Peroxymonosulfate activation by iron(III)-tetraamidomacrocyclic ligand for degradation of organic pollutants via high-valent iron-oxo complex.
Herein, we proposed a new catalytic oxidation system, i.e., iron(III)-tetraamidomacrocyclic ligand (FeIII-TAML) mediated activation of peroxymonosulfate (PMS), for highly efficient organic degradation using p-chlorophenol (4-CP) as a model one. PMS/FeIII-TAML is capable of degrading 4-CP completely in 9 min at the initial 4-CP of 50 μM and pH = 7, whereas the recently explored system, H2O2/FeIII-TAML, could only result in ∼22% 4-CP removal in 20 min under otherwise identical conditions. More attractively, inorganic anions (i.e., Cl-, SO42-, NO3-, and HCO3-) exhibited insignificant effect on 4-CP degradation, and the negative effect of natural organic matters (NOM) on the degradation of 4-CP in PMS/FeIII-TAML is much weaker than the sulfate radical-based oxidation process (PMS/Co2+). Combined with in-situ XANES spectra, UV-visible spectra, electron paramagnetic resonance (EPR) spectra, and radical quenching experiments, high-valent iron-oxo complex (FeIV(O)TAML) instead of singlet oxygen (1O2), superoxide radical (O2•-), sulfate radicals (SO4•-) and hydroxyl radicals (HO•) was the key active species responsible for 4-CP degradation. The formation rate (kI) and consumption rate (kII) of the FeIV(O)TAML in PMS/FeIII-TAML were pH-dependent in the range of 6.0-11.5. As expected, increasing the FeIII-TAML and PMS dosage resulted in a higher steady-state concentration of FeIV(O)TAML and enhanced the 4-CP degradation accordingly. In addition, the oxidation capacity of PMS was almost totally utilized in PMS/FeIII-TAML for 4-CP oxidation due to the two-electron abstraction from 4-CP by one PMS. We believe this study will shed new light on effective PMS activation by Fe-ligand complexes to efficiently degrade organic contaminants via nonradical pathway.


Variations in the mast cell population of skin and bone marrow in magnesium-deprived rats. The influence of sex hormones.
Comparative counts of Alcian Blue-Basic Fuchsin-stained mast cells of the facial skin and bone marrow have been made in young rats of different sexes and strains, fed a diet deficient in magnesium (0.8 to 1 mg/100 g dry weight) for 4 weeks. Normal rats fed a magnesium-supplemented diet (65 mg/100 g dry weight) had about three times as many mast cells in the tibial metaphysis as in the facial skin. In both males and females fed the Mg-deficient diet, the marrow mast cells increased five to six times, while their number was concomitantly decreased in the skin. The marrow mast cells became also polymorphic, an indication of a possible preferential renewal site. Gonadectomy in the males had no effect on the above pattern. The administration of large doses of testosterone to males and estradiol to females depressed the mast cell population increase in the bone marrow and at the same time, moderated the loss of skin mast cells.


Reentry in a pulmonary vein as a possible mechanism of focal atrial fibrillation.
The case of an 18-year-old woman with recurrent idiopathic catecholamine-sensitive paroxysmal atrial fibrillation is reported. Recordings of multiple initiations of atrial fibrillation at the proximal part of the right superior pulmonary vein suggested local reentry in the vein as the mechanism of atrial fibrillation. A single radiofrequency pulse delivered at this site resulted in definite cure of the arrhythmia.


An Improved Strategy for Task Scheduling in the Parallel Computational Alignment of Multiple Sequences.
Task scheduling in parallel multiple sequence alignment (MSA) through improved dynamic programming optimization speeds up alignment processing. The increased importance of multiple matching sequences also needs the utilization of parallel processor systems. This dynamic algorithm proposes improved task scheduling in case of parallel MSA. Specifically, the alignment of several tertiary structured proteins is computationally complex than simple word-based MSA. Parallel task processing is computationally more efficient for protein-structured based superposition. The basic condition for the application of dynamic programming is also fulfilled, because the task scheduling problem has multiple possible solutions or options. Search space reduction for speedy processing of this algorithm is carried out through greedy strategy. Performance in terms of better results is ensured through computationally expensive recursive and iterative greedy approaches. Any optimal scheduling schemes show better performance in heterogeneous resources using CPU or GPU.


Polymorphisms of heme oxygenase-1 and bilirubin UDP-glucuronosyltransferase genes are not associated with Kawasaki disease susceptibility.
Kawasaki disease (KD) is a systemic vasculitis and occurs among Japanese children at a high incidence. Serum bilirubin and heme oxygenase-1 (HO-1) expression are known to play a significant role in the protection of vascular endothelial cells. Japanese have unique polymorphic distribution patterns of (TA)7 or G71R of the bilirubin UDP-glucuronosyltransferase (B-UGT) gene and of (GT)n repeats of the HO-1 gene. We investigated the relationship of KD susceptibility with these polymorphisms. There were no significant differences in the distribution of allele frequencies and genotypes of these polymorphisms between KD patients and controls. These polymorphisms are not associated with KD susceptibility.


Controlled release of diclofenac sodium in glycolipid incorporated micro emulsions.
The effect of the glycolipid, hexadecyl-β-d-glucopyranoside, incorporated in microemulsions (ME(1)) towards the enhancement of skin absorption and skin permeation of Diclofenac sodium (DS(2)) was evaluated. A Franz diffusion cell with a piece of pig's ear epidermis indicated that the optimized ME formulation with glycolipid (0.05wt%) exhibited significantly higher permeability than the conventional formulations. The releasing profiles of DS from ME formulations exhibited first order release kinetics resembling a diffusion controlled release model for the first 8h. Incorporating hexadecyl-β-D glucopyranoside in ME formulations shows significant potential as a delivery vehicle in the cosmetics and pharmaceutical industry.


British Society for Sexual Medicine Guidelines on the Management of Erectile Dysfunction in Men-2017.
This is an update of the 2008 British Society for Sexual Medicine (BSSM) guidelines. To provide up-to-date guidance for U.K. (and international) health care professionals managing male sexual dysfunction. Source information was obtained from peer-reviewed articles, meetings, and presentations. A search of Embase, MEDLINE, and Cochrane Reviews was performed, covering the search terms "hypogonadism," "eugonadal or hypogonadism or hypogonadal or gonadal," and "low or lower testosterone," starting from 2009 with a cut-off date of September 2017. We offer evidence-based statements and recommendations for clinicians. Expert guidance for health care professionals managing male sexual dysfunction is included. Current U.K. management has been largely influenced by non-evidence guidance from National Health Service departments, largely based on providing access to care limited by resources. The 2008 BSSM guidelines to date have been widely quoted in U.K. policy decision making. There is now overwhelming evidence that erectile dysfunction is strongly associated with cardiovascular disease, such that newly presenting patients should be thoroughly evaluated for cardiovascular and endocrine risk factors, which should be managed accordingly. Measurement of fasting serum glucose, lipid profile, and morning total testosterone should be considered mandatory in all newly presenting patients. Patients attending their primary care physician with chronic cardiovascular disease should be asked about erectile problems. There can no longer be an excuse for avoiding discussions about sexual activity due to embarrassment. Hackett G, Kirby M, Wylie K, et al. British Society for Sexual Medicine Guidelines on the Management of Erectile Dysfunction in Men-2017. J Sex Med 2018;15:430-457.


Understanding lung cancer screening behavior: Racial, gender, and geographic differences among Indiana long-term smokers.
Lung cancer screening is a relatively new screening option. Inequalities related to screening behavior have been documented in other types of cancer screening. Because stage at presentation drives mortality in lung cancer, it is critical to understand factors that influence screening behavior in lung cancer screening in order to intervene. However, we must first understand where disparities exist in lung cancer screening participation in order to effectively guide intervention efforts. Therefore, the purpose of this study was to determine the association of sociodemographic (including key disparity-related variables) and knowledge with lung cancer screening behavior. This cross-sectional, descriptive study used survey methodology to collect data from 438 screening-eligible individuals in the state of Indiana between January and February 2017 and measured sociodemographic variables and knowledge about lung cancer and screening. Key sociodemographic and health status characteristics associated with screening behavior included race, geographic area of residence, income, health insurance, and family history of lung cancer. Of the variables generally reflective of disparities, key differences were noted by race and geographic area of residence with total knowledge scores as well as screening behavior, respectively. Results indicate key differences in race and geographic area of residence that may perpetuate screening behavior disparities. We have a unique opportunity at this early implementation stage in lung cancer screening to learn what variables influence screening behavior from our target patient population. This knowledge can be used to design equitable patient outreach programs, meaningful, tailored patient engagement materials, and effective patient-clinician decision support tools.


Juvenile hormone metabolism during adult development of Culex quinquefasciatus (Diptera: Culicidae).
In vitro whole animal juvenile hormone (JH) III epoxide hydrolase activity ranged from two to four times that of the JH esterase activity in eggs, fourth instars, pupae, and male and female adults of the southern house mosquito, Culex quinquefasciatus Say. In in vivo studies where JH III was injected into sugar- and blood-fed adult females, the JH epoxide hydrolase activity also exceeded that of JH esterase. These studies indicate that JH epoxide hydrolase is the predominant route of primary metabolism of racemic JH III in mosquitoes. The in vitro JH epoxide hydrolase activity was 6.5 times greater for JH III than for JH I. In vitro JH III epoxide hydrolase activity was elevated at adult eclosion and in 7-d-old adult females. Both the JH III epoxide hydrolase and JH III esterase activity measured in vitro and in vivo was induced by blood feeding and peaked after 36 h, whereas the 1-naphthyl acetate (1-NA) esterase activity peaked at 24 h. In in vivo experiments only, blood feeding also increased the rate of appearance of a polar metabolite of JH III. These developmental studies indicated a possible functional role for JH metabolism in mosquito reproduction. Female adult JH esterase was resistant to inhibition by O,O-diisopropyl phosphorofluoridate, was separated from 1-NA esterase by gel filtration chromatography, and was expressed differentially during development relative to 1-NA esterase, indicating the presence of a JH-specific esterase in mosquitoes.


