in the spleen compared with the untreated group. These data improve our understanding of the effect of HFD on the therapeutic efficacy of corticosteroids in SLE treatment, which could have clinical implications.


Cytomegalovirus in Pregnancy.
Cytomegalovirus is a pervasive DNA herpesvirus that, while clinically insignificant to an immunocompetent adult host, can cause significant morbidity to a congenitally infected fetus. Although detection is often possible with several common ultrasonographic markers and good diagnostic accuracy using polymerase chain reaction testing of amniotic fluid, there are no proven prenatal prevention or antenatal treatment options. Therefore, universal screening is not currently recommended in pregnancy. Strategies that have been studied in the past include immunoglobulins, antivirals, and the development of a vaccine. In this review, we will further discuss the themes above, along with future direction for prevention and treatment.


Validation of the curation pipeline of UniCarb-DB: building a global glycan reference MS/MS repository.
The UniCarb-DB database is an emerging public glycomics data repository, containing over 500 tandem mass spectra (as of March 2013) of glycans released from glycoproteins. A major challenge in glycomics research is to provide and maintain high-quality datasets that will offer the necessary diversity to support the development of accurate bioinformatics tools for data deposition and analysis. The role of UniCarb-DB, as an archival database, is to provide the glycomics community with open-access to a comprehensive LC MS/MS library of N- and O- linked glycans released from glycoproteins that have been annotated with glycosidic and cross-ring fragmentation ions, retention times, and associated experimental metadata descriptions. Here, we introduce the UniCarb-DB data submission pipeline and its practical application to construct a library of LC-MS/MS glycan standards that forms part of this database. In this context, an independent consortium of three laboratories was established to analyze the same 23 commercially available oligosaccharide standards, all by using graphitized carbon-liquid chromatography (LC) electrospray ionization (ESI) ion trap mass spectrometry in the negative ion mode. A dot product score was calculated for each spectrum in the three sets of data as a measure of the comparability that is necessary for use of such a collection in library-based spectral matching and glycan structural identification. The effects of charge state, de-isotoping and threshold levels on the quality of the input data are shown. The provision of well-characterized oligosaccharide fragmentation data provides the opportunity to identify determinants of specific glycan structures, and will contribute to the confidence level of algorithms that assign glycan structures to experimental MS/MS spectra. This article is part of a Special Issue entitled: Computational Proteomics in the Post-Identification Era. Guest Editors: Martin Eisenacher and Christian Stephan.


New technique in hepatic parenchymal transection for living related liver donor and liver neoplasms.
Many different surgical techniques have been described for hepatic parenchymal transection. A retrospective analysis of perioperative mortality, length of hospitalization and blood transfused during operation in two patient groups undergoing liver resection was carried out. In group A, we developed a new technique to resect hepatic parenchyma, using an ultrasonic surgical aspirator with monopolar floating ball cautery, while in group B the crushing clamp technique was used. In all, 42 patients with liver resection were enrolled in group A and 107 resections in group B. All patients had hepatic neoplasms except for seven living transplant donors. In group A 43% of resections involved >or=3 segments and 57% involved <or=2 segments; in group B 36.4% involved >or=3 segments and 63.6% consisted of <or=2 segments. Statistical analysis utilised independent T square (Pearson Q square) and Mann-Whitney U test. In group A 2.4% of patients died perioperatively, while 3.7% died in group B; mean length of stay (LOS) was 10.9 days in group B and 8.0 days in group A. The length of procedure was 7.5 h in group B and 6.7 h in group A. In group A, 79% did not undergo blood transfusion intraoperatively as opposed to 61% in group B. A mean of 0.5 U of blood was utilized in group A and 1.60 U in group B. The new method of parenchymal transection seems to reduce the LOS, length of procedure and need for intraoperative blood transfusion.


[Exercise-induced renal ischemia after kidney transplantation: report of two cases].
Renal transplant patients are high cardiovascular risk patients. Regular ultrasound surveillance of the renal transplant artery and the iliac artery upstream from the anastomosis is required to detect potential arterial stenosis. The purpose of this article was to illustrate the hemodynamic impact of exercise in such patients and the screening efficiency of Doppler ultrasound stress testing. Two renal transplant patients were hospitalized in our center for impaired renal function, worsening hypertension, and intermittent claudication. This association of peripheral vascular disease and renal dysfunction led us to perform a Doppler ultrasound stress test to search for vascular stenosis upstream from the graft. Hemodynamic fluctuations in the ipsilateral leg were recorded during flexion-extension exercises. Iliac artery lesions were found in both patients: the Doppler examination showed decreased systolic velocity in the graft artery during exercise, compatible with iliac steal syndrome. Surgical treatment was performed in both patients. After surgery, the control Doppler ultrasound stress test showed that systolic flow did not decline in the graft vessels during exercise. Renal function stabilized in one patient and improved in the other; claudication disappeared after surgery. Doppler ultrasound stress testing can be a valuable tool for detecting exercise-induced renal graft ischemia in transplant patients. Its screening performance should be determined in a larger population before routine use.


Diagnostic yield of a one sample immunochemical test at different cut-off values in an organised screening programme for colorectal cancer.
Quantitative immunochemical faecal occult blood tests have become the recommended tests for colorectal cancer screening. The aim of this study was to complete our knowledge on the performance of one of the quantitative immunochemical tests available, FOB-Gold, and to propose a possible strategy for an organised screening programme. Within the French organised screening programme, 23,231 average-risk individuals, aged 50-74 performed both a 3-day Hemoccult test and a 1-day FOB-Gold test. Performances of the immunochemical test were evaluated at different cut-off levels. The positivity rate for the Hemoccult was 2.1% and for the FOB-Gold varied between 4.6% (cut-off value of 100 ng/mL, the lowest studied cut-off) and 2.1% (cut-off value of 352 ng/mL). The number of colonoscopies decreased with increasing cut-off values by 21.5% (150 ng/mL), 35.4% (200 ng/mL) and 53.3% (352 ng/mL). The corresponding miss rate for CRC was respectively 6.4%, 11.1% and 22.2%, and for advanced adenoma respectively 16.3%, 29.2% and 43.6%. Compared with the reference cut-off for the FOB-Gold (100 ng/mL) the miss rate for Hemoccult was 53% for CRC and 77% for advanced adenoma. The study suggests that in countries with colonoscopy facilities compatible with a screening test positivity rate of up to 5%, use of a 1-day test with a cut-off value between 100 and 150 ng/mL could be the recommended strategy. Further increasing the cut-off value up to the same positivity rate as Hemoccult could be used in areas with limited access to colonoscopy.


Serum levels of nitric oxide metabolites during labour with or without combined spinal-epidural analgesia.
Combined spinal-epidural analgesia is effective in labour analgesia. Nitric oxide may play important roles in pregnancy and labour and is probably affected by labour pain. The aim of the present study was to explore the alteration in serum levels of nitric oxide metabolites, i.e. nitrate and nitrite, during labour with or without combined spinal-epidural analgesia. Fifty pregnant women were recruited at the cervical dilatation of 3 approximately 4 cm, 25 received combined spinal-epidural analgesia and 25 served as control. Twenty in the combined spinal-epidural analgesia group and 19 in the control group finished data collection and were included in the analysis. Blood samples were taken at study entry, full cervical dilation and 2 h after delivery. Total serum level of nitrite and nitrate was measured with enzymatic conversion and followed by Griess reaction. Visual analogue pain scores and mean blood pressure were monitored. After analgesia, pain score and mean blood pressure were significantly lower in the combined spinal-epidural analgesia group than in the control group (P 0.05) but significantly different at full cervical dilation and 2 h after delivery (P 0.05). Combined spinal-epidural analgesia provided effective analgesia and abolished the decrease in nitric oxide metabolites during active labour.


Coding of visual information by units in the cat cerebellar vermis.
Extracellular records were made of the responses to precisely controlled stationary or moving visual stimuli of 174 units in the cerebellar vermis of cats anaesthetised with chloralose. Identified Purkinje cells and unidentified units responsed similarly. Responses to ON and to OFF steps of a stationary light bar had different characteristics. Some units showed changes in the form of their ON responses related to different positions of the stimulus in their large receptive fields. In some cases changes in response latency from different field positions were also noted. Some units responded only to binocular stimulation and others gave much larger responses to binocular than to monocular stimulation. In addition, some were sensitive to the relative retinal disparity of images and, of these, several were sensitive to vertical as well as to horizontal retinal disparity. Sinusoidally-moving light bars gave responses consisting of one or two bursts of impulses per cycle; the most effective frequency was about 3 Hz. These responses may represent detection of the instant of maximum velocity. The relatively precise coding of retinal disparity in spite of the large size of receptive fields and the coding of position within these large fields is discussed. A possible function for the disparity-sensitive units in the control of vergence is suggested and the relation of this control to visual depth detection and to the estimation of the absolute distance of objects from the animal is discussed.


A chronic model of atypical absence seizures: studies of developmental and gender sensitivity.
Treatment of Long Evans hooded rats during post-natal brain development with the cholesterol synthesis inhibitor, AY-9944 (AY) results in the occurrence of atypical absence seizures, which are frequent, recurrent, and life-long. AY induced slow spike-and-wave discharges (SSWD) are significantly more frequent and prolonged in female Long Evans rats than males. Three groups of experiments were performed in order to characterize further the AY model of atypical absence seizures, (1) a developmental study was performed to ascertain whether AY-induced seizures appear before or after the onset of puberty; (2) male/female differences in severity of response to AY was determined in order to answer the question whether the gender specificity was a pre- or postpubertal phenomenon; (3) a time course study was done to determine the minimum number of postnatal AY doses needed to induce the life-long atypical absence seizure state. The data indicate that AY-induced atypical absence seizures emerge before the onset of puberty. Further, we show that the gender difference in severity of AY-induced seizures also is a pre-pubertal phenomenon. Finally, a single dose of AY (7.5 mg/kg) administered on post-natal day (P) 5 was sufficient to induce SSWD on the electrocorticogram (ECoG). Our results suggest that sex hormones are important in the AY model, although the exact role of cholesterol derived steroid hormones in the regulation and maintenance of AY induced atypical absence seizures remains to be determined.


Beiwudine, a norditerpenoid alkaloid from aconitum kusnezoffii
A novel norditerpenoid alkaloid, beiwudine (1), was isolated from the roots of Aconitum kusnezoffii. Its structure was established on the basis of chemical and NMR spectral studies.