Video game playing and oral health in school-age children: A cross-sectional study in Turkey.
The aim of this study is to evaluate the relationship of video game playing with oral/dental health and harmful oral habits in school-age children. The daily video gamer (n = 77) and occasional video gamer (n = 77) children between 6 and 12 years old were included in the study. A questionnaire inquiring socio-demographic characteristics, video gaming and abnormal oral habits of the children was filled by parents. The children were examined intraorally and decayed-missing-filled tooth, the International Caries Detection and the Assessment-II System scores, dental plaque and gingival indices were recorded. Of the children; 42.9% daily video gamers played video games for between 1 and 2 h and 57.1% played for ≥2 h while all of the occasional video gamers spent for between 1 and 2 h on video game per day. The daily video gamer and occasional video gamer children were not different in terms of socio-demographic characteristics, frequency of having daily tooth brushing habit, using children's toothpaste and having regular dental checkup (P > 0.05). No statistically significant difference was present between the groups in terms of frequencies of abnormal oral habits and having at least one abnormal oral habit (P > 0.05). Severe gingivitis and advanced caries lesions were more common in daily video gamer group (14.2% vs. 3.9%, P = 0.025 and 90.9% vs. 70.9%, P = 0.026, respectively). Daily video gaming time was weakly correlated with plaque index (r = 0.26, n = 77, P = 0.024). Daily video gaming for ≥2 h increased the risk for severe gingivitis (odds (95% confidence interval) = 4.53 (1.07-19.23), P = 0.041) while daily video gaming for between 1 and 2 h decreased the risk for having abnormal oral habit (odds (95% confidence interval) = 0.39 (0.16-0.93), P = 0.034). In school age, daily video gaming may worsen oral and dental health compared with occasional video gaming. Particularly, an excessive video gaming time seems to be associated with poor oral health in school children.


Characteristics of suppressor macrophages induced by mycobacterial and protozoal infections in relation to alternatively activated M2 macrophages.
In the advanced stages of mycobacterial infections, host immune systems tend to change from a Th1-type to Th2-type immune response, resulting in the abrogation of Th1 cell- and macrophage-mediated antimicrobial host protective immunity. Notably, this type of immune conversion is occasionally associated with the generation of certain types of suppressor macrophage populations. During the course of Mycobacterium tuberculosis (MTB) and Mycobacterium avium-intracellulare complex (MAC) infections, the generation of macrophages which possess strong suppressor activity against host T- and B-cell functions is frequently encountered. This paper describes the immunological properties of M1- and M2-type macrophages generated in tumor-bearing animals and those generated in hosts with certain microbial infections. In addition, this paper highlights the immunological and molecular biological characteristics of suppressor macrophages generated in hosts with mycobacterial infections, especially MAC infection.


Carbon dioxide-enhanced ultrasonography of liver tumors.
CO2 gas-enhanced ultrasonography was performed in 37 patients (47 studies) for the purpose of detecting small tumors and evaluating differential diagnosis. With conventional ultrasonography, 62 lesions were identified in 25 patients with HCC, 13 tumors were identified in eight patients with hemangioma, and multiple tumors were found in four patients with metastatic adenocarcinoma. CO2-enhanced ultrasonography detected five additional hemangiomas, 12 additional nodules in HCC, and the same number of metastatic nodules. The patterns of CO2 enhancement were characterized as homogeneous, heterogeneous, rim, internal spotted, negative, and mixed (more than one pattern in one lesion). The rim enhancement pattern was found to be specific for hemangioma. The internal spotted enhancement pattern was found exclusively in HCC. All the lesions that demonstrated negative enhancement were treated HCC. All the metastatic tumors demonstrated the mixed rim and internal spotted enhancement pattern. We suggest that CO2-enhanced ultrasonography is a useful tool in detecting small liver tumors. It can also help in the differentiation among various hepatic tumors.


Differential effects on β-cell mass by disruption of Bardet-Biedl syndrome or Alstrom syndrome genes.
Rare genetic syndromes characterized by early-onset type 2 diabetes have revealed the importance of pancreatic β-cells in genetic susceptibility to diabetes. However, the role of genetic regulation of β-cells in disorders that are also characterized by highly penetrant obesity, a major additional risk factor, is unclear. In this study, we investigated the contribution of genes associated with two obesity ciliopathies, Bardet-Biedl Syndrome and Alstrom Syndrome, to the production and maintenance of pancreatic β-cells. Using zebrafish models of these syndromes, we identified opposing effects on production of β-cells. Loss of the Alstrom gene, alms1, resulted in a significant decrease in β-cell production whereas loss of BBS genes, bbs1 or bbs4, resulted in a significant increase. Examination of the regulatory program underlying β-cell production suggested that these effects were specific to β-cells. In addition to the initial production of β-cells, we observed significant differences in their continued maintenance. Under prolonged exposure to high glucose conditions, alms1-deficient β-cells were unable to continually expand as a result of decreased proliferation and increased cell death. Although bbs1-deficient β-cells were similarly susceptible to apoptosis, the overall maintenance of β-cell number in those animals was sustained likely due to increased proliferation. Taken together, these findings implicate discrepant production and maintenance of β-cells in the differential susceptibility to diabetes found between these two genetic syndromes.


Aminosteroid RM-581 Decreases Cell Proliferation of All Breast Cancer Molecular Subtypes, Alone and in Combination with Breast Cancer Treatments.
Breast cancer (BC) is a heterogenous disease classified into four molecular subtypes (Luminal A, Luminal B, HER2 and triple-negative (TNBC)) depending on the expression of the estrogen receptor (ER), the progesterone receptor (PR) and the human epidermal receptor 2 (HER2). The development of effective treatments for BC, especially TNBC, remains a challenge. Aminosteroid derivative RM-581 has previously shown an antiproliferative effect in multiple cancers in vitro and in vivo. In this study, we evaluated its effect in BC cell lines representative of BC molecular subtypes, including metastatic TNBC. We found that RM-581 has an antiproliferative effect on all BC molecular subtypes, especially on Luminal A and TNBC, in 2D and 3D cultures. The combination of RM-581 and trastuzumab or trastuzumab-emtansine enhanced the anticancer effect of each drug for HER2-positive BC cell lines, and the combination of RM-581 and taxanes (docetaxel or paclitaxel) improved the antiproliferative effect of RM-581 in TNBC and metastatic TNBC cell lines. We also confirmed that RM-581 is an endoplasmic reticulum (EnR)-stress aggravator by inducing an increase in EnR-stress-induced apoptosis markers such as BIP/GRP78 and CHOP and disrupting lipid homeostasis. This study demonstrates that RM-581 could be effective for the treatment of BC, especially TNBC.


An assessment of the nutraceutical potential of Juglans regia L. leaf powder in diabetic rats.
In this study, we evaluated the nutraceutical potential of Juglans regia L. (a dietary supplement and food-additive) by evaluating the in-vitro anti-diabetic potential and by assessing the in-vivo anti-hyperglycaemic, anti-hyperlipidaemic, and organ-protective effects of freshly-dried and powdered leaves of J. regia L. in diabetic rats. In the in-vivo experiments, dry powder of J. regia L. leaf (25, 50 and 100 mg/kg) was administered orally, twice daily (9.00 a.m. and 5 p.m.) to streptozocin-induced diabetic rats over a period of 28 days, during which body weight and blood glucose were monitored weekly. At the end of the experimental period, animals were sacrificed, blood was taken for assessment of lipid profile, antioxidant activity and liver/kidney biochemistry; while samples of the pancreas, liver and kidneys were fixed, processed, sectioned, and stained for general histology. Phytochemical evaluations of three extracts were carried out using HPLC-PDA validated procedures, while enzyme-inhibitory potentials were tested against α-amylase and α-glucosidase. In-vivo assays showed that twice-daily administration of J. regia L. leaf resulted in weight gain, glycaemic control, reversal of dyslipidaemia and biochemical evidences of liver/kidney injury, and protection against pancreas, liver and kidney tissue injury.


General surgery programs in small rural New York State hospitals: a pilot survey of hospital administrators.
Hospitals play a central role in small rural communities and are frequently one of the major contributors to the local economy. Surgical services often account for a substantial proportion of hospital revenues. The current shortage of general surgeons practicing in rural communities may further threaten the financial viability of rural hospitals and communities. To describe hospital administrators' perceptions regarding the current state of general surgery programs at small rural hospitals in New York State, including the impact that surgical services have on hospital financial viability. A list of hospitals belonging to the rural hospitals group of the Healthcare Association of New York State was obtained to determine prospective survey recipients. Sixty-eight administrators at each of the identified hospitals were subsequently surveyed and 38 respondents met all inclusion criteria. Approximately 87% of hospital administrators perceive that the general surgery program is critical to the hospital's financial viability. Forty percent of respondents report that they would be forced to close the hospital if the surgical program was lost. Among the 42% of administrators trying to recruit a general surgeon, almost two thirds have been searching for more than 1 year. According to the perceptions of hospital administrators, the financial viability of rural hospitals in New York State depends in large part on their ability to provide surgical services. Additionally, general surgeons appear to be in high demand at a significant number of the surveyed institutions.


[Viability of pancreatic transplants].
28 consecutive organ donors were divided in 5 groups according to age (6 to 40, 40 to 65) shock and history of medication requiring hypertension. Electronmicroscopy, histology and immunohistochemistry of the exocrine and endocrine pancreatic tissue, of the ductal and vascular system revealed no abnormalities accept for donors with known hypertension. On the basis of these findings in the future we will remove pancreas from donors up to the age of 65 and from those having been in shock in order to meet the increasing demand for pancreas transplants.


Conventional, complementary, and alternative options for seasonal allergies.
Conventional and alternative medicine advice abounds in the area of seasonal allergies. The number and cost of choices can be daunting to any health care professional or patient. A quick overview is needed for consumers to review simplistic lifestyle changes and non-prescription options for this year's allergy season. For example, increasing laundry water temperature and using dehumidifiers are evidenced in the literature, while using air purifiers or filters has minimal to no research. Non-prescription generic antihistamines and prescription steroid nasal sprays are perhaps under-utilized and should receive more attention. Several dietary supplements, such as butterbur and vitamin C, have some preliminary evidence, whereas most other products lack clinical evidence.


Posttranslational modification of elongation factor 2 in diphtheria-toxin-resistant mutants of CHO-K1 cells.
We have identified two types of mutants of Chinese hamster ovary cells in which the unique ADP-ribose attachment site in elongation factor 2 (EF-2) is altered, thereby rendering them resistant to diphtheria and Pseudomonas toxins (TOXR). The first is mutant in the gene for EF-2 and possesses a permanently altered, TOXR gene product. The second lacks a component of a posttranslational modification system that converts TOXR EF-2 to the toxin-sensitive (TOXS) state. We postulate that this modification system is involved in the conversion of a single histidine residue in EF-2 to the specific target of toxin-catalyzed ADP-ribosylation, the novel amino acid X. We have designated the second type MOD- mutants. The missing of nonfunctional component in the MOD- mutants can be restored by hybridizing them with either normal TOXS cells or with EF-2 structural gene mutants. The TOXR EF-2 from MOD- mutants is also converted to toxin sensitivity in vitro by incubation with extracts of TOXS or EF-2 gene mutant cells in the presence of an energy-generating system. Our results demonstrate that EF-2 can be synthesized and released from ribosomes in a toxin-resistant form and then converted to toxin sensitivity by posttranslational modification.