Identification and purification of human erythroid progenitor cells by monoclonal antibody to the transferrin receptor (TU 67).
Anti-TU 67 is a murine monoclonal antibody that recognizes the transferrin receptor. With respect to hematopoietic cells TU 67 is expressed by human multipotent colony-forming cells (CFU-Mix), erythroid progenitor cells (BFU-E and CFU-E) and a fraction of granulocyte/monocyte colony forming cells, but is not expressed by mature hematopoietic cells including erythrocytes, platelets, lymphocytes, and peripheral blood myeloid cells. The TU 67-positive fraction of normal bone marrow, separated by fluorescence-activated cell sorting (FACS) or immune rosettes, contained 87% of the erythroid progenitor cells. Erythroid progenitor cells were enriched up to 50-fold by using a combination of monoclonal antibodies to deplete mature hematopoietic cells, followed by positive selection of BFU-E and CFU-E by TU 67 antibody.


Alcohol and other substance use, mental health treatment use, and perceived unmet treatment need: Comparison between baby boomers and older adults.
As the baby boomers age, the number of older adults with comorbid substance use and mental disorders is projected to grow. Little research has examined the potential impact of substance use on older adults' mental health treatment use and unmet treatment need. This study examined these associations among the rapidly growing population of baby boomers and their older counterparts. Data are from the 2008 to 2012 National Survey on Drug Use and Health (NSDUH) (N = 18,443 respondents aged 50-64 and 11,191 aged 65 +). Age-combined and age-stratified logistic regression analyses were used to examine relationships between alcohol, illicit drug, and tobacco use and mental health problems, treatment use, and perceived unmet treatment need, with sociodemographic characteristics and health status as covariates. Heavy alcohol, illicit drug, and tobacco use increased the odds of having a mental health problem in both age groups. Compared to those who used alcohol on 1-99 days during the preceding year, lifetime abstainers had significantly lower odds of having received mental health treatment in both age groups. Poorer self-rated health and past-year mental health treatment use increased the odds of perceived unmet treatment need in both age groups, while lifetime abstention in the boomers decreased the odds. This study's key finding is the lower likelihood of mental health treatment use among lifetime abstainers in both age groups. Further research may identify barriers to treatment use and ways to promote use among both age groups.


Pesticide-drug interaction in rats.
The possible interactions between a fungicide, thiram, and some drugs acting on the central nervous system were investigated in rats by means of behavioral methods. Potentiation was found after combined treatment with thiram and promethazine, and after thiram and meprobamate. In the case of trihexyphenidyl, an additive interaction was observed. It is presumed that these observations will be of practical toxicological significance.


Calmodulin antagonists inhibit adenosine uptake by rat brain cortical synaptosomes.
The purpose of these experiments was to determine if the adenosine uptake process in brain synaptosomes is regulated by calmodulin. Several calmodulin antagonists including trifluoperazine, W-7 and R24571 were tested for their ability to inhibit adenosine uptake by rat brain cortical synaptosomes. The results indicate that these agents inhibit adenosine uptake in a competitive manner. Their potencies as inhibitors of uptake were in good agreement with those reported for their inhibition of identified calmodulin regulated reactions. It is therefore concluded that the adenosine uptake process in rat brain synaptosomes is regulated by calmodulin or a calmodulin-like protein.


Thrombospondin 1 and cathepsin D improve prostate cancer diagnosis by avoiding potentially unnecessary prostate biopsies.
To investigate and further validate if two novel cancer-related glycoproteins, discovered by a genetic-guided proteomics approach, can distinguish benign disease from prostate cancer (PCa) in men with enlarged prostates. A retrospective study was performed that included men with a total prostate-specific antigen (PSA) concentration of 2.0-10 ng/mL, negative digital rectal examination and enlarged prostate (volume ≥35 mL). Serum samples were collected between 2011 and 2016 at a single centre from 474 men before they underwent prostate biopsy. Serum concentrations of thrombospondin 1 (THBS1) and cathepsin D (CTSD) glycoproteins were combined with the percentage of free PSA to total PSA ratio (%fPSA) to predict any or significant cancer at biopsy. The multivariable logistic regression model including THBS1, CTSD and %fPSA discriminated among biopsy-positive and biopsy-negative patients in the validation set with an area under the curve (AUC) of 0.86 (P < 0.001, 95% confidence interval (CI) 0.82-0.91), while %fPSA alone showed an AUC of 0.64 (P < 0.001, 95% CI 0.57-0.71). At 90% sensitivity for PCa, the specificity of the model was 62%, while %fPSA had a specificity of 23%. For high grade (Gleason score ≥ 7 in prostatectomy specimen) PCa, the specificity was 48% at 90% sensitivity, with an AUC of 0.83, (P < 0.001, 95% CI 0.77 to 0.88). Limitations of the study include the retrospective set-up and single-centre cohort. A model combining two cancer-related glycoproteins (THBS1 and CTSD) and %fPSA can improve PCa diagnosis and may reduce the number of unnecessary prostate biopsies because of its improved specificity for PCa when compared to %fPSA alone.


Posterior Insular GABA Levels Inversely Correlate with the Intensity of Experimental Mechanical Pain in Healthy Subjects.
This study aimed to investigate the relation of GABA and glutamate levels in the posterior insula and mechanical pain sensitivity in healthy subjects. Nineteen healthy female individuals underwent single voxel magnetic resonance spectroscopy (MRS) at 3 T. Metabolites were measured in the right posterior insula using MEGA-PRESS spectral editing. Mechanical pain sensitivity was experimentally assessed with pinprick stimuli on a numeric rating scale. Ratings of perceived intensity of 256 mN and 512 mN pinprick stimuli were negatively correlated with GABA levels and positively with glutamate levels in the posterior insula. Pinprick pain ratings were also positively correlated with the glutamate/GABA ratio. No significant correlation for pinprick stimuli of lower forces than 256 mN was observed. The results of our study support the hypothesis that excitatory and inhibitory neurotransmitter levels and/or the ratio of glutamate/GABA levels in the posterior insula are related to individual differences in pain sensitivity. These results are in line with chronic pain studies, where elevated glutamate/GABA ratios in the insular cortex of patients with chronic pain syndromes were observed.


The use of corporal punishment in child rearing in the West Indies.
The West Indian child is usually loved by its parents or caretakers, but is frequently subjected to corporal punishment unsuitable to the age and stage of its development and excessive in relation to the alleged offence. The debate on whether the persistent use of what is considered excessive punishment as the means of instilling obedience in children, centres around the parents' African heritage or learned behaviour from the institution of slavery. Socially and economically disadvantaged parents under stress seem to displace their frustrations and anxieties on the children through corporal punishment which often assumes ritualised characteristics. The community in general and the parents in particular need help through appropriate education, to change their attitudes of accepting excessive corporal punishment as the means of imposing discipline upon children.


Parameterization of the Age-Dependent Whole Brain Apparent Diffusion Coefficient Histogram.
The distribution of apparent diffusion coefficient (ADC) values in the brain can be used to characterize age effects and pathological changes of the brain tissue. The aim of this study was the parameterization of the whole brain ADC histogram by an advanced model with influence of age considered. Whole brain ADC histograms were calculated for all data and for seven age groups between 10 and 80 years. Modeling of the histograms was performed for two parts of the histogram separately: the brain tissue part was modeled by two Gaussian curves, while the remaining part was fitted by the sum of a Gaussian curve, a biexponential decay, and a straight line. A consistent fitting of the histograms of all age groups was possible with the proposed model. This study confirms the strong dependence of the whole brain ADC histograms on the age of the examined subjects. The proposed model can be used to characterize changes of the whole brain ADC histogram in certain diseases under consideration of age effects.


Treatment of fractures of the hallux with a simple splint.
Three hundred patients with fractures of the hallux were randomly treated with either a short plantar splint or spica strapping in a prospective crossover trial. The results showed that more patients preferred the splint and the mean pain score was lower in the group treated with a splint (P less than 0.001). It is concluded that the splint is a cheap and effective method of treatment of fractures of the hallux.


Synthesis and pharmacological evaluation of novel 1-(2-(benzoyl-substituted-2-phenyl-1H-indol-5-carbony) hydrazinyloxy) vinyl nitrate derivatives as potent non-ulcerogenic, analgesic and anti-inflammatory agents.
Six derivatives of 1-(2-(benzoyl-(substituted)-2-phenyl-1H-indole-5-carbony) hydrazinyloxy) vinyl nitrate were synthesized and tested in vivo for anti-inflammatory, analgesic, and ulcerogenic properties. Synthesized compounds shown significant anti-inflammatory activity comparable to that of Diclofenac sodium in the carrageenan-induced rat paw edema test and all of the compounds were found to be equipotent to Diclofenac sodium in the acetic acid induced writhing analgesic model. Out of six derivatives two derivatives found to produce no ulceration in stomach specimen of rats; nitric oxide seems to contribute to their excellent safety profile which supports several endogenous GIT defense mechanisms, including increase in mucus, bicarbonate secretions, increase in mucosal blood flow, and inhibition of the activation of pro-inflammatory cells by which NO-Indomethacin protects GI mucosa.


AtPTR4 and AtPTR6 are differentially expressed, tonoplast-localized members of the peptide transporter/nitrate transporter 1 (PTR/NRT1) family.
Members of the peptide transporter/nitrate transporter 1 (PTR/NRT1) family in plants transport a variety of substrates like nitrate, di- and tripepetides, auxin and carboxylates. We isolated two members of this family from Arabidopsis, AtPTR4 and AtPTR6, which are highly homologous to the characterized di- and tripeptide transporters AtPTR1, AtPTR2 and AtPTR5. All known substrates of members of the PTR/NRT1 family were tested using heterologous expression in Saccharomyces cerevisiae mutants and oocytes of Xenopus laevis, but none could be identified as substrate of AtPTR4 or AtPTR6. AtPTR4 and AtPTR6 show distinct expression patterns, while AtPTR4 is expressed in the vasculature of the plants, AtPTR6 is highly expressed in pollen and during senescence. Phylogenetic analyses revealed that AtPTR2, 4 and 6 belong to one clade of subgoup II, whereas AtPTR1 and 5 are found in a second clade. Like AtPTR2, AtPTR4-GFP and AtPTR6-GFP fusion proteins are localized at the tonoplast. Vacuolar localization was corroborated by co-localization of AtPTR2-YFP with the tonoplast marker protein GFP-AtTIP2;1 and AtTIP1;1-GFP. This indicates that the two clades reflect different intracellular localization at the tonoplast (AtPTR2, 4, 6) and plasma membrane (AtPTR1, 5), respectively.


Geum sunhangii (Rosaceae), a new species from Hubei Province, China.
Geum sunhangii - first discovered in Shennongjia National Nature Reserve, Hubei Province, China - is described as a new species of Rosaceae. Compared to all known Chinese Geum species, the new species differs by possessing jointed styles, imbricate petals and a reniform radical leaf terminal leaflet. Most significantly, the jointed style is curved at an obtuse or a right angle. In addition, the inclusion of this species within the genus Geum was supported by phylogenetic analysis using the sequence data of a nuclear ribosomal internal transcribed spacer (nrITS) and a chloroplast trnL-trnF intergenic spacer. The new species was found to be closely related to G. rivale and G. aleppicum.


Emergence of Norovirus GII.4 variants in acute gastroenteritis outbreaks in South Korea between 2006 and 2013.
New emerging strains of noroviruses (NoVs) often increase acute gastroenteritis (AGE) outbreaks worldwide. We analyzed the epidemiological features and genotypic patterns of NoVs in AGE outbreaks. To elucidate the public health impact of NoVs during AGE outbreaks in South Korea, a molecular and epidemiological investigation was performed with 318 AGE outbreaks reported from the Gyeonggi province of South Korea during the period from 2006 to 2013. NoVs were associated with 102 (32.1%) of the AGE outbreaks. Epidemiological data revealed that the majority of NoV outbreaks were in the student group (47.1%), and the majority of AGE patients were identified in schools (68.8%). NoV genogroup (G) II strains were associated with 94 (92.2%) of the NoV outbreaks, and GII.4 strains were predominantly associated with 57.6% (n=49) of NoV GII outbreaks. Four GII.4 variants (2006b, 2007, 2009 and 2012 variants) emerged and showed different contributions to NoV outbreak activity. The 2006b variant was predominantly associated with NoV outbreaks during the early years of the study period, and was subsequently displaced by the New Orleans 2009 variant, and most recently by the Sydney 2012 variant. In addition, the GII.2, GII.14, and GII.17 strains have recently been often associated with NoV AGE outbreaks. The emergence of new NoV GII.4 variants significantly affected the NoV outbreak activity in South Korea during the period from 2006 to 2013. The surveillance for new emerging strains affecting NoV outbreak activity should be intensified to develop an adequate policy to prevent further NoV outbreaks.


Changing mortality patterns that led life expectancy in Japan to surpass Sweden's: 1972-1982.
Between 1972 and 1982, Japan caught up to and then surpassed Sweden as the country with the longest life expectancy. The contributions of different causes of death and age groups to life expectancy changes in males during this time period are examined in detail for these two countries. Even though cerebrovascular disease mortality rates remained lower in Sweden over the entire interval, the rapid gain made by Japan relative to Sweden for this cause of death was a prime factor in Japan's ending the period with a higher life expectancy. Important contributions to life expectancy improvement in Japan came from declining mortality rates in those aged 55 and older.


Investigation of antimicrobial activities and molecular characterization of the species belong to Origanum, Thymus and Thymbra genera by ISSR.
The aim of this study is to investigate the antimicrobial activities of the species belonging to the genera Origanum L., Thymus L., and Thymbra L. in the Lamiaceae family and molecular characterization using ISSR markers and to determine the correlations between anti-microbial activities of the plant extracts and ISSR loci. Anti-microbial active extracts were obtained after 24-hours extraction using either of the three different solvents (ethanol, hexane, and chloroform) from the plants using the Soxhlet device. The effects of extracts on the bacterial strains (Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Enterococcus faecalis) were determined using the disc-diffusion method. The species Thymbra spicata var. spicata L., Thymus vulgaris L., Thymus citriodorus, Thymus cilicicus, Origanum syriacum L., and Origanum vulgare L. subsp. hirtum displayed significant anti-microbial activities, while the Origanum minutiflorum, Origanum onites L., Origanum saccatum and Origanum vulgare L. ssp. gracile displayed less activities on the bacterial strains. The plant species under study had a high level of genetic diversity. Significant correlations were determined between the anti-microbial activities of the plant species and the ISSR loci. Staphylococcus aureus was the most sensitive and Pseudomonas aeruginosa was the least sensitive strain. The ethanol and chloroform extracts were the most effective solvents. ISSR markers were successful for determining high levels of genetic diversity and clustering the species belonging to the genera Origanum, Thymus, and Thymbra. Conducting molecular marker analyses facilitated in distinguishing the species correctly for molecular breeding studies. The studies identified the antimicrobial activities of the plants against the bacteria used in the study and suggested their potential role in the pharmaceutical industry.


Spike-based COVID-19 immunization increases antibodies to nucleocapsid antigen.
Antibodies to the nucleocapsid (N) antigen are suggested to be used to monitor infections after COVID-19 vaccination, as first generation subunit vaccines are based on the spike (S) protein. We used multiplex immunoassays to simultaneously measure antibody responses to different fragments of the SARS-CoV-2 S and N antigens for evaluating the immunogenicity of the mRNA-1273 (Spykevax) and the BNT162b2 (Comirnaty) vaccines in 445 health care workers. We report a >4-fold increase post-vaccination of IgG levels to the full length (N FL) and C-terminus of N (N CT) in 5.2% and 18.0% of individuals, respectively, and of IgA in 3.6% (N FL) and 9.0% (N CT) of them. The increase in IgG levels and avidity was more pronounced after Spykevax than Comirnaty vaccination (36.2% vs 13.1% for N CT, and 10.6% vs 3.7% for N FL). Data suggest the induction of cross-reactive antibodies against the N CT region after administering these S-based vaccines, and this should be taken into account when using N seropositivity to detect breakthroughs.


One-year retrospective analysis of anti-FXa apixaban and rivaroxaban levels demonstrates utility for management decisions in various urgent and nonurgent clinical situations.
Quantification of direct oral anticoagulant (DOAC) plasma levels can guide clinical management, but insight into clinical scenarios surrounding DOAC-calibrated anti-FXa assays is limited. Apixaban- and rivaroxaban-calibrated chromogenic anti-Xa assays performed over a 1-year period were retrospectively analyzed. Patient demographics, DOAC history, concomitant medications, and renal/liver comorbidities were obtained. Indications for testing and associated clinical actions were reviewed. Machine learning (ML) models predicting clinical actions were evaluated. In total, 371 anti-FXa apixaban and 89 anti-FXa rivaroxaban tests were performed for 259 and 67 patients in recurring urgent (acute bleeding, unplanned procedures) and nonurgent situations, including several scenarios not captured by existing testing recommendations (eg, drug monitoring, recurrent thromboembolic events, bleeding tendency). In urgent settings, andexanet reversal was guided by radiologic and clinical findings over DOAC levels in 14 of 32 instances, while 51% of apixaban patients qualified for nonreversal strategies through the availability of levels. Levels also informed procedure/intervention timing and supported management decisions when DOAC clearance or DOAC target levels were in question. The importance of clinical context was emphasized by exploratory ML models predicting particular clinical actions. Although clinical situations are complex, DOAC testing facilitates clinical decision-making, including reversal, justifying more widespread implementation of these assays.


The multifunctional protein HMGB1: 50 years of discovery.
Fifty years since the initial discovery of HMGB1 in 1973 as a structural protein of chromatin, HMGB1 is now known to regulate diverse biological processes depending on its subcellular or extracellular localization. These functions include promoting DNA damage repair in the nucleus, sensing nucleic acids and inducing innate immune responses and autophagy in the cytosol and binding protein partners in the extracellular environment and stimulating immunoreceptors. In addition, HMGB1 is a broad sensor of cellular stress that balances cell death and survival responses essential for cellular homeostasis and tissue maintenance. HMGB1 is also an important mediator secreted by immune cells that is involved in a range of pathological conditions, including infectious diseases, ischaemia-reperfusion injury, autoimmunity, cardiovascular and neurodegenerative diseases, metabolic disorders and cancer. In this Review, we discuss the signalling mechanisms, cellular functions and clinical relevance of HMGB1 and describe strategies to modify its release and biological activities in the setting of various diseases.


LangChuangHeJi decoction ameliorates lupus via preventing accumulation of CD138+ T cells in MRL/lpr mice.
LangChuangHeJi (LCHJ) decoction has been used as a supplementary therapy to reduce the dose of prednisone and improve the therapeutic effects in systemic lupus erythematosus (SLE) maintenance. We aimed to explore the underlying mechanisms of the therapeutic effects of LCHJ. Spleen and lymph node weight, renal tissue histology, anti-dsDNA and anti-nuclear antibody levels in serum, and urinary protein levels were measured to evaluate the therapeutic effects. We further measured serum levels of multiple cytokines and antibody subsets, and performed flow cytometry analysis to observe effects of LCHJ on the frequency and activation of T cells and T cell subsets, as well as accumulation of plasma cells in splenocytes of MRL/lpr mice. LCHJ exhibited significant therapeutic effects on MRL/lpr mice. LCHJ significantly controlled the in vivo inflammation and dramatically prevented the accumulation of DN T and plasma cells in MRL/lpr mice. Moreover, LCHJ significantly suppressed the accumulation of CD138+ T cells in MRL/lpr mice, which led to the decreased production of the anti-dsDNA antibody in vivo. LCHJ significantly decreased CD4+CD138+ T cells originated from CD4+CD138- T cells, which subsequently prevented the accumulation of CD138+ T cells in MRL/lpr mice. Our results indicated that LCHJ alleviated renal injuries and prevented the enlargement of the spleen and lymph nodes by suppressing DN T cell accumulation, and reduced anti-dsDNA antibody secretion by preventing the accumulation of CD138+ T cells.