A Delayed-Excitation Data Acquisition Method for High-Frequency Ultrasound Imaging.
High-frequency ultrasound imaging (at >20 MHz) has gained widespread attention due to its high spatial resolution being useful for basic cardiovascular and cancer research involving small animals. The sampling rate of the analog-to-digital converter in a high-frequency ultrasound system usually needs to be higher than 120 MHz in order to satisfy the Nyquist sampling-rate requirement. However, the sampling rate is typically within the range of 40-60 MHz in a traditional ultrasound system, and so we propose a delayed-excitation method for performing high-frequency ultrasound imaging with a traditional data acquisition scheme. In this method, the transmitted pulse is delayed by a certain time period so that the ultrasound echo data are aligned into high-sampling-rate slots. Wire and tissue-mimicking phantoms were imaged to evaluate the performance of the proposed method, whereas a porcine small-intestine specimen and an excised rabbit eyeball were used for in vitro imaging evaluations. The test results demonstrate that the proposed method allows high-frequency ultrasound imaging to be implemented using a traditional ultrasound sampling system.


Chest Pain with Normal Thallium-201 Myocardial Perfusion Image - Is It Really Normal?
Thallium-201 myocardial perfusion image (MPI) is commonly used to detect coronary artery disease in patients with chest pain. Although a normal thallium-201 MPI result is generally considered to be a good prognosis and further coronary angiogram is not recommended, there are still a few patients who suffer from unexpected acute coronary events. The aim of this study was to investigate the clinical prognosis in patients with normal thallium-201 MPI. From January 2006 to August 2012, a total 22,003 patients undergoing thallium-201 MPI in one tertiary center were screened. Of these, 8092 patients had normal results and were investigated retrospectively. During follow-up, 54 patients underwent coronary angiogram because of refractory typical angina pectoris or unexpected acute coronary events. These 54 patients were divided into 2 groups: group I consisted of 26 (48.1%) patients with angiography-proven significant coronary artery stenosis, and group II consisted of 28 (51.9%) patients without significant stenosis. Patients in group I had a higher prevalence of prior coronary stenting and electrocardiographic features of ST depression compared with patients in group II. The multivariate analysis demonstrated that both prior coronary stenting and ST depression were risk predictors of unexpected acute coronary events in the patients with normal thallium-201 MPI [odds ratio (OR), 5.93; 95% confidence interval (CI): 1.03-34.06, p = 0.05 and OR, 7.10; 95% CI: 1.28-39.51, p = 0.03,respectively]. Although there is a low incidence of unexpected acute coronary events in patients with chest pain and normal thallium-201 MPI, physicians should be aware of the potentials risk in certain patients in this specific population.


Molecular profiling of stroma highlights stratifin as a novel biomarker of poor prognosis in pancreatic ductal adenocarcinoma.
Pancreatic ductal adenocarcinoma (PDAC) is a deadly cancer worldwide, as a result of a late diagnosis and limited therapeutic options. Tumour microenvironment (or stroma) plays a key role in cancer onset and progression and constitutes an intrinsic histological hallmark of PDAC. Thus we hypothesised that relevant prognostic biomarkers and therapeutic targets can be identified in the stroma. Laser microdissection of the stroma from freshly frozen PDAC was combined to gene expression profiling. Protein expression of candidate biomarkers was evaluated by immunohistochemistry on tissue microarrays (n = 80 tumours) and by ELISA in plasma samples (n = 51 patients). A signature made of 1256 genes that significantly discriminate the stroma from the non-tumour fibrous tissue was identified. Upregulated genes were associated with inflammation and metastasis processes and linked to NF-Kappa B and TGFβ pathways. TMA analysis validated an increased expression of SFN, ADAMTS12 and CXCL3 proteins in the stroma of PDAC. Stromal expression of SFN was further identified as an independent prognostic factor of overall (p = 0.003) and disease-free survival (DFS) (p = 0.034). SFN plasma expression was significantly associated with reduced DFS (p = 0.006). We demonstrated that gene expression changes within the stroma of PDAC correlate with tumour progression, and we identified Stratifin as a novel independent prognostic biomarker.


Cinnamaldehyde attenuates kidney senescence and injury through PI3K/Akt pathway-mediated autophagy via downregulating miR-155.
To prove the internal connection, we deciphered the effect of cinnamaldehyde on kidney senescence through establishing animal and cell models. In vivo, a rat senescence model was constructed using D-galactose (D-gal), and the modeled rats were further treated with cinnamaldehyde. In vitro, rat renal tubular epithelial cells (NRK-52E) were transfected with miR-155 mimic or inhibitor and then treated with cinnamaldehyde, D-gal or PI3K inhibitor (LY294002). The serum levels of blood urea nitrogen (BUN) and serum creatinine (Scr) of the rats were measured by an automatic biochemical analyzer. Pathological changes of kidney were determined by hematoxylin-eosin staining. The senescence and viability of NRK-52E cells were assessed by SA-β-gal staining and CCK-8 assay, respectively. The levels of miR-155, p-PI3K/PI3K, p-Akt/Akt, LC3B (LC3-II and LC3-I) and Beclin1 were detected by qRT-PCR, immunohistochemistry, or western blot. D-gal elevated the levels of BUN, Scr and miR-155 in the kidney, induced the renal pathological damage, inhibited the cell viability, increased the numbers of SA-β-gal-, LC3B- and Beclin1-positive cells and upregulated the levels of LC3-II/LC3-I and Beclin1 both in the kidney and cells. Cinnamaldehyde reversed D-gal-induced effects on the kidney and cells, and moreover, the cinnamaldehyde-induced anti-D-gal effects on cells could be suppressed by miR-155 mimic but promoted by miR-155 inhibitor. LY294002 potentiated D-gal-induced effects, and reversed cinnamaldehyde- and miR-155 inhibitor-caused impacts on the PI3K/Akt pathway and LC3-II/LC3-I level in D-gal-induced cells. Cinnamaldehyde attenuates kidney senescence and injury through PI3K/Akt pathway-mediated autophagy via downregulating miR-155.


Characterization of peptides released by in vitro digestion of pork meat.
The main objective of this work was to identify and characterize the peptides generated by simulated gastrointestinal digestion of pork meat (longissimus dorsi) by the sequential action of pepsin and pancreatin. The obtained hydrolysate was analyzed by liquid chromatography coupled to a quadrupole time-of-flight mass spectrometer equipped with a nanoelectrospray ionization source (nano LC-ESI-MS/MS). Using this technique 51 different peptides were identified in the hydrolysate, corresponding to fragments of the main structural muscle proteins and some well-known sarcoplasmic proteins. To the best of our knowledge, this constitutes the highest number of peptides identified in pork meat digests. Peptide fragment size ranged from six to sixteen amino acids, being rich in proline residues and thus making them more resistant to further degradation by digestive enzymes. The present study constitutes a clear evidence of the extensive degradation that pork muscle proteins would undergo after gastrointestinal digestion, giving rise to a wide variety of short peptides. So, the use of in vitro digestion contributes to a better knowledge about the generation of peptides from diets with high protein quality.


Interferon-induced glomerular basement membrane and endothelial cell lesions in mice. An immunogold ultrastructural study of basement membrane components.
Newborn Swiss mice were injected daily for the first week of life with mouse interferon alpha/beta. This treatment resulted in a delay in the maturation of the kidney and the development of glomerular abnormalities. The width of the glomerular basement membrane (GBM) was increased up to tenfold and was characterized by a marked thickening of the endothelial aspect of the GBM. The endothelial cells lining the capillary loops were also abnormal with many dilated regions of the rough endoplasmic reticulum that contained amorphous electron-opaque material. Immunogold studies showed that type IV collagen and laminin/entactin were distributed throughout the thickened GBM, and also within the dilated rough endoplasmic reticulum of the endothelial cells. These results show that the interferon-induced lesion within the glomerulus is associated with an accumulation of normal GBM components and that endothelial cells are involved in this pathologic process.


Apoptosis in lung injury and fibrosis.
Pulmonary fibrosis is characterised by fibroblast accumulation and alveolar epithelium denudation. Increased apoptosis of alveolar epithelial cells and decreased apoptosis of fibroblasts may play an important role in the pathogenesis of disease. Inflammatory cells can modulate apoptosis of other cell types, both by removal of apoptotic debris and by cytokine production, thus preserving a pro-fibrotic environment. In the present review, some of the mechanisms by which apoptosis may contribute to the pathogenesis of idiopathic pulmonary fibrosis are described.


Ethnic differences in the prevalence of peripheral arterial disease: a systematic review and meta-analysis.
Previous studies have demonstrated higher rates of peripheral arterial disease (PAD) in blacks and lower in Asians compared to whites. The aim of this study is to undertake a comprehensive review of literature on ethnic differences in the epidemiology of PAD. A systemic review and meta-analysis included studies reporting PAD prevalence in general or diabetic populations, and comparing PAD prevalence in ethnic groups. Mean prevalence of PAD in general population for whites, blacks and Asians was 3.5%, 6.7% and 3.7% respectively. Meta-analysis demonstrated higher prevalence of PAD in blacks (p < 0.001) and lower amongst Asians (p < 0.001), compared to whites. In diabetic population, the mean prevalence of PAD for whites, blacks, east Asians and south Asians was 17%, 25.3%, 13.5% and 7.6% respectively. In diabetic population, south Asians had a lower PAD prevalence (p < 0.001) compared to whites; there was no significant difference between blacks and whites. Overall females have higher PAD rates, in general (3.8% vs 3.2%; p < 0.001) and in diabetic population (13.7% vs 10%; p < 0.001). Blacks are vulnerable to PAD, in contrast to Asians who have lower prevalence of PAD when compared to whites. Further research is needed in order to identify the factors that generate this difference.