Expression of transporters potentially involved in the targeting of cytostatic bile acid derivatives to colon cancer and polyps.
Drug targeting might help to overcome resistance to chemotherapy. Here we investigated whether colon cancer and polyps do express functional carriers involved in the uptake of cytostatic bile acid derivatives, in this case Bamet-UD2 [cis-diammine-bisursodeoxycholate-platinum(II)], which has been reported to be taken up by colon cancer cells "in vitro", efficiently induce apoptosis and overcome resistance to cisplatin. Although at lower levels than in ileum, a detectable expression of ASBT, OATP8/1B3, OCT1 and OSTalpha in colon tissue was found, which was not impaired in colon cancer or polyps. The expression of OATP-A/1A2 and OSTbeta was also found in colon, but this was markedly decreased in neoplastic colon tissue. In contrast, the expression of OATP-C/1B1 was low in colon but significantly enhanced in neoplastic colon tissue. MDR1 and MRP2 were poorly expressed in colon as compared with ileum, whereas MRP3 expression was higher in colon than in ileum. The abundance of mRNA for these ABC proteins was not changed in colon cancer or polyps. When RNA from different tissues was injected to Xenopus laevis oocytes their ability to take up taurocholate and Bamet-UD2 was enhanced (healthy ileum>healthy colon approximately neoplastic colon tissue). In all cases, uptake was lower for taurocholate than for Bamet-UD2, probably due to that ASBT mediates sodium-dependent uptake of both substrates, whereas additional transporters expressed in these tissues can participate in Bamet-UD2 uptake. In conclusion, our results suggest that the use of cytostatic bile acid derivatives might be a good pharmacological strategy for the treatment of colon tumors.


Effects of allergic rhinitis on the progression and recovery of acute otitis media in a mouse model.
The objective of this study was to evaluate the effects of allergic rhinitis (AR) on the development, progression, and recovery of acute otitis media (OM) in an animal model and investigate the secondary effects of bacterial infection. BALB/c mice were divided into four groups: AR + OM, AR, OM, and control groups. AR + OM and AR groups were sensitized with ovalbumin (OVA) and alum and then challenged intranasally with OVA. Phosphate-buffered saline (PBS) was administered to the OM and control groups the same number of times. After AR induction, OM was induced by surgical inoculation of non-typeable Haemophilus influenza (NTHi) into the middle ear (ME) cavity of the mice in the AR + OM and OM groups. PBS was injected into the bulla in the AR and control groups. Each group was subdivided into sets of six mice, one for each of the four time points (0, 2, 7, and 10 days post-bacterial inoculation), at which point the mice were euthanized and ME and nasal cavity mucosa were obtained and evaluated. The occurrence of OM and the ME mucosa thickness were evaluated and compared among the four groups. Tissue expression of interleukin (IL)-1β, IL-6, and tumor necrosis factor-α (TNF-α) in infected ME mucosa was assessed by immunohistochemical staining. We also investigated IgE, IL-4, and IL-5 in the nasal mucosa. Most of the ears showed OM on post-inoculation day 2 in both AR + OM and OM groups. In the AR + OM group, 58.3% of ears still had OM on post-inoculation day 10, while only 16.7% of the OM group had OM. The ME mucosa of all groups increased, and the AR + OM group exhibited the thickest mucosa. The OM group showed peak thickness on post-inoculation day 2 and then decreased, whereas the ME mucosa thickness of the AR + OM group continued to increase to day 7. In the OM group, the expression of IL-1β, IL-6, and TNF-α in the ME also increased significantly, peaking on post-inoculation day 2, and then gradually decreased. In the AR + OM group, the expression of these proteins increased until day 7 and then decreased. The IgE and Th2 response (IL-4 and IL-5) cytokines were expressed at higher levels in the AR + OM and AR groups than in the OM and control groups. The inflammatory reaction to NTHi was more intense and lasted longer in the allergic group, which indicates that AR affects the progression and subsequent recovery of acute bacterial OM.


Trophic control of cholinesterase activity in a testosterone-dependent muscle of the rat: effects of castration and denervation.
The effects of testosterone withdrawal and chronic denervation on muscle weight and acetylcholinesterase (AChE) activity were studied in the hormone-sensitive levator ani muscle of the rat. Castration of adult male rats for 7 to 60 days caused a linear decrease of the weight, protein content, and AChE activity of the muscle, which stabilized after 30 days. Muscle weight and protein content decreased 2.3% per day. The total AChE activity decreased 7 days later 3.2% per day, reaching 37% of control at day 30. AChE activity per unit weight was increased in all castrated groups. Muscle weights and AChE activity of the extensor digitorum longus and soleus muscles were not altered after castration. Denervation of all three muscles caused 50% reduction of the muscle weight and protein content after 15 days. Total AChE activity decayed exponentially with a rate of 0.12 per day to 15 to 18% of control values. AChE activity per unit weight in the denervated muscles was always lower than in the control muscles. Combined castration and denervation intensified only the levator ani protein loss. The different onset and time course of the effects induced by castration and denervation indicate distinct mechanisms involved in the trophic control of muscle proteins and AChE activity. Chronic muscle denervation decreased total AChE activity to 15% of normal, whereas castration reduced the enzyme to 40% of the control values. The results indicate that neuronal and hormonal influences on AChE activity of the levator ani are not additive but overlap.


Physician and patient acceptance of emergency nurse practitioners.
Patient and physician attitudes toward emergency nurse practitioners (ENP) were surveyed in our emergency medical service. The responses to the questionnaires indicated a high degree of satisfaction with the ENP similar to that reported in a survey of patient reaction to physician assistants (PA) in the emergency department. In our emergency medical service, physicians expressed a concern over the practitioner's care of the emergent patient. Their confidence in the practitioner's clinical judgment was greater in their care of nonurgent and urgent patients.


Autosomal dominant Alport syndrome due to a COL4A4 mutation with an additional ESPN variant detected by whole-exome analysis.
Alport syndrome (AS) is a rare hereditary disease that presents with chronic kidney disease and sensorineural hearing loss, and is diagnosed by its clinical features, pathological features on renal tissue, and mode of inheritance. We report a woman in her 20 s who exhibited persistent haematuria with normal renal function and sensorineural hearing loss. Her family members exhibited the same clinical findings among three generations and were suspected of having autosomal dominant AS (ADAS). Renal biopsy showed minor glomerular abnormalities on light microscopy and extensive thinning of the glomerular basement membrane on electron microscopy. Whole-exome analysis revealed a known COL4A4 (type IV collagen α4) mutation (c. 2510 G > C: p. Gly837Ala). Two pedigrees with the same variant have been reported previously, one as ADAS and the other as autosomal recessive AS. However, these two cases exhibited no sensorineural hearing loss. The analysis in the present case revealed another missense variant in ESPN (Espin), an actin-bundling protein, which is a causative gene for sensorineural hearing loss. Although the pathophysiological significance of this novel missense variant needs to be clarified, computational analysis predicted that the variant creates a new phosphorylation site for protein kinase C. Our case suggests a possible association of hereditary sensorineural hearing loss with ADAS. Whole-exome analysis should be considered to diagnose hereditary and multiple-organ disorders.


Solitary multilocular cystic renal cell carcinoma in adults: diagnostic problems, pathological features and treatment.
Multilocular cystic renal cell carcinoma represents a rare clinical entity in adults. This report describes the authors' experience with seven tumours, including the first two tumours in the literature diagnosed during pregnancy.


Comparison of citrus pectin and apple pectin in conjugation with soy protein isolate (SPI) under controlled dry-heating conditions.
In this study, we selected two most commonly-available commercial pectin, i.e. citrus pectin and apple pectin as the grafting polysaccharides to prepare soy protein isolate-pectin conjugates. Despite the similar degrees of methoxylation and acetylation for two pectin samples, apple pectin showed much more complex structures compared to citrus pectin, with a 2.20-fold higher molecular weight and large numbers of side chains. The conjugates were prepared under controlled dry-heating conditions and achieved the degree of graft of 25.00% and 21.85% for citrus and apple pectin, respectively. Formation of the conjugates was further confirmed by SDS-PAGE gel electrophoresis and IR spectra. Attributed to the strong steric-hindrance effect of pectin, the fluorescence intensity and surface hydrophobicity of the soy protein isolate were significantly decreased after Maillard reaction. However, both solubility and emulsifying properties of the conjugates were significantly improved. Results indicated that both pectin samples played favorable roles in protein modification.


Comparison of Parent and Child Reports on Child Maltreatment in a Representative Household Sample in Hong Kong.
This study investigated and compared the rates of child maltreatment as reported by parents and children. Self-reports of 1,093 children aged 12 to 18, which were matched with both parents' records, were compared and analyzed in the study. The levels of agreement between parent and child reporting of various kinds of parental child maltreatment were low to moderate. Factors affecting the disagreement in reports were also investigated. Social desirability and violence approval were the common predictors of disagreement in father-child and mother-child reports, respectively. The low agreement between parent-child reports found in the present study highlights the need for the inclusion of both parent and child reports on maltreatment in future clinical screening and intervention programs.


Effects of Higher Minimum Quality Standards on Food Safety: Evidence From Criminal Cases Found in China's Court Documents.
Food safety is a credence good that is hard for consumers to assess even after consumption. Government have used minimum quality standards (MQSs) to prevent producers from selling products below a predetermined quality threshold, thereby improving the overall quality in the market. This study is the first to empirically examine the impact of MQSs on food safety in China. We constructed the number of mutton criminal cases (per billion people) as a proxy for food safety in a province, based on the data obtained from China Judgments Online, we evaluated the effect for the period of 2013 through 2019. Using the generalized difference-in-difference econometric method, we found that a higher minimum quality standard led to an increase in mutton criminal cases related to the production and sale of counterfeit and shoddy products. Such results highlight a potential unintended consequence of a higher MQS and call for a higher penalty cost to mitigate the unintended consequence.


PSMA-PET/CT-Based Stereotactic Body Radiotherapy (SBRT) in the Treatment of Uncomplicated Non-Spinal Bone Oligometastases from Prostate Cancer.
Stereotactic body radiotherapy (SBRT) has a consolidated role in the treatment of bone oligometastases from prostate cancer (PCa). While the evidence for spinal oligometastases SBRT was robust, its role in non-spinal-bone metastases (NSBM) is not standardized. In fact, there was no clear consensus about dose and target definition in this setting. The aim of our study was to evaluate efficacy, toxicity, and the pattern of relapse in SBRT delivered to NSBM from PCa. From 2016 to 2021, we treated a series of oligo-NSBM from PCa with 68Ga-PSMA PET/CT-guided SBRT. The primary endpoint was local progression-free survival (LPFS). The secondary endpoints were toxicity, the pattern of intraosseous relapse, distant progression-free survival (DPFS), polimetastases-free survival (PMFS), and overall survival (OS). a total of 150 NSBM in 95 patients were treated with 30-35 Gy in five fractions. With a median follow-up of 26 months, 1- and 3 years LPFS was 96.3% and 89%, respectively. A biologically effective dose (BED) ≥ 198 Gy was correlated with improved LPFS (p = 0.007). Intraosseous relapse occurred in eight (5.3%) cases. Oligorecurrent disease was associated with a better PMFS compared to de novo oligometastatic disease (p = 0.001) and oligoprogressive patients (p = 0.007). No grade ≥ 3 toxicity occurred. SBRT is a safe and effective tool for NSBM from PCa in the oligometastatic setting. Intraosseous relapse was a relatively rare event. Predictive factors of the improved outcomes were defined.