Severe congenital neutropenia or hyper-IgM syndrome? A novel mutation of CD40 ligand in a patient with severe neutropenia.
Severe congenital neutropenia (SCN) and CD40 ligand deficiency (CD40LD) are two primary immunodeficiency diseases caused by different underlying genetic defects. In this report, we present a case who clinically presented as a SCN patient, but subsequent mutation analysis of this patient was compatible with CD40LD. The patient is a 3-year-old boy, who was referred to our center because of pneumonia, oral and anal ulcers, and periodontitis. As severe consistent neutropenia and maturation arrest in the myeloid series were observed in the bone marrow, a diagnosis of SCN was made. However, no mutations were found in the ELA2 and HAX1 genes. As functional T cell defects were observed, we suspected CD40LD. DNA sequencing showed a 17-base pair deletion in the CD40L gene. Although the patient did not have a decreased serum level of IgA, and his serum IgM level was within the normal range, the diagnosis of CD40LD was confirmed, suggesting that CD40LD should be suspected in any male patient with recurrent infections and neutropenia.


The Clinical Utility of a Precision Medicine Blood Test Incorporating Age, Sex, and Gene Expression for Evaluating Women with Stable Symptoms Suggestive of Obstructive Coronary Artery Disease: Analysis from the PRESET Registry.
Background: Evaluating women with symptoms suggestive of coronary artery disease (CAD) remains challenging. A blood-based precision medicine test yielding an age/sex/gene expression score (ASGES) has shown clinical validity in the diagnosis of obstructive CAD. We assessed the effect of the ASGES on the management of women with suspected obstructive CAD in a community-based registry. Materials and Methods: The prospective PRESET (A Registry to Evaluate Patterns of Care Associated with the Use of Corus® CAD in Real World Clinical Care Settings) Registry (NCT01677156) enrolled 566 patients presenting with symptoms suggestive of stable obstructive CAD from 21 United States primary care practices from 2012 to 2014. Demographics, clinical characteristics, and referrals to cardiology or further functional and/or anatomical cardiac studies after ASGES testing were collected for this subgroup analysis of women from the PRESET Registry. Patients were followed for 1-year post-ASGES testing. Results: This study cohort included 288 women with a median age 57 years. The median body mass index was 29.2, with hyperlipidemia and hypertension present in 48% and 43% of patients, respectively. Median ASGES was 8.5 (range 1-40), with 218 (76%) patients having low (≤15) ASGES. Clinicians referred 9% (20/218) low ASGES versus 44% (31/70) elevated ASGES women for further cardiac evaluation (odds ratio 0.14, p < 0.0001, adjusted for patient demographics and clinical covariates). Across the score range, higher ASGES were associated with a higher likelihood of posttest cardiac referral. At 1-year follow-up, low ASGES women experienced fewer major adverse cardiac events than elevated ASGES women (1.3% vs. 4.2% respectively, p = 0.16). Conclusions: Incorporation of ASGES into the diagnostic workup demonstrated clinical utility by helping clinicians identify women less likely to benefit from further cardiac evaluation.


Sperm motility initiating substance may be insufficient to induce forward motility of Cynops ensicauda sperm.
Sperm motility-initiating substance (SMIS) is a key protein for internal fertilization of the newt, Cynops pyrrhogaster, and commonly enhances forward sperm motility in some amphibian species, including external fertilizers. SMIS action varies among different species in correlation with a species-specific reproductive environment. In the present study, we identified the gene of C. ensicauda SMIS (CeSMIS) and examined the mechanism of SMIS action with reference to that of the closely related Cynops species. The CeSMIS was identified by a 176-amino acid sequence including seven amino acids critical for the initiation of sperm motility. The amino acid sequence showed 91% homology to the whole sequence of C. pyrrhogaster SMIS (CpSMIS). By immunostaining with an anti-CpSMIS antibody, CeSMIS was shown to be localized in the outer layer of the egg jelly. A peptide presenting the active site of SMIS was observed to bind to the axial rod of the midpiece in C. ensicauda sperm. The localization and binding patterns of CeSMIS were fundamentally similar to those of CpSMIS. However, the SMIS peptide did not induce forward motility of C. ensicauda sperm, although it induced a fast wave of the undulating membrane. Forward sperm motility was induced in the egg jelly extract containing CeSMIS. These results suggest that the mechanism of initiation of sperm motility is differentiated between C. ensicauda and C. pyrrhogaster.


Intrahost variation and evolutionary dynamics of adenoviruses correlate to neutrophils in infected patients.
With deep sequencing of virus genomes within the hosts, intrahost single nucleotide variations (iSNVs) have been used for analyses of virus genome variation and evolution, which is indicated to correlate with viral pathogenesis and disease severity. Little is known about the features of iSNVs among DNA viruses. We performed the epidemiological and laboratory investigation of one outbreak of adenovirus. The whole genomes of viruses in both original oral swabs and cell-cultured virus isolates were deeply sequenced. We identified 737 iSNVs in the viral genomes sequenced from original samples and 46 viral iSNVs in cell-cultured isolates, with 33 iSNVs shared by original samples and cultured isolates. Meanwhile, we found these 33 iSNVs were shared by different patients, among which, three hot spot areas 6367-6401, 9213-9247, and 10 584-10 606 within the functional genes of the adenovirus genome were found. Notably, the substitution rates of iSNVs were closely correlated with the clinical and immune indicators of the patients. Especially a positive correlation to neutrophils was found, indicating a predictable biomarker of iSNV dynamics. Our findings demonstrated the neutrophil-correlated dynamic evolution features of the iSNVs within adenoviruses, which indicates a virus-host interaction during human infection of a DNA virus.


Nitrate movement in shallow ground water from swine-lagoon-effluent spray fields managed under current application regulations.
Rapid increases in the swine (Sus scrofa domestica) population in the 1990s and associated potential for nitrate N pollution of surface waters led the state of North Carolina to adopt stringent waste management regulations in 1993. Our objectives were to characterize (i) nitrate N movement from waste application fields (WAFs) in shallow ground water, and (ii) soil, hydrologic, and biological factors influencing the amount of nitrate N in the adjacent stream. A ground water monitoring study was conducted for 36 mo on a swine farm managed under new regulations. Water table contours and lack of vertical gradients indicated horizontal flow over most of the site. Nitrate N concentrations in water from shallow wells in WAFs averaged 30 +/- 19 mg L(-1) and delta15N ratios for nitrate N were between +20 and +25 per mil. Nitrate N concentration decreased from field-edge to streamside wells by 22 to 99%. Measurement of delta18O and delta15N enrichment of nitrate in ground water throughout the WAF-riparian system indicated that denitrification has not caused significant 15N enrichment of nitrate. Over a 24-mo period, delta15N ratios for nitrate N in the stream approached delta15N ratios for nitrate N in ground water beneath WAFs indicating delivery of some waste-derived nitrate N to the stream in shallow ground water. Nitrate N concentrations in the stream were relatively low, averaging 1 mg L(-1). Dilution of high nitrate N water in shallow horizontal flow paths with low nitrate N water from deeper horizontal flow paths at or near the stream, some denitrification as ground water discharges through the stream bottom, and some denitrification in riparian zone contributed to this low nitrate N concentration.


Behind dark glasses: irony as a strategy for indirect communication.
This article outlines the model of irony seen as a "fencing game." The starting point is the metaphor of the "dark glasses" (R. Barthes, 1977), according to which irony is considered as a mask revealing, paradoxically, what it apparently hides. Basing the study on both perspectives of symbolic interactionism and planning communication theory, the authors analyze the social functions of irony (to evade censure in a socially correct way, to safeguard private space, to renegotiate meanings). In this framework, irony is described as a script of actions that people use astutely in order to strike antagonists in a graceful but "stinging" way, just like fencers in a competition. The fencing game model of irony foresees 4 steps: the textual and contextual assumptions (i.e., shared knowledge), the focal event (the trigger of irony), the dialogic comment (the ironic utterance the speaker performs by combining verbal and nonverbal aspects), and the ironic effect referring to the addressee's feedback (denying, misunderstanding, touché). The advantages of the fencing game model of irony are also considered.


Establishing Biomarkers in Transplant Medicine: A Critical Review of Current Approaches.
Although the management of kidney transplant recipients has greatly improved over recent decades, the assessment of individual risks remains highly imperfect. Individualized strategies are necessary to recognize and prevent immune complications early and to fine-tune immunosuppression, with the overall goal to improve patient and graft outcomes. This review discusses current biomarkers and their limitations, and recent advancements in the field of noninvasive biomarker discovery. A wealth of noninvasive monitoring tools has been suggested that use easily accessible biological fluids such as urine and blood, allowing frequent and sequential assessments of recipient's immune status. This includes functional cell-based assays and the evaluation of molecular expression on a wide spectrum of platforms. Nevertheless, the translation and validation of exploratory findings and their implementation into standard clinical practice remain challenging. This requires dedicated prospective interventional trials demonstrating that the use of these biomarkers avoids invasive procedures and improves patient or transplant outcomes.


Germline Mutation Analysis in Sporadic Breast Cancer Cases With Clinical Correlations.
Demographics for breast cancers vary widely among nations. The frequency of germline mutations in breast cancers, which reflects the hereditary cases, has not been investigated adequately and accurately in highly-consanguineous Pakistani population. In the present discovery case series, germ-line mutations in twenty-seven breast cancer candidate genes were investigated in eighty-four sporadic breast cancer patients along with the clinical correlations. The germ-line variants were also assessed in two healthy gender-matched controls. The clinico-pathological features were evaluated by descriptive analysis and Pearson χ2 test (with significant p-value <0.05). The most frequent parameters associated with hereditary cancer cases are age and ethnicity. Therefore, the analyses were stratified on the basis of age (≤40 years vs. >40 years) and ethnicity. The breast cancer gene panel assay was carried out by BROCA, which is a genomic capture, massively parallel next generation sequencing assay on Illumina Hiseq2000 with 100bp read lengths. Copy number variations were determined by partially-mapped read algorithm. Once the mutation was identified, it was validated by Sanger sequencing. The ethnic analysis stratified on the basis of age showed that the frequency of breast cancer at young age (≤40 years) was higher in Sindhis (n = 12/19; 64%) in contrast to patients in other ethnic groups. Majority of the patients had stage III (38.1%), grade III (50%), tumor size 2-5 cm (54.8%), and invasive ductal carcinoma (81%). Overall, the analysis revealed germ-line mutations in 11.9% of the patients, which was not significantly associated with younger age or any particular ethnicity. The mutational spectrum was restricted to three genes: BRCA1, BRCA2, and TP53. The identified mutations consist of seven novel germ-line mutations, while three mutations have been reported previously. All the mutations are predicted to result in protein truncation. No mutations were identified in the remaining twenty-four candidate breast cancer genes. The present study provides the framework for the development of hereditary-based preventive and treatment strategies against breast cancers in Pakistani population.


Autotaxin in encephalitogenic CD4 T cells as a therapeutic target for multiple sclerosis.
Multiple sclerosis (MS) is an immune-mediated inflammatory disease of the CNS. A defining characteristic of MS is the ability of autoreactive T lymphocytes to cross the blood-brain barrier and mediate inflammation within the CNS. Previous work from our lab found the gene Enpp2 to be highly upregulated in murine encephalitogenic T cells. Enpp2 encodes for the protein autotaxin, a secreted glycoprotein that catalyzes the production of lysophosphatidic acid and promotes transendothelial migration of T cells from the bloodstream into the lymphatic system. The present study sought to characterize autotaxin expression in T cells during CNS autoimmune disease and determine its potential therapeutic value. Myelin-activated CD4 T cells upregulated expression of autotaxin in vitro, and ex vivo analysis of CNS-infiltrating CD4 T cells showed significantly higher autotaxin expression compared with cells from healthy mice. In addition, inhibiting autotaxin in myelin-specific T cells reduced their encephalitogenicity in adoptive transfer studies and decreased in vitro cell motility. Importantly, using two mouse models of MS, treatment with an autotaxin inhibitor ameliorated EAE severity, decreased the number of CNS infiltrating T and B cells, and suppressed relapses, suggesting autotaxin may be a promising therapeutic target in the treatment of MS.


Relative potency of 10 drugs with anti-Pneumocystis carinii activity in an animal model.
Several drugs have been shown to have anti-Pneumocystis carinii activity in clinical trials. Because of the large number of patients required, no more than 3 drugs can be compared for efficacy in human studies. However, the experimental animal model for P. carinii pneumonitis is remarkably similar to the human disease and was used to compare 10 drugs for the relative potency against this infection. All drugs were compared at doses known to prevent the pneumonitis in > 80% of animals and at one-tenth of this dose. Drugs effective at the lowest dose were further tested at one-hundredth the original doses, and drugs ineffective were retested at 10 and 100 times the original dose. Trimethoprim-sulfamethoxazole was the most effective drug, with azithromycin-sulfamethoxazole and clarithromycin-sulfamethoxazole next most effective. Intravenous pentamidine and clindamycin-primaquine were the least effective. Atovaquone, sulfadoxine-pyrimethamine, erythromycin-sulfisoxazole, PS-15, and dapsone-trimethoprim had intermediate activity.


Vital dyes in ophthalmology: a chemical perspective.
Vital dyes have advanced diagnosis and surgical technique in various specialties, including oncology, gastroenterology and ophthalmology. Intra-operative and diagnostic dyes are finding uses in all areas of ophthalmology, including cornea, cataract, retina, glaucoma, orbit and conjunctiva. We provide a summary of current knowledge of the chemical concepts of vital dyes in ophthalmology. We review the properties of dyes, techniques of application, indications and complications in ocular surgery. Vital dyes represent an expanding area of research, and novel dyes deserve further investigation.


Overexpression of prothymosin alpha accelerates proliferation and retards differentiation in HL-60 cells.
Prothymosin alpha (ProTalpha) is an acidic nuclear protein the expression of which is related to the proliferation and differentiation processes in mammalian cells. In the present study we have stably transfected HL-60 cells, a biological system that allows the study of both proliferation and differentiation, with recombinant vectors encoding sense and antisense ProTalpha mRNA. In the HL-60 cell clones overexpressing ProTalpha we observed an acceleration in the growth rate, whereas expression of the antisense orientation showed the opposite effect. Moreover, cell-cycle analysis demonstrated that the G1-phase was shortened in the cells expressing the sense construct. Before studying how ProTalpha affects differentiation, we showed that the down-regulation of ProTalpha gene during differentiation occurs in all mammalian cell lines (HL-60, K562, U937, MEL C88, N2A and PC12) analysed. The biological effect evoked by the induction of the ProTalpha sense vector was the retardation of cell differentiation, although expression of the antisense construct showed no effect on differentiation. In conclusion, our findings provide evidence that ProTalpha is directly implicated in cellular proliferation and that the maintenance of high levels of ProTalpha inside HL-60 cells is incompatible with their ability to differentiate.


A systematic review of pseudophakic monovision for presbyopia correction.
A systematic review of the recent literature regarding pseudophakic monovision as a reliable methods for presbyopia correction was performed based on the PubMed, MEDLINE, Nature and the American Academy of Ophthalmology databases in July 2015 and data from 18 descriptive and 12 comparative studies were included in this narrative review. Pseudophakic monosvision seems to be an effective method for presbyopia with high rates of spectacles independence and minimal dysphotopsia side-effects, that should be considered by the modern cataract surgeons.


Sexual activity among adolescents in Ilorin, Kwara State, Nigeria.
With the aid of a self-administered questionnaire, sexual activity was investigated among 1,200 students aged 10-19 years. Two hundred and sixty-four (23.7%) respondents indicated they were sexually active. The mean age at first intercourse was 11.3 years (SD=5.8 years), while the average number of sex partner was 2-3. Multiple sexual partners were found in 99 (69.2%) of the males and in 16 (32.7%) of the females (P < 0.05). Males were more sexually active, 189 (32.8%) compared with 73 (13.7%) females (P=0.000001; RR=2.4 (1.88-3.05). Two hundred and fifty-three (23.4%) ofthose respondents who claimed to be highly religious had sexual intercourse compared with 7 (50%) of those who claimed not to be religious (P=0.02; PR=0.47 (0.27-0.80). Those whose parents lived together were less likely to be sexually active. 184 (21.2%) versus 47 (34.8%) (P=0.005). It is therefore concluded that our adolescents especially males remain sexually active. It also demonstrates the dramatic lowering of age at first intercourse. Family supervision and level of religious activity were recognized as factors that have significant impact on sexual activity. Preventive efforts must therefore focus on these issues with the active involvement of the Pediatrician, parents and religious leaders.


Male sex, African American race or ethnicity, and triiodothyronine levels at diagnosis predict weight gain after antithyroid medication and radioiodine therapy for hyperthyroidism.
To determine whether racial or ethnic differences affect weight gain after treatment of hyperthyroidism and to reassess established risk factors such as sex, age, and cause of hyperthyroidism. We conducted a retrospective review of medical records of 111 patients treated with radioiodine (RAI) for hyperthyroidism, with or without preceding antithyroid medication, during 2002 to 2005. We ascertained age, sex, race or ethnicity, insurance status, compliance with visits, serum triiodothyronine (T3) level at diagnosis, and cause of hyperthyroidism. Weights and serum thyroidstimulating hormone levels were obtained at diagnosis, at time of RAI therapy, and at 0 to 4 months, 4 to 8 months, 8 to 12 months, and 24 months after RAI treatment. There was a significant weight increase after treatment of hyperthyroidism. Levels of T3 at initial diagnosis of hyperthyroidism, male sex, and black or Hispanic ethnicity were found to be independent predictors of weight gain after RAI treatment. We found a significant interaction between race or ethnicity and sex in multivariate models. There was no difference in thyroid function across racial or ethnic groups or the sexes. Age, cause of hyperthyroidism, posttreatment thyroid-stimulating hormone level, compliance, and insurance status were not found to be significant predictors of weight gain. The T3 level at the time of diagnosis of hyperthyroidism is a strong predictor of weight gain after treatment of hyperthyroidism. Black race or ethnicity and male sex are also risk factors for weight gain.


Comparison between two high-dose methylprednisolone schedules in the treatment of acute hepatic cellular rejection in liver transplant recipients: a controlled clinical trial.
Intravenous methylprednisolone is used in most liver transplant centers as first-line therapy of acute hepatic cellular rejection in patients who undergo liver transplant. However, no controlled study has been performed to date to define the optimal dose and duration of the steroid regimen. The schedules that actually are used in most transplant centers are drawn from those that were developed empirically for the treatment of acute renal graft rejection. Thus, the aim of the study was to compare two schedules of steroid treatment of acute hepatic cellular rejection among those most widely used. Thirty-eight eligible patients with grade II or III acute hepatic cellular rejection were randomized to receive two different high-dose methylprednisolone schedules. Eighteen patients were randomized in group A (intravenous dose of 1,000 mg of methylprednisolone followed by a 6-day taper from 200 to 20 mg/d). Twenty patients were randomized in group B (intravenous dose of 1,000 mg of methylprednisolone for three consecutive days). The response to treatment was evaluated by means of a second liver biopsy. The treatment of group A proved to be more effective than treatment of group B. The resolution of acute hepatic cellular rejection was observed in 83.3% of cases in group A and 50.0% of cases in group B (P <.05). The treatment of group A proved to be safer also than treatment of group B. Patients randomized in group B showed a higher prevalence of infections (90.0% of cases versus 55.5% of cases; P <.01) mainly because of bacterial (80.0% versus 50.0%; P <.05) and viral (50.0% versus 16.6%; P <.05) agents. In conclusion, the study shows that intravenous administration of 1,000 mg of methylprednisolone followed by a 6-day taper from 200 to 20 mg/d is more effective and safer than intravenous dose of 1,000 mg of methylprednisolone for three consecutive days in the treatment of acute cellular rejection in patients with liver transplantation.


Cryptosporidium infection and associated risk factors among children from rural areas in Peru: a nested case-control study.
This study aimed to detect the frequency of Cryptosporidium infection and associated risk factors among children from rural areas in Peru. A case-control study was conducted, nested in a cohort in two rural communities that included children between 6 and 13 months who were followed for 6 months. Cases were children whose fecal samples tested positive for Cryptosporidium infection using an immunochromatography test. Logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) to analyze risk factors associated with Cryptosporidium infection. Among 72 children, 13 (18%) were cases. Cryptosporidium infection was associated with below secondary education of the mother (OR 7.62, 95% CI 1.50-36.72) and with having more siblings living at home (OR 1.71, 95% CI 1.04-2.82). An important frequency of Cryptosporidium infection among children from rural areas in Peru was reported, more research is needed to understand its true burden and risk factors among children in Peru.