A secondary assessment of sediment trapping effectiveness by vegetated buffers.
Vegetated buffers and filter strips are a widely used Best Management Practice (BMP) for enhancing streamside ecosystem quality and water quality improvement through nonpoint source pollutant removal. Most existing studies are either site-specific, rely on limited data points, or evaluate buffer width and slope as the only design variables for predicting sediment reduction, not considering other parameters such as soil texture, vegetation types, and runoff loads that can significantly influence the buffer efficiency. In this paper, we carry out a meta-analysis of published studies and fit regression models to explore the sediment removal capacity of riparian buffers. We compiled 905 data points from over 90 studies (including data from an online BMP database) documenting sediment trapping by vegetated buffers and recorded data regarding buffer characteristics such as buffer width, slope, area, vegetation type, sediment loading, water flow rates, and sediment removal efficiency. We found that an exponential regression model describing the relationship between sediment removal efficiency by the buffer and water inflow/outflow volume ratio explained 44% of the variance. Adding the square root of roughness increased the R 2 to 0.50. The model performance was compared with other sediment reduction regression models reported in the literature. The results point towards the importance of considering flow parameters in vegetative buffer design. The improved empirical relationships derived here can be used at local scales to understand sediment trapping potential by vegetated buffers for water quality mitigation purposes and can be built into extant hydrologic models for improved watershed-scale assessments.


Evaluating Por Nuestra Salud: A Feasibility Study.
This feasibility study evaluated the impact of a culturally consistent diabetes educational program, led by a Latino pastor, on Latino community diabetes knowledge levels. Latino adults were recruited from two churches serving Latino populations, one identified as intervention, the other as nonintervention. Both churches received the American Diabetes Association's booklets on diabetes education, "Four Steps to Control Your Diabetes for Life." The intervention group also received weekly reviews of the booklet's information from the church pastor, who was educated about diabetes by a Latino family nurse practitioner. Pre- and postintervention levels of diabetes knowledge were measured using the Diabetes Knowledge Questionnaire. Mean changes in the Diabetes Knowledge Questionnaire (DKQ-24) survey from pretest to posttest indicated a significant increase in knowledge in both groups. Only the grades for the participants from the pastor-led group, however, moved from failure in knowledge to high levels of passing. One hundred percent of intervention group participants reported having read the literature. This pilot study supports the feasibility of a local Latino pastor, as a culturally consistent diabetes educator, to increase Latino parishioner's knowledge of diabetes.


Epigenetic regulation in the shoot apical meristem.
Epigenetic mechanisms form the basis of cellular memory, developmental decisions, and the cellular immune system that defends against transposons and viruses. Organs develop from the shoot apical meristem (SAM) to shape the plant's areal phenotype, and stem cells in the SAM serve as a functional germline. While many details on the regulation of stem cell pool size, organ initiation, and patterning at the meristem periphery are known, we know surprisingly little about the molecular characteristics of SAM cells, including their epigenome and how it changes during development. Here, we summarize information on epigenetic regulation of selected genes necessary for stem cell maintenance. As recent evidence suggests that SAM stem cells might be a hotspot of transposon activation, we discuss this aspect of epigenetic control in the meristem and speculate on mechanisms that maintain the flexibility of SAM stem cells in response to developmental or environmental cues.


Possible Biomechanical Origins of the Long-Range Correlations in Stride Intervals of Walking.
When humans walk, the time duration of each stride varies from one stride to the next. These temporal fluctuations exhibit long-range correlations. It has been suggested that these correlations stem from higher nervous system centers in the brain that control gait cycle timing. Existing proposed models of this phenomenon have focused on neurophysiological mechanisms that might give rise to these long-range correlations, and generally ignored potential alternative mechanical explanations. We hypothesized that a simple mechanical system could also generate similar long-range correlations in stride times. We modified a very simple passive dynamic model of bipedal walking to incorporate forward propulsion through an impulsive force applied to the trailing leg at each push-off. Push-off forces were varied from step to step by incorporating both "sensory" and "motor" noise terms that were regulated by a simple proportional feedback controller. We generated 400 simulations of walking, with different combinations of sensory noise, motor noise, and feedback gain. The stride time data from each simulation were analyzed using detrended fluctuation analysis to compute a scaling exponent, a. This exponent quantified how each stride interval was correlated with previous and subsequent stride intervals over different time scales. For different variations of the noise terms and feedback gain, we obtained short-range correlations (alpha < 0.5), uncorrelated time series (alpha = 0.5), long-range correlations (0.5 < alpha < 1.0), or Brownian motion (alpha > 1.0). Our results indicate that a simple biomechanical model of walking can generate long-range correlations and thus perhaps these correlations are not a complex result of higher level neuronal control, as has been previously suggested.


Discovery of potent and selective agonists for the free fatty acid receptor 1 (FFA(1)/GPR40), a potential target for the treatment of type II diabetes.
A series of 4-phenethynyldihydrocinnamic acid agonists of the free fatty acid receptor 1 (FFA(1)) has been discovered and explored. The preferred compound 20 (TUG-424, EC(50) = 32 nM) significantly increased glucose-stimulated insulin secretion at 100 nM and may serve to explore the role of FFA(1) in metabolic diseases such as diabetes or obesity.


Structural Biology of Bacterial Haemophores.
Iron plays a key role in a wide range of metabolic and signalling functions representing an essential nutrient for almost all forms of life. However, the ferric form is hardly soluble, whereas the ferrous form is highly toxic. Thus, in biological fluids, most of the iron is sequestered in iron- or haem-binding proteins and the level of free iron is low, making haem and iron acquisition a challenge for pathogenic bacteria during infections. Although toxic to the host, free haem is a major and readily available source of iron for several pathogenic microorganisms. Both Gram-positive and Gram-negative bacteria have developed several strategies to acquire free haem-Fe and protein-bound haem-Fe. Haemophores are a class of secreted and cell surface-exposed proteins promoting free-haem uptake, haem extraction from host haem proteins, and haem presentation to specific outer-membrane receptors that internalize the metal-porphyrins. Here, structural biology of bacterial haemophores is reviewed focusing on haem acquisition, haem internalization, and haem-degrading systems.


Neuroinflammation in neurodegenerative disorders: the roles of microglia and astrocytes.
Neuroinflammation is associated with neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. Microglia and astrocytes are key regulators of inflammatory responses in the central nervous system. The activation of microglia and astrocytes is heterogeneous and traditionally categorized as neurotoxic (M1-phenotype microglia and A1-phenotype astrocytes) or neuroprotective (M2-phenotype microglia and A2-phenotype astrocytes). However, this dichotomized classification may not reflect the various phenotypes of microglia and astrocytes. The relationship between these activated glial cells is also very complicated, and the phenotypic distribution can change, based on the progression of neurodegenerative diseases. A better understanding of the roles of microglia and astrocytes in neurodegenerative diseases is essential for developing effective therapies. In this review, we discuss the roles of inflammatory response in neurodegenerative diseases, focusing on the contributions of microglia and astrocytes and their relationship. In addition, we discuss biomarkers to measure neuroinflammation and studies on therapeutic drugs that can modulate neuroinflammation.


Histoimmunological identification of a prolactin-like substance in rodent testis.
Anti-rat prolactin (PRL) antibodies were localized by histoimmunological methods in the cytoplasm of testicular interstitial cells, Sertoli cells, spermatogonia and primary spermatocytes of the rat and mouse. Control of specificity by affinity chromatography methods showed this PRL-like material to be non-specific in these testicular tissues, but specific in adenohypophyseal cells. These results are discussed.


A clinical preceptor program: strategy for new graduate orientation.
The nurse internship program offers a practical approach to the orientation of new graduates to hospital routine. Staff nurses, as clinical preceptors, provide peer role models and clinical support for new graduates during their transition from student to staff nurse. From their experience in developing the program, the authors discuss the theoretical basis, the pragmatics, and the benefits of this approach and suggest its applicability to other situations.


A multicenter study of pandemic influenza A (H1N1) infection in patients with solid tumors in 3 countries: early therapy improves outcomes.
Pandemic influenza A (hereafter 2009/H1N1) caused significant morbidity and mortality during the 2009 pandemia. Patients with chronic medical conditions and immunosuppressive diseases had a greater risk of complications. However, data regarding the characteristics and outcome of 2009/H1N1 infection in patients with solid tumors are nonexistent. Herein, the authors describe a series of influenza 2009/H1N1 in patients with solid malignancies at 3 major cancer hospitals worldwide. The authors retrospectively reviewed the records of patients with solid organ malignancies and 2009/H1N1 from The University of Texas M. D. Anderson Cancer Center in Houston, Texas; the Mexican National Cancer Institute, Federal District of Mexico; and King Hussein Cancer Center in Amman, Jordan from the period of the 2009 H1N1 pandemia. Data on demographics, disease characteristics, and outcome were extracted. In total, 115 cases were identified during the pandemic influenza among the 3 institutions. High rates of hospitalization (50%), pneumonia (23%), and death (9.5%) were reported. Patients who developed pneumonia and those who died were moderately to severely immunocompromised (P = .001 and P = .006, respectively). A multivariate competing risk analysis demonstrated that a delay >48 hours in starting antiviral therapy was associated significantly with an increased risk of developing pneumonia (P = .013). The 2009/H1N1 pandemic caused severe illness in immunocompromised patients with cancer who had solid tumors, and heavily immunosuppressed patients were at greater risk of developing pneumonia and death. Early initiation of antiviral therapy is crucial in this patient population to decrease morbidity and probably mortality.


Carbamyl phosphate synthetase and ornithine transcarbamylase activities in enzyme-deficient human liver measured by radiochromatography and correlated with outcome.
Sensitive and specific radiochromatographic methods to measure enzymatic activities of carbamyl phosphate synthetase I (CPS I) and ornithine transcarbamylase (OTC) were developed. The activities of these enzymes were assayed in frozen liver tissue obtained from 23 individuals with hyperammonemia caused by CPS I (five patients) and OTC deficiency (18 patients). In addition, livers of one aborted fetus with OTC deficiency and four normal individuals were studied. The assays use radioactive ornithine as a substrate followed by separation of citrulline formed in the reactions by HPLC and quantitation of the radioactivity in both amino acids by a radioactivity flow monitor or by a scintillation counter. Both CPS I and OTC assays were linear with respect to length of incubation time and concentration of tissue homogenate. The sensitivity of the methods allowed measurements of CPS I and OTC activities as low as 0.1 mumol/g/min on 5 mg of liver tissue and the diagnosis of CPS I or OTC deficiency could be established on as low as 0.5 and 0.05 mg of tissue, respectively. CPS I activity in different sections of four normal livers was 3.01 +/- 0.16 mumol/g/min (mean +/- SEM, n = 19) and OTC activity was 93.4 +/- 6.3 (mean +/- SEM, n = 19). Residual enzymatic activity could be detected and measured in the liver tissues of one of the five subjects with CPS I deficiency and in 14 of 19 subjects with OTC deficiency. OTC/CPS I activity ratio in normal liver tissue was 31.2 +/- 1.3 (mean +/- SEM, n = 19), whereas this ratio ranged from 343 to greater than 5000 in CPS I deficient livers and from less than 0.02 to 1.55 in OTC deficient livers.(ABSTRACT TRUNCATED AT 250 WORDS)


Arecoline Induces Neurotoxicity to PC12 Cells: Involvement in ER Stress and Disturbance of Endogenous H2S Generation.
Arecoline is a major alkaloid of areca nut and has been effect on central nervous system. Although arecoline-induced neurotoxicity has been reported, the possible underlying neurotoxic mechanisms have not yet been elucidated. Increasing evidences have shown that both excessive endoplasmic reticulum (ER) stress and disturbance of hydrogen sulfide (H2S) production are involved in the pathophysiology of numerous neurodegenerative diseases. Here, the purpose of present study was to verify whether ER stress and the disturbance of endogenous H2S generation are also involved in arecoline-caused neurotoxicity. We found that treatment of PC12 cells with arecoline induced the down-regulation of cells viability and up-regulation of apoptosis and the activity of caspase-3, indicating the neurotoxic role of arecoline to PC12 cells. In addition, arecoline also increased the expression of Bax (pro-apoptotic protein) and attenuated the expression of Bcl-2 (anti-apoptotic protein) in PC12 cells. Simultaneously, arecoline caused excessive ER stress in PC12 cells, as evidenced by the up-regulations of Glucose-regulated protein 78 (GRP78), CCAAT/enhancer binding protein homologous protein (CHOP), and Cleaved caspase-12 expressions. Notably, the level of H2S in the culture supernatant and the expressions of cystathionine β-synthase and 3-mercaptopyruvate sulfurtransferase (two major enzymes for endogenous H2S generation in PC12 cells) were also reduced by arecoline treatment. These results indicate that arecoline-caused neurotoxicity to PC12 cells is involved in ER stress and disturbance of endogenous H2S generation and suggest that the modulation of ER stress and endogenous H2S generation may be potential therapeutic approach in treatment of arecoline-caused neurotoxicity.


The Hypoxia-inducible Factor Prolyl-Hydroxylase Inhibitor Roxadustat (FG-4592) and Warfarin in Healthy Volunteers: A Pharmacokinetic and Pharmacodynamic Drug-Drug Interaction Study.
Roxadustat is a small-molecule hypoxia-inducible factor prolyl-hydroxylase inhibitor in late-stage clinical development for the treatment of anemia in patients with chronic kidney disease (CKD). Warfarin is an oral anticoagulant with a narrow therapeutic window that is often prescribed to treat coexisting cardiovascular diseases in patients with CKD. This clinical trial was designed to evaluate the effect of roxadustat on warfarin pharmacokinetic and pharmacodynamic parameters. This open-label, single-sequence crossover study was conducted in healthy volunteers (male or female) aged 18 to 55 years with a body mass index of 18.5 to 30.0 kg/m(2). The study consisted of 2 periods separated by a minimum washout period of 14 days. After an overnight fast, volunteers received a single oral dose of 25 mg (5 × 5 mg tablets) warfarin on Day 1 of Period 1 and Day 7 of Period 2. Volunteers received oral doses of 200 mg (2 × 100 mg tablets) roxadustat on Days 1, 3, 5, 7 (concomitant with warfarin), 9, 11, 13, and 15 of Period 2. Plasma S- and R-warfarin (unbound and total concentrations) and prothrombin time were determined at multiple time points up to 216 hours postdose. Pharmacokinetic and pharmacodynamic parameters were estimated via noncompartmental methods. Tolerability was evaluated by monitoring adverse events, laboratory assays, vital signs, and 12-lead ECGs. The geometric mean ratios and 90% CIs for Cmax and AUC∞ of total and unbound S- and R-warfarin (with and without roxadustat) were within the standard bioequivalence interval of 80.00% to 125.00%. Roxadustat increased the geometric mean (GM) prothrombin (PT) and international normalized ratio (INR) AUC from time zero to last measurable sample (AUCPT,last and AUCINR,last) by 24.4%. Coadministration of roxadustat and warfarin in healthy volunteers was associated with a favorable tolerability profile, with most treatment-associated adverse events mild in severity. Based on the lack of clinically significant pharmacokinetic interactions and the limited influence on warfarin pharmacodynamic parameters, no dose adjustment of warfarin should be required when coadministered with roxadustat. ClinicalTrials.gov identifier: NCT02252731.


Factors impacting physicians' decisions to prevent variceal hemorrhage.
Reasons underlying the variability of physicians' preferences for non-selective beta-blockers (BBs) and endoscopic variceal ligation (EVL) to prevent a first variceal bleed have not been empirically studied. Our aims were to examine whether 1) gastroenterologists can be classified into distinct subgroups based on how they prioritize specific treatment attributes and 2) physician characteristics are associated with treatment preference. We surveyed physicians to determine their preferred treatment for a standardized patient with large varices and examined the influence of treatment characteristics on physicians' decision making using best-worst scaling. Latent class analysis was used to examine whether physicians could be classified into groups with similar decision-making styles. 110 physicians were interviewed (participation rate 39%). The majority spent two or more days a week performing endoscopies and had practices comprising less than 25% of patients with liver disease. Latent class analysis demonstrated that physicians could be classified into at least two distinct groups. Most (n = 80, Group 1) were influenced solely by the ability to visually confirm eradication of varices. In contrast, members of Group 2 (n = 30) were influenced by the side effects and mechanism of action of BBs. Group 1 members were more likely to have practices that included fewer patients with liver disease and more likely to choose options including EVL (p = 0.01 for both). Among physicians, where the majority performs endoscopy on two or more days per week, most prefer prevention strategies which include EVL. This may be due to the strong appeal of being able to visualize eradication of varices.


Direct determination of hydrogen-bonded structures in resonant and tautomeric reactions using ultrafast electron diffraction.
We elucidate the keto-enol tautomeric equilibrium in acetylacetone, the structure of both keto and enol forms, and the nature of the intramolecular O-H...O HB in enolic acetylacetone using our ultrafast electron diffraction apparatus, thereby shedding new light on the nature of the hydrogen bond in resonant tautomeric structures. The enolic structure exhibits some pi-resonance delocalization; however, this delocalization is not strong enough to give a symmetric skeletal geometry. The long O...O distance in the refined structure renders the homonuclear O-H...O hydrogen bond in acetylacetone localized and asymmetric.


First report of the aac(6')-Ib-cr gene in Providencia stuartii isolates in Brazil.
The aac(6')-Ib-cr and bla KPC genes are spreading among Enterobacteriaceae species, including Providencia stuartii, in some countries of world. These genes were investigated in 28 P. stuartii isolates from a public hospital in Recife, Pernambuco, Brazil, by PCR and sequencing. The aac(6')-Ib-cr gene was detected in 16 resistant isolates, and the bla KPC gene was seen in 14. The presence of these genes in P. stuartii multi- and extensively drug-resistant isolates indicates that the resistance arsenal of this species is increasing, thus limiting the therapeutic options.


Stress-induced disturbances in Morris water-maze performance: interstrain variability.
Marked differences were observed across strains of mice (i.e., DBA/2J, C57BL/6J, BALB/cByJ and CD-1 mice) in acquisition, performance and reversal of a place learning response in a Morris water-maze. While DBA/2J, C57BL/6J and CD-1 mice typically learned the response readily, only 20% of BALB/cByJ mice acquired the response. Commensurate with the effects of hippocampal disturbances, the performance deficits in BALB/cByJ mice were not evident when the position of the platform in the water-maze was cued. Exposure to uncontrollable foot shock did not affect the acquisition or performance of this response in the former three strains, but provoked a modest disruption of reversal performance in DBA/2J mice and markedly impaired reversal performance in BALB/cByJ mice. It seemed, however, that the response strategies adopted in these strains could be distinguished from one another. In the reversal paradigm BALB/cByJ mice initially persisted in returning to the original training quadrant rather than to the new goal quadrant. Following 2 days of training the perseveration was no longer apparent and animals seemed to adopt a random search strategy. In contrast, DBA/2J mice, which exhibited a smaller stress-induced disturbance, did not display a perseverative response style. These data suggest that inescapable shock does not disturb response-outcome associations, but may result from the induction of a perseverative response style. However, it appears that the mechanisms responsible for an interference of performance may not be uniform across strains.(ABSTRACT TRUNCATED AT 250 WORDS)


Polymorphism at the apical membrane antigen 1 locus reflects the world population history of Plasmodium vivax.
In malaria parasites (genus Plasmodium), ama-1 is a highly polymorphic locus encoding the Apical Membrane Protein-1, and there is evidence that the polymorphism at this locus is selectively maintained. We tested the hypothesis that polymorphism at the ama-1 locus reflects population history in Plasmodium vivax, which is believed to have originated in Southeast Asia and is widely geographically distributed. In particular, we tested for a signature of the introduction of P. vivax into the New World at the time of the European conquest and African slave trade and subsequent population expansion. One hundred and five ama-1 sequences were generated and analyzed from samples from six different Brazilian states and compared with database sequences from the Old World. Old World populations of P. vivax showed substantial evidence of population substructure, with high sequence divergence among localities at both synonymous and nonsynonymous sites, while Brazilian isolates showed reduced diversity and little population substructure. These results show that genetic diversity in P. vivax AMA-1 reflects population history, with population substructure characterizing long-established Old World populations, whereas Brazilian populations show evidence of loss of diversity and recent population expansion. NOTE: Nucleotide sequence data reported is this paper are available in the GenBanktrade mark database under the accession numbers EF031154 - EF031216 and EF057446 - EF057487.