Adsorption-Coupled Diffusion of Gold Nanoclusters within a Large-Pore Protein Crystal Scaffold.
Large-pore protein crystals (LPCs) are ordered biologically derived nanoporous materials exhibiting pore diameters greater than 8 nm. These substantial pores distinguish LPCs from typical nanoporous scaffolds, enabling engineered LPC materials to readily uptake, immobilize, and release macromolecular guests. In this study, macromolecular transport within an LPC environment was experimentally and computationally investigated by studying adsorption-coupled diffusion of Au25(glutathione)18 nanoclusters within a cross-linked LPC scaffold via time-lapse confocal microscopy, bulk equilibrium adsorption, and hindered diffusion simulation. Equilibrium adsorption data is congruent with a Langmuir adsorption model, exhibiting strong binding behavior between nanoclusters and the scaffold. The standard Gibbs free energy of binding is equivalent to -37.2 kJ/mol, and the maximum binding capacity of 1.25 × 103 mg/g corresponds to approximately 29 nanoclusters per LPC unit cell. The hindered diffusion model showed good agreement with experimental data, revealing a pore diffusion coefficient of 3.7 × 10-7 cm2/s under low nanocluster concentration. Furthermore, the model was sufficient to determine adsorption and desorption kinetic values for ka and kd equal to 13 cm3/mol·s and 1.7 × 10-7 s-1, respectively. At higher nanocluster concentrations, the simulated pore diffusion coefficient could be reduced by 3 orders of magnitude to 3.4 × 10-10 cm2/s due to the effects of pore occlusion. This study demonstrates a strategy to analyze adsorption-coupled diffusion data to better understand complex transport of fluorescent macromolecules into LPCs. This approach fits the observable fluorescence data to the key molecular details and will benefit downstream efforts to engineer LPC-based nanoporous materials.


Long term phonatory function following acoustic neuroma surgery: a cohort study.
Background: Acoustic neuroma (AN) is a well-recognized cause of neurological morbidity, peripheral facial paralysis being one of the most prevalent. Phonatory dysfunction in the late post-operative term has not been properly addressed so far.Objective: The objective of this study is to describe the outcomes of phonatory function on the long-term follow-up of AN surgery and identify its prognostic factors.Material and methods: This cohort study included patients submitted to AN surgery from 1999 to 2014, with a mean follow up of 6.4 ± 4.5 years. To evaluate the phonatory function, we performed a combination of noninvasive acoustic and aerodynamic measurements including vocal intensity and stability, maximum declination rate of the glottal airflow (MDR) and transglottal pressure scale (TP).Results: 101 patients were studied. 25 (24.7%) presented a deficit in phonatory function. Women comprised 56% and the mean age was 42.4 ± 13.8 years (range19-80). 100% presented reduced expiratory airflow capacity with excessive manifestation of the laryngeal musculature (TP > 1,23s ;MDR/z/<MDR/s/). Dysphonic patients presented more neurofibromatosis II (NF II) (40% vs 12.7% p = .002), large tumors (3.8 ± 1.1 p = .002) and needed less surgeries (≥256.7% vs 74.6%, p = .0073) in univariate analysis. NFII and tumor size were predictive of dysphonia according to multivariate analysis (NFII-OR 5.57, p = .006; tumor size-each 1 cm, OR1.68, p = .062).Conclusion: The late postoperative prevalence of dysphonia corresponded to 24.7%. Dysphonia could be secondary to the hyperfunction of laryngeal musculature explained by the reduced expiratory airflow found in our patients. Tumor size and NF II were predictors for the occurrence of dysphonia in the present study.HighlightsThe comprise of phonation function can be a morbidity of AN surgeryNF II and tumor size were predictive of dysphonia on late postoperative periodData of hypofunction secondary to the phonatory hyperfunction were unanimous in the dysphonic patients.The early diagnosis and treatment of phonation function could avoid alterations of pneumophono-articulatory coordination and projection deficiency.


Palliation of oesophagogastric neoplasms with Nd:YAG laser treatment.
The palliative effect of endoscopic Nd:YAG laser treatment of malignant strictures of the oesophagus and cardia was prospectively evaluated in 30 patients. Most (n = 28) were primarily treated for dysphagia, and swallowing was improved in 21 and normalized in 14 of these patients. Two patients were successfully treated for bleeding. Six patients developed complications (including two perforations), and four of these were fatal. The median survival was 4 months (range, 17 days to 14 months). It is concluded that in a great number of patients with inoperable cancer of the oesophagus and cardia, laser treatment is better than other palliative procedures.


Severity of ruminal acidosis in primiparous holstein cows during the periparturient period.
The objectives of this study were: 1) to determine the effect of providing additional prepartum concentrate on the occurrence and severity of ruminal acidosis (RA) and lactational performance during the periparturient period in primiparous cows; and 2) to characterize the occurrence and severity of RA during the periparturient period. We hypothesized that providing additional concentrate prepartum would reduce postpartum RA. Fourteen ruminally cannulated Holstein heifers were paired by expected calving date and body condition score. The heifers were assigned to 1 of 2 prepartum feeding regimens: 1) a control treatment consisting of a far-off diet (forage:concentrate, F:C = 80:20) fed from d -60 to d -25 and a close-up diet (F:C = 54:46) fed from d -24 until parturition; or 2) a high-concentrate (HC) feeding program consisting of 4 prepartum diets, HC-1 (F:C = 68:32) fed from d -60 to d -43, HC-2 (F:C = 60:40) fed from d -42 to d -25, HC-3 (F:C = 52:48) fed from d -24 to d -13, and HC-4 (F:C = 46:54) fed from d -12 until parturition. All cows received the same lactation diet postpartum. Ruminal pH was measured continuously from d -5 to d +5, and for 3 consecutive days starting on d +17 +/- 1.2, d +37 +/- 1.4, and d +58 +/- 1.5 relative to parturition using an indwelling ruminal pH system. Ruminal acidosis was considered to occur when ruminal pH was <5.8 (total RA). Ruminal acidosis was further partitioned into: 1) mild RA (5.8 > ruminal pH > 5.5), 2) moderate RA (5.5 > ruminal pH > 5.2), and 3) acute RA (ruminal pH < 5.2). Feeding additional concentrate prepartum did not reduce postpartum RA. In fact, cows fed the HC treatment had more daily episodes of acute RA than cows fed the control treatment. Day relative to parturition affected the occurrence and severity of RA; RA increased following parturition and was sustained thereafter. The DM intake during the last 5 d of gestation was lower for cows fed the HC treatment compared with cows fed the control treatment, but lactational performance was not affected. We conclude that, under the conditions imposed, feeding additional concentrate prepartum does not reduce postpartum RA. Furthermore, the incidence and severity of RA increases immediately postpartum, emphasizing the need to develop and implement feeding strategies that reduce this risk.


[Role of cardiac sympathetic nervous activity in exercise--changes in catecholamine level on forced swimming rat].
Endurance exercise demands full adaptive mechanisms in various organs. Sympathetic nervous system is said to play an important role on supporting the cardiac function through norepinephrine (NE) release. The purpose of this study is to investigate the role of cardiac sympathetic nervous system in exercise by measuring the activity of cardiac tyrosine hydroxylase (TH), rate-limiting enzyme in catecholamine (CA) synthesis and concentration of NE and 3,4-Dihydroxyphenylethylene glycol (DHPG), major metabolite of CA. 14 week old Wistar rats were forced to swim in 37 degrees C water bath for 90, 150, 240, 330 minutes, respectively. Some of them couldn't swim until the fixed time (group D). After swimming, they were promptly decapitated ++ and then concentration of plasma, cardiac and adrenal CA, activity of cardiac TH and concentration of cardiac DHPG were measured. Myocardial contractility was also measured using removed papillary muscle. (1) Plasma CA concentration didn't change between control and each swimming group, but elevated in group D. (2) Cardiac CA concentration decreased as swimming was prolonged and markedly reduced in group D. (3) Adrenal CA concentration in swimming group tended to elevate and decreased in group D. (4) There were no differences in activity of cardiac TH between swimming group and control. (5) Concentration of cardiac DHPG were decreased in group D compared with control. (6) There were no differences in myocardial contractility between control and group D. These results suggest; prolonged exercise seemed to be supported by cardiac sympathetic NE release and was no longer continued when the cardiac sympathetic support was reduced.


Inhibition of high-voltage-activated calcium currents by acute hypoxia in cultured retinal ganglion cells.
Hypoxia is a common factor of numerous ocular diseases that lead to dysfunctions and loss of retinal ganglion cells (RGCs) with subsequent vision loss. High-voltage-activated calcium channels are the main source of calcium entry into neurons. Their activity plays a central role in different signaling processes in health and diseases, such as enzyme activation, gene transcription, synaptic transmission, or the onset of cell death. This study aims to establish and evaluate the initial effect of the early stage of acute hypoxia on somatic HVA calcium currents in cultured RGCs. HVA calcium currents were recorded in RGCs using the whole-cell patch-clamp technique in the voltage-clamp mode. The fast local superfusion was used for a brief (up to 270 s) application of the hypoxic solution (pO2 < 5 mmHg). The switch from normoxic to hypoxic solutions and vice versa was less than 1 s. The HVA calcium channel activity was inhibited by acute hypoxia in 79% of RGCs (30 of 38 RGCs) in a strong voltage-dependent manner. The level of inhibition was independent of the duration of hypoxia or repeated applications. The hypoxia-induced inhibition of calcium currents had a strong correlation with the duration of hypoxia and showed the transition from reversible to irreversible at 75 s of hypoxia and longer. The results obtained are the first demonstration of the phenomena of HVA calcium current inhibition by acute hypoxia in RGCs and provide a conceptual framework for further research.


Dynamic contrast-enhanced CT of intracranial meningioma: comparison of distributed and compartmental tracer kinetic models--initial results.
Dynamic contrast material-enhanced computed tomographic images of intracranial meningioma were analyzed by using both distributed-parameter and conventional compartmental tracer kinetic models. The distributed-parameter models were found to yield consistently better fitting of data sets than were conventional compartmental models. Although linear correlations were found between the kinetic parameters of the two models, some of these parameters (such as perfusion and mean transit time) did not correspond quantitatively. For all models, the kinetic parameters associated with the extravasation of tracer were found to be distinctly higher in meningiomas than in normal white- and gray-matter tissues.


Reward-Related Neural Activity and Adolescent Antisocial Behavior in a Community Sample.
Behavioral research has found evidence supporting reward dominance in adolescence with externalizing disorders, but findings from neuroimaging studies have been largely heterogeneous. We examined the Feedback-Related Negativity (FRN) and P3b in relation to self-reported externalizing behavior among 78 adolescents (11-18 yrs) during a monetary gambling task with concurrent high-density electroencephalogram. As expected, the P3b and the FRN demonstrated greater evoked activity to reward and punishment, respectively. Further, high externalizing behavior was associated with greater P3b difference and reduced FRN difference in response to reward and punishment, suggesting that externalizing behaviors may be associated with both reward dominance and reduced feedback-monitoring.


Coronary Spastic Angina Induced by Adrenal Insufficiency.
Adrenal insufficiency patients are treated with glucocorticoid replacement therapy. However, mimicking the in vivo circadian rhythm of cortisol levels is challenging, and suboptimal replacement increases the risk of mortality from cardiovascular disease. We herein report a case of coronary spastic angina (CSA) with simultaneous low early-morning serum cortisol levels in a patient undergoing corticosteroid replacement therapy for primary adrenal insufficiency. Steroid therapy is reportedly effective for refractory angina, but underlying adrenal deficiency has never been revealed. Our case intimates the probable risk of CSA as a complication of relative adrenal insufficiency and highlights the effectiveness of dexamethasone in these patients.


[The Original Formulation for Toso-shu (Tusujiu), Created by the 3rd Century Chinese Physician, Hua Tuo].
The original formulation for "Tusujiu," which Japanese people still consume on the morning of January 1st, was created by Hua Tuo, but has not been studied in detail. The book Huatuo Shenyi Bizhuan, found in 1918, describes a concoction, "Biyijiu," that shows great similarity to the current Tusujiu; the ingredients for Biyijiu being rhubarb, atractylodes rhizome, cinnamon bark, platycodon root, zanthoxylum fruit, processed aconite root and smilax rhizome. The procedures for preparing and drinking it are to "pound the ingredients and then put them into a silk bag dyed with madder. During the daytime of the last day of the year, hang the bag in a well to soften the powder. Take the bag out early in the morning of the next day, the first day of the year. Heat the bag in fermented liquor until simmering. Drink the liquid with all family members, doing so while facing east. If one person drinks it, there will be no disease in the family. If the whole family drinks it, there will be no disease in their neighborhood in an area of one square 'li'. In this study, to determine the original formulation for Tusujiu, we examined a number of ancient medical texts from the 3rd to the 13th century that discuss Biyijiu and Tusujiu. As a result, we concluded that "Biyijiu" is likely to be the original formulation developed by Hua Tuo.


Re-imagining the future of diagnosis of Neglected Tropical Diseases.
Neglected Tropical Diseases (NTDs) affect an estimated 1 billion people in 149 countries. The World Health Organization (WHO) prioritised 17 NTDs for control and elimination by 2020 and defined a Road Map to help countries reach these goals. Improved diagnostics for NTDs are essential for guiding treatment strategies at different thresholds of control, interruption of transmission, elimination and post-elimination surveillance. While substantial progress has been made in the last decade with chemotherapy, the same cannot be said of diagnostics, largely due to the perceived lack of a commercially viable market for NTD diagnostics. New sample in-answer out nucleic acid amplification technologies that can be performed at the point-of-care offer improved performance over current technologies and the potential to test for multiple pathogens using a single specimen. Finding commonalities for different NTDs in terms of geographic overlap, sentinel populations and treatment strategy will allow NTD programs to leverage these innovations to build cost-effective multiplex surveillance platforms. Connectivity solutions linking data from diagnostic laboratories and POC test readers/devices provide opportunities for automated surveillance systems to make health systems more efficient, improving patient outcomes and assessing impact of interventions in real time. New models of public-private product development partnerships are critical in leveraging diagnostic innovation in other priority area for better diagnosis, control and elimination of NTDs.


Regulation of AMPA receptor trafficking and exit from the endoplasmic reticulum.
A fundamental property of the brain is its ability to modify its function in response to its own activity. This ability for self-modification depends to a large extent on synaptic plasticity. It is now appreciated that for excitatory synapses, a significant part of synaptic plasticity depends upon changes in the post synaptic response to glutamate released from nerve terminals. Modification of the post synaptic response depends, in turn, on changes in the abundances of AMPA receptors in the post synaptic membrane. In this review, we consider mechanisms of trafficking of AMPA receptors to and from synapses that take place in the early trafficking stages, starting in the endoplasmic reticulum (ER) and continuing into the secretory pathway. We consider mechanisms of AMPA receptor assembly in the ER, highlighting the role of protein synthesis and the selective properties of specific AMPA receptor subunits, as well as regulation of ER exit, including the roles of chaperones and accessory proteins and the incorporation of AMPA receptors into COPII vesicles. We consider these processes in the context of the mechanism of mGluR LTD and discuss a compelling role for the dendritic ER membrane that is found proximal to synapses. The review illustrates the important, yet little studied, contribution of the early stages of AMPA receptor trafficking to synaptic plasticity.


Chemistry, Local Molybdenum Clustering, and Electrochemistry in the Li2+xMo1-xO3 Solid Solutions.
A broad range of cationic nonstoichiometry has been demonstrated for the Li-rich layered rock-salt-type oxide Li2MoO3, which has generally been considered as a phase with a well-defined chemical composition. Li2+xMo1-xO3 (-0.037 ≤ x ≤ 0.124) solid solutions were synthesized via hydrogen reduction of Li2MoO4 in the temperature range of 650-1100 °C, with x decreasing with the increase of the reduction temperature. The solid solutions adopt a monoclinically distorted O3-type layered average structure and demonstrate a robust local ordering of the Li cations and Mo3 triangular clusters within the mixed Li/Mo cationic layers. The local structure was scrutinized in detail by electron diffraction and aberration-corrected scanning transmission electron microcopy (STEM), resulting in an ordering model comprising a uniform distribution of the Mo3 clusters compatible with local electroneutrality and chemical composition. The geometry of the triangular clusters with their oxygen environment (Mo3O13 groups) has been directly visualized using differential phase contrast STEM imaging. The established local structure was used as input for density functional theory (DFT)-based calculations; they support the proposed atomic arrangement and provide a plausible explanation for the staircase galvanostatic charge profiles upon electrochemical Li+ extraction from Li2+xMo1-xO3 in Li cells. According to DFT, all electrochemical capacity in Li2+xMo1-xO3 solely originates from the cationic Mo redox process, which proceeds via oxidation of the Mo3 triangular clusters into bent Mo3 chains where the electronic capacity of the clusters depends on the initial chemical composition and Mo oxidation state defining the width of the first charge low-voltage plateau. Further oxidation at the high-voltage plateau proceeds through decomposition of the Mo3 chains into Mo2 dimers and further into individual Mo6+ cations.


Penile Mondor's disease in a patient treated with radical chemoradiation for anal cancer.
Penile Mondor's disease is a rare condition characterized by sclerosing thrombophlebitis of the superficial dorsal penile vein. Usually its causes are benign, but it is also evident in cancer patients. We report the case of a 62-year-old man with a cT4 anal cancer (infiltration of corpora spongiosa and penile bulb), associated with extensive loco-regional lymphadenopathy, who developed painful lumps in the midline of the anterior penile surface while receiving radical chemoradiotherapy. Physical examination revealed two palpable cord-like swellings located 2 cm from the pubic symphysis. Color Doppler ultrasound established the diagnosis of Mondor's disease. The patient was successfully managed with non-steroidal anti-inflammatory drugs. The causative factors were pelvic malignancy and radiotherapy. The diagnosis was challenging since Mondor's disease is a rare condition and the differential diagnosis included malignancy progression. This is the first case report describing penile Mondor's disease in a patient with anal cancer under chemoradiotherapy.


Fas-Antisense Long Noncoding RNA and Acute Myeloid Leukemia: Is There any Relation?
In recent years, lncRNAs have been considered as potential predictive biomarkers for prognosis of different human cancers. One example is the FAS antisense RNA 1 (FAS-AS1) located in the 10q23.31 region which is transcribed from the opposite strand of the FAS gene. FAS has an important role in regulation of apoptotic pathways and there is an inverse correlation between FAS-AS1 expression level and production of the soluble form of Fas, so that it might have potential as a therapeutic target to improve chemotherapy effectiveness. In the present study we therefore evaluated FAS-AS1 expression in blood samples of de novo AML patients and healthy controls using real-time quantitative reverse transcription-PCR (qRT-PCR). Our results indicated that the expression level of FAS-AS1 lncRNA demonstrated no significant difference between AML patients and healthy individuals. We conclude from the obtained data that FAS-AS1 is not an informative and reliable biomarker for AML diagnosis, although our results need to be confirmed in further studies.


Operando Liquid Pressure Determination in Polymer Electrolyte Fuel Cells.
Extending the operating range of fuel cells to higher current densities is limited by the ability of the cell to remove the water produced by the electrochemical reaction, avoiding flooding of the gas diffusion layers. It is therefore of great interest to understand the complex and dynamic mechanisms of water cluster formation in an operando fuel cell setting as this can elucidate necessary changes to the gas diffusion layer properties with the goal of minimizing the number, size, and instability of the water clusters formed. In this study, we investigate the cluster formation process using X-ray tomographic microscopy at 1 Hz frequency combined with interfacial curvature analysis and volume-of-fluid simulations to assess the pressure evolution in the water phase. This made it possible to observe the increase in capillary pressure when the advancing water front had to overcome a throat between two neighboring pores and the nuanced interactions of volume and pressure evolution during the droplet formation and its feeding path instability. A 2 kPa higher breakthrough pressure compared to static ex situ capillary pressure versus saturation evaluations was observed, which suggests a rethinking of the dynamic liquid water invasion process in polymer electrolyte fuel cell gas diffusion layers.


A bovine monoclonal antibody detecting a class I BoLA antigen.
The bovine IgG1 monoclonal antibody (mAb) ILA70 was made by immunizing a calf with peripheral blood mononuclear cells (PBM) from a BoLA-w10 homozygous heifer and subsequently fusing lymphocytes from the local lymph-node with the heterohybridoma 53B3. Family and population studies, antibody binding inhibition and immunoprecipitation of the target antigen all indicate that ILA70 detects a polymorphic epitope on a bovine class I major histocompatibility complex (MHC) molecule. The antibody is complement fixing and so may be used in a standard cytotoxicity assay. Ascitic fluid with antibody activity many times greater than that of the tissue-culture supernatant has been prepared in nude mice. The antibody-producing heterohybridoma has been subcloned three times and appears to be stable. Such heterohybridomas may prove to be a valuable source of particularly discriminating and informative mAbs for the serological analysis of the products of the bovine MHC.