Clinical value of contrast-enhanced ultrasound enhancement patterns for differentiating solid pancreatic lesions.
To explore the diagnostic value of contrast-enhanced ultrasound (CEUS) enhancement patterns for differentiating solid pancreatic lesions and compare them with conventional ultrasound (US) and enhanced computed tomography (CT). A total of 210 patients with solid pancreatic lesions who had definite pathological or clinical diagnoses were enrolled. Six CEUS enhancement patterns were proposed for solid pancreatic lesions. Two US doctors blindly observed the CEUS patterns of solid pancreatic lesions and the interrater agreement was analyzed. The diagnostic value of CEUS enhancement patterns for differentiating solid pancreatic lesions was evaluated, and the diagnostic accuracy was compared with that of US and enhanced CT. There was good concordance for six CEUS enhancement patterns of solid pancreatic lesions between the two doctors, with a kappa value of 0.767. Hypo-enhancement (Hypo-E) or centripetal enhancement (Centri-E) as the diagnostic criteria for pancreatic carcinoma had an accuracy of 87.62%; hyper-enhancement (Hyper-E) for neuroendocrine tumors had an accuracy of 92.89%; capsular enhancement with low or uneven enhancement inside the tumor (Capsular-E) for solid pseudopapillary tumors had an accuracy of 97.63%; and iso-enhancement (Iso-E) or iso-enhancement with focal hypo-enhancement (Iso-fhypo-E) for focal pancreatitis had an accuracy of 89.10%. The diagnostic accuracy of CEUS was significantly different from that of US for 210 cases of solid pancreatic lesions (p < 0.05) and was not significantly different from that of enhanced CT for 146 cases of solid pancreatic lesions (p > 0.05). The different enhancement patterns of solid pancreatic lesions on CEUS were clinically valuable for differentiation. • Six CEUS enhancement (E) patterns, including Hyper-E, Iso-E, Iso-fhypo-E, Hypo-E, Centri-E, and Capsular-E, are proposed for the characterization of solid pancreatic lesions. • Using Hypo-E or Centri-E as the diagnostic criteria for pancreatic carcinoma, Hyper-E for neuroendocrine tumors, Capsular-E for solid pseudopapillary tumors, and Iso-E or Iso-fhypo-E for focal pancreatitis on CEUS had relatively high diagnostic accuracy. • The diagnostic accuracy of CEUS was greatly increased over that of US and was not different from that of enhanced CT.


Loss of multidrug and toxin extrusion 1 (MATE1) is associated with metformin-induced lactic acidosis.
Lactic acidosis is a fatal adverse effect of metformin, but the risk factor remains unclear. Multidrug and toxin extrusion 1 (MATE1) is expressed in the luminal membrane of the kidney and liver. MATE1 was revealed to be responsible for the tubular and biliary secretion of metformin. Therefore, some MATE polymorphisms, that cause it to function abnormally, are hypothesized to induce lactic acidosis. The purpose of this study is to clarify the association between MATE dysfunction and metformin-induced lactic acidosis. Blood lactate, pH and bicarbonate ion (HCO(3) (-) ) levels were evaluated during continuous administration of 3 mg·mL(-1) metformin in drinking water using Mate1 knockout (-/-), heterozygous (+/-) and wild-type (+/+) mice. To determine the tissue accumulation of metformin, mice were given 400 mg·kg(-1) metformin orally. Furthermore, blood lactate data were obtained from diabetic patients given metformin. Seven days after metformin administration in drinking water, significantly higher blood lactate, lower pH and HCO(3) (-) levels were observed in Mate1(-/-) mice, but not in Mate1(+/-) mice. The blood lactate levels were not affected in patients with the heterozygous MATE variant (MATE1-L125F, MATE1-G64D, MATE2-K-G211V). Sixty minutes after metformin administration (400 mg·kg(-1) , p.o.) the hepatic concentration of metformin was markedly higher in Mate1(-/-) mice than in Mate1(+/+) mice. MATE1 dysfunction caused a marked elevation in the metformin concentration in the liver and led to lactic acidosis, suggesting that the homozygous MATE1 variant could be one of the risk factors for metformin-induced lactic acidosis.


The accuracy of the "projected surgical transepicondylar axis" relative to the "true surgical transepicondylar axis" in total knee arthroplasty.
In TKA, we have used the "projected SEA", which is obtained by projecting the "true SEA" on the distal femoral cutting plane in clinical practice to determine the femoral component rotation. There are no reports examining the accuracy of the "projected SEA". In this study, we investigated the difference between the "true SEA" and "projected SEA". The present study was a CT-based computer-simulated case series. We evaluated 34 knees without osteoarthritis changes. These patients were selected from the operative schedule prior to THA. We defined the "true SEA" on the 3D model and the "projected SEA" on the cutting plane parallel to the distal femoral axis obtained based on the "true SEA". We changed the cutting angles from 20° flexion to 20° extension, and from five degrees varus to five degrees valgus. We measured the "true SEA angle" and "projected SEA angle" regarding the posterior condylar axis (PCA). The mean "true SEA angle" was 3.04°±1.34° (0.6-5.0°). The mean "projected SEA angle" was 3.43°±1.58° at 20° flexion, 3.42°±1.56° at 0° flexion, 3.43°±1.52° at 20° extension, 3.39°±1.59° at five degrees valgus, and 3.39°±1.50° at five degrees varus. At each cutting angle, the "projected SEA angle" was significantly larger than the "true SEA angle" (p<0.001). There was no significant difference between any of the "projected SEA angles" (p>0.001). We found that the true SEA and projected SEA do not differ significantly (0.39°±0.29° [range 0-1.0°]).


Oligosaccharides from "standardized intermediates". The 2-amino-2-deoxy-D-galactose analog of the blood-group O(H) determinant, type 2, and its precursors.
The selectively benzylated glycoside allyl 2-acetamido-4,6-di-O-benzyl-2-deoxy-beta-D-galactopranoside (4) was prepared from the corresponding derivative of 2-acetamido-2-deoxy-D-glucose via the p-bromobenzenesulfonate and the benzoate. 2-O-Benzoyl-3,4,6-tri-O-benzyl-alpha-D-galactopyranosyl (10) was obtained from allyl 6-O-benzyl-2-O-(2-butenyl)-alpha-D-galactopyranoside via known intermediates. To complete the sequence, the 1-propenyl 3,4,6-tri-O-benzyl galactoside was successively converted into the 2-benzoate, the free sugar, and the chloride 10. A fully protected form (11) of the trisaccharide alpha-L-Fucp-(1 leads to 2)-beta-D-Galp-(1 leads to 4)-D-GalNAc was then synthesized by coupling 10 to 4, partially deblocking the disaccharide product, and L-fucosylating the resulting intermediate. Cleavage of the O-benzyl groups from 11, with concomitant saturation of the allyl group, gave the propyl beta-glycoside of the unsubstituted trisaccharide.


Assessment and control of environmental exposure.
A review is presented of selected topics related to sampling and evaluation of airborne agents and their control. The need for an air sampling strategy that addresses usage of the results for demonstration of regulatory compliance or for epidemiologic studies is stressed. For sampling particulate matter, the concepts of total and respirable dust are explained and instruments used to obtain these data are described. Postsampling recordkeeping is essential for both regulatory and investigatory survey purposes. Engineering, administrative, and personal protective equipment controls are all options to reduce exposure. Engineering controls are preferred because they do not place day-to-day responsibilities on those potentially exposed. Finally, the approaches described should be applicable to allergic agents in the air, although the bulk of published material is for nonallergic contaminants.


MSCI: A multistate dataset for colposcopy image classification of cervical cancer screening.
Cervical cancer is the second most common female cancer globally, and it is vital to detect cervical cancer with low cost at an early stage using automated screening methods of high accuracy, especially in areas with insufficient medical resources. Automatic detection of cervical intraepithelial neoplasia (CIN) can effectively prevent cervical cancer. Due to the deficiency of standard and accessible colposcopy image datasets, we present a dataset containing 4753 colposcopy images acquired from 679 patients in three states (acetic acid reaction, green filter, and iodine test) for detection of cervical intraepithelial neoplasia. Based on this dataset, a new computer-aided method for cervical cancer screening was proposed. We employed a wide range of methods to comprehensively evaluate our proposed dataset. Hand-crafted feature extraction methods and deep learning methods were used for the performance verification of the multistate colposcopy image (MSCI) dataset. Importantly, we propose a gated recurrent convolutional neural network (C-GCNN) for colposcopy image analysis that considers time series and combined multistate cervical images for CIN grading. The experimental results showed that the proposed C-GCNN model achieves the best classification performance in CIN grading compared with hand-crafted feature extraction methods and classic deep learning methods. The results showed an accuracy of 96.87 %, a sensitivity of 95.68 %, and a specificity of 98.72 %. A multistate colposcopy image dataset (MSCI) is proposed. A CIN grading model (C-GCNN) based on the MSCI dataset is established, which provides a potential method for automated cervical cancer screening.


Modification of a deoxynivalenol-antigen-mimicking nanobody to improve immunoassay sensitivity by site-saturation mutagenesis.
A nanobody (N-28) which can act as a deoxynivalenol (DON) antigen has been generated, and its residues Thr102-Ser106 were identified to bind with anti-DON monoclonal antibody by alanine-scanning mutagenesis. Site-saturation mutagenesis was used to analyze the plasticity of five residues and to improve the sensitivity of the N-28-based immunoassay. After mutagenesis, three mutants were selected by phage immunoassay and were sequenced. The half-maximal inhibitory concentrations of the immunoassay based on mutants N-28-T102Y, N-28-V103L, and N-28-Y105F were 24.49 ± 1.0, 51.83 ± 2.5, and 35.65 ± 1.6 ng/mL, respectively, showing the assay was, respectively, 3.2, 1.5, and 2.2 times more sensitive than the wild-type-based assay. The best mutant, N-28-T102Y, was used to develop a competitive phage ELISA to detect DON in cereals with high specificity and accuracy. In addition, the structural properties of N-28-T102Y and N-28 were investigated, revealing that the affinity of N-28-T102Y decreased because of increased steric hindrance with the large side chain. The lower-binding-affinity antigen mimetic may contribute to the improvement of the sensitivity of competitive immunoassays. These results demonstrate that nanobodies would be a favorable tool for engineering. Moreover, our results have laid a solid foundation for site-saturation mutagenesis of antigen-mimicking nanobodies to improve immunoassay sensitivity for small molecules.


Treatment of external carotid arteriovenous fistula with detachable balloon.
A simple fistula between the external carotid artery and the internal jugular vein was treated for the first time using Debrun's technique with a detachable balloon catheter. The nature of the fistulous connection makes the release of the balloon inflated with silicone completely harmless. The occlusion of the fistula, while maintaining the patency of the remaining branches of the external carotid artery, proves this technique to be the most appropriate for the treatment of arteriovenous fistulae in the neck.


Protocol of End-PSCI trial: a multicenter, randomized controlled trial to evaluate the effects of DL-3-n-butylphthalide on delayed-onset post stroke cognitive impairment.
Delayed-onset post stroke cognitive impairment (PSCI) results from secondary neurodegeneration induced by stroke. Whereas targeted prevention or treatment strategies are still missing due to lack of evidences. This trial aims to evaluate the preventive effects of DL-3-n-butylphthalide (NBP) on delayed-onset PSCI. Effects of NBP on Delayed-onset Post Stroke Cognitive Impairment (End-PSCI) is a prospective, parallel-group, open-label, multicenter, randomized controlled trial with blinded outcome assessment. Hospital patients with acute cerebral infarction (within 2 weeks of onset) will be randomized into either standard medical therapy group or standard medical therapy combined NBP treatment group (NBP 200 mg, three times per day for 24 weeks). The primary outcome is the difference of incidence of delayed-onset PSCI between two groups. The secondary outcomes include difference of white matter degeneration, cognitive scores and prevalence of early-onset PSCI between two groups. End-PSCI trial will provide evidences for NBP preventing delayed-onset PSCI. The secondary outcomes will also provide valuable insights into the pathogenesis of delayed-onset PSCI and mechanism of NBP's actions. Trialsearch.who.int , ChiCTR2000032555, 2020/5/2, prospectively registered.


Mixed type of total anomalous pulmonary venous connection with hemi-pulmonary vein atresia.
This reports a successfully corrected case of an 8-day-old baby who had a rare mixed type of total anomalous pulmonary venous connection in which the left pulmonary vein connected to the portal vein and the right one was atretic as demonstrated by pulmonary artery wedge angiography. The left common pulmonary vein and right pulmonary veins were anastomosed to the left atrium, separately. The patient tolerated the operation and has been well. Early total repair after accurate diagnosis was successful for this rare combination of anomalous pulmonary venous connection.


Evaluation of Sensitivity to Endocrine Therapy Index (SET2,3) for Response to Neoadjuvant Endocrine Therapy and Longer-Term Breast Cancer Patient Outcomes (Alliance Z1031).
To evaluate prediction of response and event-free survival (EFS) following neoadjuvant endocrine therapy by SET2,3 index of nonproliferation gene expression related to estrogen and progesterone receptors adjusted for baseline prognosis. A correlative study was conducted of SET2,3 measured from gene expression profiles of diagnostic tumor (Agilent microarrays) in 379 women with cStage II-III breast cancer from the American College of Surgeons Oncology Group Z1031 neoadjuvant aromatase inhibitor trial SET2,3 was dichotomized using the previously published cutoff. Fisher exact test was used to assess the association between SET2,3 and low proliferation at week 2-4 [Ki67 ≤ 10% or complete cell-cycle arrest (CCCA; Ki67 ≤ 2.7%)] and PEPI-0 rate in cohort B, and the association between SET2,3 and ypStage 0/I in all patients. Cox models were used to assess EFS with respect to SET2,3 excluding cohort B patients who switched to chemotherapy. Patients with high SET2,3 had higher rate of pharmacodynamic response than patients with low SET2,3 (Ki67 ≤ 10% in 88.2% vs. 56.9%, P < 0.0001; CCCA in 50.0% vs. 26.2%, P = 0.0054), but rate of ypStage 0/I (24.0% vs. 20.4%, P = 0.4580) or PEPI = 0 (28.4% vs. 20.6%, P = 0.3419) was not different. Patients with high SET2,3 had longer EFS than patients with low SET2,3 (HR, 0.52, 95% confidence interval: 0.34-0.80; P = 0.0026). This exploratory analysis of Z1031 data demonstrated a higher rate of pharmacodynamic suppression of proliferation and longer EFS in high SET2,3 disease relative to low SET2,3 disease. The ypStage 0/I rate and PEPI = 0 rate were similar with respect to SET2,3.


Directed nickel-catalyzed regio- and diastereoselective arylamination of unactivated alkenes.
Few methods have been reported for intermolecular arylamination of alkenes, which could provide direct access to important arylethylamine scaffolds. Herein, we report an intermolecular syn-1,2-arylamination of unactivated alkenes with arylboronic acids and O-benzoylhydroxylamine electrophiles with Ni(II) catalyst. The cleavable bidentate picolinamide directing group facilitates formation of stabilized 4-, 5- or 6-membered nickelacycles and enables the difunctionalization of diverse alkenyl amines with high levels of regio-, chemo- and diastereocontrol. This general and practical protocol is compatible with broad substrate scope and high functional group tolerance. The utility of this method is further demonstrated by the site-selective modification of pharmaceutical agents.


A two-stage epidemiologic study on prevalence of eating disorders in female university students in Mexico.
This study investigated the prevalence of eating disorders (ED) in women. Two samples of university students (1995, n = 522; 2002, n = 880) completed the Eating Attitudes Test and the Bulimia Test (BULIT; Stage 1). During Stage 2, the women that exceeded the cut-off point of one or both questionnaires and a random sample of women that did not exceed the cut-off point were interviewed. The results showed a prevalence rate of 0.49% for ED in 1995 (0.14% for bulimia nervosa [BN] and 0.35% for EDs not otherwise specified [EDNOS]) and a prevalence rate of ED of 1.15% in 2002 (0.24% for BN and 0.91% for EDNOS). Anorexia nervosa was not found in either of the evaluated periods. Nevertheless, the results must be taken with reservation since there was a high rate of loss to follow-up (second stage). The data of this study support the findings of other studies, including studies with Spanish-speaking samples, that EDNOS is the most common ED followed by BN and AN.


Role of FcγRIIIA (CD16) in IVIg-mediated anti-inflammatory function.
The mechanism for anti-inflammatory action of intravenous immunoglobulin (IVIg) in the treatment of autoimmune and inflammatory diseases involves IgG Fc receptors (FcγR). Although the inhibitory FcγRIIB plays an important role in IVIg action, FcγRIIIA has recently been identified as another major anti-inflammatory actor. Interaction of FcγRIIIA with uncomplexed IgG1 or IVIg, or with bivalent anti-FcγRIII F(ab')2 dampened calcium responses, ROS production, endocytosis and phagocytosis, induced by heterologous activating receptors. This inhibitory action required the inhibitory configuration of the ITAM motif (ITAMi) present within the FcγRIII-associated FcRγ subunit. This allowed SHP-1 recruitment and formation of intracellular inhibisome clusters containing FcγRIII and the targeted activating receptor. Therefore, IVIg functionally interact with FcγRIIIA inducing ITAMi signaling which can prevent development of autoimmune and inflammatory disorders independently of FcγRIIB. This new mechanism of action for IVIg reveals a therapeutic potential for FcγRIIIA targeting in inflammatory diseases.


Degradation of intestinal glycoproteins by Bacteroides vulgatus.
Bacteroides vulgatus, isolated from a patient with Crohn's disease, produced in gnotobiotic rats 7 constitutive enzymes that might be concerned with the degradation of intestinal glycoproteins. Furthermore Bacteroides vulgatus caused an almost complete loss of blood group antigenicity of the intestinal glycoproteins. Enzymes with the potency to release toxic compounds from hepatic conjugates and plant glycosides, beta-glucuronidase and beta-glucosidase, respectively, were only detectable in small amounts. These findings indicate that Bacteroides vulgatus, which accounts for 40% of the total flora of patients with Crohn's disease, may play a role in the pathogenesis of Crohn's disease, by increasing the break-down of the mucus layer and therefore damaging its protective function.


Does it really matter that I do not remember my night? Consequences related to blacking out among college student drinkers.
Alcohol-induced blackouts (AIBs) are experienced frequently by college student drinkers and are more likely to occur on days with high-intensity drinking (HID; 8+ for females/10+ for males) than non-HID days. Research suggests that AIBs are associated with experiencing other alcohol-related consequences (ARCs), including more serious ARCs (SARCs; e.g., legal and sexual consequences), but we do not know whether individuals experience more ARCs and more SARCs on occasions when they black out than when they do not black out. This study examines the associations between AIBs and the total number of both ARCs and SARCs. Students (N = 462, 51.7% female, 87.7% White, Mage = 20.1) were assessed across 6 weekends via e-surveys (80%-97% response rate). Multilevel models were used to test for main effects, controlling for drinking (HID or estimated blood alcohol concentration; eBAC) and sex. Drinking days when an AIB was experienced were associated with more total ARCs (b = 3.54, 95% CI: 3.10, 3.99) and more SARCs (b = 0.77, 95% CI: 0.60, 0.95) per day than non-AIB days. The more frequently a person experienced an AIB, the more total ARCs (b = 5.33, 95% CI: 4.40, 6.25) and SARCs (1.05, 95% CI: 0.80, 1.30) they reported on average. Alcohol-induced blackout days were associated with higher levels of harm than non-AIB days, even at the same levels of drinking. Interventions that focus on reducing the occurrence of AIBs and factors that contribute to them, in addition to reducing alcohol consumption, may help reduce total harm associated with drinking among college students.