Effects of L-Cysteine and γ-Aminobutyric Acid Treatment on Postharvest Quality and Antioxidant Activity of Loquat Fruit during Storage.
Sichuan is the China's leading producer of loquat, with the largest cultivation area and yield ranked first in China. Loquat is a seasonal fruit highly appreciated by consumers; however, the fruit is prone to browning and lignification after harvest, affecting its storage quality. The effects of L-Cysteine (L-Cys, 0.01, 0.05, 0.1, 0.2%) and γ-aminobutyric acid (GABA, 0.025, 0.05, 0.075, 0.1%) on the sensory quality and antioxidant activity of loquat fruit during cold storage at 4 °C for 35 days and simulated shelf life for 5 days were investigated. The results showed that after 40 days of storage, compared with the control, 0.05% L-Cys and 0.05% GABA treatment of 'Zaozhong No. 6' loquat fruit effectively reduced the weight loss rate, browning index, decay index, respiratory rate, firmness, and lignin content and slowed the decreases in total soluble solids, soluble sugar, titratable acidityand vitamin C contents. The application of 0.05% L-Cys and 0.05% GABA significantly increased the contents of total phenols, total flavonoids, flavanols, and carotenoids; delayed the increase of relative electric conductivity, MDA, POD, and PPO activities; and significantly enhanced the activities of SOD and CAT, DPPH free radical scavenging ability, and FRAP, thereby improving antioxidant capacity. In summary, 0.05% L-Cys and 0.05% GABA treatment promotes the quality of loquat fruit after 40 days of storage, and significantly enhances antioxidant capacity, thus delaying senescence after harvest.


Risk Factors Associated With Knee Joint Degeneration After Arthroscopic Reshaping for Juvenile Discoid Lateral Meniscus.
Although arthroscopic meniscal reshaping for discoid lateral meniscus (DLM) has better outcomes than total or subtotal meniscectomy, degenerative changes on radiographs are still seen in some patients with meniscal reshaping. To assess the risk factors associated with knee joint degeneration after reshaping surgery for juvenile DLM. Case-control study; Level of evidence, 3. Forty patients (45 knees) with a mean age of 12.0 years who underwent arthroscopic meniscal reshaping for DLM were enrolled at a mean of 39.6 months after surgery. For all patients, meniscal saucerization was performed first. Then, if the residual meniscus was unstable, stabilization was provided with suture fixation. At final follow-up, we obtained radiographs to assess degenerative changes to the knee joint using the classification by Tapper and Hoover. Residual meniscal width and meniscal extrusion (defined as a relative percentage of extrusion [RPE]) were measured with magnetic resonance imaging (MRI). Then, the correlation between radiographic evidence of degenerative changes (Tapper and Hoover grade), residual meniscal width, and RPE were assessed with Pearson and Spearman correlation analyses. Logistic regression analysis was used to examine whether preoperative characteristics correlated with degeneration and residual meniscal width. The mean residual meniscal width was 4.6 mm (range, 3.8-6.0 mm), and the mean ± SD RPE was 25.5% ± 21.8% at the final follow-up. There were 28 knees with Tapper and Hoover grade 0, 10 knees with grade 1, and 7 knees with grade 2. The residual meniscal width and RPE were significantly correlated with Tapper and Hoover grade (ρ = -0.489, P = .0007; ρ = 0.414, P = .005, respectively). The residual meniscal width was also significantly correlated with RPE ( r = -0.416, P = .004). The receiver operating characteristic curve showed that a 5.0-mm residual meniscal width was the cutoff value leading to evidence of degeneration. Multiple logistic regression analysis showed that an anterocentral shift on preoperative MRI was a risk factor for degeneration (odds ratio, 27.2; 95% CI, 1.1-360.5; P = .012) and residual meniscal width less than 5.0 mm (odds ratio, 20.9; 95% CI, 1.5-281; P = .022). Smaller meniscal width and greater severity of meniscal extrusion correlated with knee joint degeneration. An anterocentral shift on preoperative MRI was a risk factor for degenerative changes and smaller residual meniscal width.


A review on the identification of transgenic oilseeds and oils.
Transgenic technology can increase the quantity and quality of vegetable oils worldwide. However, people are skeptical about the safety of transgenic oil-bearing crops and the oils they produce. In order to protect consumers' rights and avoid transgenic oils being adulterated or labeled as nontransgenic oils, the transgenic detection technology of oilseeds and oils needs careful consideration. This paper first summarized the current research status of transgenic technologies implemented at oil-bearing crops. Then, an inspection process was proposed to detect a large number of samples to be the subject rapidly, and various inspection strategies for transgenic oilseeds and oils were summarized according to the process sequence. The detection indicators included oil content, fatty acid, triglyceride, tocopherol, and nucleic acid. The detection technologies involved chromatography, spectroscopy, nuclear magnetic resonance, and polymerase chain reaction. It is hoped that this article can provide crucial technical reference and support for staff engaging in the supervision of transgenic food and for researchers developing fast and efficient monitoring methods in the future.


Mass spectrometric investigation of protein alkylation by the RNA footprinting probe kethoxal.
The reactivity of the RNA footprinting reagent kethoxal (KT) toward proteins was investigated by electrospray ionization-Fourier transform mass spectrometry. Using standard peptides, KT was shown to selectively modify the guanidino group of arginine side chains at neutral pH, while primary amino groups of lysine and N-terminus were found to be unreactive under these conditions. Gas-phase fragmentation of KT adducts provided evidence for a cyclic 1,2-diol structure. Esterification of the 1,2-diol product was obtained in borate buffer, and its structure was also investigated by tandem mass spectrometry. When model proteins were probed with this RNA footprinting reagent, the adducts proved to be sufficiently stable to allow for the application of different peptide-mapping procedures to identify the location of modified arginines. Probing of proteins under native folding conditions provided modification patterns that very closely matched the structural context of arginines in the global protein structure. A strong correlation was demonstrated between the susceptibility to modification and residue accessibility calculated from the known 3D structure. When the complexes formed by HIV-1 nucleocapsid (NC) protein and RNA stemloops SL2 and SL3 were investigated, KT footprinting provided accurate information regarding the involvement of individual arginines in binding RNA and showed different reactivity according to their mode of interaction.


HL-A frequencies in Crohn's disease and ulcerative colitis.
Sixty-two patients with Crohn's disease and 51 with ulcerative colitis were HL-A typed. Phenotype frequencies were calculated and compared with those of a control group of 335 individuals. A higher frequency of HL-A17 was found among the Crohn's disease patient but this was not significant. However, HL-A17 has been included in two studies on Crohn's disease and the combined relative risk is 3.24 which significantly deviates from 1 unity. No statistically significant differences in the HL-A antigen distribution were found among the patients with ulcerative colitis.


The Pattern of Valvular Heart Diseases in India During Pregnancy and Its Outcomes.
The incidence of rheumatic heart disease is very high in India. The data on the pattern of valvular heart diseases during pregnancy and its outcomes is very scarce. Again, the data in the Indian scenario, the differences in outcomes between different grades of valvular heart diseases and its impact on pregnancy outcomes is very less. We planned to study the different patterns of valvular heart diseases during pregnancy and their outcomes with respect to cardiac complication and perinatal outcomes. It was a hospital-based prospective observational study. We recruited 71 patients after taking written informed consent. All patients were with term gestation and valvular heart diseases. We did 2D echocardiography to analyze the valve lesion and assess the valve lesion with its maternal and perinatal outcomes. The mean age of participants in the study was 27 + 5.2 years. A total of 54 patients (76.1%) were less than 30 years and 17 (23.9%) were more than 30 years of age. Six patients (8.5%) presented with New York Heart Association (NYHA) class I, 39 patients (54.9%) presented with NYHA class II, 25 patients (35.2%) presented with NYHA class III and one patient (1.4%) presented with NYHA class IV. The most common etiology of valvular heart diseases was found to be rheumatic in 62 patients (87.3%). The most common valve involved was the mitral valve (69%). New-onset atrial fibrillation (AF) was reported in 26.8% patients and pulmonary edema developed in 15.5% patients. Live birth was observed in 66 patients (93%) compared to stillbirth reported in five patients (7%). No significant difference in maternal and perinatal outcomes between moderate and severe grades of different valvular heart diseases.


Multilevel Genome Typing Describes Short- and Long-Term Vibrio cholerae Molecular Epidemiology.
Since 1817, cholera, caused by Vibrio cholerae, has been characterized by seven distinct pandemics. The ongoing seventh pandemic (7P) began in 1961. In this study, we developed a Multilevel Genome Typing (MGT) tool for classifying the V. cholerae species with a focus on the 7P. MGT is based on multilocus sequence typing (MLST), but the concept has been expanded to include a series of MLST schemes that compare population structure from broad to fine resolutions. The V. cholerae MGT consists of eight levels, with the lowest, MGT1, composed of 7 loci and the highest, MGT8, consisting of the 7P core genome (3,759 loci). We used MGT to analyze 5,771 V. cholerae genomes. The genetic relationships revealed by lower MGT levels recapitulated previous findings of large-scale 7P transmission across the globe. Furthermore, the higher MGT levels provided an increased discriminatory power to differentiate subgroups within a national outbreak. Additionally, we demonstrated the usefulness of MGT for non-7P classification. In a large non-7P MGT1 type, MGT2 and MGT3 described continental and regional distributions, respectively. Finally, MGT described trends of 7P in virulence, and MGT2 to MGT3 sequence types (STs) grouped isolates of the same ctxB, tcpA, and ctxB-tcpA genotypes and characterized their trends over the pandemic. MGT offers a range of resolutions for typing V. cholerae. The MGT nomenclature is stable, transferable, and directly comparable between investigations. The MGT database (https://mgtdb.unsw.edu.au/) can accept and process newly submitted samples. MGT allows tracking of existing and new isolates and will be useful for understanding future spread of cholera. IMPORTANCE In 2017, the World Health Organization launched the "Ending Cholera" initiative to reduce cholera-related deaths by 90% by 2030. This strategy emphasized the importance of the speed and accessibility of newer technologies to contain outbreaks. Here, we present a new tool named Multilevel Genome Typing (MGT), which classifies isolates of the cholera-causing agent, Vibrio cholerae. MGT is a freely available online database that groups genetically similar V. cholerae isolates to quickly indicate the origins of outbreaks. We validated the MGT database retrospectively in an outbreak setting, showcasing rapid confirmation of the Nepalese origins for the 2010 Haiti outbreak. In the past 5 years, thousands of V. cholerae genomes have been submitted to the NCBI database, which underscores the importance of and need for proper genome data classification for cholera epidemiology. The V. cholerae MGT database can assist in early decision making that directly impacts controlling both the local and global spread of cholera.